(Barash) Clinical Anesthesia (6th Ed.)

Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.
;
Stock, M. Christine
Title: Clinical Anesthesia, 6th Edition
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ClInIcalanesthesIa/edItedbyPaulC.8arash[etal.].6thed.
p.;cm.
ncludesbIblIographIcalreferencesandIndex.
S8N97807817876J5(alk.paper)
1.AnesthesIology.2.AnesthesIa..8arash,PaulC.
[0NL|:1.AnesthesIology.2.AnesthesIa.J.AnesthetIcs.WD200C6J982009]
F081.C582009
617.96dc22
2008056102
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10987654J21
Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.;
Stock, M. Christine
Frontof8ookEdItors
Edited By
Paul G. Barash MD
Professor
0epartmentofAnesthesIology,YaleUnIversItySchoolof|edIcIne;AttendIng
AnesthesIologIst,YaleNewHavenHospItal,NewHaven,ConnectIcut
Bruce F. Cullen MD
EmerItusProfessor
0epartmentofAnesthesIology,UnIversItyofWashIngton,Seattle,WashIngton
Robert K. Stoelting MD
EmerItusProfessorandPastChaIr
0epartmentofAnesthesIa,ndIanaUnIversItySchoolof|edIcIne,ndIanapolIs,ndIana
Michael K. Cahalan MD
ProfessorandChaIr
0epartmentofAnesthesIology,TheUnIversItyofUtahSchoolof|edIcIne,SaltLakeCIty,
Utah
M. Christine Stock MD
ProfessorandChaIr
0epartmentofAnesthesIology,NorthwesternUnIversItyFeInbergSchoolof|edIcIne,
ChIcago,llInoIs
Contributing Authors
J. Jeffrey Andrews MD
ProfessorandChaIr
0epartmentofAnesthesIology,UnIversItyofTexasHealthScIenceCenter,SanAntonIo,San
AntonIo,Texas
Shamsuddin Akhtar MBBS
AssocIateProfessor
0epartmentofAnesthesIology,YaleUnIversItySchoolof|edIcIne,AttendIngPhysIcIan,
YaleNewHavenHospItal,NewHaven,ConnectIcut
Michael L. Ault MD, FCCP, FCCM
AssIstantProfessor
0epartmentofAnesthesIology,NorthwesternUnIversItyFeInbergSchoolof|edIcIne;
AssocIateChIef,SectIonofCrItIcalCare|edIcIne,Northwestern|emorIalHospItal,
ChIcago,llInoIs
Douglas R. Bacon MD
Professor
0epartmentofAnesthesIology,|ayoClInIc,Fochester,|Innesota
Paul G. Barash MD
Professor
0epartmentofAnesthesIology,YaleUnIversItySchoolof|edIcIne;AttendIng
AnesthesIologIst,YaleNewHavenHospItal,NewHaven,ConnectIcut
Honorio T. Benzon MD
Professor
0epartmentofAnesthesIology,NorthwesternUnIversIty,FeInbergSchoolof|edIcIne;
ChIef,0IvIsIonofPaIn|edIcIne,Northwestern|emorIalHospItal,ChIcago,llInoIs
Christopher M. Bernards MD
AnesthesIologyFaculty
0epartmentofAnesthesIology,7IrgInIa|ason|edIcal,Seattle,WashIngton
Arnold J. Berry MD, MPH
Professor
0epartmentofAnesthesIology,EmoryUnIverIstySchoolof|edIcIne,EmoryUnIversIty
HospItal,0epartmentofAnesthesIology,Atlanta,CeorgIa
David R. Bevan MB
Professor
0epartmentofAnesthesIology,UnIversItyofToronto,UnIversItyHealthNetwork,Toronto,
DntarIo,Canada
Barbara W. Brandom MD
Professor
0epartmentofAnesthesIology,UnIversItyofPIttsburgh|edIcalCenter;AttendIng
AnesthesIologIst,ChIldren'sHospItalofPIttsburgh,PIttsburgh,PennsylvanIa
Ferne R. Braveman MD, CM
Professor
0epartmentofAnesthesIology,YaleUnIversItySchoolof|edIcIne;ChIef,SectIonof
DbstetrIcalAnesthesIology;AttendIngPhysIcIan,YaleNewHavenHospItal,NewHaven,
ConnectIcut
Russell C. Brockwell MD
AnesthesIaAssocIatesofNaples
Naples,FlorIda
Sorin J. Brull MD
Professor
0epartmentofAnesthesIology,|ayoClInIcCollegeof|edIcIne,|ayoClInIcHospItal,
JacksonvIlle,FlorIda
ProfessorandChaIr
0epartmentofAnesthesIology,TheUnIversItyofUtahSchoolof|edIcIne,SaltLakeCIty,
Utah
Levon M. Capan MD
ProfessorofAnesthesIology;7IceChaIrforPromotIon
NewYorkUnIversItySchoolof|edIcIne;AssocIate0IrectorofAnesthesIaServIce,8ellevue
HopItalCenter,NewYork,NewYork
C. Richard Chapman PhD
0Irector
PaInFesearchCenter,0epartmentofAnesthesIology,UnIverIstyofUtahSchool,SaltLake
CIty,Utah
Amalia Cochran MD
AssIstantProfessor;AdjunctAssIstantProfessorofPedIatrIcs
0epartmentofSurgery,UnIversItyofUtah,SaltLakeCIty,Utah
Barbara A. Coda MD
StaffAnesthesIologIst
ThreeFIversAnesthesIa,DregonUrologynstItute,SprIngfIeld,Dregon
Edmond Cohen MD
ProfessorofAnesthesIology
The|ountSInaISchoolof|edIcIne;0IrectorofThoracIcAnesthesIa,The|ountSInaI
|edIcalCenter,NewYork,NewYork
Joseph P. Cravero MD
AssocIateProfessorofAnesthesIology
0artmouthHItchcock|edIcalCenter,Lebanon,NewHampshIre
C. Michael Crowder MD, PhD
AssocaIateProfessorofAnesthesIologyand|olecular8Iology/Pharmacology
WashIngtonUnIversItySchoolof|edIcIne,8arnesJewIshHospItal,St.LouIs,|IssourI
Marie Csete MD, PhD
AssocIateProfessor
0epartmentofAnesthesIology,EmoryUnIversIty,Atlanta,CeorgIa
Bruce F. Cullen MD
EmerItusProfessor
Steven Deem MD
AssocIateProfessor
0epartmentofAnesthesIologyand|edIcIne,UnIversItyofWashIngton;AssocIate0Irector,
NeurocrItIcalCareServIce,HarborvIew|edIcalCenter,Seattle,WashIngton
Timothy R. Deer MD
ClInIcalProfessor
0epartmentofAnesthesIology,West7IrgInIaUnIversItySchoolof|edIcIne,TheCenterfor
PaInFelIef,nc.,Charleston,West7IrgInIa
Stephen F. Dierdorf MD
Professorand7IceChaIr
Karen B. Domino MD, MPH
Professor
0epartmentofAnesthesIology,UnIversItyofWashIngtonSchoolof|edIcIne,Seattle,
WashIngton
Francois Donati MD, PhD, FRCPC
Professor
0epartmentofAnesthesIology,UnIversItyof|ontreal,HospItal|aIsonneuveFosemont,
|ontreal,Quebec,Canada
Michael B. Dorrough MD
FesIdentPhysIcIan
0epartmentofAnesthesIology,UnIversItyofUtahSchoolof|edIcIne,UnIversItyHealth
Care,SaltLakeCIty,Utah
John C. Drummond MD, FRCPC
ProfessorofAnesthesIology
TheUnIversItyofCalIfornIa,San0Iego;StaffAnesthesIologIst,7A|edIcalCenter,San
0Iego,San0Iego,CalIfornIa
Randal O. Dull MD, PhD
AssocIateProfessor
0epartmentofAnesthesIology,UnIversItyofUtah,SaltLakeCIty,Utah
Thomas J. Ebert MD, PhD
ProfessorofAnesthesIology;Program0Irector
|edIcalCollegeofWIsconsIn,7A|edIcalCenter,112A,|Ilwaukee,WIsconsIn
Jan Ehrenwerth MD
Professor
0epartmentofAnesthesIology,YaleUnIversItySchoolof|edIcIne,YaleNewHaven
HospItal,NewHaven,ConnectIcut
John H. Eichhorn MD
Professor
0epartmentofAnesthesIology,UnIversItyofKentuckyCollegeof|edIcIne,UnIverIstyof
Kentucky|edIcalCenter,LexIngton,Kentucky
James B. Eisenkraft MD
Professor
0epartmentofAnesthesIology,The|ountSInaISchoolof|edIcIne;AttendIng
AnesthesIologIst,The|ountSInaIHospItal,NewYork,NewYork
John E. Ellis MD
AdjunctProfessor
0epartmentofAnesthesIologyandCrItIcalCare,UnIversItyofPennsylvanIaSchoolof
|edIcIne,PhIladelphIa,PennsylvanIa
Matthew Eng MD
0epartmentofAnesthesIology
UnIversItyofTexasSouthwestern,0allas,Texas0epartmentofAnesthesIology,Cedars
SInaI|edIcalCenter,LosAngeles,CalIfornIa
Alex S. Evers MD
HenryE.|allInckrodtProfessorandChaIr
0epartmentofAnesthesIology,WashIngtonUnIversItySchoolof|edIcIne,AnesthesIologIst
InChIef,8arnesJewIshHospItal,St.LouIs,|IssourI
Lynne R. Ferrari MD
AssocIateProfessorofAnesthesIology
0epartmentofAnesthesIology,Harvard|edIcalSchool;ChIef,PerIoperatIveAnesthesIa,
TheChIldren'sHospItal,8oston,|assachusetts
Scott M. Fishman MD
ChIef,0IvIsIonofPaIn|edIcIne;ProfessorofClInIcalAnesthesIology
0epartmentofAnesthesIologyandPaIn|edIcIne,UnIversItyofCalIfornIa,0avIs,EllIson
AmbulatoryCareCenter,Sacramento,CalIfornIa
Michael A. Fowler MD, MBA
AssocIateProfessor
0epartmentofAnesthesIology,7IrgInIaCommonwealthUnIversIty;0Irector,Post
AnesthesIaCareUnIt,7IrgInIaCommonwealth|edIcalCenter,FIchmond,7IrgInIa
J. Sean Funston MD
AssIstantProfessor
0epartmentofAnesthesIology,UnIversItyofTexas|edIcal8ranch,Calveston,Texas
Steven I. Gayer MD, MBA
AssocIateProfessor
0epartmentsofAnesthesIologyandDphthalmology,UnIversItyof|IamI|IllerSchoolof
|edIcIne,8ascomPalmerEyenstItute,|IamI,FlorIda
Ronald George MD, FRCP
0ukeUnIversIty|edIcalCenter,0urham,NorthCarolIna
Kathryn Glas MD, FASE, MBA
AssocIateProfessor
0epartmentofAnesthesIology,EmoryUnIversItySchoolof|edIcIne;Co0Irector,
CardIothoracIcAnesthesIology,CrawfordLongHospItal,Atlanta,CeorgIa
Alexander W. Gotta MD
EmerItusProfessorofAnesthesIology
StateUnIversItyofNewYork,0ownstate|edIcalCenter,8rooklyn,NewYork
Loreta Grecu MD
AssIstantProfessor
0epartmentofAnesthesIology,YaleUnIversIty;AttendIngPhysIcIan,YaleNewHaven
HospItal,NewHaven,ConnectIcut
Steven B. Greenberg MD
AssIstantProfessor
0epartmentofAnesthesIology,NorthShoreUnIversItyHealthSystem,Evanston,llInoIs
Dhanesh K. Gupta MD
AssocIateProfessor
0epartmentofAnesthesIologyandNeurologIcalSurgery,NorthwesternUnIversItyFeInberg
Schoolof|edIcIne,Northwestern|emorIalHospItal,ChIcago,llInoIs
Steven C. Hall MD
ArthurC.KIngProfessorofPedIatrIcAnesthesIa
AnesthesIologIstInChIef,0epartmentofPedIatrIcAnesthesIa,ChIldren's|emorIal
HospItal,ChIcago,llInoIs
Tara M. Hata MD
ClInIcalAssocIateProfessor
0epartmentofAnesthesIa,CarverCollegeof|edIcIne,UnIversItyofowa,UnIversItyof
owaHospItalsandClInIcs,owaCIty,owa
Laurence M. Hausman MD
AssocIateProfessor
0epartmentofAnesthesIology,|ountSInaISchoolof|edIcIne,|ountSInaI|edIcalCenter,
NewYork,NewYork
Thomas K. Henthorn MD
ProfessorandChaIr
0epartmentofAnesthesIology,UnIversItyofColorado,0enver,UnIversItyofColorado
HospItal,Aurora,Colorado
Simon C. Hillier MB, ChB
0epartmentofAnesthesIa
SectIonofPedIatrIcAnesthesIaandCrItIcalCare,ndIanaUnIversItySchoolof|edIcIne,
ndIanapolIs,ndIana
Harriet W. Hopf MD
Professor
0epartmentofAnesthesIology,UnIversItyofUtahSchoolof|edIcIne,UnIversItyHealth
Care,SaltLakeCIty,Utah
Terese T. Horlocker MD
Professor
0epartmentsofAnesthesIologyandDrthopedIcs,|ayoClInIcCollegeof|edIcIne,
Fochester,|Innesota
Robert W. Hurley MD, PhD
AssIstantProfessor
0epartmentofAnesthesIologyandCrItIcalCare,JohnsHopkInsUnIversIty,|edIcal
0Irector,PaInClInIc,JohnsHopkIns|edIcalnstItutIons,8altImore,|aryland
Adam K. Jacob MD, MS
Fellow
Joel O. Johnson MD, PhD
Fussell0.SheldonProfessorandChaIr
0epartmentofAnesthesIologyandPerIoperatIve|edIcIne,UnIversItyof|IssourI,|IssourI
UnIverIstyHealth,ColumbIa,|IssourI
Zeev N. Kain MD, MBA
ProfessorandChaIr
0epartmentofAnesthesIology,UnIversItyofCalIfornIa,rvIne,rvIne,CalIfornIa
John P. Kampine MD, PhD
ProfessorEmerItus
0epartmentofAnesthesIology,|edIcalCollegeofWIsconsIn,|Ilwaukee,WIsconsIn
Jonathan C. Katz MD
StaffAnesthesIologIst;PrIvatePractIce
PlantatIon,FlorIda
Jonathan D. Katz MD
ClInIcalProfessor
0epartmentofAnesthesIology,YaleUnIversItySchoolof|edIcIne,NewHaven,
ConnectIcut;AttendIngAnesthesIologIst,0epartmentofAnesthesIology,St.7Incent's
|edIcalCenter,8rIdgeport,ConnectIcut
Brian S. Kaufman MD
AssocIateProfessor
0epartmentsof|edIcIne,AnesthesIologyandNeurosurgery,NewYorkUnIversItySchoolof
|edIcIne;0IrectorofCrItIcalCare,NYULangone|edIcalCenter,NewYork,NewYork
M. Sean Kincaid MD
ClInIcalnstructor
0epartmentofAnesthesIology,UnIversItyofWashIngton;AttendIngPhysIcIan,0epartment
ofAnesthesIology,HarborvIew|edIcalCenter,Seattle,WashIngton
Sandra L. Kopp MD
AssIstantProfessor
Arthur M. Lam MD, FRCPC
AnesthesIologIstInChIef;0IrectorofCerebrovascularLaboratoryHarborvIew|edIcal
Center;ProfessorofAnesthesIologyandNeurologIcalSurgery
UnIversItyofWashIngton,Seattle,WashIngton
Thomas A. Lane MD
ProfessorofPathology
UnIversItyofCalIfornIa,San0Iego;|edIcal0Irector,UCS0TransfusIonServIcesandStem
CellProcessIngLab,San0Iego,CalIfornIa
Noel W. Lawson MD
Professor
0epartmentofAnesthesIology,UnIversItyof|IssourIColumbIa;StaffAnesthesIologIst,
UnIversItyof|IssourIColumbIaHospItalsandClInIcs,ColumbIa,|IssourI
Wilton C. Levine MD
nstructorInAnesthesIa
Harvard|edIcalSchool;AssIstantInAnesthesIa,0epartmentsofAnesthesIologyand
CrItIcalCare,|assachusettsCeneralHospItal,8oston,|assachusetts
Jerrold H. Levy MD, FAHA
Professorand0eputyChaIrforFesearch
0epartmentofAnesthesIology,EmoryUnIversItySchoolof|edIcIne;0Irectorof
CardIothoracIcAnesthesIologyandCrItIcalCare,EmoryHealthcare,Atlanta,CeorgIa
Adam D. Lichtman MD
AssIstantProfessorofAnesthesIology
0epartmentofAnesthesIology,WeIllCornell|edIcalCenter,NewYorkPresbyterIan
HospItal,NewYork,NewYork
J. Lance Lichtor MD
Professor
0epartmentofAnesthesIology,UnIversItyof|assachusetts|edIcalSchool,Worcester,
|assachusetts
Yi Lin MD, PhD
ClInIcalnstructorofAnesthesIology
0epartmentofAnesthesIology,WeIll|edIcalCollegeofCornellUnIversIty,AssIstant
AttendIngAnesthesIologIst,HospItalforSpecIalSurgery,NewYork,NewYork
Spencer S. Liu MD
ClInIcalProfessor
0epartmentofAnesthesIology,WeIll|edIcalCollegeofCornellUnIversIty,HospItalfor
SpecIalSurgery,NewYork,NewYork
David A. Lubarsky MD, MBA
Emanuel|.PapperProfessorandChaIr
0epartmentofAnesthesIology,PerIoperatIve|edIcIne,andPaIn|anagement,UnIversIty
of|IamI|IllerSchoolof|edIcIne,0epartmentofAnesthesIology,Jackson|emorIal
HospItal,|IamI,FlorIda
Stephen M. Macres PharmD, MD
0Irector,PostoperatIvePaInandFegIonalAnesthesIaServIce
ClInIcalProfessorofAnesthesIology,0epartmentofAnesthesIologyandPaIn|edIcIne,
UnIversItyofCalIfornIa,0avIs,Sacramento,CalIfornIa
Srinivas Mantha MD
ProfessorandSub0ean
0epartmentofAnesthesIologyandntensIveCare,NIzam'snstItuteof|edIcalScIences,
Hyderahad,ndIa
Joseph P. Mathew MD, MHSc
Professor
0epartmentofAnesthesIology,0ukeUnIversIty;ChIef,0IvIsIonofCardIothoracIc
AnesthesIology,0ukeUnIversIty|edIcalCenter,0urham,NorthCarolIna
Michael S. Mazurek MD
AssocIateProfessor
0epartmentofAnesthesIology,ndIanaUnIversItySchoolof|edIcIne,FIleyHospItalfor
ChIldren,ndIanapolIs,ndIana
Kathryn E. McGoldrick MD
ProfessorandChaIr
0epartmentofAnesthesIology,NewYork|edIcalCollege,Westchester|edIcalCenter,
7alhalla,NewYork
Sanford M. Miller MD
ClInIcalAssocIateProfessor
NewYorkUnIversItySchoolof|edIcIne;AssIstant0IrectorofAnesthesIology,8ellevue
HospItalCenter,NewYork,NewYork
Peter G. Moore MB, BS, PhD, FANZCA
ProfessorandChaIr
0epartmentofAnesthesIologyandPaIn|edIcIne,UnIversItyofCalIfornIa,0avIs,UnIversIty
ofCalIfornIa,0avIs|edIcalCenter,Sacramento,CalIfornIa
John R. Moyers MD
Professor
0epartmentofAnesthesIa,CarverCollegeof|edIcIne,UnIversItyofowa,UnIversItyof
owaHopsItalsandClInIcs,owaCIty,owa
Holly Muir MD
AssIstantProfessor
0epartmentofAnesthesIology,0ukeUnIversIty|edIcalCenter,0urham,NorthCarolIna
Glenn S. Murphy MD
NorthShoreUnIversItyHealthSystem
Evanston,llInoIs
Michael J. Murray MD, PhD
Professor
0epartmentofAnesthesIology,|ayoClInIcCollegeof|edIcIne,|ayoClInIcHospItal,
JacksonvIlle,FlorIda
Steven M. Neustein MD
AssocIateProfessor
0epartmentofAnesthesIology,The|ountSInaISchoolof|edIcIne,|ountSInaIHospItal,
NewYork,NewYork
E. Andrew Ochroch MD, MSCE
AssocIateProfessorofAnesthesIologyandCrItIcalCare
0IrectorofClInIcalFesearch;0IrectorofThoracIcAnesthesIology,UnIversItyof
PennsylvanIaHealthSystem,PhIladelphIa,PennsylvanIa
Babatunde O. Ogunnaike MD
AssocIateProfessor
0epartmentofAnesthesIologyandPaIn|anagement,UnIversItyofTexasSouthwestern
|edIcalCenter;ChIefofAnesthesIaServIces,ParklandHealthandHospItalSystem,0allas,
Texas
Charles W. Otto MD, FCCM
Professor
0epartmentofAnesthesIology,UnIversItyofArIzonaCollegeof|edIcIne,ArIzonaHealth
ScIencesCenter,Tucson,ArIzona
Nathan Leon Pace MD, Mstat
Professor
0epartmentofAnesthesIology,UnIversItyofUtah,SaltLakeCIty,Utah
Paul S. Pagel MD, PhD
Professor
0epartmentofAnesthesIology,|edIcalCollegeofWIsconsIn;StaffAnesthesIologIst,
0epartmentofAnesthesIaandSpecIalCare,ZablockI7A|edcIalCenter,|Ilwaukee,
WIsconsIn
Albert C. Perrino Jr. MD
Professor
0epartmentofAnesthesIology,YaleUnIversItySchoolof|edIcIne;AttendIngPhysIcIan,
Charise Petrovitch MD
ClInIcalProfessor
0epartmentofAnesthesIaandClInIcalCare|edIcIne,CeorgeWashIngtonUnIversIty
HospItal;ChIef,AnesthesIaSectIon,7A|edIcalCenter,WashIngton,0C
Mihai V. Podgoreanu MD, FASE
AssocIateProfessor
0epartmentofAnesthesIology,0ukeUnIversIty;0Irector,PerIoperatIbeCenomIcsProgram,
0ukeUnIversIty|edIcalCenter,0urham,NorthCarolIna
Wanda M. Popescu MD
AssIstantProfessorofAnesthesIology
Karen L. Posner PhD
FesearchProfessor
Donald S. Prough MD
Professor,andChaIr
0epartmentofAnesthesIology,UnIversItyofTexas|edIcal8ranch,Calveston,Texas
Kevin T. Riutort MD
ChIefFesIdent
0epartmentofAnesthesIology,|ayoClInIc,|ayoClInIcHospItal,JacksonvIlle,FlorIda
J. David Roccoforte MD
AssIstantProfessor
0epartmentofAnesthesIology,NewYorkUnIversItySchoolof|edIcIne,NewYork,New
York
Michael F. Roizen MD
Professor
0IvIsIonofAnesthesIology,CrItIcalCare|edIcIneandComprehensIvePaIn|anagement;
ChaIr,WellnessnstItute,ClevelandClInIcalFoundatIon,Cleveland,DhIo
G. Alec Rooke MD, PhD
7IsItIngProfessor
0epartmentofAnesthesIology,8ethsrael0eaconess|edIcalCenter,Harvard|edIcal
School,8oston,|assachusetts;Professor,0epartmentofAnesthesIologyandCrItIcalCare,
UnIversItyofWashIngton,UnIversItyofWashIngton|edIcalCenter,Seattle,WashIngton
Stanley H. Rosenbaum MD
Professor
Henry Rosenberg MD, CPE
0Irector
0epartmentof|edIcalEducatIonandClInIcalFesearch,SaInt8arnabas|edIcalCenter,
LIvIngston,NewJersey
Meg A. Rosenblatt MD
AssocIateProfessor
0epartmentofAnesthesIology,|ountSInaISchoolof|edIcIne,NewYork,NewYork
William H. Rosenblatt MD
Professor
Richard W. Rosenquist MD
Professor
0epartmentofAnesthesIa,UnIversItyofowa;0Irector,PaIn|edIcIne0IvIsIon,UnIversIty
ofowaHospItal,owaCIty,owa
Carl E. Rosow MD, PhD
Professor
0epartmentofAnesthesIaandCrItIcalCare,Harvard|edIcalSchool,|assachusetts
CeneralHospItal,8oston,|assacusetts
Nyamkhishig Sambuughin PhD
AssIstantProfessor
0epartmentofAnesthesIology,UnIformedServIcesUnIversIty,8ethesda,|aryland
Alan C. Santos MD, MPH
ChaIrmanofAnesthesIology
DchsnerClInIcFoundatIon,NewDrleans,LouIsIana
Barbara M. Scavone MD
AssocIateProfessor
Northwestern|emorIalHospItal,ChIcago,llInoIs
Philliip G. Schmid MD
St.AlphonsusFegIonal|edIcalCenter,8oIse,daho
Jeffrey J. Schwartz MD
AssocIateProfessor
Harry A. Seifert MD
AdjunctAssIstantProfessorofClInIcalAnesthesIology
0epartmentofAnesthesIologyandCrItIcalCare,TheChIldren'sHospItalofPhIladelphIa,
PhIladelphIa,PennsylvanIa
Aarti Sharma MD
AssIstantProfessor
0epartmentofAnesthesIology,WeIllCornell|edIcalCenter,NewYorkPresbyterIan
HospItal,NewYork,NewYork
Andrew Shaw BSc, MBBS, FRCA, FCCM
AssocIateProfessor
0epartmentofAnesthesIology,0ukeUnIversIty;AttendIngAnesthesIologIst,0ukeUnIversIty
|edIcalCenter,0urham,NorthCarolIna
Nikolaos J. Skubas MD, FASE
AssocIateProfessor
0epartmentofAnesthesIology,WeIllCornell|edIcalCollege;AssocIateAttendIng,New
YorkHospItalWeIllCornell|edIcalCenter,NewYork,NewYork
Hugh M. Smith MD, PhD
nstructor
0epartmentofAnesthesIology,|ayoClInIcCollegeof|edIcIne,|ayoClInIc,Fochester,
|Innesota
Karen J. Souter BBS, FRCA
AssocIateProfessor
0epartmentofAnesthesIologyandPaIn|edIcIne,UnIversItyofWashIngton,Seattle,
WashIngton
Bruce D. Spiess MD, FAHA
ProfessorofAnesthesIologyandEmergency|edIcIne;0Irectorof7IrgInIaCommonwealth
UnIversItyFeanImatIon
EngIneerIngShockCenter,7IrgInIaCommonwealthUnIversIty|edIcalCenter,FIchmond,
7IgInIa
Mark Stafford-Smith MD, CM, FRCP, FASE
Professor
0epartmentofAnesthesIology,0ukeUnIversIty|edIcalCenter,0urham,NorthCarolIna
Professor
Northweston|emorIalHospItal,ChIcago,llInoIs
EmerItusProfessorandPastChaIr
Karen J. Souter BBS, FRCA
AssocIateProfessor
0epartmentofAnesthesIologyandPaIn|edIcIne,UnIversItyofWashIngton,Seattle,
WashIngton
David F. Stowe MD, PhD
Professor
0espartmentofAnesthesIologyandPhysIology,|edIcalCollegeofWIsconsIn,Froedtert
HospItalEZablockI7A|edIcalCenter,|IlwaukeeFegIonal|edIcalCenter,|Ilwaukee,
WIsconsIn
Wariya Sukhupragarn MD, FRCAT
AssIstantProfessor
0epartmentofAnesthesIology,ChIang|aIUnIversIty,|aharajNakornChIang|aIHospItal,
ChIang|aI,ThaIland;FesearchFellowInAIrway|anagement,0epartmentof
AnesthesIology,YaleUnIversItySchoolof|edIcIne,YaleNewHavenHospItal,NewHaven,
ConnectIcut
Santhanam Suresh MD
Professor
ChIldren's|emorIalHospItal,ChIcago,llInoIs
Christer H. Svensn MD, PhD, DEAA, MBA
AssocIateProfessor
0epartmentofAnesthesIology,WeIll|edIcalCollegeofCornellUnIversIty,NewYork
PresbyterIanHospItal,NewYork,NewYork
Stephen J. Thomas MD
TopkIn7anPoznakProfessorand7IceChaIrman
0epartmentofAnesthesIology,WeIll|edIcalCollegeofCornellUnIversIty,NewYork
PresbyterIanHospItal,NewYork,NewYork
Miriam M. Treggiari MD, PhD, MPH
AssocIateProfessor
0epartmentofAnesthesIologyandPaIn|edIcIne,UnIversItyofWashIngton,HarborvIew
|edIcalCenter,Seattle,WashIngton
Ban Tsui BSc, MSc, MD, FRCPC
Professor
0epartmentofAnesthesIologyandPaIn|edIcIne,UnIversItyofAlberta;0Irector,FegIonal
AnesthesIaandPaInServIce,UnIversItyofAlbertaHospItal,StolleryChIldren'sHospItal,
Edmonton,Alberta,Canada
Jeffrey S. Vender MD, FCCM, FCCP
NorthShoreUnIversItyHealthSystem,Evanston,llInoIs
J. Scott Walton MD
AssocIateProfessor
0epartmentofAnesthesIaandPerIoperatIve|edIcIne,|edIcalUnIversItyofSouth
CarolIna,Charleston,SouthCarolIna
Mark A. Warner MD
Professor
Denise J. Wedel MD
Professor
0epartmentofAnesthesIology,|ayoClInIcCollegeof|edIcIne,Fochester,|Innesota
Paul F. White PhD, MD
ProfessorandHolderofthe|argaret|Ilam|c0ermott;0IstInguIshedChaIrIn
AnesthesIology
0epartmentofAnesthesIologyEPaIn|anagement,UnIversItyofTexasSouthwestern
|edIcalCenter,0allas,Texas
Charles W. Whitten MD
ProfessorandChaIr
0epartmentofAnesthesIologyandPaIn|anagement,UnIversItyofTexasSouthwestern
|edIcalCenter,0allas,Texas
Scott W. Wolf MD
AssIstantProfessor
Northwestern|emorIalHospItal,ChIcago,llInoIs
Cynthia A. Wong MD
AssocIateProfessor
|edIcal0IrectorofDbstetrIcAnesthesIa,Northwestern|emorIalHospItal,ChIcago,llInoIs
James R. Zaidan MD, MBA
ProfessorandChaIr
0epartmentofAnesthesIology,EmoryUnIversItyHospItal,Atlanta,CeorgIa
Stock, M. Christine
Frontof8ookPreface
Preface
WelcometothesIxthedItIonofClinical Anesthesia.ThepublIcatIonofthIsedItIonoccurs
atatImeofgreatclInIcal,educatIonal,andresearchadvances.AtnotImeInour
specIalty'shIstoryIstheobservatIonmoretruethatthemajorachIevementsInsurgery
couldnotoccurwIthouttheaccompanyIngvIsIonofskIllfulanesthesIologIsts.EverydayIn
operatIngroomsaroundtheworldanesthesIologIstsarechallengedtomeetexemplary
levelsofclInIcalcarewhIleensurIngthehIghestlevelofpatIentsafety.Tomeetthese
needsneweducatIonalparadIgmsarebeIngemployedwhIchrequIreeducatIonInavarIety
offormatsandsettIngs.
TheprImegoalofClinical AnesthesiafromItsInceptIonhasbeen:
TodevelopatextbookthatsupportseffIcIentandrapIdacquIsItIonofknowledge.
TheedItorshaveemployedavarIetyofeducatIonalmethodstoachIevethIsobjectIve
makIngClinical Anesthesia,InrealIty,aserIesofInterconnectedpublIcatIonsusIngthe
prIntedword,electronIcmedIum,andthenternet.DureffortshavebeenrecognIzedwIth
numerousInternatIonalawards.WIththepublIcatIonofeachedItIon,wetrytodevelop
InnovatIveandcontemporarywaystodIssemInateknowledgetoourreader.WIththIs
edItIon,wearethefIrstanesthesIatexttousepodcastIngasoneofthenewestmethodsto
rapIdlytransmItclInIcallyrelevantInformatIon,whIlealsoassIstIngpractIonerswhoare
preparIngfor8oardexamInatIonsandrecertIfIcatIon.
StartIngwIththecover,youwIllseemajorchangesInthetextbook.0rs.|.ChrIstIneStock
and|IchaelK.CahalanhavejoInedtheEdItors.8othChrIsand|IkebrIngtheIrunIque
talentstoenhanceourabIlItytodelIveraforwardlookIngclInIcaltextthatenhances
acquIsItIonofclInIcallyImportantInformatIonandalIgnschaptercontentwIth
contemporaryeducatIonalgoals.0r.FobertStoeltIngwIllassumeEdItorEmerItusstatus.
8obIsInstrumentalInthesuccessoftheClinical AnesthesiaserIes.HIswrItIngandedItIng
capabIlItIesarelegendary.TheedItorshavebenefItedenormouslyfromhIsInsIghtsInto
modernanesthesIa,aswellashIshandsonapproachtothelogIstIcallycomplextaskof
edItorIalsupervIsIon.
DncethebookIsopened,thereaderwIllbeabletoapprecIateaunIfIedgraphIcformat.All
IllustratIonsandgraphIcsarepresentedtoaugmenttheeducatIonalexperIenceandrapIdly
transmItImportantInformatIon.naddItIon,toareorderedtableofcontents,twonew
chaptershavebeenadded:Inflammation, Wound Healing and Infection,and
Echocardiography.ApproxImatelyathIrdofthecontrIbutorsarenewtothIsedItIon,
IncorporatIngafreshpoIntofvIewtoImportantchaptercontent.Wehaveencouraged
contrIbutorstodevelopclInIcallyrelevantthemesandprIorItIzevarIousclInIcaloptIons
consIderedbymanytobethedefInItIvestrengthofprevIousedItIons.
WerealIzethatredundancIesmayexIstInabookofthIssIze.TheedItorshavetakenevery
opportunItytoreducerepetItIonorevendIsagreementbetweenchapters.However,
clInIcalproblemsaremanageddIfferentlybypractIoners,sothIsdIversItyofapproach
servestoenrIchtheeducatIonalexperIence.
WewIshtoexpressourapprecIatIontoallourcontrIbutorswhoseknowledge,hardwork,
dedIcatIonandtImelysubmIssIonshaveallowedustomaIntaInqualItywhIleworkIngwIth
atIghtproductIonschedule.DurreadershavealsobeenInstrumentalInprovIdIng
commentsthatallowtheedItorstocontInuallyImproveClinical Anesthesiatomeetthe
needsofouraudIence.0r.JorgeCalvezdeservesspecIalrecognItIonforhIsenormous
InputonthelogIstIcalmanagementofourpodcastIngproject.WealsothankChrIstopher
CambIc,|0whoproofreadfordetaIls,aswellasouradmInIstratIveassIstantsCaIlNorup,
FubyWIlson,0eannaWalker,and7IctorIaFamos.WewouldlIketothankouredItorsat
LIppIncottWIllIamsEWIlkInsWoltersKluwer,8rIan8rownandLIsa|cAllIster,fortheIr
commItmenttoexcellence.FInally,weoweadebtofgratItudetoNIcole0ernoskI
|anagIngEdItoratLWW,ChrIs|IllerProductIon|anageratAptara,AngelaPanetta
|arketIngatLWW,andEdSchultes,Jr.|edIaAssIstantatLWWwhosedaytoday
managementofthIsendeavorresultedInapublIcatIonthatexceededtheEdItor's
expectatIons.
Paul G. Barash MD
Bruce F. Cullen MD
Stock, M. Christine
TableofContentsSectIonntroductIontoAnesthesIologyChapter1TheHIstoryofAnesthesIa
Chapter1
The History of Anesthesia
Adam K. Jacob
Sandra L. Kopp
Douglas R. Bacon
Hugh M. Smith
Key Points
1. Anesthesiology is a young specialty historically, especially when
compared with surgery or internal medicine.
2. Discoveries in anesthesiology have taken decades to build upon the
observations and experiments of many people, and in some instances
we are still searching. For example, the ideal volatile anesthetic has
yet to be discovered.
3. Regional anesthesia is the direct outgrowth of a chance observation
by an intern who would go on to become a successful
ophthalmologist.
4. Pain medicine began as an outgrowth of regional anesthesia.
5. Much of our current anesthesia equipment is the direct result of
anesthesiologists being unhappy with and needing better tools to
properly anesthetize patients.
6. Many safety standards have been established through the work of
anesthesiologists who were frustrated by the status quo.
7. Organizations of anesthesia professionals have been critical in
establishing high standards in education and proficiency, which in
turn has defined the specialty.
8. Respiratory critical care medicine started as the need by
anesthesiologists to use positive pressure ventilation to help polio
victims.
9. Surgical anesthesia and physician specialization in its administration
have allowed for increasingly complex operations to be performed on
increasingly ill patients.
SurgerywIthoutadequatepaIncontrolmayseemcrueltothemodernreader,andIn
contemporarypractIcewearepronetoforgettherealItIesofpreanesthesIasurgery.Fanny
8urney,awellknownlIteraryartIstfromtheearly19thcentury,descrIbedamastectomy
sheenduredafterreceIvIngawInecordIalashersoleanesthetIc.Assevenmale
assIstantsheldherdown,thesurgerycommenced:Whenthedreadfulsteelwasplunged
IntothebreastcuttIngthroughveInsarterIesfleshnervesneedednoInjunctIonnotto
restraInmycrIes.beganascreamthatlastedunIntermIttentlydurIngthewholetImeof
theIncIsIonEalmostmarvelthatItrIngsnotInmyEarsstIll!SoexcrucIatIngwasthe
agony.DhHeaven!thenfelttheknIferackIngagaInstthebreastbonescrapIngIt!ThIs
performedwhIleyetremaInedInutterlyspeechlesstorture.
1
8urney'sdescrIptIon
IllustratesthedIffIcultyofoverstatIngtheImpactofanesthesIaonthehumancondItIon.
AnepItaphonamonumenttoWIllIamThomasCreen|orton,oneofthefoundersof
anesthesIa,summarIzesthecontrIbutIonofanesthesIa:8EFDFEWHD|InalltImeSurgery
wasAgony.
2
AlthoughmosthumancIvIlIzatIonsevolvedsomemethodfordImInIshIng
patIentdIscomfort,anesthesia,InItsmodernandeffectIvemeanIng,IsacomparatIvely
recentdIscoverywIthtraceableorIgInsInthemId19thcentury.Howwehavechanged
perspectIvesfromoneInwhIchsurgIcalpaIn
P.4
wasterrIbleandexpectedtooneInwhIchpatIentsreasonablyassumetheywIllbesafe,
paInfree,andunawaredurIngextensIveoperatIonsIsafascInatIngstoryandthesubjectof
thIschapter.
AnesthesIologIstsarelIkenootherphysIcIans:weareexpertsatcontrollIngtheaIrwayand
atemergencyresuscItatIon;wearerealtImecardIopulmonologIstsachIevIng
hemodynamIcandrespIratorystabIlItyfortheanesthetIzedpatIent;weare
pharmacologIstsandphysIologIsts,calculatIngapproprIatedosesanddesIredresponses;we
aregurusofpostoperatIvecareandpatIentsafety;weareInternIstsperformIng
perIanesthetIcmedIcalevaluatIons;wearethepaInexpertsacrossallmedIcaldIscIplInes
andapplyspecIalIzedtechnIquesInpaInclInIcsandlaborwards;wemanagetheseverely
sIckandInjuredIncrItIcalcareunIts;weareneurologIsts,selectIvelyblockIng
sympathetIc,sensory,ormotorfunctIonswIthourregIonaltechnIques;wearetraIned
researchersexplorIngscIentIfIcmysteryandclInIcalphenomenon.
AnesthesIologyIsanamalgamofspecIalIzedtechnIques,equIpment,drugs,andknowledge
that,lIkethegrowthrIngsofatree,havebuIltupovertIme.CurrentanesthesIapractIceIs
thesummatIonofIndIvIdualeffortandfortuItousdIscoveryofcenturIes.Everycomponent
ofmodernanesthesIawasatsomepoIntanewdIscoveryandreflectstheexperIence,
knowledge,andInventIvenessofourpredecessors.HIstorIcalexamInatIonenables
understandIngofhowtheseIndIvIdualcomponentsofanesthesIaevolved.Knowledgeofthe
hIstoryofanesthesIaenhancesourapprecIatIonofcurrentpractIceandIntImateswhere
ourspecIaltymIghtbeheaded.
Anesthesia Before Ether
Physical and Psychological Anesthesia
TheEdwInSmIthSurgIcalPapyrus,theoldestknownwrIttensurgIcaldocument,descrIbes
48casesperformedbyanEgyptIansurgeonfromJ000to25008C.WhIlethIsremarkable
surgIcaltreatIsecontaInsnodIrectmentIonofmeasurestolessenpatIentpaInorsufferIng,
EgyptIanpIctographsfromthesameerashowasurgeoncompressInganerveInapatIent's
antecubItalfossawhIleoperatIngonthepatIent'shand.AnotherImagedIsplaysapatIent
compressInghIsownbrachIalplexuswhIleaprocedureIsperformedonhIspalm.
J
nthe
16thcentury,mIlItarysurgeonAmbroIseParbecameadeptatnervecompressIonasa
meansofcreatInganesthesIa.
|edIcalscIencehasbenefItedfromthenaturalrefrIgeratIngpropertIesofIceandsnowas
well.ForcenturIesanatomIcaldIssectIonswereperformedonlyInwInterbecausecolder
temperaturesdelayeddeterIoratIonofthecadaver,andInthe|IddleAgestheanesthetIc
effectsofcoldwaterandIcewererecognIzed.nthe17thcentury,|arcoAurelIoSeverIno
descrIbedthetechnIqueofrefrIgeratIonanesthesIaInwhIchsnowwasplacedInparallel
lInesacrosstheIncIsIonalplanesuchthatthesurgIcalsItebecameInsensatewIthIn
mInutes.ThetechnIqueneverbecamewIdelyused,lIkelybecauseofthechallengeof
maIntaInIngstoresofsnowyearround.
4
SeverInoIsalsoknowntohavesavednumerous
lIvesdurInganepIdemIcofdIphtherIabyperformIngtracheostomIesandInsertIngtrocars
tomaIntaInpatencyoftheaIrway.
5
FormalmanIpulatIonofthepsychetorelIevesurgIcalpaInwasundertakenbyFrench
physIcIansCharles0upotetandJulesCloquetInthelate1820swIthhypnosIs,thencalled
mesmerism.AlthoughtheworkofAnton|esmerwasdIscredItedbytheFrenchAcademyof
ScIenceafterformalInquIryseveraldecadesearlIer,proponentslIke0upotetandCloquet
contInuedwIthmesmerIcexperImentsandpleadedtotheAcademIede|edIcIneto
reconsIderItsutIlIty.
6
nawellattendeddemonstratIonIn1828,Cloquetremovedthe
breastofa64yearoldpatIentwhIleshereportedlyremaInedInacalm,mesmerIcsleep.
ThIsdemonstratIonmadealastIngImpressIonon8rItIshphysIcIanJohnEllIotson,who
becamealeadIngfIgureofthemesmerIcmovementInEnglandInthe18J0sand1840s.
nnovatIveandquIcktoadoptnewadvances,EllIotsonperformedmesmerIc
demonstratIonsandIn184JpublIshedNumerous Cases of Surgical Operations without Pain
in the Mesmeric State.SupportformesmerIsmfadedwhenIn1846renownedsurgeon
FobertLIstonperformedthefIrstoperatIonusIngetheranesthesIaInEnglandand
remarked,ThIsYankeedodgebeatsmesmerIsmallhollow.
7
Early Analgesics and Soporifics
0IoscorIdes,aCreekphysIcIanfromthefIrstcenturyA0,commentedontheanalgesIaof
mandragora,adrugpreparedfromthebarkandleavesofthemandrakeplant.Heobserved
thattheplantsubstancecouldbeboIledInwIne,straIned,andusedInthecaseofpersons
abouttobecutorcauterIzed,whentheywIshtoproduceanesthesIa.
8
|andragorawas
stIllbeIngusedtobenefItpatIentsaslateasthe17thcentury.FromthenInthtothe
thIrteenthcenturIes,thesoporific spongewasadomInantmodeofprovIdIngpaInrelIef
durIngsurgery.|andrakeleaves,alongwIthblacknIghtshade,poppIes,andotherherbs,
wereboIledtogetherandcookedontoasponge.ThespongewasthenreconstItutedInhot
waterandplacedunderthepatIent'snosebeforesurgery.PrIortothehypodermIcsyrInge
androutInevenousaccess,IngestIonandInhalatIonweretheonlyknownroutesfor
admInIsterIngmedIcInestogaInsystemIceffects.PreparedasIndIcatedbypublIshed
reportsofthetIme,thespongegenerallycontaInedmorphIneandscopolamIneInvaryIng
amountsdrugsusedInmodernanesthesIa.
9
AlcoholwasanotherelementofthepreetherarmamentarIumbecauseItwasthoughtto
InducestuporandblunttheImpactofpaIn.AlthoughalcoholIsacentralnervoussystem
depressant,IntheamountsadmInIsteredItproducedlIttleanalgesIaInthesettIngoftrue
surgIcalpaIn.Fanny8urney'saccountunderscorestheIneffectIvenessofalcoholasan
anesthetIc.NotonlydIdthealcoholprovIdemInImalpaIncontrol,ItdIdnothIngtodullher
recollectIonofevents.LaudanumwasanalcoholbasedsolutIonofopIumfIrstcompounded
byParacelsusInthe16thcentury.twaswIldlypopularInthe7IctorIanandFomantIc
perIods,andprescrIbedforawIdevarIetyofaIlmentsfromthecommoncoldto
tuberculosIs.AlthoughapproprIatelyusedasananalgesIcInsomeInstances,Itwas
frequentlymIsusedandabused.LaudanumwasgIvenbynursemaIdstoquIetwaIlIngInfants
andabusedbymanyupperclasswomen,poets,andartIstswhofellvIctImtoItsaddIctIve
potentIal.
Inhaled Anesthetics
NItrousoxIdewasknownforItsabIlItytoInducelIghtheadednessandwasoftenInhaledby
thoseseekIngathrIll.twasnotusedasfrequentlyasetherbecauseItwasmoredIffIcult
tosynthesIzeandstore.twasmadebyheatIngammonIumnItrateInthepresenceofIron
fIlIngs.TheevolvedgaswaspassedthroughwatertoelImInatetoxIcoxIdesofnItrogen
beforebeIngstored.NItrousoxIdewasfIrstpreparedIn177JbyJosephPrIestley,anEnglIsh
clergymanandscIentIst,whoranksamongthegreatpIoneersofchemIstry.WIthoutformal
scIentIfIctraInIng,PrIestleypreparedandexamInedseveralgases,IncludIngnItrousoxIde,
ammonIa,sulfurdIoxIde,oxygen,carbonmonoxIde,andcarbondIoxIde.
Attheendofthe18thcenturyInEngland,therewasastrongInterestInthesupposed
wholesomeeffectsofmIneral
P.5
watersandgases,partIcularlywIthregardtotreatmentofscurvy,tuberculosIs,andother
dIseases.Thomas8eddoesopenedhIsPneumatIcnstItuteclosetothesmallspaof
Hotwells,InthecItyof8rIstol,tostudythebenefIcIaleffectsofInhaledgases.HehIred
Humphry0avyIn1798toconductresearchprojectsforthenstItute.0avyperformed
brIllIantInvestIgatIonsofseveralgasesbutfocusedmuchofhIsattentIononnItrousoxIde.
HIshumanexperImentalresults,combInedwIthresearchonthephysIcalpropertIesofthe
gas,werepublIshedInNitrous Oxide,a580pagebookpublIshedIn1800.ThIsImpressIve
treatIseIsnowbestrememberedforafewIncIdentalobservatIons.0avycommentedthat
nItrousoxIdetransIentlyrelIevedasevereheadache,oblIteratedamInorheadache,and
brIeflyquenchedanaggravatIngtoothache.Themostfrequentlyquotedpassagewasa
casualentry:AsnItrousoxIdeInItsextensIveoperatIonappearscapableofdestroyIng
physIcalpaIn,ItmayprobablybeusedwIthadvantagedurIngsurgIcaloperatIonsInwhIch
nogreateffusIonofbloodtakesplace.
10
ThIsIsperhapsthemostfamousofthemIssed
opportunItIestodIscoversurgIcalanesthesIa.0avy'slastIngnItrousoxIdelegacywas
coInIngthephraselaughInggastodescrIbeItsunIqueproperty.
Almost Discovery: Hickman, Clarke, Long, and Wells
Asthe19thcenturyprogressed,socIetalattItudestowardpaInchanged,perhapsbest
exemplIfIedInthewrItIngsoftheFomantIcpoets.
11
Thus,effortstorelIevepaInwere
undertakenandseveralmorenearbreakthroughsoccurreddeservementIon.AnEnglIsh
surgeonnamedHenryHIllHIckmansearchedIntentIonallyforanInhaledanesthetIcto
relIevepaInInhIspatIents.
12
HIckmanusedhIghconcentratIonsofcarbondIoxIdeInhIs
studIesonmIceanddogs.CarbondIoxIdehassomeanesthetIcpropertIes,asshownbythe
absenceofresponsetoanIncIsIonIntheanImalsofHIckman'sstudy,butItwasnever
determInedIftheanImalswereInsensatebecauseofhypoxIaratherthananesthesIa.
HIckman'sconceptwasmagnIfIcent;hIschoIceofagentwasregrettable.
ThedIscoveryofsurgIcalanesthetIcsInthemoderneraremaInslInkedtoInhaled
anesthetIcs.Thecompoundnowknownasdiethyl etherhadbeenknownforcenturIes;It
mayhavebeensynthesIzedfIrstbyaneIghthcenturyArabIanphIlosopherJabIrIbn
Hayyam,orpossIblybyFaymondLully,a1JthcenturyEuropeanalchemIst.8utdIethyl
etherwascertaInlyknownInthe16thcentury,bothto7alerIusCordusandParacelsuswho
preparedItbydIstIllIngsulfurIcacId(oIlofvItrIol)wIthfortIfIedwInetoproduceanoleum
vitrioli dulce(sweetoIlofvItrIol).DneofthefIrstmIssedobservatIonsontheeffectsof
Inhaledagents,ParacelsusobservedthatethercausedchIckenstofallasleepandawaken
unharmed.HemusthavebeenawareofItsanalgesIcqualItIesbecausehereportedthatIt
couldberecommendedforuseInpaInfulIllnesses.
ForthreecenturIesthereafter,thIssImplecompoundremaInedatherapeutIcagentwIth
onlyoccasIonaluse.SomeofItspropertIeswereexamInedbutwIthoutsustaInedInterest
bydIstInguIshed8rItIshscIentIstsFobert8oyle,saacNewton,and|IchaelFaraday,none
ofwhommadetheconceptuallInktosurgIcalanesthesIa.tsonlyroutIneapplIcatIoncame
asanInexpensIverecreatIonaldrugamongthepoorof8rItaInandreland,whosometImes
drankanounceortwoofetherwhentaxesmadegInprohIbItIvelyexpensIve.
1J
An
AmerIcanvarIatIonofthIspractIcewasconductedbygroupsofstudentswhoheldether
soakedtowelstotheIrfacesatnocturnaletherfrolIcs.
WIllIamE.Clarke,amedIcalstudentfromFochester,NewYork,mayhavegIventhefIrst
etheranesthetIcInJanuary1842.FromtechnIqueslearnedasachemIstrystudentIn18J9,
ClarkeentertaInedhIscompanIonswIthnItrousoxIdeandether.Emboldenedbythese
experIences,headmInIsteredether,fromatowel,toayoungwomannamedHobbIe.Dne
ofherteethwasthenextractedwIthoutpaInbyadentIstnamedElIjahPope.
14
However,It
wassuggestedthatthewoman'sunconscIousnesswasduetohysterIaandClarkewas
advIsedtoconductnofurtheranesthetIcexperIments.
15
Twomonthslater,on|archJ0,1842,CrawfordWIllIamsonLongadmInIsteredetherwItha
towelforsurgIcalanesthesIaInJefferson,CeorgIa.HIspatIent,James|.7enable,wasa
youngmanwhowasalreadyfamIlIarwIthether'sexhIlaratIngeffects,forhereportedIna
certIfIcatethathehadprevIouslyInhaledItandwasfondofItsuse.7enablehadtwosmall
tumorsonhIsneckbutrefusedtohavethemexcIsedbecausehefearedthepaInthat
accompanIedsurgery.KnowIngthat7enablewasfamIlIarwIthether'sactIon,0r.Long
proposedthatethermIghtallevIatepaInandgaInedhIspatIent'sconsenttoproceed.After
InhalIngetherfromthetowelandhavIngtheproceduresuccessfullycompleted,7enable
reportedthathewasunawareoftheremovalofthetumors.
16
ndetermInIngthefIrstfee
foranesthesIaandsurgery,LongsettledonachargeofS2.00.
17
AcommonmId19thcenturyproblemfacIngdentIstswasthatpatIentsrefusedbenefIcIal
treatmentoftheIrteethforfearofthepaInoftheprocedure.FromadentIst'sperspectIve,
paInwasnotsomuchlIfethreatenIngasItwaslIvelIhoodthreatenIng.DneofthefIrst
dentIststoengenderasolutIonwasHoraceWellsofHartford,ConnectIcut,whosegreat
momentofdIscoverycameon0ecember10,1844.HeobservedalectureexhIbItIonon
nItrousoxIdebyanItInerantscIentIst,CardnerQuIncyColton,whoencouragedmembers
oftheaudIencetoInhaleasampleofthegas.WellsobservedayoungmanInjurehIsleg
wIthoutpaInwhIleundertheInfluenceofnItrousoxIde.SensIngthatItmIghtprovIdepaIn
relIefdurIngdentalprocedures,WellscontactedColtonandboldlyproposedanexperIment
InwhIchWellswastobethesubject.ThefollowIngday,ColtongaveWellsnItrousoxIde
beforeafellowdentIst,WIllIamFIggs,extractedatooth.
18
AfterwardWellsdeclaredthat
hehadnotfeltanypaInanddeemedtheexperImentasuccess.ColtontaughtWellsto
preparenItrousoxIde,whIchthedentIstadmInIsteredwIthsuccesstopatIentsInhIs
practIce.HIsapparatusprobablyresembledthatusedbyColton:awoodentubeplacedIn
themouththroughwhIchnItrousoxIdewasbreathedfromasmallbagfIlledwIththegas.
Public Demonstration of Ether Anesthesia
AnotherNewEnglander,WIllIamThomasCreen|orton,brIeflysharedadentalpractIce
wIthWellsInHartford.Wells'daybookshowsthathegave|ortonacourseofInstructIonIn
anesthesIa,but|ortonapparentlymovedto8ostonwIthoutpayIngforthelessons.
19
n
8oston,|ortoncontInuedhIsInterestInanesthesIaandsoughtInstructIonfromchemIst
andphysIcIanCharlesT.Jackson.AfterlearnIngthatetherdroppedontheskInprovIded
analgesIa,hebeganexperImentswIthInhaledether,anagentthatprovedtobemuch
moreversatIlethannItrousoxIde.8ottlesoflIquIdetherwereeasIlytransported,andthe
volatIlItyofthedrugpermIttedeffectIveInhalatIon.TheconcentratIonsrequIredfor
surgIcalanesthesIaweresolowthatpatIentsdIdnotbecomehypoxIcwhenbreathIngether
vaporIzedInaIr.talsopossessedwhatwouldlaterberecognIzedasaunIqueproperty
amongallInhaledanesthetIcs:thequalItyofprovIdIngsurgIcalanesthesIawIthoutcausIng
respIratorydepressIon.ThesepropertIes,combInedwIthaslowrateofInductIon,gavethe
patIentasIgnIfIcantsafetymargInevenInthehandsofrelatIvelyunskIlledanesthetIsts.
20
AfteranesthetIzIngapetdog,|ortonbecameconfIdentofhIsskIllsandanesthetIzed
patIentsInhIsdentaloffIce.
P.6
EncouragedbyhIssuccess,|ortonsoughtanInvItatIontogIveapublIcdemonstratIonIn
the8ullfInchamphItheaterofthe|assachusettsCeneralHospItal,thesamesIteasWells'
faIleddemonstratIon.|anydetaIlsoftheDctober16,1846,demonstratIonarewellknown.
|ortonsecuredpermIssIontoprovIdeananesthetIctoEdwardCIlbertAbbott,apatIentof
surgeonJohnCollInsWarren.WarrenplannedtoexcIseavascularlesIonfromtheleftsIde
ofAbbott'sneckandwasabouttoproceedwhen|ortonarrIvedlate.Hehadbeendelayed
becausehewasoblIgedtowaItforanInstrumentmakertocompleteanewInhaler(FIg.1
1).tconsIstedofalargeglassbulbcontaInIngaspongesoakedwIthcoloredetheranda
spoutthatwasplacedInthepatIent'smouth.AnopenIngontheopposItesIdeofthebulb
allowedaIrtoenterandbedrawnovertheethersoakedspongewItheachbreath.
21
Figure 1-1.|orton'setherInhaler(1846).
TheconversatIonsofthatmornIngwerenotaccuratelyrecorded;however,popular
accountsstatethatthesurgeonrespondedtestIlyto|orton'sapologyforhIstardyarrIval
byremarkIng,SIr,yourpatIentIsready.|ortondIrectedhIsattentIontohIspatIentand
fIrstconductedaveryabbrevIatedpreoperatIveevaluatIon.HeInquIred,AreyouafraId:
AbbottrespondedthathewasnotandtooktheInhalerInhIsmouth.AfterafewmInutes,
|ortonturnedtothesurgeonandsaId,SIr,yourpatIentIsready.CIlbertAbbottlater
reportedthathewasawareofthesurgerybutexperIencednopaIn.Whentheprocedure
ended,WarrenImmedIatelyturnedtohIsaudIenceandutteredthestatement,
Centlemen,thIsIsnohumbug.
22
WhatwouldberecognIzedasAmerIca'sgreatestcontrIbutIonto19thcenturymedIcInehad
occurred.However,|orton,wIshIngtocapItalIzeonhIsdIscovery,refusedtodIvulge
whatagentwasInhIsInhaler.Someweekspassedbefore|ortonadmIttedthattheactIve
componentofthecoloredfluId,whIchhehadcalledLetheon,wassImpledIethylether.
|orton,Wells,Jackson,andtheIrsupporterssoonbecamedrawnIntoInacontentIous,
protracted,andfruItlessdebateoverprIorItyforthedIscovery.ThIsdebatehas
subsequentlybeentermedthe ether controversy.nshort,|ortonhadapplIedforapatent
forLetheon,andwhenItwasgranted,trIedtoreceIveroyaltIesfortheuseofetherasan
anesthetIc.
WhenthedetaIlsof|orton'sanesthetIctechnIquebecamepublIcknowledge,the
InformatIonwastransmIttedbytraIn,stagecoach,andcoastalvesselstootherNorth
AmerIcancItIes,andbyshIptotheworld.AsetherwaseasytoprepareandadmInIster,
anesthetIcswereperformedIn8rItaIn,France,FussIa,SouthAfrIca,AustralIa,andother
countrIesalmostassoonassurgeonsheardthewelcomenewsoftheextraordInary
dIscovery.EventhoughsurgerycouldnowbeperformedwIthpaInputtosleep,the
frequencyofoperatIonsdIdnotrIserapIdly,andseveralyearswouldpassbefore
anesthesIawasunIversallyrecommended.
Chloroform and Obstetrics
JamesYoungSImpsonwasasuccessfulobstetrIcIanofEdInburgh,Scotland,andamongthe
fIrsttouseetherfortherelIefoflaborpaIn.0IssatIsfIedwIthether,SImpsonsoonsoughta
morepleasant,rapIdactInganesthetIc.HeandhIsjunIorassocIatesconductedabold
searchbyInhalIngsamplesofseveralvolatIlechemIcalscollectedforSImpsonby8rItIsh
apothecarIes.0avIdWaldIesuggestedchloroform,whIchhadfIrstbeenpreparedIn18J1.
SImpsonandhIsfrIendsInhaledItafterdInneratapartyInSImpson'shomeontheevenIng
ofNovember4,1847.TheypromptlyfellunconscIousand,whentheyawoke,were
delIghtedwIththeIrsuccess.SImpsonquIcklysetaboutencouragIngtheuseofchloroform.
WIthIn2weeks,hesubmIttedhIsfIrstaccountofItsusetoThe Lancet.
nthe19thcentury,therelIefofobstetrIcpaInhadsIgnIfIcantsocIalramIfIcatIonsand
madeanesthesIadurIngchIldbIrthacontroversIalsubject.SImpsonarguedagaInstthe
prevaIlIngvIew,whIchheldthatrelIevInglaborpaInopposedCod'swIll.ThepaInofthe
parturIentwasvIewedasbothacomponentofpunIshmentandameansofatonementfor
DrIgInalSIn.LessthanayearafteradmInIsterIngthefIrstanesthesIadurIngchIldbIrth,
SImpsonaddressedtheseconcernsInapamphletentItledAnswers to the Religious
Objections Advanced against the Employment of Anaesthetic Agents in Midwifery and
Surgery and Obstetrics.nIt,SImpsonrecognIzedthe8ookofCenesIsasbeIngtherootof
thIssentIment,andnotedthatCodpromIsedtorelIevethedescendantsofAdamandEve
ofthecurse.AddItIonally,SImpsonassertedthatlaborpaInwasaresultofscIentIfIcand
anatomIccauses,andnottheresultofrelIgIouscondemnatIon.HestatedthattheuprIght
posItIonofhumansnecessItatedstrongpelvIcmusclestosupporttheabdomInalcontents.
Asaresult,heargued,theuterusnecessarIlydevelopedstrongmusculaturetoovercome
theresIstanceofthepelvIcfloorandthatgreatcontractIlepowercausedgreatpaIn.
SImpson'spamphletprobablydIdnothaveasIgnIfIcantImpactontheprevaIlIngattItudes,
buthedIdartIculatemanyconceptsthathIscontemporarIesweredebatIngatthetIme.
2J
ChloroformgaInedconsIderablenotorIetyafterJohnSnowusedIttodelIverthelasttwo
chIldrenofQueen7IctorIa.TheQueen'sconsort,PrInceAlbert,IntervIewedJohnSnow
beforehewascalledto8uckInghamPalacetoadmInIsterchloroformattherequestofthe
Queen'sobstetrIcIan.0urIngthemonarch'slabor,SnowgaveanalgesIcdosesofchloroform
onafoldedhandkerchIef.ThIstechnIquewassoontermedchloroform la reine.7IctorIa
abhorredthepaInofchIldbIrthandenjoyedtherelIefthatchloroformprovIded.Shewrote
Inherjournal,0r.SnowgavethatblessedchloroformandtheeffectwassoothIng,
quIetIng,anddelIghtfulbeyondmeasure.
24
WhentheQueen,asheadoftheChurchof
England,endorsedobstetrIcanesthesIa,relIgIousdebateoverthemanagementoflabor
paIntermInatedabruptly.
JohnSnow,alreadyarespectedphysIcIan,tookanInterestInanesthetIcpractIceandwas
soonInvItedtoworkwIthmanyleadIngsurgeonsoftheday.n1848,SnowIntroduceda
chloroformInhaler.HehadrecognIzedtheversatIlItyofthenewagentandcametoprefer
ItInhIspractIce.AtthesametIme,heInItIatedwhatwastobecomeanextraordInary
serIesofexperImentsthatwereremarkableIntheIrscopeandforantIcIpatIng
sophIstIcatedresearchperformedacenturylater.SnowrealIzedthatsuccessfulanesthetIcs
shouldabolIshpaInandunwantedmovements.HeanesthetIzedseveralspecIesofanImals
wIthvaryIngstrengthsofetherandchloroformtodetermInetheconcentratIonrequIredto
preventreflex
P.7
movementfromsharpstImulI.ThIsworkapproxImatedthemodernconceptofmInImum
alveolarconcentratIon.
25
SnowassessedtheanesthetIcactIonofalargenumberof
potentIalanesthetIcsbutdIdnotfIndanytorIvalchloroformorether.HIsstudIesledhIm
torecognIzetherelatIonshIpbetweensolubIlIty,vaporpressure,andanesthetIcpotency,
whIchwasnotfullyapprecIateduntIlafterWorldWar.SnowpublIshedtworemarkable
books,On the Inhalation of the Vapour of Ether(1847)andOn Chloroform and Other
Anaesthetics(1858).ThelatterwasalmostcompletedwhenhedIedofastrokeattheage
of45.
Anesthesia Principles, Equipment, and Standards
Control of the Airway
0efInItIvecontroloftheaIrway,askIllanesthesIologIstsnowconsIderparamount,
developedonlyaftermanyharrowIngandapneIcepIsodesspurredthedevelopmentof
saferaIrwaymanagementtechnIques.PrecedIngtrachealIntubatIon,however,several
ImportanttechnIqueswereproposedtowardtheendofthe19thcenturythatremaIn
IntegraltoanesthesIologyeducatIonandpractIce.JosephCloverwasthefIrstEnglIshman
tourgethenowunIversalpractIceofthrustIngthepatIent'sjawforwardtoovercome
obstructIonoftheupperaIrwaybythetongue.CloveralsopublIshedalandmarkcase
reportIn1877InwhIchheperformedasurgIcalaIrway.DncehIspatIentwasasleep,Clover
dIscoveredthathIspatIenthadatumorofthemouththatobstructedtheaIrway
completely,despItehIstrustedjawthrustmaneuver.HeaverteddIsasterbyInsertInga
smallcurvedcannulaofhIsdesIgnthroughthecrIcothyroIdmembrane.HecontInued
anesthesIavIathecannulauntIlthetumorwasexcIsed.Clover,themodeloftheprepared
anesthesIologIst,remarked,haveneverusedthecannulabeforealthoughIthasbeenmy
companIonatsomethousandsofanaesthetIccases.
26
Tracheal Intubation
ThedevelopmentoftechnIquesandInstrumentsforIntubatIonranksamongthemajor
advancesInthehIstoryofanesthesIology.ThefIrsttrachealtubesweredevelopedforthe
resuscItatIonofdrownIngvIctIms,butwerenotusedInanesthesIauntIl1878.ThefIrstuse
ofelectIveoralIntubatIonforananesthetIcwasundertakenbyScottIshsurgeonWIllIam
|acewan.HehadpractIcedpassIngflexIblemetaltubesthroughthelarynxofacadaver
beforeattemptIngthemaneuveronanawakepatIentwIthanoraltumorattheClasgow
FoyalnfIrmaryonJuly5,1878.
27
8ecausetopIcalanesthesIawasnotyetknown,the
experIencemusthavedemandedfortItudeonthepartof|acewan'spatIent.Dncethetube
wascorrectlyposItIoned,anassIstantbeganachloroformaIranesthetIcvIathetube.Dnce
anesthetIzed,thepatIentsoonstoppedcoughIng.Unfortunately,|acewanabandonedthe
practIcefollowIngafatalItyInwhIchapatIenthadbeensuccessfullyIntubatedwhIle
awakebutthetubebecamedIslodgedoncethepatIentwasasleep.Afterthetubewas
removed,anattempttoprovIdechloroformbymaskanesthesIawasunsuccessfulandthe
patIentdIed.
AnAmerIcansurgeonnamedJosephD'0wyerIsrememberedforhIsextraordInary
dedIcatIontotheadvancementoftrachealIntubatIon.n1885,D'0wyerdesIgnedaserIes
ofmetallaryngealtubes,whIchheInsertedblIndlybetweenthevocalcordsofchIldren
sufferIngadIphtherItIccrIsIs.Threeyearslater,D'0wyerdesIgnedasecondrIgIdtubewIth
aconIcaltIpthatoccludedthelarynxsoeffectIvelythatItcouldbeusedforartIfIcIal
ventIlatIonwhenapplIedwIththebellowsandTpIecetubedesIgnedbyCeorgeFell.The
FellD'0wyerapparatus,asItcametobeknown,wasuseddurIngthoracIcsurgeryby
Fudolph|atasofNewDrleans.|ataswassopleasedwIthItthathepredIcted,The
procedurethatpromIsesthemostbenefItInpreventIngpulmonarycollapseInoperatIons
onthechestIstherhythmIcalmaIntenanceofartIfIcIalrespIratIonbyatubeInthe
glottIsdIrectlyconnectedwIthabellows.
AfterD'0wyer'sdeath,theoutstandIngpIoneeroftrachealIntubatIonwasFranzKuhn,a
surgeonofKassel,Cermany.From1900untIl1912,KuhnpublIshedseveralartIclesanda
classIcmonograph,Die perorale Intubation,whIchwerenotwellknownInhIslIfetIme
buthavesIncebecomewIdelyapprecIated.
25
HIsworkmIghthavehadamoreprofound
ImpactIfIthadbeentranslatedIntoEnglIsh.KuhndescrIbedtechnIquesoforalandnasal
IntubatIonthatheperformedwIthflexIblemetaltubescomposedofcoIledtubIngsImIlar
tothosenowusedforthespoutofmetalgasolInecans.AfterapplyIngcocaInetothe
aIrway,KuhnIntroducedhIstubeoveracurvedmetalstyletthathedIrectedtowardthe
larynxwIthhIsleftIndexfInger.WhIlehewasawareofthesubglottIccuffsthathadbeen
usedbrIeflyby7IctorEIsenmenger,KuhnpreferredtosealthelarynxbyposItIonInga
supralaryngealflangenearthetube'stIpbeforepackIngthepharynxwIthgauze.Kuhneven
monItoredthepatIent'sbreathsoundscontInuouslythroughamonauralearpIececonnected
toanextensIonofthetrachealtubebyanarrowtube.
ntubatIonofthetracheabypalpatIonwasanuncertaInandsometImestraumatIcact;
surgeonsevenbelIevedthatItwouldbeanatomIcallyImpossIbletovIsualIzethevocal
cordsdIrectly.ThIsmIsapprehensIonwasovercomeIn1895byAlfredKIrsteInIn8erlInwho
devIsedthefIrstdIrectvIsIonlaryngoscope.
28
KIrsteInwasmotIvatedbyafrIend'sreport
thatapatIent'stracheahadbeenaccIdentallyIntubateddurIngesophagoscopy.KIrsteIn
promptlyfabrIcatedahandheldInstrumentthatatfIrstresembledashortenedcylIndrIcal
esophagoscope.HesoonsubstItutedasemIcIrcularbladethatopenedInferIorly.KIrsteIn
couldnowexamInethelarynxwhIlestandIngbehIndhIsseatedpatIent,whoseheadhad
beenplacedInanattItudeapproxImatIngthesnIffIngposItIon.AlthoughAlfredKIrsteIn's
autoscopewasnotusedbyanesthesIologIsts,Itwastheforerunnerofallmodern
laryngoscopes.EndoscopywasrefInedbyChevalIerJacksonInPhIladelphIa,whodesIgneda
UshapedlaryngoscopebyaddIngahandgrIpthatwasparalleltotheblade.TheJackson
bladehasremaInedastandardInstrumentforendoscopIstsbutwasnotfavoredby
anesthesIologIsts.TwolaryngoscopesthatcloselyresembledmodernLshapedInstruments
weredesIgnedIn1910and191JbytwoAmerIcansurgeons,HenryJanewayandCeorge
0orrance,butneItherInstrumentachIevedlastIngusedespItetheIrexcellentdesIgns.
29
8eforetheIntroductIonofmusclerelaxantsInthe1940s,IntubatIonofthetracheacouldbe
challengIng.ThIschallengewasmadesomewhateasIer,however,wIththeadventof
laryngoscopebladesspecIfIcallydesIgnedtoIncreasevIsualIzatIonofthevocalcords.
Fobert|IllerofSanAntonIo,Texas,andFobert|acIntoshofDxfordUnIversItycreated
theIrrespectIvelynamedbladeswIthInanIntervalof2years.n1941,|Illerbrought
forwardtheslender,straIghtbladewIthaslIghtcurvenearthetIptoeasethepassageof
thetubethroughthelarynx.Although|Iller'sbladewasarefInement,thetechnIqueofIts
usewasIdentIcaltothatofearlIermodelsastheepIglottIswaslIftedtoexposethe
larynx.
J0
The|acIntoshblade,whIchIsplacedInthevallecularatherthanundertheepIglottIs,was
InventedasanIncIdentalresultofatonsIllectomy.SIrFobert|acIntoshlaterdescrIbed
thecIrcumstancesofItsdIscoveryInanapprecIatIonofthe
P.8
careerofhIstechnIcIan,|r.FIchardSalt,whoconstructedtheblade.AsSIrFobert
recalled,A8oyle0avIsgag,asIzelargerthanIntended,wasInsertedfortonsIllectomy,
andwhenthemouthwasfullyopenedthecordscameIntovIew.ThIswasasurprIsesInce
conventIonallaryngoscopy,atthatdepthofanaesthesIa,wouldhavebeenImpossIbleIn
thoseprerelaxantdays.WIthInamatterofhours,SalthadmodIfIedthebladeofthe0avIs
gagandattachedalaryngoscopehandletoIt;andstreamlIned(aftertestIngseveral
models),theendresultcameIntowIdespreaduse.
J1
|acIntoshunderestImatedthe
popularItyoftheblade,asmorethan800,000havebeenproducedandmanyspecIal
purposeversIonshavebeenmarketed.
ThemostdIstInguIshedInnovatorIntrachealIntubatIonwastheselftraIned8rItIsh
anesthetIstvan(later,SIrvan)|agIll.
J2
n1919,whIleservIngIntheFoyalArmyasa
generalmedIcaloffIcer,|agIllwasassIgnedtoamIlItaryhospItalnearLondon.Although
hehadonlyrudImentarytraInIngInanesthesIa,|agIllwasoblIgedtoacceptanassIgnment
totheanesthesIaservIce,whereheworkedwIthanotherneophyte,StanleyFowbotham.
JJ
Together,|agIllandFowbothamattendedcasualtIesdIsfIguredbyseverefacIalInjurIes
whounderwentrepeatedrestoratIveoperatIons.TheseproceduresrequIredthatthe
surgeon,HaroldCIllIes,haveunrestrIctedaccesstothefaceandaIrway.ThesepatIents
presentedformIdablechallenges,butboth|agIllandFowbothambecameadeptat
trachealIntubatIonandquIcklyunderstoodItscurrentlImItatIons.8ecausetheylearned
fromfortuItousobservatIons,theysoonextendedthescopeoftrachealanesthesIa.
TheygaInedexpertIsewIthblIndnasalIntubatIonaftertheylearnedtosoftensemIrIgId
InsufflatIontubesforpassagethroughthenostrIl.EventhoughtheIrorIgInalIntentwasto
posItIonthetIpsofthenasaltubesIntheposterIorpharynx,theslendertubesfrequently
endedupInthetrachea.StImulatedbythIschanceexperIence,theydevelopedtechnIques
ofdelIberatenasotrachealIntubatIon.n1920,|agIlldevIsedanaIdtomanIpulatIngthe
cathetertIp,the|agIllangulatedforceps,whIchcontInuetobemanufacturedaccordIng
tohIsorIgInaldesIgnofnearly90yearsago.
WIththewarover,|agIllenteredcIvIlIanpractIceandsetouttodevelopawIdeboretube
thatwouldresIstkInkIngbutbeconformabletothecontoursoftheupperaIrway.WhIleIn
ahardwarestore,hefoundmIneralIzedredrubbertubIngthathecut,beveled,and
smoothedtoproducetubesthatclInIcIansaroundtheworldwouldcometocall|agIll
tubes.HIstubesremaInedtheunIversalstandardformorethan40yearsuntIlrubber
productsweresupplantedbyInertplastIcs.|agIllalsoredIscoveredtheadvantageof
applyIngcocaInetothenasalmucosa,atechnIquethatgreatlyfacIlItatedawakeblInd
nasalIntubatIon.
n1926,ArthurCuedelbeganaserIesofexperImentsthatledtotheIntroductIonofthe
cuffedtube.CuedeltransformedthebasementofhIsndIanapolIshomeIntoalaboratory
wherehesubjectedeachstepofthepreparatIonandapplIcatIonofhIscuffstoavIgorous
revIew.
J4
HefashIonedcuffsfromtherubberofdentaldams,condoms,andsurgIcalgloves
thatweregluedontotheouterwalloftubes.UsIngashIsmodelanImaltracheasdonated
bythefamIlybutcher,heconsIderedwhetherthecuffshouldbeposItIonedabove,below,
oratthelevelofthevocalcords.HerecommendedthatthecuffbeposItIonedjustbelow
thevocalcordstosealtheaIrway.Waterslaterrecommendedthatcuffsbeconstructedof
twolayersofsoftrubbercementedtogether.ThesedetachablecuffswerefIrst
manufacturedbyWaters'chIldren,whosoldthemtotheForeggerCompany.
CuedelsoughtwaystoshowthesafetyandutIlItyofthecuffedtube.HefIrstfIlledthe
mouthofananesthetIzedandIntubatedpatIentwIthwaterandshowedthatthecuff
sealedtheaIrway.EventhoughthIsexhIbItIonwassuccessful,hesearchedforamore
dramatIctechnIquetocapturetheattentIonofthoseunfamIlIarwIththeadvantagesof
IntubatIon.HereasonedthatIfthecuffpreventedwaterfromenterIngthetracheaofan
IntubatedpatIent,ItshouldalsopreventananImalfromdrownIng,evenIfItwere
submergedunderwater.ToencouragephysIcIansattendIngamedIcalconventIontousehIs
trachealtechnIques,CuedelpreparedthefIrstofseveraldunkeddogdemonstratIons
(FIg.12).AnanesthetIzedandIntubateddog,Cuedel'sownpet,AIrway,wasImmersed
InanaquarIum.AfterthedemonstratIonwascompleted,theanesthetIcwasdIscontInued
beforetheanImalwasremovedfromthewater.AIrwayawokepromptly,shookwaterover
theonlookers,salutedapost,thentrottedfromthehalltotheapplauseoftheaudIence.
Figure 1-2.Thedunkeddog.
AfterapatIentexperIencedanaccIdentalendobronchIalIntubatIon,FalphWaters
reasonedthataverylongcuffedtubecouldbeusedtoventIlatethedependentlungwhIle
theupperlungwasbeIngresected.
J5
DnlearnIngofhIsfrIend'ssuccesswIthIntentIonal
onelunganesthesIa,ArthurCuedelproposedanImportantmodIfIcatIonforchestsurgery,
thedoublecuffedsInglelumentube,whIchwasIntroducedbyEmeryFovenstIne.These
tubeswereeasIlyposItIoned,anadvantageoverbronchIalblockersthathadtobeInserted
byaskIlledbronchoscopIst.n195J,sInglelumentubesweresupplantedbydoublelumen
endobronchIaltubes.ThedoublelumentubecurrentlymostpopularwasdesIgnedbyFrank
Fobertshawof|anchester,England,andIspreparedInbothrIghtandleftsIdedversIons.
FobertshawtubeswerefIrstmanufacturedfrommIneralIzedredrubberbutarenowmade
ofextrudedplastIc,atechnIquerefInedby0avIdSherIdan.SherIdanwasalsothefIrst
persontoembedcentImetermarkIngsalongthesIdeoftrachealtubes,asafetyfeature
thatreducedtherIskofthetube'sbeIngIncorrectlyposItIoned.
Advanced Airway Devices
ConventIonallaryngoscopesprovedInadequateforpatIentswIthdIffIcultaIrways.Afew
clInIcIanscredItharrowIngIntubatIngexperIencesastheIncentIveforInventIon.n1928,a
rIgIdbronchoscopewasspecIfIcallydesIgnedforexamInatIonofthelargeaIrways.FIgId
bronchoscopeswererefInedandusedbypulmonologIsts.AlthoughItwasknownIn1870
thatathreadofglasscouldtransmItlIghtalongItslength,technologIcallImItatIonswere
notovercomeuntIl1964whenShIgetokedadevelopedthefIrstflexIblefIberoptIc
bronchoscope.FIberoptIcassIstedtrachealIntubatIonhasbecomeacommonapproachIn
themanagementofpatIentswIthdIffIcultaIrwayshavIngsurgery.
Foger8ullarddesIredadevIcetosImultaneouslyexamInethelarynxandIntubatethe
vocalcords.Hehadbeenfrustrated
P.9
byfaIledattemptstovIsualIzethelarynxofapatIentwIthPIerreFobInsyndrome.n
response,hedevelopedthe8ullardlaryngoscope,whosefIberoptIcbundleslIebesIdea
curvedblade.SImIlarly,theWuscopewasdesIgnedbyTzuLangWuIn1994tocombIneand
facIlItatevIsualIzatIonandIntubatIonofthetracheaInpatIentswIthdIffIcultaIrways.
J6
0r.A..J.ArchIe8raInfIrstrecognIzedtheprIncIpleofthelaryngealmaskaIrway(L|A)
In1981when,lIkemany8rItIshclInIcIans,heprovIdeddentalanesthesIavIaaColdman
nasalmask.However,unlIkeanybeforehIm,herealIzedthatjustasthedentalmaskcould
befIttedcloselyaboutthenose,acomparablemaskattachedtoawIdeboretubemIghtbe
posItIonedaroundthelarynx.HenotonlyconceIvedofthIsradIcaldepartureInaIrway
management,whIchhefIrstdescrIbedIn198J,
J7
butalsospentyearsInsInglehandedly
fabrIcatIngandtestIngscoresofIncrementalmodIfIcatIons.Scoresof8raIn'sprototypesare
dIsplayedIntheFoyal8erkshIreHospItal,FeadIng,England,wheretheyprovIdeadetaIled
recordoftheevolutIonoftheL|A.HefabrIcatedhIsfIrstmodelsfrom|agIlltubesand
Coldmanmasks,thenrefInedtheIrshapebyperformIngpostmortemstudIesofthe
hypopharynxtodetermInetheformofcuffthatwouldbemostfunctIonal.8eforesIlIcone
rubberwasselected,8raInhadevenmasteredthetechnIqueofformIngmasksfromlIquId
latex.EverydetaIloftheL|A,thenumberandposItIonoftheaperturebars,theshapeand
thesIzeofthemasks,requIredrepeatedmodIfIcatIon.
Early Anesthesia Delivery Systems
ThetransItIonfrometherInhalersandchloroformsoakedhandkerchIefstomore
sophIstIcatedanesthesIadelIveryequIpmentoccurredgradually,wIthIncremental
advancessupplantIngoldermethods.DneoftheearlIestanesthesIaapparatusdesIgnswas
thatofJohnSnow,whohadrealIzedtheInadequacIesofetherInhalersthroughwhIch
patIentsrebreathedvIaamouthpIece.AfterpractIcInganesthesIaforonly2weeks,Snow
createdthefIrstofhIsserIesofIngenIousetherInhalers.
J8
HIsbestknownapparatus
featuredunIdIrectIonalvalveswIthInamalleable,wellfIttIngmaskofhIsowndesIgn,
whIchcloselyresemblestheformofamodernfacemask.ThefacepIecewasconnectedto
thevaporIzerbyabreathIngtube,whIchSnowdelIberatelydesIgnedtobewIderthanthe
humantracheasothatevenrapIdrespIratIonswouldnotbeImpeded.AmetalcoIlwIthIn
thevaporIzerensuredthatthepatIent'sInspIredbreathwasdrawnoveralargesurface
areatopromotetheuptakeofether.ThedevIcealsoIncorporatedawarmwaterbathto
maIntaInthevolatIlItyoftheagent(FIg.1J).SnowdIdnotattempttocapItalIzeonhIs
creatIvIty,IncontrasttoWIllIam|orton;heclosedhIsaccountofItspreparatIonwIththe
generousobservatIon,ThereIsnorestrIctIonrespectIngthemakIngofIt.
J9
8etween1900and1910,contInuousposItIveornegatIvepressuredevIceswerecreatedto
maIntaInInflatIonofthelungsofaspontaneouslybreathIngpatIentoncethechestwas
opened.8rauer(1904)and|urphy(1905)placedthepatIent'sheadandneckInaboxIn
whIchposItIvepressurewascontInuallymaIntaIned.Sauerbruch(1904)createdanegatIve
pressureoperatIngchamberencompassIngboththesurgIcalteamandthepatIent'sbody
andfromwhIchonlythepatIent'sheadprojected.
45
n1907,thefIrstIntermIttentposItIvepressuredevIce,the0raegerPulmotor,was
developedtorhythmIcallyInflatethelungs.ThIsInstrumentandlaterAmerIcanmodels
suchastheEEJFesuscItatorwereusedalmostexclusIvelybyfIrefIghtersandmInerescue
workers.n19J4aSwedIshteamdevelopedtheSpIropulsator,whIchC.Crafoordlater
modIfIedforusedurIngcyclopropaneanesthesIa.
46
tsactIonwascontrolledbyamagnetIc
controlvalvecalledthe flasher,atypefIrstusedtoprovIdeIntermIttentgasflowforthe
lIghtsofnavIgatIonalbuoys.WhenTrIer|orch,a0anIshanesthesIologIst,couldnotobtaIn
aSpIropulsatordurIngWorldWar,hefabrIcatedthe|orchFespIrator,whIchuseda
pIstonpumptorhythmIcallydelIverafIxedvolumeofgastothepatIent.
45
AmajorstImulustothedevelopmentofventIlatorscameasaconsequenceofa
devastatIngepIdemIcofpolIomyelItIsthatstruckCopenhagen,0enmark,In1952.Asscores
ofpatIentswereadmItted,theonlyeffectIveventIlatorysupportthatcouldbeprovIdedto
patIentswIthbulbarparalysIswascontInuousmanualventIlatIonvIaatracheostomy
employIngdevIcessuchasWaters'toandfrocIrcuIt.ThIssucceededonlythroughthe
dedIcatedeffortsofhundredsofvolunteers.|edIcalstudentsservedInrelaystoventIlate
paralyzedpatIents.TheCopenhagencrIsIsstImulatedabroadEuropeanInterestInthe
developmentofportableventIlatorsInantIcIpatIonofanotherepIdemIcofpolIomyelItIs.
AtthIstIme,thecommonpractIceInNorthAmerIcanhospItalswastoplacepolIopatIents
wIthrespIratoryInvolvementInIronlungs,metalcylIndersthatencasedthebodybelow
theneck.nspIratIonwascausedbyIntermIttentnegatIvepressurecreatedbyanelectrIc
motoractIngonapIstonlIkedevIceoccupyIngthefootofthechamber.
SomeearlyAmerIcanventIlatorswereadaptatIonsofrespIratoryassIstmachInesorIgInally
desIgnedforthedelIveryofaerosolIzeddrugsforrespIratorytherapy.Twotypesemployed
the8ennettor8IrdflowsensItIvevalves.The8ennettvalvewasdesIgneddurIngWorld
WarwhenateamofphysIologIstsattheUnIversItyofSouthernCalIfornIaencountered
dIffIcultIesInseparatIngInspIratIonfromexpIratIonInanexperImentalapparatusdesIgned
toprovIdeposItIvepressurebreathIngforavIatorsathIghaltItude.AnengIneer,Fay
8ennett,vIsItedtheIrlaboratory,observedtheIrproblem,andresolvedItwItha
mechanIcalflowsensItIveautomatIcvalve.AsecondvalvIngmechanIsmwaslater
desIgnedbyanaeronautIcalengIneer,Forrest8Ird.
Theuseofthe8Irdand8ennettvalvesgaInedananesthetIcapplIcatIonwhenthegasflow
fromthevalvewasdIrectedIntoarIgIdplastIcjarcontaInIngabreathIngbagorbellowsas
partofananesthesIacIrcuIt.ThesebagInbottledevIcesmImIckedtheactIonofthe
clInIcIan'shandasthegasflowcompressedthebag,therebyprovIdIngposItIvepressure
InspIratIon.PassIveexhalatIonwaspromotedbythedescentofaweIghtonthebagor
bellows.
Carbon Dioxide Absorption
CarbondIoxIde(CD
2
)absorbanceIsabasIcelementofmodernanesthetIcmachInes.twas
InItIallydevelopedtoallowrebreathIngofgasandmInImIzelossofflammablegasesInto
theroom,therebyreducIngtherIskofexplosIon.ncurrentpractIce,ItpermItsdecreased
utIlIzatIonofanesthetIcandreducedcost.ThefIrstCD
2
absorberInanesthesIacameIn
1906fromtheworkofFranzKuhn,aCermansurgeon.HIsuseofcanIstersdevelopedfor
mInerescuesby0raegerwasInnovatIve,buthIscIrcuIthadunfortunatelImItatIons.The
exceptIonallynarrowbreathIngtubesandalargedeadspaceexplaInItsverylImIteduse,
andKuhn'sdevIcewasIgnored.
Afewyearslater,thefIrstAmerIcanmachInewIthaCD
2
absorberwasIndependently
fabrIcatedbyapharmacologIstnamed0ennIsJackson.n1915,Jacksondevelopedanearly
technIqueofCD
2
absorptIonthatpermIttedtheuseofaclosedanesthesIacIrcuIt.Heused
solutIonsofsodIumandcalcIum
P.11
hydroxIdetoabsorbCD
2
.AshIslaboratorywaslocatedInanareaofSt.LouIs,|IssourI,
heavIlyladenwIthcoalsmoke,JacksonreportedthattheapparatusallowedhImthefIrst
breathsofabsolutelyfreshaIrhehadeverenjoyedInthatcIty.ThecomplexItyof
Jackson'sapparatuslImItedItsuseInhospItalpractIce,buthIspIoneerIngworkInthIsfIeld
encouragedFalphWaterstoIntroduceasImplerdevIceusIngsodalImegranules9years
later.WatersposItIonedasodalImecanIster(FIg.14)betweenafacemaskandan
adjacentbreathIngbagtowhIchwasattachedthefreshgasflow.Aslongasthemaskwas
heldagaInsttheface,onlysmallvolumesoffreshgasflowwererequIredandnovalves
wereneeded.
47
Figure 1-4.Waters'carbondIoxIdeabsorbancecanIster.
Waters'devIcefeaturedawkwardposItIonIngofthecanIsterclosetothepatIent'sface.
8rIanSwordovercamethIslImItatIonIn19J0wIthafreestandIngmachInewIth
unIdIrectIonalvalvestocreateacIrclesystemandanInlIneCD
2
absorber.
48
JamesElam
andhIscoworkersattheFoswellParkCancernstItuteIn8uffalo,NewYork,furtherrefIned
theCD
2
absorber,IncreasIngtheeffIcIencyofCD
2
removalwIthamInImumofresIstance
forbreathIng.
49
Consequently,thecIrclesystemIntroducedbySwordInthe19J0s,wItha
fewrefInements,becamethestandardanesthesIacIrcuItInNorthAmerIca.
Flow Meters
AsclosedandsemIclosedcIrcuItsbecamepractIcal,gasflowcouldbemeasuredwIth
greateraccuracy.8ubbleflowmeterswerereplacedwIthdrybobbInsorballbearIng
flowmeters,whIch,althoughtheydIdnotleakfluIds,couldcauseInaccuratemeasurements
Iftheyadheredtotheglasscolumn.n1910,|.NeuhadbeenthefIrsttoapplyrotameters
InanesthesIafortheadmInIstratIonofnItrousoxIdeandoxygen,buthIsmachInewasnota
commercIalsuccess,perhapsbecauseofthegreatcostofnItrousoxIdeInCermanyatthat
tIme.FotametersdesIgnedforuseInCermanIndustrywerefIrstemployedIn8rItaInIn
19J7byFIchardSalt;butasWorldWarapproached,theEnglIshweredenIedaccessto
thesesophIstIcatedflowmeters.AfterWorldWarrotametersbecameregularlyemployed
In8rItIshanesthesIamachInes,althoughmostAmerIcanequIpmentstIllfeatured
nonrotatIngfloats.ThenowunIversalpractIceofdIsplayInggasflowInlIterspermInute
wasnotacustomarypartofallAmerIcanmachInesuntIlmorethanadecadeafterWorld
War.
Vaporizers
TheartofasmoothInductIonwIthapotentanesthetIcwasagreatchallenge,partIcularly
IftheInspIredconcentratIoncouldnotbedetermInedwIthaccuracy.EventheclInIcal
IntroductIonofhalothaneafter1956mIghthavebeensImIlarlythwartedexceptfora
fortunatecoIncIdence:theprIordevelopmentofcalIbratedvaporIzers.Twotypesof
calIbratedvaporIzersdesIgnedforotheranesthetIcshadbecomeavaIlableInthehalf
decadebeforehalothanewasmarketed.ThepromptacceptanceofhalothanewasInpart
becauseofanabIlItytoprovIdeItIncarefullytItratedconcentratIons.
TheCopperKettlewasthefIrsttemperaturecompensated,accuratevaporIzer.thadbeen
developedbyLucIen|orrIsattheUnIversItyofWIsconsInInresponsetoFalphWaters'plan
totestchloroformbygIvIngItIncontrolledconcentratIons.
50
|orrIsachIevedthIsgoalby
passIngameteredflowofoxygenthroughavaporIzerchamberthatcontaInedasIntered
bronzedIsktoseparatetheoxygenIntomInutebubbles.Thegasbecamefullysaturated
wIthanesthetIcvaporasItpercolatedthroughthelIquId.TheconcentratIonofthe
anesthetIcInspIredbythepatIentcouldbecalculatedbyknowIngthevaporpressureofthe
lIquIdanesthetIc,thevolumeofoxygenflowIngthroughthelIquId,andthetotalvolumeof
gasesfromallsourcesenterIngtheanesthesIacIrcuIt.AlthoughexperImentalmodelsof
|orrIs'vaporIzerusedawaterbathtomaIntaInstabIlIty,theexcellentthermal
conductIvItyofcopperwassubstItutedInlatermodels.WhenfIrstmarketed,theCopper
KettledIdnotfeatureamechanIsmtoIndIcatechangesInthetemperature(andvapor
pressure)ofthelIquId.ShuhHsunNgaIproposedtheIncorporatIonofathermometer,a
suggestIonthatwaslateraddedtoallvaporIzersofthatclass.
51
TheCopperKettle
(ForeggerCompany)andthe7ernItrol(DhIo|edIcalProducts)wereunIversalvaporIzers
thatcouldbechargedwIthanyanesthetIclIquId,and,provIdedthatItsvaporpressureand
temperaturewereknown,theInspIredconcentratIoncouldbecalculatedquIckly.
WhenhalothanewasfIrstmarketedIn8rItaIn,aneffectIvetemperaturecompensated,
agentspecIfIcvaporIzerhadrecentlybeenplacedInclInIcaluse.TheTECDTA
(TEmperatureCDmpensatedTrIchloroethyleneAIr)vaporIzerfeaturedabImetallIcstrIp
composedofbrassandanIckelsteelalloy,twometalswIthdIfferentcoeffIcIentsof
expansIon.AstheanesthetIcvaporcooled,thestrIpbenttomoveawayfromtheorIfIce,
therebypermIttIngmorefreshgastoenterthevaporIzIngchamber.ThIsmaIntaIneda
constantInspIredconcentratIondespItechangesIntemperatureandvaporpressure.After
theIrTECDTAvaporIzerwasacceptedIntoanesthetIcpractIce,thetechnologywasusedto
createtheFluotec,thefIrstofaserIesofagentspecIfIctecvaporIzersforuseInthe
operatIngroom.
Patient Monitors
nmanyways,thehIstoryoflatenIneteenthandearly20thcenturyanesthesIologyIsthe
questforthesafestanesthetIc.ThedIscoveryandwIdespreaduseofelectrocardIography,
pulseoxImetry,bloodgasanalysIs,capnography,andneuromuscularblockademonItorIng
havereducedpatIentmorbIdItyandmortalItyandrevolutIonIzedanesthesIapractIce.
WhIlesafermachInesassuredclInIcIansthatapproprIategasmIxturesweredelIveredto
thepatIent,monItorsprovIdedanearly
P.12
warnIngofacutephysIologIcdeterIoratIonbeforepatIentssufferedIrrevocabledamage.
JosephCloverwasoneofthefIrstclInIcIanstoroutInelyperformbasIchemodynamIc
monItorIng.CloverdevelopedthehabItofmonItorInghIspatIents'pulsebutsurprIsIngly,
thIswasacontentIousIssueatthetIme.PromInentScottIshsurgeonsscornedClover's
emphasIsontheactIonofchloroformontheheart.8aronLIsterandotherspreferredthat
senIormedIcalstudentsgIveanesthetIcsandurgedthemtostrIctlycarryoutcertaIn
sImpleInstructIons,amongwhIchIsthatofnevertouchIngthepulse,InorderthattheIr
attentIonmaynotbedIstractedfromtherespIratIon.
52
LIsteralsocounseled,Itappears
thatprelImInaryexamInatIonofthechest,oftenconsIderedIndIspensable,IsquIte
unnecessary,andmorelIkelytoInducethedreadedsyncope,byalarmIngthepatIents,
thantoavertIt.
5J
LIttleprogressInanesthesIacouldcomefromsuchreactIonary
statements.ncontrast,CloverhadobservedtheeffectofchloroformonanImalsand
urgedotheranesthetIststomonItorthepulseatalltImesandtodIscontInuetheanesthetIc
temporarIlyIfanyIrregularItyorweaknesswasobservedInthestrengthofthepulse.
TwoAmerIcansurgeons,CeorgeW.CrIleandHarveyCushIng,developedastrongInterest
InmeasurIngbloodpressuredurInganesthesIa.8othmenwrotethoroughanddetaIled
examInatIonsofbloodpressuremonItorIng;however,CushIng'scontrIbutIonIsbetter
rememberedbecausehewasthefIrstAmerIcantoapplytheFIvaFoccIcuff,whIchhesaw
whIlevIsItIngtaly.CushIngIntroducedtheconceptIn1902andhadbloodpressure
measurementsrecordedonanesthesIarecords.
54
n1894,CushIngandafellowstudentat
Harvard|edIcalSchool,CharlesCodman,InItIatedasystemofrecordIngpatIents'pulsesto
assessthecourseoftheanesthetIcstheyadmInIstered.n1902,CushIngcontInuedthe
practIceofmonItorIngandrecordIngpatIentbloodpressuresandpulses.ThetransItIon
frommanualtoautomatedbloodpressuredevIces,whIchfIrstappearedIn19J6and
operateonanoscIllometrIcprIncIple,hasbeengradual.
ThefIrstprecordIalstethoscopewasbelIevedtohavebeenusedbyS.CrIffIth0avIsat
JohnsHopkInsUnIversIty.
J8
HeadaptedatechnIquedevelopedbyHarveyCushIngIna
laboratoryInwhIchdogswIthsurgIcallyInducedvalvularlesIonshadstethoscopesattached
totheIrchestwallsothatmedIcalstudentsmIghtlIstentobruItscharacterIstIcofa
specIfIcmalformatIon.0avIs'technIquewasforgottenbutwasrehabIlItatedby0r.Fobert
SmIth,anenergetIcpIoneerofpedIatrIcanesthesIologyIn8ostonInthe1940s.ACanadIan
contemporary,AlbertCodesmIth,oftheHospItalforSIckChIldren,Toronto,became
frustratedbytherepeateddIslodgIngofthechestpIeceunderthesurgIcaldrapesand
fabrIcatedhIsfIrstesophagealstethoscopefromurethralcathetersandPenrosedraIns.HIs
brIefreportheraldedItsclInIcalroleasamonItorofbothnormalandadventItIous
respIratoryandcardIacsounds.
55
Electrocardiography, Pulse Oximetry, and Capnography
ClInIcalelectrocardIographybeganwIthWIllemEInthoven'sapplIcatIonofthestrIng
galvanometerIn190J.WIthIntwodecades,ThomasLewIshaddescrIbedItsroleInthe
dIagnosIsofdIsturbancesofcardIacrhythm,whIleJamesHerrIckandHaroldPardeefIrst
drewattentIontothechangesproducedbymyocardIalIschemIa.After1928,cathoderay
oscIlloscopeswereavaIlable,buttherIskofexplosIonowIngtothepresenceofflammable
anesthetIcsforestalledtheIntroductIonoftheelectrocardIogramIntoroutIneanesthetIc
practIceuntIlafterWorldWar.AtthattIme,thesmallscreenoftheheavIlyshIelded
bulletoscIlloscopedIsplayedonlyJsecondsofdata,butthatInformatIonwashIghly
prIzed.
PulseoxImetry,theoptIcalmeasurementofoxygensaturatIonIntIssues,Isoneofthemore
recentaddItIonstotheanesthesIologIst'sarrayofroutInemonItors.AlthoughresearchIn
thIsareabeganIn19J2,ItsfIrstpractIcalapplIcatIoncamedurIngWorldWar.An
AmerIcanphysIologIst,Clen|IllIkan,respondedtoarequestfrom8rItIshcolleaguesIn
avIatIonresearch.|IllIkansetaboutpreparIngaserIesofdevIcestoImprovethesupplyof
oxygenthatwasprovIdedtopIlotsflyIngathIghaltItudeInunpressurIzedaIrcraft.To
monItoroxygendelIveryandtopreventthepIlotfromsuccumbIngtoanunrecognIzed
faIlureofhIsoxygensupply,|IllIkancreatedanoxygensensIngmonItorwornonthepIlot's
earlobe,andcoInedthenameoximetertodescrIbeItsactIon.8eforehIstragIcdeathIna
clImbIngaccIdentIn1947,|IllIkanhadbeguntoassessanesthetIcapplIcatIonsofoxImetry.
FefInementsofoxImetrybyaJapaneseengIneer,TakuoAoyagI,ledtothedevelopmentof
pulseoxImetry.AsJohnSeverInghausrecountedtheepIsode,AoyagIhadattemptedto
elImInatethechangesInasIgnalcausedbypulsatIlevarIatIonswhenherealIzedthatthIs
fluctuatIoncouldbeusedtomeasureboththepulseandoxygensaturatIon.
5J
AnesthesIologIstshaverecognIzedaneedforbreathbybreathmeasurementofrespIratory
andanesthetIcgases.After1954,InfraredabsorptIontechnIquesgaveImmedIatedIsplays
oftheexhaledconcentratIonofCD
2
.TheabIlItytoconfIrmendotrachealIntubatIonand
monItorventIlatIon,asreflectedbyconcentratIonsofCD
2
InrespIredgas,beganIn194J.
AtthattIme,K.LuftdescrIbedtheprIncIpleofInfraredabsorptIonbyCD
2
andhe
developedanapparatusformeasurement.
56
FoutIneapplIcatIonofcapnographyIn
anesthesIapractIcewaspIoneeredby0r.8obSmalhoutand0r.ZdenKalendaInthe
Netherlands.8reathtobreathcontInuousmonItorIngandawaveformdIsplayofCD
2
levels
helpanesthesIologIstsrecognIzeabnormalItIesInmetabolIsm,ventIlatIon,andcIrculatIon.
|orerecently,InfraredanalysIshasbeenperfectedtoenablebreathbybreath
measurementofanesthetIcgasesaswell.ThIstechnologyhaslargelyreplacedmass
spectrometry,whIchInItIallyhadonlyIndustrIalapplIcatIonsbeforeAlbertFaulconerof
the|ayoClInIcfIrstusedIttomonItortheconcentratIonofanexhaledanesthetIcIn1954.
Safety Standards
TheIntroductIonofsafetyfeatureswascoordInatedbytheAmerIcanNatIonalStandards
nstItute(ANS)CommItteeZ79,whIchwassponsoredfrom1956untIl198JbytheAmerIcan
SocIetyofAnesthesIologIsts.SInce198J,representatIvesfromIndustry,government,and
healthcareprofessIonshavemetonCommItteeZ79oftheAmerIcanSocIetyforTestIng
and|aterIals.TheyestablIshvoluntarygoalsthatmaybecomeacceptednatIonal
standardsforthesafetyofanesthesIaequIpment.
FalphTovellvoIcedthefIrstcallforstandardsdurIngWorldWarwhIlehewastheU.S.
ArmyConsultantInAnesthesIologyforEurope.Tovellfoundthat,astherewerefour
dIfferentdImensIonsforconnectors,tubes,masks,andbreathIngbags,supplIesdIspatched
tofIeldhospItalsmIghtnotmatchtheIranesthesIamachInes.AsTovellobserved,Whena
suddenneedforaccessoryequIpmentarose,nursesandcorpsmenwerelIkelytorespondto
ItbybrIngIngpartsthatwouldnotfIt.
57
AlthoughTovell'sreportsdIdnotgaInan
ImmedIateresponse,afterthewar7IncentCollInsandHamIlton0avIstookuphIsconcern
andformedtheANSCommItteeZ79.DneofthecommIttee'smostactIvemembers,LeslIe
Fendell8aker,wroteanaccountofthecommIttee'sdomestIcandInternatIonal
achIevements.
58
HereportedthatTovellencouragedallmanufacturers
P.1J
toselectthenowunIformorIfIceof22mmforalladultandpedIatrIcfacemasksandto
makeeverytrachealtubeconnector15mmIndIameter.ForthefIrsttIme,aZ79desIgned
masktubeelbowadapterwouldfIteverymaskandtrachealtubeconnector.
TheZ79CommItteeIntroducedotheradvances.TrachealtubesofnontoxIcplastIcbeara
Z79orT(mplantatIonTested)mark.ThecommItteealsomandatedtouchIdentIfIcatIon
ofoxygenflowcontrolatthesuggestIonofFoderIckCalverley,
59
whIchreducedtherIsk
thatthewronggaswouldbeselectedbeforeInternalmechanIcalcontrolspreventedthe
selectIonofanhypoxIcmIxture.PInIndexIngreducedthehazardofattachIngawrong
cylInderIntheplaceofoxygen.0IameterIndexIngofconnectorspreventedsImIlarerrors
InhIghpressuretubIng.Formanyyears,however,errorscommIttedInreassemblIng
hospItaloxygensupplylInesledtoaserIesoftragedIesbeforepolarographIcoxygen
analyzerswereaddedtotheInspIratorylImboftheanesthesIacIrcuIt.
The History of Anesthetic Agents and Adjuvants
Inhaled Anesthetics
Throughoutthesecondhalfofthe19thcentury,othercompoundswereexamInedfortheIr
anesthetIcpotentIal.ThepatternoffortuItousdIscoverythatbroughtnItrousoxIde,dIethyl
ether,andchloroformforwardbetween1844and1847contInued.ThenextInhaled
anesthetIcstobeusedroutInely,ethylchlorIdeandethylene,werealsodIscoveredasa
resultofunexpectedobservatIons.EthylchlorIdeandethylenewerefIrstformulatedInthe
18thcentury.EthylchlorIdewasusedasatopIcalanesthetIcandcounterIrrItant;Itwasso
volatIlethattheskIntransIentlyfrozeafterethylchlorIdewassprayedonIt.ts
redIscoveryasananesthetIccameIn1894,whenaSwedIshdentIstnamedCarlsonsprayed
ethylchlorIdeIntoapatIent'smouthtofreezeadentalabscess.CarlsonwassurprIsedto
dIscoverthathIspatIentsuddenlylostconscIousness.
AsthemechanIsmstodelIverdrugswererefIned,entIrelynewclassesofmedIcatIonswere
alsodeveloped,wIththeIntentIonofprovIdIngsafer,morepleasantpaIncontrol.Ethylene
gaswasthefIrstalternatIvetoetherandchloroform,butIthadsomemajor
dIsadvantages.TheredIscoveryofethyleneIn192JalsocamefromaserendIpItous
observatIon.AfterItwaslearnedthatethylenegashadbeenusedtoInhIbIttheopenIngof
carnatIonbudsInChIcagogreenhouses,Itwasspeculatedthatagasthatputflowersto
sleepmIghtalsohaveananesthetIcactIononhumans.ArnoLuckhardtwasthefIrstto
publIshaclInIcalstudyInFebruary192J.WIthInamonth,sabellaHerbInChIcagoandW.
Easson8rownInTorontopresentedtwootherIndependentstudIes.Ethylenewasnota
successfulanesthetIcbecausehIghconcentratIonswererequIredandItwasexplosIve.An
addItIonalsIgnIfIcantshortcomIngwasapartIcularlyunpleasantsmell,whIchcouldonlybe
partIallydIsguIsedbytheuseofoIloforangeoracheapperfume.Whencyclopropanewas
Introduced,ethylenewasabandoned.
TheanesthetIcactIonofcyclopropanewasInadvertentlydIscoveredIn1929.
60
8rownand
HendersonhadprevIouslyshownthatpropylenehaddesIrablepropertIesasananesthetIc
whenfreshlyprepared,butafterstorageInasteelcylInder,ItdeterIoratedtocreatea
toxIcmaterIalthatproducednauseaandcardIacIrregularItIesInhumans.7elyIen
Henderson,aprofessorofpharmacologyattheUnIversItyofToronto,suggestedthatthe
toxIcproductbeIdentIfIed.AfterachemIst,CeorgeLucas,IdentIfIedcyclopropaneamong
thechemIcalsInthetank,hepreparedasampleInlowconcentratIonwIthoxygenand
admInIsteredIttotwokIttens.TheanImalsfellasleepquIetlybutquIcklyrecovered
unharmed.FatherthanbeIngatoxIccontamInant,Lucassawthatcyclopropanewasa
potentanesthetIc.AfterItseffectsInotheranImalswerestudIedandcyclopropaneproved
tobestableafterstorage,humanexperImentatIonbegan.
HendersonwasthefIrstvolunteer;Lucasfollowed.TheythenarrangedapublIc
demonstratIonInwhIchFrederIck8antIng,aNobellaureateforthedIscoveryofInsulIn,
wasanesthetIzedbeforeagroupofphysIcIans.0espItethIspromIsIngbegInnIng,further
researchwasabruptlyhalted.SeveralanesthetIcdeathsInTorontohadbeenattrIbutedto
ethylchlorIde,andconcernaboutCanadIanclInIcaltrIalsofcyclopropaneprevented
humanstudIesfromproceedIng.Fatherthanabandonthestudy,Hendersonencouragedan
AmerIcanfrIend,FalphWaters,tousecyclopropaneattheUnIversItyofWIsconsIn.The
WIsconsIngroupInvestIgatedthedrugthoroughlyandreportedtheIrclInIcalsuccessIn
19J4.
61
n19J0,ChaunceyLeakeand|eIYuChenperformedsuccessfullaboratorytrIalsof
vInethene(dIvInylether)butwerethwartedInItsfurtherdevelopmentbyaprofessorof
surgeryInSanFrancIsco.ronIcally,CanadIans,whohadlostcyclopropanetoWIsconsIn,
learnedofvInethenefromLeakeandChenInCalIfornIaandconductedthefIrsthuman
studyIn19J2attheUnIversItyofAlberta,Edmonton.nternatIonalresearchcollaboratIon
enabledearlyanesthetIcuseofbothcyclopropaneanddIvInylether,advancesthatmay
nothaveoccurredIndependentlyIneIthertheUnItedStatesorCanada.
AllpotentanesthetIcsofthIsperIodwereexplosIvesaveforchloroform,whosehepatIcand
cardIactoxIcItylImIteduseInAmerIca.AnesthetIcexplosIonsremaInedararebut
devastatIngrIsktobothanesthesIologIstandpatIent.ToreducethedangerofexplosIon
durIngtheIncendIarydaysofWorldWar,8rItIshanesthetIststurnedtotrIchloroethylene.
ThIsnonflammableanesthetIcfoundlImItedapplIcatIonInAmerIca,asItdecomposedto
releasephosgenewhenwarmedInthepresenceofsodalIme.8ytheendofWorldWar,
however,anotherclassofnonInflammableanesthetIcswaspreparedforlaboratorytrIals.
Tenyearslater,fluorInatedhydrocarbonsrevolutIonIzedInhalatIonanesthesIa.
FluorIne,thelIghtestandmostreactIvehalogen,formsexceptIonallystablebonds.These
bonds,althoughsometImescreatedwIthexplosIveforce,resIstseparatIonbychemIcalor
thermalmeans.Forthatreason,manyearlyattemptstofluorInatehydrocarbonsIna
controlledmannerwerefrustratedbythemarkedchemIcalactIvItyoffluorIne.n19J0,
thefIrstcommercIalapplIcatIonoffluorInechemIstrycameIntheformoftherefrIgerant,
Freon.ThIswasfollowedbythefIrstattempttoprepareafluorInatedanesthetIcbyHarold
8oothandE.|ay8IxbyIn19J2.AlthoughtheIrdrug,monochlorodIfluoromethane,was
devoIdofanesthetIcactIon,aswereotherdrugsstudIedthatdecade,theIrreport
predIctedfuturedevelopments.AsurveyofthepropertIesof166knowngasessuggested
thatthebestpossIbIlItyoffIndInganewnoncombustIbleanesthetIcgaslayInthefIeldof
organIcfluorIdecompounds.FluorInesubstItutIonforotherhalogenslowerstheboIlIng
poInt,IncreasesstabIlIty,andgenerallydecreasestoxIcIty.
62
Afterthewar,ateamattheUnIversItyof|arylandunderProfessorofPharmacologyJohn
C.Krantz,Jr.,InvestIgatedtheanesthetIcpropertIesofdozensofhydrocarbonsovera
perIodofseveralyears,butonlyone,ethylvInylether,enteredclInIcaluseIn1947.
8ecauseItwasflammable,KrantzrequestedthatItbefluorInated.nresponse,JulIus
ShukyspreparedseveralfluorInatedanalogs.Dneofthese,trIfluoroethylvInylether,or
fluroxene,becamethefIrstfluorInatedanesthetIc.Fluroxenewasmarketedfrom1954untIl
1974.
n1951,CharlesSucklIng,a8rItIshchemIstofmperIalChemIcalndustrIes,wasaskedto
createanewanesthetIc.
P.14
SucklIng,whoalreadyhadanexpertunderstandIngoffluorInatIon,beganbyaskIng
clInIcIanstodescrIbethepropertIesofanIdealanesthetIc.HelearnedfromthIsInquIry
thathIssearchmustconsIderseverallImItIngfactors,IncludIngthevolatIlIty,
InflammabIlIty,stabIlIty,andpotencyofthecompounds.After2yearsofresearchand
testIng,CharlesSucklIngcreatedhalothane.HefIrstdetermInedthathalothanepossessed
anesthetIcactIonbyanesthetIzIngmealwormsandhouseflIesbeforeheforwardedItto
pharmacologIstJamesFaventos.SucklIngalsomadeaccuratepredIctIonsastothe
concentratIonsrequIredforanesthesIaInhIgheranImals.AfterFaventoscompleteda
favorablerevIew,halothanewasofferedto|IchaelJohnstone,arespectedanesthetIstof
|anchester,England,whorecognIzedItsgreatadvantagesoverotheranesthetIcsavaIlable
In1956.AfterJohnstone'sendorsement,halothaneusespreadquIcklyandwIdelywIthInthe
practIceofanesthesIa.
6J
HalothanewasfollowedIn1960bymethoxyflurane,ananesthetIcthatremaInedpopular
foradecade.8y1970,however,ItwaslearnedthatdoserelatednephrotoxIcItyfollowIng
protractedmethoxyfluraneanesthesIawascausedbyInorganIcfluorIde.SImIlarly,because
ofpersIstIngconcernthatrarecasesofhepatItIsfollowInganesthesIamIghtbearesultofa
metabolIteofhalothane,thesearchfornewerInhaledanesthetIcsfocusedonthe
resIstancetometabolIcdegradatIon.
TwofluorInatedlIquIdanesthetIcs,enfluraneandItsIsomerIsoflurane,wereresultsofthe
searchforIncreasedstabIlIty.TheyweresynthesIzedbyFossTerrellIn196Jand1965,
respectIvely.8ecauseenfluranewaseasIertocreate,ItprecededIsoflurane.ts
applIcatIonwasrestrIctedafterItwasshowntobeamarkedcardIovasculardepressantand
tohavesomeconvulsantpropertIes.sofluranewasnearlyabandonedbecauseof
dIffIcultIesInItspurIfIcatIon,butafterLouIseSpeersovercamethIsproblem,several
successfultrIalswerepublIshedIn1971.ThereleaseofIsofluraneforclInIcalusewas
delayedagaInformorethanhalfadecadebycallsforrepeatedtestIngInloweranImals,
owIngtoanunfoundedconcernthatthedrugmIghtbecarcInogenIc.Asaconsequence,
IsofluranereceIvedmorethoroughtestIngthananyotherdrugheretoforeusedIn
anesthesIa.TheerawhenananesthetIccouldbeIntroducedfollowIngasInglefortuItous
observatIonhadgIvenwaytoacautIousprogramofassessmentandreassessment.
Femarkably,noanesthetIcswereIntroducedIntoclInIcaluseforanother20years.FInally,
desfluranewasreleasedIn1992andsevofluranewasreleasedIn1994.Xenon,agashavIng
manypropertIesoftheIdealanesthetIc,wasadmInIsteredtoafewpatIentsIntheearly
1950sbutItnevergaInedpopularItybecauseoftheextremecostsassocIatedwIthIts
removalfromaIr.However,InterestInxenonhasbeenrenewednowthatgas
concentratIonscanbeaccuratelymeasuredwhenadmInIsteredatlowflows,anddevIces
areavaIlabletoscavengeandreusethegas.
Intravenous Anesthetics
PrIortoWIllIamHarvey'sdescrIptIonofacompleteandcontInuousIntravascularcIrcuItIn
De Motu Cordis(1628),ItwaswIdelyheldthatbloodemanatedfromtheheartandwas
propelledtotheperIpherywhereItwasconsumed.TheIdeathatsubstancescouldbe
InjectedIntravascularlyandtravelsystemIcallyprobablyorIgInatedwIthChrIstopherWren.
n1657,WrenInjectedaqueousopIumIntoadogthroughagoosequIllattachedtoapIg's
bladder,renderIngtheanImalstupefIed.
64
WrensImIlarlyInjectedIntravenouscrocus
metallorum,anImpurepreparatIonofantImony,andobservedtheanImalstovomItand
thendIe.KnowledgeofacIrculatorysystemandIntravascularaccessspurredInvestIgatIons
Inotherareas,andWren'scontemporary,FIchardLower,performedthefIrstblood
transfusIonsoflamb'sbloodIntodogsandotheranImals.
nthemId19thcentury,equIpmentnecessaryforeffectIveIntravascularInjectIonswas
conceIved.7accInatIonlancetswereusedInthe18J0stopuncturetheskInandforce
morphInepastesubcutaneouslyforanalgesIa.
65
ThehollowneedleandhypodermIcsyrInge
weredevelopedInthefollowIngdecadesbutwerenotInItIallydesIgnedforIntravenous
use.n1845,0ublInsurgeonFrancIsFyndcreatedthehollowneedleforInjectIonof
morphIneIntonervesInthetreatmentofneuralgIas.SImIlarly,CharlesCabrIelPravaz
desIgnedthefIrstfunctIonalsyrIngeIn185JforperIneuralInjectIons.AlexanderWood,
however,IsgenerallycredItedwIthperfectIngthehypodermIcglasssyrInge.n1855,Wood
publIshedanartIcleontheInjectIonofopIatesIntopaInfulspotsbyuseofhollowneedle
andhIsglasssyrInge.
66
n1872,PIerreDrofLyonsperformedwhatIsperhapsthefIrstsuccessfulIntravenous
surgIcalanesthetIcbyInjectIngchloralhydrateImmedIatelyprIortoIncIsIon.HIs1875
publIcatIondescrIbesItsuseInJ6patIentsbutseveralpostoperatIvedeathslentlIttleto
recommendthIsmethodtootherpractItIoners.
67
n1909,LudwIg8urkhardtproduced
surgIcalanesthesIabyIntravenousInjectIonsofchloroformandetherInCermany.Seven
yearslater,ElIsabeth8redenfeldofSwItzerlandreportedtheuseofIntravenousmorphIne
andscopolamIne.ThetrIalsfaIledtoshowanImprovementoverInhaledtechnIques.
ntravenousanesthesIafoundlIttleapplIcatIonorpopularIty,prImarIlybecauseofalackof
suItabledrugs.nthefollowIngdecades,thIswouldchange.
ThefIrstbarbIturate,barbItal,wassynthesIzedIn190JbyFIscherandvon|erIng.
PhenobarbItalandallothersuccessorsofbarbItalhadveryprotractedactIonandfound
lIttleuseInanesthesIa.After1929,oralpentobarbItalwasusedasasedatIvebefore
surgery,butwhenItwasgIvenInanesthetIcconcentratIons,longperIodsof
unconscIousnessfollowed.ThefIrstshortactIngoxybarbIturatewashexobarbItal(EvIpal),
avaIlableclInIcallyIn19J2.HexobarbItalwasenthusIastIcallyreceIvedbytheanesthesIa
communItIesInEuropeandNorthAmerIcabecauseItsabbrevIatedInductIontImewas
unrIvaledbyanyothertechnIque.ALondonanesthetIst,FonaldJarman,foundthatIthad
adramatIcadvantageoverInhalatIonInductIonsformInorprocedures.JarmanInstructed
hIspatIentstoraIseonearmwhIleheInjectedhexobarbItalIntoaveInoftheopposIte
forearm.WhentheupraIsedarmfell,IndIcatIngtheonsetofhypnosIs,thesurgeoncould
begIn.PatIentswerealsoamazedInthatmanyawokeunabletobelIevetheyhadbeen
anesthetIzed.
68
EventhoughthepromptactIonofhexobarbItalhadadramatIceffectontheconductof
anesthesIa,ItwassoonreplacedbytwothIobarbIturates.n19J2,0onaleeTabernand
ErnestH.7olwIleroftheAbbottCompanysynthesIzedthIopental(Pentothal)andthIamylal
(SurItal).ThesulfatedbarbIturatesprovedtobemoresatIsfactory,potent,andrapId
actIngthanweretheIroxybarbIturateanalogs.ThIopentalwasfIrstadmInIsteredtoa
patIentattheUnIversItyofWIsconsInIn|arch19J4,butthesuccessfulIntroductIonof
thIopentalIntoclInIcalpractIcefollowedathoroughInvestIgatIonconductedbyJohnLundy
andhIscolleaguesatthe|ayoClInIcInJune19J4.
WhenfIrstIntroduced,thIopentalwasoftengIvenInrepeatedIncrementsastheprImary
anesthetIcforprotractedprocedures.tshazardsweresoonapprecIated.AtfIrst,
depressIonofrespIratIonwasmonItoredbythesImpleexpedIentofobservIngthemotIonof
awIspofcottonplacedoverthenose.DnlyafewskIlledpractItIonerswerepreparedto
passatrachealtubeIfthepatIentstoppedbreathIng.SuchpractItIonersrealIzedthat
thIopentalwIthoutsupplementatIondIdnotsuppressaIrwayreflexes,andtheytherefore
encouragedtheprophylactIcprovIsIonoftopIcalanesthesIaoftheaIrway
P.15
beforehand.ThevasodIlatoryeffectsofthIobarbIturateswerewIdelyapprecIatedonly
whenthIopentalcausedcardIovascularcollapseInhypovolemIcburnedcIvIlIanand
mIlItarypatIentsInWorldWar.nresponse,fluIdreplacementwasusedmore
aggressIvelyandthIopentaladmInIsteredwIthgreatercautIon.
n1962,ketamInewassynthesIzedby0r.CalvInStevensattheParke0avIsLaboratorIesIn
AnnArbor,|IchIgan.DneofthecyclohexylamInecompoundsthatIncludesphencyclIdIne,
ketamInewastheonlydrugofthIsgroupthatgaInedclInIcalutIlIty.Theothercompounds
producedundesIrablepostanesthetIcdelIrIumandpsychomImetIcreactIons.n1966,the
neologIsmdIssocIatIveanesthesIawascreatedbyCuenterCorrsenandEdward0omInoto
descrIbethetrancelIkestateofprofoundanalgesIaproducedbyketamIne.
69
twas
releasedforuseIn1970,andalthoughItremaInsprImarIlyanagentforanesthetIc
InductIon,ItsanalgesIcpropertIesareIncreasInglystudIedandusedbypaInspecIalIsts.
EtomIdatewasfIrstdescrIbedbyPaulJanssenandhIscolleaguesIn1964,andorIgInally
gIventhenameHypnomIdate.tskeyadvantages,mInImalhemodynamIcdepressIonand
lackofhIstamInerelease,accountforItsongoIngutIlItyInclInIcalpractIce.twasreleased
foruseIn1974anddespIteItsdrawbacks(paInonInjectIon,myoclonus,postoperatIve
nauseaandvomItIng,andInhIbItIonofadrenalsteroIdogenesIs),etomIdateIsoftenthe
drugofchoIceforanesthetIzInghemodynamIcallyunstablepatIents.
Propofol,or2,6dIIsopropylphenol,wasfIrstsynthesIzedbymperIalChemIcalndustrIes
andtestedclInIcallyIn1977.nvestIgatorsfoundthatItproducedhypnosIsquIcklywIth
mInImalexcItatIonandthatpatIentsawokepromptlyoncethedrugwasdIscontInued.n
addItIontoItsexcellentInductIoncharacterIstIcs,theantIemetIcactIonofpropofolmade
ItanagentofchoIceInpatIentpopulatIonspronetonauseaandemesIs.Fegrettably,
CremophorEL,thesolventwIthwhIchItwasformulated,producedseveralsevere
anaphylactIcreactIonsandItwaswIthdrawnfromuse.Dncepropofolwasreformulated
wIthegglecIthIn,glycerol,andsoybeanoIl,thedrugreenteredclInIcalpractIceand
gaInedgreatsuccess.tspopularItyIn8rItaIncoIncIdedwIththeIntroductIonoftheL|A,
andItwassoonnotedthatpropofolsuppressedpharyngealreflexestoadegreethat
permIttedtheInsertIonofanL|AwIthoutaneedforeIthermusclerelaxantsorpotent
InhaledanesthetIcs.
Local Anesthetics
CenturIesaftertheconquestofPeru,EuropeansbecameawareofthestImulatIng
propertIesofalocal,IndIgenousplantthatthePeruvIanscalledkhoka.Khoka,whIch
meantthe plant,quIcklybecameknownascocaInEurope.n1860,shortlyafterthe
AustrIanCarlvonScherzerImportedenoughcocaleavestoallowforanalysIs,Cerman
chemIstsAlbertNIemannandWIlhelmLossenIsolatedthemaInalkaloIdandnamedIt
cocaine.TwentyfIveyearslater,attherecommendatIonofhIsfrIendSIgmundFreud,Carl
KollerbecameInterestedIntheeffectsofcocaIne.AfterseveralanImalexperIments,
KollersuccessfullydemonstratedtheanalgesIcpropertIesofcocaIneapplIedtotheeyeIna
patIentwIthglaucoma.
70
Unfortunately,nearlysImultaneouswIththefIrstreportsof
cocaIneuse,therewerereportsofcentralnervoussystemandcardIovasculartoxIcIty.
71,72
AsthepopularItyofcocaInegrew,sodIdthefrequencyoftoxIcreactIonsandcocaIne
addIctIons.
7J
SkeptIcIsmabouttheuseofcocaInequIcklygrewwIthInthemedIcal
communIty,forcIngthepharmacologIcalIndustrytodevelopalternatIvelocalanesthetIcs.
n1898,AlfredEIhornsynthesIzednIvaquIne,thefIrstamInoamIdelocalanesthetIc.
74
NIrvaquIneprovedtobeanIrrItanttotIssuesandItsusewasImmedIatelystopped.
FeturnInghIsattentIontowardthedevelopmentofamInoesterlocalanesthetIcs,EIhorn
synthesIzedbenzocaIneIn1900andprocaIne(novocaIne)shortlyafterIn1905.AmIno
esterswerecommonlyusedforlocalInfIltratIonandspInalanesthesIadespItetheIrlow
potencyandhIghlIkelIhoodtocauseallergIcreactIons.TetracaIne,thelast(andprobably
safest)amInoesterlocalanesthetIcdeveloped,provedtobequIteusefulformanyyears.
n1944,NIlsLofgrenand8engtLundquIstdevelopedlIdocaIne,anamInoamIdelocal
anesthetIc.
7J
LIdocaInegaInedImmedIatepopularItybecauseofItspotency,rapIdonset,
decreasedIncIdenceofallergIcreactIons,andoveralleffectIvenessforalltypesofregIonal
anesthetIcblocks.SIncetheIntroductIonoflIdocaIne,alllocalanesthetIcsdevelopedand
marketedhavebeenoftheamInoamIdevarIety.
8ecauseoftheIncreaseInlengthyandsophIstIcatedsurgIcalprocedures,thedevelopment
ofalongactInglocalanesthetIctookprecedence.Fromthatdemand,bupIvacaInewas
IntroducedIn1965.SynthesIzedby8.EkenstamIn1957,
76
bupIvacaInewasInItIally
dIscardedafterItwasfoundtobehIghlytoxIc.8y1980,severalyearsafterbeIng
IntroducedtotheUnItedStates,therewereseveralreportsofalmostsImultaneous
seIzuresandcardIovascularcollapsefollowIngunIntendedIntravascularInjectIon.
77
Shortly
afterthIs,asaresultofthecardIovasculartoxIcItyassocIatedwIthbupIvacaIneandthe
profoundmotorblockassocIatedwIthetIdocaIne,thepharmaceutIcalIndustrybegan
searchIngforanewlongactIngalternatIve.ntroducedIn1996,ropIvacaIneIsstructurally
sImIlartomepIvacaIneandbupIvacaIne,althoughItIspreparedasasInglelevorotatory
IsomerratherthanaracemIcmIxture.ThelevorotatoryIsomerhaslesspotentIalfor
toxIcItythanthedextrorotatoryIsomer.
78
ThepotentIalsafetyofropIvacaIneIs
controversIalbecauseropIvacaIneIsapproxImately25lesspotentthanbupIvacaIne.
Therefore,atequalpotentdosesthemargInofsafetybetweenropIvacaIneand
bupIvacaInebecomeslessapparent,althoughsystemIctoxIcItywIthropIvacaInemay
respondmorequIcklytoconventIonalresuscItatIon.
79
EachlocalanesthetIcdevelopedhashadItsownposItIveandnegatIveattrIbutes,whIchIs
whysomearestIllusedtodayandothershavefallenoutoffavor.Currently,the
pharmaceutIcalIndustryIsIntheprocessofdevelopIngextendedreleaselocalanesthetIcs
usInglIposomesandmIcrospheres.
80,81
Opioids
DpIoIds(hIstorIcallyreferredtoasnarcotics,althoughsemantIcallyIncorrectseeChapter
19)remaIntheanalgesIcworkhorseInanesthesIapractIce.TheyareusedroutInelyInthe
perIoperatIveperIod,InthemanagementofacutepaIn,andInavarIetyoftermInaland
chronIcpaInstates.TheavaIlabIlItyofshort,medIum,andlongactIngopIoIds,aswellas
themanyroutesofadmInIstratIon,gIvesphysIcIansconsIderableflexIbIlItyIntheuseof
theseagents.TheanalgesIcandsedatIngpropertIesofopIumhavebeenknownformore
thantwomIllennIa.CertaInlytheCreeksandChInesecIvIlIzatIonsharnessedthese
propertIesInmedIcalandculturalpractIces.DpIumIsderIvedfromtheseedsofthepoppy
(Papaver somniferum),andIsanamalgamofmorethan25pharmacologIcalkaloIds.The
fIrstalkaloIdIsolated,morphIne,wasextractedbyPrussIanchemIstFreIdrIchA.W.
SerturnerIn180J.HenamedthIsalkaloIdaftertheCreekgodofdreams,|orpheus.
|orphInebecamecommonlyusedasasupplementtoInhaledanesthesIaandfor
postoperatIvepaIncontroldurIngthelatterhalfofthe19thcentury.CodeIne,another
alkaloIdofopIum,wasIsolatedIn18J2byFobIquetbutItsrelatIvelyweakeranalgesIc
potencyandnauseaathIgherdoseslImItsItsroleInmanagIngmoderatetosevere
perIoperatIvesurgIcalpaIn.
P.16
|eperIdInewasthefIrstsynthetIcopIoIdandwasdevelopedIn19J9bytwoCerman
researchersatCFarben,DttoEIslebandD.Schaumann.AlthoughmanypharmacologIsts
arerememberedfortheIntroductIonofasIngledrug,oneprolIfIcresearcher,Paul
Janssen,hassInce195Jbroughtforwardmorethan70agentsfromamong70,000chemIcals
createdInhIslaboratory.HIsproductshavehadprofoundeffectsondIscIplInesas
dIsparateasparasItologyandpsychIatry.ThepaceofproductIveInnovatIonInJanssen's
researchlaboratoryIsastonIshIng.ChemIcalF426J(fentanyl),synthesIzedIn1960,was
followedonlyayearlaterbyF4749(droperIdol),andthenetomIdateIn1964.nnovar,the
fIxedcombInatIonoffentanylanddroperIdol,IslesspopularnowbutJanssen's
phenylpIperIdInederIvatIves,fentanyl,sufentanIlandalfentanIl,arestaplesInthe
anesthesIapharmacopoeIa.FemIfentanIl,anultrashortactIngopIoIdIntroducedbyClaxo
WellcomeIn1996,IsadeparturefromotheropIoIdsInthatIthasveryrapIdonsetand
equallyrapIdoffsetduetometabolIsmbynonspecIfIctIssueesterases.Ketorolac,a
nonsteroIdalantIInflammatorydrug(NSA0)approvedforuseIn1990,wasthefIrst
parenteralNSA0IndIcatedforpostoperatIvepaIn.WItha6to8mgmorphIneequIvalent
analgesIcpotency,KetorolacprovIdessIgnIfIcantpostoperatIvepaIncontrolandhas
partIcularusewhenanopIoIdsparIngapproachIsessentIal.KetorolacuseIslImItedbysIde
effectsandmaybeInapproprIateInpatIentswIthunderlyIngrenaldysfunctIon,bleedIng
problems,orcompromIsedbonehealIng.
Muscle Relaxants
|usclerelaxantsenteredanesthesIapractIcenearlyacenturyafterInhalatIonal
anesthetIcs(Table11).Curare,thefIrstknownneuromuscularblockIngagent,was
orIgInallyusedInhuntIngandtrIbalwarfarebynatIvepeoplesofSouthAmerIca.The
curaresarealkaloIdspreparedfromplantsnatIvetoequatorIalraInforests.The
refInementoftheharmlesssapofseveralspecIesofvInesIntotoxInsthatwerelethalonly
whenInjectedwasanextraordInarytrIumphIntroducedbypaleopharmacologIstsIn
loIncloths.TheIrdIscoverywasthemoreremarkablebecauseItwasIndependently
repeatedonthreeseparatecontInentsSouthAmerIca,AfrIca,andAsIa.Thesejungle
trIbesalsodevelopednearlyIdentIcalmethodsofdelIverIngthetoxInbydarts,whIch,
afterbeIngdIppedIncurare,maIntaInedtheIrpotencyIndefInItelyuntIltheywere
propelledthroughblowpIpestostrIkethefleshofmonkeysandotheranImalsofthe
treetops.|oreover,theAmerIcanndIansknewofthejuIceofanherbthatwould
counteracttheeffectsofthepoIsonIfadmInIsteredIntIme.
82
TheearlIestclInIcaluseofcurareInhumanswastoamelIoratethetortuousmusclespasms
ofInfectIoustetanus.n1858,NewYorkphysIcIanLouIsAlbertSayresreportedtwocasesIn
whIchheattemptedtotreatseveretetanuswIthcurareatthe8ellevueHospItal.8othof
hIspatIentsdIed.SImIlareffortswereundertakentousemusclerelaxantstotreat
epIlepsy,rabIes,andchoreIformdIsorders.TreatmentofParkInsonlIkerIgIdItyandthe
preventIonoftraumafromseIzuretherapyalsoprecededtheuseofcurareInanesthesIa.
8J
nterestIngly,curareantagonIstsweredevelopedwellbeforemusclerelaxantswereever
usedInsurgery.n1900,JacobPal,a7IennesephysIcIan,recognIzedthatcurarecouldbe
antagonIzedbyphysostIgmIne.ThIssubstancehadbeenIsolatedfromthecalabarbean
someJ6yearsearlIerbyScottIshpharmacologIstSIrT.F.Fraser.NeostIgmIne
methylsulphatewassynthesIzedIn19J1andwassIgnIfIcantlymorepotentInantagonIzIng
theeffectsofcurare.
84
n19J8,FIchardandFuthCIllreturnedtoNewYorkfromSouthAmerIca,brIngIngwIth
them11.9kgofcrudecurarecollectedneartheIrEcuadorIanranch.TheIrmotIvatIonwas
amIxtureofpersonalandaltruIstIcgoals.Somemonthsbefore,whIleonanearlIervIsItto
theUnItedStates,FIchardCIlllearnedthathehadmultIplesclerosIs.HIsphysIcIan,0r.
WalterFreeman,mentIonedthepossIbIlItythatcuraremIghthaveatherapeutIcroleIn
themanagementofspastIcdIsorders.WhentheCIllsreturnedtotheUnItedStateswIth
theIrsupplyofcrudecurare,theyencouragedscIentIstsatE.F.SquIbbECo.totakean
InterestInItsunIquepropertIes.SquIbbsoonofferedsemIrefInedcuraretotwogroupsof
AmerIcananesthesIologIsts,whoassessedItsactIonbutquIcklyabandonedtheIrstudIes
whenItcausedtotalrespIratoryparalysIsIntwopatIentsandthedeathoflaboratory
anImals.
TheearlIesteffectIveclInIcalapplIcatIonofcurareInmedIcIneoccurredInphysIatry.After
A.F.|cntyrerefInedaportIonoftherawcurareIn19J9,AbramE.8ennettofDmaha,
Nebraska,InjectedItIntochIldrenwIthspastIcdIsorders.WhIlenopersIstentbenefItcould
beobservedInthesepatIents,henextadmInIsteredIttopatIentsabouttoreceIve
|etrazol,aprecursortoelectroconvulsIvetherapy.8ecauseItelImInatedseIzureInduced
fractures,theytermedItashockabsorber.8y1941,otherpsychIatrIstsfollowedthIs
practIceand,whentheyfoundthattheactIonofcurarewasprotracted,occasIonallyused
neostIgmIneasanantIdote.
CurarewasusedInItIallyInsurgerybyArthurLawenIn1912,butthepublIshedreportwas
wrIttenInCermanandwasIgnoredfordecades.Lawen,aphysIologIstandphysIcIanfrom
LeIpzIg,usedcurareInhIslaboratorybeforeboldlyproducIngabdomInalrelaxatIonata
lIghtlevelofanesthesIaInasurgIcalpatIent.Lawen'seffortswerenotapprecIatedfor
decades,andwhIlehIspIoneerIngworkantIcIpatedlaterclInIcalapplIcatIon,safeuse
wouldhavetoawaIttheIntroductIonofregularIntubatIonofthetracheaandcontrolled
ventIlatIonofthelungs.
85
ThIrtyyearsafterLawen,HaroldCrIffIth,thechIefanesthetIstofthe|ontreal
HomeopathIcHospItal,learnedofA.E.8ennett'ssuccessfuluseofcurareandresolvedto
applyItInanesthesIa.AsCrIffIthwasalreadyamasteroftrachealIntubatIon,hewasmuch
betterpreparedthanweremostofhIscontemporarIestoattendtopotentIal
complIcatIons.DnJanuary2J,1942,CrIffIthandhIsresIdent,EnIdJohnson,anesthetIzed
andIntubatedthetracheaofayoungmanbeforeInjectIngcurareearlyInthecourseofhIs
appendectomy.SatIsfactoryabdomInalrelaxatIonwasobtaInedandthesurgeryproceeded
wIthoutIncIdent.CrIffIthandJohnson'sreportofthesuccessfuluseofcurareInthe25
patIentsoftheIrserIeslaunchedarevolutIonInanesthetIccare.
86
AnesthesIologIstswhopractIcedbeforemusclerelaxantsrecalltheanxIetytheyfeltwhena
prematureattempttoIntubatethetracheaundercyclopropanecausedpersIstIng
laryngospasm.8efore1942,abdomInalrelaxatIonwaspossIbleonlyIfthepatIenttolerated
hIghconcentratIonsofanInhaledanesthetIc,whIchmIghtbrIngprofoundrespIratory
depressIonandprotractedrecovery.Curareandthedrugsthatfollowedtransformed
anesthesIaprofoundly.8ecauseIntubatIonofthetracheacouldnowbetaughtIna
delIberatemanner,aneophytecouldfaIlonafIrstattemptwIthoutcompromIsIngthe
safetyofthepatIent.ForthefIrsttIme,abdomInalrelaxatIoncouldbeattaInedwhen
curarewassupplementedbylIghtplanesofInhaledanesthetIcsorbyacombInatIonof
IntravenousagentsprovIdIngbalancedanesthesIa.NewfrontIersopened.Sedatedand
paralyzedpatIentscouldnowsuccessfullyundergothemajorphysIologIctrespassesof
cardIopulmonarybypass,delIberatehypothermIa,orlongtermrespIratorysupportafter
surgery.
CredItforsuccessfulandsafeIntroductIonofcurareanddtubocurarIneIntoanesthesIa
mustInpartbegIventoaSquIbbresearchernamedH.A.Holaday.Crude,unstandardIzed
preparatIonsofcurareproduceduncertaInclInIcaleffectsandundesIrablesIdeeffects
relatedtovarIousImpurItIes.solatIon
P.17
ofdtubocurarIneIn19J5renewedclInIcalInterestbutamethodforstandardIzIng
ntocostrInandItspurerderIvatIve,dtubocurarIne,hadyettobedevIsed.ntheearly
1940s,InpartasaresultofCrIffIthandJohnson'ssuccessfultrIals,SquIbbembarkedon
wIdescaleproductIon.HoladaydevelopedarelIable,easIlyreproducIblemethodfor
standardIzIngcuraredosesthatbecameknownastherabbItheaddropassay(FIg.15).The
assayconsIstedofaqueouscuraresolutIonInjectedIntravenouslyIn0.1mLdosesevery15
secondsuntIltheendpoInt,whentherabbItbecameunabletoraIseItshead,was
reached.
87
Table 1-1 Events in the Development of Muscle Relaxants
YEAR EVENT
1516
Peter|artyrd'Anghera,De orbe novo,publIshedaccountofSouth
AmerIcanndIanarrowpoIsons
1596
SIrWalterFaleIghprovIdesdetaIledaccountofarrowpoIsoneffectsand
antIdote
1745
Charles|arIedelaCondamInereturnsfromEcuadorandconductscurare
experImentswIthchIckensandattemptedtousesugarasanantIdote
1780
AbbeFelIxFontanaInsertscuraredIrectlyIntoexposedscIatIcnerveof
rabbItwIthouteffect,concludesthatmechanIsmIsthedestructIonofthe
IrrItabIlItyofvoluntarymuscles.PublIshesOn the American Poison Ticunas
(nameofSouthAmerIcantrIbe)
1811
8enjamInCollIns8rodIedemonstratesthatanImalsmechanIcally
ventIlatedmaysurvIvesIgnIfIcantdosesofcurare
1812
WIllIamSewellsuggestsuseofcurareInhydrophobIa(rabIes)and
tetanus
1844
Claude8ernarddetermInesthatdeathoccursbyrespIratoryfaIlure,
motornervesareunabletotransmItstImulIfromhIghercenters,
dIfferentIaleffectonmuscleswIthperIpheralandthoracIcmusclesbeIng
affectedbeforerespIratorymuscles.8ernardconcludesthatthesIteof
actIonIsthejunctIonbetweenmusclesandnerves,neuromuscular
junctIon
1858
LouIsAlbertSayres,NewYorkphysIcIan,usescuraretotreattetanusIn
twopatIents
1864
PhysostIgmIneIsolatedfromCalabarbeansbySIrT.F.Fraser,aScottIsh
pharmacologIst
1886
F.8oehm,aCermanchemIst,demonstratedthreeseparateclassesof
1897 alkaloIdsIneachofthreetypesofIndIgenouscontaIners:tubecurares,
potcurares,andcalabashcurares
1900
JacobPalrecognIzesthatphysostIgmInecanantagonIzetheeffectsof
curare
1906
SuccInylcholInepreparedbyFeIdHuntandF.Taveau,experImentedon
rabbItspretreatedwIthcuraretolearnofcardIaceffectsandsoparalysIs
wentunrecognIzed
1912
ArthurLawenusescurareInsurgerybutreportpublIshedInCermansoIt
goeslargelyunrecognIzed
19J8
FIchardandFuthCIllbrInglargequantItyofcuraretoNewYorkfor
furtherstudybypharmaceutIcalcompany
19J9
AbramE.8ennettusescurareInchIldrenwIthspastIcdIsordersandto
preventtraumafrom|etrazoltherapy(precursortoECT)
1942
HaroldCrIffIthandEnIdJohnsonusecurareforabdomInalrelaxatIonIn
surgery
1942
H.A.HalodydevelopsrabbItheaddropassayforstandardIzatIonand
largescaleproductIonofcurareanddtubocurarIne
1948 0ecamethonIum,adepolarIzIngrelaxant,IssynthesIzed
1949
SuccInylcholInepreparedby0anIel8ovet,andthefollowIngyearbyJ.C.
CastIlloandEdwInde8eer
1956
0IstInctIonbetweendepolarIzIngandnondepolarIzIngneuromuscular
blockadeIsmadebyWIllIam0.|.Paton
1964
PancuronIumreleasedforuseInhumans,synthesIzedbySavageand
Hewett
1979
7ecuronIumIntroduced,specIfIcallydesIgnedtobemorehepatIcally
metabolIzedthanpancuronIum
199J |IvacurIumreleasedforclInIcaluse
1994 FocuronIumIntroducedtoclInIcalpractIce
SuccessfulclInIcaluseofcurareledtotheIntroductIonofothermusclerelaxants.8y1948,
gallamIneanddecamethonIumhadbeensynthesIzed.|etubIne,acurareredIscoveredIn
the1970s,wasusedclInIcallyInthesameyear.SuccInylcholInewaspreparedbytheNobel
laureate0anIel8ovetIn1949andwasInwIdeInternatIonalusebeforehIstorIansnoted
thatthedrughadbeensynthesIzedandtestedlongbeforehand.n1906,FeIdHuntandF.
TaveauxpreparedsuccInylcholIneamongaserIesofcholIneesters,whIchtheyhad
InjectedIntorabbItstoobservetheIrcardIaceffects.ftheIrrabbItshadnotbeen
prevIouslyparalyzedwIthcurare,the
P.18
depolarIzIngactIonofsuccInylcholInemIghthavebeenrecognIzeddecadesearlIer.
Figure 1-5.TheFabbItheaddropassay.H.A.HallodayofSquIbbpharmaceutIcal
companydevelopedamethodofstandardIzIngdosesofcurareanddtubocurarInea
normalrabbIt(A)had0.1mlofaqueouscecuranesolutIonInjectedevery15seconds
untIlItcouldnolongerraIseItshead(B).
TheabIlItytomonItorIntraoperatIveneuromuscularblockadewIthnervestImulators
beganIn1958.WorkIngatSt.Thomas'HospItalInLondon,T.H.ChrIstIeandH.ChurchIll
0avIdsondevelopedamethodformonItorIngperIpheralneuromuscularblockadedurIng
anesthesIa.twasnotuntIl1970,however,thatH.H.AlIandcolleaguesdevIsedthe
technIqueofdelIverIngfoursupramaxImalImpulsesdelIveredat2Hz(0.5secondsapart),
oraTraInofFour,asamethodofquantIfyIngthedegreeofresIdualneuromuscular
blockade.
88
FesearchInrelaxantswasrekIndledIn1960whenresearchersbecameawareoftheactIon
ofmaloetIne,arelaxantfromtheCongobasIn.twasremarkableInthatIthadasteroIdal
nucleus.nvestIgatIonsofmaloetIneledtopancuronIumIn1968.nthe1970sand1980s,
researchshIftedtowardIdentIfIcatIonofspecIfIcreceptorbIochemIstryanddevelopment
ofreceptorspecIfIcdrugs.FromtheseIsoquInolInes,fourrelatedproductsemerged:
vecuronIum,pIpecuronIum,rocuronIum,andrapacuronIum.FapacuronIum,releasedInthe
early1990s,waswIthdrawnfromclInIcaluseafterseveralcasesofIntractable
bronchospasmledtobraIndamageordeath.FourclInIcalproductsbasedonthesteroId
parentdrugdtubocurarIne(atracurIum,mIvacurIum,doxacurIum,andcIsatracurIum)also
madeIttoclInIcaluse.FecognItIonthatatracurIumandcIsatracurIumundergo
spontaneousdegradatIonbyHoffmannelImInatIonhasdefInedaroleforthesemuscle
relaxantsInpatIentswIthlIverandrenalInsuffIcIency.
Antiemetics
EffectIvetreatmentforpostoperatIvenauseaandvomItIng(PDN7)evolvedrelatIvely
recentlyandhasbeendrIvenbyIncentIvestolImIthospItalIzatIonexpensesandImprove
patIentsatIsfactIon.8utPDN7IsanoldproblemforwhIchlate19thcenturypractItIoners
recognIzedmanycausesIncludInganxIety,severepaIn,suddenchangesInbloodpressure,
Ileus,IngestIonofblood,andtheresIdualeffectsofopIoIdsandInhalatIonalanesthetIcs.
FIskofpulmonaryaspIratIonofgastrIccontentsandsubsequentdeathfromasphyxIaor
aspIratIonpneumonIawasafearedconsequenceofanesthetIcs,especIallythoseprecedIng
useofcuffedendotrachealtubes.7omItIngandaspIratIondurInganesthesIaledtothe
practIceofmaIntaInInganemptystomachpreoperatIvely,apolIcythatcontInuestoday
despIteevIdencethatclearfluIdsuptoJhoursbeforesurgerydonotIncreasegastrIc
volumes,changegastrIcpH,orIncreasetherIskofaspIratIon.
AvarIetyoftreatmentsfornauseaandvomItIngwereproposedbyearlyanesthetIsts.
JamesCwathemy's1914publIcatIon,Anesthesia,commentedthat8rItIshsurgeons
customarIlygavetInctureofIodIneInateaspoonfulofwatereveryhalfhourforthreeor
fourdoses.nhalatIonofvInegarfumes,andrectalInjectIonofJ0to40dropsoftInctureof
opIumwIth60graInsofsodIumbromIde,werealsothoughttoquIetthevomItIngcenter.
89
DtherpractItIonersattemptedolfactorycontrolbyplacIngapIeceofgauzemoIstenedwIth
essenceoforangeoranaromatIcoIlontheupperlIpofthepatIent.
90
A19J7anesthesIa
textbookencouragedtreatmentofPDN7wIthlateralposItIonIng,Icedsodawater,strong
blackcoffee,andchloretone.
91
CounterIrrItatIon,suchasmustardleafonthe
epIgastrIum,wasalsobelIevedusefulInlImItIngemesIs.
92
Aslateas1951,anesthesIatexts
recommendedoxygenadmInIstratIon,whIffsofammonIaspIrIts,andcontrolofblood
pressureandposItIonIng.
9J
ThecomplexcentralmechanIsmsofnauseaandvomItIngwere
largelyunaffectedbymostofthesetreatments.NewerdrugscapableofIntervenIngat
specIfIcpathwayswereneededtohaveanImpactonPDN7.AsmoreshortactIng
anesthetIcsweredeveloped,theproblemreceIvedsharperfocusInawakepostoperatIve
patIentsIntherecoveryroom.ThenauseaattendInguseofnewerchemotherapyagents
provIdedaddItIonalImpetustothedevelopmentofantIemetIcmedIcatIons.
n1955,anonrandomIzedstudyusIngtheantIhIstamInecyclIzIneshowedareductIonIn
PDN7from27to21InagroupofJ,000patIents.ThefollowIngyear,amorerIgorous
studybyKnappand8eecherreportedasIgnIfIcantbenefItfromprophylaxIswIththe
neuroleptIcchlorpromazIne.n1957,promethazIne(Phenergan)andchlorpromazInewere
bothfoundtoreducePDN7whenusedprophylactIcally.ThIrteenyearslater,adouble
blIndstudyevaluatIngmetoclopramIdewaspublIshedandthatdrugbecameafIrstlIne
drugInthemanagementofPDN7.0roperIdol,releasedIntheearly1960s,becamewIdely
useduntIl2001whenconcernsregardIngprolongatIonofQTIntervalspromptedawarnIng
fromtheFoodand0rugAdmInIstratIonaboutItscontInueduse.
TheantIemetIceffectsofcortIcosteroIdswerefIrstrecognIzedbyoncologIststreatIng
IntracranIaledemafromtumors.
94
SubsequentstudIeshaveborneouttheantIemetIc
propertIesofthIsclassofdrugsIntreatIngPDN7.FecognItIonoftheserotonIn5HTJ
pathwayInPDN7hasledtoaunIque
P.19
classofdrugsdevotedonlytoaddressIngthIspartIcularproblem.Dndansetron,thefIrst
representatIveofthIsdrugclass,wasapprovedbytheFoodand0rugAdmInIstratIonIn
1991.AddItIonalserotonIn5HTJantagonIstshavebeenapprovedandareavaIlabletoday.
Anesthesia Subspecialties
Regional Anesthesia
CocaIne,anextractofthecocaleaf,wasthefIrsteffectIvelocalanesthetIc.AfterAlbert
NIemannrefInedtheactIvealkaloIdandnamedItcocaine,ItwasusedInexperImentsbya
fewInvestIgators.twasnotedthatcocaIneprovIdedtopIcalanesthesIaandeven
producedlocalInsensIbIlItywhenInjected,butCarlKoller,a7IennesesurgIcalIntern,fIrst
recognIzedtheutIlItyofcocaIneInclInIcalpractIce.
n1884,CarlKollerwascompletInghIsmedIcaltraInIngatatImewhenmanyoperatIonson
theeyewereperformedwIthoutgeneralanesthesIa.Almostfourdecadesafterthe
dIscoveryofether,generalanesthesIabymaskstIllhadlImItatIonsforophthalmIcsurgery:
lackofpatIentcooperatIon,InterferenceoftheanesthesIaapparatuswIthsurgIcalaccess,
andthehIghIncIdenceofPDN7.AtthattIme,sIncefInesutureswerenotavaIlableand
surgIcalIncIsIonsoftheeyewerenotclosed,postoperatIvevomItIngthreatenedthe
extrusIonoftheglobe'scontents,puttIngthepatIentatrIskforIrrevocableblIndness.
95
WhIleamedIcalstudent,KollerhadworkedIna7IenneselaboratoryInasearchofa
topIcalophthalmIcanesthetIctoovercomethelImItatIonsofgeneralanesthesIa.
Unfortunately,thesuspensIonsofmorphIne,chloralhydrate,andotherdrugsthathehad
usedhadbeenIneffectual.n1884,Koller'sfrIend,SIgmundFreud,becameInterestedIn
thecerebralstImulatIngeffectsofcocaIneandgavehImasmallsampleInanenvelope,
whIchheplacedInhIspocket.Whentheenvelopeleaked,afewgraInsofcocaInestuckto
Koller'sfIngerandheabsentmIndedlylIckedhIstongue.WhenhIstonguebecamenumb,
KollerInstantlyrealIzedthathehadfoundtheobjectofhIssearch.nhIslaboratory,he
madeasuspensIonofcocaInecrystalsthatheandalaboratoryassocIatetestedIntheeyes
ofafrog,arabbIt,andadog.SatIsfIedwIththeanesthetIceffectsseenIntheanImal
models,KollerdroppedthesolutIonontohIsowncornea.TohIsamazement,hIseyeswere
InsensItIvetothetouchofapIn.
96
AsanIntern,CarlKollercouldnotaffordtoattenda
CongressofCermanDphthalmologIstsInHeIdelbergonSeptember15,1884.However,a
frIendpresentedhIsartIcleatthemeetIngandarevolutIonInophthalmIcsurgeryand
othersurgIcaldIscIplInesbegan.WIthInthenextyear,morethan100artIclessupportIng
theuseofcocaIneappearedInEuropeanandAmerIcanmedIcaljournals.n1888,Koller
ImmIgratedtoNewYork,wherehepractIcedophthalmologyfortheremaInderofhIs
career.
AmerIcansurgeonsquIcklydevelopednewapplIcatIonsforcocaIne.tseffIcacyIn
anesthetIzIngthenose,mouth,larynx,trachea,rectum,andurethrawasdescrIbedIn
Dctober1884.Thenextmonth,thefIrstreportsofItssubcutaneousInjectIonwere
publIshed.n0ecember1884,twoyoungsurgeons,WIllIamHalstedandFIchardHall,
descrIbedblocksofthesensorynervesofthefaceandarm.Halstedevenperformeda
brachIalplexusblockbutdIdsounderdIrectvIsIonwhIlethepatIentreceIvedanInhaled
anesthetIc.
97
Unfortunately,selfexperImentatIonwIthcocaInewashazardous,asboth
surgeonsbecameaddIcted.
98
AddIctIonwasanIllunderstoodbutfrequentproblemInthe
late19thcentury,especIallywhencocaIneandmorphInewerepresentInmanypatent
medIcInesandfolkremedIes.
DtherregIonalanesthetIctechnIqueswereattemptedbeforetheendofthe19thcentury.
Thetermspinal anesthesiawascoInedIn1885byLeonardCornIng,aneurologIstwhohad
observedHallandHalsted.CornIngwantedtoassesstheactIonofcocaIneasaspecIfIc
therapyforneurologIcproblems.AfterfIrstassessIngItsactIonInadog,producInga
blockadeofrapIdonsetthatwasconfInedtotheanImal'srearlegs,heperformeda
neuraxIalblockusIngcocaIneonamanaddIctedtomasturbatIon.CornIngadmInIstered
onedosewIthouteffect,thenafteraseconddose,thepatIent'slegsfeltsleepy.Theman
hadImpaIredsensIbIlItyInhIslowerextremItyafterabout20mInutesandleftCornIng's
offIcenonetheworsefortheexperIence.
99
AlthoughCornIngdIdnotdescrIbeescapeof
cerebrospInalfluId(CSF)IneIthercase,ItIslIkelythatthedoghadaspInalanesthetIcand
thatthemanhadanepIduralanesthetIc.NotherapeutIcbenefItwasdescrIbed,but
CornIngclosedhIsaccountandhIsattentIontothesubjectbysuggestIngthatcocaInIzatIon
mIghtIntImebeasubstItuteforetherIzatIonIngenItourInaryorotherbranchesof
surgery.
100
Twootherauthors,August8IerandTheodorTuffIer,descrIbedauthentIcspInalanesthesIa,
wIthmentIonofCSF,InjectIonofcocaIne,andanapproprIatelyshortonsetofactIon.na
comparatIverevIewoftheorIgInalartIclesby8Ier,TuffIer,andCornIng,Itwasconcluded
thatCornIng'sInjectIonwasextradural,and8IermerItedthecredItforIntroducIngspInal
anesthesIa.
101
FourteenyearspassedbeforespInalanesthesIawasperformedforsurgery.ntheInterval,
HeInrIchQuInckeofKIel,Cermany,haddescrIbedhIstechnIqueoflumbarpuncture.He
offeredthevaluableobservatIonthatItwasmostsafelyperformedatthelevelofthethIrd
orfourthlumbarInterspacebecauseentryatthatlevelwasbelowthetermInatIonofthe
spInalcord.QuIncke'stechnIquewasusedInKIelforthefIrstdelIberatecocaInIzatIonof
thespInalcordIn1899byhIssurgIcalcolleague,August8Ier.SIxpatIentsreceIvedsmall
dosesofcocaIneIntrathecally,butbecausesomecrIedoutdurIngsurgerywhIleothers
vomItedandexperIencedheadaches,8IerconsIderedItnecessarytoconductfurther
experImentsbeforecontInuIngthIstechnIqueforsurgery.
Professor8IerpermIttedhIsassIstant,0r.HIldebrandt,toperformalumbarpuncture,but
aftertheneedlepenetratedthedura,HIldebrandtcouldnotfItthesyrIngetotheneedle
andalargevolumeoftheprofessor'sspInalfluIdescaped.TheywereatthepoIntof
abandonIngthestudywhenHIldebrandtvolunteeredtobethesubjectofasecondattempt.
TheIrpersIstencewasrewardedwIthanastonIshIngsuccess.TwentythreemInutesafter
thespInalInjectIon,8Iernoted:AstrongblowwIthanIronhammeragaInstthetIbIawas
notfeltaspaIn.After25mInutes:StrongpressureandpullIngonatestIclewerenot
paInful.
94
TheycelebratedtheIrsuccesswIthwIneandcIgars.ThatnIght,bothdeveloped
vIolentheadaches,whIchtheyattrIbutedatfIrsttotheIrcelebratIon.8Ier'sheadachewas
relIevedafter9daysofbedrest.HIldebrandt,asahouseoffIcer,dIdnothavetheluxuryof
contInuedrest.8IerpostulatedthattheIrheadacheswerearesultofthelossoflarge
volumesofCSFandurgedthatthIsbeavoIdedIfpossIble.ThehIghIncIdenceof
complIcatIonsfollowInglumbarpuncturewIthwIdeboreneedlesandthetoxIcreactIons
attrIbutedtococaIneexplaInhIslaterlossofInterestInspInalanesthesIa.
102
SurgeonsInseveralothercountrIessoonpractIcedspInalanesthesIaandprogressoccurred
bymanysmallcontrIbutIonstothetechnIque.TheodorTuffIerpublIshedthefIrstserIesof
125spInalanesthetIcsfromFranceandhelatercounseledthatthesolutIonshouldnotbe
InjectedbeforeCSFwasseen.ThefIrstAmerIcanreportwasbyFudolph|atasofNew
Drleans,whosefIrstpatIentdevelopedpostanesthetIcmenIngIsmus,afrequent
complIcatIonthatwasovercomeInpartbytheuseofhermetIcallysealedsterIlesolutIons
recommendedbyE.W.LeeofPhIladelphIaandsterIleglovesasadvocatedbyHalsted.
0urIng1899,0udleyTaItandCuIdloCaglIerIofSanFrancIsco
P.20
performedexperImentalstudIesInanImalsandtherapeutIcspInalsfororthopaedIc
patIents.TheyencouragedtheuseoffIneneedlestolessentheescapeofCSFandurged
thattheskInanddeepertIssuesbeInfIltratedbeforehandwIthlocalanesthesIa.
10J
ThIshad
beensuggestedearlIerbyWIllIamHalstedandtheforemostadvocateofInfIltratIon
anesthesIa,CarlLudwIgSchleIchof8erlIn.AnearlyAmerIcanspecIalIstInanesthesIa,
DrmondColdan,publIshedananesthesIarecordapproprIateforrecordIngthecourseof
IntraspInalcocaInIzatIonIn1900.nthesameyear,HeInrIch8raunlearnedofanewly
descrIbedextractoftheadrenalgland,epInephrIne,whIchheusedtoprolongtheactIonof
localanesthetIcswIthgreatsuccess.8raundevelopedseveralnewnerveblocks,coInedthe
termconduction anesthesia,andIsrememberedbyEuropeanwrItersasthefatherof
conductIonanesthesIa.8raunwasthefIrstpersontouseprocaIne,whIch,alongwIth
stovaIne,wasoneofthefIrstsynthetIclocalanesthetIcsproducedtoreducethetoxIcItyof
cocaIne.
8efore1907,anesthesIologIstsweresometImesdIsappoIntedtoobservethattheIrspInal
anesthetIcswereIncomplete.|ostbelIevedthatthedrugspreadsolelybylocaldIffusIon
beforethepropertyofbarIcItywasInvestIgatedbyArthur8arker,aLondonsurgeon.
104
8arkerconstructedaglasstubeshapedtofollowthecurvesofthehumanspIneandusedIt
todemonstratethelImItedspreadofcoloredsolutIonsthathehadInjectedthroughaT
pIeceInthelumbarregIon.8arkerapplIedthIsobservatIontousesolutIonsofstovaIne
madehyperbarIcbytheaddItIonof5glucose,whIchworkedInamorepredIctable
fashIon.AftertheInjectIonwascomplete,8arkerplacedhIspatIent'sheadonpIllowsto
contaIntheanesthetIcbelowthenIpplelIne.LIncolnSIseacknowledged8arker'sworkIn
19J5whenheIntroducedtheuseofhyperbarIcsolutIonsoftetracaIne(PontocaIne).John
AdrIanIadvancedtheconceptfurtherIn1946whenheusedahyperbarIcsolutIonto
producesaddleblock,orperInealanesthesIa.AdrIanI'spatIentsremaInedseatedafter
InjectIonasthedrugdescendedtothesacralnerves.
TaIt,Jonnesco,andotherearlymastersofspInalanesthesIausedacervIcalapproachfor
thyroIdectomyandthoracIcprocedures,butthIsradIcalapproachwassupplantedIn1928
bythelumbarInjectIonofhypobarIcsolutIonsoflIghtnupercaInebyC.P.PItkIn.
AlthoughtheuseofhypobarIcsolutIonsIsnowlImItedprImarIlytopatIentsposItIonedIn
thejackknIfeposItIon,theIrformeruseforthoracIcproceduresdemandedskIllandprecIse
tImIng.TheenthusIastsofhypobarIcanesthesIadevIsedformulastoattempttopredIctthe
tImeInsecondsneededforawarmedsolutIonofhypobarIcnupercaInetospreadIn
patIentsofvaryIngsIzefromItssIteofInjectIonInthelumbarareatothelevelofthe
fourththoracIcdermatome.
TherecurrIngproblemofInadequateduratIonofsIngleInjectIonspInalanesthesIaleda
PhIladelphIasurgeon,WIllIamLemmon,todevIseanapparatusforcontInuousspInal
anesthesIaIn1940.
105
LemmonbeganwIththepatIentInthelateralposItIon.ThespInal
tapwasperformedwIthamalleablesIlverneedle,whIchwasleftInposItIon.Asthe
patIentwasturnedsupIne,theneedlewasposItIonedthroughaholeInthemattressand
table.AddItIonalInjectIonsoflocalanesthetIccouldbeperformedasrequIred.|alleable
sIlverneedlesalsofoundalesscumbersomeandmorecommonapplIcatIonIn1942when
WaldoEdwardsandFobertHIngsonencouragedtheuseofLemmon'sneedlesforcontInuous
caudalanesthesIaInobstetrIcs.n1944EdwardTuohyofthe|ayoClInIcIntroducedtwo
ImportantmodIfIcatIonsofthecontInuousspInaltechnIques.Hedevelopedthenow
famIlIarTuohyneedle
106
asameansofImprovIngtheeaseofpassageoflacqueredsIlk
ureteralcathetersthroughwhIchheInjectedIncrementaldosesoflocalanesthetIc.
107
n1949,|artInezCurbeloofHavana,Cuba,usedTuohy'sneedleandaureteralcatheterto
performthefIrstcontInuousepIduralanesthetIc.SIlkandgumelastIccatheterswere
dIffIculttosterIlIzeandsometImescausedduralInfectIonsbeforebeIngsupersededby
dIsposableplastIcs.Yet,delIberatesIngleInjectIonperIduralanesthesIahadbeenpractIced
occasIonallyfordecadesbeforecontInuoustechnIquesbroughtItgreaterpopularIty.Atthe
begInnIngofthe20thcentury,twoFrenchclInIcIansexperImentedIndependentlywIth
caudalanesthesIa.TheneurologIstJeanAthanaseSIcardapplIedthetechnIquefora
nonsurgIcalpurpose,therelIefofbackpaIn.FernandCathelInusedcaudalanesthesIaasa
lessdangerousalternatIvetospInalanesthesIaforhernIarepaIrs.Healsodemonstrated
thattheepIduralspacetermInatedIntheneckbyInjectIngasolutIonofndIaInkIntothe
caudalcanalofadog.ThelumbarapproachwasfIrstusedsolelyformultIpleparavertebral
nerveblocksbeforethePags0oglIottIsIngleInjectIontechnIquebecameaccepted.As
theyworkedseparately,thetechnIquecarrIesthenamesofbothmen.CaptaInFIdelPags
preparedanelegantdemonstratIonofsegmentalsIngleInjectIonperIduralanesthesIaIn
1921,butdIedsoonafterhIsartIcleappearedInaSpanIshmIlItaryjournal.
108
Tenyears
later,AchIlle|.0oglIottIofTurIn,taly,wroteaclassIcstudythatmadetheepIdural
technIquewellknown.
7J
WhereasPagsusedatactIleapproachtoIdentIfytheepIdural
space,0oglIottIIdentIfIedItbythelossofresIstancetechnIque.
SurgeryontheextremItIeslentItselftootherregIonalanesthesIatechnIques.n1902,
HarveyCushIngcoInedthephraseregional anesthesiaforhIstechnIqueofblockIngeIther
thebrachIalorscIatIcplexusunderdIrectvIsIondurInggeneralanesthesIatoreduce
anesthesIarequIrementsandprovIdepostoperatIvepaInrelIef.
75
FIfteenyearsbeforehIs
publIcatIon,CeorgeCrIleadvancedasImIlarapproachtoreducethestressandshockof
surgery.CrIle,adedIcatedadvocateofregIonalandInfIltratIontechnIquesdurInggeneral
anesthesIa,coInedthetermanoci-association.
109
AnIntravenousregIonaltechnIquewIthprocaInewasreportedIn1908byAugust8Ier,the
surgeonwhohadpIoneeredspInalanesthesIa.8IerInjectedprocaIneIntoaveInofthe
upperlImbbetweentwotournIquets.EventhoughthetechnIqueIstermedtheBier block,
ItwasnotusedformanydecadesuntIlItwasreIntroduced55yearslaterby|ackInnon
Holmes,whomodIfIedthetechnIquebyexsanguInatIonbeforeapplyIngasIngleproxImal
cuff.HolmesusedlIdocaIne,theverysuccessfulamIdelocalanesthetIcsynthesIzedIn194J
byLofgrenandLundquIstofSweden.
SeveralInvestIgatorsachIevedupperextremItyanesthesIabypercutaneousInjectIonsof
thebrachIalplexus.n1911,basedonhIsIntImateknowledgeoftheanatomyofthe
axIllaryarea,HIrschelpromotedablIndaxIllaryInjectIon.nthesameyear,Kulenkampff
descrIbedasupraclavIcularapproachInwhIchtheoperatorsoughtoutparesthesIasofthe
plexuswhIlekeepIngtheneedleatapoIntsuperfIcIaltothefIrstrIbandthepleura.The
rIskofpneumothoraxwIthKulenkampff'sapproachled|ulleytoattemptblocksmore
proxImallybyalateralparavertebralapproach,theprecursorofwhatIsnowpopularly
knownastheWinnie block.
HeInrIch8raunwrotetheearlIesttextbookoflocalanesthesIa,whIchappearedInItsfIrst
EnglIshtranslatIonIn1914.After1922,CastonLabat'sRegional AnesthesiadomInatedthe
AmerIcanmarket.LabatmIgratedfromFrancetothe|ayoClInIcIn|Innesota,wherehe
servedbrIeflybeforetakIngapermanentposItIonatthe8ellevueHospItalInNewYork.He
formedthefIrstAmerIcanSocIetyforFegIonalAnesthesIa.
110
AfterLabat'sdeath,EmeryA.
FovenstInewasrecruItedto8ellevuetocontInueLabat'swork,amongother
responsIbIlItIes.FovensteIncreatedthefIrstAmerIcanclInIcforthetreatmentofchronIc
paIn,whereheandhIsassocIatesrefInedtechnIquesoflytIcandtherapeutIcInjectIonsand
usedtheAmerIcanSocIetyofFegIonalAnesthesIatofurthertheknowledgeofpaIn
managementacrosstheUnItedStates.
111
P.21
ThedevelopmentofthemultIdIscIplInarypaInclInIcwasoneofmanycontrIbutIonsto
anesthesIologymadebyJohnJ.8onIca,arenownedteacherofregIonaltechnIques.0urIng
hIsperIodsofmIlItary,cIvIlIan,andunIversItyservIceattheUnIversItyofWashIngton,
8onIcaformulatedaserIesofImprovementsInthemanagementofpatIentswIthchronIc
paIn.HIsclassIctextThe Management of Pain,nowInItsthIrdedItIon,Isregardedasa
standardofthelIteratureofanesthesIa.
Cardiovascular Anesthesia
TheearlIestattemptstooperateontheheartwerelImItedtorepaIrIngcardIacwounds.
TheseattemptsgenerallyfaIleduntIlCermansurgeonLudwIgFehnrepaIredarIght
ventrIcularstabwoundInSeptember1896.
112
0espItethIssuccess,thefIeldwasnotready
toadvance.ThetabooofcardIacsurgerywassummarIzedbyTheodore8Illrothwhenhe
supposedlysaIdanysurgeonwhowouldattemptanoperatIonontheheartshouldlosethe
respectofhIscolleagues.
11J
TheresIstancetosuchoperatIonswaspartlybecauseof
fledglInganesthetIcmedIcatIons,lackofadequatemonItors,andevenaclear
understandIngofcardIovascularphysIologythatpervadesmodernanesthesIapractIce.
Fortunately,theturnofthe20thcenturysawmanyadvancesInanesthesIapractIce,blood
typIngandtransfusIon,antIcoagulatIon,antIbIosIs,aswellassurgIcalInstrumentatIonand
technIque.SomecontInuedtoattemptprocedureslIkeclosedmItralvalvotomyInthe
mIdstofthesetechnologIcaladvancements,butoutcomeswerestIllverypoorwIth
mortalItyratesexceedIng80.|anybelIevethatthesuccessfullIgatIonofa7yearold
gIrl'spatentductusarterIosusbyFobertCrossIn19J8servedasthelandmarkcasefor
moderncardIacsurgery.SoonafterCross'achIevement,ahostofnewprocedureswere
developedforrepaIrIngcongenItalcardIaclesIons,IncludIngthefIrst8lalockTaussIgshunt
performedona15montholdbluebabyIn1944.
114
Althoughtheshunthadbeen
successfullydemonstratedInanImalmodels,AustInLamont,ChIefofAnesthesIaatJohns
HopkIns,wasnotsupportIveoftheprocedure.HeemphatIcallystatedwIllnotputthat
chIldtodeathandlefttheopendropetheroxygenanesthetIctoresIdentanesthesIologIst
|erelHarmel.
115
Lamontattendedonthesecond8lalockTaussIgshunt2monthslater.
Together,HarmelandLamontwouldpublIshthefIrstartIcleonanesthesIaforcardIac
surgeryIn1946basedon100caseswIthAlfred8lalockandrepaIrofcongenItalpulmonIc
stenosIs.
116
ClosedcardIacsurgeryensuedandanesthesIapIoneerslIkeWIllIam|cQuIstonandKenneth
KeownworkedsIdebysIdewIthsurgeonsdurIngprocedureslIkethefIrstaortIcpulmonary
anastomosIsandthefIrsttransmyocardIalmItralcommIssurotomy.Neverbeforehad
anesthesIaprovIdersworkedasIntImatelywIthsurgeonsforthepatIent'swelfare.
AnesthesIologIstandWorldWarphysIcIan|axSamuelSadoveremarkedthesmallarms
fIreoftheanesthesIologIstjoInsthespysystemofthelabtobackupthesurgeon'sbIg
artIlleryInacoordInatedattacktoconquerdIsease.
117
Throughthe19J0sand1940s,JohnCIbbonhadbeenexperImentIngwIthseveral
extracorporealcIrcuItdesIgnsandby1947wasabletosuccessfullyplacedogsonheartlung
bypass.ThefIrstsuccessfuluseofCIbbon'scardIopulmonarybypassmachIneInhumansIn
|ay195JwasamonumentaladvanceInthesurgIcaltreatmentofcomplexcardIac
pathologythatstImulatedInternatIonalInterestInopenheartsurgeryandthespecIaltyof
cardIacanesthesIa.
Dverthenextdecade,rapIdgrowthandexpandedapplIcatIonsofcardIacsurgery,
IncludIngartIfIcIalvalvesandcoronaryarterybypassgraftIng,requIredmanymore
anesthesIologIstsacquaIntedwIththesespecIalIzedtechnIques.n1967,J.EarlWaynards
publIshedoneofthefIrstartIclesonanesthetIcmanagementofpatIentsundergoIng
surgeryforcoronaryarterydIsease.
AscardIacsurgeryevolved,sodIdtheperIoperatIvemonItorIngandcareofpatIents
undergoIngcardIacsurgery.PostoperatIvemechanIcalventIlatIonandsurgIcalIntensIve
careunItsappearedbythelate1960s.0evIceslIketheleftatrIalpressuremonItorandthe
IntraaortIcballoonpumpofferednewmethodsofunderstandIngcardIopulmonary
physIologyandtreatIngpostoperatIveventrIcularfaIlure.CardIacanesthesIologIstswere
quIcktobrIngthepulmonaryarterycatheter(PAC)IntotheoperatIngroom,permIttIng
moreprecIsehemodynamIcmonItorIngandInterventIon.JoelKaplan,alreadyknownfor
usIngthe7
5
leadtomonItorformyocardIalIschemIaandnItroglycerInInfusIonstotreat
IschemIa,popularIzedtheuseofthePACtodetectmyocardIalIschemIa.AtTexasHeart
nstItute,SlogoffandKeatsdemonstratedthenegatIveImpactofmyocardIalIschemIaon
clInIcaloutcome.8ytheendofthe1980s,thesameduowouldrevealthatthechoIceof
anesthetIcagenthadlIttleImpactonoutcome,challengIngtheearlIerparadIgmof
IsofluranestealproposedbyFeIz.
0evelopmentslIkecoldpotassIumcardIoplegIa,monItorIngandreversalofheparIn,and
reductIonofbloodlosswIthaprotInInwouldchangethepractIceofcardIacanesthesIa.
TransesophagealechocardIography,IntroducedIntocardIacsurgerybyFoIzen,Cahalan,
andKremerInthe1980s,helpedtofurtherdefInethesubspecIaltyofcardIacanesthesIa.
Neuroanesthesia
8raInsurgeryIsconsIderedbysometobetheoldestofthepractIcedmedIcalarts.
EvIdenceoftrepanatIon,aformofneurosurgeryInwhIchaholeIsdrIlledorscrapedInto
theskulltoaccessthedura,wasdIscoveredInskullsdatIngbackto65008CataFrench
burIalsIte.PrehIstorIcbraInsurgerywasalsopractIcedbycIvIlIzatIonsInSouthAmerIca,
AfrIca,andAsIa.
118
WIththeIntroductIonofInhalatIonalanesthesIaInthemId1800s,ScottIshsurgeonand
neurosurgerypIoneerSIrWIllIam|acewenusedthIsnovelpractIcewhIleperformIngthe
fIrstsuccessfulcranIotomyfortumorremovalIn1879.|acewen,wellknownfor
IntroducIngthetechnIqueoforotrachealIntubatIon,promotedtheIdeaofteachIng
medIcalstudentsatClasgowFoyalnfIrmarytheartofchloroformanesthesIa.
LIke|acewen,SIr7IctorHorselywasaneurosurgeonwIthanInterestInanesthesIa.HIs
experImentsofhowether,chloroform,andmorphIneaffectedIntracranIalcontentsled
hImtoconcludethattheagentofchoIcewaschloroformandthatmorphInehadsome
valuebecauseofItscerebralconstrIctIoneffects.
119
HefIrstpublIshedhIsanesthetIc
technIqueforbraInsurgeryIntheBritish Medical JournalIn1886.
120
Later,heomItted
morphInefromhIsregImenafterdIscoverIngItstendencytoproducerespIratory
depressIon.
|eanwhIle,HarvardmedIcalstudentandaspIrIngneurosurgeonHarveyCushIngdeveloped
thefIrstchartstorecordheartrate,temperature,andrespIratIondurInganesthesIa.Soon
after,hewouldaddbloodpressurereadIngstotherecord.CushIngwasoneofthefIrst
surgeonstorecognIzetheImportanceofdedIcated,specIallytraInedanesthesIapersonnel
versedInneurosurgery.CharlesFrazIer,aneurosurgIcalcontemporaryofCushIng,also
recognIzedthIsneed,statIngthatno[cranIal]operatIonbeundertakenunlesstheservIces
ofaskIlledanesthetIzerareavaIlable.
121
SInceetherandchloroformanesthesIahadsIgnIfIcantdrawbacks,begInnIngIn1918CushIng
andhIscontemporarIesexploredtheadvantagesofregIonalorlocalanesthesIafor
IntracranIalsurgery.PartofthemotIvatIondrIvIngthIschangewastheIncreasedduratIon
InsurgIcaltIme.CushIng
P.22
andcolleaguesusedaslowsurgIcaltechnIqueformostsurgIcalprocedures,wherethe
averageduratIonforcranIaloperatIonswas5hours.
122
ncontrast,earlyneurosurgeons
lIkeHorseleyandSIrPercySargeantcouldperformsImIlarproceduresInlessthan90
mInutes.Therefore,prolongedpatIentexposuretochloroformoretheranesthesIawere
lIkelytoresultInIncreasedbleedIng,postoperatIveheadache,confusIon,and/orvomItIng.
CushIngandcontemporarIesthoughttheuseoflocalorregIonalanesthesIalessenedthe
rIskofthesecomplIcatIons.
Afteradecade,ItwasrealIzedthattheremoteposItIonIngoftheanesthetIstwas
troublesomewhenmanagIngtheaIrwayofanawakeorlIghtlysedatedpatIentundergoIng
cranIalsurgerywIthregIonalanesthesIa.Also,endotrachealtubes,althoughIntroducedat
thebegInnIngofthecentury,hadbecomepopularInstrumentsforsecurIngapatIent's
aIrwayandprovIdIngInhalatIonanesthesIa.CombIned,thesecIrcumstancesledtothe
rapIdresurgenceofpopularItyIngeneralanesthesIaforcranIalsurgery,atrendthatwould
contInuetopresentday.
WhIletheIntroductIonofagentslIkethIopental,curare,andhalothaneadvancedthe
practIceofanesthesIologyIngeneral,thedevelopmentofmethodstomeasurebraIn
electrIcalactIvIty,cerebralbloodflowandmetabolIcratebyKetyandSchmIdt,and
IntracranIalpressurebyLundburgputneuroanesthesIapractIceonascIentIfIcfoundatIon
andopeneddoorstoneuroanesthesIaresearch.
12J
ClInIcIanscIentIstslIkeJohn0.(Jack)
|Ichenfelder,laterknownasthefatherofneuroanesthesIa,conductedbasIcscIenceand
clInIcalresearchoncerebralbloodflowandbraInfunctIonandprotectIonInresponseto
varIousanesthetIcagentsandtechnIques.|anylessonslearneddurIngthIsperIodof
groundbreakIngresearcharestIllcommonlyusedInmodernneuroanesthesIapractIce.
Obstetric Anesthesia
SocIalattItudesaboutpaInassocIatedwIthchIldbIrthbegantochangeInthe1860sand
womenstarteddemandInganesthesIaforchIldbIrth.SocIetalpressuresweresogreatthat
physIcIans,althoughunconvIncedofthebenefItsofanalgesIa,feltoblIgatedtoofferthIs
servIcetotheIrobstetrIcpatIents.
124
n1907anAustrIanphysIcIan,FIchardvon
SteInbuchelusedacombInatIonofmorphIneandscopolamInetoproduceDmmerschlaffor
TwIlIghtSleep.
125
Althoughthesetwodrugswerewellknown,physIcIansremaIned
skeptIcalthatTwIlIghtSleepwasessentIaltolaboranddelIvery,whIchunfortunately
contrastedwIththeopInIonofmostwomen.ThIsmethodgaInedpopularItyafterCerman
obstetrIcIansCarlCaussand8ernhardtKronIgwIdelypublIcIzedthetechnIque.Numerous
advertIsementstoutedthebenefItsofTwIlIghtSleep(analgesIa,partIalpaInrelIef,and
amnesIa)ascomparedtoetherandchloroform,whIchresultedIntotalunconscIousness.
126
CaussrecognIzedthenarrowtherapeutIcmargInofthesemedIcatIonsandgaveprecIse
InstructIonsonItsuse:thefIrstInjectIon(morphIne10mgandscopolamIne)wastobe
gIvenshortlyafteractIvelaborbeganthIswasIntendedtobluntthepaInoflaborand
subsequentInjectIonsconsIstedofonlyscopolamIne,whIchwasdosedtooblIteratethe
memoryoflabor.8ecauseoftheeffectsofscopolamIne,manypatIentsbecamedIsorIented
andwouldscreamandthrashaboutdurInglaboranddelIvery.CaussbelIevedthathecould
mInImIzethIsreactIonbydecreasIngthesensoryInput;therefore,hewouldputpatIentsIn
adarkroom,covertheIreyeswIthgauze,andInsertoIlsoakedcottonIntotheIrears.The
patIentswereoftenconfInedtoapaddedbedandrestraInedwIthleatherstrapsdurIngthe
delIvery.
127
DvertIme,thedosesofmorphIneadmInIsteredseemedtoIncrease,although
therewerefew,Ifany,reportsofadverseneonataleffects.7IrgInIaApgar'ssystemfor
evaluatIngnewborns,developedIn195J,demonstratedthatthereactuallywasa
dIfferenceIntheneonatesofmotherswhohadbeenanesthetIzed.
128
ThebulkoftheInterestInthIstechnIqueappearstohavebeenpopularratherthan
medIcaland,forabrIefperIod,wasIntenselyfollowedIntheUnItedStates.
129
PublIc
enthusIasmforTwIlIghtSleepquIcklysubsIdedafterapromInentadvocateofthemethod
dIeddurIngchIldbIrth.HerphysIcIansclaImedherdeathwasnotrelatedtocomplIcatIons
fromthemethodofTwIlIghtSleepthatwasused.
1J0
ThefIrstartIclesdescrIbIngtheobstetrIcapplIcatIonofspInal,epIdural,caudal,
paravertebral,parasacral,andpudendalnerveblocksappearedbetween1900and19J0.
However,theIrbenefItswereunderapprecIatedformanyyearsbecausetheobstetrIcIans
seldomusedthesetechnIques.
1J0
ContInuouscaudalanesthesIawasIntroducedIn1944by
HIngsonandEdwards
1J1
andspInalanesthesIabecamepopularshortlythereafter.nItIally,
spInalanesthesIacouldbeadmInIsteredbyInexperIencedpersonnelwIthoutmonItorIng.
ThecombInatIonofInexperIencedprovIdersandlackofpatIentmonItorIngledtohIgher
ratesofmorbIdItyandmortalItythanthoseobservedforgeneralanesthesIa.
1J2
Therefore,
theuseofspInalanesthesIawashIghlydIscouragedInthe1950s,leadIngtothedarkages
ofobstetrIcanesthesIawhenpaInrelIefInobstetrIcswasessentIallyabandonedand
womenwereforcedtoendurenaturalchIldbIrthtoavoIdserousanesthesIarelated
complIcatIons.
1JJ
WIthanIncreasedunderstandIngofneuraxIalanesthesIa,InvolvementbywelltraIned
anesthesIologIsts,andanapprecIatIonforthephysIologIcchangesdurIngpregnancy,
maternalandfetalsafetygreatlyImproved.nthepastdecade,anesthesIarelateddeaths
durIngcesareansectIonsundergeneralanesthesIahavebecomemorelIkelythanneuraxIal
anesthesIarelateddeaths,makIngregIonalanesthesIathemethodofchoIce.
1J4,1J5
WIth
theavaIlabIlItyofsafeandeffectIveoptIonsforpaInrelIefdurInglaboranddelIvery,
today'sfocusIsImprovIngthequalItyofthebIrthexperIenceforexpectantparents.
Transfusion Medicine
PaleolIthIccavedrawIngsfoundInFrancedepIctabearlosIngbloodfrommultIplespear
wounds,IndIcatIngthatprImItIvemanunderstoodthesImplerelatIonshIpbetweenblood
andlIfe.
1J6
|orethan10,000yearslater,modernanesthesIologIstsattempttopreservethIs
IntImaterelatIonshIpbyreplacIngfluIdsandbloodproductswhenfacedwIthIntravascular
volumedepletIonordImInIshedoxygencarryIngcapacItyfrombloodloss.
8loodtransfusIonwasfIrstattemptedIn1667byphysIcIantoLouIsX7,Jean8aptIste0enIs.
0enIshadlearnedofFIchardLower'stransfusIonoflamb'sbloodIntoadogtheprevIous
year.Lamb'sbloodwasmostfrequentlyusedbecausethedonatInganImal'sessentIal
qualItIeswerethoughttobetransferredtotherecIpIent.0espItethIsdangeroustrans
specIestransfusIon,0enIs'fIrstpatIentgotbetter.HIsnexttwopatIentswerenotas
fortunate,however,and0enIsavoIdedfurtherattempts.CIventhepooroutcomesofthese
earlybloodtransfusIons,andheatedrelIgIouscontroversyregardIngtheImplIcatIonsof
transferrInganImalspecIfIcqualItIesacrossspecIes,bloodtransfusIonInhumanswas
bannedformorethanahundredyearsInbothFranceandEnglandbegInnIngIn1670.
114
n1900,KarlLandsteInerandSamuelShattockIndependentlyhelpedlaythescIentIfIcbasIs
ofallsubsequenttransfusIonsbyrecognIzIngthatbloodcompatIbIlItywasbasedon
dIfferentbloodgroups.LandsteIner,anAustrIanphysIcIan,orIgInallyorganIzedhuman
bloodIntothreegroupsbasedon
P.2J
substancespresentontheredbloodcells.Thefourthtype,A8group,wasIdentIfIedIn1902
bytwostudents,A.0ecastrelloandA.SturlI.8asedonthesefIndIngs,FeubenDttenberg
performedthefIrsttypespecIfIcbloodtransfusIonIn1907.TransfusIonofphysIologIc
solutIonsoccurredIn18J1,IndependentlyperformedbyD'ShaughnessyandLewInsInCreat
8rItaIn.nhIslettertoThe Lancet,LewInsdescrIbedtransfusInglargevolumesofsalIne
solutIonsIntopatIentswIthcholera.HereportedthathewouldInjectIntoadultsfrom5to
10poundsofsalInesolutIonandrepeatasneeded.
1J7
0espIteItspublIcatIonInapromInent
journal,LewIns'technIquewasapparentlyoverlookedfordecades,andbalanced
physIologIcsolutIonavaIlabIlItywouldhavetoawaItthecomIngofanalytIcalchemIstry.
Professionalism and Anesthesia Practice
Organized Anesthesiology
PhysIcIananesthetIstssoughttoobtaInrespectamongtheIrsurgIcalcolleaguesby
organIzIngprofessIonalsocIetIesandImprovIngthequalItyoftraInIng.ThefIrstAmerIcan
organIzatIonwasfoundedbynInemembersonDctober6,1905,andcalledtheLongsland
SocIetyofAnesthetIstswIthannualduesofS1.00.n1911,theannualassessmentroseto
SJ.00whentheLongslandSocIetybecametheNewYorkSocIetyofAnesthetIsts.Although
theneworganIzatIonstIllcarrIedalocaltItle,Itdrewmembersfromseveralstatesand
hadamembershIpof70physIcIansIn1915.
1J8
DneofthemostnoteworthyfIguresInthestruggletoprofessIonalIzeanesthesIologywas
FrancIsHoffer|c|echan.|c|echanhadbeenapractIcInganesthesIologIstInCIncInnatI
untIl1911,whenhesufferedaseverefIrstattackofrheumatoIdarthrItIs,whIcheventually
lefthImconfInedtoawheelchaIrandforcedhIsretIrementfromtheoperatIngroomIn
1915.|c|echanhadbeenInpractIceonly15years,buthehadwrItten18clInIcalartIcles
InthIsshorttIme.AprolIfIcresearcherandwrIter,|c|echandIdnotpermIthIscrIpplIng
dIseasetosIdelInehIscareer.nsteadofpursuInggoalsInclInIcalmedIcIne,heapplIedhIs
talentstoestablIshInganesthesIologysocIetIes.
1J9
|c|echansupportedhImselfandhIsdevotedwIfethroughedItIngtheQuarterly Anesthesia
Supplementfrom1914untIlAugust1926.HebecameedItorofthefIrstjournaldevotedto
anesthesIa,Current Researches in Anesthesia and Analgesia,theprecursorofAnesthesia
and Analgesia,theoldestjournalofthespecIalty.AswellasfosterIngtheorganIzatIonof
thenternatIonalAnesthesIaFesearchSocIety(AFS)In1925,|c|echanandhIswIfe,
Laurette,becameoverseasambassadorsofAmerIcananesthesIa.SInceLaurettewas
French,Itwasunderstandablethat|c|echancombInedhIsownIdeasabout
anesthesIologywIthconceptsfromabroad.
12J
n1926,|c|echanheldtheCongressofAnesthetIstsInajoIntconferencewIththeSectIon
onAnaesthetIcsofthe8rItIsh|edIcalAssocIatIon.Subsequently,hetraveledthroughout
Europe,gIvInglecturesandnetworkIngphysIcIansInthefIeld.DnhIsfInalreturnto
AmerIca,hewasgravelyIllandwasconfInedtobedfor2years.HIshardworkandconstant
travelpaIddIvIdends,however:In1929,theAFS,whIch|c|echanfoundedIn1922,had
membersnotonlyfromNorthAmerIcabutalsofromseveralEuropeancountrIes,Japan,
ndIa,ArgentIna,and8razIl.
122
nthe19J0s,|c|echanexpandedhIsmIssIonfromorganIzInganesthesIologIststo
promotIngtheacademIcaspectsofthespecIalty.n19J1,workbeganonwhatwould
becomethenternatIonalCollegeofAnesthetIsts.ThIsbodybegantoawardfellowshIpsIn
19J5.ForthefIrsttIme,physIcIanswererecognIzedasspecIalIstsInanesthesIology.The
certIfIcatIonqualIfIcatIonswereunIversal,andfellowswererecognIzedasspecIalIstsIn
severalcountrIes.AlthoughthecrIterIaforcertIfIcatIonwerenotstrIct,theCollegewasa
successInraIsIngthestandardsofanesthesIapractIceInmanynatIons.
140
n19J9,
|c|echanfInallysuccumbedtoIllness,andtheanesthesIaworldlostItstIrelessleader.
DtherAmerIcanspromotedthegrowthoforganIzedanesthesIology.FalphWatersandJohn
Lundy,amongothers,partIcIpatedInevolvIngorganIzedanesthesIa.Waters'greatest
contrIbutIontothespecIaltywasraIsIngItsacademIcstandards.AftercompletInghIs
InternshIpIn191J,heenteredmedIcalpractIceInSIouxCIty,owa,wherehegradually
lImItedhIspractIcetoanesthesIa.HIspersonalexperIenceandextensIvereadIngwere
supplementedbytheonlypostgraduatetraInIngavaIlable,a1monthcourseconductedIn
DhIobyE..|cKesson.AtthattIme,thecustomofbecomIngaselfproclaImedspecIalIst
InmedIcIneandsurgerywasnotuncommon.Waters,whowasfrustratedbylowstandards
andwhowouldeventuallyhaveagreatInfluenceonestablIshIngbothanesthesIaresIdency
traInIngandtheformalexamInatIonprocess,recalledthat,before1920,The
requIrementsforspecIalIzatIonInmany|IdwesternhospItalsconsIstedofthepossessIonof
suffIcIentaudacItytoattemptaprocedureandpersuasIvepoweradequatetogaInthe
consentofthepatIentorhIsfamIly.
141
Academic Anesthesia
nanefforttoImproveanesthetIccare,WatersregularlycorrespondedwIth0ennIsJackson
andotherscIentIsts.n1925,herelocatedtoKansasCItywIthagoalofgaInIngan
academIcpostattheUnIversItyofKansas,buttheprofessorofsurgeryfaIledtosupporthIs
proposal.ThelargercItydIdallowhImtoInItIatehIsfreestandIngoutpatIentsurgIcal
facIlIty,The0owntownSurgIcalClInIc,whIchfeaturedoneofthefIrstpostanesthetIc
recoveryrooms.
1J0
n1927,ErwInSchmIdt,professorofsurgeryattheUnIversItyof
WIsconsIn'smedIcalschool,encouraged0eanCharles8ardeentorecruItWaters.
nacceptIngthefIrstAmerIcanacademIcposItIonInanesthesIa,WatersdescrIbedfour
objectIvesthathavebeensInceadoptedbymanyotheracademIcdepartments.HIsgoals
wereasfollows:(1)toprovIdethebestpossIbleservIcetopatIentsoftheInstItutIon;(2)
toteachwhatIsknownoftheprIncIplesofAnesthesIologytoallcandIdatesfortheIr
medIcaldegree;(J)tohelplongtermgraduatestudentsnotonlytogaInafundamental
knowledgeofthesubjectandtomastertheartofadmInIstratIon,butalsotolearnasmuch
aspossIbleoftheeffectIvemethodsofteachIng;(4)toaccompanytheseeffortswIththe
encouragementofasmuchcooperatIveInvestIgatIonasIsconsIstentwIthachIevIngthe
fIrstobjectIves.
129
Waters'personalandprofessIonalqualItIesImpressedtalentedyoungmenandwomenwho
soughtresIdencypostsInhIsdepartment.HeencouragedresIdentstoInItIateresearch
InterestsInwhIchtheycollaboratedwIthtwopharmacologIstswhomWatershadknown
beforearrIvIngInWIsconsIn,ArthurLoevenhartandChaunceyLeake,aswellasotherswIth
whomhebecameassocIatedIn|adIson.ClInIcalconcernswerealsoInvestIgated.Asan
example,anesthesIarecordswerecodedontopunchcardstoformadatabasethatwas
usedtoanalyzedepartmentalactIvItIes.|orbIdItyandmortalItymeetIngs,nowa
requIrementofalltraInIngprograms,alsoorIgInatedIn|adIson.|embersofthe
departmentanddIstInguIshedvIsItorsfromothercentersattendedthesemeetIngs.Asa
consequenceoftheIrcrItIcalrevIewsoftheconductofanesthesIa,responsIbIlItyforan
operatIve
P.24
tragedygraduallypassedfromthepatIenttothephysIcIan.nmorecasualtImes,a
practItIonercouldcomplaIn,ThepatIentdIedbecausehedIdnottakeagoodanesthetIc.
AlternatIvely,thedeathmIghtbeattrIbutedtoamysterIousforcesuchasstatus
lymphatIcus,ofwhIchArthurCuedel,amasterofsardonIchumor,observed,CertaInly
statuslymphatIcusIsattImesagreathelptotheanesthetIst.WhenhehasafatalItyunder
anesthesIawIthnoothercleansIngexplanatIonheIsgladtorecognIzethecondItIonasan
entIty.
129
n1929,JohnLundyatthe|ayoClInIcorganIzedtheAnaesthetIsts'TravelClub,whose
memberswereleadIngAmerIcanorCanadIanteachersofanesthesIa.Eachyearone
memberwasthehostforagroupof20to40anesthesIologIstswhogatheredforaprogram
ofInformaldIscussIons.ThereweredemonstratIonsofpromIsIngInnovatIonsforthe
operatIngroomandlaboratory,whIchwereallsubjectedtowhatIsrememberedasa
hIghspIrIted,energetIc,crItIcalrevIew.
127
TheTravelClubwouldbecrItIcalInthe
upcomIngbattletoformtheAmerIcan8oardofAnesthesIology.
EvendurIngtheleanyearsofthe0epressIon,InternatIonalguestsalsovIsItedWaters'
department.ForCeoffreyKayeofAustralIa,TorstenCordhofSweden,Fobert|acIntosh
and|IchaelNosworthyofEngland,andscoresofothers,Waters'departmentwastheIr
meccaofanesthesIa.FalphWaterstraIned60resIdentsdurIngthe22yearshewasthe
ChIef.From19J7onward,thealumnI,whodeclaredthemselvestheAqualumnIInhIs
honor,returnedannuallyforaprofessIonalandsocIalreunIon.ThIrtyfourAqualumnItook
academIcposItIonsand,ofthese,14becamechaIrpersonsofdepartmentsofanesthesIa.
TheymaIntaInedWaters'professIonalprIncIplesandencouragedteachIngcareersformany
oftheIrowngraduates.
142
HIsendurInglegacywasoncerecognIzedbythedeanwhohad
recruItedhImIn1927,Charles8ardeen,whoobserved,FalphWaterswasthefIrstperson
theUnIversItyhIredtoputpeopletosleep,but,Instead,heawakenedaworldwIde
InterestInanesthesIa.
14J
Establishing a Society
WatersandLundy,alongwIthPaulWoodofNewYorkCIty,hadanImportantroleIn
establIshIngorganIzedanesthesIaandthedefInItIonofthespecIalty.ntheheartofthe
Creat0epressIon,thesethreephysIcIansrealIzedthatanesthesIologyneededtohavea
processtodetermInewhowasananesthetIcspecIalIstwIthAmerIcan|edIcalAssocIatIon
(A|A)backIng.UsIngtheNewYorkSocIetyofAnesthetIsts,ofwhIchPaulWoodwas
secretarytreasurer,anewclassofmembers,Fellows,wascreated.TheFellowscrIterIa
followedestablIshedA|AguIdelInesforspecIaltycertIfIcatIon.However,theA|Awanted
anatIonalorganIzatIontosponsoraspecIaltyboard.TheNewYorkSocIetyofAnesthetIsts
changedItsnametotheAmerIcanSocIetyofAnesthetIsts(ASA)In19J6.CombInedwIththe
AmerIcanSocIetyofFegIonalAnesthesIa,whosepresIdentwasEmeryFovensteIn,the
AmerIcan8oardofAnesthesIology(A8A)wasorganIzedasasubordInateboardtothe
AmerIcan8oardofSurgeryIn19J8.WIth|c|echan'sdeathIn19J9,theA|Afavored
IndependencefortheA8A,andIn1940,Independencewasgranted.
126,1J1
Afewyearslater,theoffIcersoftheAmerIcanSocIetyofAnesthetIstswerechallengedby
0r.|.J.SeIfert,whowrote,AnAnesthetIstIsatechnIcIanandanAnesthesIologIstIsthe
specIfIcauthorItyonanesthesIaandanesthetIcs.cannotunderstandwhyyoudonotterm
yourselvestheAmerIcanSocIetyofAnesthesIologIsts.
1JJ
FalphWaterswasdeclaredthe
fIrstpresIdentofthenewlynamedASAIn1945.nthatyear,whenWorldWarended,7J9
(J7)of1,977ASAmemberswereInthearmedforces.nthesameyear,theASA'sfIrst
0IstInguIshedServIceAwardwaspresentedtoPaul|.WoodforhIstIrelessservIcetothe
specIalty,oneelementofwhIchcanbeexamInedtodayIntheextensIvearchIves
preservedIntheSocIety'sWoodLIbrary|useumatASAheadquarters,ParkFIdge,
llInoIs.
14J
Conclusions
ThIsovervIewofthedevelopmentofanesthesIologyIsbutabrIefoutlIneofourcurrent
rolesInwhIchanesthesIologIstsserveInhospItals,clInIcs,andlaboratorIes.TheoperatIng
roomandobstetrIcdelIverysuIteremaInthecentralInterestofmostspecIalIsts.AsIde
frombeIngthelocatIonwherethetechnIquesdescrIbedInthIschapterfIndregular
applIcatIon,servIceIntheseareasbrIngsusIntoregularcontactwIthnewadvancesIn
pharmacologyandbIoengIneerIng.
Aftersurgery,patIentsaretransportedtothepostanesthesIacareunItorrecoveryroom,
anareathatIsnowconsIderedtheanesthesIologIst'sward.FIftyyearsago,patIentswere
carrIeddIrectlyfromtheoperatIngroomtoasurgIcalwardtobeattendedonlybyajunIor
nurse.ThatpersonlackedboththeskIllsandequIpmenttoIntervenewhencomplIcatIons
occurred.AftertheexperIencesofWorldWartaughtthevalueofcentralIzedcare,
physIcIansandnursescreatedrecoveryrooms,whIchweresoonmandatedforallmajor
hospItals.8y1960theevolutIonofcrItIcalcareprogressedthroughtheuseofmechanIcal
ventIlators.PatIentswhorequIredmanydaysofIntensIvemedIcalandnursIng
managementwerecaredforInacurtaInedcorneroftherecoveryroom.ntIme,curtaIns
drawnaboutoneortwobedsgavewaytofIxedpartItIonsandtherelocatIonofthoseareas
toformIntensIvecareunIts.TheprIncIplesofresuscItatIveandsupportIvecareestablIshed
byanesthesIologIststransformedcrItIcalcaremedIcIne.
ThefutureofanesthesIologyIsabrIghtone.ThesaferdrugsthatoncerevolutIonIzedthe
careofpatIentsundergoIngsurgeryareconstantlybeIngImproved.Theroleofthe
anesthesIologIstcontInuestobroadenasphysIcIanswIthbackgroundsInthespecIaltyhave
developedclInIcsforchronIcpaIncontrolandoutpatIentsurgery.AnesthesIapractIcewIll
contInuetoIncreaseInscope,bothInsIdeandoutsIdetheoperatIngsuIte,suchthat
anesthesIologIstswIllbecomeanIntegralpartoftheentIreperIoperatIveexperIence.
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TableofContentsSectIonntroductIontoAnesthesIologyChapter2ScopeofPractIce
Chapter2
Scope of Practice
John H. Eichhorn
Key Points
1. Anesthesia trainees, and many postgraduates also, tend to lack
sufficient knowledge (with sometimes unfortunate results) about
modes of practice or employment, financial matters of all types, and
contracting in particular. They must educate themselves and also
seek expert advice and counsel to survive (and hopefully flourish) in
today's exceedingly complex medical practice milieu.
2. There are several very helpful detailed information resources
concerning practice and OR management available from the
American Society of Anesthesiologists and other sources. Factors
influencing anesthesiology practice conditions are changing rapidly,
and today's anesthesia professionals must be armed with detailed
information about concepts (such as pay for performance) that did
not exist just a few years ago.
3. Securing hospital privileges is far more than a bureaucratic
annoyance and must be taken seriously by anesthesiologists.
4. Anesthesiology is the leading medical specialty in establishing and
promulgating standards of practice that have significantly influenced
practice in a positive manner.
5. The immediate response to a major adverse anesthesia event is
critical to the eventual result. An extremely valuable protocol is
available at www.apsf.org, Resource Center: Clinical Safety Tools.
6. Anesthesiologists need to be involved, concerned, active participants
and leaders in their institution and medical community in order to
enhance their practice function and image.
7. Managed care's influence has waxed and waned but it must always
be considered by modern anesthesia professionals. While cost, value,
outcome, and quality issues are certainly central to all anesthesiology
practices, difficulties in constructing and applying definitive
measurements and rigorous statistical analysis of these parameters
have prevented, so far at least, some of the potential negative
influences of the core features of fully managed health care on
anesthesiology practice.
8. Anesthesiologists must participate in operating room (OR)
management in their facilities and should play a central leadership
role. OR scheduling, staffing, utilization, and patient flow issues are
complex, and anesthesiologists should work hard both to thoroughly
understand and positively influence them.
9. Anesthesiology personnel issues involve an elaborate balancing act
and groups/departments should give these issues, as well as their
constituent personnel, more attention and energy than has been
done traditionally in the past or the anesthesia provider shortage will
likely continue to worsen.
10. Attention to the many often-underemphasized details of
infrastructure, organization, and administration can transform a
merely endurable anesthesia practice into one that is efficient,
effective, productive, collegial, and even fun.
|edIcalpractIce,IncludIngItsInfrastructureandfunctIonaldetaIls,IsevolvIngrapIdlyIn
theUnItedStates.AnesthesIapractIceIsnoexceptIon.nthepast,anesthesIaprofessIonals
tradItIonallywerelIttleInvolvedInthemanagementofmanycomponentsoftheIrpractIce
beyondthestrIctlymedIcalelementsofapplIedphysIologyandpharmacology,
pathophysIology,andtherapeutIcs.ThIswasperhapssomewhatunderstandablebecause
anesthesIaprofessIonalstradItIonallyspentmostoftheIrusuallyverylongworkhoursIna
hospItaloperatIngroom(DF).8usInessmatterswereoftenlefttotheoneor
P.28
twogroupmemberswhowereInterestedorwIllIngtodealwIthanoutsIdecontractor
bIllIngagency.nthatera,verylIttleformalteachIngInpractIcemanagementofanykInd
occurredInanesthesIatraInIngprograms.TodaytheAnesthesIologyFesIdencyFevIew
CommItteeoftheAccredItatIonCouncIlonCraduate|edIcalEducatIonrequIresthatthe
dIdactIccurrIculaofanesthesIologyresIdencIesIncludematerIalonpractIcemanagement.
|osttraInIngprogramsofferatleastacursoryIntroductIontoIssuesofpractIce
management,butthesecanbeInsuffIcIenttopreparesatIsfactorIlytheprofessIonalbeIng
graduatedfortherealInfrastructure,admInIstratIve,busIness,andmanagement
challengesofthemodernpractIceofanesthesIology.
ThIschapterpresentsawIdevarIetyoftopIcsthat,untIlrecently,werenotIncludedIn
anesthesIologytextbooks.SeveralbasIccomponentsareoutlInedofthebackground,
admInIstratIve,organIzatIonal(IncludIngbothpractIcearrangementsanddaIlyfunctIonIng
oftheDF),andfInancIalaspectsofanesthesIologypractIceInthecomplexmodern
envIronment.AlthoughmanyIssuesareundergoIngalmostconstantchange,ItIsImportant
tounderstandthebasIcvocabularyandprIncIplesInthIsdynamIcunIverse.Lackof
understandIngoftheseIssuesmayputanesthesIaprofessIonalsatadIsadvantagewhen
attemptIngtomaxImIzetheeffIcIencyandImpactoftheIrdaIlyactIvItIes,tocreateand
executepractIcearrangements,andtosecurefaIrcompensatIonInanIncreasIngly
complexhealthcaresystemwIthgreaterandgreatercompetItIonforscarcerandscarcer
resources.
Administrative Components of Anesthesiology Practice
Operational and Information Resources
DvervIewsummarIessuchasthIschapterareIntendedasanIntroductIontopractIce
management.Further,fortunately,theAmerIcanSocIetyofAnesthesIologIsts(ASA),the
professIonalassocIatIonforphysIcIananesthesIologIstsIntheUnItedStates,formanyyears
hasmadeavaIlabletoItsmembersextensIveresourcematerIalregardIngpractIceIn
generalandspecIfIcarrangementsforItsexecutIon.CItatIonandavaIlabIlItyofthIs
materIalcanbefoundontheASAWebsIte,www.asahq.org.Elementsareupdated
perIodIcallybytheASAthroughItsphysIcIanoffIcers,commIttees,taskforces,
admInIstratIveandsupportstaff,andItsvarIousoffIces.Althoughmanyofthedocuments
generatedandeventheadvIcegIvenInresponsetomembers'questIonscontaInbroad
brushgeneralItIesthatmustbeInterpretedIneachIndIvIdualpractIcesItuatIon,these
nonethelessstandasasolIdfoundatIononwhIchmanyanesthesIologypractIcescanbe
formulated.ProspectIvefamIlIarItywIththeprIncIplesoutlInedIntheASAmaterIallIkely
couldhelpavoIdsomeoftheproblemsleadIngtocallsforhelp.Selectedkeydocuments
havebeencompIledandboundIntoonevolume.
1
Also,eachsprIng,theASAoffersa
PractIce|anagementConference,followIngwhIchthelecturematerIalsarepublIshedIn
anannualvolume(seewww.asahq.org,PublIcatIonsandServIces,PublIcatIonson
PractIce|anagement).
Background
TheASAGuidelines for the Ethical Practice of Anesthesiology
1
IncludessectIonsonthe
prIncIplesofmedIcalethIcs;thedefInItIonofmedIcaldIrectIonofnonphysIcIanpersonnel
(IncludIngthespecIfIcstatementthatananesthesIologIstengagedInmedIcaldIrectIon
shouldnotpersonallybeadmInIsterInganotheranesthetIc);theanesthesIologIst's
relatIonshIptopatIentsandotherphysIcIans;theanesthesIologIst'sdutIes,responsIbIlItIes,
andrelatIonshIptothehospItal;andtheanesthesIologIst'srelatIonshIptonurse
anesthetIstsandothernonphysIcIanpersonnel.Further,theASApublIshesThe Organization
of an Anesthesia Department
1
andstatesthroughItthattheASAhasadoptedaStatement
ofPolIcy,whIchcontaInsprIncIplesthattheSocIetyurgesItsmemberstoconsIderIn
structurIngtheIrownIndIvIdualmedIcalpractIces.ThIsdocumenthassectIonson
physIcIanresponsIbIlItIesformedIcalcareandonmedIcaladmInIstratIveorganIzatIonand
responsIbIlItIes.8eyondsummarIessuchasthIschapter,referencetotheconsIderablebody
ofmaterIalcreatedandpresentedbytheASA(whIchIncludesathIckvolumespecIfIcally
onthedetaIlsofbusInessarrangements
2
)IsanexcellentstartIngpoInttohelpyoung
anesthesIaprofessIonalsdurIngtraInIngpreparefortheIncreasIngrIgorsofstartIngand
managIngacareerInpractIce.LIkewIse,thereIsagreatdealofInformatIonontheASA
WebsIteconcernIngthemostrecentgovernmentalregulatIons,rulIngs,andbIllIngcodes.
TheASANewslettercontaInsthemonthlycolumnsWashIngtonFeportandPractIce
|anagement,whIchdIssemInaterelatedcurrentdevelopments.
naddItIontotheASAandtheAmerIcanAssocIatIonofNurseAnesthetIsts,most
anesthesIologysubspecIaltysocIetIesandInterestgroupshaveWeblocatIons,asdomost
journals.PartIcularly,theWebsIteoftheAnesthesIaPatIentSafetyFoundatIon,
www.apsf.org,hasbeencItedasespecIallyusefulInpromotIngsafeclInIcalpractIce.
ElectronIcbulletInboardsallowanesthesIologypractItIonersfromaroundtheworldto
ImmedIatelyexchangeIdeasondIversetopIcs,bothmedIcalandadmInIstratIve.
TradItIonally,theASAhasnotmaIntaInedone.However,oneoftheorIgInalsItesthat
remaInsverypopularIswww.gasnet.org,andaWebsearch(anesthesIology+bulletIn
board)usIngasearchengInesuchaswww.google.comrevealsagreatnumberofsItes
thatcontaInavarIetyofdIscussIonsaboutallmannerofanesthesIologyrelatedtopIcs,
IncludIngpractIceorganIzatIon,admInIstratIon,andmanagement.AddItIonally,references
totheentIretyofthemedIcallIteraturearereadIlyaccessIbletoanypractItIoner(suchas
bystartIngwIthwww.nlm.nIh.govtoaccess|edlIne).AmodernanesthesIologypractIce
cannotreasonablyexIstwIthoutreadIlyavaIlablehIghspeednternetconnectIons.
The Credentialing Process and Clinical Privileges
ThesystemofcredentIalIngahealthcareprofessIonalandgrantIngclInIcalprIvIlegesIna
healthcarefacIlItyIsmotIvatedbyafundamentalassumptIonthatapproprIateeducatIon,
traInIng,andexperIence,alongwIththeabsenceofexcessIvenumbersofbadpatIent
outcomes,IncreasethechancesthattheIndIvIdualwIlldelIveracceptablequalItycare.
TheprocessofcredentIalInghealthcareprofessIonalshasbeenthefocusofconsIderable
publIcattentIon(partIcularlyInthemassmedIa),InparttheresultofveryrareIncIdents
ofuntraInedpersons(Impostors)InfIltratIngthehealthcaresystemandsometImesharmIng
patIents.ThemorecommonsItuatIon,however,InvolveshealthprofessIonalswho
exaggeratepastexperIenceandcredentIalsorfaIltodIscloseadversepastexperIences.
TherehasbeensomejustIfIedpublIcItyconcernIngphysIcIanswholosttheIrlIcenses
sequentIallyInseveralstatesandsImplymovedoneachtImetostartpractIceelsewhere
(whIchshouldbemuch,muchmoredIffIcultnow).
ntensepublIcandpolItIcalpressurehasbeenbroughttobearonvarIouslawmakIng
bodIes,regulatoryandlIcensIngagencIes,andhealthcareInstItutIonadmInIstratIonsto
dIscoverandpurgeboth(1)fraudulent,crImInal,anddevIanthealthcareprovIders,and(2)
IncompetentorsImplypoorqualIty
P.29
practItIonerswhosehIstorIesshowsuffIcIentpoorpatIentoutcomestoattractattentIon,
usuallythroughmalpractIcesuIts.dentIfyIngandavoIdIngorcorrectInganIncompetent
practItIonerIsthegoal.7erIfIcatIonofapproprIateeducatIon,traInIng,andexperIenceon
thepartofacandIdateforaposItIonrenderInganesthesIacareassumesspecIal
ImportanceInlIghtofthelegaldoctrIneofvicarious liability,whIchcanbedescrIbedas:If
anIndIvIdual,group,orInstItutIonhIresananesthesIaprovIderorevensImplyapprovesof
thatperson(e.g.,bygrantIngclInIcalprIvIlegesthroughahospItalmedIcalstaff),those
InvolvedInthedecIsIonmaylaterbeheldlIableInthecourts,alongwIththeIndIvIdual,
fortheIndIvIdual'sactIons.ThIswouldbeespecIallytrueIfItwerelaterdIscoveredthat
theoffendIngpractItIoner'spastadverseoutcomeshadnotbeenadequatelyInvestIgated
durIngthecredentIalIngprocess.
DutofthesevarIouslongstandIngconcernshasarIsenthesometImescumbersomeprocess
ofobtaInIngstatelIcensestopractIceandofobtaInInghospItalprIvIleges.ThestrIngent
credentIalIngprocessforhealthcarepractIceIsIntendedbothtoprotectpatIentsandto
safeguardtheIntegrItyoftheprofessIon.Fecently,centralcredentIalIngsystemshave
beendeveloped,IncludIngthoseaffIlIatedwIththeAmerIcan|edIcalAssocIatIon,
AmerIcanDsteopathIcAssocIatIon,and,partIcularly,theFederatIonCredentIals
7erIfIcatIonServIceoftheFederatIonofState|edIcal8oards.ThesesystemsverIfya
physIcIan'sbasIccredentIals(e.g.,IdentIty,cItIzenshIporImmIgratIonstatus,medIcal
educatIon,postgraduatetraInIng,lIcensureexamInatIonhIstory,prIorlIcenses,andboard
actIons)once,andthenthereaftercancertIfythevalIdItyofthesecredentIalstoastate
lIcensIngboardormedIcalfacIlIty.AfewstatesdonotyetacceptthIsverIfIcatIonand
moststatesseekspecIfIcsupplementalInformatIon.
TherearechecklIstsoftherequIrementsforthegrantIngofmedIcalstaffprIvIlegesby
hospItals(seetheAmerIcanHospItalAssocIatIonFesourceCenter,www.aharc.lIbrary.net).
naddItIon,theNatIonalPractItIoner0ata8ankandreportIngsystemadmInIsteredbythe
U.S.governmentnowcontaInsmanyyears'worthofInformatIon.ThIsdatabankIsa
centralreposItoryoflIcensIngandcredentIalsInformatIonaboutphysIcIans.|anyadverse
sItuatIonsInvolvIngaphysIcIanpartIcularlyInstancesofsubstanceabuse,malpractIce
lItIgatIon,ortherevocatIon,suspensIon,orlImItatIonofthatphysIcIan'slIcensetopractIce
medIcIneorabIlItytoholdhospItalprIvIlegesmustbereported(vIathestateboardof
medIcalregIstratIon/lIcensure)totheNatIonalPractItIoner0ata8ank.tIsastatutory
requIrementthatallapplIcatIonsforhospItalstaffprIvIlegesbecrosscheckedagaInstthIs
natIonaldatabank.ThepotentIalmedIcolegallIabIlItyonthepartofafacIlIty'smedIcal
staff,andtheanesthesIologygroupInpartIcular,forfaIlIngtodosoIssIgnIfIcant.The0ata
8ank,however,IsnotacompletesubstItutefordIrectdocumentatIonandbackground
checkIng.Dften,practItIonersreachprIvatenegotIatedsolutIonsfollowIngqualItydrIven
medIcalstaffproblems,therebyavoIdIngthemandatorypublIcreportIng.nsuchcases,a
suspectphysIcIanmaybegIventheoptIontoresIgnmedIcalstaffprIvIlegesandavoId0ata
8ankreportIngratherthanundergofullInvoluntaryprIvIlegerevocatIon(althoughmost
applIcatIonscontaInaquestIonspecIfIcallyaboutthIs).
Documentation
ThedocumentatIonforthecredentIalIngprocessforeachanesthesIapractItIonermustbe
complete.PrIvIlegestoadmInIsteranesthesIamustbeoffIcIallygrantedanddelIneatedIn
wrItIng.
1
ThIscanbestraIghtforwardorItcanbemorecomplextoaccommodate
InstItutIonalneedstoIdentIfypractItIonersspecIallyqualIfIedtopractIceIndesIgnated
anesthesIasubspecIaltyareassuchascardIac,Infant/pedIatrIc,obstetrIc,IntensIvecare,
orpaInmanagement.SpecIfIcdocumentatIonoftheprocessofgrantIngorrenewIng
clInIcalprIvIlegesIsrequIredand,unlIkesomeotherrecords,thedocumentatIonlIkelyIs
protectedasconfIdentIalpeerrevIewInformatIon.AnyquestIonsaboutcomplexsensItIve
IssuessuchasthIsshouldbereferredtoanexperIencedattorneyfamIlIarwIthapplIcable
federalandstatelaw.7erIfIcatIonofanapplIcant'scredentIalsandexperIenceIs
mandatory.8ecauseofanothertypeoflegalcase,someexamplesofwhIchhavebeen
hIghlypublIcIzed,medIcalpractItIonersmaybehesItanttogIveanhonestevaluatIon(or
anyevaluatIonatall)ofIndIvIdualsknowntothemwhoareseekIngaprofessIonalposItIon
elsewhere.DbvIously,someonewrItIngareferenceforacurrentorformercoworkershould
behonest.StIckIngtoclearlydocumentablefactsIsadvIsable.StatIngafactthatIsInthe
publIcrecord(suchasamalpractIcecaselostattrIal)shouldnotjustIfyanobjectIonfrom
thesubjectofthereference.WhethersuchpotentIallynegatIvefactscanbeomIttedby
areferencewrIterIscomplex.ncludIngposItIveopInIonsandenthusIastIc
recommendatIons,ofcourse,Isnoproblem.SomefearthatIncludIngfactsthatmaybe
perceIvedasnegatIve(e.g.,thelostmalpractIcecaseorpersonalproblemssuchasa
hIstoryoftreatmentforsubstanceabuse)and/ornegatIveopInIonswIllprovokea
retalIatorylawsuIt(suchasforlIbel,defamatIonofcharacter,orlossoflIvelIhood)from
thesubjectofthereference.Further,however,therehavebeencasesofthefacIlItydoIng
thehIrIngsuIngreferencewrItersforfaIlIngtomentIon(perceIvedasconcealIng)negatIve
InformatIonaboutanapplIcantwholaterwaschargedwIthsubstandardpractIce.8ecause
ofthecomplexItIesandevenapparentcontradIctIons,manyreferencewrItersInthese
questIonablesItuatIonsconfInetheIrwrIttenmaterIaltobrIef,sImplefactssuchasdates
employedandposItIonheld.Asalways,questIonsaboutcomplexsensItIveIssuessuchas
thIsshouldbereferredtoanexperIencedattorneyfamIlIarwIthapplIcablefederaland
statelaw.
8ecausethereshouldbenohesItatIonforareferencewrItertoIncludeposItIvefactsand
opInIons,receIptofareferencethatIncludesnothIngmorethandatesworkedandposItIon
heldcanbeasuggestIonthattheremaybemoretothestory(althoughsomeentItIeshave
adoptedsuchapolIcyInallcasessImplytoelImInateanyvaluejudgmentsastowhatIs
posItIveornegatIveInformatIon).FeceIptofsuchadates/posItIononlyreferenceabout
apersonapplyIngforaposItIonshouldusuallyprovokeatelephonecalltothewrIter.A
telephonecallIslIkelyadvIsableInallcases,IndependentofwhateverthewrItten
referencecontaIns.Frequently,pertInentquestIonsoverthetelephonecanelIcItmore
candIdInformatIon.nrareInstances,theremaybedIshonestythroughomIssIonbythe
referencegIverevenatthIslevel.ThIsmayInvolveanapplIcantwhoanIndIvIdual,a
departmentorgroup,oranInstItutIonwouldlIketoseeleave.
nallcases,newpersonnelInananesthesIapractIceenvIronmentmustbegIvena
thoroughorIentatIonandcheckout.PolIcy,procedures,andequIpmentmaybeunfamIlIar
toeventhemostthoroughlytraIned,experIenced,andsafepractItIoner.ThIsmay
occasIonallyseemtedIous,butItIssoundandcrItIcallyImportantsafetypolIcy.8eIngIn
themIdstofacrIsIssItuatIoncausedbyunfamIlIarItywIthanewsettIngIsnottheoptImal
orIentatIonsessIon.
AftertheInItIalgrantIngofclInIcalprIvIlegestopractIceanesthesIa,anesthesIa
professIonalsmustperIodIcallyrenewtheIrprIvIlegeswIthIntheInstItutIonorfacIlIty(e.g.,
annuallyoreveryotheryear).Therearemoral,ethIcal,andsocIetaloblIgatIonsonthe
partoftheprIvIlegegrantIngentItytotakethIsprocessserIously.StatelIcensIngbodIes
oftenbecomeawareofproblemswIthhealthprofessIonalsverylateIntheevolutIonofany
dIffIcultIes.AnanesthesIaprofessIonal'speersInthehospItalorfacIlItyaremuchmore
lIkelytonotIceuntowarddevelopmentsastheyfIrstappear.However,prIvIlege
P.J0
renewalsareoftenessentIallyautomatIcandreceIvelIttleofthenecessaryattentIon.
JudIcIouscheckIngofrenewalapplIcatIonsandawarenessofrelevantpeerrevIew
InformatIonIsabsolutelynecessary.TheanesthesIaprofessIonalsoradmInIstrators
responsIbleforevaluatIngstaffmembersandrevIewIngtheIrpractIcesandprIvIlegesmay
bejustIfIablyconcernedaboutretalIatorylegalactIonbyastaffmemberwhoIscensured
ordenIedprIvIlegerenewal.AccordIngly,suchevaluatInggroupsmustbethoroughly
objectIve(totallyelImInatInganyhIntofpolItIcalorfInancIalmotIves)andmusthave
documentatIonthatthestaffpersonInquestIonIsInfactpractIcIngbelowthestandardof
care.CourtdecIsIonshavefoundlIabIlItybyahospItal,ItsmedIcalstaffgroup,orboth,
whentheIncompetenceofastaffmemberwasknownorshouldhavebeenknownandwas
notactedupon.
J
AgaIn,questIonsaboutcomplexsensItIveIssuessuchasthIsshouldbe
referredtoanexperIencedattorneyfamIlIarwIthapplIcablefederalandstatelaw.
AmajorIssueInthegrantIngofclInIcalprIvIleges,especIallyInprocedureorIented
specIaltIessuchasanesthesIology,IswhetherItIsreasonabletocontInuethecommon
practIceofblanketprIvIleges.ThIsprocessIneffectauthorIzesthepractItIonerto
attemptanytreatmentorprocedurenormallyconsIderedwIthInthepurvIewofthe
applIcant'smedIcalspecIalty.TheseconsIderatIonsmayhaveprofoundpolItIcaland
economIcImplIcatIonswIthInmedIcIne,suchaswhIchtypeofsurgeonshouldbedoIng
carotIdendarterectomIesorlumbardIscectomIes.|oreImportant,however,Iswhether
thepractItIonerbeIngevaluatedIsqualIfIedtodoeverythIngtradItIonallyassocIatedwIth
thespecIalty.SpecIfIcally,shouldthegrantIngofprIvIlegestopractIceanesthesIa
automatIcallyapprovethepractItIonertohandlepedIatrIccardIaccases,crItIcallyIll
newborns(suchasadayoldprematureInfantwIthalargedIaphragmatIchernIa),ablatIve
paIntherapy(suchasanalcoholcelIacplexusblockunderfluoroscopy),hIghrIskobstetrIc
cases,andsoforth:ThIsquestIonraIsestheIssueofprocedurespecIfIcorlImIted
prIvIleges.ThequalItyassurance(QA)andrIskmanagementconsIderatIonsInthIsquestIon
areweIghtyIfInexperIencedorInsuffIcIentlyqualIfIedpractItIonersareallowedoreven
expected,becauseofpeerorschedulIngpressures,toundertakemajorchallengesfor
whIchtheyarenotprepared.ThelIkelIhoodofcomplIcatIonsandadverseoutcomewIllbe
hIgher,andthedIffIcultyofdefendIngthepractItIoneragaInstamalpractIceclaImInthe
eventofcatastrophewIllbesIgnIfIcantlyIncreased.
ThereIsnoclearanswertothequestIonofprocedurespecIfIccredentIalIngandgrantIngof
prIvIleges.gnorIngIssuesregardIngqualIfIcatIonstoundertakecomplexandchallengIng
procedureshasclearnegatIvepotentIal.Dntheotherhand,strIngentprocedurespecIfIc
credentIalIngIsImpractIcalInsmallergroups,andInlargergroupsencouragesmanysmall
fIefdoms,wIthaconsequentfurtheratrophyoftheclInIcalskIllsoutsIdethe
practItIoner'sspecIfIcarea(s).EachanesthesIadepartmentorgroupneedstoaddressthese
Issues.Attheveryleast,thecommonpractIceofeveryapplIcantforprIvIleges(newor
renewal)checkIngoffeverylIneontheprIntedlIstofanesthesIaproceduresshouldbe
revIewed.AddItIonally,boardcertIfIcatIonforphysIcIansIsnowessentIallyastandardof
qualItyassuranceofthemInImumskIllsrequIredfortheconsultantpractIceof
anesthesIology.SubspecIaltyboards,suchasthoseInpaInmanagement,crItIcalcare,and
transesophagealechocardIography,furtherobjectIfythecredentIalIngprocess.ThIsIsnow
sIgnIfIcantbecauseInItIalboardcertIfIcatIonaftertheyear2000bytheAmerIcan8oardof
AnesthesIology(A8A)IstImelImItedandsubjecttoperIodIctestIngandrecertIfIcatIon.
Clearly,thIswIllencourageanongoIngprocessofcontInuIngmedIcaleducatIon.|any
states,someInstItutIons,evensomeregulatorybodIeshaverequIrementsforamInImum
numberofhoursofcontInuIngmedIcaleducatIon.0ocumentatIonofmeetIngsucha
standardagaInactsasonetypeofqualItyassurancemechanIsmfortheIndIvIdual
practItIoner,whIleprovIdInganotherobjectIvecredentIalIngmeasurementforthose
grantInglIcensesorprIvIleges.
Professional Staff Participation and Relationships
AllmedIcalcarefacIlItIesandpractIcesettIngsdependontheIrprofessIonalstaffs,of
course,fordaIlyactIvItIesofthedelIveryofhealthcarebut,veryImportantly,theyalso
dependonthosestaffstoprovIdeadmInIstratIvestructureandsupport.|edIcalstaff
actIvItIesareIncreasInglyImportantInachIevIngfavorableaccredItatIonstatus(e.g.,from
theJoIntCommIssIonfortheAccredItatIonofHealthcareDrganIzatIons[JCAHD]),now
oftenknownastheJoIntCommIssIon,andInmeetIngawIdevarIetyofgovernmental
regulatIonsandrevIews.PrIncIpalmedIcalstaffactIvItIesInvolvesometImestIme
consumIngefforts,suchasdutIesasastaffoffIcerorcommItteemember.AnesthesIologIsts
shouldbepartIcIpantsInInfact,shouldplayasIgnIfIcantroleIncredentIalIng,peer
revIew,tIssuerevIew,transfusIonrevIew,DFmanagement,andmedIcaldIrectIonofsame
daysurgeryunIts,postanesthesIacareunIts(PACUs),IntensIvecareunIts(CUs),andpaIn
managementunIts.Also,ItIsveryImportantthatanesthesIologypersonnelbeInvolvedIn
fundraIsIngactIvItIes,benefIts,communItyoutreachprojectssponsoredbythefacIlIty,
andsocIaleventsofthefacIlItystaff.
AnesthesIaprofessIonalsasagrouphaveareputatIonforlackofInvolvementInmedIcal
staffandfacIlItyIssuesbecauseoflackoftIme(becauseoflonghoursIntheDF)orsImply
lackofInterest.nfact,anesthesIologypersonnelarealltoooftenperceIvedInafacIlItyas
theoneswhoslIpInandoutofthebuIldIngessentIallyanonymously(oftendressedvery
casuallyorevenInthepajamalIkecomfortofscrubsuIts)andvIrtuallyunnotIced.ThIsIs
anunfortunatestateofaffaIrs,andIthasfrequentlycomebackInvarIouspaInfulwaysto
hauntthosewhohavenotbeenInvolved,orevennotIced.AnesthesIaprofessIonals
sometImesrespondthatthedemandsforanesthesIologyservIcearesogreatthatthey
sImplyneverhavethetImeortheopportunItytobecomeInvolvedIntheIrfacIlItyand
wIththeIrpeers.fthIsIsreallytrue,ItIsclearthatmoreanesthesIaprofessIonalsmustbe
addedatthatfacIlIty,evenIfdoIngsoslIghtlyreducestheIncomeofthosealreadythere.
fanesthesIaprofessIonalsarenotInvolvedandnotperceIvedasInterested,dedIcated
teamplayers,theywIllbeshutoutofcrItIcalnegotIatIonsanddecIsIons.Althoughone
obvIousInstanceInwhIchotherswIllmakedecIsIonsforanesthesIaprofessIonalsIsthe
dIstrIbutIonofcapItatedorbundledpractIcefeeIncomecollectedbyacentralumbrella
organIzatIon,therearemanysuchsItuatIons,andtheanesthesIaprofessIonalswIllbe
forcedtocomplywIththeresultIngmandates.
SImIlarly,InvolvementwIthafacIlIty,aprofessIonalstaff,oramultIspecIaltygroupgoes
beyondformalorganIzedgovernanceandcommItteeactIvIty.CollegIalrelatIonshIpswIth
professIonalofotherspecIaltIesandwIthadmInIstratorsarecentraltomaIntenanceofa
recognIzedposItIonandavoIdanceofthesItuatIonofexclusIonprevIouslydescrIbed.8eIng
readIlyavaIlableforformalandInformalconsults,partIcularlyregardIngpreoperatIve
patIentworkupandthemaxImallyeffIcIentwaytogetsurgeons'patIentstotheDFIna
tImely,expedIentmanner,IsextremelyImportant.NooneIndIvIdualcanbeeverywhere
allthetIme,butananesthesIologygroupordepartmentshouldstrIvetobealways
responsIvetoanyrequestforhelpfromphysIcIansoradmInIstrators.toftenappearsthat
anesthesIaprofessIonalsfaIltoapprecIatejusthowgreataposItIveImpactarelatIvely
sImpleInvolvement
P.J1
(startInganIntravenouslIneforapedIatrIcIan,helpInganInternIstmanageanCU
ventIlator,orhelpIngafacIlItyadmInIstratorunclogajammedrecoveryroom)mayhave.
Establishing Standards of Practice and Understanding the
Standard of Care
TheIncreasIngfrequencyandIntensItyofproductIonpressure,
4
wIththetacIt(oreven
explIcIt)dIrectIvetoanesthesIaprofessIonalstogofastnomatterwhatandtodomore
wIthless,createssItuatIonsInwhIchanesthesIaprofessIonalsmayconcludethatthey
mustcutcornersandcompromIsemaxImallysafepatIentcarejusttostayInbusIness.ThIs
typeofpressurehasbecomeevengreaterwIththeImplementatIonofmoreandmore
protocolsorparametersforpractIce,somefromprofessIonalsocIetIessuchastheASAand
somemandatedbyordevelopedInconjunctIonwIthpurchasersofhealthcare
(government,InsurancecompanIes,ormanagedcareorganIzatIons).|anyofthese
protocolsaredevIsedtofasttrackpatIentsthroughthemedIcalcaresystem,especIally
whenanelectIveprocedureIsInvolved,InasabsolutelylIttletImeaspossIble,thus
mInImIzIngcosts.0othesefasttrackprotocolsconstItutestandardsofcarethathealth
careprovIdersaremandatedtoImplement:WhataretheImplIcatIonsofdoIngso:Dfnot
doIngso:
TobetterunderstandanswerstosuchquestIons,ItIsImportanttohaveabasIcbackground
Intheconceptofthestandardofcare.
Thestandard of careIstheconductandskIllofaprudentpractItIonerthatcanbeexpected
byareasonablepatIent.ThIsIsaveryImportantmedIcolegalconceptbecauseabad
medIcalresultduetofaIluretomeetthestandardofcareIsmalpractIce.Courtshave
tradItIonallyrelIedonmedIcalexpertsknowledgeableaboutthepoIntInquestIontogIve
opInIonsastowhatIsthestandardofcareandIfIthasbeenmetInanIndIvIdualcase.ThIs
typeofstandardIssomewhatdIfferentfromthestandardspromulgatedbyvarIous
standardsettIngbodIesregardIng,forexample,thecolorofgashosesconnectedtoan
anesthesIamachIneortheInabIlItytoopentwovaporIzersonthatmachIne
sImultaneously.However,IgnorIngtheequIpmentstandardsandtoleratInganunsafe
sItuatIonIsavIolatIonofthestandardofcare.Promulgatedstandards,suchasthevarIous
safetycodesandanesthesIamachInespecIfIcatIons,rapIdlybecomethestandardofcare
becausepatIents(throughtheIrattorneys,Inthecaseofanuntowardevent)expectthe
publIshedstandardstobeobservedbytheprudentpractItIoner.
UltImately,thestandardofcareIswhatajurysaysItIs.However,ItIspossIbleto
antIcIpate,atleastInpart,whatknowledgeandactIonswIllbeexpected.Therearetwo
maInsourcesofInformatIonastoexactlywhatIstheexpectedstandardofcare.
TradItIonally,thebelIefsofferedbyexpertwItnessesInmedIcallIabIlItylawsuItsregardIng
whatIsactuallybeIngdoneInreallIfe(defactostandardsofcare)werethemaInInput
jurIeshadIndecIdIngwhatwasreasonabletoexpectfromthedefendant.TheresultIng
problemIswellknown:exceptInthemostegregIouscases,ItIsusuallypossIbleforthe
lawyerstofIndexpertswhowIllsupporteachofthetwoopposIngsIdes,makIngtheprocess
moresubjectIvethanobjectIve.(8ecauseofthIs,thereareevenASAGuidelines for Expert
Witness Qualifications and TestimonyandanequIvalentdocumentfromtheAmerIcan
AssocIatIonofNurseAnesthetIsts).Dfcourse,therecanbelegItImatedIfferencesofopInIon
amongthoughtful,InsIghtfulexperts,butevenInthesecasesthejurystIllmustdecIdewho
IsmorebelIevable,looksbetter,orsoundsbetter.Thesecond,muchmoreobjectIve,
sourcefordefInIngcertaIncomponentpartsofthestandardofcareIsthepublIshed
standardsofcare,guIdelInes,practIceparameters,andprotocolsnowbecomIngmore
common.TheseserveashardevIdenceofwhatcanbereasonablyexpectedof
practItIonersandcanmakeIteasIerforajuryevaluatIngwhetheramalpractIcedefendant
faIledtomeettheapplIcablestandardofcare.SeveraltypesofdocumentsexIstandhave
dIfferIngImplIcatIons.
Leading the Way
AnesthesIologymaybethemedIcalspecIaltymostInvolvedwIthpublIshedstandardsof
care.thasbeensuggestedthatthenatureofanesthesIapractIce(havIngcertaIncentral
crItIcalfunctIonsrelatIvelyclearlydefInedandcommontoallsItuatIonsandalsohavIngan
emphasIsontechnology)makesItthemostamenableofallthefIeldsofmedIcInetothe
useofpublIshedstandards.TheorIgInalIntraoperatIvemonItorIngstandards
5
areaclassIc
example.TheASAfIrstadoptedItsownsetofbasIcIntraoperatIvemonItorIngstandardsIn
1986andhasmodIfIedthemseveraltImes.ThetextofallASAstandards,guIdelInes,and
statementsIsreadIlyavaIlable(seewww.asahq.org,ClInIcalnformatIon,and
Standards,CuIdelInes,andStatements).
ThIsmonItorIngstandardsdocument(www.asahq.org/
publIcatIonsAndServIces/standards/02.pdf)IncludesclearspecIfIcatIonsforthepresenceof
personneldurIngananesthetIcepIsodeandforcontInualevaluatIonofoxygenatIon,
ventIlatIon,cIrculatIon,andtemperature.TheseASAmonItorIngstandardsveryquIckly
becamepartoftheacceptedstandardofcareInanesthesIapractIce.ThIsmeanstheyare
ImportanttopractIcemanagementbecausetheyhaveprofoundmedIcolegalImplIcatIons:
acatastrophIcaccIdentoccurrIngwhIlethestandardsarebeIngactIvelyIgnoredIsvery
dIffIculttodefendIntheconsequentmalpractIcesuIt,whereasanaccIdentthatoccurs
durIngwelldocumentedfullcomplIancewIththestandardswIllautomatIcallyhavea
strongdefensebecausethestandardofcarewasbeIngmet.SeveralstatesIntheUnIted
StateshavemadecomplIancewIththeseASAstandardsmandatoryunderstateregulatIons
orevenstatutes.7arIousmalpractIceInsurancecompanIesofferdIscountsonmalpractIce
InsurancepolIcypremIumsforcomplIancewIththesestandards,somethIngquItenaturalto
InsurersbecausetheyarefamIlIarwIththeIdeaofmanagIngknownrIskstohelpmInImIze
fInancIallosstothecompany.TheASAmonItorIngstandardshavebeenwIdelyemulatedIn
othermedIcalspecIaltIesandevenInfIeldsoutsIdemedIcIne.
WIthmanyofthesameelementsofthInkIng,theASAadopted8asIcStandardsfor
PreanesthesIaCare(www.asahq.org/publIcatIonsAndServIces/standards/0J.pdf).ThIswas
supplementedsIgnIfIcantlybyanothertypeofdocument,theASAPractice Advisory for
Preanesthesia Evaluation(seewww.asahq.org,PublIcatIonsandServIces,andPractIce
Parameters),a40pagemetaanalysIsofclInIcalaspectsofpreoperatIveevaluatIon.Also,
theASAadoptedStandardsforPostanesthesIaCare,InwhIchtherewasconsIderatIonof
andcollaboratIonwIththeverydetaIledstandardsofpractIceforPACUcarepublIshedby
theAmerIcanSocIetyofPostAnesthesIaNurses(anothergoodexampleofthesourcesof
standardsofcare).ThIsalsowaslatersupplementedbyanextensIvePractice Guideline.
6
AslIghtlydIfferentsItuatIonexIstswIthregardtothestandardsforconductofanesthesIaIn
obstetrIcs.ThesestandardswereorIgInallypassedbytheASAIn1988,Inthesamemanner
astheotherASAstandards,buttheASAmembershIpeventuallyquestIonedwhetherthey
reflectedarealIstIcanddesIrablestandardofcare.AccordIngly,theobstetrIcanesthesIa
standardsweredowngradedIn1990toguIdelInes,specIfIcallytoremovethemandatory
natureofthedocument.8ecausetherewasnoagreementastowhatshouldbeprescrIbed
asthestandardofcare,themedIcolegalImperatIveofpublIshedstandards
P.J2
InthIsInstancehasbeentemporarIlysetasIde.FromamanagementperspectIve,thIs
makestheguIdelInes(www.asahq.org/publIcatIonsAndServIces/standards/45.pdf)noless
valuablebecausetheIntentofoptImIzIngcarethroughtheavoIdanceofcomplIcatIonsIs
nolessoperatIve.However,IntheeventoftheneedtodefendagaInstamalpractIceclaIm
InthIsarea,ItIsclearfromthIssequenceofeventsthattheexactstandardofcareIs
debatableandnotyetfInallyestablIshed(anextremelyImportantmedIcolegal
consIderatIon).AdIfferentASAdocumenthasbeengenerated,Practice Guidelines for
Obstetrical Anesthesia,wIthmoredetaIlandspecIfIcItyaswellasanemphasIsonthe
metaanalytIcapproach.
7
Practice Guidelines
AnImportanttypeofrelatedASAdocumentIsthePractice Guideline(formerlyPractIce
Parameter).ThIshassomeofthesameelementsasastandardofpractIcebutIsmore
IntendedtoguIdejudgment,largelythroughalgorIthmswIthsomeelementofguIdelInes,In
addItIontodIrectIngthedetaIlsofspecIfIcproceduresaswouldaformalstandard.8eyond
thedetaIlsofthemInImumstandardsforcarryIngouttheprocedure,thesepractIce
parameterssetforthalgorIthmsandguIdelInesforhelpIngtodetermIneunderwhat
cIrcumstancesandwIthwhattImIngtoperformIt.Understandably,purchasersofhealth
care(government,InsurancecompanIes,andmanagedcareorganIzatIons[|CDs])wItha
strongdesIretolImItthecostsofmedIcalcarehavegreatInterestInpractIceparameters
aspotentIalvehIclesforhelpIngtoelImInateunnecessaryproceduresandlImIteventhe
necessaryones.
TheASAhasbeenveryactIveIncreatIngandpublIshIngpractIceguIdelInes.ThefIrst
publIshedparameter(sIncerevIsed)concernedtheuseofpulmonaryartery(PA)catheters.
8
tconsIderedtheclInIcaleffectIvenessofPAcatheters,publIcpolIcyIssues(costsand
concernsofpatIentsandprovIders),andrecommendatIons(IndIcatIonsandpractIce
settIngs).Also,theASADifficult Airway AlgorithmwaspublIshed(alsosIncerevIsed).
9
ThIs
thoughtfuldocumentsynthesIzedastrategysummarIzedInadecIsIontreedIagramfor
dealIngacutelywIthaIrwayproblems.thasgreatclInIcalvalueandItIsreasonableto
antIcIpatethatItwIllbeusedtohelpmanypatIents.However,allthesedocumentsare
readIlynotIcedbyplaIntIffs'lawyers,thedIffIcultaIrwayparameterfromtheASAbeIngan
excellentexample.
AnImportantandsofarundecIdedquestIonIswhetherguIdelInesandpractIceparameters
fromrecognIzedentItIessuchastheASAdefinethestandardofcare.ThereIsnosImple
answer.ThIswIllbedecIdedovertImebypractItIoners'actIons,debatesInthelIterature,
mandatesfrommalpractIceInsurers,and,ofcourse,courtdecIsIons.SomeguIdelInes,such
astheU.S.Foodand0rugAdmInIstratIon(F0A)preanesthetIcapparatuscheckout,are
acceptedasthestandardofcare.TherewIllbedebateamongexperts,butthepractItIoner
mustmakethedecIsIonastohowtoapplypractIceparametersandguIdelInessuchas
thosefromtheASA.PractItIonershaveIncorrectlyassumedthattheymustdoeverythIng
specIfIed.ThIsIsclearlynottrue,yetthereIsavalIdconcernthatthesewIllsomedaybe
heldupasdefInIngthestandardofcare.AccordIngly,prudentattentIonwIthInthebounds
ofreasontotheprIncIplesoutlInedInguIdelInesandparameterswIllputthepractItIoner
InatleastareasonablydefensIbleposItIon,whereasradIcaldevIatIonfromthemshouldbe
basedonobvIousexIgencIesofthesItuatIonatthatmomentorclear,defensIble
alternatIvebelIefs(wIthdocumentatIon).
ThemostrecenttypeofdocumenthasbeenthepractIceadvIsory,whIchcanseem
functIonallysImIlar,butappearstohavetheImplIcatIonofmoreconsensuscompromIse
thanprevIousdocuments.ExamplesofpractIceadvIsorIesInclude:ntraoperatIve
Awarenessand8raInFunctIon|onItorIng,PerIoperatIve|anagementofPatIentswIth
CardIacFhythm|anagement0evIces:PacemakersandmplantableCardIoverter
0efIbrIllators,andPerIoperatIve7IsualLossAssocIatedwIthSpIneSurgery.The
potentIalqualItyassuranceandmedIcolegalImplIcatIonsofthesedocumentsareso
ImportanttoanesthesIaprofessIonalsandtheIrpractIces,theASAhaswhatIsessentIallya
guIdelInefortheguIdelInesInIts2007updateofthePolIcyStatementonPractIce
Parameters(seewww.asahq.org,PublIcatIonsandServIces,andStandards,CuIdelInes,
andStatements)InwhIchthedIstInctIonIsmadebetweenevIdencebaseddocumentsand
consensusbaseddocumentswIthexplanatIonsofthebackgroundandformulatIonprocesses
foreach.
Dntheotherhand,practIceprotocols,suchasthoseforthefasttrackmanagementof
coronaryarterybypassgraftpatIents,thatarehandeddownby|CDsorhealthInsurance
companIesareadIfferentmatter.EventhoughthedesIredImplIcatIonIsthatpractItIoners
mustobserve(oratleaststronglyconsIder)them,theydonothavethesameImplIcatIons
IndefInIngthestandardofcareastheotherdocuments.PractItIonersmustavoIdgettIng
trapped.tmaywellnotbeavalIdlegaldefensetojustIfyactIonorthelackofactIon
becauseofacompanyprotocol.AsdIffIcultasItmaybetoreconcIlewIththepayer,the
practItIonerstIllIssubjecttotheclassIcdefInItIonsofstandardofcare.
TheothertypeofstandardsassocIatedwIthmedIcalcarearethoseoftheJoInt
CommIssIon,whIchIsthebestknownmedIcalcarequalItyregulatoryagency.Asnoted,
thesestandardswereformanyyearsconcernedlargelywIthstructure(e.g.,gastanks
chaIneddown)andprocess(e.g.,documentatIoncomplete),butInrecentyearstheyhave
beenexpandedtoIncluderevIewsoftheoutcomeofcare.JoIntCommIssIonstandardsalso
focusoncredentIalIngandprIvIleges,verIfIcatIonthatanesthesIaservIcesareofunIform
qualItythroughoutanInstItutIon,thequalIfIcatIonsofthedIrectoroftheservIce,
contInuIngeducatIon,andbasIcguIdelInesforanesthesIacare(needforpreoperatIveand
postoperatIveevaluatIons,documentatIon,andsoforth).FullJoIntCommIssIon
accredItatIonofahealthcarefacIlItyIsusuallyforJyears.EventhebesthospItalsand
facIlItIesreceIvesomecItatIonsofproblemsordefIcIencIesthatareexpectedtobe
corrected,andanInterImreportofeffortstodosoIsrequIred.fthereareenough
problems,accredItatIoncanbecondItIonalfor1year,wIthacompletereInspectIonatthat
tIme.PreparIngforJoIntCommIssIonInspectIonsstartswIthverIfIcatIonthatessentIal
group/departmentstructureIsInplace;excellentexamplesexIst.
1
TheprocessultImately
Involvesagreatdealofwork,butbecausethestandardsusuallydopromotehIghqualIty
care,themajorItyofthIsworkIshIghlyconstructIveandofbenefIttotheInstItutIonand
ItsmedIcalstaff.
Review Implications
AnothertypeofregulatoryagencyIsthepeerrevIeworganIzatIon.ProfessIonalstandards
revIeworganIzatIons(PSFDs)wereestablIshedIn1972asutIlIzatIonrevIew/QAoverseers
ofthecareoffederallysubsIdIzedpatIents(|edIcareand|edIcaId).0espItetheIrefforts
todealwIthqualItyofcare,thesegroupswereseenbyallInvolvedasprImarIlyInterested
IncostcontaInment.7arIousnegatIvefactorsledtothePSFDsbeIngreplacedIn1984wIth
thepeerrevIeworganIzatIon(PFD).
10
ThereIsaPFDIneachstate,manybeIngassocIated
wIthastatemedIcalassocIatIon.TheobjectIvesofaPFDInclude14goalsrelatedto
hospItaladmIssIons(e.g.,toshIftcaretoanoutpatIentbasIsasmuchaspossIble)and5
relatedtoqualItyofcare(e.g.,toreduceavoIdabledeathsandavoIdablecomplIcatIons).
ThePFDscomprIsefulltImesupportstaffandphysIcIanrevIewerspaIdasconsultantsor
dIrectors.deally,PFDmonItorIngwIlldIscoversuboptImalcare,whIchwIllleadtospecIfIc
recommendatIonsforImprovementInqualIty.ThereIs
P.JJ
aperceptIonthatqualItyofcareeffortsarehamperedbythelackofrealIstIcobjectIves
andalsothatthesePFDgroups,lIkeothersbeforethem,wIlllargelyorentIrelyfunctIonto
lImItthecostofhealthcareservIces.
ThepractIcemanagementImplIcatIonshavebecomeclear.AsIdefromtheasyet
unrealIzedpotentIalforqualItyImprovementeffortsandtheoccasIonaldenIalofpayment
foraprocedure,themostlIkelyInteractIonbetweenthelocalPFDandanesthesIa
professIonalswIllInvolvearequestforperIoperatIveadmIssIonofapatIentwhosecareIs
mandatedtobeoutpatIentsurgery(thIscouldalsooccurIndealIngwIthan|CD).fthe
anesthesIologIstfeels,forexample,thateIther(1)preoperatIveadmIssIonfortreatmentto
optImIzecardIac,pulmonary,dIabetIc,orothermedIcalstatusor(2)postoperatIve
admIssIonformonItorIngoflabIlesItuatIonssuchasuncontrolledhypertensIonwIllreduce
clearanesthetIcrIsksforthepatIent,anapplIcatIontothePFDforapprovalofadmIssIon
mustbemadeandvIgorouslysupported.Alltoooften,however,suchIssuessurfaceaday
orsobeforethescheduledprocedureInapreanesthesIascreenIngclInIcorevenIna
preoperatIveholdIngareaoutsIdetheDFonthedayofsurgery.ThIswIllcontInuetooccur
untIlanesthesIaprovIderseducatetheIrconstItuentsurgeoncommunItyastowhattypesof
assocIatedmedIcalcondItIonsmaydIsqualIfyaproposedpatIentfromtheoutpatIent
(ambulatory)surgIcalschedule.fadequatenotIceIsgIvenbythesurgeon,thepatIentcan
beseenfarenoughInadvancebyananesthesIologIsttoallowapproprIateplannIng.
nthecIrcumstanceInwhIchthefIrstknowledgeofaquestIonablepatIentcomes1or2
daysbeforesurgery,theanesthesIologIstcantrytohavetheprocedurepostponed,If
possIble,orcanundertakethetImeconsumIngtaskofmultIpletelephonecallstogetthe
surgeon'sagreement,getPFDapproval,andmakethenecessaryarrangements.8ecause
neItheralternatIveIspartIcularlyattractIve,especIallyfromadmInIstratIveand
reImbursementperspectIves,theremaybeastrongtemptatIontoletItslIdeandtryto
dealwIththepatIentasanoutpatIenteventhoughthIsmaybequestIonable.nalmostall
cases,ItIslIkelythattherewouldbenoadverseresult(thegetawaywIthIt
phenomenon).However,thepatIentmIghtwellbeexposedtoanavoIdablerIsk.8oth
becauseoftheworkIngsofprobabIlItyandbecauseoftheInevItabletendencytoletsIcker
andsIckerpatIentsslIpbyaslaxpractItIonersrepeatedlygetawaywIthItandarelulled
IntoafalsesenseofsecurIty,soonerorlatertherewIllbeanunfortunateoutcomeorsome
preventablemajormorbIdItyorevenmortalIty.
ThesItuatIonIsworsenedwhenthefIrstcontactwIthaquestIonableambulatorypatIentIs
preoperatIvely(possIblyevenalreadyIntheDF)onthedayofsurgery.Theremaybe
IntensepressurefromthepatIent,thesurgeon,ortheDFadmInIstratorandstaffto
proceedwIthacaseforwhIchtheanesthesIapractItIonerbelIevesthepatIentIspoorly
prepared.TheargumentsmaderegardIngpatIentInconvenIenceandanxIetyarevalId.
However,theyshouldnotoutweIghthebestmedIcalInterestsofthepatIent.AlthoughthIs
IsapoIntInfavorofscreenIngalloutpatIentsbeforethedayofsurgery,theanesthesIa
professIonalfacIngthIssItuatIononthedayofoperatIonshouldstateclearlytoall
concernedthereasonsforpostponIngthesurgery,stressIngtheIssueofavoIdablerIskand
standardsofcare,andthenhelpwIthalternatIvearrangements(IncludIng,Ifnecessary,
dealIngwIththePFDormanagedcareorganIzatIon).
PotentIallIabIlItyInthIsregardIstheothersIdeofthestandardofcareIssue.PartIcularly
concernIngIsthequestIonofpostoperatIveadmIssIonofambulatorypatIentswhohave
beenunstable.tIsanextremelypoordefenseagaInstamalpractIceclaImtostatethat
thepatIentwasdIschargedhome,onlylatertosufferacomplIcatIon,becausethe
PFD/managedcareorganIzatIondeemedthatoperatIveprocedureoutpatIentandnot
InpatIentsurgery.AsbureaucratIcallyannoyIngasItmaybe,ItIsaprudentmanagement
strategytoadmItthepatIentIfthereIsanylegItImatequestIon,thusmInImIzIngthe
chanceforcomplIcatIons,andlaterhagglewIththePFDordIrectlywIththeInvolved
thIrdpartypayer.
Policy and Procedure
DneImportantorganIzatIonalpoIntthatIsoftenoverlookedIstheneedforacomplete
polIcyandproceduremanual.SuchacompIlatIonofdocumentsIsnecessaryforall
practIces,fromthelargestdepartmentscoverIngmultIplehospItalstoasIngleroom
outpatIentfacIlItywIthoneanesthesIaprovIder.SuchamanualcanbeextraordInarIly
valuable,as,forexample,whenItprovIdescrucIalInformatIondurInganemergency.Some
suggestIonsforthecontentofthIscompendIumexIst
11
but,atmInImum,organIzatIonal
andproceduralelementsmustbeIncluded.
TheorganIzatIonalelementsthatshouldbepresentIncludeachartoforganIzatIonand
responsIbIlItIesthatIsnotjustacallschedulebutaclearexplanatIonofwhoIsresponsIble
forwhatfunctIonsofthedepartmentandwhen,wIthattendantdetaIlssuchas
expectatIonsforthepractItIoner'spresencewIthIntheInstItutIonatdesIgnatedhours,
telephoneavaIlabIlIty,pageravaIlabIlIty,themaxImumpermIssIbledIstancefromthe
InstItutIonwhenoncall,andsoforth.ExperIencesuggestsItIsespecIallyImportantfor
theretobeanabsolutelyclearspecIfIcatIonoftheavaIlabIlItyofqualIfIedanesthesIology
personnelforemergencycesareansectIon,partIcularlyInpractIcearrangementsInwhIch
thereareseveralpeopleoncallcoverIngmultIplelocatIons.Sadly,theseIssuesoftenare
onlyconsIderedafteradIsasterhasoccurredthatInvolvedmIscommunIcatIonandthe
mIstakenbelIefbyoneormorepeoplethatsomeoneelsewouldtakecareofanacute
problem.
TheorganIzatIonalcomponentofthepolIcyandproceduremanualshouldalsoIncludea
clearexplanatIonoftheorIentatIonandcheckoutprocedurefornewpersonnel,contInuIng
medIcaleducatIonrequIrementsandopportunItIes,themechanIsmsforevaluatIng
personnelandforcommunIcatIngthIsevaluatIontothem,dIsasterplans(orreferencetoa
separatedIsastermanualorprotocol),QAactIvItIesofthedepartment,andtheformatfor
statIstIcalrecordkeepIng(numberofprocedures,typesofanesthetIcsgIven,typesof
patIentsanesthetIzed,numberandtypesofInvasIvemonItorIngprocedures,numberand
typeofresponsestoemergencycalls,complIcatIons,orwhateverthegroup/department
decIdes).
TheproceduralcomponentofthepolIcyandproceduremanualshouldgIvebothhandy
practIcetIpsandspecIfIcoutlInesofproposedcoursesofactIonforpartIcular
cIrcumstances;ItalsoshouldstorelIttleusedbutvaluableInformatIon.Feferenceshould
bemadetothestatements,guIdelInes,practIceparameters,andstandardsappearIngon
theASAWebsIte.AlsoIncludedshouldbereferencestoorspecIfIcprotocolsfortheareas
mentIonedIntheJCAHDstandards:preanesthetIcevaluatIon,ImmedIatepreInductIonre
evaluatIon,safetyofthepatIentdurIngtheanesthetIcperIod,releaseofthepatIentfrom
anyPACU,recordIngofallpertInenteventsdurInganesthesIa,recordIngofpostanesthesIa
vIsIts,guIdelInesdefInIngtheroleofanesthesIaservIcesInhospItalInfectIoncontrol,and
guIdelInesforsafeuseofgeneralanesthetIcagents.DtherapproprIatetopIcsIncludethe
followIng:
1. FecommendatIonsforpreanesthesIaapparatuscheckout,suchasfromtheF0A
12
(see
Chapter26)
2. CuIdelInesforadmIssIonto,mInImalmonItorIngandduratIonofstayofanInfant,chIld,
oradultIn,andthendIschargefromthePACU
J. ProceduresfortransportIngpatIentsto/fromtheDF,PACU,orCU
P.J4
5. PolIcyonambulatorysurgIcalpatIentsforexample,screenIng,useofregIonal
anesthesIa,dIschargehomecrIterIa
6. PolIcyonevaluatIonandprocessIngofsamedayadmIssIons
7. PolIcyonCUadmIssIonanddIscharge
8. PolIcyonphysIcIansresponsIbleforwrItIngordersInrecoveryroomandCU
9. PolIcyonInformedconsentforanesthesIaandItsdocumentatIon
10. PolIcyontheuseofpatIentsInclInIcalresearch(IfapplIcable)
11. CuIdelInesforthesupportofcadaverIcorgandonorsandItstermInatIon(plusorgan
donatIonaftercardIacdeath)
12. CuIdelInesonenvIronmentalsafety,IncludIngpollutIonwIthtracegasesandelectrIcal
equIpmentInspectIon,maIntenance,andhazardpreventIon
1J. ProcedureforchangeofpersonneldurIngananesthetIcanddocumentatIon(partIcularly
IfaprIntedhandoffprotocolIsused)
14. ProcedurefortheIntroductIonofnewequIpment,drugs,orclInIcalpractIces
15. ProcedureforepIduralandspInalnarcotIcadmInIstratIonandsubsequentpatIent
monItorIng(e.g.,type,mInImumtIme,nursIngunIts)
16. ProcedureforInItIaltreatmentofcardIacorrespIratoryarrest(updatedAdvanced
CardIacLIfeSupportguIdelInes)
17. PolIcyforhandlIngpatIent'srefusalofbloodorbloodproducts,IncludIngthemechanIsm
toobtaInacourtordertotransfuse
18. ProcedureforthemanagementofmalIgnanthyperthermIa
19. ProcedurefortheInductIonandmaIntenanceofbarbIturatecoma
20. ProcedurefortheevaluatIonofsuspectedpseudocholInesterasedefIcIency
21. ProtocolforrespondIngtoanadverseanesthetIcevent(suchasacopyoftheupdateof
theAdverseEventProtocol
1J
)
22. PolIcyonresuscItatIonofdonotresuscItatepatIentsIntheDF
ndIvIdualdepartmentswIlladdtothesesuggestIonsasdIctatedbytheIrspecIfIcneeds.A
thorough,carefullyconceIvedpolIcyandproceduremanualIsavaluabletool.Themanual
shouldberevIewedandupdatedasneededbutatleastannually,wIthapartIcularly
thoroughrevIewprecedIngeachJoIntCommIssIonInspectIon.Eachmemberofagroupor
departmentshouldrevIewthemanualatleastannuallyandsIgnoffInalogIndIcatIng
famIlIarItywIthcurrentpolIcIesandprocedures.
Meetings and Case Discussion
TheremustberegularlyscheduleddepartmentalorgroupmeetIngs.AlthoughdIdactIc
lecturesandcontInuIngeducatIonmeetIngsarevaluableandnecessary,therealsomustbe
regularopportunItIesforopenclInIcaldIscussIonaboutInterestIngcasesandproblem
cases.Also,theJoIntCommIssIonrequIresthattherebeatleastmonthlymeetIngsat
whIchrIskmanagementandQAactIvItIesaredocumentedandreported.Whetherthese
meetIngsarecalledcaseconferences,morbIdItyandmortalItyconferences,ordeathsand
complIcatIonsconferences,theentIredepartmentorgroupshouldgatherforan
InterchangeofIdeas.|orerecentlythesegatherIngshavebeencalledQA meetings.An
openrevIewofdepartmentalstatIstIcsshouldbedone,IncludIngallcomplIcatIons,even
thosethatmayappeartrIvIal.UnusualpatternsofsmalleventsmaypoInttowardalarger
orsystematIcproblem,especIallyIftheyaremorefrequentlyassocIatedwIthone
IndIvIdualpractItIoner.
AproblemcasepresentedatthedepartmentalmeetIngmIghtbeanovertaccIdent,anear
accIdent(crItIcalIncIdent),oranuntowardoutcomeofunknownorIgIn.Honestbut
constructIvedIscussIon,evenofananesthesIaprofessIonal'stechnIcaldefIcIencIesorlack
ofknowledge,shouldtakeplaceInthespIrItofconstructIvepeerrevIew.TheclassIc
questIon,WhatwouldyoudodIfferentlynexttIme:IsagoodwaytostartthedIscussIon.
TheremaybesItuatIonsInwhIchInvItIngthesurgeonortheInternIstInvolvedInaspecIfIc
casewouldbeadvantageous.TheopportunItyforeachtypeofprovIdertohearthe
perspectIveofanotherdIscIplIneIsnotonlyInherentlyeducatIonal,butalsocanpromote
communIcatIonandcooperatIonInfuturepotentIalproblemcases.
FecordsofthesemeetIngsmustbekeptforaccredItatIonpurposes,buttheenshrInIngof
overlydetaIledmInutes(potentIallysubjecttodIscoverybyaplaIntIff'sattorneyatalater
date)mayInhIbIttrueeducatIonalandcorrectIveInterchangesaboutuntowardevents.n
thecIrcumstanceofdIscussIonofacasethatseemslIkelytoprovokelItIgatIon,ItIs
approprIatetobecertaInthatthemeetIngIsclassIfIedasoffIcIalpeerrevIewand
possIblyevenInvItethehospItalattorneyorlegalcounselfromtherelevantmalpractIce
InsurancecarrIer(toguaranteetheprIvacyofthedIscussIonandmInutes).
Support Staff
ThereIsafundamentalneedforsupportstaffIneveryanesthesIapractIce.Even
IndependentpractItIonersrelyInsomemeasureonfacIlItIes,equIpment,andservIces
provIdedbytheorganIzatIonmaIntaInIngtheanesthetIzInglocatIon.nlarge,well
organIzeddepartments,relIanceonsupportstaffIsoftenverygreat.WhatIsoften
overlooked,however,IsaprocessanalogoustothatofcredentIalIngandprIvIlegesfor
anesthesIaprofessIonals,althoughataslIghtlydIfferentlevel.Thepeopleexpectedto
provIdeclInIcalanesthesIapractIcesupportmustbequalIfIedandmustatalltImes
understandwhattheyareexpectedtodoandhowtodoIt.tIssIngularlyunfortunateto
realIzeonlyafterananesthesIacatastrophehasoccurredthatbasIcdetaIlsofsImplework
assIgnments,suchasthechangIngofcarbondIoxIdeabsorbent,wereroutInelyIgnored.
ThIsIndIcatestheneedforsupervIsIonandmonItorIngofthesupportstaffbytheInvolved
practItIoners.Further,suchsupportpersonnelarefavorItetargetsofcostcuttIng
admInIstratorswhodonotunderstandthefunctIonofanesthesIatechnIcIansortheIr
equIvalent.nthemodernera,manyadmInIstratorsseemdrIvenalmostexclusIvelybythe
bottomlIneandcannotapprecIatetheconnectIonbetweenvaluableworkerssuchas
theseandtherevenuestream.EventhoughItIsobvIoustoallwhoworkInanDFthat
theanesthesIasupportpersonnelmakeItpossIblefortheretobepatIentsflowIngthrough
theDF,ItIstheIrresponsIbIlItytoconvIncethefacIlIty'sfIscaladmInIstratorthat
elImInatIonofsuchposItIonsIsgenuInelyfalseeconomybecauseoftheattendantlossIn
effIcIency,partIcularlyInturnIngovertheroombetweensurgerIes.Further,ItIsalsofalse
economytoreducethenumberofpersonnelbelowthatgenuInelyneededtoretrIeve,
clean,sort,dIsassemble,sterIlIze,reassemble,store,anddIstrIbutethetoolsofdaIly
anesthesIapractIce.7Igorousdefense(orInItIatIonofnewposItIonsIfthestaffIs
Inadequate)bytheanesthesIaprofessIonalsshouldbeundertaken,alwayswIththe
realIzatIonthatItmaybenecessaryInsomecIrcumstancesforthemtosupplementthe
budgetfromthefacIlItywIthsomeoftheIrpractIceIncometoguaranteeanadequate
complementofcompetentworkers.
8usInessandorganIzatIonalIssuesInthemanagementofananesthesIapractIcearealso
crItIcallydependentontheexIstenceofasuffIcIentnumberofapproprIatelytraIned
supportstaff.DnefrequentlyoverlookedIssuethatcontrIbutestothe
P.J5
negatIveImpressIongeneratedbysomeanesthesIologypractIcescentersonbeIngcertaIn
thereIssomeoneavaIlabletoanswerthetelephoneat all timesdurIngthehourssurgeons,
otherphysIcIans,andDFschedulIngdesksarelIkelytocall.ThIsseemInglytrIvIal
componentofpractIcemanagementIsveryImportanttothesuccessofananesthesIology
practIceasabusInesswhoseprIncIpalcustomersarethesurgeons.CertaInlythereIsa
commercIalserverclIentrelatIonshIpbothwIththepatIentandthepurchaserofhealth
care;however,theunIquelysymbIotIcnatureoftherelatIonshIpbetweensurgeonsand
anesthesIologIstsIssuchthatavaIlabIlItyevenforsImplejustwantedtoletyouknow
telephonecallsIsgenuInelyImportant.ThepersonwhoanswersthetelephoneIsthe
representatIveofthepractIcetotheworldandmusttakethatresponsIbIlItyserIously.
FromamanagementstandpoInt,sIgnIfIcantImpactonthesuccessofthepractIceasa
busInessoftenhIngesonsuchdetaIls.Further,anesthesIologIstsshouldalwayshave
permanentpersonalelectronIcpagersandrelIablemobIletelephones(ortheradIo
equIvalent)tofacIlItatecommunIcatIonsfromothermembersofthedepartmentorgroup
andfromsupportpersonnel.ThIsmaysoundIntrusIve,buttheunusualposItIonof
anesthesIaprofessIonalsInthespectrumofhealthcareworkersmandatesthIsfeatureof
managIngananesthesIologypractIce.AnesthesIologyprofessIonalsshouldhaveno
hesItatIonaboutspendIngtheIrownpractIceIncometodoso.ThesymbolIsmaloneIs
obvIous.
Anesthesia Equipment and Equipment Maintenance
ProblemswIthanesthesIaequIpmenthavebeendIscussedforsometIme.
14,15,16
However,
comparedwIthhumanerror,overtequIpmentfaIlurerarelycausesIntraoperatIvecrItIcal
IncIdents
17
ordeathsresultIngfromanesthesIacare.AsIdefromtheobvIoushumanerrors
InvolvIngmIsuseoforunfamIlIarItywIththeequIpment,whentherareequIpmentfaIlure
doesoccur,ItoftenappearsthatcorrectmaIntenanceandservIcIngoftheapparatushas
notbeendone.TheseIssuesbecomethefocusofanesthesIapractIcemanagementefforts,
whIchcouldhavesIgnIfIcantlIabIlItyImplIcatIonsbecausetherecanoftenbeconfusIonor
evendIsputesaboutprecIselywhoIsresponsIbleforarrangIngmaIntenanceofthe
anesthesIaequIpmentthefacIlItyorthepractItIonerswhouseItandcollectpractIce
IncomefromthatactIvIty.nmanycases,thefacIlItyassumestheresponsIbIlIty.n
sItuatIonsInwhIchthatIsnottrue,however,ItIsnecessaryforthepractItIonersto
recognIzethatresponsIbIlItyandseekhelpsecurIngaservIcearrangement,becausethIsIs
lIkelyanunfamIlIaroblIgatIonforclInIcIans.
ProgramsforanesthesIaequIpmentmaIntenanceandservIcehavebeenoutlIned.
1,18
A
dIstInctIonIsmadebetweenfaIlureresultIngfromprogressIvedeterIoratIonofequIpment,
whIchshouldbepreventablebecauseItIsobservableandshouldprovokeapproprIate
remedIalactIon,andcatastrophIcfaIlure,whIch,realIstIcally,oftencannotbepredIcted.
PreventIvemaIntenanceformechanIcalpartsIscrItIcalandInvolvesperIodIcperformance
checksevery4to6months.Also,anannualsafetyInspectIonofeachanesthetIzIng
locatIonandtheequIpmentItselfIsnecessary.ForequIpmentservIce,anexcellent
mechanIsmIsarelatIvelyelaboratecrossreferencesystem(possIblykepthandwrIttenIna
notebookbutIdealformaIntenanceonanelectronIcspreadsheetprogram)toIdentIfyboth
thedevIceneedIngservIceandalsothemechanIsmtosecuretheneededmaIntenanceor
repaIr.
EquIpmenthandlIngprIncIplesarestraIghtforward.8eforepurchase,ItmustbeverIfIed
thataproposedpIeceofequIpmentmeetsallapplIcablestandards,whIchwIllusuallybe
truewhendealIngwIthrecognIzedmajormanufacturers.Therenewedeffortsofsome
facIlItyadmInIstratorstosavemoneybyattemptIngtofIndrefurbIshedanesthesIa
machInesandmonItorIngsystemsshouldprovokethoroughrevIewbytheInvolved
practItIoners.DnarrIval,electrIcalequIpmentmustbecheckedforabsenceofhazard
(especIallyleakageofcurrent)andcomplIancewIthapplIcableelectrIcalstandards.
ComplexequIpmentsuchasanesthesIamachInesandventIlatorsshouldbeassembledand
checkedoutbyarepresentatIvefromthemanufacturerormanufacturer'sagent.Thereare
potentIaladversemedIcolegalImplIcatIonswhenrelatIvelyuntraInedpersonnelcertIfya
partIcularpIeceofnewequIpmentasfunctIonIngwIthInspecIfIcatIon,evenIftheydoIt
perfectly.DnarrIval,asheetorsectIonInthedepartmentalmasterequIpmentlogmustbe
createdwIththemake,model,serIalnumber,andInhouseIdentIfIcatIonforeachpIeceof
capItalequIpment.ThIsnotonlyallowsImmedIateIdentIfIcatIonofanyequIpment
InvolvedInafuturerecallorproductalert,butalsoservesasthepermanentreposItoryof
therecordofeveryproblem,problemresolutIon,maIntenance,andservIcIngoccurrIng
untIlthatpartIcularequIpmentIsscrapped.ThIslogmustbekeptuptodateatalltImes.
TherehavebeenrarebutfrIghtenIngexamplesofpotentIallylethalproblemswIth
anesthesIamachInesleadIngtoproductalertnotIcesrequIrIngImmedIateIdentIfIcatIonof
certaInequIpmentandItsservIcestatus.tIsalsoveryImportanttoInvolvethe
manufacturer'srepresentatIveInpreandInservIcetraInIngforthosewhowIllusethenew
equIpment.AnesthesIasystemswIththeIrventIlatIonandmonItorIngcomponentshave
becomesIgnIfIcantlymoreIntegratedandmorecomplex,partIcularlyastheyare
IncreasInglyelectronIcandlessmechanIcal.AccordIngly,ItIscrItIcalthatanesthesIa
professIonalsareproperlytraInedtousetheIrequIpmentsafely.TheperceptIonthat
InadequatetraInIngIscommonandthatthIsrepresentsathreattopatIentsafetyhasled
theAnesthesIaPatIentSafetyFoundatIontoInItIateacampaIgnurgInganesthesIa
departmentsandgroupstoensureorganIzedverIfIedcompletetraInIngofallprofessIonals
whowIllusethIsnewtechnology.
19
Service
8eyondtheadmInIstratIvelIabIlItyImplIcatIons,precIselywhattypeofsupportpersonnel
shouldmaIntaInandservIcemajoranesthesIaequIpmenthasbeenwIdelydebated.Some
groupsordepartmentsrelyonfactoryservIcerepresentatIvesfromtheequIpment
manufacturersforallattentIontoequIpment,othersengageIndependentservIce
contractors,andstIllother(oftenlarger)departmentshaveaccesstopersonnel(eIther
engIneersand/ortechnIcIans)permanentlywIthIntheIrfacIlIty.ThesIngleunderlyIng
prIncIpleIsclear:theperson(s)doIngpreventIvemaIntenanceandservIceonanesthesIa
equIpmentmustbequalIfIed.AnesthesIapractItIonersmaywonderhowtheycanassess
thesequalIfIcatIons.ThebestwayIstounhesItatInglyaskpertInentquestIonsaboutthe
educatIon,traInIng,andexperIenceofthoseInvolved,IncludIngaskIngforreferencesand
speakIngtosupervIsorsandmanagersresponsIbleforthosedoIngthework.Whetheran
engIneerIngtechnIcIanwhospentaweekatacourseatafactorycanperformthemost
complexrepaIrsdependsonavarIetyoffactors,whIchcanbeInvestIgatedbythe
practItIonersultImatelyusIngtheequIpmentInthecareofpatIents.FaIluretobeInvolved
InthIsoversIghtfunctIonexposesthepractIcetoIncreasedlIabIlItyIntheeventofan
untowardoutcomeassocIatedwIthImproperlymaIntaInedorservIcedequIpment.
FeplacementofobsoleteanesthesIamachInesandmonItorIngequIpmentIsakeyelement
ofarIskmodIfIcatIonprogram.TenyearsIsoftencItedasanestImatedusefullIfeforan
anesthesIamachIne,butalthoughanASAstatementrepeatsthatIdea,Italsonotesthat
theASApromulgatedCuIdelInesfor0etermInIngAnesthesIa|achIneDbsolescenceIn
2004that
P.J6
doesnotsubscrIbetoanyspecIfIctImeInterval.AnesthesIamachInesconsIderablymore
than20yearsoldlIkelydonotmeetcertaInofthesafetystandardsnowInforcefornew
machInes(suchasvaporIzerlockout,freshgasratIoprotectIon,andautomatIcenablIngof
theoxygenanalyzer)and,unlessextensIvelyretrofItted,donotIncorporatethenew
technologythatadvancedveryrapIdlydurIngthe1980s,muchofItdIrectlyrelatedtothe
efforttopreventuntowardIncIdents.Further,ItappearsthatthIstechnologywIllcontInue
toadvance,partIcularlybecauseoftheadoptIonofanesthesIaworkstatIonstandardsby
theEuropeanEconomIcUnIonthatareaffectInganesthesIamachInedesIgnworldwIde.
NotethatsomeanesthesIaequIpmentmanufacturers,anxIoustomInImIzetheIrown
potentIallIabIlIty,haverefusedtosupport(wIthpartsandservIce)someoftheoldestof
theIrpIeces(partIcularlygasmachInes)stIllInuse.ThIsdIsownIngofequIpmentbyItsown
manufacturerIsaverystrongmessagetopractItIonersthatsuchequIpmentmustbe
replacedassoonaspossIble.
ShouldapIeceofequIpmentfaIl,ItmustberemovedfromservIceandareplacement
substItuted.Croups,departments,andfacIlItIesareoblIgatedtohavesuffIcIentbackup
equIpmenttocoveranyreasonableIncIdenceoffaIlure.TheequIpmentremovedfrom
servIcemustbeclearlymarkedwIthapromInentlabel(soItIsnotreturnedIntoservIceby
awellmeanIngtechnIcIanorpractItIoner)contaInIngthedate,tIme,persondIscoverIng,
andthedetaIlsoftheproblem.TheresponsIblepersonnelmustbenotIfIedsotheycan
removetheequIpment,makeanentryInthelog,andInItIatetherepaIr.AsIndIcatedIn
theprotocolforresponsetoanadverseevent,
1J
apIeceofequIpmentInvolvedor
suspectedInananesthesIaaccIdentmustbeImmedIatelysequesteredandnottouchedby
anybodypartIcularlynotbyanyequIpmentservIcepersonnel.fasevereaccIdent
occurred,ItmaybenecessaryfortheequIpmentInquestIontobeInspectedatalatertIme
byagroupconsIstIngofqualIfIedrepresentatIvesofthemanufacturer,theservIce
personnel,theplaIntIff'sattorney,theInsurancecompanIesInvolved,andthepractItIoner's
defenseattorney.TheequIpmentshouldthusbeImpoundedfollowInganadverseevent
andtreatedsImIlarlytoanyobjectInaforensIcchaInofevIdence,wIthcareful
documentatIonofpartIesIncontactwIthandresponsIbleforsecurIngtheequIpmentIn
questIonfollowIngsuchanevent.Also,majorequIpmentproblemsmay,Insome
cIrcumstances,reflectapatternoffaIlureduetoadesIgnormanufacturIngfault.These
problemsshouldbereportedtotheF0A's|edIcal0evIceProblemFeportIngsystem
20
vIa
|edWatchonFormJ500(foundatwww.fda.gov/medwatch/Index.html,ortelephone800
F0A1088).ThIssystemacceptsvoluntaryreportsfromusersandrequIresreportsfrom
manufacturerswhenthereIsknowledgeofamedIcaldevIcebeIngInvolvedInaserIous
IncIdent.WhetherornotfIlIngsuchareportwIllhaveaposItIveImpactInsubsequent
lItIgatIonIsImpossIbletoknow,butItIsaworthwhIlepractIcemanagementpoIntthat
needstobeconsIderedIntheunlIkelybutImportantInstanceofarelevanteventInvolvIng
equIpmentfaIlure.
Malpractice Insurance
AllpractItIonersneedlIabIlItyInsurancecoveragespecIfIcforthespecIaltyandroleIn
whIchtheyarepractIcIng.tIsabsolutelycrItIcalthatapplIcantsformedIcallIabIlIty
InsurancebecompletelyhonestInInformIngtheInsurerwhatdutIesandproceduresthey
perform.FaIluretodoso,eItherfromcarelessnessorfromafoolIshlymIsguIdeddesIreto
reducetheresultIngpremIum,maywellresultInretrospectIvedenIalofInsurance
coverageIntheeventofanuntowardoutcomefromanactIvItytheInsurerdIdnotknow
theInsuredengagedIn.
ProofofadequateInsurancecoverageIsusuallyrequIredtosecureorrenewprIvIlegesto
practIceatahealthcarefacIlIty.ThefacIlItymayspecIfycertaInmInImumpolIcylImItsIn
anattempttolImItItsownlIabIlItyexposure.tIsdIffIculttosuggestspecIfIcdollar
amountsforpolIcylImItsbecausethedetaIlsofpractIcevarysomuchamongsItuatIons
andlocatIons.ThemalpractIcecrIsIsofthe1980seasedsIgnIfIcantlyIntheearly1990sfor
anesthesIaprofessIonals,largelybecauseofthedecreaseInnumberandseverItyof
malpractIceclaImsresultIngfromanesthesIacatastrophesasanesthesIacareIntheUnIted
Statesbecamesafer.
21,22,2J
TheexactanalysIsofthIsphenomenoncanbedebated,
24,25
but
ItIsasImplefactthatmalpractIceInsurancerIskratIngshavebeendecreasedand
premIumsforanesthesIaprofessIonalshavenotbeenIncreasedatthesamerateasfor
otherspecIaltIesoverthepast15yearsand,Inmanycases,haveactuallydecreased.n
2008,coveragelImItsofS1mIllIon/SJmIllIonarestIllcommonandwouldseemthe
mInImumadvIsable.ThIspolIcyspecIfIcatIonusuallymeansthattheInsurerwIllcoverup
toS1mIllIonlIabIlItyperclaImanduptoSJmIllIontotalperyear,butthIstermInologyIs
notnecessarIlyunIversal.Therefore,anesthesIaprofessIonalsmustbeabsolutelycertaIn
whattheyarebuyIngwhentheyapplyformalpractIceInsurance.Eventhough
anesthesIologIstshavenotrecentlysufferedagreatnumberofverylargemalpractIce
paymentsorjuryverdIcts,
26
InspecIfIcpartsoftheUnItedStatesknownforapatternof
exorbItantsettlementsandjuryverdIcts,lIabIlItycoveragelImItsofS2mIllIon/S5mIllIon
orevengreatermaybeprudent.AnaddItIonalfeatureInthIsregardIsthepotentIalto
employumbrellalIabIlItycoverageabovethelImItsofthebasepolIcy,aswIllbenoted.
Background
ThefundamentalmechanIsmofmedIcalmalpractIceInsurancechangedsIgnIfIcantlyInthe
lastJdecadesbecauseoftheneedforInsurancecompanIestohavebetterwaystopredIct
theIrlosses(amountspaIdInsettlementsandjudgments).TradItIonally,medIcallIabIlIty
InsurancewassoldonanoccurrencebasIs,meanIngthatIftheInsurancepolIcywasIn
forceatthetImeoftheoccurrenceofanIncIdentresultIngInaclaIm,wheneverwIthIn
thestatuteoflImItatIonsthatclaImmIghtbefIled,thepractItIonerwouldbecovered.
DccurrenceInsurancewassomewhatmoreexpensIvethanthealternatIveclaImsmade
polIcIes,butwasseenasworthItbysome(many)practItIoners.ThesepolIcIescreated
someopenendedexposurefortheInsurerthatsometImesledtounexpectedlargelosses,
evensomelargeenoughtothreatentheexIstenceoftheInsurancecompany.Asaresult,
medIcalmalpractIceInsurershaveconvertedalmostexclusIvelytoclaImsmadeInsurance,
whIchcoversclaImsthatarefIledwhIletheInsuranceIsInforce.PremIumratesforthe
fIrstyearaphysIcIanIsInpractIcearerelatIvelylowbecausethereIslesslIkelIhoodofa
claImcomIngIn(amajorItyofmalpractIcesuItsarefIled1toJyearsaftertheeventIn
questIon).ThepremIumsusuallyIncreaseyearlyforthefIrst5yearsandthenthepolIcyIs
consIderedmature.TheIssuecomeswhenthephysIcIanlater,forwhateverreason,must
changeInsurancecompanIes(e.g.,becauseofrelocatIontoanotherstate).fthephysIcIan
sImplydIscontInuesthepolIcyandaclaImIsfIledthenextyear,therewIllbenoInsurance
coverage.Therefore,thephysIcIanmustsecuretaIlcoverage,sometImesforamInImum
numberofyears(e.g.,5)or,moreoften,IndefInItelytoguaranteelIabIlItyInsurance
protectIonforclaImsfIledafterthephysIcIanIsnolongerprImarIlycoveredbythat
InsurancepolIcy.tmaybepossIbleInsomecIrcumstancestopurchasetaIlcoveragefrom
adIfferentInsurerthanwasInvolvedwIththeprImarypolIcy,butbyfarthemostcommon
thIngdoneIstosImplyextendtheexIstIngInsurancecoveragefortheperIodofthetaIl.
ThIsveryoftenyIeldsabIllfortheentIretaIl
P.J7
coveragepremIum,whIchcanbequItesIzable,potentIallystaggerIngaphysIcIanwho
sImplywantstomovetoanotherstatewherehIsorherexIstIngInsurancecompanyIsnot
lIcensedtoorrefusestodobusIness.ndIvIdualsItuatIonswIllvarywIdely,butItIs
reasonableforanesthesIologIstsorganIzedIntoafIscalentItytoconsIderthIsIssueatthe
tImeoftheInceptIonofthegroupandrecordtheIrpolIcydecIsIonsInwrItIng,ratherthan
facIngthepotentIallydIffIcultquestIonofhowtotreatoneIndIvIduallater.Dther
strategIeshaveoccasIonallybeenemployedwhenInsurIngthetaIlperIod,IncludIng
convertIngtheprevIouspolIcytoparttImestatusforaperIodofyears,andpurchasIng
nosecoveragefromthenewInsurerthatIs,payInganInItIalhIgheryearlypremIum
wIththenewInsurer,whothenwIllcoverclaImsthatmayoccurdurIngthetaIlperIod.
WhateverstrategyIsadopted,ItIscrItIcalthattheIndIvIdualpractItIonerIsabsolutely
certaInthoughpersonalverIfIcatIonthatheorsheIsthoroughlycoveredatthetImeofany
transItIon.ThepotentIalstakesaremuchtoogreattoleavesuchImportantIssuessolelyto
anoffIceclerk.Further,apractItIonerarrIvIngInanewlocatIonIsoftenfIllInganeedor
voIdandIsurgedtobegInclInIcalworkassoonaspossIblebyotherswhohavebeen
shoulderInganIncreasedload.tIsessentIalthatthenewarrIvalverIfywIthconfIrmatIon
InwrItIng(oftencalledabInder)thatmalpractIcelIabIlItyInsurancecoverageIsInforce
beforethereIsanypatIentcontact.
AnothercomponenttothelIabIlItyInsurancesItuatIonIsconsIderatIonoftheadvIsabIlIty
ofpurchasIngyetanothertypeofInsurancecalledumbrella coverage,whIchIsactIvatedat
thetImeoftheneedtopayaclaImthatexceedsthelImItsofcoverageonthestandard
malpractIcelIabIlItyInsurancepolIcy.8ecausesuchanenormousclaImIsextremely
unlIkely,manypractItIonersaretemptedtoforgothecomparatIvelymodestcostofsuch
InsurancecoverageInthenameofeconomy.Asbefore,ItIseasytoseethatthIsIs
potentIallyaveryfalseeconomyIfthereIsahugeclaIm.PractItIonersshouldconsultwIth
theIrfInancIalmanagersandadvIsors,butItIslIkelythatItwouldbeconsIderedwIse
managementtopurchaseumbrellalIabIlItyInsurancecoverage.
|edIcalmalpractIceInsurersarebecomIngIncreasInglyactIveIntryIngtoprevent
IncIdentsthatwIllleadtoInsuranceclaIms.TheyoftensponsorrIskmanagementsemInars
toteachpractIcesandtechnIquestolessenthechancesoflIabIlItyclaImsand,Insome
cases,suggest(orevenmandate)specIfIcpractIces,suchasstrIctdocumentedcomplIance
wIththeASAStandardsfor8asIcAnesthetIc|onItorIng.nreturnforattendanceatsuch
eventsand/orthesIgnIngofcontractsstatIngthatthepractItIonerwIllfollowcertaIn
guIdelInesorstandards,theInsureroftengIvesadIscountonthelIabIlItyInsurance
premIum.Clearly,ItIssoundpractIcemanagementstrategyforpractItIonerstopartIcIpate
maxImallyInsuchprograms.LIkewIse,someInsurersmakecoveragecondItIonalonthe
consIstentImplementatIonofcertaInstrategIessuchasmInImalmonItorIng,even
stIpulatIngthatthepractItIonerwIllnotbecoveredIfItIsfoundthattheguIdelIneswere
beIngconscIouslyIgnoredatthetImeofanuntowardevent.AgaIn,ItIsobvIouslywIse
fromapractIcemanagementstandpoInttocooperatefullywIthsuchstIpulatIons.
Response to an Adverse Event
nspIteofthedecreasedIncIdenceofanesthesIacatastrophes,evenwIththeverybestof
practIce,ItIsstatIstIcallylIkelythateachanesthesIologIstatleastonceInhIsorher
professIonallIfewIllbeInvolvedInamajoranesthesIaaccIdent(seeChapter4).PrecIsely
becausesuchaneventIsrare,veryfewarepreparedforIt.tIsprobablethattheInvolved
personnelwIllhavenorelevantpastexperIenceregardIngwhattodo.AlthoughanobvIous
resourceIsanotheranesthetIstwhohashadsomeexposureorexperIence,oneofthese
maynotbeavaIlableeIther.7arIousauthorshavedIscussedwhattodoInthat
event.
27,28,29
Cooper,etal.
J0
havethoughtfullypresentedtheapproprIateImmedIate
responsetoanaccIdentInastraIghtforward,logIcal,compactformat(thathasbeen
updated
1J
)thatshouldperIodIcallyberevIewedbyallanesthesIologypractItIonersand
shouldbeIncludedInallanesthesIapolIcyandproceduremanuals.ThIsadverseevents
protocolIsalsoalwaysImmedIatelyavaIlableatwww.apsf.org(FesourceCenter,and
ClInIcalSafetyTools).Unfortunately,however,theprIncIpalpersonnelInvolvedIna
sIgnIfIcantuntowardeventmayreactwIthsuchsurprIseorshockastotemporarIlylose
sIghtoflogIc.AtthemomentofrecognItIonthatamajoranesthetIccomplIcatIonhas
occurredorIsoccurrIng,helpmustbecalled.AsuffIcIentnumberofpeopletodealwIth
thesItuatIonmustbeassembledonsIteasquIcklyaspossIble.Forexample,IntheunlIkely
butstIllpossIbleeventthatanesophagealIntubatIongoesunrecognIzedlongenoughto
causeacardIacarrest,theImmedIateneedIsforenoughskIlledpersonneltoconductthe
resuscItatIveefforts,IncludIngmakIngthecorrectdIagnosIsandreplacIngthetubeIntothe
trachea.WhethertheanesthesIologIstapparentlyresponsIbleforthecomplIcatIonshould
dIrecttheImmedIateremedIaleffortswIlldependonthepersonandthesItuatIon.nsuch
acIrcumstance,ItwouldseemwIseforasenIororsupervIsInganesthesIologIstquIcklyto
evaluatethescenarIoandmakeadecIsIon.ThIspersonbecomestheIncIdentsupervIsor
andhasresponsIbIlItyforhelpIngpreventcontInuatIonorrecurrenceoftheIncIdent,for
InvestIgatIngtheIncIdent,andforensurIngdocumentatIonwhIletheorIgInalandhelpIng
anesthesIologIstsfocusoncarIngforthepatIent.Asnoted,InvolvedequIpmentmustbe
sequesteredandnottoucheduntIlsuchtImeasItIscertaInthatItwasnotInvolvedInthe
IncIdent.
ftheaccIdentIsnotfatal,contInuIngcareofthepatIentIscrItIcal.|easuresmaybe
InstItutedtohelplImItdamagefrombraInhypoxIa.Consultantsmaybehelpfulandshould
becalledwIthouthesItatIon.fnotalreadyInvolved,thechIefofanesthesIologymustbe
notIfIedaswellasthefacIlItyadmInIstrator,rIskmanager,andtheanesthesIologIst's
Insurancecompany.TheselatterarecrItIcaltoallowconsIderatIonofImmedIateeffortsto
lImItlaterfInancIalloss.(LIkewIse,thereareoftenprovIsIonsInmedIcalmalpractIce
InsurancepolIcIesthatmIghtlImItorevendenyInsurancecoverageIfthecompanyIsnot
notIfIedofanyreportableeventImmedIately.)fthereIsanInvolvedsurgeonofrecord,he
orsheprobablywIllfIrstnotIfythefamIly,buttheanesthesIologIstandothers(rIsk
manager,InsurancelosscontroloffIcer,orevenlegalcounsel)mIghtapproprIatelybe
Includedattheoutset.FulldIsclosureoffactsastheyarebestknownwIthnoconfessIons,
opInIons,speculatIon,orplacIngofblameIscurrentlystIllbelIevedtobethebest
presentatIon.AnyattempttoconcealorshadethetruthwIlllateronlyconfoundan
alreadydIffIcultsItuatIon.DbvIously,comfortandsupportshouldbeoffered,IncludIng,If
approprIate,theservIcesoffacIlItypersonnelsuchasclergy,socIalworkers,and
counselors.ThereIsanewmovementInmedIcalrIskmanagementandInsurance
advocatIngImmedIatefulldIsclosuretothevIctImorsurvIvors,IncludIngconfessIonsof
medIcaljudgmentandperformanceerrorswIthattendantsIncereapologIes.fIndIcated,
earlyoffersofreasonablecompensatIonmaybeIncluded.TherehavebeenInstanceswhen
thIsoverallstrategyhaspreventedthefIlIngofamalpractIcelawsuItandhasbeen
applaudedbyallInvolvedasanexampleofashIftfromthecultureofblamewIth
punIshmenttoajustculturewIthrestItutIon.AwIdespreadmovementtoImplement
ImmedIatedIsclosureandapologyhasreceIvedsupport.
J1,J2
CertaInstateshaveenactedorproposedsocalled'msorry!legIslatIonIntendedto
preventanyexplanatIonorapologyfrombeIngusedasplaIntIff'sevIdenceInasubsequent
malpractIcesuIt.TheImportanceofthepatIent'sperspectIve
P.J8
onaserIousadverseanesthesIaeventwashIghlIghtedInarIvetIngaccountofthestorIes
ofbothsurvIvorsofanesthesIacatastrophesandthefamIlIesofpatIentswhodIed.
JJ
n
eachcase,onemaInmessagewastheenormousnegatIveImpactoftheperceIvedfaIlure
oftheInvolvedanesthesIaprofessIonalsandtheIrInstItutIonstosharedetaIledInformatIon
aboutwhatexactlyhappened.ArecentrevIewsummarIzeswhatpatIentswantandexpect
followInganadverseevent.
J4
LaudableasthIspolIcyofImmedIatefulldIsclosureand
apologymaysound,ItwouldbemandatoryforanIndIvIdualpractItIonertocheckwIththe
InvolvedlIabIlItyInsurancecarrIer,thepractIcegroup,andthefacIlItyadmInIstratIon
beforeattemptIngIt.
TheprImaryanesthesIaprovIderandanyothersInvolvedmustdocumentrelevant
InformatIon.Never,everchangeanyexIstIngentrIesInthemedIcalrecord.WrItean
amendmentnoteIfneeded,wIthcarefulexplanatIonofwhyamendmentIsnecessary,
partIcularlystressIngexplanatIonsofprofessIonaljudgmentsInvolved.Stateonlyfactsas
theyareknown.|akenojudgmentsaboutcausesorresponsIbIlItyanddonotpoInt
fIngers.ThesameguIdelInesholdtrueforthefIlIngoftheIncIdentreportInthefacIlIty,
whIchshouldbedoneassoonasIspractIcal.Further,alldIscussIonswIththepatIentor
famIlyshouldbecarefullydocumentedInthemedIcalrecord.FecognIzIngthatdetaIled
memorIesoftheeventsmayfadeInthe1toJyearsbeforethepractItIonermayface
deposItIonquestIonsaboutexactlywhathappened,ItIspossIblethatItwIllbe
recommended,ImmedIatelyaftertheIncIdent,thattheInvolvedclInIcalpersonnelsIt
downassoonaspractIcalandwrIteouttheIrownpersonalnotes,whIchwIllInclude
opInIonsandImpressIonsaswellasmaxImallydetaIledaccountsoftheeventsasthey
unfolded.ThesepersonalnotesarenotpartofthemedIcalrecordorthefacIlItyfIles.
ThesenotesshouldbewrIttenInthephysIcalpresenceofanInvolvedattorney
representIngthepractItIoner,evenIfthIsIsnotyetthespecIfIcdefenseattorneysecured
bythemalpractIceInsurancecompany,andthenthatattorneyshouldtakepossessIonof
andkeepthosenotesascasematerIal.ThIsstrategyIsIntendedtomakethepersonal
notesattorneyclIentworkproduct,andthusnotsubjecttoforceddIscovery
(revelatIon)byotherpartIestothecase.
FollowupaftertheImmedIatehandlIngoftheIncIdentwIllInvolvetheprImary
anesthesIologIstbutshouldagaInbedIrectedbyasenIorsupervIsor,whomayormaynot
bethesamepersonastheIncIdentsupervIsor.ThefollowupsupervIsorverIfIesthe
adequacyandcoordInatIonofongoIngcareofthepatIentandfacIlItatescommunIcatIon
amongallInvolved,especIallywIththerIskmanager.Lastly,ItIsnecessarytoverIfythat
adequateposteventdocumentatIonIstakIngplace.
Dfcourse,ItIsexpectedthatsuchanadverseeventwIllbedIscussedIntheapplIcable
morbIdItyandmortalItymeetIng.tIsnecessary,however,tocoordInatethIsactIvItywIth
theInvolvedrIskmanagerandattorneysoastobecompletelycertaInthatthecontents
andconclusIonsofthedIscussIonareclearlyconsIderedpeerrevIewactIvIty,andthusare
shIeldedfromdIscoverybytheplaIntIffs'attorney.
UnpleasantasthIsIstocontemplate,ItIsbettertohaveaclearplanandexecuteItInthe
eventofanaccIdentcausIngInjurytoapatIent.7IgorousImmedIateInterventIonmay
Improvetheoutcomeforallconcerned.
Practice Essentials
The Job Market for Anesthesia Professionals
WhIleItIstruethatInthemId1990s,forthefIrsttIme,uncertaIntyfacedresIdents
fInIshInganesthesIologytraInIngbecauseofaperceptIonthattherewerenotenoughjobs
forphysIcIananesthesIologIstsavaIlable,thatconceptfadedquIckly.AtensIonbetween
supplyanddemanddeveloped,wIthasIgnIfIcantongoIngcomponentoftheIdeathatthere
IsanoverallshortageofanesthesIaprofessIonals.tappearsthatlateInthefIrstdecadeof
the2000sthIsfundamentalparadIgmwIllpersIst.WIththefadIngoftheconceptthat
managedcarewouldsIgnIfIcantlyreducethedemandformedIcalservIcesandalsothe
agIngofthe8aby8oompopulatIon,ItIsclearthatthereIsasIgnIfIcantshortageofall
medIcalprofessIonalsIntheUnItedStates,andthIsespecIallyIncludesanesthesIa
professIonals.
Types of Practice
AtleastthroughthefIrstdecadeofthe21stcentury,resIdentsfInIshInganesthesIology
traInIngwIllstIllneedtochooseamongthreefundamentalpossIbIlItIes:academIcpractIce
InateachInghospItalenvIronment;apractIceexclusIvelyofpatIentcareIntheprIvate
practIcemarketplace;andapractIceexclusIvelyofpatIentcareasanemployeeofa
healthcaresystem,organIzatIon,orfacIlIty.
TeachInghospItalswIthanesthesIologyresIdencyprogramsconstItuteonlyaverysmall
fractIonofthetotalnumberoffacIlItIesrequIrInganesthesIaservIces.TheseacademIc
departmentstendtobeamongthelargestgroupsofanesthesIologIsts,buttheaggregate
fractIonoftheentIreanesthesIologIstpopulatIonIssmall.tIsInterestIng,however,that
bythenatureofthesystem,mostresIdentsfInIshIngtheIrtraInInghavealmostexclusIvely
beenexposedonlytoacademIcanesthesIology.AccordIngly,fInIshIngresIdentsInthepast
oftenwerecomparatIvelyunpreparedtoevaluateandentertheanesthesIologyjob
market.
SpecIaltycertIfIcatIonbytheA8AshouldbethegoalofallanesthesIaresIdencygraduates.
SomefInIshIngresIdentswhoknowtheyareeventuallyheadedforprIvatepractIcehave
startedtheIrattendIngcareersasfulltImejunIorfacultyInanacademIcdepartment.ThIs
allowsthemtoobtaInsomeclInIcalpractIceandsupervIsoryexperIenceandoffersthem
theopportunItytopreparefortheA8AexamInatIonsInthenurturIng,protectedacademIc
envIronmentwIthwhIchtheyarefamIlIar.|ostresIdents,however,donotbecomejunIor
faculty;theyacceptpractIceposItIonsImmedIately.8utsuchnewlytraInedresIdents
shouldtakeIntoaccounttheneedtobecomeA8AcertIfIedandbuIldIntotheIrnew
practIcearrangementsthestIpulatIonthattherewIllbetImeandconsIderatIongIven
towardthIsgoal.
Academic Practice
ForthosewhochoosetostayInacademIcpractIce,anumberofspecIfIccharacterIstIcsof
academIcanesthesIadepartmentscanbeusedasscreenIngquestIons.
How big is the department?JunIorfacultysometImescangetlostInverybIgdepartments
andbetreatedaslIttlebetterthanglorIfIedsenIorresIdents.Dntheotherhand,the
avaIlabIlItyofsubspecIaltyservIceopportunItIesandsIgnIfIcantresearchandeducatIonal
resourcescanmakelargedepartmentsextremelyattractIve.nsmalleracademIc
departments,theremaybefewerresources,butthelIkelIhoodofbeIngquIcklyacceptedas
avaluedandcontrIbutIngmemberoftheteachIngfaculty(andresearchteam,If
approprIate)maybehIgher.nverysmalldepartments,thenumberofexpectatIons,
projects,andInvolvementscouldpotentIallybeoverwhelmIng.AddItIonally,asmall
departmentmaylackadedIcatedresearchInfrastructure,soItmaybenecessaryforthe
facultyInthIssItuatIontocollaboratewIthother,largerdepartmentstoaccomplIsh
meanIngfulacademIcwork.
P.J9
What exactly is expected of junior faculty?fteachIngoneresIdentclasseveryotherweek
Isstandard,thecandIdatemustenthusIastIcallyacceptthatassIgnmentandtheattendant
preparatIonworkandtImeupfront.LIkewIse,IfItIsexpectedthatjunIorfacultywIll,by
defInItIon,beactIvelyInvolvedInpublIshableresearch,specIfIcplansforprojectstowhIch
thecandIdateIsamenablemustbemade.nsuchsItuatIons,clearstIpulatIonsabout
startupresearchfundIngandnonclInIcaltImetocarryouttheprojectsshouldbeobtaIned
asmuchaspossIble(althoughclInIcalworkloaddemandsandrevenuegeneratIon
expectatIonsmaymakethIsverydIffIcultInsomesettIngs).PartIcularlyImportantIs
determInIngwhattheexpectatIonIsconcernIngoutsIdefundIng.Forexample,Itcanbea
rudeshocktorealIzethatprojectswIllsuddenlyhaltafter2yearsIfextramuralfundIng
hasnotbeensecured.
What are the prospects for advancement?|anynewjunIorfacultydIrectlyoutofresIdency
startwIthmedIcalschoolappoIntmentsasInstructorsunlessthereIssomethIngelseIn
theIrbackgroundthatImmedIatelyqualIfIesthemasassIstantprofessors.tIswIseto
understandfromthebegInnIngwhatIttakesInthatdepartmentandmedIcalschoolto
facIlItateacademIcadvancement.TheremaybemorethanoneacademIctrack;the
tenuretrack,forexample,usuallydependsonpublIshedresearchwhereastheclInIcalor
teachertrackrelIesmoreheavIlyonone'svalueInpatIentcareandasaclInIcaleducator.
ThecrIterIaforpromotIonmaybeclearlyspelledoutbytheInstItutIonnumberofpapers
needed,InvolvementandrecognItIonatvarIouslevels,grantssubmIttedandfunded,and
soonorthesystemmaybelessrIgIdanddependmoreheavIlyonthedepartment
chaIrman'sandotherfacultyevaluatIonsandrecommendatIons.neIthercase,careful
InquIrybeforeacceptIngtheposItIoncanavertlatersurprIseanddIsappoIntment.
How much does it pay?TradItIonally,academIcanesthesIologIstshavenotearnedquIteas
muchasthoseInprIvatepractIceInreturnfortheadvantageofmorepredIctable
schedules,contInuedIntellectualstImulatIon,andtheIntangIblerewardsofacademIc
success.ThereIsnowgreatactIvItyandattentIonconcernIngreImbursementof
anesthesIologIsts,andItIsdIffIculttopredIctfutureIncomeforanyanesthesIology
practIcesItuatIon.However,alloftheforcesInfluencIngpaymentforanesthesIacaremay
sIgnIfIcantlydImInIshthetradItIonalIncomedIfferentIalbetweenacademIcandprIvate
practIce.nsomecases,afacultymemberIsexclusIvelyanemployeeoftheInstItutIon,
whIchbIllsandcollectsornegotIatesgroupcontractsforthepatIentcarerenderedbythe
facultymember,andthenpaysanegotIatedamount(eItheranabsolutedollarfIgureora
floatIngamountbasedonvolumeand/orcollectIonsoracombInatIonofthetwo)that
constItutesthefacultyperson'sentIreIncome.Underothermuchlesscommon
arrangements,facultymembersthemselvesmaybeabletobIllandcollectornegotIate
contractsfortheIrclInIcalwork.SomeInstItutIonshavea(comparatIvelysmall)academIc
salaryfromthemedIcalschoolforbeIngonthefaculty,butmanydonot;somechannel
varIableamountsofmoney(fromsocalledPartAclInIcalrevenue)IntotheacademIc
practIceInrecognItIonofteachIngandadmInIstratIonorsImplyasasubsIdyforneeded
servIce.AsalaryfromthemedIcalschool,Ifextant,IsthensupplementedsIgnIfIcantlyby
thepractIceIncome.Usually,thefacultywIllbemembersofsometypeofgroupor
practIceplan(eItherfortheanesthesIadepartmentaloneortheentIrefacultyasawhole)
thatbIllsandcollectsornegotIatescontractsandthendIstrIbutesthepractIceIncometo
thefacultyunderanarrangementthatmustbeexamInedbythecandIdate.nmost
academIcInstItutIons,practIceexpensessuchasalloverheadandmalpractIceInsuranceas
wellasreasonablebenefIts,IncludIngdIscretIonaryfundsformeetIngs,subscrIptIons,
books,dues,andsoforth,areautomatIcallypartofthecompensatIonpackage,whIch
oftenmaynotbetrueInprIvatepractIceandmustbecountedInmakInganycomparIson.
AnImportantcorollaryIssueIsthatofthesourceofthesalarIesofthedepartment's
prImaryanesthesIaprovIdersresIdentsand,Insomecases,nurseanesthetIsts.Although
thehospItalusuallypaysforatleastsomeofthese,arrangementsvary,andItIsImportant
toascertaInwhetherthefacultypractIceIncomeIsalsoexpectedtocoverthecostofthe
prImaryprovIders.Dverall,ItIsreasonabletosoundoutfaculty,bothanesthesIologyand
others,regardIngthepastandlIkelyfuturecommItmentoftheInstItutIontothe
establIshmentandmaIntenanceofreasonablecompensatIonfortheexpectedInvolvement.
Private Practice in the Marketplace
DbvIously,rotatIonstoaprIvatepractIcehospItalInthefInalyearofanesthesIaresIdency
couldhelpgreatlyInthIsregard,butnotallresIdencyprogramsoffersuchopportunItIes.n
thatcase,thefInIshIngresIdentwhoIscertaInaboutgoIngIntoprIvatepractIcemustseek
InformatIononcareerdevelopmentandmentorsfromtheprIvatesector.
ArmedwIthasmuchInformatIonaspossIble,onefundamentalInItIalchoIceIsbetween
IndependentIndIvIdualpractIceandaposItIonwIthagroup(eItherasoleproprIetorshIp,
partnershIp,orcorporatIon)thatfunctIonsasasInglefInancIalentIty.ndependent
practIcemaybecomeIncreasInglylessvIableInmanylocatIonsbecauseoftheneedtobe
abletobIdforcontractswIthmanagedcareentItIes.However,whereIndependent
practIceIspossIble,ItusuallyfIrstInvolvesattemptIngtosecureclInIcalprIvIlegesata
numberofhospItalsorfacIlItIesIntheareaInwhIchonechoosestolIve.ThIsmaynot
alwaysbeeasy,andthIsIssuehasbeenthesubjectofmany(frequentlyunsuccessful)
antItrustsuItsoverrecentyears(seeAntItrustConsIderatIons).ThentheanesthesIologIst
makesItknowntotherespectIvesurgeoncommunItIesthatheorsheIsavaIlabletorender
anesthesIaservIcesandwaItsuntIlthereIsarequestforhIsorherservIces.The
anesthesIologIstobtaInstherequIsItefInancIalInformatIonfromthepatIentandthen
eItherIndIvIduallybIllsandcollectsforservIcesrenderedoremploysaservIcetodobIllIng
andcollectIonforapercentagefee(whIchwIllvarydependIngonthecIrcumstances,
especIallythevolumeofbusIness;forbIllIng[wIthoutschedulIngservIces]Itwouldbe
unlIkelytobe7or,atthemost,8ofactualcollectIons).
HowmuchoftheneededequIpmentandsupplIeswIllbeprovIdedbythehospItalorfacIlIty
andhowmuchbytheIndependentanesthesIologIstvarIeswIdely.fananesthesIologIst
spendsconsIderabletImeInoneoperatIngsuIte,heorshemaypurchaseananesthesIa
machIneexclusIvelyforhIsorherownuseandmoveItfromroomtoroomasneeded.tIs
lIkelytobeImpractIcaltomoveafullyequIppedanesthesIamachInefromhospItalto
hospItalonadaytodaybasIs.AmongthefeaturesofthIsstyleofpractIcearethe
collegIalItyandrelatIonshIpsofagenuIneprIvatepractIcebasedonreferralsandalsothe
abIlItytodecIdeIndependentlyhowmuchtImeonewantstobeavaIlabletowork.The
downsIdeIsthepotentIalunpredIctabIlItyofthedemandforservIceandthetImeneeded
toestablIshreferralpatternsandobtaInbookIngssuffIcIenttogeneratealIvableIncome.
WhenseekIngaposItIonwIthaprIvategroup,theapplIcantshouldsearchforpotentIal
practIceopportunItIesthroughwordofmouth,recruItIngletterssenttothetraInIng
programsupervIsor,journaladvertIsements,andplacementservIces(eIthercommercIalor
professIonal,suchasthatprovIdedattheASAannualmeetIng).SomeofthescreenIng
questIonsarethesameasforanacademIcposItIon,buttheremustbeevenmoreemphasIs
ontheexactdetaIlsofclInIcalexpectatIonsandfInancIalarrangements.SomeresIdents
fInIshresIdency(orfellowshIptraInIngtoanevengreaterextent)veryhIghlyskIlledIn
complex,dIffIcultanesthesIaprocedures.They
P.40
canbesurprIsedtofIndthatInsomeprIvatepractIcegroupsItuatIons,thejunIormost
anesthesIologIstmustwaItsometIme,perhapsevenyears,beforebeIngelIgIbletodo,for
example,openheartanesthesIa,andInthemeantImewIllmostlybeassIgnedmoreroutIne
orlesschallengInganesthetIcs.
FInancIalarrangementsInprIvategrouppractIcesvarywIdely.Somegroupsareloose
organIzatIonalallIancesofIndependentpractItIonerswhobIllandcollectseparatelyand
rotateclInIcalassIgnmentsandcallformutualconvenIence.|anygroupsactalsoasa
fIscalentIty,andtherearemanypossIblevarIatIonsonthIstheme.nmanycIrcumstances
Inthepast,newjunIormembersstartedoutasfunctIonalemployeesofthegroupfora
probatIonaryIntervalbeforebeIngconsIderedforfullmembershIporpartnershIp.ThIsIs
notaclassIcemploymentsItuatIonbecauseItIsIntendedtobetemporaryasapreludeto
fullfInancIalpartIcIpatIonInthegroup.However,therehavebeenenoughInstancesof
establIshedgroupsabusIngthIsarrangementthattheASAIncludesInItsfundamental
StatementofPolIcytheprovIso:ExploItatIonofanesthesIologIstsbyother
anesthesIologIstsIsImproper.
1
ThIsgoesontosaythatafterareasonabletrIalperIod,
IncomeshouldreflectservIcesrendered.Unfortunately,thesestatementsmayhavelIttle
meanIngorImpactongroupsInthemarketplace.SomegroupshaveahIstoryofdemandIng
excessIvelylongtrIalperIodsdurIngwhIchthejunIoranesthesIologIst'sIncomeIsartIfIcIally
lowandthendenyIngpartnershIpandtermInatIngtherelatIonshIptogoontoemploya
newprobatIonerandstartthecycleoveragaIn.AccordIngly,newjunIorstaffattemptIngto
joIngroupsshouldtrytohavesuchanarrangementspelledoutcarefullyIntheagreement
draftedbyanexpertrepresentIngtheanesthesIologIst.AnothervarIatIonofthIs,Inan
attempttodIsguIsethefundamentallyunethIcalnatureofthepractIce,Istoemploy
anesthesIologIstsonafIxedsalarywIththefalseIncentIveofnonIghtorweekendcall.ThIs
IsdIsIngenuous,asmostIncomeIsusuallygenerateddurIngroutInescheduleddaywork,for
whIchtheanesthesIologIstemployeeIspoorlycompensated.YetanotherusurIousscheme
IsforagrouptoemployananesthesIologIstforaperIodofyearsatalowsalaryandthen
requIreafurthercashoutlaytopurchasepartnershIpInthecorporatIon.Asthecashoutlay
canbequItesubstantIal,ItIsfrequentlyborrowedfromthecorporatIon,leadIngtoa
sophIstIcatedformofIndenturedservItude.Sadly,whenthejobmarketcondItIonsarepoor
astheyweresomeyearsago,thetendencyIsfortheretobelesslIkelIhoodofsecurInga
prospectIvecommItmentofpartnershIpataspecIfIedfuturetIme.
Private Practice as an Employee
TherehasbeensometrendtowardanesthesIologIstsbecomIngpermanentemployeesof
anyoneofvarIousfIscalentItIes.ThekeydIfferenceIsthatthereIsnoIntentIonorhopeof
achIevInganequItyposItIon(shareofownershIp,usuallyofapartnershIp,thusbecomInga
fullpartner).HospItals,outpatIentsurgerycenters,multIdIscIplInaryclInIcs,otherfacIlItIes
tIedtoaspecIfIclocatIonwheresurgeryIsperformed,physIcIangroupsthathaveumbrella
fIscalentItIesspecIfIcallycreatedtoserveastheemployerofphysIcIans,andeven
surgeonsmayseektohIreanesthesIologIstsaspermanentemployees.Thecommonthread
InthIssystemIsthatthesefIscalentItIesseetheanesthesIologIstsasaddItIonalwaysof
generatIngprofIts.AgaIn,InmanycasesItwouldappearthatemployeesarenotpaIda
salarythatIscommensuratewIththeIrproductIonofreceIvables.ThatIs,thefIscalentIty
wIllpayasalarysubstantIallybelowcollectIonsgeneratedplusapproprIateoverhead.
ThesearrangementsarepartIcularlyfavoredbysomelarge|CDsIncertaIncItIesthatvIew
anesthesIologIstssImplyasexpensIvenecessItIesthatpreventhospItalsfromrealIzIng
maxImumprofIt(althoughsometImesthereIsapromIseofalIghterormoremanageable
scheduleIntheseposItIonscomparedwIthmarketplaceprIvatepractIce).
NegotIatIngforaposItIonasapermanentfulltImeemployeeIssomewhatsImplerand
morestraIghtforwardthanItIsInmarketplaceprIvatepractIce.tparallelstheusual
understandIngsthatapplytomostregularemployeremployeesItuatIons:jobdescrIptIon,
roleexpectatIons,workIngcondItIons,hours,pay,andbenefIts.TheIdeaof
anesthesIologIstsfunctIonallybecomIngshIftworkersdIsturbsmanyIntheprofessIon
becauseItcontradIctsthetradItIonalprofessIonalmodel.AgaIn,thecomplexnatureand
multIplelevelsofsuchconsIderatIonsmakeItapersonalIssuethatmustbecarefully
evaluatedbyeachIndIvIdualwIthfullawarenessandconsIderatIonoftheIssuesoutlIned
hereandcommensurateresearchofASAresourcesandavaIlabledataaboutcommon
regIonalcIrcumstancesanddetaIlsofanyspecIfIcmedIcalcommunIty.
Practice for a Management Company
DnepromInentnewerdevelopmentIsthegrowthandImpactoflargestate,regIonal,or
evennatIonalmanagementcompanIesthatadvertIsetheprovIsIonofcomprehensIve
anesthesIaservIcesonacontractbasIswIthhospItals,surgerycenters,andclInIcs.These
companIes,somestartedand/ormanagedbyanesthesIaprofessIonals,promIsethefacIlIty
avaIlabIlItyofanesthesIacaredurIngthespecIfIedhoursInreturnforalucratIvecontract
todoso.ThIsrelIevesthefacIlItyfromanyconcernaboutrecruItIng,hIrIng/contractIng,
andretaInInganesthesIaprofessIonals,vIrtuallyelImInatIngconcernaboutdIsruptIonofDF
schedulesduetolImItedavaIlabIlItyofanesthesIacare.TheonlyrequIrementofthe
facIlItyIsapprovalofthealreadypreparedcredentIalIngInformatIonforeachanesthesIa
professIonal.UnlIkemanylocumtenenscompanIesInwhIchanesthesIaprofessIonalsare
consIderedIndependentcontractorsandpaIdfIxedcontractamountsperhour,perday,or
perjobforalImItedIntervalwIthnobenefIts,someofthemanagementcompanIesmay
employanesthesIaprofessIonalsfulltImeonasalarywIthbenefIts(paIdvacatIon,health
Insurance,retIrementcontrIbutIon,andsoforth).Theemploymentagreementwould
stIpulatewhethertravelforassIgnmentsInlocatIonsawayfromtheemployee'spermanent
homewouldberequIredasacondItIonofthefulltImejobortheposItIonwIllalwaysbeIn
thepractItIoner'shomecommunIty.
Practice as a Hospital Employee
WhIlecertIfIedregIsterednurseanesthetIstsInsomelocatIonshavetradItIonallypractIced
ashospItalemployees,untIlrecently,ItwaslesscommonoutsIdefullvertIcallyIntegrated
|CDsforphysIcIananesthesIologIststobehospItal(orfacIlIty)employees.nrecentyears,
oneoftheresponsesofhospItalstorequestsforsubsIdIesfromexclusIvecontractpractIce
groupsofanesthesIologIstshasbeentooffertheanesthesIologIstsfulltImeemployment
statusratherthansubsIdIzeanIndependentpractIcegroupthathasItsownsIgnIfIcant
admInIstratIveandoverheadcosts.
J5
ThehospItallIkelysuggeststhatIntegratIngthe
bIllIng,collectIng,andmanagementfunctIonsaswellasmajoroverheadcostssuchas
malpractIceInsuranceIntotheexIstInglargerhospItaloperatIonwouldbeverycost
effIcIent,allowIngmorefInancIalresourcestogotophysIcIansalarIes,andalsowIth
possIblyasomewhatgreaterpredIctabIlItyInuncertaIntImes.ThehospItalcanalso
guaranteetheavaIlabIlItyofanesthesIacare(arequIrementtosustaIntheDF,oneofthe
maInhospItalrevenuesources)InanerawhensomeanesthesIologIstgroupsmaysImply
walkawayfromahospItalInsearchofgreaterIncomeelsewhere,leavIngthehospItalto
seekacontractprobablywIthoneofthelargeandveryexpensIveanesthesIamanagement
companIes(prevIouslydescrIbed).Dfcourse,Inreturnforemployeestatus,the
anesthesIologIstssurrendersomedegreeofIndependenceandalso,forthegroup'spartners,
theIrequItystakeInsharIngInanysubsequentIncreased
P.41
practIcerevenue.AhospItalmIghtcounterthatconcernwIththecontentIonthat
tradItIonalfeeforservIcepractIcethathasbeensocommonforsolongforprIvate
practIceanesthesIologIstswIllnever againyIeldenoughrevenuetomaIntaIntheIncome
levelsanesthesIologIstshavecometoexpect,sotheywIllnotbelosInganythIng.
Billing and Collecting
npractIcesInwhIchanesthesIologIstsaredIrectlyInvolvedwIththefInancIal
management,theyneedtounderstandasmuchaspossIbleaboutthecomplexworldof
healthcarereImbursement.ThIssIgnIfIcanttaskhasbeenmadeeasIerbytheASA,whIch
sometImeagoaddedasIgnIfIcantcomponenttoItsWashIngton,0.C.,offIce(see
www.asahq.org/government.htm)byaddIngapractIcemanagementcoordInatortothe
staff.DneoftheassocIatedassIgnmentsIshelpIngASAmembersunderstandandworkwIth
thesometImesconfusIngandconvolutedIssuesofeffectIvebIllIngforanesthesIologIsts'
servIces.ThereareoftenupdateswIththelatestInformatIonandcodesInthemonthlyASA
Newsletter.
TherecontInuetobeproposalsforsIgnIfIcantchangesInbIllIngforanesthesIologycare.
However,thebasIcshavechangedonlyslIghtlyInrecentyears.tIsImportantto
understandthatmanyofthemostcontentIousIssues,suchastherequIrementforphysIcIan
supervIsIonofnurseanesthetIstsandtheImplIcatIonsofthatforreImbursement,applyIn
manycIrcumstancesmostlyto|edIcareand,Insomestates,|edIcaId.Thus,thefractIon
ofthepatIentpopulatIoncoveredbythesegovernmentpayersIsImportantInany
consIderatIon.0IfferentpractIcesItuatIonshavedIfferentarrangementsregardIngthe
fInancIalrelatIonshIpsbetweenanesthesIologIstsandnurseanesthetIsts,andthIscanaffect
thecomplexsItuatIonofwhobIllsforwhat.ThenursesmaybeemployeesofahospItal,of
theanesthesIologIstswhomedIcallydIrectthem,orofnooneInthattheyareIndependent
contractorsbIllIngseparately(evenIncasesInwhIchphysIcIansupervIsIonnotmedIcal
dIrectIonIsrequIredbutwherethosephysIcIansdonotbIllforthatcomponent).n1998,
|edIcaremandatedthatananesthesIacareteamofanurseanesthetIstmedIcallydIrected
byananesthesIologIstcouldbIllasateamnomorethan100ofthefeethatwouldapplyIf
theanesthesIologIstdIdthecasealone.TheImplIcatIonsofthIschangearecomplexand
varIableamonganesthesIologypractIces,partIcularlybecausethereIsanothertrendfor
healthcarefacIlItIesthattradItIonallyhademployednurseanesthetIststoseektoshIft
totalfInancIalresponsIbIlItyforthemtotheanesthesIologIstpractIcegroup.Also,complex
relatedIssuesplayedoutIntheearly2000years.ThefederalgovernmentIssuedanew
regulatIonallowIngIndIvIdualstatestooptoutoftherequIrementthatnurse
anesthetIstsbesupervIsedbyphysIcIansandseveralstatesdIdso.ThIswasopposedbythe
ASA.8ecauseperIoperatIvepatIentcare,onecomponentofwhIchIsadmInIsterIng
anesthesIa,IstradItIonallyconsIderedthepractIceofmedIcIne,theImplIcatIonsofthIs
changeasfarastheroleofsurgeonssupervIsIngnurseanesthetIstsandthemalpractIce
lIabIlItystatusofnurseanesthetIstspractIcIngIndependentlywereunclear.Further,the
ImplIcatIonsofallthIsforbIllIngInsurersotherthan|edIcareand|edIcaIdare
exceedInglycomplex.
Classic Methodology
8ecausethereIsstIllwIdespreadapplIcatIonofthetradItIonalmethodofbIllIngfor
anesthesIologyservIces,understandIngItIsveryImportantforanesthesIologIstsstartIng
practIce.nthIssystem,eachanesthetIcgeneratesavalueofsomanyunIts,whIch
representeffortandtIme.AconversIonfactor(dollarsperunIt)thatcanvarywIdely
multIplIedbythenumberofunItsgeneratesanamounttobebIlled.EachanesthetIchasa
basevaluenumberofunIts(e.g.,8foracholecystectomy)andthenthetImetakenforthe
anesthetIcIsdIvIdedIntounIts,usually15mInutesperunIt.Thus,acholecystectomywIth
anesthesIatImeof1hourand50mInuteswouldhave8baseunItsand7.JJtImeunItsfora
totalof15.JJunIts.nsomepractIcesettIngs,ItmaybeallowedtoaddmodIfIers,suchas
extraunItsforcomplexpatIentswIthmultIpleproblemsasreflectedbyanASAphysIcal
statusclassIfIcatIonofJ5and/orE(emergency)orforInsertIonofanarterIalorPA
catheter.ThesumIsthetotalbIllIngunItvalue.0etermInIngthebasevalueforan
anesthetIcInunItsdependsonfullandcorrectunderstandIngofwhatoperatIonwasdone.
AlthoughthIssoundseasy,ItIsthemostdIffIcultcomponentoftradItIonalanesthesIa
bIllIng.TheprocessofdetermInIngtheproceduredoneIsknownascodingbecausethe
procedurenamelIstedontheanesthesIarecordIsassIgnedanIdentIfyIngcodenumber
fromtheunIversallyusedcurrentproceduraltermInology(CPT)4codIngbook.ThIscodeIs
thentranslatedthroughtheASAFelatIve7alueCuIde,whIchassIgnsabaseunItvalueto
thetypeofprocedureIdentIfIedbytheCPT4code.nthepast,someanesthesIologIsts
faIledtounderstandtheImportanceofcorrectcodIngtothesuccessofthebIllIngprocess.
PlacIngthIstaskInthehandsofsomeoneunfamIlIarwIththesystemandwIthsurgIcal
termInologycaneasIlyleadtoIncorrectcodIng.ThIscanfaIltocapturechargesandthe
resultIngIncometowhIchtheanesthesIologIstIsentItledor,worse,cansystematIcally
overchargethepayers,whIchwIllbrIngsanctIons,penaltIesand,IncertaIncases,crImInal
prosecutIon.
nrecentyearsaprevaIlIngoffIcIalattItudehasbeenthattherearenosImple,Innocent
codIngerrors.AllupcodIng(chargIngformoreexpensIveservIcesthanwereactually
delIvered)IsconsIderedtobeprImafacIeevIdenceoffraudandIssubjecttosevere
dIscIplInaryandlegalactIon.AllpractIcesshouldhavedetaIledcomplIanceprogramsIn
placetoensurecorrectcodIngforservIcesrendered.
J6
DutsIdeexperthelp(suchasfroma
healthcarelawfIrmthatspecIalIzesIncomplIanceprograms)IshIghlydesIrableforthe
processofformulatIngandImplementIngacomplIanceplanregardIngcorrectcodIng.
AssemblyandtransferoftheInformatIonnecessarytogeneratebIllsmustbeeffIcIentand
complete.TradItIonally,thIsInvolveddeposItIngInasecurecentrallocatIonapaperextra
copyoftheanesthesIarecordandoftenabIllIngsheetwIthIt,onwhIchwasInscrIbed
thenamesofalltheInvolvedpersonnelandanyaddItIonalInformatIonaboutother
potentIallybIllableservIces,suchasInvasIvemonItors.AnypractIceInvolvedwItha
comprehensIveelectronIcperIoperatIveInformatIonmanagementsystemInthefacIlIty
shouldbeusIngthattoassemblethIsfrontendbIllIngInformatIon.Shortofthat,some
practIcescollectelectronIcInformatIonspecIfIcallygeneratedbytheanesthesIaprovIders
forthatpurpose.TheyhaveequIppedeachstaffmemberwIthahandheldorganIzerInto
whIchdataareenteredandthenthedevIceIssynchedwIthadepartmentalcomputerat
theendoftheday.ftheDFsuItehasWIFI(wIrelesselectronIcconnectIon),thesame
functIoncouldbeaccomplIshedInrealtImewIththeprovIdersenterIngtherequIsIte
InformatIonIntoamInIprogramonalaptopcomputeraffIxedtoeachanesthesIamachIne
(oronecarrIedbyeachstaffmember).DncetheInformatIonhasbeensecured,a
mechanIsmmustbeemployedtogeneratetheactualbIllandcommunIcateIttothepayer
(onpaper,ondIsk,or,usually,dIrectlycomputertocomputer:electronIcclaIms
submIssIon).ThepossIbleexactarrangementsfordoIngthIsvarywIdely.
WhetherananesthesIapractIcethatwIllbebIllIngandcollectIngforanesthesIaservIces
shouldemployItsownInhouseclerIcalandbookkeepIngpersonneltoperformthIsfunctIon
orshouldcontractwIthanoutsIdecompanywhosesolefunctIonIsmedIcalbIllIngand
collectIng(possIbly,Ideally,for
P.42
anesthesIologyonly)canbedebatedendlessly.WhIcheverIschosen,knowledgeable
oversIghtbytheanesthesIaprofessIonalswhoultImatelywIllderIveIncomefromthe
revenuecollectedIsrequIred.UltImately,theentItyactuallysubmIttIngthebIllwIllverIfy
thatIthasbeenpaId(postIngofreceIpts)andmayormaynotactuallyhandletheIncomIng
money.7eryoften,anesthesIapractIcesorIndIvIdualswhouseabIllIngservIce(andeven
somewhohaveInhousebIllIngstaffs)wIllarrangethattheactualpaymentsgodIrectlyto
abanklockbox,whIchIsapostoffIcebox(betterIndIvIdualthanshared,evenIfmore
expensIve)towhIchthepaymentscomeandthengodIrectlyIntoabankaccount.ThIs
systemavoIdsthesItuatIonofhavIngthepeoplewhogeneratethebIllactuallyhandlethe
IncomIngreceIpts,apractIcethathasledtotheftandfraudInafewcases.Eventual
decIsIonsabouthowhardtotrytocollectfrompayerswhodenycoverageandthenfrom
patIentsdIrectlywIlldependonthecIrcumstances,IncludInglocalcustoms.
Table 2-1 Types of Data an Anesthesiology Group Should Track and
Maintain Concerning Its Own Practice
Types of Data the Anesthesiology Group's Computer System Should Track
TransactIonbasedsystem(trackeachcaseandchargeasseparaterecord)
TrackIndIvIdualchargesbyCPT4code
TrackIndIvIdualpaymentsbypayer
TrackalldataelementsonanInterrelatedbasIs
8yplaceofservIce
8ycharge,brokendown
bynumberofunIts(tImeandbase)
byASAmodIfIers
bynumberoflInes
8yCPT4code
8ypayer
8ypaymentcode(fullpayment,dIscount,wrIteoff,orrefund)
8ydIagnosIs(C09code)
8ysurgeon
8yanesthesIologIst
8yanesthesIacareteamprovIder
8ystartandstoptImes
8yage
8ygender
8yemployer
8yZPcode
Type of Information to Generate From These Data
Aggregatenumberofcasesperyearforthegroup
TotalnumberofcasesperyearforeachprovIderwIthInthegroup
NumberofcasesperformedbyanesthesIologIsts
NumberofcasesperformedbytheanesthesIacareteam
AveragenumberofunItspercase(asonemeasureofIntensItypercase)
AveragenumberofunItsperCPT4code
AveragetImeunItspercaseandperCPT4code
CroupshouldbeabletocalculatetImeunItsperIndIvIdualsurgeon
AveragelInechargepercase
ChargespercasebyCPT4code
Paymentspercasebypayer
PatIentmIx
PercenttradItIonalIndemnIty
Percentmanagedcare(brokendownbyeach|CDforwhIchservIcesare
provIded)
Percentselfpay
Percent|edIcare
Percent|edIcaId
CollectIonrateforeachpopulatIonserved
DverallcollectIonrate
CostsperunIt(totalcosts,excludIngcompensatIon+totalunIts)(costsInclude
lIabIlItyInsurance,rent,collectIoncosts,andlegalandaccountIngfees)
CompensatIoncostsperunIt(totalcompensatIon+totalunIts)for|CD
populatIons,utIlIzatIonpatternsbyage,gender,anddIagnosIs
CPT,currentproceduraltermInology;ASA,AmerIcanSocIetyofAnesthesIologIsts;
C09,nternatIonalClassIfIcatIonof0Iseases,nInthrevIsIon;|CD,managedcare
organIzatIon.
FeprIntedfrom|anagedCareFeImbursement|echanIsms:ACuIdefor
AnesthesIologIsts.ParkFIdge,L,AmerIcanSocIetyofAnesthesIologIsts,1994,wIth
permIssIon.
0etaIledsummarystatIstIcsoftheworkdonebyananesthesIologypractIcegroupare
crItIcalforlogIstIcmanagementofpersonnel,schedulIng,andfInancIalanalysIs.
SpreadsheetanddatabasecomputerprogramscustomIzedforanIndIvIdualpractIce's
characterIstIcswIllbeInvaluable.AsummaryofthetypesofdataananesthesIapractIce
shouldtrackIsshownIn
P.4J
Table21.DnceallthedataareassembledandrevIewed,atleastmonthlyanalysIsbya
busInessmanagerorequIvalentaswellasoffIcers/leadersofthepractIcegroupcanspot
trendsveryearlyIntheIrdevelopmentandallowapproprIatecorrectIonorplannIng.Dften
theresponsIblemembersofananesthesIologygroupquestIonhoweffectIvetheIrfInancIal
servIcesoperatIonIs,partIcularlyregardIngnetcollectIons.ThIsIsacomplexIssue
J7
that,
agaIn,oftenrequIresoutsIdehelp.FoutIneInternalaudItscanbeusefulbutcouldbeself
servIng.NobIllIngoffIceorcompanythatIshonestandcompletelyaboveboardshould
everobjecttoaclIent,InthIscasetheanesthesIologypractIcegroup,engagIngan
IndependentoutsIdeaudItortocomeInandthoroughlyexamIneboththeeffIcIencyofthe
operatIonandalsothebooksconcernIngcorrectnessandcompletenessofcollectIons.
AnesthesIabIllIngandcollectIngareamongthemostcomplexchallengesInthemedIcal
reImbursementfIeld.TradItIonalanesthesIareImbursementIsunIqueInallofmedIcIne.
TheexperIenceofmanypeopleovertheyearshassuggestedthatItoftenIswelladvIsedto
dealwIthanentItythatIsnotonlyveryexperIencedInanesthesIabIllIng,butalsodoes
anesthesIabIllIngexclusIvelyorasalargefractIonofItsefforts.tIsverydIffIcultforan
anesthesIologIstorafamIlymembertodobIllIngandcollectIngasasIdeactIvItytoa
normallIfe.ThIshasledtoIneffIcIentandInadequateeffortsInmanycases,IllustratIng
thevalueofpayIngareasonablefeetoaprofessIonalwhowIlldevotegreattImeand
energytothIschallengIngendeavor.
Antitrust Considerations
TherecanbeantItrustImplIcatIonsofbusInessarrangementsInvolvInganesthesIologIsts
partIcularlywIthalltherealIgnments,consolIdatIons,mergers,andcontractsassocIated
wIththeattemptedImplementatIonofmanagedcare.TheapplIcablestatutesand
regulatIonsareoftenpoorlyunderstood.ContrarytopopularbelIef,theantItrustlawsdo
notInvolvetherIghtsofIndIvIdualstoengageInbusIness.Father,thelawsareconcerned
solelywIththepreservatIonofcompetItIonwIthInadefInedmarketplaceandtherIghtsof
theconsumer,IndependentofwhetheranyonevendororprovIderofservIceIsInvolved.
WhenananesthesIologIsthasbeenexcludedfromapartIcularhospItal'sstafforanesthesIa
groupandthensuesbasedonanallegedantItrustvIolatIon,theanesthesIologIstloses
vIrtuallyautomatIcally.ThIsIsbecausethereIsstIllsIgnIfIcantcompetItIonIntherelevant
medIcalcaremarketplace(communItyorregIon)andcompetItIonInthatmarketIsnot
threatenedbytheexclusIonofonephysIcIanfromonestaff.
nessence,IfthereareseveralhospItalsofferIngrelatIvelysImIlarservIcestoan
ImmedIatecommunIty(themarket),denIalofprIvIlegestoonephysIcIanbyonehospItalIs
notantIcompetItIve.f,ontheotherhand,thereIsonlyonehospItalInasmallermarket,
thenthesameact,thesamesetofcIrcumstances,couldbeseenverydIfferently.nthat
case,therewouldbealImItatIonofcompetItIonbecausethehospItaldomInatesand,In
fact,maycontrolthemarketforhospItalservIces.ExclusIonofonephysIcIan,then,could
lImItaccessbytheconsumerstoalternatIvecompetIngservIcesandhencewouldlIkelybe
judgedanantItrustvIolatIon.
TheShermanAntItrustActIsafederallawmorethan100yearsold.SectIon1dealswIth
contracts,combInatIons,conspIracy,andrestraIntoftrade.8ydefInItIon,twoormore
separateeconomIcentItIesmustbeInvolvedInanagreementthatIschallengedasIllegal
forthIssectIontoapply.SectIon2prohIbItsmonopolIesorconspIracytocreatea
monopoly,andItIspossIblethatthIscouldapplytoasIngleeconomIcentItythathas
IllegallygaIneddomInatIonofamarket.ConsIderatIonofpossIblemonopolIstIcdomInatIon
ofamarketInvolvesasItuatIonInwhIchasIngleentItycontrolsatleast50ofthe
busInessInthatmarket.ThestakesarehIghInthattheantItrustlegIslatIonprovIdesfor
trIpledamagesIfalawsuItIssuccessful.TheU.S.0epartmentofJustIceandtheFederal
TradeCommIssIonarekeenlyInterestedInthecurrentrapIdevolutIonInthehealthcare
Industry,andthusareactIvelyInvolvedInevaluatIngsItuatIonsofpossIbleantItrust
vIolatIons.
TherearetwowaystojudgevIolatIons.Undertheper se rule,whIchIsapplIedrelatIvely
rarely,conductthatIsobvIouslylImItIngcompetItIonInamarketIsautomatIcallyIllegal.
TheothertypeofvIolatIonIsbasedontherule of reason,whIchInvolvesacarefulanalysIs
ofthemarketandthestateofcompetItIon.ThemajorItyofcomplaIntsagaInstphysIcIans
arejudgedbythIsrule.ThemorecompetItorsthereareInamarket,thelesslIkelythat
anyoneactIsantIcompetItIve.nacommunItywIthtwohospItals,onesmallerthanthe
other,wIthananesthesIologygrouppractIceexclusIvelyateach,Ifthelarger
anesthesIologypractIcegroupbuysoutandabsorbsthesmaller,leavIngonlyonegroupfor
theonlytwohospItalsInthecommunIty,thatmaybeantIcompetItIve,partIcularlyIfa
newanesthesIologIstseekstopractIcesoloatthosehospItals.
Legal Implications
nthecurrenteraofrapIdlyevolvIngpractIcearrangements,theantItrustlawsare
Important.fphysIcIans(IndIvIdualsorgroups)whonormallywouldbecompetItorsbecause
theyareseparateeconomIcentItIesmeetandagreeontheprIcestheywIllchargeorthe
termstheywIllseekInamanagedcareorInstItutIonalcontract,thatcanbe
antIcompetItIve,monopolIstIc,andhencepossIblyIllegal.NotethatsharIngacommon
offIceandcommonbIllIngservIcealoneIsnotenoughtoconstItuteatruegroup.f,onthe
otherhand,thesamephysIcIansjoInInatrueeconomIcpartnershIptoformanewgroup
(totalIntegratIon)thatIsasIngleeconomIcentIty(andmeetscertaInothercrIterIa)that
wIllsetprIcesandnegotIatecontracts,thatIsperfectlylegal.TheothercrIterIaare
crItIcal.TheremustbecapItalInvestmentandalsorIsksharIng(IfthereIsaprofItorloss,
ItIsdIstrIbutedamongthegroupmembers)thatIs,totalIntegratIonIntoagenuIne
partnershIp(thatIsusuallyIncorporated,sometImesasalImItedlIabIlItycorporatIon).
ThIsIssueIsveryImportantInconsIderIngthedrIveforneworganIzatIonstoputtogether
networksofphysIcIansthatthenseekcontractswIthmajoremployerstoprovIdemedIcal
care.SometImes,hospItalsorclInIcsattempttoformanetworkcomprIsIngallthe
membersofthemedIcalstaffsothattheresultIngentItycanbIdgloballyfortotalcare
contracts.AnynetworkIsajoIntventureofIndependentpractItIoners.fthepartIcIpatIng
physIcIansofonespecIaltyInanetworkareseparateeconomIcentItIesandthenetwork
advertIsesoneprIcefortheIrservIces,thIswouldseemtosuggestanantItrustvIolatIon
(horIzontalprIcefIxIng).nthepast,IfanetworkInvolvedfewerthan20ofonetypeof
medIcalspecIalIstInamarket,thatwascalledasafe harbor,meanIngthatItwas
permIssIblefornonpartnerstogettogetherandnegotIateprIces.Thefederalgovernment
hastrIedtoencourageformatIonofsuchnetworkstohelpreducehealthcarecosts,andas
aresultmadesomerelevantexceptIonstotheapplIcatIonoftheserules.Aslongasthe
networkIsnonexclusIve(othernonnetworkphysIcIansofagIvenspecIaltyarefreeto
practIceInthesamefacIlItIesandcompeteforthesamepatIents),thenetworkcan
comprIseuptoJ0ofthephysIcIansofonespecIaltyInamarket.NotespecIfIcallythat
thIsdoesnotallowalocalspecIaltysocIetyInabIgcItytoserveasabargaInIngagenton
feesforItsmembersbecauseItIsverylIkelythatJ0ofthespecIalIstsInanareawIllbe
membersofthesocIety.TheonlyrealexceptIontothIsprovIsIonIsInthInlypopulated
ruralareaswheretheremaybejustonephysIcIannetwork.nsuchcases
P.44
(whIchare,sofar,rarebecausethemajormanagedcareandnetworkactIvItyhas
occurredmaInlyInheavIlypopulatedurbanareas),thereIsnolImItonhowmanyofone
specIaltycanbecomenetworkmembersandhavethenetworknegotIatefees,aslongas
thenetworkIsnonexclusIve.
FelevantlegIslatIon,regulatIons,andcourtactIonsallhappenrapIdlyandoften.|ergers
amonganesthesIologygroupsInamarketareaforthepurposesofbotheffIcIencyand
strengthInnegotIatIngfeeshavebeenverypopularasaresponsetotherapIdlychangIng
marketplace.AlIstofquestIonsmustbeansweredtodetermIneIfsuchamergerwould
haveantIcompetItIveImplIcatIons.AlthoughcompendIaofrelevantInformatIonare
avaIlabletoanesthesIologIsts,
J8,J9,40
theycannotsubstItuteforexpertadvIceandhelp.
DbvIously,anesthesIologIstscontemplatIngamergerorfacInganyoneofagreatnumberof
othersItuatIonsInthemodernhealthcarearenamustsecureassIstancefromprofessIonal
advIsors,usuallyattorneys,whosejobItIstobeawareofthemostrecentdevelopments,
howtheyapply,andhowbesttoforgeagreementsInformalcontracts.AnesthesIologIsts
hopIngtofIndreputableadvIsorscanstarttheIrsearchwIthwordofmouthreferralsfrom
colleagueswhohaveusedsuchservIces.LocalorstatemedIcalsocIetIesfrequentlyknow
ofattorneyswhospecIalIzeInthIsarea.FInally,theASAWashIngton,0.C.,offIcehas
compIledastatebystatelIstofadvIsorswhohaveworkedsuccessfullywIth
anesthesIologIstsInthepast.
Exclusive Service Contracts
Dften,oneofthelargerIssuesfacedbyanesthesIologIstsseekIngtodefInepractIce
arrangementsconcernsthedesIrabIlItyofconsIderInganexclusIvecontractwIthahealth
carefacIlItytoprovIdeanesthesIaservIces.AnexclusIvecontractstatesthat
anesthesIologIstsseekIngtopractIceatagIvenfacIlItymustbemembersofthegroup
holdIngtheexclusIvecontractand,usually,thatmembersofthegroupwIllpractIce
nowhereelse.AhospItalmaywanttogIveanexclusIvecontractInreturnforaguarantee
ofcoverageaspartofthecontract.Also,thehospItalmaybelIevethatsuchacontractcan
helpensurethequalItyofpractItIonerbecausethecontractcancontaIncredentIalIngand
performancecrIterIa.tIsImportanttounderstandthatthehospItallIkelywIllexercIsea
degreeofcontrolovertheanesthesIologIstswIthsuchacontractInforce,suchasrequIrIng
themtopartIcIpateasprovIdersInanycontractsthehospItalmakeswIththIrdparty
payersandalsotyInghospItalprIvIlegestotheexIstenceofthecontract(thesocalled
cleansweepprovIsIonthatbypassesanydueprocessofthemedIcalstaffshouldthe
hospItaltermInatethecontract).CertaInofthesetypesofprovIsIonsconstItuteeconomic
credentialing,whIchIsdefInedastheuseofeconomIccrIterIaunrelatedtothequalItyof
careorprofessIonalcompetencyofphysIcIansIngrantIngorrenewInghospItalprIvIleges
(suchastheacceptanceofbelowmarketfeesassocIatedwIthahospItalnegotIatedcare
contractorevenrequIrIngfInancIalcontrIbutIonsInsomeformtothehospItal).
TheASAIn199JIssuedastatementcondemnIngeconomIccredentIalIng.
1
The
anesthesIologIstsInvolvedmayacceptsuchanexclusIveservIcescontracttoguarantee
thattheyalonewIllgetthebusInessfromthesurgeonsonstaffatthathospItal,andhence
theresultIngIncome.TheremaybeotherconsIderatIonsonbothsIdes,andthesehave
beenoutlInedInextensIverelevantASApublIcatIonsthatalsoIncludeasamplecontract
forInformatIonpurposesonly.
J6,J9
AlthoughmanyexclusIvecontractswIthanesthesIology
groupsareInforce,thesentIment,partIcularlyfromtheASA,IsagaInstthem.Asstated,It
IscrItIcalthatanesthesIologIstsfacedwIthImportantpractIcemanagementdecIsIonssuch
aswhethertoenterIntoanexclusIvecontractmustseekoutsIdeadvIceandcounsel.There
areagreatmanynuancestotheseIssues,
J9,40,41,42,4J
andanesthesIologIstsareatrIsk
attemptIngtonegotIatesuchcomplexmattersalone,justaspatIentswouldbeatrIskIfa
contractattorneyattemptedtoInducegeneralanesthesIa.
0enIalofhospItalprIvIlegesasaresultoftheexIstenceofanexclusIvecontractwIththe
anesthesIologIstsInplaceatthefacIlItyhasbeenthesourceofmanylawsuIts,IncludIng
thewellknownLouIsIanacaseofHyde v Jefferson Parish.nthatcase,thecourtfoundfor
thedefendantanesthesIologIstsandthehospItal,sayIngthattherewasnoantItrust
vIolatIonbecausetherewasnorealadverseeffectoncompetItIonasfaraspatIentswere
concernedbecausetherewereseveralotherhospItalswIthInthemarkettowhIchthey
couldgo,andthereforetheycouldexercIsetheIrrIghtstotakeadvantageofcompetItIon
Intherelevantmarket.Thus,exIstenceofanexclusIvecontractonlyIntheraresettIng
whereantIcompetItIveeffectsonpatIentscanbeprovedmIghtleadtoalegItImate
antItrustclaImbyaphysIcIandenIedprIvIleges.ThIswasproventrueIntheKessel v
Monongalia County General HospitalcaseInWest7IrgInIaInwhIchanexclusIve
anesthesIologycontractwasheldIllegal.Therefore,agaIn,thesearrangementsareby
defInItIoncomplexandfraughtwIthhazard.AccordIngly,outsIdeadvIceandcounselare
alwaysnecessary.
Hospital Subsidies
|oderneconomIcrealItIeshaveforcedagreatnumberofanesthesIologypractIcegroups
(InbothprIvateandacademIcsettIngs)torecognIzethattheIrpatIentcarerevenue,after
overheadIspaId,doesnotprovIdesuffIcIentcompensatIontoattractandretaInthe
numberandqualItyofstaffnecessarytoprovIdetheexpectedclInIcalservIce(andfulfIll
anyothergroup/departmentmIssIons).AttemptIngtodothesame(ormore)workwIth
fewerstaffmaytemporarIlyprovIdeIncreasedfInancIalcompensatIon.CuttIngbenefIts
(dIscretIonarypersonalprofessIonalexpenses,retIrementcontrIbutIons,orevenInsurance
coverage)mayalsobeacomponentofaresponsetoInadequatepractIcerevenue.
However,theresultIngdecrementsInpersonalsecurIty,InconvenIence,andInqualItyof
lIfeasfarasacuteandchronIcfatIgue,decreasedfamIlyandrecreatIontIme,andtensIon
amongcolleaguesfearfulsomeoneelseIsgettIngabetterdealwIllquIcklyovercomeany
brIefadvantageofasomewhathIgherIncome.Therefore,manypractIcegroupsInsuch
sItuatIonsarerequestIngtheIrhospItal(orotherhealthcarefacIlItywheretheypractIce)
topaythemadIrectcashsubsIdythatIsusedtoaugmentpractIcerevenueInorderto
maIntaInbenefItsandamenItIeswhIlemaIntaInIngorevenIncreasIngthedIrect
compensatIontostaffmembers,hopefullytoamarketcompetItIvelevelthatwIllpromote
recruItmentandretentIonofgroupmembers.
DbvIously,requestsbyapractIcegroupforadIrectsubsIdymustbethoroughlyjustIfIedto
thefacIlItyadmInIstratIonreceIvIngthepetItIon.Thegroup'sbusInessoperatIonshould
alreadyhavebeenexamInedcarefullyforanypossIbledefectsormeanstoenhance
revenuegeneratIon.ExplanatIonofthegeneraltrendofdeclInIngreImbursementsfor
anesthesIaservIcesshouldbecarefullydocumented.FactsandfIguresonthatandalsothe
shortageofanesthesIaprovIderscanbeobtaInedfromjournalartIclesandASA
publIcatIons,partIcularlytheNewsletter.0emandforanesthesIacoverageforthesurgIcal
scheduleIsakeycomponentofthIsproposal.SchedulIngandutIlIzatIon,partIcularlyIf
earlymornIngstaffIngIsrequIredformanyDFsthatareroutInelyunusedlaterdurIngthe
tradItIonalworkday,IsamajorIssuetobeunderstoodandpresented.AnyotherDF
IneffIcIencIescreatedbyhospItalsupportstaffandprevIouseffortstodealwIththem
shouldalsobehIghlIghted.UnfavorablepayermIx,Impactofcontracts,andprograms
InItIatedbythehospItalalsooftenaremajorfactors
P.45
InsItuatIonsofInadequatepractIcerevenue.Always,thegroup'sgoodwIllwIththe
surgeonsandthecommunItyIngeneralshouldbeemphasIzed,aswellasoftheIndIrector
behIndthescenesservIcesandbenefItstheanesthesIologygroupprovIdestothe
hospItal.NotethatthenecessItyforsuchasubsIdyrequestIsprecIselythetImewhenthe
anesthesIaprofessIonalswIllbenefItfrombeIngperceIvedasgoodcItIzensofthehealth
carefacIlIty.AnoverlyaggressIveeffortbeyondtheboundsoflogIccouldprovokethe
facIlItytoconsIderalternatIvearrangements,evenuptothepoIntofputtIngoutarequest
forproposalfromotheranesthesIologypractIcegroups.Therefore,thoughtfulcalculatIons
arerequIredandacarefulbalancemustbesought,seekIngenoughfInancIalsupportto
supplementpractIcerevenuessothatmembers'compensatIonIscompetItIvebutnotso
muchastobeexcessIve.SupportIngstatementsanddocumentsaboutoffersandpotentIal
earnIngselsewheremustbecompletelyhonestandnotexaggeratedorcredIbIlItyandgood
faIthwIllbelost.Further,partofanyagreementwIllbethefullsharIngofthegroup's
detaIledfInancIalInformatIonwIththefacIlItyadmInIstratIon,bothatthetImeofthe
requestandonanongoIngbasIsIfthepaymentIsmorethanaonetImebaIlout.Plans
forrevIewandrenewalshouldbemadeonceasubsIdyIspaId.
AnysubsIdywIlllIkelyrequIreaformalcontract.TheremaybeconcernaboutmalpractIce
lIabIlItyImplIcatIonsforthehospItaleventhoughthepractIcegroupstaysanIndependent
entItyasbefore.TheremaybeInurementorprIvatebenefItconcernsthatcouldbe
perceIvedasathreattothetaxexemptstatusofanonprofIthospItal.Lackof
understandIngoftheapplIcablelawsmayleadtofearsthatasubsIdycouldbeanIllegal
kIckbackoravIolatIonoftheStarkselfreferralprohIbItIon.AsIsalmostalwaysthe
case,expertoutsIdeprofessIonalconsultantadvIce,usuallyfromanattorneywho
specIalIzesexclusIvelyInhealthcarefInancecontractIng,IsmandatoryInsuch
cIrcumstances.TheASAWashIngton,0.C.,offIcemaIntaInslIstsofconsultantswhohave
helpedotheranesthesIologIstsorgroupsInthepastwIthvarIoussubjects,andtheASAhas
somebasIcInformatIononsubsIdIestoanesthesIologypractIcegroups.
44,45,46
New Practice Arrangements
EventhoughtheImpactofmanagedcareplanshaswanedsomewhatoverthefIrstdecade
ofthe21stcentury,varIousIteratIonsstIllexIstandhaveongoIngImpactonanesthesIology
practIce.Further,renewedconcernattheendofthedecadeaboutdIsproportIonate
IncreasesInhealthcarespendIngasapercentageofU.S.grossdomestIcproductandthe
fearofthepostulatedbankruptcyof|edIcareand|edIcaIdagaInraIsethespecterofnew
effortstoImposemanagedcare.
ntheInItIalstagesoftheevolutIonofamanagedcaremarketplace,the|CDusuallyseeks
contractswIthprovIdersbasedondIscountedfeeforservIcearrangements.ThIspreserves
thebasIctradItIonalIdeaofproductIonbasedphysIcIanreImbursement(domore,bIll
more)buttheprIceofeachactofservIcesIslower(theprovIdersareInducedtogIvedeep
dIscountswIththepromIseofsIgnIfIcantvolumesofpatIents);also,the|CDgatekeeper
prImarycarephysIcIansandthe|CDrevIewersarestronglyencouragedtolImItcomplex
andcostlyservIcesasmuchaspossIble.ThereareotherfeaturesIntermIttentlyalongthe
way,suchasglobalfeesandnegotIatedfeeschedules(agreeduponsIngleprIcesfor
IndIvIdualprocedures,IndependentoflengthorcomplexIty).nanapplIcatIonofthe
conceptofrIsksharIng(spendtoomuchforpatIentcareandloseIncome),thIsusuallyIs
InItIallymanIfestIntheformofwIthholds,thepractIceofthe|CDholdIngbacka
fractIonoftheagreeduponpaymenttotheprovIders(e.g.,10or15)andkeepIngthIs
moneyuntIltheendofthefIscalyear.AtthattIme,IfthereIsanymoneyleftIntherIsk
poolorwIthholdaccountafterallthe(partIal)provIderfeesand|CDexpensesarepaId,It
IsdIstrIbutedtotheprovIdersInproportIontotheIrdegreeofpartIcIpatIondurIngthe
year.ThIsIsacleverandpowerfulIncentIvetoprovIderstoreducehealthcareexpenses.
tIsnotaspowerfulasthestageoffullrIsksharIng,however.Asthemanagedcare
marketplacematuresand|CDsgrowandsucceed,theexIstIngorganIzatIonsand,
especIallyanynewones,shIfttoprospectIvecapItatedpaymentsforprovIders.
Prospective Payments
ProspectIvecapItatedpaymentsconstItutesanentIrelynewworldtohealthcareprovIders,
InvolvIngprospectIvecapItatedpaymentsforlargepopulatIonsofpatIents,InwhIcheach
groupofprovIdersInthe|CDreceIvesafIxedamountperenrolledcoveredlIfe(member)
permonth(P|P|)andagrees,exceptInthemostunusualcIrcumstances,toprovIde
whatevercareIsneededbythatpopulatIonforthatprospectIvepayment.Themost
unusualcIrcumstancesInvolvecarveoutarrangementsInwhIchspecIfIcverycostlyand
unusualcondItIonsorprocedures(suchasthebIrthofachIldwIthdIsastrousmultIple
congenItalanomalIes)arecoveredseparatelyonadIscountedfeeforservIcebasIs.WIth
fullcapItatIon,theentIrefInancIalunderpInnIngofAmerIcanmedIcalcaredoesa
completeaboutfacefromthetradItIonalrewardsforgIvIngmorecareanddoIngmore
procedurestonewrewardsforgIvInganddoIngless.SomemanagedcarecontractscontaIn
otherfeaturesIntendedtoprotecttheprovIdersagaInstunexpectedoverutIlIzatIonby
patIentsthatwouldstretchtheprovIdersbeyondtheboundsoftheorIgInalcontractwIth
the|CD.TheprovIsIonssettIngtheboundarIesarecalledrisk corridors,andthestoploss
clausesaddsomedIscountedfeeforservIcepaymentfortheexcesscarebeyondtherIsk
corrIdor(capItatedcontractlImIt).ProvIderswhowereusedtogettIngpaIdmorefordoIng
morecansuddenlyfIndthemselvesgettIngpaIdafIxedamountnomatterhowmuchor
howlIttletheydowIthregardtoaspecIfIedpopulatIonhence,theperceIvedIncentIveto
do,andconsequentlyspend,less.ftheprovIdersrendertoomuchcarewIthInthedefIned
boundaryofthecontract,theyessentIallywIllbeworkIngforfree,theultImateInrIsk
sharIng.
ThereareclearlypotentIalInternalconflIctsInsuchasystem,
47
andhowpatIentsreacted
InItIallytothIsradIcalchangeInattItudeonthepartofphysIcIansdemonstratedthatthIs
overallmechanIsmIsunlIkelytobereadIlyembracedbythegeneralpublIc.Healthcare
provIders(physIcIans,otherhealthcareprofessIonals,andfacIlItIes),Inturn,allIed
themselvesInawIdevarIetyoforganIzatIonstocreatestrengthanddesIrableresourcesto
presenttothe|CDsIncontractnegotIatIons.|anagementservIceorganIzatIonsarejoInt
venturenetworkarrangementsthatdonotInvolvetrueeconomIcIntegratIonamongthe
practItIoners,butmerelyoffercommonservIcestophysIcIanswhomay,asaloosely
organIzedInformalgroup,electtoseek|CDcontracts.PreferredprovIderorganIzatIons
arenetworkarrangementsofotherwIseeconomIcallyIndependentphysIcIanswhoforma
newcorporateentItytoseekmanagedcarecontractsInwhIchtherearesIgnIfIcant
fInancIalIncentIvestopatIentstousethenetworkprovIdersandfInancIalpenaltIesfor
goIngtooutofnetworkprovIders.ThIshasprovedarelatIvelypopularmodelandappears
tobegaInIngwIdeacceptance.PhysIcIanhospItalorganIzatIonsaresImIlarentItIesbut
InvolveunderstandIngsbetweengroupsofphysIcIansandahospItalsothatalargepackage
orbundleofservIcescanbeconstructedasessentIallyonestoppoIntsofcare.ndependent
practIceassocIatIonsarelIkepreferredprovIderorganIzatIonsbutarespecIfIcallyorIented
towardcapItatedcontractsforcoveredlIveswIthsIgnIfIcantrIsksharIngbythe
P.46
provIders.Croups(orclInIcs)wIthoutwallsarecollectIonsofpractItIonerswhofully
IntegrateeconomIcallyIntoasInglefIscalentIty(truepartnershIp)andthencompetefor
|CDcontractsonthebasIsofrIsksharIngIncentIvesamongthepartners.FullyIntegrated
groupsorhealthmaIntenanceorganIzatIons(suchasKaIserPermanenteInCalIfornIaor
HarvardPIlgrImHealthInNewEngland)housethegroupofpartnerprovIderphysIcIansand
assocIatedsupportstaffatasInglelocatIonfortheconvenIenceofpatIents,abIgsellIng
poIntwhentheyseek|CDoremployercontracts.
Changing Paradigm
TheeraofsoloIndependentpractItIonersmaybeendIngInsomelocatIonswhere|CDs
domInatebecausetheorganIzatIonssImplywIllnotcontractwIthoneperson.ndependent
hospItalbasedgroups(lIkelystIllthemostcommonprIvatepractIcemodel)mayface
growIngsImIlardIffIcultIes.
48
ThesesmallergroupsofanesthesIologIstsmayfInd
themselvesatacompetItIvedIsadvantageunlesstheybecomepartofavertIcally
Integrated(multIspecIalty)orhorIzontallyIntegrated(wIthotheranesthesIologIsts)
organIzatIon.AnextensIvecompendIumofrelevantInformatIonhasbeenpreparedbythe
ASA.
J8
8ecauseItappearslIkelythatmanyanesthesIologIstsIntheUnItedStateswIllbe
affectedbyevolvIngchangesInpractIcearrangements,theInformatIonInthIsandrelated
publIcatIons
49
IsveryImportant.NegotIatIonswIth|CDsrequIreexpertadvIce,probably
evenmoresothanthetradItIonalexclusIvecontractswIthhospItalsasprevIouslynoted.
8eforeanynegotIatIoncanevenbeconsIdered,the|CDmustprovIdesIgnIfIcantamounts
ofInformatIonaboutthecoveredpatIentpopulatIon.TheprojectedhealthcareutIlIzatIon
patternofalargegroupofwhItecollarworkers(andtheIrfamIlIes)frommajorupscale
employersInanurbanareawIllbequItedIfferentfromthatofarelatIvelyrural|edIcaId
populatIon.SpecIfIcdemographIcsandpastutIlIzatIonhIstorIesareabsolutelymandatory
foreachproposedpopulatIontobecovered,andthIsInformatIonshouldgodIrectlytothe
advIsIngexpertsforevaluatIon,whethertheproposednegotIatIonIsfordIscountedfeefor
servIce,afeeschedule,globalbundledfees,orfullcapItatIon.
SIgnIfIcantquestIonswerepoIntedlyraIsedaboutthereImbursementImplIcatIonsfor
anesthesIologIstsoftheputatIvemanagedcare/practIcereorganIzatIonrevolutIon.AgaIn,
theASAhasassembledrelevantInformatIon,theunderstandIngofwhIchIsessentIalto
successfulnegotIatIons.
J8
Table21hasalIstofInformatIonananesthesIapractIceshould
haveaboutItsactIvItIes.nItIalconsIderatIonofacapItatedcontractshouldInvolvean
attempttotakeallthedataabouttheexIstIngpractIceandtheproposed|CDcovered
populatIonfromacapItatIonchecklIst
J8
andtranslatebackfromtheproposedcapItated
ratetoIncomefIguresthatwouldcorrelatewIththeexIstIngpractIcestructure,toallowa
comparIsonandanunderstandIngoftherelatIonshIpoftheprojectedworkInthecontract
thetoprojectedIncomefromIt.tIs,ofcourse,ImpossIbletosuggestdollarvaluesfor
capItatedratesforanesthesIologycarebecausedetaIlsandcondItIonsvarysowIdely.Dne
ASApublIcatIon
J8
usedexamples,purelyforIllustratIvepurposes,InvolvIngS2.50orS4.00
P|P|,buttherewereunconfIrmedreportsatthepeakofthemanagedcarebubbleof
capItatedratesaslowasS0.75P|P|foranesthesIology.
0IscountedfeeforservIcearrangementsareeasIerforanesthesIologIststounderstand
becausethesearedIrectlyreferabletoexIstIngfeestructures.FeportsofgroupsInstItutIng
10to50dIscountsoffthestartIngpoIntof80ofusualandcustomaryreImbursementIn
varIouspractIcecIrcumstanceswerecIrculatedatnatIonalmeetIngsofanesthesIologIsts.
WererIgIdlycontrolledfullymaturemanagedcaretodomInatethepractIcecommunIty,It
wouldbelIkelythattheaverageIncomeforanesthesIologIstswoulddecreasefrompast
levels.However,ItlIkelyalsowouldbetruethatanesthesIaprofessIonalswouldcontInue
tohaveIncomesstIllaboveaverageamongallhealthcareprofessIonalsInthatmarket.
AnotherrecentfeatureofthIsdIscussIonIsthetendencyofprIvate(nongovernmental)
contractIngorganIzatIonstoattempttotIetheIrpaymentsforprofessIonalservIcestothe
government's|edIcarerateforspecIfIcCPT4codes.tIscommonforbothcommercIal
IndemnItyInsuranceentItIes(e.g.,8lueShIeld,Aetna,Humana,UnItedHealth)aswellas
|CDstoofferprImarycarephysIcIans,forexample,125ofthe|edIcarepaymentratefor
specIfIcservIces.AlthoughgroupsofprImarycarephysIcIansmayvIewthIsassomewhat
reasonableand,thus,theysIgnsuchcontracts,anesthesIologIstsfaceunIquechallengesIn
thIsregard.EvenwIththemostrecentpromIsefromtheresponsIbleoffIceswIthIn
|edIcareofareImbursementupgradeforanesthesIaservIces,mostanesthesIa
professIonalsstIllbelIevethatthe|edIcarereImbursementrateIsunfaIrlylowforthe
workInvolvedInprovIdInganesthesIacare.ThenewratewouldstIllbelessthanhalfthe
perunItconversIonfactorthatthelargeIndemnItycarrIershavebeenpayIngfor
anesthesIacareInrecentyears.Therefore,125ofwhatmanyanesthesIaprofessIonals
consIderwoefullyInadequatewouldstIllbeInadequate.Thus,InspIteofsometImes
Intensepressure,anesthesIaprofessIonalsInmanymarketshavebeenreluctanttoaccept
IndemnItyInsurancecontractratestIedto|edIcarerates.Asalways,anesthesIa
professIonalsfacedwIthcomplexreImbursementsItuatIonsanddecIsIonsshouldseek
expertadvIcefromthenatIonaloffIcesoftheIrprofessIonalpractIceorganIzatIonsand
fromknowledgeablepaIdconsultantsandattorneys.
Pay for Performance
CommercIalIndemnItyInsuranceentItIes(e.g.,8lueShIeld,Aetna,Humana,UnIted
Health),|CDs,andpartIcularly,thefederalCenterfor|edIcareand|edIcaIdServIces
(C|S)areallcurrentlyfIxatedontheconceptofperformancebasedpaymentsasa
sIgnIfIcantnewwaytolImItthegrowthof(andevenreduce)healthcarecosts,
50
especIally
byreducIngexpensIvecomplIcatIonsofmedIcalcare.ThIspayforperformance
movementbeganwIththefederalTaxFelIefandHealthcareActof2006andcontInues
wIththePhysIcIanQualItyFeportIngnItIatIveIn2008.ThepotentIalImplIcatIonsfor
anesthesIapractIcehavebeensummarIzed.
51
ngeneral,C|SmadestrenuouseffortstoattempttodefIneandpromulgateobjectIve
qualItymeasuresthatcouldbedocumentedasIndIcatorsofthequalItyofhealthcare
delIvered.ThemaInIssueIsthepromotIonofspecIfIccareelementsthathelpavoId
expensIveoutcomesorcomplIcatIonsthatcurrentlygenerateadIsproportIonate
(preventable)fractIonofhealthcarecosts.TheadmInIstratIonofaspIrInandbetablockers
wIthInafIxedbrIefIntervalafterthearrIvalofanacutemyocardIalInfarctIonpatIentIsa
goodexample,asarevarIousparametersInthecareofpatIentswIthcommunItyacquIred
pneumonIaorcongestIveheartfaIlure.0efInIngandvalIdatIngobjectIveandeasIly
quantIfIablesocalledqualItymeasuresthatwIllpreventexpensIvecomplIcatIonsof
anesthesIacareprovedtobemoredIffIcult.TheInItIaltargetedparameterwassomewhat
IndIrect:thetImIngoftheadmInIstratIonofprophylactIcantIbIotIcsprIortosurgIcal
IncIsIon.TheanesthesIaprofessIonalIsjudgedtobeIncomplIancewhentheantIbIotIcIs
admInIsteredwIthInthe1hour(2hoursforvancomycInandfluoroquInolones)prIorto
IncIsIon.ThIsmustbeverIfIablydocumentedontheanesthesIarecord.8enchmarkcrIterIa
suchasanInItIal80complIance(butlIkelyIncreasIngtoatleast95)foraspecIfIc
fInancIalentItybIllIng|edIcareand|edIcaIdmustbemetorthereImbursementfor
anesthesIaservIcesbythatfInancIalentItywIllbe
P.47
reducedbyaspecIfIcfractIon(orapromIsedbonuswIllbewIthheld)asacomplIance
IncentIve,butalsosomewhatasanoffsettotheIncreasedcostoftheconsequent
complIcatIonsassocIatedwIthfaIluretocomply.fperformanceIsIncomplIance,C|SwIll
paythemaxImumallowablereImbursement(payforperformance).
ThesecondtargetIscatheterrelatedbloodstreamInfectIon,andtheperformance
behavIorexpectedofanesthesIaprofessIonalsIsobservanceofstrIctaseptIcprotocol
durIngcentralvascularcatheterplacement(andavoIdIngthefemoralrouteIfatall
possIble).AsofthIswrItIng,thethIrdobjectIveparameterofanesthesIacarequalItyIs
scheduledtotargettemperaturemanagementofthesurgIcalpatIentwIththecomplIance
behavIorbeIngmetbyachIevIngoneofthreepossIblegoals:useofactIvewarmIng
IntraoperatIveordocumentedtemperatureJ6`CeItherInthelastJ0mInutesof
anesthesIaorthefIrstJ0mInutesInthePACU.FuturepotentIalobjectIveperformance
crIterIaIntendedtoencourageavoIdanceofcostlycomplIcatIonsofanesthesIacaremay
IncludeglucosecontrolInmajorsurgery,useofpencIlpoIntspInalneedlesInobstetrIc
anesthesIa,useofelectronIcmedIcalrecords,preoperatIvescreenIngforsleepapnea,
preoperatIvefastIngInstructIons,meperIdIneadmInIstratIonforpostoperatIveshIverIng,
andseveralothers.nallcaseswhenaparameterIsadopted,benchmarkcrIterIafor
degreeofcomplIancewIllbeestablIshedandreImbursementwIllbereducedonewayor
anotherforfaIluretocomply,asdocumentedontherelevantrecordsandselfreportedby
thebIllIngfInancIalentIty(subjecttoaudIt,ofcourse).
HospItalswIllhaveevenmoreatstakeInthesensethatthepayforperformance
movementIscreatIngparadIgmsInwhIchhospItalswIllnotreceIvereImbursementsfor
careassocIatedwIthpreventablecomplIcatIonssuchascatheterrelatedsepsIs,ventIlator
acquIredpneumonIa,anddecubItusulcers.ThIsconcepthasseveralImplIcatIons.DneIs
thatsmallerhospItalsoftenpopulatedbylessacutepatIentswIllbemorelIkelyand
quIckertotransfersIckerpatIentstolargerreferralfacIlItIesInordertoavoIdlosIng
reImbursementassocIatedwIththedevelopmentofpatIentcomplIcatIons.ConcomItantly,
documentatIonofthetImIngofthedevelopmentofcomplIcatIonswIllbecomecrItIcal.fa
hospItalordepartmenthasdocumentedthepreexIstIngpresenceofacomplIcatIonatthe
tImeofapatIent'sadmIssIon,ItshouldnotbepenalIzedforthedevelopmentofthat
condItIon.nthIscontext,anesthesIaprofessIonalscanhaveanImportantrole
documentIngtheexIstenceofpneumonIaorsacraldecubItusulcersIntheIrrecordswhen
theyfIrstseeanewlyadmIttedpatIent,usuallyforpreoperatIveevaluatIon.ThIswIllbe
perceIvedasexcellentInstItutIonalcItIzenshIpbytheanesthesIaprofessIonalbecauseIt
maypreventsIgnIfIcantreImbursementreductIontothehospItal.
HIPAA
The200JImplementatIonofthePrIvacyFuleoftheHealthnsurancePortabIlItyand
AccountabIlItyAct(HPAA)of1996requIredsIgnIfIcantchangesInhowmedIcalrecordsand
patIentInformatIonarehandledInthedaytodaydelIveryofhealthcare.TheImpacton
andrequIrementsforanesthesIologIstsaresummarIzedInacomprehensIvepublIcatIon
fromtheASA
52
thatfollowedtwoeducatIonalsummarIes.
5J,54
AttentIonIsfocusedonprotectedhealthInformatIon(IdentIfIableasfromaspecIfIc
patIentbyname).PatIentsmustbenotIfIedoftheIrprIvacyrIghts.UsuallythIswIllbe
coveredbythehealthcarefacIlItyInwhIchanesthesIologIstswork,butIfseparateprIvate
recordsaremaIntaIned,separatenotIfIcatIonmaybenecessary.PrIvacypolIcIesmustbe
created,adopted,andpromulgatedtoallpractItIoners,allofwhomthenmustbetraIned
InapplIcatIonofthosepolIcIes.Dften,anesthesIologygroupscancombInewIththe
facIlItIesInwhIchtheypractIceasanorganIzedhealthcarearrangementsothatthe
anesthesIapractItIonerscanbecoveredInpartbytheHPAAcomplIanceactIvItIesofthe
facIlIty.AprIvacyoffIcermustbeappoIntedforthepractIcegroup.FInally,andmost
Importantly,medIcalrecordscontaInIngprotectedhealthInformatIonmustbesecuredso
theyarenotreadIlyavaIlabletothosewhodonotneedthemtorendercare.
DneofthemostobvIousapplIcatIonsformanyanesthesIologIstsIsconcernaboutthe
assembledpreoperatIveInformatIonandchartsfortomorrow'scasesthatfrequentlywere
placedpromInentlyIntheDFholdIngareaattheendofoneworkdayInreadInessforthe
nextday'scases.HPAAprovIsIonsrequIrethatallthatpatIentInformatIonbelockedaway
overnIght.AnotherclassIcexampleIswhatmanyDFsrefertoastheboard.Dften,a
largewhItedrymarkerboardoccupIesapromInentwallnearthefrontdeskofanDFsuIte,
andtherooms,cases,andpersonnelassIgnmentsareInscrIbedthereonatthebegInnIngof
thedayandmodIfIedorcrossedoffasthedayprogresses.UnderHPAA,patIents'names
maynotbeusedonsuchaboardIfthereIsanychancethatanyonenotdIrectlyInvolvedIn
theIrcarecouldseethem.AlternatIvely,somefacIlItIestapeacopyoftheday'sDF
schedule(IncludIngpatIents'names,ages,andoperatIons)onthewall,whIchwouldalsobe
avIolatIon.ThesameIstrueforsImIlarboardsorpostedschedulesInDFholdIngareasand
PACUs.AnotherIssueoftenoverlookedthatIsveryproblematIcandprobablytheonethat
concernspatIentsthemostIstheobtaInIngofhIstoryInformatIonInalocatIon,suchasa
bedslotbehIndjustacurtaInIntheDFholdIngarea,wheresensItIvemedIcaland
personalInformatIonIsspokenoutloudwIthInearshotofotherpatIents,otherpatIents'
famIlIes,andnonInvolvedcaregIvers.ThIsconcernIsdIffIculttoaddressandthereIsno
oneunIversallyapplIcablesuggestIon.However,anesthesIaprofessIonalswhoInteractwIth
patIentsInsuchenvIronmentsshouldbeassensItIveasphysIcallypossIbletobeIng
overheardandalsoshouldbrIngsuchconcernstotheattentIonofthefacIlIty
admInIstrators.
Further,manyanesthesIologypractIcesalsomustapplyHPAAprovIsIonstotheIrbIllIng
operatIons;thedetaIlswIllvarydependIngonthemechanIsmsusedandagreatdealwIll
dependonwhIchtypeofelectronIcclaImssubmIssIonsoftwareIsbeIngusedbythebIllIng
entItyactuallysubmIttIngtheclaIms.
55
TelephonecallsandfaxesIntooffIcesmustbe
handledspecIallyIfcontaInIngIdentIfIablepatIentInformatIon.PresentatIonofpatIent
InformatIonforQAorteachIngpurposesmustbefreeofallIdentIfIersunlessspecIfIc
IndIvIdualpermIssIonhasbeenobtaInedonprescrIbedprIntedforms.FequestsforpatIent
InformatIonfromawIdevarIetyofoutsIdeentItIes,IncludIngInsurancecompanIesand
collectIonagencIes,mustbeprocessedInHPAAcomplIantways.HPAApolIcyandactIons,
aswellasenforcementactIvItIes,arebeIngdevelopedovertImeandassItuatIons
develop.ThIssystemdependsInpartonpatIentcomplaIntsforbothenforcementand
polIcyevolutIon.nmanypractIcesandpractIcelocatIons,therehavebeenfeworevenno
formalcomplaIntsofvIolatIonsofpatIentprIvacy,IndIcatIngtheInItIalImplementatIonof
HPAAcomplIancemayhavelargelyhadthedesIredeffect.
Electronic Medical Records
0atabases,spreadsheets,andelectronIctransferofInformatIonarenonspecIfIcfeatures
thathavebeenapplIedtohealthcare.TheclassIcmedIcalrecord,ontheotherhand,has
requIredthecreatIonofentIrelynewsoftwareInanattempttoduplIcatethefunctIonof
thehandwrIttenordIctatedtradItIonalchart.ThIshasaffordedopportunItIestomultIple
P.48
competIngcommercIalentItIestoattempttofIllthIsneed.Usually,competIngproprIetary
systemsareIncompatIbleanddonottalktoeachother.ThIsfactseverelylImItsoneof
thehIghlytoutedbenefItsofmedIcalpractIcesgoIngelectronIc.CostIsanothergreat
barrIer,asIstheformIdabletaskofenterIngtherequIredInformatIonfromtheoldpaper
recordsIntotheelectronIcsystem.TherehasbeengovernmentalandpublIcpressurefor
healthcareInstItutIons,facIlItIes,andpractIcestoadoptelectronIcrecordsbecauseofthe
potentIalforIncreasedlegIbIlItycausIngreductIonInerrorsandconfusIon,greaterspeedof
fIlIngandretrIeval,easytransmIssIonoflargeamountsofInformatIon(suchasfroma
surgeon'soffIcetoananesthesIapractIce'sbookIngoffIceandalsotoahospItal's
preoperatIveclInIcorDFholdIngarea),andQAmonItorIngofvastdatabases.ncreased
easeoftransmIssIonandfIlIngofreImbursementclaImsandcostsavIngsfromclerIcalstaff
downsIzIngareclaImsIntendedtoencouragephysIcIanpractIcegroupstoadoptelectronIc
medIcalrecords(E|Fs).However,experIencetodatehassuggestedthatthecommercIally
avaIlablesoftwaresystems(bothforInstItutIonsandpractIcegroups)arenotasrobustor
relIableasadvertIsedbytheIroftenaggressIvemanufacturers.AccordIngly,theexpected
benefItshavenotmaterIalIzedquIteaspredIcted,partIcularlyInthatcostshavebeen
great,oftenfarInexcessofestImates,andcostsavIngshavebeenmInImalatbest.
PractIcegroupsofanesthesIaprofessIonalsshouldconsIderallofthesenotedpoIntsprIor
toInvestIngInanE|Fsystem.AtmInImum,carefulstudyandevaluatIonofthesame
systemalreadyInplaceInanotheranesthesIologypractIceshouldbeundertaken.
fbasIcE|FImplementatIonhasbeenproblematIcforpractIces,trueelectronIcanesthesIa
InformatIonmanagementsystemshavebeenevenmoredIffIcult.TheseInclude
preoperatIve,IntraoperatIve,postoperatIve,bIllIng,andQAcomponents.Fortheactual
DFanesthesIarecord,severalcommercIalversIonsareavaIlable.0IfferentanesthesIa
professIonalshavevarIousopInIonsabouteaseofImplementatIonandsubsequentuse.
UnlessonemassIvebolusoffullyIntegratednewtechnologyfromasInglemanufacturerIs
InstalledallatonetIme,IntegratIonofanewE|FwIththeexIstInganesthesIamachInes
andmonItorstoensurefullaccuratecaptureofalldataparameterscanoftenbedIffIcult
andfrustratIng.ThefunctIonandvalueofelectronIcanesthesIarecordscanbedebated
endlessly.AllofthemtodaywIllrequIrecomputersonorIntheanesthesIamachIne.These
computersshouldbenternetenabledsothatdemographIcandbIllIngInformatIoncanbe
automatIcallyuploadedtothefacIlIty'sandthepractIce'sdatabase.Anysuchsystemmust
alsoIntegratewIththebIllIngsystemsofthefacIlItyandthepractIceorthetouted
benefItswIllbelargelynegated.AgaIn,thebest,andInsomesenses,theonlywayto
evaluateserIouslyandthoroughlyaproposedmajorInvestmentofmoney,effort,andtIme
IstovIsItafullyupandworkIngInstallatIonofthatelectronIcanesthesIaInformatIon
managementsystemandtalkdIrectlyIndetaIlwIththeusers.Thecosts,Inallsensesof
theword,aresogreatthatItremaInsasIgnIfIcantgambletobethefIrsttopurchaseand
Implementsuchasystem.
Expansion Into Perioperative Medicine, Hospital Care, and
Hyperbaric Medicine
SomeanesthesIologIstsnowfunctIonatleastsomeofthetImeInpreoperatIvescreenIng
clInIcsbecauseofthegreatfractIonofDFpatIentswhodonotspendthenIghtbefore
surgeryInthehospItalorwhodonotcometoahospItalatall.nsuchsettIngs,these
anesthesIologIstsfrequentlyassumearoleanalogoustothatofaprImarycarephysIcIan,
plannIngandexecutIngaworkupofoneormoresIgnIfIcantmedIcalorsurgIcalproblems
beforethepatIentcanreasonablybeexpectedtoundergosurgery.LIkewIse,thIsconcept
wouldbeexcellentforthepostoperatIveperIod.AnanesthesIologIst,completelyfreeofDF
orotherdutIes,couldnotonlymakeatleasttwIcedaIlyroundsofpatIentsaftersurgery
andprovIdeexceedInglycomprehensIvepaInmanagementservIce,butalsocouldfollow
thesurgIcalprogressandmakereports(lIkelyvIaanE|ForemaIl)tothesurgeon'soffIce
oralphanumerIcpocketcommunIcator.AfundamentalaspectofthepractIceof
anesthesIologyIsthemanagementofacuteproblemsInthehospItalsettIng.tIslogIcal
thatanesthesIologIstswouldbeamongthephysIcIansbestsuItedtoprovIdeprImarycare
forpatIentsInthehospItalsettIng.
AnaddItIonalevolvIngopportunItyIsthecreatIonandImplementatIonofrapIdresponse
teamswIthInacutecarehospItals.nessence,studIeshaverevealedthatpatIentson
generalcarenursIngfloorssometImesbegIntodeterIorateand,foronereasonoranother
butoftenbecauseoftheresponsIblephysIcIanbeIngunavaIlableorataconsIderable
dIstanceatthatmoment,thepatIentsarenotevaluatedortreatedInatImelymannerand
oftennotuntIltheyhavefurtherdeterIorated,sometImestoacrItIcalstatus.Therefore,a
natIonaltrendhasdevelopedInwhIchhospItalscreateateamofknowledgeable
professIonals(whohaveotherregularresponsIbIlItIes)whousuallyhavenoprIorknowledge
ofthedeterIoratIngpatIentbutwhowIllrespondwIthInaveryfewmInutestothecall
from(usually)afloornursewhodetectsadeterIoratIngpatIent(e.g.,IncreasIngfever,
relatIvehypotensIonandtachycardIa,absenturIneoutput).Frequently,therapIdresponse
teamInstItutesImmedIatesymptomatIctreatment,arrangesforahIgheracuItylevelof
care,andcontactstheprImaryresponsIblephysIcIan.mportantly,InlargerhospItals,It
hasbeensuggestedthattheInhouseanesthesIologIstsareunIquelyqualIfIedtobekey
membersoftherapIdresponseteambecausetheInterventIonsalmostalwaysInvolve
acutebreadandbutterresuscItatIvecare.AlthoughmanyanesthesIologIstsmaybelIeve
theyalreadyhaveplentyofworkIntheDF,suchpartIcIpatIonwhenpossIblewouldbean
outstandIngandhIghlyvIsIblecontrIbutIontothehospItal'smIssIonofenhancedpatIent
care.Also,suchInterventIonscouldbeseparatelybIllableencountersasconsultatIonsor,
alternatIvely,excellentsupportforthemaIntenanceorevenIncreaseofthehospItal's
fInancIalsubsIdytoItsanesthesIaprofessIonalgroup.
FInally,anesthesIologIstsInsomelocatIonshavebecomeInvolvedInthepractIceof
hyperbarIcmedIcIneandwoundcare.ThIsIslIkelyrelatedtothefamIlIarItyof
anesthesIologIstswIthconceptsofgaslawsandphysIcs,alongwIththeIrconstantpresence
InthehospItal.ThetreatmentofvarIousmedIcalcondItIonsbytheapplIcatIonofoxygen
underIncreasedpressure,usually2toJatmospheresabsolute,atonetImewasoneofthe
morerapIdlygrowInghospItalservIces.AnesthesIologIstsareamongtheleadersofthIs
fIeld,wIthunlImItedopportunItIesforclInIcalcare,teachIng,andresearch.EvenabrIef
dIscussIonofthIsfIeldIsoutsIdethescopeofthIschapter,andInterestedreadersare
referredtotheUnderseaandHyperbarIc|edIcalSocIety(www.umhs.org).
Operating Room Management
TheroleofanesthesIologIstsInDFmanagementhaschangeddramatIcallyInthepastfew
years.WIththecurrentclImateofaconsIderableshortageofanesthesIaprofessIonals,
hospItalssubsIdIzIngmanyanesthesIologygrouppractIces,andanIncreasIngworkload,
partIcIpatIonInDFmanagementIsessentIallymandatory.ThecurrentemphasIsoncost
contaInmentandeffIcIencywIllforceanesthesIologIststotakean
P.49
actIveroleInelImInatIngmanydysfunctIonalaspectsofDFpractIcethatwereprevIously
Ignored.FIrstcasemornIngstarttImeshavechangedfromasuggestIontoamandate.
0elaysofanysortarenowoftentrackedelectronIcallyInrealtImeandcarefully
scrutInIzedtoelImInatewasteandIneffIcIency.Together,anesthesIologIsts,surgeons,DF
nursesandtechnIcIans,andIncreasIngly,professIonaladmInIstrators/managersneedto
determInewhoIsbestqualIfIedtobealeaderInthedaytodaymanagementoftheDF.
56
Clearly,dIfferentgroupshavedIfferentperspectIves.However,anesthesIologIstsareInthe
bestposItIontoseethebIgpIcture,bothoverallandonanygIvenday.Surgeonsare
commonlyelsewherebeforeandaftertheIrIndIvIdualcases(andsometImesforthe
begInnIngandtheendoftheIrcases);nursesandadmInIstratorsmaylackthemedIcal
knowledgetomakeapproprIate,tImelydecIsIons,oftenonthefly.tIsthe
anesthesIologIstwIththeInsIght,overvIew,andunIqueperspectIvewhoIsbestqualIfIedto
provIdeleadershIpInanDFcommunIty.ThesubsequentrecognItIonandapprecIatIonfrom
theothergroups(especIallyhospItaladmInIstratIon)wIllclearlyestablIshthe
anesthesIologIstsasconcernedphysIcIansgenuInelyInterestedInthewelfareoftheDFand
theInstItutIon.
Organization
ThesymbIotIcrelatIonshIpbetweenanesthesIaprofessIonalsandsurgeonsremaIns
unchanged.8othgroupsrecognIzethIsfactandalsothecommongoalofhavIngtheDF
functIonInasafe,expedItIousmanner.TheageoldquestIon,WhoIsInchargeofthe
operatIngroom:stIllconfrontsmanyhospItals/InstItutIons.8ecausesomeanesthesIology
groupsaresubsIdIzedbythehospItal,theDForganIzatIonInsuchcaseshaschanged
accordIngly.|anyhospItaladmInIstratorswanttohaveInputregardIngwhoIsInchargeof
theDFwIthaneyetoIncreasIngeffIcIencyandthroughputwhIlereducIngcost.TheIr
wIsheshaveanevenaddedsIgnIfIcancewhenmoreoftheIrdollarsareInvolvedthrough
theanesthesIologygroupsubsIdy.SometImestherecanbenorealanswerto,Who'sIn
charge:becauseofthecomplexItyoftheInterpersonalrelatIonshIpsIntheDF.Some
InstItutIonshaveaprofessIonalmanager(oftenaformerDFregIsterednurse)whosesole
jobIstoorganIzeandruntheDF.ThIsIndIvIdualmaybevestedwIthenoughauthorItyto
berecognIzedbyallasthepersonIncharge.DtherInstItutIonsostensIblyhaveamedIcal
dIrectoroftheDF.However,theImplIcatIonstothesurgeonsthatananesthesIologIstIs
Incharge,orvIceversa,havecausedmanyInstItutIonstoabandonthetItleorretaInthe
posItIonbutassIgnnoauthorItytoIt.nsuchInstances,InstItutIonsusuallyresolvedIsputes
throughsomeauthorItywIthaphysIcIan'sperspectIve.fthereIsnomedIcaldIrectorwIth
authorItytomakedecIsIonsstIck,centralauthorItyusuallyresIdeswIththeDFcommIttee,
mostoftenpopulatedbyphysIcIans,senIornurses,andadmInIstrators.EveryDFhasthIs
forumformajorpolIcyandfIscaldecIsIons.AspartofcommItteefunctIon,thestandard
practIcesofnegotIatIon,dIplomacy,andlobbyIngforvotesareregularlycarrIedout.The
ImpactofsuchanDFcommItteevarIeswIdelyamongInstItutIons.
0espItetheconstantlychangIngdynamIcsoftheDFmanagementandthefrequentmajor
frustratIons,anesthesIologIstsshouldpursueagreaterroleIndaytodaymanagementIn
everypossIbleapplIcablepractIcesettIng.AnanesthesIologIstwhoIscapableoffacIlItatIng
thestartofcaseswIthmInImaldelaysandsolvIngproblemsontheflyastheyarIsewIll
beInanexcellentposItIontoservehIsorherdepartment.SucceedIngInthIsrolewIllhave
adramatIcposItIveImpactonalltheDFconstItuents.ThesurgeonswIllbelessconcerned
aboutwhoIsInchargebecausetheIrcasesaregettIngdone.ThehospItaladmInIstratIon
wIllwelcometheeffortbecausetheywantsomethIngextraInreturnforanymoneythey
arenowgIvIngtotheanesthesIologygroupsasasubsIdy.Furthermore,theDFcommIttee
(orwhateversystemfordIsputeresolutIonIsInplace)IsstIllfunctIonalandhasnotbeen
cIrcumvented(andwIllbethankfulfortheabsenceofdIsputesneedIngresolutIon).
SomeInstItutIonsusethetermClinical Director of the OR.ThepersonawardedthIs
desIgnatIonshouldbeasenIorlevelIndIvIdualwIthfIrsthandknowledgeoftheDF
envIronmentandfunctIon.AnesthesIologIstshaveabetterunderstandIngofthe
perIoperatIveprocess.TheypossessthemedIcalknowledgetomakeapproprIatedecIsIons.
TheIrIntImateassocIatIonwIthsurgeonsandtheIrpatIentsallowsthemtobestallocate
resources.TheAmerIcanAssocIatIonofClInIcal0IrectorsIn2002reportedthat71of
surveyrespondentsstatedthatananesthesIologIstwasdesIgnatedastheClInIcal0Irector
oftheDF.
Contact and Communication
AnImportantIssuefortheanesthesIaprofessIonalsInanyDFsettIngIswhoamongthe
groupwIllbethecontactpersontoInteractwIththeDFandItsrelatedadmInIstratIve
functIons.nsItuatIonsInwhIcheveryoneIsanIndependentcontractor,theremaybea
tItularchIefwhobydesIgnIsthecontactperson.TheanesthesIologIstInthIsrole
commonlychangesyearlytospreadthedutIesamongallthemembers.Largegroupsor
departmentsthatfunctIonasthesoleprovIdIngentItyforthathospItal/facIlItyoften
IdentIfyanIndIvIdualasthecontactpersontoactasthevoIceforthedepartment.
Furthermore,thesesamegroupsdelIneatesomeoneonadaIlybasIstobetheclInIcal
dIrector,orthepersonrunnIngtheboard.Frequently,thIsposItIonIsbestfIlledbyone
ofasmalldedIcatedfractIonofthegroup(e.g.,threepeople)ratherthanrotatIngthe
responsIbIlItyamongeverymemberofthegroup.ExperIencedboardrunnershavean
InstInctuallyderIvedbetterperspectIveonthenuancesofmanagIngtheoperatIngschedule
InrealtIme.CertaInproceduresmayrequIrespecIfIctraInIng(e.g.,transesophageal
echocardIographyskIlls)thatnotallmembersofthegrouppossess.Clearly,changes
sometImeshavetobemadetomatchtheabIlItyoftheanesthesIaprovIderandthe
requIrementsoftheprocedurewhenurgentoremergentcasesareposted.
AnotherbenefItofaverysmallnumberofdaIlyclInIcaldIrectorsIsarelatIveconsIstency
IntheapplIcatIonofDFpolIcIes,partIcularlyInrelatIonshIptotheschedulIngofcases,
especIallyaddons.DneofthemostfrustratIngaspectstobothsurgeonsandDFpersonnel
IsunpredIctabIlItyandInconsIstencyInthedecIsIonsmadebytheanesthesIa
group/departmentmembers.ApatIentdeemedunacceptableforsurgeryby
anesthesIologIstXon|ondaymaybeperfectlyacceptable,InthesamemedIcalcondItIon,
foranesthesIologIstYonTuesday.0IsagreementsareInevItableInanylargegroup.
However,daytodayDFfunctIonmaybehamperedbyalargenumberofthesetypesof
cIrcumstances.HavIngonememberofaverysmallgroupInchargewIllleadtomore
consIstencyInthIsprocess,especIallyIftheboardrunner/clInIcaldIrectorhasthe
authorItytoswItchpersonneltoaccommodatethesItuatIon.WIthoutstIflIngIndIvIdual
practIces,phIlosophIes,andcomfortlevels,acertaInamountofconsIstencyapplIedto
sImIlarclInIcalscenarIoswIllImproveDFfunctIonImmeasurably.ThesefewdedIcated
dIrectorsshouldbeabletoaccomplIshbothgoalsbetterthanalargerotatInggroup.
AnewerpotentIalcomponentofIntraDFcommunIcatIonsIstheconceptofchecklIstsand
teambrIefIngs.AnalogoustothenowrequIredtImeoutIneachDFprIortosurgIcal
IncIsIonwhenthecorrectIdentItyofthepatIent,theIntendedprocedure,andany
lateralItyInvolvedIsverIfIed,someDFsareattemptIngtohaveasImIlarInterprofessIonal
communIcatIon
P.50
InvolvIngallrelevantDFpersonnel(theteam)prIortothepatIententerIngtheactualDF,
durIngwhIchtheInvolvedsurgeon,anesthesIaprofessIonal,cIrculatIngnurse,scrubperson,
andsupportpersonsasIndIcatedeachacknowledgeasummaryofwhatIsprojectedtotake
placeInthIscase,anyantIcIpatedneedforextraorunusualresourcesorequIpment,any
antIcIpateddIffIcultIesorIncreasedrIsks,andspecIfIcplanstodealwIthanyfeatureofany
ofthesepoIntsthatwouldrequIreInterventIon.nmanymodels,aprIntedsInglepage
checklIstwIthroutInepromptsandfIllInboxesIsusedtofacIlItatetheprocess.Dnestudy
reportedatwothIrds'reductIonIncommunIcatIonfaIluresthathaveotherwIselIkely
causedproblems,rIsks,orIneffIcIencIes.
57
Materials Management
Usually,theInstItutIonalcomponentoftheanesthesIaservIcestaffsandmaIntaInsa
locatIoncontaInIngthespecIfIcsupplIesunIquetothepractIceofanesthesIa(the
workroom).DbjectIvesnecessaryforeffIcIentmaterIalsmanagementIncludethe
standardIzatIonofequIpment,drugs,andsupplIes.AvoIdanceofduplIcatIon,volume
purchasIng,andInventoryreductIonarealsoworthwhIle.ThereneedstobecoordInatIon
wIththeDFstaffastowhoIsresponsIbleforacquIsItIonofroutInehospItalsupplIessuchas
syrInges,needles,tubIng,andIntravenousfluIds.0ecIsIonsastowhIchbrandsofwhIch
supplIestopurchaseIdeallyshouldbemadeasagroup.Dften,whenseveralcompanIes
competeagaInsteachotherInanopenmarket,lowerprIcesarenegotIable.These
negotIatIonsmayoccurbetweentheanesthesIaprofessIonalsandthehospItal
admInIstratIon,orbythephysIcIancomponentsoftheDFcommIttee.nmanycases,
however,hospItalsbelongtolargebuyInggroupsthatdetermInewhatbrandsandmodels
ofequIpmentandsupplIeswIllbeavaIlable,wIthnoexceptIonspossIbleexceptatgreatly
Increasedcost.SometImes,thIsIsfalseeconomyIftheprovIdedItemsareInferIor(cheap)
orannoyIngand,forexample,IfItroutInelytakesopenIngthreeorfourIntravenous
cannulaeIntheprocessofstartIngapreoperatIveIntravenouslIneasopposedtothe
hIgherqualItyandrelIablesIngleonethatmaycostmorepercannulabutIslessexpensIve
overallbecausefarfewerwIllbeused.0IspassIonatepresentatIonofsuchlogIcbya
respectedteamplayersenIoranesthesIologIsttotheDFcommItteeordIrectorofmaterIals
managementmayhelpresolvesuchconundrums.
Scheduling Cases
AnesthesIologIstsneedtopartIcIpateIntheDFschedulIngprocessattheIrfacIlItyor
InstItutIon.nsomefacIlItIestheschedulIngoffIceandtheassocIatedclerIcalpersonnel
workundertheanesthesIagroup.Commonly,schedulIngfallsundertheDFstaff's
responsIbIlIty.0IrectcontrolofthescheduleusuallyresIdeswIththeDFsupervIsoror
chargeperson,frequentlyanurse.Whateverthearrangements,theanesthesIagroupmust
haveadIrectlIneofcommunIcatIonwIththeschedulIngsystem.Thenecessarynumberof
anesthesIaprofessIonalsthatmustbesupplIedoftenchangesonadaIlybasIsperthe
caseloadandsometImesbecauseofInstItutIonalpolIcydecIsIons.Afterhourscallmustbe
arranged,polIcychangesfactoredIn,andaddItIons/subtractIonstothesurgIcalload(day
today,weektoweek,andlongtermassurgIcalpractIcescomeandgoInthatDF)dealt
wIthaswell.TheseIssuesareImportantevenwhenalltheanesthesIaprofessIonalsare
IndependentlycontractedandarenotaffIlIatedwItheachother.nsuchsItuatIons,the
tItularchIefofanesthesIashouldbetheonetoactasthelInktotheschedulIngsystem.
WhentheanesthesIagroup/departmentfunctIonsasasIngleentIty,thechaIrman/chIef,
clInIcaldIrector,orappoIntedspokespersonwIllbetheIndIvIdualwhorepresentshIsorher
groupatmeetIngsInwhIchschedulIngdecIsIonsaremadeInconjunctIonwIththeDF
supervIsors,surgeons,andhospItaladmInIstrators.
ThereareasmanydIfferentwaystocreateschedulIngpolIcIesasthereareDFsuItes.|ost
hospItals/facIlItIesfollowpatternsestablIshedovertheyears.0espItealltheefforts
dIrectedtowardItscreatIon,theDFschedule(bothweeklytImeallotmentsanddaytoday
schedulIngofspecIfIccases)remaInsoneofthemostcontentIoussubjectsfortheDF.
FecognIzIngthefactthatItIsImpossIbletosatIsfyeveryone,theanesthesIagroupshould
endeavortofacIlItatetheprocessasmuchaspossIble.nItIally,anesthesIologIstsneedto
besympathetIctowardallthesurgeons'desIres/demands(statedorImplIed)andattempt
tocoordInatetheserequestswIththeInstItutIon'sabIlItytoprovIderooms,equIpment,and
staff.Secondly,theanesthesIagroupshouldmakeeverypossIbleefforttoprovIdeenough
anesthesIaservIcesandpersonneltorealIstIcallymeetthegoalsoftheInstItutIon.nlIght
ofthecurrentshortageofanesthesIaprofessIonalsInthIscountry,theseeffortsneedtobe
madewIthagreatdealofopencommunIcatIonamongallcontIngencIesoftheDF
commItteeaswellaseverymemberoftheanesthesIagroup.
FegardIngschedulIng,surgeonsessentIallyfallIntooneofthreegroups.Dnegroupwantsto
operateanytImetheycangettheIrcasesscheduled.ThIsgroupwantstheDFopen24/7.
AnotherlargergroupwantsfIrstcaseofthedayasoftenaspossIblesotheycangetto
theIroffIces.AsmallerthIrdgroupwantseItherthefIrsttImeslotoranopenIngfollowIng
thattImeslot,aseveralhourhIatus,thentoreturntotheDFafteroffIcehoursto
completeaddItIonalcases;usuallystartIngafter5P|.ClearlyacompromIseamongthese
dIsparateconstItuencIesmustbereached.AnesthesIologIstswhoapproachtheDF
commItteeregardIngthIsdIlemmawIthanonconfrontatIonalattItudewIllgreatly
facIlItateagreementonacompromIse.
Types of Schedules
ThemajorItyofDFsuseeItherblockschedulIng(preassIgnedguaranteedDFtImefora
surgeonorsurgIcalservIcetoschedulecasesprIortoanagreeduponcutofftIme;e.g.,24
or48hoursbefore)oropenschedulIng(fIrstcome,fIrstserve).|ostlargeInstItutIonshave
acombInatIonofboth.8lockschedulIngInherentlycontaInsseveraladvantageousaspects
forcreatIngaschedule.8lockschedulIngallowsformorepredIctabIlItyInthedaIlyDF
functIonaswellasaneasyrevIewofutIlIzatIonofallottedtIme.HIstorIcutIlIzatIondata
shouldberevIewedwIthsurgeons,DFstaff,andtheDFcommItteetodetermIneIts
valIdIty.|anyoperatIngsuIteshavefoundItusefultoassemblerathercomprehensIve
statIstIcsaboutwhatoccursIneachDF.SomecomputerIzedschedulIngsystems(see
followIngdIscussIon)arepartofalargercomputerIzedperIoperatIveInformatIon
managementsystemthatautomatIcallygeneratesstatIstIcs.CraphIcexamplesare1J
monthstatIstIcalcontrolchartsorrunchartsthatshowthenumberofcases,number
ofDFmInutesusedforthosecases(andwhen,suchasInblock,exceedIngblock,evenIngs,
nIghts,weekends,andsoforth),numberofcancellatIons(andmultIpleotherrelated
parametersIfdesIred)byservIce,byIndIvIdualsurgeon,andtotalforthecurrentmonth
andthe12prIormonths,alwayswIthcontrollImIts(usually2S0fromthe1Jmonth
movIngaverage)clearlyIndIcated.AllthesedataarevaluableInthattheygeneratea
clearpIctureofwhatIsactuallygoIngonIntheDF.tIsalsoextremelyvaluableInthat
blocktImeallocatIonshouldberevIewedperIodIcallyandadjustedbasedonchanges,
degreeofutIlIzatIon,andprojectedneeds.nflexIbleblocktImeschedulIngcancreatea
majorpoIntofcontentIonIftheassIgnedblocksarenotregularlyreevaluated.Thesurgeon
orsurgIcalservIcewIththeearlystartIngblockthathabItually
P.51
runsbeyondhIsorherblocktImewIllcreateproblemsforthefollowIngcases.fthIs
surgeonweremadetoscheduleIntothelaterblockonarotatIngbasIs,delaysInhIsorher
startcausedbyothersmayprovokeImprovedaccuracyofhIsorhersubsequentearlycase
postIngs.AdjustmentsInavaIlabIlItyofblocktImecanalsobemadeInthesettIngofthe
releasetIme,thetImeprIortotheoperatIvedatethatagIvenblockIsdeclarednotfull
andbecomesavaIlableforopenschedulIng.SurgeonspreferaslateareleasetImeas
possIbleInordertomaIntaIntheIraccesstotheIrDFblocktIme.However,unused
reservedblocktImewastesresourcesandpreventsanotherservIcefromschedulIng.A
sInglereleasetImerarelyfItsallcIrcumstances,butnegotIatIngservIcespecIfIcrelease
tImesmayleadtoImprovedsatIsfactIonforall.ntheIdealsystem,enoughDFtImeand
equIpmentshouldexIsttoprovIdeforeachsurgIcalservIce'sgenuIneneedswhIleretaInIng
theabIlItytoaddtotheschedule(vIaopenschedulIng)asneeded.SuchanenvIronment
doesnotexIst.nvarIably,InbusyenvIronments,surgIcaldemandexceedsavaIlableblock
andopentIme,leadIngservIcestorequestaddItIonalblocktIme.WhenthIstImeIsnot
granted,servIcesperverselythenscheduleproceduresInopentImebeforefIllIngtheIr
blocktIme.SurgeonswhopreferopentImewouldthenbeshutoutofDFtIme.Dpen
schedulIngmayrewardthosesurgeonswhorunaneffIcIentservIce,butItalsomaybea
sourceofproblemstothosesurgeonswhohaveasIgnIfIcantportIonoftheIrservIcearrIve
unscheduled,suchasorthopaedIcsurgeons.SomedegreeofflexIbIlItywIllbenecessary
whIcheversystemIsused.TheanesthesIagroupshouldadoptaneutralposItIonInthese
dIscussIonswhIlebeIngrealIstIcaboutwhatcanbeaccomplIshedgIventhenumberofDFs
andthelengthofthenormaloperatIngday.
ThehandlIngoftheurgent/emergentcasepostIngprecIpItatesagreatdealofdIscussIonIn
mostDFenvIronments.NostudIesallowdetermInatIonofexactlywhatrateofDF
utIlIzatIonIsthemostcosteffectIve.However,manyInstItutIonssubscrIbetofollowIng
parameters:adjustedutIlIzatIonratesaveragIngbelow70arenotassocIatedwIthfulluse
ofavaIlableblocktIme,wastIngresources,whIleratesabove90arefrequentlyassocIated
wIththeneedforovertImehours.
58
0IfferentDFconstItuencIeshavedIfferentcomfort
zonesfordegreesofutIlIzatIon(Table22).|ostInstItutIonscannotaffordtohaveoneor
twoDFsstaffedandwaItIngunlessthereIsarelIablesteadysupplyoflateopenschedule
addItIons,thatIs,urgentcases/emergencIes,durIngtheregularworkday.AprevIously
agreedupon,clearalgorIthmfortheacceptanceandorderIngofthesecaseswIllneedto
beadopted.ngeneral,crItIcallIfethreatenIngemergencIesandelectIveaddonsare
faIrlystraIghtforwardandatthetwoendsofthespectrum.ThecrItIcalemergencygoesIn
thenextavaIlableroom,whereastheelectIvecasegetsaddedtotheendoftheschedule.
ThesocalledurgentpatIentrequIresthemostjudgment.ndIvIdualservIcesshould
provIdeguIdelInesandlImItatIonsfortheIrexpectedurgentcases.Theseaddoncase
polIcyguIdelInes
59
shouldbecommonknowledgetoeveryoneInvolvedInrunnIngtheDF.
Consequently,thesecases,suchasectopIcpregnancIes,openfractures,thepatIentwIth
obstructedbowel,andeyeInjurIes,canthenbetrIagedandInsertedIntotheelectIve
scheduleasneededwIthmInImaldIscussIonfromthedelayedsurgeon.Thesurgeonswhose
urgentcaseIspresentedasonethatmustImmedIatelybumpanotherservIce'spatIent,yet
couldwaItseveralhoursIfItIstheIrownpatIentthatwIllbedelayed,wIllhavetoface
theIrownprevIouslyagreeduponstandardsInafutureDFcommItteemeetIng.AsImple
waytoexpressonelogIcalpolIcyforurgentcases(e.g.,acuteappendIcItIs,unruptured
ectopIcpregnancy,IntestInalobstructIon)Is:1)bumpthesamesurgeon'selectIve
scheduledcase;2)Ifnone,bumpascheduledcaseonthesameservIce(gynecology,
generalA,andsoforth);J)Ifnone,bumpascheduledcasefromanopenschedulesurgIcal
servIce;and4),Ifnone,bumpascheduledcasefromablockscheduleservIce.
59
Some
InstItutIonsrequIretheattendIngsurgeonofthepostedurgent/emergentpatIenttospeak
personallywIththesurgeonofanybumpedcase.
Table 2-2 Operating Room (or) Utilization: Comfort Zones of the
Operating Room Personnel Constituencies
BLOCK TIME UTILIZATION
(%)
FACILITY
ADMINISTRATION
ANESTHESIOLOGY
GROUP
OR
STAFF
SURGEONS
100 ++
85100 ++++ ++
7084 +++ ++++ + +/
5J69 + +++ +++ ++
55 ++ ++++
+,favorable;,unfavorable.
FeprIntedfrom|azzeIWJ:DFmanagement:Stateoftheart.ProceedIngsofthe
200JConferenceonPractIce|anagement.ParkFIdge,L,AmerIcanSocIetyof
AnesthesIologIsts,200J,p.65wIthpermIssIon.
AnotherareaofburgeonInggrowththatmustbeaccountedforInthedaIlyworkscheduleIs
thenonDFoffsItedIagnostIctest,ortherapeutIcInterventIonthatrequIresanesthesIa
care.nmanyInstancestheseproceduresreplaceoperatIonsthat,Intherecentpast,
wouldhavebeenpostedontheDFscheduleasurgent/emergencycases.Forexample,
cerebralaneurysmcoIlIngandcomputedtomographyguIdedabscessdraInage,among
otherprocedures,aredoneInImagIngsuItes;somepatIents,adultaswellaspedIatrIc,
requIredeepsedatIonorevengeneralanesthesIaformagnetIcresonanceImagIngor
computedtomographyInradIologyorforInvasIveproceduresIncatheterIzatIon
laboratorIes.AddItIonally,dependIngondIstancesInvolvedandlogIstIcs,Itmayevenbe
necessarytoassIgntwopeople,aprImaryprovIderandanattendIng,exclusIvelytothat
oneremotelocatIonwhen,hadthecasecometotheDF,theattendIngmayhavebeen
abletocoveranotherorothercasesalso.HospItaladmInIstratIonortheDFcommIttee
maytrytovIewthesecasesasunrelatedtoDFfunctIonand,thus,purelyaproblemforthe
anesthesIagrouptosolve.ThesecasesmustbetreatedwIththesamemethodology
regardIngaccessandprIorItIzatIonasallotherDFprocedures.
nordertoapportIonhospItalbasedanesthesIaresourcesreasonably,theseoffsIte
proceduresshouldbesubjecttothesameguIdelInesandprocessesasanyotherDFpostIng.
|ostInstItutIonshaveaddedatleastoneextraanesthetIzInglocatIontotheIrformal
operatIngscheduletodesIgnatetheseoffsIte
P.52
procedures(occasIonallywIthanImagInatIvenamesuchasroadshow,outfIeld,or
safarI).FormanyoftheseoffsItecases,thereIslIttleornoreImbursementfor
anesthesIacare.|ostgovernmentplansandInsurancecarrIerswIllprobablynotpayfor
theclaustrophobIcadulttoreceIvemonItoredanesthesIacareorevenageneralanesthetIc
foranobvIouslyneededdIagnostIcmagnetIcresonanceImage,eventhoughthepatIent,
thesurgeon,andthehospItalbenefItfromthetestresults.TheanesthesIagroup,theDF
commIttee,andthehospItaladmInIstratIonneedtoreachcompromIsesregardIngoffsIte
procedures,regardIngschedulIng,allocatIonofanesthesIaresourcesthatwouldotherwIse
gototheDF,andevensubsIdIzatIonofthepersonnelcostsInordertocontInuethIs
obvIouslybenefIcIalservIce.
Computerization
ComputerIzedschedulIngwIlllIkelybenefIteveryDFregardlessofsIze.WhetherthIs
schedulIngfunctIonshouldbeonecomponentofacomprehensIveE|FsystemIsacomplex
questIon,asprevIouslynoted.ntheDF,however,computerIzatIonallowsforafaster,
moreeffIcIentmethodofcasepostIngthananyhandwrIttensystem.Changestothe
schedulecanbemadequIcklywIthoutanylossofInformatIon.FearrangIngthedaIly
scheduleIsmuchsImpleronacomputerthanerasIngandrewrItIngonaledger.
Furthermore,mosthospItalshaveadoptedacomputerdetermInedaveragetImefora
gIvensurgIcalprocedureforthatpartIcularsurgeon.Commonly,thIstImeIstheaverageof
thelast10(or10ofthelast12,wIththelongestandshortestdIscarded)ofthespecIfIc
procedure(e.g.,totalkneereplacement)wIththepotentIaltoaddamodIfIer(e.g.,ItIsa
repeatsurgery)thatshowsamaterIaldIfferenceIntheprojectedtImelength(almost
alwayslonger)foronepartIcularpatIenttype.SupposesurgeonXhasblocktImeof8hours
onagIvendayandwantstoschedulefourproceduresInthatallottedtIme.The
computerIzedschedulIngprogramlooksatsurgeonsX'spastperformancesanddetermInesa
projectedlengthforeachoftheproceduresthatareIdentIfIedtothecomputerusuallyby
CPT4codesorpossIblysomeothercodedevelopedlocallyforfrequentproceduresdoneby
surgeonX.(NotethattherecordedtImelengthIncludestheturnovertIme,thusmakIngthe
casetImedefInItIonfromthetImethepatIententerstheDFuntIlthetImeanyfollowIng
patIententersthatDF[unlessanexceptIonIsenteredspecIfIcallyforanunusual
cIrcumstance].)TheuseofagreeduponcodesInsteadofjusttextdescrIptIonshelpsensure
accuracybecauseItelImInatesanyneedfortheschedulIngclerktoguesswhatthesurgeon
Intendstodo.8ookIngsInmostcIrcumstancesshouldnotbetakenwIthoutthe
accompanyIngcodes(surgeons'offIcesobjectIonsnotwIthstandIng).Thecomputerthen
decIdeswhethersurgeonXwIllfInIshthefourproceduresIntheallottedblocktIme.fthe
computerconcludesthatthefourthcasewouldfInIshsIgnIfIcantly(thedefInItIonofwhIch
canbedetermInedandenteredIntotheprogram)beyondtheavaIlableblocktIme,ItwIll
notacceptthefourthcaseIntothatroom'sscheduleonthatpartIcularday.Thesurgeon
wIllacceptthecomputer'sassIgnedtImesandadjustaccordIngly,plannIngonlythree
cases,orappealforanexceptIonbasedonsomefactornotInthebookIngthatIsclaImed
wIllmaterIallydecreasethetImeneededforatleastoneofthefourcases,whIchthe
surgeonmustexplaIntotheexceptIonczar(anesthesIologyclInIcaldIrectororDFcharge
nurse)oftheday.AnalternatIvemethodhasthecomputersImplyadd(toeachcaseexcept
thelast)aprojectedturnovertImethatIsagreeduponbyallInvolvedatan(often
contentIous)DFcommItteemeetIng.ComputerIzIngtheschedulIngprocesssIgnIfIcantly
reducesanypersonalbIasesandsmoothesouttheentIreoperatIngday.ThelongstandIng
rItualoflateafternoondIsputesbetweenthesurgeonsandtheanesthesIagroupand/orDF
staffwhetherornottostartthelastcasemaybeelImInatedoratleastreducedbythIs
morerealIstIcprospectIveDFschedulIngmethod.
TherearemanyvarIablestoconsIderInanyDFschedulIngsystem.ThepatIentpopulatIon
servedandthenatureoftheInstItutIondIctatetheoverallstructureoftheDFschedule.
nnercItylevel1traumacentersmustaccommodateemergencIesonaregularbasIs,24
hoursaday.ThesecentersareunlIkelytocreateaworkableschedulemorethanadayIn
advance.AnambulatorysurgerycenterservIngplastIcsurgerypatIentsmayseeonlythe
rareemergencybrIngbackbleedIngpatIent.TheIrschedulemaybeaccuratemanydaysIn
advance,wIthahIghdegreeofexpectatIonthatthepatIentwIllarrIveontImeproperly
preparedforsurgery.TheanesthesIagroupatthIsambulatorycentermayrarelyhaveto
makechangestotheschedule,allowIngthemtoproceedwIthafaIrlypredIctabledaIly
workload.AttheInnercItytraumahospItal,agreatdealofflexIbIlItyandconstant
communIcatIonwIththesurgeonswIllberequIredInanattempttogetthecasesdoneIna
reasonabletImeframewIththeInherentconstraIntsplacedontheDFstaff'sresourcesand
thetImeavaIlable.ThesetwoextremeexamplesfromopposIteendsoftheschedulIng
processspectrumcanprovIdeguIdelInesforthemajorItyoftheInstItutIonsthatfall
somewhereInbetween.8eyondopencommunIcatIon,howbesttoworktowardthIsmutual
understandIngdependsonthepartIcularsofthepeopleInvolvedandtheenvIronment,but
someDFsreportbenefItsfromteambuIldIngexercIses,leadershIpretreats,andevenDF
wIdesocIalevents.DFswIthapartIcularlymalIgnanthIstoryoffIngerpoIntIngandbad
feelIngsamongthepersonnelgroupsmayconstItuteoneofthefewInstancesanoutsIde
consultantreallymaybevaluableInthatthereareworkplacepsychologIstswhospecIalIze
InanalyzIngdysfunctIonalworkenvIronmentsandImplementIngchangestoImprovethe
sItuatIonforallInvolved.
Preoperative Clinic
AnanesthesIapreoperatIveevaluatIonclInIc(APEC)thatprovIdesacomprehensIve
perIoperatIvemedIcalevaluatIonusuallyresultsInamoreeffIcIentrunnIngoftheDF
schedule.
60,61
UnantIcIpatedcancellatIonsordelaysareavoIdedwhentheanesthesIagroup
evaluatescomplexpatIentsprIortosurgery.EvenIfthepatIentarrIvestotheDFontIme
thedayofsurgery,InadequatepreoperatIveclearancemandatIngtheorderIngof
addItIonaltestswIllconsumeprecIousDFtImedurIngthedelaywaItIngforresults.
CancellatIonsordelaysadverselyaffecttheeffIcIencyofanyDF.SubsequentcasesInthe
delayedroom,whetherforthesameoradIfferentsurgeon,maygetsIgnIfIcantlydelayed
orforcedtobesqueezedIntoanalreadybusyscheduleonanotherday.ThefInancIal
ImpactofdelaysorcancellatIonsontheInstItutIonIsconsIderable.FevenueIslostwIthno
offsettIngabsenceofexpenses.Worse,expensesmayactuallyIncreasewhenovertImehas
tobepaId,orthesterIleequIpmenthastoberepackagedafterhavIngbeenopenedforthe
canceledprocedure.Evenworse,theInconvenIencedpatIentand/orsurgeonmaygoto
anotherfacIlIty.
DptImaltImIngforpreoperatIveevaluatIonshouldberelatedtotheInstItutIon'sschedulIng
preferences,patIentconvenIence,andtheoverallhealthofthepatIent.EarlIercompletIon
ofthepreoperatIveevaluatIonmaynotreducetheoverallcancellatIonratewhen
comparedwIthamoreproxImateevaluatIon.However,anearlyevaluatIonandclearance
maywellprovIdealargerpoolofpatIentsavaIlabletoplaceontheDFschedule(blockor
open)resultIngInamoreeffIcIentuseofDFtIme.AddItIonally,aprotocoldrIven
evaluatIonprocesscanantIcIpatepossIbleneedfortImeconsumIngInvestIgatIons(suchas
acardIologyevaluatIonforthepatIentwIthprobableangIna).EarlyrecognItIonofafaIled
preoperatIvetestallows
P.5J
tImeforanotherpatIenttobemovedIntothenowvacanttImeslot.Also,early
IdentIfIcatIonofcertaInproblemsrequIrIngspecIalcareonthedayofsurgery(e.g.,
preoperatIveepIduralorPAcatheterplacement)shouldleadtofewerunantIcIpated
delays.Unfortunately,manyIssuesprecIpItatIngdelaysaredIscoveredonthedayof
surgery.SomeofthesepreventabledelaysareunrelatedtothepatIents'healthstatus.
SeemInglysImpleIssuessuchasverIfIcatIonofarIdehomeorIncompletefInancIal
InformatIonalsocontrIbutetounexpecteddelays.AproperlyfunctIonIngAPECmaybeable
toelImInateamajorItyoftheseannoyIngcausesofpreventabledelays.
FegardlessoftheInstItutIonalspecIfIcssurroundIngtheservIceprovIdedbytheAPEC,
furthercostsavIngscanbeobtaInedthroughItsproperusagebytheanesthesIagroup.The
APECfrequentlyreducesdramatIcallythenumberofpreoperatIvetestsperformedby
focusIngonwhIchdIagnostIctestsandmedIcalconsultsarereallyrequIredforanyspecIfIc
patIent.nsomecIrcumstances,theAPECmayalsofunctIonasanaddItIonalsourceof
revenuefortheanesthesIagroupwhenaformalpreoperatIveconsultonacomplIcated
patIentIsorderedwellInadvancebythesurgeon,Inthesamemanneraswouldhave
otherwIsebeendIrectedtoaprImarycarephysIcIanforclearanceforsurgery.The
abIlItytocentralIzepertInentInformatIonIncludIngadmIssIonprecertIfIcatIon/clearance,
fInancIaldata,dIagnostIcandlaboratoryresults,consultreports,andpreoperatIve
recommendatIonsImprovesDFfunctIonbydecreasIngthetImespentsearchIngforall
theseItemsafterchangeshavebeenmadetotheschedule.PatIentandfamIlyeducatIon
performedbytheAPECfrequentlyleadstoanIncreaseInpatIents'overallsatIsfactIonof
theperIoperatIveexperIence.naddItIon,patIentanxIetymaybereducedsecondaryto
themoreIndepthcontactpossIbleInherentIntheAPECprocesswhencomparedwIth
anesthesIapractItIonersmeetInganambulatoryoutpatIentforthefIrsttImeInanDF
holdIngareaImmedIatelyprIortosurgery.TheAPECmodelenablestheanesthesIagroupto
bemoreactIveandproactIveIntheperIoperatIveprocess,ImprovIngtheIrrelatIonswIth
theotherDFconstItuents.
Anesthesiology Personnel Issues
nlIghtofthecurrentandfutureshortageofanesthesIacareprovIders,creatIng,
managIng,andmaIntaInIngastablesupplyofanesthesIapractItIonerspromIsesto
domInatetheDFlandscapeforyearstocome.
62
ActIverecruItIngforanesthesIologIsts
appearstobewIdespreadandIntense,sometImesInvolvIngcreatIvemarketIngand
IncentIves.
6J
TheleanresIdentrecruItIngyearsofthemIdtolate1990scontInuetoImpact
theprofessIon.EventhoughapplIcatIonstoanesthesIologyresIdencIesfromhIghlyqualIfIed
applIcantsreboundedsIgnIfIcantly,
62
ItwIlltakemanymoreyearsofrelatIvelylarge
numbersofanesthesIaresIdencygraduatestoevenbegIntoaddressactualneeds.
64
Further,justastheoverallprojecteddramatIcshortageofphysIcIansIngeneralhasledto
theopenIngandplannIngofseveralnewmedIcalschoolsIntheUnItedStates,perhapsthe
shortageofanesthesIologIsts(stIllestImatedatseveralthousand)wIllprovokethe
establIshmentofnewresIdencytraInIngprograms.Furthermore,thesupplyofnonphysIcIan
anesthesIaprofessIonalsIsalsodwIndlIng.WIththeagIngpopulatIonofnurseanesthetIsts
andthelImItednumberofapplIcatIonstoschoolsInthatprofessIon,aswellasthevery
lImItednumberoftraInIngfacIlItIesforanesthesIologyassIstants,theoverallsupplyof
anesthesIaprofessIonalsremaInsInadequatetomeetcurrentand,atleast,shortterm
futuredemands.TheneedforanesthesIagroupstocreateaflexIble,attractIvework
envIronmentInordertoretaInprovIderswhomIghtleaveorretIrewIllcontInueto
Increase.
ArelatedIssueIsconsIderatIonofwhatIsareasonableworkloadforananesthesIologIst
andhowbesttomeasure,IfpossIble,theclInIcalproductIvItyofananesthesIagroup/
department.ThesequestIonshavebeenthesubjectofconsIderabledIscussIon.
65,66,67,68
8eyondthesImplenumberoffulltImeequIvalents,cases,andDFmInutes,consIderatIon
offactorssuchasthenatureofthefacIlIty,typesofsurgIcalpractIce,patIentacuIty,and
speedofthesurgeonsmustbeIncorporatedtoallowfaIrcomparIsons.ThoughtfulfIlterIng
ofresultIngdatashouldtakeplacebeforedIssemInatIonoftheaggregateInformatIontoall
membersofagroupbecauseoftheunderstandableextremesensItIvItyamongstressedand
fatIguedanesthesIologIststoasuggestIonthattheyarenotworkIngashardastheIr
group/departmentpeers.
ExceptInhIghlyunusualcIrcumstances,flexIbleschedulIngofanesthesIaprofessIonalsand
alsofulfIllIngthedemandsplacedonthegroupbytheInstItutIoncontInuestobea
constantbalancIngact.ThIsdemandassumesaddedsIgnIfIcancebecauseInstItutIonsnow
subsIdIzemanyanesthesIagroups.EvenwhenamajorItyofprovIdersInafacIlItyare
IndependentcontractorswhereItIsrequIredthataspecIfIcsurgeonrequesttheIrservIces,
therearetImeconflIctsrangIngfromnooneatallbeIngavaIlabletounwanteddowntIme.
WhentheanesthesIagroup/departmentacceptstheresponsIbIlItyofprovIdInganesthesIa
servIcesforanInstItutIon,theymustscheduleenoughprovIdersforthatDFsuIteoneach
gIvenday.deally,asuffIcIentnumberofprofessIonalswouldbehIredsothattherewould
alwaysbeenoughpersonneltostaffthemInImumnumberofroomsscheduledonanygIven
day,aswellasafterhourscallduty.ThIssItuatIonrarelyexIstsbecauseItwouldbe
fInancIallydIsadvantageoustohaveanexcessnumberofprovIderswIthnoclInIcal
actIvIty.HavIngexactlytherIghtnumberofanesthesIaprofessIonalsInagroupforthe
clInIcalloadworkswelluntIlone(ormore)ofthemIsoutwIthanunplannedabsencesuch
asanextendedIllnessorafamIlyemergency.|anyacademIcdepartmentshaveanatural
bufferwIthsomeclInIcIansassIgnedIntervalsofnonclInIcaltImeforresearch,teachIng,or
admInIstratIvedutIes.However,repeatedlossofthesenonclInIcaldaysbecauseof
InadequateclInIcalstaffIngIntheDFleadstoundermInIngtheacademIc/researchmIssIon
ofthedepartment.ContInuedlossofthIstImewIlleventuallyleadtofacultyresIgnatIons
(andpossIblemIgratIontoprIvatepractIce),thuselImInatIngtheorIgInalbuffer.
Consequently,anesthesIagroups/departmentsneedtoantIcIpateavaIlableclInIcal
personnelandmatchthemtotheDFdemands.deally,thIsInformatIonshouldbeaccurate
forseveralmonthsIntothefuture.|eetIngthIsspecIfIcatIonhasbecomemoredIffIcultIn
therecentpast.HospItaladmInIstratorsmustofferreasonableassurancestotheanesthesIa
groupprovIdIngservIcethatagIvenDFutIlIzatIonrateIslIkely,aswellasaccuratedata
regardIngreImbursement(payermIxandanypackagecontractsnegotIatedbythe
hospItal).ThesedatamustbeprovIdedaccuratelyandupdatedfrequentlyIfahealthcare
InstItutIonIstoacquIreandretaInananesthesIagroupstaffedwIththepersonneltomeet
theexpecteddemands.
Timing
EachoperatIngenvIronmenthasItsownpersonnelschedulIngsystemandexpectatIonsfor
theanesthesIagroup.0aIlycoordInatIonbetweentheanesthesIagroup'sclInIcaldIrector
andtheDFsupervIsorpermItstheconstructIonofareasonablescheduleshowIngthe
numberofDFsthatdayandwhenthescheduleexpectseachofthemtofInIsh.nvarIably,
somecasestakelongerthanantIcIpatedoraddonsareposted,requIrIngtheDFtorunInto
thelateafternoonorearlyevenIng.|anyanesthesIaprofessIonalsacceptthIsoccurrence
asamatterofcourse.FewanesthesIaprofessIonalswIlltoleratethIssequenceofeventsas
anessentIallydaIlyroutInewhethertheyarepaId
P.54
overtImeornot.ThesepractItIonersbecomeexhaustedandresenttheburdens
contInuouslyplacedonthem.ftheDFscheduleIssuchthataddonsfrequentlyoccurand
electIvecasesrunwellIntotheevenIng,manyanesthesIaprofessIonalswIllopttoprotect
theIrpersonalandfamIlytImeandcutbacktheIrworkInghoursorresIgn.NeItherwouldbe
welcomeInsuchatIghtmarket.UnderthesecIrcumstances,hIrIngaddItIonalpersonnel
whoarescheduledtoarrIveatalatertIme,forexample,11:00A|,andthenprovIdIng
lunchrelIefandstayInglate(e.g.,7:J0P|orlaterIfneeded)tofInIshtheschedulemay
wellbeaveryworthwhIleInvestment.
AnotherpossIblesolutIontothedemandsofanextendedDFscheduleonananesthesIa
group'spersonnelmayrevolvearoundemployIngparttImeanesthesIaprofessIonals.Part
tImeopportunItIescouldenhanceagroup'sabIlItytoattractaddItIonalstaff.nthepast,a
dIsproportIonatelyhIghpercentageofwomenchoseanesthesIologyasacareer.n1970,
womenrepresented7.6ofthephysIcIanpopulatIonbutwere14ofanesthesIologIsts;
muchmorerecently,theymakeup45ofthephysIcIanpopulatIonandonly20of
anesthesIologIsts,proportIonatelyasIgnIfIcantreductIon.
69
8eyondthebasIcdemographIc
shIftamongallphysIcIans,onelIkelypartIalexplanatIonforthedecreasednumberof
womenanesthesIologIstsmaybethelackofparttImeposItIons,whIchwIllhamperan
anesthesIagroup'sabIlItytoattractandkeepatleastsomeofthefemaleanesthesIa
professIonals.
SchedulIngafterhourscoveragealsoaddstothepersonneldIffIcultIesfacIngthe
anesthesIagroup.ThevarIatIonsofcallschemesareendless.ThenatureoftheInstItutIon
andtheworkloaddetermInethedegreeoflatenIghtcoverage.|ajorreferralcentersand
level1traumacentersrequIreInhouseprImaryprovIders.ftheseprovIdersInclude
resIdentsand/ornurseanesthetIsts,thenthesupervIsIngattendIngstaffwIllalsobeIn
house24hoursaday.AcommonsolutIonemployedatmanyInstItutIonsIstostaffthe
evenIng/nIghtcallshIftsforanaverageworkload,recognIzIngthatonsomeoccasIons
therewIllbeIdleDFs,andonothernIghts,thesurgIcaldemandwIllexceedthecallteam's
numbers.
TherearealsomedIcolegalIssuessurroundIngthecallteam'savaIlabIlIty.Atasmall
communItyhospItalwIthalImItednumberofIndependentattendIngpractItIoners,the
practItIonersmayagreetocovercallonarotatIngbasIs.TheIndIvIdualsnotoncallare
usuallynotoblIgatedtotheDFandmaywellbetrulyunreachable.Whathappensthen
whentheoncallanesthesIologIstIsadmInIsterIngananesthetIcandanothertrue
emergencycasearrIvesIntheDFsuIteandtheremaInIngstaffanesthesIologIstsare
legItImatelyunavaIlable:0oesthatanesthesIologIstleavehIsorhercurrentpatIentunder
thecareofanDFnurseandgonextdoortotendtoamoreacutely(possIblycrItIcally)Ill
patIent:ShouldthepatIentbetransferredfromtheemergencydepartmenttoanother
(hopefullynearby)hospItal:ThesequestIonshavenoeasyanswers.Clearly,those
practItIonersonthescenehavetoassessInrealtImetherelatIverIsksandbenefItsand
makethedIffIcultdecIsIons.fthecalldutyrequIresthepractItIoner(s)frequentlytowork
muchorallofthenIght,leavIngtheIndIvIdual(s)stressedandfatIgued,theyshouldnotbe
requIredtoworkthenextdaydurIngnormalworkInghours.
AmorecomplIcatedanswerInvolveswhattodowhenthecallassIgnmentrarelyrequIresa
longnIght'sworkandtheoncallanesthesIaprofessIonalsroutInelyhaveroomsassIgnedto
themthenextday,butatleastonepersonhasjustfInIshedadIffIcult24hourshIftbeIng
awakeandworkIngallnIght.AnesthesIagroupsneedtodecIdehowtohandlethepossIble
callshIftscenarIos,wIthpermutatIonsandcombInatIons,andclearlycommunIcate
prospectIvelytheIrdecIsIonstotheDFcommItteebeforeanydIffIcultdecIsIonhastobe
madeonemornIng.Asalways,themedIcolegalaspectsofanydecIsIonsuchasthIsneedto
betakenIntoconsIderatIon.WhetherornotfatIguewasafactor,thepractItIonerwho
workedthroughoutthenIghtbeforeandappearedtocontrIbutetoananesthetIc
catastrophethenextmornIngwouldhaveaverydIffIcultdefenseIncourt.Further,the
anesthesIologygroupmayalsobeheldlIableInthattheIrpractIce/polIcywasInplace,
allegedlyauthorIzIngthesupposedlydangerousconduct.
Cost and Quality Issues
DneofthemorepervasIveaspectsofAmerIcanmedIcalcareIntoday'senvIronmentIsthe
drIvetomaIntaInandImprovehIghqualItyhealthcarewhIlereducIngthecostofthat
care.Healthcarecostsaccountforaremarkable16ofthegrossdomestIcproduct,nearly
trIplethefractIonageneratIonago.EvenmorealarmIng,IfcostscontInuetoIncreaseat
thecurrentrate,by2016,ItwIllbe20ofthegrossdomestIcproduct.Consequently,all
physIcIans,IncludInganesthesIologIsts,areurgedconstantlytoIncludecostconscIousness
IndecIsIonsbalancIngthenaturaldesIretoprovIdethehIghestpossIblequalItyofcare
wIththeoverallprIorItIesofboththehealthcaresystemandtheIndIvIdualpatIent,all
whIlefacIngIncreasInglylImItedresources.
70
AnesthesIologIstsremaInatargetforlImItIng
healthcareexpendItures.AnesthesIaprofessIonals(dIrectlyandIndIrectly)have
representedJto5ofthetotalhealthcarecostsInthecountry.
71
ComplIcateddecIsIons
arerequIredregardIngwhIchpatIentsaresuItableforambulatorysurgery,what
preoperatIvestudIestoorder,whatanesthetIcdrugsortechnIqueIsbestforthepatIent,
whatmonItorsorequIpmentarereasonablyrequIredtorunanDF,andthelIstgoesonand
on.WIththIsasbackground,anesthesIologIstslegItImatelycanIncludeeconomIc
consIderatIonsIntheIrdecIsIonprocesses.WhenpresentedwIthmultIpleoptIonstoprovIde
fortherapeutIcInterventIonorpatIentassessment,oneshouldnotautomatIcallychoose
themoreexpensIveapproach(justtocoverallthebases)unlessthereIscompellIng
evIdenceprovIngItsvalue.0ecIsIonsthatclearlymaterIallyIncreasecostshouldonlybe
pursuedwhenthebenefItoutweIghstherIsk.nanesthesIacareaswellasmedIcIneIn
general,suchdecIsIonscanbedIffIcultregardIngInterventIonsthatprovIdemargInal
benefItbutcontaInsIgnIfIcantcostIncreases.
72
8ecausecostcontaInmentInItIallyrequIres
accuratecostawareness,anesthesIologIstsneedtofIndouttheactualcostsandbenefItsof
theIranesthesIacaretechnIques.0etaIlswIllbeunIquetoeachpractIcesettIng.8ecause
theywIllbeexcItedthattheanesthesIologIstsactuallycare,usuallyItIspossIbletogetthe
cooperatIonofthefacIlItyadmInIstratIon'sfInancIaldepartmentmembersInresearchIng
andcalculatIngtheactualcostofanesthesIacaresothatthoughtfulevaluatIonsof
potentIalreductIonscanbeInItIated.
AnesthesIadrugexpensesrepresentasmallportIonofthetotalperIoperatIvecosts.
However,thegreatnumberofdosesactuallyadmInIsteredcontrIbutessubstantIallyto
aggregatetotalcosttotheInstItutIonInactualdollars.PrudentdrugselectIoncombIned
wIthapproprIateanesthetIctechnIquecanresultInsubstantIalsavIngs.FeducIngfreshgas
flowfrom5L/mInto2L/mInwhereverpossIblewouldsaveapproxImatelyS100mIllIon
annuallyIntheUnItedStates.
7J
AmajorItyofanesthesIaprofessIonalsusuallyattempta
practIcalapproachtocostsavIngs,buttheyaremorefrequentlyfacedwIthdIffIcult
choIcesregardIngmethodsofanesthesIathatlIkelyproducesImIlaroutcomesbutat
substantIallydIfferentcost.WhencomparIngthetotalcostsofmoreexpensIveanesthetIc
drugsandtechnIquestolesserexpensIveones,manyvarIablesneedtobeaddedtothe
formula.ThecostofanesthetIcdrugsneedstoIncludethecostsofaddItIonalequIpment
suchasspecIalvaporIzersorextraInfusIonpumpsandtheassocIatedmaIntenance.There
areotherIndIrectcoststhatmaybedIffIculttoquantItateandarecommonlyoverlooked.
Someof
P.55
theseIndIrectcostsIncludeIncreasedsetuptIme,possIblyIncreasIngroomturnovertIme,
extendedPACUrecoverytIme,andaddItIonalexpensIvedrugsrequIredtotreatsIde
effects.SometImes,moreexpensIvetechnIquesreduceIndIrectcosts.ApropofolInfusIon,
althoughmoreexpensIvethanvapor,commonlyresultsInadecreasedPACUstayfora
shortnonInvasIveprocedure.ffewerPACUstaffareneededorpatIentthroughputIs
Increased,themoreexpensIvedrugcanreduceoverallcost.Conversely,usIng
comparatIvelyexpensIvepropofolforalongproceduredefInItelyrequIrIngpostoperatIve
admIssIontoanCUIshardlyjustIfIed.TheImpactofshorteractIngdrugsandthosewIth
fewersIdeeffectsIscontextspecIfIc.0urInglongsurgIcalprocedures,suchdrugsmayoffer
lImItedbenefItsoverolder,lessexpensIve,longeractIngalternatIves.
74
Underthese
condItIons,advocatIngcostcontaInmentusIngeducatIonaleffortsmaydecreasedrug
expendIturesforseveralcategorIesofdrugs.
75
0rugsInthesametherapeutIcclasshave
wIdelyvaryIngcosts.TheacquIsItIonexpensesmayvaryasmuchas50foldInsome
pharmacologIccategorIes.tIsestImatedthatthe10hIghestexpendIturedrugsaccountfor
80oftheanesthetIcdrugcostsatsomeInstItutIons.
76
Althoughnewer,moreexpensIve
drugsmaybeeasIertouse,nodataexIsttosupportorrefutethehypothesIsthatthese
drugsprovIdeabetteranesthetIcexperIencewhencomparedwIthcarefullytItrated
older,lessexpensIve,longeractIngdrugsInthesameclass.
EvaluatIonofoutcomesandtheIrsubsequentapplIcatIontocostanalysIscanbederIved
fromtwoprIncIplesources:datapublIshedInthelIteratureanddatacollectedfrom
experIence.Asnoted,computerIzedInformatIonmanagementsystemsareusefultoolsto
trackoutcomesandanalyzetheImpactonthecost/benefItledger.UsIngthecollateddata
InthesamemannerasforDFutIlIzatIonandcaseload,practItIonerscanreadIlyapplya
statIstIcalprocesstoevaluateoutcomesIntheIrpractIce,possIblyIncludIngcorrelatIon
wIthcost.ThIsInformatIonmaytakeonaddedImportanceInthatpublIshedIncIdence
studIesmaynotexIstforthespecIfIcoutcomeananesthesIagroupIssearchIngfor.Cause
andeffectdIagramscantracktheparametersInvolvedIntheprocessandrelatethemto
thevarIousoutcomesdesIred.|ultIplepertInentexamplescouldbeconstructedfromthe
nowextensIvebodyoflIteratureonthefactorscontrIbutIngtopostoperatIvenauseaand
vomItIngandthevarIouspossIblepreventIonsandtreatments,manyofwhIchInvolvevery
expensIvemedIcatIons.Dfcourse,thIscanbedonelocallywIthInanInstItutIon.
nformatIonwouldbecollectedandstoredInthedatabase.deally,thedatabasewould
IdentIfyandtrackasmanyvarIablesasneeded/possIbletodelIneatesourcesforpossIble
ImprovementandItsultImatecostanalysIs.DncethesesourcesforImprovementandthe
ensuIngcostImpactareknown,theanesthesIagroupcandetermInewhetherornotto
pursuechangIngtheIrpractIce.DutcomesrelatedtoadverseeffectscanalsobemonItored.
fanalysIsrevealsasIgnIfIcantdIfferenceInanadverseoutcomeamongpractItIoners,
afteralltheothervarIablessuchassurgeon,patIentmIx,andsoforthareelImInated,the
outcomedatabasecanInvestIgatetheanesthetIctechnIqueusedbythatpractItIoner.f
sIgnIfIcantvarIatIonsareIdentIfIed,thatpractItIonerwouldbeabletolearnofthese
varIatIonsInanonthreatenIngmannerbecausecomputerderIveddataIsusedasopposed
toaspecIfIccaseanalysIs,whIchmIghtleadthatpractItIonertofeelsIngledoutforpublIc
crItIcIsm.ThedatabasebecomesatoolbothforQAandprofessIonaleducatIon.
Conclusion
PractIceandDFmanagementInanesthesIologytodayIsmorecomplexandmoreImportant
thaneverbefore.AttentIontodetaIlsthatprevIouslyeItherdIdnotexIstorwere
perceIvedasunImportantcanlIkelymakethedIfferencebetweensuccessandfaIlureIn
anesthesIologypractIce.
DutlInedherearebasIcdescrIptIonsandunderstandIngsofmanydIfferentadmInIstratIve,
organIzatIonal,fInancIal,andpersonnelcomponentsandfactorsInthepractIceof
anesthesIology.DngoIngsIgnIfIcantchangesInthehealthcaresystemwIllprovIdea
contInuIngarrayofchallenges.ApplIcatIonoftheprIncIplespresentedherewIllallow
anesthesIologIststoextrapolatecreatIvelyfromthesebasIcstotheIrownIndIvIdual
cIrcumstancesandthenforgeaheadInanesthesIologypractIcethatIseffIcIent,effectIve,
productIve,collegIal,andevenfun.
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Stock, M. Christine
TableofContentsSectIonntroductIontoAnesthesIologyChapterJDccupatIonalHealth
ChapterJ
Occupational Health
Arnold J. Berry
Jonathan D. Katz
Key Points
1. With the use of scavenging equipment, routine machine
maintenance, and appropriate work practices, exposure to waste
anesthetic gases can be reduced to levels below those recommended
by National Institute for Occupational Safety and Health (NIOSH).
2. Twenty-four percent of anesthesia personnel manifest evidence of
contact dermatitis in response to latex exposure and approximately
15% are sensitized and vulnerable to allergic reactions.
3. Vigilance is one of the most critical tasks performed by
anesthesiologists. The vigilance task is adversely affected by several
factors including poor equipment engineering and design, excessive
noise in the operating room, impediments to interpersonal
communication, production pressure, and fatigue.
4. Sleep deprivation and fatigue are common among anesthesiologists.
Sleep deprivation can have deleterious effects on cognition,
performance, mood, and health.
5. The risk of exposure to infectious pathogens can be reduced by the
routine use of standard precautions, transmission-based precautions
for infected patients, and safety devices designed to prevent
needlestick injuries.
6. Hepatitis B vaccine is recommended for all anesthesia personnel
because of the increased risk for occupational transmission of this
blood-borne pathogen.
7. Many consider chemical dependency to be the primary occupational
hazard among anesthesiologists. An incidence of 1 to 2% of
controlled substance abuse has been repeatedly reported within
anesthesia training programs.
8. It remains controversial whether anesthesiologists are, on average,
vulnerable to premature death. However, by correcting for the fact
that living anesthesiologists are, on average, younger than most
other specialists, it is apparent that anesthesiologists do not die
younger.
AnesthesIapersonnelspendlonghours,Infact,mostoftheIrwakIngdays,Inan
envIronmentfIlledwIthmanypotentIalhazardstheoperatIngroom.ThIssettIngIsunIque
amongworkplacesasaresultofthepotentIalexposuretochemIcalvapors,IonIzIng
radIatIon,andInfectIousagents.AddItIonally,anesthesIapersonnelaresubjectto
heIghtenedlevelsofpsychologIcalstressengenderedbythehIghstakesnatureofthe
practIceandthelongperIodsofsustaInedtImeonduty.AlthoughsuchphysIcalhazardsas
fIresandexplosIonsfromflammableanesthetIcagentsarecurrentlyoflImItedconcern,
occupatIonalIllnesses,suchasalcoholanddrugabuse,arewellrecognIzedassIgnIfIcant
wIthIntheanesthesIacommunIty.Somehazards,suchasexposuretotracelevelsofwaste
anesthetIcgases,havebeenextensIvelystudIed.Dthers,lIkesuIcIde,havebeenrecognIzed
butnotadequatelypursued.DnlywIthInthepastfewdecadeshaveepIdemIologIcsurveys
beenconductedtoassessthehealthofanesthesIapersonnel.ngeneral,thepotentIal
healthrIskstothoseworkIngIntheoperatIngroommaybesIgnIfIcant,butwIthawareness
oftheproblemsandtheuseofproperprecautIons,theyarenotformIdable.
P.58
Physical Hazards
Anesthetic Gases
AlthoughtheInhalatIonanesthetIcsdIethylether,nItrousoxIde,andchloroformwerefIrst
usedInthe1840s,thebIologIceffectsofoccupatIonalexposuretoanesthetIcagentswere
notInvestIgateduntIlthe1960s.FeportsontheeffectsofchronIcenvIronmentalexposure
toanesthetIcshaveIncludedepIdemIologIcsurveys,InvItrostudIes,cellularresearch,and
studIesInlaboratoryanImalsandhumans.AreasaddressedIncludethepotentIalInfluence
oftraceanesthetIcconcentratIonsontheIncIdenceInaffectedpopulatIonsofthe
followIng:death,InfertIlIty,spontaneousabortIon,congenItalmalformatIons,cancer,
hematopoIetIcdIseases,lIverdIsease,neurologIcdIsease,psychomotor,andbehavIoral
changes.
Anesthetic Levels in the Operating Room
ThefIrstreportofoccupatIonalexposuretomodernanesthetIcswasbyLIndeand8ruceIn
1969.
1
TheysampledaIratvarIousdIstancesfromthepopoffvalveofanesthesIa
machInesandnotedanaverageconcentratIonofhalothaneof10partspermIllIon(ppm)
andofnItrousoxIdeof1J0ppm.(PartspermIllIonIsavolumepervolumeunItof
measurement;10,000ppmequals1.)EndexpIredaIrsamplestakenfrom24
anesthesIologIstsafterworkrevealed0to12ppmofhalothane.twaslaterdemonstrated
thatwIthapproprIatescavengIngequIpmentIntegratedwIththeanesthesIabreathIng
cIrcuItandwIthadequateaIrexchangeIntheoperatIngroom,levelsofwasteanesthetIc
gasescouldbesIgnIfIcantlyreduced.
WasteanesthetIcconcentratIonsInmodernoperatIngroomswhereroutInescavengIngIs
performedareconsIderablylessthanthosefoundIntheearlystudIes.
2,J
ThIsraIsesthe
questIonsofwhetherchronIcexposuretotheselowlevelsofwasteanesthetIcgases
actuallyconstItutesasIgnIfIcantoccupatIonalhazardandwhetherresultsfromstudIes
performedInunscavengedoperatIngroomsareapplIcabletocurrentpractIce.
Epidemiologic Studies
EpIdemIologIcsurveyswereamongthefIrststudIestosuggestthepossIbIlItyofahazard
resultIngfromexposuretotracelevelsofanesthetIcs.AlthoughepIdemIologIcstudIesmay
beusefulInassessIngproblemsofthIstype,theyhavethepotentIalforerrorsassocIated
wIththecollectIonofdataandtheIrInterpretatIon.7alIdepIdemIologIcstudIesrequIre
approprIatedesIgnstrategIesIncludIngthepresenceofanapproprIatecontrolgroupfor
thecohortbeIngstudIed.WhenquestIonnaIresareusedtoobtaInpersonalmedIcal
InformatIon,thedatamaybemIsleadIngbecauseIndIvIdualsmayknowInglyor
unknowInglygIveIncorrectInformatIonbasedsolelyonremembereddata(recallbIas).
CauseandeffectrelatIonshIpsorcausalItycannotbedocumentedbyepIdemIologIc
observatIonalstudIesunlessallotherpossIbleetIologIes(confounders)canberuledoutor
otherlInesofevIdenceareusedforsubstantIatIon.FewepIdemIologIcstudIesonthe
effectsofoccupatIonalexposuretowasteanesthetIcgasesfulfIllthesedesIgncrIterIa.
Reproductive Outcome
DneofthelargestepIdemIologIcstudIestoassesstheeffectsoftraceanesthetIcson
reproductIveoutcomewasconductedbytheAmerIcanSocIetyofAnesthesIologIsts(ASA).
4
QuestIonnaIresweresentto49,585operatIngroompersonnelwhohadpotentIalexposure
towasteanesthetIcgases(membersoftheASA,theAmerIcanAssocIatIonofNurse
AnesthetIsts,theAssocIatIonofDperatIngFoomNurses,andtheAssocIatIonofDperatIng
FoomTechnIcIans).Anonexposedgroupof2J,911fromtheAmerIcanAcademyof
PedIatrIcsandtheAmerIcanNurses'AssocIatIonservedascontrols.Analysesofthesedata
IndIcatedthattherewasanIncreasedrIskofspontaneousabortIonandcongenItal
abnormalItIesInchIldrenofwomenwhoworkedIntheoperatIngroomandanIncreased
rIskofcongenItalabnormalItIesInoffsprIngofunexposedwIvesofmaleoperatIngroom
personnel.SeveralrevIewshaveIdentIfIedInconsIstencIesInthedatausedtocompare
exposedandunexposedgroupsandtomakewIthIngroupcomparIsons.Expectedlevelsof
anesthetIcexposuredIdnotcorrelatewIthreproductIveoutcome.
TheASAsubsequentlycommIssIonedagroupofepIdemIologIstsandbIostatIstIcIansto
evaluateandassessconflIctIngdatafrompublIshedepIdemIologIcsurveys.
5
AfteranalysIs
ofmethods,theyfoundonlyfIvestudIesonspontaneousabortIonandcongenItal
abnormalItIesInoffsprIngofanesthesIapersonnelthatwerefreeoferrorsInstudydesIgn
orstatIstIcalanalysIs.FromthesestudIes,therelatIverIsks(theratIooftherateofdIsease
amongthoseexposedtothatfoundInthosenotexposed)ofspontaneousabortIonfor
femalephysIcIansandfemalenursesworkIngIntheoperatIngroomwere1.4and1.J,
respectIvely(arelatIverIskof1.JrepresentsaJ0IncreaseInrIskwhencomparedwIth
therIskofthecontrolpopulatIon).TheIncreasedrelatIverIskforcongenItalabnormalItIes
wasofborderlInestatIstIcalsIgnIfIcanceforexposedphysIcIansonly.Althoughtheyfounda
statIstIcallysIgnIfIcantrelatIverIskofspontaneousabortIonandcongenItalabnormalItIes
InwomenworkIngIntheoperatIngroom,therelatIverIskwassmallcomparedwIthother,
betterdocumentedenvIronmentalhazards.TheyalsopoIntedoutthatduratIonandlevel
ofanesthetIcexposurewerenotmeasuredInanyofthestudIesandthatotherconfoundIng
factors,suchasstress,InfectIons,andradIatIonexposure,werenotconsIderedas
confounders.
8ecausepersonnelworkIngInsomedentaloperatorIeshaveexposuretonItrousoxIde,the
dentallIteraturehasalsoaddressedtheseIssues.DnepertInentstudyuseddatacollected
vIatelephoneIntervIewswIth418femaledentalassIstantstoassesstheeffectofnItrous
oxIdeexposureonfertIlIty.
6
FecundabIlIty(theabIlItytoconceIve)wassIgnIfIcantly
reducedInwomenwIth5ormorehoursofexposuretounscavengednItrousoxIdeper
week.nanotherstudyof7,000femaledentalassIstants,questIonnaIreswereusedto
determIneratesofspontaneousabortIon.
7
TherewasanIncreasedrateofspontaneous
abortIonamongwomenwhoworkedforJormorehoursperweekInoffIcesnotusIng
scavengIngdevIcesfornItrousoxIde(relatIverIsk[FF]=2.6,adjustedforage,smokIng,
andnumberofamalgamspreparedperweek).ThesefIndIngsmustbevIewedwIthcautIon
becausetheestImatesofnItrousoxIdeexposurewerebasedsolelyonrespondents'reports,
andmeasurementsofnItrousoxIdeconcentratIonsIntheworkspacewerenotperformed.
Therefore,doseeffectrelatIonshIpscannotbeconfIrmed.tIsImportanttonotethatIn
bothstudIesoffemaledentalassIstants,useofnItrousoxIdeInoffIceswIthscavengIng
devIceswasnotassocIatedwIthanIncreasedrIskforadversereproductIveoutcomes.
6,7
AmetaanalysIsof19epIdemIologIcstudIes,whIchIncludedhospItalworkers,dental
assIstants,andveterInarIansandveterInaryassIstants,demonstratedanIncreasedrIskof
spontaneousabortIonInwomenwIthoccupatIonalexposuretoanesthetIcgases(FF=1.48;
95confIdenceInterval,1.40to1.58).
8
AddItIonalanalysIsdemonstratedthattherelatIve
rIskof1.48correspondedtoanIncreasedabsoluterIskofabortIonof6.2.StratIfIcatIonby
jobcategoryIndIcatedthattherelatIverIskwasgreatestforveterInarIans(FF=2.45),
followed
P.59
bydentalassIstants(FF=1.89)andhospItalworkers(FF=1.J0).WhenthemetaanalysIs
wasconfInedtofIvestudIesthatcontrolledforseveralnonoccupatIonalconfoundIng
varIables,hadapproprIatecontrolgroups,andhadsuffIcIentresponserate,therelatIve
rIskforspontaneousabortIonwas1.90(95confIdenceInterval,1.72to2.09).Theauthor
notedthattheroutIneuseofscavengIngdevIceshasbeenImplementedsIncethetImethat
mostofthestudIesInthIsanalysIswereperformedandthattherewasnorIskof
spontaneousabortIonInstudIesofpersonnelwhoworkedInscavengedenvIronments.
FetrospectIvesurveysoflargenumbersofwomenwhoworkeddurIngpregnancyIndIcate
thatadversereproductIveoutcomesmayberelatedtojobassocIatedcondItIonsother
thanexposuretotraceanesthetIcgases.AsurveyofJ,985SwedIshmIdwIvesdemonstrated
thatnIghtworkwassIgnIfIcantlyassocIatedwIthspontaneousabortIonsafterthe12th
weekofpregnancy(oddsratIo=J.JJ),whIleexposuretonItrousoxIdeappearedtohaveno
effect.
9
UsIngacasecontrolstudydesIgn,Lukeetal
10
foundthatIncreasedworkhours,
hoursworkedwhIlestandIng,andoccupatIonalfatIguewereassocIatedwIthpretermbIrth
InobstetrIcandneonatalnurses.TheseandotherstudIeshaveprovIdeddatathatlInk
spontaneousabortIonInwomenworkIngInhealthcaretojobrelatedfactorsotherthan
exposuretotraceanesthetIcgases.ThIscastsdoubtonthevalIdItyofearlIerstudIesthat
dIdnotcontrolforoccupatIonalstressessuchasfatIgue,longworkhours,andnIghtshIfts.
AlthoughmanyoftheexIstIngepIdemIologIcstudIeshavepotentIalflawsIndesIgn,the
evIdencetakenasawholesuggeststhatthereIsaslIghtIncreaseIntherelatIverIskof
spontaneousabortIonandcongenItalabnormalItIesInoffsprIngforfemalephysIcIans
workIngIntheoperatIngroom.
11
WhetherthesefIndIngsareattrIbutabletoanesthetIc
exposureorotherworkrelatedcondItIonscannotbedefInItelydetermInedfromthIstype
ofInvestIgatIon.WelldesIgnedsurveysoflargenumbersofpersonnelandapproprIate
controlgroups,controlledforotherfactorssuchasworkhoursandnIghtshIfts,are
necessarytolInktraceanesthetIcexposurestoadversereproductIveoutcomes.The
routIneuseofscavengIngtechnIqueshasgenerallyloweredenvIronmentalanesthetIc
levelsIntheoperatIngroomandmaymakeItmoredIffIculttoproveanyadverse
reproductIveeffectsusIngepIdemIologIcdata.AlthoughItIseasytomeasureandquantIfy
thelevelsofanesthetIcIntheoperatIngroomaIr,ItIshardertomeasureandassessthe
effectofotherpossIblefactors,suchasstress,alteratIonsInworkIngschedule,andfatIgue.
Neoplasms and Other Nonreproductive Diseases
EarlysurveysenumeratIngcausesofdeathamonganesthesIologIstsIndIcatedthatmale
anesthesIologIstshadagreaterrIskofmalIgnancIesofthelymphoIdandretIculoendothelIal
tIssuesandfromsuIcIde,butalowerdeathratefromlungcancerandcoronaryartery
dIsease.
12
0atafromasubsequentprospectIvestudyprovIdednoevIdencetosupportthe
prevIousconclusIonthatlymphoIdmalIgnancIeswereanoccupatIonalhazardfor
anesthesIologIsts.
1J
AnASAsponsoredstudy,publIshedIn1974,foundnodIfferencesIncancerratesbetween
menexposedandthosenotexposedtotraceconcentratIonsofanesthetIcgases.
4
For
womenrespondents,therewasa1.Jfoldto2foldIncreaseIntheoccurrenceofcancerIn
theexposedgroup,resultIngpredomInantlyfromanIncreaseInleukemIaandlymphoma.
TheanalysIsof8urIngetal
5
ofthesedataconfIrmedanIncreaseInrelatIverIskofcancer
Inexposedwomen(FF=1.4)butattrIbutedtheIncreasesolelytocervIcalcancer(FF=
2.8).TheyalsonotedthattheASAstudydIdnotassesstheeffectofconfoundIngvarIables,
suchassexualhIstoryorsmokIng,thatmayhavecontrIbutedtothefIndIngs.tIsdoubtful
thatthecarcInogenIceffectofanesthetIcswouldbesexrelated,andtheconflIctIngresults
formenandwomen,especIallyInlIghtofthelowstatIstIcalsIgnIfIcanceofthedata,cast
doubtthatanesthetIcswerethecausatIveagents.
AnotherASAsponsoredmortalItystudyofanesthesIologIsts,coverIngtheperIodfrom1976
to1995,useddataoncauseofdeathfromtheNatIonal0eathndex.
14
ThemortalItyrIsks
ofacohortof40,242anesthesIologIstswerecomparedwIthamatchedcohortofInternIsts.
TherewasnodIfferencebetweenthetwogroupsInoverallmortalItyrIskormortalItyfrom
cancerorheartdIsease,butthemeanageatdeathwassIgnIfIcantlylowerfor
anesthesIologIstscomparedwIthInternIsts(66.5yearsvs.69.0years).nasubsequent
study,Katz
15
useddatafromtheAmerIcan|edIcalAssocIatIon(A|A)toconcludethat
therewasnostatIstIcaldIfferenceInagespecIfIcmortalItyamonganesthesIologIsts,
InternIsts,andotherphysIcIanswhenagesofthelIvIngmembersofthephysIcIangroups
wereconsIderedIntheanalyses.
EpIdemIologIcobservatIonalstudIesareusefultoolsforattemptIngtoIdentIfyadverse
effectsoftheoperatIngroomenvIronment,IncludIngexposuretomanysubstances,of
whIchwasteanesthetIcgasescomprIsebutonefactor.ThedatafromobservatIonal
surveyscan,atbest,IdentIfyassocIatIonsbutcanneverprovecauseandeffect
relatIonshIpsbetweenanexposuretoacondItIonorsubstanceandadIseaseprocess.|any
surveysthatattempttoassesstheeffectsofwasteanesthetIcgaseshavemethoddesIgn
flawssuchasfaIluretocontrolforpossIbleconfoundIngfactors,andthesehaveresultedIn
conflIctIngconclusIons.Dverall,thereappearstobesomeevIdencethattheoperatIng
roomenvIronmentproducesaslIghtIncreaseIntherateofspontaneousabortIonand
cancerInfemaleanesthesIologIstsandnurses.
5
|ortalItyrIsksfromcancerandheart
dIseaseforanesthesIologIstsdonotdIfferfromthoseforothermedIcalspecIalIsts.
Laboratory Studies
AlongwIthepIdemIologIcstudIes,InvestIgatorshavebeenactIveInthelaboratory,
assessIngtheeffectsofanesthetIcagentsoncell,tIssue,andanImalmodels.tIsthought
thatthIsworkmIghtprovIdethescIentIfIcevIdencelInkInganesthetIcexposuretothe
adverseeffectsthathavebeensuggestedbysomeobservatIonalstudIes.
Cellular Effects
NItrousoxIdeadmInIsteredInclInIcallyusefulconcentratIonsaffectshematopoIetIcand
neuralcellsbyIrreversIblyoxIdIzIngthecobaltatomofvItamIn8
12
fromanactIveto
InactIvestate.ThIsInhIbItsmethIonInesynthetaseandpreventstheconversIonof
methyltetrahydrofolatetotetrahydrofolate,whIchIsrequIredfor0NAsynthesIs,assembly
ofthemyelInsheath,andmethylsubstItutIonsInneurotransmItters.nhIbItIonof
methIonInesynthetaseInIndIvIdualsexposedtohIghconcentratIonsofnItrousoxIdemay
resultInanemIaandpolyneuropathy,butchronIcexposuretotracelevelsfoundIn
scavengedoperatIngroomsdoesnotappeartoproducetheseeffects.
|anystudIeshavebeenperformedInanImalstoassessthecarcInogenIcItyofanesthetIcs.
8ecauseoftheextremevarIabIlItyofstudyprotocols,useofanImalsofdIfferIngspecIes,
andfaIluretoconsIderpossIbleconfoundersInstudydesIgn,adefInItIvelInkbetween
anesthetIcsandcancerhasnotbeenproven.
SeveralInvestIgatorshaveusedtheAmesbacterIalassaysystemforstudyIngthe
mutagenIcItyofanesthetIcs.ThIsassayIsrapId,InexpensIve,andhasahIghtrueposItIve
ratewhencomparedwIthInvIvotests.Halothane,enflurane,methoxyflurane,Isoflurane,
sevofluraneandurInefrompatIents
P.60
anesthetIzedwIththeseagentswasnotmutagenIcusIngthIsassay.UrInefrompeople
workIngInscavengedorunscavengedoperatIngroomswasalsonegatIveformutagens.
DtherstudIeshaveusedanalysesofsIsterchromatIdexchangesorformatIonof
mIcronucleatedlymphocytestoassessforgenotoxIcItyInassocIatIonwIthanesthetIc
exposure.ThesetestsmaybeofInterestbecausetheremaybeanassocIatIonbetween
thesegenetIcchangesandcancer.ThemajorItyofstudIesusIngsIsterchromatIdexchange
testInghavebeennegatIveforenflurane,Isoflurane,andsevofluraneexposure.
16
AnesthetIstsatanInstItutIonwherewastegasscavengIngwasnotusedhadanIncreased
fractIonofmIcronucleatedlymphocytescomparedwIththosepractIcIngInahospItal
wherewasteanesthetIcgaseswerescavenged.
17
LowlevelexposureasoccursIn
scavengedoperatIngroomswasnotassocIatedwIthIncreasedformatIonofmIcronucleated
lymphocytes.ThepredIctIvevaluefortheassocIatIonofthIstesttotheIncIdenceof
cancerIsunclear.
ThedatafromseverallInesofevIdenceIndIcatethatoccupatIonalexposuretothelow
levelsofanesthetIcsfoundwItheffectIvewastegasscavengIngIsnotassocIatedwIth
sIgnIfIcantcellulareffects.
Reproductive Outcome
8ecauseofthesuggestIonfromepIdemIologIcdatathatoccupatIonalexposuretowaste
anesthetIcgasesmayhaveresultedInanIncreasedrateofspontaneousabortIonand
congenItalabnormalItIes,numerousstudIeshavebeenperformedInlaboratoryanImalsto
assessreproductIveoutcome.|ostanImalexperImentsfaIltodemonstratealteratIonsIn
femaleormalefertIlItyorreproductIveoutcomewIthexposuretothesubanesthetIc
concentratIonsofthecurrentlyusedanesthetIcagentsachIevablewIthscavengIngand
approprIateworkpractIces.tIsImportanttorealIzethatdatafromlaboratory
InvestIgatIonsInanImalsmaynotbedIrectlyapplIcabletohumans.
Effects of Trace Anesthetic Levels on Psychomotor Skills
SeveralstudIeshavebeenconductedtoattempttoclarIfywhetherlowconcentratIonsof
anesthetIcsalterthepsychomotorskIllsrequIredforprovIdInghIghqualItycare.none
InvestIgatIon,psychomotortestswereusedtoassesstheeffectofnItrousoxIde(500,50,or
25ppm)aloneorwIthhalothane(10,1.0,or0.5ppm).
18
AfterexposuretothehIghest
concentratIonsofnItrousoxIdeandhalothane,subjects'performancedeclInedonfourof
theseventests.nterestIngly,therewasadecreaseInabIlItyInsIxofseventestsafter
exposuretothesamelevelofnItrousoxIdealone.ExposuretothelowestconcentratIons
studIed,25ppmnItrousoxIdeand0.5ppmhalothane,producednoeffectsasmeasuredby
thIsbatteryoftests.
DtherInvestIgatorsusIngsImIlarprotocolshavefoundnoeffectonpsychomotortest
performanceafterexposuretotraceconcentratIonsofhalothaneornItrousoxIde.The
reasonfordIfferencesInoutcomebetweenstudIesIsunclear,but8ruceandStanley,
19
amongtheorIgInalInvestIgators,haveattrIbutedthepsychologIcaleffectsoflowlevelsof
anesthetIcstounusualsensItIvItyInthegroupofpaIdvolunteersusedInthestudy.
Recommendations of the National Institute for Occupational
Safety and Health
TheNatIonalnstItuteforDccupatIonalSafetyandHealth(NDSH)Isthefederalagency
responsIbleforensurIngthatworkershaveasafeandhealthfulworkIngenvIronment.t
meetsthesegoalsthroughtheconductandfundIngofresearch,througheducatIonof
employersandemployeesaboutoccupatIonalIllnesses,andthroughestablIshIng
occupatIonalhealthstandards.Asecondfederalagency,theDccupatIonalSafetyand
HealthAdmInIstratIon(DSHA),IsresponsIbleforenactIngjobhealthstandards,
InvestIgatIngworksItestodetectvIolatIonofstandards,andenforcIngthestandardsby
cItIngvIolators.n1977,NDSHpublIshedacrIterIadocumentthatIncludedrecommended
exposurelImIts(FEL)forwasteanesthetIcgasesof2ppm(1hourceIlIng)forhalogenated
anesthetIcagents(halothane,enflurane)whenusedaloneor0.5ppmofahalogenated
agentand25ppmofnItrousoxIde(tImeweIghtedaveragedurIngtheperIodofanesthetIc
admInIstratIon).
20
naddItIon,ItstatedthatoperatIngroomemployeesshouldbeadvIsed
ofthepotentIalharmfuleffectsofanesthetIcs.TheguIdelInesproposedthatannual
medIcalandoccupatIonalhIstorIesbeobtaInedfromallpersonnelandthatanyabnormal
outcomesofpregnancIesshouldbedocumented.ThepublIcatIonalsoIncludedInformatIon
onscavengIngproceduresandequIpmentandmethodsformonItorIngconcentratIonsof
wasteanesthetIcgasesIntheaIr.
The1977NDSHcrIterIadocumenthasnotbeenadoptedbyDSHA,whIchhasnotseta
standardpermIssIbleexposurelImItforwasteanesthetIcgases.Somestates,however,
haveInstItutedregulatIonscallIngforroutInemeasurementofambIentnItrousoxIdeIn
operatIngroomsandhavemandatedthatlevelsnotexceedanarbItrarymaxImum.n1994,
NDSHpublIshedanalerttowarnhealthcarepersonnelthatexposuretonItrousoxIdemay
produceharmfuleffects.
21
nthIsdocument,NDSHrecommendsthefollowIngtoreduce
nItrousoxIdeexposure:(1)monItorIngtheaIrInoperatIngrooms;(2)ImplementatIonof
approprIateengIneerIngcontrols,workpractIces,andequIpmentmaIntenanceprocedures;
and(J)InstItutIonofaworkereducatIonprogram.
NDSHhasnotdevelopedFELsfortheagentsmostcommonlyusedIncurrentpractIce
(Isoflurane,sevoflurane,anddesflurane).ThesevolatIleagentshavepotencIes,chemIcal
characterIstIcs,andratesandproductsofmetabolIsmthatdIffersIgnIfIcantlyfromolder
anesthetIcs.n2006,NDSHIssuedarequestforInformatIontopermIttheagencyto
evaluatepossIblehealthrIsksofoccupatIonalexposuretoIsoflurane,sevoflurane,and
desfluraneandtoestablIshFELs.
tIsImportanttonotethatotherorganIzatIonsbothInandoutsIdetheUnItedStateshave
setoccupatIonalexposurelImItsforwasteanesthetIcgasesand,Inmostcases,theseare
greaterthanthoserecommendedbyNDSH.Forexample,theAmerIcanConferenceof
CovernmentalndustrIalHygIenIstshasrecommendedathresholdlImItvaluetIme
weIghtedaverage(calculatedforan8hourshIft)fornItrousoxIdeof50ppm,forenflurane
of75ppm,andforhalothaneof50ppm.
nvIewoftheconflIctIngscIentIfIcdataandpublIshedrecommendatIons,ItIsreasonable
toaskwhatIsanacceptableexposurelevelforwasteanesthetIcgases.AlthoughItmaybe
dIffIculttobecertaInofathresholdconcentratIonbelowwhIchchronIcexposureIssafe,
ItIsprudenttoInstItutemeasuresthatreducewasteanesthetIclevelsIntheoperatIng
roomenvIronmenttoaslowaspossIblewIthoutcompromIsIngpatIentsafety.
|ethodsforreducIngandmonItorIngwastegasesIntheoperatIngroomhavebeen
suggested.
J,21
ThroughtheuseofscavengIngequIpment,equIpmentmaIntenance
procedures,approprIateanesthetIcworkpractIces,andeffIcIentoperatIngroom
ventIlatIonsystems,theenvIronmentalanesthetIcconcentratIoncanbereducedto
mInImallevels.ToensurereducedoccupatIonalexposure,departmentalprogramsshould
IncorporatetheabIlItytomonItorfordetectIonofleaksInthehIghandlowpressure
systemsofanesthetIcmachInes,contamInatIonasaresultoffaultyanesthetIctechnIques
suchaspoormaskfItorleaksaroundthecuffsofendotrachealtubesand
P.61
laryngealmaskaIrways,andscavengIngsystemmalfunctIons(TableJ1).Whentherehave
beenleaksofanesthetIcgases,dIspersIonandremovalofthepollutantsdependonthe
adequacyofroomventIlatIon.StandardsforoperatIngroomconstructIonfromthe
AmerIcannstItuteofArchItectsrequIre15to21aIrexchangesperhourwIthJbrIngIngIn
outsIdeaIr.
22
EnvIronmentallevelsofanesthetIcscanbemeasuredusIngInstantaneously
collectedsamples,contInuousaIrmonItorIng,ortImeweIghtedaverages.
J
WIth
approprIatecare,envIronmentallevelsofanesthetIcsIntheoperatIngroomcanbe
reducedtocomplywIththeFELsestablIshedbyNDSH.
Table 3-1 Sources of Operating Room Contamination
ANESTH ETIC TECHNIQUES
FaIluretoturnoffgasflowcontrolvalvesattheendofananesthetIc
TurnInggasflowonbeforeplacIngmaskonpatIent
PoorlyfIttIngmasks,especIallywIthmaskInductIonofanesthesIa
FlushIngofthecIrcuIt
FIllIngofanesthesIavaporIzers
UncuffedorleakIngtrachealtubes(e.g.,pedIatrIc)orpoorlyfIttInglaryngeal
maskaIrways
PedIatrIccIrcuIts(e.g.,JacksonFeesversIonofthe|apleson0system)
SIdestreamsamplIngcarbondIoxIdeandanesthetIcgasanalyzers
ANESTHESIA MACHINE DELIVERY SYSTEM AND SCAVENGING SYSTEM
Dpen/closedsystem
DcclusIon/malfunctIonofhospItaldIsposalsystem
|aladjustmentofhospItaldIsposalsystemvacuum
Leaks
HIghpressurehosesorconnectors
NItrousoxIdetankmountIng
DrIngs
CD
2
absorbentcanIsters
LowpressurecIrcuIt
OTHER SOURCES
CryosurgeryunIts
CardIopulmonarybypasscIrcuIts
|odIfIedfromTaskForceonTraceAnesthetIcCasesoftheCommItteeon
DccupatIonalHealthofDperatIngFoomPersonnel:WasteAnesthetIcCases:
nformatIonfor|anagementInAnesthetIzIngAreasandthePostanesthesIaCare
UnIt(PACU).ParkFIdge,L,AmerIcanSocIetyofAnesthesIologIsts,1999,wIth
permIssIonfromtheAmerIcanSocIetyofAnesthesIologIsts.Acopyofthefulltext
canbeobtaInedfromtheASA,520N.NorthwestHIghway,ParkFIdge,L60068
257J.
Anesthetic Levels in the Postanesthesia Care Unit
PatIentswhohavereceIvedvolatIleanesthetIcsreleasethesegasesIntotheenvIronment
astheyawakenfromgeneralanesthesIaInthepostanesthesIacareunIt(PACU).na1998
study,thetImeweIghtedaverageconcentratIonsforIsoflurane,desflurane,andnItrous
oxIdewere1.1ppm,2.1ppm,and29ppm,respectIvely,InthebreathIngzoneofPACU
nurses.
2J
HalfofthepatIentswereIntubatedonarrIvalInthePACU,suggestIngthatthey
werestIllpartIallyanesthetIzedandwereexhalIngagreaterconcentratIonofanesthetIc
gasesthanIftheyhadalreadyawakened.ncontrast,otherInvestIgatorsreportedtIme
weIghtednItrousoxIdelevels2.0ppmfromtwoPACUs.
24
ThepractIceIntheseInstItutIons
wastoroutInelydIscontInuenItrousoxIdeattheendofsurgery,approxImately5mInutes
beforethepatIentlefttheoperatIngroom.Also,therewasadequateaIrexchange
documentedInthePACUs.NDSHthresholdlImItsforanesthetIcgasescanbeobtaInedIn
thePACUbyensurIngadequateroomventIlatIonandfreshgasexchangeandby
dIscontInuIngtheanesthetIcgasesInsuffIcIenttImeprIortoleavIngtheoperatIngroom.
Chemicals
Methyl Methacrylate
|ethylmethacrylateIscommonlyusedtocementprosthesestoboneortorepaIrbone
defects.KnowncardIovascularcomplIcatIonsofmethylmethacrylateInsurgIcalpatIents
IncludehypotensIon,bradycardIa,andcardIacarrest.TheeffectsofoccupatIonalexposure
arelesswelldocumented.FeportedrIsksfromrepeatedoccupatIonalexposuretomethyl
methacrylateIncludeskInIrrItatIonandburns,allergIcreactIonsandasthma,eyeIrrItatIon
IncludIngpossIblecornealulceratIon,headache,andneurologIcsIgns.AIrborne
concentratIonsgreaterthan170ppmhavebeenassocIatedwIthchronIclung,lIver,and
kIdneydamage.nonereport,ahealthcareworker(HCW)sufferedsIgnIfIcantlowerlImb
neuropathyafterrepeatedoccupatIonalexposuretomethylmethacrylate.
25
DSHAhas
establIshedan8hour,tImeweIghtedaverageallowableexposureof100ppm.
ConcentratIonsashIghas280ppmhavebeenmeasuredwhenmethylmethacrylateIs
preparedforuseIntheoperatIngroom,butpeakenvIronmental
P.62
concentratIoncanbedecreasedby75whenscavengIngdevIcesareproperlyused.
Allergic Reactions
naddItIontoconcernsabouttoxIceffectsassocIatedwIthexposuretovolatIleanesthetIcs
orchemIcals,anesthesIologIstsmaydevelopsensItIvItIesorallergIcreactIonstosubstances
foundInthehealthcareenvIronment.
Halothane
AllergIcreactIonstovolatIleanesthetIcagentshavebeenassocIatedwIthcontact
dermatItIs,hepatItIs,andanaphylaxIsInIndIvIdualanesthesIologIsts.
26,27
Analysesofsera
frompedIatrIcandgeneralanesthesIologIstsdemonstratedthatexposuretohalothanewas
assocIatedwIthanIncreasedprevalenceofautoantIbodIestocytochromeP4502E1and
hepatIcendoplasmIcretIculumproteIn(EFp58).
28
0espItethepresenceofthese
autoantIbodIes,only1of105pedIatrIcanesthesIologIstshadsymptomsofhepatIcInjury.
ThesedatasuggestthatalthoughautoantIbodIesmayoccurInanesthesIologIstsexposedto
volatIleanesthetIcs,theydonotappeartobethecauseofanesthetIcInducedhepatItIs.
Latex
LatexInsurgIcalandexamInatIongloveshasbecomeacommonsourceofallergIcreactIons
amongoperatIngroompersonnel.nmanycases,HCWswhoareallergIctolatex
experIencetheIrfIrstadversereactIonswhIletheyarepatIentsundergoIngsurgery.The
prevalenceoflatexsensItIvItyamonganesthesIologIstsIsapproxImately15.
29,J0
ThelatexfoundInmedIcalproductsIsactuallyacomposIteofmanysubstancesIncludIng
proteIns,polyIsoprenes,lIpIdsandphospholIpIdscombInedwIthpreservatIves,
accelerators,antIoxIdants,vulcanIzIngcompounds,andlubrIcatIngagents(suchas
cornstarchortalc).TheproteIncontentIsresponsIbleformostofthegeneralIzedallergIc
reactIonstolatexcontaInIngsurgIcalgloves.ThesereactIonsareexacerbatedbythe
presenceofpowderthatenhancesthepotentIaloflatexpartIclestoaerosolIzeandto
spreadtotherespIratorysystemofpersonnelandtoenvIronmentalsurfacesdurIngthe
donnIngorremovalofgloves.
Table 3-2 Types of Reactions to Latex Gloves
REACTION SIGNS/SYMPTOMS CAUSE MANAGEMENT
rrItantcontact
dermatItIs
ScalIng,dryIng
crackIngofskIn
0IrectskIn
IrrItatIonby
gloves,
powder,soaps
dentIfyreactIon,avoId
IrrItant,possIbleuseof
glovelIner,useof
alternatIveproduct
Type7
delayed
hypersensItIvIty
tchIng,
blIsterIng,
crustIng
(delayed672
hours)
ChemIcal
addItIvesused
In
manufacturIng
(suchas
accelerators)
dentIfyoffendIng
chemIcal,possIbleuseof
alternatIveproduct
wIthoutchemIcal
addItIve,possIbleuseof
glovelIner
Type
ImmedIate
hypersensItIvIty
ProteInsfound
Inlatex
dentIfyreactIon;avoId
latexcontaInIng
products;useof
nonlatexorpowder
free,lowproteIngloves
bycoworkers
A.LocalIzed
contact
urtIcarIa
tchIng,hIvesIn
areaofcontact
wIthlatex
(ImmedIate)
AntIhIstamInes,
topIcal/systemIc
steroIds
8.CeneralIzed
reactIon
Funnynose,
swolleneyes,
generalIzedrash
orhIves,
AnaphylaxIsprotocol
bronchospasm,
anaphylaxIs
FeproducedfromAmerIcanSocIetyofAnesthesIologIstsTaskForceonLatex
SensItIvItyoftheCommItteeonDccupatIonalHealthofDperatIngFoomPersonnel:
NaturalFubberLatexAllergy:ConsIderatIonsforAnesthesIologIsts.ParkFIdge,L,
AmerIcanSocIetyofAnesthesIologIsts,2005
(http://www.asahq.org/publIcatIonsAndServIces/latexallergy.pdf)wIthpermIssIon
fromtheAmerIcanSocIetyofAnesthesIologIsts.Acopyofthefulltextcanbe
obtaInedfromtheASA,520N.NorthwestHIghway,ParkFIdge,L60068257J.
rrItantorcontactdermatItIsaccountsforthemajorItyofreactIonsresultIngfromwearIng
latexcontaInInggloves.(TableJ2).TrueallergIcreactIonspresentasTcellmedIated
contactdermatItIs(type7)orasanImmunoglobulInEmedIatedanaphylactIcreactIon.
AnesthesIologIstswhobelIevethattheyareallergIctolatexshouldtakeImmedIatesteps
toassessthIspossIbIlIty.
J1
fadIagnosIsofallergyhasbeenestablIshed,theaffected
anesthesIologIstmustavoIdalldIrectcontactwIthlatexcontaInIngproducts.tIsalso
Importantthatcoworkerswearnonlatexorpowderless,lowlatexallergenglovestolImIt
thelevelsofambIentallergens.8ecausesensItIzatIonIsanIrreversIbleprocess,lImIted
exposureandprImarypreventIonofallergyIsthebestoverallstrategy.AnaphylactIc
reactIonstolatexcanbelIfethreatenIng.
Radiation
|anymodernsurgIcalproceduresrelyheavIlyonfluoroscopIcguIdancetechnIques.Asa
result,anesthesIologIstsareatrIskforbeIngexposedtoexcessIveradIatIon.The
magnItudeofradIatIonabsorbedbyIndIvIdualsIsafunctIonofthreevarIables:(1)total
radIatIonexposureIntensItyandtIme,(2)dIstancefromthesourceofradIatIon,and(J)the
useofradIatIonshIeldIng.ThelattertwoareamenabletomodIfIcatIonbythe
P.6J
anesthesIologIst.Unfortunately,theleadapronsandthyroIdcollarscommonlywornleave
exposedmanyvulnerablesItes,suchasthelongbonesoftheextremItIes,thecranIum,the
skInoftheface,andtheeyes.8ecauseradIatIonexposureIsInverselyproportIonaltothe
squareofthedIstancefromthesource,IncreasIngthIsdIstanceIsmoreunIversally
protectIve.FadIatIonexposurebecomesmInImalatadIstancegreaterthanJ6Inchesfrom
thesource,adIstancethatIseasIlyattaInableInmostanesthetIzInglocatIons.
TheU.S.FegulatoryCommIssIonhasestablIshedanoccupatIonalexposurelImItof5,000
mrem/year.DccupatIonalexposuresamonganesthesIapersonnelhavebeenreportedtobe
consIderablybelowthIslImIt.
J2
However,thesestudIeswereconductedbeforethe
IntroductIonofmanyofthemodernsurgIcalproceduresthatrelyheavIlyonfluoroscopIc
guIdancetechnIques.AmorerecentstudyreportedadoublIngoftheaggregateradIatIon
exposuretothemembersofadepartmentofanesthesIologyIntheyearfollowIngthe
IntroductIonofanelectrophysIologylaboratory.
JJ
PregnantworkerspresentspecIal
concerns,andthedosetothefetusshouldbe500mremdurIngthegestatIonperIod.
DncogenesIs,teratogenesIs,andlongtermgenetIcdefectscanoccurwIthsuffIcIentlyhIgh
exposuretoradIatIon.TherIsksassocIatedwIthradIatIonvaryconsIderably,dependIngon
age,gender,andspecIfIcorgansIteexposure.
J4
However,evenlowlevelsofradIatIon
exposurearenotInconsequentIal.ThestochastIcbIologIceffectsofradIatIonare
cumulatIveandpermanent.
a
TherearenopublIsheddatathatdefInethelowerthreshold
forradIatIonInduceddIsease.Therefore,thegeneraladmonItIonregardIngoccupatIonal
radIatIonexposure,andthebasIsofprotectIonprograms,Isaslowasreasonably
achIevable.
Noise Pollution
NoIsepollutIonIsapotentIalhealthhazardthatIsvIrtuallyuncontrolledInthemodern
hospItalandspecIfIcallyIntheoperatIngroom.NoIseIsquantIfIedbydetermInIngboththe
IntensItyofthesoundIndecIbels(d8)andtheduratIonoftheexposure.NDSHhas
determInedthatthemaxImumlevelforsafenoIseexposureIs90d8for8hours.
J5
Each
IncreaseInnoIseof5d8halvesthepermIssIbleexposuretIme,sothat100d8Isacceptable
forjust2hoursperday.ThemaxImumallowableexposureInanIndustrIalsettIngIs115d8.
ThenoIselevelInmanyoperatIngroomsIssurprIsInglyclosetowhatconstItutesahealth
hazard.
J6
7entIlators,suctIonequIpment,musIc,andconversatIonproducebackground
noIseatalevelof75to90d8.SuperImposedonthIsaresporadIcandunexpectednoIses
causedbydroppedequIpment,surgIcalsawsanddrIlls,andmonItoralarms.FesultantnoIse
levelsfrequentlyexceed120d8andarecomparabletotheclamorofabusyfreeway.
J7
ExcessIvelevelsofnoIsecanhaveanadverseInfluenceontheanesthesIologIst'scapacIty
toperformclInIcaltasks.NoIsecanInterferewIththeabIlItytodIscernconversatIonal
speechandtohearaudItoryalarms.|entaleffIcIencyandshorttermmemoryare
dImInIshedbyexposuretoexcessnoIse.
J6
ComplexpsychomotortasksassocIatedwIth
anesthesIology,suchasmonItorIngandvIgIlance,arepartIcularlysensItIvetotheadverse
InfluencesofnoIsepollutIon.
TherearealsochronIcramIfIcatIonsoflongtermexposuretoexcessIvenoIseInthe
workplace.Attheveryleast,noIsepollutIonIsanImportantfactorIndecreasedworker
productIvIty.AthIghernoIselevels,workersarelIkelytoshowsIgnsofIrrItabIlItyand
demonstrateevIdenceofstress,suchaselevatedbloodpressure.UltImately,hearIngloss
mayensue.
J8
Figure 3-1.DffIcIalsealoftheAmerIcanSocIetyofAnesthesIologIsts.7CLANCEhas
alwaysbeenrecognIzedasthemostcrItIcaloftheanesthesIologIst'stasks.
Dntheotherhand,oneformofbackgroundnoIse,musIc,canprovIdeanumberof
benefIcIaleffects.|usIchasprovedadvantageousasasupplementtosedatIonand
analgesIaforsurgIcalpatIents.
J9,40
SelfselectedbackgroundmusIccancontrIbuteto
reducIngautonomIcresponsesInsurgeonsandImprovIngtheIrperformance.
41
The
benefIcIaleffectsarelesspronouncedwhenthemusIcIschosenbyathIrdparty.The
selectIonofmusIc,andthevolumeatwhIchItIsplayed,shouldbebymutualagreementof
allpartIespresentIntheoperatIngroom.
Human Factors
TheworkperformedbyananesthesIologIstcanbeIntrIcateandIncludesanumberof
complextasks.ExtensIveresearchandmarketIngeffortshavebeendIrectedtowardfIndIng
hIghtechnologysolutIonstoassIsttheanesthesIologIstInmanagIngthIsdemandIng
workload.LessattentIonhasbeengIventoapplyInghumanfactortechnologytoImprove
theworkplaceandensurepatIentsafety.HumanerrorhasbeenIdentIfIedasasIgnIfIcant
causeofpatIentmorbIdItyandmortalIty.
42
AnumberofhumanfactordIffIcultIespotentIallyexIstIntheoperatIngroom.Forexample,
anesthesIaequIpmentIsoftenpoorlydesIgnedorposItIoned.AnesthesIamonItorsand
recordkeepIngequIpmentarefrequentlyplacedsothatattentIonmustbedIrectedaway
fromthepatIentandsurgIcalfIeld.ThIswaswelldemonstratedbyobservatIonsthatthe
InsertIonandmonItorIngofatransesophagealechocardIographaddedsIgnIfIcantlytothe
anesthesIologIst'sworkloadanddIvertedattentIonawayfromotherpatIentspecIfIc
tasks.
4J
TheabIlItytorespondtocrItIcalIncIdentsandtosustaIncomplexmonItorIngtasks,suchas
maIntaInIngvIgIlance
b
areamongthosetasksthataremostvulnerabletothedIstractIons
createdbypoorequIpmentdesIgnorplacement.ThecrItIcalImportanceofthevIgIlance
tasktothepractIceofanesthesIologyIsevIdencedbythefactthatthesealoftheASA
bearsasItsonlymotto,7IgIlance(FIg.J1).
P.64
SeveralaspectsofthevIgIlancetaskdeserveattentIon.ThIsfunctIonIsrepetItIveand
monotonous.ThetaskdoesnotfullyoccupytheanesthesIologIst'smentalactIvIty,but
neItherdoesItleavehImorherfreetoperformothermentalfunctIons.FInally,thetaskIs
complex,requIrIngvIsualattentIonaswellasmanualdexterIty.
7IgIlancetasksaregenerallyperformedatthelevelof90accuracy.
44
nasettIngwhere
thestakesarehIgh,suchasdurInganesthesIa,thIsleavesanunacceptablemargInoferror.
nfact,humanerror,InpartresultIngfromlapsesInattentIon,accountsforalarge
proportIonofthepreventabledeathsandserIousInjurIesresultIngfromanesthetIcmIshaps
IntheUnItedStatesannually.
naddItIontopoorequIpmentdesIgn,anumberofotherfactorsconspIretohamperthe
abIlItyoftheanesthesIologIsttoperformmultIplecomplextasks.AnyfactorthatrequIres
theexpendItureofexcessIveenergytoperformagIventaskproducesapredIctable
decrementInperformance.EventhemosttrIvIalaspectofanoperator'sperformanceplays
asIgnIfIcantroleoverthecourseoftIme.Forexample,IftheanesthesIologIstmustmake
frequentrapIdchangesInobservatIonfromadIm,dIstantscreentoabrIght,nearbyone,
thecontInuousmuscularactIvItyrequIredforpupIldIlatIonandconstrIctIonandlens
accommodatIonpromotesfatIgueandhIndersperformance.
ThedetrImentaleffectsofunnecessaryenergyexpendIturecanbementalaswellas
physIcal.AsmorefunctIonsaremonItoredandmoredataprocesseddurIngthecourseofa
surgIcalprocedure,IncreasInglylargeramountsofmentalworkareexpended.Themental
workvarIesdIrectlywIththedIffIcultyencounteredInextractIngInformatIonfromthe
monItorsanddIsplayscompetIngfortheanesthesIologIst'sattentIon.PoorengIneerIngof
themonItordIsplays,sothatmodeofpresentatIon,sIgnalfrequency,orstrengthIs
suboptImal,canadverselyInfluencetheoperator'sperformance.
EventhealarmsthathavebeendevelopedwIththespecIfIcgoalofsupplementIngthetask
ofvIgIlancecanhaveconsIderabledrawbacks.ngeneral,alarmsarenonspecIfIc(thesame
alarmsIgnalIngasmanyas12dIfferentdevIatIonsfromnormal)andcanbeasourceof
frustratIonandconfusIon.TheyarefrequentlysusceptIbletoartIfactsandfrequentfalse
posItIvealarmsthatcandIstracttheobserverfrommoreclInIcallysIgnIfIcantInformatIon.
tIsnotunusualforfrequentlydIstractIvealarmstobeInactIvated.n2005,theASA
revIsedItsStandardsfor8asIc|onItorIngtomandatethatpulseoxImeterandcapnography
alarmsshouldnotbeturnedoff.
c
NoIsecanhaveadetrImentalInfluenceontheanesthesIologIstworkIngatmultIpletasks.
TheaveragenoIselevelof77decIbelsfoundInoperatIngroomscanreducemental
effIcIencyandshorttermmemory.ngeneral,obtrusIvenoIses,suchasloudtalkIng,
excessIveclangIngofInstruments,andbroadbandnoIse,areassocIatedwIthdecrements
Inperformance.
DrganIzatIonalIssues,suchasfaIledcommunIcatIonamongteammembers,canhavea
detrImentaleffectonananesthesIologIst'sperformance.ThepotentIalfordIsasterasa
resultofpoorcommunIcatIonhasbeenwellIllustratedInanumberofaIrlIne
catastrophes.
45
ThepossIbIlItyformIscommunIcatIonandresultantaccIdentIsheIghtened
IntheoperatIngroomwhere,IncontrasttothestructureInherentInanaIrlInecrew,there
IsanabsenceofawelldefInedhIerarchIcalorganIzatIonandthereareoverlapsInareasof
expertIseandresponsIbIlIty.PoorcommunIcatIoncanleadtoconflIct,compromIsed
patIentsafety,
46
andhasbeenIdentIfIedasarootcauseofJ5ofanesthesIarelated
sentInelevents.
47
EffectIveconflIctresolutIonIsanImportantelementoftheteamworknecessaryfor
successfulsurgIcaloutcomes.ConflIctandunpleasantInterpersonalInteractIonsamong
teammembersareamongthemoststressfulaspectsofthejobofananesthesIologIstand
canhIndersafeanesthetIccare.
48
ConflIctoccursdurIngthemanagementofasmanyas
78ofpatIentsInhIghIntensItyareassuchasoperatIngroomsorcrItIcalcareunIts.
49
SuccessfulresolutIonofconflIctIsaskIllthatcanbelearned.
50
TheaIrlIneIndustryhas
successfullyImplementedcrewresourcemanagementprogramstoImprovethe
performanceofcockpItteams.
51
Fundamentally,mutualrespectIsrequIredamongteam
membersalongwIthawIllIngnesstocarefullylIstenandrecognIzethedIfferencesof
opInIon.nterventIonbyaneutralthIrdpartyIsfrequentlyhelpfulInfIndInganInnovatIve
solutIon.
52
ProductIonpressureIsanorganIzatIonalconcernthathasthepotentIaltocreatean
envIronmentInwhIchIssuesofproductIvItysupersedethoseofsafety.
5J
ProductIon
pressurehasbeenassocIatedwIththecommIssIonoferrorsresultIngfromhasteand/or
delIberatedevIatIonsfromknownsafepractIces.
TheapplIcatIonofsImulatIontechnologyIsgaInIngacceptanceasatooltostudyandteach
humanperformanceIssuesInanesthesIology.
54
tappearstobepartIcularlysuItedto
traInIngnontechnIcalskIllssuchasresourcemanagement,teamwork,and
communIcatIon.
55
Work Hours and Night Call
ProlongedworkhoursthatresultInsleepdeprIvatIonandfatIgueareaubIquItous
componentofmanyanesthesIologIsts'professIonallIves.Tento12hourworkdaysare
common.AddItIonalemergencyandoncallcoveragefrequentlyresultIn24toJ2hour
shIfts.CravensteInetal
56
reportedtheaverageanesthesIologIst'sworkweekwas56hours.
SeventyfourpercentofthestudyrespondentsreportedthattheyhadworkedwIthouta
breakforlongerperIodsthantheypersonallythoughtwassafeand64attrIbutedanerror
InanesthetIcmanagementtofatIgue.Howardetal
57
demonstratedthatresIdentsIntheIr
routIne,nonpostcallstatesufferedfromchronIcsleepdeprIvatIonandhadthesame
degreeofsleepInessasmeasuredInresIdentsfInIshIng24hoursofInhousecall.
LonghoursofworkandnIghtcallareespecIallychallengIngfortheagInganesthesIologIst.
DlderIndIvIdualsarepartIcularlysensItIvetodIsturbancesofthesleepwakecycleandare
IngeneralbettersuItedtophaseadvances(mornIngwork)thanphasedelays(nocturnal
work).
58
0emandsassocIatedwIthnIghtcallhavebeenIdentIfIedasthemoststressful
aspectofpractIceandmostfrequentlycItedImpetustowardretIrement.
58
SleepdeprIvatIonandcIrcadIandIsruptIonhavedeleterIouseffectsoncognItIon,
performance,mood,andhealth.
59
8othacutesleeploss(24hoursofoncallduty)and
chronIcpartIalsleepdeprIvatIon(6hoursofsleeppernIght)resultInasImIlardegreeof
neurobehavIoralImpaIrment.ThenatureanddegreeofImpaIrmentonpsychomotortestIng
wIthacutesleepdeprIvatIonbearsastrIkIngsImIlarItytothatseenwIthalcohol
IntoxIcatIon.
60
ThedeleterIouseffectofsleeplossandfatIgueonworkeffIcIencyandaccuracyIswell
documentedInmanyIndustrIes.
54,61
SleepdeprIvatIonhasbeenImplIcatedasa
contrIbutIngfactorInmanywellpublIcIzedIndustrIalaccIdentssuchasthosethatoccurred
atChernobylandThree|Ilesland.0atacollectedfromresIdentsInmanyclInIcalsettIngs
demonstratethatworkshIftsofgreaterthan24hoursareassocIatedwIthanIncreasedrIsk
ofattentIonalfaIlures,sIgnIfIcantmedIcalerrors,andadversepatIentevents.
62
Dther
studIesIndIcatethatresIdentsworkIngextendedduratIonshIfts
P.65
hadanIncreasedrIskofpercutaneousInjurIesandweremorelIkelytoreportmotor
vehIclecrashesornearmIssIncIdentsdurIngtheIrcommutefromwork.
ComplexcognItIvetasksthatarespecIfIctoanesthesIology,suchasmonItorIngand
accurateclInIcaldecIsIonmakIng,maybeadverselyaffectedbysleepdeprIvatIon.Surveys
ofanesthesIapersonnelhavelInkedfatIgueandanesthetIcerrors,butthesecontaInself
reporteddatathatmaynotbeverIfIable.
56
nastudyofperformanceonananesthesIa
sImulator,resIdentsInthesleepdeprIvedcondItIondemonstratedprogressIveImpaIrment
ofalertness,mood,andperformanceandhadlongerresponselatencytovIgIlance
probes.
54
nspIteofthIs,therewerenosIgnIfIcantdIfferencesIntheclInIcalmanagement
ofthesImulatedpatIentsbetweentherestedandsleepdeprIvedgroups.Subsequenttoa
perIodofsleepdeprIvatIon,performancedoesnotreturntonormallevelsuntIl24hoursof
restandrecoveryhasoccurred.AnInterestIngphenomenonIstheendspurt,InwhIch
prevIouslydeterIoratedperformanceshowsImprovementwhenthesubjectrealIzesthat
thetaskIs90completed.Theconverseundoubtedlyalsooccurs,aletdownwIth
addItIonaldeterIoratIonInperformancewhentheprocedureIsunexpectedlyprolonged.
ThesleeplosspatternexperIencedbyanesthesIologIstswhotakenIghtcallIscomplexand
IncludeselementsofeachofthethreegeneralclassesofsleepdeprIvatIon:total,partIal,
andselectIvesleepdeprIvatIon.SelectIvesleepdeprIvatIonresultIngfromfrequent
InterruptIonsIsmostdIsruptIvetoImportantcomponentsofsleepIncludIngslowwave
sleep(assocIatedwIthbodyrepaIr)andrapIdeyemovementsleep(mIndrepaIr).
ndIcatorsofpsychosocIaldIstress,IncludIngIrrItabIlIty,dIsplacedanger,depressIon,and
anxIety,haveallbeenIdentIfIedInhouseoffIcerssufferIngfromsleepdeprIvatIon.
6J
An
addItIonalareaofconcernIsthepotentIaleffectofsleepdeprIvatIonandchronIcfatIgue
onhealthandpsychosocIaladjustment.WorkschedulesthatdIsruptcIrcadIanrhythmsare
assocIatedwIthImpaIredhealth,emotIonalproblems,andadeclIneInperformance.
NatIonalattentIonwasfocusedontheproblemsassocIatedwIthsleepdeprIvedmedIcal
housestaffbythewellpublIcIzedLIbbyZIoncase.AlargeportIonofthIsclaImhIngedon
theallegatIonthatfatal,avoIdablemIstakesweremadebyexhausted,unsupervIsed
resIdents.AnumberofmedIcalorganIzatIonsandstatelegIslaturessubsequentlytook
actIontolImItexcessIveworkhoursandresultantsleepdeprIvatIonamongphysIcIans,
especIallytraInees.Forexample,theAccredItatIonCouncIlforCraduate|edIcalEducatIon
(ACC|E)hassetunIversalstandardsthatlImItresIdentdutyhourstoanaverageof80
hoursperweekandnomorethanJ0hoursatanyonetIme,lImItthefrequencyofInhouse
call,andmandatethatoffdutytImebeprovIded.Unfortunately,noregulatIonspertaIn
tothepractIcInganesthesIologIstornurseanesthetIst.nthIsarea,medIcIneremaIns
sIgnIfIcantlybehIndotherIndustrIes,mostnotablythetransportandaIrlIneIndustrIes,In
IdentIfyIngandregulatIngworkpractIcesthatpermItexcessIvelylongshIfts.
59
AfterACC|EsetdutyhourlImItsforresIdentsIn200J,InvestIgatorshaveattemptedto
assesstheeffects.AlthoughstudIessuggestthatresIdents'qualItyoflIfehasgenerally
Improved,theeffectoneducatIonIsuncertaInbecausemanyofthestudIescontaIn
sIgnIfIcantmethodflaws.
64
TherehavebeenconflIctIngreportsonwhetherdutyhourlImIts
haveresultedInImprovedpatIentoutcome.
65,66
AlthoughItwasexpectedthatreducIng
resIdentfatIguewouldbeassocIatedwIthfewermedIcalerrors,dutyhourlImItsmayhave
createdunIntendedconsequences,suchasthelossofcontInuItyofcare,anIncreased
lIkelIhoodforfaIluretotransmItcrItIcalInformatIonwhenresponsIbIlItyforcareIs
transferredattheendofshIfts,andtheallocatIonofmanymedIcaltaskstypIcally
performedbyresIdentstononphysIcIanextenders.
SeveralstrategIescanbeusedtopreventfatIgueandtheeffectsofsleepdeprIvatIon
durInglongworkperIods.
59
PersonnelshouldbeeducatedontheproblemsassocIatedwIth
poorsleephabItsoutsIdethehospItal.NapsprIortothestartofcallaswellastheuseof
caffeInecanImprovealertnessdurInglongshIfts.|odafInIlmaybeusefultotreat
sleepInessInIndIvIdualswIthshIftworksleepdIsorder.
67
Infection Hazards
AnesthesIapersonnelareatrIskforacquIrIngInfectIonsbothfrompatIentsandfromother
personnel.7IralInfectIons,reflectIngtheIrprevalenceInthecommunIty,arethemost
sIgnIfIcantthreattoHCWs.|ostcommonly,thesearespreadthroughtherespIratoryroute
amechanIsmthatIs,unfortunately,themostdIffIculttocontroleffectIvely.Dther
InfectIonsarepropagatedbyhandtohandtransmIssIon,andhandwashIngIsconsIdered
thesInglemostImportantInterventIonforprotectIonagaInstthIsformofcontagIon.
68
mmunItyagaInstsomevIralpathogenscanbeprovIdedthroughvaccInatIon.
69
8loodborne
pathogenssuchashepatItIsandhumanImmunodefIcIencyvIrus(H7)causeserIous
InfectIons,buttransmIssIoncanbepreventedwIthmechanIcalbarrIersblockIngportalsof
entryor,InthecaseofhepatItIs8,byproducIngImmunItybyvaccInatIon.
70
Current
recommendatIonsfromtheCentersfor0IseaseControlandPreventIon(C0C)forpre
employmentscreenIng,InfectIoncontrolpractIces,vaccInatIon,postexposuretreatment,
andworkrestrIctIonsforInfectedpersonnelshouldbeconsultedforspecIfIcInformatIon
relatedtoeachpathogen.
70,71,72
Respiratory Viruses
FespIratoryvIruses,whIchareresponsIbleformanycommunItyacquIredInfectIons,are
usuallytransmIttedbytworoutes.SmallpartIcleaerosolsproducedbycoughIng,sneezIng,
ortalkIngcanpropelvIrusesoverlargedIstances.TheInfluenzaandmeaslesvIrusesare
spreadInthIsway.ThesecondmechanIsmInvolveslargedropletsproducedbycoughIngor
sneezIng,contamInatIngthedonor'shandsoranInanImatesurface,whereuponthevIrusIs
transferredtotheoral,nasal,orconjunctIvalmucousmembranesofasusceptIbleperson
byselfInoculatIon.FhInovIrusandrespIratorysyncytIalvIrus(FS7)arespreadbythIs
process.
Influenza Viruses
8ecauseInfluenzavIrusesareeasIlytransmItted,communItyepIdemIcsofInfluenzaare
common,wIthlargeoutbreaksoccurrIngannually.AcutelyIllpatIentsshedvIrusthrough
smallpartIcleaerosolsbycoughIngorsneezIngforaslongas5daysaftertheonsetof
symptoms.FespIratoryIsolatIonprecautIonscanbeusedfortheduratIonoftheclInIcal
IllnessInanattempttopreventspreadtosusceptIbleIndIvIduals.8ecauseoftheIrcontact
wIthnasopharyngealsecretIons,anesthesIologIstscanplayaroleInthespreadofInfluenza
vIrusInhospItals.
nfluenzararelyproducessIgnIfIcantmorbIdItyInhealthypersonnelbutcanresultInhIgh
ratesofabsenteeIsm.HospItalstaff,especIallythosewhocareforpatIentsInhIghrIsk
groups,shouldbeImmunIzedannually(DctoberorNovember)wIththeInactIvated(kIlled
vIrus)InfluenzavIrusvaccIne.
72
AntIgenIcvarIatIonofInfluenzavIrusesoccursovertIme,
sothatnewvIralstraIns(usuallytwotypeAandonetype8)areselectedforInclusIonIn
eachyear'svaccIne.
P.66
ntheUnItedStates,therearefourantIvIralagentsforchemoprophylaxIsandtreatmentof
Influenza:amantadIne,rImantadIne,zanamIvIr,andoseltamIvIr.
72
8ecauseofahIgh
lIkelIhoodofInfluenzaAvIralresIstance,amantadIneandrImantadInearenotcurrently
recommended.TheneuramInIdaseInhIbItorszanamIvIrandoseltamIvIrhavebeenshown
tobeeffectIveInpreventIngandtreatIngbothInfluenzaAand8.0urInghospItaloutbreaks
ofInfluenza,theantIvIralagentszanamIvIrandoseltamIvIrareabout80effectIveIn
preventIngInfluenzaInfectIonInunvaccInatedhospItalpersonneland,IfadmInIstered
wIthIn48hoursoftheonsetofIllness,canreducetheduratIonandseverItyofIllness.
8ecauseofpossIblemorbIdItytohospItalIzedpatIentsandtohospItalpersonnel,ItIs
recommendedthatdurIngcommunItyInfluenzaepIdemIcs,hospItalsshouldconsIder
lImItIngelectIveadmIssIonsandsurgery.
Influenza Pandemic
nthepastcentury,therehavebeenthreeInfluenzapandemIcs(1918,1957,and1968)wIth
theCreatnfluenzaIn1918kIllIngbetween40and50mIllIonpeopleworldwIde.Although
thetImIngandseverItycannotbepredIcted,anotherInfluenzapandemIcIslIkelyand
representsoneofthegreatestpublIchealththreats.
d
ntheeventofapandemIc,thelarge
numberofInfectedpatIentswouldstraInglobalresourcessuchashealthcarefacIlItIesand
equIpment(respIratorsforpersonnelandventIlatorsforpatIents).ContaInmenttoprevent
thespreadofInfectIonrequIresearlyIdentIfIcatIonandIsolatIonofInfectedIndIvIdualsto
lImItdIseasetransmIssIon.ForpatIentsrequIrInghospItalIzatIon,specIfIcwardsshouldbe
establIshedwIthdedIcatedstaff.NDSHcertIfIedrespIrators(N95orhIgher)shouldbeused
bypersonneldurIngactIvItIesorprocedureslIkelytogenerateInfectIousrespIratory
aerosols.
Avian Influenza A
AvIanInfluenzavIrusoccursnaturallyInbIrds,buttherehavebeenoutbreaksInhumans.
7J
ThefIrsthumancaseswerereportedfromAsIa,butthevIrushasbeenIdentIfIedInEurope,
theNearEast,andAfrIca.AvIanInfluenzaAtypeH5N1hasahumanmortalItyofover50.
ClInIcalIllnessbegInsasaseverepneumonIathatmayrapIdlyprogresstoacuterespIratory
dIstresssyndrome.DutbreaksofavIanfluhaveusuallyoccurredInpeoplewhohavehad
closecontactwIthInfectedpoultry.HumantohumantransmIssIonIsuncommon,but
becauseInfluenzavIruseshavetheabIlItytomutate,thereIsconcernthatfutureH5N1
vIrusesmaybecapableofspreadfromonepersontoanother.ThereIsvarIable
susceptIbIlItyofthevIrustocurrentlyavaIlableantIvIralagents.AvaccIneforprophylaxIs
agaInstavIanInfluenzaH5N1wasapprovedforuseIntheUnItedStatesIn2007.
Respiratory Syncytial Virus
FS7IsthemostcommoncauseofserIousbronchIolItIsandlowerrespIratorytractdIsease
InInfantsandyoungchIldrenworldwIde.0urIngperIodswhenFS7IsprevalentInthe
communIty(usuallylateNovemberthrough|ayIntheUnItedStates),manyhospItalIzed
InfantsandchIldrenmaycarrythevIrus.LargenumbersofvIrusarepresentInrespIratory
secretIonsofInfectedchIldren,andalthoughvIablevIruscanberecoveredforupto6
hoursoncontamInatedenvIronmentalsurfaces,ItIsreadIlyInactIvatedwIthsoapand
wateranddIsInfectants.nfectIonofsusceptIblepeopleoccursbyselfInoculatIonwhen
FS7InsecretIonsIstransferredtothehands,whIchthencontactthemucousmembranesof
theeyesornose.
74
AlthoughmostchIldrenhavebeenexposedtoFS7earlyInlIfe,
ImmunItyIsnotpermanentandreInfectIonIscommon.
FS7mayalsobeasIgnIfIcantcauseofIllnessInhealthyelderlypatIentsandthosewIth
chronIccardIacorpulmonarydIsease.
75
FS7IsshedforapproxImately7daysafter
InfectIon.HospItalIzedpatIentswIththevIrusshouldbeIsolated,butdurIngseasonal
outbreakslargenumbersofpatIentsmaymakeIsolatIonImpractIcal.
76
Carefulhand
washIngandtheuseofgowns,gloves,masks,andgoggles(standardprecautIons)haveall
beenshowntoreduceFS7InfectIonInhospItalpersonnel.
Herpes Viruses
7arIcellazostervIrus(7Z7),herpessImplexvIrustypes1and2,andcytomegalovIrus(C|7)
aremembersoftheHerpetovIrIdInefamIly.ClosepersonalcontactIsrequIredfor
transmIssIonofalltheherpesvIrusesexceptfor7Z7,whIchIsspreadbydIrectcontactor
smallpartIcleaerosols.AfterprImaryInfectIonwIthherpesvIruses,theorganIsmbecomes
latentandmayreactIvateatalatertIme.|ostpeopleIntheUnItedStateshavebeen
InfectedwIthalloftheherpesvIrusesbymIddleage.Therefore,nosocomIaltransmIssIonIs
uncommonexceptInthepedIatrIcpopulatIonandInImmunosuppressedpatIents.
Varicella-Zoster Virus
7Z7producesbothchIckenpoxandherpeszoster(shIngles).AlthoughtheprImaryInfectIon
(chIckenpox)IsusuallyuncomplIcatedInhealthychIldren,7Z7InfectIonInadultsmaybe
assocIatedwIthmajormorbIdItyordeath.nfectIondurIngpregnancymayresultInfetal
deathor,rarely,IncongenItaldefects.HealthcareworkerswIthactIve7Z7InfectIoncan
transmItthevIrustoothers.
AftertheprImaryInfectIon,7Z7remaInslatentIndorsalrootorextramedullarycranIal
ganglIa.HerpeszosterresultsfromreactIvatIonofthe7Z7InfectIonandproducesapaInful
vesIcularrashIntheInnervateddermatome.AnesthesIologIstsworkIngInpaInclInIcsmay
beexposedto7Z7whencarIngforpatIentswhohavedIscomfortfromherpeszoster.
7Z7IshIghlycontagIous,especIallyfrompatIentswIthchIckenpoxordIssemInatedzoster.
TheC0CestImatesthattheperIodofcommunIcabIlItybegIns1to2daysbeforetheonset
oftherashandendswhenallthelesIonsarecrusted,usually4to6daysaftertherash
appears.
77
8ecause7Z7maybespreadthroughaIrbornetransmIssIon,respIratoryIsolatIon
shouldbeusedforpatIentswIthchIckenpoxordIssemInatedherpeszoster.
76
Useofgloves
toavoIdcontactwIthvesIcularfluIdIsadequatetoprevent7Z7spreadfrompatIentswIth
localIzedherpeszoster.
|ostadultsIntheUnItedStateshaveprotectIveantIbodIesto7Z7.8ecausetherehave
beenmanyreportsofnosocomIaltransmIssIonof7Z7,ItIsrecommendedthatallHCWs
haveImmunItytothevIrus.AnesthesIapersonnelshouldbequestIonedaboutprIor7Z7
InfectIon,andthosewIthanegatIveorunknownhIstoryofInfectIonshouldbeserologIcally
tested.
77
AllemployeeswIthnegatIvetItersshouldberestrIctedfromcarIngforpatIents
wIthactIve7Z7InfectIonandshouldbeofferedImmunIzatIonwIthtwodosesofthelIve,
attenuatedvarIcellavaccIne.
SusceptIblepersonnelwIthasIgnIfIcantexposuretoanIndIvIdualwIth7Z7InfectIonare
potentIallyInfectIvefrom10to21daysafterexposureandshouldnotcontactpatIents
P.67
durIngthIsperIod.TheyshouldbeofferedvaccInatIonwIthInJto5daysoftheexposure
sInceItmIghtmodIfythedIsease.7arIcellazosterImmuneglobulIncanalsobeconsIdered
butItIsmosteffectIvewhenadmInIsteredwIthIn96hoursafterexposure.
77
Personnel
wIthout7Z7ImmunItyshouldbereassIgnedtoalternatIvelocatIonssothattheydonot
careforpatIentswhohaveactIve7Z7InfectIons.
Herpes Simplex
HerpessImplexvIrus(HS7)InfectIonIsquItecommonInadults.AftervIralentrythrough
themucousmembranesofthemouth,theprImaryInfectIonwIthHS7type1Isusually
clInIcallyInapparentbutmayInvolvesevereorallesIons,fever,andadenopathy.n
healthypeople,theprImaryInfectIonsubsIdesandthevIruspersIstsInalatentstate
wIthInthesensorynerveganglIonInnervatIngthesIteofInfectIon.Anyofseveral
mechanIsmscanreactIvatethevIrustoproducerecurrentInfectIon,whIchmanIfestsInthe
vIcInItyoftheprImarylesIon.
AsecondHS7,type2,IsusuallyassocIatedwIthgenItalInfectIonsandIsspreadbysexual
contact.NewbornsmaybecomeInfectedwIthHS7type2durIngvagInaldelIvery.
HealthcarepersonnelmaybeInoculatedbydIrectcontactwIthbodyfluIdscarryIngeIther
HS7type1or2.
HerpetIcInfectIonofthefInger,herpetIcparonychIaorherpetIcwhItlow,Isan
occupatIonalhazardforanesthesIapersonnel.TheInfectIonusuallybegInsattheportalof
vIralentry,asIteonthedIstalfIngerwheretheIntegrItyoftheskInhasbeenbroken,and
resultsInvesIcleformatIon.WIthInJweeks,thethrobbIngpaInlessensandthelesIons
begIntoheal.UseofacyclovIr,anantIvIraldrugthatInhIbItsreplIcatIonofHS7,may
shortenthecourseoftheprImarycutaneousvIralInfectIon.PersonnelwIthHS7InfectIons
ofthefIngersorhandsshouldnotcontactpatIentsuntIltheIrlesIonsarehealed.
Cytomegalovirus
C|7Infectsbetween50and85ofIndIvIdualsIntheUnItedStatesbeforeage40,wIth
mostInfectIonsproducIngmInImalsymptoms.AftertheprImaryInfectIon,thevIrus
remaInsdormant,andrecurrentdIseaseonlyoccurswIthcompromIseoftheIndIvIdual's
Immunesystem.TransmIssIonofC|7cantakeplacethroughclosecontactwIthan
IndIvIdualexcretIngthevIrusorthroughcontactwIthcontamInatedsalIvaorurIne.tIs
unlIkelythataerosolsorsmalldropletsplayaroleInC|7transmIssIon.
PrImaryorrecurrentC|7InfectIondurIngpregnancyresultsInfetalInfectIonInupto2.5
ofoccurrences.CongenItalC|7syndromemaybefoundInupto10ofInfectedInfants.
Thus,althoughC|7InfectIonusuallydoesnotresultInmorbIdItyInhealthyadults,Itmay
havesIgnIfIcantsequelaeInpregnantwomen.C|7InfectIoncanalsobedeadlyIn
ImmunocompromIsedpatIents,suchasthoseundergoIngbonemarrowtransplantatIon.
ThetwomajorpopulatIonswIthC|7InfectIonInthehospItalIncludeInfectedInfantsand
ImmunocompromIsedpatIents,suchasthosewhohaveundergoneorgantransplantsor
thoseononcologyunIts.FoutIneInfectIoncontrolprocedures(standardprecautIons)are
suffIcIenttopreventC|7InfectIonInHCWs(TablesJJandJ4).
71
Pregnantpersonnel
shouldbemadeawareoftherIsksassocIatedwIthC|7InfectIondurIngpregnancyandof
approprIateInfectIoncontrolprecautIonstobeusedwhencarIngforhIghrIskpatIents.
ThereIsnoevIdencetoIndIcatethatItIsnecessarytoreassIgnpregnantwomenfrom
patIentcareareasInwhIchtheymayhavecontactwIthC|7posItIvepatIents.
Rubella
Dutbreaksofrubella,orCermanmeasles,InhospItalpersonnelhaveresultedInsIgnIfIcant
lossInemployeeworkIngtIme,employeemorbIdIty,andcosttothehospItal.Although
mostadultsIntheUnItedStatesareImmunetorubella,upto20ofwomenof
chIldbearIngagearestIllsusceptIble.FubellaInfectIondurIngthefIrsttrImesterof
pregnancyIsassocIatedwIthcongenItalmalformatIonsorfetaldeath.
FubellaIstransmIttedbycontactwIthnasopharyngealdropletsspreadbyInfected
IndIvIdualscoughIngorsneezIng.PatIentsaremostcontagIouswhIletherashIseruptIng
butcantransmItthevIrusfrom1weekbeforeto5to7daysaftertheonsetoftherash.
0ropletprecautIonsshouldbeusedtopreventtransmIssIon(TableJ4).
76
Table 3-3 Prevention of Occupationally Acquired Infections
INFECTIOUS AGENT
PREVENTIVE MEASURES
a
CytomegalovIrus StandardprecautIons
HepatItIsA 7accIneInsomecases;contactprecautIons
HepatItIs8 7accIne;hepatItIs8ImmuneglobulIn,standardprecautIons
HepatItIsC StandardprecautIons
HerpessImplex
StandardprecautIons;contactprecautIonsIfdIssemInated
dIsease
Human
ImmunodefIcIency
vIrus
StandardprecautIons;postexposureprophylactIc
antIretrovIrals
nfluenza,human 7accIne;prophylactIcantIretrovIrals;dropletprecautIons
|easles 7accIne;aIrborneprecautIons
Fubella 7accIne;dropletprecautIons
Severeacute
respIratory
syndrome
StandardprecautIons;aIrborneprecautIons
TuberculosIs
AIrborneprecautIons;IsonIazIdethambutolforpurIfIed
proteInderIvatIveconversIon
7arIcellazoster
7accIne;varIcellazosterImmuneglobulIn;aIrborneand
contactprecautIons;standardprecautIonsIflocalIzed
dIsease
0ataderIvedfromreference76.
a
solatIonprecautIonsoutlInedInTableJ4.
P.68
P.69
Table 3-4 Health Care Isolation Precautions
a
STANDARD PRECAUTIONS
ThesearetobeusedforthecareofallpatIentsregardlessoftheIrdIagnosIsor
presumedInfectIonstatus.
StandardprecautIonsshouldbeusedInconjunctIonwIthotherformsof
transmIssIonbasedprecautIons(descrIbedlaterIntable)forthecareofspecIfIc
patIents.
1. Hand washing (hand hygiene)
AftertouchIngblood,bodyfluIds,orcontamInatedItemsandenvIronmental
surfacesevenIfglovesareworn.
2. Gloves
WeargloveswhenItIsreasonablyantIcIpatedthattherewIllbecontactwIth
bloodorInfectIousmaterIal,mucousmembranes,nonIntactskIn,or
contamInatedIntactskIn.
ChangeglovesbetweentasksonthesamepatIentwhenthehandswIllmove
fromacontamInatedbodysItetoacleanone.
Femoveglovesafteruse,beforetouchIngnoncontamInatedItemsand
envIronmentalsurfaces.
J. Mask, eye protection, face shield
UsedurIngprocedureslIkelytogeneratesplashesofbloodorbodyfluIdsthat
maycontamInatefaceormucousmembranes.
4. Gown
UsedurIngprocedureslIkelytogeneratesplashesofbloodorbodyfluIdsthat
maycontamInateclothIngorarms.
5. Respiratory hygiene/cough etiquette
EducatehealthcarepersonnelandImplementmethodstocontaInrespIratory
secretIonsInpatIentsandvIsItorsespecIallydurIngseasonaloutbreaksofvIral
respIratorytractInfectIons.
6. Patient-care equipment and instruments/devices
UsePPEwhenhandlIngsoIleddevIcestopreventcontamInatIonofskIn,mucous
membranes,orclothIng.
7. Environmental control
ContamInatedenvIronmentalsurfacesshouldroutInelybecleanedand/or
dIsInfected.
8. Linen
SoIledlInenshouldbehandledInamannerthatpreventscontamInatIonof
personnel,otherpatIents,andenvIronmentalsurfaces.
9. Occupational health and blood-borne pathogens
UsecaretopreventInjurIeswhenusIngordIsposIngofneedlesandsharp
devIces.
ContamInatedneedlesshouldnotberecappedormanIpulatedbyusIngboth
hands.frecappIngIsnecessaryfortheprocedurebeIngperformed,aone
handedscooptechnIqueormechanIcaldevIceforholdIngtheneedlesheath
shouldbeused.
ContamInatedneedlesshouldnotberemovedfromdIsposablesyrIngesbyhand.
0onotbreakorbendcontamInatedneedlesbeforedIsposal.
Afteruse,dIsposablesyrIngesandneedlesandothersharpdevIcesshouldbe
placedInapproprIatepunctureresIstantcontaInerslocatedascloseaspractIcal
totheareaInwhIchtheItemswereused.
|outhpIeces,resuscItatIonbags,orotherventIlatIondevIcesshouldbeavaIlable
foruseasanalternatIvetomouthtomouthventIlatIon.
10. Patient placement
SInglepatIentroomsshouldbeusedforpatIentswhoposearIskfortransmIssIon
ofInfectIousagentstoothers.
TRANSMISSION-BASED PRECAUTIONS
TheseshouldbeusedalongwIthstandardprecautIonsforpatIentsknownor
suspectedtobeInfectedorcolonIzedwIthhIghlytransmIssIblepathogensrequIrIng
addItIonalprecautIons.
AIRBORNE PRECAUTIONS
TheseshouldbeusedforpatIentsknownorsuspectedtobeInfectedwIthmIcro
organIsmstransmIttedbyaIrbornedropletnucleI(partIcles5morsmallerInsIze)
thatcanbedIspersedoverlargedIstancesbyaIrcurrents.
ThepatIentshouldbeplacedInasInglepatIentroomwIth(1)documented
negatIveaIrpressurerelatIvetosurroundIngareas,(2)6to12aIrchangesper
hour,(J)dIschargeofaIroutdoorsormonItoredhIgheffIcIencyfIltratIonofroom
aIrbeforetheaIrIscIrculatedtootherareasInthehospItal.
ThedoortotheroomshouldbekeptclosedandthepatIentshouldremaInInthe
room.
2. Respiratory protection
AfIttestedNDSHapprovedN95orhIgherlevelrespIratorshouldbewornwhen
enterIngtheroomofapatIentwIthknownorsuspectedInfectIouspulmonaryor
laryngealtuberculosIsorsmallpox.
SusceptIblepersonnelshouldnotentertheroomofpatIentsknownorsuspected
tohavemeasles,varIcella,dIssemInatedzoster,orsmallpoxIfotherImmune
caregIversareavaIlable.fsusceptIblepersonsmustentertheroomofapatIent
knownorsuspectedtohavemeaslesorvarIcella,theyshouldwearrespIratory
protectIon.PersonsknowntobeImmunetomeaslesorvarIcellaneednotwear
respIratoryprotectIon.
J. Patient transport
PatIentsshouldbetransportedfromtheIsolatIonroomonlyformedIcally
necessarypurposes.WhentransportIsnecessary,asurgIcalmaskshouldbe
placedonthepatIenttopreventdIspersalofdropletsandthepatIentshouldbe
InstructedtofollowrespIratoryhygIene/coughetIquette.
4. Patients with tuberculosis
CurrentC0CguIdelInesshouldbeconsultedforaddItIonalprecautIons.
76
DROPLET PRECAUTIONS
TheseshouldbeusedforpatIentsknownorsuspectedtobeInfectedwIth
mIcroorganIsmstransmIttedbylargepartIcledroplets(partIcleslargerthan5m)
thatcanbegenerateddurIngcoughIng,sneezIng,talkIng,orbyperformIngcertaIn
procedures.
ThepatIentshouldbeplacedInasInglepatIentroom.
2. Respiratory protection
PersonnelshouldwearamaskwhenenterIngthepatIent'sroom.
J. Patient transport
PatIentsshouldbetransportedfromtheIsolatIonroomonlyformedIcally
necessarypurposes.WhentransportIsnecessary,asurgIcalmaskshouldbe
placedonthepatIentandtheyshouldbeInstructedtofollowrespIratory
hygIene/coughetIquette.
NomaskIsrequIredforthepersontransportIngthepatIent.
CONTACT PRECAUTIONS
TheseshouldbeusedforpatIentsknownorsuspectedtobeInfectedorcolonIzed
wIthepIdemIologIcallyImportantmIcroorganIsmstransmIttedbydIrectcontact
wIththepatIentorIndIrectcontactwIthenvIronmentalsurfacesorpatIentcare
Items.
ThepatIentshouldbeplacedInasInglepatIentroom.
2. Gloves and hand washing
naddItIontowearIngglovesasoutlInedunderstandardprecautIons,gloves
shouldbewornwhenenterIngthepatIent'sroom.
ClovesshouldbechangedaftercontactIngInfectIvematerIalorenvIronmental
surfacesthatmaycontaInhIghconcentratIonsofmIcroorganIsms.
ClovesshouldberemovedbeforeleavIngthepatIent'senvIronmentandhands
shouldbewashedImmedIatelywIthanantImIcrobIalagentorawaterless
antIseptIcagent.
AfterremovalofglovesandhandwashIng,careshouldbetakensothat
contamInatedenvIronmentalsurfacesshouldnotbetouchedtoavoIdtransferof
mIcroorganIsmstootherpatIents.
J. Gown
naddItIontowearIngagownasoutlInedunderstandardprecautIons,agown
(nonsterIle)shouldbewornwhenenterIngtheroomwhenItIsantIcIpatedthat
clothIngwIllhavecontactwIththepatIent,envIronmentalsurfaces,or
contamInatedItemsorIfthepatIentIsIncontInentorhasdIarrhea,an
Ileostomy,acolostomy,orwounddraInagenotcontaInedbyadressIng.
ThegownshouldberemovedbeforeleavIngthepatIent'senvIronment.
ClothIngshouldnotcontactpotentIallycontamInatedsurfacesafterremovalof
thegown.
4. Patient transport
ThepatIentshouldbetransportedfromtheroomforonlymedIcallynecessary
purposes.
fItIsnecessarytotransportthepatIent,InfectedorcolonIzedareasofthe
patIent'sbodyshouldbecoveredtopreventtransmIssIonofmIcroorganIsmsto
otherpatIentsandcontamInatIonofenvIronmentalsurfacesorequIpment.
FemovecontamInatedPPEprIortotransportIngpatIentsanddoncleanPPEto
handlethepatIentatthetransportdestInatIon.
5. Patient-care equipment
UsedIsposablenoncrItIcalpatIentcareequIpment(e.g.,bloodpressurecuffs)or
dedIcatenondIsposableequIpmenttoasInglepatIenttoavoIdtransmIssIonof
mIcroorganIsmstoanotherpatIent.fuseofcommonequIpmentIsunavoIdable,
thenItemsshouldbeadequatelycleanedordIsInfectedbeforeuseonanother
patIent.
PPE,personalprotectIveequIpmentsuchasgloves,gown,eyeshIeld,orface
mask;NDSH,NatIonalnstItuteforDccupatIonalSafetyandHealth;C0C,Centers
for0IseaseControl.
a
ThIstablesummarIzesIsolatIonprecautIons,butthecompleteguIdelIneshouldbe
consultedformoredetaIledInformatIon.
76
EnsurIngImmunItyatthetImeofemployment(evIdenceofprIorvaccInatIonwIthlIve
rubellavaccIneorserologIcconfIrmatIon)shouldpreventnosocomIaltransmIssIonof
rubellatopersonnel.thasbeenshownthathIstoryIsapoorIndIcatorofImmunIty.AlIve,
attenuatedrubellavIrusvaccIne,contaInedInmeasles,mumps,rubellavaccIne,Is
avaIlabletoproduceImmunItyInsusceptIblepersonnel.
69,78
|anystateorlocalhealth
departmentsmandaterubellaImmunItyforallHCWs,andlocalregulatIonsshouldbe
consulted.
Measles (Rubeola)
|easlesvIrusIshIghlytransmIssIblebothbylargedropletsandbytheaIrborneroute.The
vIrusIsfoundInthemucusofthenoseandpharynxoftheInfectedIndIvIdualandIsspread
bycoughIngandsneezIng.ThedIseasecanbetransmIttedfrom4daysprIortotheonsetof
therashto4daysafterItsonset.AIrborneprecautIonsshouldbeusedforInfectedpatIents
(TableJ4).
71,76
ntroductIonofthemeaslesvaccIneIntheUnItedStateshassuccessfully
elImInatedIndIgenouscasesofmeaslesbutImportatIonofmeaslesfromothercountrIes
contInuestooccur.
P.70
HCWsareatIncreasedrIskforacquIrIngmeaslesandtransmIttIngthevIrustosusceptIble
coworkersandpatIents.TheC0CrecommendsthatmedIcalpersonnelhaveadequate
ImmunItytomeasles,asdocumentedbyoneofthefollowIng:evIdenceoftwodosesoflIve
measlesvaccIne,arecordofphysIcIandIagnosedmeasles,orserologIcevIdenceofmeasles
ImmunIty(TableJJ).
69
SusceptIblepersonnelbornInorafter1957shouldreceIvetwo
dosesofthelIvemeaslesvaccIneatthetImeofemployment.
78
Severe Acute Respiratory Syndrome
SevereacuterespIratorysyndrome(SAFS)IsarespIratorytractInfectIonproducedbya
coronavIrus,SAFSassocIatedcoronavIrus(SAFSCo7).AfterthefIrstcaseswerereported
fromAsIaInlate2002,thedIseasequIcklyspreadgloballyIn200JbeforebeIngcontrolled.
SIncethen,globalsurveIllanceforSAFSCo7hasdetectednoconfIrmedcases.8ecauseof
therapIdspreadandthesIgnIfIcantmorbIdItyandmortalItyassocIatedwIththeInfectIon,
thereIsaneedtounderstandthedIsease.HealthcarefacIlItIesshouldbepreparedto
rapIdlyImplementcontrolmeasuresIfnewoutbreaksoccur.
SAFStypIcallypresentswIthahIghfever,greaterthanJ8.0`C,andIsfollowedwIth
symptomsofheadache,generalIzedaches,andcough.SeverepneumonIamayleadto
acuterespIratorydIstresssyndromeanddeath.SAFSIsspreadbyclosepersontoperson
contactthroughvIruscarrIedInlargerespIratorydropletsandpossIblybyaIrborne
transmIssIon.ThevIruscanalsobespreadwhenanIndIvIdualtouchesacontamInated
objectandthenInoculatesthemouth,nose,oreyes.AerosolIzatIonofrespIratory
secretIonsdurIngcoughIngorendotrachealsuctIonInghasbeenassocIatedwIth
transmIssIonofthedIseasetoHCWs,IncludInganesthesIologIstsandcrItIcalcarenurses.
DneofthemostImportantInterventIonstopreventthespreadofSAFSInthehealthcare
settIngIsearlydetectIonandIsolatIonofpatIentswhomaybeInfectedwIthSAFSCo[7
wIthdotabove]
79
Cloves,gown,respIratoryprotectIon(asamInImum,useaNDSH
certIfIedN95fIlterIngrespIrator),andeyeprotectIonshouldbedonnedbeforeenterInga
SAFSpatIent'sroomordurIngprocedureslIkelytogeneraterespIratoryaerosols.
79
Viral Hepatitis
AlthoughmanyvIrusesmayproducehepatItIs,themostcommonaretypeAorInfectIous
hepatItIs,type8(H87)orserumhepatItIs,andtypeC(HC7),whIchIsresponsIbleformost
casesofparenterallytransmIttednonA,non8hepatItIs(NAN8H)IntheUnItedStates.
0eltahepatItIs,causedbyanIncompletevIrus,occursonlyInpeopleInfectedwIthH87.
DutbreaksofanenterIcallytransmIttedNAN8H(hepatItIsE)havebeenreportedfrom
outsIdetheUnItedStatesandareusuallycausedbycontamInatedwater.ThegreatestrIsks
ofoccupatIonaltransmIssIontoanesthesIapersonnelareassocIatedwIthH87andHC7.
Hepatitis A
About20to40ofvIralhepatItIsInadultsIntheUnItedStatesIscausedbythetypeA
vIrus.HepatItIsAIsusuallyaselflImItedIllness,andnochronIccarrIerstateexIsts.Spread
IspredomInantlybythefecaloralroute,eItherbypersontopersoncontactorbyIngestIon
ofcontamInatedfoodorwater.DutbreaksareusuallyfoundInInstItutIonsorotherclosed
groupswheretherehasbeenabreakdownInnormalsanItarycondItIons.HospItalpersonnel
donotappeartobeatIncreasedrIskforhepatItIsAandnosocomIaltransmIssIonIsrare.
PersonnelexposedtopatIentswIthhepatItIsAshouldreceIveImmuneglobulIn
IntramuscularlyassoonaspossIblebutnotmorethan2weeksaftertheexposuretoreduce
thelIkelIhoodofInfectIon.
80
mmuneglobulInprovIdesprotectIonagaInsthepatItIsA
throughpassIvetransferofantIbodIesandIsusedforpostexposureprophylaxIs.HepatItIsA
vaccIneIsnotroutInelyrecommendedforHCWsexceptforthosethatmaybeworkIngIn
countrIeswherehepatItIsAIsendemIc.
69,80
Hepatitis B
HepatItIs8IsasIgnIfIcantoccupatIonalhazardfornonImmuneanesthesIologIstsandother
medIcalpersonnelwhohavefrequentcontactwIthbloodandbloodproducts.The
prevalence(theproportIonofpeoplewhohaveorhavehadthecondItIonatthetImeof
thesurvey)ofhepatItIs8InthegeneralpopulatIonoftheUnItedStatesIsJto5,andthe
carrIerrateIs0.2to0.9basedonserologIcscreenIng.SerosurveysconductedInthe
UnItedStatesandseveralothercountrIesInthe1980sIncludedmorethan2,400
unvaccInatedanesthesIapersonnelanddemonstratedameanprevalenceofH87serologIc
markersof17.8(range,J.2to48.6).
81.
8eforethewIdespreadusageofhepatItIs8
vaccInetheprevalenceofhepatItIs8serologIcmarkersInanesthesIapersonnelranged
from19to49andreflectedtheprevalenceofH87carrIersInthereferralpopulatIonfor
thearea.
AcuteH87InfectIonmaybeasymptomatIcandusuallyresolveswIthoutsIgnIfIcanthepatIc
damage.Lessthan1ofacutelyInfectedpatIentsdevelopfulmInanthepatItIs.
ApproxImately10becomechronIccarrIersofH87(I.e.,serologIcevIdencedemonstrated
for6months).WIthIn2years,halfofthechronIccarrIersresolvetheIrInfectIonwIthout
sIgnIfIcanthepatIcImpaIrment.ChronIcactIvehepatItIs,whIchmayprogresstocIrrhosIs
andIslInkedtohepatocellularcarcInoma,IsfoundmostcommonlyInIndIvIdualswIth
chronIcvIralInfectIonfor2years.
ThedIagnosIsandclassIfIcatIonofthestageofH87InfectIoncanbemadeonthebasIsof
serologIctestIng.AntIbodytothesurfaceantIgen(antIH8s)appearswIthresolutIonofthe
acuteInfectIonandconferslastIngImmunItyagaInstsubsequentH87InfectIons.ChronIc
H87carrIersarelIkelytohavehepatItIs8surfaceantIgen(H8sAg)andantIbodytothecore
antIgen(antIH8c)presentInserumsamples.ThepresenceofhepatItIs8eantIgen(H8eAg)
InserumIsIndIcatIveofactIvevIralreplIcatIonInhepatocytes.
AnesthesIapersonnelareatrIskforoccupatIonallyacquIredH87InfectIonasaresultof
accIdentalpercutaneousormucosalcontactwIthbloodorbodyfluIdsfromInfected
patIents.PatIentgroupswIthahIghprevalenceofH87IncludeImmIgrantsfromendemIc
areas,usersofIllIcItparenteraldrugs,homosexualmen,andpatIentsonhemodIalysIs.
70
CarrIersarefrequentlynotIdentIfIeddurInghospItalIzatIonbecausetheclInIcalhIstoryand
routInepreoperatIvelaboratorytestsmaybeInsuffIcIentfordIagnosIs.TherIskfor
InfectIonafteranH87contamInatedpercutaneousexposure,suchasanaccIdentalneedle
stIck,IsJ7to62IfthesourcepatIentIsH8eAgposItIveand2JtoJ7IfH8eAgnegatIve.
H87canbefoundInsalIva,buttherateoftransmIssIonIssIgnIfIcantlylessaftermucosal
contactwIthInfectedoralsecretIonsthanafterpercutaneousexposurestoblood.H87Isa
hardyvIrusthatmaybeInfectIousforatleast1weekIndrIedbloodonenvIronmental
surfaces.
HepatItIs8IsnowapreventableandatreatabledIsease.TheImplementatIonofroutIne
vaccInatIonhasdramatIcallyreducedtheIncIdenceofnewcasesIntheU.S.populatIon.n
addItIontovaccInatIon,useofstandardprecautIons,useofsafetydevIces,and
postexposureprophylaxIshavesIgnIfIcantlyreducedtherIskofoccupatIonallyacquIred
H87InfectIonandItssequelaeInHCW.
Hepatitis B Vaccine
UseofhepatItIs8vaccIneIstheprImarystrategytopreventoccupatIonaltransmIssIonof
H87toanesthesIapersonnelandotherHCWsatIncreasedrIsk.
70
AdmInIstratIonofthree
dosesofvaccIneIntothedeltoIdmuscleresultsIntheproductIonofprotectIveantIbodIes
(antIH8s)In90ofhealthyHCWs.HospItalsoranesthesIadepartmentsshouldhave
polIcIesforeducatIng,screenIng,andcounselIngpersonnelabouttheIrrIskofacquIrIng
H87InfectIonandshouldmakevaccInatIonavaIlableforsusceptIblepersonnel.
70,82
ToensureadequatepostvaccInatIonImmunIty,serologIctestIngforantIH8sshouldtake
placewIthIn1to2months
P.71
afterthethIrddoseofvaccIne.
70
ProtectIveantIbodIesdevelopInJ0to50of
nonresponders(I.e.,antIH8s10mU/mL)wIthasecondthreedosevaccIneserIes.
NonresponderstovaccInatIon,whoareH8sAgnegatIve,remaInatrIskforH87InfectIon
andshouldbecounseledonstrategIestopreventInfectIonsandtheneedforpostexposure
prophylaxIs.
7accIneInducedantIbodIesdeclIneovertIme,wIthmaxImumtItersaftervaccInatIon
correlatIngdIrectlywIthduratIonofantIbodypersIstence.TheC0Cstatesthatfor
vaccInatedadultswIthnormalImmunestatus,routIneboosterdosesarenotnecessaryand
perIodIcmonItorIngofantIbodyconcentratIonIsnotrecommended.
70
WhensusceptIbleornonvaccInatedanesthesIapersonnelhaveadocumentedexposuretoa
contamInatedneedleortobloodfromanH8sAgposItIvepatIent,postexposureprophylaxIs
wIthH87hyperImmuneglobulInIsrecommended.
70
HepatItIs8vaccIneshouldbeoffered
toanyunvaccInated,susceptIblepersonwhosustaInsabloodorbodyfluIdexposure.
Hepatitis C
HC7causesmostcasesofparenterallytransmIttedNAN8HandIsaleadIngcauseofchronIc
lIverdIseaseIntheUnItedStates.AlthoughantIbodytoHC7(antIHC7)canbedetectedIn
mostpatIentswIthhepatItIsC,ItspresencedoesnotcorrelatewIthresolutIonoftheacute
InfectIonorprogressIonofhepatItIs,andItdoesnotconferImmunItyagaInstHC7
InfectIon.
8J
SeroposItIvItyforHC7FNAIsamarkerofchronIcInfectIonandcontInuedvIral
presence.SIxmajorgenotypesofHC7havebeenIdentIfIedwIththespecIfIcgenotype
beIngpredIctIvefortheresponsetoandtheneededduratIonofantIvIraltherapy.
|ostcasesofacuteHC7InfectIonareasymptomatIc,andupto40wIllcleartheInfectIon
wIthIn6months.ChronIcallyInfectedIndIvIdualshaveahIghrateofprogressIontochronIc
hepatItIswIthabout20developIngcIrrhosIs.HepatocellularcarcInomaoccursIn1to4
ofcIrrhotIcpatIentsperyear.CombInatIontherapywIthInterferonalpha(standardor
pegylated)andrIbavIrInhasbeeneffectIveInthetreatmentofsomecasesofacuteand
chronIchepatItIsC.
84
LIkeH87,HC7IstransmIttedthroughblood,buttherateofoccupatIonalHC7InfectIonIs
lessthanforH87.AlthoughHC7transmIssIonhasbeendocumentedInhealthcaresettIngs,
theprevalenceofantIHC7InHCWsIntheUnItedStatesIsnotgreaterthanthatfoundIn
thegeneralpopulatIon(1.6).ThegreatestrIskofoccupatIonalHC7transmIssIonIs
assocIatedwIthexposuretobloodfromanHC7posItIvesource,andtheaveragerateof
seroconversIonafteraccIdentalpercutaneousexposureIs1.8.
70
HC7hasbeentransmItted
throughbloodsplashestotheeyeandwIthexposurevIanonIntactskIn.HC7IndrIedblood
onenvIronmentalsurfacesmayremaInInfectIousforupto16hours,butenvIronmental
contamInatIondoesnotappeartobeacommonrouteoftransmIssIon.AlthoughHC7can
befoundInthesalIvaofInfectedIndIvIduals,ItIsnotbelIevedtorepresentagreatrIskfor
occupatIonaleahIghra s cu | agreurngheUr Ivapugas e | evItI v
70 8 asao
7ref*!gh aI
o traaaaaaaaadI vr
no I n gwI I nenvIr | th tf aca aelI Iaterfateu cu | agre a s e | * er I I | * eu | * er I I a a a agh aI
o Ibl enceh aI aa | o m
ooc| * *!r I a| * e t
o n f* Ia a ssa smI rtedu | Iopto16hours,o tI
or
o Ib ! Ievedto t s Ion.Althoug r n.Althou re a s e u r atment ou re a s ec
on otIc ca s eu e# t# tr aonn. r nn. # o*! ] | * tmI *!# o*! ]r r o*! r nn !r t th Ib A! or * n. I oI r n. r nn. hou rtf ac n. |a s eu e0 ho r r nn. . s po us Io aho r raIoI r n. rhou rt! nhr n I r nhkIn]r rtm I Iao m uI o . !I r nha s eura c nIbaneute e egw . .# uI
h s Ion.r * ] s p sm ] ] b o as p nhnhkI. I m ( I I sIa u | Iwm
oo cuI o .
o IbIb kIuI o . rt uI
h J s . s
oauI atmena sm ] o va
o as . ] I Al l I . s entalsurv s va .b I ] | * |I ach
70 8 A l e c atmenl h a#* nmenl
o | rI l h a * Altav t atf an I ] I ] *!b A ]rrac. ont me tmI u! r nha s atmenmenas e u ru ae traaaaaaa tmI u! r nhu* ]I * k IItI o | mI c n nasnhn e# na t
stt
nI!e gsI] Io n tI o kn. r ne a m n
l
o
o s s * a .] Io
I ]Ir a I o I l l uII o . |||||n m ou rer ] q ] q n krt tt I Ier b l lt Ie l lt n n c | n nn tt ! ltI m
I rm
rr rIt *Jtr I It * a nt * na
o . ||I t r||
mm| t nt = ] v = * #nt ] m# t rnm S t I

t ttnm* n mana It *=m I o nt |I
] n ] ktm t n t t t t |aI o !m I=n m# mI s m#i . m tm tm *mI o n EmEm m. m t mtm S t *n m mI m# m
tm mm#i . t=m | =r tm * nt m * =
= n| rt *
=nt= t =
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=r = . ] * I t u n= Im#i . t * t ! m n S= l mr . Im t tt *
TheU.S.PublIcHealthServIcerecommendsthatantIretrovIralpostexposureprophylaxIs
(PEP)beofferedtoHCWswhohaveIncurredasIgnIfIcantpercutaneousexposuretoH7
Infectedblood.
92
ThespecIfIcantIretrovIralregImenIsbasedontheseverItyofexposure
andthesourcepatIent.8ecauseprotocolsforchemoprophylaxIsarelIkelytochangewIth
addItIonalresearchandtheIntroductIonofnewantIretrovIraldrugs,themostcurrent
recommendatIonsshouldbeconsultedprIortoInstItutIngpostexposureprophylactIc
therapy.TobemosteffectIve,PEPshouldbeInItIatedassoonaspossIbleafterexposure
(24hours)andcontInuedfor4weeks.HCWsshouldbecounseledonthepotentIaltoxIc
effectsofantIretrovIralssothattheycanmakeanInformeddecIsIonontherIsks
assocIatedwIthPEP.FaIlureofPEPhasbeenattrIbutedtolargevIralInoculum,useofa
sIngleantIvIralagent,drugresIstanceInthevIrusfromthesourcepatIent,anddelayed
InItIatIonorshortduratIonofPEPtherapy.
Occupational Safety and Health Administration Standards,
Standard Precautions, and Transmission-Based Precautions
nthelate1980stheC0CformulatedrecommendatIons,orunIversalprecautIons,for
preventIngtransmIssIonofbloodborneInfectIons(IncludIngH7,H87,andHC7)toHCWs.
TheguIdelIneswerebasedontheepIdemIologyofH87asaworstcasemodelfor
transmIssIonofbloodborneInfectIonsandavaIlableknowledgeoftheepIdemIologyofH7
andHC7.8ecausesomecarrIersofbloodbornevIrusescouldnotbeIdentIfIed,unIversal
precautIonswererecommendedforusedurIngallpatIentcontact.Althoughexposureto
bloodcarrIesthegreatestrIskofoccupatIonallyrelatedtransmIssIonofH7,H87,andHC7,
ItwasrecognIzedthatunIversalprecautIonsshouldalsobeapplIedtosemen,vagInal
secretIons,humantIssues,andthefollowIngbodyfluIds:cerebrospInal,synovIal,pleural,
perItoneal,perIcardIal,andamnIotIc.Subsequently,theC0CsynthesIzedthemajor
featuresofunIversalprecautIonsIntostandardprecautIons,asInglesetofprecautIonsthat
shouldbeapplIedtoallpatIentssInceeverypersonIspotentIallyInfectedorcolonIzed
wIthanorganIsmthatmIghtbetransmItteddurIngcare(TableJ4).
76
StandardprecautIons
wereIncludedInamorecompletesetofIsolatIonprecautIons,whIchcontaInguIdelInes
(contactprecautIons,dropletprecautIons,andaIrborneprecautIons)toreducetherIskof
transmIssIonofbloodborneandotherpathogensInhealthcaresettIngs.
76
StandardprecautIonsIncludetheapproprIateapplIcatIonanduseofhandwashIng,
personalprotectIveequIpment(PPE),andrespIratoryhygIene/coughetIquette.The
selectIonofspecIfIcbarrIersorPPEshouldbecommensuratewIththetaskbeIng
performed.ClovesshouldbeworndurInganycontactwIthmucousmembranesandoral
fluIds,suchasdurIngendotrachealIntubatIonandpharyngealsuctIonIng.Clovesmaybeall
thatIsnecessarydurIngInsertIonofaperIpheralIntravenouscatheter,whereasgloves,
gown,mask,andfaceshIeldmayberequIreddurIngendotrachealIntubatIonInapatIent
wIthhematemesIsordurIngbronchoscopyorendotrachealsuctIonIng.Clovesshouldbe
removedaftertheybecomecontamInatedtopreventdIssemInatIonofbloodorbodyfluIds
toequIpmentorotherItemsthatmaybecontactedbyunglovedpersonnel.Waterless
antIseptIcsshouldbeavaIlabletopermItanesthesIapersonneltowashtheIrhandswIthout
leavIngtheoperatIngroomaftergloveremoval.FespIratoryhygIene/coughetIquette,to
contaInrespIratorysecretIonsInpatIents,hasbeenaddedtostandardprecautIonsto
preventdroplettransmIssIonofrespIratorypathogens,especIallydurIngseasonal
outbreaks.
DSHAhaspromulgatedstandardstoprotectemployeesfromoccupatIonalexposureto
bloodbornepathogens.
82
EmployerssubjecttoDSHAmustcomplywIththesefederal
regulatIons.ThestandardrequIresthattheremustbeanexposurecontrolplanspecIfIcally
detaIlIngthemethodsthattheemployerIsprovIdIngtoreduceemployees'rIskofexposure
tobloodbornepathogens.TheemployermustevaluateengIneerIngcontrolssuchas
needlelessdevIcestoelImInatehazards.WorkpractIcecontrolsareencouragedtoreduce
bloodexposuresbyalterIngthemannerInwhIchpersonnelperformtasks(e.g.,an
InstrumentratherthanfIngersshouldbeusedtohandleneedles).Theemployermust
furnIshapproprIatePPE(e.g.,gloves,gowns)InvarIoussIzestopermItemployeesto
complywIthstandardprecautIons.TheH87vaccInemustbeoffered
P.7J
atnochargetopersonnel.AmechanIsmforpostexposuretreatmentandfollowupmustbe
provIded.AnannualeducatIonalprogramshouldInformemployeesoftheIrrIskforblood
borneInfectIonandtheresourcesavaIlabletopreventbloodexposures.mplementatIonof
standardprecautIonsandDSHAregulatIonshavebeeneffectIveIndecreasIngthenumber
ofexposureIncIdentsthatresultInHCWcontactwIthpatIentbloodandbodyfluIds.
Creutzfeldt-Jakob Disease
CreutzfeldtJakobdIsease(CJ0),causedbyanInfectIousproteInorprIon,maybe
unsuspectedInpatIentspresentIngwIthdementIa.
9J
TheprIonproteInentersbraIncells
andInducesabnormalfoldIngofcellularproteInsleadIngtoIrreversIbledamagewIthloss
ofneurons.|orerecently,IthasbeenrecognIzedthattheprIonstraInassocIatedwIth
bovInespongIformencephalopathymayInfecthumanstoproduceavarIantCJ0(vCJ0).
TherehavebeennoreportedcasesofdIrecthumantohumantransmIssIonofCJ0orvCJ0
bycasualorenvIronmentalcontact,droplet,oraIrborneroutes.atrogenIctransmIssIonof
CJ0orvCJ0topatIentshastakenplacethroughcontamInatedbIologIcproductsand
neurosurgIcalInstrumentsandvIabloodtransfusIon.TherIskoftransmIssIontohospItal
personnelIsunknownbecausesurveIllanceIscomplIcatedbythelongperIodfromthetIme
ofInfectIonuntIltheonsetofsymptoms.StandardprecautIonsshouldbeused.TIssueswIth
greatestrIskofInfectIvItyarebraIn,spInalcord,andeyes.
TheprIonIsdIffIculttoeradIcatefromequIpment,andspecIalsterIlIzatIonmethodsare
requIredforInstrumentsthatcomeIntocontactwIthhIghInfectIvItytIssues.TheWorld
HealthDrganIzatIonhasdevelopedInfectIoncontrolandsterIlIzatIonguIdelInesforCJ0.
e
Tuberculosis
TheIncIdenceoftuberculosIs(T8)InU.S.bornresIdentshasdeclInedsInce1992whIlethe
rateamongforeIgnbornIndIvIdualslIvIngIntheUnItedStateshasIncreasedoverthesame
perIod.AlthoughmostIndIvIdualsInfectedwIthT8aretreatedonanoutpatIentbasIs,
undIagnosedpatIentsmaybehospItalIzedfortheworkupofpulmonarypathologyor
unrelatedcauses.HospItalpersonnelareespecIallyatrIskforInfectIonfromunrecognIzed
cases.
94,95
CroupswIthahIgherprevalenceofT8Include(1)personalcontactsofpeople
wIthactIveT8,(2)peoplefromcountrIeswIthahIghprevalenceofT8,and(J)certaIn
populatIonssuchasthemedIcallyunderservedorthoselIvIngIncongregatesettIngslIke
homelesssheltersorcorrectIonalfacIlItIes.
94
ClobalsurveIllancehasdocumentedthe
emergenceofmultIdrugresIstantT8(resIstancetoatleasttwooftheprImarytreatments,
IsonIazIdandrIfampIn)aswellasextensIvelydrugresIstantorganIsms(resIstancetoat
leasttwooftheprImarytreatments,IsonIazIdandrIfampIn,andtoanyfluoroquInolone
andatleastoneofthreeInjectabledrugs).SeveralhospItaloutbreaksofmultIdrug
resIstantMycobacterium tuberculosisInfectIonhavebeenreported.
95,96
|ortalIty
assocIatedwIththeseoutbreaksIshIgh.
Mycobacterium tuberculosiscanbetransmIttedovergreatdIstancesthroughvIablebacIllI
carrIedonaIrbornepartIcles,1to5mInsIze,bycoughIng,speakIng,orsneezIng.
AIrborneprecautIonsshouldbeusedforIndIvIdualssuspectedofhavIngT8untIltheyare
confIrmedasnontransmIttersbyrepeatsputumexamInatIonthatdemonstratesno
bacIllI.
94
DutbreaksofT8InhealthcarefacIlItIeshavebeenattrIbutedtodelayeddIagnosIs
ofT8InthesourcepatIent,delayedInItIatIonoforInadequateaIrborneprecautIons,
lapsesInprecautIonsdurIngaerosolgeneratIngprocedures,andlackofadequate
respIratoryprotectIonInHCWs.AdmInIstratIonofapproprIatechemotherapyforsuffIcIent
duratIonIsrequIredtocuretheIndIvIdualpatIent,buttreatmentalsobenefItsthe
communItybypreventIngspreadoftheInfectIon.
97
AdecreaseInthehealthcareassocIatedtransmIssIonofT8hasbeenattrIbutedtothe
rIgorousImplementatIonofInfectIoncontrolmeasures.EffectIvepreventIonofspreadto
HCWsrequIresearlyIdentIfIcatIonofInfectedpatIentsandImmedIateInItIatIonofaIrborne
InfectIonIsolatIon(negatIvepressureroomswIthaIrventedoutsIde;seeTableJ4).
94
PatIentsmustremaInInIsolatIonuntIladequatetreatmentIsdocumented.fpatIentswIth
T8mustleavetheIrrooms,theyshouldwearfacemaskstopreventspreadoforganIsms
IntotheaIr.HCWsshouldwearfIttestedrespIratoryprotectIvedevIceswhentheyenteran
IsolatIonroomorwhenperformIngproceduresthatmayInducecoughIng,suchas
endotrachealIntubatIonortrachealsuctIonIng.
94
TheC0CrecommendsthatrespIratory
protectIvedevIcesworntoprotectagaInstM. tuberculosisshouldbeabletofIlter95of
partIcles1mmInsIzeatflowratesof50L/mInandshouldfItthefacewIthaleakagerate
aroundthesealof10documentedbyfIttestIng.
94
HIgheffIcIencypartIculateaIr
respIrators(classIfIedasN95)areNDSHapproveddevIcesthatmeettheC0CcrIterIafor
respIratoryprotectIvedevIcesagaInstM.tuberculosis.
98.
ElectIvesurgeryshouldbe
postponeduntIlInfectedpatIentshavehadanadequatecourseofchemotherapy.fsurgery
IsrequIred,bacterIalfIlters(hIgheffIcIencypartIculatefIlters)shouldbeusedonthe
anesthetIcbreathIngcIrcuItforpatIentswIthT8.
94
PatIentsmustberecoveredInaroom
thatmeetsalltherequIrementsforaIrborneprecautIons.
FoutIneperIodIcscreenIngofemployeesforT8shouldbeIncludedaspartofahospItal's
employeehealthpolIcywIththefrequencyofscreenIngdependentontheprevalenceof
InfectedpatIentsInthehospItalIzedpopulatIon.WhenanewconversIonIsdetectedbyskIn
testIng,ahIstoryofexposureshouldbesoughttodetermInethesourcepatIent.Treatment
orpreventIvetherapyIsbasedonthedrugsusceptIbIlItypatternoftheM. tuberculosisIn
thesourcepatIent,Ifknown.
Viruses in Smoke Plumes
ThelaserIscommonlyusedforvaporIzIngcarcInomatoustumorsandlesIonsthatmay
contaInactIvevIruses.UseoflasersandelectrosurgIcaldevIcesIsassocIatedwIthseveral
hazards,bothtopatIentsandtooperatIngroompersonnel.FIsksIncludethermalburns,
eyeInjurIes,electrIcalhazards,andfIresandexplosIons.ThereIsevIdencethatthesmoke
plumesresultIngfromtIssuevaporIzatIoncontaIntoxIcchemIcalssuchasbenzeneand
formaldehyde,andIn1996,NDSHreleasedahealthhazardalertonthedangersofsmoke
plumes.
99
ClInIcalandlaboratorystudIeshavedemonstratedthatwhenthecarbondIoxIdelaserIs
usedtotreatverrucae(papIllomaandwarts),IntactvIral0NAcouldberecoveredfromthe
plume.7IablevIrusescanbefoundInplumesproducedbybothcarbondIoxIdeandargon
laservaporIzatIonofavIrusloadedcultureplate,butvIablevIrusesarecarrIedonlarger
partIclesthattravel100mmfromthesItebeIngvaporIzed.
100
AcasereportdescrIbeslaryngealpapIllomatosIsInasurgeonwhohadusedalaserto
removeanogenItalcondylomasfromseveralpatIents.
101
Although0NAanalysIsofthe
surgeon'spapIllomasrevealedavIraltypesImIlartothatofthecondylomas,proofof
transmIssIonIslackIng.
P.74
ToprotectoperatIngroompersonnelfromexposuretothevIralandchemIcalcontentof
thelaserplume,ItIsrecommendedthatasmokeevacuatIonsystemwIthahIgheffIcIency
fIlterbeusedwIththesuctIonnozzlebeIngheldascloseaspossIbletothetIssuebeIng
vaporIzed.
102
naddItIon,operatIngroompersonnelworkIngInthevIcInItyofthelaser
plumeshouldweargloves,goggles,andhIgheffIcIencyfIltermasks(N95respIrators).
90,102
Emotional Considerations
Stress
StressIsawellrecognIzedelementoftheoperatIngroomworkplace.However,thereIs
verylIttleobjectIveInformatIonspecIfIcallydIrectedtowardunderstandIngthenatureof
jobrelatedstressamonganesthesIologIsts.
10J,104
StressIsanonspecIfIcresponsetoany
change,demand,pressure,challenge,threat,ortrauma.
48
TherearethreedIstInct
componentsofthestressresponse:theInItIatIngstressors,thepsychologIcalfIltersthat
processandevaluatethestressors,andthecopIngmechanIsmsthatareemployedInan
attempttocontrolthestressfulsItuatIon.
StressonthejobIsunavoIdableandtoacertaIndegreeIsdesIrable.Amoderate,
manageablelevelofstressIsthefuelnecessaryforIndIvIdualachIevement.HansSeyle,
105
apIoneerInthemodernstudyofstress,descrIbedabenefIcIaleffectresultIngfrommIld,
brIef,andcontrollableepIsodesofstress.AssuccInctlystatedbySeyle,
105
Theabsenceof
stressIsdeath.Dntheotherhand,extremedegreesofstress,especIallyIntheworkplace,
canresultInmentalorphysIcaldIsease.
106
ExactlyhowanIndIvIdualrespondstoa
partIcularstressorIstheproductofanumberoffactors,IncludIngage,gender,experIence,
preexIstIngpersonalItystyle,avaIlabledefenseandcopIngmechanIsms,supportsystems,
andconcomItantevents(suchassleepdeprIvatIon).
TheworkplaceofananesthesIologIstfrequentlymIrrorsthecIrcumstancesthatclassIcally
defIneastressfulworkplace.ThereIsabackgroundofchronIc,lowlevelstresspunctuated
byIntermIttentepIsodesofextremestress.Thedemandsareexternallypaced,usuallyout
oftheanesthesIologIst'scontrol.HabItuatIontothedemandsIsdIffIcult.PerturbatIonsare
IntermIttentlybutcontInuouslyInsertedIntothesystem.FInally,faIluretomeetthe
demandsImposedbytheworkplacecanresultInserIousconsequences.
CertaInstressorsarespecIfIctothepractIceofanesthesIology.ConcernsaboutlIabIlIty,
longworkInghoursandnIghtcall,productIonpressures,economIcuncertaInty,and
InterpersonalrelatIonsarefrequentlycItedassourcesofchronIcstressfor
anesthesIologIsts.TheprocessofInducInganesthesIa(partIcularlywIthadIffIcultaIrway)
canbeamongthemostprofoundsourcesofacutestresstoanesthesIologIsts.PhysIologIc
changes,IncludIngheartrateandrhythm,elevatIonsInbloodpressure,andmyocardIal
IschemIa,arenotuncommon.DnestudyreportedIncreasesInthebloodpressureandheart
rateofanesthesIologIstsdurIngallstagesoftheanesthetIcprocedure,especIallydurIngthe
InductIon.
107
TherewasanInverserelatIonshIpbetweentheyearsofexperIenceofthe
anesthesIologIstandthedegreeofstressasmanIfestedbyheartratechange.
nterpersonalrelatIonshIpsImposeasetofdemandsthatcanbeamajorsourceofstressto
ananesthesIologIst.TheoperatIngroomIsunIqueasoneofthefewhospItalsIteswhere
twocoequalphysIcIanssImultaneouslyshareresponsIbIlItyforthecareofapatIent.Asa
result,thereexIstoverlappIngrealmsofclInIcalresponsIbIlItythatcanupsetthe
customaryhIerarchyofcommand.TomanyanesthesIologIsts,aswellassurgeons,thIs
sharedresponsIbIlItyIsthesourceofgreatestconflIctandprofessIonalstress.
50
Dther
workplacesettIngs,mostnotablytheaIrlIneIndustry,havemadebetterprogressIn
IdentIfyIngandcorrectIngsourcesofInterpersonalfrIctIonthatfacIlItatestressandleadto
professIonalerrors.
108
SeveralpersonalItytraIts,InmanycasesIdentIfIablebeforeentrancetomedIcalschool,
canbepredIctIveofthepotentIaltowardmaladaptIveresponsestostress.PromInent
amongtheseIstheobsessIvecompulsIve,dependentcharacterstructure.TheseIndIvIduals
typIcallymanIfestpessImIsm,passIvIty,selfdoubt,andfeelIngsofInsecurIty.They
commonlyrespondtostressbyInternalIzIngangerandbecomInghypochondrIacaland
depressed.UndergraduatestudentswhodemonstratethesecharacterIstIcsweremore
lIkelytohavetheIrmedIcalcareersdIsruptedbyalcoholIsmordrugabuse,psychIatrIc
Illness,andmarItaldIsturbances.
109,110
AnumberofadaptIvecopIngfunctIonsareuseful
forsuccessfulstressmanagement.
48
DnlywhenapproprIatecopIngmechanIsmsbecome
overwhelmedbythemagnItudeofthestressdothedefensestendtobecome
InapproprIate.ThIssItuatIoncangIverIsetomaladaptIvebehavIorandthepersonaland
professIonaldeterIoratIonthatcanleadtodIsorderssuchasdrugaddIctIon,professIonal
burnout,andsuIcIde.
Substance Use, Abuse, and Addiction
llIcItdruguseremaInsoneofoursocIety'smajorafflIctIons.tIsestImatedthat20mIllIon
AmerIcansaredrugabusers,wIthsome5mIllIonaddIcted.Substance abuseIs
characterIzedbysIgnIfIcantadverseconsequencesresultIngfromtherepeateduseofa
substance.
111
WIthaddiction,theIndIvIdualcontInuestouseasubstanceInspIteofhavIng
sIgnIfIcantsubstancerelatedproblemsIncludIngsymptomsofwIthdrawal,theneedfor
largeramountsofthesubstance,unsuccessfulattemptstocontrolItsuse,andtheneedto
spendIncreasIngamountsoftImeseekIngthesubstance.WIthtIme,addIctIonleadsto
health,socIal,andeconomIcproblems.Theterm,chemical dependence,IssometImesused
ratherthanaddIctIon,butItIsamoregenerIctermcoverIngphysIcalorpsychologIcal
dependencytoapsychoactIvesubstance.
Epidemiology
TheabuseofdrugsandconsequentaddIctIonbyphysIcIanshasattractedconsIderable
medIaattentIonandnotorIety.FecognItIonoftheproblemofsubstanceabuseamong
physIcIansIsnotnew.nthefIrstedItIonofThe Principles and Practice of Medicine,edIted
bySIrWIllIamDslerandpublIshedIn1892,ItIsstated:ThehabIt(morphIa)IspartIcularly
prevalentamongwomenandphysIcIanswhousethehypodermIcsyrIngefortheallevIatIon
ofpaIn,asInneuralgIaorscIatIca.
tIsdebatablewhethersubstanceabuseIsmoreprevalentamongphysIcIansthanthe
generalpopulatIon.Hughesetal
112
foundthatphysIcIansabusedalcohol,mInoropIates,
andbenzodIazepInetranquIlIzersmorefrequentlythanthegeneralpopulatIon.nmany
cases,theprescrIptIondrugswereselfprescrIbedandwereconsIderedbythephysIcIanto
beselftreatment.Dntheotherhand,physIcIanswerelesslIkelytousetobaccoorIllIcIt
substances.AreportfromtheNatIonalnstItuteon0rugAbuseconcludesthatHCWssuffer
fromchemIcaldependency(IncludIngalcoholabuse)atarateroughlyequIvalenttothatof
thegeneralpopulatIon(8to12).
11J
ntheeventthatadrugrelatedproblemdoesexIst,physIcIansarelesslIkelythanthe
populatIonIngeneraltoseekprofessIonalassIstance.0enIalplaysamajorroleInthIs
reluctancetoundergocounselIngortherapy.|edIcalstudentslearnearlyIntheIr
educatIontousedenIaltoenablethemtoendurelong,sleeplessnIghtsandthepersonal
shortcomIngsthatInevItablyaccompanythepractIceofmedIcIne.These
P.75
welldevelopeddenIalmechanIsmsenablethephysIcIanaddIcttoconcludethathIsorher
problemIsmInorandthatselftreatmentIspossIble.PhysIcIanstypIcallyenterprograms
fortreatmentonlyaftertheyhavereachedtheendstagesoftheIrIllness.
tIscommonlyreportedthatchemIcaldependencyIsaspecIfIcproblemforthespecIaltyof
anesthesIologyandrepresentsItsprImaryoccupatIonalhazard.
114
Dneexampleofthe
IncreasedIncIdenceofsubstanceabuseamonganesthesIologIstscomesfromearlyreports
fromthe|edIcalAssocIatIonofCeorgIa0Isabled0octors'Program.
115
AnesthesIologIsts
constItuted12ofphysIcIanpatIentstreatedatthecenteralthoughtheyrepresentedonly
J.9ofAmerIcanphysIcIans.Dntheotherhand,otherstudIeshavefaIledtoIdentIfyan
overallexcessprevalenceofsubstanceabuseamonganesthesIologIstswIththenotable
exceptIonofmajoropIates.
116,117
DneverytroublIngaspectofthIsproblemIstheIncreasedIncIdenceofsubstanceabuse
reportedamonganesthesIologyresIdents.nthereportfromthe|edIcalAssocIatIonof
CeorgIa0Isabled0octors'Program,
115
anesthesIologyresIdentsconstItutedJJ.7ofthe
resIdentpopulatIonofthetreatmentgroup,despIterepresentIngonly4.6oftheresIdent
populatIon.TheIncIdenceofcontrolledsubstanceabusewIthInanesthesIologytraInIng
programsIsestImatedtobe1to2.
118
ThIsstatIstIcIspartIcularlysIgnIfIcantbecauseIt
haspersIsteddespIteanIncreasedemphasIsplacedoneducatIonandaccountabIlItyof
controlledsubstances.ACC|ErequIrementsmandatethatanesthesIologyresIdency
programshaveawrIttenpolIcyandaneducatIonalprogramregardIngsubstanceabuse,but
theseeffortshavenotsuccessfullyaddressedtheproblemofsubstanceabuseIntraInIng
programs.
The Disease of Addiction
WhataccountsforthIsunacceptablyhIghprevalenceofsubstanceabuseandaddIctIon
amonganesthesIologIsts:ToanswerthIs,ItIsImportanttounderstandaddIctIonasa
chronIcpsychosocIal,bIogenetIcdIsease.
119
AddIctIonsharesmanycharacterIstIcswIth
othercommonchronIcIllnesses:ItIsaprImarycondItIon(notasymptom),Ithas
establIshedcauses,ItIsassocIatedwIthspecIfIcanatomIcandphysIologIcchanges,Ithasa
setofrecognIzablesIgnsandsymptoms,andIfleftuntreated,IthasapredIctable,
progressIvecourse.
ThecausatIvefactorsInthIsdIseaseprocessInvolveagenetIcpredIsposItIonaswellasthe
envIronment.ThedIseaseresultsfromadynamIcInterplaybetweenasusceptIblehostand
afavorableenvIronment.7ulnerabIlItyInthehostIsanImportantfactorandmay
accountfor40to60oftherIskforaddIctIon.WhatconstItutesanInstIgatIngexposureto
adrugInonepersonmayhaveabsolutelynoeffectonanother.Unfortunately,thereIsnot
apredIctIvetooltoIdentIfythesusceptIbleIndIvIdualuntIlheorshegetsthedIsease.
CausatIvefactorsthoughttobespecIfIctocertaInanesthesIologIstsIncludejobstress,an
orIentatIontowardselfmedIcatIon,lackofexternalrecognItIonandselfrespect,the
avaIlabIlItyofaddIctIngdrugs,andasusceptIblepremorbIdpersonalIty.SelfprescrIptIon
andrecreatIonaluseofdrugsarecommonlyseenasapreludetomoreextensIvesubstance
abuseanddependence.DfconcernIstheIncreasIngrecreatIonaluseofdrugsamong
youngerphysIcIansandmedIcalstudentsandthechoIceofmorepotentdrugswIth
enhancedpotentIalforaddIctIon,suchascocaIne,thesynthetIcopIoIds,andsomeofthe
newerInhalatIonanesthetIcs.|ostnotablehasbeenthesIgnIfIcantIncreaseInpropofol
abuseamongresIdents.
120
ThIsmaybeattrIbutabletothelackofpharmacyaccountIngor
controlofthIsdrugInmanycenters.
AnesthesIologIstsworkInaclImateInwhIchlargequantItIesofpowerfulpsychoactIve
drugsarereadIlyavaIlableandareunIqueamongphysIcIansbecausetheyusuallyprescrIbe
aswellaspersonallyadmInIsterthesedrugs.ncontrast,physIcIansInmostother
specIaltIesprescrIbemedIcatIonswhIleotherpersonneladmInIsterthem.8ecause
avaIlabIlItyofdrugsplaysaroleIntheonsetofthIsdIsease,attentIonhasbeendIrected
towardprogramstoenforceIncreasedaccountabIlItyandregulatIonofcontrolled
substances.
121
However,despItewIdespreadapplIcatIonofprotocolstoenforcegreater
accountabIlIty,suchassatellItepharmacIesforoperatIngsuItes,thefrequencyof
substanceabusehaschangedlIttle,Ifatall,Inrecentyears.
118
ThereIsanapparentassocIatIonbetweenbehavIorbeforeenterIngmedIcalschooland
subsequentdevelopmentofsubstanceabuse.
122
PersonalItyprofIlesofanesthesIologIsts
havesuggestedadIsturbInglyhIghproportIonthatmaybeassocIatedwIthapredIsposItIon
towardmaladaptIvebehavIor.Talbottetal
115
haveobservedthatmanyoftheanesthesIa
resIdentsIntheIrtreatmentprogramspecIfIcallychosethespecIaltyofanesthesIology
becauseoftheknownavaIlabIlItyofpowerfuldrugs.
TheconsequencesofuntreatedaddIctIonareultImatelydevastatIng.ThereIsagradual
andInexorabledeterIoratIonInprofessIonal,famIly,andsocIalrelatIonshIps.The
substanceabuserbecomesIncreasInglywIthdrawnandIsolated,fIrstInhIsorherpersonal
lIfe,andultImatelyInhIsorherprofessIonalexIstence(TableJ5).EveryattemptIsmade
tomaIntaInafacadeofnormalItyatworkbecausedIscoverymeansIsolatIonfromthe
sourceoftheabuseddrug.WhenprofessIonalconductIsfInallyImpaIredsuchthatItIs
apparenttothephysIcIan'scolleagues,thedIseaseIsapproachIngItsendstage.
fnotdetectedandtreated,addIctIonIsoftenafatalIllness.UsIngmortalItydata
collectedbetween1979and1995,Alexanderetal
14
calculatedarelatIverIskof2.79for
drugrelateddeathsamonganesthesIologIstscomparedtoamatchedcohortofInternIsts.
|enketal
12J
found14drugrelateddeathsamongthe79drugabuserswhohadbeenre
enrolledInanesthesIologyresIdencIesaftertreatment.UsIngdatafromamorerecent
survey,CollInsetal
124
reportedthattherewerenInedeathsIn100resIdentswhoretured
toandremaInedInanesthesIologytraInIngprogramsaftertreatmentforchemIcal
dependence.naddItIontohealthhazards,therearesIgnIfIcantlegalandmedIcolegal
consIderatIonsthatmayaffectchemIcallydependentphysIcIans.
114
LawsandregulatIons
varybystatebuttheydetaIlthenecessarystepsforhandlIngthedrugabusIngphysIcIan.n
manystatesdIscIplInaryactIonandcrImInalpenaltIescanbeImposedonphysIcIanswho
knowInglyfaIltoreportanImpaIredcolleague.0IscIplInaryactIontakenagaInstan
ImpaIredphysIcIanmustalsobereportedtotheNatIonalPractItIoner0ata8anktobeIn
complIancewIthfederallaw.|oststatemedIcalsocIetIeshavesanctIonedphysIcIans
healthprograms.WhenchemIcallydependentphysIcIansseektreatmentthroughthIs
venue,thelegalImpactmaybemItIgated,andthedIseasecanbeeffectIvelytreated.
0ebatecontInuesregardIngtheIssueofcompulsoryrandomdrugtestIngofphysIcIans.
125
Preemploymentand/orrandomdrugscreenIngIsalreadywellestablIshedInvarIous
IndustrIes,especIallythosewIthhIghpublIchealthprofIles(nuclear,avIatIon,mIlItary).
|anychaIrsofacademIcanesthesIologyprogramshaveIndIcatedawIllIngnesstoInItIatea
programofrandomdrugscreenIngoftheIrstaff.
118
AlthoughrandomdrugtestIngIsan
establIshedelementofmostreentrycontractsforrecoverInganesthesIologIsts,serIous
questIonsremaInaboutthelegalItyofthIsapproachandItseffectIvenessInpreventIng
substanceabuse.8ecausefentanylandsufentanIlarethedrugsabusedbymanychemIcally
dependentanesthesIologIstsandbecauseroutInedrugscreensdonotdetecttheseagents,
teststhateffectIvelyIdentIfytheIruseareexpensIveandhavelImItedavaIlabIlIty.
WhentherearesuffIcIentdatatoIdentIfyananesthesIologIstashavIngthedIseaseof
addIctIon,anInterventIonshouldbeconductedbyanexperIencedIndIvIdual.Thepurpose
oftheInterventIonIstodemonstratetotheanesthesIologIstthatheorshehasthedIsease
andtoImmedIatelyhavetheperson
P.76
enterafacIlItyforevaluatIonandtreatment.ThephysIcIan,orhIsorhercolleagues,
shouldconsIderreferraltoastateaffIlIatedphysIcIanshealthprogram.
f
Treatmentusually
begInswIthInpatIenttherapyprogressIngtooutpatIentsessIons.ThefamIlyIsactIvely
InvolvedwIthtreatment,andtheIndIvIdualbegInsassocIatIonwIthAlcoholIcsAnonymous
(AA)orNarcotIcsAnonymous(NA).
Table 3-5 Signs of Substance Abuse and Dependence
WHAT TO LOOK FOR OUTSIDE THE HOSPITAL
1. AddIctIonIsadIseaseoflonelInessandIsolatIon.AddIctsquIcklywIthdrawfrom
famIly,frIends,andleIsureactIvItIes.
2. AddIctshaveunusualchangesInbehavIor,IncludIngwIdemoodswIngsand
perIodsofdepressIon,anger,andIrrItabIlItyalternatIngwIthperIodsof
euphorIa.
J. UnexplaInedoverspendIng,legalproblems,gamblIng,extramarItalaffaIrs,and
IncreasedproblemsatworkarecommonlyseenInaddIcts.
4. AnobvIousphysIcalsIgnofalcoholIsmIsthefrequentsmellofalcoholonthe
breath.
5. 0omestIcstrIfe,fIghts,andargumentsmayIncreaseInnumberandIntensIty.
6. SexualdrIvemaysIgnIfIcantlydecrease.
7. ChIldrenmaydevelopbehavIoralproblems.
8. SomeaddIctsfrequentlychangejobsoveraperIodofseveralyearsInan
attempttofIndageographIccurefortheIrdIseaseortohIdeItfrom
coworkers.
9. AddIctsneedtobeneartheIrdrugsource.ForahealthcareprofessIonal,thIs
meanslonghoursatthehospItal,evenwhenoffduty.ForalcoholIcs,Itmeans
callIngInsIcktowork.AlcoholIcsmaydIsappearwIthoutanyexplanatIontobars
orhIdIngplacestodrInksecretly.
10. AddIctsmaysuddenlydevelopthehabItoflockIngthemselvesInthebathroom
orotherroomswhIletheyareusIngdrugs.
11. AddIctsfrequentlyhIdepIlls,syrInges,oralcoholbottlesaroundthehouse.
12. PersonswhoInjectdrugsmayleavebloodyswabsandsyrIngescontaInIngblood
tIngedlIquIdInconspIcuousplaces.
1J. AddIctsmaydIsplayevIdenceofwIthdrawal,especIallydIaphoresIs(sweatIng)
andtremors.
14. NarcotIcaddIctsoftenhavepInpoIntpupIls.
15. WeIghtlossandpaleskInarealsocommonsIgnsofaddIctIon.
16. AddIctsmaybeseenInjectIngdrugs.
17. TragIcally,someaddIctsarefoundcomatoseordeadbeforeanyofthesesIgns
havebeenrecognIzedbyothers.
WHAT TO LOOK FOR INSIDE THE HOSPITAL
1. AddIctssIgnouteverIncreasIngquantItIesofnarcotIcs.
2. AddIctsfrequentlyhaveunusualchangesInbehavIor,suchaswIdemoodswIngs
andperIodsofdepressIon,anger,andIrrItabIlItyalternatIngwIthperIodsof
euphorIa.
J. ChartIngbecomesIncreasInglysloppyandunreadable.
4. AddIctsoftensIgnoutnarcotIcsInInapproprIatelyhIghdosesfortheoperatIon
beIngperformed.
5. TheyrefuselunchandcoffeerelIef.
6. AddIctslIketoworkaloneInordertouseanesthetIctechnIqueswIthout
narcotIcs,falsIfyrecords,anddIvertdrugsforpersonaluse.
7. Theyvolunteerforextracases,oftenwherelargeamountsofnarcotIcsare
avaIlable(e.g.,cardIaccases).
8. TheyfrequentlyrelIeveothers.
9. TheyareoftenatthehospItalwhenoffduty,stayIngclosetotheIrdrugsupply
topreventwIthdrawal.
10. Theyvolunteerfrequentlyforextracall.
11. TheyareoftendIffIculttofIndbetweencases,takIngshortnapsafterusIng.
12. AddIctedanesthesIapersonnelmayInsIstonpersonallyadmInIsterIngnarcotIcs
Intherecoveryroom.
1J. AddIctsmakefrequentrequestsforbathroomrelIef.ThIsIsusuallywherethey
usedrugs.
14. AddIctsmaywearlongsleevedgownstohIdeneedletracksandalsotocombat
thesubjectIvefeelIngofcoldtheyexperIencewhenusIngnarcotIcs.
15. NarcotIcaddIctsoftenhavepInpoIntpupIls.
16. AnaddIct'spatIentsmaycomeIntotherecoveryroomcomplaInIngofpaInoutof
proportIontotheamountofnarcotIcchartedontheanesthesIarecords.
17. WeIghtlossandpaleskInarealsocommonsIgnsofaddIctIon.
18. AddIctsmaybeseenInjectIngdrugs.
19. UntreatedaddIctsarefoundcomatose.
20. UndetectedaddIctsarefounddead.
AdaptedfromFarleyWJ,ArnoldWP:7Ideotape:UnmaskIngaddIctIon:ChemIcal
0ependencyInAnesthesIology.Producedby0avIdsProductIons,ParsIppany,NJ,
fundedbyJanssenPharmaceutIca,PIscataway,NJ,1991.
FeprIntedwIthpermIssIonfromAmerIcanSocIetyofAnesthesIologIsts:TaskForce
onChemIcal0ependenceoftheCommItteeonDccupatIonalHealthofDperatIng
FoomPersonnel:ChemIcal0ependenceInAnesthesIologIsts:WhatYouNeedto
KnowWhenYouNeedtoKnowt.ParkFIdge,L,AmerIcanSocIetyof
AnesthesIologIsts,1998.
ControversyremaInsabouttheultImatecareerpathoftheanesthesIologIstInrecovery.
WIthInthegeneralpopulatIon,therecIdIvIsmrateapproaches60forpatIentswhohave
beentreatedforaddIctIon.However,physIcIansarehIghly
P.77
motIvatedandbetterrehabIlItatIonratesmIghtbeexpected.EarlyreportsprovIded
optImIsmthatInmanycasesanesthesIologIstscouldbesuccessfullyrehabIlItatedand
safelyreturnedtotheIrpractIces.nastudythatexamInedrelapseInaddIctedphysIcIans,
therateofrelapseamonganesthesIologIstswas40andthatofcontrolphysIcIanswas
44.
126
SustaInedrecoveryforlongerthan2yearsoccurredIn81and86,respectIvely.
AlthoughthesedatasuggestedthattheoutcomeforrecoverInganesthesIologIstswas
sImIlartootherphysIcIans,astudyby|enkandcolleagues
12J
drewadIfferentconclusIon.
Among79opIoIddependentanesthesIologyresIdents,therewasa66(52of79)faIlurerate
forsuccessfulrehabIlItatIonandreturntopractIce.EvenmoredIscouragIng,therewere14
suIcIdeoroverdosedeathsamongthe79returnIngtraInees.TheIrconclusIonwasthat
redIrectIonIntoanotherspecIaltyIsthesafercourseafterrehabIlItatIonofnarcotIc
dependentresIdents.UsIngsurveydatafromU.S.traInIngprograms,CollInsetal
124
found
thatonly46ofanesthesIaresIdentstreatedforsubstanceabusesuccessfullycompleted
theIranesthesIologytraInIng,J4chosetoenteratraInIngprogramInanothermedIcal
specIalty,and16leftmedIcIne.Therewere9deathsamongthe100anesthesIaresIdents
thatcontInuedInanesthesIatraInIngprogramsaftertreatment.
0atafromaretrospectIvestudyofhealthcareprofessIonalshasIdentIfIedthreefactors
assocIatedwIthrelapseaftercompletIonoftreatmentforchemIcaldependency.
127
Althoughtheoverallrateforrelapsewas25,therIskwasIncreasedwhentherewasa
famIlyhIstoryofsubstanceabuse(hazardratIo[HF]=2.J)andwhenamajoropIoIdwasthe
abuseddrugInanIndIvIdualwIthacoexIstIngpsychIatrIcdIsorder(dualdIagnosIs,[HF=
5.8]).TherIskofrelapsewasgreatest(HF=1J.J)whenallthreefactorswerepresent,that
Is,famIlyhIstory,majoropIoIduse,anddualdIagnosIs.TreatedanesthesIologIstswho
returnedtothepractIceofanesthesIologyhadagreaterrIskofrelapse(HF=8.5)
comparedwIththosewhodIdnotreturn.8ecauseofthesmallsamplesIze,amoredetaIled
analysIsofrIskfactorsforanesthesIologIstscouldnotbeperformed.
NounIversalrecommendatIonscanbemadeaboutreentryIntothepractIceofanesthesIa
aftertreatment.ToreenterpractIce,therecoverIngphysIcIanmustqualIfyforavalId
lIcensetopractIcemedIcIneandmustberecredentIaledattheIrmedIcalfacIlIty.ThIs
mustbedoneIncomplIancewIththeIrstatelawsandregulatIonsthatdetaIlthe
cIrcumstancesunderwhIcharecoverIngphysIcIancanreturntopractIce.Federallaws,
suchastheAmerIcanswIth0IsabIlItIesAct,ImposeaddItIonalconsIderatIons.AddItIonally,
acarefullywordedcontractIsanImportantfIrststepInthereentryprocesstodefInethe
oblIgatIonsofthephysIcIanandthedepartment.
114,128
ContractsusuallyIncludean
agreementtorefraInfromselfprescrIptIonofmedIcatIon,submIttorandomurInedrug
screens,anddIrectlyobservedadmInIstratIonofnaltrexoneordIsulfIramforatleast6
months.ThereshouldalsoberegularmeetIngswIththedepartmentalsupervIsorto
monItorthereturnprocess.tIsalsogenerallyrecommendedthatthereturnIng
anesthesIologIstnottakenIghtorweekendcallorhandleopIoIdswIthoutdIrectsupervIsIon
foratleastthefIrstJmonths.|onItorIngandtreatmentforanextendedperIodIsmore
lIkelytoreducetherIskforrelapse.0espItealloftheseprecautIons,thepotentIalfor
relapsemustbeantIcIpated.
CuIdelInesfromphysIcIantreatmentcentersmaybehelpfultoassIstInthedecIsIons
surroundIngreentry.
111
ndIvIdualswho,InmostsItuatIons,cansuccessfullyreturntothe
practIceofanesthesIologyImmedIatelyaftertreatment(Category)acceptandunderstand
theIrdIseaseandhavenoevIdenceofaccompanyIngpsychIatrIcdIsorders.Theyhave
strongsupportfromtheIrfamIly,demonstrateabalancedlIfestyle,arecommIttedtotheIr
recoverycontract,andbondwIthAAorNA.TheIranesthesIologydepartmentandhospItal
mustbesupportIveoftheIrreturn,andtheIndIvIdualmusthaveasponsorthatsupports
thereturntoanesthesIology.
CategoryIncludesthoseIndIvIdualswhocouldpossIblyreturntoanesthesIologywIthIna
fewyears.TheymusthavenoormInImaldenIalregardIngtheIrdIseaseandhavenoother
psychIatrIcdIagnoses.TheIrrecoveryskIllsarecontInuallyImprovIngandtheyare
Involved,butnotnecessarIlybonded,wIthAA/NA.AlthoughtheIrfamIlysItuatIonmaybe
characterIzedasdysfunctIonal,thereshouldbetangIbleevIdenceofImprovement.
ndIvIdualswhoshouldnotreturntoanesthesIologyandwouldbestberedIrectedInto
anothermedIcalspecIaltyareIncludedInCategory.TheseIndIvIdualsmayhavehada
hIstoryofprolongedIntravenoussubstanceuseandhaveexperIencedrelapsesandprIor
treatmentfaIlures.TheIrdIseaseremaInsactIve,andtheyhavecoexIstIngsevere
psychIatrIcdIagnoses.
Impairment and Disability
mpaIrment
g
anddIsabIlIty
h
canarIsefromphysIcal,mental,emotIonal,sensoryor
developmentalcauses.Theonsetcanbesudden,asoccurswIthInjuryoracuteIllness,or
moregradual,asIsthecasewIthmanychronIcdIseases.
0ataregardIngtheprevalenceofdIsablIngdIsordersamongphysIcIansaredIffIcultto
obtaIn.SubstancerelateddIsorders(seeSubstanceUse,Abuse,andAddIctIon)occursas
frequentlyamongphysIcIansasInthegeneralpopulatIon
11J
(8to12)andaccountsfor
manycasesofphysIcIanImpaIrment.
i
thasbeenquestIonedwhether,wIththenotable
exceptIonofopIoIdabuse,substancerelateddIseaseIsmorecommonamong
anesthesIologIststhanotherphysIcIans.
124
However,unpublIsheddatacollectedfromone
largeInsuranceunderwrIterIndIcatethattherateofsubstancerelateddIsabIlItyamong
anesthesIologIstsIsJtImesthatseenamongotherphysIcIans(personalcommunIcatIon,
UnumProvIdent).DtherfactorsthatmayleadtoImpaIrmentIncludephysIcalormental
IllnessanddeterIoratIonassocIatedwIthagIng.UnwIllIngnessorInabIlItytokeepupwIth
currentlIteratureandtechnIquescanbeconsIderedaformofImpaIrment.
AmongphysIcIanswhoareImpaIredasaresultofemotIonalIllness,depressIonIsa
promInentfIndIng.nonestudy,approxImatelyJ0ofmedIcalInternswereclInIcally
depressed.
129
ndeed,whenexaggerated,manyofthepersonalItytraItsthatensuresuccess
InthephysIcIan'sworld,suchasselfsacrIfIce,competItIveness,achIevementorIentatIon,
denIaloffeelIngs,andIntellectualIzatIonofemotIons,mayalsoserveasrIskfactorsfor
depressIon.SeveralstudIesonalcoholIcphysIcIanshaveprovIdedsomeInsIghtIntothIslInk
betweenachIevementorIentatIonandemotIonaldIsturbance.nonestudy,morethanhalf
ofthealcoholIcphysIcIansgraduatedIntheupperonethIrdoftheIrmedIcalschoolclass,
2JwereIntheupperonetenthoftheIrclass,andonly5wereIntheloweronethIrdof
theIrclass.
1J0
SImIlarly,areportonalcoholuseInmedIcalschooldemonstratedbetter
fIrstyeargradesandhIgherscoresonPartNatIonal8oardof|edIcalExamInerstests
amongthosestudentsIdentIfIedasalcoholabusers.
1J1
tcanbedIffIculttoapproprIatelyrespondtotheproblemsImposedbytheImpaIredor
unsafeanesthesIologIst.
1J2
P.78
Fortunately,manystatelegIslaturesandmedIcalsocIetIeshaveformalprotocolsthat
addresstheImpaIredphysIcIanInatherapeutIcandnonpunItIvefashIon.ThelIcense
suspensIonpowerofthestateboardofmedIcalexamInersIsusuallyexercIsedonlyIncases
InwhIchthereIsasubstantIalrIsktothepublIcwelfareandtheInvolvedphysIcIanIs
unwIllIngtovoluntarIlysuspendpractIce.|anagementprotocolsfordealIngwIththe
ImpaIredphysIcIanarecoveredInaserIesofartIclesbyCanavanand8axter.
1JJ
The Aging Anesthesiologist
LIttleattentIonhasbeengIventothechallengesfacedbyolderanesthesIologIsts.
58
ThIsIs
IncontrasttothesItuatIonInmostotherIndustrIesInwhIchmuchconsIderatIonIsdIrected
towardthecompetenceandwellbeIngofolderworkers.Forexample,commercIalpIlots
arerequIredtotakeregularmedIcalexamInatIonsandconformtopolIcIesregardInghours
ofwork.
AdvancIngchronologIcageIspredIctablyaccompanIedbychangesInmostorgansystems.
|ostnotableforthesafepractIceofanesthesIologyarethechangescommonlyobservedIn
thecentralnervoussystem.NeuronaldensItyandbraInweIghtdecreasefrom1,J75gat
age20yearsto1,200gatage80years.
1J4
ThereIsanagerelateddeclIneIntraInIng
dependentplastIcItyInthemotorcortexaccompanIedbyadImInIshedabIlItytoreorganIze
InresponsetotraInIng.
1J5
TheseandotheranatomIcchangesareassocIatedwIthcommondecrementsInphysIologIc
functIon.TherearemeasurabledecreasesInhearIng,vIsIon,shorttermmemory,creatIve
thInkIngandproblemsolvIngabIlItIes.LearnIngIsslowerandrequIresmoreeffort.
ntellectualquIcknessandonthespotreasonIngandreactIontImeslow.Thesehavethe
potentIalofadverselyaffectIngtheolderanesthesIologIst'sabIlItytoassImIlateandapply
newknowledgeandtoInstantaneouslyprocessInformatIon,rapIdlymakecomplex
decIsIons,andInItIatetheapproprIateresponse.
1J6
ThesedefIcIencIesareespecIally
exposedInastressfulenvIronmentsuchastheoperatIngroom.
1J7
ThecardIovascularandmusculoskeletalsystemsalsoundergoagerelatedchangesthatcan
affecttheabIlItytopractIceanesthesIology.DneareaofpartIculardIffIcultyfor
anesthesIologIstsIsmaIntaInIngthestamInarequIredforlongworkshIftsandnIghtcall.
SuperImposedonapropensItytosleepdIsturbance,thedemandsofnIghtcalland
assocIatedsleepdeprIvatIonarepartIcularlydIffIcultforolderanesthesIologIsts.NIghtcall
IsconsIderedoneofthemoststressfulaspectsofpractIceandIsoftencItedasareasonfor
retIrementamongolderanesthesIologIsts.
58,1J8
ThephysIologIcchangesthataccompanythenormalagIngprocessareoftencompensated
byadvantagesconferredbyolderage.TheseIncludewIsdom,judgment,andthe
experIenceacquIredbyalIfelongpractIceofthespecIalty.ThereIsastrongcorrelatIon
betweenexperIenceandperformance.
1J9,140
However,thIscorrelatIondoesnotnecessarIly
exIstbetweenexperIenceandcomplexcognItIveskIlls.AspoIntedoutbyWeInger,
141
experIenceIsnotsynonymouswIthexpertIse.
AgIngamonganesthesIologIstsraIsesInterestInglegalIssues.TherearenoagespecIfIc
condItIonsplacedonstatemedIcallIcensureoronthepractIceofanesthesIology.nmost
cases,thedecIsIontolImItpractIceorretIreremaInsatthedIscretIonoftheIndIvIdual
anesthesIologIstbasedonhIsorherselfevaluatIon.AnumberoffederallawsImpactthe
agInganesthesIologIst'srIghtsandresponsIbIlItIesregardIngcontInuatIonofwork.These
IncludetheAge0IscrImInatIonAct,TItle7oftheCIvIlFIghtsAct(EqualPayAct),the
|edIcalandFamIlyLeaveAct,theFaIrLaborStandardsAct,andtheEmployeeFetIrement
ncomeSecurItyAct(EFSA).
AnesthesIology,sImIlartootherhIghstressprofessIons,IscommonlyconsIderedayoung
person'sspecIalty.AnesthesIologIststendtoretIreatayoungeragethandomanyother
specIalIsts.
142
ThedecIsIontoretIreforananesthesIologIstIsfrequentlyprecIpItatedby
thegrowIngburdensofnIghtcallorconcernsaboutdeterIoratIngclInIcalskIlls.nmany
cases,theretIrInganesthesIologIstjustfeltItwastIme.
1J8
AgrowIngnumberofpractIces
areestablIshIngphasedretIrementplansthatpermItsenIoranesthesIologIststoavoIdsome
ofthemoreonerousaspectswhIleremaInIngvItalmembersofapractIce.
14J
AsaresultofanumberofdemographIcfactors,IncludIngthesmallerresIdencyclasssIzes
observeddurIngthemId1990s,themeanageoftheanesthesIologyworkforceIsIncreasIng.
Thegreatestnumber(J0)ofanesthesIologIstsarebetweenage45and54yearsofage,and
56areage45andolder(upfrom4910yearsago).
15
Mortality Among Anesthesiologists
AnumberofstudIeshaveexamInedmortalItyamonganesthesIologIsts.EmployIngdIfferent
databasesandmethods,thesestudIeshavereportedconflIctIngconclusIonsIncludInga
shortened,
14,144
anaverage,
15,145
oraprolonged
146,147
lIfeexpectancy.A2006study
reportedasIgnIfIcantIncreaseInlIfeexpectancyamonganesthesIologIstsdurIngthelast
decade,suchthattheaverageageatdeathIn2001(thelastyearofthestudy)was78
years,thesameasthenatIonalaverageforallAmerIcans.
148
ThecauseofdeathamonganesthesIologIstshasalsobeenextensIvelystudIed.EarlIerwork
foundanIncreasedIncIdenceofcertaIntypesofcancer,IncludIngleukemIaand
lymphoma.
4,12
AmorerecentreportbyAlexanderetal
14
foundnoIncreasedrIskofcancer
relateddeathsamonganesthesIologIstsascomparedwIththecontrolgroup(InternIsts).
SIgnIfIcantlyIncreasedrIsksforanesthesIologIstsresultedfromdrugrelateddeath,suIcIde,
drugrelatedsuIcIde,otherexternalcauses,H7related,andcerebrovasculardIsease.The
rIsktoanesthesIologIstsofdrugrelateddeathswashIghestInthefIrst5yearsafter
graduatIonfrommedIcalschoolandremaInedIncreasedforentIreprofessIonalcareers.
Suicide
thasbeenwelldocumentedthattherateofsuIcIderanksdIsproportIonatelyhIghasa
causeofdeathamongbothmale
149
andfemale
150
physIcIans.SeveralreportshavesIngled
outanesthesIologIstsasbeIngpartIcularlyvulnerable.
14,147,151
However,thIsconclusIonhas
beenquestIonedastheresultofthemethodologIcaldIffIcultIesIncollectIngaccuratedata
onsuIcIdeandthefrequentfaIluretoadequatelycorrectforconfoundIngvarIablesInthe
studypopulatIons.
152
WhymIghttherebeahIghrateofsuIcIdeamonganesthesIologIsts:ApartIalexplanatIon
lIeswIththehIghdegreeofstressthatIsanIntegralpartofthejob.
48
ThereIsaclose
assocIatIonInmanyIndIvIdualsbetweenstressfullIfeeventsandmajordepressIve
dIsorders.
15J
nsusceptIbleIndIvIduals,feelIngsofInabIlItytocoperesultIngfromthe
stressInduceddepressIoncangIvewaytodespaIrandsuIcIdeIdeatIon.
ExtensIvepersonalItyprofIlescollectedfromsuIcIdesusceptIbleIndIvIdualsIndIcate
characterIstIcssuchashIghanxIety,InsecurIty,lowselfesteem,ImpulsIveness,andpoor
selfcontrol.tIsdIsturbIngtonotethatInthestudyofpersonalItytraItsof
anesthesIologIstsbyFeeve,
154
some20manIfestedpsychologIcalprofIlesthatreflecteda
predIsposItIontobehavIoraldIsIntegratIonandattemptedsuIcIdewhenplacedunder
P.79
extremesofstress.ThIsstudyraIsesthedIscomfortIngnotIonthatpremorbIdpersonalIty
characterIstIcsexIstbeforeenterIngspecIaltytraInIngandarenotbeIngIdentIfIedInthe
admIssIonsprocess.
DnespecIfIctypeofstress,thatresultIngfromamalpractIcelawsuIt,mayhaveadIrect
causatIveassocIatIonwIthsuIcIdeamongphysIcIansIngeneralandanesthesIologIstsIn
partIcular.NewspaperreportshavedescrIbedtheemotIonaldeterIoratIonandultImate
suIcIdeofexperIencedphysIcIanswhohavebecomeInvolvedInamalpractIcesuIt.Dne
studyreportedthat4of185anesthesIologIstsbeIngsuedformedIcalmalpractIce
attemptedorcommIttedsuIcIde.
151
SubstanceabuseamonganesthesIapersonnelIs
anotherpotentIalcontrIbutortotheIncreasedsuIcIderate.ndIvIdualswIthchemIcal
dependence,whoarenotIdentIfIedandareIntheendstagesofthedIsease,maydIeof
drugoverdose,acauseofdeaththatcanbedIffIculttodIstInguIshfromsuIcIde.none
recentstudy,drugabusewasamongthehIghestcausesofdeathandthemostfrequent
methodofsuIcIdeamonganesthesIologIsts.
14
0rugoverdoseanddeathwastheInItIal
relapsesymptomIn16(1Jof79)oftheparenteralopIoIdabuserswhohadreentered
theIrresIdencyInanesthesIology.
12J
PhysIcIanswhoareImpaIredfromchemIcal
dependenceandwhoseprIvIlegestopractIcemedIcInehavebeenrevokedarealsoat
heIghtenedrIskforattemptIngsuIcIde.Crawshawetal
155
reported8successfuland2near
mIsssuIcIdeattemptsamong4JphysIcIansplacedonprobatIonfordrugrelateddIsabIlIty.
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TableofContentsSectIonntroductIontoAnesthesIologyChapter4AnesthetIcFIsk,QualItymprovementand
LIabIlIty
Chapter4
Anesthetic Risk, Quality Improvement and Liability
Karen L. Posner
Karen B. Domino
Key Points
1. Anesthetic mortality has decreased, but accidental deaths and
disabling complications still occur.
2. Risk management programs are broadly oriented toward reducing the
liability exposure of the organization. Risk management programs
complement quality improvement programs in minimizing liability
exposure while maximizing quality of patient care.
3. Quality improvement programs are generally guided by the
requirements of the Joint Commission that accredits healthcare
organizations. Quality improvement programs focus on improving the
structure, process, and outcome of care.
4. Continuous quality improvement (CQI) is a systems approach to
identifying and improving quality of care.
5. Medical malpractice refers to the legal concept of professional
negligence. The patient-plaintiff must prove that the anesthesiologist
owed the patient a duty, failed to fulfill this duty, that the
anesthesiologist's actions caused an injury, and that the injury
resulted from a breach in the standard of anesthesia care.
6. The most common lawsuits against anesthesiologists (excluding
dental injuries) are for death, brain damage, nerve damage, and
airway injury.
nanesthesIa,asInotherareasoflIfe,everythIngdoesnotalwaysgoasplanned.
UndesIrableoutcomesoccurregardlessofthequalItyofcareprovIded.AnanesthesIarIsk
managementprogramcanworkInconjunctIonwIthaprogramforqualItyImprovementto
mInImIzethelIabIlItyrIskofpractIce,whIleassurIngthehIghestqualItyofcarefor
patIents.Payerssuchas|edIcareareIncreasInglydependIngonaccredItatIonthrough
bodIessuchastheJoIntCommIssIontoensurethatmechanIsmsareInplacetodelIver
qualItyandsafecaretoallpatIents.naddItIon,therehasbeenamovetoward
performancemeasurementlInkedtoreImbursement.ThelegalaspectsofAmerIcan
medIcalpractIcehavealsobecomeIncreasInglyImportantasthepublIchasturnedtothe
courtsforeconomIcredresswhentheIrexpectatIonsofmedIcaltreatmentarenotmet.
ThIschapterdIscussesanesthetIcmortalItyandmorbIdIty,rIskmanagement,contInuous
qualItyImprovement,performancemeasurement,andmedIcallIabIlIty.Thechapter
provIdesbackgroundforthepractItIonerconcernIngtheroleofrIskmanagementactIvIty
InmInImIzIngandmanagInglIabIlItyexposure.AlsodescrIbedIsthemedIcallegalsystem,
themostfrequentcausesoflawsuItsforanesthesIologIsts,andapproprIateactIonsfor
physIcIanstotakeIntheeventofamalpractIcesuIt.
Anesthesia Risk
Mortality and Major Morbidity Related to Anesthesia
EstImatesofanesthesIarelatedmorbIdItyandmortalItyaredIffIculttoquantIfy.Notonly
aretheredIffIcultIesobtaInIngdataoncomplIcatIons,butdIfferentmethodsyIelddIfferent
estImatesofanesthesIarIsk.StudIesdIfferIntheIrdefInItIonsofcomplIcatIons,lengthof
followup,andespecIallyInapproachestoevaluatIonofthecontrIbutIonofanesthesIa
caretopatIentoutcomes.AcomprehensIverevIewofanesthesIacomplIcatIonsIsbeyond
thescopeofthIschapter.AsamplIngofstudIesofanesthesIamortalItyandmorbIdItywIll
bepresentedtoprovIdehIstorIcalperspectIveplusalImItedovervIewofrelatIvelyrecent
fIndIngs.
EarlystudIesestImatedtheanesthesIarelatedmortalItyrateas1per1,560anesthetIcs.
1
|orerecentstudIesusIngdatafromthe1990sestImatetheanesthesIarelateddeathrate
IntheUnItedStatestobe1per10,000anesthetIcs.
2,J,4,5
Someexamplesofmodern
estImatesofanesthesIarelateddeathfromthroughouttheworldareprovIdedInTable4
1.
2,J,4,5,6,7,8,9,10,11,12,1J
0IfferencesInestImatesmaybeInfluencedbydIfferentreportIng
P.8J
methods,defInItIons,anesthesIapractIces,patIentpopulatIon,aswellasactual
dIfferencesInunderlyIngcomplIcatIonrates.Nevertheless,ItIsgenerallyacceptedthat
anesthesIasafetyhasImprovedoverthepast50years.
Table 4-1 Estimates of Anesthesia-Related Death
REFERENCE COUNTRY TIME DATA SOURCES/METHODS RATE OF DEATH
FlIcketal
4
USA
1988
2005
PerIoperatIvecardIac
arrestInpedIatrIc
patIentsatatertIary
referralhospItal(n=
92,881anesthetIcs)
AnesthesIa
attrIbuted
deaths=
0.22/10,000
anesthetIcs
8Ibouletet
al
8
France
1989
1995
ASA14patIents
undergoInganesthesIa(n
=101,769anesthetIcs);
cardIacarrestwIthIn12
hrpostanesthesIa(n=24)
AnesthesIa
relateddeath=
0.6/10,000
anesthetIcs
Newland
etal
2
USA
1989
1999
CardIacarrestswIthIn24
hrofsurgery(n=72,959
anesthetIcs)InateachIng
hospItal
0eathrelatedto
anesthesIa
attrIbutable
perIoperatIve
cardIacarrest=
0.55/10,000
anesthetIcs
Eagleand
0avIs
6
Western
AustralIa
1990
1995
0eathswIthIn48hror
deathsInwhIch
anesthesIawas
consIderedacontrIbutIng
factor(n=500deaths)
AnesthesIa
relateddeath=
1/40,000
anesthetIcs
Lagasse
J
USA
(a)
1992
1994
(a)SuburbanteachIng
hospItal(n=115deaths;n
=J7,924anesthetIcs)
AnesthesIa
relateddeath=
(a)0.79/10,000
anesthetIcs
(b)
1995
1999
(b)UrbanteachIng
hospItal(n=2J2deaths;n
=146,548anesthetIcs)
(b)0.75/10,000
anesthetIcs
0avIs
7
AustralIa
1994
1996
0eathsreportedtothe
commIttee(n=8,500,000
anesthetIcs)
AnesthesIa
relateddeath=
0.16/10,000
anesthetIcs
|orrayet
1994
PedIatrIcpatIentsfrom6J
AnesthesIa
relateddeath=
al
5
USA 1997 hospItals(n=1,089,200
anesthetIcs)
0.J6/10,000
anesthetIcs
KawashIma
etal
10
Japan
1994
1998
QuestIonnaIrestotraInIng
hospItals(n=2,J6J,0J8
anesthetIcs)
0eathtotally
attrIbutableto
anesthesIa=
0.21/10,000
anesthetIcs
Arbouset
al
9
Holland
1995
1997
AlldeathswIthIn24hror
patIentswhoremaIned
unIntentIonallycomatose
24hrpostanesthesIa(n=
811In869,48J
anesthetIcs)64hospItals
AnesthesIa
relateddeath=
1.4/10,000
anesthetIcs
LIenhartet
al
1J
France 1999
NatIonwIdesurveyof
anesthesIarelateddeaths
0eathtotally
relatedto
anesthesIa=
0.069/10,000
0eathpartIally
relatedto
anesthesIa=
0.47/10,000
KawashIma
etal
11
Japan 1999
QuestIonnaIrestotraInIng
hospItals(n=79J,840
anesthetIcs)
0eathtotally
attrIbutableto
anesthesIa=
0.1J/10,000
anesthetIcs
rItaet
al
12
Japan
1999
2002
0eathsasaresultoflIfe
threatenIngeventsInthe
operatIngroom(n=
J,855,J84anesthetIcs)In
traInInghospItals
0eathtotally
attrIbutableto
anesthetIc
management=
0.1/10,000
anesthetIcs
DthercomplIcatIonsrelatedtoanesthesIathathavereceIvedrelatIvelyrecentattentIon
IncludepostoperatIvenerveInjury,awarenessdurInggeneralanesthesIa,eyeInjurIesand
vIsualdefIcIts,dentalInjury,andpostoperatIvecognItIvedysfunctIonInelderlypatIents.
UlnarneuropathyIsoneofthemostcommonnerveInjurIesleadIngtoanesthesIa
malpractIceclaImsIntheUnItedStates.
14
TheIncIdenceofulnarneuropathyhasbeen
estImatedbetweenJ.7and50per10,000patIents(Table42).
15,16,17
LowerextremIty
neuropathyfollowIngsurgeryInthelIthotomyposItIonwasobservedIn2.7per10,000
patIents(Table42).
18
PermanentneurologIcInjuryfollowIngneuraxIalanesthesIawas
estImatedat0to4.2per10,000spInalanesthetIcsand0to7.6per10,000epIdural
anesthetIcs.
19
AwarenessdurInggeneralanesthesIahasbeenestImatedtooccurIn1to2
per1,000patIentsIntertIarycaresettIngs,
20,21
butmayoccurwIthlowerfrequencyIn
ambulatorypatIents.
22
EyeInjurIesarearIskofanesthesIa,IncludIngcornealabrasIonsaswellasmorerare
complIcatIonssuchasblIndnessfromIschemIcoptIcneuropathyorcentralretInalartery
occlusIon(Table42).
2J,24
EyeInjuryafternonocularsurgerywasobservedIn5.6per10,000
patIents.
2J
Newonsetblurred
P.84
vIsIonhasbeenobservedIn4.2ofpatIents(Table42).
24
NewonsetvIsuallossorchanges
lastIngmorethanJ0daysafternoncardIacsurgerywereobservedIn1per125,2J4
patIents.
24
Table 4-2 Rates of Selected Anesthesia Complications
COMPLICATION REFERENCE COUNTRY TIME SPECIFIC COMPLICATION RESULTS
Warneret
al
18
USA
1957
1991
LowerextremIty
motorneuropathy
followIngsurgery
InlIthotomy
posItIon
1/J,608
procedures
Warneret
al
16
USA
1957
1991
PersIstentulnar
neuropathy
followIng
dIagnostIcor
noncardIac
procedureswIth
anesthesIa
1/2,729
patIents
AlvIne
and
Schurrer
15
USA
1980
1981
Ulnarneuropathy
aftergeneral
anesthesIa
0.26
FadIculopathyor
Nerve
Injury
8rullet
al
19
7arIous
1987
1999
perIpheral
neuropathyafter
spInalanesthesIa
J.78/10,000
anesthetIcs
FadIculopathyor
perIpheral
neuropathyafter
epIdural
anesthesIa
2.19/10,000
anesthetIcs
Permanent
neurologIcInjury
afterspInal
anesthesIa
0
4.2/10,000
anesthetIcs
Permanent
neurologIcInjury
afterepIdural
anesthetIc
0
7.6/10,000
anesthetIcs
7arIes
TransIent
neurologIcdefIcIt
afterInterscalene
block
2.84/10,000
anesthetIcs
Warneret
al
17
USA 1995
Ulnarneuropathy
InadultsfollowIng
noncardIacsurgery
0.5
Awareness
andrecall
SandInet
al
20
Sweden
1997
1998
Awarenessand
recallassocIated
wIthgeneral
anesthesIa
18/11,785
procedures
Sebelet
al
21
USA
2001
2002
AwarenesswIth
recallInpatIents
18yroldInseven
academIcmedIcal
centers
0.1J
Pollardet
USA
2002
Awarenessand
recallInaregIonal
1/14,560
al
22
2004 medIcalcenter patIents
Eye
InjurIes
andvIsual
changes
Warneret
al
2J
USA
1986
1998
NewonsetvIsual
lossorvIsual
changeslastIng
J0daysafter
noncardIacsurgery
1/125,2J4
patIents
Warneret
al
24
USA 1999
Newonsetblurred
vIsIonlastIngJ
days
4.2
0ental
Injury
Warneret
al
25
USA
1987
1997
0entalInjurIes
wIthIn7daysof
anesthesIathat
requIred
InterventIon
1/4,5J7
patIents
0amagetoteethordenturesIsperhapsthemostcommonInjuryleadIngtoanesthesIa
malpractIceclaIms.0entalInjurycomplaIntsareusuallyresolvedbyahospItalrIsk
managementdepartment.0entalInjurIesrequIrIngInterventIonwereobservedIn1per
4,5J7patIents.
25
CognItIvedysfunctIonIsobservedInmanyadultpatIentsaftermajorsurgery,butonlythe
elderlyareatsIgnIfIcantrIskforlongtermcognItIveproblems.
26
Thecausefor
postoperatIvecognItIvedysfunctIonIsunknown.
Risk Management
Conceptual Introduction
FIskmanagementandqualItyImprovementprogramsworkhandInhandInmInImIzIng
lIabIlItyexposurewhIlemaxImIzIngqualItyofpatIentcare.AlthoughthefunctIonsofthese
programsvaryfromoneInstItutIontoanother,theyoverlapIntheIrfocusonpatIent
safety.TheycangenerallybedIstInguIshedbytheIrbasIcdIfferenceInorIentatIon.A
hospItalrIskmanagementprogramIsbroadlyorIentedtowardreducIngthelIabIlIty
exposureoftheorganIzatIon.ThIsIncludesnotonlyprofessIonallIabIlIty(andtherefore
patIentsafety)butalsocontracts,employeesafety,publIcsafety,andanyotherlIabIlIty
exposureoftheInstItutIon.QualItyImprovementprogramshaveastheIrmaIngoalthe
contInuousmaIntenanceandImprovementofthequalItyofpatIentcare.Theseprograms
maybebroaderIntheIrpatIentsafetyfocusthanstrIctlyrIskmanagement.QualIty
Improvement(sometImescalledpatient safety)departmentsareresponsIbleforprovIdIng
theresourcestoprovIdesafe,patIentcentered,tImely,effIcIent,effectIve,andequItable
patIentcare.
27
Risk Management in Anesthesia
ThoseaspectsofrIskmanagementthataremostdIrectlyrelevanttothelIabIlItyexposure
oftheanesthesIologIstIncludepreventIonofpatIentInjury,adherencetostandardsof
care,documentatIon,andpatIentrelatIons.
P.85
ThekeyfactorsInthepreventIonofpatIentInjuryarevIgIlance,uptodateknowledge,
andadequatemonItorIng.
28
PhysIologIcmonItorIngofcardIopulmonaryfunctIon,combIned
wIthmonItorIngofequIpmentfunctIon,mIghtbeexpectedtoreduceanesthetIcInjurytoa
mInImum.ThIswastheratIonalefortheadoptIonbytheAmerIcanSocIetyof
AnesthesIologIsts(ASA)ofStandards for Basic Anesthetic Monitoring.
a
TheASAWebsIteshouldberevIewedyearlyforanychangesInthesestandards.twould
alsobereasonabletorevIewtheGuidelines and StatementspublIshedontheASAWebsIte.
tshouldbenotedthat,althoughmembershIpIntheASAIsnotrequIredforthepractIceof
anesthesIology,expertwItnesseswIll,wIthvIrtualcertaInty,holdanypractItIonertothe
ASAstandards.tIsalsopossIblethat,asarIskmanagementstrategy,aprofessIonal
lIabIlItyInsurerorhospItalmayholdanIndIvIdualanesthesIologIsttostandardshIgherthan
thosepromulgatedbytheASA.
AnotherrIskmanagementtoolIstheuseofchecklIstsprIortoeachcase,oratleastdaIly,
InanattempttoreduceequIpmentrelatedmIshaps.
29,J0,J1
Aregularscheduleof
equIpmentmaIntenanceshouldbeestablIshedaswellasprocedurestofollowwhenever
equIpmentmalfunctIonIssuspectedofcontrIbutIngtopatIentInjury.TheASAWebsItehas
recommendatIonsforpreanesthesIacheckoutprocedures
b
aswellasguIdelInesfor
determInInganesthesIamachIneobsolescence.
c
fequIpmentmalfunctIonIssuspectedto
havecontrIbutedtoacomplIcatIon,thedevIceshouldbeImpoundedandexamIned
concurrentlybytherepresentatIvesofthehospItal,theanesthesIologIst,andthe
manufacturer.
AlthoughItmayseemobvIous,qualIfIedanesthesIapersonnelshouldbeIncontInuous
attendancedurIngtheconductofallanesthetIcs.TheonlyexceptIonsshouldbethosethat
laypeople(I.e.,judgeandjury)canunderstand,suchasradIatIonhazardsoran
unexpectedlIfethreatenIngemergencyelsewhere.Eventhen,provIsIonsshouldbemade
formonItorIngthepatIentadequately.AdequatesupervIsIonofnurseanesthetIstsand
resIdentsIsalsoImportant,asIsgoodcommunIcatIonwIthsurgeonswhenadverse
anesthetIcoutcomesoccur.
Informed Consent
nformedconsentregardInganesthesIashouldbedocumentedwIthageneralsurgIcal
consent,whIchshouldIncludeastatementtotheeffectthat,understandthatall
anesthetIcsInvolverIsksofcomplIcatIons,serIousInjury,or,rarely,deathfromboth
knownandunknowncauses.naddItIon,thereshouldbeanoteInthepatIent'srecord
thattherIsksofanesthesIaandalternatIvesweredIscussed,andthatthepatIentaccepted
theproposedanesthetIcplan.AbrIefdocumentatIonIntherecordthatthecommon
complIcatIonsoftheproposedtechnIqueweredIscussedIshelpful.nsomeInstItutIons,a
separatewrIttenanesthesIaconsentformmaybeused,whIchmayIncludemoredetaIl
aboutrIsks.fItIsnecessarytochangetheagreedonanesthesIaplansIgnIfIcantlyafterthe
patIentIspremedIcatedoranesthetIzed,thereasonsforthechangeshouldbedocumented
Intherecord.
Record Keeping
CoodrecordscanformastrongdefenseIftheyareadequate;however,recordscanbe
dIsastrousIfInadequate.TheanesthesIarecordItselfshouldbeasaccurate,complete,and
asneataspossIble.TheuseofautomatedanesthesIarecordsmaybehelpfulInthedefense
ofmalpractIcecases,
J2
buttheymayalsoserveasdamagIngevIdenceforthelackof
vIgIlanceprIortoanadverseevent.naddItIontodocumentIngvItalsIgnsatleastevery5
mInutes,specIalattentIonshouldbepaIdtoensurethatthepatIent'sASAclassIfIcatIon,
themonItorsused,fluIdsadmInIstered,anddosesandtImesofalladmInIstereddrugsare
accuratelycharted.8ecausetheprIncIpalcausesofhypoxIcbraIndamageanddeathdurIng
anesthesIaarerelatedtoventIlatIonand/oroxygenatIon,allrespIratoryvarIablesthatare
monItoredshouldbedocumentedaccurately.tIsImportanttonotewhenthereIsa
changeofanesthesIapersonneldurIngtheconductofacase.Sloppy,InaccurateanesthesIa
records,wIthgapsdurIngcrItIcalevents,canbeextremelydamagIngtothedefensewhen
enlargedandplacedbeforeajury.
What To Do After an Adverse Outcome
facrItIcalIncIdentoccursdurIngtheconductofananesthetIc,theanesthesIologIstshould
document,InnarratIveform,whathappened,whIchdrugswereused,thetImesequence,
andwhowaspresent.ThIsshouldbedocumentedInthepatIent'sprogressnotes,asa
catastrophIcIntraanesthetIceventcannotbesummarIzedadequatelyInasmallamountof
spaceontheusualanesthesIarecord.ThecrItIcalIncIdentnoteshouldbewrIttenassoon
aspossIble.ThereportshouldbeasconsIstentaspossIblewIthconcurrentrecords,suchas
theanesthesIa,operatIngroom,recoveryroom,andcardIacarrestrecords.fsIgnIfIcant
InconsIstencIesexIst,theyshouldbeexplaIned.Fecordsshouldneverbealteredafterthe
fact.fanerrorIsmadeInrecordkeepIng,alIneshouldbedrawnthroughtheerror,
leavIngItlegIble,andthecorrectIonshouldbeInItIaledandtImed.LItIgatIonIsalengthy
process,andacourtappearancetoexplaIntheIncIdenttoajurymaybeyearsaway,when
memorIeshavefaded.
fanesthetIccomplIcatIonsoccur,theanesthesIologIstshouldbehonestwIthboththe
patIentandfamIlyaboutthecause.TheprovIdersshouldprovIdethefactsaboutthe
event,expressregrettothepatIentandfamIlyabouttheoutcome,andgIveaformal
apologyIftheunantIcIpatedoutcomeIstheresultofanerrororsystemfaIlure.
JJ
Some
stateshavelawsmandatIngdIsclosureofserIousadverseeventstopatIents,anddIsclosure
hasbeenIncorporatedIntoqualItyreportIng.SomestatesprohIbItuseofdIsclosure
dIscussIonsasevIdenceInmalpractIcelItIgatIon.WheneverananesthetIccomplIcatIon
becomesapparent,approprIateconsultatIonshouldbeobtaInedquIckly,andthe
departmentalorInstItutIonalrIskmanagementgroupshouldbenotIfIed.fthe
complIcatIonIsapttoleadtoprolongedhospItalIzatIonorpermanentInjury,thelIabIlIty
InsurancecarrIershouldbenotIfIed.ThepatIentshouldbefollowedcloselywhIleInthe
hospItal,wIthtelephonefollowup,IfIndIcated,afterdIscharge.TheanesthesIologIst(s),
surgeon(s),consultIngphysIcIansandtheInstItutIonshouldcoordInateandbeconsIstentIn
theIrexplanatIonstothepatIentorthepatIent'sfamIlyastothecauseofany
complIcatIon.
Special Circumstances: Do Not Attempt Resuscitation and
Jehovah's Witnesses
tIsImportanttorecognIzethatpatIentshavewellestablIshedrIghts,andthatamong
theseIstherIghttorefusespecIfIctreatments.TwosItuatIonsmostrelevanttoanesthesIa
careare0oNotAttemptFesuscItatIon(0NAF)ordersandthespecIalcIrcumstanceof
bloodtransfusIonforJehovah'sWItnesses.
PatIentswIthseveremedIcalcondItIonsmayelecttoforgoresuscItatIonattemptsInthe
eventofcardIacarrest.Such0NAFordersmaybespecIfIedathospItaladmIssIonormay
P.86
beInplaceIntheformofanadvancedIrectIveprIortoadmIssIon.0NAFordersoradvance
dIrectIvesmaybegeneralorspecIfIc,suchasrefusaloftrachealIntubatIonormechanIcal
ventIlatIon.WhenapatIentwIth0NAFstatuspresentsforanesthesIacare,ItIsImportant
todIscussthIswIththepatIentorpatIent'ssurrogatetoclarIfythepatIent'sIntentIons.n
manyhospItals,theInstItutIonalpolIcyIstosuspendthe0NAForderdurIngtheImmedIate
perIoperatIveperIodsIncethecauseforacardIacarrestmaybeeasIlyIdentIfIedand
treated.notherInstItutIons,thepatIentmaychoosetosuspendthe0NAForderdurIngthe
entIreperIoperatIveperIod.tshouldbeclarIfIedwhenthe0NAFordershouldbe
reInstated(e.g.,dIschargefromrecoveryorpossIblylater,whenthepatIenthasrecovered
fromtheprocedure)anddocumentedInthepatIent'schart.TheperIoperatIvestatusof
0NAFordersshouldalsobeclarIfIedwIththesurgeonandotherprovIderswhowIllbe
InvolvedInthepatIent'sperIoperatIvecare.TheASAhaspublIshedEthical Guidelines of
the Anesthesia Care of Patients with Do-Not-Resuscitate Orders.
d
nthecaseofJehovah'sWItnesses,thetreatmentthatmayberefusedIstheadmInIstratIon
ofbloodorbloodproducts.AcentralrelIgIousbelIefofmanyJehovah'sWItnessesIsthat
thefaIthfulwIllbeforbIddenthepleasuresoftheafterlIfeIftheyreceIvebloodorblood
products.Thus,forthemtoreceIveatransfusIonIsamortalsIn,andmanyJehovah's
WItnesseswouldactuallyratherdIeIngracethanlIvewIthnopossIbIlItyofsalvatIon.
AnesthesIologIstsmustrecognIzeandrespectthesebelIefs,butmayalsobecognIzantthat
theseconvIctIonsmayconflIctwIththeIrownpersonal,relIgIous,orethIcalcodes.
Asageneralrule,physIcIansarenotoblIgatedtotreatallpatIentswhoapplyfortreatment
InelectIvesItuatIons.tIswellwIthIntherIghtsofaphysIcIantodeclInetocareforany
patIentwhowIshestoplaceburdensomeconstraIntsonthephysIcIanortounacceptably
lImItthephysIcIan'sabIlItytoprovIdeoptImalcare.WhenpresentedwIththeopportunIty
toprovIdeelectIvecareforaJehovah'sWItness,thephysIcIanmaydeclInetoprovIdeany
careormaylImIt,bymutualconsentwIththepatIent,hIsorheroblIgatIontoadhereto
thepatIent'srelIgIousbelIefs.fsuchanagreementIsreached,Itmustbedocumented
clearlyInthemedIcalrecord,andItIsdesIrabletohavethepatIentcosIgnthenote.Not
allJehovah'sWItnesseshaveIdentIcalbelIefsregardIngbloodtransfusIonsorwhIch
methodsofbloodpreservatIonorsequestratIonwIllbeallowed.SomepatIentswIllnot
allowanybloodthathasleftthebodytobereInfused,yetotherswIllaccept
autotransfusIonIftheIrbloodremaInsInconstantcontactwIththebody(vIatubIng).
Therefore,ItIsImportanttoreachaclearunderstandIngofwhIchtechnIquesforblood
preservatIonaretobeusedandtodocumentthIsplanIntherecord.ParentsofamInor
chIldmaynotlegallypreventthatchIldfromreceIvIngblood.tmaybenecessaryto
obtaInacourtorderInthIscIrcumstance.
National Practitioner Data Bank
tIsusuallytheoblIgatIonofthehospItalrIskmanagementdepartmenttomakereports
andInquIrIestotheNatIonalPractItIoner0ata8ank(NP08),anatIonwIdeInformatIon
systemthattheoretIcallyallowslIcensIngboardsandhospItalsameansofdetectIng
adverseInformatIonaboutphysIcIans.
J4
SImplymovIngIntoanotherstatewouldnolonger
provIdesafehavenforIncompetentphysIcIans.
TheNP08requIresInputfromfIvesources:(1)medIcalmalpractIcepayments,(2)lIcense
actIonsbymedIcalboards,(J)professIonalrevIeworclInIcalprIvIlegeactIonstakenby
hospItalsandotherhealthcareentItIes(IncludIngprofessIonalsocIetIes),(4)actIonstaken
bythe0rugEnforcementAgency,and(5)|edIcare/|edIcaIdexclusIons.Therehasbeena
greatdealofefforttoestablIshamInImummalpractIcepaymentbelowwhIchnoreportIs
necessary,buttodate,anypaymentmadeonbehalfofaphysIcIanInresponsetoawrItten
complaIntorclaImmustbereported.SettlementsmadebycancellatIonofbIllsor
settlementsmadeonverbalcomplaIntsarenotconsIderedareportablepayment.
DnceareporthasbeensubmItted,thephysIcIanIsnotIfIedandmaydIsputetheaccuracy
ofthereport.AtthIstIme,thereportIngentItymaycorrecttheformorvoIdIt.FaIlIng
that,thephysIcIanhastheoptIonofputtIngabrIefstatementInthefIleorappealIngto
theU.S.SecretaryofHealthandHumanServIces,whomayalsoeIthercorrectorvoIdthe
form.ApractItIonermaymakeaqueryabouthIsorherfIleatanytIme.AphysIcIanmay
alsoaddastatementtoareportatanytIme.SuchstatementswIllbeIncludedInany
reportsthataresentInresponsetoInquIrIes.TheexIstenceoftheNP08reportIng
requIrementshasmadephysIcIansreluctanttoallowsettlementofnuIsancesuItsbecause
ItwIllcausetheIrnamestobeaddedtothedatabank.
Quality Improvement and Patient Safety in Anesthesia
QualItyIsaconceptthathascontInuedtoeludeprecIsedefInItIonInmedIcalpractIce.
However,ItIsgenerallyacceptedthatattentIontoqualItywIllImprovepatIentsafetyand
satIsfactIonwIthanesthesIacare.ThefIeldofqualItyImprovementIscontInuallyevolvIng,
asIsthetermInologyusedtodescrIbesuchefforts.AmorerecenttrendIsemphasIson
patIentsafety,thepreventIonofharmfrommedIcalcare.AtthetImeofthIswrItIng,
patIentsafetyInItIatIvesareevolvIngandamovementtowardpayforperformance
(dIrectlInkagebetweencareprocessesandoutcomesandreImbursement)Isonthe
horIzon.ThesewIllbedIscussedInaseparatesectIon.
AnesthesIaqualItyImprovementprogramsattheservIcelevelaregenerallyguIdedby
requIrementsoftheJoIntCommIssIonthataccredItshospItalsandhealthcare
organIzatIons.QualItyImprovementprogramsarebasIcallyorIentedtowardImprovement
ofthestructure,process,andoutcomeofhealthcaredelIvery.AnunderstandIngofthe
fundamentalprIncIplesofqualItyImprovementmayclarIfytherelatIonshIpbetweenthe
contInuallyevolvIngJoIntCommIssIonrequIrementsandmandatedqualItyImprovement
andotherreportIngInItIatIves.
Structure, Process, and Outcome: The Building Blocks of
Quality
AlthoughqualItyofcareIsdIffIculttodefIne,ItIsgenerallyacceptedthatItIscomposedof
threecomponents:structure,process,andoutcome.
J5
StructurereferstothesettIngIn
whIchcarewasprovIded;forexample,personnelandfacIlItIesusedtoprovIdehealthcare
servIcesandthemannerInwhIchtheyareorganIzed.ThIsIncludesthequalIfIcatIonsand
lIcensIngofpersonnel,ratIoofpractItIonerstopatIents,standardsforthefacIlItIesand
equIpmentusedtoprovIdecare,andtheorganIzatIonalstructurewIthInwhIchcareIs
delIvered.TheprocessofcareIncludesthesequenceandcoordInatIonofpatIentcare
actIvItIes;thatIs,whatwasactuallydone.WasapreanesthetIcevaluatIonperformedand
documented:WasthepatIentcontInuouslyattendedandmonItoredthroughoutthe
anesthetIc:OutcomeofcarereferstochangesInhealthstatusofthepatIentfollowIngthe
delIveryofmedIcalcare.AqualIty
P.87
ImprovementprogramfocusesonmeasurIngandImprovIngthesebasIccomponentsof
care.
Continuous quality improvement(CQ)takesasystemsapproachtoIdentIfyIngand
ImprovIngqualItyofcare.
J6,J7
TheoperatorIsjustonepartofacomplexsystem.An
ImportantunderlyIngpremIseIsthatpoorresultsmaybearesultofeItherrandomor
systematIcerror.FandomerrorsareInherentlydIffIculttopreventandprogramsfocused
InthIsdIrectIonaremIsguIded.Systemerrors,however,shouldbecontrollableand
strategIestomInImIzethemshouldbewIthInreach.CQIsbasIcallytheprocessof
contInuallyevaluatInganesthesIapractIcetoIdentIfysystematIcproblems(opportunItIes
forImprovement)andImplementIngstrategIestopreventtheIroccurrence.
ACQprogrammayfocusonundesIrableoutcomesasawaytoIdentIfyopportunItIesfor
ImprovementInthestructureandprocessofcare.ThefocusIsnotonblamebutratheron
IdentIfIcatIonofthecausesofundesIrableoutcomes.nsteadofaskIngwhIchpractItIoners
havethehIghestpatIentmortalItyrates,aCQprogrammayfocusontherelatIonshIp
betweentheprocessofcareandpatIentmortalIty.WhatproportIonofdeathswasrelated
tothepatIent'sdIseaseprocessordebIlItatedcondItIon:ArethesepatIentsbeIng
approprIatelyevaluatedforanesthesIaandsurgery:Werethereanycontrollablecauses,
suchasalackofextrahelpdurIngresuscItatIon:ThelattermayleadtoamodIfIcatIonof
personnelresources(structure)orassIgnments(process)tobesurethatadequatepersonnel
areavaIlableatalltImes.
Formally,theprocessofCQInvolvestheIdentIfIcatIonofopportunItIesforImprovement
throughthecontInualassessmentofImportantaspectsofcare.tIsaprocessthatIs
InstItutedfromthebottomup,bythosewhoareactuallyInvolvedIntheprocesstobe
Improved,ratherthanfromthetopdownbyadmInIstrators.dentIfIcatIonofopportunItIes
forImprovementmaybecarrIedoutbyvarIousmeans,frombraInstormIngsessIons
focusIngonasystematIcevaluatIonofcareactIvItIestothecarefulmeasurementof
IndIcatorsofqualIty(suchasmorbIdItyandmortalIty).nanyevent,onceareasare
IdentIfIedforImprovement,theIrcurrentstatusIsmeasuredanddocumented.ThIsmay
Involvemeasurementofoutcomes,suchasdelayedrecoveryfromanesthesIaorperIpheral
nerveInjury.TheprocessofcareleadIngtotheseproblemsIsthenanalyzed.fachangeIs
IdentIfIedthatshouldleadtoImprovement,ItIsImplemented.AfteranapproprIatetIme,
thestatusIsthenmeasuredagaIntodetermInewhetherImprovementactuallyresulted.
AttentIonmaythenbedIrectedtocontInuIngtoImprovethIsprocessorturnIngtoa
dIfferentprocesstotargetforImprovement.
Difficulty of Outcome Measurement in Anesthesia
mprovementInqualItyofcareIsoftenmeasuredbyareductIonIntherateofadverse
outcomes.However,adverseoutcomesarerelatIvelyrareInanesthesIa,makIng
measurementofImprovementdIffIcult.Forexample,IfanInstItutIonlowersItsmortalIty
rateofsurgerypatIentsfrom1In1,000to0.5In1,000,thIsdIfferencemaynotbe
statIstIcallysIgnIfIcant.notherwords,ItmaybeImpossIbletoknowIfthechangeIn
outcomeresultedfromchangesIncare,oraresImplyrandomfluctuatIons.|anyadverse
outcomesInanesthesIaaresuffIcIentlyraretorenderthemproblematIcasqualIty
Improvementmeasures.
Tocomplementoutcomemeasurement,anesthesIaCQprogramscanfocusoncrItIcal
IncIdents,sentInelevents,andhumanerrors.Critical incidentsareeventsthatcause,or
havethepotentIaltocause,patIentInjuryIfnotnotIcedandcorrectedInatImely
manner.Forexample,apartIaldIsconnectofthebreathIngcIrcuItmaybecorrected
beforepatIentInjuryoccurs,yethasthepotentIalforcausInghypoxIcbraInInjuryor
death.CrItIcalIncIdentsaremorecommonthanadverseoutcomes.|easurementofthe
occurrencerateofImportantcrItIcalIncIdentsmayserveasaproxymeasureforrare
outcomesInanesthesIaInaCQprogramdesIgnedtoImprovepatIentsafetyandprevent
Injury.
Sentinel eventsaresIngle,IsolatedeventsthatmayIndIcateasystemIcproblem.TheJoInt
CommIssIonhasaspecIfIcdefInItIonofsentIneleventsthatwIllbedIscussedlater.n
general,asentIneleventmaybeasIgnIfIcantoralarmIngcrItIcalIncIdentthatdIdnot
resultInpatIentInjury,suchasasyrIngeswapandadmInIstratIonofapotentIallylethal
doseofmedIcatIonthatwasnotedandtreatedpromptly,avoIdIngcatastrophe.Dra
sentIneleventmaybeanunexpectedsIgnIfIcantpatIentInjurysuchasIntraoperatIve
death.neIthercase,aCQprogrammayInvestIgatesentIneleventsInanattemptto
uncoversystemIcproblemsInthedelIveryofcarethatcanbecorrected.Forexample,a
syrIngeswapmaybeanalyzedforconfusIngorunclearlabelIngofmedIcatIonsor
unnecessarymedIcatIonsroutInelystockedontheanesthesIacart,settIngthescenefor
unIntendedmIxup.nthecaseofdeath,allaspectsofthepatIent'shospItalcoursefrom
selectIonforsurgerytoanesthetIcmanagementmaybeanalyzedtodetermIneIfsImIlar
deathscanbepreventedbyachangeInthecaredelIverysystem.
HumanerrorhasgarneredmuchattentIonsInceagovernmentreportthat98,000
AmerIcansmaydIeannuallyfrommedIcalerrorsInhospItals.
J8
Humanerrorsare
InevItableyetpotentIallypreventablebyapproprIatesystemsafeguards.ErrorsofplannIng
InvolveuseofawrongplantoachIeveanaIm.
J9
ErrorsofexecutIonarethefaIlureofa
plannedactIontobecompletedasIntended.
J9
|odernanesthesIaequIpmentIsdesIgned
wIthsafeguardssuchasalarmsystemstodetecterrorsthatcouldleadtopatIentInjury.
DtheranesthesIacareprocessesarealsoamenabletohumanfactorsdesIgnprIncIples,such
ascolorcodIngofdruglabels.AqualItyImprovementprogrammayIdentIfyhumanerrors
andInstItutesafetysystemstoaIdInerrorpreventIon.
Joint Commission Requirements for Quality Improvement
JoIntCommIssIonrequIrementsforqualItyImprovementactIvItIesareupdatedonan
annualbasIs.ngeneral,ahospItalmustadoptamethodforsystematIcallyassessIngand
ImprovIngImportantfunctIonsandprocessesofcareandtheIroutcomesInacyclIcal
fashIon.ThegeneraloutlIneforthIsCQcycleIsthedesIgnofaprocessorfunctIon,
measurementofperformance,assessmentofperformancemeasuresthroughstatIstIcal
analysIsorcomparIsonwIthotherdatasources,andImprovementoftheprocessor
functIon.Thenthecyclerepeats.TheJoIntCommIssIonprovIdesspecIfIcstandardsthat
mustbemet,wIthexamplesofapproprIatemeasuresofperformance.ThegoalofthIs
cycleofdesIgn,measurement,assessment,andImprovementofperformanceofImportant
functIonsandprocessesIstoImprovepatIentsafetyandqualItyofcare.
AnesthesIacareIsoneImportantfunctIonofthecareofpatIentsmonItoredbytheJoInt
CommIssIon.tIsImportantthatpolIcIesandproceduresforadmInIstratIonofanesthesIa
beconsIstentInalllocatIonswIthIntheorganIzatIon.
TheJoIntCommIssIonhasadoptedandannuallyupdatespatIentsafetygoalsforaccredIted
organIzatIons.FecentpatIentsafetygoalsIncludeImprovedaccuracyofpatIent
IdentIfIcatIon,ImprovedeffectIvenessofcommunIcatIon
P.88
amongcaregIversIncludInghandoffs,ImprovedsafetyofmedIcatIonusageIncludIng
antIcoagulatIontherapy,reductIonofhealthcareassocIatedInfectIons,andImproved
recognItIonandresponsetochangesInapatIent'scondItIon.JoIntCommIssIon
accredItatIonvIsItsareunannounced,andInvolvetheInspectorwatchIngpatIentcareto
seethatsafeandacceptablepractIcesareroutInelyImplemented.ntheIntraoperatIve
envIronment,thIsmayInvolvesuchprocessesastImelyadmInIstratIonofantIbIotIcsand
properlabelIngofallsyrIngesontheanesthesIacart.TheJoIntCommIssIonalsorequIres
allsentInelevents(anyunexpectedoccurrencesInvolvIngdeathorserIousphysIcalor
psychologIcalInjuryorrIskthereof)toundergoroot cause analysis.
e
ArootcauseanalysIsIs
typIcallyfacIlItatedbythehospItalandIncludeseveryoneInvolvedInthecareofthe
affectedpatIentInreconstructIngtheeventstoIdentIfysystemprocessflawsthat
facIlItatedmedIcalerror.AnysurgeryonthewrongpatIentorwrongbodypartIsIncluded
InthIspolIcy.TheJoIntCommIssIonpublIshesasentIneleventalertsohealthcare
organIzatIonscanlearnfromtheexperIencesofothersandpreventfuturemedIcalerrors.
Pay for Performance
ArelatIvelyrecentdevelopmentrelatedtoqualItyImprovementIsP4Porpayfor
performance.P4PprogramsprovIdemonetaryIncentIvesforImplementatIonofsafe
practIces,measurIngperformance,and/orachIevIngperformancegoals.ThIsIsarecent
andevolvIngtrend,soonlyaconceptualIntroductIonwIllbeprovIdedhere.AnesthesIa
provIdersandservIcegroupswIllneedtobecognIzantofanyP4PInItIatIvesthatare
operatIveIntheIrlocatIonandwIththeIrpayers.
AtthetImeofthIswrItIng,P4PIsbeIngdrIvenbytheLeapfrogCroup,thenstItuteof
Healthcaremprovement,theCenterfor|edIcareand|edIcaIdServIces(C|S),andthe
NatIonalQualItyForum.ThebasIcconceptInvolvespaymentforqualItyratherthansImply
paymentforservIces.nsomecases,qualItyIncentIvepaymentsareprovIdedforsImply
measurIngprocesses.However,asmeasurementsystemsareImplemented,ItIsexpected
thatbenchmarksforqualItyperformancewIllbeestablIshedandprovIderswIllneedto
showthattheyaremeetIngsuchperformancebenchmarkstoreceIveIncentIvepayments.
Eventually,provIdersfallIngshortofbenchmarkperformancemayseetheIr
reImbursementsreduced.P4PIsbeIngImplementedatboththehospItalandspecIfIc
provIderlevel.C|SandotherpayersmayeventuallylInkreImbursementtoIndIvIdual
provIderprofIles.
AmultItudeofperformancemeasuresarebeIngdevelopedtomeetthebenchmarkIng
challenge.Atpresent,IndIvIdualInstItutIonsarenotbeIngheldtopartIcularbenchmarks
butareexpectedtoadoptsomeofthemajorqualItyIndIcatorsformeasurementand
Improvement.TheseIncludeneverevents,whIchareserIousadverseeventsthatshould
neveroccur.NevereventsIncludesurgeryonthewrongpatIentorlocatIon,unIntentIonal
retentIonofaforeIgnbodyaftersurgery,patIentdeathresultIngfromamedIcatIonerror,
andperIoperatIvedeathofanASA1patIent.Attheendof2007,therewere28never
eventsestablIshedbytheNatIonalQualItyForum.|any,butnotalloftheseeventsare
relevanttoanesthesIacare.ThelIstofnevereventsIsperIodIcallyupdated.
f
Professional Liability
ThIssectIonaddressesthebasIcconceptsofmedIcallIabIlIty.AmoredetaIleddIscussIonof
thestepsofthelawsuItprocessandapproprIateactIonsforphysIcIanstotakewhensuedIs
avaIlablefromtheASA.
g
The Tort System
AlthoughphysIcIansmaybecomeInvolvedInthecrImInallawsystemInaprofessIonal
capacIty,theymorecommonlybecomeInvolvedInthelegalsystemofcIvIllaws.CIvIllaw
IsbroadlydIvIdedIntocontract lawandtort law.AtortmaybelooselydefInedasacIvIl
wrongdoIng;neglIgenceIsonetypeoftort.MalpracticeactuallyreferstoanyprofessIonal
mIsconductbutItsuseInlegaltermstypIcallyreferstoprofessIonalneglIgence.
TobesuccessfulInamalpractIcesuIt,thepatIentplaIntIffmustprovefourthIngs:
1. 0uty:thattheanesthesIologIstowedthepatIentaduty;
2. 8reachofduty:thattheanesthesIologIstfaIledtofulfIllhIsorherduty;
J. CausatIon:thatareasonablyclosecausalrelatIonexIstsbetweentheanesthesIologIst's
actsandtheresultantInjury;and
4. 0amages:thatactualdamageresultedbecauseofabreachofthestandardofcare.
FaIluretoproveanyoneofthesefourelementswIllresultInadecIsIonforthedefendant
anesthesIologIst.
Duty
AsaphysIcIan,theanesthesIologIstestablIshesadutytothepatIentwhenadoctorpatIent
relatIonshIpexIsts.WhenthepatIentIsseenpreoperatIvely,andtheanesthesIologIst
agreestoprovIdeanesthesIacareforthepatIent,adutytothepatIenthasbeen
establIshed.nthemostgeneralterms,thedutytheanesthesIologIstowestothepatIentIs
toadheretothestandard of careforthetreatmentofthepatIent.8ecauseItIsvIrtually
ImpossIbletodelIneatespecIfIcstandardsforallaspectsofmedIcalpractIceandall
eventualItIes,thecourtshavecreatedtheconceptofthereasonable and prudent
physIcIan.ForallspecIaltIes,thereIsanatIonalstandardthathasdIsplacedthelocal
standard.
TherearecertaIngeneraldutIesthatallphysIcIanshavetotheIrpatIents,andbreachIng
thesedutIesmayalsoserveasthebasIsforalawsuIt.DneofthesegeneraldutIesIsthatof
obtaInIngInformedconsentforaprocedure.ConsentmaybewrItten,verbal,orImplIed.
DralconsentIsjustasvalId,albeIthardertoproveyearsafterthefact,aswrIttenconsent.
mplIedconsentforanesthesIacaremaybepresentIncIrcumstancesInwhIchthepatIent
IsunconscIousorunable,foranyreason,togIvehIsorherconsent,butwhereItIs
presumedthatanyreasonableandprudentpatIentwouldgIveconsent.
AlthoughthereareexceptIonstotherequIrementthatconsentbeobtaIned,
anesthesIologIstsshouldbesuretoobtaInconsentwheneverpossIble.FaIluretodoso
could,Intheory,exposetheanesthesIologIsttopossIbleprosecutIonforbattery.
TherequIrementthattheconsentbeinformedIssomewhatmoreopaque.TheguIdelIneIs
determInIngwhetherthepatIentreceIvedafaIrandreasonableaccountoftheproposed
proceduresandtherIsksInherentIntheseprocedures.|oststates
P.89
haveadoptedareasonablepatIentstandard,whIchrequIresthatthephysIcIandIsclose
rIsksthatareasonablepatIentundersImIlarcIrcumstanceswouldwanttoknowtomakean
InformeddecIsIon.8esIdesdIsclosureofcommonrIsks,rIsksthatwouldbeImportantIn
decIdIngwhetherornottoundertaketheproposedtherapyshouldalsobedIscussed.For
regIonalanesthesIa,theseshouldIncludeboththecommonrIsks(e.g.,local
paIn/dIscomfort,InfectIon,headache,transIentneuropathy),aswellasthosethatare
rare,butofmajorconsequence(e.g.,seIzure,cardIacarrest,permanentneuropathy,
paralysIs,anddeath).
Breach of Duty
namalpractIceactIon,expertwItnesseswIllrevIewthemedIcalrecordsofthecaseand
determInewhethertheanesthesIologIstactedInareasonableandprudentmannerInthe
specIfIcsItuatIonandfulfIlledhIsorherdutytothepatIent.ftheyfIndthatthe
anesthesIologIsteItherdIdsomethIngthatshouldnothavebeendone,orfaIledtodo
somethIngthatshouldhavebeendone,thenthedutytoadheretothestandardofcarehas
beenbreached.Therefore,thesecondrequIrementforasuccessfulsuItwIllhavebeen
met.
Causation
JudgesandjurIesareInterestedIndetermInIngwhetherthebreachofdutywasthe
proximate causeoftheInjury.ftheoddsarebetterthaneventhatthebreachofdutyled,
howevercIrcuItously,totheInjury,thIsrequIrementIsmet.
TherearetwocommontestsemployedtoestablIshcausatIon.ThefIrstIsthebut fortest,
andthesecondIsthesubstantial factortest.ftheInjurywouldnothaveoccurredbutfor
theactIonofthedefendantanesthesIologIst,orIftheactoftheanesthesIologIstwasa
substantIalfactorIntheInjurydespIteothercauses,thenproxImatecauseIsestablIshed.
AlthoughtheburdenofproofofcausatIonordInarIlyfallsonthepatIentplaIntIff,Itmay,
underspecIalcIrcumstances,beshIftedtothephysIcIandefendantunderthedoctrIneof
res ipsa loquitur(lIterally,thethIngspeaksforItself).ApplyIngthIsdoctrInerequIres
provIngthat:
1. theInjuryIsofakIndthattypIcallywouldnotoccurIntheabsenceofneglIgence,
2. theInjurymustbecausedbysomethIngundertheexclusIvecontrolofthe
anesthesIologIst,
J. theInjurymustnotbeattrIbutabletoanycontrIbutIononthepartofthepatIent,and
4. theevIdencefortheexplanatIonofeventsmustbemoreaccessIbletothe
anesthesIologIstthantothepatIent.
8ecauseanesthesIologIstsrenderpatIentsInsensIbletotheIrsurroundIngsandunableto
protectthemselvesfromInjury,thedoctrIneofres ipsa loquiturmaybeInvokedIn
anesthesIamalpractIcecases.WhIlethIsargumentwascommonlyusedInthepastIn
lawsuItsfornerveInjurIes,ItIslesscommonlyusedsuccessfullytoday.
Damages
ThelawallowsforthreedIfferenttypesofdamages.General damagesarethosesuchas
paInandsufferIngthatdIrectlyresultfromtheInjury.Special damagesarethoseactual
damagesthatareaconsequenceoftheInjury,suchasmedIcalexpenses,lostIncome,and
funeralexpenses.Punitive damagesareIntendedtopunIshthephysIcIanforneglIgence
thatwasreckless,wanton,fraudulent,orwIllful.PunItIvedamagesareexceedInglyrareIn
medIcalmalpractIcecases.|orelIkelyInthecaseofgrossneglIgenceIsalossofthe
lIcensetopractIceanesthesIa.nextremecases,crImInalchargesmaybebroughtagaInst
thephysIcIan,althoughthIsIsrare.0etermInatIonofthedollaramountIsusuallybasedon
someassessmentoftheplaIntIff'scondItIonversusthecondItIonheorshewouldhavebeen
InhadtherebeennoneglIgence.PlaIntIffs'attorneysgenerallychargeapercentageofthe
damagesandwIll,therefore,seektomaxImIzetheawardgIven.
Standard of Care
8ecausemedIcalmalpractIceusuallyInvolvesIssuesbeyondthecomprehensIonoflay
jurorsandjudges,thecourtestablIshesthestandardofcareInapartIcularcasebythe
testImonyofexpert witnesses.ThesewItnessesdIfferfromfactualwItnessesmaInlyInthat
theymaygIveopInIons.ThetrIalcourtjudgehassoledIscretIonIndetermInIngwhethera
wItnessmaybequalIfIedasanexpert.AlthoughanylIcensedphysIcIanmaybeanexpert,
InformatIonwIllbesoughtregardIngthewItness'seducatIonandtraInIng,thenatureand
scopeoftheperson'spractIce,membershIpsandaffIlIatIons,andpublIcatIons.Thepurpose
IngatherIngthIsInformatIonIsnotonlytoestablIshthequalIfIcatIonsofthewItnessto
provIdeexperttestImony,butalsotodetermInetheweIghttobegIventothattestImony
bythejury.nmanycasesthesuccessofalawsuItdependsprImarIlyonthestatureand
belIevabIlItyoftheexpertwItnesses.
Unfortunately,thereIsatendencyforexpertstolInksevereInjurywIthInapproprIatecare
(I.e.,abIasthatbadoutcomesmeanbadcare).ToInvestIgatetheInfluenceofthe
severItyoftheInjuryontheassessmentofstandardofcare,agroupof112practIcIng
anesthesIologIstsjudgedapproprIatenessofcareIn21casesInvolvIngadverseanesthetIc
outcomes.
40
TheorIgInaloutcomeIneachcasewaseIthertemporaryorpermanent.For
eachorIgInalcase,amatchIngalternatecasewascreatedthatwasIdentIcaltothe
orIgInalIneveryrespect,exceptthataplausIbleoutcomeoftheopposIteseverItywas
substItuted.FevIewersjudgedthestandardofcareIneachcase.KnowledgeoftheseverIty
ofInjuryproducedasIgnIfIcantInverseeffectonthejudgmentofapproprIatenessofcare
(FIg.41).
40
TheproportIonofratIngsforapproprIatecaredecreasedwhentheoutcome
waschangedfromtemporarytopermanent,andIncreasedwhentheoutcomewaschanged
frompermanenttotemporary.TheseresultssuggestthatoutcomebIasIntheassessment
ofstandardofcaremaycontrIbutetothefrequencyandsIzeofpayments.
Figure 4-1.EffectofoutcomeonphysIcIanjudgmentsofapproprIatenessofcare.
(AdaptedfromCaplanetal.EffectofoutcomeonphysIcIanjudgementsof
approprIatenessofcare.JA|A1991;265:19571960.)
P.90
ncertaIncIrcumstances,thestandardofcaremayalsobedetermInedfrompublIshed
socIetalguIdelInes,wrIttenpolIcIesofahospItalordepartment,ortextbooksand
monographs.SomemedIcalspecIaltysocIetIeshavecarefullyavoIdedapplyIngtheterm
standardstotheIrguIdelInesInthehopethatnobIndIngbehavIorormandatorypractIces
havebeencreated.TheessentIaldIfferencebetweenstandardsandguIdelInesIsthat
guIdelInesshouldbeadheredtoandstandardsmustbeadheredto.TheASApublIshes
standardsandguIdelInesforavarIetyofanesthesIarelatedactIvItIes.
Causes of Anesthesia-Related Lawsuits
FelatIvelyfewadverseoutcomesendupInamalpractIcesuIt.thasbeenestImatedthat
lessthan1of25patIentInjurIesresultInmalpractIcelItIgatIon.
41
TheASACommItteeon
ProfessIonalLIabIlItyhasconductedanatIonwIdeanalysIsofmalpractIceclaImsagaInst
anesthesIologIsts,excludIngdentaldamage,sInce1985(I.e.,theClosed Claims
Project).
42,4J
TheleadIngInjurIesInmalpractIceclaImsInthe1990sweredeath(24),
nervedamage(22),permanentbraIndamage(8),andaIrwayInjury(7;FIg.42).The
causesofdeathandpermanentbraIndamagewerepredomInantlyproblemsInaIrway
management(e.g.,InadequateventIlatIon,dIffIcultIntubatIon,prematureextubatIon)and
othercomplIcatIonssuchaspulmonaryembolIsm,InadequatefluIdtherapy,stroke,
hemorrhage,andmyocardIalInfarctIon.
44
Nervedamage,especIallytotheulnarnerve,
oftenoccursdespIteapparentlyadequateposItIonIng.
14,16
SpInalcordInjurywasthemost
commoncauseofnervedamageclaImsagaInstanesthesIologIstsInthe1990s.
14
ChronIc
paInmanagementIsanIncreasIngsourceofmalpractIceclaImsagaInstanesthesIologIsts.
45
TheanesthesIologIstIslIkelytobethetargetofalawsuItIfanuntowardoutcomeoccurs
becausethephysIcIanpatIentrelatIonshIpIsusuallytenuousatbest.ThepatIentrarely
choosestheanesthesIologIst,thepreoperatIvevIsItIsbrIef,andtheanesthesIologIstwho
seesthepatIentpreoperatIvelymaynotactuallyanesthetIzethepatIent.CommunIcatIon
betweenanesthesIologIstsandsurgeonsaboutcomplIcatIonsIsoftenlackIngandthe
tendencyIsforthesurgeontoblameanesthesIa.naddItIon,anesthesIologIstsareoften
suedalongwIththesurgeonInthecaseofanadverseoutcome.ThIsmayoccurevenIfthe
outcomewasInnowayrelatedtotheanesthetIccare.
Figure 4-2.|ostcommonInjurIesleadIngtoanesthesIamalpractIceclaIms.Dther
categoryIncludesJeachfornewbornInjury,pneumothorax,myocardIalInfarctIon,
stroke,burns,headache,andbackpaIn;and1.5forawareness/recall.0amageto
teethanddenturesexcluded.AmerIcanSocIetyofAnesthesIologIsts'ClosedClaIms
Project(N=7,J28).
What to Do When Sued
AlawsuItbegInswhenthepatIentplaIntIff'sattorneyfIlesacomplaintanddemandforjury
trIalwIththecourt.TheanesthesIologIstIsthenservedwIththecomplaIntandasummons
requIrIngananswertothecomplaInt.UntIlthIshappens,nolawsuIthasbeenfIled.
nsurancecarrIersmustbenotIfIedImmedIatelyafterthereceIptofthecomplaInt.The
anesthesIologIstwIllneedassIstanceInanswerIngthecomplaInt,andthereIsatImelImIt
placedontheresponse.
SpecIfIcactIonsatthIspoIntIncludethefollowIng:
1. 0onotdIscussthecasewIthanyone,IncludIngcolleagueswhomayhavebeenInvolved,
operatIngroompersonnel,orfrIends.
2. Neveralteranyrecords.
J. CathertogetherallpertInentrecords,IncludIngacopyoftheanesthetIcrecord,bIllIng
statements,andcorrespondenceconcernIngthecase.
4. |akenotesrecordIngalleventsrecalledaboutthecase.
5. CooperatefullywIththeattorneyprovIdedbytheInsurer.
ThefIrsttasktheanesthesIologIstmustperformwIthanattorneyIstoprepareananswer
tothecomplaInt.ThecomplaIntcontaInscertaInfactsandallegatIonswIthwhIchthe
defensemayeItheragreeordIsagree.0efenseattorneysrelyonthefrankandtotally
candIdobservatIonsofthephysIcIanInpreparIngananswertothecomplaInt.PhysIcIans
shouldbewIllIngtoeducatetheIrattorneysaboutthemedIcalfactsofthecase,although
mostmedIcalmalpractIceattorneyswIllbeknowledgeableandmedIcallysophIstIcated.
ThenextphaseofthemalpractIcesuItIscalleddiscovery.ThepurposeofdIscoveryIsthe
gatherIngoffactsandclarIfIcatIonofIssuesInadvanceofthetrIal.nalllIkelIhoodthe
anesthesIologIstwIllInItIallyreceIveawrIttenInterrogatory,whIchwIllrequestfactual
InformatIon.nconsultatIonwIththedefenseattorney,theInterrogatoryshouldbe
answeredInwrItIngbecausecarelesslyorInadvertentlymIsstatedfactscanbecome
troublesomelater.
0eposItIonsareasecondmechanIsmofdIscovery.ThedefendantanesthesIologIstwIllbe
deposedasafactwItness,anddeposItIonswIllbeobtaInedfromotheranesthesIologIsts
whowIllactasexpertwItnesses.AnatIonallyrecognIzedexpertIntheareaInquestIon,
recommendedbythedefendantbutwhoIsnotapersonalfrIend,andwhoagreeswIththe
defenseposItIon,maybeveryvaluable.
TheplaIntIff'sattorney,notthedefenseattorney,wIlldeposetheanesthesIologIst.0espIte
theapparentInformalItyofthedeposItIon,theanesthesIologIstmustbeconstantlyaware
thatwhatIssaIddurIngthedeposItIoncarrIesasmuchweIghtaswhatwouldbesaIdIn
court.tIsImportanttobefactuallypreparedforthedeposItIonbyrevIewofpersonal
notes,theanesthetIcrecord,andthemedIcalrecord.ThephysIcIanshoulddress
conservatIvelyandprofessIonallybecauseappearanceandImageareveryImportant.The
opposItIonIsassessIngthephysIcIantoseehowheorshewIllappeartoajury.Answeronly
thequestIonasked,anddonotvolunteerInformatIon.Felyonone'sattorneyforassIstance
whenpreparIngforadeposItIon.
TherewIllbedeposItIonsfromexpertwItnesses,bothfortheplaIntIffandforthedefense.
TheanesthesIologIstshouldworkwIthhIsorherattorneytosuggestquestIonsand
rebuttals.ThebettereducatedtheattorneyIsaboutthemedIcalfacts,thereasonsthe
anesthesIologIstdIdwhatwasdone,and
P.91
thealternatIveapproaches,thebetterabletheattorneywIllbetoconducttheseexpert
deposItIons.
fthereIssomemerItInthecasebutthedamagesaremInImal,orIfproofofInnocence
wIllbedIffIcult,therewIllprobablybeasettlementoffer.ThereIsahIghcostIncurredby
bothplaIntIffsanddefendantsInpursuIngamalpractIceclaImupthroughajurytrIal.
UnlessthereIsastrongprobabIlItyofalargedollaraward,reputableplaIntIffs'attorneys
arenotlIkelytopursuetheclaIm.Thus,evenIfphysIcIansbelIevethattheyaretotally
InnocentofanywrongdoIng,theyshouldnotbeoffendedorangeredaboutsettlIngofthe
case:thIsIssolelyamatterofmoney,notmedIcIne.
fasettlementIsnotreacheddurIngthedIscoveryphase,atrIalwIlloccur.Dnlyabout1In
20malpractIcecaseseverreachthepoIntofajurytrIal.DnlythosecasesInwhIchboth
sIdesthInktheycanwIn,andwhIcharelIkelytohavesIgnIfIcantfInancIalImpact,wIll
proceedtotrIal.
ThedIscussIonofdeposItIontestImonyalsoapplIestotestImonyIncourt,buttherearea
fewaddItIonalpoIntstoconsIderdurIngthetrIal.ThemembersofthejurywIllnotbeas
sophIstIcatedmedIcallyastheattorneyswhodeposedtheanesthesIologIstdurIng
dIscovery.However,donotunderestImatetheIntellIgenceofthejury.TalkIngdownto
themwIllcreateanunfavorableImpressIon.ftheanswertoaquestIonIsnotknown,
avoIdguessIng.fspecIfIcfactscannotberemembered,sayso.Nobodyexpectstotalrecall
ofeventsthatmayhaveoccurredyearsbefore.
ThedefendantphysIcIanshouldbepresentdurIngtheentIretrIal,evenwhennot
testIfyIng,andshoulddressprofessIonally.0Isplaysofanger,remorse,relIef,orhostIlIty
wIllhurtthephysIcIanIncourt.ThephysIcIanshouldbeabletogIvehIsorhertestImony
wIthoutusIngnotesordocuments.WhenItIsnecessarytorefertothemedIcalrecord,It
wIllbeadmIttedIntoevIdence.TheanesthesIologIst'sgoalIstoconvIncethejurythathe
orshebehavedInthIscaseasanyothercompetentandprudentanesthesIologIstwould
havebehaved.
tIsImportanttokeepInmIndthatproofInamalpractIcecasemeansonlymorelIkely
thannot.ThepatIentplaIntIffmustprovethefourelementsofneglIgence,notto
absolutecertaInty,butonlytoaprobabIlItygreaterthan50.DntheposItIvesIde,thIs
meansthatthedefendantanesthesIologIstmustonlyshowthathIsorheractIonswere,
morelIkelythannot,wIthInanacceptablestandardofcare.
Acknowledgments
TheauthorswIshtothankF.W.Cheney,|0,and0.A.Kroll,|0,whosematerIalfrom
prevIousedItIonsofthIschapterhasbeenretaInedInthecurrentedItIon.Theauthorsalso
thankCenePeterson,|0,Ph0forhIshelpfulsuggestIonsonthIsrevIsIon.
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TableofContentsSectIonScIentIfIcFoundatIonsofAnesthesIaChapter5|echanIsmsofAnesthesIaand
ConscIousness
Chapter5
Mechanisms of Anesthesia and Consciousness
Alex S. Evers
C. Michael Crowder
Key Points
1. The components of the anesthetic state include unconsciousness,
amnesia, analgesia, immobility, and attenuation of autonomic
responses to noxious stimulation.
2. Minimum alveolar concentration (MAC) remains the most robust
measurement and the standard for determining the potency of
volatile anesthetics.
3. Anesthetic actions on the spinal cord cannot produce either amnesia
or unconsciousness. However, several lines of evidence indicate that
the spinal cord is probably the site at which anesthetics act to inhibit
purposeful responses to noxious stimulation.
4. A developing body of evidence indicates that inhalational anesthetics
can depress the excitability of thalamic neurons, thus blocking
thalamocortical communication and potentially resulting in loss of
consciousness.
5. Whereas certain anesthetic effects may be attributable to specific
anatomic locations (e.g., purposeful response to noxious stimulation
maps to the spinal cord), existing evidence provides no basis for a
single anatomic site responsible for anesthesia.
6. While current data still support the prevailing view that neuronal
excitability is only slightly affected by general anesthetics, this small
effect may nevertheless contribute significantly to the clinical actions
of volatile anesthetics.
7. The synapse is generally thought to be the most likely relevant site
of anesthetic action. Existing evidence indicates that even at this one
site, anesthetics produce various effects, including presynaptic
inhibition of neurotransmitter release, inhibition of excitatory
neurotransmitter effect, and enhancement of inhibitory
neurotransmitter effect. Furthermore, the effects of anesthetics on
synaptic function differ among various anesthetic agents,
neurotransmitters, and neuronal preparations.
8. Existing evidence suggests that most voltage-dependent calcium
channels (VDCCs) are modestly sensitive or insensitive to
anesthetics. However, some sodium channels subtypes are inhibited
by volatile anesthetics and this effect may be responsible in part for a
reduction in neurotransmitter release at some synapses.
9. A large body of evidence shows that clinical concentrations of many
anesthetics potentiate GABA-activated currents in the central
nervous system. Other members of the ligand-activated ion channel
family, including glycine receptors, neuronal nicotinic receptors, and
5-HT
3
receptors, are also affected by clinical concentrations of
anesthetics and remain plausible anesthetic targets.
10. Activation of background K
+
channels in mammalian vertebrates
could be an important and general mechanism through which
inhalational and gaseous anesthetics regulate neuronal resting
membrane potential and thereby excitability.
11. Direct interactions of anesthetic molecules with proteins would not
only satisfy the Meyer-Overton rule, but would also provide the
simplest explanation for compounds that deviate from this rule.
12. Current evidence strongly indicates protein rather than lipid as the
molecular target for anesthetic action.
P.96
14. All anesthetic actions cannot be localized to a specific anatomic site in
the central nervous system; indeed, some evidence suggests that
different components of the anesthetic state may be mediated by
actions at disparate anatomic sites.
15. At a molecular level, volatile anesthetics show some selectivity, but
still affect the function of multiple ion channels and synaptic proteins.
The intravenous anesthetics, etomidate, propofol, and barbiturates,
are more specific with the GABA
A
receptor as their major target.
TheIntroductIonofgeneralanesthetIcsIntoclInIcalpractIceover150yearsagostandsas
oneofthesemInalInnovatIonsofmedIcIne.ThIssIngledIscoveryfacIlItatedthe
developmentofmodernsurgeryandspawnedthespecIaltyofanesthesIology.0espItethe
ImportanceofgeneralanesthetIcsanddespItemorethan100yearsofactIveresearch,the
molecularmechanIsmsresponsIbleforanesthetIcactIonremaInoneoftheunsolved
mysterIesofpharmacology.
WhyhavemechanIsmsofanesthesIabeensodIffIculttoelucIdate:AnesthetIcs,asaclass
ofdrugs,arechallengIngtostudyforthreemajorreasons:
1. AnesthesIa,bydefInItIon,IsachangeIntheresponsesofanintact animaltoexternal
stImulI.|akIngadefInItIvelInkbetweenanesthetIceffectsobservedInvItroandthe
anesthetIcstateobservedanddefInedin vivohasprovendIffIcult.
2. NostructureactIvItyrelatIonshIpsareapparentamonganesthetIcs;awIdevarIetyof
structurallyunrelatedcompounds,rangIngfromsteroIdstoelementalxenon,arecapable
ofproducIngclInIcalanesthesIa.ThIssuggeststhattherearemultIplemolecular
mechanIsmsthatcanproduceclInIcalanesthesIa.
J. AnesthetIcsworkatveryhIghconcentratIonsIncomparIsontodrugs,neurotransmItters,
andhormonesthatactatspecIfIcreceptors.ThIsImplIesthatIfanesthetIcsdoactby
bIndIngtospecIfIcreceptorsItes,theymustbIndwIthverylowaffInItyandprobablystay
boundtothereceptorforveryshortperIodsoftIme.LowaffInItybIndIngIsmuchmore
dIffIculttoobserveandcharacterIzethanhIghaffInItybIndIng.
0espItethesedIffIcultIes,molecularandgenetIctoolsarenowavaIlablethatshouldallow
formajorInsIghtsIntoanesthetIcmechanIsmsInthenextdecade.TheaImofthIschapter
IstoprovIdeaconceptualframeworkforthereadertocatalogcurrentknowledgeand
IntegratefuturedevelopmentsaboutmechanIsmsofanesthesIa.FIvespecIfIcquestIonswIll
beaddressedInthIschapter:
1. WhatIsanesthesIaandhowdowemeasureIt:
2. WhatIstheanatomIcsIteofanesthetIcactIonInthecentralnervoussystem:
J. WhatarethecellularneurophysIologIcmechanIsmsofanesthesIa(e.g.,effectson
synaptIcfunctIonvs.effectsonactIonpotentIalgeneratIon)andwhatanesthetIceffects
onIonchannelsandotherneuronalproteInsunderlIethesemechanIsms:
4. WhatarethemoleculartargetsofanesthetIcs:
5. HowarethemolecularandcellulareffectsofanesthetIcslInkedtothebehavIoraleffects
ofanesthetIcsobservedInvIvo:
What is Anesthesia?
CeneralanesthesIacanbroadlybedefInedasadrugInducedreversIbledepressIonofthe
centralnervoussystem(CNS)resultIngInthelossofresponsetoandperceptIonofall
externalstImulI.Unfortunately,suchabroaddefInItIonIsInadequatefortworeasons.
FIrst,thedefInItIonIsnotactuallybroadenough.AnesthesIaIsnotsImplyadeafferented
state;amnesIaandunconscIousnessareImportantaspectsoftheanesthetIcstate.Second,
thedefInItIonIstoobroad,asallgeneralanesthetIcsdonotproduceequaldepressIonofall
sensorymodalItIes.Forexample,barbIturatesareconsIderedtobeanesthetIcs,butthey
arenotpartIcularlyeffectIveanalgesIcs.TheseconflIctIngproblemswIthdefInItIoncanbe
bypassedbyamorepractIcaldescrIptIonoftheanesthetIcstateasacollectIonof
componentchangesInbehavIororperceptIon.ThecomponentsoftheanesthetIcstate
IncludeunconscIousness,amnesIa,analgesIa,ImmobIlIty,andattenuatIonofautonomIc
responsestonoxIousstImulatIon.
FegardlessofwhIchdefInItIonofanesthesIaIsused,essentIaltoanesthesIaarerapIdand
reversIbledrugInducedchangesInbehavIororperceptIon.Assuch,anesthesIacanonlybe
defInedandmeasuredIntheIntactorganIsm.ChangesInbehavIorsuchasunconscIousness
oramnesIacanbeIntuItIvelyunderstoodInhIgherorganIsmssuchasmammals,but
becomeIncreasInglydIffIculttodefIneasonedescendsthephylogenetIctree.Thus,whIle
anesthetIcshaveeffectsonorganIsmsrangIngfromwormstoman,ItIsdIffIculttomap
wIthcertaIntytheeffectsofanesthetIcsobservedInlowerorganIsmstoanyofour
behavIoraldefInItIonsofanesthesIa.ThIscontrIbutestothedIffIcultyofusIngsImple
organIsmsasmodelsInwhIchtostudythemolecularmechanIsmsofanesthesIa.SImIlarly,
anycellularormoleculareffectsofanesthetIcsobservedInhIgherorganIsmscanbe
extremelydIffIculttolInkwIththeconstellatIonofbehavIorsthatconstItutethe
anesthetIcstate.TheabsenceofasImpleandconcIsedefInItIonofanesthesIaIsclearly
oneofthestumblIngblockstoelucIdatIngthemechanIsmsofanesthesIaatamolecular
andcellularlevel.
AnaddItIonaldIffIcultyIndefInInganesthesIaIsthatourunderstandIngofthemechanIsms
ofconscIousnessIsratheramorphousatpresent.DnecannoteasIlydefIneanesthesIawhen
theneurobIologIcalphenomenaablatedbyanesthesIaarenotwellunderstood.
Nevertheless,recentadvancesInthestudyofsleepandattentIonhaveIdentIfIedwhat
mayformtheanatomIcandneurophysIologIcalbasIsforsleepandperhapsotherformsof
unconscIousness.
1
CentraltothemechanIsmofsleepIsasetofhypothalamIcnucleIthat
appeartoformanawake/sleepswItchmechanIsm(FIg.51).TheventrolateralpreoptIc
nucleus(7LPD)IntheanterIorhypothalamuspromotessleepwhIlethetuberomammIllary
nucleus(T|N)IntheposterIorhypothalamuspromoteswakefulness.mportantly,the7LPD
andtheT|NaremutuallyInhIbItory.Thus.forexample,IfbyInfluenceofother
modulatorysleeppromotIngnucleItheactIvItyofthe7LPDgaInsgroundrelatIvetothe
T|N,the7LPDwIllultImatelyshutdowntheoutputoftheT|NandsleepwIllbefavored.
DntheotherhanddurIngwakefulness,theT|NIsdomInantandsIlencesthe7LPD.
|odulatoryInfluencesontheT|Nand7LPDIncludeorexInergIcneuronsInthelateral
hypothalamus,thecIrcadIanclock,whIchIsdIrectlymodulatedbylIghtandcontaIned
wIthInthehypothalamIcsuprachIasmatIcnucleus,andmultIplebraInstemnucleI,In
partIcularthelocuscoeruleusanddorsalraphe.ThesebraInstemnucleIasawhole
promotearousalandareapartoftheretIcularactIvatIngformatIon.naddItIonto
synaptIcmodulators,adenosInehasbeenproposedasaneurohumoralfactorthatpromotes
sleepbydIsInhIbItIngthe7LPD.TheT|Nandthe7LPDarethoughttopromotetheawake
orsleepstatebyactIngonthalamIcandcortIcalcIrcuIts,eItherdIrectlyorthroughthe
retIcularactIvatIngformatIon.ThethalamusandcortexmaIntaInwakefulnessand
conscIousnessthroughcomplexInteractIonsthatmayInvolve
P.97
IntrInsIcoscIllatorsandwIdespreadsynaptIccommunIcatIon.AwarenessandconscIousness
IsthoughttoemergefromcommunIcatIonbetweentheprefrontalcortexandmultIple
cortIcalandsubcortIcalareasthathavedIstrIbutedrepresentatIonsofaperceptIon.AgaIn,
theprecIsemechanIsmsoftheemergentpropertIesofconscIousnessareunclear.As
dIscussedlater,somerecentevIdenceImplIcatescomponentsofthesleepswItchas
anatomIctargetsofcertaIngeneralanesthetIcs.
Figure 5-1.SImplIfIedsleep/wakecontrolcIrcuIt.Thewake/sleepswItchIscomposed
ofthemutuallyInhIbItoryventrolateralpreoptIcnucleus(7LPD)andthe
tuberomammIllarynucleus(T|N)hypothalamIcneurons.ThedIrectIonofthIsswItchIs
InfluencedbyhumoralfactorssuchasadenosIne,thecIrcadIanclock,other
hypothalamIcneuronsreleasIngorexIn(notshown),andbraInstemarousalnucleIsuch
asthedorsalraphe(0F)andthelocuscoeruleus(LC).8oththewake/sleepswItchand
thebraInstemarousalsystemactonhIgherordercIrcuItsInthethalamusandcerebral
cortex.CeneralanesthetIcsappeartoactonmultIplecomponentsofthesleep/wake
controlsystem.5HT,5hydroxytryptamIne/serotonIn;Cal,galanIn;NE,
norepInephrIne;HIs,hIstamIne;CA8A,amInobutyrIcacId.
How is Anesthesia Measured?
nordertostudythepharmacologyofanesthetIcactIon,quantItatIvemeasurementsof
anesthetIcpotencyareabsolutelyessentIal.TothIsend,Quashaandcolleagues
2
have
defInedtheconceptof|AC,ormInImumalveolarconcentratIon.|ACIsdefInedasthe
alveolarpartIalpressureofagasatwhIch50ofhumansdonotrespondtoasurgIcal
IncIsIon.nanImals,|ACIsdefInedasthealveolarpartIalpressureofagasatwhIch50of
anImalsdonotrespondtoanoxIousstImulus,suchastaIlclamp,
J
oratwhIchtheylose
theIrrIghtIngreflex.Theuseof|ACasameasureofanesthetIcpotencyhastwomajor
advantages.FIrst,ItIsanextremelyreproducIblemeasurementthatIsremarkably
constantoverawIderangeofspecIes.
2
Second,theuseofendtIdalgasconcentratIon
provIdesanIndexofthefreeconcentratIonofdrugrequIredtoproduceanesthesIasInce
theendtIdalgasconcentratIonIsInequIlIbrIumwIththefreeconcentratIonInplasma.
The|ACconcepthasseveralImportantlImItatIons,partIcularlywhentryIngtorelate|AC
valuestoanesthetIcpotencyobservedInvItro.FIrst,theendpoIntIna|ACdetermInatIon
Isquantal:asubjectIseItheranesthetIzedorunanesthetIzed;ItcannotbepartIally
anesthetIzed.Furthermore,|ACrepresentstheaverageresponseofawholepopulatIonof
subjectsratherthantheresponseofasInglesubject.Thequantalnatureofthe|AC
measurementmakesItverydIffIculttocompare|ACmeasurementstoconcentratIon
responsecurvesobtaInedInvItro,wherethegradedresponseofasInglepreparatIonIs
measuredasafunctIonofanesthetIcconcentratIon.ThesecondlImItatIonof|AC
measurementsIsthattheycanonlybedIrectlyapplIedtoanesthetIcgases.Parenteral
anesthetIcs(barbIturates,neurosteroIds,propofol)cannotbeassIgneda|ACvalue,makIng
ItdIffIculttocomparethepotencyofparenteralandvolatIleanesthetIcs.A|AC
equIvalentforparentalanesthetIcsIsthefreeconcentratIonofthedrugInplasmarequIred
topreventresponsetoanoxIousstImulusIn50ofsubjects;thIsvaluehasbeenestImated
forseveralparenteralanesthetIcs.
4
AthIrdlImItatIonof|ACIsthatItIshIghlydependent
ontheanesthetIcendpoIntusedtodefIneIt.Forexample,Iflossofresponsetoaverbal
commandIsusedasananesthetIcendpoInt,the|ACvaluesobtaIned(|AC
awake
)wIllbe
muchlowerthanclassIc|ACvaluesbasedonresponsetoanoxIousstImulus.ndeed,each
behavIoralcomponentoftheanesthetIcstatewIlllIkelyhaveadIfferent|ACvalue.
0espIteItslImItatIons,|ACremaInsthemostrobustmeasurementandthestandardfor
determInIngthepotencyofvolatIleanesthetIcs.
8ecauseofthelImItatIonsof|AC,monItorsthatmeasuresomecorrelateofanesthetIc
depthhavebeenIntroducedIntoclInIcalpractIce.
5
ThemostpopularofthesemonItors
convertsspontaneouselectroencephalogramwaveformsIntoasInglevaluethatcorrelates
wIthanesthetIcdepthforsomegeneralanesthetIcs.AnesthetIcdepthmonItorshavegreat
potentIal.TheymayreducetheIncIdenceofawarenessdurInganesthesIa,whIchIs
estImatedtobeapproxImately0.1to0.2.
6
Theymayalsoreducetheamountof
anesthetIcusedandmayhastenemergenceandrecoveryroomdIscharge.However,atthIs
tImewhetheranyoftheavaIlableanesthetIcdepthmonItorsIssuperIorto|AC,to
standardIzeddosIngofIntravenousanesthetIcs,ortoclInIcalIndIcatorsofanesthetIcdepth
IscontroversIalandIsstIllanactIveareaofInvestIgatIon.
Where in the Central Nervous System do Anesthetics Work?
nprIncIple,generalanesthesIacouldresultfromInterruptIonofnervoussystemactIvItyat
myrIadlevels.PlausIbletargetsIncludeperIpheralsensoryreceptors,spInalcord,
braInstem,andcerebralcortex.DfthesepotentIalsItes,onlyperIpheralsensoryreceptors
canbeelImInatedasanImportantsIteofanesthetIcactIon.AnImalstudIeshaveshown
thatfluorInatedvolatIleanesthetIcshavenoeffectoncutaneousmechanosensorsIncats
7
andcanevensensItIzenocIceptorsInmonkeys.
8
Furthermore,selectIveperfusIonstudIes
Indogshaveshownthat|ACforIsofluraneIsunaffectedbythepresenceorabsenceof
IsofluraneatthesIteofnoxIousstImulatIon,provIdedthattheCNSIsperfusedwIthblood
contaInIngIsoflurane.
9
Spinal Cord
Clearly,anesthetIcactIonsonthespInalcordcannotproduceeItheramnesIaor
unconscIousness.However,severallInesofevIdenceIndIcatethatthespInalcordIs
probablythesIteat
P.98
whIchanesthetIcsacttoInhIbItpurposefulresponsestonoxIousstImulatIon.ThIsIs,of
course,theendpoIntusedInmostmeasurementsofanesthetIcpotency.FampIland
colleagues
10,11
haveshownthat|ACvaluesforfluorInatedvolatIleanesthetIcsare
unaffectedIntheratbyeItherdecerebratIon
10
orcervIcalspInalcordtransectIon.
11
AntognInIandSchwartz
12
haveusedthestrategyofIsolatIngthecerebralcIrculatIonof
goatstoexplorethecontrIbutIonofbraInandspInalcordtothedetermInatIonof|AC.
TheyfoundthatwhenIsofluraneIsadmInIsteredonlytothebraIn,|ACIs2.9,whereas
whenItIsadmInIsteredtotheentIrebody,|ACIs1.2.SurprIsIngly,whenIsofluranewas
preferentIallyadmInIsteredtothebodyandnottothebraIn,Isoflurane|ACwasreduced
to0.8.
1J
TheactIonsofvolatIleanesthetIcsInthespInalcordaremedIated,atleastIn
part,bydIrecteffectsontheexcItabIlItyofspInalmotorneurons.ThIsconclusIonhasbeen
substantIatedbyexperImentsInrats,
14
goats,
15
andhumans
16
showIngthatvolatIle
anesthetIcsdepresstheamplItudeoftheFwaveInevokedpotentIalmeasurements(F
waveamplItudecorrelateswIthmotorneuronexcItabIlIty).TheseprovocatIveresults
suggestnotonlythatanesthetIcactIonatthespInalcordunderlIes|AC,butalsothat
anesthetIcactIononthebraInmayactuallysensItIzethecordtonoxIousstImulI.The
plausIbIlItyofthespInalcordasalocusforanesthetIcImmobIlIzatIonIsalsosupportedby
severalelectrophysIologIcalstudIesshowIngInhIbItIonofexcItatorysynaptIctransmIssIon
InthespInalcord.
17,18,19,20
Brainstem, Hypothalamic, and Thalamic Arousal Systems
TheretIcularactIvatIngsystem,adIffusecollectIonofbraInstemneuronsInvolvedIn
arousalbehavIor,haslongbeenspeculatedtobeasIteofgeneralanesthetIcactIonon
conscIousness.EvIdencetosupportthIsnotIoncamefromearlywholeanImalexperIments
showIngthatelectrIcalstImulatIonoftheretIcularactIvatIngsystemcouldInducearousal
behavIorInanesthetIzedanImals.
21
AroleforthebraInstemInanesthetIcactIonIsalso
supportedbystudIesexamInIngsomatosensoryevokedpotentIals.Cenerally,thesestudIes
showthatanesthetIcsproduceIncreasedlatencyanddecreasedamplItudeofcortIcal
potentIals,IndIcatIngthatanesthetIcsInhIbItInformatIontransferthroughthebraInstem.
22
ncontrast,studIesusIngbraInstemaudItoryevokedpotentIalshaveshownvarIableeffects
rangIngfromdepressIontoenhancementofInformatIontransferthroughtheretIcular
formatIon.
2J,24,25
WhIlethereIsevIdencethattheretIcularformatIonofthebraInstemIsa
locusforanesthetIceffects,ItcannotbetheonlyanatomIcsIteofanesthetIcactIonfor
tworeasons.FIrst,asdIscussed,thebraInstemIsnotevenrequIredforanesthetIcsto
InhIbItresponsIvenesstonoxIousstImulI.Second,theretIcularformatIoncanbelargely
ablatedwIthoutelImInatIngawareness.
26
WIthIntheretIcularformatIonIsasetofpontInenoradrenergIcneuronscalledthelocus
coeruleus.ThelocuscoeruleuswIdelyInnervatestargetsInthecortex,thalamus,and
hypothalamusIncludIngthesleeppromotIng7LPD.AsdIscussedprevIously,themutually
InhIbItory7LPDandT|Nmayformasleep/awakeswItchcIrcuIt.ThIsswItchwasdIrectly
ImplIcatedInanesthetIcactIonbyasetofelegantexperImentsfromNelsonetal.
27
They
showedthattheapplIcatIonofaCA8AergIcantagonIstdIrectlyontotheT|NdImInIshed
theeffIcacyoftheanesthetIcspropofolandpentobarbItal.ndeed,dIscreteapplIcatIonof
theCA8AergIcantagonIstgabazIneontotheT|NmarkedlyreducedtheduratIonof
sedatIonproducedbysystemIcallyadmInIsteredpropofolorpentobarbItal.ThIseffectIs
unlIkelytobeaconsequenceofanonspecIfIcIncreaseInarousalstatebecause
systemIcallyadmInIsteredgabazInedIdnotantagonIzethepotencyofketamInewhereasIt
dIdantagonIzepropofolandpentobarbItalInamannersImIlartoapplIcatIondIrectlyonto
theT|N.ThIsresultstronglyImplIcatesthe7LPD/T|NsleepswItchasasIteforthe
sedatIveactIonofCA8AergIcanesthetIcslIkepropofolandbarbIturates.However,general
anesthesIaIsclearlynotequIvalenttosleep.8ydefInItIon,onecannotbearousedfrom
generalanesthesIa.Thus,addItIonalneuroanatomIcallocIbesIdesthosemedIatIngsleep
arelIkelytobetargeted.DneareaofthebraInthathasbeenpostulatedasapotentIalsIte
ofanesthetIcactIonIsthethalamus.ThethalamusIsImportantInrelayIngsensory
modalItIesandmotorInformatIontothecortexvIathalamocortIcalpathways.A
developIngbodyofevIdenceIndIcatesthatInhalatIonalanesthetIcscandepressthe
excItabIlItyofthalamIcneurons,thusblockIngthalamocortIcalcommunIcatIonand
potentIallyresultIngInlossofconscIousness.
Cerebral Cortex
ThecerebralcortexIsthemajorsIteforIntegratIon,storage,andretrIevalofInformatIon.
Assuch,ItIsalIkelysIteatwhIchanesthetIcsmIghtInterferewIthcomplexfunctIonslIke
memoryandawareness.AnesthetIcsclearlyaltercortIcalelectrIcalactIvIty,asevIdenced
bythechangesInsurfaceelectroencephalogrampatternsrecordeddurInganesthesIa.
AnesthetIceffectsonpatternsofcortIcalelectrIcalactIvItyvarywIdelyamong
anesthetIcs,
28
provIdInganInItIalsuggestIonthatallanesthetIcsarenotlIkelytoact
throughIdentIcalmechanIsms.|oredetaIledInvItroelectrophysIologIcalstudIes
examInInganesthetIceffectsondIfferentcortIcalregIonssupportthenotIonthat
anesthetIcscandIfferentIallyalterneuronalfunctIonInvarIouscortIcalpreparatIons.For
example,volatIleanesthetIcshavebeenshowntoInhIbItexcItatorytransmIssIonatsome
synapsesIntheolfactorycortex
29
butnotatothers.
J0
SImIlarly,whereasvolatIle
anesthetIcsInhIbItexcItatorytransmIssIonInthedentategyrusofthehIppocampus,
J1
thesesamedrugscanactuallyenhanceexcItatorytransmIssIonatothersynapsesInthe
hIppocampus.
J2
AnesthetIcsalsoproduceavarIetyofeffectsonInhIbItorytransmIssIonIn
thecortex.AvarIetyofparenteralandInhalatIonanesthetIcshavebeenshowntoenhance
InhIbItorytransmIssIonInolfactorycortex
J0
andInthehIppocampus.
JJ
Conversely,volatIle
anesthetIcshavealsobeenreportedtodepressInhIbItorytransmIssIonInhIppocampus.
J4
Summary
AnesthetIcsproduceeffectsonavarIetyofanatomIcstructuresIntheCNS,IncludIngspInal
cord,braInstem,hypothalamus,andcerebralcortex.WhereascertaInanesthetIceffects
maybeattrIbutabletospecIfIcanatomIclocatIons(e.g.,purposefulresponsetonoxIous
stImulatIonmapstothespInalcord),exIstIngevIdenceprovIdesnobasIsforasIngle
anatomIcsIteresponsIbleforanesthesIa.ThIsdIffIcultyInIdentIfyIngasIteforanesthesIa
mIghtplausIblyresultfromthevarIouscomponentsoftheanesthetIcstatebeIngproduced
byanesthetIceffectsondIfferentregIonsoftheCNS.Nevertheless,despItethedIffIcultyIn
IdentIfyIngacommonanatomIcsIteforanesthesIa,InvestIgatorshavecontInuedtolook
forotherunIfyIngprIncIplesInanesthetIcactIon.SpecIfIcally,attentIonhasbeenfocused
onIdentIfyIngcommoncellularormolecularanesthetIctargetsthatmayhaveawIde
anatomIcdIstrIbutIon,explaInIngtheabIlItyofanesthetIctoaffectnervoussystem
functIonInananatomIcallydIffusemanner.
P.99
How do Anesthetics Interfere with the Electrophysiologic
Function of the Nervous System?
nthesImplesttermsanesthetIcsInhIbItorturnoffvItalCNSfunctIons.Theymustdo
thIsbyactIngatspecIfIcphysIologIcswItches.AgreatdealofInvestIgatIveefforthas
beendevotedtoIdentIfyIngtheseswItches.nprIncIple,theCNScouldbeswItchedoffby
severalmeans:
1. 8ydepressIngthoseneuronsorpatterngeneratorsthatsubserveapacemakerfunctIonIn
theCNS.
2. 8yreducIngoverallneuronalexcItabIlIty,eItherbychangIngrestIngmembranepotentIal
orbyInterferIngwIththeprocessesInvolvedIngeneratInganactIonpotentIal.
J. 8yreducIngcommunIcatIonbetweenneurons;specIfIcally,byeItherInhIbItIngexcItatory
synaptIctransmIssIonorenhancIngInhIbItorysynaptIctransmIssIon.
Pattern Generators
nformatIonconcernIngtheeffectsofanesthetIcsonpatterngeneratIngneuronalcIrcuIts
IntheCNSIslImIted,butclInIcalconcentratIonsofanesthetIcsarelIkelytohave
sIgnIfIcanteffectsonthesecIrcuIts.ThesImplestevIdenceforthIsIstheobservatIonthat
mostanesthetIcsexertprofoundeffectsonrespIratoryrateandrhythm,stronglysuggestIng
aneffectonrespIratorypatterngeneratorsInthebraInstem.nvertebratestudIessuggest
thatvolatIleanesthetIcscanselectIvelyInhIbItthespontaneous(pacemaker)fIrIngof
specIfIcneurons.AsshownInFIgure52,halothane(1|AC)completelyInhIbIts
spontaneousactIonpotentIalgeneratIonbyoneneuronIntherIghtparIetalganglIonofthe
greatpondsnaIlwhIleproducIngnoobservableeffectonthefIrIngfrequencyofadjacent
neurons.
J5
Neuronal Excitability
TheabIlItyofaneurontogenerateanactIonpotentIalIsdetermInedbythreeparameters:
restIngmembranepotentIal,thethresholdpotentIalforactIonpotentIalgeneratIon,and
thefunctIonofvoltagegatedsodIumchannels.AnesthetIcscanhyperpolarIze(createa
morenegatIverestIngmembranepotentIal)bothspInalmotorneuronsandcortIcal
neurons,
J6,J7
andthIsabIlItytohyperpolarIzeneuronscorrelateswIthanesthetIcpotency.
ngeneral,theIncreaseInrestIngmembranepotentIalproducedbyanesthetIcsIssmallIn
magnItudeandIsunlIkelytohaveaneffectonaxonalpropagationofanactIonpotentIal.
SmallchangesInrestIngpotentIalmay,however,InhIbIttheinitiationofanactIon
potentIaleItheratapostsynaptIcsIteorInaspontaneouslyfIrIngneuron.ndeed,
hyperpolarIzatIonIsresponsIblefortheInhIbItIonofspontaneousactIonpotentIal
generatIonshownInFIgure52.FecentevIdencealsoIndIcatesthatIsoflurane
hyperpolarIzesthalamIcneurons,leadIngtoanInhIbItIonoftonIcfIrIngofactIon
potentIals.
J8
ThereIsnoevIdenceIndIcatIngthatanesthetIcsalterthethresholdpotentIal
ofaneuronforactIonpotentIalgeneratIon.However,thedataareconflIctIngonwhether
thesIzeoftheactIonpotentIal,onceInItIated,IsdImInIshedbygeneralanesthetIcs.A
classIcartIclebyLarabeeandPosternak
J9
demonstratedthatconcentratIonsofetherand
chloroformthatcompletelyblocksynaptIctransmIssIonInmammalIansympathetIcganglIa
havenoeffectonpresynaptIcactIonpotentIalamplItude.SImIlarresultshavebeen
obtaInedwIthfluorInatedvolatIleanesthetIcsInmammalIanbraInpreparatIons.
29,J1
ThIs
dogmathattheactIonpotentIalIsrelatIvelyresIstanttogeneralanesthetIcshasbeen
challengedbymorerecentreportsthatvolatIleanesthetIcsatclInIcalconcentratIons
produceasmallbutsIgnIfIcantreductIonInthesIzeoftheactIonpotentIalInmammalIan
neurons.
40,41
nonecase,thereductIonIntheactIonpotentIalwasshowntobeamplIfIed
atthepresynaptIctermInalresultIngInalargereductIonInneurotransmItterrelease.
41
Thus,whIlecurrentdatastIllsupporttheprevaIlIngvIewthatneuronalexcItabIlItyIsonly
slIghtlyaffectedbygeneralanesthetIcs,thIssmalleffectmayneverthelesscontrIbute
sIgnIfIcantlytotheclInIcalactIonsofvolatIleanesthetIcs.
Figure 5-2.SelectIvItyofvolatIleanesthetIcInhIbItIonofneuronalautomatIcIty.A:
Halothane(1|AC)reversIblyInhIbItsthespontaneousfIrIngactIvItyofaneuronfrom
theparIetalganglIonofLymnaea stagnalis).B:ThesameconcentratIonofhalothane
hasnoeffectonthefIrIngactIvItyofanadjacent,andapparentlyIdentIcal,neuron).
NotethatInA,halothanemarkedlyreducesrestIngmembranepotentIalInaddItIonto
InhIbItIngfIrIng.(FeprIntedwIthpermIssIonfromFranksNP,LIebWF:|echanIsmsof
generalanesthesIa.EnvIronHealthPerspect87:204,1990.)
Synaptic Function
SynaptIcfunctIonIswIdelyconsIderedtobethemostlIkelysubcellularsIteofgeneral
anesthetIcactIon.NeurotransmIssIonacrossbothexcItatoryandInhIbItorysynapsesIs
markedlyalteredbygeneralanesthetIcs.CeneralanesthetIcsInhIbItexcItatorysynaptIc
transmIssIonInavarIetyofpreparatIons,IncludIngsympathetIcganglIa,
J9
olfactory
cortex,
29
P.100
hIppocampus,
J1
andspInalcord.
19
However,notallexcItatorysynapsesappeartobe
equallysensItIvetoanesthetIcs;Indeed,transmIssIonacrosssomehIppocampalexcItatory
synapsesIsenhancedbyInhalatIonalanesthetIcs.
J2
nasImIlarfashIon,generalanesthetIcs
bothenhanceanddepressInhIbItorysynaptIctransmIssIonInvarIouspreparatIons.na
classIcartIcleIn1975,NIcolletal
42
showedthatbarbIturatesenhancedInhIbItorysynaptIc
transmIssIonbyprolongIngthedecayoftheCA8AergIcInhIbItorypostsynaptIccurrent.
EnhancementofInhIbItorytransmIssIonhasalsobeenobservedwIthmanyothergeneral
anesthetIcsIncludIngetomIdate,
4J
propofol,
44
InhalatIonalanesthetIcs,
J0
and
neurosteroIds.
45
AlthoughanesthetIcenhancementofInhIbItorycurrentshasreceIveda
greatdealofattentIonasapotentIalmechanIsmofanesthesIa,
4
ItIsImportanttonote
thatthereIsalsoalargebodyofexperImentatIonshowIngthatclInIcalconcentratIonsof
generalanesthetIcscandepressInhIbItorypostsynaptIcpotentIalsInhIppocampus
J4,46,47
andInspInalcord.
20
AnesthetIcsdoappeartohavepreferentIaleffectsonsynapses,but
thereIsagreatdealofheterogeneItyInthemannerInwhIchanesthetIcagentsaffect
dIfferentsynapses.ThIsIsnotsurprIsInggIventhelargevarIatIonInsynaptIcstructure,
functIon(I.e.,effIcacy),andchemIstry(neurotransmItters,modulators)extantInthe
nervoussystem.
Presynaptic Effects
CeneralanesthetIcsaffectsynaptIctransmIssIonbothpreandpostsynaptIcally.However,
themagnItudeandeventhetypeofeffectvaryaccordIngtothetypeofsynapseandthe
partIcularanesthetIc.PresynaptIcally,neurotransmItterreleasefromglutamatergIc
synapseshasconsIstentlybeenfoundtobeInhIbItedbyclInIcalconcentratIonsofvolatIle
anesthetIcs.Forexample,astudybyPerouanskyandcolleagues
48
conductedInmouse
hIppocampalslIcesshowedthathalothaneInhIbItedexcItatorypostsynaptIcpotentIals
elIcItedbypresynaptIcelectrIcalstImulatIon,butnotthoseelIcItedbydIrectapplIcatIon
ofglutamate.ThIsIndIcatesthathalothanemustbeactIngtopreventthereleaseof
glutamate,themajorexcItatoryneurotransmItterInthebraIn.|acverandcolleagues
extendedtheseobservatIonsbyfIndIngthattheInhIbItIonofglutamatereleasefrom
hIppocampalneuronsIsnotduetoeffectsatCA8AergIcsynapsesthatcouldIndIrectly
decreasetransmItterreleasefromglutamatergIcneurons.
J2
EffectsofIntravenous
anesthetIcsonglutamatereleasehavealsobeendemonstrated,buttheevIdenceIsmore
lImItedandtheeffectspotentIallyIndIrect.
49,50
ThedataforanesthetIceffectson
InhIbItoryneurotransmItterreleaseIsmIxed.nhIbItIon,
51
stImulatIon,
52,5J
andnoeffect
54
havebeenreportedforvolatIleanesthetIcandIntravenousanesthetIcactIononCA8A(
amInobutyrIcacId)release.nabraInsynaptosomalpreparatIonwhereeffectsonboth
CA8AandglutamatereleasecouldbestudIedsImultaneously,WestphalenandHemmIngs
55
foundthatglutamateand,toalesserdegree,CA8AreleasewereInhIbItedbyclInIcal
concentratIonsofIsoflurane.ThemechanIsmunderlyInganesthetIceffectsontransmItter
releasehasnotbeenestablIshed.TheeffectsofanesthetIcsonneurotransmItterreleasedo
notappeartobemedIatedbyreducedneurotransmIttersynthesIsorstorage,butratherby
adIrecteffectontheprocessofneurosecretIon.AvarIetyofevIdencearguesthatatsome
synapsesasubstantIalportIonoftheanesthetIceffectIsupstreamofthetransmItter
releasemachInery,perhapsonpresynaptIcsodIumchannelsorpotassIumleakchannels
(seelaterdIscussIon).However,genetIcdataInCaenorhabditis elegansshowsthatthe
transmItterreleasemachInerystronglyInfluencesvolatIleanesthetIcsensItIvIty
56
;at
present,ItIsunclearwhetherthesefIndIngsrepresentspecIesdIfferencesordIfferent
aspectsofthesamemechanIsm.
Postsynaptic Effects
AnesthetIcsalterthepostsynaptIcresponsetoreleasedneurotransmItter.Theeffectsof
generalanesthetIcsonexcItatoryneurotransmItterreceptorfunctIonvarydependIngon
neurotransmIttertype,anesthetIcagent,andpreparatIon.FIchardsandSmaje
57
examIned
theeffectsofseveralanesthetIcagentsontheresponseofolfactorycortIcalneuronsto
applIcatIonofglutamate,themajorexcItatoryneurotransmItterIntheCNS.Theyfound
thatwhIlepentobarbItal,dIethylether,methoxyflurane,andalphaxalonedepressedthe
electrIcalresponsetoglutamate,halothanewaswIthouteffect.ncontrast,when
acetylcholInewasapplIedtothesameolfactorycortIcalpreparatIon,halothaneand
methoxyfluranestImulatedtheelectrIcalresponsewhereaspentobarbItalhadnoeffect;
onlyalphaxalonedepressedtheelectrIcalresponsetoacetylcholIne.
58
Theeffectsof
anesthetIcsonneuronalresponsestoInhIbItoryneurotransmIttersaremoreconsIstent.A
wIdevarIetyofanesthetIcs,IncludIngbarbIturates,etomIdate,neurosteroIds,propofol,
andthefluorInatedvolatIleanesthetIcs,havebeenshowntoenhancetheelectrIcal
responsetoexogenouslyapplIedCA8A(forarevIew,seeref.59).Forexample,FIgure5J
IllustratestheabIlItyofenfluranetoIncreaseboththeamplItudeandtheduratIonofthe
currentelIcItedbyapplIcatIonofCA8AtohIppocampalneurons.
60
Summary
AttemptstoIdentIfyaphysIologIcswItchatwhIchanesthetIcsacthavesufferedfromtheIr
ownsuccess.AnesthetIcsproduceavarIetyofeffectsonmanyphysIologIcprocessesthat
mIghtlogIcallycontrIbutetotheanesthetIcstate,IncludIngneuronalautomatIcIty,
neuronalexcItabIlIty,andsynaptIcfunctIon.ThesynapseIsgenerallythoughttobethe
mostlIkelyrelevantsIteofanesthetIcactIon.ExIstIngevIdenceIndIcatesthatevenatthIs
onesIte,anesthetIcsproducevarIouseffects,IncludIngpresynaptIcInhIbItIonof
neurotransmItterrelease,InhIbItIonofexcItatoryneurotransmIttereffect,and
enhancementofInhIbItoryneurotransmIttereffect.Furthermore,theeffectsofanesthetIcs
onsynaptIcfunctIondIfferamongvarIousanesthetIcagents,neurotransmItters,and
neuronalpreparatIons.
Anesthetic Actions on Ion Channels
onchannelsareonelIkelytargetofanesthetIcactIon.Theadventofpatchclamp
technIquesIntheearly1980smadeItpossIbletodIrectlymeasurethecurrentsfromsIngle
IonchannelproteIns.twasattractIvetothInkthatanesthetIceffectsonasmallnumber
ofIonchannelsmIghthelptoexplaInthecomplexphysIologIceffectsofanesthetIcsthat
wehavealreadydescrIbed.AccordIngly,durIngthe1980sand1990samajoreffortwas
dIrectedatdescrIbIngtheeffectsofanesthetIcsonthevarIouskIndsofIonchannels.The
followIngsectIonsummarIzesanddIstIllsthIseffort.ForthepurposesofthIsdIscussIon,Ion
channelsarecatalogedaccordIngtothestImulItowhIchtheyrespondbyopenIngor
closIng(I.e.,theIrmechanIsmofgatIng).
Anesthetic Effects on Voltage-Dependent Ion Channels
AvarIetyofIonchannelscansenseachangeInmembranepotentIalandrespondbyeIther
openIngorclosIngtheIrpore.ThesechannelsIncludevoltagedependentsodIum,
potassIum,
P.101
andcalcIumchannels,allofwhIchsharesIgnIfIcantstructuralhomologIes.7oltage
dependentsodIumandpotassIumchannelsarelargelyInvolvedIngeneratIngandshapIng
actIonpotentIals.TheeffectsofanesthetIcsonthesechannelshavebeenextensIvely
studIedbyHaydonandUrban
61
InthesquIdgIantaxon.ThesestudIesshowthatthese
InvertebratesodIumchannelsandpotassIumchannelsareremarkablyInsensItIveto
volatIleanesthetIcs.Forexample,50InhIbItIonofthepeaksodIumchannelcurrent
requIredhalothaneconcentratIons8tImesthoserequIredtoproduce
P.102
anesthesIa.ThedelayedrectIfIerpotassIumchannelwasevenlesssensItIve,requIrIng
halothaneconcentratIonsmorethan20tImesthoserequIredtoproduceanesthesIa.SImIlar
resultshavebeenobtaInedInamammalIancelllIne(CH
J
pItuItarycells)whereboth
sodIumandpotassIumcurrentswereInhIbItedbyhalothaneonlyatconcentratIonsgreater
than5tImesthoserequIredtoproduceanesthesIa.
62
However,anumberofrecentstudIes
wIthvolatIleanesthetIcshavechallengedthenotIonthatvoltagedependentsodIum
channelsareInsensItIvetoanesthetIcs.Fehbergandcolleagues
6J
expressedratbraInA
sodIumchannelsInamammalIancelllIne,andshowedthatclInIcallyrelevant
concentratIonsofavarIetyofInhalatIonalanesthetIcssuppressedvoltageelIcItedsodIum
currents.FatnakumarIandHemmIngs
64
showedthatsodIumfluxmedIatedbyratbraIn
sodIumchannelswassIgnIfIcantlyInhIbItedbyclInIcalconcentratIonsofhalothane.
ShIraIshIandHarrIs
65
documentedtheeffectsofIsofluraneonavarIetyofsodIumchannel
subtypesandfoundthatseveralbutnotallsubtypesaresensItIvetoclInIcal
concentratIons.FInally,asprevIouslydescrIbed,InaratbraInstemneuron,Wuand
colleagues
41
foundthatasmallInhIbItIonofsodIumcurrentsbyIsofluraneresultedIna
largeInhIbItIonofsynaptIcactIvIty.Thus,sodIumchannelactIvItynotonlyappearstobe
InhIbItedbyvolatIleanesthetIcs,butthIsInhIbItIonresultsInasIgnIfIcantreductIonIn
synaptIcfunctIon,atleastatsomemammalIansynapses.ntravenousanesthetIcshavealso
beenshowntoInhIbItsodIumchannels,buttheconcentratIonsforthIseffectaresupra
clInIcal.
66,67
Figure 5-3.EnfluranepotentIatestheabIlItyofCA8A(amInobutyrIcacId)toactIvate
achlorIdecurrentInculturedrathIppocampalcells.ThIspotentIatIonIsrapIdly
reversedbyremovalofenflurane(wash;A).EnfluraneIncreasesboththeamplItudeof
thecurrent(B)andthetIme(
1/2
)Ittakesforthecurrenttodecay(C).(Feproduced
wIthpermIssIonfromJones|7,8rooksPA,HarrIsonL:EnhancementofamInobutyrIc
acIdactIvatedCl
currentsInculturedrathIppocampalneuronesbythreevolatIle
anaesthetIcs.JPhysIol449:289,1992.)
Voltage-dependent calcium channels(70CCs)servetocoupleelectrIcalactIvItytospecIfIc
cellularfunctIons.nthenervoussystem,70CCslocatedatpresynaptIctermInalsrespond
toactIonpotentIalsbyopenIng.ThIsallowscalcIumtoenterthecell,actIvatIngcalcIum
dependentsecretIonofneurotransmItterIntothesynaptIccleft.AtleastsIxtypesof
calcIumchannels(desIgnatedL,N,P,Q,F,andT)havebeenIdentIfIedonthebasIsof
electrophysIologIcalpropertIesandalargernumberbasedonamInoacIdsequence
sImIlarItIes.N,P,Q,andFtypechannels,aswellassomeoftheuntItledchannels,are
preferentIallyexpressedInthenervoussystemandarethoughttoplayamajorroleIn
synaptIctransmIssIon.LtypecalcIumchannels,althoughexpressedInbraIn,havebeen
beststudIedIntheIrroleInexcItatIoncontractIoncouplIngIncardIac,skeletal,and
smoothmuscleandarethoughttobelessImportantInsynaptIctransmIssIon.Theeffects
ofanesthetIcsonLandTtypecurrentshavebeenwellcharacterIzed,
62,68,69
andthereare
somereportsconcernIngtheeffectsofanesthetIcsonNandPtypecurrents.
70,71,72
Asa
generalrule,thesestudIeshaveshownthatvolatIleanesthetIcsInhIbIt70CCs(50
reductIonIncurrent)atconcentratIons2to5tImesthoserequIredtoproduceanesthesIaIn
humans,wIthlessthana20InhIbItIonofcalcIumcurrentatclInIcalconcentratIonsof
anesthetIcs.However,somestudIeshavefound70CCsthatareextremelysensItIveto
anesthetIcs.TakenoshItaandSteInbach
7J
reportedaTtypecalcIumcurrentIndorsalroot
ganglIonneuronsthatwasInhIbItedbysubanesthetIcconcentratIonsofhalothane.
AddItIonally,ffrench|ullenandcolleagues
74
havereporteda70CCofunspecIfIedtypeIn
guIneapIghIppocampusthatIsInhIbItedbypentobarbItalatconcentratIonsIdentIcalto
thoserequIredtoproduceanesthesIa.Thus,70CCscouldwellmedIatesomeactIonsof
generalanesthetIcs,buttheIrgeneralInsensItIvItymakesthemunlIkelytobemajor
targets.
Potassium channelsarethemostdIverseoftheIonchannelstypesandIncludevoltage
gated,backgroundorleakchannelsthatopenoverawIderangeofvoltagesIncludIngat
therestIngmembranepotentIalofneurons,secondmessengerandlIgandactIvated,and
socalledInwardrectIfyIngchannels;somechannelsfallIntomorethanonecategory.HIgh
concentratIonsofbothvolatIleanesthetIcsandIntravenousanesthetIcsarerequIredto
affectsIgnIfIcantlythefunctIonofvoltagegatedK
+
channels.
61,75,76
SImIlarly,classIc
InwardrectIfyIngK
+
channelsarerelatIvelyInsensItIvetosevofluraneand
barbIturates.
77,78,79
However,somebackgroundK
+
channelsarequItesensItIvetovolatIle
anesthetIcs.
Summary
ExIstIngevIdencesuggeststhatmost70CCsaremodestlysensItIveorInsensItIveto
anesthetIcs.However,somesodIumchannelssubtypesareInhIbItedbyvolatIleanesthetIcs
andthIseffectmayberesponsIbleInpartforareductIonInneurotransmItterreleaseat
somesynapses.AddItIonalexperImentaldatawIllberequIredtoestablIshwhether
anesthetIcsensItIve70CCsarelocalIzedtospecIfIcsynapsesatwhIchanesthetIcshave
beenshowntoInhIbItneurotransmItterrelease.
Anesthetic Effects on Ligand-Gated Ion Channels
FastexcItatoryandInhIbItoryneurotransmIssIonIsmedIatedbytheactIonsoflIgandgated
Ionchannels.SynaptIcallyreleasedglutamateorCA8AdIffuseacrossthesynaptIccleftand
bIndtochannelproteInsthatopenasaconsequenceofneurotransmItterrelease.The
channelproteInsthatbIndCA8A(CA8A
A
receptors)aremembersofasuperfamIlyof
structurallyrelatedlIgandgatedIonchannelproteInsthatIncludenIcotInIcacetylcholIne
receptors,glycInereceptors,and5HT
J
receptors.8asedonthestructureofthenIcotInIc
acetylcholInereceptor,eachlIgandgatedchannelIsthoughttobecomposedoffIve
nonIdentIcalsubunIts.TheglutamatereceptorsalsocomprIseafamIly,eachreceptor
thoughttobeatetramerIcproteIncomposedofstructurallyrelatedsubunIts.ThelIgand
gatedIonchannelsprovIdealogIcaltargetforanesthetIcactIonbecauseselectIveeffects
onthesechannelscouldInhIbItfastexcItatorysynaptIctransmIssIonand/orfacIlItatefast
InhIbItorysynaptIctransmIssIon.TheeffectsofanesthetIcagentsonlIgandgatedIon
channelsarethoroughlycatalogedInarevIewbyKrasowskIandHarrIson.
59
ThefollowIng
sectIonprovIdesabrIefsummaryofthIslargebodyofwork.
Glutamate-Activated Ion Channels
ClutamateactIvatedIonchannelshavebeenclassIfIed,basedonselectIveagonIsts,Into
threecategorIes:A|PAreceptors,kaInatereceptors,andN|0Areceptors.A|PAand
kaInatereceptorsarerelatIvelynonselectIvemonovalentcatIonchannelsInvolvedInfast
excItatorysynaptIctransmIssIon,whereasN|0AchannelsconductnotonlyNa
+
andK
+
but
alsoCa
++
andareInvolvedInlongtermmodulatIonofsynaptIcresponses(longterm
potentIatIon).StudIesfromtheearly1980sInmouseandratbraInpreparatIonsshowed
thatA|PAandkaInateactIvatedcurrentsareInsensItIvetoclInIcalconcentratIonsof
halothane,
80
enflurane,
81
andtheneurosteroIdallopregnanolone.
82
ncontrast,kaInate
andA|PAactIvatedcurrentswereshowntobesensItIvetobarbIturates;Inrat
hIppocampalneurons,50|pentobarbItal(pentobarbItalproducesanesthesIaat
approxImately50|)InhIbItedkaInateandA|PAresponsesby50.
82
|orerecentstudIes
usIngclonedandexpressedglutamatereceptorsubunItsshowthatsubmaxImalagonIst
responsesofCluFJ(A|PAtype)receptorsareInhIbItedbyfluorInatedvolatIleanesthetIcs
whereasagonIstresponsesofCluF6(kaInatetype)receptorsareenhanced.
8J
ncontrast
bothCluFJandCluF6receptorsareInhIbItedbypentobarbItal.ThedIrectIonallyopposIte
effectsofthevolatIleanesthetIcsondIfferentglutamatereceptorsubtypesmayexplaIn
theearlIerInconclusIveeffectsobservedIntIssue,wheremultIplesubunIttypesare
expressed.TheseopposIteeffectshavealsobeenusedasastrategytoIdentIfycrItIcalsItes
onthemoleculesInvolvedInanesthetIceffect.8yproducIngCluFJ/CluF6receptor
chImeras(receptorsmadeupofvarIouscombInatIonsofsectIonsoftheCluFJandCluF6
receptors)andscreenIngforvolatIleanesthetIceffect,specIfIcareasoftheproteIn
requIredforvolatIleanesthetIcpotentIatIonofCluF6havebeenIdentIfIed.Subsequent
sItedIrectedmutagenesIsstudIeshaveIdentIfIedaspecIfIcglycIneresIdue(Cly819)as
crItIcalforvolatIleanesthetIcactIononCluF6contaInIngreceptors.
84
N|0AactIvatedcurrentsalsoappeartobesensItIvetoasubsetofanesthetIcs.
ElectrophysIologIcalstudIesshowvIrtuallynoeffectsofclInIcalconcentratIonsofvolatIle
anesthetIcs,
80,81
neurosteroIds,orbarbIturates
82
onN|0AactIvatedcurrents.tshouldbe
notedthatthereIssomeevIdencefromfluxstudIesthatvolatIleanesthetIcsmayInhIbIt
N|0AactIvatedchannels.AstudyInratbraInmIcrovesIclesshowedthatanesthetIc
concentratIons(0.2to0.Jm|)ofhalothaneandenfluraneInhIbItedN|0AactIvated
calcIumfluxby50.
85
ncontrast,ketamIneIsapotentandselectIveInhIbItorofN|0A
actIvatedcurrents.KetamInestereoselectIvelyInhIbItsN|0AcurrentsbybIndIngtothe
phencyclIdInesIteontheN|0AreceptorproteIn.
86,87,88
TheanesthetIceffectsofketamIne
InIntactanImalsshowthesamestereoselectIvItyasthatobservedInvItro,
89
suggestIng
thattheN|0AreceptormaybetheprIncIpalmoleculartargetfortheanesthetIcactIonsof
ketamIne.TwootherrecentfIndIngssuggestthatN|0AreceptorsmaybeanImportant
targetfornItrousoxIdeandxenon.ThesestudIesshowthatN
2
D
90,91
andxenon
92
arepotent
andselectIveInhIbItorsofN|0AactIvatedcurrents.ThIsIsIllustratedInFIgure54,
showIngthatN
2
DInhIbItsN|0AelIcIted,butnotCA8AelIcIted,currentsInhIppocampal
neurons.
GABA-Activated Ion Channels
CA8AIsthemostImportantInhIbItoryneurotransmItterInthemammalIanCNS.CA8A
actIvatedIonchannels(CA8A
A
receptors)medIatethepostsynaptIcresponsetosynaptIcally
releasedCA8AbyselectIvelyallowIngchlorIdeIonstoenterandtherebyhyperpolarIzIng
neurons.CA8A
A
receptorsaremultIsubunItproteInsconsIstIngofvarIouscombInatIonsof
,,andsubunIts,andtherearemanysubtypesofeachofthesesubunIts.ThefunctIon
ofCA8A
A
receptorsIsmodulatedbyawIdevarIetyofpharmacologIcagentsIncludIng
convulsants,antIconvulsants,sedatIves,anxIolytIcs,andanesthetIcs.
9J
Theeffectsofthese
varIousdrugsonCA8A
A
receptorfunctIonvarIesacrossbraInregIonsandcelltypes.The
followIngsectIonbrIeflyrevIewstheeffectsofanesthetIcsonCA8A
A
receptorfunctIon.
8arbIturates,anesthetIcsteroIds,benzodIazepInes,propofol,etomIdate,andthevolatIle
anesthetIcsallmodulateCA8A
A
receptorfunctIon.
60,9J,94,95,96
Thesedrugsproducethree
kIndsofeffectsontheelectrophysIologIcalbehavIoroftheCA8A
A
receptorchannels:
potentIatIon,dIrectgatIng,andInhIbItIon.PotentiationreferstotheabIlItyofanesthetIcs
toIncreasemarkedlythecurrentelIcItedbylowconcentratIonsofCA8A,buttoproduce
P.10J
noIncreaseInthecurrentelIcItedbyamaxImallyeffectIveconcentratIonofCA8A.
PotentIatIonIsIllustratedInFIgure55,showIngtheeffectsofhalothaneoncurrents
elIcItedbyarangeofCA8AconcentratIonsIndIssocIatedcortIcalneurons.AnesthetIc
potentIatIonofCA8A
A
currentsgenerallyoccursatconcentratIonsofanesthetIcswIthInthe
clInIcalrange.Direct gatingreferstotheabIlItyofanesthetIcstoactIvateCA8A
A
channels
IntheabsenceofCA8A.Cenerally,dIrectgatIngofCA8A
A
currentsoccursatanesthetIc
concentratIonshIgherthanthoseusedclInIcally,buttheconcentratIonresponsecurvesfor
potentIatIonandfordIrectgatIngcanoverlap.tIsnotknownwhetherdIrectgatIngof
CA8A
A
channelsIseItherrequIredfororcontrIbutestotheeffectsofanesthetIcsonCA8A
medIatedInhIbItorysynaptIctransmIssIonInvIvo.nthecaseofanesthetIcsteroIds,strong
evIdenceIndIcatesthatpotentIatIon,ratherthandIrectgatIngofCA8A
A
currents,Is
requIredforproducInganesthesIa.
97
AnesthetIcscanalsoInhIbItCA8AactIvatedcurrents.
InhibitionreferstotheabIlItyofanesthetIcstopreventCA8AfromInItIatIngcurrentflow
throughCA8A
A
channels,andhasgenerallybeenobservedathIghconcentratIonsofboth
CA8AandanesthetIc.
98,99
nhIbItIonofCA8A
A
channelsmayhelptoexplaInwhyvolatIle
anesthetIcshave,Insomecases,beenobservedtoInhIbItratherthanfacIlItateInhIbItory
synaptIctransmIssIon.
J4
Figure 5-4.NItrousoxIdeInhIbItsN|0AelIcIted,butnotCA8AelIcIted,currentsInrat
hIppocampalneurons.A:EIghtypercentN
2
DhasnoeffectonholdIngcurrent(upper
trace),butInhIbItsthecurrentelIcItedbyN|0A.B:N
2
DcausesarIghtwardand
downwardshIftoftheN|0AconcentratIonresponsecurve,IndIcatIngamIxed
competItIve/noncompetItIveantagonIsm.C:EIghtypercentN
2
DhaslIttleeffecton
CA8AelIcItedcurrents.ncontrast,anequIpotentanesthetIcconcentratIonof
pentobarbItalmarkedlyenhancestheCA8AelIcItedcurrent.(FeproducedwIth
permIssIonfromJevtovIcTodorovIc7,TodorovIcS|,|ennerIckSet al:NItrousoxIde
(laughInggas)IsanN|0AantagonIst,neuroprotectant,andneurotoxIn.Nat|ed4:460,
1998.)
Figure 5-5.Theeffectsofhalothane(Hal),enflurane(Enf),andfluorothyl(HFE)on
CA8AactIvatedchlorIdecurrentsIndIssocIatedratCNSneurons.A:ClInIcal
concentratIonsofhalothaneandenfluranepotentIatetheabIlItyofCA8AtoelIcIta
chlorIdecurrent.TheconvulsantfluorothylantagonIzestheeffectsofCA8A(
amInobutyrIcacId.B:CA8AcausesaconcentratIondependentactIvatIonofachlorIde
current.HalothaneshIftstheCA8AconcentratIonresponsecurvetotheleft(Increases
theapparentaffInItyofthechannelforCA8A),whereasfluorothylshIftsthecurveto
therIght(decreasestheapparentaffInItyofthechannelforCA8A).(FeproducedwIth
permIssIonfromWakamorI|,kemotoY,AkaIkeN:EffectsoftwovolatIleanesthetIcs
andavolatIleconvulsantontheexcItatoryandInhIbItoryamInoacIdresponsesIn
dIssocIatedCNSneuronsoftherat.JNeurophysIol66:2014,1991.)
EffectsofanesthetIcshavealsobeenobservedonthefunctIonofsIngleCA8A
A
channels.
ThesestudIesshowthatbarbIturates,
94
propofol,
96
andvolatIleanesthetIcs
100
donotalter
theconductance(rateatwhIchIonstraversetheopenchannel)ofthechannel,butthat
theyIncreasethefrequencywIthwhIchthechannelopensand/ortheaveragelengthof
tImethatthechannelremaInsopen.CollectIvely,thewholecellandsInglechanneldata
aremostconsIstentwIththeIdeathatclInIcalconcentratIonsofanesthetIcsproducea
changeIntheconformatIonofCA8A
A
receptorsthatIncreasestheaffInItyofthereceptor
forCA8A.ThIsIsconsIstentwIththeabIlItyofanesthetIcstoIncreasetheduratIonof
InhIbItorypostsynaptIcpotentIals,sIncehIgheraffInItybIndIngofCA8Awouldslowthe
dIssocIatIonofCA8AfrompostsynaptIcCA8A
A
channels.twouldnotbeexpectedthat
anesthetIcswouldIncreasethepeakamplItudeofaCA8AergIcInhIbItorypostsynaptIc
potentIalsIncesynaptIcally
P.104
releasedCA8AprobablyreachesveryhIghconcentratIonsInthesynapse.HIgher
concentratIonsofanesthetIcscanproduceaddItIonaleffects,eItherdIrectlyactIvatIngor
InhIbItIngCA8A
A
channels.ConsIstentwIththeseIdeas,astudyby8anksandPearce
101
showedthatIsofluraneandenfluranesImultaneouslyIncreasedtheduratIonanddecreased
theamplItudeofCA8AergIcInhIbItorypostsynaptIccurrentsInhIppocampalslIces.
0espItethesImIlareffectsofmanyanesthetIcsonCA8A
A
receptorfunctIon,thereIs
sIgnIfIcantevIdencethatthevarIousanesthetIcsdonotactbybIndIngtoasInglecommon
bIndIngsIteonthechannelproteIn.FIrst,evenanesthetIcsthatdIrectlyactIvatethe
channelprobablydonotbIndtotheCA8AbIndIngsIte.ThIsIsmostclearlydemonstrated
bymolecularbIologIcstudIesInwhIchtheCA8AbIndIngsIteIselImInatedfromthechannel
proteInbutpentobarbItalcanstIllactIvatethechannel.
102
0IrectradIolIgandbIndIng
studIeshavedemonstratedthatbenzodIazepInesbIndtotheCA8A
A
receptoratnanomolar
concentratIonsandthatotheranesthetIcscanmodulatebIndIngbutdonotbInddIrectlyto
thebenzodIazepInesIte.
9J,10J
AserIesofmorecomplexstudIesexamInIngtheInteractIons
betweenbarbIturates,anesthetIcsteroIds,andbenzodIazepInesIndIcatesthatthesethree
classesofdrugscannotbeactIngatthesamesItes.
9J
TheactIonsofanesthetIcsonCA8A
A
receptorsarefurthercomplIcatedbytheobservatIonthatsteroIdanesthetIcscanproduce
dIfferenteffectsonCA8A
A
receptorsIndIfferentbraInregIons.
104
ThIssuggeststhe
possIbIlItythatthespecIfIcsubunItcomposItIonofaCA8A
A
receptormayencode
pharmacologIcselectIvIty.ThIsIswellIllustratedbybenzodIazepInesensItIvIty,whIch
requIresthepresenceofthe2subunItsubtype.
105
SImIlarly,sensItIvItytoetomIdatehas
beenshowntorequIrethepresenceofa2orJsubunIt.
106
|orerecently,Ithasbeen
shownthatthepresenceofaorsubunItInaCA8A
A
receptorconfersInsensItIvItytothe
potentIatIngeffectsofsomeanesthetIcs.
107,108
nterestIngly,CA8A
A
receptorscomposedoftypesubunIts(referredtoasGABA
C
receptors)havebeenshowntobeInhIbItedratherthanpotentIatedbyvolatIle
anesthetIcs.
109
ThIspropertyhasbeenexploIted,usIngmolecularbIologIctechnIques,by
constructIngchImerIcreceptorscomposedofpartofthereceptorcoupledtopartofan
,,orglycInereceptorsubunIt.8yscreenIngthesechImerasforanesthetIcsensItIvIty,
regIonsofthe,,andglycInesubunItsresponsIbleforanesthetIcsensItIvItyhavebeen
IdentIfIed.8asedontheresultsofthesechImerIcstudIes,sItedIrectedmutagenesIsstudIes
wereperformedtoIdentIfythespecIfIcamInoacIdsresponsIbleforconferrInganesthetIc
sensItIvIty.ThesestudIesrevealedtwocrItIcalamInoacIds,neartheextracellularregIons
oftransmembranedomaIns2andJ(T|2,T|J)oftheglycIneandCA8A
A
receptorsthatare
requIredforvolatIleanesthetIcpotentIatIonofagonIsteffect.
110
tIsnotyetclearIfthese
amInoacIdsrepresentavolatIleanesthetIcbIndIngsIte,orwhethertheyaresItescrItIcal
totransducInganesthetIcInducedconformatIonalchangesInthereceptormolecule.
nterestIngly,oneoftheamInoacIdsshowntobecrItIcaltovolatIleanesthetIceffect(T|J
sIte)hasalsobeenshowntoberequIred(Inthe
2
/
J
subunIt)forthepotentIatIngeffects
ofetomIdate.
111
ncontrast,theT|2andT|JsItesdonotappeartoberequIredforthe
actIonsofpropofol,barbIturates,orneurosteroIds.
112
nterestIngly,adIstInctamInoacIdIn
theT|JregIonofthe
1
subunItoftheCA8A
A
receptorhasbeenshowntoselectIvely
modulatetheabIlItyofpropofoltopotentIateCA8AagonIsteffects.
112
FecentevIdence
alsoIndIcatesthatneurosteroIdsactIonsonCA8A
A
receptorsoccurvIaInteractIonswIth
specIfIcsIteswIthInthetransmembranespannIngregIonsofthe
1
and
2
subunItsthatare
dIstInctfromthosewIthwhIchbenzodIazepInesandpentobarbItalact.
11J
CollectIvely,
thesemolecularbIologIcdataprovIdestrongevIdencethattherearemultIpleunIque
bIndIngsItesforanesthetIcsontheCA8A
A
receptorproteIn.
Other Ligand-Activated Ion Channels
DthermembersofthelIgandgatedreceptorsuperfamIlyIncludethenIcotInIcacetylcholIne
receptors(muscleandneuronaltypes),glycInereceptors,and5HT
J
receptors.Alarge
bodyofworkhasgoneIntoexamInIngtheeffectsofanesthetIcsonnIcotInIcacetylcholIne
receptors.ThemuscletypeofnIcotInIcreceptorhasbeenshowntobeInhIbItedby
anesthetIcconcentratIonsIntheclInIcalrange
114
andtobedesensItIzedbyhIgher
concentratIonsofanesthetIcs.
115
ThemusclenIcotInIcreceptorIsanInformatIvemodelto
studybecauseofItsabundanceandthewealthofknowledgeaboutItsstructure.tIs,
however,notexpressedIntheCNSandhencenotInvolvedInthemechanIsmofanesthesIa.
However,aneuronaltypeofnIcotInIcreceptor,whIchIswIdelyexpressedInthenervous
system,mIghtplausIblybeInvolvedInanesthetIcmechanIsms.DlderstudIeslookIngat
neuronalnIcotInIcreceptorsInmolluscanneurons
116
andInbovInechromaffIncells
117
IndIcatethatthesechannelsareInhIbItedbyclInIcalconcentratIonsofvolatIle
anesthetIcs.|orerecentstudIesusIngclonedandexpressedneuronalnIcotInIcreceptor
subunItshaveshownahIghdegreeofsubunItandanesthetIcselectIvIty.AcetylcholIne
elIcItedcurrentsareInhIbIted,InreceptorscomposedofvarIouscombInatIonsof
2
,
4
,
2
,
and
4
subunIts,bysubanestheticconcentratIonsofhalothane
118
orIsoflurane.
119
n
contrast,thesereceptorsarerelatIvelyInsensItIvetopropofol.|ostInterestIngly,
receptorscomposedof
7
subunItsarecompletelyInsensItIvetobothIsofluraneand
propofol.
119,120
SubsequentpharmacologIcexperImentsusIngselectIveInhIbItorsof
neuronalnIcotInIcreceptorsledtotheconclusIonthatthesereceptorsareunlIkelytohave
amajorroleInImmobIlIzatIonbyvolatIleanesthetIcs.
121,122
However,theymIghtplaya
roleIntheamnestIcorhypnotIceffectsofvolatIleanesthetIcs.
12J
ClycIneIsanImportantInhIbItoryneurotransmItter,partIcularlyInthespInalcordand
braInstem.TheglycInereceptorIsamemberofthelIgandactIvatedchannelsuperfamIly
that,lIketheCA8A
A
receptor,IsachlorIdeselectIveIonchannel.Alargenumberof
studIeshaveshownthatclInIcalconcentratIonsofvolatIleanesthetIcspotentIateglycIne
actIvatedcurrentsInIntactneurons
80
andInclonedglycInereceptorsexpressedIn
oocytes.
124,125
ThevolatIleanesthetIcsappeartoproducetheIrpotentIatIngeffectby
IncreasIngtheaffInItyofthereceptorforglycIne.
125
Propofol,
96
alphaxalone,and
pentobarbItalalsopotentIateglycIneactIvatedcurrents,whereasetomIdateandketamIne
donot.
124
PotentIatIonofglycInereceptorfunctIonmaycontrIbutetotheanesthetIc
actIonofvolatIleanesthetIcsandsomeparenteralanesthetIcs.The5HT
J
receptorsare
alsomembersofthegenetIcallyrelatedsuperfamIlyoflIgandgatedreceptorchannels.
ClInIcalconcentratIonsofvolatIleanesthetIcspotentIatecurrentsactIvatedby5
hydroxytryptamIneInIntactcells
126
andInclonedreceptorsexpressedInoocytes.
127
n
contrast,thIopentalInhIbIts5HT
J
receptorcurrents
126
andpropofolIswIthouteffecton
thesereceptorchannels.
127
The5HT
J
receptorsmayplaysomeroleIntheanesthetIcstate
producedbyvolatIleanesthetIcsandmayalsocontrIbutetosomeunpleasantanesthetIc
sIdeeffectssuchasnauseaandvomItIng.
Summary
SeverallIgandgatedIonchannelsaremodulatedbyclInIcalconcentratIonsofanesthetIcs.
KetamIne,N
2
D,andxenonInhIbItN|0Atypeglutamatereceptors,andthIseffectmayplay
amajorroleIntheIrmechanIsmofactIon.AlargebodyofevIdenceshowsthatclInIcal
concentratIonsofmanyanesthetIcspotentIateCA8AactIvatedcurrentsIntheCNS.ThIs
suggeststhatCA8A
A
receptorsareaprobablemoleculartargetofanesthetIcs.Dther
membersofthelIgandactIvatedIonchannelfamIly,IncludIngglycInereceptors,neuronal
nIcotInIcreceptors,
P.105
and5HT
J
receptors,arealsoaffectedbyclInIcalconcentratIonsofanesthetIcsandremaIn
plausIbleanesthetIctargets.
Anesthetic Effects on Background Potassium Ion Channels
CertaInpotassIumchannelscalledbackgroundorleak channelsareactIvatedbyboth
volatIleandgaseousanesthetIcs.
128
8ackgroundorleakchannelsaresonamedbecause
theytendtobeopenatallvoltagesIncludIngtherestIngmembranepotentIalofneurons,
producIngaleakcurrent.LeakcurrentscansIgnIfIcantlyregulatetheexcItabIlItyof
neuronsInwhIchtheyareexpressed.AnesthetIcactIvatIonofaleakchannelwasfIrst
observedInaganglIonofthepondsnaIl,Lymnea stagnalis.
129
ClInIcalconcentratIonsof
halothaneactIvatedthIschannelcalled
K(AN)
,resultIngInsIlencIngofthespontaneous
burstIngoftheseneurons(FIg.56A).AsImIlaranesthetIcactIvatedbackgroundpotassIum
channelwassubsequentlyfoundbyWInegarandYost
1J0
InthemarInemolluskAplysia.The
ImportanceofvolatIleanesthetIcactIvatIonoftheseInvertebratepotassIumchannelshas
nowbecomeapparentwIththedIscoveryofalargefamIlyofbackgroundpotassIum
channelsInmammals.ThesemammalIanpotassIumchannelshaveaunIquestructurewIth
twoporeformIngdomaInsIntandemplusfourtransmembranesegments(2P/4T|;FIg.5
6C).
1J1
Pateletal
1J2
havestudIedtheeffectsofvolatIleanesthetIcsonseveralmembersof
themammalIan2P/4T|famIly.TheyhaveshownthatTFEK1channelsareactIvatedby
clInIcalconcentratIonsofchloroform,dIethylether,halothane,andIsoflurane(FIg.568).
ncontrast,closelyrelatedTFAAKchannelsareInsensItIvetoallthevolatIleanesthetIcs,
andTASKchannelsareactIvatedbyhalothaneandIsoflurane,InhIbItedbydIethylether,
andunaffectedbychloroform.TheseauthorswentontoshowthattheCtermInalregIons
ofTASKandTFEK1contaInamInoacIdsessentIalforanesthetIcactIon.
1J2
|orerecently,
TFEK1butnotTASKwasfoundtobeactIvatedbyclInIcalconcentratIonsofthegaseous
anesthetIcs:xenon,nItrousoxIde,andcyclopropane.
1JJ
Thus,actIvatIonofbackgroundK
+
channelsInmammalIanvertebratescouldbeanImportantandgeneralmechanIsmthrough
whIchInhalatIonalandgaseousanesthetIcsregulateneuronalrestIngmembranepotentIal
andtherebyexcItabIlIty.ndeed,genetIcevIdencearguesforaroleofthesechannelsIn
producInganesthesIa(seelaterdIscussIon).
Figure 5-6.7olatIleanesthetIcsactIvatebackgroundK
+
channels.A:Halothane
reversIblyhyperpolarIzesapacemakerneuronfromLymnaea stagnalis(thepondsnaIl)
byactIvatIng
Kan
.B:Halothane(J00|)actIvateshumanrecombInantTFEK1
channelsexpressedInCDScells.ThefIgureshowscurrentvoltagerelatIonshIpswIth
reversalpotentIal(V
rev
)of88m7,IndIcatIveofaK
+
channel.C:PredIctedstructureof
atypIcalsubunItofthemammalIanbackgroundK
+
channels.Notethefour
transmembranespannIngsegments(Inblack)andthetwoporeformIngdomaIns(P1
andP2).Somebutnotallofthese2P/4T|K
+
channelsareactIvatedbyvolatIle
anesthetIcs.D:PhylogenetIctreeforthe2P/4T|famIly.(FeproducedwIthpermIssIon
fromFranksNP,LIebWF:8ackgroundK
+
channels:AnImportanttargetforanesthetIcs:
NatNeuroscI2:J95,1999.)
Summary
FecentevIdencesuggeststhatmembersofthe2P/4T|famIlyofbackgroundpotassIum
channelsmaybeImportantInproducIngsomecomponentsoftheanesthetIcstate.
What is the Chemical Nature of Anesthetic Target Sites?
The Meyer-Overton Rule
|orethan100yearsago,|eyer
1J4
andDverton
1J5
Independentlyobservedthatthepotency
ofgasesasanesthetIcswasstronglycorrelatedwIththeIrsolubIlItyInolIveoIl(FIg.57).
P.106
ThIsobservatIonhassIgnIfIcantlyInfluencedthInkIngaboutanesthetIcmechanIsmsIntwo
ways.FIrst,sInceawIdevarIetyofstructurallyunrelatedcompoundsobeythe|eyer
Dvertonrule,IthasbeenreasonedthatallanesthetIcsarelIkelytoactatthesame
molecularsIte.ThIsIdeaIsreferredtoastheUnitary Theory of Anesthesia.Second,Ithas
beenarguedthatsIncesolubIlItyInaspecIfIcsolventstronglycorrelateswIthanesthetIc
potency,thesolventshowIngthestrongestcorrelatIonbetweenanesthetIcsolubIlItyand
potencyIslIkelytomostcloselymImIcthechemIcalandphysIcalpropertIesofthe
anesthetIctargetsIteIntheCNS.8asedonthIsreasonIng,theanesthetIctargetsItewas
assumedtobehydrophobIcInnature.
Figure 5-7.The|eyerDvertonrule.ThereIsalInearrelatIonshIp(onaloglogscale)
betweentheoIl/gaspartItIoncoeffIcIentandtheanesthetIcpotency(mInImum
alveolarconcentratIon,|AC)ofanumberofgases.ThecorrelatIonbetweenlIpId
solubIlItyand|ACextendsovera70,000folddIfferenceInanesthetIcpotency.
(FeproducedwIthpermIssIonfromTanfIujIY,EgerE,TerrellFC:SomecharacterIstIcs
ofanexceptIonallypotentInhaledanesthetIc:thIomethoxyflurane.AnesthAnalg
56:J87,1977.)
The|eyerDvertoncorrelatIonsuffersfromtwolImItatIons:(1)ItonlyapplIestogasesand
volatIlelIquIdssInceolIveoIl/gaspartItIoncoeffIcIentscannotbedetermInedforlIquId
anesthetIcs,and(2)olIveoIlIsapoorlycharacterIzedmIxtureofoIls.TocIrcumventthese
lImItatIons,attemptshavebeenmadetocorrelateanesthetIcpotencywIthwater/solvent
partItIoncoeffIcIents.Todate,theoctanol/waterpartItIoncoeffIcIentbestcorrelateswIth
anesthetIcpotency.ThIscorrelatIonholdsforavarIetyofclassesofanesthetIcsandspans
a10,000foldrangeofanesthetIcpotencIes.
1J6
ThepropertIesofthesolventoctanol
suggestthattheanesthetIcsIteIslIkelytobeamphIpathIc,havIngbothpolarandnonpolar
characterIstIcs.
Exceptions to the Meyer-Overton Rule
HalogenatedcompoundsexIstthatarestructurallysImIlartotheInhaledanesthetIcsyet
areconvulsantsratherthananesthetIcs.
1J7
TherearealsoconvulsantbarbIturates
1J8
and
neurosteroIds.
1J9
Dneconvulsantcompound,fluorothyl(hexafluorodIethylether)hasbeen
showntocauseseIzuresIn50ofmIceat0.12vol,buttoproduceanesthesIaathIgher
concentratIons(EC
50
=1.22vol).
140
TheconcentratIonoffluorothylrequIredtoproduce
anesthesIaIsapproxImatelypredIctedbythe|eyerDvertonrule.ncontrast,several
polyhalogenatedalkaneshavebeenIdentIfIedthatareconvulsants,butthatdonot
produceanesthesIa.8asedontheolIveoIl/gaspartItIoncoeffIcIentsofthesecompounds,
anesthesIashouldhavebeenachIevedwIthIntherangeofconcentratIonsstudIed.
141
The
endpoIntusedtodetermInetheanesthetIceffectofthesecompoundswasmovementIn
responsetoanoxIousstImulus(|AC).nterestIngly,someofthesepolyhalogenated
compoundsdoproduceamnesIaInanImals.
142
Thesecompoundsarethusreferredtoas
nonimmobilizersratherthanasnonanesthetIcs.Severalpolyhalogenatedalkaneshavealso
beenIdentIfIedthatanesthetIzemIce,butonlyatconcentratIons10tImesthosepredIcted
bytheIroIl/gaspartItIoncoeffIcIents
141
;thesecompoundsarereferredtoastransitional
compounds.ThenonImmobIlIzersandtransItIonalcompoundshavebeenproposedasa
lItmustestfortherelevanceofanesthetIceffectsobservedInvItrotothoseobservedIn
thewholeanImal.
nseveralhomologousserIesofanesthetIcs,anesthetIcpotencyIncreaseswIthIncreasIng
chaInlengthuntIlacertaIncrItIcalchaInlengthIsreached.8eyondthIscrItIcalchaIn
length,compoundsareunabletoproduceanesthesIa,evenatthehIghestattaInable
concentratIons.ntheserIesofnalkanols,forexample,anesthetIcpotencyIncreasesfrom
methanolthroughdodecanol;alllongeralkanolsareunabletoproduceanesthesIa.
14J
ThIs
phenomenonIsreferredtoasthecutoff effect.CutoffeffectshavebeendescrIbedfor
severalhomologousserIesofanesthetIcsIncludIngnalkanes,nalkanols,
cycloalkanemethanols,
144
andperfluoroalkanes.
145
WhIletheanesthetIcpotencyIneachof
thesehomologousserIesofanesthetIcsshowsacutoff,acorrespondIngcutoffIn
octanol/wateroroIl/gaspartItIoncoeffIcIentshasnotbeendemonstrated.Therefore,
compoundsabovethecutoffrepresentadevIatIonfromthe|eyerDvertonrule.
AfInaldevIatIonfromthe|eyerDvertonruleIstheobservatIonthatenantIomersof
anesthetIcsdIfferIntheIrpotencyasanesthetIcs.EnantIomers(mIrrorImagecompounds)
areaclassofstereoIsomersthathaveIdentIcalphysIcalpropertIes,IncludIngIdentIcal
solubIlItyInsolventssuchasoctanolorolIveoIl.AnImalstudIeswIththeenantIomersof
barbIturateanesthetIcs,
146,147
ketamIne,
89
neurosteroIds,
97
etomIdate,
148
andIsoflurane
149
allshowenantIoselectIvedIfferencesInanesthetIcpotency.ThesedIfferencesInpotency
rangeInmagnItudefromamorethantenfolddIfferencebetweentheenantIomersof
etomIdateortheneurosteroIdstoa60dIfferencebetweentheenantIomersofIsoflurane.
tIsarguedthatamajordIfferenceInanesthetIcpotencybetweenapaIrofenantIomers
couldonlybeexplaInedbyaproteInbIndIngsIte(seeProteInTheorIesofAnesthesIa);
thIsappearstobethecaseforetomIdateandtheneurosteroIds.EnantIomerIcpaIrsof
anesthetIcshavealsobeenusedtostudyanesthetIcactIonsonIonchannels.tIsargued
thatIfananesthetIceffectonanIonchannelcontrIbutestotheanesthetIcstate,the
effectontheIonchannelshouldshowthesameenantIoselectIvItyasIsobservedInwhole
anImalanesthetIcpotency.EarlystudIesshowedthatthe(+)IsomerofIsofluraneIs1.5to2
tImesmorepotentthanthe()IsomerInelIcItIngananesthetIcactIvatedpotassIum
current,InpotentIatIngCA8A
A
currents,andInInhIbItIngthecurrentmedIatedbya
neuronalnIcotInIcacetylcholInereceptor.
99,116
ncontrast,thestereoIsomersofIsoflurane
areequIpotentIntheIreffectsonavoltageactIvatedpotassIumcurrentandIntheIr
effectsonlIpIdphasetransItIontemperature.
116
StudIeswIththeneurosteroIds
97
and
etomIdate
148
showthattheseanesthetIcsexertenantIoselectIveeffectsonCA8A
A
currents
thatparalleltheenantIoselectIveeffectsobservedforanesthetIcpotency.
P.107
TheexceptIonstothe|eyerDvertonruledonotobvIatetheImportanceoftherule.They
do,however,IndIcatethatthepropertIesofasolventsuchasoctanoldescrIbesome,but
notall,ofthepropertIesofananesthetIcbIndIngsIte.CompoundsthatdevIatefromthe
|eyerDvertonrulesuggestthatanesthetIctargetsIte(s)arealsodefInedbyother
propertIesIncludIngsIzeandshape.
ndefInIngthemoleculartarget(s)ofanesthetIcmoleculesonemustbeabletoaccount
bothforthe|eyerDvertonruleandforthewelldefInedexceptIonstothIsrule.thas
sometImesbeensuggestedthatacorrectmolecularmechanIsmofanesthesIashouldalso
beabletoaccountforpressurereversal.Pressure reversalIsaphenomenonwherebythe
concentratIonofagIvenanesthetIcneededtoproduceanesthesIaIsgreatlyIncreasedIf
theanesthetIcIsadmInIsteredtoananImalunderhyperbarIccondItIons.TheIdeathat
pressurereversalIsausefultoolforelucIdatIngmechanIsmsofanesthesIaIsbasedonthe
assumptIonthatpressurereversesthespecIfIcphysIcochemIcalactIonsoftheanesthetIc
thatareresponsIbleforproducInganesthesIa;thatIstosay,pressureandanesthetIcsact
onthesamemoleculartargets.However,recentevIdencesuggeststhatpressurereverses
anesthesIabyproducIngexcItatIonthatphysIologIcallycounteractsanesthetIcdepressIon,
ratherthanbyactIngasananesthetIcantagonIstattheanesthetIcsIteofactIon.
150
Therefore,InthefollowIngdIscussIonofmoleculartargetsofanesthesIa,pressurereversal
wIllnotbefurthermentIoned.
Lipid versus Protein Targets
AnesthetIcsmIghtInteractwIthseveralpossIblemoleculartargetstoproducetheIreffects
onthefunctionofIonchannelsandotherproteIns.AnesthetIcsmIghtdIssolveInthelipid
bIlayer,causIngphysIcochemIcalchangesInmembranestructurethataltertheabIlItyof
embeddedmembraneproteInstoundergoconformatIonalchangesImportantfortheIr
functIon.AlternatIvely,anesthetIcscouldbInddIrectlytoproteins(eItherIonchannel
proteInsormodulatoryproteIns),thuseIther(1)InterferIngwIthbIndIngofalIgand(e.g.,a
neurotransmItter,asubstrate,asecondmessengermolecule)or(2)alterIngtheabIlItyof
theproteIntoundergoconformatIonalchangesImportantforItsfunctIon.ThefollowIng
sectIonsummarIzestheargumentsforandagaInstlIpIdtheorIesandproteIntheorIesof
anesthesIa.
Lipid Theories of Anesthesia
TheelucIdatIonofthe|eyerDvertonrulesuggestedthatanesthetIcsInteractwItha
hydrophobIctarget.ToInvestIgatorsIntheearlypartofthe20thcentury,themostlogIcal
hydrophobIctargetwasalIpId.nItssImplestIncarnatIon,thelIpIdtheoryofanesthesIa
postulatesthatanesthetIcsdIssolveInthelIpIdbIlayersofbIologIcalmembranesand
produceanesthesIawhentheyreachacrItIcalconcentratIonInthemembrane.ConsIstent
wIththIshypothesIs,themembrane/gaspartItIoncoeffIcIentsofanesthetIcgasesInpure
lIpIdbIlayerscorrelatestronglywIthanesthetIcpotency.
151
Also,consIstentwIththelIpId
theorIes,varIousmembraneperturbatIonsareproducedbygeneralanesthetIcs;however,
themagnItudeofthesechangesproducedbyclInIcalconcentratIonsofanesthetIcsare
quItesmallandarethoughttobeveryunlIkelytodIsruptnervoussystemfunctIon.
152
WhIle
someofthemoresophIstIcatedlIpIdtheorIescanaccountforthecutoffeffectand
ImpotenceofnonImmobIlIzers,nolIpIdtheorycanplausIblyexplaInallanesthetIc
pharmacology.Thus,mostInvestIgatorsdonotconsIdermembranes/lIpIdsasthemost
lIkelytargetofgeneralanesthetIcs.
Protein Theories of Anesthesia
The|eyerDvertonrulecouldalsobeexplaInedbythedIrectInteractIonofanesthetIcs
wIthhydrophobIcsItesonproteIns.ThreetypesofhydrophobIcsItesonproteInsmIght
InteractwIthanesthetIcs:
1. HydrophobIcamInoacIdscomprIsethecoreofwatersolubleproteIns.AnesthetIcscould
bIndInhydrophobIcpocketsthatarefortuItouslypresentIntheproteIncore.
2. HydrophobIcamInoacIdsalsoformthelInIngofbIndIngsItesforhydrophobIclIgands.For
example,therearehydrophobIcpocketsInwhIchfattyacIdstIghtlybIndonproteInssuch
asalbumInandthelowmolecularweIghtfattyacIdbIndIngproteIns.AnesthetIcscould
competewIthendogenouslIgandsforbIndIngtosuchsItesoneItherwatersolubleor
membraneproteIns.
J. HydrophobIcamInoacIdsaremajorconstItuentsofthehelIces,whIchformthe
membranespannIngregIonsofmembraneproteIns;hydrophobIcamInoacIdsIdechaIns
formtheproteInsurfacethatfacesthemembranelIpId.AnesthetIcmoleculescould
InteractwIththehydrophobIcsurfaceofthesemembraneproteIns,dIsruptIngnormal
lIpIdproteInInteractIonsandpossIblydIrectlyaffectIngproteInconformatIon.ThIslast
possIbIlItywouldInvolvetheInteractIonofmanyanesthetIcmoleculeswItheach
membraneproteInmoleculeandwouldprobablybeanonselectIveInteractIonbetween
anesthetIcmoleculesandallmembraneproteIns.
0IrectInteractIonsofanesthetIcmoleculeswIthproteInswouldnotonlysatIsfythe|eyer
Dvertonrule,butwouldalsoprovIdethesImplestexplanatIonforcompoundsthatdevIate
fromthIsrule.AnyproteInbIndIngsIteIslIkelytobedefInedbypropertIessuchassIzeand
shapeInaddItIontoItssolventpropertIes.LImItatIonsInsIzeandshapecouldreducethe
bIndIngaffInItyofcompoundsbeyondthecutoff,thusexplaInIngtheIrlackofanesthetIc
effect.EnantIoselectIvItyIsalsomosteasIlyexplaInedbyadIrectbIndIngofanesthetIc
moleculestodefInedsItesonproteIns;aproteInbIndIngsIteofdefIneddImensIonscould
readIlydIstInguIshbetweenenantIomersonthebasIsoftheIrdIfferentshape.ProteIn
bIndIngsItesforanesthetIcscouldalsoexplaIntheconvulsanteffectsofsome
polyhalogenatedalkanes.0IfferentcompoundsbIndIng(InslIghtlydIfferentways)tothe
samebIndIngpocketcanproducedIfferenteffectsonproteInconformatIonandhenceon
proteInfunctIon.Forexample,therearethreekIndsofcompoundsthatcanbIndatthe
benzodIazepInebIndIngsIteontheCA8A
A
channel:agonists,whIchpotentIateCA8Aeffects
andproducesedatIonandanxIolysIs;inverse agonists,whIchpromotechannelclosureand
produceconvulsanteffects;andantagonists,whIchproducenoeffectontheIrownbutcan
competItIvelyblocktheeffectsofagonIstsandInverseagonIsts.8yanalogy,
polyhalogenatedalkanescouldbeInverseagonIsts,bIndIngatthesameproteInsItesat
whIchhalogenatedalkaneanesthetIcsareagonIsts.TheevIdencefordIrectInteractIons
betweenanesthetIcsandproteInsIsbrIeflyrevIewedInthefollowIngsectIon.
Evidence for Anesthetic Binding to Proteins
AbreakthroughInproteIntheorIesofanesthesIawasthedemonstratIonthatapurIfIed
watersolubleproteIn,fIreflylucIferase,couldbeInhIbItedbygeneralanesthetIcs.ThIs
provIdedtheImportantproofofprIncIplethatanesthetIcscouldbIndtoproteInsInthe
absenceofmembranes.NumerousstudIeshaveextensIvelycharacterIzedanesthetIc
InhIbItIonof
P.108
fIreflylucIferaseactIvItyandhaverevealedthefollowIng
15J,154
:
1. AnesthetIcsInhIbItfIreflylucIferaseactIvItyatconcentratIonsverysImIlartothose
requIredtoproduceclInIcalanesthesIa.
2. ThepotencyofanesthetIcsasInhIbItorsoffIreflylucIferaseactIvItycorrelatesstrongly
wIththeIrpotencyasanesthetIcs,InkeepIngwIththe|eyerDvertonrule.
J. HalothaneInhIbItIonoflucIferaseactIvItyIscompetItIvewIthrespecttothesubstrate0
lucIferIn.
4. nhIbItIonoffIreflylucIferaseactIvItyshowsacutoffInanesthetIcpotencyforbothn
alkanesandnalkanols.
8asedonthesestudIesItcanbeInferredthatawIdevarIetyofanesthetIcscanbIndInthe
lucIferInbIndIngpocketoffIreflylucIferase.ThefactthatanesthetIcInhIbItIonof
lucIferaseactIvItyIsconsIstentwIththe|eyerDvertonrule,occursatclInIcalanesthetIc
concentratIons,andexplaInsthecutoffeffectsuggeststhatthelucIferInbIndIngpocket
mayhavephysIcalandchemIcalcharacterIstIcssImIlartothoseofaputatIveanesthetIc
bIndIngsIteIntheCNS.
|oredIrectapproachestostudyanesthetIcbIndIngtoproteInshaveIncludedN|F
spectroscopyandphotoaffInItylabelIng.8asedonearlystudIesbyWIshnIaand
PInder,
155,156
ItwassuspectedthatanesthetIcscouldbIndtoseveralfattyacIdbIndIng
proteIns,IncludInglactoglobulInandbovIneserumalbumIn(8SA).
19
FN|FspectroscopIc
studIesconfIrmed
157
thIs,anddemonstratedthatIsofluranebIndstoapproxImatelythree
saturablebIndIngsIteson8SA.sofluranebIndIngIselImInatedbycoIncubatIonwItholeIc
acId,suggestIngthatIsofluranebIndstothefattyacIdbIndIngsItesonalbumIn.Dther
anesthetIcs,IncludInghalothane,methoxyflurane,sevoflurane,andoctanol,competewIth
IsofluraneforbIndIngto8SA.
158
ThestudIeswIth8SAprovIdedIrectevIdencethata
varIetyofanesthetIcscancompeteforbIndIngtothesamesIteonaproteIn.UsIngthIs8SA
model,ItwassubsequentlyshownthatanesthetIcbIndIngsItescouldbeIdentIfIedand
characterIzedusIngaphotoaffInItylabelIngtechnIque.TheanesthetIchalothanecontaIns
acarbonbromInebond.ThIsbondcanbebrokenbyultravIoletlIghtgeneratIngafree
radIcal.ThatfreeradIcalallowstheanesthetIctopermanently(covalently)labelthe
anesthetIcbIndIngsIte.EckenhoffandShuman
159
used
14
Clabeledhalothaneto
photoaffInItylabelanesthetIcbIndIngsIteson8SA,andobtaInedresultsvIrtuallyIdentIcal
tothoseobtaInedusIngN|Fspectroscopy.Eckenhoff
160
subsequentlyhasIdentIfIedthe
specIfIcamInoacIdsthatarephotoaffInItylabeledby[
14
C]halothane.N|Fand
photoaffInItylabelIngtechnIqueshavealsobeenapplIedtoseveralotherproteIns.For
example,saturablebIndIngofhalothanetothelucIferInbIndIngsIteonfIreflylucIferase
hasbeendIrectlyconfIrmedusIngN|FandphotoaffInItylabelIngtechnIques.
161
|ost
recently,HusaInandcolleagues
162
havedevelopedageneralanesthetIcthatIsananalogof
octanolandfunctIonsasaphotoaffInItylabel.ThIscompound,JdIazyrInyloctanol,bIndsto
specIfIcsItesonthenIcotInIcacetylcholInereceptor.
AlthoughN|FandphotoaffInItytechnIquescanprovIdeextensIveInformatIonabout
anesthetIcbIndIngsItesonproteIns,theycannotrevealthedetaIlsofthethree
dImensIonalstructureofthesesItes.XFaydIffractIoncrystallographycanprovIdethIskInd
ofthreedImensIonaldetaIlandhasbeenusedtostudyanesthetIcInteractIonswIthasmall
numberofproteIns.Todate,IthasbeendIffIculttocrystallIzemembraneproteIns;thus,
thesestudIeshavebeenlImItedtowatersolubleproteIns.FIreflylucIferasehasbeen
crystallIzedInthepresenceandabsenceoftheanesthetIcbromoform.XFaydIffractIon
studIesofthesecrystalsshowedthattheanesthetIcdoesbIndInthelucIferInbIndIng
pocket,ashadbeenInferredfromfunctIonalstudIes.nterestIngly,twomoleculesof
bromoformbIndInthelucIferInpocketonethatIslIkelytocompetedIrectlywIthlucIferIn
forbIndIngandonethatIsnot.
16J
ThebIndIngdatawIthfIreflylucIferaseIsofpartIcular
InterestbecauseItdemonstratesthatanesthetIcscanbIndtoendogenouslIgandbIndIng
sItesandthatthIsbIndIngstronglycorrelateswIthanesthetIcInhIbItIonofproteInfunctIon.
ThesamegrouphasalsocrystallIzedhumanserumalbumInInthepresenceofeIther
propofolorhalothane.ThexraycrystallographIcdatademonstratebIndIngofboth
anesthetIcstopreformedpocketsthathadbeenshownprevIouslytobIndfattyacIds.
164
CIventhatbothoftheseanesthetIcsbIndtoserumalbumInatclInIcalconcentratIons,
thesedatagIvethebestInsIghtyetIntothestructureofananesthetIcbIndIngpocket.
ArecentapproachtostudyanesthetIcInteractIonswIthproteInshasbeentoemploysIte
dIrectedmutagenesIsofcandIdateanesthetIctargets,coupledwIthmolecularmodelIngto
makepredIctIonsaboutthelocatIonandstructureofanesthetIcbIndIngsItes.Forexample,
WIckandcolleagues
165
haveusedthIsapproachtopredIctthelocatIonandstructureofthe
alcoholbIndIngsIteonCA8A
A
andglycInereceptors.SImIlarly,thelIkelyneurosteroId
bIndIngsItesforactIvatIonandpotentIatIonoftheCA8A
A
receptorwerefoundby
extensIvesItedIrectedmutagenesIsexperIments.
11J
Arelatedapproachhasbeento
developmodelproteInstodefInethestructuralrequIrementsforananesthetIcbIndIng
sIte.UsIngthIsapproach,Johanssonetal
166
haveshownthatafourhelIxbundlewItha
hydrophobIccorecanbIndvolatIleanesthetIcsatconcentratIons(K
0
)sImIlartothose
requIredtoproduceanesthesIa.
166
Summary
UnequIvocalevIdencefromstudIesusIngwatersolubleproteInsdemonstratesthat
anesthetIcscanbIndtohydrophobIcpocketsonproteIns.FunctIonalandbIndIngstudIes
wIthfIreflylucIferasedemonstratethatanesthetIcscanbIndtoaproteInsIteatclInIcally
relevantconcentratIonsInamannerthatcanaccountforthe|eyerDvertonruleand
devIatIonsfromIt.EvIdencethatdIrectanesthetIcproteInbIndIngInteractIonsmaybe
responsIbleforanesthetIceffectsonIonchannelsIntheCNSremaInsIndIrect;
stereoselectIvItycurrentlyoffersthestrongestIndIrectargument.
Dverall,currentevIdencestronglyIndIcatesproteInratherthanlIpIdasthemolecular
targetforanesthetIcactIon.WhIlethelongstandIngcontroversybetweenlIpIdandproteIn
theorIesofanesthesIamaybebehIndus,numerousunansweredquestIonsremaInaboutthe
detaIlsofanesthetIcproteInInteractIons,IncludIng:
1. WhatIsthestoIchIometryofanesthetIcbIndIngtoaproteIn(I.e.,0omanyanesthetIc
moleculesInteractwIthasIngleproteInmoleculeoronlyafew):
2. 0oanesthetIcscompetewIthendogenouslIgandsforbIndIngtohydrophobIcpocketson
proteIntargetsordotheybIndtofortuItouscavItIesIntheproteIn:
J. 0oallanesthetIcsbIndtothesamepocketonaproteInoraretheremultIple
hydrophobIcpocketsfordIfferentanesthetIcs:
4. HowmanyproteInshavehydrophobIcpocketsInwhIchanesthetIcscanbIndatclInIcally
usedconcentratIons:
How Are the Molecular Effects of Anesthetics Linked to
Anesthesia in the Intact Organism?
TheprevIoussectIonshavedescrIbedhowanesthetIcsaffectthefunctIonofanumberof
IonchannelsandsIgnalIngproteIns,probablyvIadIrectanesthetIcproteInInteractIons.t
Is
P.109
unclearwhIch,Ifany,oftheseeffectsofanesthetIcsonproteInfunctIonarenecessary
and/orsuffIcIenttoproduceanesthesIaInanIntactorganIsm.Anumberofapproaches
havebeenemployedtotrytolInkanesthetIceffectsobservedatamolecularlevelto
anesthesIaInIntactanImals.TheseapproachesandtheIrpItfallsarebrIeflyexploredInthe
followIngsectIon.
Pharmacologic Approaches
AnexperImentalparadIgmfrequentlyusedtostudyanesthetIcmechanIsmsIstoadmInIster
adrugthoughttoactspecIfIcallyataputatIveanesthetIctarget(e.g.,areceptoragonIst
orantagonIst,anIonchannelactIvatororantagonIst),thendetermInewhetherthedrug
haseItherIncreasedordecreasedtheanImal'ssensItIvItytoagIvenanesthetIc.The
underlyIngassumptIonIsthatIfachangeInanesthetIcsensItIvItyIsobserved,thenthe
anesthetIcIslIkelytoactvIaanactIononthespecIfIctargetoftheadmInIstereddrug.
ThIsIsalargelyflawedstrategythathasnonethelessproducedahugelIterature.Thedrugs
usedtomodulateanesthetIcsensItIvItyusuallyhavetheIrowndIrecteffectsonCNS
excItabIlItyandthusindirectlyaffectanesthetIcrequIrements.Forexample,whIle
2
adrenergIcagonIstsdecreasehalothane|AC,
167
theyareprofoundCNSdepressantsIntheIr
ownrIghtandproduceanesthesIabymechanIsmsdIstInctfromthoseusedbyvolatIle
anesthetIcs.Thus,the|ACsparIngeffectsof
2
agonIstsprovIdelIttleInsIghtIntohow
halothaneworks.AmoreusefulpharmacologIcstrategywouldbetoIdentIfydrugsthat
havenoeffectonCNSexcItabIlItybutpreventtheeffectsofgIvenanesthetIcs.Currently,
however,therearenosuchanesthetIcantagonIsts.0evelopmentofspecIfIcantagonIstsfor
anesthetIcagentswouldprovIdeamajortoolforlInkInganesthetIceffectsatthe
molecularleveltoanesthesIaIntheIntactorganIsm,andmIghtalsobeofsIgnIfIcant
clInIcalutIlIty.
AnalternatIvepharmacologIcapproachIstodeveloplItmustestsfortherelevanceof
anesthetIceffectsobservedInvItro.Dnesuchtesttakesadvantageofcompoundsthatare
nonanesthetIcdespItethepredIctIonsofthe|eyerDvertonrule.tIsarguedthatasIte
affectedbythesenonanesthetIccompoundsIsunlIkelytoberelevanttotheproductIonof
anesthesIa.
141
AsImIlarargumentusesstereoselectIvItyasthedIscrImInatorandargues
thatasItethatdoesnotshowthesamestereoselectIvItyasthatobservedforwholeanImal
anesthesIaIsunlIkelytoberelevanttotheproductIonofanesthesIa.
168
Althoughthese
testsmaybeuseful,theyareverydependentontheassumptIonthatanesthesIaIs
producedvIadrugactIonatasinglesIte.Forexample,anonanesthetIcmIghtdepressCNS
excItabIlItyvIaItsactIonsonanImportantanesthetIctargetsItewhIlesImultaneously
producIngcounterbalancIngexcItatoryeffectsatasecondsIte.nthIscasethelItmus
testwouldIncorrectlyelImInatetheanesthetIcsIteasIrrelevanttowholeanImal
anesthesIa.ThIsexampleIsquIteplausIblegIventheconvulsanteffectsofmanyofthe
nonanesthetIcpolyhalogenatedhydrocarbons.AnothersortoflItmustestIstoselectIvely
antagonIzetheputatIveanesthetIctargetsothatthIstargetIsnolongerfunctIonal.f
anesthetIceffectsaremedIatedthroughthIstarget,InactIvatIonofthetargetbythe
antagonIstshouldresultInanesthetIcresIstance.UsIngthIslogIc,themodest|ACsparIng
effectsofCA8A
A
andglycInereceptorantagonIstswereusedtoarguethatbothCA8A
A
and
glycInereceptorsmedIatesomebutnotalloftheImmobIlIzIngeffectsofvolatIle
anesthetIcsInrodents.
169,170
ThIssamegroupusedthelackofeffectofneuronalnIcotInIc
antagonIstsonIsoflurane|ACtoconcludethatthesereceptorshadnoroleInvolatIle
anesthetIcImmobIlIzatIon.
122
AswIthmanypharmacologIcresults,theIssuesofspecIfIcIty
andeffIcacyoftheantagonIstspreventtheseexperImentsfrombeIngdefInItIve.
Nevertheless,theseresultsareconsIstentwIththefIndIngsthatvolatIleanesthetIcsaffect
thefunctIonofalargenumberofImportantneuronalproteInsandnoonetargetIslIkelyto
medIatealloftheeffectsofthesedrugs.
Genetic Approaches
AnalternatIveapproachtostudytherelatIonshIpbetweenanesthetIceffectsobservedIn
vItroandwholeanImalanesthesIaIstoalterthestructureorabundanceofputatIve
anesthetIctargetsanddetermInehowthIsaffectswholeanImalanesthetIcsensItIvIty.
CenetIctechnIquesprovIdethemostrelIableandversatIlemethodsforchangIngthe
structureorabundanceofputatIveanesthetIctargets.ThefIrsttruegenetIcscreenfor
mutantswIthalteredgeneralanesthetIcsensItIvItywasperformedInthenematodeC.
elegansbyPhIl|organand|argaretSedensky.
171
TheyscreenedforalteredsensItIvItyto
supraclInIcalconcentratIonsofhalothane.HIghhalothaneconcentratIonswereused
becausetheyarerequIredtoImmobIlIzeC. elegans.ThefIrstmutantIsolatedhada
threefoldreductIonInItsEC
50
forhalothane.ThemutatIonwasgenetIcallymappedand
foundtobealossoffunctIonalleleoftheunc-79gene,whIchencodesalargeneuronal
proteInverysImIlarInsequencetoahumanproteIn.
172
ThecellularfunctIonofeItherthe
C. elegansorhumanproteInIsunknown.ntheabsenceofanesthetIcs,unc-79mutants
haveanInterestInglocomotIondefectcalledfainting.NormalC. eleganswormscrawl
almostcontInuouslywhereasunc-79mutantsappeartofaIntwheretheyspontaneouslystop
movIngforextendedperIodsoftIme.ntestIngothersuchmutants,Humphreyetal
172
and
|organandSedensky
17J
foundthat,Ingeneral,faInterswerehypersensItIveto
halothane.SubsequentextensIvegenetIcscreensandmappIngoffaIntIngmutantshaveled
toafocusonanovelpresumptIvecatIonchannel,NCA1/NCA2,thatcontrolshalothane
sensItIvItyInbothC. elegansandInthefruItflyDrosophila.
172
ThIsremarkable
conservatIonoftheanesthetIchypersensItIvItyphenotypeacrosssuchdIvergentspecIes
arguesforafundamentalroleofNCA1/NCA2IntheactIonofhalothane.
ClInIcalconcentratIonsofvolatIleanesthetIcsdonotImmobIlIzeC. elegans,buttheydo
producebehavIoraleffectsIncludInglossofcoordInatedmovement.
174
Crowderand
colleagues
174
havescreenedformutantsthatareresIstanttoanesthetIcInduced
uncoordInatIonandfoundthatmutatIonsInasetofgenesencodIngproteInsregulatIng
neurotransmItterreleasecontrolanesthetIcsensItIvIty.ThegenewIththelargesteffect
encodedsyntaxIn1A,aneuronalproteInhIghlyconservedfromC. eleganstohumansand
essentIalforfusIonofneurotransmIttervesIcleswIththepresynaptIcmembrane.
175
mportantly,somesyntaxInmutatIonsproducedhypersensItIvItytovolatIleanesthetIcs
whIleothersconferredresIstance.TheseallelIcdIfferencesInanesthetIcsensItIvItycould
notbeaccountedforbyeffectsontheprocessoftransmItterreleaseItself
56,175
;rather,
thegenetIcdataarguedthatsyntaxInInteractswIthaproteIncrItIcalforvolatIle
anesthetIcactIon,perhapsananesthetIctarget.Fecently,ahIghlyevolutIonarIly
conservedpresynaptIcproteIncalledUNC-13InC. eleganswasImplIcatedInthIs
presynaptIcvolatIleanesthetIcmechanIsm.
176
UNC1JIsrequIredfornormalIsoflurane
sensItIvIty,unc-13mutantsarefullyresIstanttotheeffectsofclInIcalconcentratIonof
Isoflurane,andIsofluranepreventsthenormalsynaptIclocalIzatIonofUNC1J.Whether
UNC1JIsadIrecttargetofvolatIleanesthetIcsIsunknown.ThIssamelaboratoryhasalso
shownbymutantanalysIsthatanN|0AglutamatereceptorsubunItIsessentIalfornItrous
oxIdesensItIvItyInC. elegans
177
andthatanotherglutamatereceptorsubunItIsrequIred
fortheeffectsofXenon.
178
nDrosophila,clInIcalconcentratIonsofvolatIleanesthetIcsdIsruptnegatIvegeotaxIs
behavIorandresponsetoanoxIouslIght
P.110
orheatstImulus.
179,180,181
UsIngoneormoreoftheseanesthetIcseffects,KrIshnanand
Nash
179
performedaforwardgenetIcscreenforhalothaneresIstance.TheresultsofthIs
screenhaveledtoafocusontheDrosophilahomologofnca-1/2.AsprevIouslydIscussed,
mutantsIntheDrosophilahomologofnca-1/2arehypersensItIvetohalothanelIketheC.
elegansmutants.
172
ThesynergyofbothDrosophilaandC. elegansgenetIcsshouldleadto
anunderstandIngofhowthIschannelcontrolsvolatIleanesthetIcsensItIvIty.
nmammals,themostpowerfulgenetIcmodelorganIsmIsmouse,wheretechnIqueshave
beendevelopedtoalterordeleteanygeneofInterest.TheCA8A
A
receptorhasbeen
extensIvelystudIedusIngmousegenetIctechnIques.
182,18J
ThegenesencodIngforvarIous
subunItsoftheCA8A
A
receptorhavebeenmutatedsothattheyareeIthernonfunctIonal
(geneknockouts)orsothattheyhavealteredamInoacIdsthatmIghtproducealtered
functIon(geneknockIns).KnockoutsofthreesubunItsoftheCA8A
A
receptorhavebeen
testedfortheIranesthetIcsensItIvIty.0eletIonofthe1subunItdoesnotaltersensItIvIty
ofmIcetothehypnotIceffectsofpentobarbItal.
184
SImIlarly,6subunItknockoutmIceare
normallysensItIvetohalothaneandenflurane.
185
However,5knockoutmIceareresIstant
tolearnIngImpaIrmentbyetomIdate.
186
KnockInmousestraInshavebeengeneratedfor
severalofthesubunIts,prImarIlyforexamInIngbenzodIazepIneactIon.Thelossof
varIousaspectsofbenzodIazepIneactIonInthesestraInsdemonstratedthatthe1subunIt
medIatesthesedatIveandamnestIcactIons,andIspartIallyrequIredforItsantIconvulsant
propertIes.SImIlarly,the2subunIthasbeenshowntobeessentIalforanxIolysIsby
dIazepam,andJand5knockInstraInsarepartIallyresIstanttoItsmyorelaxanteffects.
FInally,amouseexpressIngadoublemutated1subunIt,1(S270H,L277A),hasrecently
beentestedforItsanesthetIcsensItIvIty.
187,188
The1S270HmutatIonhasbeenshownto
blockCA8ApotentIatIonbyvolatIleanesthetIcs,butthemutatIonalsoIncreasesnatIve
sensItIvItytoCA8A,confoundIngInterpretatIonofthedata.|oreover,1S270HsIngle
mutantmIcearequIteabnormalbehavIorallyandarepronetoanesthetIcInducedseIzure
actIvIty.
189
Thus,asecondmutatIon,L277A,wasIntroducedIntothe1subunItthat
compensatedforthechangeInnatIvegatIngpropertIes.The1(S270H,L277A)mIceare
vIableandbehavIorallynormal.ThesemIcearemIldlyresIstanttotheataxIceffectsof
Isofluraneandenflurane;however,thepotencyofthedrugsIn|ACandfearcondItIonIng
assays(ameasureoflearnIng)arenotalteredbythedoublemutant1subunIt.
nvItroelectrophysIologIcalexperImentsshowthataspecIfIcJsubunItpoIntmutatIon,
J(N265|),blockstheactIonofetomIdateandpropofolontheCA8A
A
receptorwIthout
greatlyalterIngreceptorfunctIonIntheabsenceofdrug.
111,190
AJ(N265|)knockInstraIn
wasgeneratedandfoundtobeInsensItIvetotheImmobIlIzIngeffectsofetomIdate,
propofol,andpentobarbItal.
191,192
However,theJ(N265|)mIcearenotcompletely
resIstanttothelossofrIghtIngreflexbytheseanesthetIcs,IndIcatIngthatothertargets
medIatethIsbehavIoraleffect.nterestIngly,therespIratorydepressanteffectsof
etomIdateandpropofolarealsoblockedbytheJ(N265|)mutatIon,butthe
cardIovascularandhypothermIcactIonsofthedrugsarenot.
19J
TheJ(N265|)mIceshow
aslIghtlyreducedsensItIvItytotheImmobIlIzIngactIonsofvolatIleanesthetIcs,suggestIng
thattheJsubunItmayplayamInorroleInImmobIlIzatIon,butthemutanthasunaltered
sensItIvItytotheamnestIceffectsofIsoflurane.
194
AsImIlarapproachforthe2subunIt
hasshownthatItIscrItIcalforthesedatIngbutnotanesthetIcactIonofetomIdate.
195,196
FInally,straInscarryIngaknockoutmutatIonofthesubunItoftheCA8A
A
receptorhavea
shorterduratIonofneurosteroIdInducedlossofrIghtIngreflexwhereastheIrsensItIvItyto
otherIntravenousandvolatIleanesthetIcsIsunchanged.
197
Thus,thesubunItmayplaya
relatIvelyspecIfIcroleInneurosteroIdactIon.
TherolesInanesthetIcsensItIvItyoftwoofthebackgroundpotassIumchannelshavebeen
testedInlImItedmousegenetIcstudIes.ATFEK1knockoutmousewasfoundtobe
sIgnIfIcantlyresIstanttomultIplevolatIleanesthetIcsfor|ACandlossofrIghtIngreflex
endpoInts.
198
ThevolatIleanesthetIcresIstanceoftheTFEK1knockoutIssubstantIal,
partIcularlyforhalothanewhere|ACwasIncreasedby48.mportantly,theTFEK1
knockoutmIcehaveanormalsensItIvItytopentobarbItal,IndIcatIngspecIfIcItyforvolatIle
anesthetIcsconsIstentwIthprevIouselectrophysIologIcaldata.Fecently,Westphalenet
al
199
oftheHemmIngslaboratoryhasusedtheTFEK1knockoutstraIntotestthe
hypothesIsthatTFEK1medIatessomeofthepresynaptIcInhIbItoryeffectsofvolatIle
anesthetIcs.ndeed,glutamatereleasefromsynaptosomespreparedfromtheTFEK1
knockoutstraInIssIgnIfIcantlyresIstanttoInhIbItIonbyhalothanecomparedtorelease
fromwIldtypecontrolsynaptosomes.TheroleofTASK2,anothertwoporebackground
potassIumchannel,hasbeensImIlarlytestedbymeasurIngthe|ACofaTASK2knockout
mouse.However,unlIkeforTFEK1,theTASK2knockouthas|ACvaluessImIlartowIld
typecontrolsfordesflurane,halothane,andIsoflurane.
77
ThIsresultIssomewhatsurprIsIng
gIventhatTASK2IsstronglyactIvatedbyhalothaneandIsofluraneandmaybeexplaIned
byanoverallreducedexpressIonInthenervoussystemcomparedtoTFEK1.
128
Summary
FesultsfrombothInvertebrateandvertebrategenetIcsIndIcatethatmultIpleproteIns
controlvolatIleanesthetIcsensItIvIty.SomeofthesemaybeanesthetIctargetsandsome
not.CertaInCA8A
A
receptorsubunItsandtheTFEK1backgroundpotassIumchannelare
verylIkelytobetargetsrelevanttogeneralanesthesIa,butareprobablynottheonlyones.
ThemammalIanelectrophysIologIcaldataandthegenetIcevIdenceInC. elegansboth
ImplIcatetheN|0AglutamatereceptorastheprImarytargetofnItrousoxIde.SImIlarly,
elegantelectrophysIologIcalandgenetIcexperImentshaveshownthattheCA8A
A
receptor
IstheprImarymedIatorforImmobIlIzatIonbyetomIdate,propofol,andpentobarbItal.
Conclusions
nthIschapterevIdencehasbeenrevIewedconcernIngtheanatomIc,physIologIc,and
molecularlocIofanesthetIcactIon.tIsclearthatallanesthetIcactIonscannotbe
localIzedtoaspecIfIcanatomIcsIteIntheCNS;Indeed,someevIdencesuggeststhat
dIfferentcomponentsoftheanesthetIcstatemaybemedIatedbyactIonsatdIsparate
anatomIcsItes.TheactIonsofanesthetIcsalsocannotbelocalIzedtoaspecIfIcphysIologIc
process.WhIlethereIsconsensusthatanesthetIcsultImatelyaffectsynaptIcfunctIonas
opposedtoIntrInsIcneuronalexcItabIlIty,theeffectsofanesthetIcsdependontheagent
andsynapsestudIedandcanaffectpresynaptIcand/orpostsynaptIcfunctIon.Ata
molecularlevel,volatIleanesthetIcsshowsomeselectIvIty,butstIllaffectthefunctIonof
multIpleIonchannelsandsynaptIcproteIns.TheIntravenousanesthetIcs,etomIdate,
propofol,andbarbIturates,aremorespecIfIcwIththeCA8A
A
receptorastheIrmajor
target.AlthoughItIslIkelythattheseeffectsaremedIatedvIadIrectproteInanesthetIc
InteractIons,ItappearsthattherearenumerousproteInsthatcandIrectlyInteractwIth
anesthetIcs.CenetIcdataplaInlydemonstratethattheunItarytheoryofanesthesIaIsnot
correct.NosInglemechanIsmIsresponsIblefortheeffectsofallgeneralanesthetIcs,nor
doesasInglemechanIsmaccountforalloftheeffectsofasIngleanesthetIc,atleastwhere
IthasbeenexamIned.FIgure58provIdesasImplemodelofthemolecular
P.111
andcellulareffectsofgeneralanesthetIcs.ThIscartoonIsnotmeanttoIncludeall
potentIaltargetsofgeneralanesthetIcs.Father,onlythosemoleculeswIthstrongevIdence
forImportanceInanesthetIcactIonfrommultIpledIfferentapproachesareshown.
Figure 5-8.AmultIsItemodelforanesthesIa.AnesthetIcsaregroupedaccordIngto
sImIlarItyofmechanIsm.ArrowsIndIcateactIvatIonorpotentIatIonandT'sIndIcate
InhIbItIonorantagonIsm.TheneurophysIologIcaleffectsofgeneralanesthetIcsare
lumpedIntoneuronalexcItabIlIty(theprobabIlItyofaneuronfIrIngandpropagatIng
anaxonpotentIal)andexcItatoryneurotransmIssIon(synaptIcactIvItyatexcItatory
synapsessuchasglutamatergIc).NeuronalexcItabIlItyInthIscontextIsthesumof
bothIntrInsIcandextrInsIcfactors(e.g.,CA8AergIcInhIbItIon).
AlthoughtheprecIsemolecularInteractIonsresponsIbleforproducInganesthesIahavenot
beenfullyelucIdated,IthasbecomeclearthatanesthetIcsdoactvIaselectIveeffectson
specIfIcmoleculartargets.ThetechnologIcrevolutIonsInmolecularbIology,genetIcs,and
cellphysIologymakeItlIkelythatthenextdecadewIllprovIdesomeanswerstothe
centuryoldpharmacologIcpuzzleofthemolecularmechanIsmofanesthesIa.
Acknowledgment
TheauthorsacknowledgegenerousongoIngfundIngsupportfromNatIonalnstItuteof
Ceneral|edIcalScIences,8ethesda,|aryland,forASEP01C|047969andC|CF01
C|59781.
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Stock, M. Christine
TableofContentsSectIonScIentIfIcFoundatIonsofAnesthesIaChapter6CenomIc8asIsofPerIoperatIve
|edIcIne
Chapter6
Genomic Basis of Perioperative Medicine
Mihai V. Podgoreanu
Joseph P. Mathew
Key Points
1. Genetic variation can significantly modulate risk of adverse
perioperative events.
2. Several methodological approaches are used to study the genetic
architecture of perioperative outcomes.
3. Current perioperative risk profiling has limited ability to explain
individual variability in adverse outcomes.
4. Genetic variants in inflammatory and coagulation pathways are
associated with susceptibility to perioperative myocardial infarction.
5. Biomarkers associated with perioperative atrial fibrillation were
identified through genetic association studies and gene expression
analysis.
6. Variants in inflammation and platelet activation pathways modify
susceptibility to perioperative cerebral injury.
7. A genetic basis for perioperative acute kidney injury has been
identified.
8. Pharmacogenomics describes the relationship between inherited
variations in genes modulating drug actions and individual variability
in drug response.
9. Individual variability in response to anesthetic agents is as high as
24% and has a genetic component.
10. Individual variability in analgesic responsiveness is attributed to
genetic control of peripheral nociceptive pathways and descending
central pain modulatory pathways.
11. Host responses to injury and the clinical trajectory of critically ill
injured patients are genetically determined.
12. Genomic technology applications are beginning to fulfill the Five Ps
of perioperative medicine and pain management (personalized,
preventive, predictive, participatory, and prospective).
Genetic Basis of Disease
HumanbIologIcaldIversItyInvolvesInterIndIvIdualvarIabIlItyInmorphology,behavIor,
physIology,development,susceptIbIlItytodIsease,andresponsetostressfulstImulIand
drugtherapy(I.e.,phenotypes).ThIsphenotypIcvarIatIonIsdetermIned,atleastInpart,
bydIfferencesInthespecIfIcgenetIcmakeup(I.e.,genotype)ofanIndIvIdual.n200J,the
50thannIversaryofWatsonandCrIck'sdescrIptIonofthe0NAdoublehelIxstructurealso
markedthecompletIonoftheHumanCenomeProject.
1
ThIsmajoraccomplIshment
provIdesthedIscIplIneofgenomIcswIthbasIcresourcestostudythefunctIonsand
InteractIonsofallgenesInasystematIcfashIon,IncludIngtheIrInteractIonwIth
envIronmentalfactors,andtranslatethefIndIngsIntoclInIcalandsocIetalbenefIts.
Functional genomicsemployslargescaleexperImentalmethodsandstatIstIcalanalysesto
InvestIgatetheregulatIonofgeneexpressIonInresponsetophysIologIcal,pharmacologIc,
andpathologIcchanges.talsousesgenetIcInformatIonfromclInIcalstudIestoexamIne
theImpactofgenetIcvarIabIlItyondIseasecharacterIzatIonandoutcome.
2
|anycommondIseaseslIkeatherosclerosIs,coronaryarterydIsease,hypertensIon,
dIabetes,cancer,asthma,andourresponsestoInjury,drugs,andnonpharmacologIc
therapIesaregenetIcallycomplex,characterIstIcallyInvolvInganInterplayofmany
genetIcvarIatIonsInmolecularandbIochemIcalpathways(I.e.,polygenic)andgenetIc
envIronmentalInteractIons
P.116
(I.e.,multifactorial).notherwords,complexphenotypescanbevIewedastheIntegrated
effectofmanysusceptIbIlItygenesandmanyenvIronmentalexposures.TheproportIonof
phenotypIcvarIanceexplaInedbygenetIcfactorsIsreferredtoasheritability,andcanbe
estImatedbyexamInIngtheIncreasedsImIlarItyofaphenotypeInrelatedascompared
wIthunrelatedIndIvIduals.DneofthemajorchallengesandongoIngresearcheffortsfacIng
thepostgenomIcperIodaretoconnectthenearly25,000proteIncodInggenesof
mammalIanorganIsmstothegenetIcbasIsofcomplexpolygenIcdIseasesandthe
IntegratedfunctIonofcomplexbIologIcalsystems.AccordIngtothecommon
dIsease/commonvarIantshypothesIs,
J
IndIvIdualsusceptIbIlItytocommoncomplex
dIseasesandthemanIfestatIon,severIty,andprognosIsofthedIseaseprocessIsmodulated
bymultIplecommonfunctIonalpolymorphIsms,eachwIthonlymodesteffectondIsease
rIsk.However,ItIslIkelythatraremodestrIskallelesareImportantaswellInpolygenIc
dIsease,buttheIrdetectIonIsmoredIffIcultbecauseofsamplesIzeandsequencIng
constraInts.
TheperIoperatIveperIodrepresentsaunIqueandextremeexampleofsuchgene
envIronmentInteractIon.AsweapprecIateInourdaIlypractIceIntheoperatIngroomsand
IntensIvecareunIts,onehallmarkofperIoperatIvephysIologyIsthestrIkIngvarIabIlItyIn
patIentresponsestotheacute,robust,andgeneralIzedperIoperatIve(envIronmental)
perturbatIonsInducedbysurgIcalInjury,hemodynamIcchallenges,vascularcannulatIon,
extracorporealcIrculatIon,IntraaortIcballooncounterpulsatIon,mechanIcalventIlatIon,
partIal/totalorganresectIon,transIentlImb/organIschemIa,transfusIons,anesthetIc
agents,andthepharmacopoeIausedIntheperIoperatIveperIod.ThIstranslatesInto
substantIalInterIndIvIdualvarIabIlItyInImmedIateperIoperatIveadverseevents
(mortalItyorIncIdence/severItyoforgandysfunctIon),aswellaslongtermoutcomes
(Table61).FordecadeswehaveattrIbutedthIsvarIabIlItytomanycomplexItIessuchas
age,nutrItIonalstate,comorbIdItIeswhatwecolloquIallycallprotoplasm.Nowweare
begInnIngtoapprecIatethatgenetIcvarIatIonIsalsopartlyresponsIbleforthIsobserved
varIabIlItyInoutcomes.Dverall,anIndIvIdual'sgenetIcsusceptIbIlItytoadverse
perIoperatIveeventsstemsnotonlyfromgenetIccontrIbutIonstothedevelopmentof
comorbIdrIskfactors(lIkecoronaryarterydIsease[CA0]andreducedpreoperatIve
cardIopulmonaryreserve)durIngthepatIent'slIfetIme,butalsofromgenetIcvarIabIlItyIn
specIfIedbIologIcalpathwayspartIcIpatIngInpathophysIologIcaleventsdurIngandafter
surgery(FIg.61).WIthIncreasIngevIdencesuggestIngthatgenetIcvarIatIoncan
sIgnIfIcantlymodulaterIskofadverseperIoperatIveevents,
4,5,6,7
theemergIngfIeldof
perioperative genomicsaImstoapplyfunctIonalgenomIcapproachestodIscover
underlyIngbIologIcalmechanIsms.TheseapproacheswIllexplaInwhysImIlarpatIentshave
suchdramatIcallydIfferentoutcomesaftersurgery,andIsjustIfIedbyaunIque
combInatIonofenvIronmentalInsultsandpostoperatIvephenotypesthatcharacterIze
surgIcalandcrItIcallyIllpatIentpopulatIons.
ToIntegratethIsnewgeneratIonofgenetIcresultsIntoclInIcalpractIce,perIoperatIve
physIcIansneedtounderstandthepatternsofhumangenomevarIatIon,themethodsof
populatIonbasedgenetIcInvestIgatIon,andtheprIncIplesofgeneandproteInexpressIon
analysIs.ThIschapterrevIewsgeneralgenetIc/genomIcconceptsandhIghlIghtscurrentand
futureapplIcatIonsofgenomIctechnologIesforperIoperatIverIskstratIfIcatIon,outcome
predIctIon,mechanIstIcunderstandIngofsurgIcalstressresponses,aswellasIdentIfIcatIon
andvalIdatIonofnoveltargetsforperIoperatIveorganprotectIon.
Overview of Human Genetic Variation
Althoughthehuman0NAsequenceIs99.9IdentIcalbetweenIndIvIduals,thevarIatIons
maygreatlyaffecta
P.117
person'sdIseasesusceptIbIlIty.nelucIdatIngthegenetIcbasIsofdIsease,muchofwhathas
beenInvestIgatedInthepreHumanCenomeProjecterafocusedonIdentIfyIngrare
genetIcvarIants(mutations)responsIblefor1,500monogenIcdIsorderssuchas
hypertrophIccardIomyopathy,longQTsyndrome,sIcklecellanemIa,cystIcfIbrosIs,or
famIlIalhypercholesterolemIa,whIcharehIghlypenetrant(carrIersofthemutantgenewIll
lIkelyhavethedIsease)andInherItedInmendelIanfashIon(hence,termedmendelian
diseases).However,mostofthegenetIcdIversItyInthepopulatIonIsattrIbutabletomore
wIdespread0NAsequencevarIatIons(polymorphisms),typIcallysInglenucleotIdebase
substItutIons(single nucleotide polymorphisms[SNPs])ortoabroadercategoryof
prevIouslyoverlookedstructural genetic variants.ThesestructuralvarIantsIncludeshort
sequencerepeats(microsatellites),InsertIon/deletIonofoneormorenucleotIdes(indels),
InversIons,andtherecentlydIscoveredcopynumbervarIants(CNVs,largesegmentsof0NA
thatvaryInnumberofcopIes),
8
allofwhIchmayormaynotbeassocIatedwIthaspecIfIc
phenotype(FIg.62).TobeclassIfIedasapolymorphIsm,the0NAsequencealternatIves
(I.e.,alleles)mustexIstwIthafrequencyofatleast1InthepopulatIon.About15mIllIon
SNPsareestImatedtoexIstInthehumangenome,approxImatelyonceeveryJ00base
paIrs,locatedIngenes,aswellasInthesurroundIngregIonsofthegenome.PolymorphIsms
maydIrectlyaltertheamInoacIdsequenceandthereforepotentIallyalterproteIn
functIon,oralterregulatory0NAsequencesthatmodulateproteInexpressIon.Setsof
nearbySNPsonachromosomeareInherItedInblocks,referredtoashaplotypes.AswIllbe
shownlater,haplotypeanalysIsIsausefulwayofapplyInggenotypeInformatIonIndIsease
genedIscovery.Dntheotherhand,CN7sInvolveapproxImately12ofthehumangenome,
oftenencompassgenes(especIallyregulatIngInflammatIonandbraIndevelopment),and
mayInfluencedIseasesusceptIbIlItythroughdosageImbalances.Theyear2007wasmarked
bytherealIzatIonthat0NAdIffersfrompersontopersonmuchmorethanprevIously
suspected;equIppedwIthfasterandcheaper0NAsequencIngtechnologIes,researchers
havecataloguedJmIllIonSNPsaspartoftheHap|apProject,
9
publIshedthefIrstdIploId
genomesequenceofanIndIvIdualhuman,
10
launchedthe1000CenomesProject
(sequencIngthegenomesof1,000peoplefromaroundtheworld),andbegunchartIngCN7s
andotherstructuralvarIants,thusmakIngunderstandIngofhumangenetIcvarIatIonthe
2007SciencemagazIne8reakthroughoftheYear.nthefollowIngsectIonwerevIewthe
commonstrategIesusedtoIncorporategenetIcanalysIsIntoclInIcalstudIes.
Table 6-1 Categories of Perioperative Phenotypes
mmedIate
perIoperatIve
nhospItalmortalIty
PerIoperatIvemyocardIalInfarctIon
PerIoperatIvelowcardIacoutputsyndrome/acute
decompensatedheartfaIlure
PerIoperatIvevasoplegIcsyndrome
PerIoperatIvearrhythmIas(atrIalfIbrIllatIon)
PostoperatIvebleedIng
PerIoperatIvevenousthrombosIs
AcutepostoperatIvestroke
PostoperatIvedelIrIum
outcomes PerIoperatIveacutekIdneyInjury
AcuteperIoperatIvelungInjury/prolonged
postoperatIvemechanIcalventIlatIon
AcuteallograftdysfunctIon/rejectIon
PostoperatIvesepsIs
|ultIpleorgandysfunctIonsyndrome
7arIabIlItyInresponsetoanesthetIcs,analgesIcsand
otherperIoperatIvedrugs
ntermedIatephenotypes(plasmabIomarkerlevels)
Longterm
postoperatIve
outcomes
EventfreesurvIval/majoradversecardIacevents
ProgressIonofveIngraftdIsease
ChronIcallograftdysfunctIon/rejectIon
PostoperatIvecognItIvedysfunctIon
PostoperatIvedepressIon
QualItyoflIfe
Figure 6-1.PerIoperatIveadverseeventsarecomplextraIts,characterIstIcally
InvolvInganInteractIonbetweenrobustoperatIveenvIronmentalperturbatIons
(surgIcaltrauma,hemodynamIcchallenges,exposuretoextracorporealcIrculatIon,
drugadmInIstratIon)andmultIplesusceptIbIlItygenes.TheobservedvarIabIlItyIn
perIoperatIveoutcomescanbepartlyattrIbutedtogenetIcvarIabIlItymodulatIngthe
hostresponsetosurgIcalInjury.DF,operatIngroom;CP8,cardIopulmonarybypass.
Methodologic Approaches to Study the Genetic Architecture of
Common Complex Diseases
|ostongoIngresearchoncomplexdIsordersfocusesonIdentIfyInggenetIcpolymorphIsms
thatenhancesusceptIbIlItyto
P.118
gIvencondItIons.DftenthedesIgnofsuchstudIesIscomplIcatedbythepresenceof
multIplerIskfactors,geneenvIronmentInteractIons,andalackofevenroughestImatesof
thenumberofgenesunderlyIngsuchcomplextraIts.TwobroadstrategIesarebeIng
employedtoIdentIfycomplextraItlocI.Thecandidate geneapproachIsmotIvatedbywhat
IsknownaboutthetraItbIologIcallyandcanbecharacterIzedasahypothesIstestIng
approach,butIsIntrInsIcallybIased.ThesecondstrategyIsthegenomewide scan,InwhIch
thousandsofmarkersunIformlydIstrIbutedthroughoutthegenomeareusedtolocate
regIonsthatmayharborgenesInfluencIngthephenotypIcvarIabIlIty.ThIsIsahypothesIs
freeandunbIasedapproach,InthesensethatnoprIorassumptIonsarebeIngmadeabout
thebIologIcalprocessesInvolvedandnoweIghtIsgIventoknowngenes,thusallowIngthe
detectIonofprevIouslyunknowntraItlocI.8oththecandIdategeneandgenomescan
approachescanbeImplementedusIngoneoftwofundamentalmethodsofIdentIfyIng
polymorphIsmsaffectIngcommondIseases:lInkageanalysIsorassocIatIonstudIesInhuman
populatIons.
Figure 6-2.CategorIesofcommonhumangenetIcvarIatIon.A.Single nucleotide
polymorphisms (SNP)canbesIlentorhavefunctIonalconsequences:changesInamIno
acIdsequenceorprematuretermInatIonofproteInsynthesIs(IftheyoccurInthe
codIngregIonsofthegene)oralteratIonsIntheexpressIonofthegene,resultIngIn
moreorlessproteIn(IftheyoccurInregulatoryregIonsofthegenesuchasthe
promoterregIonortheIntron/exonboundarIes).StructuralgenetIcvarIantsInclude
MicrosatelliteswIthvaryIngnumberofdInucleotIde(CA)nrepeats(B);
Insertions/deletions(C);andCopynumbervarIatIon(CN7;D).A0arelong0NA
segments,segmentCshowsvarIatIonIncopynumber.Clossary:locus,thelocatIonofa
gene/genetIcmarkerInthegenome;alleles,alternatIveformsofagene/genetIc
marker;genotype,theobservedallelesforanIndIvIdualatagenetIclocus;
heterozygous,twodIfferentallelesarepresentatalocus;homozygous,twoIdentIcal
allelesarepresentatalocus.ASNPatposItIon1691ofagenewIthallelesCandA
wouldbewrIttenas1691CA.
Linkage Analysis
LInkageanalysIsIsusedtoIdentIfythechromosomallocatIonofgenevarIantsrelatedtoa
gIvendIseasebystudyIngthedIstrIbutIonofdIseaseallelesInaffectedIndIvIduals
throughoutapedIgreeandhassuccessfullymappedhundredsofgenesforrare,monogenIc
dIsorders.However,commoncomplexdIseasesarecharacterIzedbyamultItudeofgenes
wIthrareand/orcommonalleles,whIchcreateanapparentlychaotIcpatternof
heterogeneItywIthInandbetweenfamIlIes.TheoveralleffectofthIsheterogeneIty,
togetherwIththepotentIallyweakInfluenceofmanylocI,placesaheavyburdenonthe
statIstIcalpowerneededtodetectIndIvIdualcontrIbutInggenes,andmaybethereason
whyveryfewgenomelInkagescanssofarhaveyIeldeddIseaselocIthatmeetgenomewIde
sIgnIfIcancecrIterIa.
11
Furthermore,thenatureofmostcomplexdIseases(especIallyfor
perIoperatIveadverseevents)precludesthestudyofextendedmultIgeneratIonalfamIly
pedIgrees.Nevertheless,afewposItIvefIndIngshaveemergedusIngthIsapproach:astroke
susceptIbIlItylocuswasmappedonchromosome5q12,
12
rIskofmyocardIalInfarctIonwas
mappedtoasIngleregIononchromosome14,
1J
andarecentmetaanalysIsofseveral
genomewIdescansforpulsepressurevarIatIon,anemergIngrIskfactorforperIoperatIve
complIcatIons,hasIdentIfIedseverallInkagebInsonchromosomes22and10.
14
Genetic Association Studies
AssocIatIonstudIesexamInethefrequencyofspecIfIcgenetIcpolymorphIsmsIna
populatIonbasedsampleofunrelateddIseasedIndIvIdualsandapproprIatelymatched
unaffectedcontrols.TheIncreasedstatIstIcalpowertouncoversmallclInIcaleffectsof
multIplegenes
15
andthefactthattheydonotrequIrefamIlybasedsamplecollectIonsare
themaInadvantagesofthIsapproachoverlInkageanalysIs.UntIlveryrecently,most
sIgnIfIcantresultsIndIssectIngcommoncomplexdIseasesweregatheredfromcandIdate
geneassocIatIonstudIes,wIthgenesselectedbecauseofaprIorIhypothesesabouttheIr
potentIaletIologIcroleIndIseasebasedoncurrentunderstandIngofthedIsease
pathophysIology.
16
Forexample,genetIcvarIantswIthIntherenInangIotensInsystem,
17
nItrIcoxIdesynthase,
18
and
2
adrenergIcreceptors,
19
knowntomodulatevasculartone,
weretestedandfoundtobeassocIatedwIthhypertensIon.SImIlarly,thepossIbleeffectsof
polymorphIsmsongenetIcpredIsposItIonforCA0
20
orrestenosIsafterangIoplasty
21
have
beenextensIvelyInvestIgated;morerecently,twolargescaleassocIatIonstudIeshave
IdentIfIedgenevarIantsthatmIghtaffectsusceptIbIlItytomyocardIalInfarctIon.
22
AswIllbepresentedInmoredetaIllater,accumulatIngevIdencefromcandIdategene
assocIatIonstudIesalsosuggeststhatspecIfIcgenotypesareassocIatedwIthavarIetyof
organspecIfIcperIoperatIveadverseoutcomes,IncludIngmyocardIalInfarctIon,
2J,24
neurocognItIvedysfunctIon,
25,26,27
renalcompromIse,
28,29,J0
veIngraftrestenosIs,
J1,J2
postoperatIvethrombosIs,
JJ
vascularreactIvIty,
J4
severesepsIs,
J5,J6
transplantrejectIon,
J7
anddeath(forrevIews,seePodgoreanuandSchwInn
4
andZIegeleretal.
7
).
DneofthemaInweaknessesofthecandIdategeneassocIatIonapproachIsthat,unlessthe
markerofInteresttravels(I.e.,IsInlinkage disequilibrium)wIthafunctIonalvarIant,or
themarkeralleleistheactualfunctIonalvarIant,thepowertodetectandmapcomplex
traItlocIwIllbereduced.DtherknownlImItatIonsofgenetIcassocIatIonstudIesInclude
potentIalfalseposItIvefIndIngsresultIngfrompopulatIonstratIfIcatIon(I.e.,admIxtureof
dIfferentethnIcorgenetIcbackgroundsInthecaseandcontrolgroups),andmultIple
comparIsonIssueswhenlargenumbersofcandIdategenesarebeIngassessed.
J8
FeplIcatIon
offIndIngsacrossdIfferentpopulatIonsorrelatedphenotypesremaInsthemostrelIable
methodofvalIdatIngatruerelatIonshIpbetweengenetIcpolymorphIsmsanddIsease,
16
but
poorreproducIbIlItyInsubsequentstudIeshasbeenoneofthemaIncrItIcIsmsofthe
candIdategeneassocIatIonapproach.
J9
However,arecentmetaanalysIssuggestedthat
lackofstatIstIcalpowermaybethemaIncontrIbutortothIsInconsIstentreplIcatIon,and
proposedmorestrIngentstatIstIcalcrIterIatoexcludefalseposItIveresultsandthedesIgn
oflargecollaboratIveassocIatIonstudIes.
40
Atlast,afterseveraldecadesoffrustratInglImItatIonsIntheabIlItytofIndgenetIc
varIatIonsresponsIbleforcommondIseaserIsk,wIththecompletIonofthesecondphaseof
thenternatIonalHap|apProject(ahIghresolutIonmapsofhumangenetIcvarIatIonand
haplotypes)
9
andadvancesInhIghthroughputgenotypIngtechnologIes,theyear2007
markedanexplosIonofadequatelypoweredandsuccessfullyreplIcatedgenomewide
association studies(CWAS)thatIdentIfIedverysIgnIfIcantgenetIccontrIbutorstorIskfor
commonpolygenIcdIseaseslIkeCA0,
41,42,4J
myocardIalInfarctIon,
44
dIabetes(typeand
),
45,46
atrIalfIbrIllatIon,
47
obesIty,
48
asthma,commoncancers,rheumatoIdarthrItIs,
CrohndIsease,andothers.CWASmakeuseoftheknownlInkagedIsequIlIbrIumpattern
betweenSNPsfromthehumanHap|apandthenewhIghdensItySNPchIptechnologyto
comprehensIvelyInterrogatebetween65and80ofcommonvarIatIonacrossthegenome,
wIthevenhIghercoveragebeIngpossIbleusIngstatIstIcalImputatIontechnIques.The
largest,mostcomprehensIveCWAStodatewasconductedbytheWellcomeTrustCase
ControlConsortIum,InvestIgatIngtheassocIatIonbetween500,000SNPsandsevencommon
dIseasesIn2,000casesandJ,000sharedcontrols.ThIsstudyIdentIfIed25Independent
assocIatIonsIgnalsatstrIngentlevelsofsIgnIfIcance(p510
7
).
41
nterestIngly,varIants
InornearCDKN2A/B(cyclIndependentkInaseInhIbItor2A/8)conferredIncreasedrIskfor
bothtypedIabetes(oddsratIo[DF],1.2;p=7.810
15
)andmyocardIalInfarctIon(DF,
1.64;p=1.210
20
),whIchmayleadtoamechanIstIcexplanatIonforthelInkbetweenthe
twodIsorders.ThIsfIndIngalsohIghlIghtsthepowerofCWAStoIdentIfyvarIantsoutsIde
descrIbedgenes:whIleoneofthesIgnalsoccursIntheCDKN2A/BregIon,theothermuch
strongerassocIatIonsIgnaloccurs200k8fromthesegenes,Inagenedesert,andthus
wouldnothavebeenpIckedupbyacandIdategeneapproach.dentIfyIngthemechanIsm
bywhIchthIsvarIantmayaffectCDKN2A/BexpressIonwIllprovIdenewInsIghtsIntothe
regulatIonoftheseImportantgenes.
P.119
Large-Scale Gene and Protein Expression Profiling: Static
versus Dynamic Genomic Markers of Perioperative Outcomes
CenomIcapproachesareanchoredInthecentraldogmaofmolecularbIology,the
conceptoftranscrIptIonofmessengerFNA(mFNA)froma0NAtemplate,followedby
translatIonofFNAIntoproteIn(FIg.6J).SIncetranscrIptIonIsakeyregulatorystepthat
mayeventuallysIgnalmanyothercascadesofevents,thestudyofFNAlevelsInacellor
organ(I.e.,quantIfyInggeneexpressIon)canImprovetheunderstandIngofawIdevarIety
ofbIologIcalsystems.Furthermore,whIlethehumangenomecontaInsonlyabout25,000
genes,functIonalvarIabIlItyattheproteInlevelIsfarmoredIverse,resultIngfrom
extensIveposttranscrIptIonal,translatIonal,andposttranslatIonalmodIfIcatIons.tIs
belIevedthatthereareapproxImately200,000dIstInctproteInsInhumans,whIchare
furthermodIfIedposttranslatIonallybyphosphorylatIon,glycosylatIon,oxIdatIon,and
dIsulfIdestructures.ThereIsIncreasIngevIdencethatvarIabIlItyIngeneexpressIonlevels
underlIescomplexdIseaseandIsdetermInedbyregulatory0NApolymorphIsmsaffectIng
transcrIptIon,splIcIng,andtranslatIoneffIcIencyInatIssueandstImulusspecIfIc
manner.
49
Thus,InaddItIontotheassessmentofgenetIcvarIabIlItyatthe0NAsequence
levelusIngvarIousgenotypIngtechnIquesasdescrIbedInprevIoussectIons(static
genomics),analysIsoflargescalevarIabIlItyInthepatternofFNAandproteInexpressIon
bothatbaselIneandInresponsetothemultIdImensIonalperIoperatIvestImulI(dynamic
genomics)usIngmIcroarrayandproteomIcapproachesprovIdesamuchneeded
complementaryunderstandIngoftheoverallregulatorynetworksInvolvedInthe
pathophysIologyofadversepostoperatIveoutcomes.SuchdynamIcgenomIcmarkerscanbe
IncorporatedIngenomIcclassIfIersandusedclInIcallytoImproveperIoperatIverIsk
stratIfIcatIonormonItorpostoperatIverecovery.
50
ThIsemergentconceptofmolecular
classificationInvolvesthedescrIptIonofInformatIonalfeaturesInatraInIngdatasetusIng
changesInrelatIveFNAandproteInabundanceInthecontextofgenetIcpredIsposItIonand
applyIngtoatestdatasettorecognIzeadefInedfIngerprIntcharacterIstIcofa
partIcularperIoperatIvephenotype(Table62).Forexample,Feezoretal.
51
useda
combInedgenomIcandproteomIcapproachtoIdentIfyexpressIonpatternsof1J8genes
fromperIpheralbloodleukocytesandtheconcentratIonsof7cIrculatIngplasmaproteIns
thatdIscrImInatedpatIentswhodevelopedmultIpleorgandysfunctIonsyndromeafter
thoracoabdomInalaortIcaneurysmrepaIrfromthosewhodIdnot.|oreImportantly,these
patternsofgenomewIdegeneexpressIonandplasmaproteInconcentratIonwereobserved
beforesurgIcaltraumaandvIsceralIschemIareperfusIonInjury,suggestIngthatpatIents
whodevelopedmultIpleorgandysfunctIonsyndromedIfferedIneIthertheIrgenetIc
predIsposItIonortheIrpreexIstIngInflammatorystate.
51
Figure 6-3.CentraldogmaofmolecularbIology.ProteInexpressIonInvolvestwomaIn
processes,FNAsynthesIs(transcription)andproteInsynthesIs(translation),wIthmany
IntermedIateregulatorysteps.AsInglegenecangIverIsetomultIpleproteInproducts
(Isoforms)vIaalternatIvesplIcIngandFNAedItIng.Thus,functIonalvarIabIlItyatthe
proteInlevel,ultImatelyresponsIbleforbIologIcaleffects,IsthecumulatIveresultof
genetIcvarIabIlItyaswellasextensIveposttranscrIptIonal,translatIonal,and
posttranslatIonalmodIfIcatIons.
AlternatIvely,dynamIcgenomIcmarkerscanbeusedtoImprovemechanIstIc
understandIngofperIoperatIvestressandtoevaluateandcatalogueorganspecIfIc
responsestosurgIcalstressandseveresystemIcstImulIsuchascardIopulmonarybypass
(CP8)andendotoxemIa,whIchcanbesubsequentlyusedtoIdentIfyandvalIdatenovel
targetsfororganprotectIvestrategIes.
52
UsIngasImIlarIntegratedapproachof
transcrIptomIcandproteomIcanalyses,TomIcetal.
5J
characterIzedthemolecular
responsesIgnaturesInperIpheralbloodtocardIacsurgerywIthandwIthoutCP8,arobust
trIggerofsystemIcInflammatIon.Theauthorsdemonstratedthat,ratherthanbeIngthe
prImarysourceofserumcytokInes,perIpheralbloodleukocytesonlyassumeaprImed
phenotypeoncontactwIththeextracorporealcIrcuIt,whIchfacIlItatestheIrtrappIngand
subsequenttIssueassocIatedInflammatoryresponse.nterestIngly,manyInflammatory
medIatorsachIevedsImIlarsystemIclevelsfollowIngoffpumpsurgerybutwIthdelayed
kInetIcs,offerIngnovelInsIghtsIntotheconceptsofcontactactIvatIonand
compartmentalIzatIonofInflammatoryresponsestomajorsurgery.SeveralstudIeshave
profIledmyocardIalgeneexpressIonIntheIschemIcheart,demonstratIngalteratIonsInthe
expressIonofImmedIateearlygenes(cfos,jun8),aswellasgenescodIngforcalcIum
handlIngproteIns(calsequestrIn,phospholamban),extracellularmatrIxandcytoskeletal
proteIns.
54
UpregulatIonoftranscrIptsmechanIstIcallyInvolvedIncytoprotectIon(heatshock
proteIns),resIstancetoapoptosIs,andcellgrowthhasbeenfoundInstunned
myocardIum.
55
|oreover,cardIacgeneexpressIonprofIlIngafterCP8andcardIoplegIc
arresthasIdentIfIedtheupregulatIonofInflammatoryandtranscrIptIonactIvators,
apoptotIcgenes,andstressgenes,
56
whIchappeartobeagerelated.
57
|Icroarray
technologyhasalsobeenusedInthequestfornovelcardIoprotectIvegenes,wIththe
ultImategoalofdesIgnIngstrategIestoactIvatethesegenesandpreventmyocardIal
Injury.PrecondItIonIngIsoneofsuchwellstudIedmodelsofcardIoprotectIon,whIchcan
beInducedbyvarIoustrIggersIncludIngIntermIttentIschemIa,osmotIcorredoxstress,
heatshock,toxIns,andInhaledanesthetIcs.ThemaInfunctIonalcategorIesofgenes
IdentIfIedaspotentIallyInvolvedIncardIoprotectIvepathwaysIncludeahostof
transcrIptIonfactors,heatshockproteIns,antIoxIdantgenes(hemeoxygenase,glutathIone
peroxIdase),andgrowthfactors,butdIfferentgeneprogramsappeartobeactIvatedIn
IschemIcversusanesthetIcprecondItIonIng,resultIngIntwodIstInctcardIoprotectIve
phenotypes.
58
|orerecently,atranscrIptIonalresponsepatternconsIstentwIthlate
precondItIonInghasbeenreportedInperIpheralbloodleukocytesfollowIngsevoflurane
admInIstratIonInhealthyvolunteers,characterIzedbyreducedexpressIonofLselectInas
wellasdownregulatIonofgenesInvolvedInfattyacIdoxIdatIonandthePCC1
(peroxIsomeactIvatedreceptorgammacoactIvator1)pathway,
59
whIchmIrrorschanges
observedInthemyocardIumfrompatIentsundergoIngoffpumpcoronaryarterybypass
surgery(CA8C;Table62).
60
0eregulatIonofthesenovelsurvIvalpathways
P.120
thusappearstogeneralIzeacrosstIssues,makIngthemImportanttargetsfor
cardIoprotectIon,butfurtherstudIesareneededtocorrelateperIoperatIvegene
expressIonresponsepatternsInendorganssuchasthemyocardIumtothoseInreadIly
avaIlablepotentIalsurrogatetIssuessuchasperIpheralbloodleukocytes.
Table 6-2 Summary of Gene Expression Studies with Implications for
Perioperative Cardiovascular Outcomes
Tissue (Species) Stimulus/Method Genomic Signature: Number/Types of Genes Reference
|yocardIum
(rat)
schemIa/A 14(woundhealIng,CahandlIng) 54
|yocardIum
(human)
CP8/cIrculatory
arrest/A
58(InflammatIon,transcrIptIon
actIvators,apoptosIs,stress
response)adults
50(cardIoprotectIve,
antIprolIferatIve,antIhypertrophIc)
neonates
56
57
|yocardIum
(rat)
PCvsAPC/A
566dIfferentIallyregulated/56
joIntlyregulated(celldefense)
58
|yocardIum
(rat)
APCvs
ApostC/A
DpposInggenomIcprofIles,8gene
clusters,2joIntlyregulatedgenes
184
|yocardIum
(human)
APC,DPCA8,
postoperatIve
L7functIon/A
J19upregulatedand281down
regulatedgenesetsInresponseto
DPCA8;deregulatIonoffattyacId
oxIdatIon,0NAdamagesIgnalIngand
CCSFsurvIval(perIoperatIve)and
PCC1(constItutIve)pathways
predIctImprovedL7functIonIn
sevofluranetreatedpatIents
60
P8|C
(human)
APC,
sevoflurane/A
0eregulatIonoflateprecondItIonIng,
PCC1,fattyacIdoxIdatIon,andL
selectInpathways
59
AtrIal
myocardIum
(pIg)
PacIngInduced
AF/A+P
81(|CL2ventrIcular/atrIalIsoform
shIft)
185
AtrIal
myocardIum
(human)
AF/A
1,4J4(ventrIcularlIkegenomIc
sIgnature)
101
P8|C
(human)
CardIac
surgery,
PoAF/A
1,J02genesunIquelyderegulatedIn
PoAF/401upregulated(oxIdatIve
stress),902downregulated
102
P8|C
(human)
CardIac
surgery,
PDC0/A
1,201genesunIquelyderegulatedIn
PDC0/5J1
Upregulated,670downregulated
(InflammatIon,antIgenpresentatIon,
celladhesIon,andapoptosIs)
122
P8|C
(human)
Heart
transplant/A
J0(profIlecorrelatedwIthbIopsy
provenrejectIon;persIstentImmune
actIvatIonInresponsetotreatment)
186
187
P8|C
(human)
Heart
transplant/FT
PCF
20(Allo|ap,Allo|apscore)
|yocardIum
(human)
Heart
transplant/P
2(Increased8crystallInand
tropomyosInserumlevels)
188
P8|C,
plasma
(human)
TAAA/A+P
1J8genesand7plasmaproteIns
predIcted|D0S
51
A,mIcroarray;CP8,cardIopulmonarybypass;PC,IschemIcprecondItIonIng;APC,
anesthetIcprecondItIonIng;APostC,anesthetIcpostcondItIonIng;DPCA8,offpump
coronaryarterybypass;L7,leftventrIcle;CCSFgranulocytecolonystImulatIng
factor;PCC1,peroxIsomeprolIferatorsactIvatedreceptorcofactor1;AF,
atrIalfIbrIllatIon;|CL2,myosInlIghtchaIn2;P,proteomIcs;P8|C,perIpheral
bloodmononuclearcells;PoAF,postoperatIveatrIalfIbrIllatIon;PDC0,
postoperatIvecognItIvedeclIne;FTPCF,realtImepolymerasechaInreactIon;
TAAA,thoracoabdomInalaortIcaneurysmrepaIr;|D0S,multIpleorgandysfunctIon
syndrome.
Thetranscriptome(thecompletecollectIonoftranscrIbedelementsofthegenome)Isnot
fullyrepresentatIveoftheproteome(thecompletecomplementofproteInsencodedbythe
genome)becausemanytranscrIptsarenottargetedfortranslatIon,asevIdencedrecently
wIththeconceptofgenesIlencIngbyFNAInterference.AlternatIvesplIcIng,awIdevarIety
ofposttranslatIonalmodIfIcatIons,andproteInproteInInteractIonsresponsIblefor
bIologIcalfunctIon,thereforewouldremaInundetectedbygeneexpressIonprofIlIng(FIg.6
J).ThIshasledtotheemergenceofanewfIeld,proteomics,studyIngthesequence,
modIfIcatIon,andfunctIonofmanyproteInsInabIologIcalsystematagIventIme.Father
thanfocusIngonstatIc0NA,proteomIcstudIesexamInedynamIcproteInproductswIth
thegoalofIdentIfyIngproteInsthatundergochangesInabundance,modIfIcatIon,or
localIzatIonInresponsetoapartIculardIseasestate,trauma,stress,ortherapeutIc
InterventIon(forarevIew,seeAtkInsandJohansson
61
).Thus,proteomIcsoffersamore
globalandIntegratedvIewofbIology,complementIngotherfunctIonalgenomIc
approaches.CurrentlyavaIlablemethodsforproteomIcanalysIsIncludeproteInextractIon,
separatIonbytwodImensIonalgelelectrophoresIsorchromatography,followedby
IdentIfIcatIonusIngmassspectrometry.AlthoughrapIdlyImprovIng,thesemethodsare
currentlylImItedbysensItIvIty,specIfIcIty,andthroughput.SeveralpreclInIcalproteomIc
studIesrelevanttoperIoperatIvemedIcInehavecharacterIzedthetemporalchangesIn
braInproteInexpressIonInresponsetovarIousInhaledanesthetIcs,
62,6J
orfollowIng
cardIacsurgerywIthhypothermIccIrculatoryarrest.
64
ThIsmayfocusfurtherstudIesaImed
toIdentIfynewanesthetIcbIndIngsItes,andthedevelopmentofneuroprotectIve
strategIes.Furthermore,detaIledknowledgeoftheplasmaproteomehasprofound
ImplIcatIonsInperIoperatIvetransfusIonmedIcIne,
65
partIcularlythoserelatedtopeptIde
andproteInchangesthatoccurdurIngstorageofbloodproducts.Thedevelopmentof
proteInarraysandrealtImeproteomIcanalysIstechnologIeshasthepotentIaltoallowthe
useoftheseversatIleandrIgoroushIghthroughputmethodsforclInIcalapplIcatIons,andIs
theobjectofIntenseInvestIgatIon.
P.121
Genomics and Perioperative Risk Profiling
|orethan40mIllIonpatIentsundergosurgeryannuallyIntheUnItedStatesatacostof
S450bIllIon.EachyearapproxImately1mIllIonpatIentssustaInmedIcalcomplIcatIons
aftersurgery,resultIngIncostsofS25bIllIonannually.TheproportIonoftheU.S.
populatIonolderthan65IsestImatedtodoubleInthenexttwodecades,leadIngtoa25
IncreaseInthenumberofsurgerIes,a50IncreaseInsurgeryrelatedcosts,anda100
IncreaseIncomplIcatIonsfromsurgery.FecognIzIngthesIgnIfIcantIncreaseInsurgIcal
burdenduetoacceleratedagIngofthepopulatIonandIncreasedrelIanceonsurgeryfor
treatmentofdIsease,theNatIonalHeart,8loodandLungnstItutehasrecentlyconveneda
WorkIngCrouponperIoperatIvemedIcIne.ThegroupconcludedthatperIoperatIve
complIcatIonsaresIgnIfIcant,costly,varIablyreported,andoftenImprecIselydetected,
andIdentIfIedacrItIcalneedforaccuratecomprehensIveperIoperatIveoutcome
databases.Furthermore,presurgIcalrIskprofIlIngIsInconsIstentanddeservesfurther
attentIon,especIallyfornoncardIac,nonvascularsurgeryandolderpatIents
66
(seeChapter
J5).
AlthoughmanypreoperatIvepredIctorshavebeenIdentIfIedandareconstantlybeIng
refIned,rIskstratIfIcatIonbasedonclInIcal,procedural,andbIologIcalmarkersexplaIns
onlyasmallpartofthevarIabIlItyIntheIncIdenceofperIoperatIvecomplIcatIons.As
prevIouslymentIoned,ItIsbecomIngIncreasInglyrecognIzedthatperIoperatIvemorbIdIty
arIsesasadIrectresultoftheenvIronmentalstressofsurgeryoccurrIngonalandscapeof
susceptIbIlItythatIsdetermInedbyanIndIvIdual'sclInIcalandgenetIccharacterIstIcs,and
mayevenoccurInotherwIsehealthyIndIvIduals.SuchadverseoutcomeswIlldeveloponly
InpatIentswhosecombInedburdenofgenetIcandenvIronmentalrIskfactorsexceedsa
certaInthreshold,whIchmayvarywIthage.dentIfIcatIonofsuchgenetIccontrIbutIonsto
notonlydIseasecausatIonandsusceptIbIlIty,butalsoInfluencIngtheresponsetodIsease
anddrugtherapyandIncorporatIonofgenetIcrIskInformatIonInclInIcaldecIsIonmakIng,
mayleadtoImprovedhealthoutcomesandreducedcosts.ForInstance,understandIngthe
geneenvIronmentInteractIonsInvolvedInatherosclerotIccardIovasculardIseaseand
neurologIcInjurymayfacIlItatepreoperatIvepatIentoptImIzatIonandresourceutIlIzatIon.
Furthermore,understandIngtheroleofallotypIcvarIatIonInproInflammatoryand
prothrombotIcpathways,themaInpathophysIologIcalmechanIsmsresponsIblefor
perIoperatIvecomplIcatIons,maycontrIbutetothedevelopmentoftargetspecIfIc
therapIes,therebylImItIngtheIncIdenceofadverseeventsInhIghrIskpatIents.To
IncreaseclInIcalrelevanceforthepractIcIngperIoperatIvephysIcIan,wesummarIze
exIstIngevIdencebyspecIfIcoutcomewhIlehIghlIghtIngcandIdategenesInrelevant
mechanIstIcpathways(Tables6J,64and65).
Genetic Susceptibility to Adverse Perioperative
Cardiovascular Outcomes
Perioperative Myocardial Infarction
AspartofthepreoperatIveevaluatIon,anesthesIologIstsareInvolvedInassessIngtherIsks
ofperIoperatIvecomplIcatIons.tIscommonlyacceptedthatpatIentswhohaveunderlyIng
cardIovasculardIseaseareatrIskforadversecardIaceventsaftersurgery,andseveral
multIfactorIalrIskIndIceshavebeendevelopedandvalIdatedforpatIentsundergoIngboth
noncardIacsurgIcalprocedures(suchastheColdmanortheLeeCardIacFIskndex),as
wellascardIacsurgery(suchastheHannanorSergeantscores).However,IdentIfyIng
patIentsatthehIghestrIskofperIoperatIveInfarctIonremaInsdIffIcult.FIskscores,whIle
potentIallyvaluableforpopulatIonstudIes,arenotanIdealtoolfordIrectIngcareInan
IndIvIdualpatIent.
67
CenomIcapproacheshavebeenusedInthesearchforabetter
assessmentoftheIndIvIdualcoronaryrIskprofIle.NumerousreportsfromanImalmodels,
lInkageanalysIs,famIly,twIn,andpopulatIonassocIatIonstudIeshavedefInItelyproven
theroleofgenetIcInfluencesIntheIncIdenceandprogressIonofCA0,wIthaherItabIlItyof
deathfromCA0ashIghas0.58.Furthermore,hazardouspatternsofangIographIcCA0(left
maInandproxImaldIsease),knownmajorrIskfactorsforperIoperatIvecardIac
complIcatIons,arealsohIghlyherItable.SImIlarly,genetIcsusceptIbIlItytomyocardIal
InfarctIonhasbeenestablIshedthroughmultIplelInesofevIdence,
1J,22
IncludIngarecent
wellpoweredandreplIcatedCWAS.
44
AlthoughthesestudIesdonotdIrectlyaddressthe
herItabIlItyofadverseperIoperatIvemyocardIalevents,theydosuggestastronggenetIc
contrIbutIontotherIskofadversecardIovascularoutcomesIngeneral.
0espIteadvancesInsurgIcal,cardIoprotectIve,andanesthetIctechnIques,theIncIdenceof
perIoperatIvemyocardIalInfarctIon(P|)followIngcardIacandvascularsurgeryInseveral
largerandomIzedclInIcaltrIalshasbeenreportedat7to19
68,69
andIsconsIstently
assocIatedwIthreducedshortandlongtermsurvIval.nthesettIngofcardIacsurgery,
P|InvolvesthreemajorconvergIngpathophysIologIcalprocesses,IncludIngsystemIcand
localInflammatIon,vulnerableblood,andneuroendocrInestress
4
(seeChapter12).n
noncardIacsurgery,pathophysIologyofP|Isnotsoclearlyunderstood,butacombInatIon
oftwomechanIsmsappearspredomInant:(1)plaqueruptureandcoronarythrombosIs
trIggeredbyperIoperatIveendothelIalInjuryfromcatecholamInesurges,proInflammatory
andprothrombotIcstates;and(2)prolongedstressInducedIschemIaandtachycardIaInthe
settIngofcompromIsedperfusIon.ExtensIvegenetIcvarIabIlItyexIstsIneachofthese
mechanIstIcpathways,whIchmaycombInetomodulatethemagnItudeofmyocardIal
Injury.However,onlyapaucItyofstudIesexIstsrelatInggenetIcrIskfactorstoadverse
perIoperatIvemyocardIaloutcomes,maInlyfollowIngCA8Csurgery(Table6J).
J1,70,71
Inflammation Variability and Perioperative Myocardial Outcomes.ConsIstentwIththe
InflammatoryhypothesIsInthepathogenesIsofperIoperatIveorganInjury,ourgrouphas
recentlyIdentIfIedthreeInflammatorygenepolymorphIsmsthatareIndependently
predIctIveofP|followIngcardIacsurgerywIthCP8(seeChapter41).TheseIncludethe
proInflammatorycytokIneIL6572CC(DF2.47)andtwoadhesIonmolecules:Intercellular
adhesIonmolecule1(ICAM1Lys469Clu,DF1.88)andEselectIn(SELE98CT,DF0.16).
2J
mportantly,InclusIonofgenotypIcInformatIonfromtheseSNPsImprovespredIctIon
modelsforpostcardIacsurgerymyocardIalInfarctIonbasedontradItIonalrIskfactors
alone.UsIngasImIlardefInItIonofP|,Collardetal.
24
havereportedthatacombIned
haplotypeInthemannosebIndInglectIngene(MBL2LYQAsecretorhaplotype),an
ImportantrecognItIonmoleculeInthelectIncomplementpathway,IsIndependently
assocIatedwIthP|InacohortofwhItepatIentsundergoIngprImaryCA8CwIthCP8.
Furthermore,genetIcvarIantsInIL6andTNFAareassocIatedwIthIncreasedIncIdenceof
postoperatIvecardIovascularcomplIcatIons(acomposIteoutcomethatIncludedP|)
followInglungresectIonforcancer.
72
DthergenetIcvarIantsmodulatIngthemagnItudeof
postoperatIveInflammatoryresponsehavebeenIdentIfIed.PolymorphIsmsInthepromoter
oftheInterleukIn6(IL6)gene(572CCand174CC)sIgnIfIcantlyIncreasethe
InflammatoryresponseafterheartsurgerywIthCP8,
7J
andhavebeenassocIatedwIth
lengthofhospItalIzatIonafterCA8C.
74
Furthermore,apolIpoproteInEgenotype(the4
allele),
75
P.122
P.12J
severalvarIantsInthetumornecrosIsfactorgenes(TNFAJ08CA,LTA+250CA),
76
anda
functIonalSNPInthemacrophagemIgratIonInhIbItoryfactor
77
havebeenassocIatedwIth
proInflammatoryeffectsInpatIentsundergoIngCP8,andInsomeInstanceswIth
postoperatIveventrIculardysfunctIon.
78
naddItIon,agenetIcvarIantmodulatIngthe
releaseoftheantIInflammatorycytokIneInterleukIn10(IL10)InresponsetoCP8hasbeen
reported(IL101082CA),wIthhIghlevelsofL10beIngassocIatedwIthpostoperatIve
ventrIculardysfunctIon.
79
Table 6-3 Representative Genetic Polymorphisms Associated with Altered
Susceptibility to Adverse Perioperative Cardiovascular Events
Gene Polymorphism Type of Surgery OR Reference
Perioperative Myocardial Infarction/Dysfunction, Early Vein Graft Failure
IL6 572CC,174CC CardIac/CP8,thoracIc 2.47,1.8 2J,72
ICAM-1 E469L CardIac/CP8 1.88 2J
SELE 98CT 0.16 2J
MBL2
LYQAsecretor
haplotype
CA8C/CP8 J.97 24
ITGB3
LJJP(Pl
A1
/Pl
A2
)
CA8C/CP8,major
vascular
2.5
a
,2.4 8J,85
GP1BA T145| |ajorvascular J.4 85
TNFA J08CA ThoracIc 2.5 72
TNFB
(LTA)
TNF82 CardIac/CP8 J.84 78
IL10 1082CA CardIac/CP8 n.r. 79
F5 F506Q(F7L) CA8C/CP8 J.29 87
CMA1 1905AC CA8C/CP8 n.r. J1
PAI-1 4C/5C CA8C n.r. 81
Perioperative Vasoplegia, Vascular Reactivity, Coronary Tone
DDAH II 449CC CardIac/CP8 0.4 9J
NOS3 E2980 n.r.
90,
189
ACE n/del n.r. J4,91
ADRB2 Q27E TrachealIntubatIon 11.7
b
92
GNB3 825CT
FesponsetoAF
agonIsts
n.r. 189
PON1 Q192F FestIngcoronarytone n.r. 189
Postoperative Arrhythmias: Atrial Fibrillation, QTc Prolongation
IL6 174CC
CA8C/CP8betablocker
faIlure,
J.25n.r.
1.8
96,98
ThoracIc 190,72
RANTES 40JCA 8etablockerfaIlure n.r. 190
TNFA J08CA ThoracIc 2.5 72
IL1B 511TC5810CA CardIac/CP8
1.44,
0.66
191
Postoperative MACE, Late Vein Graft Failure
ADRB1 FJ89C
NoncardIacwIthspInal
block
1.87
C
89
ACE n/del CA8C/CP8 J.1
d
71
ITGB3 LJJP 4.7 84
MTHFR A2227 PTCAandCA8C/C8P 2.8 192
ADRB2 F16C,Q27E CardIacsurgery/CP8
1.96,
2.82
105
HP Hp1/Hp2 CA8C n.r. 70
CR1, KDR, MICA
HLA-DPB1,
VTN
CA8C/CP8 n.r. J2
LPL HInd n.r. 19J
Cardiac Allograft Rejection
TNFA J08CA CardIactransplant n.r. 194
IL10 1082CA n.r. 194
ICAM1 K469E n.r. 195
IL1RN 86bp7NTF ThoracIctransplant 2.02 196
IL1B J95JCT 20.5
e
196
DF,oddsratIo;L6,InterleukIn6;CP8,cardIopulmonarybypass;CA|1,
IntercellularadhesIonmolecule1;SELE,EselectIn;|8L2,mannosebIndInglectIn
2;CA8C,coronaryarterybypassgraft;TC8J,glycoproteIna;CP18A,
glycoproteInb;TNFA,tumornecrosIsfactor;TNF8,tumornecrosIsfactor;
LTA,lymphotoxIn;L10,InterleukIn10;n.r.,notreported;F5,factor7;F7L,
factor7LeIden;C|A1,heartchymase;PA1,plasmInogenactIvatorInhIbItor1;
00AH,dImethylargInInedImethylamInohydrolase;NDSJ,endothelIalnItrIc
oxIdesynthase;ACE,angIotensInconvertIngenzyme;n/del,InsertIon/deletIon;
A0F82,
2
adrenergIcreceptor;CN8J,CproteInJsubunIt;AF,adrenergIc
receptor;PDN1,paraoxonase1;FANTES,regulatedonactIvatIonnormallyT
expressedandsecreted;L18,InterleukIn1;A0F81,
1
adrenergIcreceptor;
|THFF,methylenetetrahydrofolatereductase;PTCA,percutaneoustranslumInal
coronaryangIoplasty;HP,haptoglobIn;CF1,complementcomponentJb/4b;K0F,
kInaseInertdomaInreceptor;|CA,|HCpolypeptIde;HLA0P81,chaInofclass
majorhIstocompatIbIlItycomplex;7TN,vItronectIn;LPL,lIpoproteInlIpase;
L1FN,InterleukIn1receptorantagonIst;7NTF,varIablenumbertandemrepeat.
a
FelatIverIsk.
b
Fvalue.
C
HazardratIo.
d
coeffIcIent.
e
nhaplotypewIthL1FN7NTF.
Coagulation Variability and Perioperative Myocardial Outcomes.naddItIontorobust
InflammatoryactIvatIon,thehostresponsetosurgeryIsalsocharacterIzedbyanIncrease
InfIbrInogenconcentratIon,plateletadhesIveness,andplasmInogenactIvatorInhIbItor1
(PA1)productIon(seeChapter16).0urIngcardIacsurgery,alteratIonsInthehemostatIc
systemareevenmorecomplexandmultIfactorIal,IncludIngtheeffectsofhypothermIa,
hemodIlutIon,andCP8InducedactIvatIonofcoagulatIon,fIbrInolytIc,andInflammatory
pathways.PerIoperatIvethrombotIcoutcomesfollowIngcardIacsurgery(e.g.,coronary
graftthrombosIs,myocardIalInfarctIon,stroke,pulmonaryembolIsm)representone
extremeonacontInuumofcoagulatIondysfunctIon,wIthcoagulopathyattheotherendof
thespectrum(seeChapter16).PathophysIologIcally,thebalancebetweenbleedIng,normal
hemostasIs,andthrombosIsIsmarkedlyInfluencedbytherateofthrombInformatIonand
plateletactIvatIon.FecentevIdencesuggeststhatgenetIcvarIabIlItymodulatesthe
actIvatIonofeachofthesemechanIstIcpathways,
80
suggestIngsIgnIfIcantherItabIlItyof
theprothrombotIcstate(seeTable65foranovervIewofgenetIcvarIantsassocIatedwIth
postoperatIvebleedIng).
SeveralgenotypeshavebeenassocIatedwIthIncreasedrIskofcoronarygraftthrombosIs
andmyocardIalInjuryfollowIngCA8C.PA1IsanImportantnegatIveregulatorof
fIbrInolytIcactIvIty;avarIantInthepromoterofthePAI-1gene,consIstIngofanInsertIon
(5C)/deletIon(4C)polymorphIsmatposItIon675,hasbeenconsIstentlyassocIatedwIth
changesIntheplasmalevelsofPA1.The4CalleleIsassocIatedwIthIncreasedrIskof
earlygraftthrombosIsafterCA8C
81
and,InarecentmetaanalysIs,wIthIncreased
IncIdenceofmyocardIalInfarctIon.
82
SImIlarly,apolymorphIsmIntheplateletglycoproteIn
agene(ITGB3),resultIngInIncreasedplateletaggregatIon(Pl
A2
polymorphIsm),Is
assocIatedwIthhIgherpostoperatIvelevelsoftroponInfollowIngCA8C
8J
andIncreased
rIskfor1yearthrombotIccoronarygraftocclusIon,myocardIalInfarctIon,anddeath
followIngCA8C.
84
Dntheotherhand,InpatIentsundergoIngmajorvascularsurgery,two
SNPsInplateletglycoproteInreceptors(ITGB3andGP1BA)areIndependentrIskpredIctors
ofP|andresultInImproveddIscrImInatIonofanIschemIarIskassessmenttoolwhen
addedtohIstorIcandproceduralrIskfactors.
85
DneofthemostcommonInherIted
prothrombotIcrIskfactorsIsapoIntmutatIonIncoagulatIonfactor7(1691CA)resultIngIn
resIstancetoactIvatedproteInC,andreferredtoasfactor7LeIden(F7L).F7Lhasbeen
assocIatedwIthvarIouspostoperatIvethrombotIccomplIcatIonsfollowIngnoncardIac
surgery(forarevIew,see0onahue
JJ
),butInterestIngly,alsoassocIatedwIthasIgnIfIcant
reductIonInpostoperatIvebloodlossandoverallrIskoftransfusIonIncardIacsurgery
patIents.
86
naprospectIvestudyofCA8CpatIentswIthroutIneJmonthpostoperatIve
angIographIcfollowup,ahIgherproportIonofF7LcarrIershadgraftocclusIoncomparedto
noncarrIers.
87
Genetic Variability and Perioperative Vascular Reactivity.PerIoperatIvestressresponses
arealsocharacterIzedbyrobustsympathetIcnervoussystemactIvatIon,knowntoplaya
roleInthepathophysIologyofP|,thuspatIentswIthCA0andspecIfIcadrenergIcreceptor
(AF)genetIcpolymorphIsmsmaybepartIcularlysusceptIbletocatecholamInetoxIcItyand
cardIaccomplIcatIons.SeveralfunctIonallyImportantSNPsmodulatIngAFpathwayshave
beencharacterIzed(forrevIew,seeZauggetal.
88
).DnesuchvarIant,theArgJ89Cly
polymorphIsmIn1AFgene(ADRB1),wasrecentlyassocIatedwIthIncreasedrIskofa
composItecardIovascularmorbIdItyoutcomeat1yearfollowIngnoncardIacsurgeryunder
spInalanesthesIa,whIleperIoperatIvebetablockadehadnosIgnIfIcanteffect.
89
The
authorssuggestthatproperanalysIsoffutureperIoperatIvebetablockertrIalsshouldbe
stratIfIedbyAFgenotype,whIchmayhelpIdentIfypatIentslIkelytobenefItfromthIs
therapy.SIgnIfIcantlyIncreasedvascularresponsIvenesstoadrenergIcstImulatIon
(phenylephrIne)wasfoundIncarrIersoftheendothelIalnItrIcoxIdesynthase894CT
polymorphIsm,
90
andangIotensInconvertIngenzyme(ACE)InsertIon/deletIon(/0)
polymorphIsm
J4,91
undergoIngcardIacsurgerywIthCP8.TwostudIeshavereportedonthe
roleof2AF(ADRB2)genetIcvarIantsInperIoperatIvevascularreactIvIty.ncreasedblood
pressureresponsestoendotrachealIntubatIonhavebeenassocIatedwIthacommon
functIonalADRB2SNP(Clu27).
92
Thesecondstudy,conductedIntheobstetrIcpopulatIon,
showedthatIncIdenceandseverItyofmaternalhypotensIonfollowIngspInalanesthesIafor
cesareandelIvery,aswellastheresponsetotreatment,wasaffectedbyADRB2genotype
(Cly16and/orClu27ledtolowervasopressoruseforthetreatmentofhypotensIon).n
cardIacsurgerypatIents,thedevelopmentofvasoplegIcsyndromeIsonemanIfestatIonof
theperIoperatIvesystemIcInflammatoryresponse,butremaInspoorlypredIctedbyclInIcal
andproceduralrIskfactors.7asopressorrequIrementaftersurgeryIsassocIatedwItha
commonpolymorphIsmInthedImethylargInInedImethylamInohydrolase(DDAH II)gene,
anImportantregulatorofnItrIcoxIdesynthaseactIvIty.
9J
Perioperative Atrial Fibrillation
NewonsetperIoperatIveatrIalfIbrIllatIon(PoAF)remaInsacommoncomplIcatIonof
cardIacandmajornoncardIacthoracIcsurgIcalprocedures(IncIdence27to40),andIs
assocIatedwIthIncreasedmorbIdIty,hospItallengthofstay,rehospItalIzatIon,healthcare
costs,andreducedsurvIval.SeverallargeprospectIvemultIcentertrIalshavedeveloped
andvalIdatedcomprehensIverIskIndIcesforoccurrenceofPoAFbasedondemographIc,
clInIcal,electrocardIographIc,andproceduralrIskfactors,buttheIrpredIctIveaccuracy
remaInsatbestmoderate,
94
suggestInganInherentgenetIcpreoperatIverIsk.HerItable
formsofAFoccurIntheambulatorynonsurgIcalpopulatIon,andItappearsthatboth
monogenIcformslIkeloneAFaswellaspolygenIcpredIsposItIontomorecommon
acquIredformslIkePoAFdoexIst.
95
Fecently,ateamledbyresearchersatdeCD0E
genetIcs(FeykjavIk,celand)reportedtheresultsofagenomewIdeassocIatIonstudyfor
AF;twopolymorphIsmsonchromosome4q25demonstratedahIghlysIgnIfIcantassocIatIon
(p=J.J10
41
)wIthAF,
47
wIthfIndIngsreplIcatedInotherpopulatIonsfromSweden,the
UnItedStates,andHongKong,althoughthemechanIsmofactIonforthesevarIants
remaInsunknown.Dntheotherhand,candIdatesusceptIbIlItygenesforPoAFIncludethose
determInIngactIon,potentIalduratIon(voltagegatedIonchannels,Iontransporters),
responsestoextracellularfactors(adrenergIcandotherhormonereceptors,heatshock
proteIns),remodelIngprocesses,andmagnItudeofInflammatoryandoxIdatIvestress.n
partIcular,aroleforInflammatIonforPoAFIssuggestedbythefactthatbaselIneC
reactIveproteIn(CFP)levelsInmalepatIentsandexaggeratedpostoperatIveleukocytosIs
bothpredIctPoAF,whereaspostoperatIveadmInIstratIonofnonsteroIdalantI
InflammatorydrugsshowsaprotectIveeffect.However,specIfIcevIdenceforagenetIc
roleInPoAFIssparse.AfunctIonalSNPIn
P.124
theIL6promoter(174CC)IsassocIatedwIthplasmaperIoperatIveL6levelsandseveral
clInIcaloutcomesafterCA8Csurgery,IncludIngPoAF
96,97
,andIndependentlyvalIdated.
98
AddItIonally,polymorphIsmsIntwoInflammatorygenes(IL6andTNFA)areassocIatedwIth
composItepostoperatIvemorbIdIty(IncludIngnewonsetarrhythmIas)followInglung
resectIonprocedures.
72
ThereIshoweveracontradIctorylackofassocIatIonbetweenCFP
levels(stronglyregulatedbyL6)andPoAFInwomenundergoIngcardIacsurgery.
99
Dnthe
otherhand,arecentstudyreportedthatof21serumbIomarkersInvestIgatedIn
relatIonshIpwIthPoAF,bothpreandpostoperatIvePA1levelsareIndependently
assocIatedwIthdevelopmentofPoAFfollowIngcardIacsurgery.
100
SeveralgroupshaveInvestIgatedtranscrIptIonalresponsestoAFInhumanatrIal
appendagemyocardIumobtaInedatthetImeofcardIacsurgeryorInpreclInIcalanImal
models(Table62),andIdentIfIedaventrIcularlIkegenomIcsIgnatureInfIbrIllatIngatrIa,
wIthIncreasedratIosofventrIculartoatrIalIsoforms,suggestIngdedIfferentIatIon.
101
AlthoughItremaInsunclearwhetherthIsventrIcularIzatIonofatrIalgeneexpressIon
reflectscauseoreffectofAF,ItneverthelessseemstorepresentanadaptIveenergysavIng
processtothehIghmetabolIcdemandoffIbrIllatIngatrIalmyocardIum,akIntochronIc
hIbernatIon.ArecentstudyInvestIgatInggeneexpressIonchangesInperIpheralblood
leukocytesInrelatIonshIptoPoAFfollowIngcardIacsurgeryhassuggestedthatpatIents
whoexhIbItPoAFdIsplayadIfferentIalgenomIcresponsetoCP8,characterIzedbyup
regulatIonofoxIdatIvestressgenes,whIchcorrelatedwIthasIgnIfIcantlylargerIncreaseIn
oxIdantstressbothsystemIcally(asmeasuredbytotalperoxIdelevels)aswellasatthe
myocardIallevel(asmeasuredIntherIghtatrIum).
102
Cardiac Allograft Rejection
dentIfIcatIonofperIpheralbloodgeneandproteInbasedbIomarkerstononInvasIvely
monItor,dIagnose,andpredIctperIoperatIvecardIacallograftrejectIonIsanareaofrapId
scIentIfIcgrowth(seeChapter54).WhIleseveralpolymorphIsmsIngenesInvolvedIn
alloImmuneInteractIons,therenInangIotensInaldosteronesystemandthetransformIng
growthfactorsuperfamIlyhavebeenassocIatedwIthcardIactransplantoutcomes,theIr
relevanceasusefulclInIcalmonItorIngtoolsremaInsuncertaIn.However,perIpheralblood
mononuclearcellbasedmolecularassayshaveshownmuchpromIseformonItorIngthe
dynamIcresponsesoftheImmunesystemtothetransplantedheart,dIscrImInatIng
ImmunologIcallograftquIescenceandpredIctIngfuturerejectIon.
10J
AnonInvasIve
moleculartesttoIdentIfypatIentsatrIskforacutecellularrejectIonIscommercIally
avaIlable(Allo|ap,X0x8rIsbane,CA),InwhIchtheexpressIonlevelsof20genesIs
measuredbyquantItatIverealtImepolymerasechaInreactIon(qFTPCF)andtranslated
usIngamathematIcalalgorIthmIntoaclInIcallyactIonableAllo|apscorethatenhances
theabIlItytodelIverpersonalIzedmonItorIngandtreatmenttohearttransplantpatIents.
Furthermore,severalclInIcallyavaIlableproteInbasedbIomarkersofalloImmune
actIvatIon,mIcrovascularInjury(troponIns),systemIcInflammatIon(CFP),andwallstress
andremodelIng(braInnatrIuretIcpeptIde)correlatewellwIthallograftfaIlureand
vasculopathyandhavegoodnegatIvepredIctIvevalues,butrequIreaddItIonalstudIesto
guIdetheIrclInIcaluse.SImIlarly,molecularsIgnaturesoffunctIonalrecoveryInendstage
heartfaIlurefollowIngleftventrIcularassIstdevIcesupportusInggeneexpressIonprofIlIng
havebeenreported,
104
andcouldbeusedtomonItorpatIentswhoreceIvedaleft
ventrIcularassIstdevIceasdestInatIontherapyorassessthetImIngofpotentIaldevIce
explantatIon.
Genetic Variability and Postoperative Event-Free Survival
SeverallargerandomIzedclInIcaltrIalsexamInIngthebenefItsofCA8Csurgeryand
percutaneouscoronaryInterventIonsrelatIvetomedIcaltherapyand/ortooneanother
haverefInedourknowledgeofearlyandlongtermsurvIvalafterCA8C.WhIlethesestudIes
havehelpeddefInethesubgroupsofpatIentswhobenefItfromsurgIcalrevascularIzatIon,
theyalsodemonstratedasubstantIalvarIabIlItyInlongtermsurvIvalafterCA8C,altered
byImportantdemographIcandenvIronmentalrIskfactors.ncreasIngevIdencesuggests
thattheACEgeneIndelpolymorphIsmmayInfluencepostCA8CcomplIcatIons,wIth
carrIersoftheDallelehavInghIghermortalItyandrestenosIsratesafterCA8Csurgery
comparedwIththeIallele.
71
AsprevIouslydIscussed,aprothrombotIcamInoacId
alteratIonIntheJIntegrInchaInoftheglycoproteInb/aplateletreceptor(thePl
A2
polymorphIsm)IsassocIatedwIthanIncreasedrIsk(DF4.7)formajoradversecardIac
events(acomposIteofmyocardIalInfarctIon,coronarybypassgraftocclusIon,ordeath)
followIngCA8Csurgery(Table6J).
84
WefoundprelImInaryevIdenceforassocIatIonoftwo
functIonalpolymorphIsmsmodulatIng
2
adrenergIcreceptoractIvIty(Arg16Clyand
Cln27Clu)wIthIncIdenceofdeathormajoradversecardIaceventsfollowIngcardIac
surgery,
105
andrecentlyIdentIfIedtwofunctIonalpolymorphIsmsInapolIpoproteInE(APOE
219CT,DF0.46)andthrombomodulIn(THBDAla4557al,DF2.64)genesassocIatedwIth
altered5yearmortalItyafterCA8CIndependentofEuroSCDFE.
106
Genetic Susceptibility to Adverse Perioperative Neurologic
Outcomes
0espIteadvancesInsurgIcalandanesthetIctechnIques,sIgnIfIcantneurologIcmorbIdIty
contInuestooccurfollowIngcardIacsurgery,rangIngInseverItyfromcomaandfocal
stroke(IncIdence1toJ)tomoresubtlecognItIvedefIcIts(IncIdenceupto69),wItha
substantIalImpactontherIskofperIoperatIvedeath,qualItyoflIfe,andresource
utIlIzatIon.7arIabIlItyInthereportedIncIdenceofbothearlyandlateneurologIcdefIcIts
remaInspoorlyexplaInedbyproceduralrIskfactors,suggestIngthatenvIronmental
(operatIve)andgenetIcfactorsmayInteracttodetermInedIseaseonset,progressIon,and
recovery(seeChapter41).ThepathophysIologyofperIoperatIveneurologIcInjuryIs
thoughttoInvolvecomplexInteractIonsbetweenprImarypathwaysassocIatedwIth
atherosclerosIsandthrombosIs,andsecondaryresponsepathwayslIkeInflammatIon,
vascularreactIvIty,anddIrectcellularInjury.|anyfunctIonalgenetIcvarIantshavebeen
reportedIneachofthesemechanIstIcpathwaysInvolvedInmodulatIngthemagnItudeand
theresponsetoneurologIcInjury,whIchmayhaveImplIcatIonsInchronIcaswellasacute
perIoperatIveneurocognItIveoutcomes.Forexample,Crocottatal.
107
examIned26SNPs
InrelatIonshIptotheIncIdenceofacutepostoperatIveIschemIcstrokeIn1,6J5patIents
undergoIngcardIacsurgeryandfoundthattheInteractIonofmInorallelesoftheCFP
(1846CT)andL6promoterSNP174CCsIgnIfIcantlyIncreasestherIskofacutestroke.
SImIlarly,arecentstudysuggeststhatPselectInandCRPgenesbothcontrIbuteto
modulatIngthesusceptIbIlItytopostoperatIvecognItIvedeclIne(PDC0)followIngcardIac
surgery.
27
SpecIfIcally,thelossoffunctIonmInorallelesofCRP1059CCandSELP1087CA
areIndependentlyassocIatedwIthareductionIntheobservedIncIdenceofPDC0after
adjustmentforknownclInIcalanddemographIccovarIates(Table64).
P.125
Table 6-4 Representative Genetic Polymorphisms Associated with Altered
Susceptibility to Adverse Perioperative Neurologic Events
Perioperative Stroke
IL6 174CC CardIac/CP8 J.J 107
CRP 1846CT
Perioperative Cognitive Dysfunction, Neurodevelopmental Dysfunction
SELP E2980 CardIac/CP8 0.51 27
CRP 1059CC CardIac/CP8 0.J7 27
ITGB3
LJJP
(Pl
A1
/Pl
A2
)
CardIac/CP8 n.r. 26
APOE 4 CA8C/CP8(adults) n.r.7, 25,
2 CardIac/CP8(chIldren) 11 115,116
Postoperative Delirium
APOE 4
|ajornoncardIac,crItIcally
Ill
J.64,7.J2 11J,114
DF,oddsratIo;L6,InterleukIn6;CP8,cardIopulmonarybypass;CFP,CreactIve
proteIn;SELP,PselectIn;TC8J,plateletglycoproteIna;n.r.,notreported;
APDE,apolIpoproteInE;CA8C,coronaryarterybypassgraft.
DurgrouphasdemonstratedasIgnIfIcantassocIatIonbetweentheapolIpoproteInE(APOE)
E4genotypeandadversecerebraloutcomesIncardIacsurgerypatIents.
25,108
ThIsIs
consIstentwIththeroleoftheAPOEgenotypeInrecoveryfromacutebraInInjury,suchas
IntracranIalhemorrhage,
109
closedheadInjury,
110
andstroke,
111
aswellasexperImental
modelsofcerebralIschemIareperfusIonInjury
112
;twosubsequentstudIesInCA8C
patIents,however,havenotreplIcatedtheseInItIalfIndIngs.Furthermore,theIncIdenceof
postoperatIvedelIrIumfollowIngmajornoncardIacsurgeryIntheelderly
11J
andIncrItIcally
IllpatIents
114
IsIncreasedIncarrIersoftheAPOE4allele.UnlIkeadultcardIacsurgery
patIents,InfantspossessIngtheAPOE2alleleareatIncreasedrIskfordevelopIngadverse
neurodevelopmentalsequelaefollowIngcardIacsurgery.
115,116
ThemechanIsmsbywhIch
theAPOEgenotypesmIghtInfluenceneurologIcoutcomeshaveyettobedetermIned,but
donotseemtoberelatedtoalteratIonsInglobalcerebralbloodflowofoxygen
metabolIsmdurIngCP8
117
;however,genotypIceffectsInmodulatIngtheInflammatory
response,
75
extentofaortIcatheromaburden,
118
andrIskforprematurecoronary
atherosclerosIs
119
mayplayarole.
FecentstudIeshavesuggestedaroleforplateletactIvatIonInthepathophysIologyof
adverseneurologIcsequelae.CenetIcvarIantsInsurfaceplateletmembraneglycoproteIns,
ImportantmedIatorsofplateletadhesIonandplateletplateletInteractIons,havebeen
showntoIncreasethesusceptIbIlItytoprothrombotIcevents.Amongthese,thePl
A2
polymorphIsmInglycoproteInb/ahasbeenrelatedtovarIousadversethrombotIc
outcomes,IncludIngacutecoronarythrombosIs
120
andatherothrombotIcstroke.
121
We
foundthePl
A2
alleletobeassocIatedwIthmoresevereneurocognItIvedeclIneafterCP8,
26
whIchcouldrepresentexacerbatIonofplateletdependentthrombotIcprocessesassocIated
wIthplaqueembolIsm.
CardIacsurgIcalpatIentswhodevelopPDC0demonstrateInherentlydIfferentgenetIc
responsestoCP8fromthosewIthoutPDC0,asevIdencedbyacutederegulatIonIn
perIpheralbloodleukocytesofgeneexpressIonpathwaysInvolvIngInflammatIon,antIgen
presentatIon,andcellularadhesIon.
122
ThesefIndIngscorroboratewIthproteomIcchanges,
InwhIchpatIentswIthPDC0sImIlarlyhavesIgnIfIcantlyhIgherserologIcInflammatory
IndIcescomparedwIththosepatIentswIthoutPDC0,
12J,124
andaddtotheIncreasInglevel
ofevIdencethatCP8doesnotcauseanIndIscrImInatevarIatIonIngeneexpressIon,but
ratherdIstInctpatternsInspecIfIcpathwaysthatarehIghlyassocIatedwIththe
developmentofpostoperatIvecomplIcatIonssuchasPDC0.TheImplIcatIonsfor
perIoperatIvemedIcIneIncludeIdentIfyIngpopulatIonsatrIskwhomIghtbenefItnotonly
fromanImprovedInformedconsent,stratIfIcatIon,andresourceallocatIon,butalsofrom
targetedantIInflammatorystrategIes.
Genetic Susceptibility to Adverse Perioperative Renal
Outcomes
AcuterenaldysfunctIonIsacommon,serIouscomplIcatIonofcardIacsurgery;about8to
15ofpatIentsdevelopmoderaterenalInjury(1.0mg/dLpeakcreatInInerIse),andupto
5ofthemdeveloprenalfaIlurerequIrIngdIalysIs.
125
AcuterenalfaIlureIsIndependently
assocIatedwIthInhospItalmortalItyrates,exceedIng60InpatIentsrequIrIngdIalysIs.
125
SeveralstudIeshavedemonstratedthatInherItanceofgenetIcpolymorphIsmsIntheAPOE
gene(4allele)
J0
andInthepromoterregIonoftheIL6gene(174Callele)
97
areassocIated
wIthacutekIdneyInjuryfollowIngCA8Csurgery(Table65).StaffordSmIthetal.
28
have
reportedthatmajordIfferencesInpeakpostoperatIveserumcreatInInerIseafterCA8Care
predIctedbypossessIonofcombInatIonsofpolymorphIsmsthatInterestInglydIfferbyrace:
theangIotensInogen(AGT)842TCandIL6572CCvarIantsInwhItes,andtheendothelIal
nItrIcoxIdesynthase(NOS3)894CTandangIotensInconvertIngenzyme(ACE)
InsertIon/deletIonInAfrIcanAmerIcansareassocIatedwIthmorethan50reductIonIn
postoperatIveglomerularfIltratIonrate.FurtherIdentIfIcatIonofgenotypespredIctIveof
adverseperIoperatIverenaloutcomesmayfacIlItateIndIvIduallytaIloredtherapy,rIsk
stratIfythepatIentsforInterventIonaltrIalstargetIngthegeneproductItself,andaIdIn
medIcaldecIsIonmakIng(e.g.,selectIngmedIcaloversurgIcalmanagement;seeChapter
52).
Genetic Variants and Risk for Prolonged Postoperative
Mechanical Ventilation
ProlongedmechanIcalventIlatIon(InabIlItytoextubatepatIentby24hours
postoperatIvely)IsasIgnIfIcantcomplIcatIonfollowIngcardIacsurgery,occurrIngIn5.6
and10.5of
P.126
patIentsundergoIngfIrstandrepeatCA8Csurgery,respectIvely.
126
Severalpulmonaryand
nonpulmonarycauseshavebeenIdentIfIed,andscorIngsystemsbasedonpreoperatIveand
proceduralrIskfactorshavebeenproposedandvalIdated.Fecently,genetIcvarIantsInthe
renInangIotensInpathwayandInproInflammatorycytokInegeneshavebeenassocIated
wIthrespIratorycomplIcatIonspostCP8.TheDalleleofacommonfunctIonal
InsertIon/deletIonpolymorphIsmIntheangIotensInconvertIngenzyme(ACE)gene,
accountIngfor47ofvarIanceIncIrculatIngACElevels,
127
IsassocIatedwIthprolonged
mechanIcalventIlatIonfollowIngCA8C
128
andwIthsusceptIbIlItytoandprognosIsofacute
respIratorydIstresssyndrome.
129
Furthermore,ahyposecretoryhaplotypeInthe
neIghborInggenestumornecrosIsfactor(TNFA)andlymphotoxIn(LTA)onchromosome
6(TNFAJ08G/LTA+250Ghaplotype)
1J0
andafunctIonalpolymorphIsmmodulatIng
postoperatIveL6levels(IL6174CC)
97
areIndependentlyassocIatedwIthhIgherrIskof
prolongedmechanIcalventIlatIonpostCA8C.TheassocIatIonIsmoredramatIcInpatIents
undergoIngconventIonalCA8CthanInthoseundergoIngoffpumpCA8C,suggestIngthatIn
hIghrIskpatIentsIdentIfIedbypreoperatIvegenetIcscreenIng,offpumpCA8Cmaybethe
optImalsurgIcalprocedure.
Table 6-5 Representative Genetic Polymorphisms Associated with Other
Adverse Perioperative Outcomes
Perioperative Thrombotic Events
F5 F7L NoncardIac,CardIac n.r. JJ
Perioperative Bleeding
F5 F506Q(F7L) CardIac/CP8
1.25
a
86
PAI-1 4C/5C 10
b
197
ITGA2 52CT,807CT 0.15
a
198
GP1BA T145| 0.22
a
198
TF 60JAC 0.0J
a
198
TFPI J99CT CA8C/CP8 0.05
a
198
F2 20210CA 0.J8
a
198
ACE n/del 0.15
a
198
ITGB3
LJJP(Pl
A1
/Pl
A2
)
n.r. 199
PAI-1 4C/5C CardIac/CP8 10
b
197
TNFA 2J8CA 8raInA7|treatment J.5
C
200
APOE 2 10.9
C
200
Perioperative Acute Kidney Injury
IL6 572CC 20.04
d
28
AGT |2J5T CA8C/CP8 J2.19
d
28
NOS3 E2980 4.29
d
28
APOE 4 0.1J
a
28,J0
Perioperative Severe Sepsis
APOE J
0.28
e
J6
DF,oddsratIo;F5,factor7;F7L,factor7LeIden;n.r.,notreported;CP8,
cardIopulmonarybypass;PA1,plasmInogenactIvatorInhIbItor1;TCA2,
glycoproteInaa;CP18A,glycoproteInb;TF,tIssuefactor;TFP,tIssuefactor
pathwayInhIbItor;CA8C,coronaryarterybypassgraft;F2,prothrombIn;ACE,
angIotensInconvertIngenzyme;n/del,InsertIon/deletIon;TC8J,glycoproteIn
a;TNFA,tumornecrosIsfactor;A7|,arterIovenousmalformatIon;APDE,
apolIpoproteInE;L6,InterleukIn6;ACT,angIotensInogen;NDSJ,endothelIalnItrIc
oxIdesynthase.
a
coeffIcIent.
b
DddsratIo.
c
HazardratIo.
d
Fvalue.
e
FelatIverIsk.
AnextcrucIalstepInunderstandIngthecomplexItyofadverseperIoperatIveoutcomesIs
toassessthecontrIbutIonofvarIatIonsInmanygenessImultaneouslyandtheIrInteractIon
wIthtradItIonalrIskfactorstothelongItudInalpredIctIonofoutcomesInIndIvIdual
patIents.TheuseofsuchoutcomepredIctIvemodelsIncorporatInggenetIcInformatIon
mayhelpstratIfymortalItyandmorbIdItyInsurgIcalpatIents,ImproveprognostIcatIon,
dIrectmedIcaldecIsIonmakIngbothIntraoperatIvelyanddurIngpostoperatIvefollowup,
andevensuggestnoveltargetsfortherapeutIcInterventIonIntheperIoperatIveperIod.
Pharmacogenomics and Anesthesia
nterIndIvIdualvarIabIlItyInresponsetodrugtherapy,bothIntermsofeffIcacyandsafety,
IsarulebywhIchanesthesIologIstslIve.nfact,muchoftheartofanesthesIologyIsthe
astuteclInIcIanbeIngpreparedtodealwIthoutlIers.ThetermpharmacogenomicsIsused
todescrIbehowInherItedvarIatIonsIngenesmodulatIngdrugactIonsarerelatedto
InterIndIvIdualvarIabIlItyIndrugresponse(seeChapter7).SuchvarIabIlItyIndrugactIon
maybepharmacokineticorpharmacodynamic(FIg.64).PharmacokInetIcvarIabIlItyrefers
tovarIabIlItyInadrug'sabsorptIon,dIstrIbutIon,metabolIsm,andexcretIonthatmedIates
ItseffIcacyand/ortoxIcIty.ThemoleculesInvolvedIntheseprocessesIncludedrug
metabolIzIngenzymes(suchasmembersofthecytochromeP450,orCYPsuperfamIly),and
drugtransportmoleculesthatmedIatedruguptakeInto,andeffluxfrom,Intracellular
sItes.PharmacodynamIcvarIabIlItyreferstovarIabledrugeffectsdespIteequIvalentdrug
delIverytomolecularsItesofactIon.ThIsmayreflectvarIabIlItyInthefunctIonofthe
moleculartargetofthedrug,orInthepathophysIologIcalcontextInwhIchthedrug
P.127
InteractswIthItsreceptortarget(e.g.,affInIty,couplIng,expressIon).
1J1
Thus,
pharmacogenomIcsInvestIgatescomplex,polygenIcallydetermInedphenotypesofdrug
effIcacyortoxIcIty,wIththegoalofIdentIfyIngnoveltherapeutIctargetsandcustomIzIng
drugtherapy.
Figure 6-4.PharmacogenomIcdetermInantsofIndIvIdualdrugresponseoperateby
pharmacokInetIcandpharmacodynamIcmechanIsms.A.CenetIcvarIantsIndrug
transporters(e.g.,ATPbIndIngcassettesubfamIly8member1orABCB1gene)and
drug-metabolizing enzymes(e.g.,cytochromeP450206orCYP2D6gene,CYP2C9gene,
NacetyltransferaseorNAT2gene,plasmacholInesteraseorBCHEgene)are
responsIbleforpharmacokineticvarIabIlItyIndrugresponse.B.PolymorphIsmsIndrug
targets(e.g.,
1
and
2
adrenergIcreceptorADRB1,ADRB2genes;angIotensIn
convertIngenzymeACEgene),postreceptor signaling molecules(e.g.,guanIne
nucleotIdebIndIngproteInJorGNB3gene),ormolecules indirectly affecting drug
response(e.g.,varIousIonchannelgenesInvolvedIndrugInducedarrhythmIas)are
sourcesofpharmacodynamicvarIabIlIty.
Pseudocholinesterase Deficiency
HIstorIcally,characterIzatIonofthegenetIcbasIsforplasmapseudocholInesterase
defIcIencyIn1956wasoffundamentalImportancetoanesthesIaandthefurther
developmentandunderstandIngofgenetIcallydetermIneddIfferencesIndrugresponse.
1J2
ndIvIdualswIthanatypIcalformofpseudocholInesteraseresultIngInamarkedlyreduced
rateofdrugmetabolIsmareatrIskforexcessIveneuromuscularblockadeandprolonged
apnea.|orethan20varIantshavesIncebeenIdentIfIedInthebutyrylcholInesterasegene
(BCHE),themostcommonofwhIcharetheAvarIant(209AC)andtheKvarIant
(1615CA),wIthvarIousandsomewhatpoorlydefInedphenotypIcconsequenceson
prolongedneuromuscularblockade.Therefore,pharmacogenetIctestIngIscurrentlynot
recommendedInthepopulatIonatlarge,butonlyasanexplanatIonforanadverse
event.
1JJ
Genetics of Malignant Hyperthermia
|alIgnanthyperthermIa(|H)IsarareautosomaldomInantgenetIcdIseaseofskeletal
musclecalcIummetabolIsm,trIggeredbyadmInIstratIonofgeneralanesthesIawIthvolatIle
anesthetIcagentsorsuccInylcholIneInsusceptIbleIndIvIduals.TheclInIcal|HsyndromeIs
characterIzedbyskeletalmusclehypermetabolIsmandmanIfestedasskeletalmuscle
rIgIdIty,tachycardIa,tachypnea,hemodynamIcInstabIlIty,IncreasedoxygenconsumptIon
andCD
2
productIon,lactIcacIdosIsandfever,progressIngtomalIgnantventrIcular
arrhythmIas,dIssemInatedIntravascularcoagulatIon,andmyoglobInurIcrenalfaIlure.|H
susceptIbIlItyhasbeenInItIallylInkedtotheryanodInereceptor(RYRI)genelocuson
chromosome19q.
1J4
However,subsequentstudIeshaveshownthat|Hmayrepresenta
commonseverephenotypethatorIgInatesnotonlyfrompoIntmutatIonsIntheRYRIgene
(Arg614Cys),butalsowIthInItsfunctIonallyand/orstructurallyassocIatedproteIns
regulatIngexcItatIoncontractIoncouplIng(suchas1DHPRandFKBP12).tIsbecomIng
IncreasInglyapparentthat|HsusceptIbIlItyresultsfromacomplexInteractIonbetween
multIplegenesandenvIronment(suchasenvIronmentaltoxIns),suggestedbythe
heterogeneItyobservedIntheclInIcal|HsyndromeandthevarIablepenetranceofthe|H
phenotype.
1J5
CurrentdIagnostIcmethods(thecaffeInehalothanecontracturetest)are
InvasIveandpotentIallynonspecIfIc.Unfortunately,becauseofthepolygenIcdetermInIsm
andvarIablepenetrance,dIrect0NAtestIngInthegeneralpopulatIonforsusceptIbIlItyto
|HIscurrentlynotrecommended;Incontrast,testIngInIndIvIdualsfromfamIlIeswIth
affectedIndIvIdualshasthepotentIaltogreatlyreducemortalItyandmorbIdIty.
1JJ
Furthermore,genomIcapproachesmayhelpelucIdatethemolecularmechanIsmsInvolved
InalteredFYFmedIatedcalcIumsIgnalIngandIdentIfynovel,morespecIfIctherapeutIc
targets.
Genetic Variability and Response to Anesthetic Agents
AnesthetIcpotency,defInedbythemInImumalveolarconcentratIon(|AC)ofanInhaled
anesthetIcthatabolIshespurposefulmovementInresponsetoanoxIousstImulus,varIes
amongIndIvIduals,wIthacoeffIcIentofvarIatIon(theratIoofstandarddevIatIontothe
mean)ofapproxImately10
J6
(seeChapter7).ThIsobservedvarIabIlItymaybeexplaIned
by
P.128
InterIndIvIdualdIfferencesInmultIplegenesthatunderlIeresponsIvenesstoanesthetIcs,by
envIronmentalorphysIologIcalfactors(braIntemperature,age),orbymeasurement
errors.WIthgrowIngpublIcconcernoverIntraoperatIveawareness,understandIngthe
mechanIsmsresponsIbleforthIsvarIabIlItymayfacIlItateImplementatIonofpatIent
specIfIcpreventIvestrategIes.EvIdenceofagenetIcbasIsforIncreasedanesthetIc
requIrementsIsbegInnIngtoemerge,suggestedforInstancebytheobservatIonthat
desfluranerequIrementsareIncreasedInsubjectswIthredhaIrversusdarkhaIr,
1J7
andby
recentlyreportedvarIabIlItyIntheImmobIlIzIngdoseofsevoflurane(asmuchas24)In
populatIonswIthdIfferentethnIc(andthusgenetIc)backgrounds.
1J8
SeveralstudIes
evaluatIngthegenetIccontrolofanesthetIcresponses,coupledwIthmolecularmodelIng,
proteomIc,neurophysIology,andpharmacologIcapproaches,haveprovIdedImportant
developmentsInourunderstandIngofgeneralanesthetIcmechanIsms.
TrIggeredbythesemInalworkofFranksandLIeb,
1J9
researchshIftedfromthemembrane
lIpIdbIlayertoproteInreceptors(specIfIcally,lIgandandvoltagegatedIonchannels)as
potentIalanesthetIctargets,endIngafewdecadesofstagnatIonthatwereprImarIlydueto
analmostunIversalacceptanceofthedogmaofnonspecIfIcanesthetIcactIon(theso
calledlIpIdtheory).SomeofthegenesresponsIbleforphenotypIcdIfferencesInanesthetIc
effectshavebeenmappedInvarIousanImalmodelsand,followInggenomIcmanIpulatIon
ofplausIblecandIdatereceptorstoInvestIgatetheIrfunctIonInvItro,wereevaluatedIn
genetIcallyengIneeredanImalsfortheIrrelatIonshIptovarIousanesthetIcendpoInts,such
asImmobIlIty(I.e.,|AC),hypnosIs,amnesIa,andanalgesIa(forrevIew,seeSonneret
al.
140
).SeveralthousanddIfferentstraInsofknockoutmIcehavebeencreatedandareused
toInvestIgatespecIfIcfunctIonsofpartIculargenesandmechanIsmsofdrugactIon,
IncludIngthesensItIvItytogeneralanesthetIcInanImalslackIngtheJsubunIt
141
orthe6
subunIt
142
oftheCA8A
A
receptor.Dntheotherhand,knockinanImalsexpressasIte
dIrectedmutatIonInthetargetedgenethatremaInsunderthecontrolofendogenous
regulatoryelements,allowIngthemutatedgenetobeexpressedInthesameamount,at
thesametIme,andInthesametIssuesasthenormalgene.ThIsmethodhasprovIded
remarkableInsIghtIntothemechanIsmsofactIonofbenzodIazepInes
14J
andIntravenous
anesthetIcs.nasemInalstudybyJurdetal.,
145
apoIntmutatIonInthegeneencodIngthe
JsubunItoftheCA8A
A
receptorprevIouslyknowntorenderthereceptorInsensItIveto
etomIdateandpropofolInvItro,
144
wasvalIdatedInvIvobycreatIngaknockInmouse
straInthatprovedalsoessentIallyInsensItIvetotheImmobIlIzIngactIonsofetomIdateand
propofol.ApoIntmutatIonInthe2subunItoftheCA8A
A
receptorresultsInaknockIn
mousewIthreducedsensItIvItytothesedatIve
146
andhypothermIceffects
147
ofetomIdate.
KnockInmIceharborIngpoIntmutatIonsInthe
2
AadrenergIcreceptorhaveenabledthe
elucIdatIonoftheroleofthIsreceptorInanesthetIcsparIng,analgesIc,andsedatIve
responsestodexmedetomIdIne.
148
ThesItuatIonIsfarmorecomplexforInhaledanesthetIcs,whIchappeartomedIatetheIr
effectsbyactIngonseveralreceptortargets.8asedoncombInedpharmacologIcand
genetIcin vivostudIestodate,severalreceptorsareunlIkelytobedIrectmedIatorsof
|AC,IncludIngtheCA8A
A
(despItetheIrcompellIngroleInIntravenousanesthetIcInduced
ImmobIlIty),5HTJ,A|PA,kaInate,acetylcholIneand2adrenergIcreceptors,and
potassIumchannels.
149
ClycIne,N|0AreceptorsandsodIumchannelsremaInlIkely
candIdates.
140
TheseconclusIons,however,donotapplytootheranesthetIcendpoInts,
suchashypnosIs,amnesIaandanalgesIa.SeveralpreclInIcalproteomIcanalyseshave
IdentIfIedInamoreunbIasedwayagroupofpotentIalanesthetIctargetsforhalothane,
61
desflurane,
62
andsevoflurane,
6J
whIchshouldprovIdethebasIsformorefocusedstudIesof
anesthetIcbIndIngsItes.SuchomIcapproacheshavethepotentIaltoevolveInto
preoperatIvescreenIngprofIlesusefulInguIdIngIndIvIdualIzedtherapeutIcdecIsIons,such
aspreventIonofanesthetIcawarenessInpatIentswIthagenetIcpredIsposItIonto
IncreasedanesthetIcrequIrements.
Genetic Variability and Response to Pain
SImIlartotheobservedvarIabIlItyInanesthetIcpotency,theresponsetopaInfulstImulI
andanalgesIcmanIpulatIonsvarIesamongIndIvIduals(seeChapter57).Thesourcesof
varIabIlItyInthereportandexperIenceofpaInandanalgesIa(I.e.,thepaInthreshold)
aremultIfactorIal,IncludIngfactorsextrInsIctotheorganIsm(suchasculturalfactorsor
cIrcadIanrhythms)andIntrInsIcfactors(suchasage,gender,hormonalstatus,orgenetIc
makeup).ncreasIngevIdencesuggeststhatpaInbehavIorInresponsetonoxIousstImulI
andItsmodulatIonbythecentralnervoussystemInresponsetodrugadmInIstratIonor
envIronmentalstress,aswellasthedevelopmentofpersIstentpaIncondItIonsthrough
paInamplIfIcatIon,arestronglyInfluencedbygenetIcfactors.
150,151,152
FesultsfromstudIesIntwIns
15J
andInbredmousestraIns
154
IndIcateamoderate
herItabIlItyforchronIcpaInsyndromesandnocIceptIvesensItIvIty,whIchappearstobe
medIatedbymultIplegenes(seeChapter58).7arIousstraInsofknockoutmIcelackIng
targetgeneslIkeneurotrophInsandtheIrreceptors(e.g.,nervegrowthfactor),perIpheral
medIatorsofnocIceptIonandhyperalgesIa(e.g.,substanceP),opIoIdandnonopIoId
transmIttersandtheIrreceptors,andIntracellularsIgnalIngmoleculeshavesIgnIfIcantly
contrIbutedtotheunderstandIngofpaInprocessIngmechanIsms.
155
AlocusresponsIblefor
28ofphenotypIcvarIanceInmagnItudeofsystemIcmorphIneanalgesIaInmIcehasbeen
mappedtochromosome10,InorneartheOPRM(opIoIdreceptor)gene.TheopIoId
receptorIsalsosubjecttopharmacodynamIcvarIabIlIty;polymorphIsmsInthepromoter
regIonoftheOPRMgenemodulatIngInterleukIn4medIatedgeneexpressIonhavebeen
correlatedwIthmorphIneantInocIceptIon.ThemuchquotedOPRM188ACpolymorphIsmIs
assocIatedwIthdecreasedresponsestomorphIne6glucuronIde,resultIngInaltered
analgesIcrequIrements,butalsoreducedIncIdenceofpostoperatIvenauseaandvomItIng,
andreducedrIsksoftoxIcItyInpatIentswIthrenalfaIlure.Conversely,varIantsofthe
melanocortIn1receptor(MC1R)gene,whIchproducearedhaIrfaIrskInphenotype,are
assocIatedwIthIncreasedanalgesIcresponsestoopIoIdagonIstsInwomenbutnotmen,
provIdIngevIdenceforagenebygenderInteractIonInregulatInganalgesIcresponse(fora
revIew,seeSomogyIetal.
156
).7eryrecentreportssuggestthatperIpherallylocated
2
adrenergIcreceptors(ADRB2)alsocontrIbutetobasalpaInsensItIvIty,thedevelopmentof
chronIcpaInstates,aswellasopIoIdInducedhyperalgesIa.
152
FunctIonallyImportant
haplotypesIntheADRB2(151)andcatecholDmethyltransferase(COMT)
157
genesare
assocIatedwIthenhancedpaInsensItIvItyInhumans.
naddItIontothegenetIccontrolofperIpheralnocIceptIvepathways,consIderable
evIdenceexIstsforgenetIcvarIabIlItyInthedescendIngcentralpaInmodulatorypathways,
furtherexplaInIngtheInterIndIvIdualvarIabIlItyInanalgesIcresponsIveness.Dnegood
examplerelevanttoanalgesIceffIcacyIscytochromeP45006(CYP2D6),amemberofthe
superfamIlyofmIcrosomalenzymesthatcatalyzephasedrugmetabolIsm,andresponsIble
forthemetabolIsmofalargenumberoftherapeutIccompounds.TherelatIonshIpbetween
theCYP2D6genotypeandtheenzymemetabolIcratehasbeenextensIvelycharacterIzed,
wIthatleast12knownmutatIonsleadIngtoa
P.129
tetramodaldIstrIbutIonCYP206actIvIty:ultrarapIdmetabolIzers(5to7ofthe
populatIon),extensIvemetabolIzers(60),IntermedIatemetabolIzers(25),andpoor
metabolIzers(10).Currently,pharmacogenomIcscreenIngtestspredIctCYP206phenotype
wIth95relIabIlIty.TheconsequencesofInherItInganallelethatcompromIsesCYP206
functIonIncludetheInabIlItytometabolIzecodeIne(aprodrug)tomorphInebyD
demethylatIon,leadIngtolackofanalgesIabutIncreasedsIdeeffectsfromtheparentdrug
(e.g.,fatIgue)InpoormetabolIzers.
1JJ,150
Genetic Variability in Response to Other Drugs Used
Perioperatively
AwIdevarIetyofdrugsusedIntheperIoperatIveperIoddIsplaysIgnIfIcant
pharmacokInetIcorpharmacodynamIcvarIabIlItythatIsgenetIcallymodulated(Table6
6.).AlthoughsuchgenetIcvarIatIonIndrugmetabolIzIngenzymesordrugtargetsusually
resultInunusuallyvarIabledrugresponse,genetIcmarkersassocIatedwIthrarebutlIfe
threatenIngsIdeeffectshavealsobeendescrIbed.Dfnote,themostcommonlycIted
categorIesofdrugsInvolvedInadversedrugreactIonsIncludecardIovascular,antIbIotIc,
psychIatrIc,andanalgesIcmedIcatIons;InterestIngly,eachcategoryhasaknowngenetIc
basIsforIncreasedrIskofadversereactIons.
TherearemorethanJ0famIlIesofdrugmetabolIzIngenzymesInhumans,mostwIth
genetIcpolymorphIsmsshowntoInfluenceenzymatIcactIvIty.DfspecIalImportancetothe
anesthesIologIstIstheCYP2D6,oneofthemostIntensIvelystudIedandbestunderstood
examplesofpharmacogenetIcvarIatIon,InvolvedInthemetabolIsmofseveraldrugs
IncludInganalgesIcs(codeIne,dextromethorphan),betablockers,antIarrhythmIcs
(flecaInIde,propafenone,quInIdIne),anddIltIazem.AnotherImportantpharmacogenetIc
varIatIonhasbeendescrIbedIncytochromeP450C9(CYP2C9),InvolvedInmetabolIzIng
antIcoagulants(warfarIn),antIconvulsants(phenytoIn),antIdIabetIcagents(glIpIzIde,
tolbutamIde),andnonsteroIdalantIInflammatorydrugs(celecoxIb,Ibuprofen),among
others.ThreeknownCYP2C9varIantallelesresultIndIfferentenzymeactIvItIes
(extensIve,IntermedIate,andslowmetabolIzerphenotypes),andhaveclInIcalImplIcatIons
IntheIncreasedrIskoflIfethreatenIngbleedIngcomplIcatIonsInslowmetabolIzersdurIng
standardwarfarIntherapy.ThIsIllustratestheconceptofhIghrIskpharmacokInetIcs,
whIchapplIestodrugswIthlowtherapeutIcratIoselImInatedbyasInglepathway(InthIs
case,CYP2C9medIatedoxIdatIon);genetIcvarIatIonInthatpathwaymayleadtolarge
changesIndrugclearance,concentratIons,andeffects.
1J1
0oseadjustmentsbasedonthe
pharmacogenetIcphenotypehavebeenproposedfordrugsmetabolIzedvIabothCYP206
andCYP2C9pathways,
1JJ
andacommercIallyavaIlable,Foodand0rugAdmInIstratIon
(F0A)approvedtest(CYP450AmplIChIp,Foche|olecular0IagnostIcs)allowsclInIcIansfor
thefIrsttImetotestpatIentsforawIdespectrumofgenetIcvarIatIonIndrugmetabolIzIng
enzymes.UsIngthIstechnology,CandIottIetal.
158
showedthatpatIentscarryIngeIther
threecopIesoftheCYP2D6gene,agenotypeconsIstentwIthultrarapIdmetabolIsm,or
both,haveanIncreasedrIskofondansetronfaIlureforthepreventIonofpostoperatIve
vomItIngbutnotnausea.
158
ThestrongestevIdencetodateforuseofpharmacogenomIc
testIngIstoaIdInthedetermInatIonofwarfarIndosagebyusInggenotypesIntheCYP2C9
andvItamInKepoxIdereductasecomplex1(VKORC1)genes,andatleastfourF0A
approvedtestsarenowcommercIallyavaIlable.
CenetIcvarIatIonIndrugtargets(receptors)canhaveprofoundeffectondrugeffIcacy,
andmorethan25exampleshave
P.1J0
alreadybeenIdentIfIed.Forexample,functIonalpolymorphIsmsInthe2AF(Arg16Cly,
Cln27Clu)InfluencethebronchodIlatorandvascularresponsestoagonIsts,and1AF
varIants(ArgJ89Cly)modulateresponsestobetablockersandmayImpactpostoperatIve
cardIovascularadverseevents.
88,89
FInally,clInIcallyImportantgenetIcpolymorphIsmswIthIndIrecteffectsondrugresponse
havebeendescrIbed.TheseIncludevarIantsIncandIdategeneslIkesodIum(SCN5A)and
potassIumIonchannels(KCNH2,KCNE2,KCNQ1),whIchaltersusceptIbIlItytodrugInduced
longQTsyndromeandventrIculararrhythmIas(torsadedepoIntes)assocIatedwIththeuse
ofdrugslIkeerythromycIn,terfenadIne,dIsopyramIde,sotalol,cIsaprIde,orquInIdIne.
CarrIersofsuchsusceptIbIlItyalleleshavenomanIfestQTIntervalprolongatIonorfamIly
hIstoryofsuddendeathuntIlQTprolongIngdrugchallengeIssuperImposed.
1J1
PredIsposItIontoQTIntervalprolongatIon(consIderedasurrogateforrIskoflIfe
threatenIngventrIculararrhythmIas)hasbeenresponsIbleformoredrugwIthdrawalsfrom
themarketthananyothercategoryofadverseeventInrecenttImes,sounderstandIng
genetIcpredIsposIngfactorsconstItutesoneofthehIghestprIorItIesofcurrent
pharmacogenomIcefforts.
Table 6-6 Examples of Genetic Polymorphisms Involved in Variable
Responses to Drugs Used in the Perioperative Period
Drug Class Gene Name (Gene Symbol) Effect of Polymorphism
Pharmacokinetic variability
8etablockers
CytochromeP450206
(CYP2D6)
Enhanceddrugeffect
CodeIne,
dextromethorphan
CYP2D6 0ecreaseddrugeffect
Cachannelblockers
CytochromeP450JA4
(CYP3A4)
UncertaIn
AlfentanIl CYP3A4 Enhanceddrugresponse
AngIotensInreceptor
type1blockers
CytochromeP4502C9
(CYP2C9)
Enhancedbloodpressure
response
EnhancedantIcoagulant
WarfarIn CYP2C9 effect,rIskofbleedIng
PhenytoIn CYP2C9 Enhanceddrugeffect
ACEInhIbItors
AngIotensIn
convertIngenzyme
(ACE)
8loodpressureresponse
ProcaInamIde
Nacetyltransferase2
(NAT2)
Enhanceddrugeffect
SuccInylcholIne
8utyrylcholInesterase
(BCHE)
Enhanceddrugeffect
0IgoxIn
PglycoproteIn(ABCB1,
MDR1)
ncreasedbIoavaIlabIlIty
Pharmacodynamic variability
8etablockers
1
and
2
adrenergIc
receptors(ADRB1,
ADRB2)
8loodpressureandheart
rateresponse,aIrway
responsIvenessto
2
agonIsts
QTprolongIngdrugs
(e.g.,antIarrhythmIcs,
cIsaprIde,
erythromycIn)
SodIumandpotassIum
Ionchannels(SCN5A,
KCNH2, KCNE2, KCNQ1)
LongQTsyndrome,rIskof
torsadedepoIntes
AspIrIn,glycoproteIn
b/aInhIbItors
ClycoproteIna
subunItofplatelet
glycoproteInb/a
(ITGB3)
7arIabIlItyInantIplatelet
effects
PhenylephrIne
EndothelIalnItrIcoxIde
synthase(NOS3)
8loodpressureresponse
PharmacogenomIcsIsemergIngasanaddItIonalmodIfyIngcomponenttoanesthesIaalong
wIthage,gender,comorbIdItIes,andmedIcatIonusage.SpecIfIctestIngandtreatment
guIdelInesallowIngclInIcIanstoapproprIatelymodIfydrugutIlIzatIon(e.g.,adjustdoseor
changedrug)alreadyexIstforafewcompounds,
1JJ
andwIlllIkelybeexpandedtoall
relevanttherapeutIccompounds,togetherwIthIdentIfIcatIonofnoveltherapeutIctargets.
Genomics and Critical Care
Genetic Variability in Response to Injury
SystemIcInjury(IncludIngtraumaandsurgIcalstress),shock,orInfectIontrIgger
physIologIcalresponsesoffever,tachycardIa,tachypnea,andleukocytosIsthatcollectIvely
defInethesystemIcInflammatoryresponsesyndrome(seeChapter12).ThIscanprogressto
severesepsIs,septIcshock,andmultIpleorgandysfunctIonsyndrome,thepathophysIology
ofwhIchremaInspoorlyunderstood.WIththegenomIcrevolutIon,anewparadIgmhas
emergedIncrItIcalcaremedIcIne:outcomesofcrItIcalIllnessaredetermInedbythe
InterplaybetweentheinjuryandrepairprocessestrIggeredbytheInItIalInsults.
159
NegatIveoutcomesarethusthecombInedresultofdIrecttIssueInjury,thesIdeeffectsof
resultIngrepaIrprocesses,andsecondaryInjurymechanIsmsleadIngtosuboptImalrepaIr.
ThIsconceptformsthebasIsofthenewPFD(PredIsposItIon,InfectIon/nsult,Response,
OrgandysfunctIon)stagIngsystemIncrItIcalIllness.
160
CenomIcfactorsplayarolealong
thIscontInuum,fromInflammatorygenevarIantsandmodulatorsofpathogenhost
InteractIon,tomIcrobIalgenomIcsandrapIddetectIonassaystoIdentIfypathogens,to
bIomarkersdIfferentIatIngInfectIonfromInflammatIon,todynamIcmeasuresofcellular
responsestoInsult,apoptosIs,cytopathIchypoxIa,andcellstress.FegulatIonofthese
mechanIsmsIscurrentlybeIngextensIvelyInvestIgatedatthegenomIc,proteomIc,and
pharmacogenomIclevels,aImIngtomodeladaptIveandmaladaptIveresponsestoInjury,
aIdIndevelopmentofdIagnostIcIndIcespredIctIveofInjury,monItorprogressofrepaIr,
andeventuallydesIgnnoveltherapeutIcmodalItIesthattakeIntoaccounttheIndIvIdual
genetIcmakeup.
ThelargeInterIndIvIdualvarIabIlItyInthemagnItudeofresponsetoInjury,IncludIng
actIvatIonofInflammatoryandcoagulatIoncascades,apoptosIsandfIbrosIs,suggeststhe
InvolvementofgenetIcregulatoryfactors.SeveralfunctIonalgenetIcpolymorphIsmsIn
moleculesInvolvedInvarIouscomponentsoftheInflammatoryresponsehavebeen
assocIatedwIthdIfferencesInsusceptIbIlItytoandmortalItyfromsepsIsofdIfferent
etIologIes,IncludIngpostoperatIvesepsIs.TheseIncludepolymorphIsmsInbacterIal
recognItIonmoleculeslIkelIpopolysaccharIdebIndIngproteIn(LBP),
bacterIcIdal/permeabIlItyIncreasIngproteIn(BPI),CD14,tolllIkereceptors(TLR2,TLR4),
mannosebIndInglectIn(MBL),andproInflammatorycytokIneslIketumornecrosIs(TNFA),
lymphotoxInalpha(LTA),InterleukIn1(IL1)andL1receptorantagonIst(IL1RN),and
InterleukIn6(IL6)(forrevIews,seeLInandAlbertson
161
and0e|aIoetal.
162
).SImIlarly,
functIonalgenetIcvarIantsInthePA1(PAI-1)andangIotensInconvertIngenzyme(ACE)
geneshavebeenassocIatedwIthpooroutcomesInsepsIs,reflectIngthecomplex
InteractIonbetweenInflammatIon,coagulatIon,endothelIalfunctIon,andvasculartoneIn
thepathogenesIsofsepsIsInducedorgandysfunctIon.
ThIscontInuIngefforttoIdentIfyInItIalSNPdIseaseassocIatIonsIsfollowedbyaprocessof
selectIngrelIablepredIctIveSNPsbyvalIdatIonInIndependentpopulatIonsand
determInIngwhIchandhowmanymarkerswIllmaxImIzethepowertopredIctrIskfor
sepsIsormortalItyfollowIngInjury.
Functional Genomics of Injury
Atacellularlevel,InjurIousstImulItrIggeradaptIvestressresponsesdetermInedby
quantItatIveandqualItatIvechangesInInterdIgItatIngcascadesofbIologIcalpathways
InteractIngIncomplex,oftenredundantways.Asaresult,numerousclInIcaltrIals
attemptIngtoblocksIngleInflammatorymedIators,suchasTNFInsepsIs,havebeen
largelyunsuccessful.
16J
CIventhesecomplexInterconnectIons,thestandardsInglegene
paradIgmIsInsuffIcIenttoadequatelydescrIbethetIssueresponsetoseveresystemIc
stImulI.nstead,organInjurymIghtbetterbedefInedbypatternsofalteredgeneand
proteInexpressIon.
164
AsprevIouslydIscussed,0NAmIcroarraytechnologyhasbecomea
powerfulhIghthroughputmethodofanalyzIngchangesInducedbyvarIousInjurIesona
genomewIdescale,byquantIfyIngmFNAabundanceandgeneratInganexpressIonprofIle
forthecellortIssueofInterest.SeveralstudIeshavereportedthegeneexpressIonprofIles
InbothcrItIcallyIllpatIentsandInanImalmodelsofsepsIs,
165,166
acutelungInjury,
167
and
burnInjury.
168
UsInggeneexpressIonprofIlIngInperIpheralbloodneutrophIls,Tanget
al.
169
haveIdentIfIedasetof50sIgnaturegenesthatcorrectlyIdentIfIedsepsIswItha
predIctIonaccuracyof91.mportantly,thIsgenomIcclassIfIerwasastrongerpredIctorof
sepsIsthanphysIologIcIndIcesandcytokInes,suchasprocalcItonIn.DncegenelIstsare
IdentIfIed,extractIngbIologIcalInformatIonhasproventobeoneofthemostperplexIng
challenges.nhumansubjectsadmInIsteredendotoxIn,thenumberofgeneswhose
expressIonchangedInbloodleukocyteswas4,000,
170
andInseverelytraumatIzed
patIents,theexpressIonof6,000geneschangedInperIpheralbloodleukocytes.
171
tthus
becameevIdentthattoolshadtobedevelopedthatcouldcategorIzethesegenesand
responsesIntofunctIonalmodules,Interactomemaps,andsIgnalIngpathways.
170
Two
largescalenatIonalprogramsareusInggeneandproteInexpressIonprofIlesIncIrculatIng
leukocytestoInvestIgatethebIologIcalreasonsbehIndtheextremevarIabIlItyInpatIent
outcomesaftersImIlartraumatIcInsults(theNatIonalnstItutesofHealthfundedTrauma
ClueCrant
a
),andtoelucIdateregulatorymechanIsmsInresponsetoseptIcchallengeIn
hIghrIskpatIents(theCermanNatIonalCenomeFesearchNetwork
b
).
164
AnalytIcaland
organIzatIonalapproachestoasystematIcevaluatIonofthevarIanceassocIatedwIth
genomewIdeexpressIonanalysIsInhumanbloodleukocytesIn
P.1J1
therealworldhavebeenreportedbythesegroups,andareveryInformatIveInthestudy
ofcrItIcalIllness.
172
SInceonlylessthanhalfofthechangesatmFNAlevelareusuallytranslatedIntochanges
InproteInexpressIon,transcrIptIonalprofIlInghastobecomplementedbycharacterIzIng
theInjuryproteome,foramorecompleteunderstandIngofthehostresponsetoInjury.
ntegratedanalysIsofneutrophIlstranscrIptomeandproteomeInresponseto
lIpopolysaccharIdestImulatIonhasIdentIfIedupregulatIonofavarIetyofgenes,IncludIng
transcrIptIonalregulators(NF8),cytokInes(TNF,L6,L1),andchemokInes(|CP1,
|PJ),andconfIrmedthepoorconcordancebetweentranscrIptIonalandtranslatIonal
responses.
17J
ArecentstudyhasestablIshedanextensIvereferenceproteIndatabasefor
traumapatIents,provIdIngafoundatIonforfuturehIghthroughputquantItatIveplasma
proteomIcInvestIgatIonsofthemechanIsmsunderlyIngsystemIcInflammatory
responses.
174
ChangesInserumproteomeassocIatedwIthsepsIsandseptIcshockhavebeen
reported,
175
andmayallowrapIdsubclassIfIcatIonofsepsIssyndromeIntovarIantsthat
maybetterpredIctresponsIvenesstofluIdresuscItatIon,IntravenoussteroIds,actIvated
proteInC,antITNFdrugs,orspecIfIcantIbIotIcs.
61
|odelIngdIseaseentItIeslIkesepsIsandmultIpleorgandysfunctIonsyndrome,whIchare
complex,nonlInearsystems,requIresnotonlytheabIlItytomeasuremanydIverse
moleculareventssImultaneously,butalsotoIntegratethedatausIngnovelanalytIcaltools
basedoncomplexsystemstheoryandnonlIneardynamIcs.
176
SuchanalysIsmIghthelp
IdentIfythekeysIgnalIngnodesagaInstwhIchtherapeutIcscanbedIrected.
Figure 6-5.LevelsofIntegratIonInperIoperatIvesystemsbIology:theperIoptome.
CellularfunctIonIsorganIzedasamultIlayeredsetofInterdependentprocesses
controlledatthelevelofthegenome(0NA),transcriptome(messengerFNA),
proteome(thecollectIonofallproteInsencodedwIthInthe0NAofagenome),and
metabolome(thecompletesetofsmallmoleculemetabolItestobefoundIna
bIologIcalsystem),whIchcanallbeInterrogatedusInghIghthroughputtechnologIes.
AccuraterepresentatIonoftheperIoperatIvephenome(thesetofallperIoperatIve
phenotypesexpressedbyanIndIvIdualpatIent)requIresIntegratIonofstandardIzed
phenotypedefInItIons(phenotypeontology),stateoftheartImagIngtechnologIes,and
comprehensIveclInIcaldatawarehousIng.FelatInggenomevarIabIlItytospecIfIc
perIoperatIvephenotypesthroughsystemsbIologyapproachesInvolvestheorthogonal
IntegratIonofmultIplelevelsofbIologIcalorganIzatIonprovIdedbygenomewIdedata
setswIthclInIcaldataandlIteraturedata,modelIngtheregulatorynetworksInvolved
InadverseperIoperatIveoutcomes,andIdentIfyIngcrItIcalregulatorynodesfor
therapeutIcmanIpulatIon.WC,wholegenome;SNP,sInglenucleotIdepolymorphIsms;
0CE,dIfferentIalIngelelectrophoresIs;|S,massspectrometry.
Future Directions
Systems Biology Approach to Perioperative Medicine: The
Perioptome
SystemsbIologyIsaconceptualframeworkwIthInwhIchscIentIstsattempttocorrelate
massIveamountsofapparentlyunrelateddataIntoasIngleunIfyIngexplanatIonofhow
bIologIcalprocessesoccur.
177
ThIsevolvIngdIscIplInethatmergesexperImentaland
computatIonalapproachestoobserve,record,andIntegrateInformatIonfromthe
molecular,cellular,tIssue,andwholeorganIsmlevelsIntotestablemodelsofadynamIc
bIologIcalprocesscanbeapplIedtounderstandthewaypatIentsrespondtoa
multIdImensIonalstImulussuchasasurgIcalprocedureandthemechanIstIcbasIsof
perIoperatIvemorbIdIty(FIg.65).SuchanapproachInvolvesmultIplelevels
P.1J2
ofdataIntegratIon.FIrst,delIneatIngthecomposItIonoftheperioperative phenome(the
representatIonofallperIoperatIvephenotypesexpressedbyagIvenpatIent)requIres
standardIzeddefInItIons,controlledvocabularIes,anddatadIctIonarIes(aperIoperatIve
phenotypeontology),new(molecular)ImagIngtechnologIes,andtheavaIlabIlItyof
comprehensIvedatawarehousIngcapabIlItIesthatwIllallowcataloguIngIndIvIdual
perIoperatIvephenotypesaswellascorrelatIonsbetweencombInatIonsofphenotypes
(organcrosstalk,multIpleorganfaIlure).Second,orthogonalIntegratIonofwholegenome
genotypIc,transcrIptomIc,proteomIc,andmetabolomIcdata,augmentedbymorerecent
functIonalgenomIcandproteomIcapproachesIncludIngproteInproteIn,proteIn0NA,or
othercomponentcomponentInteractIonmappIng(interactome),transcrIptorproteIn
threedImensIonallocalIzatIonmappIng(localizome),
178
andlIteraturedatawIthIn
IndIvIdualbIologIcalsystemsInvolvedInperIoperatIvemorbIdIty.ThIshIghestlevelofdata
IntegratIonIsthemappIngoftheIntegratedhIghthroughputstatIcanddynamIcgenomIc
dataIntoregulatorynetworksInordertomodelInteractIonsofthedIfferentcomponentsof
thesystem,IdentIfymodulesofhIghlyInterconnectedgenes,andhubpoIntsthatcanbe
prIorItIzedastherapeutIctargets.UltImately,mathematIcalmodelsrequIreexperImental
valIdatIonInanImalmodelsofdIseaseortIssueculture,InanIteratIveprocessthatIsone
ofthecorecharacterIstIcsofsystemsbIology.
179
SuchIntegratIveapproachestostudy
cardIovascularfunctIon(theCardIomeProject),butalsoperIoperatIvemorbIdIty(the
perIoptome)
180
havealreadybeenoutlInedandpromIsetoIncreasetheIdentIfIcatIonof
keydrIversofperIoperatIveadverseeventsbeyondwhatcouldbeachIevedbygenetIc
assocIatIonsalone.
Targeted Therapeutic Applications: The Five Ps of
Perioperative Medicine and Pain Management
CenomIcandproteomIcapproachesarerapIdlybecomIngplatformsforallaspectsofdrug
dIscoveryanddevelopment,fromtargetIdentIfIcatIonandvalIdatIontoIndIvIdualIzatIon
ofdrugtherapy.AsprevIouslymentIoned,thehumangenomecontaInsabout25,000genes
encodIngforapproxImately200,000proteInsthatrepresentpotentIaldrugtargets.
However,onlyabout120drugtargetsarecurrentlybeIngmarketed,thusmakIng
IdentIfIcatIonofnoveltherapeutIctargetsanareaofIntenseresearch.FollowInggene
IdentIfIcatIon,ItstherapeutIcpotentIalneedstobevalIdatedbydefInIngthesequence
functIon,ItsroleIndIsease,anddemonstratIngthatthegeneproductcanbemanIpulated
wIthbenefIcIaleffectandnotoxIceffects.AdevelopIngfIeld,toxicogenomics,studIesthe
InfluenceoftoxIcorpotentIallytoxIcsubstancesondIfferentmodelorganIsmsby
evaluatIngthegeneexpressIonchangesInducedbynoveldrugsInagIventIssue.Sponsored
bytheNatIonalnstItutesofHealth,anatIonwIdecollaboratIveeffortcalledthe
PharmacogenetIcsFesearchNetwork
c
IsaImIngtoestablIshastrongpharmacogenomIcs
knowledgebase
d
,aswellascreateasharedcomputatIonalandexperImental
Infrastructure,requIredtoconnecthumansequencevarIatIonwIthdrugresponsesand
translateInformatIonIntonoveltherapeutIcs.
TheepIdemIologIcframeworkforassessIngtheapplIcabIlItyofprevIouslyIdentIfIed
bIomarkersofperIoperatIvemorbIdItyandthesuccessfulImplementatIonofmolecular
dIagnostIcsInperIoperatIvemedIcIneIscontIngentondemonstratIngtheIrclinical validity,
analytical validity,andclinical utility.
181
PerIoperatIvegenomIcInvestIgatorsarecurrently
conductIngreplIcatIonstudIesIndIfferentsurgIcalpatIentpopulatIonstoformallyassess
theclInIcalvalIdItyofthemarkersreportedsofar.ForgenomIcclassIfIers,theemphasIs
durIngexternalvalIdatIonIsplacedonprospectIvelytestIngtheaccuracyoftheentIre
molecularfIngerprIntInanewpatIentpopulatIonratherthancorroboratIngresultsIn
IndIvIdualgenes.nperIoperatIveandcrItIcalcaresettIngsItIsvItaltohavefast
turnaroundtIme(severalhours)andeasytousetestIngcapabIlItIes,sothatmeanIngful
therapeutIcInterventIonscantakeplace.nthIsregard,newmoleculardIagnostIcsystems
basedontherandomaccesstechnologysuchastheCeneXpert(CepheId,Sunnyvale,CA),
eSensor(Dsmetech,Pasadena,CA),andLIatAnalyzer(quum,|arlborough,|A)are
alreadybecomIngavaIlable.ClInIcalutIlIty(targetedInterventIonstoreduceperIoperatIve
morbIdItyamongpatIentswIthacertaIngenomIcprofIle)remaInstobeevaluatedInfuture
genomIcallystratIfIedperIoperatIvetrIals.ndeed,alandmarkstudyontheeffectsofa5
lIpoxygenaseactIvatIngproteIn(FLAP)InhIbItoronbIomarkersassocIatedwIththerIskof
myocardIalInfarctIondemonstratesthatbydefInIngatrIskpatIentsfortwogenesInthe
leukotrIenepathway,onecanpredIctwhowIllrespondtotargeteddrugtherapy.
SpecIfIcally,InpatIentscarryIngtheatrIskvarIantsIntheFLAPandIntheleukotrIeneA4
hydrolasegenes,useofaFLAPInhIbItorInarandomIzedcontrolledtrIalresultedIn
sIgnIfIcantanddosedependentsuppressIonofbIomarkersassocIatedwIthIncreasedrIskof
myocardIalInfarctIon.
182
tIsexpectedthatsImIlarprIncIplesoftargetedtherapeutIcs
couldbeoperatIonalIntheperIoperatIveperIod,thusbegInnIngtofulfIllthefIvePsof
modernmedIcIne(PersonalIzed,PreventIve,PredIctIve,PartIcIpatory,andProspectIve).
Ethical Considerations
AlthoughoneoftheaImsoftheHumanCenomeProjectIstoImprovetherapythrough
genomebasedpredIctIon,thebIrthofpersonalgenomIcsopensupaPandora'sboxof
ethIcalIssues,IncludIngprIvacyandtherIskfordIscrImInatIonagaInstIndIvIdualswhoare
genetIcallypredIsposedforamedIcaldIsorder.SuchdIscrImInatIonmayIncludebarrIersto
obtaInInghealth,lIfe,orlongtermcareInsurance,orobtaInIngemployment.Thus,
extensIveeffortsaremadetoprotectpatIentspartIcIpatIngIngenetIcresearchfrom
prejudIce,dIscrImInatIon,orusesofgenetIcInformatIonthatwIlladverselyaffectthem.
ToaddresstheconcernsofbothbIomedIcalresearchandhealthcommunItIes,theU.S.
SenatehasapprovedIn200JtheCenetIcnformatIonandNondIscrImInatIonAct,whIch
provIdesthestrongsafeguardsrequIredtoprotectthepublIcpartIcIpatIngInhuman
genomeresearch.
AnotherethIcalconcernIsthetransferabIlItyofgenetIctestsacrossethnIcgroups,
partIcularlyInthepredIctIonofadversedrugresponses.tIsknownthatmost
polymorphIsmsassocIatedwIthvarIabIlItyIndrugresponseshowsIgnIfIcantdIfferencesIn
allelefrequencIesamongpopulatIonsandracIalgroups.Furthermore,thepatternsof
lInkagedIsequIlIbrIumaremarkedlydIfferentbetweenethnIcgroups,whIchmayleadto
spurIousfIndIngswhenmarkers,InsteadofcausalvarIants,areusedIndIagnostIctests
extrapolatedacrosspopulatIons.nexplorIngracIaldIsparItIesInhealthanddIsease
outcomes,consIderabledebatehasfocusedonwhetherraceandethnIcIdentItyare
prImarIlysocIalorbIologIcalconstructs,andthecontrIbutIonofgenetIcvarIabIlItyIn
explaInIngobserveddIfferencesIntheratesofdIseasebetweenracIalgroups.WIththe
goalofpersonalIzedmedIcInebeIngthepredIctIonofrIskandtreatmentofdIseaseonthe
basIsofanIndIvIdual'sgenetIcprofIle,somehavearguedthatbIologIcalconsIderatIonof
racewIllbecomeobsolete.However,InthIsdIscoveryphaseofthe
P.1JJ
postgenomeera,contInuIngtoIncorporateracIalInformatIonIngenetIcstudIesshould
ImproveourunderstandIngofthearchItectureofthehumangenomeandItsImplIcatIons
fornovelstrategIesaImIngatIdentIfyIngvarIantsprotectIngagaInst,orconferrIng
susceptIbIlItyto,commondIseasesandmodulatIngdrugeffects.
18J
Conclusions
TheHumanCenomeProjecthasrevolutIonIzedallaspectsofmedIcIne,allowIngusto
assesstheImpactofgenetIcvarIabIlItyondIseasetaxonomy,characterIzatIon,and
outcome,andIndIvIdualresponsestovarIousdrugsandInjurIes.|echanIstIcally,
InformatIongleanedthroughgenomIcapproachesIsalreadyunravelInglongstandIng
mysterIesbehIndgeneralanesthetIcactIonandadverseresponsestodrugsused
perIoperatIvely.However,astrongneedremaInsforprospectIve,wellpoweredgenetIc
studIesInhIghlyphenotypedsurgIcalpopulatIons,whIchrequIrethedevelopmentof
multIdImensIonalperIoperatIvedatabases.FortheanesthesIologIst,thIsmaysoon
translateIntoprospectIverIskassessmentIncorporatInggenetIcprofIlIngofmarkers
ImportantInthrombotIc,Inflammatory,vascular,andneurologIcresponsesto
perIoperatIvestress,wIthImplIcatIonsrangIngfromIndIvIdualIzedaddItIonalpreoperatIve
testIngandphysIologIcaloptImIzatIon,tochoIceofperIoperatIvemonItorIngstrategIesand
crItIcalcareresourceutIlIzatIon.Furthermore,genetIcprofIlIngofdrugmetabolIzIng
enzymes,carrIerproteIns,andreceptors,usIngcurrentlyavaIlablehIghthroughput
moleculartechnologIes,wIllenablepersonalIzedchoIceofdrugsanddosageregImens
taIloredtosuItapatIent'spharmacogenetIcprofIle.AtthatpoInt,perIoperatIvephysIcIans
wIllhavefarmorerobustInformatIontouseIndesIgnIngthemostapproprIateandsafest
anesthetIcplanforgIvenpatIent.
FuturetrendsandchallengesInperIoperatIvegenomIcsarestIllbeIngdefIned,butmaInly
concernInterdIscIplInarystudIesdesIgnedtocombIneananalytIcalsystemapproach,
mathematIcalmodelIng,andengIneerIngprIncIpleswIththemultIplemolecularand
genetIcfactorsandstImulI,andthemacroscaleInteractIonsthatdetermInethe
pathophysIologIcalresponsetosurgery.
Acknowledgments
SupportedInpartbyNatIonalnstItutesofHealthgrantsHL07527JandHL092071to|7P.
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Stock, M. Christine
TableofContentsSectIonScIentIfIcFoundatIonsofAnesthesIaChapter7PharmacologIcPrIncIples
Chapter7
Pharmacologic Principles
Dhanesh K. Gupta
Thomas K. Henthorn
Key Points
1. Most drugs must pass through cell membranes to reach their sites of
action. Consequently, drugs tend to be relatively lipophilic, rather
than hydrophilic.
2. The highly lipophilic anesthetic drugs have a rapid onset of action
because they rapidly diffuse into the highly perfused brain tissue.
They have a very short duration of action because of redistribution of
drug from the central nervous system to the blood.
3. The cytochrome P450 (CYP) superfamily is the most important group
of enzymes involved in drug metabolism. It and other drug-
metabolizing enzymes exhibit genetic polymorphism.
4. The kidneys eliminate hydrophilic drugs and relatively hydrophilic
metabolites of lipophilic drugs. Renal elimination of lipophilic
compounds is negligible.
5. The liver is the most important organ for metabolism of drugs.
Hepatic drug clearance depends on three factors: the intrinsic ability
of the liver to metabolize a drug, hepatic blood flow, and the extent
of binding of the drug to blood components.
6. The volume of distribution quantifies the extent of drug distribution.
The greater the affinity of tissues for a drug relative to blood, the
greater its volume of distribution (i.e., lipophilic drugs have greater
volumes of distribution).
7. Elimination clearance is the parameter that characterizes the ability
of drug-eliminating organs to irreversibly remove drugs from the
body. The efficiency of the body to remove a drug from the body is
proportional to the elimination clearance.
8. All else being equal, an increase in the volume of distribution of a
drug will increase its elimination half-life; an increase in elimination
clearance will decrease elimination half-life.
9. Most drugs bring about a pharmacologic effect by binding to a specific
receptor that brings about a change in cellular function to produce
the pharmacologic effect.
10. Although most pharmacologic effects can be characterized by both
dose-response curves and concentration-response curves, the dose-
response curves are unable to determine whether variations in
pharmacologic response are caused by differences in
pharmacokinetics, pharmacodynamics, or both.
11. Integrated pharmacokinetic-pharmacodynamic models allow temporal
characterization of the relationship between dose, plasma
concentration, and pharmacologic effect.
12. Simulations of multicompartmental pharmacokinetic models that
describe intravenous anesthetics demonstrate that for most
anesthetic dosing regimens, the distribution of drug from the plasma
to the pharmacologically inert peripheral tissues has a greater
influence on the plasma concentration profile of the drug than the
elimination of drug from the body.
13. Target-controlled infusions are achieved with computer-controlled
infusion pumps worldwide (not yet approved by the Food and Drug
Administration [FDA] in the United States) and permit clinicians to
make use of the drug concentrationeffect relationship, optimally
accounting for pharmacokinetics and predicting the offset of drug
effect.
14. By understanding the interactions between the opioids and the
sedative-hypnotics (e.g., response surface models), it is possible to
select target concentration pairs of the two drugs that produce the
desired clinical effect while minimizing unwanted side effects
associated with high concentrations of a single drug.
15. The time until a patient regains responsiveness from a single drug
anesthetic is determined by the pharmacokinetics of the individual
drug, the concentration-effect relationship, and the duration of
administration of the drug (context-sensitive decrement time). For
two-drug anesthetics, the time to awakening not only depends on the
individual drug pharmacokinetics and the duration of administration
of the anesthetics, but it also depends on the pharmacodynamic
interactions of the two drugs.
P.1J8
n194J,Halford
1
labeledthIopentalasanIdealmethodofeuthanasIaforwarsurgIcal
patIentsandpronouncedthatopendropetherstIllretaInsprImacy!8asedonthIs
recountoftheexperIencewIththIopentalatPearlHarbor,ItIsImpressIvethatcooler
headsprevaIledAdamsandCray
2
detaIledacaseofacIvIlIangunshotwoundInwhIch
theycarefullytItratedIncrementaldosesofthIopentalwIthoutanyadverserespIratoryor
cardIovascularevents.TohIghlIghttheImportanceofthequIetcasereportversusthe
anImatedcondemnatIonofIntravenousanesthesIaforpatIentswIthhemorrhagIcshock,an
anonymousedItorIalappearedInthesameIssueofAnesthesiologythatattemptedtogIve
somescIentIfIcjustIfIcatIonforthedIscrepancyInopInIons.
J
AstheedItorIaldetaIled,
thIopentalhadasmalltherapeutIcIndexandthetolerancetonormaldoseswasdecreased
InextremephysIcalcondItIons(e.g.,bloodloss,sepsIs).Therefore,aswIthopendrop
ether,smalldosesofthIopentalshouldbetItratedtoachIevethedesIredaffectsandavoId
sIdeeffectsassocIatedwIthoverdose.FortuItously,theanesthesIacommunItydIdnot
sImplyabandontheuseofthIopental,andIn1960,PrIce
4
usedmathematIcalmodelsIn
ordertodescrIbetheeffectsofhypovolemIaonthIopentaldIstrIbutIon.
AnesthetIcdrugsareadmInIsteredwIththegoalofrapIdlyestablIshIngandmaIntaInInga
therapeutIceffectwhIlemInImIzIngundesIredsIdeeffects.Althoughopendropetherand
chloroformwereadmInIsteredusIngknowledgeofadoseeffectrelatIonshIp,themore
potentvolatIleagents,alongwIththeIntravenoushypnotIcs,neuromuscularjunctIon
blockIngagents,andIntravenousopIoIds,requIreasoundknowledgeofpharmacokInetIcs
andpharmacodynamIcsInordertoaccuratelyachIevethedesIredthepharmacologIc
effectforthedesIredperIodoftImewIthoutanydrugtoxIcIty.
ThIschapterattemptstoguIdethereaderthroughthefundamentalknowledgeofwhatthe
bodydoestoadrug(I.e.,pharmacokInetIcs)andwhatadrugdoestothebody(I.e.,
pharmacodynamIcs).TheInItIalsectIonofthIschapterdIscussesthebIologIcand
pharmacologIcfactorsthatInfluencetheabsorptIon,dIstrIbutIon,andelImInatIonofadrug
fromthebody.Wherenecessary,quantItatIveanalysesoftheseprocessesaredIscussedto
gIvereadersInsIghtIntotheIntrIcacIesofpharmacokInetIcsthatcannotbeeasIly
descrIbedbytextalone.ThesecondsectIonconcentratesonthefactorsthatdetermInethe
relatIonshIpbetweendrugconcentratIonandpharmacologIceffect.DnceagaIn,
mathematIcalmodelsarepresentedasneededInordertoclarIfypharmacodynamIc
concepts.ThefInalsectIonbuIldsonthereader'sknowledgegaInedfromthefIrsttwo
sectIonstoapplytheprIncIplesofpharmacokInetIcsandpharmacodynamIcstodetermIne
thetargetconcentratIonofIntravenousanesthetIcsrequIredandthedosIngstrategIes
necessarytoproduceanadequateanesthetIcstate.UnderstandIngtheseconceptsshould
allowthereadertoIntegratetheanesthetIcdrugsofthefutureIntoaratIonalanesthetIc
regImen.AlthoughspecIfIcdrugsareusedtoIllustratepharmacokInetIcand
pharmacodynamIcprIncIplesthroughoutthIschapter,detaIledpharmacologIcInformatIon
ofanesthetIcpharmacopeIaarepresentedInsubsequentchaptersofthIsbook.
Pharmacokinetic Principles
Drug Absorption and Routes of Administration
Transfer of Drugs Across Membranes
ForeventhesImplestdrugthatIsdIrectlyadmInIsteredIntothebloodtoexertItsactIon,
ItmustmoveacrossatleastonecellmembranetoItssIteofactIon.8ecausebIologIc
membranesarelIpIdbIlayerscomposedofalIpophIlIccoresandwIchedbetweentwo
hydrophIlIclayers,onlysmalllIpophIlIcdrugscanpassIvelydIffuseacrossthemembrane
downItsconcentratIongradIent.norderforwatersolubledrugstopassIvelydIffuseacross
themembranedownItsconcentratIongradIent,transmembraneproteInsthatforma
hydrophIlIcchannelarerequIred.8ecauseoftheabundanceofthesenonspecIfIc
hydrophIlIcchannelsInthecapIllaryendothelIumofallorgansexceptforthecentral
nervoussystem(CNS),wherethebloodbraInbarrIercapIllaryendothelIalcellshavevery
lImItednumbersoftransmembranehydrophIlIcchannels,passive transportofdrugsfrom
theIntravascularspaceIntotheInterstItIumofvarIousorgansIslImItedbybloodflow,not
bythelIpIdsolubIlItyofthedrug.
5
HydrophIlIcdrugscanonlyentertheCNSafterbIndIngtodrugspecIfIctransmembrane
proteInsthatactIvelytransportthehydrophIlIcdrugacrossthecapIllaryendothelIumInto
theCNSInterstItIum.WhenthesetransmembranecarrIerproteInsrequIreenergyto
transportthedrugacrossthemembrane,theyareabletoshuttleproteInsagaInsttheIr
concentratIongradIents,aprocesscalledactive transport.ncontrast,whenthesecarrIer
proteInsdonotrequIreenergytoshuttledrugs,theycannotovercomeconcentratIon
gradIents,aprocesscalledfacilitated diffusion.Therefore,actIvetransportIsnotlImIted
totheCNSbutIsalsofoundIntheorgansrelatedtodrugelImInatIon(e.g.,hepatocytes,
renaltubularcells,pulmonarycapIllaryendothelIum),wheretheabIlItytotransportdrugs
agaInsttheconcentratIongradIenthasspecIfIcbIologIcadvantages.8othactIvetransport
andfacIlItateddIffusIonofdrugsaresaturableprocessesthatarelImItedonlybythe
numberofcarrIerproteInsavaIlabletoshuttleaspecIfIcdrug.
5
ForlIpophIlIccompounds,transportersarenotneededforthedrugtodIffuseacrossthe
capIllarywallIntotIssues,butthepresenceoftransportersdoesaffecttheconcentratIon
gradIentsthatexIst.ForInstance,somelIpophIlIcdrugsaretransportedoutoftIssuesby
adenosInetrIphosphatedependenttransporterssuchaspglycoproteIn.ThelIpophIlIc
potentopIoIdagonIst,loperamIde,usedforthetreatmentofdIarrhea,haslImIted
bIoavaIlabIlItybecauseofpglycoproteIntransportersattheIntestIneportalcapIllary
Interface,andthenwhatdoesreachthecIrculatIonhasItsCNSpenetrancelImItedbyp
glycoproteInatthebloodbraInbarrIer.
6
Conversely,lIpophIlIccompoundscanbe
transportedIntotIssues,IncreasIngthetIssueconcentratIonofthedrugbeyondwhatwould
beaccomplIshedbypassIvedIffusIon.Theclassoftransporterscalledorganic anion
polypeptide transporters,lIkepglycoproteIn,IslocatedInthemIcrovascularendothelIum
ofthebraInandtransportendogenousopIoIdsIntothebraIn.
7,8
TheseorganIcanIon
polypeptIdetransportersalsotransportdrugs.ThedegreetowhIchtransporterproteIns
mayaccountforIntraandInterIndIvIdualresponsestoanesthetIcdrugshasnotbeenwell
studIedtodate.
9
Intravenous Administration
norderforadrugtobedelIveredtothesIteofdrugactIon,thedrugmustbeabsorbed
IntothesystemIccIrculatIon.Therefore,IntravenousadmInIstratIonresultsInrapId
IncreasesIndrugconcentratIon.AlthoughthIscanleadtoaveryrapIdonsetofdrugeffect,
fordrugsthathavealowtherapeutic index(theratIooftheIntravenousdosethat
producesatoxIceffectIn50ofthepopulatIontotheIntravenousdosethatproducesa
therapeutIceffectIn50ofthepopulatIon),rapIdovershootofthedesIredplasma
concentratIoncanpotentIallyresultInImmedIateandseveresIdeeffects.Exceptfor
IntravenousadmInIstratIon,theabsorptIonofadrugIntothesystemIccIrculatIonIsan
ImportantdetermInantofthetImecourseofdrugactIonandthemaxImumdrugeffect
produced.AstheabsorptIonofdrugIsslowed,themaxImum
P.1J9
plasmaconcentratIonachIevedandthereforethemaxImumdrugeffectachIevedIs
lImIted.However,aslongastheplasmaconcentratIonIsmaIntaInedatalevelabovethe
mInImumeffectIveplasmaconcentratIon,thedrugwIllproduceadrugeffect.
10
Therefore,
nonIntravenousmethodsofdrugadmInIstratIoncanproduceasustaInedandsIgnIfIcant
drugeffectthatmaybemoreadvantageousthanadmInIsterIngdrugsbytheIntravenous
route.
11
BioavailabilityIstherelative amountofadrugdosethatreachesthesystemIccIrculatIon
unchangedandtherateatwhIchthIsoccurs.FormostIntravenouslyadmInIstereddrugs,
theabsolutebIoavaIlabIlItyofdrugavaIlableIsclosetounItyandtherateIsnearly
Instantaneous.However,thepulmonaryendothelIumcanslowtherateatwhIch
IntravenouslyadmInIstereddrugsreachthesystemIccIrculatIonIfdIstrIbutIonIntothe
alveolarendothelIumIsextensIve,suchasoccurswIththepulmonaryuptakeoffentanyl.
ThepulmonaryendothelIumalsocontaInsenzymesthatmaymetabolIzeIntravenously
admInIstereddrugs(e.g.,propofol)onfIrstpassandreducetheIrabsolutebIoavaIlabIlIty.
12
Oral Administration
ForalmostalltherapeutIcagentsInallfIeldsofmedIcIne,oraladmInIstratIonIsthesafest
andmostconvenIentmethodofadmInIstratIon.However,thIsrouteIsnotused
sIgnIfIcantlyInanesthetIcpractIcebecauseofthelImItedandvarIablerateof
bIoavaIlabIlIty.TheabsorptIonrateInthegastroIntestInaltractIshIghlyvarIablebecause
themaIndetermInantofthetImIngofabsorptIonIsgastrIcemptyIngIntothesmall
IntestIneswherethesurfaceareaforabsorptIonIsseveralordersofmagnItudegreater
thanthatofthestomachorlargeIntestInes.AddItIonally,theactIvemetabolIsmofdrugby
thesmallIntestInemucosalepIthelIum,andtheoblIgatorypaththroughtheportal
cIrculatIonbeforeenterIngthesystemIccIrculatIon,contrIbutetodecreased
bIoavaIlabIlItyoforallyadmInIstereddrugs.
1J
nfact,themetabolIccapacItyofthelIver
fordrugsIssohIghthatonlyasmallfractIonofmostlIpophIlIcdrugsactuallyreachthe
systemIccIrculatIon.8ecauseofthIsextensIvefirst-pass metabolism,theoraldoseofmost
drugsmustbesIgnIfIcantlyhIghertogenerateatherapeutIcplasmaconcentratIon.Coupled
wIththeprolongedandvarIabletImeuntIlpeakconcentratIonsareusuallyachIevedfrom
oraladmInIstratIon(betweentensofmInutestohours),ItIsnearlyImpractIcaltousethIs
modetoadmInIsterperIoperatIveanesthetIcagents.
HIghlylIpophIlIcdrugsthatcanmaIntaInahIghcontacttImewIthnasalororal(sublIngual)
mucosacanbeabsorbedwIthoutneedIngtotraversethegastroIntestInaltract.SublIngual
admInIstratIonofdrughastheaddItIonaladvantageovergastroIntestInalabsorptIonIn
thatabsorbeddrugdIrectlyentersthesystemIcvenouscIrculatIonandthereforeIsableto
bypassthemetabolIcallyactIveIntestInalmucosaandthehepatIcfIrstpassmetabolIsm.
Therefore,smallamountsofdrugcanrapIdlyproduceasIgnIfIcantplasmaconcentratIon
andtherapeutIceffect.
14
However,becauseofformulatIonlImItatIonsandthesmall
amountofsurfaceareaavaIlableforabsorptIon,sublIngualadmInIstratIonIslImItedto
drugsthatfortuItouslymeettheserequIrementsandrequIrearapIdonsetofdrugactIon
(e.g.,nItroglycerIn,fentanyl).
Transcutaneous Administration
AfewlIpophIlIcdrugshavebeenmanufacturedInformulatIonsthataresuffIcIenttoallow
penetratIonofIntactskIn.AlthoughscopolamIne,nItroglycerIn,opIoIds,andclonIdIneall
producetherapeutIcsystemIcplasmaconcentratIonswhenadmInIsteredasdrugpatches,
theextendedamountoftImethatIttakestoachIeveaneffectIvetherapeutIc
concentratIonlImItspractIcalapplIcatIonexceptformaIntenancetherapy.Attemptsto
speedthepassIvedIffusIonofthesedrugsusInganelectrIccurrenthasbeendescrIbedfor
fentanyl,
15
butIsstIlllImItedInItspractIcalIty.
Intramuscular and Subcutaneous Administration
AbsorptIonofdrugsfromthedepotsInthesubcutaneoustIssueorInmuscletIssueIs
dIrectlydependentonthedrugformulatIonandthebloodflowtothedepot.8ecauseofthe
hIghbloodflowtomusclesInmostphysIologIcstates,IntramuscularabsorptIonofdrugsIn
solutIonIsrelatIvelyrapIdandcomplete.Therefore,someaqueousdrugscanbe
admInIsteredasIntramuscularInjectIonwIthrapIdandpredIctableeffects(e.g.,
neuromuscularjunctIonblockIngagents).ThesubcutaneousrouteofdrugabsorptIonIs
morevarIableInItsonsetbecauseofthevarIabIlItyofsubcutaneousbloodflowdurIng
varyIngphysIologIcstatesthIsIstheprImaryreasonthatsubcutaneousregularInsulIn
admInIsteredIntheoperatIngroomhasavarIabletImeofonsetandmaxImumeffect.
Intrathecal, Epidural, and Perineural Injection
8ecausethespInalcordIstheprImarysIteofactIonofmanyanesthetIcagents,dIrect
InjectIonoflocalanesthetIcsandopIoIdsdIrectlyIntotheIntrathecalspacebypassesthe
lImItatIonsofdrugabsorptIonanddrugdIstrIbutIonofanyotherrouteofadmInIstratIon.
ThIsIsnotthecaseforepIduralandperIneuraladmInIstratIonoflocalanesthetIcsbecause
notdelIverIngthedrugdIrectlyIntothecerebrospInalfluIdnecessItatesthatthedrugbe
absorbedthroughtheduraornervesheathInordertoreachthesIteofdrugactIon.The
majordownsIdetoallofthesetechnIquesIstherelatIveexpertIserequIredtoperform
regIonalanesthetIcsrelatIvetooral,Intravenous,andInhalatIonaladmInIstratIonofdrug.
Inhalational Administration
ThelargesurfaceareaofthepulmonaryalveolIavaIlableforexchangewIththelarge
volumetrIcflowofbloodfoundInthepulmonarycapIllarIesmakesInhalatIonal
admInIstratIonanextremelyattractIvemethodbywhIchtoadmInIsterdrugs.
16
New
technologIeshavebeendevelopedthatcanrapIdlyandpredIctablyaerosolIzeawIderange
ofdrugsandthusapproxImateIntravenousadmInIstratIon.
17
ThesedevIcesarecurrentlyIn
phase2F0AtrIals.
Drug Distribution
DncethedrughasenteredthesystemIccIrculatIon,ItIstransportedthroughbulkflowof
bloodtoalloftheorgansthroughoutthebody.TherelatIvedIstrIbutIonofcardIacoutput
amongorganvascularbedsdetermInesthespeedatwhIchorgansareexposedtothedrug.
ThehIghlyperfusedcorecIrculatorycomponentsthebraIn,lungs,heart,andkIdneys
receIvethehIghestrelatIvedIstrIbutIonofcardIacoutputandthereforearetheInItIal
organstoreachequIlIbrIumwIthplasmadrugconcentratIons.
4
0rugconcentratIonsthen
equIlIbratewIththelesswellperfusedmusclesandlIverandthen,fInally,wIththe
relatIvelypoorlyperfusedsplanchnIcvasculature,adIposetIssue,andbone.
WhetherbypassIvedIffusIonortransportermedIatIon,drugtransportatthecapIllarIesIs
notusuallysaturable,sotheamountofdruguptakebytIssuesandorgansIslImItedbythe
bloodflowtheyreceIve(I.e.,flowlImIteddruguptake).
AlthoughtherateofInItIaldrugdelIverymaydependontherelatIvebloodflowofthe
organ,therateofdrugequIlIbratIonbythetIssuedependsontheratIoofbloodflowto
tIssuecontent.Therefore,druguptakerapIdlyapproachesequIlIbrIum
P.140
InthehIghlyperfusedbutlowvolumebraIn,kIdneys,andlungsInamatterofmInutes,
whereasdrugtransfertothelesswellperfused,IntermedIatevolumemuscletIssuemay
takehourstoapproachequIlIbrIum,anddrugtransfertothepoorlyperfused,largecellular
volumesofadIposetIssuedoesnotequIlIbratefordays.
11
Redistribution
HIghlylIpophIlIcdrugssuchasthIopentalandpropofolrapIdlybegIntodIffuseIntothe
hIghlyperfusedbraIntIssueusuallylessthanamInuteafterIntravenousInjectIon(see
Chapter18).8ecauseofthelowtIssuevolumebuthIghperfusIonofthebraIn,thedrug
concentratIonInthecerebralarterIalbloodrapIdlyequIlIbrates,usuallywIthInJmInutes,
wIththeconcentratIonInthebraIntIssue.AsdrugcontInuestobetakenupbyother
tIssueswIthlowerbloodflowsandhIghertIssuemass,theplasmaconcentratIonofthedrug
contInuestodecreaserapIdly.DncetheconcentratIonofdrugInthebraIntIssueIshIgher
thantheplasmaconcentratIonofdrug,thereIsareversalofthedrugconcentratIon
gradIentsothatthelIpophIlIcdrugreadIlydIffusesbackIntothebloodandIsredistributed
totheothertIssuesthatarestIlltakIngupdrug.
4,18,19
ThIsprocesscontInuesforeachof
theorganbedsuntIl,ultImately,theadIposetIssuewIllcontaInthemajorItyofthe
lIpophIlIcdrugthathasnotbeenremovedfromthebodybymetabolIsmorexcretIon.
However,afterasInglebolusofahIghlylIpophIlIcdrug,thebraIn'stIssueconcentratIon
rapIdlydecreasesbelowtherapeutIclevelsbecauseofredIstrIbutIonofdrugtomuscle
tIssue,whIchhasalargerperfusIonthanadIposetIssue.
4,19
AlthoughsIngle,moderate
dosesofhIghlylIpophIlIcdrugshaveaveryshortCNSduratIonofactIonbecauseof
redIstrIbutIonofdrugfromtheCNStothebloodandother,lesswellperfusedtIssues,
repeatedInjectIonsofadrugallowstherapIdestablIshmentofsIgnIfIcantperIpheraltIssue
concentratIons.WhenthetIssueconcentratIonsofadrugarehIghenough,thedecreaseIn
plasmadrugconcentratIonbelowtherapeutIcthresholdbecomessolelydependentondrug
elImInatIonfromthebody.
20
Drug Elimination
8esIdesbeIngexcretedunchangedfromthebody,adrugcanbebIotransformed
(metabolIzed)IntooneormorenewcompoundsthatarethenelImInatedfromthebody.
EIthermechanIsmofelImInatIonwIlldecreasethedrugconcentratIonInthebodysuchthat
theconcentratIonwIlleventuallybeneglIgIbleandthereforeunabletoproducedrug
effect.EliminationIsthepharmacokInetIctermthatdescrIbesalltheprocessesthat
removeadrugfromthebody.AlthoughthelIverandthekIdneysareconsIderedthemajor
organsofdrugelImInatIon,drugmetabolIsmcanoccuratmanyotherlocatIonsthat
contaInactIvedrugmetabolIzIngenzymes(e.g.,pulmonaryvasculature,redbloodcells)
anddrugcanbeexcretedunchangedfromotherorgans(e.g.,lungs).
Elimination clearance(drugclearance)IsthetheoretIcalvolumeofbloodfromwhIchdrug
IscompletelyandIrreversIblyremovedInaunItoftIme.
21
ElImInatIonclearancehasthe
unItsofflow[volumepertIme].TotaldrugclearancecanbecalculatedwIth
pharmacokInetIcmodelsofbloodconcentratIonversustImedata.
Biotransformation Reactions
|ostdrugsthatareexcretedunchangedfromthebodyarehydrophIlIcandtherefore
readIlypassedIntourIneorstool.0rugsthatarenotsuffIcIentlyhydrophIlIctobeableto
beexcretedunchangedrequIremodIfIcatIonIntomorehydrophIlIc,excretablecompounds.
EnzymatIcreactIonsthatmetabolIzedrugscanbeclassIfIedIntophaseandphase
bIotransformatIonreactIons.PhasereactIonstendtotransformadrugIntooneormore
polar,andhencepotentIallyexcretablecompounds.PhasereactIonstransformthe
orIgInaldrugbyconjugatIngavarIetyofendogenouscompoundstoapolarfunctIonalgroup
ofthedrug,makIngthemetabolIteevenmorehydrophIlIc.DftendrugswIllundergoa
phasereactIontoproduceanewcompoundwIthapolarfunctIonalgroupthatwIllthen
undergoaphasereactIon.However,ItIspossIbleforadrugtoundergoeItheraphase
reactIonaloneoraphasereactIonalone.
Phase I Reactions
PhasereactIonsmayhydrolyze,oxIdIze,orreducetheparentcompound.HydrolysisIsthe
InsertIonofamoleculeofwaterIntoanothermolecule,whIchformsanunstable
IntermedIatecompoundthatsubsequentlysplItsapart.Thus,hydrolysIscleavestheorIgInal
substanceIntotwoseparatemolecules.HydrolytIcreactIonsaretheprImarywayamIdes,
suchaslIdocaIneandotheramIdelocalanesthetIcs,andesters,suchassuccInylcholIne,
aremetabolIzed.
|anydrugsarebIotransformedbyoxIdatIvereactIons.OxidationsaredefInedasreactIons
thatremoveelectronsfromamolecule.Thecommonelementofmost,Ifnotall,
oxIdatIonsIsanenzymatIcallymedIatedreactIonthatInsertsahydroxylgroup(DH)Into
thedrugmolecule.nsomeInstances,thIsproducesachemIcallystable,morepolar
hydroxylatedmetabolIte.However,hydroxylatIonusuallycreatesunstablecompoundsthat
spontaneouslysplItIntoseparatemolecules.|anydIfferentbIotransformatIonsare
affectedbythIsbasIcmechanIsm.0ealkylatIon(removalofacarboncontaInInggroup),
deamInatIon(removalofnItrogencontaInInggroups),oxIdatIonofnItrogencontaInIng
groups,desulfuratIon,dehalogenatIon,anddehydrogenatIonallfollowanInItIal
hydroxylatIon.HydrolysIsandhydroxylatIonarecomparableprocesses.8othhavean
InItIal,enzymatIcallymedIatedstepthatproducesanunstablecompoundthatrapIdly
dIssocIatesIntoseparatemolecules.
SomedrugsaremetabolIzedbyreductive reactions,thatIs,reactIonsthataddelectronsto
amolecule.ncontrasttooxIdatIons,whereelectronsaretransferredfromnIcotInamIde
adenInedInucleotIdephosphate(NA0PH)toanoxygenatom,theelectronsaretransferred
tothedrugmolecule.DxIdatIonofxenobIotIcsrequIresoxygen,butreductIve
bIotransformatIonIsInhIbItedbyoxygen,soItIsfacIlItatedwhentheIntracellularoxygen
tensIonIslow.
Cytochrome P450 Enzymes
ThecytochromesP450(CYP)IsthesuperfamIlyofconstItutIveandInducIbleenzymesthat
catalyzemostphasebIotransformatIons.CYPJA4IsthesInglemostImportantenzyme,
accountIngfor40to45ofallCYPmedIateddrugmetabolIsm.CYPsareIncorporatedInto
thesmoothendoplasmIcretIculumofhepatocytesandthemembranesoftheupper
IntestInalenterocytesInhIghconcentratIons.CYPsarealsofoundInthelungs,kIdneys,and
skIn,butInmuchsmalleramounts.CYPIsoenzymesoxIdIzetheIrsubstratesprImarIlyby
theInsertIonofanatomofoxygenIntheformofahydroxylgroup,whIleanotheroxygen
atomIsreducedtowater.
SeveralconstItutIveCYPsareInvolvedIntheproductIonofvarIousendogenouscompounds,
suchascholesterol,steroIdhormones,prostaglandIns,andeIcosanoIds.naddItIontothe
constItutIveforms,productIonofvarIousCYPscanbeInducedbyawIdevarIetyof
xenobIotIcs.CYPdrugmetabolIzIngactIvItyIncreasesafterexposuretovarIousexogenous
chemIcals,
P.141
IncludIngmanydrugs.ThenumberandtypeofCYPspresentatanytImedependson
exposuretodIfferentxenobIotIcs.TheCYPsystemIsabletoprotecttheorganIsmfromthe
deleterIouseffectsofaccumulatIonofexogenouscompoundsbecauseofItstwo
fundamentalcharacterIstIcsbroadsubstratespecIfIcItyandthecapabIlItytoadaptto
exposuretodIfferentsubstancesbyInductIonofdIfferentCYPIsoenzymes.Table71groups
drugsencounteredInanesthetIcpractIceaccordIngtotheCYPIsoenzymesresponsIblefor
theIrbIotransformatIon.
Table 7-1 Substrates for Cytochrome P450 (CYP) Isoenzymes Encountered
in Anesthesia
CYP3A4 CYP2D6 CYP2C9 CYP2C19
AcetamInophen
AlfentanIl
Alprazolam
8upIvacaIne
CIsaprIde
CodeIne
0Iazepam
0IgItoxIn
0IltIazem
Fentanyl
LIdocaIne
|ethadone
|Idazolam
NIcardIpIne
NIfedIpIne
Dmeprazole
FopIvacaIne
StatIns
SufentanIl
7erapamIl
WarfarIn
CaptoprIl
CodeIne
Hydrocodone
|etoprolol
Dndansetron
Propranolol
TImolol
CaptoprIl
CodeIne
Hydrocodone
0Iclofenac
buprofen
ndomethacIn
0Iazepam
Dmeprazole
Propranolol
WarfarIn
8IotransformatIonscanbeInhIbItedIfdIfferentsubstratescompeteforthedrugbIndIng
sIteonthesameCYPmember.TheeffectoftwocompetIngsubstratesoneachother's
metabolIsmdependsontheIrrelatIveaffInItIesfortheenzyme.8IotransformatIonofthe
compoundwIththeloweraffInItyIsInhIbItedtoagreaterdegree.ThIsIsthemechanIsmby
whIchtheH
2
receptorantagonIstcImetIdIneInhIbItsthemetabolIsmofmanydrugs,
IncludIngmeperIdIne,propranolol,anddIazepam.ThenewerH
2
antagonIstranItIdInehasa
dIfferentstructureandcausesfewerclInIcallysIgnIfIcantdrugInteractIons.Dtherdrugs,
notablycalcIumchannelblockersandantIdepressants,alsoInhIbItoxIdatIvedrug
metabolIsmInhumans.ThIsInformatIonallowsclInIcIanstopredIctwhIchcombInatIonsof
drugsaremorelIkelytoleadtoclInIcallysIgnIfIcantInteractIonsbecauseofaltereddrug
metabolIsmbythecytochromeP450system.
Phase II Reactions
PhasereactIonsarealsoknownasconjugationorsynthetic reactions.|anydrugsdonot
haveapolarchemIcalgroupsuItableforconjugatIon,soconjugatIonoccursonlyaftera
phasereactIon.Dtherdrugs,suchasmorphIne,alreadyhaveapolargroupthatservesas
ahandleforconjugatIon,andtheyundergothesereactIonsdIrectly.7arIousendogenous
compoundscanbeattachedtoparentdrugsortheIrphasemetabolItestoformdIfferent
conjugatIonproducts.TheseendogenoussubstratesIncludeglucuronIcacId,acetate,and
amInoacIds.|ercapturIcacIdconjugatesresultfromthebIndIngofexogenouscompounds
toglutathIone.DtherconjugatIonreactIonsproducesulfatedormethylatedderIvatIvesof
drugsortheIrmetabolItes.LIkethecytochromeP450system,theenzymesthatcatalyze
phasereactIonsareInducIble.PhasereactIonsproduceconjugatesthatarepolar,
watersolublecompounds.ThIsfacIlItatestheultImateexcretIonofthedrugvIathe
kIdneysorhepatobIlIarysecretIon.LIkeCYP,therearedIfferentfamIlIesandsuperfamIlIes
oftheenzymesthatcatalyzephasebIotransformatIons.
Genetic Variations in Drug Metabolism
FormostenzymesInvolvedInphaseandphasereactIons,thereareseveralbIologIcally
avaIlableIsoforms.0rugmetabolIsmvarIessubstantIallyamongIndIvIdualsbecauseof
varIabIlItyInthegenescontrollIngthenumerousenzymesresponsIblefor
bIotransformatIon(seeChapter6).Formostdrugs,IndIvIdualsubjects'ratesofmetabolIsm
haveaunImodaldIstrIbutIon.However,dIstInctsubpopulatIonswIthdIfferentratesof
elImInatIonofsomedrugshavebeenIdentIfIed.TheresultIngmultImodaldIstrIbutIonof
IndIvIdualratesofmetabolIsmIsknownaspolymorphism.Forexample,dIfferentgenotypes
resultIneIthernormal,low,or(rarely)absentplasmapseudocholInesteraseactIvIty,
accountIngforthewellknowndIfferencesInIndIvIduals'responsestosuccInylcholIne,
whIchIshydrolyzedbythIsenzyme.|anydrugmetabolIzIngenzymesexhIbItgenetIc
polymorphIsm,IncludIngCYPandvarIoustransferasesthatcatalyzephasereactIons.
However,noneofthesehaveasexrelateddIfference.
Chronologic Variations in Drug Metabolism
TheactIvItyandcapacItyoftheCYPenzymesIncreasefromsubnormallevelsInthefetal
andneonatalperIodtoreachnormallevelsatabout1yearofage.AlthoughageIsa
covarIateInmathematIcalmodelsofdrugelImInatIon,ItIsnotclearIfthesechangesare
relatedtochronologIcchangesInorgan
P.142
functIon(agerelatedorgandysfunctIon)oradecreaseInCYPlevelswIthIncreasIngage.n
contrast,ItIsclearthattheneonatehasalImItedabIlItytoperformphaseconjugatIon
reactIons,butafternormalIzIngphaseactIvItyovertheInItIalyearoflIfe,advancedage
doesnotaffectthecapacItytoperformphasereactIons.
Renal Drug Clearance
TheprImaryroleofthekIdneysIndrugelImInatIonIstoexcreteIntourInetheunchanged,
hydrophIlIcdrugs,andthehepatIcderIvedmetabolItesfromphaseandphasereactIons
oflIpophIlIcdrugs.ThepassIveelImInatIonofdrugsbypassIveglomerularfIltratIonIsa
veryIneffIcIentprocessanysIgnIfIcantdegreeofbIndIngofthedrugtoplasmaproteInsor
erythrocyteswIlldecreasetherenalclearancebelowtheglomerularfIltratIonrateof20
ofrenalbloodflow.nordertomakerenalelImInatIonmoreeffIcIent,dIscreteactIve
transportersoforganIcacIdsandbasesexIstIntheproxImalrenaltubularcells.Although
thesetransportersaresaturable,theyallowfortherenalclearanceofdrugstoapproach
theentIrerenalbloodflow.
nrealIty,renaldrugclearanceofactIvelysecreteddrugscanbeInhIbItedbybothpassIve
tubularreabsorptIonoflIpophIlIcdrugsandactIve,carrIermedIatedtubularreabsorptIon
ofhydrophIlIcdrugs.Therefore,thesmallamountoffIlteredandsecretedlIpophIlIcdrugIs
easIlyreabsorbedInthedIstaltubules,makIngthenetrenalclearanceneglIgIble.n
contrast,thelargeamountoffIlteredandsecretedhydrophIlIcdrugcanbepassIvely
reabsorbedIfrenaltubularflowdecreasessubstantIally(e.g.,olIgurIa)and/ortheurInepH
favorstheunIonIzedformofthehydrophIlIcdrug.8ecauseoverallrenalfunctIonIsreadIly
estImatedbyclearanceofendogenouscreatInIne,renaldrugclearance,evenfordrugs
elImInatedprImarIlybytubularsecretIon,dependsonrenalfunctIon.Therefore,In
patIentswIthacuteandchronIccausesofdecreasedrenalfunctIon,IncludIngage,low
cardIacoutputstates,andhepatorenalsyndrome,drugdosIngmustbealteredInorderto
avoIdaccumulatIonofparentcompoundsandpotentIallytoxIcmetabolItes(e.g.,lIdocaIne,
meperIdIne;Table72;seeChapter52).
Hepatic Drug Clearance
0rugelImInatIonbythelIverdependsontheIntrInsIcabIlItyofthelIvertometabolIzethe
drug(IntrInsIcclearance,Cl
l
),andtheamountofdrugavaIlabletodIffuseIntothelIver.
|anytypesofmathematIcalmodelshavebeendevelopedtoattempttoaccuratelymodel
therelatIonshIpbetweenhepatIcarterybloodflow,portalarterybloodflow,IntrInsIc
clearance,anddrugbIndIngtoplasmaproteIns.
22,2J
AccordIngtothesemodels,the
unboundconcentratIonofdrugInthehepatIcvenousblood(C
v
)IsInequIlIbrIumwIththe
drugwIthInthelIverthatIsavaIlableforelImInatIon.Thesemodelsalsomakethe
assumptIonthatallofthedrugsdelIveredtothelIverareavaIlableforelImInatIonand
thattheelImInatIonIsafIrstorderprocessaconstantfractionoftheavaIlabledrugIs
elImInatedperunIttIme.ThefractIonofthedrugremovedfromthebloodpassIngthrough
thelIverIsthehepatIcextractIonratIo,E:
Table 7-2 Drugs with Significant Renal Excretion Encountered in
Anesthesiology
AmInoglycosIdes NormeperIdIne
Atenolol PancuronIum
CephalosporIns PenIcIllIns
0IgoxIn ProcaInamIde
EdrophonIum PyrIdostIgmIne
Nadolol QuInolones
NeostIgmIne FocuronIum
whereC
a
IsthemIxedhepatIcarterIalportalvenousdrugconcentratIonandC
v
Isthe
mIxedhepatIcvenousdrugconcentratIon.ThetotalhepatIcdrugclearance,Cl
H
,Is:
whereQIshepatIcbloodflow.Therefore,hepatIcclearanceIsafunctIonofhepatIcblood
flowandtheabIlItyofthelIvertoextractdrugfromtheblood.
TheabIlItytoextractdrugdependsontheactIvItyofdrugmetabolIzIngenzymesandthe
capacItyforhepatobIlIaryexcretIontheIntrInsIcclearanceofthelIver(Cl
l
).
ntrInsIcclearancerepresentstheabIlItyofthelIvertoremovedrugfromthebloodInthe
absenceofanylImItatIonsImposedbybloodflowordrugbIndIng.TherelatIonshIpoftotal
hepatIcdrugclearancetotheextractIonratIoandIntrInsIcclearance,Cl
l
,Is:
TherIghthandsIdeofEquatIon7JIndIcatesthatIfIntrInsIcclearanceIsveryhIgh(many
tImeslargerthanhepatIcbloodflow,Cl
l
Q),totalhepatIcclearanceapproacheshepatIc
bloodflow.Dntheotherhand,IfIntrInsIcclearanceIsverysmall(Q+Cl
l
Q),hepatIc
clearancewIllbesImIlartoIntrInsIcclearance.TheserelatIonshIpsareshownInFIgure71.
Thus,hepatIcdrugclearanceandextractIonaredetermInedbytwoIndependentvarIables,
IntrInsIcclearanceandhepatIcbloodflow.ChangesIneItherwIllchangehepatIc
clearance.However,theextentofthechangedependsontheInItIalrelatIonshIpbetween
IntrInsIcclearanceandhepatIcbloodflow,accordIngtothenonlInearrelatIonshIp:
ftheInItIalIntrInsIcclearanceIssmallrelatIvetohepatIcbloodflow,thentheextractIon
ratIoIsalsosmall,andEquatIon74reducestothefollowIngrelatIonshIp:
EquatIon74aIndIcatesthatdoublIngIntrInsIcclearancewIllproduceanalmost
proportIonalIncrementIntheextractIonratIo,and,consequently,hepatIcelImInatIon
clearance(FIg.71,Inset).However,IfIntrInsIcclearanceIsmuchgreaterthanhepatIc
bloodflow,EquatIon74reducestothefollowIngrelatIonshIp:
EquatIon74bdemonstratesthattheextractIonratIoIsIndependentofIntrInsIcclearance
andthereforeachangeIn
P.14J
IntrInsIcclearancehasaneglIgIbleeffectontheextractIonratIoandhepatIcdrug
clearance(FIg.71).nnonmathematIcalterms,hIghIntrInsIcclearanceIndIcateseffIcIent
hepatIcelImInatIon.tIshardtoenhanceanalreadyeffIcIentprocess,whereasItIs
relatIvelyeasytoImproveonIneffIcIentdrugclearancebecauseoflowIntrInsIcclearance.
Figure 7-1.TherelatIonshIpbetweenhepatIcextractIonratIo(E,rIghtyaxIs),
IntrInsIcclearance(Cl
l
,xaxIs),andhepatIcclearance(Cl
H
,leftyaxIs)atthenormal
hepatIcbloodflow(Q)of1.5L/mIn.FordrugswIthahIghIntrInsIcclearance(Cl
l
Q),
IncreasIngIntrInsIcclearancehaslIttleeffectonhepatIcextractIonandtotalhepatIc
clearanceandtotalhepatIcclearanceapproacheshepatIcbloodflow.ncontrast,If
theIntrInsIcclearanceIssmall(Cl
l
Q),theextractIonratIoIssImIlartotheIntrInsIc
clearance(Inset).(AdaptedfromWIlkInsonCF,Shand0C:AphysIologIcapproachto
hepatIcdrugclearance.Clin Pharmacol Ther1975;18:J77.)
FordrugswIthahIghextractIonratIoandahIghIntrInsIcclearance,hepatIcelImInatIon
clearanceIsdIrectlyproportIonaltohepatIcbloodflow.Therefore,anymanIpulatIonof
hepatIcbloodflowwIllbedIrectlyreflectedbyaproportIonalchangeInhepatIc
elImInatIonclearance(FIg.72).ncontrast,whentheIntrInsIcclearanceIslow,changesIn
hepatIcbloodflowproduceInverselyproportIonalchangesInextractIonratIo(FIg.7J),
andthereforethehepatIcelImInatIonclearanceIsessentIallyIndependentofhepatIcblood
flowandexquIsItelyrelatedtoIntrInsIcclearance(FIg.7J).Therefore,classIfyIngdrugsas
havIngeItherlow,IntermedIate,orhIghextractIonratIos(Table7J),allowspredIctIonsto
bemadeonhowIntrInsIchepatIcclearanceandhepatIcbloodfloweffecthepatIc
elImInatIonclearance.ThIsallowsgrossadjustmentstobemadeInhepatIcally
metabolIzeddrugdosIngtoavoIdexcessaccumulatIonofdrugs(decreasedhepatIc
elImInatIonwIthoutdoseadjustment)orsubtherapeutIcdosIngstrategIes(Increased
hepatIcelImInatIonwIthoutdoseadjustment).
Figure 7-2.TherelatIonshIpbetweenlIverbloodflow(Q,xaxIs)andhepatIc
clearance(Cl
H
,yaxIs)fordIfferentvaluesofIntrInsIcclearance(Cl
l
).Whenthe
IntrInsIcclearanceIslow,hepatIcelImInatIonclearanceIsIndependentoflIverblood
flowthedrugelImInatIonIslImItedbythecapacItyofthelIvertometabolIzethe
drug(I.e.,theIntrInsIcclearance).ncontrast,asIntrInsIcclearanceIncreases,the
hepatIcelImInatIonbecomesmoredependentonhepatIcbloodflowthelIverIsable
tometabolIzeallofthedrugthatItIsexposedtoandthereforeonlylImItedbythe
amountofdrugthatIsdelIveredtothelIver(I.e.,flowlImItedmetabolIsm).
PharmacologIcandpathologIcmanIpulatIonsofcardIacoutputwIthItsconsequenceson
hepatIc/splanchnIcbloodflow
P.144
andrenalbloodflowareImportantcovarIateswhendesIgnIngdrugdosIngstrategIes.
24
As
prevIouslydetaIled,InstateswherecardIacoutputIsdecreased(e.g.,heartfaIlure,shock,
spInalanesthesIa),hIghextractIonratedrugswIllhaveadecreaseInhepatIcelImInatIon,
whereaslowextractIonratedrugswIllhavemInImalchangeInclearance.
25,26
ncontrast,
autoregulatIonofrenalbloodflowmaIntaInsarelatIvelyconstantrenalelImInatIon
clearanceuntIllowurIneoutputstateseventuallyallowIncreasedreabsorptIonofdrugs
fromthedIstaltubules.
27
Table 7-3 Classification of Drugs Encountered in Anesthesiology According
to Hepatic Extraction Ratios
LOW INTERMEDIATE HIGH
0Iazepam
Lorazepam
|ethadone
PhenytoIn
FocuronIum
TheophyllIne
ThIopental
AlfentanIl
|ethohexItal
|Idazolam
7ecuronIum
Alprenolol
8upIvacaIne
0IltIazem
Fentanyl
KetamIne
LIdocaIne
|eperIdIne
|etoprolol
|orphIne
Naloxone
NIfedIpIne
Propofol
Propranolol
SufentanIl
Figure 7-3.TherelatIonshIpbetweenlIverbloodflow(Q,xaxIs)andhepatIc
extractIonratIo(E,yaxIs)fordIfferentvaluesofIntrInsIcclearance(Cl
l
).Whenthe
IntrInsIcclearanceIslow,IncreasesInhepatIcbloodflowscauseadecreaseInthe
extractIonratIobecausethelIverhaslImItedmetabolIccapabIlItIes.ncontrast,when
theIntrInsIcclearanceIshIgh,theextractIonratIoIsessentIallyIndependentof
hepatIcbloodflowbecausethelIver'sabIlItytoelImInatedrugIswellabovethe
amountofdrugprovIdedbynormalhepatIcbloodflow.
Pharmacokinetic Models
TheconcentratIonofdrugatItssIteorsItesofactIonIsthefundamentaldetermInantofa
drug'spharmacologIceffects.AlthoughthebloodIsrarelythesIteofactIonofdrugeffect,
thetIssuedrugconcentratIonofanIndIvIdualorganIsafunctIonofthebloodflowtothe
organ,theconcentratIonofdrugInthearterIalInflowoftheorgan,thecapacItyofthe
organtotakeupdrug,andthedIffusIvItyofthedrugbetweenthebloodandtheorgan.
Physiologic versus Compartment Models
nItIalpharmacokInetIcmodelsofIntravenousandInhalatIonalanesthetIcsusedphysIologIc
orperfusIonmodels.
4
nthesemodels,bodytIssueswerelumpedIntogroupsthathad
sImIlardIstrIbutIonofcardIacoutputandcapacItyfordruguptake.HIghlyperfusedtIssues
wIthalargeamountofbloodflowpervolumeoftIssuewereclassIfIedasthevessel-rich
group,whereastIssueswIthabalancedamountofbloodflowpervolumeoftIssuewere
classIfIedasthelean tissue grouporfast tissue group.Thevesselpoorgroup(slowtIssue
group)wascomposedoftIssuesthathadalargecapacItyfordruguptakebutalImIted
tIssueperfusIon.AlthoughIdentIfIcatIonoftheexactorgansthatmadeupeachtIssue
groupwasnotpossIblefromthemathematIcalmodel,ItwasapparentthatthehIghly
perfusedtIssueswerecomposedofthebraIn,lungs,kIdneys,andasubsetofmuscle,the
fastequIlIbratIngtIssuewouldbeconsIstentwIththemajorItyofmuscleandsomeofthe
splanchnIcbed(e.g.,lIver),andtheslowlyequIlIbratIngtIssuescontaInedthemajorItyof
theadIposetIssueandtheremaInderofthesplanchnIcorgans.
8asedonthecomputatIonallyandexperImentallyIntensephysIologIcmodels,PrIce
4
and
PrIceetal.
18
wereabletodemonstratethatawakenIngafterasIngledoseofthIopental
wasprImarIlyaresultofredIstrIbutIonofthIopentalfromthebraIntothemusclewIth
lIttlecontrIbutIonbydIstrIbutIontolesswellperfusedtIssuesordrugmetabolIsm.ThIs
fundamentalconceptofredIstrIbutIonapplIestoalllIpophIlIcdrugsandwasnotdelIneated
untIlanaccuratepharmacokInetIcmodelhadbeenconstructed.
PerfusIonbasedphysIologIcpharmacokInetIcmodelshaveprovIdedsIgnIfIcantInsIghtsInto
howphysIologIc,pharmacologIc,andpathologIcdIstrIbutIonofcardIacoutputcaneffect
drugdIstrIbutIonandelImInatIon.
28,29
However,verIfIcatIonofthepredIctIonsofthese
modelsrequIresmeasurementofdrugconcentratIonsInmanydIfferenttIssues,whIchIs
experImentallyIneffIcIentanddestructIvetothesystem.Therefore,sImplermathematIcal
modelshavebeendeveloped.nthesemodels,thebodyIscomposedofoneormore
compartments.0rugconcentratIonsInthebloodareusedtodefInetherelatIonshIp
betweendoseandthetImecourseofchangesInthedrugconcentratIon.The
compartmentsofthecompartmentalpharmacokInetIcmodelscannotbeequatedwIththe
tIssuegroupsthatmakeupphysIologIcpharmacokInetIcmodelsbecausethecompartments
aretheoretIcalentItIesthatareusedtomathematIcallycharacterIzetheblood
concentratIonprofIleofadrug.ThesemodelsallowthederIvatIonofpharmacokInetIc
parametersthatcanbeusedtoquantIfydrugdIstrIbutIonandelImInatIonvolumeof
dIstrIbutIon,clearance,andhalflIves.
AlthoughthesImplIcItyofcompartmentalmodels,comparedwIthphysIologIc
pharmacokInetIcmodels,hasItsadvantages,ItalsohassomedIsadvantages.Forexample,
cardIacoutputIsnotaparameterofcompartmentalmodels,andcompartmentalmodels
thereforecannotbeusedtopredIctdIrectlytheeffectofcardIacfaIlureondrug
dIsposItIon.
J0
However,compartmentalpharmacokInetIcmodelscanstIllquantIfythe
effectsofreducedcardIacoutputonthedIsposItIonofadrugIfagroupofpatIentswIth
cardIacfaIlureIscomparedwIthagroupofotherwIsehealthysubjects.
ThedIscIplIneofpharmacokInetIcsIs,tothedespaIrofmany,mathematIcallybased.nthe
succeedIngsectIons,formulasareusedtoIllustratetheconceptsneededtounderstandand
InterpretpharmacokInetIcstudIes.Feadersareencouragedtoconcentrateonthe
concepts,nottheformulas.
Pharmacokinetic Concepts
Rate Constants and Half-Lives
ThedIsposItIonofmostdrugsfollowsfirst-orderkInetIcs.AfIrstorderkInetIcprocessIsone
InwhIchaconstantfractIonofthedrugIsremoveddurIngafInIteperIodoftImeregardless
ofthedrugamountorconcentratIon.ThIsfractIonIsequIvalenttotherateconstantofthe
process.FateconstantsareusuallydenotedbytheletterkandhaveunItsofInverse
tIme,suchasmIn
1
orh
1
.f10ofthedrugIselImInatedpermInute,thentherate
constantIs0.1mIn
1
.8ecauseaconstantfractIonIsremovedperunItoftImeInfIrstorder
kInetIcs,theabsoluteamountofdrugremovedIsproportIonaltotheconcentratIonofthe
drug.tfollowsthat,InfIrstorderkInetIcs,therateofchangeoftheamountofdrugatany
gIventImeIsproportIonaltotheconcentratIonpresentatthattIme.Whenthe
concentratIonIshIgh,moredrugswIllberemovedthanwhenItIslow.FIrstorderkInetIcs
applynotonlytoelImInatIon,butalsotoabsorptIonanddIstrIbutIon.FatherthanusIng
rateconstants,therapIdItyofpharmacokInetIcprocessesIsoftendescrIbedwIthhalflIves
thetImerequIredfortheconcentratIontochangebyafactorof2.HalflIvesare
P.145
calculateddIrectlyfromthecorrespondIngrateconstantswIththIssImpleequatIon:
Thus,forarateconstant(k)of0.1mIn
1
thehalflIfeIs6.9JmInutes.ThehalflIfeofanyfIrstorderkInetIcprocess,IncludIngdrug
absorptIon,dIstrIbutIon,andelImInatIon,canbecalculated.FIrstorderprocesses
asymptotIcallyapproachcompletIonbecauseaconstantfractIonofthedrug,notan
absoluteamount,IsremovedperunItoftIme.However,afterfIvehalflIves,theprocess
wIllbealmost97complete(Table74).ForpractIcalpurposes,thIsIsessentIally100and
thereforethereIsaneglIgIbleamountofdrugremaInIngInthebody.
Volume of Distribution
ThevolumeofdIstrIbutIonquantIfIestheextentofdrugdIstrIbutIon.ThephysIologIcfactor
thatgovernstheextentofdrugdIstrIbutIonIstheoverallcapacItyoftIssuesversusthe
capacItyofbloodforthatdrug.DveralltIssuecapacItyforuptakeofadrugIsInturna
functIonofthetotalmassofthetIssuesIntowhIchadrugdIstrIbutesandtheIraverage
affInItyforthedrug.ncompartmentalpharmacokInetIcmodels,drugsareenvIsagedas
dIstrIbutIngIntooneormoreboxes,orcompartments.Thesecompartmentscannotbe
equateddIrectlywIthspecIfIctIssues.Father,theyarehypothetIcalentItIesthatpermIt
analysIsofdrugdIstrIbutIonandelImInatIonanddescrIptIonofthedrugconcentratIon
versustImeprofIle.
ThevolumeofdIstrIbutIonIsanapparentvolumebecauseItrepresentsthesIzeofthese
hypothetIcalboxes,orcompartments,thatarenecessarytoexplaIntheconcentratIonof
drugInareferencecompartment,usuallycalledthecentralorplasma compartment.The
volumeofdIstrIbutIon,V
d
,relatesthetotalamountofdrugpresenttotheconcentratIon
observedInthecentralcompartment:
fadrugIsextensIvelydIstrIbuted,thentheconcentratIonwIllbelowerrelatIvetothe
amountofdrugpresent,whIchequatestoalargervolumeofdIstrIbutIon.Forexample,Ifa
totalof10mgofdrugIspresentandtheconcentratIonIs2mg/L,thentheapparent
volumeofdIstrIbutIonIs5L.Dntheotherhand,IftheconcentratIonwas4mg/L,thenthe
volumeofdIstrIbutIonwouldbe2.5L.
Table 7-4 Half-Lives and Percent of Drug Removed
NUMBER OF HALF-LIVES PERCENT OF DRUG REMAINING PERCENT OF DRUG REMOVED
0 100 0
1 50 50
2 25 75
J 12.5 87.5
4 6.25 9J.75
5 J.125 96.875
SImplystated,theapparentvolumeofdIstrIbutIonIsanumerIcIndexoftheextentofdrug
dIstrIbutIonthatdoesnothaveanyrelatIonshIptotheactualvolumeofanytIssueorgroup
oftIssues.tmaybeassmallasplasmavolume,or,IfoveralltIssueuptakeIsextensIve,
theapparentvolumeofdIstrIbutIonmaygreatlyexceedtheactualtotalvolumeofthe
body.ngeneral,lIpophIlIcdrugshavelargervolumesofdIstrIbutIonthanhydrophIlIc
drugs.8ecausethevolumeofdIstrIbutIonIsamathematIcalconstructtomodelthe
dIstrIbutIonofadrugInthebody,thevolumeofdIstrIbutIoncannotprovIdeany
InformatIonregardIngtheactualtIssueconcentratIonInanyspecIfIcrealorganInthe
body.However,thIssImplemathematIcalconstructprovIdesausefulsummarydescrIptIon
ofthebehavIorofthedrugInthebody.nfact,theloadIngdoseofdrugrequIredto
achIeveatargetplasmaconcentratIoncanbeeasIlycalculatedbyrearrangIngEquatIon77
asfollows:
8asedonthIsequatIon,ItIsclearthatanIncreaseInthevolumeofdIstrIbutIonmeansthat
alargerloadIngdosewIllberequIredtofIlluptheboxandachIevethesame
concentratIon.ThereforeanychangeInstatebecauseofchangesInphysIologIcand
pathologIccondItIonscanalterthevolumeofdIstrIbutIon,necessItatIngtherapeutIc
adjustments.
Total Drug (Elimination) Clearance
Elimination clearance(drugclearance)IsthetheoretIcalvolumeofbloodfromwhIchdrug
IscompletelyandIrreversIblyremovedInaunItoftIme.ElImInatIonclearancehasthe
unItsofflow[volumepertIme].TotaldrugclearancecanbecalculatedwIth
pharmacokInetIcmodelsofbloodconcentratIonversustImedata.0rugclearanceIsoften
correctedforweIghtorbodysurfacearea,InwhIchcasetheunItsaremL/mIn/kgor
mL/mIn/m
2
,respectIvely.
ElImInatIonclearance,Cl,canbecalculatedfromthedeclInIngbloodlevelsobservedafter
anIntravenousInjectIon,asfollows:
fadrugIsrapIdlyremovedfromtheplasma,ItsconcentratIonwIllfallmorequIcklythan
theconcentratIonofadrugthatIslessreadIlyelImInated.ThIsresultsInasmallerarea
undertheconcentratIonversustImecurve,whIchequatestogreaterclearance(FIg.74).
Figure 7-4.TheplasmaconcentratIon(yaxIs)versustIme(xaxIs)curvefortwodrugs
thatdIfferonlyIntheIrelImInatIonclearance.NotIcethattheareasunderthecurves
aredIfferent,sIgnIfyIngthatthedrugthathasthesmallerareaunderthecurveIs
morerapIdlyelImInatedfromthebodythanthedrugthathastheslowerelImInatIon
clearance.
P.146
WIthoutaddItIonalorganspecIfIcdata(e.g.,urInedrugconcentratIonmeasurements,drug
arterIalInflowconcentratIon),calculatIngelImInatIonclearancefromcompartmental
pharmacokInetIcmodelsusuallydoesnotspecIfytherelatIvecontrIbutIonofdIfferent
organstodrugelImInatIon.Nonetheless,estImatIonofdrugclearancewIththesemodels
hasmadeImportantcontrIbutIonstoclInIcalpharmacology.npartIcular,thesemodels
haveprovIdedagreatdealofclInIcallyusefulInformatIonregardIngaltereddrug
elImInatIonInvarIouspathologIccondItIons.
Elimination Half-Life
AlthoughtheelImInatIonclearanceIsthepharmacokInetIcparameterthatbestdescrIbes
thephysIologIcprocessofdrugelImInatIon(I.e.,drugdelIverytoorgansofelImInatIon
coupledwIththecapacItyoftheorgantoelImInatethedrug),thepharmacokInetIc
varIablemostoftenreportedIntextbooksandlIteratureIstheelimination half-lifeofa
drug(t
1/2
).TheelImInatIonhalflIfeIsthetImedurIngwhIchtheamountofdrugInthe
bodydecreasesby50.AlthoughthIsparameterappearstobeasImplesummaryofthe
physIologyofdrugelImInatIon,ItIsactuallyacomplexparameter,Influencedbythe
dIstrIbutIonandtheelImInatIonofthedrug,asfollows:
Therefore,whenaphysIologIcorpathologIcperturbatIonchangestheelImInatIonhalflIfe
ofadrug,ItIsnotasImplereflectIonofthechangeInthebody'sabIlItytometabolIzeor
elImInatethedrug.Forexample,theelImInatIonhalflIfeofthIopentalIsprolongedInthe
elderly;however,theelImInatIonclearanceIsunchangedandthevolumeofdIstrIbutIonIs
Increased.
J1
Therefore,elderlypatIentsneeddosIngstrategIesthataccommodateforthe
changeInthedIstrIbutIonofthedrugratherthanadecreasedmetabolIsmofthedrug.n
contrast,InpatIentswIthrenalInsuffIcIency,theIncreaseIntheelImInatIonhalflIfeof
pancuronIumIsduetoasImpledecreaseInrenalelImInatIonofthedrugandthevolumeof
dIstrIbutIonIsunchanged.
J2
8esIdesItsInabIlItytogIveInsIghtIntothemechanIsmbywhIchadrugIsretaInedInthe
body,theelImInatIonhalflIfeIsunabletogIveInsIghtIntothetImethatIttakesfora
sIngleoraserIesofrepeateddrugdosestotermInateItseffect.AlthoughelImInatIonof
drugfromthebodybegInsthemomentthedrugIsdelIveredtotheorgansofelImInatIon,
therapIdtermInatIonofeffectofabolusofanIntravenousagentIsduetoredIstrIbutIonof
drugfromthebraIntothebloodandsubsequentlyothertIssue(e.g.,muscle).Therefore,
theeffectsofmostanesthetIcshavewanedlongbeforeevenoneelImInatIonhalflIfehas
beencompleted,makIngthIsmeasureofdrugkInetIcsIncapableofprovIdInguseful
InformatIonregardIngtheduratIonofactIonfollowIngtheadmInIstratIonofIntravenous
agents.ThustheelImInatIonhalflIfehaslImItedutIlItyInanesthetIcpractIce.
10
Effect of Hepatic or Renal Disease on Pharmacokinetic
Parameters
0IversepathophysIologIcchangesprecludeprecIsepredIctIonofthepharmacokInetIcsofa
gIvendrugInIndIvIdualpatIentswIthhepatIcorrenaldIsease.naddItIon,lIverfunctIon
tests(e.g.,transamInases)areunrelIablepredIctorsofthedegreeoflIverfunctIonandthe
remaInIngmetabolIccapacItyfordrugelImInatIon.However,somegeneralIzatIonscanbe
made.npatIentswIthhepatIcdIsease,theelImInatIonhalflIfeofdrugsmetabolIzedor
excretedbythelIverIsoftenIncreasedbecauseofdecreasedclearance,and,possIbly,
IncreasedvolumeofdIstrIbutIoncausedbyascItesandalteredproteInbIndIng.
10,JJ
0rug
concentratIonatsteadystateIsInverselyproportIonaltoelImInatIonclearance.
Therefore,whenhepatIcdrugclearanceIsreduced,repeatedbolusdosIngorcontInuous
InfusIonofsuchdrugsasbenzodIazepInes,opIoIds,andbarbIturatesmayresultInexcessIve
accumulatIonofdrugaswellasexcessIveandprolongedpharmacologIceffects.SInce
recoveryfromsmalldosesofdrugssuchasthIopentalandfentanylIslargelytheresultof
redIstrIbutIon,recoveryfromconservatIvedoseswIllbemInImallyaffectedbyreductIons
InelImInatIonclearance.npatIentswIthrenalfaIlure,sImIlarconcernsapplytothe
admInIstratIonofdrugsexcretedbythekIdneys.tIsalmostalwaysbetterto
underestImateapatIent'sdoserequIrement,observetheresponse,andgIveaddItIonal
drugIfnecessary.
Nonlinear Pharmacokinetics
ThephysIologIcandcompartmentalmodelsthusfardIscussedarebasedontheassumptIon
thatdrugdIstrIbutIonandelImInatIonarefIrstorderprocesses.Therefore,theIr
parameters,suchasclearanceandelImInatIonhalflIfe,areIndependentofthedoseor
concentratIonofthedrug.However,therateofelImInatIonofafewdrugsIsdose
dependent,ornonlinear.
ElImInatIonofdrugsInvolvesInteractIonswItheItherenzymescatalyzIng
bIotransformatIonreactIonsorcarrIerproteInsfortransmembranetransport.fsuffIcIent
drugIspresent,thecapacItyofthedrugelImInatIngsystemscanbeexceeded.WhenthIs
occurs,ItIsnolongerpossIbletoexcreteaconstantfractIonofthedrugpresenttothe
elImInatIngsystem,andaconstantamountofdrugIsexcretedperunIttIme.PhenytoInIsa
wellknownexampleofadrugthatexhIbItsnonlInearelImInatIonattherapeutIc
concentratIons,
J4
whereasInanesthetIcpractIce,theextremelyhIghdosesofthIopental
usedforcerebralprotectIoncandemonstratezeroorderelImInatIon.
J5
ntheory,alldrugs
areclearedInanonlInearfashIon.npractIce,thecapacItytoelImInatemostdrugsIsso
greatthatthIsIsusuallynotevIdent,evenwIthtoxIcconcentratIons.
Compartmental Pharmacokinetic Models
One-Compartment Model
AlthoughformostdrugstheonecompartmentmodelIsanoversImplIfIcatIon,Itdoesserve
toIllustratethebasIcrelatIonshIpsamongclearance,volumeofdIstrIbutIon,andthe
elImInatIonhalflIfe.nthIsmodel,thebodyIsenvIsagedasasInglehomogeneous
compartment.0rugdIstrIbutIonafterInjectIonIsassumedtobeInstantaneous,sothere
arenoconcentratIongradIentswIthInthecompartment.TheconcentratIoncandecrease
onlybyelImInatIonofdrugfromthesystem.TheplasmaconcentratIonversustImecurve
forahypothetIcaldrugwIthonecompartmentkInetIcsIsshownInFIgure75.Thedecrease
InplasmaconcentratIon(C)wIthtImefromtheInItIalconcentratIon(C
0
)canbe
characterIzedbythesImplemonoexponentIalfunctIon:
WIththeconcentratIonplottedonalogarIthmIcscale,theconcentratIonversustImecurve
becomesastraIghtlIne.TheslopeofthelogarIthmofconcentratIonversustImeIsequalto
thefIrstorderelImInatIonrateconstant(k
e
).
ntheonecompartmentmodel,drugclearance,Cl,Isequaltotheproductofthe
elImInatIonrateconstant,k
e
,andthevolumeofdIstrIbutIon:
CombInIngEquatIons6and10yIeldsEquatIon79(wherek
e
=k
):
Therefore,whenItIsapproprIatetomakethesImplIfyIngassumptIonofInstantaneous
mIxIngofdrugIntoasInglecompartment,theelImInatIonhalflIfeIsInverselyproportIonal
totheslopeoftheconcentratIontImecurve.FordrugsthatrequIre
P.147
consIderatIonoftheIrmultIcompartmentalpharmacokInetIcs,therelatIonshIpamong
clearance,volumeofdIstrIbutIon,andtheelImInatIonhalflIfeIsnotasImplelInearone
suchasEquatIon79.However,thesameprIncIplesapply.AllelsebeIngequal,thegreater
theclearance,theshortertheelImInatIonhalflIfe;thelargerthevolumeofdIstrIbutIon,
thelongertheelImInatIonhalflIfe.Thus,theelImInatIonhalflIfedependsontwoother
varIables,clearanceandvolumeofdIstrIbutIon,thatcharacterIze,respectIvely,theextent
ofdrugdIstrIbutIonandeffIcIencyofdrugelImInatIon.
Figure 7-5.TheplasmaconcentratIonversustImeprofIleplottedonbothlInear
(dashed line,leftyaxIs)andlogarIthmIc(dotted line,rIghtyaxIs)scalesfora
hypothetIcaldrugexhIbItIngonecompartment,fIrstorderpharmacokInetIcs.Note
thattheslopeofthelogarIthmIcconcentratIonprofIleIsequaltotheelImInatIonrate
constant(k
e
)andrelatedtotheelImInatIonhalflIfe(t
1/2
)asdescrIbedInEquatIon7
9.
Two-Compartment Model
Formanydrugs,agraphofthelogarIthmoftheplasmaconcentratIonversustImeafteran
IntravenousInjectIonIssImIlartotheschematIcgraphshownInFIgure76.Therearetwo
dIscretephasesInthedeclIneoftheplasmaconcentratIon.ThefIrstphaseafterInjectIon
IscharacterIzedbyaveryrapIddecreaseInconcentratIon.TherapIddecreaseIn
concentratIondurIngthIsdIstrIbutIonphaseIslargelycausedbypassageofdrugfromthe
plasmaIntotIssues.ThedIstrIbutIonphaseIsfollowedbyaslowerdeclIneofthe
concentratIonowIngtodrugelImInatIon.ElImInatIonalsobegInsImmedIatelyafter
InjectIon,butItscontrIbutIontothedropInplasmaconcentratIonIsInItIallymuchsmaller
thanthefallInconcentratIonbecauseofdrugdIstrIbutIon.
Figure 7-6.ThelogarIthmIcplasmaconcentratIonversustImeprofIlefora
hypothetIcaldrugexhIbItIngtwocompartment,fIrstorderpharmacokInetIcs.Note
thatthedIstrIbutIonphasehasaslopethatIssIgnIfIcantlylargerthanthatofthe
elImInatIonphase,IndIcatIngthattheprocessofdIstrIbutIonIsnotonlymorerapId
thanelImInatIonofthedrugfromthebody,butalsoresponsIbleforthemajorItyofthe
declIneInplasmaconcentratIonIntheseveralmInutesafterdrugadmInIstratIon.7,
Intravenous.
Figure 7-7.AschematIcofatwocompartmentpharmacokInetIcmodel.Seetextfor
explanatIon.
ToaccountforthIsbIphasIcbehavIor,onemustconsIderthebodytobemadeupoftwo
compartments,acentralcompartment,whIchIncludestheplasma,andaperIpheral
compartment(FIg.77).ThIstwocompartmentmodelassumesthatItIsthecentral
compartmentIntowhIchthedrugIsInjectedandfromwhIchthebloodsamplesfor
measurementofconcentratIonareobtaIned,andthatdrugIselImInatedonlyfromthe
centralcompartment.0rugdIstrIbutIonwIthInthecentralcompartmentIsconsIderedtobe
Instantaneous.nrealIty,thIslastassumptIoncannotbetrue.However,druguptakeInto
someofthehIghlyperfusedtIssuesIssorapIdthatItcannotbedetectedasadIscrete
phaseontheplasmaconcentratIonversustImecurve.
ThedIstrIbutIonandelImInatIonphasescanbecharacterIzedbygraphIcanalysIsofthe
plasmaconcentratIonversustImecurve,asshownInFIgure76.TheelImInatIonphaselIne
IsextrapolatedbacktotImezero(thetImeofInjectIon).nFIgure76,thezerotIme
InterceptsofthedIstrIbutIonandelImInatIonlInesarepoIntsAandB,respectIvely.The
hybrid rate constants,and,areequaltotheslopesofthetwolInes,andareusedto
calculatethedIstrIbutIonandelImInatIonhalflIves;andarecalledhybrid rate
constantsbecausetheydependonbothdIstrIbutIonandelImInatIonprocesses.
AtanytImeafteranIntravenousInjectIon,theplasmaconcentratIonofdrugswIthtwo
compartmentkInetIcsIsequaltothesumoftwoexponentIalterms:
wheret=tIme,Cp(t)=plasmaconcentratIonattImet, A=yaxIsInterceptofthe
dIstrIbutIonphaselIne,=hybrIdrateconstantofthedIstrIbutIonphase,B=yaxIs
InterceptoftheelImInatIonphaselIne,and=hybrIdrateconstantoftheelImInatIon
phase.ThefIrsttermcharacterIzesthedIstrIbutIonphaseandthesecondterm
characterIzestheelImInatIonphase.mmedIatelyafterInjectIon,thefIrsttermrepresents
amuchlargerfractIonofthetotalplasmaconcentratIonthanthesecondterm.After
severaldIstrIbutIonhalflIves,thevalueofthefIrsttermapproacheszero,andtheplasma
concentratIonIsessentIallyequaltothevalueofthesecondterm(seeFIg.76).
Figure 7-8.AschematIcofathreecompartmentpharmacokInetIcmodel.Seetextfor
detaIls.
P.148
nmultIcompartmentalmodels,thedrugIsInItIallydIstrIbutedonlywIthInthecentral
compartment.Therefore,theInItIalapparentvolumeofdIstrIbutIonIsthevolumeofthe
centralcompartment.mmedIatelyafterInjectIon,theamountofdrugpresentIsthedose,
andtheconcentratIonIstheextrapolatedconcentratIonattImet=0,whIchIsequaltothe
sumoftheInterceptsofthedIstrIbutIonandelImInatIonlInes.Thevolumeofthecentral
compartment,V
1
,IscalculatedbymodIfyIngEquatIon77:
ThevolumeofthecentralcompartmentIsImportantInclInIcalanesthesIologybecauseIt
IsthepharmacokInetIcparameterthatdetermInesthepeakplasmaconcentratIonafteran
IntravenousbolusInjectIon.HypovolemIa,forexample,reducesthevolumeofthecentral
compartment.fdosesarenotcorrespondInglyreduced,thehIgherplasmaconcentratIons
wIllIncreasetheIncIdenceofadversepharmacologIceffects.
mmedIatelyafterIntravenousInjectIon,allofthedrugIsInthecentralcompartment.
SImultaneously,threeprocessesbegIn.0rugmovesfromthecentraltotheperIpheral
compartment,whIchalsohasavolume,V
2
.ThIsIntercompartmentaltransferIsafIrst
orderprocess,andItsmagnItudeIsquantIfIedbytherateconstantk
12
.Assoonasdrug
appearsIntheperIpheralcompartment,somepassesbacktothecentralcompartment,a
processcharacterIzedbytherateconstantk
21
.Thetransferofdrugbetweenthecentral
andperIpheralcompartmentsIsquantIfIedbythedistributionalorintercompartmental
clearance:
ThethIrdprocessthatbegInsImmedIatelyafteradmInIstratIonofthedrugIsIrreversIble
removalofdrugfromthesystemvIathecentralcompartment.AsIntheonecompartment
model,theelImInatIonrateconstantIsk
e
,andelimination clearanceIs:
TherapIdItyofthedecreaseInthecentralcompartmentconcentratIonafterIntravenous
InjectIondependsonthemagnItudeofthecompartmentalvolumes,the
Intercompartmentalclearance,andtheelImInatIonclearance.
AtequIlIbrIum,thedrugIsdIstrIbutedbetweenthecentralandtheperIpheral
compartments,andbydefInItIon,thedrugconcentratIonsInthecompartmentsareequal.
Therefore,theultImatevolumeofdIstrIbutIon,termedthevolume of distribution at
steady-state(V
ss
),IsthesumofV
1
andV
2
.ExtensIvetIssueuptakeofadrugIsreflectedby
alargevolumeoftheperIpheralcompartment,whIch,Inturn,resultsInalargeV
ss
.
Consequently,V
ss
cangreatlyexceedtheactualvolumeofthebody.
AsInthesInglecompartmentmodel,InmultIcompartmentmodelstheelImInatIon
clearanceIsequaltothedosedIvIdedbytheareaundertheconcentratIonversustIme
curve.ThIsarea,aswellasthecompartmentalvolumesandIntercompartmental
clearances,canbecalculatedfromtheInterceptsandhybrIdrateconstants,wIthout
havIngtoreachsteadystatecondItIons.
Three-Compartment Model
AfterIntravenousInjectIonofsomedrugs,theInItIal,rapIddIstrIbutIonphaseIsfollowed
byasecond,slowerdIstrIbutIonphasebeforetheelImInatIonphasebecomesevIdent.
Therefore,theplasmaconcentratIonIsthesumofthreeexponentIalterms:
wheret=tIme,C
p
(t)=plasmaconcentratIonattImet, A=InterceptoftherapId
dIstrIbutIonphaselIne,=hybrIdrateconstantoftherapIddIstrIbutIonphase,B=
InterceptoftheslowerdIstrIbutIonphaselIne,=hybrIdrateconstantoftheslower
dIstrIbutIonphase,G=InterceptoftheelImInatIonphaselIne,and=hybrIdrateconstant
oftheelImInatIonphase.ThIstrIphasIcbehavIorIsexplaInedbyathreecompartment
pharmacokInetIcmodel(FIg.78).AsInthetwocompartmentmodel,thedrugIsInjected
IntoandelImInatedfromthecentralcompartment.0rugIsreversIblytransferredbetween
thecentralcompartmentandtwoperIpheralcompartments,whIchaccountsfortwo
dIstrIbutIonphases.0rugtransferbetweenthecentralcompartmentandthemorerapIdly
equIlIbratIng,orshallow,perIpheralcompartmentIscharacterIzedbythefIrstorderrate
constantsk
12
andk
21
.TransferInandoutofthemoreslowlyequIlIbratIng,deep
compartmentIscharacterIzedbytherateconstantsk
1J
andk
J1
.nthIsmodel,thereare
threecompartmentalvolumes:V
1
,7
2
,andV
J
,whosesumequalsV
ss
;andthreeclearances:
therapIdIntercompartmentalclearance,theslowIntercompartmentalclearance,and
elImInatIonclearance.
ThepharmacokInetIcparametersofInteresttoclInIcIans,suchasclearance,volumesof
dIstrIbutIon,anddIstrIbutIonandelImInatIonhalflIves,aredetermInedbycalculatIons
analogoustothoseusedInthetwocompartmentmodel.AccurateestImatesofthese
parametersdependonaccuratecharacterIzatIonofthemeasuredplasmaconcentratIon
versustImedata.AfrequentlyencounteredproblemIsthattheduratIonofsamplIngIsnot
longenoughtodefIneaccuratelytheelImInatIonphase.SImIlarproblemsarIseIftheassay
cannotdetectlowconcentratIonsofthedrug.Conversely,samplesaresometImesobtaIned
tooInfrequentlyfollowIngdrugadmInIstratIontobeabletocharacterIzethedIstrIbutIon
phasesaccurately.
J6,J7
WhetheradrugexhIbItstwoorthreecompartmentkInetIcsIsofno
clInIcalconsequence.
10
nfact,somedrugshavetwocompartmentkInetIcsInsome
patIentsandthreecompartmentkInetIcsInothers.nselectIngapharmacokInetIcmodel,
themostImportantfactorIsthatItaccuratelycharacterIzesthemeasuredconcentratIons.
ngeneral,themodelwIththesmallestnumberofcompartmentsorexponentsthat
accuratelyreflectsthedataIsused.However,ItIsgoodtoconsIderthatthedatacollected
InapartIcularstudymaynotbereflectIveoftheclInIcalpharmacologIcIssuesofconcern
InanothersItuatIon,makIngpublIshedpharmacokInetIcmodelparameterspotentIally
Irrelevant.ForInstance,newdataIndIcatethathypotensIonfollowIngIntravenous
admInIstratIonofdrugXIsrelatedtopeakarterIalplasmadrugXconcentratIons
P.149
1mInuteafterInjectIon,butprevIouspharmacokInetIcmodelsarebasedonvenousplasma
drugXconcentratIonsbegInnIng5mInutesafterthedose.nthIscase,thepharmacokInetIc
modelswIllnotbeofuseIndesIgnIngdosIngregImensfordrugXthatavoIdtoxIcdrug
concentratIonsat1mInute.
10,J8,J9
AlmostallearlIerpharmacokInetIcstudIesusedtwo-stage modeling.WIththIstechnIque,
pharmacokInetIcparameterswereestImatedIndependentlyforeachsubjectandthen
averagedtoprovIdeestImatesofthetypIcalparametersforthepopulatIon.Dneproblem
wIththIsapproachIsthatIfoutlIersarepresent,averagIngparameterscouldresultIna
modelthatdoesnotaccuratelypredIcttypIcaldrugconcentratIons.Currently,most
pharmacokInetIcmodelsaredevelopedusIngpopulation pharmacokinetic modeling,whIch
hasbeenmadefeasIblebecauseofadvancesInmodelIngsoftwareandIncreasedcomputIng
power.WIththesetechnIques,thepharmacokInetIcparametersareestImatedusIngallthe
concentratIonversustImedatafromtheentIregroupofsubjectsInasInglestage,usIng
sophIstIcatednonlInearregressIonmethods.ThIsmodelIngtechnIqueprovIdessIngle
estImatesofthetypIcalparametervaluesforthepopulatIon.
Noncompartmental (Stochastic) Pharmacokinetic Models
DftenInvestIgatorsperformIngpharmacokInetIcanalysesofdrugswanttoavoIdthe
experImentalrequIrementsofaphysIologIcmodeldataorempIrIcalestImatIonsof
IndIvIdualorganInflowandoutflowconcentratIonprofIlesandorgantIssuedrug
concentratIonsarerequIredInordertoIdentIfythecomponentsofthemodel.
40
Although
compartmentalmodelsdonotassumeanyphysIologIcoranatomIcbasIsforthemodel
structure,InvestIgatorsoftenattrIbuteanatomIcandphysIologIcfunctIontotheseempIrIc
models.
41
EvenIfthedIscIplInedclInIcalpharmacologIstavoIdsoverInterpretatIonofthe
meanIngofcompartmentmodels,thesImplefactthatseveralcompetIngmodelscan
provIdeequallygooddescrIptIonsofthemathematIcaldataorthatsomesubjectsInadata
setmaybebetterfItwIthathreecompartmentmodelratherthanthetwocompartment
modelthatprovIdesthebestfItfortheotherdatasetsubjectsleadsmanytoquestIon
whetherthereIsatruebestmodelarchItectureforanygIvendrug.Therefore,some
InvestIgatorschoosetoemploymathematIcaltechnIquestocharacterIzea
pharmacokInetIcdatasetthatattempttoavoIdanypreconceIvednotIonofstructureand
yetyIeldthepharmacokInetIcparametersthatsummarIzedrugdIstrIbutIonand
elImInatIon.ThesetechnIquesareclassIfIedasnoncompartmentaltechnIquesorstochastic
technIquesandaresImIlartothemethodsbasedonmomentanalysIsusedInprocess
analysIsofchemIcalengIneerIngsystems.AlthoughthesetechnIquesareoftencalled
model-independent,lIkeanymathematIcalconstruct,assumptIonsmustbemadeto
sImplIfythemathematIcs.ThebasIcassumptIonsofnoncompartmentalanalysIsarethatall
oftheelImInatIonclearanceoccursdIrectlyfromtheplasma,thedIstrIbutIonand
elImInatIonofdrugIsalInearandfIrstorderprocess,andthepharmacokInetIcsofthe
systemdoesnotvaryoverthetImeofthedatacollectIon(tImeInvarIant).Allofthese
assumptIonsarealsomadeInthebasIccompartmentalandmostphysIologIcmodels.
Therefore,themaInadvantageofthenoncompartmentalpharmacokInetIcmethodsIsthat
ageneraldescrIptIonofdrugabsorptIon,dIstrIbutIon,andelImInatIoncanbemadewIthout
resortIngtomorecomplexmathematIcalmodelIngtechnIques.
40
AnotherappealIngfacetofnoncompartmentalanalysIsIsthattheparametersthatdescrIbe
drugdIstrIbutIon(volumeofdIstrIbutIonatsteadystate,Vd
ss
)anddrugelImInatIon
(elImInatIonclearance,Cl
E
)areanalogoustoparametersfoundInotherpharmacokInetIc
technIques.nfact,whenproperlydefIned,theestImatesoftheseparametersfromthe
noncompartmentalapproachandawelldefInedcompartmentalmodelyIeldsImIlarvalues.
ThemaInunIqueparameterofnoncompartmentalanalysIsIsthemeanresIdencetIme
(|FT),whIchIstheaveragetImeadrugmoleculespendsInthebodybeforebeIng
elImInated.
42
The|FTunfortunatelysuffersfromthemaInfaIlIngsoftheelImInatIonhalf
lIfederIvedfromcompartmentalmodelsnotonlydoesItfaIltocapturethecontrIbutIon
ofextensIvedIstrIbutIonversuslImItedelImInatIontoallowadrugtolIngerInthebody,
butbothparametersalsofaIltodescrIbethesItuatIonInwhIchthedrugeffectcan
dIssIpatebyredIstrIbutIonofdrugfromthesIteofactIonbackIntobloodandthenInto
other,lesswellperfusedtIssues.
4J
Pharmacodynamic Principles
|uchoftheclInIcalpharmacologyeffortsofthelate1980sthrough1990sweredevotedto
applyIngnewcomputatIonalpowerofdesktoppersonalcomputerstodecIpherIngthe
pharmacokInetIcsofIntravenousanesthetIcs.However,thepremIsebehInddevelopIng
modelstobettercharacterIzeandunderstandtheeffectsofvarIousphysIologIcand
pathologIcstatesondrugdIstrIbutIonandelImInatIonwasthattheeffortsoftheprevIous
J0yearshadclearlycharacterIzedtherelatIonshIpbetweenadoseofdrugandIts
effect(s).AscomputatIonalpoweranddrugassaytechnologygrew,ItbecamepossIbleto
characterIzetherelatIonshIpbetweenadrugconcentratIonandtheassocIated
pharmacologIceffect.Asaresult,pharmacodynamIcstudIessIncethe1990shavefocused
onthequantItatIveanalysIsoftherelatIonshIpbetweenthedrugconcentratIonInthe
bloodandtheresultanteffectsofthedrugonphysIologIcprocesses.
Drug-Receptor Interactions
|ostpharmacologIcagentsproducetheIrphysIologIceffectsbybIndIngtoadrugspecIfIc
receptor,whIchbrIngsaboutachangeIncellularfunctIon.ThemajorItyofpharmacologIc
receptorsarecellmembraneboundproteIns,althoughsomereceptorsarelocatedInthe
cytoplasmorthenucleoplasmofthecell.
8IndIngofdrugstoreceptors,lIkethebIndIngofdrugstoplasmaproteIns,Isusually
reversIble,andfollowsthelawof|assActIon:
ThIsrelatIonshIpdemonstratesthatthehIghertheconcentratIonoffreedrugor
unoccupIedreceptor,thegreaterthetendencytoformthedrugreceptorcomplex.PlottIng
thepercentageofreceptorsoccupIedbyadrugagaInstthelogarIthmoftheconcentratIon
ofthedrugyIeldsasIgmoIdcurve,asshownInFIgure79.
44
ThepercentageofreceptorsoccupIedbyadrugIsnotequIvalenttothepercentageof
maxImaleffectproducedbythedrug.nfact,mostreceptorsystemshavemorereceptors
thanrequIredtoobtaInthemaxImumdrugeffect.
45
ThepresenceofextraunoccupIed
receptorswIllpromotetheformatIonofthedrugreceptorcomplex(lawof|assActIon,
EquatIon717),therefore,nearmaxImaldrugeffectscanoccuratverylowdrug
concentratIons.ThIsnotonlyallows
P.150
extremelyeffIcIentresponsestodrugs,butItprovIdesalargemargInofsafetyan
extremelylargenumberofadrugsreceptorsmustbeboundtoanantagonIstbeforethe
drugIsunabletoproduceItspharmacologIceffect.Forexample,attheneuromuscular
junctIon,only20to25ofthepostjunctIonalnIcotInIccholInergIcreceptorsneedtobInd
acetylcholInetoproducecontractIonofallthefIbersInthemusclewhereas75ofthe
receptorsmustbeblockedbyanondepolarIzIngneuromuscularantagonIsttoproducea
sIgnIfIcantdropInmusclestrength.ThIsaccountsforthemargInofsafetyof
neuromusculartransmIssIon
45
(seeChapter20).
Figure 7-9.AschematIccurveoftheeffectofadrugplottedagaInstdose.ntheleft
panel,theresponsedataareplottedagaInstthedosedataonalInearscale.nthe
rIghtpanel,thesameresponsedataareplottedagaInstthedosedataonalogarIthmIc
scaleyIeldIngasIgmoIddoseresponsecurvethatIslInearbetween20and80ofthe
maxImaleffect.
ThebIndIngofdrugstoreceptorsandtheresultIngchangesIncellularfunctIonarethelast
twostepsInthecomplexserIesofeventsbetweenadmInIstratIonofthedrugand
productIonofItspharmacologIceffects.TherearetwoprImaryschemesbywhIchthe
bIndIngofanagonIsttoareceptorchangescellularfunctIon:receptorlInkedmembrane
Ionchannelscalledionophores,andguanInenucleotIdebIndIngproteIns,referredtoasG-
proteins.ThenIcotInIccholInergIcreceptorIntheneuromuscularpostsynaptIcmembrane
IsoneexampleofareceptorIonophorecomplex.8IndIngofacetylcholIneopensthecatIon
Ionophore,leadIngtoanInfluxofNa
+
Ions,propagatIonofanactIonpotentIal,and,
ultImately,musclecontractIon.TheamInobutyrIcacId(CA8A)receptorchlorIde
IonophorecomplexIsanotherexampleofthIstypeofeffectormechanIsm.8IndIngof
eItherendogenousneurotransmItters(CA8A)orexogenousagonIsts(benzodIazepInesand
IntravenousanesthetIcs)IncreasesCl
conductance,whIchhyperpolarIzestheneuronand
decreasesItsexcItabIlIty.AdrenergIcreceptorsaretheprototypIcalCproteIncoupled
receptors.CproteInschangetheIntracellularconcentratIonsofvarIoussocalledsecond
messengers,suchasCa
2+
andcyclIcA|PInordertotransducertheIrsIgnalandproduce
modIfycellularbehavIor(seeChapter15).
Desensitization and Down-Regulation of Receptors
FeceptorsarenotstatIcentItIes.Father,theyaredynamIccellularcomponentsthatadapt
totheIrenvIronment.ProlongedexposureofareceptortoItsagonIstleadsto
desensItIzatIon;subsequentdosesoftheagonIstwIllproducelowermaxImaleffects.WIth
sustaInedelevatIonofthecytosolIcsecondmessengersdownstreamoftheCproteIns,
pathwaystopreventfurtherCproteInsIgnalIngareactIvated.PhosphorylatIonbyC
proteInreceptorkInasesandarrestInmedIatedblockageofthecouplIngsIteneededto
formtheactIveheterotrImerIcCproteIncomplexpreventsCproteIncoupledreceptors
frombecomIngactIve.ArrestInsandothercellmembraneproteInscantagreceptorsthat
havesustaInedactIvItysothatthesenonCproteInreceptorsareInternalIzedand
sequesteredsotheyarenolongeraccessIbletoagonIsts.SImIlarmechanIsmswIllprevent
thetraffIckIngofstoredreceptorstothecellmembrane.ThecombInedIncreasedrateof
InternalIzatIonanddecreasedrateofreplenIshIngofreceptorresultsIndown-regulationa
decreaseInthetotalnumberofreceptors.SIgnalsthatproducedownregulatIonwIth
sustaInedreceptoractIvatIonareessentIallyreversedInthefaceofconstantreceptor
InactIvIty.Therefore,chronIcallydenervatedneuromuscularjunctIonsjustlIkecardIac
tIssueconstantlybathedwIthadrenergIcantagonIstswIllbothupregulatethespecIfIc
receptorsInanattempttoproduceasIgnalInthefaceoflowerconcentratIonsofagonIsts.
Agonists, Partial Agonists, and Antagonists
0rugsthatbIndtoreceptorsandproduceaneffectarecalledagonists.0rugsmaybe
capableofproducIngthesamemaxImaleffect(E
|AX
),althoughtheymaydIfferIn
concentratIonthatproducestheeffect(I.e.,potency).AgonIststhatdIfferInpotencybut
bIndtothesamereceptorswIllhaveparallelconcentratIonresponsecurves(curvesAand
BInFIg.710).0IfferencesInpotencyofagonIstsreflectdIfferencesInaffInItyforthe
receptor.Partial agonistsaredrugsthatarenotcapableofproducIngthemaxImaleffect,
evenatveryhIghconcentratIons(curveCInFIg.710).
CompoundsthatbIndtoreceptorswIthoutproducInganychangesIncellularfunctIonare
referredtoasantagonistsantagonIstsblockIngtheactIvebIndIngsIte(s)InhIbItagonIst
bIndIngtothereceptors.Competitive antagonistsbIndreversIblytoreceptors,andtheIr
blockIngeffectcanbeovercomebyhIghconcentratIonsofanagonIst(I.e.,competItIon).
Therefore,competItIveantagonIstsproduceaparallelshIftInthedoseresponsecurve,but
themaxImumeffectIsnotaltered(seecurvesAandBInFIg.710).Noncompetitive
antagonistsbIndIrreversIblytoreceptors.ThIshasthesameeffectasreducIngthenumber
ofreceptorsandshIftsthedoseresponsecurvedownwardandtotherIght,decreasIngboth
theslopeandthemaxImumeffect(curvesAandCInFIg.710).Theeffectof
noncompetItIveantagonIstsIsreversedonlybysynthesIsofnewreceptormolecules.
AgonIstsproduceastructuralchangeInthereceptormoleculethatInItIateschangesIn
cellularfunctIon.PartIalagonIstsmayproduceaqualItatIvelydIfferentchangeInthe
receptor,whereasantagonIstsbIndwIthoutproducIngachangeInthereceptorthatresults
InalteredcellularfunctIon.TheunderlyIngmechanIsmsbywhIchdIfferentcompoundsthat
bIndtothesamereceptoractasagonIsts,partIalagonIsts,orantagonIstsarenotfully
understood.
P.151
Figure 7-10.SchematIcpharmacodynamIccurves,wIthdoseorconcentratIononthe
xaxIsandeffectorreceptoroccupancyontheyaxIs,thatIllustrateagonIsm,partIal
agonIsm,andantagonIsm.0rugAproducesamaxImumeffect,E
|AX
,anda50of
maxImaleffectatdoseorconcentratIonE
50,A
.0rug8,afullagonIst,canproducethe
maxImumeffect,E
|AX
;however,ItIslesspotent(E
50,8
E
50,A
).0rugC,apartIal
agonIst,canonlyproduceamaxImumeffectofapproxImately50E
|AX
.fa
competItIveantagonIstIsgIventoapatIent,thedoseresponsefortheagonIstwould
shIftfromcurveAtocurve8.AlthoughthereceptorswouldhavethesameaffInItyfor
theagonIst,thepresenceofthecompetItorwouldnecessItateanIncreaseInagonIstIn
ordertoproduceaneffect.nfact,theagonIstwouldstIllbeabletoproducea
maxImaleffectIfasuffIcIentoverdosewasgIventodIsplacethecompetItIve
antagonIst.However,thecompetItIveantagonIstwouldnotchangethebIndIng
characterIstIcsofthereceptorfortheagonIstandsocurve8IssImplyshIftedtothe
rIghtbutremaInsparalleltocurveA.ncontrast,IfanoncompetItIveantagonIstbInds
tothereceptor,theagonIstwouldnolongerbeabletoproduceamaxImaleffect,no
matterhowmuchofanoverdoseIsadmInIstered(curveC).
Dose-Response Relationships
0oseresponsestudIesdetermInetherelatIonshIpbetweenIncreasIngdosesofadrugand
theensuIngchangesInpharmacologIceffects.SchematIcdoseresponsecurvesareshown
InFIgure79,wIththedoseplottedonbothlInearandlogarIthmIcscales.ThereIsa
curvIlInearrelatIonshIpbetweendoseandtheIntensItyofresponse.Lowdosesproduce
lIttlepharmacologIceffect.DnceeffectsbecomeevIdent,asmallIncreaseIndose
producesarelatIvelylargechangeIneffect.AtnearmaxImalresponse,largeIncreasesIn
doseproducelIttlechangeIneffect.UsuallythedoseIsplottedonalogarIthmIcscale(see
FIg.79,rIghtpanel),whIchdemonstratesthelInearrelatIonshIpbetweenthelogarIthmof
thedoseandtheIntensItyoftheresponsebetween20and80ofthemaxImumeffect.
AcquIrIngthepharmacologIceffectdatafromapopulatIonofsubjectsexposedtoavarIety
ofdosesofadrugprovIdesfourkeycharacterIstIcsofthedrugdoseresponserelatIonshIp:
potency,drugreceptoraffInIty,effIcacy,andpopulatIonpharmacodynamIcvarIabIlIty.The
potencyofthedrugthedoserequIredtoproduceagIveneffectIsusuallyexpressedas
thedoserequIredtoproduceagIveneffectIn50ofsubjects,theED
50
.Theslopeofthe
curvebetween20and80ofthemaxImaleffectIndIcatestherateofIncreaseIneffectas
thedoseIsIncreasedandIsareflectIonoftheaffInItyofthereceptorforthedrug.The
maxImumeffectIsreferredtoastheefficacyofthedrug.FInally,IfcurvesfrommultIple
subjectsaregenerated,thevariabilityInpotency,effIcacy,andtheslopeofthedose
responsecurvecanbeestImated.
ThedoseneededtoproduceagIvenpharmacologIceffectvarIesconsIderably,evenIn
normalpatIents.ThepatIentmostresIstanttothedrugusuallyrequIresadosetwoto
threefoldgreaterthanthepatIentwIththelowestdoserequIrements.ThIsvarIabIlItyIs
causedbydIfferencesamongIndIvIdualsIntherelatIonshIpbetweendrugconcentratIon
andpharmacologIceffect,superImposedondIfferencesInpharmacokInetIcs.0oseresponse
studIeshavethedIsadvantageofnotbeIngabletodetermInewhethervarIatIonsIn
pharmacologIcresponsearecausedbydIfferencesInpharmacokInetIcs,
pharmacodynamIcs,orboth.
Concentration-Response Relationships
TheonsetandduratIonofpharmacologIceffectsdependnotonlyonpharmacokInetIc
factorsbutalsoonthepharmacodynamIcfactorsgovernIngthedegreeoftemporal
dIsequIlIbrIumbetweenchangesInconcentratIonandchangesIneffect.ThemagnItudeof
thepharmacologIceffectIsafunctIonoftheamountofdrugpresentatthesIteofactIon,
soIncreasIngthedoseIncreasesthepeakeffect.LargerdoseshaveamorerapIdonsetof
actIonbecausepharmacologIcallyactIveconcentratIonsatthesIteofactIonoccursooner.
ncreasIngthedosealsoIncreasestheduratIonofactIonbecausepharmacologIcally
effectIveconcentratIonsaremaIntaInedforalongertIme.
deally,theconcentratIonofdrugatItssIteofactIonshouldbeusedtodefInethe
concentratIonresponserelatIonshIp.Unfortunately,thesedataarerarelyavaIlable,sothe
relatIonshIpbetweentheconcentratIonofdrugInthebloodandpharmacologIceffectIs
studIedInstead.ThIsrelatIonshIpIseasIesttounderstandIfthechangesInpharmacologIc
effectthatoccurdurIngandafteranIntravenousInfusIonofahypothetIcaldrugare
consIdered.fadrugIsInfusedataconstantrate,theplasmaconcentratIonInItIally
IncreasesrapIdlyandasymptotIcallyapproachesasteadystatelevelafterapproxImately
fIveelImInatIonhalflIveshaveelapsed(FIg.711).TheeffectofthedrugInItIallyIncreases
veryslowly,thenmorerapIdly,andeventuallyalsoreachesasteadystate.Whenthe
InfusIonIsdIscontInued,IndIcatedbypoIntCInFIgure711,theplasmaconcentratIon
ImmedIatelydecreasesbecauseofdrugdIstrIbutIonandelImInatIon.However,theeffect
staysthesameforashortperIod,andthenalsobegInstodecrease;
P.152
thereIsalwaysatImelagbetweenchangesInplasmaconcentratIonandchangesIn
pharmacologIcresponse.FIgure711alsodemonstratesthatthesameplasma
concentratIonIsassocIatedwIthdIfferentresponsesIftheconcentratIonIschangIng.At
poIntsAandBInFIgure711,theplasmaconcentratIonsarethesame,buttheeffectsat
eachtImedIffer.WhentheconcentratIonIsIncreasIng,thereIsaconcentratIongradIent
frombloodtothesIteofactIon.WhentheInfusIonIsdIscontInued,theconcentratIon
gradIentIsreversed.Therefore,atthesameplasmaconcentratIon,theconcentratIonat
thesIteofactIonIshIgherafter,comparedwIthdurIng,theInfusIon.ThIsIsassocIated
wIthacorrespondInglygreatereffect.
Figure 7-11.ThechangesInplasmadrugconcentratIon(C
p
)andpharmacologIceffect
durIngandafteranIntravenousInfusIon.SeetextforexplanatIon.(FeprIntedwIth
permIssIonfromStanskI0F,SheInerL8.PharmacokInetIcsandpharmacodynamIcsof
musclerelaxants.AnesthesIology1979;51:10J.)
ntheory,theremustbesomedegreeoftemporaldIsequIlIbrIumbetweenplasma
concentratIonanddrugeffectforalldrugswIthextravascularsItesofactIon.However,for
somedrugs,thetImelagmaybesoshortthatItcannotbedemonstrated.ThemagnItude
ofthIstemporaldIsequIlIbrIumdependsonseveralfactors:
1. TheperfusIonoftheorganonwhIchthedrugacts
2. ThetIssue:bloodpartItIoncoeffIcIentofthedrug
J. TherateofdIffusIonortransportofthedrugfromthebloodtothecellularsIteofactIon
4. TherateandaffInItyofdrugreceptorbIndIng
5. ThetImerequIredforprocessesInItIatedbythedrugreceptorInteractIontoproduce
changesIncellularfunctIon
TheconsequenceofthIstImelagbetweenchangesInconcentratIonandchangesIneffects
IsthattheplasmaconcentratIonwIllhaveanunvaryIngrelatIonshIpwIthpharmacologIc
effectonlyundersteadystatecondItIons.Atsteadystate,theplasmaconcentratIonIsIn
equIlIbrIumwIththeconcentratIonsthroughoutthebody,andIsthusdIrectlyproportIonal
tothesteadystateconcentratIonatthesIteofactIon.PlottIngthelogarIthmofthe
steadystateplasmaconcentratIonversusresponsegeneratesacurveIdentIcalIn
appearancetothedoseresponsecurveshownIntherIghtpanelofFIgure79.TheCp
ss
50,
thesteadystateplasmaconcentratIonproducIng50ofthemaxImalresponse,Is
determInedfromtheconcentratIonresponsecurve.LIketheED
50
,theCp
ss
50Isameasure
ofsensItIvItytoadrug,buttheCp
ss
50hastheadvantageofbeIngunaffectedby
pharmacokInetIcvarIabIlIty.8ecauseIttakesfIveelImInatIonhalflIvestoapproach
steadystatecondItIons,ItIsnotpractIcaltodetermInetheCp
ss
50dIrectly.FordrugswIth
longelImInatIonhalflIves,thepseudoequIlIbrIumdurIngtheelImInatIonphasecanbeused
toapproxImatesteadystatecondItIonsbecausetheconcentratIonsInplasmaandatthe
sIteofactIonarechangIngveryslowly.
Combined Pharmacokinetic-Pharmacodynamic Models
ntegratedpharmacokInetIcpharmacodynamIcmodelsfullycharacterIzetherelatIonshIps
amongtIme,dose,plasmaconcentratIon,andpharmacologIceffect.ThIsIsaccomplIshed
byaddIngahypothetIcaleffectcompartment(bIophase)toastandardcompartmental
pharmacokInetIcmodel(FIg.712).
46,47
Transferofdrugbetweencentralcompartmentand
theeffectcompartmentIsassumedtobeafIrstorderprocess,andthepharmacologIc
effectIsassumedtobedIrectlyrelatedtotheconcentratIonInthebIophase.ThebIophase
IsavIrtualcompartment,althoughlInkedtothepharmacokInetIcmodel,doesnot
actuallyreceIveorreturndrugtothemodeland,therefore,ensuresthattheeffectsIte
processesdonotInfluencethepharmacokInetIcsoftherestofthesystem.8y
sImultaneouslycharacterIzIngthepharmacokInetIcsofthedrugandthetImecourseof
drugeffect,thecombInedpharmacokInetIcpharmacodynamIcmodelIsabletoquantIfy
thetemporaldIssocIatIonbetweentheplasma(centralcompartment)concentratIonand
effectwIththerateconstantforequIlIbratIonbetweentheplasmaandthebIophase,k
e0
.
8yquantIfyIngthetImelagbetweenchangesInplasmaconcentratIonandchangesIn
pharmacologIceffect,thesemodelscanalsodefInetheCp
ss
50,evenwIthoutsteadystate
condItIons.ThesemodelshavecontrIbutedgreatlytoourunderstandIngoffactors
InfluencIngtheresponsetoIntravenousanesthetIcs,
48,49,50
opIoIds,
20,51,52,5J
and
nondepolarIzIngmusclerelaxants
47,54,55
Inhumans.
Figure 7-12.AschematIcofathreecompartmentpharmacokInetIcmodelwIththe
effectsItelInkedtothecentralcompartment.Therateconstantfortransferbetween
theplasma(centralcompartment)andtheeffectsIte,k
1e
,andthevolumeofthe
effectsItearebothpresumedtobeneglIgIbletoensurethattheeffectsItedoesnot
InfluencethepharmacokInetIcmodel.Therateconstantfordrugremovalfromthe
effectsIte,whIchrelatestheconcentratIonInthecentralcompartmenttothe
pharmacologIceffect,Isk
e0
.
TherateofequIlIbratIonbetweentheplasmaandthebIophase,k
e0
,canalsobe
characterIzedbythehalflIfeofeffectsIteequIlIbratIon(T
1/2ke0
)usIngtheformula:
T
1/2ke0
IsthetImefortheeffectsIteconcentratIontoreach50oftheplasma
concentratIonwhentheplasmaconcentratIonIsheldconstant.ForanesthetIcswIthashort
T
1/2ke0
(hIghk
e0
),equIlIbratIonbetweentheplasmaandthebIophaseIsrapIdandtherefore
thereIslIttledelaybeforeaneffectIsreachedwhenabolusofdrugIsadmInIsteredoran
InfusIonofdrugIsInItIated.However,becausethedeclIneIntheeffectsIteconcentratIon
wIllalsodependontheconcentratIongradIentbetweentheeffectsIteandtheplasma,
drugsthatrapIdlyequIlIbratewIththebIophasemaytakelongertoredIstrIbuteaway.
56
Therefore,theoffsetofdrugeffectIsmoredependentonthepharmacokInetIcsofthebody
thanontherapIdItyofbIophaseplasmaequIlIbratIon.
20,56
Drug Interactions
TakIngIntoaccountpremedIcatIon,perIoperatIveantIbIotIcs,Intravenousagentsusedfor
InductIonormaIntenance,InhalatIonalanesthetIcs,opIoIds,musclerelaxants,thedrugs
usedtorestoreneuromusculartransmIssIon,andpostoperatIve
P.15J
analgesIcs,10ormoredrugsmaybegIvenforarelatIvelyroutIneanesthetIc.
Consequently,thoroughunderstandIngofthemechanIsmsofdrugInteractIonsand
knowledgeofspecIfIcInteractIonswIthdrugsusedInanesthesIaareessentIaltothesafe
practIceofanesthesIology(seeChapter22).ndeed,anesthesIologIstsoftendelIberately
takeadvantageofdrugInteractIons.Forexample,moderatetohIghdosesofopIoIdare
oftenusedtodecreasetheamountofvolatIleanesthetIcrequIredtoprovIdeImmobIlIty
andhemodynamIcstabIlItytosurgIcalIncIsIon(e.g.,|AC
a
and|AC
8AF
b
),therebyavoIdIng
thesIdeeffectsofhIgherconcentratIonsofInhaledanesthetIcs(e.g.,vasodIlatIon,
prolongedawakenIng;seeChapter17).
0rugInteractIonsbecauseofphysIcochemIcalpropertIescanoccurInvItro.|IxIngacIdIc
drugs,suchasthIopental,andbasIcdrugs,suchasopIoIdsormusclerelaxants,resultsIn
theformatIonofInsolublesaltsthatprecIpItate.AnothertypeofInvItroreactIonIs
absorptIonofdrugsbyplastIcs.ExamplesIncludetheuptakeofnItroglycerInbypolyvInyl
chlorIdeInfusIonsetsandtheabsorptIonoffentanylbytheapparatususedfor
cardIopulmonarybypass.
0rugscanaltereachother'sabsorptIon,dIstrIbutIon,andelImInatIon.0rugslIkeranItIdIne,
whIchaltersgastrIcpH,andmetoclopramIde,whIchspeedsgastrIcemptyIng,alter
absorptIonfromthegastroIntestInaltract.7asoconstrIctorsareaddedtolocalanesthetIc
solutIonstoprolongtheIrduratIonofactIonatthesIteofInjectIonandtodecreasetherIsk
ofsystemIctoxIcItyfromrapIdabsorptIon.
0rugsthatInhIbItorInducetheenzymesthatcatalyzebIotransformatIonreactIonscan
affectclearanceofotherconcomItantlyadmInIstereddrugs.Forexample,the
antIconvulsantphenytoInshortenstheduratIonofactIonofthenondepolarIzIng
neuromuscularjunctIonblockIngagentsbyInducIngCYPandthereforeIncreasIng
elImInatIonclearanceofthedrug.
55
ClearancecanalsobeaffectedbydrugInduced
changesInhepatIcbloodflow.0rugsthatareclearedbythekIdneysandhavesImIlar
physIcochemIcalcharacterIstIcscompeteforthetransportmechanIsmsInvolvedInrenal
tubularsecretIon.
PharmacodynamIcInteractIonsfallIntotwobroadclassIfIcatIons.0rugscanInteract,
eItherdIrectlyorIndIrectly,atthesamereceptors.DpIoIdantagonIstsdIrectlydIsplace
opIoIdsfromopIatereceptors.CholInesteraseInhIbItorsIndIrectlyantagonIzetheeffectsof
neuromuscularblockersbyIncreasIngtheamountofacetylcholIne,whIchdIsplacesthe
blockIngdrugfromnIcotInIcreceptors.PharmacodynamIcInteractIonscanalsooccurIftwo
drugsaffectaphysIologIcsystematdIfferentsItes.
57,58
HypnotIcsandopIoIds,eachactIng
ontheIrownspecIfIcreceptors,appeartoInteractsynergIstIcally.
59
ThepharmacodynamIc
InteractIonbetweentwodrugscanbecharacterIzedusIngresponsesurface
models.
60,61,62,6J,64,65
ThethreedImensIonalmodelsareusefulIndelIneatIngthe
concentratIonpaIrsofahypnotIc(e.g.,volatIleanesthetIc,propofol,mIdazolam)andan
opIoId(e.g.,remIfentanIl,alfentanIl,fentanyl)thatproduceadequateanesthesIawhIle
mInImIzIngundesIredsIdeeffects.
66
(SeeFesponseSurface|odelsof0rug0rug
nteractIons.)
Clinical Applications of Pharmacokinetic and Pharmacodynamics
to the Administration of Intravenous Anesthetics
AlthoughnonewInhaledanesthetIcshavebeensynthesIzedsIncethe1970s,
67
Intravenous
drugsthatactontheCNScontInuetobedeveloped.AnesthesIologIstshavebecome
accustomedtotheexquIsItecontrolofanesthetIcblood(andeffectsIte)concentratIons
affordedbymodernvolatIleanesthetIcagentsandtheIrvaporIzers,coupledtoendtIdal
anesthetIcgasmonItorIng.AlthoughpharmacokInetIcandpharmacodynamIcprIncIplesand
datahavecontrIbutedgreatlytoourunderstandIngofthebehavIorofIntravenous
anesthetIcs,theIrprImaryutIlItyandultImatepurposearetodetermIneoptImaldosIng
wIthasmuchmathematIcalprecIsIonandclInIcalaccuracyaspossIble.nmost
pharmacotherapeutIcscenarIosoutsIdeanesthesIacare,thetImescalesforonsetofdrug
effect,ItsmaIntenance,andItsoffsetaremeasuredIndays,weeks,orevenyears.nsuch
cases,globalpharmacokInetIcvarIables(andonecompartmentmodels)suchastotal
volumeofdIstrIbutIon(V
SS
),elImInatIonclearance(Cl
e
),andhalflIfe(t
1/2
)aresuffIcIent
andutIlItarIanparametersforcalculatIngdoseregImens.However,IntheoperatIngroom
andIntensIvecareunIt,thetemporaltolerancesforonsetandoffsetofdesIreddrug
effectsaremeasuredInmInutes.
J8,J9
Consequently,theseglobalvarIablesareInsuffIcIent
todescrIbethedetaIlsofkInetIcbehavIorofdrugsInthemInutesfollowIngIntravenous
admInIstratIon.ThIsIspartIcularlytrueoflIpIdsolublehypnotIcsandopIoIdsthatrapIdly
andextensIvelydIstrIbutethroughoutthevarIoustIssuesofthebodybecausedIstrIbutIon
processesdomInatepharmacokInetIcbehavIordurIngthetImeframeofmostanesthetIcs.
AddItIonally,thetherapeutIcIndIcesofmanyIntravenousanesthetIcdrugsaresmalland
twotaIled(I.e.,anunderdose,resultIngInawareness,whIchIsatoxIceffect).DptImal
dosIngInthesesItuatIonsrequIresuseofallthevarIablesofamultIcompartmental
pharmacokInetIcmodeltoaccountfordrugdIstrIbutIonInbloodandothertIssues.
tIsnoteasytoIntuItthepharmacokInetIcbehavIorofamultIcompartmentalsystemby
sImpleexamInatIonofthekInetIcvarIables.
10
ComputersImulatIonIsrequIredto
meanIngfullyInterpretdosIngortoaccuratelydevIsenewdosIngregImens.naddItIon,
thereareseveralpharmacokInetIcconceptsthatareunIquelyapplIcabletoIntravenous
admInIstratIonofdrugswIthmultIcompartmentalkInetIcsandmustbetakenIntoaccount
whenadmInIsterIngIntravenousInfusIons.
ToachIevesImIlardegreesofcontrolofIntravenouslyadmInIsteredanesthetIcdrug
concentratIonsInbloodandIntheCNS,newtechnologIesaImedatImprovIngIntravenous
InfusIondevIces,aswellasnewsoftwaretomanagethedauntIngpharmacokInetIc
prIncIplesInvolved,areneeded.ThIssectIonexamInesthecurrentstateofInfusIondevIces
andthepharmacokInetIcandpharmacodynamIcprIncIplesspecIfIcallyrequIredforprecIse
delIveryofanesthetIcagents.
Rise to Steady-State Concentration
ThedrugconcentratIonversustImeprofIlefortherIsetosteadystateIsthemIrrorImage
ofItselImInatIonprofIle.naonecompartmentmodelwIthadeclIneInconcentratIon
versustImethatIsmonoexponentIalfollowIngasIngledose,therIseofdrugconcentratIon
tothesteadystateconcentratIon(C
SS
)IslIkewIsemonoexponentIaldurIngacontInuous
P.154
InfusIon.ThatIs,InoneelImInatIonhalflIfeanInfusIonIshalfwaytoItseventualsteady
stateconcentratIon,InanotherhalflIfeItreacheshalfofwhatremaInsbetweenhalfway
andsteadystate(I.e.,75oftheeventualsteadystateIsreachedIntwoelImInatIonhalf
lIves),andsoonforeachhalflIfeIncrement.TheequatIondescrIbIngthIsbehavIorIs:
whereC
p
(t)=theconcentratIonattImet,kIstherateconstantrelatedtotheelImInatIon
halflIfe,andtIsthetImefromthestartoftheInfusIon.ThIsrelatIonshIpcanalsobe
descrIbedby:
InwhIchC
p
(n)IstheconcentratIonatnhalflIves.EquatIon720IndIcatesthatdurInga
constantInfusIon,theconcentratIonreaches90ofC
SS
afterJ.JhalflIves,whIchIsusually
deemedcloseenoughforclInIcalpurposes.
However,foradrugsuchaspropofol,whIchpartItIonsextensIvelytopharmacologIcally
InertbodytIssues(e.g.,muscle,gut),amonoexponentIalequatIon,orsInglecompartment
model,IsInsuffIcIenttodescrIbethetImecourseofpropofolconcentratIonsInthefIrst
mInutesandhoursafterbegInnIngdrugadmInIstratIon.nstead,amultIcompartmentalor
multIexponentIalmodelmustbeused.WIthsuchamodel,thepIcturechangesdrastIcally
fortheplasmadrugconcentratIonrIsetowardsteadystate.TherateofrIsetowardsteady
stateIsdetermInedbythedIstrIbutIonrateconstantstothedegreethattheIrrespectIve
exponentIaltermscontrIbutetothetotalareaundertheconcentratIonversustImecurve.
Thus,forthethreecompartmentmodeldescrIbIngthepharmacokInetIcsofpropofol,
EquatIon719becomes:
InwhIcht=tIme;C
p
(t)=plasmaconcentratIonattIme;A=coeffIcIentoftherapId
dIstrIbutIonphaseand=hybrIdrateconstantoftherapIddIstrIbutIonphase;B=
coeffIcIentoftheslowerdIstrIbutIonphase,and=hybrIdrateconstantoftheslower
dIstrIbutIon;andG=coeffIcIentofelImInatIonphaseand=hybrIdrateconstantofthe
elImInatIonphase.A+B+GIsthesumofthecoeffIcIentsofalltheexponentIalterms.For
mostlIpophIlIcanesthetIcsandopIoIds,AIstypIcallyoneorderofmagnItudegreaterthan
B,andBIsInturnanorderofmagnItudegreaterthanG.Therefore,dIstrIbutIonphase
kInetIcsforIntravenousanesthetIcshaveamuchgreaterInfluenceonthetImetoreachC
SS
thandoelImInatIonphasekInetIcs.
56
Forexample,wIthpropofolhavInganelImInatIonhalflIfeofapproxImately6hours,the
sImpleonecompartmentruleInEquatIon720tellsusthatItwouldtake6hoursfromthe
startofaconstantrateInfusIontoreacheven50oftheeventualsteadystatepropofol
plasmaconcentratIonand12hourstoreach75.ncontrast,wIthafullthree
compartmentpropofolkInetIcmodel,EquatIon721accuratelypredIctsthat50ofsteady
stateIsreachedInJ0mInutesand75wIllbereachedIn4hours.ThIsexample
emphasIzesthenecessItyofusIngmultIcompartmentmodelstodescrIbetheclInIcal
pharmacokInetIcsofIntravenousanesthetIcs.
Manual Bolus and Infusion Dosing Schemes
8asedonaonecompartmentpharmacokInetIcmodel,astablesteadystateplasma
concentratIon(C
p,SS
)canbemaIntaInedbyadmInIsterInganInfusIonatarate(I)thatIs
proportIonaltotheelImInatIonofdrugfromthebody(Cl
E
):
However,IfthedrugwasadmInIsteredonlybyInItIatIngandmaIntaInIngthIsInfusIon,It
wouldtakeoneelImInatIonhalftImetoreach50ofthetargetplasmaconcentratIonand
threetImesthatlongtoreach90ofthetargetplasmaconcentratIon.nordertodecrease
thetImeuntIlthetargetplasmaconcentratIonIsachIeved,anInItIalbolus(loadIngdose)
ofdrugcanbeadmInIsteredthatwouldproducethetargetplasmaconcentratIon:
AlthoughthIsmethodIsveryeffIcIentInachIevIngandmaIntaInIngthetargetplasma
concentratIonofadrugthatInstantaneouslymIxesandequIlIbratesthroughoutthetIssues
ofthebody(e.g.,drugsmodeledwIthaonecompartmentpharmacokInetIcmodel),usIng
thesteadystateelImInatIonclearanceandvolumeofdIstrIbutIontocalculatetheloadIng
doseandmaIntenanceInfusIonratewIllresultInplasmadrugconcentratIonsthatare
hIgherthroughouttheInItIaldIstrIbutIonphase(seeFIg.71J).
UsIngEquatIons722and72JandV
d,SS
=262LandCl
E
=1.7L/mIn(fora50yearoldman
whoIs178cmtallandweIghs70kgfromSchnIderetal.
49
),theloadIngdoseandInfusIon
rateofpropofolthatIsneededtoachIeveasteadystateplasmaconcentratIonof5g/mL
Is1,J00mg(18mg/kg)and120g/kg/mIn.DbvIously,theloadIngdoseofpropofolIstoo
hIgh,comparedwIthclInIcallyuseddoses(1to2mg/kg)whIletheInfusIonrateappearsto
beaclInIcallyacceptabledose.TheerroneousestImateoftheloadIngdoseIsbecausethe
InItIalbolusofdrugIsnotInstantaneouslymIxedandequIlIbratedwIththeentIrevolume
oftIssuethatwIlleventuallytakeupdrug.Therefore,
P.155
manualdosIngstrategIesforIntravenousanesthetIcsneedtobemodIfIedtoaccountfor
thefactthatwhenabolusofdrugIsadmInIstered,ItrapIdlymIxesandequIlIbrateswIth
thebloodandonlyasmallvolumeoftIssue(e.g.,thecentralcompartment),andthenwIll
dIstrIbuteovertImeIntoothertIssues.
Table 7-5 BET
a
Scheme to Achieve C
p
5 g/mL for 120 Minutes
DOSE AMOUNT TIME (min)
8olus 2.8mg/kg
nfusIon
2J8g/kg/mIn 010
187g/kg/mIn 1020
1J6g/kg/mIn 2060
112g/kg/mIn 60120
a
8IstheloadIngbolusdose,EIstheInfusIontoreplacedrugremovedby
elImInatIonclearance,andTIsacontInuouslydecreasIngInfusIonthat
compensatesfortransferofdrugtotheperIpheraltIssues.
Figure 7-13.AcomputersImulatIonoftheplasmapropofolconcentratIonprofIle
durIngandaftertheadmInIstratIonofasInglebolusandInfusIonschemecalculated
usIngthesteadystate,onecompartmentpharmacokInetIcparameters(solid line)and
the8ETschemefromTable75(dashed line)toachIeveaplasmaconcentratIonof5
mcg/mL.V
d,SS
=262LandCl
E
=1.7L/mInfora50yearoldmanwhoIs178cmtalland
weIghs70kg.SeetextfordescrIptIonof8ETscheme.
TodesIgnamanualbolusthatmoreprecIselyachIevesthedesIredtargetplasma
concentratIon,ItIsnecessarytochooseabolusthatIsbasedonthesmall,InItIalvolumeof
dIstrIbutIon(V
c
).TomaIntaInthetargetplasmaconcentratIon,aserIesofInfusIonsof
decreasIngratecanbeusedthatmatchtheelImInatIonclearanceandcompensatesfor
druglossfromthecentraltotheperIpheralcompartmentsdurIngtheInItIalperIodof
extensIvedrugdIstrIbutIonandthesecondperIodofmoderatedrugdIstrIbutIon.ThIs
manualdosIngschemehasbeentermedtheBET scheme,where8IstheloadIngbolusdose,
EIstheInfusIontoreplacedrugremovedbyelImInatIonclearance,andTIsacontInuously
decreasIngInfusIonthatcompensatesfortransferofdrugtotheperIpheraltIssues(I.e.,
dIstrIbutIon).
68
Anexampleofa8ETschemeforpropofoltoachIeveatargetplasma
concentratIonof5g/mLIsshownInTable75.
Isoconcentration Nomogram
TomakethecalculatIonsofthevarIousInfusIonratesrequIredtomaIntaInatargetplasma
concentratIonforadrugthatfollowsmultIcompartmentpharmacokInetIcs,aclInIcIan
wouldneedaccesstoabasIccomputerandthesoftwaretoperformtheapproprIate
sImulatIons.WIththeapproprIateformulas,thIsIsquItefeasIbletodoonanybasIc
computerwIthanybasIcspreadsheet.However,evenwIthmoresophIstIcated
pharmacokInetIcsoftware(e.g.,SAA|,WInNonLIn,FugLoop,Stanpump),thIsIsatIme
consumIngprocessthatdIvertstheclInIcIan'sattentIonfromthepatIent.n1994,Shafer
69
IntroducedanIsoconcentratIonnomogramforpropofolthatusedtherIsetowardsteady
statedescrIbedbyamultIcompartmentalsystem(FIg.714).ThIsgraphIcaltoolallows
userstoemployconcentratIoneffect,ratherthandoseeffect,relatIonshIpswhen
determInIngoptImaldosIngofIntravenousanesthetIcagents.ThenomogramIsconstructed
bycalculatIngtheplasmadrugconcentratIonversustImecurveforaconstantrateInfusIon
fromasetofpharmacokInetIcvarIablesforapartIculardrug.FromthIssInglesImulatIon,
onecanreadIlyvIsualIze(andestImate)therIsetowardsteadystateplasmadrug
concentratIondescrIbedbythedrug'spharmacokInetIcmodel.8ysImulatIngarangeof
potentIalInfusIonrates,aserIesofcurvesofIdentIcalshapearethenplottedonasIngle
graphwIthdrugconcentratIonsatanytImethataredIrectlyproportIonaltotheInfusIon
rate.
8yplacIngahorIzontallIneatthedesIredplasmadrugconcentratIon(yaxIs)thetImes(x
axIs)atwhIchthehorIzontalIntersectsthelIneforapartIcularInfusIonratewIllrepresent
thetImesatwhIchtheInfusIonrateshouldbesettotherateontheInterceptInglIne.n
theexampleshown(seeFIg.714)wIth25mcg/kg/mInIncrements,thepredIctedplasma
propofolconcentratIonsremaInwIthIn10ofthetargetfrom2mInutesonwardwIthabIas
ofunderestImatIon.fneverallowIngtheestImatedconcentratIontofallbelowthetarget
IsdesIred,thenthetImetodecreasetothenextlowerInfusIonshouldbeatthemIdpoInt
ofthesubsequentInterval.ExtendIngtheInfusIonstothesubsequentmIdpoInttImeswIll
IntroduceamaxImumoverestImatIonbIasofapproxImately17wIththeIllustrated
InfusIonIncrements(FIg.714).8IaseswouldbeIncreasedordecreasedbyconstructIng
nomogramswIthlargerorsmallerInfusIonIncrements,respectIvely.
Figure 7-14.soconcentratIonnomogramfordetermInIngpropofolInfusIonrates
desIgnedtomaIntaInadesIredplasmapropofolconcentratIon.ThIsnomogramIsbased
onthepharmacokInetIcsofSchnIderetal.andplottedonaloglogscaletobetter
delIneatetheearlytImepoInts.Curved linesrepresenttheplasmapropofol
concentratIonversustImeplots,resultIngfromthevarIouscontInuousInfusIonrates
IndIcatedalongtherIghtandupperborders(unItsIng/kg/mIn).AhorIzontallIneIs
placedatthedesIredtargetplasmapropofolconcentratIon(Jg/mLInthIscase)and
vertIcallInesareplacedateachIntersectIonofacurvedconcentratIontImeplot.The
vertIcallInesIndIcatethetImesthattheInfusIonrateshouldbesettotheone
representedbythenextIntersectedcurveasonemovesfromlefttorIghtalongthe
horIzontallInedrawnatJg/mL.nthIsexampletheInfusIonratewouldbereduced
fromJ00to275g/kg/mInat2.5mInutes,to250g/kg/mInatJmInutes,to225
g/kg/mInat4.5mInutes,andsoonuntIlItIsturnedto100g/kg/mInat260mInutes.
ThenomogramcanalsobeusedtoIncreaseorreducethetargetedplasmapropofol
concentratIon.TotargetanewplasmadrugconcentratIon,anewhorIzontallInecanbe
drawnatthedesIredconcentratIon.TheInfusIonratethatIsclosesttothecurrenttIme
IntersectIstheonethatshouldbeusedInItIally,followedbythedecrementedrates
dIctatedbythesubsequentIntercepttImes.ForbestresultswhenIncreasIngthetarget
concentratIon,abolusequaltotheproductofV
c
(thecentralcompartmentvolume)and
theIncrementalchangeInconcentratIonshouldbeadmInIstered.LIkewIse,when
decreasIngtheconcentratIonthebeststrategyIstoturnofftheInfusIonfortheduratIon
predIctedbytheapplIcablecontextsensItIvedecrementtImeandresumetheInfusIonrate
predIctedforthecurrenttImeplusthecontextsensItIvedecrementtIme.ForInstance,If
afterJ0mInutesonewIshestodecreasethetargetplasmapropofolconcentratIonfromJ
g/mLto2g/mL(aJJdecrementatatImecontextofJ0mInutes),onewouldshutoff
theInfusIonfor1mInuteand10secondstolettheconcentratIonfallbyJJandthen
restartat75g/kg/mIn.TheestImatedplasma
P.156
propofolconcentratIonsfromthIsnomogramguIdeddosIngschemeareshownInFIgure7
15.
Figure 7-15.SImulatedplasmapropofolconcentratIonhIstoryresultIngfromthe
InformatIonIntheIsoconcentratIonnomogramInFIgure714andextendIngthetImes
toswItchtheInfusIontothenextlowerIncrementtothemIdpoIntofthesubsequent
tImesegment(I.e.,theswItchfrom250to225g/kg/mInwasat5mInutes,rather
thanat4.5mInutes).NotethatforthefIrstJ0mInutes,thIssequencepredIctsplasma
propofolconcentratIonsthatarealwaysslIghtlyaboveJg/mL(seetext).TheInfusIon
Isstoppedat90mInutesInthIscase.
Context-Sensitive Decrement Times
0urInganInfusIon,drugIstakenupbytheInert,perIpheraltIssues.
18
DncedrugdelIveryIs
termInated,recoveryoccurswhentheeffectsIteconcentratIondecreasesbelowa
thresholdconcentratIonforproducIngapharmacologIceffect(e.g.,|AC
AWAKE
the
concentratIonwhere50ofpatIentsfollowcommands).
56,65
Althoughtherateof
elImInatIonofthedrugfromthebodycangIvesomeIndIcatIonforthetImerequIredto
reachasubtherapeutIceffectsItedrugconcentratIon,dIstrIbutIontoandfromthe
perIpheraltIssuesalsocontrIbutestothetImecourseofdecreasIngdrugconcentratIonsof
thecentralandtheeffectsIte.FordrugswIthmultIcompartmentalkInetIcs,the
elImInatIonhalflIfewIllalwaysoverestImatethetImetorecoveryfromanesthetIcdrugs.
ThIsIsbestunderstoodbyconsIderIngthelImItIngcondItIonofsteadystate.WIthasteady
stateInfusIontheamountofdrugbeIngInfusedIntothecentralcompartmentexactly
matchestheamountofdrugbeIngremovedbytheelImInatIngorgans,andthereIsnonet
transferbetweentIssuecompartmentsandplasma(central)astheIrdrugconcentratIons
areInequIlIbrIum.WhentheInfusIonstops,theelImInatIonclearancerapIdlydecreases
onlythecentralcompartmentdrugconcentratIonsonwhIchItIsoperatIng.The
compartmentsthusbecomedIsequIlIbratedanddrugreturnsfromthetIssuestothe
plasmacompartmentInamountsdetermInedbythedIstrIbutIonclearances,the
concentratIongradIents,andthesIzeoftheperIpheralcompartmentdepots.ThIsreturnof
drugfromthetIssuewIllgraduallyslowtherateofdecreaseInplasmadrugconcentratIon
untIlpseudoequIlIbrIumIsreachedandtheprocesscanthenproceedattherateofthe
elImInatIonhalflIfe.FordrugswIthlargeelImInatIonclearancesrelatIvetotheperIpheral
drugdepotsIze,thetImetoreachaconcentratIonhalfthesteadystateconcentratIon(or
halftIme)wIllbemuchshorterthantheelImInatIonhalflIfe.PropofolfItsthIscategory
wIthanInItIalhalftImeofJ0mInutesascomparedwIthItshalflIfeof6hoursevenafter
anInfInItelylongInfusIon.ForInfusIonsofshorterduratIonthanInfInItythetIssuedepots
wIllcontrIbutedrugbacktotheplasmatoalesserdegree,dependIngonhowlongthe
InfusIonhadrun,thatIs,howclosetoequIlIbratIonwIththecentralcompartmentthey
were,andthehalftImeswIllgetprogressIvelyshorteruntIlthecondItIonofanInfInItely
shortInfusIon(bolusdose)Isreached.
20
Therefore,thecontrIbutIonofredIstrIbutIontothe
rateofdecayoftheplasmaconcentratIondependsontheduratIonofInfusIonofadrug.
NotethathereredIstrIbutIondescrIbesthedrugreturnIngfromalltIssuecompartments,
notjustfromthebraIn,IntoplasmaasopposedtotheprevIoususagethatdescrIbed
redIstrIbutIonofdrugfrombraIntobloodandIntoInerttIssues.
TocharacterIzethecontrIbutIonofredIstrIbutIontothetImerequIredtoreacha
subtherapeutIcdrugconcentratIon,theduratIonofInfusIonmustbetakenIntoaccount.
|ultIcompartmentpharmacokInetIcmodelsofanesthetIcdrugscanbeusedtosImulatethe
tImerequIredforadecreaseIntheplasmaoreffectsIteconcentratIonbydIfferent
percentagesaftertermInatIngInfusIonsofvarIousduratIons.
20
ThetImerequIredforthe
drugconcentratIonoftheplasmatodecreaseby50IncreasesastheduratIonofInfusIon
Increases.DncethetIssuedrugconcentratIonsarecompletelyequIlIbratedwIththe
plasma,redIstrIbutIonplaysaneglIgIbleroleIndecreasIngtheplasmaconcentratIon,and
thetImerequIredfora50dropInplasmaconcentratIonIsequaltotheelImInatIonhalf
lIfe.Thecontext-sensitive half-timeIsdefInedasthetImerequIredforthedrug
concentratIonoftheplasmatodecreaseby50,wherethecontextIstheduratIonofthe
InfusIon.
51
ThecontextsensItIvehalftImeforthecommonsynthetIcopIoIdsfentanyl,
alfentanIl,sufentanIl,andremIfentanIlIsIllustratedInFIgure716.
Althougha50decreaseInplasmaconcentratIonIsanappealIngandcomprehensIble
parameter,largerorsmallerdecreasesInplasmaconcentratIonsmayberequIredfor
recoveryfromthedrug.SImulatIonsshowthatthetImefordIfferentpercentdecreasesIn
plasmaconcentratIonIsnotlInear.
10,20
Therefore,Ifa25or75decreaseInplasma
concentratIonIsrequIred,sImulatIonsmustbeperformedtocalculatethecontext
sensItIve25decrementtImeorcontextsensItIve75decrementtIme(FIg.717).n
addItIon,IftheconcentratIonofInterestIstheeffectsIteconcentratIonratherthanthe
plasmaconcentratIon,sImulatIonscanbeperformedtocalculatethecontextsensItIve
effectsItedecrementtIme.FInally,IfaconstantplasmaoreffectsIteconcentratIonIsnot
maIntaInedthroughoutthedelIveryofthedrug(whIchIstypIcallythecasewIthmanual
bolusandInfusIonschemesandalsowIthvaryIngdrugrequIrementsdependIngonsurgIcal
stImulatIonandsoforth),thecontextsensItIvedecrementtImesareguIdelInesofrecovery
ratherthananabsolutepredIctIonofthe
P.157
decayIndrugconcentratIon.fprecIsedrugadmInIstratIondataareknown,ItIspossIbleto
computethecontextsensItIvedecrementtImefortheIndIvIdualsItuatIonorcontext.Even
thoughthecontextsensItIvedecrementtImesarelImIted,thIsconcepthaschangedthe
waythatIntravenousanesthetIcsaredescrIbedandhashelpedfosteranIncreaseIn
accuratelyandsafelyadmInIsterIngIntravenousanesthetIcs.
Figure 7-16.ThecontextsensItIveplasmahalftImeforfentanyl,alfentanIl,
sufentanIl,andremIfentanIl.
Figure 7-17.ThecontextsensItIve25,50,and75plasmadecrementtImesfor
fentanyl(A),alfentanIl(B),sufentanIl(C),andremIfentanIl(D).
Target-Controlled Infusions
PrIortoperformInganadmInIsterIng,ItIspossIbletoperformthecalculatIonspresented
hereandderIvea8ETschemetargetedtoapredetermInedplasmaoreffectsIte
concentratIon.However,IntheoperatIngroom,oncetheanesthetIchascommenced,
wIthoutthehelpofacomputer,software,andpossIblyanassIstant,ItIslaborIousand
dIffIculttomakeanycalculatIonstodetermInehowtoadjusttheInfusIonorhowtobolus
(orstoptheInfusIon)toIncreaseordecreasethetargetplasmaconcentratIon.
70
8ylInkIng
acomputerwIththeapproprIatepharmacokInetIcmodeltoanInfusIonpump,ItIspossIble
forthephysIcIantoenterthedesIredtargetplasmaconcentratIonofadrugandforthe
computertonearlyInstantaneouslycalculatetheapproprIateInfusIonschemetoachIeve
thIstargetInamatterofseconds.
71
8ecausedrugaccumulatesatvarIousratesamongthe
varIoustIssuesandorgansInthebody,thecomputercontInuallycalculatesthecurrent
drugconcentratIonandadjuststheInfusIonpumpInordertoaccountforthecurrentstatus
ofdruguptake,dIstrIbutIon,andelImInatIon.Therefore,thecomputerdrIven8ETscheme
canInfactcontroltheInfusIonpumpInordertoachIeveasteadytargetconcentratIon
(FIg.718).
ThesuccessofthIsapproachIsInfluencedbytheextenttowhIchthedrugpharmacokInetIc
andpharmacodynamIcparametersprogrammedIntothecomputermatchthoseofthe
partIcularpatIentathand.WhIlethIssamelImItatIonapplIestothemorerudImentary
(nontargetcontrolledInfusIons[TCs])dosIngdoneroutInelyIneveryclInIcalsettIng,we
mustexamInethespecIalramIfIcatIonsofpharmacokInetIcpharmacodynamIcmodel
mIsspecIfIcatIonwIthTCInanydIscussIonofItsfutureImportanceIntheclInIcalsettIng.
ThemathematIcalprIncIplesgovernIngTCareactuallyquItesImple.Foracomputer
controlpumptoproduceandmaIntaInaplasmadrugconcentratIonItmustfIrstadmInIster
adoseequaltotheproductofthecentralcompartment,V
1,
andthetargetconcentratIon
(FIg.719).Thenforeachmomentafterthat,theamountofdrugtobeadmInIsteredInto
thecentralcompartmenttomaIntaInthetargetconcentratIonIsequaltodrugelImInated
fromthecentralcompartmentplusdrugdIstrIbutedfromthecentralcompartmentto
perIpheralcompartmentsminusdrugreturnIngtothecentralcompartment
P.158
fromperIpheralcompartments.ThesoftwarekeepstrackoftheestImateddrugIneach
compartmentovertImeandapplIestherateconstantsforIntercompartmentaldrug
transferfromthepharmacokInetIcmodeltotheseamountstodetermInedrugmovement
atanygIventIme.tthenmatchestheestImatedconcentratIonstothetarget
concentratIonatanytImetodetermInetheamountofdrugthatshouldbeInfused.The
softwarecanalsopredIctfutureconcentratIons,usuallywIththeassumptIonthatthe
InfusIonwIllbestoppedsothatemergencefromanesthesIaorthedIssIpatIonofdrugeffect
wIlloccuroptImallyaccordIngtothecontextsensItIvedecrementtIme.
Figure 7-18.ThIsIsasImulatIonofatargetcontrolledInfusIonInwhIchtheplasma
concentratIonIstargetedat5g/mL.Thesolid linerepresentsthepredIctedplasma
propofolconcentratIonof5g/mL,whIchIntheoryIsattaInedattImet=0andIsthen
maIntaInedbyavarIablerateInfusIon.Thedashed lineIsthepredIctedeffectsIte
concentratIonunderthecondItIonsofaconstantpseudosteadystateplasma
concentratIon.Notethat95ofthetargetconcentratIonIsreachedIntheeffectsIte
atapproxImately4mInutes.
8ecausethereIsadelayorhysteresIsbetweentheattaInmentofadrugconcentratIonIn
theplasmaandtheproductIonofadrugeffect,ItIsadvantageoustohavethe
mathematIcsofthIsdelayIncorporatedIntoTC.8yaddIngthekInetIcsoftheeffectsIteIt
IspossIbletotargeteffectsIteconcentratIonsaswouldbeInkeepIngwIththeprIncIpleof
workIngascloselytotherelevantconcentratIoneffectrelatIonshIpaspossIble.Adose
schemethattargetsconcentratIonsInacompartmentremotefromthecentral
compartment(I.e.,theeffectsIte)hasnoclosedformsolutIonforcalculatIngtheInfusIon
rate(s)needed.nstead,thesolutIonIssolvednumerIcallyandInvolvessomeaddItIonal
conceptsthatmustbeconsIdered,namelythetImetopeakeffect,T
|AX
,andthevolumeof
dIstrIbutIonatpeakeffect,V
DPE
.ThesearedIscussedlater.nprIncIple,targetIngthe
effectsItenecessItatesproducInganovershootInplasmadrugconcentratIonsdurIng
InductIonandforsubsequenttargetIncreases.ThIsIssImIlarInconcepttooverpressurIzIng
InhaledanesthetIcconcentratIonstoachIeveatargetedendtIdalconcentratIon.However,
unlIketheInspIratorylImbofananesthesIacIrcuIt,theplasmacompartmentseemstobe
closelylInkedtocardIovasculareffects,andlargeovershootsInplasmadrugconcentratIon
mayproduceunwantedsIdeeffects.
Figure 7-19.ThIsIsasImulatIonofatargetcontrolledInfusIonInwhIchtheeffectsIte
concentratIon(C
e
)Istargetedat5g/mL.Thesolid linerepresentsthepredIcted
plasmapropofolconcentratIon(C
p
)thatresultsfromabolusdose,gIvenattImet=0,
thatIspredIctedtopurposelyovershoottheplasmapropofolconcentratIontargetuntIl
tImet=T
|AX
(1.6mInutes).AtT
|AX
pseudoequIlIbratIonbetweentheeffectsIteand
theplasmaoccursandbothconcentratIonsarethenpredIctedtobethesameuntIlthe
targetIschanged.NotethattheeffectsIteattaInsthetargetInlessthanhalfthetIme
wItheffectsItetargetIngcomparedtotheplasmaconcentratIontargetIngseenIn
FIgure718.
TheperformanceofTCIsInfluencedbythepharmacokInetIcmodelchosen.Althoughmost
modernTCmodels,whethertheytargettheplasmaortheeffectsIte,seemtobesImIlar
Inperformance:theyallproduceovershootfor10to20mInuteswhenIncreasIngthetarget
concentratIon.
J6
ThIsIsbecausethedoseadjustmentsmadearebasedoncalculatIonsthat
useacentralcompartmentthatIgnoresthecomplexItyofIntravascularmIxIng,thereby
overestImatIngthecentralcompartment'struevolume(V
C
)andoverestImatIngtherateof
transfertothefastperIpheraltIssue(Cl
F
)andthesIzeoftheperIpheraltIssue
compartment(V
F
)(FIg.720).TheperformanceofTCIsalsoInfluencedbythevarIance
betweenpharmacokInetIcparametersdetermInedfromgrouporpopulatIonstudIesandthe
IndIvIdualpatIent.|edIan
P.159
absoluteperformanceerrorsforfentanyl,
72
alfentanIl,
7J
sufentanIl,
74
mIdazolam,
75,76
and
propofol
76,77
areIntherangeofJ0whenlIteraturevaluesforpharmacokInetIc
parametersareusedtodrIvetheTCdevIceandfalltoapproxImately7whenthe
averagekInetIcsofthetestsubjectsthemselvesareused.
7J
0Ivergence(thepercentage
changeoftheabsoluteperformanceerror)IsgenerallyquItelow(approxImately1)when
targetconcentratIonsremaInrelatIvelystable,butIncreasetonearly20whenthe
frequencyofconcentratIonstepsIsasfrequentasevery12mInutes.
J6,77
Thesedata
suggestthatwhIleaconsIderableerrormayexIst(J0)betweenthetargeteddrug
concentratIonandtheoneactuallyachIevedInapatIent,theconcentratIonattaInedwIll
notvarymuchovertIme.Thus,IncrementaladjustmentsInthetargetshouldresultIn
IncrementalandstablenewconcentratIonsInthepatIentaslongastheIncremental
adjustmentsarenottoofrequent.
Figure 7-20.TheInfluenceofthemIsspecIfIcatIonofeachofthecomponentsofthe
tradItIonalthreecompartmentpharmacokInetIcmodelsontheprolongeddIscrepancy
(overshoot)betweenpredIctedandtargetedconcentratIonswIthtargetcontrolled
InfusIons(TCs).TheerrorresultIngfromelImInatIonclearancewasneglIgIbleand
thereforenotIllustrated.NotIcethattheloadIngdose(basedonV
C
)producesalarge
amountoferrorIntheInItIalmInutes;however,from1to20mInutes,thedevIatIon
fromthetargetconcentratIonIslargelyduetotheoverestImatIonofCl
F
.The
equatIonslIstedarefortherespectIve8ETInfusIonsoftheTCsystem.Seetextfor
descrIptIonof8ET.(FromAvram|J,KrejcIeTC:UsIngfrontendkInetIcstooptImIze
targetcontrolleddrugInfusIons.AnesthesIology200J;99:1078.)
TheIntroductIonoftheconceptofTCswasfIrstdescrIbedbySchwIldenetal.Inearly
1980s.DthersoftwaresystemsweredevelopedInNorthAmerIcabygroupsatStanford
UnIversItyand0ukeUnIversIty.8ythelate1990sacommercIallyavaIlableTCsystemfor
propofol(0IprIfusor)wasIntroduced.ThIsgreatlyIncreasedbothanesthesIologIsts'Interest
InthIsmodeofdelIveryandtheIrunderstandIngoftheconcentratIoneffectrelatIonshIps
forhypnotIcsandopIoIds.nmostoftheworld,devIcesfordelIverIngpropofolbyTCare
commercIallyavaIlablefromatleastthreecompanIes(Craseby,AlarIs,andFresenIus)wIth
sImIlarperformanceparameters.
78
ntheUnItedStates,therearestIllnoF0Aapproved
devIces.ForInvestIgatIonalpurposes,STANPU|P
c
(developedbySteveShaferatStanford
UnIversIty)canbeInterfacedvIaanFS2J2porttoanInfusIonpump.STANPU|Pcurrently
provIdespharmacokInetIcparametersfor19dIfferentdrugs,buthastheabIlItytoaccept
anykInetIcmodelforanydrugprovIdedbytheuser.FUCLDDP
d
IsTCsoftware(developed
by|IchelStruysofChentUnIversIty),whIchIssImIlartoSTANPU|PbutoperatesIn
WIndowsratherthan0DSandIscapableofcontrollIngmultIpledrugInfusIons
sImultaneously.
AlthoughthepharmacologIcprIncIpleofrelatIngaconcentratIonratherthanadoseIs
scIentIfIcallysound,fewstudIeshaveactuallyattemptedtodetermInewhetherTC
ImprovesclInIcalperformanceoroutcome.DnlyafewlImItedstudIeshaveactually
comparedmanualInfusIoncontrolversusTC.Somehaveshownbettercontrolandamore
predIctableemergencewIthTC,
78,79
whereasothershavesImplyshownnoadvantage.
80,81
TCprIncIplescontInuetobedevelopedbeyondthescopeofIntravenousanesthesIa
technIques.TChasbeenusedtoprovIdepostoperatIveanalgesIawIthalfentanIl.
82,8J
n
thIssystem,adesIredtargetplasmaalfentanIlconcentratIonwassetIntherangeof40to
100ng/mL.AdemandbythepatIentautomatIcallyIncreasedthetargetlevelby5ng/mL.
Lackofademandcausedthesystemtograduallyreducethetargetedlevel.ThequalItyof
analgesIawasjudgedtobesuperIortostandardmorphInepatIentcontrolledanalgesIa.
SImIlarly,TChasbeenusedtoprovIdepatIentcontrolledsedatIonwIthpropofol.
84,85
The
TCwassetto1g/mLandademandbythepatIentIncreasedthelevelby0.2g/mL.As
wIththeTCanalgesIasystem,thelackofademandcausedthesystemtograduallyreduce
thetargetedplasmapropofolconcentratIon.ThetImIngandIncrementofthedecrease
wereadjustedbytheclInIcIan.Dver90ofpatIentsweresatIsfIedwIththIsmethodof
sedatIon.
Time to Maximum Effect Compartment Concentration
EarlIerInthIschapter,thedelaybetweenattaInIngaplasmaconcentratIonandaneffect
sIteconcentratIonwasdescrIbed(FIg.711).ThIsdelay,orhysteresIs,Ispresumedtobea
resultoftransferofdrugbetweentheplasmacompartment,V
C
,andaneffect
compartment,V
e
,aswellasthetImerequIredforacellularresponse.8ysImultaneously
modelIngtheplasmadrugconcentratIonversustImedata(pharmacokInetIcs)andthe
measureddrugeffect(pharmacodynamIcs),anestImateofthedrugtransferrateconstant,
k
e0
,betweenplasmaandtheputatIveeffectsItecanbeestImated.
47
However,estImates
ofk
e0
,lIkeallrateconstants,aremodelspecIfIc.
86,87
ThatIs,k
e0
cannotbetransported
fromonesetofkInetIcparametersdetermInedInonespecIfIcpharmacokInetIc
pharmacodynamIcstudytoanyanothersetofpharmacokInetIcparameters.LIkewIse,ItIs
notvalIdtocompareestImatesofk
e0
amongstudIesofthesamedrugoracrossdIfferent
drugs;therefore,oneshouldnotbesurprIsedthatreportedvaluesfork
e0
forthesamedrug
varymarkedlyamongstudIes.ThemodelIndependentparameterthatcharacterIzesthe
delaybetweentheplasmaandeffectsIteIsthetImetomaxImaleffect,orT
|AX.
87
AccordIngly,IftheT
|AX
andthepharmacokInetIcsforadrugareknownfromIndependent
studIes,ak
e0
canbeestImatedbynumerIctechnIquesfortheIndependentkInetIcsetthat
wouldproducetheknowneffectsIteT
|AX
.
Theconceptofatransportable,modelIndependentparameterthatcharacterIzesthe
kInetIcsoftheeffectsIteIsImportantforrobusteffectsItetargeted,computercontrolled
InfusIons.ThIsIsbecausetherearemanymorepharmacokInetIcstudIescharacterIzInga
wIdervarIetyofpatIenttypesandgroupsInthelIteraturethantherearecomplete
pharmacokInetIcpharmacodynamIcstudIes.8ymakIngthegenerallyvalIdassumptIonthat
IntraIndIvIdualdIfferencesaresmallInadrug'srateofeffectsIteequIlIbratIon,ItIs
possIblewIthaknownT
|AX
toestImateeffectsItekInetIcsforadrugacrossawIdevarIety
ofpatIentgroupsInwhIchonlythepharmacokInetIcsareknown.ThIscannotbedoneIna
valIdmannerusIngk
e0
ort
1/2ke0
alone.
86,87
Volume of Distribution at Peak Effect
AlthoughtheplasmaconcentratIoncanbebroughtrapIdlytothetargeteddrug
concentratIonbyadmInIsterIngabolusdosetothecentralcompartment(CV
C
)andthen
heldtherebyacomputercontrolledInfusIon(FIg.718),thetImefortheeffectsIteto
reachthetargetconcentratIonwIllbemuchlongerthanT
|AX
(4mInutesforpropofol
effectsIteconcentratIontoreach95ofthattargeted).tIspossIbletocalculateabolus
dosethatwIllattaIntheestImatedeffectsIteconcentratIonatT
|AX
wIthoutovershootIn
theeffectsIte.However,plasmadrugconcentratIonwIllovershoot(FIg.719).ThIsIsdone
bycombInIngtheconceptofdescrIbIngdrugdIstrIbutIonasanexpandIngvolumeof
dIstrIbutIonthatstartsatV
C
andapproachesV
(theapparentvolumeofdIstrIbutIondurIng
theelImInatIonphase)overtImewIththeconceptofT
|AX
.
88,89
7olumeofdIstrIbutIonovertImeIscalculatedbydIvIdIngthetotalamountofdrug
remaInIngInthebodybytheplasmadrugconcentratIonateachtIme,t.ThetIme
dependentvolumeatthetImeofpeakeffect(orT
|AX
)IsV
DPE
.Theproduct
P.160
ofthetargetedeffectsIteconcentratIonandV
DPE
plustheamountlosttoelImInatIonIn
thetImetoT
|AX
becomestheproperbolusdosethatwIllattaInthetargetconcentratIonat
theeffectsIteasrapIdlyaspossIblewIthoutovershoot.npractIcaltermsthIsbolusIs
gIvenattImet=0,afterwhIchtheInfusIonstopsuntIltImet=T
MAX
.tthenresumes
InfusIngdrugInItsnormalstoplossmanner.
SomesoftwareprogramsforcontrollIngtargetcontrolledInfusIonsIncludethIsconceptIn
theIralgorIthms.nthecaseofthepropofolkInetIcsusedtoconstructtheIsoconcentratIon
nomogramInFIgure714,thepharmacokInetIcpharmacodynamIcparametersetof
SchnIderetal.,
49
predIctsaT
MAX
of1.6mInutes,aV
DPE
of16.62L,andanelImInatIonloss
of2J.8ofthedoseover1.6mInutesIna70kgman.Thus,theproperpropofolbolusfora
targetedeffectsItepropofolconcentratIonof5g/mLIs109mg.Thecomputercontrolled
InfusIonpumpwIlldelIverthIsdoseasrapIdlyaspossIbleandthenbegInatargeted
InfusIonfor5g/mLatt=1.6mInutes(seeFIg.719).
Front-End Pharmacokinetics
Thetermfront-end pharmacokineticsreferstotheIntravascularmIxIng,pulmonaryuptake,
andrecIrculatIoneventsthatoccurInthefIrstfewmInutesdurIngandafterIntravenous
drugadmInIstratIon.
J9
ThesekInetIceventsandthedrugconcentratIonversustImeprofIle
thatresultsareImportantbecausethepeakeffectofrapIdlyactIngdrugsoccursdurIngthIs
temporalwIndow.
17,90,91,92,9J
AlthoughIthasbeensuggestedthatfrontend
pharmacokInetIcsbeusedtoguIdedrugdosIng,
J6
currentTCdoesnotIncorporatefront
endkInetIcsIntothemodelsfromwhIchdrugInfusIonratesarecalculated.AsprevIously
descrIbed,notdoIngsoIntroducesfurthererror.
TCrelIesonpharmacokInetIcmodelsthatarebasedonthesImplIfyIngassumptIonof
InstantaneousandcompletemIxIngwIthInV
C
.However,thedetermInatIonofV
C
Is
routInelyoverestImatedInmostpharmacokInetIcstudIes.DverestImatIonofV
C
,whenused
tocalculateTCInfusIonrates,resultsInplasmadrugconcentratIonsthatovershootthe
desIredtargetconcentratIon,especIallyInthefIrstfewmInutesafterbegInnIngTC.
Furthermore,correctdescrIptIonofdrugdIstrIbutIontotIssuesdependsonanaccurateV
C
estImate,soInaccuracIescausedbynottakIngfrontendpharmacokInetIcsIntoaccount
maybepersIstentandresultInundershootaswellasovershoot.SImulatIonIndIcatesthat
pharmacokInetIcparametersderIvedfromstudIesInwhIchthedrugIsadmInIsteredbya
short(approxImately2mInutes)InfusIonbetterestImateV
C
andtIssuedIstrIbutIonkInetIcs
thanthosefromarapIdIntravenousbolusInfusIon.
J6,J7
Whenthelatterdrug
admInIstratIonmethodIsused,fullcharacterIzatIonofthefrontendrecIrculatory
pharmacokInetIcsIsrequIredtoobtaInvalIdestImatesofVforuseInTC.
J6,J7
Closed-Loop Infusions
WhenavalId,andnearlycontInuous,measureofdrugeffectIsavaIlable,drugdelIverycan
beautomatIcallytItratedbyfeedbackcontrol.Suchsystemshavebeenused
experImentallyforcontrolofbloodpressure,
94
oxygendelIvery,
95
bloodglucose,
96
neuromuscularblockade,
97
anddepthofanesthesIa.
98,99,100,101,102,10J,104
Atargetvaluefor
thedesIredeffectmeasure(theoutputofthesystem)Isselectedandtherateofdrug
delIvery(theInputIntothesystem)dependsonwhethertheeffectmeasureIsabove,
below,oratthetargetvalue.Thus,theoutputfeedsbackandcontrolstheInput.Standard
controllers(referredtoasproportional-integral-derivative[orP0]controllers)adjustdrug
delIverybasedonboththeIntegral,ormagnItude,ofthedevIatIonfromtargetandthe
rateofdevIatIon,orthederIvatIve.
Underarangeofresponses,standardP0controllersworkquItewell.However,theyhave
beenshowntodevelopunstablecharacterIstIcsInsItuatIonsInwhIchtheoutputmayvary
rapIdlyandwIdely.SchwIldenetal.
105
haveproposedacontrollerInwhIchtheoutput
(measuredresponse)controlsnotonlytheInput(drugInfusIonrate),butalsothe
pharmacokInetIcmodeldrIvIngtheInfusIonrate.ThIsIsasocalledmodel-drivenor
adaptiveclosedloopsystem.SuchasystemhasperformedwellInclInIcaltrIals,
99
andIna
sImulatIonofextremecondItIonsItwasdemonstratedtooutperformastandardP0
controller.
102
ClosedloopsystemsforanesthesIaarethemostdIffIculttodesIgnandImplementbecause
theprecIsedefInItIonofanesthesIaremaInselusIve,asdoesarobustmonItorfor
anesthetIcdepth.
65
8ecausemodIfIcatIonofconscIousnessmustaccompanyanesthesIa,
processedelectroencephalographIcparametersthatcorrelatewIthlevelofconscIousness,
suchasthebIspectralIndex,electroencephalographIcentropy,andaudItoryevoked
potentIals,makeItpossIbletoundertakeclosedloopcontrolofanesthesIa.ThereIskeen
InterestInfurtherdevelopIngthesetoolstomakethemmorerelIablebecauseadvancesIn
pharmacokInetIcmodelIng,IncludIngtheeffectcompartment,theImplementatIonofsuch
modelsIntodrugdelIverysystems,andthecreatIonofadaptIvecontrollersbasedonthese
models,havemaderoutIneclosedloopdelIveryofanesthesIaImagInable.
98
SofarIthas
beendIffIculttobrIngatrueclosedloopsystemtomarketInmedIcalapplIcatIonsbecause
oftheregulatoryagencyhurdles.FromaregulatorypoIntofvIew,anopenloopTCsystem
IsmucheasIertoattaInandoffersmanyofthebenefItsofactualclosedloopsystems.
UnlessthereIsaregulatoryoradesIgnbreakthrough,closedloopsystemsforanesthesIa
wIlllIkelyremaInInthetheoretIcalandexperImentalrealms.
Response Surface Models of Drug-Drug Interactions
0urIngthecourseofanoperatIon,thelevelofanesthetIcdrugadmInIsteredIsadjustedto
ensureamnesIatoongoIngevents,provIdeImmobIlItytonoxIousstImulatIon,andblunt
thesympathetIcresponsetonoxIousstImulatIon.AlthoughItIspossIbletoachIevean
adequateanesthetIcstatewIthahIghdoseofasedatIvehypnotIcalone(I.e.,avolatIle
anesthetIcorpropofol),theeffectsItedrugconcentratIonnecessaryIsoftenassocIated
wIthexcessIvehemodynamIcdepressIon
58
andexcessIvelydeepplaneofhypnosIsthatmay
beassocIatedwIthlongstandIngmorbIdItyormortalIty.
106,107
Therefore,tolImItsIde
effects,anopIoIdandasedatIvehypnotIcareadmInIsteredtogether.Althoughthe
admInIstratIonoftwovolatIleanesthetIcsoravolatIleanesthetIcandpropofolproducea
netaddItIveeffect,thecombInatIonofanopIoIdandasedatIvehypnotIcaresynergIstIc
formostpharmacologIceffects.8yunderstandIngtheInteractIonsbetweentheopIoIdsand
thesedatIvehypnotIcs,ItIspossIbletoselecttargetconcentratIonpaIrsofthetwodrugs
thatproducethedesIredclInIcaleffectwhIlemInImIzIngunwantedsIdeeffectsassocIated
wIthhIghconcentratIonsofasIngledrug(e.g.,hemodynamIcInstabIlIty,prolonged
respIratorydepressIon).
StudIesdesIgnedtoevaluatethepharmacodynamIcInteractIonsbetweenanopIoIdanda
sedatIvehypnotIchavetradItIonallyfocusedontheeffectsofaddIngoneortwofIxed
dosesorconcentratIonsoftheopIoIdtoseveraldefInedconcentratIonsordosesofthe
sedatIvehypnotIc.
57,58,108,109,110,111,112,11J,114,115
CraphIcaldemonstratIonofthese
InteractIondataaremostcommonlyperformed
P.161
bydemonstratIngashIftofparalleldoseresponsecurves(FIg.721).AnalternatIve
mathematIcalmodelIstheIsobologramIsoeffectcurvesthatshowdosecombInatIonsthat
resultInequaleffect(FIg.722).sobolographIcanalysIshastheaddItIonalbenefItof
characterIzIngtheInteractIonbetweenthetwodrugsasaddItIve,antagonIstIc,or
synergIstIc(FIg.72J),whereasshIftsofdoseresponsecurvesrequIresmorecomplex
concentratIonstodetermIneIftheInteractIondemonstratedbyaleftwardshIftInthe
curveIsmorethanaddItIve.
Figure 7-21.TheeffectofaddIngremIfentanIlontheconcentratIoneffectcurvefor
sevofluraneInducedanalgesIa(nohemodynamIcresponsetoa5second,50mAtetanIc
stImulatIonInvolunteers).EachcurverepresentstheconcentratIoneffectrelatIonfor
sevofluranewIthafIxedeffectsIteconcentratIonofremIfentanIl.TheleftwardshIftIn
thecurvesIndIcatesthatremIfentanIldecreasestheamountofsevofluraneneededto
produceadequateanalgesIa.ThechangesIntheslopesoftheconcentratIonresponse
curvesIndIcatethatthereIssIgnIfIcantpharmacodynamIcsynergybetween
sevofluraneremIfentanIl.AlsonotethatthereIsaceIlIngeffecttothIs
pharmacodynamIcInteractIonthemagnItudeoftheleftwardshIftdecreasesasthe
remIfentanIlconcentratIonIncreases.HF,heartrate;|AC,mInImumalveolar
concentratIon.(Adaptedfrom|anyamSC,Cupta0K,JohnsonK8,WhIteJL,PaceNL,
Westenskow0F,EganT0:DpIoIdvolatIleanesthetIcsynergy:Aresponsesurfacemodel
wIthremIfentanIlandsevofluraneasprototypes.AnesthesIology2006;105:267.)
AnalternatIvemathematIcalmodelthatcanfullycharacterIzethecompletespectrumof
InteractIonbetweentwodrugsforallpossIblelevelsofconcentratIonandeffectsIsthe
responsesurfacemodel.
61,64
Thesurfacemorphologyofaresponsesurfacenotonly
demonstrateswhethertheInteractIonIsaddItIve,synergIstIc,orantagonIstIc,butthe
modelItselfcanquantItatIvelydescrIbethedegreeofInteractIonbetweenthetwodrugs.
Furthermore,IsobologramscanbederIvedfromtheprojectIonoftheresponsesurfaceonto
theapproprIatehorIzontaleffectplane(FIg.724)andconcentratIonresponsecurvescan
bederIvedfromtakIngavertIcalslIcethrougharesponsesurfaceIntheplane
perpendIculartothefIxedopIoIdconcentratIonofInterest(FIg.724).
61,64,65
Therefore,
responsesurfacemodelscanbevIewedasgeneralIzatIonsofthetradItIonal
pharmacodynamIcmethodsofanalysIs.ThemajorlImItatIonofresponsesurfacemodelsIs
thattheyrequIrealargenumberofpharmacodynamIcmeasurementsacrossallpossIble
concentratIonpaIrcombInatIonstoaccuratelycharacterIzetheentIresurface.
116
ThIsIs
mosteffIcIentlydoneInthelaboratorysettIngusIngvolunteerswhocanbeexposedto
subtherapeutIc(e.g.,belowthelevelthatguaranteesamnesIa)andsupratherapeutIcdrug
concentratIonpaIrs.However,becauseresponsesurfacemodelscharacterIzethedrug
concentratIonpaIrsthatprovIdeadequateanesthesIaandalsoadequaterecoveryfrom
anesthesIa,thesemodelsprovIdeInformatIonthatarenotnormallyavaIlablefromstudIes
thatgenerateanIsobologramfromsurgIcalpatIents.
Figure 7-22.FemIfentanIlsevofluraneInteractIonforsedatIon(dashed line)and
analgesIatoelectrIcaltetanIcstImulatIon(solid line)forvolunteers.TherespectIve
95IsobolesdemonstratethemyrIadoftargetconcentratIonpaIrsofremIfentanIland
sevofluranethathavea95probabIlItyofproducIngthedesIredpharmacodynamIc
endpoInt.(Adaptedfrom|anyamSC,Cupta0K,JohnsonK8,WhIteJL,PaceNL,
Westenskow0F,EganT0:DpIoIdvolatIleanesthetIcsynergy:Aresponsesurfacemodel
wIthremIfentanIlandsevofluraneasprototypes.AnesthesIology2006;105:267.)
sobologramsandresponsesurfacemodelsclearlydemonstratethattherearemultIple
targetconcentratIonpaIrsofanopIoIdandasedatIvehypnotIcthatcanprovIdeadequate
anesthesIaa95probabIlItyofnohemodynamIcresponsetoanoxIousstImulusand95
probabIlItyofclInIcally
P.162
adequatesedatIon.
62,6J,66
CombInIngtheresponsesurfacepharmacodynamIcmodelswIth
pharmacokInetIcmodelsallowscomputersImulatIonstobeperformedtoIdentIfythe
targetconcentratIonpaIroftheopIoIdandthesedatIvehypnotIcthatproducesan
adequateanesthetIcandyetoptImIzesoneormorepharmacodynamIcendpoInts,suchas
thespeedofawakenIngfromanesthesIa,drugInducedrespIratorydepressIon,ordrug
acquIsItIoncosts.
59,6J
ForsevofluraneremIfentanIlanesthetIcs,thesetypesof
pharmacokInetIcpharmacodynamIcsImulatIonsdemonstratethebenefItofmInImIzIngthe
admInIstereddoseofeventhelowsolubIlItyvolatIleanesthetIcsevofluranetonear0.5
|ACtotakeadvantageofthepharmacokInetIceffIcIencyofremIfentanIl,especIallyasthe
duratIonofanesthesIaIncreases(FIg.725andTable76).
6J
Figure 7-23.sobolestodemonstrateaddItIve(solid line),synergIstIc(dashed line),
andantagonIstIc(dotted line)InteractIonsbetween0rugAand0rug8.
Figure 7-24.AresponsesurfacemodelcharacterIzIngtheremIfentanIlsevoflurane
InteractIonforanalgesIatoelectrIcaltetanIcstImulatIon.TheprojectIonofthe
responsesurfaceontothe50probabIlItyhorIzontalplaneresultsInthe50effect
IsobolewhIletheprojectIonoftheresponsesurfaceontothe2.5ng/mLremIfentanIl
effectsIteconcentratIonvertIcalplaneresultsInthesevofluraneconcentratIon
responsecurveunder2.5ng/mLofremIfentanIl.(Adaptedfrom|anyamSC,Cupta0K,
JohnsonK8,WhIteJL,PaceNL,Westenskow0F,EganT0:DpIoIdvolatIleanesthetIc
synergy:AresponsesurfacemodelwIthremIfentanIlandsevofluraneasprototypes.
AnesthesIology2006;105:267.)
Figure 7-25.TheoptImaltargetconcentratIonpaIrsofremIfentanIlandsevoflurane
tomaIntaInadequateanalgesIa(95IsoboleforanalgesIatoelectrIcaltetanIc
stImulatIon)andresultInthemostrapIdemergenceforanesthetIcsofvarIous
duratIons.Forexample,fora2houranesthetIc,targetconcentratIonsof0.9Jvol
sevofluraneand4.9ng/mLremIfentanIlwouldresultIna5.8mInutetImeto
awakenIng.AstheduratIonofanesthesIaIncreases,amInImumsevofluranetarget
concentratIonof0.75volIsreached.(Adaptedfrom|anyamSC,Cupta0K,Johnson
K8,WhIteJL,PaceNL,Westenskow0F,EganT0:DpIoIdvolatIleanesthetIcsynergy:A
responsesurfacemodelwIthremIfentanIlandsevofluraneasprototypes.
Conclusion
SInceWorldWar,wehavemovedfromcharacterIzIngallanesthetIcsbyadoseresponse
relatIonshIptodevelopIngsophIstIcatedmodelstocharacterIzethesynergIstIcInteractIon
betweensedatIvehypnotIcsandopIoIdsandhavIngthephysIcaldevIcesandthecomputer
supporttoaccuratelyadmInIsterdrugstoachIevethedesIredconcentratIonsattheeffect
sIteofdrugactIon.TheratIonalselectIonofdrugtargetconcentratIonsrequIredto
achIeveadequateanesthesIaandmInImIzesIdeeffects(e.g.,prolongedawakenIng,
hemodynamIcdepressIon)andthemethodsbywhIchtoeffIcIentlyachIevethose
concentratIontargetswIthmInImalovershootrequIresasolIdunderstandIngoftheclInIcal
pharmacologyofanesthetIcs.AsnewdrugsentertheanesthetIcarmamentarIum,careful
characterIzatIonoftheIrpharmacokInetIcandpharmacodynamIcpropertIeswIllallow
themtobesafelyandapproprIatelyusedaspartofabalancedanesthetIc.
65
Table 7-6 Optimal Target Concentration Pairs of Sevoflurane and
Remifentanil for Anesthetics 30 to 900 Minutes in Duration
DURATION OF
ANESTHETIC (hr)
SHORTEST
RECOVERY TIME
(min)
REMIFENTANIL
C
e
(ng/mL)
REMIFENTANIL INFUSION
RATE (/kg/min)
SEVOFLURANE
ET (vol%)
0.5 4.5 4.1 0.15 1.1
1 5.0 4.J 0.16 1.05
2 5.8 4.9 0.18 0.9J
4 6.7 5.2 0.19 0.88
724 7.27.7 6.1 0.22 0.75
P.16J
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Stock, M. Christine
TableofContentsSectIonScIentIfIcFoundatIonsofAnesthesIaChapter8ElectrIcalandFIreSafety
Chapter8
Electrical and Fire Safety
Jan Ehrenwerth
Harry A. Seifert
Key Points
1. A basic principle of electricity is known as Ohm's law (Voltage =
Current Resistance).
2. To have the completed circuit necessary for current flow, a closed
loop must exist and a voltage source must drive the current through
the impedance.
3. To receive a shock, one must contact the electrical circuit at two
points, and there must be a voltage source that causes the current to
flow through an individual.
4. In electrical terminology, grounding is applied to two separate
concepts: the grounding of electrical power and the grounding of
electrical equipment.
5. To provide an extra measure of safety from gross electrical shock
(macroshock), the power supplied to most operating rooms (ORs) is
ungrounded.
6. The line isolation monitor is a device that continuously monitors the
integrity of an isolated power system.
7. The ground fault circuit interrupter is a popular device used to
prevent individuals from receiving an electrical shock in a grounded
power system.
8. An electrically susceptible patient (i.e., one who has a direct, external
connection to the heart) they may be at risk from very small
currents; this is called microshock.
9. Problems can arise if the electrosurgical return plate is improperly
applied to the patient or if the cord connecting the return plate to the
electrosurgical unit (ESU) is damaged or broken.
10. Fires in the OR are just as much a danger today as they were 100
years ago when patients were anesthetized with flammable
anesthetic agents.
11. The necessary components for a fire consist of the triad of heat or an
ignition source, a fuel, and an oxidizer.
12. The two major ignition sources for OR fires are the ESU and the
laser.
13. It is known that desiccated carbon dioxide absorbent can, in rare
circumstances, react with sevoflurane to produce a fire.
14. All OR personnel should be familiar with the location and operation of
the fire extinguishers.
ThemyrIadofelectrIcalandelectronIcdevIcesInthemodernoperatIngroom(DF)greatly
ImprovepatIentcareandsafety.However,thesedevIcesalsosubjectboththepatIentand
DFpersonneltoIncreasedrIsks.ToreducetherIskofelectrIcalshock,mostDFshave
electrIcalsystemsthatIncorporatespecIalsafetyfeatures.tIsIncumbentuponthe
anesthesIologIsttohaveathoroughunderstandIngofthebasIcprIncIplesofelectrIcItyand
anapprecIatIonoftheconceptsofelectrIcalsafetyapplIcabletotheDFenvIronment.
Principles of Electricity
AbasIcprIncIpleofelectrIcItyIsknownasOhm's law,whIchIsrepresentedbytheequatIon:
E=IR
whereEIselectromotIveforce(Involts),IIscurrent(Inamperes),andRIsresIstance(In
ohms).Dhm'slawformsthebasIsforthephysIologIcequatIon8P=CDS7F;thatIs,blood
pressure(8P)IsequaltothecardIacoutput(CD)tImesthesystemIcvascularresIstance
(S7F).nthIscase,thebloodpressureofthevascularsystemIsanalogoustovoltage,the
cardIacoutputtocurrent,andthesystemIcvascularresIstancetotheforcesopposIngthe
flowofelectrons.ElectrIcalpowerIsmeasuredInwatts.Wattage(W)Istheproductofthe
voltage(E)andthecurrent(I),asdefInedbytheformula:
W=EI
TheamountofelectrIcalworkdoneIsmeasuredInwattsmultIplIedbyaunItoftIme.The
wattsecond(ajoule,J)IsacommondesIgnatIonforelectrIcalenergyexpendedIndoIng
work.TheenergyproducedbyadefIbrIllatorIsmeasuredInwattseconds(orjoules).The
kIlowatthourIsusedbyelectrIcalutIlItycompanIestomeasurelargerquantItIesof
electrIcalenergy.
P.166
WattagecanbethoughtofasameasurenotonlyofworkdonebutalsoofheatproducedIn
anyelectrIcalcIrcuIt.SubstItutIngDhm'slawIntheformula:
W=EI
W=(IR)I
W=I
2
R
Thus,wattageIsequaltothesquareofthecurrentI
2
(amperage)tImestheresIstanceR.
UsIngtheseformulas,ItIspossIbletocalculatethenumberofamperesandtheresIstance
ofagIvendevIceIfthewattageandthevoltageareknown.Forexample,a60wattlIght
bulboperatIngonahousehold120voltcIrcuItwouldrequIre0.5ampereofcurrentfor
operatIon.FearrangIngtheformulasothat:
I=W/E
wehave:
I=(60watts)/(120volts)
I=0.5ampere
UsIngthIsInDhm'slaw:
R=E/I
theresIstancecanbecalculatedtobe240ohms:
R=(120volts)/(0.5ampere)
R=240ohms
tIsobvIousfromtheprevIousdIscussIonthat1voltofelectromotIveforce(E|F)flowIng
througha1ohmresIstancewIllgenerate1ampereofcurrent.SImIlarly,1ampereof
currentInducedby1voltofelectromotIveforcewIllgenerate1wattofpower.
Direct and Alternating Currents
AnysubstancethatpermItstheflowofelectronsIscalledaconductor.CurrentIs
characterIzedbyelectronsflowIngthroughaconductor.ftheelectronflowIsalwaysIn
thesamedIrectIon,ItIsreferredtoasdirect current(0C).However,Iftheelectronflow
reversesdIrectIonataregularInterval,ItIstermedalternating current(AC).EItherof
thesetypesofcurrentcanbepulsedorcontInuousInnature.
TheprevIousdIscussIonofDhm'slawIsaccuratewhenapplIedto0CcIrcuIts.However,
whendealIngwIthACcIrcuIts,thesItuatIonIsmorecomplexbecausetheflowofthe
currentIsopposedbyamorecomplIcatedformofresIstance,knownasimpedance.
Impedance
mpedance,desIgnatedbytheletterZ,IsdefInedasthesumoftheforcesthatoppose
electronmovementInanACcIrcuIt.mpedanceconsIstsofresIstance(ohms)butalsotakes
capacItanceandInductanceIntoaccount.nactualIty,whenreferrIngtoACcIrcuIts,Dhm's
lawIsdefInedas:
E=IZ
AninsulatorIsasubstancethatopposestheflowofelectrons.Therefore,anInsulatorhasa
hIghImpedancetoelectronflow,whereasaconductorhasalowImpedancetoelectron
flow.
nACcIrcuItsthecapacItanceandInductancecanbeImportantfactorsIndetermInIngthe
totalImpedance.8othcapacItanceandInductanceareInfluencedbythefrequency(cycles
persecondorhertz,Hz)atwhIchtheACcurrentreversesdIrectIon.TheImpedanceIs
dIrectlyproportIonaltothefrequency(f)tImestheInductance(N0):
Z(fN0)
andtheImpedanceIsInverselyproportIonaltotheproductofthefrequency(f)andthe
capacItance(CAP):
Z1/(fCAP)
AstheACcurrentIncreasesInfrequency,theneteffectofbothcapacItanceand
InductanceIncreases.However,becauseImpedanceandcapacItanceareInverselyrelated,
totalImpedancedecreasesastheproductofthefrequencyandthecapacItanceIncreases.
Thus,asfrequencyIncreases,ImpedancefallsandmorecurrentIsallowedtopass.
Capacitance
AcapacitorconsIstsofanytwoparallelconductorsthatareseparatedbyanInsulator(FIg.
81).AcapacItorhastheabIlItytostorecharge.CapacitanceIsthemeasureofthat
substance'sabIlItytostorecharge.na0CcIrcuItthecapacItorplatesarechargedbya
voltagesource(I.e.,abattery)andthereIsonlyamomentarycurrentflow.ThecIrcuItIs
notcompletedandnofurthercurrentcanflowunlessaresIstanceIsconnectedbetween
thetwoplatesandthecapacItorIsdIscharged.
ncontrastto0CcIrcuIts,acapacItorInanACcIrcuItpermItscurrentflowevenwhenthe
cIrcuItIsnotcompletedbyaresIstance.ThIsIsbecauseofthenatureofACcIrcuIts,In
whIchthecurrentflowIsconstantlybeIngreversed.8ecausecurrentflowresultsfromthe
movementofelectrons,thecapacItorplatesarealternatelychargedfIrstposItIveand
thennegatIvewItheveryreversaloftheACcurrentdIrectIonresultIngInaneffectIve
currentflowasfarastheremaInderofthecIrcuItIsconcerned,eventhoughthecIrcuItIs
notcompleted.
8ecausetheeffectofcapacItanceonImpedancevarIesdIrectlywIththeACfrequencyIn
hertz,thegreatertheACfrequency,thelowertheImpedance.Therefore,hIghfrequency
currents(0.5to2mIllIonHz),suchasthoseusedbyelectrosurgIcalunIts(ESUs),wIllcause
amarkeddecreaseInImpedance.
ElectrIcaldevIcesusecapacItorsforvarIousbenefIcIalpurposes.ThereIs,however,a
phenomenonknownasstray capacitancecapacItancethatwasnotdesIgnedIntothe
systembutIsIncIdentaltotheconstructIonoftheequIpment.AllACoperatedequIpment
producesstraycapacItance.AnordInarypowercord,forexample,consIstIngoftwo
InsulatedwIresrunnIngnexttoeachotherwIllgeneratesIgnIfIcantcapacItancesImplyby
beIngpluggedIntoa120voltcIrcuIt,eventhoughthepIeceofequIpmentIsnotturnedon.
AnotherexampleofstraycapacItanceIsfoundInelectrIcmotors.ThecIrcuItwIrIngIn
electrIcmotorsgeneratesstraycapacItancetothemetalhousIngofthemotor.TheclInIcal
ImportanceofcapacItancewIllbeemphasIzedlaterInthechapter.
Figure 8-1.AcapacItorconsIstsoftwoparallelconductorsseparatedbyanInsulator.
ThecapacItorIscapableofstorIngchargesupplIedbyavoltagesource.
P.167
Inductance
WheneverelectronsflowInawIre,amagnetIcfIeldIsInducedaroundthewIre.fthewIre
IscoIledrepeatedlyaroundanIroncore,asInatransformer,themagnetIcfIeldcanbe
verystrong.InductanceIsapropertyofACcIrcuItsInwhIchanopposIngE|Fcanbe
electromagnetIcallygeneratedInthecIrcuIt.TheneteffectofInductanceIstoIncrease
Impedance.8ecausetheeffectofInductanceonImpedancealsodependsonACfrequency,
IncreasesInfrequencywIllIncreasethetotalImpedance.Therefore,thetotalImpedance
ofacoIlwIllbemuchgreaterthanItssImpleresIstance.
Electrical Shock Hazards
Alternating and Direct Currents
WheneveranIndIvIdualcontactsanexternalsourceofelectrIcIty,anelectrIcalshockIs
possIble.AnelectrIcalcurrentcanstImulateskeletalmusclecellstocontract,andthuscan
beusedtherapeutIcallyIndevIcessuchaspacemakersordefIbrIllators.However,casual
contactwIthanelectrIcalcurrent,whetherACor0C,canleadtoInjuryordeath.Although
IttakesapproxImatelyJtImesasmuch0CasACtocauseventrIcularfIbrIllatIon,thIsbyno
meansrenders0Charmless.0evIcessuchasanautomobIlebatteryora0CdefIbrIllator
canbesourcesofdIrectcurrentshocks.
ntheUnItedStates,utIlItycompanIessupplyelectrIcalenergyIntheformofalternatIng
currentsof120voltsatafrequencyof60Hz.The120voltsofE|Fand1ampereofcurrent
aretheeffectIvevoltageandamperageInanACcIrcuIt.ThIsIsalsoreferredtoasRMS
(rootmeansquare).ttakes1.414amperesofpeakamperageInthesInusoIdalcurveto
gIveaneffectIveamperageof1ampere.SImIlarly,Ittakes170volts(1201.414)atthe
peakoftheACcurvetogetaneffectIvevoltageof120volts.The60Hzreferstothe
numberoftImesIn1secondthatthecurrentreversesItsdIrectIonofflow.8oththe
voltageandcurrentwaveformsformasInusoIdalpattern(FIg.82).
TohavethecompletedcIrcuItnecessaryforcurrentflow,aclosedloopmustexIstanda
voltagesourcemustdrIvethecurrentthroughtheImpedance.fcurrentIstoflowInthe
electrIcalcIrcuIt,therehastobeavoltage differential,oradropInthedrIvIngpressure
acrosstheImpedance.AccordIngtoDhm'slaw,IftheresIstanceIsheldconstant,thenthe
greaterthecurrentflow,thelargerthevoltagedropmustbe.
ThepowercompanyattemptstomaIntaInthelInevoltageconstantat120volts.
Therefore,byDhm'slawthecurrentflowIsInverselyproportIonaltotheImpedance.A
typIcalpowercordconsIstsoftwoconductors.Dne,desIgnatedashotcarrIesthecurrent
totheImpedance;theotherIsneutral,andItreturnsthecurrenttothesource.The
potentIaldIfferencebetweenthetwoIseffectIvely120volts(FIg.8J).Theamountof
currentflowIngthroughagIvendevIceIsfrequentlyreferredtoastheload.Theloadof
thecIrcuItdependsontheImpedance.AveryhIghImpedancecIrcuItallowsonlyasmall
currenttoflowandthushasasmallload.AverylowImpedancecIrcuItwIlldrawalarge
currentandIssaIdtobealargeload.Ashort circuitoccurswhenthereIsazeroImpedance
loadwIthaveryhIghcurrentflow.
1
Figure 8-2.SInewaveflowofelectronsIna60HzalternatIngcurrent.
Figure 8-3.AtypIcalalternatIngcurrent(AC)cIrcuItwherethereIsapotentIal
dIfferenceof120voltsbetweenthehotandneutralsIdesofthecIrcuIt.Thecurrent
flowsthrougharesIstance,whIchInACcIrcuItsIsmoreaccuratelyreferredtoas
impedance,andthenreturnstotheelectrIcalpowercompany.
Source of Shocks
ElectrIcalaccIdentsorshocksoccurwhenapersonbecomespartof,orcompletes,an
electrIcalcIrcuIt.ToreceIveashock,onemustcontacttheelectrIcalcIrcuItattwopoInts,
andtheremustbeavoltagesourcethatcausesthecurrenttoflowthroughanIndIvIdual
(FIg.84).
WhenanIndIvIdualcontactsasourceofelectrIcIty,damageoccursInoneoftwoways.
FIrst,theelectrIcalcurrentcandIsruptthenormalelectrIcalfunctIonofcells.0ependIng
onItsmagnItude,thecurrentcancontractmuscles,alterbraInfunctIon,paralyze
respIratIon,ordIsruptnormalheartfunctIon,leadIngtoventrIcularfIbrIllatIon.Thesecond
mechanIsmInvolvesthedIssIpatIonofelectrIcalenergythroughoutthebody'stIssues.An
electrIcalcurrentpassIngthroughanyresIstanceraIsesthetemperatureofthatsubstance.
fenoughthermalenergyIsreleased,the
P.168
temperaturewIllrIsesuffIcIentlytoproduceaburn.AccIdentsInvolvInghouseholdcurrents
usuallydonotresultInsevereburns.However,InaccIdentsInvolvIngveryhIghvoltages
(I.e.,powertransmIssIonlInes),severeburnsarecommon.
Figure 8-4.AnIndIvIdualcancompleteanelectrIccIrcuItandreceIveashockby
comIngIncontactwIththehotsIdeofthecIrcuIt(poIntA).ThIsIsbecauseheorsheIs
standIngontheground(poIntB)andthecontactpoIntAandthegroundpoIntB
provIdethetwocontactpoIntsnecessaryforacompletedcIrcuIt.TheseverItyofthe
shockthattheIndIvIdualreceIvesdependsonhIsorherskInresIstance.
TheseverItyofanelectrIcalshockIsdetermInedbytheamountofcurrent(numberof
amperes)andtheduratIonofthecurrentflow.ForthepurposesofthIsdIscussIon,
electrIcalshocksaredIvIdedIntotwocategorIes.Macroshockreferstolargeamountsof
currentflowIngthroughaperson,whIchcancauseharmordeath.Microshockreferstovery
smallamountsofcurrentandapplIesonlytotheelectrIcallysusceptIblepatIent.ThIsIsan
IndIvIdualwhohasanexternalconduItthatIsIndIrectcontactwIththeheart.ThIscanbe
apacIngwIreorasalInefIlledcathetersuchasacentralvenousorpulmonaryartery
catheter.nthecaseoftheelectrIcallysusceptIblepatIent,evenmInuteamountsof
current(mIcroshock)maycauseventrIcularfIbrIllatIon.
Table81showstheeffectstypIcallyproducedbyvarIouscurrentsfollowInga1second
contactwItha60Hzcurrent.WhenanIndIvIdualcontactsa120volthouseholdcurrent,
theseverItyoftheshockwIlldependonhIsorherskInresIstance,theduratIonofthe
contact,andthecurrentdensIty.SkInresIstancecanvaryfromafewthousandto1mIllIon
ohms.fapersonwIthaskInresIstanceof1,000ohmscontactsa120voltcIrcuIt,heorshe
wouldreceIve120mIllIamperes(mA)ofcurrent,whIchwouldprobablybelethal.However,
Ifthatsameperson'sskInresIstanceIs100,000ohms,thecurrentflowwouldbe1.2mA,
whIchwouldbarelybeperceptIble.
I=E/R=(120volts)/(1,000ohms)=120mA
I=E/R=(120volts)/(100,000ohms)=1.2mA
ThelongeranIndIvIdualIsIncontactwIththeelectrIcalsource,themoredIrethe
consequencesbecausemoreenergywIllbereleasedandmoretIssuedamaged.Also,there
wIllbeagreaterchanceofventrIcularfIbrIllatIonfromexcItatIonoftheheartdurIngthe
vulnerableperIodoftheelectrocardIogram(ECC)cycle.
Current densityIsawayofexpressIngtheamountofcurrentthatIsapplIedperunItarea
oftIssue.ThedIffusIonofcurrentInthebodytendstobeInalldIrectIons.Thegreaterthe
currentorthesmallertheareatowhIchItIsapplIed,thehIgherthecurrentdensIty.n
relatIontotheheart,acurrentof100mA(100,000A)IsgenerallyrequIredtoproduce
ventrIcularfIbrIllatIonwhenapplIedtothesurfaceofthebody.However,only100A(0.1
mA)IsrequIredtoproduceventrIcularfIbrIllatIonwhenthatmInutecurrentIsapplIed
dIrectlytothemyocardIumthroughanInstrumenthavIngaverysmallcontactarea,such
asapacIngwIreelectrode.nthIscase,thecurrentdensItyIs1,000foldgreaterwhen
applIeddIrectlytotheheart;therefore,only1/1,000oftheenergyIsrequIredtocause
ventrIcularfIbrIllatIon.nthIscase,theelectrIcallysusceptIblepatIentcanbe
electrocutedwIthcurrentswellbelow1mA,whIchIsthethresholdofperceptIonfor
humans.ThefrequencyatwhIchthecurrentreversesIsalsoanImportantfactorIn
determInIngtheamountofcurrentanIndIvIdualcansafelycontact.UtIlItycompanIesIn
theUnItedStatesproduceelectrIcItyatafrequencyof60Hz.Theyuse60Hzbecause
hIgherfrequencIescausegreaterpowerlossthroughtransmIssIonlInesandlower
frequencIescauseadetectableflIckerfromlIghtsources.
2
TheletgocurrentIsdefIned
asthatcurrentabovewhIchsustaInedmuscularcontractIonoccursandatwhIchan
IndIvIdualwouldbeunabletoletgoofanenergIzedwIre.Theletgocurrentfora60HzAC
powerIs10to20mA,
1,J,4
whereasatafrequencyof1mIllIonHz,uptoJamperes(J,000
mA)IsgenerallyconsIderedsafe.tshouldbenotedthatveryhIghfrequencycurrentsdo
notexcItecontractIletIssue;consequently,theydonotcausecardIacdysrhythmIas.
tcanbeseenthatDhm'slawgovernstheflowofelectrIcIty.ForacompletedcIrcuItto
exIst,theremustbeaclosedloopwIthadrIvIngpressuretoforceacurrentthrougha
resIstance,justasInthecardIovascularsystemtheremustbeabloodpressuretodrIvethe
cardIacoutputthroughtheperIpheralresIstance.FIgure85IllustratesthatahotwIre
carryInga120voltpressurethroughtheresIstanceofa60wattlIghtbulbproducesa
currentflowof0.5ampere.ThevoltageIntheneutralwIreIsapproxImately0volts,whIle
thecurrentIntheneutralwIreremaInsat0.5ampere.ThIscorrelateswIthour
cardIovascularanalogy,whereameanbloodpressuredecreaseof80mmHgbetweenthe
aortIcrootandtherIghtatrIumforcesacardIacoutputof6L/mInthroughasystemIc
vascularresIstanceof1J.JresIstanceunIts.However,theflow(InthIscase,thecardIac
output,orInthecaseoftheelectrIcalmodel,thecurrent)IsstIllthesameeverywhereIn
thecIrcuIt.ThatIs,thecardIacoutputonthearterIalsIdeIsthesameasthecardIac
outputonthevenoussIde.
Table 8-1 Effects of 60-Hz Current on an Average Human for A 1-Second
Contact
CURRENT EFFECT
Macroshock
1mA
(0.001A)
ThresholdofperceptIon
5mA
(0.005A)
AcceptedasmaxImumharmlesscurrentIntensIty
1020mA
(0.010.02
A)
LetgocurrentbeforesustaInedmusclecontractIon
50mA PaIn,possIblefaIntIng,mechanIcalInjury;heartandrespIratory
(0.05A) functIonscontInue
100J00
mA(0.1
0.JA)
7entrIcularfIbrIllatIonwIllstart,butrespIratorycenterremaIns
Intact
6,000mA
(6A)
SustaInedmyocardIalcontractIon,followedbynormalheartrhythm;
temporaryrespIratoryparalysIs;burnsIfcurrentdensItyIshIgh
Microshock
100A
(0.1mA)
7entrIcularfIbrIllatIon
10A
(0.01mA)
FecommendedmaxImum60Hzleakagecurrent
A,amperes;mA,mIllIamperes;A,mIcroamperes.
P.169
Grounding
TofullyunderstandelectrIcalshockhazardsandtheIrpreventIon,onemusthavea
thoroughknowledgeoftheconceptsofgroundIng.TheseconceptsofgroundIngprobably
constItutethemostconfusIngaspectsofelectrIcalsafetybecausethesametermIsusedto
descrIbeseveraldIfferentprIncIples.nelectrIcaltermInology,groundIngIsapplIedtotwo
separateconcepts.ThefIrstIsthegroundIngofelectrIcalpower,andthesecondIsthe
groundIngofelectrIcalequipment.Thus,theconceptsthat(1)powercanbegroundedor
ungroundedandthat(2)powercansupplyelectrIcaldevIcesthatarethemselvesgrounded
orungroundedarenotmutuallyexclusIve.tIsvItaltounderstandthIspoIntasthebasIsof
electrIcalsafety(Table82).WhereaselectrIcalpowerIsgroundedInthehome,ItIs
usuallyungroundedIntheDF.nthehome,electrIcalequipmentmaybegroundedor
ungrounded,butItshouldalwaysbegroundedIntheDF.
Figure 8-5.A60wattlIghtbulbhasanInternalresIstanceof240ohmsanddraws0.5
ampereofcurrent.ThevoltagedropInthecIrcuItIsfrom120InthehotwIreto0In
theneutralwIre,butthecurrentIs0.5ampereInboththehotandneutralwIres.
Electrical Power: Grounded
ElectrIcalutIlItIesunIversallyprovIdepowerthatIsgrounded(byconventIon,theearth
groundpotentIalIszero,andallvoltagesrepresentadIfferencebetweenpotentIals).That
Is,oneofthewIressupplyIngthepowertoahomeIsIntentIonallyconnectedtotheearth.
TheutIlItycompanIesdothIsasasafetymeasuretopreventelectrIcalchargesfrom
buIldIngupIntheIrwIrIngdurIngelectrIcalstorms.ThIsalsopreventstheveryhIgh
voltagesusedIntransmIttIngpowerbytheutIlItyfromenterIngthehomeIntheeventof
anequIpmentfaIlureIntheIrhIghvoltagesystem.
ThepowerentersthetypIcalhomevIatwowIres.ThesetwowIresareattachedtothe
maInfuseorthecIrcuItbreakerboxattheservIceentrance.ThehotwIresupplIespower
tothehotdIstrIbutIonstrIp.TheneutralwIreIsconnectedtotheneutraldIstrIbutIon
strIpandtoaservIceentranceground(I.e.,apIpeburIedIntheearth;FIg.86).Fromthe
fusebox,threewIresleavetosupplytheelectrIcaloutletsInthehouse.ntheUnIted
States,thehotwIreIscolorcodedblackandcarrIesavoltage120voltsaboveground
potentIal.ThesecondwIreIstheneutralwIrecolorcodedwhIte;thethIrdwIreIsthe
groundwIre,whIchIseIthercolorcodedgreenorIsunInsulated(barewIre).Theground
andtheneutralwIresareattachedatthesamepoIntInthecIrcuItbreakerboxandthen
furtherconnectedtoacoldwaterpIpe(FIgs.87and88).Thus,thIsgroundedpower
systemIsalsoreferredtoasaneutral grounded power system.TheblackwIreIsnot
connectedtotheground,asthIswouldcreateashortcIrcuIt.TheblackwIreIsattachedto
thehot(I.e.,120voltsaboveground)dIstrIbutIonstrIponwhIchthecIrcuItbreakersor
fusesarelocated.Fromhere,numerousbranchcIrcuItssupplyelectrIcalpowertothe
outletsInthehouse.EachbranchcIrcuItIsprotectedbyacIrcuItbreakerorfusethat
lImItscurrenttoaspecIfIcmaxImumamperage.|ostelectrIcalcIrcuItsInthehouseare
15or20amperecIrcuIts.ThesetypIcallysupplypowertotheelectrIcaloutletsandlIghts
Inthehouse.SeveralhIgheramperagecIrcuItsarealsoprovIdedfordevIcessuchasan
electrIcstoveoranelectrIcclothesdryer.ThesedevIcesarepoweredby240voltcIrcuIts,
whIchcandrawfromJ0to50amperesofcurrent.ThecIrcuItbreakerorfusewIllInterrupt
theflowofcurrentonthehotsIdeofthelIneIntheeventofashortcIrcuItorIfthe
demandplacedonthatcIrcuItIstoohIgh.Forexample,a15amperebranchcIrcuItwIllbe
capableofsupportIng1,800wattsofpower.
Table 8-2 Differences Between Power and Equipment Grounding in the
Home and the Operating Room
POWER EQUIPMENT
Home +
DperatIngroom +
+,grounded;,ungrounded;,mayormaynotbegrounded.
W=E/I
W=120volts15amperes
W=1,800watts
Therefore,Iftwo1,500watthaIrdryersweresImultaneouslypluggedIntooneoutlet,the
loadwouldbetoogreatfora15amperecIrcuIt,andthecIrcuItbreakerwouldopen(trIp)
orthefusewouldmelt.ThIsIsdonetopreventthesupplywIresInthecIrcuItfrommeltIng
andstartIngafIre.TheamperageofthecIrcuItbreakeronthebranchcIrcuItIsdetermIned
bythethIcknessofthewIrethatItsupplIes.fa20amperebreakerIsusedwIthwIrerated
foronly15amperes,thewIrecouldmeltandstartafIrebeforethecIrcuItbreakerwould
trIp.tIsImportanttonotethata15amperecIrcuItbreakerdoesnotprotectanIndIvIdual
fromlethalshocks.The15amperesofcurrentthatwouldtrIpthecIrcuItbreakerfar
exceedsthe100to200mAthatwIllproduceventrIcularfIbrIllatIon.
ThewIresthatleavethecIrcuItbreakersupplytheelectrIcaloutletsandlIghtIngforthe
restofthehouse.nolderhomestheelectrIcalcableconsIstsoftwowIres,ahotanda
neutral,whIchsupplypowertotheelectrIcaloutlets(FIg.89).nnewerhomes,athIrd
wIrehasbeenaddedtotheelectrIcalcable(FIg.810).ThIsthIrdwIreIseIthergreenor
unInsulated(bare)andservesasagroundwIreforthepowerreceptacle
P.170
P.171
(FIg.811).Dnoneend,thegroundwIreIsattachedtotheelectrIcaloutlet(FIg.812);on
theother,ItIsconnectedtotheneutraldIstrIbutIonstrIpInthecIrcuItbreakerboxalong
wIththeneutral(whIte)wIres(FIg.81J).
Figure 8-6.naneutralgroundedpowersystem,theelectrIccompanysupplIestwo
lInestothetypIcalhome.TheneutralwIreIsconnectedtogroundbythepower
companyandagaInconnectedtoaservIceentrancegroundwhenItentersthefuse
box.8oththeneutralandgroundwIresareconnectedtogetherInthefuseboxatthe
neutralbusbar,whIchIsalsoattachedtotheservIceentranceground.
Figure 8-7.nsIdeafuseboxwIththecIrcuItbreakersremoved.Thearrowheads
IndIcatethehotwIresenergIzIngthestrIpswherethecIrcuItbreakersarelocated.The
arrowspoInttotheneutralbusbarwheretheneutralandgroundwIresareconnected.
Figure 8-8.ThearrowheadIndIcatesthegroundwIrefromthefuseboxattachedtoa
coldwaterpIpe.
Figure 8-9.AnolderstyleelectrIcaloutletconsIstIngofjusttwowIres(ahotanda
neutral).ThereIsnogroundwIre.
Figure 8-10.|odernelectrIcalcableInwhIchathIrd,orground,wIrehasbeenadded.
Figure 8-11.|odernelectrIcaloutletInwhIchthegroundwIreIspresent.The
arrowheadpoIntstothepartofthereceptaclewherethegroundwIreconnects.
tshouldberealIzedthatInboththeoldandnewsItuatIons,thepowerIsgrounded.That
Is,a120voltpotentIalexIstsbetweenthehot(black)andtheneutral(whIte)wIreand
betweenthehotwIreandground.nthIscase,thegroundIstheearth(FIg.814).n
modernhomeconstructIon,thereIsstIlla120voltpotentIaldIfferencebetweenthehot
(black)andtheneutral(whIte)wIreaswellasa120voltdIfferencebetweenthe
equIpmentgroundwIre(whIchIsthethIrdwIre),andbetweenthehotwIreandearth(FIg.
815).
Figure 8-12.0etaIlofmodernelectrIcalpowerreceptacle.ThearrowpoIntstothe
groundwIre,whIchIsattachedtothegroundIngscrewonthepowerreceptacle.
Figure 8-13.ThegroundwIresfromthepoweroutletareruntotheneutralbusbar,
wheretheyareconnectedwIththeneutralwIres(arrowheads).
A60wattlIghtbulbcanbeusedasanexampletofurtherIllustratethIspoInt.Normally,
thehotandneutralwIresareconnectedtothetwowIresofthelIghtbulbsocket,and
throwIngtheswItchwIllIllumInatethebulb(FIg.816).SImIlarly,IfthehotwIreIs
connectedtoonesIdeofthebulbsocketandtheotherwIrefromthelIghtbulbIs
connectedtotheequIpmentgroundwIre,thebulbwIllstIllIllumInate.fthereIsno
equIpmentgroundwIre,thebulbwIllstIlllIghtIfthesecondwIreIsconnectedtoany
groundedmetallIcobjectsuchasawaterpIpeorafaucet.ThIsIllustratesthefactthatthe
120voltpotentIaldIfferenceexIstsnotonlybetweenthehotandtheneutralwIresbutalso
betweenthehotwIreandanygroundedobject.Thus,Inagroundedpowersystem,the
currentwIllflowbetweenthehotwIreandanyconductorwIthanearthground.
AsprevIouslystated,currentflowrequIresaclosedloopwIthasourceofvoltage.Foran
IndIvIdualtoreceIveanelectrIcshock,heorshemustcontacttheloopattwopoInts.
8ecausewemaybestandIngongroundorbeIncontactwIthanobjectthatIsreferenced
toground,onlyoneaddItIonalcontactpoIntIsnecessarytocompletethecIrcuItandthus
receIveanelectrIcalshock.ThIsIsanunfortunateandInherentlydangerousconsequence
ofgroundedpowersystems.|odernwIrIngsystemshaveaddedthethIrdwIre,the
equIpmentgroundwIre,asasafetymeasuretoreducetheseverItyofapotentIalelectrIcal
shock.ThIsIsaccomplIshedbyprovIdInganalternate,lowresIstancepathwaythrough
whIchthecurrentcanflowtoground.
DvertImetheInsulatIoncoverIngwIresmaydeterIorate.tIsthenpossIbleforabare,hot
wIretocontactthemetalcaseorframeofanelectrIcaldevIce.Thecasewouldthen
becomeenergIzedandconstItuteashockhazardtosomeonecomIngIncontactwIthIt.
FIgure817IllustratesatypIcalshortcIrcuIt,wheretheIndIvIdualhascomeIncontactwIth
thehotcaseofanInstrument.ThIsIllustratesthetypeofwIrIngfoundInolderhomes.
ThereIsnogroundwIreIntheelectrIcaloutlet,norIstheelectrIcalapparatusequIpped
wIthagroundwIre.Here,theIndIvIdualcompletesthecIrcuItandreceIvesasevere
P.172
P.17J
shock.FIgure818IllustratesasImIlarexample,exceptthatnowtheequIpmentground
wIreIspartoftheelectrIcaldIstrIbutIonsystem.nthIsexample,theequIpmentground
wIreprovIdesapathwayoflowImpedancethroughwhIchthecurrentcantravel;
therefore,mostofthecurrentwouldtravelthroughthegroundwIre.nthIscase,the
personmaygetashock,butItIsunlIkelytobefatal.
Figure 8-14.0IagramofahousewItholderstylewIrIngthatdoesnotcontaInaground
wIre.A120voltpotentIaldIfferenceexIstsbetweenthehotandtheneutralwIres,as
wellasbetweenthehotwIreandtheearth.
Figure 8-15.0IagramofahousewIthmodernwIrIngInwhIchthethIrd,orground,
wIrehasbeenadded.The120voltpotentIaldIfferenceexIstsbetweenthehotand
neutralwIres,thehotandthegroundwIres,andthehotwIreandtheearth.
Figure 8-16.AsImplelIghtbulbcIrcuItInwhIchthehotandneutralwIresare
connectedwIththecorrespondIngwIresfromthelIghtbulbfIxture.
Figure 8-17.WhenafaultypIeceofequIpmentwIthoutanequIpmentgroundwIreIs
pluggedIntoanelectrIcaloutletnotcontaInIngagroundwIre,thecaseofthe
InstrumentwIllbecomehot.AnIndIvIdualtouchIngthehotcase(poIntA)wIllreceIve
ashockbecauseheorsheIsstandIngontheearth(poIntB)andcompletesthecIrcuIt.
Thecurrent(dashed line)wIllflowfromtheInstrumentthroughtheIndIvIdualtouchIng
thehotcase.
TheelectrIcalpowersupplIedtohomesIsalwaysgrounded.A120voltpotentIalalways
exIstsbetweenthehotconductorandgroundorearth.ThethIrdorequIpmentgroundwIre
usedInmodernelectrIcalwIrIngsystemsdoesnotnormallyhavecurrentflowIngthrough
It.ntheeventofashortcIrcuIt,anelectrIcaldevIcewIthathreeprongplug(I.e.,a
groundwIreconnectedtoItscase)wIllconductthemajorItyoftheshortcIrcuItedor
faultcurrentthroughthegroundwIreandawayfromtheIndIvIdual.ThIsprovIdesa
sIgnIfIcantsafetybenefIttosomeoneaccIdentallycontactIngthedefectIvedevIce.fa
largeenoughfaultcurrentexIsts,thegroundwIrealsowIllprovIdeameanstocomplete
theshortcIrcuItbacktothecIrcuItbreakerorfuse,andthIswIlleIthermeltthefuseor
trIpthecIrcuItbreaker.Thus,Inagroundedpowersystem,ItIspossIbletohaveeIther
groundedorungroundedequIpment,dependIngonwhenthewIrIngwasInstalledand
whethertheelectrIcaldevIceIsequIppedwIthathreeprongplugcontaInIngaground
wIre.DbvIously,attemptstobypassthesafetysystemoftheequIpmentgroundshouldbe
avoIded.0evIcessuchasacheaterplug(FIg.819)shouldneverbeusedbecausethey
defeatthesafetyfeatureoftheequIpmentgroundwIre.
Figure 8-18.WhenafaultypIeceofequIpmentcontaInInganequIpmentgroundwIre
IsproperlyconnectedtoanelectrIcaloutletwIthagroundIngconnectIon,thecurrent
(dashed line)wIllpreferentIallyflowdownthelowresIstancegroundwIre.An
IndIvIdualtouchIngthecase(poIntA)whIlestandIngontheground(poIntB)wIllstIll
completethecIrcuIt;however,onlyasmallpartofthecurrentwIllgothroughthe
IndIvIdual.
Electrical Power: Ungrounded
NumerouselectronIcdevIces,togetherwIthpowercordsandpuddlesofsalInesolutIonson
thefloor,maketheDFanelectrIcallyhazardousenvIronmentforbothpatIentsand
personnel.8runeretal.
5
foundthat40ofelectrIcalaccIdentsInhospItalsoccurredInthe
DF.ThecomplexItyofelectrIcalequIpmentInthemodernDFdemandsthatelectrIcal
safetybeafactorofparamountImportance.ToprovIdeanextrameasureofsafetyfrom
macroshock,thepowersupplIedtomostDFsIsungrounded.nthIsungroundedpower
system,thecurrentIsIsolatedfromgroundpotentIal.The120voltpotentIaldIfference
exIstsonlybetweenthetwowIresoftheIsolatedpowersystem,butnocIrcuItexIsts
betweenthegroundandeItheroftheIsolatedpowerlInes.
SupplyIngungroundedpowertotheDFrequIrestheuseofanisolation transformer(FIg.8
20).ThIsdevIceuseselectromagnetIcInductIontoInduceacurrentIntheungroundedor
secondarywIndIngofthetransformerfromenergysupplIedtotheprImarywIndIng.There
IsnodIrectelectrIcalconnectIonbetweenthepowersupplIedbytheutIlItycompanyon
theprImarysIdeandthepowerInducedbythetransformerontheungroundedor
secondarysIde.Thus,thepowersupplIedtotheDFIsIsolatedfromground(FIg.821).
8ecausethe120voltpotentIalexIstsonlybetweenthetwowIresoftheIsolatedcIrcuIt,
neItherwIreIshotorneutralwIthreferencetoground.nthIscase,theyaresImply
referredtoaslIne1and
P.174
P.175
lIne2(FIg.822).UsIngtheexampleofthelIghtbulb,IfoneconnectsthetwowIresofthe
bulbsockettothetwowIresoftheIsolatedpowersystem,thelIghtwIllIllumInate.
However,IfoneconnectsoneofthewIrestoonesIdeoftheIsolatedpowerandtheother
wIretoground,thelIghtwIllnotIllumInate.fthewIresoftheIsolatedpowersystemare
connected,theshortcIrcuItwIlltrIpthecIrcuItbreaker.ncomparIngthetwosystems,the
standardgroundedpowerhasadIrectconnectIontoground,whereastheIsolatedsystem
ImposesaveryhIghImpedancetoanycurrentflowtoground.TheaddedsafetyofthIs
systemcanbeseenInFIgure82J.nthIscase,apersonhascomeIncontactwIthonesIde
oftheIsolatedpowersystem(poIntA).8ecausestandIngonground(poIntB)doesnot
constItuteapartoftheIsolatedcIrcuIt,theIndIvIdualdoesnotcompletetheloopandwIll
notreceIveashock.ThIsIsbecausethegroundIspartoftheprImarycIrcuIt(solid lines),
andthepersonIscontactIngonlyonesIdeoftheIsolatedsecondarycIrcuIt(cross-hatched
lines).ThepersondoesnotcompleteeIthercIrcuIt(I.e.,havetwocontactpoInts);
therefore,thIssItuatIondoesnotposeanelectrIcshockhazard.Dfcourse,Iftheperson
contactsbothlInesoftheIsolatedpowersystem(anunlIkelyevent),heorshewould
receIveashock.
Figure 8-19. Right.Acheaterplugthatconvertsathreeprongpowercordtoatwo
prongcord.Left.ThewIreattachedtothecheaterplugIsrarelyconnectedtothe
screwInthemIddleoftheoutlet.ThIstotallydefeatsthepurposeoftheequIpment
groundwIre.
Figure 8-20. A.solatedpowerpanelshowIngcIrcuItbreakers,lIneIsolatIonmonItor,
andIsolatIontransformer(arrow).B.0etaIlofanIsolatIontransformerwIththe
attachedwarnInglIghts.ThearrowpoIntstogroundwIreconnectIonontheprImary
sIdeofthetransformer.NotethatnosImIlarconnectIonexIstsonthesecondarysIdeof
thetransformer.
Figure 8-21.ntheoperatIngroom,theIsolatIontransformerconvertsthegrounded
powerontheprImarysIdetoanungroundedpowersystemonthesecondarysIdeof
thetransformer.A120voltpotentIaldIfferenceexIstsbetweenlIne1andlIne2.There
IsnodIrectconnectIonfromthepoweronthesecondarysIdetoground.The
equIpmentgroundwIre,however,IsstIllpresent.
Figure 8-22.0etaIloftheInsIdeofacIrcuItbreakerboxInanIsolatedpowersystem.
Thebottom arrowpoIntstogroundwIresmeetIngatthecommongroundtermInal.
Arrows 1and2IndIcatelInes1and2fromtheIsolatedpowercIrcuItbreaker.NeIther
lIne1norlIne2IsconnectedtothesametermInalsasthegroundwIres.ThIsIsIn
markedcontrasttoFIgure81J,wheretheneutralandgroundwIresareattachedat
thesamepoInt.
Figure 8-23.AsafetyfeatureoftheIsolatedpowersystemIsIllustrated.AnIndIvIdual
contactIngonesIdeoftheIsolatedpowersystem(poIntA)andstandIngontheground
(poIntB)wIllnotreceIveashock.nthIsInstance,theIndIvIdualIsnotcontactIngthe
cIrcuItattwopoIntsandthusIsnotcompletIngthecIrcuIt.PoIntA(cross-hatched
lines)IspartoftheIsolatedpowersystem,andpoIntBIspartoftheprImaryor
groundedsIdeofthecIrcuIt(solid lines).
fafaultyelectrIcalapplIancewIthanIntactequIpmentgroundwIreIspluggedIntoa
standardhouseholdoutlet,andthehomewIrInghasaproperlyconnectedgroundwIre,
thentheamountofelectrIcalcurrentthatwIllflowthroughtheIndIvIdualIsconsIderably
lessthanwhatwIllflowthroughthelowresIstancegroundwIre.Here,anIndIvIdualwould
befaIrlywellprotectedfromaserIousshock.However,IfthatgroundwIrewerebroken,
theIndIvIdualmIghtreceIvealethalshock.NoshockwouldoccurIfthesamefaultypIece
ofequIpmentwerepluggedIntotheIsolatedpowersystem,evenIftheequIpmentground
wIrewerebroken.Thus,theIsolatedpowersystemprovIdesasIgnIfIcantamountof
protectIonfrommacroshock.AnotherfeatureoftheIsolatedpowersystemIsthatthe
faultypIeceofequIpment,eventhoughItmaybepartIallyshortcIrcuIted,wIllnotusually
trIpthecIrcuItbreaker.ThIsIsanImportantfeaturebecausethefaultypIeceofequIpment
maybepartofalIfesupportsystemforapatIent.tIsImportanttonotethateventhough
thepowerIsIsolatedfromground,thecaseorframeofallelectrIcalequIpmentIsstIll
connectedtoanequIpmentground.ThethIrdwIre(equIpmentgroundwIre)Isnecessary
foratotalelectrIcalsafetyprogram.
FIgure824IllustratesascenarIoInvolvIngafaultypIeceofequIpmentconnectedtothe
Isolatedpowersystem.ThIsdoesnotrepresentahazard;ItmerelyconvertstheIsolated
powerbacktoagroundedpowersystemasexIstsoutsIdetheDF.nfact,asecondfaultIs
necessarytocreateahazard.
TheprevIousdIscussIonassumesthattheIsolatedpowersystemIsperfectlyIsolatedfrom
ground.Actually,perfectIsolatIonIsImpossIbletoachIeve.AllACoperatedpowersystems
andelectrIcaldevIcesmanIfestsomedegreeofcapacItance.AsprevIouslydIscussed,
electrIcalpowercords,wIres,andelectrIcalmotorsexhIbItcapacItIvecouplIngtothe
groundwIreandmetalconduItsandleaksmallamountsofcurrenttoground(FIg.825).
ThIssocalledleakage currentpartIallyungroundstheIsolatedpowersystem.ThIsdoesnot
usuallyamounttomorethanafewmIllIamperesInanDF.SoanIndIvIdualcomIngIn
contactwIthonesIdeoftheIsolatedpowersystemwouldreceIveonlyaverysmallshock
(1to2mA).AlthoughthIsamountofcurrentwouldbeperceptIble,Itwouldnotbe
dangerous.
The Line Isolation Monitor
Theline isolation monitor(L|)IsadevIcethatcontInuouslymonItorstheIntegrItyofan
Isolatedpowersystem.fafaulty
P.176
pIeceofequIpmentIsconnectedtotheIsolatedpowersystem,thIswIll,Ineffect,change
thesystembacktoaconventIonalgroundedsystem.Also,thefaultypIeceofequIpment
wIllcontInuetofunctIonnormally.Therefore,ItIsessentIalthatawarnIngsystembeIn
placetoalertthepersonnelthatthepowerIsnolongerungrounded.TheL|contInuously
monItorstheIsolatedpowertoensurethatItIsIndeedIsolatedfromground,andthe
devIcehasameterthatdIsplaysacontInuousIndIcatIonoftheIntegrItyofthesystem(FIg.
826).TheL|IsactuallymeasurIngtheImpedancetogroundofeachsIdeoftheIsolated
powersystem.AsprevIouslydIscussed,wIthperfectIsolatIon,Impedancewouldbe
InfInItelyhIghandtherewouldbenocurrentflowIntheeventofafIrstfaultsItuatIon(Z=
E/;IfI=0,thenZ=).8ecauseallACwIrIngandallACoperatedelectrIcaldevIceshave
somecapacItance,smallleakagecurrentsarepresentthatpartIallydegradetheIsolatIon
ofthesystem.ThemeteroftheL|wIllIndIcate(InmIllIamperes)thetotalamountof
leakageInthesystemresultIngfromcapacItance,electrIcalwIrIng,andanydevIces
pluggedIntotheIsolatedpowersystem.
Figure 8-24.AfaultypIeceofequIpmentpluggedIntotheIsolatedpowersystemdoes
notpresentashockhazard.tmerelyconvertstheIsolatedpowersystemIntoa
groundedpowersystem.ThefIgureInsetIllustratesthattheIsolatedpowersystemIs
nowIdentIcaltothegroundedpowersystem.Thedashed lineIndIcatescurrentflowIn
thegroundwIre.
ThereadIngontheL|meterdoesnotmeanthatcurrentIsactuallyflowIng;rather,It
IndIcateshowmuchcurrentwouldflowIntheeventofafIrstfault.TheL|Issettoalarm
at2or5mA,dependIngontheageandbrandofthesystem.DncethIspresetlImItIs
exceeded,vIsualandaudIblealarmsaretrIggeredtoIndIcatethattheIsolatIonfrom
groundhasbeendegradedbeyondapredetermInedlImIt(FIg.827).ThIsdoesnot
necessarIlymeanthatthereIsahazardoussItuatIon,butratherthatthesystemIsno
longertotallyIsolatedfromground.twouldrequIreasecondfaulttocreateadangerous
sItuatIon.
Figure 8-25.ThecapacItancethatexIstsInalternatIngcurrent(AC)powerlInesand
ACoperatedequIpmentresultsInsmallleakagecurrentsthatpartIallydegradethe
Isolatedpowersystem.
Forexample,IftheL|weresettoalarmat2mA,usIngDhm'slaw,theImpedancefor
eIthersIdeoftheIsolatedpowersystemwouldbe60,000ohms:
Z=E/I
Z=(120volts)/(0.002ampere)
Z=60,000ohms
Therefore,IfeIthersIdeoftheIsolatedpowersystemhadlessthan60,000ohmsImpedance
toground,theL|wouldtrIggeranalarm.ThIsmIghtoccurIntwosItuatIons.nthefIrst
sItuatIon,afaultypIeceofequIpmentIspluggedIntotheIsolatedpowersystem.nthIs
case,atruefaulttogroundexIsts
P.177
fromonelInetoground.NowthesystemwouldbeconvertedtotheequIvalentofa
groundedpowersystem.ThIsfaultypIeceofequIpmentshouldberemovedandservIcedas
soonaspossIble.However,thIspIeceofequIpmentcouldstIllbeusedsafelyIfItwere
essentIalforthecareofthepatIent.tshouldberemembered,however,thatcontInuIngto
usethIsfaultypIeceofequIpmentwouldcreatethepotentIalforaserIouselectrIcalshock.
ThIswouldoccurIfasecondfaultypIeceofequIpmentweresImultaneouslyconnectedto
theIsolatedpowersystem.
Figure 8-26.ThemeterofthelIneIsolatIonmonItor(L|)IscalIbratedIn
mIllIamperes.ftheIsolatIonofthepowersystemIsdegradedsuchthat2mA(5mAIn
newersystems)ofcurrentcouldflow,thehazardlIghtwIllIllumInateandawarnIng
buzzerwIllsound.NotethebuttonfortestIngthehazardwarnIngsystem.A.DlderL|
thatwIlltrIggeranalarmat2mA.B.NewerL|thatwIlltrIggeranalarmat5mA.
ThesecondsItuatIonInvolvesconnectIngmanyperfectlynormalpIecesofequIpmentto
theIsolatedpowersystem.AlthougheachpIeceofequIpmenthasonlyasmallamountof
leakagecurrent,Ifthetotalleakageexceeds2mA,theL|wIlltrIggeranalarm.Assume
thatInthesameDFthereareJ0electrIcaldevIces,eachhavIng100Aofleakagecurrent.
Thetotalleakagecurrent(J0100A)wouldbeJmA.TheImpedancetogroundwould
stIllbe40,000ohms(120/0.00J).TheL|alarmwouldsoundbecausethe2mAsetpoInt
wasvIolated.However,thesystemIsstIllsafeandrepresentsastatesIgnIfIcantlydIfferent
fromthatInthefIrstsItuatIon.ForthIsreason,thenewerL|saresettoalarmat5mA
Insteadof2mA.
Figure 8-27.WhenafaultypIeceofequIpmentIspluggedIntotheIsolatedpower
system,ItwIllmarkedlydecreasetheImpedancefromlIne1orlIne2toground.ThIs
wIllbedetectedbythelIneIsolatIonmonItor,whIchwIllsoundanalarm.
ThenewestL|sarereferredtoasthird-generation monitors.ThefIrstgeneratIon
monItor,orstatIcL|,wasunabletodetectbalancedfaults(I.e.,asItuatIonInwhIch
thereareequalfaultstogroundfrombothlIne1andlIne2).ThesecondgeneratIon,or
dynamIc,L|dIdnothavethIsproblembutcouldInterferewIthphysIologIcmonItorIng.
8othofthesemonItorswouldtrIggeranalarmat2mA,whIchledtoannoyIngfalse
alarms.ThethIrdgeneratIonL|correctstheproblemsofItspredecessorsandhasthe
alarmthresholdsetat5mA.
6
ProperfunctIonIngoftheL|dependsonhavIngbothIntact
equIpmentgroundwIres
P.178
aswellasItsownconnectIontoground.FIrstandsecondgeneratIonL|scouldnotdetect
thelossoftheL|groundconnectIon.ThethIrdgeneratIonL|candetectthIslossof
groundtothemonItor.nthIscasetheL|alarmwouldsoundandtheredhazardlIght
wouldIllumInate,buttheL|meterwouldreadzero.ThIscondItIonwIllalertthestaff
thattheL|needstoberepaIred.However,theL|stIllcannotdetectbrokenequIpment
groundwIres.AnexampleofthethIrdgeneratIonL|IstheIso-GardmadebytheSquare0
Company(|onroe,NC).
TheequIpmentgroundwIreIsagaInanImportantpartofthesafetysystem.fthIswIreIs
broken,afaultypIeceofequIpmentthatIspluggedIntoanoutletwouldoperatenormally,
buttheL|wouldnotalarm.Asecondfaultcouldthereforecauseashock,wIthoutany
alarmfromtheL|.Also,Intheeventofasecondfault,theequIpmentgroundwIre
provIdesalowresIstancepathtogroundformostofthefaultcurrent(seeFIg.824).The
L|wIllonlybeabletoregIsterleakagecurrentsfrompIecesofequIpmentthatare
connectedtotheIsolatedpowersystemandhaveIntactgroundwIres.
ftheL|alarmIstrIggered,thefIrstthIngtodoIstocheckthegaugetodetermIneIfItIs
atruefault.TheotherpossIbIlItyIsthattoomanypIecesofelectrIcalequIpmenthave
beenpluggedInandthe2mAlImIthasbeenexceeded.fthegaugeIsbetween2and5mA,
ItIsprobablethattoomuchelectrIcalequIpmenthasbeenpluggedIn.fthegaugereads
5mA,mostlIkelythereIsafaultypIeceofequIpmentpresentIntheDF.ThenextstepIs
toIdentIfythefaultyequIpment,whIchIsdonebyunpluggIngeachpIeceofequIpment
untIlthealarmceases.fthefaultypIeceofequIpmentIsnotofalIfesupportnature,It
shouldberemovedfromtheDF.fItIsavItalpIeceoflIfesupportequIpment,Itcanbe
safelyused.However,ItmustberememberedthattheprotectIonoftheIsolatedpower
systemandtheL|IsnolongeroperatIve.Therefore,IfpossIble,nootherelectrIcal
equIpmentshouldbeconnecteddurIngtheremaInderofthecase,oruntIlthefaultypIece
ofequIpmentcanbesafelyremoved.
Ground Fault Circuit Interrupter
ThegroundfaultcIrcuItInterrupter(CFC,oroccasIonallyabbrevIatedasCF)Isanother
populardevIceusedtopreventIndIvIdualsfromreceIvInganelectrIcalshockInagrounded
powersystem.ElectrIcalcodesformostnewconstructIonrequIrethataCFCcIrcuItbe
presentInpotentIallyhazardous(e.g.,wet)areassuchasbathrooms,kItchens,oroutdoor
electrIcaloutlets.TheCFCmaybeInstalledasanIndIvIdualpoweroutlet(FIg.828)or
maybeaspecIalcIrcuItbreakertowhIchalltheIndIvIdualprotectedoutletsare
connectedatasInglepoInt.ThespecIalCFCcIrcuItbreakerIslocatedInthemaIn
fuse/cIrcuItbreakerboxandcanbedIstInguIshedbyItsredtestbutton(FIg.829).As
FIgure85demonstrates,thecurrentflowIngInboththehotandneutralwIresIsusually
equal.TheCFCmonItorsbothsIdesofthecIrcuItfortheequalItyofcurrentflow;Ifa
dIfferenceIsdetected,thepowerIsImmedIatelyInterrupted.fanIndIvIdualshould
contactafaultypIeceofequIpmentsuchthatcurrentflowedthroughtheIndIvIdual,an
ImbalancebetweenthetwosIdesofthecIrcuItwouldbecreated,whIchwouldbedetected
bytheCFC.8ecausetheCFCcandetectverysmallcurrentdIfferences(Intherangeof5
mA),theCFCwIllopenthecIrcuItInafewmIllIseconds,therebyInterruptIngthecurrent
flowbeforeasIgnIfIcantshockoccurs.Thus,theCFCprovIdesahIghlevelofprotectIonat
averymodestcost.
Figure 8-28.AgroundfaultcIrcuItInterrupterelectrIcaloutletwIthIntegratedtest
andresetbuttons.
Figure 8-29.SpecIalgroundfaultcIrcuItInterruptercIrcuItbreaker.Thearrowhead
poIntstothedIstInguIshIngredtestbutton.
ThedIsadvantageofusIngaCFCIntheDFIsthatItInterruptsthepowerwIthoutwarnIng.
AdefectIvepIeceofequIpmentcouldnolongerbeused,whIchmIghtbeaproblemIfIt
wereofalIfesupportnature,whereasIfthesamefaultypIeceofequIpmentwereplugged
IntoanIsolatedpowersystem,theL|wouldalarmbuttheequIpmentcouldstIllbeused.
Double Insulation
ThereIsoneInstanceInwhIchItIsacceptableforapIeceofequIpmenttohaveonlyatwo
prongandnotathreeprongplug.ThIsIspermIttedwhentheInstrumenthaswhatIs
termeddouble insulation.TheseInstrumentshavetwolayersofInsulatIonandusuallyhave
aplastIcexterIor.0oubleInsulatIonIsfoundInmanyhomepowertoolsandIsseenIn
hospItalequIpmentsuchasInfusIonpumps.0oubleInsulatedequIpmentIspermIssIbleIn
theDFwIthIsolatedpowersystems.However,IfwaterorsalIneshouldgetInsIdetheunIt,
therecouldbeahazardbecausethedoubleInsulatIonIsbypassed.ThIsIsevenmore
serIousIftheDFhasnoIsolatedpowerorCFCs.
7
Microshock
AsprevIouslydIscussed,macroshockInvolvesrelatIvelylargeamountsofcurrentapplIedto
thesurfaceofthebody.ThecurrentIsconductedthroughallthetIssuesInproportIonto
theIrconductIvItyandareaInaplaneperpendIculartothecurrent.Consequently,the
densItyofthecurrent(amperespermetersquared)thatreachestheheartIs
consIderablylessthanwhatIsapplIedtothebodysurface.However,anelectrIcally
susceptIblepatIent(I.e.,onewhohasadIrect,externalconnectIonto
P.179
theheart,suchasthroughacentralvenouspressurecatheterortransvenouscardIac
pacIngwIres)maybeatrIskfromverysmallcurrents;thIsIscalledmicroshock.
8
The
catheterorIfIceorelectrIcalwIrewIthaverysmallsurfaceareaIncontactwIththeheart
producesarelatIvelylargecurrentdensItyattheheart.
9
Statedanotherway,evenvery
smallamountsofcurrentapplIeddIrectlytothemyocardIumwIllcauseventrIcular
fIbrIllatIon.|IcroshockIsapartIcularlydIffIcultproblembecauseoftheInsIdIousnatureof
thehazard.
Figure 8-30.TheelectrIcallysusceptIblepatIentIsprotectedfrommIcroshockbythe
presenceofanIntactequIpmentgroundwIre.TheequIpmentgroundwIreprovIdesa
lowImpedancepathInwhIchthemajorItyoftheleakagecurrent(dashed lines)can
flow.F,resIstance.
ntheelectrIcallysusceptIblepatIent,ventrIcularfIbrIllatIoncanbeproducedbyacurrent
thatIsbelowthethresholdofhumanperceptIon.Theexactamountofcurrentnecessaryto
causeventrIcularfIbrIllatIonInthIstypeofpatIentIsunknown.Whalenetal.
10
wereable
toproducefIbrIllatIonwIth20AofcurrentapplIeddIrectlytothemyocardIumofdogs.
Fafteryetal.
11
producedfIbrIllatIonwIth80AofcurrentInsomepatIents.Hull
12
used
dataobtaInedbyWatsonetal.
1J
toshowthat50ofpatIentswouldfIbrIllateatcurrentsof
200A.8ecause1,000A(1mA)IsgenerallyregardedasthethresholdofhumanperceptIon
wIth60HzAC,theelectrIcallysusceptIblepatIentcanbeelectrocutedwIthonetenththe
normallyperceptIblecurrents.ThIsIsnotonlyofacademIcInterestbutalsoofpractIcal
concernbecausemanycasesofventrIcularfIbrIllatIonfrommIcroshockhavebeen
reported.
14,15,16,17,18
ThestraycapacItancethatIspartofanyACpoweredelectrIcalInstrumentmayresultIn
sIgnIfIcantamountsofchargebuIlduponthecaseoftheInstrument.fanIndIvIdual
sImultaneouslytouchesthecaseofanInstrumentwherethIshasoccurredandthe
electrIcallysusceptIblepatIent,heorshemayunknowInglycauseadIschargetothe
patIentthatresultsInventrIcularfIbrIllatIon.DnceagaIn,theequIpmentgroundwIre
constItutesthemajorsourceofprotectIonagaInstmIcroshockfortheelectrIcally
susceptIblepatIent.nthIscase,theequIpmentgroundwIreprovIdesalowresIstancepath
bywhIchmostoftheleakagecurrentIsdIssIpatedInsteadofstoredasacharge.
Figure 8-31.AbrokenequIpmentgroundwIreresultsInasIgnIfIcanthazardtothe
electrIcallysusceptIblepatIent.nthIscase,theentIreleakagecurrentcanbe
conductedtotheheartandmayresultInventrIcularfIbrIllatIon.F,resIstance.
FIgure8J0IllustratesasItuatIonInvolvIngapatIentwIthasalInefIlledcatheterInthe
heartwItharesIstanceof-500ohms.ThegroundwIrewItharesIstanceof1ohmIs
connectedtotheInstrumentcase.Aleakagecurrentof100AwIlldIvIdeaccordIngtothe
relatIveresIstancesofthetwopaths.nthIscase,99.8AwIllflowthroughtheequIpment
groundwIreandonly0.2AwIllflowthroughthefluIdfIlledcatheter.ThIsextremelysmall
currentdoesnotendangerthepatIent.However,IftheequIpmentgroundwIrewere
broken,theelectrIcallysusceptIblepatIentwouldbeatgreatrIskbecauseall100Aof
leakagecurrentcouldflowthroughthecatheterandcauseventrIcularfIbrIllatIon(FIg.8
J1).Currently,electronIcequIpmentIspermItted100Aofleakagecurrent.
|odernpatIentmonItorsIncorporateanothermechanIsmtoreducetherIskofmIcroshock
forelectrIcallysusceptIblepatIents.
19
ThIsmechanIsmInvolveselectrIcallyIsolatIngall
dIrectpatIentconnectIonsfromthepowersupplyofthemonItorbyplacIngaveryhIgh
ImpedancebetweenthepatIentand
P.180
anydevIce.ThIslImItstheamountofInternalleakagethroughthepatIentconnectIontoa
verysmallvalue.ThestandardcurrentlyIs10A.ForInstance,theoutputofanECC
monItor'spowersupplyIselectrIcallyIsolatedfromthepatIentbyplacIngaveryhIgh
ImpedancebetweenthemonItorandthepatIent'sECCleads.
20
solatIontechnIquesare
desIgnedtoInhIbIthazardouselectrIcalpathwaysbetweenthepatIentandthemonItor
whIleallowIngthepassageofthephysIologIcsIgnal.
Figure 8-32. A.AhospItalgradeplugthatcanbevIsuallyInspected.ThearrowpoInts
totheequIpmentgroundwIrewhoseIntegrItycanbereadIlyverIfIed.B.AhospItal
gradeplugthatcanbeeasIlydIsassembledforInspectIon.Notethattheprongforthe
groundwIre(arrow)Islongerthanthehotorneutralprong,sothatItIsthefIrstto
enterthereceptacle.C.ThearrowpoIntstothegreendotdenotIngahospItalgrade
poweroutlet.
AnIntactequIpmentgroundwIreIsprobablythemostImportantfactorInpreventIng
mIcroshock.Thereare,however,otherthIngsthattheanesthesIologIstcandotoreduce
theIncIdenceofmIcroshock.DneshouldneversImultaneouslytouchanelectrIcaldevIce
andasalInefIlledcentralcatheterorexternalpacIngwIres.WheneveroneIshandlInga
centralcatheterorpacIngwIres,ItIsbesttoInsulateoneselfbywearIngrubbergloves.
Also,oneshouldneverletanyexternalcurrentsource,suchasanervestImulator,come
IntocontactwIththecatheterorwIres.FInally,oneshouldbealerttopotentIalsourcesof
energythatcanbetransmIttedtothepatIent.EvenstrayradIofrequencycurrentfromthe
ESU(cautery)can,wIththerIghtcondItIons,beasourceofmIcroshock.
21
tmustbe
rememberedthattheL|IsnotdesIgnedtoprovIdeprotectIonfrommIcroshock.The
mIcroamperecurrentsInvolvedInmIcroshockarefarbelowtheL|thresholdof
protectIon.naddItIon,theL|doesnotregIstertheleakageofIndIvIdualmonItors,but
ratherIndIcatesthestatusofthetotalsystem.TheL|readIngIndIcatesthetotalamount
ofleakagecurrentresultIngfromtheentIrecapacItanceofthesystem.ThIsIstheamount
ofcurrentthatwouldflowtogroundIntheeventofafIrstfaultsItuatIon.
TheessenceofelectrIcalsafetyIsathoroughunderstandIngofalltheprIncIplesof
groundIng.TheobjectIveofelectrIcalsafetyIstomakeItdIffIcultforelectrIcalcurrentto
passthroughpeople.ForthIsreason,boththepatIentandtheanesthesIologIstshouldbe
IsolatedfromgroundasmuchaspossIble.ThatIs,theIrresIstancetocurrentflowshould
beashIghasIstechnologIcallyfeasIble.ntheInherentlyunsafeelectrIcalenvIronmentof
anDF,severalmeasurescanbetakentohelpprotectagaInstcontactInghazardouscurrent
flows.FIrst,thegroundedpowerprovIdedbytheutIlItycompanycanbeconvertedto
ungroundedpowerbymeansofanIsolatIontransformer.TheL|wIllcontInuouslymonItor
thestatusofthIsIsolatIonfromgroundandwarnthattheIsolatIonofthepower(from
ground)hasbeenlostIntheeventthatadefectIvepIeceofequIpmentIspluggedIntoone
oftheIsolatedcIrcuItoutlets.naddItIon,theshockthatanIndIvIdualcouldreceIvefrom
afaultypIeceofequIpmentIsdetermInedbythecapacItanceofthesystemandIslImIted
toafewmIllIamperes.Second,allequIpmentpluggedIntotheIsolatedpowersystemhas
anequIpmentgroundwIrethatIsattachedtothecaseoftheInstrument.ThIsequIpment
groundwIreprovIdesanalternatIvelowresIstancepathwayenablIngpotentIallydangerous
currentstoflowtoground.Thus,thepatIentandtheanesthesIologIstshouldbeas
InsulatedfromgroundaspossIbleandallelectrIcalequIpmentshouldbegrounded.
TheequIpmentgroundwIreservesthreefunctIons.FIrst,ItprovIdesalowresIstancepath
forfaultcurrentstoreducetherIskofmacroshock.Second,ItdIssIpatesleakagecurrents
thatarepotentIallyharmfultotheelectrIcallysusceptIblepatIent.ThIrd,ItprovIdes
InformatIontotheL|onthestatusoftheungroundedpowersystem.ftheequIpment
groundwIreIsbroken,asIgnIfIcantfactorInthepreventIonofelectrIcalshockIslost.
AddItIonally,theIsolatedpowersystemwIllappearsaferthanItactuallyIsbecausethe
L|IsunabletodetectbrokenequIpmentgroundwIres.
8ecausepowercordplugsandreceptaclesaresubjectedtogreaterabuseInthehospItal
thanInthehome,theUnderwrItersLaboratorIes(|elvIlle,NY)hasIssuedastrIct
specIfIcatIonforspecIalhospItalgradeplugsandreceptacles(FIg.8J2).Theplugsand
receptaclesthatconformtothIsspecIfIcatIonaremarkedbyagreendot.
22
ThehospItal
gradeplugIsonethatcanbevIsuallyInspectedoreasIlydIsassembledtoensurethe
IntegrItyofthegroundwIreconnectIon.|oldedopaqueplugsarenotacceptable.
Edwards
2J
reportedthatofJ,000nonhospItalgradereceptaclesInstalledInanewhospItal
buIldIng,1,800(60)weredefectIveafterJyears.When2,000ofthenonhospItalgrade
receptacleswerereplacedwIthonesofhospItalgrade,nofaIlureshadoccurredafter18
monthsofuse.
P.181
Electrosurgery
DnthatfatefulDctoberdayIn1926when0r.HarveyW.CushIngfIrstusedan
electrosurgIcalmachIneInventedbyProfessorWIllIamT.8ovIetoresectabraIntumor,
thecourseofmodernsurgeryandanesthesIawasforeveraltered.
24
TheubIquItoususeof
electrosurgeryatteststothesuccessofProfessor8ovIe'sInventIon.However,thIs
technologywasnotadoptedwIthoutacost.ThewIdespreaduseofelectrocauteryhas,at
theveryleast,hastenedtheelImInatIonofexplosIveanesthetIcagentsfromtheDF.n
addItIon,aseveryanesthesIologIstIsaware,fewthIngsIntheDFareImmuneto
Interferencefromthe8ovIe.ThehIghfrequencyelectrIcalenergygeneratedbytheESU
InterfereswItheverythIngfromtheECCsIgnaltocardIacoutputcomputers,pulse
oxImeters,andevenImplantedcardIacpacemakers.
25
TheESUoperatesbygeneratIngveryhIghfrequencycurrents(radIofrequencyrange)of
anywherefrom500,000to1mIllIonHz.HeatIsgeneratedwheneveracurrentpasses
througharesIstance.Theamountofheat(H)producedIsproportIonaltothesquareofthe
currentandInverselyproportIonaltotheareathroughwhIchthecurrentpasses(H=
I
2
/A).
26
8yconcentratIngtheenergyatthetIpofthe8ovIepencIl,thesurgeoncan
produceeItheracutoracoagulatIonatanygIvenspot.ThIsveryhIghfrequencycurrent
behavesdIfferentlyfromthestandard60HzACcurrentandcanpassdIrectlyacrossthe
precordIumwIthoutcausIngventrIcularfIbrIllatIon.
26
ThIsIsbecausehIghfrequency
currentshavealowtIssuepenetratIonanddonotexcItecontractIlecells.
ThelargeamountofenergygeneratedbytheESUcanposeotherproblemstotheoperator
andthepatIent.0r.CushIngbecameawareofonesuchproblem.Hewrote,Dncethe
operatorreceIvedashockwhIchpassedthroughametalretractortohIsarmandoutbya
wIrefromhIsheadlIght,whIchwasunpleasanttosaytheleast.
27
TheESUcannotbesafely
operatedunlesstheenergyIsproperlyroutedfromtheESUthroughthepatIentandbackto
theunIt.deally,thecurrentgeneratedbytheactIveelectrodeIsconcentratedattheESU
tIp,constItutIngaverysmallsurfacearea.ThIsenergyhasahIghcurrentdensItyandIs
abletogenerateenoughheattoproduceatherapeutIccutorcoagulatIon.Theenergythen
passesthroughthepatIenttoadIspersIveelectrodeoflargesurfaceareathatreturnsthe
energysafelytotheESU(FIg.8JJ).
DneunfortunatequIrkIntermInologyconcernsthereturn(dIspersIve)plateoftheESU.
ThIsplate,oftenIncorrectlyreferredtoasaground plate,IsactuallyadIspersIve
electrodeoflargesurfaceareathatsafelyreturnsthegeneratedenergytotheESUvIaa
lowcurrentdensItypathway.WhenInquIrIngwhetherthedIspersIveelectrodehasbeen
attachedtothepatIent,DFpersonnelfrequentlyask,sthepatIentgrounded:8ecause
theaImofelectrIcalsafetyIstoIsolatethepatIentfromground,thIsexpressIonIsworse
thanerroneous;ItcanleadtoconfusIon.8ecausetheareaofthereturnplateIslarge,the
currentdensItyIslow;therefore,noharmfulheatIsgeneratedandnotIssuedestructIon
occurs.naproperlyfunctIonIngsystem,theonlytIssueeffectIsatthesIteoftheactIve
electrodethatIsheldbythesurgeon.
Figure 8-33.AproperlyapplIedelectrosurgIcalunIt(ESU)returnplate.Thecurrent
densItyatthereturnplateIslow,resultIngInnodangertothepatIent.
ProblemscanarIseIftheelectrosurgIcalreturnplateIsImproperlyapplIedtothepatIent
orIfthecordconnectIngthereturnplatetotheESUIsdamagedorbroken.nthese
Instances,thehIghfrequencycurrentgeneratedbytheESUwIllseekanalternatereturn
pathway.AnythIngattachedtothepatIent,suchasECCleadsoratemperatureprobe,can
provIdethIsalternatereturnpathway.ThecurrentdensItyattheECCpadwIllbe
consIderablyhIgherthannormalbecauseItssurfaceareaIsmuchlessthanthatoftheESU
returnplate.ThIsmayresultInaserIousburnatthIsalternatereturnsIte.SImIlarly,a
burnmayoccuratthesIteoftheESUreturnplateIfItIsnotproperlyapplIedtothe
patIentorIfItbecomespartIallydIslodgeddurIngtheoperatIon(FIg.8J4).ThIsIsnot
merelyatheoretIcalpossIbIlItybutIsevIdencedbythenumerouscasereportsInvolvIng
patIentswhohavereceIvedESUburns.
28,29,J0,J1,J2,JJ
TheorIgInalESUsweremanufacturedwIththepowersupplyconnecteddIrectlytoground
bytheequIpmentgroundwIre.ThesedevIcesmadeItextremelyeasyforESUcurrentto
returnbyalternatepathways.TheESUwouldcontInuetooperatenormallyevenwIthout
thereturnplateconnectedtothepatIent.nmostmodernESUs,thepowersupplyIs
IsolatedfromgroundtoprotectthepatIentfromburns.twashopedthatbyIsolatIngthe
returnpathwayfromground,theonlyrouteforcurrentflowwouldbevIathereturn
electrode.TheoretIcally,thIswouldelImInatealternatereturnpathwaysandgreatly
reducetheIncIdenceofburns.However,|Itchell
J4
foundtwosItuatIonsInwhIchthe
currentcouldreturnvIaalternatepathways,evenwIththeIsolatedESUcIrcuIt.fthe
returnplatewerelefteItherontopofanunInsulatedESUcabInetorIncontactwIththe
bottomoftheDFtable,thentheESUcouldoperatefaIrlynormallyandthecurrentwould
returnvIaalternatepathways.twIllberecalledthattheImpedanceIsInversely
proportIonaltothecapacItancetImesthecurrentfrequency.TheESUoperatesat500,000
to1,000,000Hz,whIchgreatlyenhancestheeffectofcapacItIvecouplIngandcausesa
markedreductIonInImpedance.Therefore,evenwIthIsolatedESUs,thedecreaseIn
ImpedanceallowsthecurrenttoreturntotheESUbyalternatepathways.naddItIon,the
IsolatedESUdoesnotprotectthepatIentfromburnsIfthereturnelectrodedoesnotmake
propercontactwIththepatIent.AlthoughtheIsolatedESUdoesprovIdeaddItIonal
P.182
patIentsafety,ItIsbynomeansfoolproofprotectIonagaInstthepatIentreceIvIngaburn.
Figure 8-34.AnImproperlyapplIedelectrosurgIcalunIt(ESU)returnplate.Poor
contactwIththereturnplateresultsInahIghcurrentdensItyandapossIbleburnto
thepatIent.
PreventIngpatIentburnsfromtheESUIstheresponsIbIlItyofallprofessIonalstaffInthe
DF.NotonlythecIrculatIngnurse,butalsothesurgeonandtheanesthesIologIstmustbe
awareofpropertechnIquesandbevIgIlanttopotentIalproblems.ThemostImportant
factorIstheproperapplIcatIonofthereturnplate.tIsessentIalthatthereturnplatehas
theapproprIateamountofelectrolytegelandanIntactreturnwIre.Feusablereturnplates
mustbeproperlycleanedaftereachuse,anddIsposableplatesmustbecheckedtoensure
thattheelectrolytehasnotdrIedoutdurIngstorage.naddItIon,ItIsprudenttoplacethe
returnplateascloseaspossIbletothesIteoftheoperatIon.ECCpadsshouldbeplacedas
farfromthesIteoftheoperatIonasIsfeasIble.DFpersonnelmustbealerttothe
possIbIlItythatpoolsofflammableprepsolutIonssuchasalcoholandacetonecanIgnIte
whentheESUIsused.ftheESUmustbeusedonapatIentwIthademandpacemaker,the
returnelectrodeshouldbelocatedbelowthethorax,andpreparatIonsfortreatIng
potentIaldysrhythmIasshouldbeavaIlable,IncludIngamagnettoconvertthepacemaker
toafIxedrate,adefIbrIllator,andanexternalpacemaker.tIsbesttokeepthe
pacemakeroutofthepathbetweenthesurgIcalsIteandthedIspersalplate.
TheESUhasalsocausedotherproblemsInpatIentswIthpacemakers,IncludIng
reprogrammIngandmIcroshock.
J5,J6
fthesurgeonrequestshIgherthannormalpower
settIngsontheESU,thIsshouldalertboththecIrculatIngnurseandtheanesthesIologIstto
apotentIalproblem.ThereturnplateandcablemustbeImmedIatelyInspectedtoensure
thatItIsfunctIonIngandproperlyposItIoned.fthIsdoesnotcorrecttheproblem,the
returnplateshouldbereplaced.
J7,J8
ftheproblemremaIns,theentIreESUshouldbe
takenoutofservIce.FInally,anESUthatIsdroppedordamagedmustberemoved
ImmedIatelyfromtheDFandthoroughlytestedbyaqualIfIedbIomedIcalengIneer.
FollowIngthesesImplesafetystepswIllpreventmostpatIentburnsfromtheESU.
TheprevIousdIscussIonconcernedonlyunipolarESUs.ThereIsasecondtypeofESU,In
whIchthecurrentpassesonlybetweenthetwobladesofapaIrofforceps.ThIstypeof
devIceIsreferredtoasabipolarESU.8ecausetheactIveandreturnelectrodesarethe
twobladesoftheforceps,ItIsnotnecessarytoattachanotherdIspersIveelectrodetothe
patIent,unlessaunIpolarESUIsalsobeIngused.ThebIpolarESUgeneratesconsIderably
lesspowerthantheunIpolarandIsmaInlyusedforophthalmIcandneurologIcsurgery.
n1980|IrowskIetal.
J9
reportedthefIrsthumanImplantatIonofadevIcetotreat
IntractableventrIculartachydysrhythmIas.ThIsdevIce,knownastheautomatic
implantable cardioverter-defibrillator(AC0),IscapableofsensIngventrIculartachycardIa
andventrIcularfIbrIllatIonandthenautomatIcallydefIbrIllatIngthepatIent.SInce1980
thousandsofpatIentshavereceIvedAC0Implants.
40,41
8ecausesomeofthesepatIents
maypresentfornoncardIacsurgery,ItIsImportantthattheanesthesIologIstbeawareof
potentIalproblems.
42
TheuseofaunIpolarESUmaycauseelectrIcalInterferencethat
couldbeInterpretedbytheAC0asaventrIculartachydysrhythmIa.ThIswouldtrIggera
defIbrIllatIonpulsetobedelIveredtothepatIentandwouldlIkelycauseanactualepIsode
ofventrIculartachycardIaorventrIcularfIbrIllatIon.ThepatIentwIthanAC0Isalsoat
rIskforventrIcularfIbrIllatIondurIngelectroconvulsIvetherapy.
42
nbothcases,theAC0
shouldbedIsabledbyplacIngamagnetoverthedevIceorbyuseofaspecIfIcprotocolto
shutItoff.Therefore,ItIsbesttoconsultwIthsomeoneexperIencedwIththedevIce
beforestartIngsurgery.ThedevIcecanbereactIvatedbyreversIngtheprocess.Also,an
externaldefIbrIllatorandanonInvasIvepacemakershouldbeIntheDFwheneverapatIent
wIthanAC0IsanesthetIzed.
ElectrIcalsafetyIntheDFIsamatterofcombInIngcommonsensewIthsomebasIc
prIncIplesofelectrIcIty.DnceDFpersonnelunderstandtheImportanceofsafeelectrIcal
practIce,theyareabletodevelopaheIghtenedawarenesstopotentIalproblems.All
electrIcalequIpmentmustundergoroutInemaIntenance,servIce,andInspectIontoensure
thatItconformstodesIgnatedelectrIcalsafetystandards.Fecordsofthesetestresults
mustbekeptforfutureInspectIonbecausehumanerrorcaneasIlycompoundelectrIcal
hazards.Starmeretal.
4J
cItedonecaseconcernInganewlyconstructedlaboratorywhere
thegroundwIrewasnotattachedtoareceptacle.nanotherstudyAlbIsseretal.
44
founda
14(198/1,424)IncIdenceofImproperlyorIncorrectlywIredoutlets.Furthermore,
potentIallyhazardoussItuatIonsshouldberecognIzedandcorrectedbeforetheybecomea
problem.ForInstance,electrIcalpowercordsarefrequentlyplacedonthefloorwhere
theycanbecrushedbyvarIouscartsortheanesthesIamachIne.Thesecordscouldbe
locatedoverheadorplacedInanareaoflowtraffIcflow.|ultIpleplugextensIonboxes
shouldnotbeleftonthefloorwheretheycancomeIncontactwIthelectrolytesolutIons.
ThesecouldeasIlybemountedonacartortheanesthesIamachIne.PIecesofequIpment
thathavebeendamagedorhaveobvIousdefectsInthepowercordmustnotbeuseduntIl
theyhavebeenproperlyrepaIred.feveryoneIsawareofwhatconstItutesapotentIal
hazard,dangeroussItuatIonscanbepreventedwIthmInImaleffort.
SparksgeneratedbytheESUmayprovIdetheIgnItIonsourceforafIrewIthresultIngburns
tothepatIentandDFpersonnel.ThIsIsapartIcularrIskwhentheESUIsusedIn
P.18J
anoxygenenrIchedenvIronmentasmaybepresentInthepatIent'saIrwayorInclose
proxImItytothepatIent'sface.TheadmInIstratIonofhIghflownasaloxygentoasedated
patIentdurIngproceduresonthefaceandeyeIspartIcularlyhazardous.|ostplastIcssuch
astrachealtubesandcomponentsoftheanesthetIcbreathIngsystemthatwouldnotburn
InroomaIrwIllIgnIteInthepresenceofoxygenand/ornItrousoxIde.TentIngofthe
drapestoallowdIspersIonofanyaccumulatedoxygenand/orItsdIlutIonbyroomaIroruse
ofacIrcleanesthesIabreathIngsystemwIthmInImaltonoleakofgasesaroundthe
anesthesIamaskwIlldecreasetherIskofIgnItIonfromasparkgeneratedbyanearbyESU.
Conductive Flooring
npastyears,conductIvefloorIngwasmandatedforDFswhereflammableanesthetIc
agentswerebeIngadmInIstered.ThIswouldmInImIzethebuIldupofstatIcchargesthat
couldcauseaflammableanesthetIcagenttoIgnIte.Thestandardshavenowbeenchanged
toelImInatethenecessItyforconductIvefloorIngInanesthetIzIngareaswhereflammable
agentsarenolongerused.
Environmental Hazards
ThereareanumberofpotentIalelectrIcallyrelatedhazardsIntheDFthatareofconcern
totheanesthesIologIst.ThereIsthepotentIalforelectrIcalshocknotonlytothepatIent
butalsotoDFpersonnel.naddItIon,cablesandpowercordstoelectrIcalequIpmentand
monItorIngdevIcescanbecomehazardous.FInally,allDFpersonnelshouldhaveaplanof
whattodoIntheeventofapowerfaIlure.
ntoday'sDFtherearelIterallydozensofpIecesofelectrIcalequIpment.tIsnot
uncommontohavenumerouspowercordslyIngonthefloor,wheretheyarevulnerableto
damage.ftheInsulatIononthepowercablebecomesdamaged,ItIsfaIrlyeasyforthehot
wIretocomeIncontactwIthapIeceofmetalequIpment.ftheDFdIdnothaveIsolated
power,thatpIeceofequIpmentwouldbecomeenergIzedandapotentIalelectrIcalshock
hazard.
45
HavIngIsolatedpowermInImIzestherIsktothepatIentandDFpersonnel.
Clearly,gettIngelectrIcalpowercordsoffthefloorIsdesIrable.ThIscanbeaccomplIshed
byhavIngelectrIcaloutletsIntheceIlIngorbyhavIngceIlIngmountedartIculatedarms
thatcontaInelectrIcaloutlets.Also,theuseofmultIoutletextensIonboxesthatsItonthe
floorcanbehazardous.ThesecanbecontamInatedwIthfluIds,whIchcouldeasIlytrIpthe
cIrcuItbreaker.nonecase,ItapparentlytrIppedthemaIncIrcuItbreakerfortheentIre
DF,resultIngInalossofallelectrIcalpowerexceptfortheoverheadlIghts.
46
|odernmonItorIngdevIceshavemanysafetyfeaturesIncorporatedIntothem.7Irtuallyall
ofthemhaveIsolatedthepatIentInputfromthepowersupplyofthedevIce.ThIswasan
ImportantfeaturethatwaslackIngfromtheorIgInalECCmonItors.ntheearlydays,
patIentscouldactuallybecomepartoftheelectrIcalcIrcuItofthemonItor.Therehave
beenrelatIvelyfewproblemswIthpatIentsandmonItorIngdevIcessIncetheadventof
IsolatedInputs.However,between1985and1994,theFoodand0rugAdmInIstratIon(F0A)
receIvedapproxImately24reportsInwhIchInfantsandchIldrenhadreceIvedanelectrIcal
shock,IncludIngfIvechIldrenwhodIedbyelectrocutIon.
47,48
TheseelectrIcalaccIdents
occurredbecausetheelectrodeleadwIresfromeItheranECCmonItororanapnea
monItorwerepluggeddIrectlyIntoa120voltelectrIcaloutletInsteadoftheapproprIate
patIentcable.n1997,theF0AIssuedanewperformancestandardforelectrodeleadwIres
andpatIentcablesthatrequIresthattheexposedmaleconnectorpInsfromtheelectrode
leadwIresbeelImInated.Therefore,theleadwIresmusthavefemaleconnectIonsandthe
connectorpInsmustbehousedInaprotectedpatIentcable(FIg.8J5).ThIseffectIvely
elImInatesthepossIbIlItyofthepatIentbeIngconnecteddIrectlytoanalternatIngcurrent
sourcesIncetherearenoexposedconnectorpInsontheleadwIres.
Figure 8-35.ThecurrentstandardforpatIentleadwIres(left)requIresafemale
connector.ThepatIentcable(right)hasshIeldedconnectorpInsthattheleadwIres
plugInto.
AllhealthcarefacIlItIesarerequIredtohaveasourceofemergencypower.ThIsgenerally
consIstsofoneormoreelectrIcalgenerators.ThesegeneratorsareconfIguredtostartup
automatIcallyandprovIdepowertothefacIlItywIthIn10secondsafterdetectIngtheloss
ofpowerfromtheutIlItycompany.ThefacIlItyIsrequIredtotestthesegeneratorsona
regularbasIs.However,Inthepast,notallhealthcarefacIlItIestestedthemunderactual
load.TherearenumerousanecdotalreportsofgeneratorsnotfunctIonIngproperlydurIng
anactualpowerfaIlure.fthegeneratorsarenottestedunderactualload,ItIspossIble
thatmanyyearswIllpassbeforearealpoweroutageputsaseveredemandonthe
generator.fthefacIlItyhasseveralgeneratorsandoneofthemfaIls,theIncreased
demandontheothersmaybeenoughtocausethemtofaIlInrapIdsuccessIon.HospItals
(underthecurrentNatIonalFIreProtectIonAssocIatIon[NFPA]99standards)musttesttheIr
emergencypowersupplysystems(generators)underconnectedloadonceamonthforat
leastJ0mInutes.fthegeneratorIsoversIzedfortheapplIcatIonandcannotbeloadedto
atleastJ0ofItsratIng,Itmustbeloadbankedandrunforatotalof2hourseveryyear.
AfaIrlyrecentrequIrementIsforemergencypowersupplysystemstobetestedonceevery
Jyearsfor4contInuoushours,wItharecommendatIonthIsbeperformeddurIngpeak
usageofthesystem.
49,50
tIsvItallyImportantthateachDFhaveacontIngencyplanforapowerfaIlure.nmost
cases,theemergencygeneratorwIlltakeover,butthatIsnotalwaysgoIngtohappen.
ThereshouldbeasupplyofbatteryoperatedlIghtsourcesavaIlableIneachDF.A
laryngoscopecanserveasareadIlyavaIlablesourceoflIghtthatallowsonetofInd
flashlIghtsandotherpIecesofequIpment.TheoverheadlIghtsIntheDFshouldalsobe
connectedtosomesortofbatteryoperatedlIghtIngsystem.Asupplyofbatteryoperated
monItorIngdevIcesandpneumatIcallypoweredventIlatorsandanesthesIamachIneswould
enablelIfesupportfunctIonstocontInue.ThecostofthesecontIngencIesIsrelatIvely
smallbutthebenefItscanbeIncomparableInanemergency.
P.184
Electromagnetic Interference
FapIdadvancesIntechnologyhaveledtoanexplosIonInthenumberofwIreless
communIcatIondevIcesInthemarketplace.ThesedevIcesIncludecellulartelephones,
cordlesstelephones,walkIetalkIes,andwIrelessnternetaccessdevIces.Allofthese
devIceshavesomethIngIncommon:theyemItelectromagnetIcInterference(E|).ThIs
mostcommonlymanIfestsItselfwhentravelIngonaIrplanes.|ostaIrlInesrequIrethat
thesedevIcesbeturnedoffwhentheplaneIstakIngofforlandIngor,Insomecases,durIng
theentIreflIght.ThereIsconcernthattheE|emIttedbythesedevIcesmayInterfere
wIththeplane'snavIgatIonandcommunIcatIonequIpment.
nrecentyears,thenumberofpeoplewhoownthesedevIceshasIncreasedexponentIally.
ndeed,InsomehospItals,theyformavItallInkIntheregularoremergency
communIcatIonsystem.tIsnotuncommonforphysIcIans,nurses,paramedIcs,andother
personneltohavetheIrowncellulartelephones.naddItIon,patIentsandvIsItorsmayalso
havecellulartelephonesandothertypesofcommunIcatIondevIces.HospItalmaIntenance
andsecurItypersonnelfrequentlyhavewalkIetalkIetyperadIosandsomehospItalshave
evenInstItutedanInhousecellulartelephonenetworkthataugmentsorreplacesthe
pagIngsystem.TherehasbeenconcernthattheE|emIttedbythesedevIcesmay
InterferewIthImplantedpacemakersorvarIoustypesofmonItorIngdevIcesand
ventIlatorsIncrItIcalcareareas.
51
DnecaseofapatIentdeathhasbeenreportedwhena
ventIlatormalfunctIonedsecondarytoE|.
52
SeveralstudIeshavebeendonetofIndoutIfcellulartelephonescauseproblemswIth
cardIacpacemakers.DnereportbyHayesetal.
5J
studIed980patIentswIthfIvedIfferent
typesofcellulartelephones.Theyconductedmorethan5,000testsandfoundthatInmore
than20ofthecasestheycoulddetectsomeInterferencefromthecellulartelephone.
PatIentsweresymptomatIcIn7.2ofthecases,andclInIcallysIgnIfIcantInterference
occurredIn6.6ofthecases.WhenthetelephonewasheldInthenormalposItIonoverthe
ear,clInIcallysIgnIfIcantInterferencewasnotdetected.nfact,theInterferencethat
causedclInIcalsymptomsoccurredonlyIfthetelephonewasdIrectlyoverthepacemaker.
DtherstudIeshavedemonstratedchangessuchaserroneoussensIngandpacer
InhIbItIon.
54,55
AgaIn,theseoccurredonlywhenthetelephonewasclosetothepacemaker.
Thechangesweretemporary,andthepacemakerrevertedtonormalwhenthecellular
telephonewasmovedtoasafedIstance.Currently,theF0AguIdelInesarethatthecellular
telephonesbekeptatleast6Inchesfromthepacemaker.Therefore,apatIentwItha
pacemakershouldnotcarryacellulartelephoneIntheshIrtpocket,whIchIsadjacentto
thepacemaker.ThereappearstobelIttlerIskIfhospItalpersonnelcarryacellular
telephoneandIftheyensurethatItIskeptatareasonabledIstancefrompatIentswItha
pacemaker.
AC0scomprIseanothergroupofdevIcesofconcerntobIomedIcalengIneers.Fetteret
al.
56
conductedastudyof41patIentswhohadAC0s.Theyconcludedthatthecellular
telephonesdIdnotInterferewIththeAC0s.TheydId,however,recommendkeepIngthe
cellulartelephoneatleast6InchesfromthedevIce.
E|extendswellbeyondthatofcellulartelephones.WalkIetalkIes,whIcharefrequently
usedbyhospItalmaIntenanceandsecurItypersonnel,pagIngsystems,polIceradIos,and
eventelevIsIonsallemItE|,whIchcouldpotentIallyInterferewIthmedIcaldevIcesofany
nature.Althoughtherearemanyanecdotalreports,theamountofavaIlablescIentIfIc
InformatIononthIsproblemIsscant.FeportsofInterferenceIncludeventIlatorand
InfusIonpumpsthathavebeenshutdownorreprogrammed,InterferencewIthECC
monItors,andevenanelectronIcwheelchaIrthatwasaccIdentallystartedbecauseofE|.
tIsadIffIcultproblemtostudybecausetherearemanydIfferenttypesofdevIcesthat
emItE|andavastarrayofmedIcalequIpmentthathasthepotentIaltoInteractwIth
thesedevIces.EventhoughadevIcemayseemsafeInthemedIcalenvIronment,Iftwo
orthreecellulartelephonesorwalkIetalkIesarebroughttogetherInthesameareaatthe
sametIme,theremaybeunantIcIpatedproblemsorInterference.
AnytImeacellulartelephoneIsturnedon,ItIsactuallycommunIcatIngwIththecellular
network,eventhoughacallIsnotInprogress.Therefore,thepotentIaltoInterferewIth
devIcesexIsts.TheEmergencyCareFesearchnstItute(ECF)reportedInDctober1999that
walkIetalkIeswerefarmorelIkelytocauseproblemswIthmedIcaldevIcesthancellular
telephones.
57
ThIsIsbecausetheyoperateonalowerfrequencythancellulartelephones
andhaveahIgherpoweroutput.TheECFrecommendsthatcellulartelephonesbe
maIntaInedatadIstanceof1meterfrommedIcaldevIces,whIlewalkIetalkIesbekeptat
adIstanceof6to8meters.
SomehospItalshavemaderestrIctIvepolIcIesontheuseofcellulartelephones,
partIcularlyIncrItIcalcareareas.
58
ThesepolIcIesaresupportedbylIttlescIentIfIc
documentatIonandarenearlyImpossIbletoenforce.TheubIquItouspresenceofcellular
telephonescarrIedbyhospItalpersonnelandvIsItorsmakesenforcIngabanvIrtually
ImpossIble.EvenwhenpeopletrytocomplywIththeban,faIlureIsnearlyInevItable
becausethegeneralpublIcIsusuallyunawarethatacellulartelephoneInthestandby
modeIsstIllcommunIcatIngwIththetowerandgeneratIngE|.
TherealsolutIonIstohardendevIcesagaInstE|.ThIsIsdIffIculttodobecauseofthe
manydIfferentfrequencIesonwhIchthesedevIcesoperate.EducatIonofmedIcal
personnelIsessentIal.WhenworkIngInanDForcrItIcalcarearea,allpersonnelmustbe
alerttothefactthatelectronIcdevIcesandpacemakerscanbeInterferedwIthbyE|.
CreatIngarestrIctIvepolIcywouldcertaInlyIrrItatepersonnelandvIsItors,and,Insome
cases,mayactuallycompromIseemergencycommunIcatIons.
59
Construction of New Operating Rooms
Frequently,ananesthesIologIstIsaskedtoconsultwIthhospItaladmInIstratorsand
archItectsIndesIgnIngnew,orremodelIngolder,DFs.nthepastastrIctelectrIcalcode
wasenforcedbecauseoftheuseofflammableanesthetIcagents.ThIscodeIncludeda
requIrementforIsolatedpowersystemsandL|s.TheNFPArevIsedItsstandardforhealth
carefacIlItIesIn1984(NFPA991984).ThesestandardsdonotrequIreIsolatedpower
systemsorL|sInareasdesIgnatedforuseofnonflammableanesthetIcagentsonly.
60,61
Althoughnotmandatory,NFPAstandardsareusuallyadoptedbylocalauthorItIeswhen
revIsIngtheIrelectrIcalcodes.
ThIschangeInthestandardcreatesadIlemma.TheNFPA99Standard for Health Care
Facilities,2005edItIon,mandatesthatwetlocatIonpatIentcareareasbeprovIdedwIth
specIalprotectIonagaInstelectrIcalshock.SectIonJ4.1.2.6furtherstatesthatthIs
specIalprotectIonshallbeprovIdedbyapowerdIstrIbutIonsystemthatInherentlylImIts
thepossIblegroundfaultcurrentduetoafIrstfaulttoalowvalue,wIthoutInterruptIng
thepowersupply;orbyapowerdIstrIbutIonsystemInwhIchthepowersupplyIs
InterruptedIfthegroundfaultcurrentdoes,Infact,exceedavalueof6mIllIamperes.
ThedecIsIonofwhethertoInstallIsolatedpowerhIngesontwofactors.ThefIrstIs
whetherornottheDFIsconsIdereda
P.185
wetlocatIon,and,Ifso,whetheranInterruptIblepowersupplyIstolerable.Wherepower
InterruptIonIstolerable,aCFCIspermIttedastheprotectIvemeans.However,the
standardalsostatesthattheuseofanIsolatedpowersystem(PS)shallbepermIttedasa
protectIvemeanscapableoflImItInggroundfaultcurrentwIthoutpowerInterruptIon.
|ostpeoplewhohaveworkedInanDFwouldattesttoItsbeIngawetlocatIon.The
presenceofblood,bodyfluIds,andsalInesolutIonsspIlledonthefloorallcontrIbuteto
makIngthIsawetenvIronment.ThecystoscopysuIteservesasagoodexample.
DncethepremIsethattheDFIsawetlocatIonIsaccepted,ItmustbedetermInedwhether
aCFCcanprovIdethemeansofprotectIon.TheargumentagaInstusIngCFCsIntheDFIs
IllustratedbythefollowIngexample.AssumethatdurInganopenheartprocedurethe
cardIopulmonarybypasspumpandthepatIentmonItorsarepluggedIntooutletsonthe
samebranchcIrcuIt.AlsoassumethatdurIngbypass,thecIrculatIngnursenowplugsIna
faultyheadlIght.fthereIsaCFCprotectIngthecIrcuIt,thefaultwIllbedetectedandthe
CFCwIllInterruptallpowertothepumpandthemonItors.ThIsundoubtedlywouldcause
agreatdealofconfusIonandconsternatIonamongtheDFpersonnelandmayplacethe
patIentatrIskforInjury.ThepumpwouldhavetobemanuallyoperatedwhIletheproblem
wasbeIngresolved.naddItIon,theCFCcouldnotbereset(andpowerrestored)untIlthe
headlIghtwasIdentIfIedasthecauseofthefaultandunpluggedfromtheoutlet.However,
IftheDFwereprotectedwIthanIsolatedpowersystemandL|,thesamescenarIowould
causetheL|toalarm,butthepumpandpatIentmonItorswouldcontInuetooperate
normally.TherewouldbenoInterruptIonofpowerandtheproblemcouldberesolved
wIthoutrIsktothepatIent.
tshouldberealIzedthataCFCIsanactIvesystem.ThatIs,apotentIallyhazardous
currentIsalreadyflowIngandmustbeactIvelyInterrupted,whereastheIsolatedpower
system(wIthL|)IsdesIgnedtobesafedurIngafIrstfaultsItuatIon.Thus,ItIsapassIve
systembecausenomechanIcalactIonIsrequIredtoactIvatetheprotectIon.
62
tIslIkelythathospItaladmInIstratorsmaywanttoelImInateIsolatedpowersystemsIn
newDFconstructIonasacostsavIngmeasure.Dthers,however,haveadvocatedthe
retentIonofIsolatedpowersystems.
62,6J,64
NottodothIswouldbeashortsIghted,
foolhardymeasure.ThIsIsespecIallytruebecausethecostofaddIngIsolatedpowerIs
estImatedtobe1ofthecostofconstructInganDF.
62
Althoughnotperfect,
65
theIsolated
powersystemandL|doprovIdeboththepatIentandDFpersonnelwIthasIgnIfIcant
amountofprotectIonInanelectrIcallyhazardousenvIronment.solatedpowersystems
provIdecleanstablevoltages,whIchIsImportantforsensItIvedIagnostIcequIpment.
66
Also,modernL|s,whIcharemIcroprocessorbased,requIreonlyyearlyInsteadofmonthly
testIng.
ThevalueoftheIsolatedpowersystemIsIllustratedInareportby0ay
67
In1994.He
reportedfourInstancesofelectrIcalshocktoDFpersonnelIna1yearperIod.The
operatIngsuItehadbeenrenovatedandtheIsolatedpowersystemremoved,andItwasnot
untIltheDFpersonnelreceIvedashockthataproblemwasdIscovered.
AnesthesIologIstsneedtobeawareofthIscostsavIngattItudeandstronglyencouragethat
newDFsbeconstructedwIthIsolatedpowersystems.TherelatIvelysmallcostsavIngsthat
thealternatIvewouldrepresentdonotjustIfytheelImInatIonofsuchausefulsafety
system.TheuseofCFCsIntheDFenvIronmentcanbeacceptableIfcarefullyplannedand
engIneered.nordertoavoIdthelossofpowertomultIpleInstrumentsandmonItorsat
onetIme,eachoutletmustbeanIndIvIdualCFC.fthatIsdone,thenafaultwIllresultIn
onlyonepIeceofequIpmentlosIngpower.UsIngCFCsalsoprecludestheuseofmultIple
plugstrIpsIntheDF.
ElectrIcalsafetyshouldbetheconcernofeveryoneIntheDF.AccIdentscanbeprevented
onlyIfproperInstallatIonandmaIntenanceoftheapproprIatesafetyequIpmentIntheDF
haveoccurredandtheDFpersonnelunderstandtheconceptsofelectrIcalsafetyandare
vIgIlantIntheIreffortstodetectnewhazards.
68
Fire Safety
FIresIntheDFarejustasmuchadangertodayastheywere100yearsagowhenpatIents
wereanesthetIzedwIthflammableanesthetIcagents.
69,70
8ecausethepotentIal
consequencesofafIreorexplosIonwIthetherorcyclopropanewerewellknownand
potentIallydevastatIng,DFfIresafetypractIceswereroutInelyfollowed.
71,72
Today,therIskofanDFfIreIsprobablyasgreatorgreaterthanthedayswhenetherand
cyclopropanewereused,InpartbecauseoftheroutIneuseofpotentIalsourcesofIgnItIon
(IncludIngelectrosurgIcalcauterIes)InanenvIronmentrIchInfuelsources(I.e.,flammable
materIals)andoxIdIzers(e.g.,oxygenandnItrousoxIde).AlthoughthenumberofDFfIres
thatoccurannuallyIntheUnItedStatesIsunknown,someestImatessuggestthatthereare
50to200fIreseachyear,wIthasmanyas20assocIatedwIthserIousInjuryordeath.n
contrasttotheeraofflammableanesthetIcs,therecurrentlyappearstobealackof
awarenessofthepotentIalforanDFfIre.nresponsetotherIskspresentedbythIs
sItuatIon,In2008theAmerIcanSocIetyofAnesthesIologIstsreleasedaPractIceAdvIsoryon
thePreventIonand|anagementofDperatIngFoomFIres
7J
(Table8J).
ForafIretostart,threecomponentsarenecessary.ThelImbsofthefIretrIadareaheat
orIgnItIonsource,fuel,andanoxIdIzer.
74
AfIreoccurswhenthereIsachemIcalreactIon
ofafuelrapIdlycombInIngwIthanoxIdIzertoreleaseenergyIntheformofheatandlIght.
ntheDF,therearemanyheatorIgnItIonsources,suchastheESU,lasers,andtheendsof
fIberoptIclIghtcords.ThemaInoxIdIzersIntheDFareaIr,oxygen,andnItrousoxIde.
DxygenandnItrousoxIdefunctIonequallywellasoxIdIzers,soacombInatIonof50oxygen
and50nItrousoxIdewouldsupportcombustIon,aswould100oxygen.FuelforafIrecan
befoundeverywhereIntheDF.Paperdrapes,whIchhavelargelyreplacedclothdrapes,
aremucheasIertoIgnIteandcanburnwIthgreaterIntensIty.
75,76
Dthersourcesoffuel
IncludegauzedressIngs,endotrachealtubes,gelmattresspads,andevenfacIalorbody
haIr
77
(Table84).
FIrepreventIonIsaccomplIshedbynotallowIngallthreeoftheelementsofthefIretrIad
tocometogetheratthesametIme.
78
ThechallengeIntheDFIsthatfrequentlyeachof
thelImbsofthefIretrIadIscontrolledbyadIfferentIndIvIdual.ForInstance,thesurgeon
IsfrequentlyInchargeoftheIgnItIonsource,theanesthesIologIstIsusuallyadmInIsterIng
theoxIdIzer,andtheDFnursefrequentlycontrolsthefuelsources.tIsnotalwaysevIdent
toanyoneIndIvIdualthatalloftheseelementsmaybecomIngtogetheratthesametIme.
ThIsIsespecIallytrueInanycaseInwhIchthereIsthepossIbIlItyofoxygenoranoxygen
nItrousoxIdemIxturebeIngdelIveredaroundthesurgIcalsIte.nthesecIrcumstances,the
rIskofanDFfIreIsmarkedlyIncreasedandtheneedforcommunIcatIonamongthe
surgeon,theanesthesIologIst,andtheDFnursesthroughouttheprocedureIsessentIal.
ThereareseveraldangersthatmayresultfromanDFfIre.ThemostobvIousIsthatthe
patIentandDFpersonnelcansuffersevereburns.However,alessobvIousbutpotentIally
moredeadlyrIskcanbeposedbytheproductsofcombustIon(calledtoxicants).When
materIals,suchasplastIcsburn,avarIetyofInjurIouscompoundscanbeproduced.These
IncludecarbonmonoxIde,ammonIa,hydrogenchlorIde,and
P.186
P.187
evencyanIde.ToxIcantscanproduceInjurybydamagIngaIrwaysandlungtIssue,andcan
causeasphyxIa.DFfIrescanoftenproducesIgnIfIcantamountsofsmokeandtoxIcants,but
maynotcauseenoughheattoactIvateoverheadsprInklersystems.fenoughsmokeIs
produced,theDFpersonnelmayhavetoevacuatethearea.Thus,ItIsessentIaltohavea
prethoughtoutevacuatIonplanforboththeDFpersonnelandthepatIent.
Table 8-3 Recommendations for the Prevention and Management of
Operating Room Fires
Preparation
TraInpersonnelInDFfIremanagement
PractIceresponsestofIres(fIredrIlls)
AssurethatfIremanagementequIpmentIsreadIlyavaIlable
0etermIneIfahIghrIsksItuatIonexIsts
TeamdecIdeshowtoprevent/manageafIre
EachpersonassIgnedatask(e.g.,removeendotrachealtubeordIsconnect
cIrcuIt)
Prevention
AllowflammableskInpreparatIonstodrybeforedrapIng
ConfIguresurgIcaldrapestoavoIdbuIldupofoxIdIzer
AnesthesIologIstcollaborateswIthteamthroughouttheproceduretomInImIze
oxIdIzerenrIchedenvIronmentnearIgnItIonsource
KeepD
2
concentratIonaslowasclInIcallypossIble
AvoIdN
2
D
NotIfysurgeonIfoxIdIzerIgnItIonsourceareInproxImItytoeachother
|oIstengauzeandspongesthatarenearanIgnItIonsource
Management
LookforearlywarnIngsIgnofafIre(e.g.,pop,flash,orsmoke)
StopprocedureandeachteammemberImmedIatelycarrIesoutassIgnedtask
Airway fire
Simultaneouslyremovetheendotrachealtubeandstopgases/dIsconnectcIrcuIt
PoursalIneIntoaIrway
FemoveburnIngmaterIals
|askventIlatepatIent,assessInjury,consIderbronchoscopy,reIntubate
Fire on the patient
Turnoffgases
FemovedrapesandburnIngmaterIals
ExtInguIshflameswIthwater,salIne,orfIreextInguIsher
AssesspatIent'sstatus,devIsecareplan,assessforsmokeInhalatIon
Failure to extinguish
UseCD
2
fIreextInguIsher
ActIvatefIrealarm
ConsIderevacuatIonofroom:closedooranddonotreopen
TurnoffmedIcalgassupplytoroom
Risk management
Preservescene
NotIfyhospItalrIskmanager
FollowlocalregulatoryreportIngrequIrements
TreatfIreasanadverseevent
FFE0FLLS
AdaptedfromPractIceAdvIsoryforthePreventIonand|anagementofDperatIng
FoomFIres,ParkFIdge,L,AmerIcanSocIetyofAnesthesIologIsts.Approvedbythe
ASAHouseof0elegatesInDctober2007;publIshedInAnesthesiology,|ay2008.
Table 8-4 Fuel Sources Commonly Found in the Operating Room
Prepagents
Alcohol
0egreasers(acetone,ether)
AdhesIves(tInctureofbenzoIn,Aeroplast)
ChlorhexIdInedIgluconate(HIbItane)
odophor(0uraPrep)
0rapesandcovers
PatIentdrapes(paper,plastIc,cloth)
EquIpmentdrapes(paper,plastIc,cloth)
8lanketsandsheets
PIllows,mattresses,andpaddIng
Cowns
|asks
Shoecovers
Cloves(latex,nonlatex)
ClothIng
CompressIon(antIembolIsm)stockIngs
PatIent
HaIr
AlImentarytractgases(methane,hydrogen)
0esIccatedtIssue
0ressIngs
Cauzeandsponges
PetrolatumImpregnateddressIngs
Xeroform
AdhesIvetape(cloth,plastIc,paper)
ElastIcbandages
StockInettes
Sutures
SterIStrIps
CollodIon
DIntments
Petrolatum
AntIbIotIcs(bacItracIn,neomycIn,polymyxIn8)
NItropaste(NItro8Id)
E|LA
LIpbalms
AnesthesIaequIpment
8reathIngcIrcuIthoses
|asks
Endotrachealtubes
DralandnasalaIrways
LaryngealmaskaIrways
NasogastrIctubes
SuctIoncathetersandtubIng
Scavengerhoses
7olatIleanesthetIcs
CD
2
absorbers
ntravenoustubIng
PressuremonItortubIngandplastIctransducers
DtherequIpment
Chartsandrecords
Cardboard,wooden,andpartIcleboardboxesandcabInets
PackIngmaterIals(cardboard,expandedpolystyrene[Styrofoam])
FIberoptIccablecovers
WIrecoversandInsulatIon
FIberoptIcendoscopecoverIngs
SphymomanometercuffsandtubIng
PneumatIctournIquetcuffsandtubIng
StethoscopetubIng
7ascularshunts(Coretex,0acron)
0IalysIsandextracorporealcIrculatIoncIrcuIts
WounddraInsandcollectIonsystems
|opsandbrooms
TextbooksandInstructIonmanuals
DFfIrescanbedIvIdedIntotwodIfferenttypes.ThemorecommontypeoffIreoccursinor
onthepatIent,especIallydurInghIghrIskproceduresInwhIchanIgnItIonsourceIsusedIn
anoxIdIzerrIchenvIronment.ThesewouldIncludeaIrwayfIres(IncludIngendotracheal
tubefIres,fIresIntheoropharynx,whIchmayoccurdurIngatonsIllectomy,andfIresInthe
breathIngcIrcuIt),andfIresdurInglaparoscopy.FIresoccurrIngonthepatIentmaInly
InvolveheadandnecksurgerydoneunderregIonalanesthesIaormonItoredanesthesIa
carewhenthepatIentIsreceIvInghIghflowsofsupplementaloxygen.8ecausethesefIres
occurInanoxygenenrIchedenvIronment,ItemssuchassurgIcaltowels,drapes,oreven
thebodyhaIrcanbereadIlyIgnItedandproduceasevereburn.TheothertypeofDFfIreIs
onethatIsremotefromthepatIent.ThIswouldIncludeanelectrIcalfIreInapIeceof
equIpment,oracarbondIoxIde(CD
2
)absorberfIre.
ThetwomajorIgnItIonsourcesforDFfIresaretheESUandthelaser.However,theendsof
somefIberoptIclIghtcordscanalsobecomehotenoughtostartafIreIftheyareplacedon
paperdrapes.AlthoughtheESUIsresponsIbleforIgnItIngthemajorItyofthefIres,
79
ItIs
thelaserthathasgeneratedthemostattentIonandresearch.LaserIstheacronymfor
lIghtamplIfIcatIonbystImulatedemIssIonofradIatIon.AlaserconsIstsofanenergysource
andmaterIalthattheenergyexcItestoemItlIght.
80,81,82
ThematerIalthattheenergy
excItesIscalledthelasing mediumandprovIdesthenameofthepartIculartypeoflaser.
TheImportantpropertyoflaserlIghtIsthatItIscoherent,meanIngthatIsmonochromatIc
(orevenofasInglewavelength).ThIscoherentlIghtcanbefocusedIntoverysmallspots
thathaveveryhIghpowerdensIty.
TherearemanydIfferenttypesofmedIcallasers,andeachhasaspecIfIcapplIcatIon.The
argonlaserIsusedIneyeanddermatologIcproceduresbecauseItIsabsorbedby
hemoglobInandhasamodesttIssuepenetratIonofbetween0.05and2.0mm.The
potassIumtItanylphosphate(KTP)orfrequencydoubledyttrIumalumInumgarnet(YAC)
lasersarealsoabsorbedbyhemoglobInandhavetIssuepenetratIonssImIlartothatofthe
argonlaser.The0IlaserhasawavelengththatIseasIlychangedandcanbeusedIn
dIfferentapplIcatIons,partIcularlyIndermatologIcprocedures.TheneodymIumdoped
yttrIumalumInumgarnet(Nd:YAC)laserIsthemostpowerfulofthemedIcallasers.SInce
thetIssuepenetratIonIsbetween2and6mm,ItcanbeusedfortumordebulkIng,
partIcularlyInthetracheaandmaInstembronchI,orIntheupperaIrway.Theenergycan
betransmIttedthroughafIberoptIccablethatIsplaceddownthesuctIonportofa
fIberoptIcbronchoscope.ThelasercanthenbeusedInacontactmodetotreatatumor
mass.TheCD
2
laserhasverylIttletIssuepenetratIonandcanbeusedwheregreat
precIsIonIsneeded.tIsalsoabsorbedbywater,sothatmInImalheatIsdIspersedto
surroundIngtIssues.TheCD
2
laserIsusedprImarIlyforproceduresIntheoropharynxandIn
andaroundthevocalcords.ThehelIumneonlaser(HeNe)producesanIntenseredlIght
andthuscanbeusedforaImIngtheCD
2
andtheNd:YAClasers.thasverylowpowerand
thuswIllpresentnosIgnIfIcantdangertoDFpersonnel.
DneofthemostdevastatIngtypesofDFfIresoccurswhenanendotrachealtubeIsIgnIted
inthepatIent.
8J,84,85,86,87,88
fthepatIentIsbeIngventIlatedwIthoxygenand/ornItrous
oxIde,theendotrachealtubewIllessentIallyemItablowtorchtypeofflamethatcanresult
InsevereInjurytothetrachea,lungs,andsurroundIngtIssues.Fedrubber,polyvInyl
chlorIde,andsIlIconeendotrachealtubesallhaveoxygenflammabIlItyIndIces(defInedas
themInImumD
2
fractIonInN
2
thatwIlljustsupportacandlelIkeflameforagIvenfuel
sourceusIngastandardIgnItIonsource)
89
of26.
90
HIstorIcally,anesthesIologIsts
attemptedtoImprovethesafetyofthesetubesbywrappIngredrubberorpolyvInyl
chlorIdetubeswIthsomesortofreflectIvetape.However,tapedwrappedtubesoften
becamekInked,gapsInthetapeexposedareasofthetubetothelaser,andnonlaser
resIstanttapewassometImesunIntentIonallyused.TopreventtheseproblemsdurInghIgh
rIskprocedures,laserresIstantendotrachealtubeshavebeendeveloped.
91,92,9J
AnesthesIologIstscannowuseanendotrachealtubethatIsdesIgnedtoberesIstantto
IgnItIonbythespecIfIctypeoflaserthatwIllbeuseddurIngsurgery.ForInstance,when
usIngtheCD
2
laser,theLaserFlex(|allInckrodt,Pleasanton,CA)IsanexcellentchoIce.
ThIsIsaflexIblemetaltubethathastwocuffsthatcanbeInflatedwIthsalInecoloredwIth
methyleneblue.ThemethyleneblueenablesthesurgeontoeasIlyrecognIzeIfheorshe
hasaccIdentallypenetratedoneofthecuffs.TheLaserFlextubeIshIghlyresIstantto
beIngstruckbythelaser.ftheNd:YAClaserIsbeIngused,thentheLasertubus(Fusch
nc.,0uluth,CA)canbeused.TheLasertubushasasoftrubbershaftthatIscoveredbya
corrugatedsIlverfoIlthatIsInturncoveredIna|erocelspongejacket.nordertoprovIde
maxImumprotectIon,the|erocelmustbekeptmoIstwIthsalIne.
AnotherpotentIalsourceofIgnItIonforanDFfIreIstheESU.
94,95
AtypIcalexampleofhow
anESUcouldcauseIgnItIonwouldbedurIngatonsIllectomyInachIldInwhomthe
anesthesIologIstwasusInganuncuffed,flammableendotrachealtube.nthIscase,the
oxygenoroxygennItrousoxIdemIxturecouldleakaroundtheendotrachealtubeandpool
attheoperatIvesIte,provIdInganoxIderenrIchedenvIronment.Whenthesurgeonuses
theESU(orlaser)tocauterIzethetonsIlbed,thecombInatIonofahIghconcentratIonof
oxIdIzer(oxygenoroxygennItrousoxIdemIxture),fuel(endotrachealtube),andIgnItIon
source(theESUorlaser)couldeasIlystartafIre.
96,97
ThebestwaytopreventthIstypeoffIreIstotakestepstopreventthethreelegsofthe
fIretrIadfromcomIngtogether.Forexample,mIxIngtheoxygenwIthaIrwIllkeepthe
InspIredoxygenconcentratIonaslowaspossIble,thusreducIngtheavaIlableoxIdIzer.
AnotherpossIbIlItywouldbetoplacewetpledgetsaroundtheendotrachealtube,whIch
wouldpreventtheescapeofoxygenoroxygennItrousoxIdemIxturefromthetracheaInto
theoperatIvefIeld.ThIsreducestheavaIlableoxIdIzerandwouldkeeptheendotracheal
tubeandtIssuesfrombecomIngdesIccated,thusreducIngtheIrsuItabIlItyasfuelsources.
However,thepledgetsmustbekeptmoIst,lesttheydryoutandbecomeanaddItIonal
sourceoffuelforafIre.
ArelatedsItuatIonthatrequIresadIfferentsolutIoncanarIsewhenacrItIcallyIllpatIent
requIresatracheostomy.
98,99
ThesepatIentsmayrequIreveryhIghconcentratIonsof
InspIredoxygentomaIntaIntIssueoxygenatIonsothatanydecreaseInInspIredoxygen
concentratIonorInterruptIonofventIlatIonwouldnotbetolerated.nthIscIrcumstance,
thebestoptIonforpreventIngafIrewouldbetoavoIdtheuseofelectrocautery(IgnItIon
source)whenthesurgeonentersthetrachea.
TheNd:YAClasercanbeusedtotreattumorsofthelowertracheaandmaInstembronchI.
|ostcommonly,thesurgeonwIlluseafIberoptIcbronchoscope(FD8)andpassthelaser
fIberthroughthesuctIonportofthebronchoscope.ThefIberoptIcbronchoscopecanbe
usedInconjunctIonwItharIgIdmetalbronchoscopeorpassedthroughan8.5or9.0mm
polyvInylchlorIdeendotrachealtube.AspecIallaserresIstanttubewouldnotbeusedIn
thIscIrcumstancebecausetheFD8andlaserfIberpassthroughtheendotrachealtubeand
focusontIssuedIstaltothetube.FIresafetyprecautIons
P.188
avaIlableInthIssettIngIncludetItratIngtheconcentratIonofInspIredoxygentoaslowa
concentratIonasthepatIentcantoleratewhIlemaIntaInIngasaturatIonofbetween90and
95(IdeallykeepIngtheInspIredoxygenbelowJ0),keepIngthetIpoftheendotracheal
tubeandFD8awayfromthesIteofsurgeryandoutofthelIneoffIreofthelaser,and
removIngcharredanddesIccatedtIssuefromthesurgIcalfIeld.
TheuseofarIgIdmetalbronchoscopeInsteadofanendotrachealtubewIllelImInatethe
possIbIlItyofsettIngthetubeonfIrebutdoesnotelImInatethepossIbIlItyofsettIngthe
FD8onfIre.ThIswouldalsonecessItatetheuseofajetventurIsystemtoventIlatethe
patIent,whIchwould,Inturn,delIveranInspIredoxygenconcentratIonofbetween40and
60.
ThereareanumberofbasIcsafetyprecautIonsthatshouldbetakenwheneveralaserIs
usedInsurgery.SIncelaserlIghtcanbereflectedoffanymetalsurface,ItIsImportant
thatallDFpersonnelwearprotectIvegogglesthatarespecIfIctothetypeoflaserbeIng
used.TheanesthesIologIstneedstobeawarethatthelasergogglesmaymakeItdIffIcultto
readcertaInmonItordIsplays.naddItIon,ItIsImportantthatthepatIent'seyesbe
coveredwIthwetgauzeoreyepacks.DFpersonnelshouldalsowearhIghfIltratIonmasks
becausethelaserplumemaycontaInvaporIzedvIruspartIclesorchemIcaltoxIns.
FInally,alldoorstotheDFshouldhavewarnIngsIgnsthatalaserIsInuse,andallwIndows
shouldbecoveredwIthblackwIndowshades.
LaparoscopIcsurgeryIntheabdomenIsanotherpotentIalrIskforasurgIcallyrelatedfIre.
DrdInarIly,theabdomenIsInflatedwIthCD
2
,whIchdoesnotsupportcombustIon.tIs
ImportanttoverIfythat,Indeed,onlyCD
2
IsbeIngused,aserroneousInclusIonofoxygen
canbedIsastrous.
100
Also,nItrousoxIdeadmInIsteredtothepatIentaspartofthe
anesthetIccan,overJ0mInutes,dIffuseIntotheabdomInalcavItyandattaIna
concentratIonthatcouldsupportcombustIon.
101
nfact,whensamplIngtheabdomInalgas
contentsafterJ0mInutes,themeannItrousoxIdeconcentratIonwasJ6;however,In
certaInpatIentsItreachedaconcentratIonof47.8othmethaneandhydrogenare
flammablegasesthatarefrequentlypresentInbowelgasInsIgnIfIcantconcentratIons.
|ethaneconcentratIonInbowelgascanbeupto56andhydrogenhasbeenreportedas
hIghas69.WIththemaxImumabdomInalconcentratIonof47nItrousoxIdemIxedwIth
CD
2
,ItwouldrequIrethemaxImumof56ofmethanetobeflammable.Therefore,thIs
representsarelatIvelysmallhazard.ncontrast,aconcentratIonof69hydrogenIs
flammableIfthenItrousoxIdeconcentratIonIs29.Therefore,afIreIspossIbleIfthe
surgeon,whIleusIngtheESU,entersthebowelwIthahIghconcentratIonofhydrogenand
theIntraabdomInalnItrousoxIdecontentIs29.
nrecentyears,fIresonthepatIentseemtohavebecomethemostfrequenttypeofDF
fIre.ThesecasesoccurmostoftendurIngsurgeryInandaroundtheheadandneck,where
thepatIentIsreceIvIngmonItoredanesthesIacareandsupplementaloxygenIsbeIng
admInIsteredbyeItherafacemaskornasalcannulae.
102,10J,104,105,106
nthesecases,the
oxygencancollectunderthedrapesIfnotproperlyvented,andwhenthesurgeonusesthe
ESUorthelaser,afIrecaneasIlystart.TherearemanythIngsthatcanactasfuel,suchas
thesurgIcaltowels,paperdrapes,dIsInfectIngpreparatIonsolutIons,sponges,plastIc
tubIngfromtheoxygenfacemask,andeventhebodyhaIr.ThesefIresstartveryquIckly
andcanturnIntoanIntenseblazeInonlyafewseconds.EvenIfthefIreIsquIckly
extInguIshed,thepatIentwIllusuallysustaInasIgnIfIcantburn.
ThemostImportantprIncIplethattheanesthesIologIsthastokeepInmIndtomInImIzethe
rIskoffIreIstotItratetheInspIredoxygentothelowestamountnecessarytokeep
patIent'soxygenatIonwIthInsafelevels.ftheanesthesIamachInehastheabIlItytodelIver
aIr,thenthenasalcannulaorfacemaskcanbeattachedtotheanesthesIacIrcuItbyusIng
asmallno.Jorno.4,15mmendotrachealtubeadapter.ThIsIsattachedtotherIght
angleelbowofthecIrcuIt.ftheanesthesIamachIneIsequIppedwIthanauxIlIaryoxygen
flowmeterthathasaremovablenIppleadapter,thenahumIdIfIercanbeInstalledInplace
ofthenIppleadapter.ThehumIdIfIerhasa7enturImechanIsmthroughwhIchroomaIrIs
entraInedandthustheoxygenconcentratIonthatIsdelIveredtothefacemaskcanbe
varIedfrom28to100.FInally,IfthIsmachInehasacommongasoutletthatIseasIly
accessIble,anasalcannulaorfacemaskcanbeattachedatthIspoIntusIngthesamesmall
Jor4mmendotrachealtubeadaptor.fItIsnotpossIbletodIlutetheoxygenwIthaIr,
thenItIsImportantthatthedrapesbearrangedInsuchamannerthatthereIsnooxygen
buIldupbeneaththem.TentIngthedrapesandhavIngthesurgeonuseanadhesIvestIcky
drapethatsealstheoperatIvesItefromtheoxygenflowarestepsthatwIllhelpreducethe
rIskofafIre.
tIspotentIallypossIbletodIscontInuetheuseofoxygenbeforethesurgeonplanstouse
theelectrocauteryorlaser.ThIswouldhavetobedoneseveralmInutesbeforehandIn
ordertoallowanyoxygenthathasbuIltuptodIssIpate.fthesurgeonIsplannIngtouse
theelectrocauteryorlaserdurIngtheentIrecase,thIsmaynotbepractIcal.
SomenewersurgIcalpreparatIonsolutIonscancontrIbutetosurgIcallyrelatedfIres.These
solutIonstypIcallycomeprepackagedInapaIntstIckapplIcatorwIthaspongeontheend
(e.g.,0uraPrep,St.Paul,|N).tconsIstsofodophormIxedwIth74Isopropylalcohol.
ThIsIshIghlyflammableandcaneasIlybethefuelforanDFfIre.n2001,8arkerand
Polson
102
reportedjustsuchacase.nalaboratoryrecreatIon,theyfoundthatIfthe
0uraPrephadbeenallowedtodrycompletely(4to5mInutes),thefIredIdnotoccur(FIg.
8J6).TheotherproblemwIththesetypesofpreparatIonsolutIonsIsthatsmallpoolsofthe
solutIoncanaccumulateIfthepersondoIngthepreparatIonIsnotcareful.ThealcoholIn
thesesmallpuddleswIllcontInuetoevaporateforaperIodoftIme,andthealcoholvapors
arealsoextremelyflammable.FlammableskInpreparatIonsolutIonsshouldbeallowedto
dryandpuddlesremovedbeforethesIteIsdraped(FIg.8J7).
tIsImportanttobearInmIndthathalogenatIonofhydrocarbonanesthetIcsconfers
relatIve,butnotabsolute,resIstancetocombustIon.Eventhenewer,nonflammable
volatIleanesthetIcscan,undercertaIncIrcumstances,presentfIrehazards.Forexample,
sevofluraneIsnonflammableInaIr,butcanserveasafuelatconcentratIonsaslowas11
Inoxygenand10InnItrousoxIde.
107
naddItIon,sevofluraneanddesIccatedCD
2
absorbent(eIthersodalImeor8aralyme)canundergoexothermIcchemIcalreactIonsthat
havebeenImplIcatedInseveralfIresthatInvolvedtheanesthesIabreathIng
cIrcuIt.
108,109,110,111
n200J,themanufacturerofsevofluranepublIsheda0earHealth
CareProvIderletterandadvIsoryalert.
112
TopreventfuturesfIres,themanufacturerof
sevofluranehasrecommendedthatanesthesIologIstsemployseveralmeasures,IncludIng
avoIdIngtheuseofdesIccatedCD
2
absorbentandmonItorIngthetemperatureofthe
absorbersandtheInspIredconcentratIonofsevoflurane;Ifelevatedtemperatureoran
InspIredsevofluraneconcentratIonthatdIfferedunexpectedlyfromthevaporIzersettIngIs
detected,ItIsrecommendedthatthepatIentbedIsconnectedfromtheanesthesIacIrcuIt
andmonItoredforsIgnsofthermalorchemIcalInjury,andthattheCD
2
absorbentIs
removedfromthecIrcuItand/orreplaced.
AnotherwaytopreventthIstypeoffIreIstouseaCD
2
absorbentthatdoesnotcontaIna
strongalkalI,asdosodalImeand8aralyme(Chemetron|edIcal0IvIsIon,AllIed
HealthcareProducts,St.LouIs,|IssourI).Amsorb(Amstrong|edIcalLImIted,ColeraIne,
Northernreland)IsaCD
2
absorbentthatcontaInscalcIumhydroxIdeandcalcIumchlorIde,
butnostrongalkalI.
11J
nexperImentalstudIes,ItwasfoundthatAmsorbIsunreactIve
wIthcurrentlyusedvolatIleanesthetIcs
P.189
anddoesnotproducecarbonmonoxIdeorCompoundAwIthdesIccatedabsorbent.
Therefore,ItwouldnotInteractwIthsevofluraneandundergoanexothermIcchemIcal
reactIon.
Figure 8-36.SImulatIonoffIrecausedbyESUelectrodedurIngsurgery.A.|annequIn
preparedanddrapedforsurgery.ElectrosurgIcalunItmonopolarpencIlelectrode
applIedtooperatIvesIteatstartofsurgery.B.SIxsecondsafterelectrosurgIcalunIt
applIcatIon.Smokeappearsfromunderthedrapes.C.Fourteensecondsafter
electrosurgIcalunItapplIcatIon.Flamesburstthroughthedrapes.D.Twentyfour
secondsafterelectrosurgIcalunItapplIcatIon.EntIrepatIentheadanddrapesIn
flames.(From8arkerSJ,PolsonJS:FIreIntheoperatIngroom:Acasereportand
laboratorystudy.AnesthAnalg2001;9J:960,wIthpermIssIon.)
fafIredoesoccur,ItIsImportanttoextInguIshItassoonaspossIble.ThefIrststepIsto
InterruptthefIretrIadbyremovIngonecomponent.ThIsIsusuallybestaccomplIshedby
removIngtheoxIdIzerfromthefIre.Therefore,IfanendotrachealtubeIsonfIre,
dIsconnectIngthecIrcuItfromthetubeordIsconnectIngtheInspIratorylImbofthecIrcuIt
wIllusuallyresultInthefIreImmedIatelygoIngout.SImultaneouslythesurgeonshould
removetheburnIngendotrachealtube.DncethefIreIsextInguIshed,theaIrwayInspected
vIabronchoscopy,andthepatIentreIntubated.
Figure 8-37.AdemonstratIonoftheIntenseheatandflamethatIspresentInan
alcoholfIre.(Photographcourtesyof|arc8ruleyofEmergencyCareFesearch
nstItute.FeprIntedwIthpermIssIon,CopyrIght2009,ECFnstItute.www.ecrI.org.)
fthefIreIsonthepatIent,thenextInguIshIngItwIthabasInofsalInemaybethemost
rapIdandeffectIvemethodtodealwIththIstypeoffIre.ThereIsalsoamethodtousea
sheetortoweltoextInguIshthefIre.fthedrapesareburnIng,partIcularlyIftheyare
paperdrapes,thentheymustberemovedandplacedonthefloor.Paperdrapesare
ImpervIoustowater;thus,throwIngwaterorsalIneonthemwIlldolIttletoextInguIshthe
fIre.DncetheburnIngdrapesareremovedfromthepatIent,thefIrecanthenbe
extInguIshedwIthafIreextInguIsher.nmostDFfIres,thesprInklersystemIsnot
actIvated.ThIsIsbecausethesprInklersarenotlocateddIrectlyovertheDFtableand
becauseDFfIresseldomgethotenoughtoactIvatethesprInklers.
AllDFpersonnelshouldreceIveDFfIresafetyeducatIon,whIchshouldIncludetraInIngIn
InstItutIonalfIresafetyprotocolsandlearnIngthelocatIonandoperatIonofthefIre
extInguIshers.FIresafetyeducatIon,IncludIngfIredrIlls,allowseachmemberoftheDF
teamtolearnandpractIcewhathIsorherresponsIbIlItIesandactIonsshouldbeIfafIre
wereto
P.190
occur.FIredrIllsareanImportantpartoftheplanandcanhelppersonnelbecomefamIlIar
wIththeexIts,evacuatIonroutes,locatIonoffIreextInguIshers,andhowtoshutoff
medIcalgasandelectrIcalsupplIes.AlthoughInstItutIonalfIresafetyprotocolsvary,the
generalprIncIplesofrespondIngtoanDFfIrecanbesummarIzedbythemnemonIcEFASE:
extInguIsh,rescue,actIvate,shut,andevaluate.nsequence:FIrst,theteamshould
generallyattempttoextInguIshafIreon,In,ornearthepatIent.0ependIngonthe
sItuatIon,thIsmayIncludetheuseofsalIneoraCD
2
fIreextInguIsher(seelaterdIscussIon).
ftheInItIalattemptsatextInguIshIngthefIreareunsuccessful,thepatIentandallother
personsatrIskshouldberescuedandtheDFevacuated,IfpossIble,andthefIrealarm
shouldbeactIvated.DncetheDFIsemptIedofpersonnel,thedoorsshouldbeshutandthe
medIcalgassupplytotheroomshouldbeshutoff.ThepatIentshouldthenbeevaluated
andanyInjurIesshouldbeapproprIatelymanaged.
FIreextInguIshersaredIvIdedIntothreeclasses,termedA, B,andC,basedonthetypesof
fIresforwhIchtheyarebestsuIted.ClassAextInguIshersareusedonpaper,cloth,and
plastIcmaterIals;Class8extInguIshersareusedforfIreswhenlIquIdsorgreaseare
Involved;ClassCextInguIshersareusedforenergIzedelectrIcalequIpment.AsInglefIre
extInguIshermaybeusefulforanyone,two,orallthreetypesoffIres.Probablythebest
fIreextInguIsherfortheDFIstheCD
2
extInguIsher.ThIscanbeusedonClass8andCfIres
andsomeClassAfIres.DtherextInguIshersarewatermIstandnewenvIronmentally
frIendlyfluorocarbonsthatreplacedtheHalonfIreextInguIsher.FInally,manyDFsare
equIppedwIthafIrehosethatsupplIespressurIzedwateratarateof50gallonsper
mInute.SuchequIpmentIsbestlefttothefIredepartmenttouse,unlessthereIsaneedto
rescuesomeonefromafIre.nordertoeffectIvelyuseafIreextInguIsher,theacronym
PASScanbeused.ThIsstandsforpullthepIntoactIvatethefIreextInguIsher,aImat
thebaseofthefIre,squeezethetrIgger,andsweeptheextInguIsherbackandforthacross
thebaseofthefIre.WhenrespondIngtoafIre,theacronymFACEIsuseful.ThIsstandsfor
rescue;alarm;confIne;extInguIsh.Clearly,havIngaplanthateveryoneIsfamIlIarwIth
wIllgreatlyfacIlItateextInguIshIngthefIreandmInImIzetheharmtothepatIentand
equIpment.
However,neItherfIredrIllsnorthepresenceanduseoffIreextInguIshersshouldberelIed
ontoprovIdeafIresafeoperatIngenvIronment.DnlythroughheIghtenedawareness,
contInuIngeducatIon,andongoIngcommunIcatIoncanthelegsofthefIretrIadbekept
apartandtherIskofanDFfIremInImIzed.
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Stock, M. Christine
TableofContentsSectIonScIentIfIcFoundatIonsofAnesthesIaChapter9ExperImental0esIgnandStatIstIcs
Chapter9
Experimental Design and Statistics
Nathan Leon Pace
Key Points
1. Statistics and mathematics are the language of scientific medicine.
2. Good research planning includes a clear biologic hypothesis, the
specification of outcome variables, the choice of anticipated statistical
methods, and sample size planning.
3. To avoid bias in the performance of clinical research, the crucial
elements of good research design include concurrent control groups,
random allocation of subjects to treatment groups, and blinding of
random allocation to patients, caregivers, and outcome assessors.
4. Descriptive (e.g., mean, standard deviation) and inferential statistics
(e.g., t test, confidence interval) are both essential methods for the
presentation of research results.
5. The central limit theorem allows the use of parametric statistics for
most statistical testing.
6. Systematic review and meta-analysis can synthesize and summarize
the results of smaller, nonsignificant individual studies and permit
more powerful inferences.
|edIcaljournalsarerepletewIthnumbers.TheseIncludeweIghts,lengths,pressures,
volumes,flows,concentratIons,counts,temperatures,rates,currents,energIes,and
forces.TheanalysIsandInterpretatIonofthesenumbersrequIretheuseofstatIstIcal
technIques.ThedesIgnoftheexperImenttoacquIrethesenumbersIsalsopartof
statIstIcalcompetence.TheneedforthesestatIstIcaltechnIquesIsmandatedbythe
natureofourunIverse,whIchIsbothorderlyandrandomatthesametIme.Themethods
ofprobabIlItyandstatIstIcshavebeenformulatedtosolveconcreteproblems,suchas
bettIngoncards,understandIngbIologIcInherItance,andImprovIngfoodprocessIng.
StudIesInanesthesIahaveevenInspIrednewstatIstIcs.ThedevelopmentofstatIstIcal
technIquesIsmanIfestIntheIncreasInguseofmoresophIstIcatedresearchdesIgnsand
statIstIcaltestsInanesthesIaresearch.
faphysIcIanIstobeapractItIonerofscIentIfIcmedIcIne,heorshemustreadthe
languageofscIencetobeabletoIndependentlyassessandInterpretthescIentIfIcreport.
WIthoutexceptIon,thelanguageofthemedIcalreportIsIncreasInglystatIstIcal.Feaders
oftheanesthesIalIterature,whetherInacommunItyhospItaloraunIversItyenvIronment,
cannotandshouldnottotallydependontheedItorsofjournalstobanIshallerrorsof
statIstIcalanalysIsandInterpretatIon.naddItIon,thereareregularlyquestIonsabout
sImplestatIstIcsInexamInatIonsrequIredforanesthesIologIsts.FInally,certaInstatIstIcal
methodshaveeverydayapplIcatIonsInclInIcalmedIcIne.ThIschapterbrIeflyscanssome
elementsofexperImentaldesIgnandstatIstIcalanalysIs.
Design of Research Studies
ThescIentIfIcInvestIgatorshouldvIewhImselforherselfasanexperImenterandnot
merelyasanaturalIst.ThenaturalIstgoesoutIntothefIeldreadytocaptureandreport
thenumbersthatflItIntovIew;thIsIsaworthyactIvIty,typIfIedbythecase report.Case
reportsengenderInterest,suspIcIon,doubt,wonder,andperhapsthedesIretoexperIment;
however,thecasereportIsnotsuffIcIentevIdencetoadvancescIentIfIcmedIcIne.The
experImenterattemptstoconstraInandcontrol,asmuchas
P.19J
possIble,theenvIronmentInwhIchheorshecollectsnumberstotestahypothesIs.The
elementsofexperImentaldesIgnareIntendedtopreventandmInImIzethepossIbIlItyof
bIas,thatIs,adevIatIonofresultsorInferencesfromthetruth.
Sampling
TwowordsofgreatImportancetostatIstIcIansarepopulationandsample.nstatIstIcal
language,eachhasaspecIalIzedmeanIng.nsteadofreferrIngonlytothecountof
IndIvIdualsInageographIcorpolItIcalregIon,populatIonreferstoanytargetgroupof
thIngs(anImateorInanImate)InwhIchthereIsInterest.ForanesthesIaresearchers,a
typIcaltargetpopulatIonmIghtbemothersInthefIrststageoflabororheadtrauma
vIctImsundergoIngcranIotomy.AtargetpopulatIoncouldalsobecellcultures,Isolated
organpreparatIons,orhospItalbIlls.AsampleIsasubsetofthetargetpopulatIon.Samples
aretakenbecauseoftheImpossIbIlItyofobservIngtheentIrepopulatIon;ItIsgenerallynot
affordable,convenIent,orpractIcaltoexamInemorethanarelatIvelysmallfractIonof
thepopulatIon.Nevertheless,theresearcherwIshestogeneralIzefromtheresultsofthe
smallsamplegrouptotheentIrepopulatIon.
AlthoughthesubjectsofapopulatIonarealIkeInatleastoneway,thesepopulatIon
membersaregenerallyquItedIverseInotherways.8ecausetheresearchercanworkonly
wIthasubsetofthepopulatIon,heorshehopesthatthesampleofsubjectsInthe
experImentIsrepresentatIveofthepopulatIon'sdIversIty.HeadInjurypatIentscanhave
openorclosedwounds,avarIetyofcoexIstIngdIseases,andnormalorIncreased
IntracranIalpressure.ThesesubgroupswIthInapopulatIonarecalledstrata.Dftenthe
researcherwIshestoIncreasethesamenessorhomogeneItyofthetargetpopulatIonby
furtherrestrIctIngIttojustafewstrata;perhapsonlyclosedandnotopenheadInjurIes
wIllbeIncluded.FestrIctIngthetargetpopulatIontoelImInatetoomuchdIversItymustbe
balancedagaInstthedesIretohavetheresultsbeapplIcabletothebroadestpossIble
populatIonofpatIents.
ThebesthopeforarepresentatIvesampleofthepopulatIonwouldberealIzedIfevery
subjectInthepopulatIonhadthesamechanceofbeIngIntheexperIment;thIsIscalled
random sampling.ftherewereseveralstrataofImportance,randomsamplIngfromeach
stratumwouldbeapproprIate.Unfortunately,InmostclInIcalanesthesIastudIes
researchersarelImItedtousIngthosepatIentswhohappentoshowupattheIrhospItals;
thIsIscalledconvenience sampling.ConvenIencesamplIngIsalsosubjecttothenuancesof
thesurgIcalschedule,thegoodwIllofthereferrIngphysIcIanandattendIngsurgeon,and
thewIllIngnessofthepatIenttocooperate.Atbest,theconvenIencesampleIs
representatIveofpatIentsatthatInstItutIon,wIthnoassurancethatthesepatIentsare
sImIlartothoseelsewhere.ConvenIencesamplIngIsalsotheruleInstudyIngnew
anesthetIcdrugs;suchstudIesaretypIcallyperformedonhealthy,youngvolunteers.
Experimental Constraints
TheresearchermustdefInethecondItIonstowhIchthesamplememberswIllbeexposed.
PartIcularlyInclInIcalresearch,onemustdecIdewhetherthesecondItIonsshouldbe
rIgIdlystandardIzedorwhethertheexperImentalcIrcumstancesshouldbeadjustedor
IndIvIdualIzedtothepatIent.nanesthetIcdrugresearch,shouldafIxeddosebegIvento
allmembersofthesampleorshouldthedosebeadjustedtoproduceaneffectorto
achIeveaspecIfIcendpoInt:StandardIzIngthetreatmentgroupsbyfIxeddosessImplIfIes
theresearchwork.TherearerIskstothIsstandardIzatIon,however:(1)afIxeddosemay
produceexcessIvenumbersofsIdeeffectsInsomepatIents,(2)afIxeddosemaybe
therapeutIcallyInsuffIcIentInothers,and(J)atreatmentstandardIzedforanexperImental
protocolmaybesoartIfIcIalthatIthasnobroadclInIcalrelevance,evenIfdemonstrated
tobesuperIor.Theresearchershouldcarefullychooseandreportthe
adjustment/IndIvIdualIzatIonofexperImentaltreatments.
Control Groups
EvenIfaresearcherIsstudyIngjustoneexperImentalgroup,theresultsoftheexperIment
areusuallynotInterpretedsolelyIntermsofthatonegroupbutarealsocontrastedand
comparedwIthotherexperImentalgroups.ExamInIngtheeffectsofanewdrugonblood
pressuredurInganesthetIcInductIonIsImportant,butwhatIsmoreImportantIscomparIng
thoseresultswIththeeffectsofoneormorestandarddrugscommonlyusedInthesame
sItuatIon.WherecantheresearcherobtaInthesecomparatIvedata:Thereareseveral
possIbIlItIes:(1)eachpatIentcouldreceIvethestandarddrugunderIdentIcalexperImental
cIrcumstancesatanothertIme,(2)anothergroupofpatIentsreceIvIngthestandarddrug
couldbestudIedsImultaneously,(J)agroupofpatIentscouldhavebeenstudIedprevIously
wIththestandarddrugundersImIlarcIrcumstances,and(4)lIteraturereportsofthe
effectsofthedrugunderrelatedbutnotnecessarIlyIdentIcalcIrcumstancescouldbeused.
UnderthefIrsttwopossIbIlItIes,thecontrolgroupIscontemporaneouseItheraself-
control(crossover)orparallel controlgroup.ThesecondtwopossIbIlItIesareexamplesof
theuseofhistorical controls.
8ecausehIstorIcalcontrolsalreadyexIst,theyareconvenIentandseemInglycheaptouse.
Unfortunately,thehIstoryofmedIcIneIslItteredwIththedebrIsoftherapIes
enthusIastIcallyacceptedonthebasIsofcomparIsonwIthpastexperIence.AclassIc
exampleIsoperatIvelIgatIonoftheInternalmammaryarteryforthetreatmentofangIna
pectorIsaprocedurenowknowntobeofnovalue.ProposedasamethodtoImprove
coronaryarterybloodflow,thelackofbenefItwasdemonstratedInatrIalwheresome
patIentshadtheprocedureandsomehadashamprocedure;bothgroupsshowedbenefIt.
1
ThereIsnowfIrmempIrIcalevIdencethatstudIesusInghIstorIcalcontrolsusuallyshowa
favorableoutcomeforanewtherapy,whereasstudIeswIthconcurrentcontrols,thatIs,
parallelcontrolgrouporselfcontrol,lessoftenrevealabenefIt.
2
NothIngseemsto
IncreasetheenthusIasmforanewtreatmentasmuchastheomIssIonofaconcurrent
controlgroup.ftheoutcomewIthanoldtreatmentIsnotstudIedsImultaneouslywIththe
outcomeofanewtreatment,onecannotknowIfanydIfferencesInresultsarea
consequenceofthetwotreatments,orofunsuspectedandunknowabledIfferences
betweenthepatIents,orofotherchangesovertImeInthegeneralmedIcalenvIronment.
DnepossIbleexceptIonwouldbeInstudyIngadIseasethatIsunIformlyfatal(100
mortalIty)overaveryshorttIme.
Random Allocation of Treatment Groups
HavIngacceptedthenecessItyofanexperImentwIthacontrolgroup,thequestIonarIses
astothemethodbywhIcheachsubjectshouldbeassIgnedtothepredetermIned
experImentalgroups.ShouldItdependonthewhImoftheInvestIgator,thedayofthe
week,thepreferenceofareferrIngphysIcIan,thewIshofthepatIent,theassIgnmentof
theprevIoussubject,theavaIlabIlItyofastudydrug,ahospItalchartnumber,orsome
otherarbItrarycrIterIon:AllsuchmethodshavebeenusedandarestIllused,butallcan
ruInthepurItyandusefulnessoftheexperIment.tIsImportanttorememberthepurpose
ofsamplIng:byexposIngasmallnumberofsubjectsfromthetarget
P.194
populatIontothevarIousexperImentalcondItIons,onehopestomakeconclusIonsabout
theentIrepopulatIon.Thus,theexperImentalgroupsshouldbeassImIlaraspossIbleto
eachotherInreflectIngthetargetpopulatIon;IfthegroupsaredIfferent,bIasIs
IntroducedIntotheexperIment.AlthoughrandomlyallocatIngsubjectsofasampletoone
oranotheroftheexperImentalgroupsrequIresaddItIonalwork,thIsprIncIpleprevents
selectIonbIasbytheresearcher,mInImIzes(butcannotalwaysprevent)thepossIbIlItythat
ImportantdIfferencesexIstamongtheexperImentalgroups,anddIsarmsthecrItIcs'
complaIntsaboutresearchmethods.FandomallocatIonIsmostcommonlyaccomplIshedby
theuseofcomputergeneratedrandomnumbers.
Blinding
BlindingreferstothemaskIngfromthevIewofpatIentandexperImentersthe
experImentalgrouptowhIchthesubjecthasbeenorwIllbeassIgned.nclInIcaltrIals,the
necessItyforblIndIngstartsevenbeforeapatIentIsenrolledIntheresearchstudy;thIsIs
calledtheconcealment of random allocation.ThereIsgoodevIdencethat,Iftheprocessof
randomallocatIonIsaccessIbletovIew,thereferrIngphysIcIans,theresearchteam
members,orbotharetemptedtomanIpulatetheentranceofspecIfIcpatIentsIntothe
studytoInfluencetheIrassIgnmenttoaspecIfIctreatmentgroup
J
;theydosohavIng
formedapersonalopInIonabouttherelatIvemerItsofthetreatmentgroupsanddesIrIng
togetthebestforsomeonetheyfavor.ThIscreatesbIasIntheexperImentalgroups.
EachsubjectshouldremaIn,IfpossIble,IgnorantoftheassIgnedtreatmentgroupafter
entranceIntotheresearchprotocol.ThepatIent'sexpectatIonofImprovement,aplacebo
effect,IsarealandusefulpartofclInIcalcare.8utwhenstudyInganewtreatment,one
mustensurethatthefameorInfamyofthetreatmentsdoesnotInduceabIasInoutcome
bychangIngpatIentexpectatIons.Aresearcher'sknowledgeofthetreatmentassIgnment
canbIashIsorherabIlItytoadmInIstertheresearchprotocolandtoobserveandrecord
datafaIthfully;thIsIstrueforclInIcal,anImal,andInvItroresearch.fthetreatment
groupIsknown,thosewhoobservedatacannottrustthemselvestorecordthedata
ImpartIallyanddIspassIonately.TheappellatIonssingle-blindanddouble-blindtodescrIbe
blIndIngarecommonlyusedInresearchreports,butoftenapplIedInconsIstently;the
researchershouldcarefullyplanandreportexactlywhoIsblInded.
Types of Research Design
UltImately,researchdesIgnconsIstsofchoosIngwhatsubjectstostudy,whatexperImental
condItIonsandconstraIntstoenforce,andwhIchobservatIonstocollectatwhatIntervals.
AfewkeyfeaturesInthIsresearchdesIgnlargelydetermInethestrengthofscIentIfIc
Inferenceonthecollecteddata.ThesekeyfeaturesallowtheclassIfIcatIonofresearch
reports(Table91).ThIsclassIfIcatIonrevealsthevarIetyofexperImentalapproachesand
IndIcatesstrengthsandweaknessesofthesamedesIgnapplIedtomanyresearchproblems.
ThefIrstdIstInctIonIsbetweenlongitudinalandcrosssectionalstudIes.TheformerIsthe
studyofchangesovertIme,whereasthelatterdescrIbesaphenomenonatacertaInpoInt
IntIme.Forexample,reportIngthefrequencywIthwhIchcertaIndrugsareuseddurIng
anesthesIaIsacrosssectIonalstudy,whereasInvestIgatIngthehemodynamIceffectsof
dIfferentdrugsdurInganesthesIaIsalongItudInalone.
LongItudInalstudIesarenextclassIfIedbythemethodwIthwhIchtheresearchsubjectsare
selected.ThesemethodsforchoosIngresearchsubjectscanbeeItherprospectiveor
retrospective;thesetwoapproachesarealsoknownascohort(prospectIve)orcase-control
(retrospectIve).AprospectIvestudyassemblesgroupsofsubjectsbysomeInput
characterIstIcthatIsthoughttochangeanoutputcharacterIstIc;atypIcalInput
characterIstIcwouldbetheopIoIddrugadmInIstereddurInganesthesIa;forexample,
remIfentanIlorfentanyl.AretrospectIvestudygatherssubjectsbyanoutput
characterIstIc;anoutputcharacterIstIcIsthestatusofthesubjectafteranevent;for
example,theoccurrenceofamyocardIalInfarctIon.AprospectIve(cohort)studywouldbe
oneInwhIchagroupofpatIentsundergoIngneurologIcsurgerywasdIvIdedIntwogroups,
gIventwodIfferentopIoIds(remIfentanIlorfentanyl),andfollowedforthedevelopmentof
aperIoperatIvemyocardIalInfarctIon.naretrospectIve(casecontrol)study,patIentswho
sufferedaperIoperatIvemyocardIalInfarctIonwouldbeIdentIfIedfromhospItalrecords;a
groupofsubjectsofsImIlarage,gender,anddIseasewhodIdnotsufferaperIoperatIve
myocardIalInfarctIonalsowouldbechosen,andthetwogroupswouldthenbecompared
fortherelatIveuseofthetwoopIoIds(remIfentanIlorfentanyl).FetrospectIvestudIesare
aprImarytoolofepIdemIology.AcasecontrolstudycanoftenIdentIfyanassocIatIon
betweenanInputandoutputcharacterIstIc,butthecausallInkorrelatIonshIpbetweenthe
twoIsmoredIffIculttospecIfy.
Table 9-1 Classification of Clinical Research Reports
1. LongItudInalstudIes
1. ProspectIve(cohort)studIes
1. StudIesofdelIberateInterventIon
1. Concurrentcontrols
2. HIstorIcalcontrols
2. DbservatIonalstudIes
2. FetrospectIve(casecontrol)studIes
2. CrosssectIonalstudIes
ProspectIvestudIesarefurtherdIvIdedIntothoseInwhIchtheInvestIgatorperformsa
delIberateInterventIonandthoseInwhIchtheInvestIgatormerelyobserves.nastudyof
deliberate intervention,theInvestIgatorwouldchooseseveralanesthetIcmaIntenance
technIquesandcomparetheIncIdenceofpostoperatIvenauseaandvomItIng.fItwas
performedasanobservational study,theInvestIgatorwouldobserveagroupofpatIents
receIvInganesthetIcschosenatthedIscretIonofeachpatIent'sanesthesIologIstand
comparetheIncIdenceofpostoperatIvenauseaandvomItIngamongtheanesthetIcsused.
DbvIously,InthIsexampleofanobservatIonalstudy,therehasbeenanInterventIon;an
anesthetIchasbeengIven.ThecrucIaldIstInctIonIswhethertheInvestIgatorcontrolled
theInterventIon.AnobservatIonalstudymayrevealdIfferencesamongtreatmentgroups,
butwhethersuchdIfferencesaretheconsequenceofthetreatmentsorofotherdIfferences
amongthepatIentsreceIvIngthetreatmentswIllremaInobscure.
StudIesofdelIberateInterventIonarefurthersubdIvIdedIntothosewIthconcurrent
controlsandthosewIthhIstorIcalcontrols.ConcurrentcontrolsareeItherasImultaneous
parallelcontrolgrouporaselfcontrolstudy;hIstorIcalcontrolsIncludeprevIousstudIes
andlIteraturereports.Arandomized controlled trialIsthusalongItudInal,prospectIve
studyofdelIberateInterventIonwIthconcurrentcontrols.
AlthoughmostofthIsdIscussIonaboutexperImentaldesIgnhasfocusedonhuman
experImentatIon,thesameprIncIplesapplyandshouldbefollowedInanImal
experImentatIon.TherandomIzed,controlledclInIcaltrIalIsthemostpotentscIentIfIc
toolforevaluatIngmedIcaltreatment;randomIzatIonIntotreatmentgroupsIsrelIedonto
equallyweIghtthesubjectsof
P.195
thetreatmentgroupsforbaselIneattrIbutesthatmIghtpredIsposeorprotectthesubjects
fromtheoutcomeofInterest.
Data and Descriptive Statistics
StatIstIcsIsamethodforworkIngwIthsetsofnumbers,asetbeIngagroupofobjects.
StatIstIcsInvolvesthedescrIptIonofnumbersets,thecomparIsonofnumbersetswIth
theoretIcalmodels,comparIsonbetweennumbersets,andcomparIsonofrecentlyacquIred
numbersetswIththosefromthepast.AtypIcalscIentIfIchypothesIsaskswhIchoftwo
methods(treatments),XandY,Isbetter.AstatIstIcalhypothesIsIsformulatedconcernIng
thesetsofnumberscollectedunderthecondItIonsoftreatmentsXandY.StatIstIcs
provIdesmethodsfordecIdIngIfthesetofvaluesassocIatedwIthXaredIfferentfromthe
valuesassocIatedwIthY.StatIstIcalmethodsarenecessarybecausetherearesourcesof
varIatIonInanydataset,IncludIngrandombIologIcvarIatIonandmeasurementerror.
TheseerrorsInthedatacausedIffIcultIesInavoIdIngbIasandInbeIngprecIse.8Iaskeeps
thetruevaluefrombeIngknownandfostersIncorrectdecIsIons;precIsIondealswIththe
problemofthedatascatterandwIthquantIfyIngtheuncertaIntyaboutthevalueInthe
populatIonfromwhIchasampleIsdrawn.ThesestatIstIcalmethodsarerelatIvely
IndependentofthepartIcularfIeldofstudy.FegardlessofwhetherthenumbersInsetsX
andYaresystolIcpressures,bodyweIghts,orserumchlorIdes,theapproachforcomparIng
setsXandYIsusuallythesame.
Data Structure
0atacollectedInanexperImentIncludethedefInIngcharacterIstIcsoftheexperImentand
thevaluesofeventsorattrIbutesthatvaryovertImeorcondItIons.Theformerarecalled
explanatory variablesandthelatterarecalledresponse variables.Theresearcherrecords
hIsorherobservatIonsondatasheetsorcaserecordforms,whIchmaybeonetomany
pagesInlength,andassemblesthemtogetherforstatIstIcalanalysIs.7arIablessuchas
gender,age,anddosesofaccompanyIngdrugsreflectthevarIabIlItyoftheexperImental
subjects.ExplanatoryvarIables,ItIshoped,explaInthesystematIcvarIatIonsInthe
responsevarIables.nasense,theresponsevarIablesdependontheexplanatoryvarIables.
FesponsevarIablesarealsocalleddependent variables.FesponsevarIablesreflectthe
prImarypropertIesofexperImentalInterestInthesubjects.FesearchInanesthesIologyIs
partIcularlylIkelytohaverepeatedmeasurementvarIables;thatIs,apartIcular
measurementrecordedmorethanonceforeachIndIvIdual.SomevarIablescanbeboth
explanatoryandresponse;thesearecalledintermediate response variables.Supposean
experImentIsconductedcomparIngelectrocardIographyandmyocardIalresponses
betweenfIvedosesofanopIoId.DnemIghtanalyzehowSTsegmentsdependedonthedose
ofopIoIds;here,maxImumSTsegmentdepressIonIsaresponsevarIable.|axImumST
segmentdepressIonmIghtalsobeusedasanexplanatoryvarIabletoaddressthesubtler
questIonoftheextenttowhIchtheeffectofanopIoIddoseonpostoperatIvemyocardIal
InfarctIoncanbeaccountedforbySTsegmentchanges.
ThemathematIcalcharacterIstIcsofthepossIblevaluesofavarIablefItIntofIve
classIfIcatIons(Table92).ProperlyassIgnIngavarIabletothecorrectdatatypeIs
essentIalforchoosIngthecorrectstatIstIcaltechnIque.Forinterval variables,thereIs
equaldIstancebetweensuccessIveIntervals;thedIfferencebetween15and10Isthesame
asthedIfferencebetween25and20.Discrete interval datacanhaveonlyIntegervalues;
forexample,numberoflIvIngchIldren.Continuous interval dataaremeasuredona
contInuumandcanbeadecImalfractIon;forexample,bloodpressurecanbedescrIbedas
accuratelyasdesIred(e.g.,1J6,1J6.1,or1J6.14mmHg).ThesamestatIstIcaltechnIques
areusedfordIscreteandcontInuousdata.
PuttIngobservatIonsIntotwoormoredIscretecategorIesderIvescategorical variables;for
statIstIcalanalysIs,numerIcvaluesareassIgnedaslabelstothecategorIes.Dichotomous
dataallowonlytwopossIblevalues;forexample,maleversusfemale.Ordinal datahave
threeormorecategorIesthatcanlogIcallyberankedorordered;however,therankIngor
orderIngofthevarIableIndIcatesonlyrelatIveandnotabsolutedIfferencesbetween
values;thereIsnotnecessarIlythesamedIfferencebetweenAmerIcanSocIetyof
AnesthesIologIstsPhysIcalStatusscoreandasthereIsbetweenand7.Although
ordInaldataareoftentreatedasIntervaldataInchoosIngastatIstIcaltechnIque,such
analysIsmaybesuspect;alternatIvetechnIquesforordInaldataareavaIlable.Nominal
variablesareplacedIntocategorIesthathavenologIcalorderIng.Theeyecolorsblue,
hazel,andbrownmIghtbeassIgnedthenumbers1,2,andJ,butItIsnonsensetosaythat
bluehazelbrown.
Table 9-2 Data Types
DATA TYPE DEFINITION EXAMPLES
Interval
0Iscrete 0atameasuredwIthanIntegeronlyscale
ParIty,numberof
teeth
ContInuous
0atameasuredwIthaconstantscale
Interval
8loodpressure,
temperature
Categorical
0Ichotomous 8Inarydata |ortalIty,gender
NomInal
QualItatIvedatathatcannotbeordered
orranked
Eyecolor,drug
category
DrdInal
0ataordered,ranked,ormeasured
wIthoutaconstantscaleInterval
ASAphysIcalstatus
score,paInscore
ASA,AmerIcanSocIetyofAnesthesIologIsts.
P.196
Descriptive Statistics
AtypIcalhypothetIcaldatasetcouldbeasampleofages(theresponseordependent
varIable)of12resIdentsInananesthesIatraInIngprogram(thepopulatIon).Althoughthe
resultsofapartIcularexperImentmIghtbepresentedbyrepeatedlyshowIngtheentIreset
ofnumbers,thereareconcIsewaysofsummarIzIngtheInformatIoncontentofthedataset
Intoafewnumbers.Thesenumbersarecalledsampleorsummary statistics;summary
statIstIcsarecalculatedusIngthenumbersofthesample.8yconventIon,thesymbolsof
summarystatIstIcsareromanletters.ThetwosummarystatIstIcsmostfrequentlyusedfor
IntervalvarIablesarethecentral locationandthevariability,butthereareothersummary
statIstIcs.DtherdatatypeshaveanalogoussummarystatIstIcs.AlthoughthefIrstpurpose
ofdescrIptIvestatIstIcsIstodescrIbethesampleofnumbersobtaIned,thereIsalsothe
desIretousethesummarystatIstIcsfromthesampletocharacterIzethepopulatIonfrom
whIchthesamplewasobtaIned.Forexample,whatcanbesaIdabouttheageofall
anesthesIaresIdentsfromtheInformatIonInasample:ThepopulatIonalsohasmeasuresof
centrallocatIonandvarIabIlItycalledtheparametersofthepopulatIon;Creekletters
denotepopulatIonparameters.Usually,thepopulatIonparameterscannotbedIrectly
calculatedbecausedatafromallpopulatIonmemberscannotbeobtaIned.Thebeautyof
properlychosensummarystatIstIcsIsthattheyarethebestpossIbleestImatorsofthe
populatIonparameters.
ThesesamplIngstatIstIcscanbeusedInconjunctIonwIthaprobabIlItydensItyfunctIonto
provIdeaddItIonaldescrIptIonsofthesampleandItspopulatIon.AlsocommonlydescrIbed
asaprobabIlItydIstrIbutIon,aprobabIlItydensItyfunctIonIsanalgebraIcequatIon,f(x),
whIchgIvesatheoretIcalpercentagedIstrIbutIonofx.EachvalueofxhasaprobabIlItyof
occurrencegIvenbyf(x).ThemostImportantprobabIlItydIstrIbutIonIsthenormalor
Gaussian function
ters(populatIonmeanandpopulatIonvarIance)IntheequatIonofthenormalfunctIonthat
aredenotedand
2
.Dftencalledthenormal equation,Itcanbeplottedandproducesthe
famIlIarbellshapedcurve.WhyarethemathematIcalpropertIesofthIscurvesoImportant
tobIostatIstIcs:FIrst,IthasbeenempIrIcallynotedthatwhenabIologIcvarIableIs
sampledrepeatedly,thepatternofthenumbersplottedasahIstogramresemblesthe
normalcurve;thus,mostbIologIcdataaresaIdtofollowortoobeyanormaldIstrIbutIon.
Second,IfItIsreasonabletoassumethatasampleIsfromanormalpopulatIon,the
mathematIcalpropertIesofthenormalequatIoncanbeusedwIththesamplIngstatIstIc
estImatorsofthepopulatIonparameterstodescrIbethesampleandthepopulatIon.ThIrd,
amathematIcaltheorem(thecentrallImIttheorem)allowstheuseoftheassumptIonof
normalItyforcertaInpurposes,evenIfthepopulatIonIsnotnormallydIstrIbuted.
Central Location
ThethreemostcommonsummarystatIstIcsofcentrallocatIonforIntervalvarIablesare
thearIthmetIcmean,themedian,andthemode.ThemeanIsmerelytheaverageofthe
numbersInthedataset.8eIngasummarystatIstIcofthesample,thearIthmetIcmeanIs
denotedbytheFomanletterxunderabaror
countofobjectsInthesample.fallvaluesInthepopulatIoncouldbeobtaIned,thenthepopulatIonmeancouldbe
calculatedsImIlarly.8ecauseallvaluesofthepopulatIoncannotbeobtaIned,thesamplemeanIsused.(StatIstIcIans
descrIbethesamplemeanastheunbIased,consIstent,mInImumvarIance,suffIcIentestImatorofthepopulatIonmean.
EstImatorsaredenotedbyahatoveraromanletter;forexample, .Thus,thesamplemean[xwIthbarabove]Isthe
estImator ofthepopulatIonmean.)
ThemedIanIsthemIddlemostnumberorthenumberthatdIvIdesthesampleIntotwo
equalpartsfIrst,rankIngthesamplevaluesfromlowesttohIghestandthencountIngup
halfwaytoobtaInthemedIan.TheconceptofrankIngIsusedInnonparametrIcstatIstIcs.A
vIrtueofthemedIanIsthatItIshardlyaffectedbyafewextremelyhIghorlowvalues.The
modeIsthemostpopularnumberofasample;thatIs,thenumberthatoccursmost
frequently.AsamplemayhavetIesforthemostcommonvalueandbebIorpolymodal;
thesemodesmaybewIdelyseparatedoradjacent.TherawdatashouldbeInspectedfor
thIsunusualappearance.ThemodeIsalwaysmentIonedIndIscussIonsofdescrIptIve
statIstIcs,butItIsrarelyusedInstatIstIcalpractIce.
Spread or Variability
AnysetofIntervaldatahasvarIabIlItyunlessallthenumbersareIdentIcal.Therangeof
agesfromlowesttohIghestexpressesthelargestdIfference.ThIsspread,dIversIty,and
varIabIlItycanalsobeexpressedInaconcIsemanner.7arIabIlItyIsspecIfIedbycalculatIng
thedeviationordeviateofeachIndIvIdualx
i
fromthecenter(mean)ofallthex
i
's.The
sum of the squared deviatesIsalwaysposItIveunlessallsetvaluesareIdentIcal.ThIssum
IsthendIvIdedbythenumberofIndIvIdualmeasurements.TheresultIstheaveraged
squared deviation;theaveragesquareddevIatIonIsubIquItousInstatIstIcs.
TheconceptofdescrIbIngthespreadofasetofnumbersbycalculatIngtheaverage
dIstancefromeachnumbertothecenterofthenumbersapplIestobothasampleanda
populatIon;thIsaveragesquareddIstanceIscalledthevariance.ThepopulatIonvarIanceIs
aparameterandIsrepresentedby
2
.AswIththepopulatIonmean,thepopulatIon
varIanceIsnotusuallyknownandcannotbecalculated.JustasthesamplemeanIsusedIn
placeofthepopulatIonmean,thesamplevarIanceIsusedInplaceofthepopulatIon
varIance.ThesamplevarIance
StatIstIcaltheorydemonstratesthatIfthedIvIsorIntheformulaforSD
2
Is(n1)rather
thann,thesamplevarIanceIsanunbIasedestImatorofthepopulatIonvarIance.WhIlethe
varIanceIsusedextensIvelyInstatIstIcalcalculatIons,theunItsofvarIancearesquared
unItsoftheorIgInalobservatIons.ThesquarerootofthevarIancehasthesameunItsas
theorIgInalobservatIons;thesquarerootsofthesampleandpopulatIonvarIancesare
calledthesample(SD)andpopulation()standard deviations.
twasprevIouslymentIonedthatmostbIologIcobservatIonsappeartocomefrom
populatIonswIthnormaldIstrIbutIons.8yacceptIngthIsassumptIonofanormal
dIstrIbutIon,furthermeanIngcanbegIventothesamplesummarystatIstIcs(meanandS0)
thathavebeencalculated.ThIsInvolvestheuseoftheexpressIon[xwIthbarabove]K
SDwherek=1,2,J,andsoforth.fthepopulatIonfromwhIchthesampleIstakenIs
unImodalandroughlysymmetrIc,thentheboundsfor1,2,andJencompassesroughly68,
95,and99ofthesampleandpopulatIonmembers.
P.197
Hypotheses and Parameters
Hypothesis Formulation
TheresearcherstartsworkwIthsomeIntuItIvefeelforthephenomenontobestudIed.
WhetherstatedexplIcItlyornot,thIsIsthebiologic hypothesis;ItIsastatementof
experImentalexpectatIonstobeaccomplIshedbytheuseofexperImentaltools,
Instruments,ormethodsaccessIbletotheresearchteam.Anexamplewouldbethehope
thatIsofluranewouldproducelessmyocardIalIschemIathanfentanyl;theexperImental
methodmIghtbetheelectrocardIographydetermInatIonofSTsegmentchanges.The
bIologIchypothesIsoftheresearcherbecomesastatistical hypothesisdurIngresearch
plannIng.TheresearchermeasuresquantItIesthatcanvaryvarIablessuchasheartrateor
temperatureorSTsegmentchangeInsamplesfrompopulatIonsofInterest.nastatIstIcal
hypothesIs,statementsaremadeabouttherelatIonshIpamongparametersofoneormore
populatIons.(Torestate,aparameterIsanumberdescrIbIngavarIableofapopulatIon;
Creeklettersareusedtodenoteparameters.)ThetypIcalstatIstIcalhypothesIscanbe
establIshedInasomewhatrotefashIonforeveryresearchproject,regardlessofthe
methods,materIals,orgoals.ThemostfrequentlyusedmethodofsettIngupthealgebraIc
formulatIonofthestatIstIcalhypothesIsIstocreatetwomutuallyexclusIvestatements
aboutsomeparametersofthestudypopulatIon(Table9J);estImatesforthevaluesfor
theseparametersareacquIredbysamplIngdata.nthehypothetIcalexamplecomparIng
Isofluraneandfentanyl,
1
and
2
wouldrepresenttheSTsegmentchangeswIthIsoflurane
andwIthfentanyl.Thenull hypothesisIsthehypothesIsofnodIfferenceofSTsegment
changesbetweenIsofluraneandfentanyl.Thealternative hypothesisIsusually
nondIrectIonal,thatIs,eIther
1
2
or
1
2
;thIsIsknownasatwo-tail alternative
hypothesis.ThIsIsamoreconservatIvealternatIvehypothesIsthanassumIngthatthe
InequalItycanonlybeeItherlessthanorgreaterthan.
Logic of Proof
DnepartIculardecIsIonstrategyIsusedmostcommonlytochoosebetweenthenulland
alternatIvehypothesIs.ThedecIsIonstrategyIssImIlartoamethodofIndIrectproofused
InmathematIcscalledreductio ad absurdum(proofbycontradIctIon).fatheoremcannot
beproveddIrectly,assumethatItIsnottrue;showthatthefalsItyofthIstheoremwIll
leadtocontradIctIonsandabsurdItIes;thus,rejecttheorIgInalassumptIonofthefalseness
ofthetheorem.ForstatIstIcs,theapproachIstoassumethatthenullhypothesIsIstrue
eventhoughthegoaloftheexperImentIstoshowthatthereIsadIfference.DneexamInes
theconsequencesofthIsassumptIonbyexamInIngtheactualsamplevaluesobtaInedfor
thevarIable(s)ofInterest.ThIsIsdonebycalculatIngwhatIscalledasample test statistic;
sampleteststatIstIcsarecalculatedfromthesamplenumbers.AssocIatedwIthasample
teststatIstIcIsaprobability.Dnealsochoosesthelevel of significance;thelevelof
sIgnIfIcanceIstheprobabIlItylevelconsIderedtoolowtowarrantsupportofthenull
hypothesIsbeIngtested.fsamplevaluesaresuffIcIentlyunlIkelytohaveoccurredby
chance(I.e.,theprobabIlItyofthesampleteststatIstIcIslessthanthechosenlevelof
sIgnIfIcance),thenullhypothesIsIsrejected;otherwIse,thenullhypothesIsIsnotrejected.
Table 9-3 Algebraic Statement of Statistical Hypotheses
H
0
:
1
=
2
(nullhypothesIs)
H
a
:
1
2
(alternatIvehypothesIs)
1
=ParameterestImatedfromsampleoffIrstpopulatIon
2
=ParameterestImatedfromsampleofsecondpopulatIon
8ecausethestatIstIcsdealwIthprobabIlItIes,notcertaIntIes,thereIsachancethatthe
decIsIonconcernIngthenullhypothesIsIserroneous.TheseerrorsarebestdIsplayedIn
tableform(Table94);condItIon1andcondItIon2couldbedIfferentdrugs,twodosesof
thesamedrug,ordIfferentpatIentgroups.DfthefourpossIbleoutcomes,twodecIsIons
areclearlyundesIrable.TheerrorofwronglyrejectIngthenullhypothesIs(falseposItIve)Is
calledthetype Ioralpha error.TheexperImentershouldchooseaprobabIlItyvaluefor
alphabeforecollectIngdata;theexperImenterdecIdeshowcautIoustobeagaInstfalsely
claImIngadIfference.ThemostcommonchoIceforthevalueofalphaIs0.05.Whatare
theconsequencesofchoosInganalphaof0.05:AssumIngthatthereIs,Infact,no
dIfferencebetweenthetwocondItIonsandthattheexperImentIstoberepeated20tImes,
thendurIngoneofthese
P.198
experImentalreplIcatIons(5of20)amIstakenconclusIonthatthereIsadIfferencewould
bemade.TheprobabIlItyofatypeerrordependsonthechosenlevelofsIgnIfIcanceand
theexIstenceornonexIstenceofadIfferencebetweenthetwoexperImentalcondItIons.
Thesmallerthechosenalpha,thesmallerwIllbetherIskofatypeerror.
Table 9-4 Errors in Hypothesis Testing: the Two-Way Truth Table

REALITY (POPULATION PARAMETERS)
CONDITIONS 1 AND 2
EQUIVALENT
CONDITIONS 1 AND 2
NOT EQUIVALENT
CONCLUSION FROM
SAMPLE (SAMPLE
STATISTICS)
CONDITIONS 1
AND 2
EQUIVALENT
a
Correct
conclusIon
FalsenegatIve
typeerror
(betaerror)
CONDITIONS 1
AND 2 NOT
EQUIVALENT
b
FalseposItIve
typeerror
(alphaerror)
Correct
conclusIon
a
0onotrejectthenullhypothesIs:condItIon1=condItIon2.
b
FejectthenullhypothesIs:condItIon1condItIon2.
TheerroroffaIlIngtorejectafalsenullhypothesIs(falsenegatIve)Iscalledatype IIor
beta error.(ThepowerofatestIs1mInusbeta).TheprobabIlItyofatypeerrordepends
onfourfactors.Unfortunately,thesmallerthealpha,thegreaterthechanceofafalse
negatIveconclusIon;thIsfactkeepstheexperImenterfromautomatIcallychoosIngavery
smallalpha.Second,themorevarIabIlItythereIsInthepopulatIonsbeIngcompared,the
greaterthechanceofatypeerror.ThIsIsanalogoustolIstenIngtoanoIsyradIo
broadcast;themorestatIcthereIs,theharderItwIllbetodIscrImInatebetweenwords.
Next,IncreasIngthenumberofsubjectswIlllowertheprobabIlItyofatypeerror.The
fourthandmostImportantfactorIsthemagnItudeofthedIfferencebetweenthetwo
experImentalcondItIons.TheprobabIlItyofatypeerrorgoesfromveryhIgh,whenthere
IsonlyasmalldIfference,toextremelylow,whenthetwocondItIonsproducelarge
dIfferencesInpopulatIonparameters.
Sample Size Calculations
Formerly,researcherstypIcallyIgnoredthelattererrorInexperImentaldesIgn.The
practIcalImportanceofworryIngabouttypeerrorsreachedtheconscIousnessofthe
medIcalresearchcommunItyseveraldecadesago.SomecontrolledclInIcaltrIalsthat
claImedtofIndnoadvantageofnewtherapIescomparedwIthstandardtherapIeslacked
suffIcIentstatIstIcalpowertodIscrImInatebetweentheexperImentalgroupsandwould
havemIssedanImportanttherapeutIcImprovement.TherearefouroptIonsfordecreasIng
typeerror(IncreasIngstatIstIcalpower):(1)raIsealpha,(2)reducepopulatIon
varIabIlIty,(J)makethesamplebIgger,and(4)makethedIfferencebetweenthe
condItIonsgreater.UndermostcIrcumstances,onlythesamplesIzecanbevarIed.Sample
sIzeplannInghasbecomeanImportantpartofresearchdesIgnforcontrolledclInIcaltrIals.
SomepublIshedresearchstIllfaIlsthetestofadequatesamplesIzeplannIng.
Inferential Statistics
ThetestIngofhypothesesorsignificance testinghasbeenthemaInfocusofInferentIal
statIstIcs.HypothesIstestIngallowstheexperImentertousedatafromthesampletomake
InferencesaboutthepopulatIon.StatIstIcIanshavecreatedformulasthatusethevaluesof
thesamplestocalculateteststatIstIcs.StatIstIcIanshavealsoexploredthepropertIesof
varIoustheoretIcalprobabIlItydIstrIbutIons.0ependIngontheassumptIonsabouthowdata
arecollected,theapproprIateprobabIlItydIstrIbutIonIschosenasthesourceofcrItIcal
valuestoacceptorrejectthenullhypothesIs.fthevalueoftheteststatIstIccalculated
fromthesample(s)IsgreaterthanthecrItIcalvalue,thenullhypothesIsIsrejected.The
crItIcalvalueIschosenfromtheapproprIateprobabIlItydIstrIbutIonafterthemagnItudeof
thetypeerrorIsspecIfIed.
ThereareparameterswIthIntheequatIonthatgenerateanypartIcularprobabIlIty
dIstrIbutIon;forthenormalprobabIlItydIstrIbutIon,theparametersareand
2
.Forthe
normaldIstrIbutIon,eachsetofvaluesforand
2
wIllgenerateadIfferentshapeforthe
belllIkenormalcurve.AllprobabIlItydIstrIbutIonscontaInoneormoreparametersand
canbeplottedascurves;theseparametersmaybedIscrete(Integeronly)orcontInuous.
EachvalueorcombInatIonofvaluesfortheseparameterswIllcreateadIfferentcurvefor
theprobabIlItydIstrIbutIonbeIngused.Thus,eachprobabIlItydIstrIbutIonIsactuallya
famIlyofprobabIlItycurves.SomeaddItIonalparametersoftheoretIcalprobabIlIty
dIstrIbutIonshavebeengIventhespecIalnamedegrees of freedomandarerepresentedby
LatInletterssuchasm, n,ands.
AssocIatedwIththeformulaforcomputIngateststatIstIcIsaruleforassIgnIngInteger
valuestotheoneormoreparameterscalleddegreesoffreedom.Thenumberofdegreesof
freedomandthevalueforeachdegreeoffreedomdependon(1)thenumberofsubjects,
(2)thenumberofexperImentalgroups,(J)thespecIfIcsofthestatIstIcalhypothesIs,and
(4)thetypeofstatIstIcaltest.ThecorrectcurveoftheprobabIlItydIstrIbutIonfromwhIch
toobtaInacrItIcalvalueforcomparIsonwIththevalueoftheteststatIstIcIsobtaIned
wIththevaluesofoneormoredegreesoffreedom.
ToacceptorrejectthenullhypothesIs,thefollowIngstepsareperformed:(1)confIrmthat
experImentaldataconformtotheassumptIonsoftheIntendedstatIstIcaltest;(2)choosea
sIgnIfIcancelevel(alpha);(J)calculatetheteststatIstIc;(4)determInethedegree(s)of
freedom;(5)fIndthecrItIcalvalueforthechosenalphaandthedegree(s)offreedomfrom
theapproprIateprobabIlItydIstrIbutIon;(6)IftheteststatIstIcexceedsthecrItIcalvalue,
rejectthenullhypothesIs;(7)IftheteststatIstIcdoesnotexceedthecrItIcalvalue,donot
rejectthenullhypothesIs.TherearegeneralguIdelInesthatrelatethevarIabletypeand
theexperImentaldesIgntothechoIceofstatIstIcaltest(Table95).
Confidence Intervals
TheothermajorareasofstatIstIcalInferencearetheestImatIonofparameterswIth
assocIatedconfidence intervals(Cs).nstatIstIcs,aCIsanIntervalestImateofa
populatIonparameter.ACdescrIbeshowlIkelyItIsthatthepopulatIon
P.199
parameterIsestImatedbyanypartIcularsamplestatIstIcsuchasthemean.(ThetechnIcal
defInItIonoftheCofthemeanIsmorerIgorous.A95CImplIesthatIftheexperIment
weredoneoverandoveragaIn,95ofeach100CswouldbeexpectedtocontaInthetrue
valueofthemean.)CsarearangeofthefollowIngform:summarystatIstIc(confIdence
factor)(precIsIonfactor).
Table 9-5 When to use What
VARIABLE TYPE
ONE-SAMPLE
TESTS
TWO-SAMPLE TESTS MULTIPLE-SAMPLE TESTS
0Ichotomous
ornomInal
8InomIal
dIstrIbutIon
ChIsquaretest,
FIsher'sexacttest
ChIsquaretest
DrdInal
ChIsquare
test
ChIsquaretest,
nonparametrIctests
ChIsquaretest,
nonparametrIctests
ContInuous
ordIscrete
z
dIstrIbutIon
ort
dIstrIbutIon
UnpaIredttest,
paIredttest,
nonparametrIctests
AnalysIsofvarIance,
nonparametrIcanalysIs
ofvarIance
Theprecision factorIsderIvedfromthesampleItself,whereastheconfidence factorIs
takenfromaprobabIlItydIstrIbutIonandalsodependsonthespecIfIedconfIdencelevel
chosen.ForasampleofIntervaldatatakenfromanormallydIstrIbutedpopulatIonfor
whIchCsaretobechosenfor[xwIthbarabove],theprecIsIonfactorIscalledthe
standard error of the meanandIsobtaInedbydIvIdIngS0bythesquarerootofthesample
sIze
TheconfIdencefactorsarethesameasthoseusedforthedIspersIonorspreadofthe
sampleandareobtaInedfromthenormaldIstrIbutIon.TheCsforconfIdencefactors1,2,
andJhaveroughlya68,95,and99chanceofcontaInIngthepopulatIonmean.StrIctly
speakIng,whentheS0mustbeestImatedfromsamplevalues,theconfIdencefactors
shouldbetakenfromthet distribution,anotherprobabIlItydIstrIbutIon.ThesecoeffIcIents
wIllbelargerthanthoseusedprevIously.ThIsIsusuallyIgnoredIfthesamplesIzeIs
reasonable;forexample,n25.EvenwhenthesamplesIzeIsonlyfIveorgreater,theuse
ofthecoeffIcIents1,2,andJIssImpleandsuffIcIentlyaccurateforquIckmental
calculatIonsofCsonparameterestImates.
AlmostallresearchreportsIncludetheuseofSE,regardlessoftheprobabIlItydIstrIbutIon
ofthepopulatIonssampled.ThIsuseIsaconsequenceofthecentral limit theorem,oneof
themostremarkabletheoremsInallofmathematIcs.ThecentrallImIttheoremstatesthat
theSEcanalwaysbeused,IfthesamplesIzeIssuffIcIentlylarge,tospecIfyCsaroundthe
samplemean.TheseCsarecalculatedasprevIouslydescrIbed.ThIsIstrueevenIfthe
populatIondIstrIbutIonIssodIfferentfromnormalthatS0cannotbeusedtocharacterIze
thedIspersIonofthepopulatIonmembers.DnlyroughguIdelInescanbegIvenforthe
necessarysamplesIze;forIntervaldata,25andaboveIslargeenoughand4andbelowIs
toosmall.
AlthoughtheSEIsoftendIscussedalongwIthotherdescrIptIvestatIstIcs,ItIsreallyan
InferentIalstatIstIc.SEandS0areusuallymentIonedtogetherbecauseoftheIrsImIlarItIes
ofcomputatIon,butthereIsoftenconfusIonabouttheIruseInresearchreportsIntheform
meannumber.SomeconfusIonresultsfromthefaIlureoftheauthortospecIfywhether
thenumberafterthesIgnIstheoneortheother.|oreImportant,thechoIcebetween
usIngS0andusIngSEhasbecomecontroversIal.8ecauseSEIsalwayslessthanS0,Ithas
beenarguedthatauthorsseektodeceIvebyusIngSEtomakethedatalookbetterthan
theyreallyare.ThechoIceIsactuallysImple.WhendescrIbIngthespread,scatter,or
dIspersIonofthesample,useS0;whendescrIbIngtheprecIsIonwIthwhIchthepopulatIon
meanIsknown,useSE.
Confidence Intervals on Proportions
Categorical binary data,alsocalledenumeration data,provIdecountsofsubjectresponses.
CIvenasampleofsubjectsofwhomsomehaveacertaIncharacterIstIc(e.g.,death,
femalesex),aratIoofresponderstothenumberofsubjectscanbeeasIlycalculatedasp=
x/n;thIsratIoorratecanbeexpressedasadecImalfractIonorasapercentage.tshould
beclearthatthIsIsameasureofcentrallocatIonofabInarydataInthesamewaythat
wasameasureofcentrallocatIonforcontInuousdata.nthepopulatIonfromwhIchthe
sampleIstaken,theratIoofresponderstototalsubjectsIsapopulatIonparameter,
denoted;IsthemeasureofcentrallocatIonforthepopulatIon.(ThIsIsnotrelatedto
thegeometryconstant=J.14159).AswIthotherdatatypes,Isusuallynotknown,but
mustbeestImatedfromthesample.ThesampleratIopIsthebestestImateof.The
probabIlItyofbInarydataIsprovIdedbythebinomial distribution function.
8ecausethepopulatIonIsnotgenerallyknown,theexperImenterusuallywIshesto
estImatebythesampleratIopandtospecIfywIthwhatconfIdenceIsknown.fthe
sampleIssuffIcIentlylarge(np5;n(1p)5),advantageIstakenofthecentrallImIt
theoremtoderIveanSEanalogousto
sampleSEIsexactlyanalogoustothesampleSEofthemeanforIntervaldata,exceptthat
ItIsanSEoftheproportIon.Justasa95Cofthemeanwascalculated,somayaCon
theproportIonmaybeobtaIned.LargersampleswIllmaketheCmoreprecIse.
Statistical Tests and Models
Dichotomous Data Testing
ntheexperImentnegatIngthevalueofmammaryarterylIgatIon,fIveofeIghtpatIents
(62.5)havInglIgatIonshowedbenefItwhIlefIveofnInepatIents(55.6)havIngsham
surgeryalsohadbenefIt.
1
sthIsdIfferencereal:ThIsexperImentsampledpatIentsfrom
twopopulatIonsthosehavIngtherealprocedureandthosehavIngtheshamprocedure.A
varIetyofstatIstIcaltechnIquesallowacomparIsonofthesuccessrate.TheseInclude
Fisher's exact testand(Pearson's) chi-square test.ThechIsquaretestofferstheadvantage
ofbeIngcomputatIonallysImpler;ItcanalsoanalyzecontIngencytableswIthmorethan
tworowsandtwocolumns;however,certaInassumptIonsofsamplesIzeandresponserate
arenotachIevedbythIsexperIment.FIsher'sexacttestfaIlstorejectthenullhypothesIs
forthIsdata.
TheresultsofsuchexperImentsareoftenpresentedasrateratIos.Therateof
ImprovementfortheexperImentalgroup(5/8=62.5)IsdIvIdedbytherateof
Improvementforthecontrolgroup(5/9=55.6).ArateratIoof1.00(100)faIlstoshowa
dIfferenceofbenefItorharmbetweenthetwogroups.nthIsexampletherateratIoIs
1.125.Thus,theexperImentalgrouphada12.5greaterchanceofImprovementcompared
wIththecontrolgroup.ACcanbecalculatedfortherateratIo;InthIsexampleItIs(0.40,
J.1J),thuswIdelyspreadtoeIthersIdeoftherateratIoofnodIfference.(fsuch
experImentwereperformednow,thesamplesIzewouldbemuchlargertohaveadequate
statIstIcalpower.)
Interval Data Testing
ParametrIcstatIstIcsaretheusualchoIceIntheanalysIsofIntervaldata,bothdIscreteand
contInuous.ThepurposeofsuchanalysIsIstotestthehypothesIsofadIfferencebetween
populatIonmeans.ThepopulatIonmeansareunknownandareestImatedbythesample
means.AtypIcalexamplewouldbethecomparIsonofthemeanheartratesofpatIents
receIvIngandnotreceIvIngatropIne.ParametrIcteststatIstIcshavebeendevelopedby
usIngthepropertIesofthenormalprobabIlItydIstrIbutIonandtworelatedprobabIlIty
dIstrIbutIons,thetandtheFdIstrIbutIons.nusIngsuchparametrIcmethods,the
assumptIonIsmadethatthesampleorsamplesIs/aredrawnfrompopulatIon(s)wItha
normaldIstrIbutIon.TheparametrIc
P.200
teststatIstIcsthathavebeencreatedforIntervaldataallhavetheformofaratIo.n
generalterms,thenumeratorofthIsratIoIsthevarIabIlItyofthemeansofthesamples;
thedenomInatorofthIsratIoIsthevarIabIlItyamongallthemembersofthesamples.
ThesevarIabIlItIesaresImIlartothevarIancesdevelopedfordescrIptIvestatIstIcs.The
teststatIstIcIsthusaratIoofvarIabIlItIesorvarIances.AllparametrIcteststatIstIcsare
usedInthesamefashIon;IftheteststatIstIcratIobecomeslarge,thenullhypothesIsofno
dIfferenceIsrejected.ThecrItIcalvaluesagaInstwhIchtocomparetheteststatIstIcare
takenfromtablesofthethreerelevantprobabIlItydIstrIbutIons(normal,t,orF).n
hypothesIstestIngatleastoneofthepopulatIonmeansIsunknown,butthepopulatIon
varIance(s)mayormaynotbeknown.ParametrIcstatIstIcscanbedIvIdedIntotwogroups
accordIngtowhetherornotthepopulatIonvarIancesareknown.fthepopulatIon
varIanceIsknown,theteststatIstIcusedIscalledthezscore;crItIcalvaluesareobtaIned
fromthenormaldIstrIbutIon.nmostbIomedIcalapplIcatIons,thepopulatIonvarIanceIs
rarelyknownandthezscoreIslIttleused.
t Test
AnImportantadvanceInstatIstIcalInferencecameearlyInthe20thcenturywIththe
creatIonofStudent's t test statisticandthet distribution,whIchallowedthetestIngof
hypotheseswhenthepopulatIonvarIanceIsnotknown.ThemostcommonuseofStudent's
ttestIstocomparethemeanvaluesoftwopopulatIons.Therearetwotypesofttest.f
eachsubjecthastwomeasurementstaken,forexample,onebefore(x
i
)andoneafter(y
i
)a
drug,thenaonesampleorpaired t testprocedureIsused;eachcontrolmeasurement
takenbeforedrugadmInIstratIonIspaIredwIthameasurementInthesamepatIentafter
drugadmInIstratIon.Dfcourse,thIsIsaselfcontrolexperIment.ThIspaIrIngof
measurementsInthesamepatIentreducesvarIabIlItyandIncreasesstatIstIcalpower.The
dIfferenced
i
=x
i
y
i
ofeachpaIrofvaluesIscalculatedandtheaverage[dwIthbar
above]Iscalculated.ntheformulaforStudent'ststatIstIc,thenumeratorIs[dwIthbar
above],whereasthedenomInatorIstheSE
AlltstatIstIcsarecreatedInthIsway;thenumeratorIsthedIfferenceoftwomeans,
whereasthedenomInatorIstheSEofthetwomeans.fthedIfferencebetweenthetwo
meansIslargecomparedwIththeIrvarIabIlIty,thenthenullhypothesIsofnodIfferenceIs
rejected.ThecrItIcalvaluesforthetstatIstIcaretakenfromthetprobabIlItydIstrIbutIon.
ThetdIstrIbutIonIssymmetrIcandbellshapedbutmorespreadoutthanthenormal
dIstrIbutIon.ThetdIstrIbutIonhasasIngleIntegerparameter;forapaIredttest,thevalue
ofthIssIngledegreeoffreedomIsthesamplesIzemInusone.TherecanbesomeconfusIon
abouttheuseofthelettert.trefersbothtothevalueoftheteststatIstIccalculatedby
theformulaandtothecrItIcalvaluefromthetheoretIcalprobabIlItydIstrIbutIon.The
crItIcaltvalueIsdetermInedbylookIngInattableafterasIgnIfIcancelevelIschosenand
thedegreeoffreedomIscomputed.
|orecommonly,measurementsaretakenontwoseparategroupsofsubjects.For
example,onegroupreceIvesbloodpressuretreatmentwIthsamplevaluesx
i
,whereasno
treatmentIsgIventoacontrolgroupwIthsamplevaluesy
i
.ThenumberofsubjectsIn
eachgroupmIghtormIghtnotbeIdentIcal;regardlessofthIs,InnosenseIsanIndIvIdual
measurementInthefIrstgroupmatchedorpaIredwIthaspecIfIcmeasurementInthe
secondgroup.Anunpairedortwo-sample t testIsusedtocomparethemeansofthetwo
groups.ThenumeratorofthetstatIstIcIs[xwIthbarabove][YwIthbarabove].The
denomInatorIsaweIghtedaverageoftheS0sofeachsamplesothatthetest
ThedegreeoffreedomforanunpaIredttestIscalculatedasthesumofthesubjectsofthe
twogroupsmInustwo.AswIththepaIredttest,IfthetratIobecomeslarge,thenull
hypothesIsIsrejected.
Analysis of Variance
ExperImentsInanesthesIa,whethertheyarewIthhumansorwIthanImals,maynotbe
lImItedtooneortwogroupsofdataforeachvarIable.tIsverycommontofollowa
varIablelongItudInally;heartrate,forexample,mIghtbemeasuredfIvetImesbeforeand
durInganesthetIcInductIon.Thesearealsocalledrepeated measurement experiments;the
experImenterwIllwIshtocomparechangesbetweentheInItIalheartratemeasurement
andthoseobtaIneddurIngInductIon.TheexperImentaldesIgnmIghtalsoIncludeseveral
groupsreceIvIngdIfferentInductIondrugs;forexample,comparIngheartrateacrossgroups
ImmedIatelyafterlaryngoscopy.FesearchershavemIstakenlyhandledtheseanalysIs
problemswIthjustthettest.fheartrateIscollectedfIvetImes,thesecollectIontImes
couldbelabeledA, B, C, D,andE.ThenAcouldbecomparedwIthB, C, D,andE; Bcould
becomparedwIthC, D,andE;andsoforth.ThetotalofpossIblepaIrIngsIsten;thus,ten
paIredttestscouldbecalculatedforallthepossIblepaIrIngsofA, B, C, D,andE.AsImIlar
approachcanbeusedforcomparIngmorethantwogroupsforunpaIreddata.
TheuseofttestsInthIsfashIonIsInapproprIate.ntestIngastatIstIcalhypothesIs,the
experImentersetstheleveloftypeerror;thIsIsusuallychosentobe0.05.WhenusIng
manyttests,asIntheexamplegIvenearlIer,thechosenerrorrateforperformIngall
thesettestsIsmuchhIgherthan0.05,eventhoughthetypeerrorIssetat0.05foreach
IndIvIdualcomparIson.nfact,thetypeerrorrateforallttestssImultaneously;thatIs,
thechanceoffIndIngatleastoneofthemultIpletteststatIstIcssIgnIfIcantmerelyby
chanceIsgIvenbytheformula=10.95
.f1Jttestsareperformed(=1J),thereal
errorrateIs49.ApplyIngttestsoverandoveragaIntoallthepossIblepaIrIngsofa
varIablewIllmIsleadInglyIdentIfystatIstIcalsIgnIfIcancewhenInfactthereIsnone.
ThemostversatIleapproachforhandlIngcomparIsonsofmeansbetweenmorethantwo
groupsorbetweenseveralmeasurementsInthesamegroupIscalledanalysis of variance
andIsfrequentlycItedbytheacronymAND7A.AnalysIsofvarIanceconsIstsofrulesfor
creatIngteststatIstIcsonmeanswhentherearemorethantwogroups.Thesetest
statIstIcsarecalledF ratios,afterFonaldFIsher;thecrItIcalvaluesfortheFteststatIstIc
aretakenfromtheFprobabIlItydIstrIbutIonthatFIsherderIved.
SupposethatdataforthreegroupsareobtaIned.WhatcanbesaIdaboutthemeanvalues
ofthethreetargetpopulatIons:TheFtestIsactuallyaskIngseveralquestIons
sImultaneously:Isgroup1dIfferentfromgroup2;Isgroup2dIfferentfromgroupJ;andIs
group1dIfferentfromgroupJ:AswIththettest,theFteststatIstIcIsaratIo;Ingeneral
terms,thenumeratorexpressesthevarIabIlItyofthemeanvaluesofthethreegroups,
whereasthedenomInatorexpressestheaveragevarIabIlItyordIfferenceofeachsample
valuefromthemeanofallsamplevalues.TheformulastocreatetheteststatIstIcare
computatIonallyelegantbutareratherhardtoapprecIateIntuItIvely.TheFstatIstIchas
twodegreesoffreedom,denotedmandn;thevalueofmIsafunctIonofthenumber
P.201
ofexperImentalgroups;thevaluefornIsafunctIonofthenumberofsubjectsInall
experImentalgroups.TheanalysIsofmultIgroupdataIsnotnecessarIlyfInIshedafterthe
AND7Asarecalculated.fthenullhypothesIsIsrejectedandItIsacceptedthatthereare
dIfferencesamongthegroupstested,howcanItbedecIdedwherethedIfferencesare:A
varIetyoftechnIquesareavaIlabletomakewhatarecalledmultiple comparisonsafterthe
AND7AtestIsperformed.
Robustness and Nonparametric Tests
|oststatIstIcaltestsdependoncertaInassumptIonsaboutthenatureofthedIstrIbutIonof
valuesIntheunderlyIngpopulatIonsfromwhIchexperImentalsamplesaretaken.Forthe
parametrIcstatIstIcs,thatIs,ttestsandanalysIsofvarIance,ItIsassumedthatthe
populatIonsfollowthenormaldIstrIbutIon.However,forsomedata,experIenceor
hIstorIcalreasonssuggeststhattheseassumptIonsofanormaldIstrIbutIondonothold;
someexamplesIncludeproportIons,percentages,andresponsetImes.Whatshouldthe
experImenterdoIfheorshefearsthatthedataarenotnormallydIstrIbuted:
TheexperImentermIghtchoosetoIgnoretheproblemofnonnormaldataand
InhomogeneItyofvarIance,hopIngthateverythIngwIllworkout.SuchInsoucIanceIs
actuallyaverypractIcalandreasonableapproachtotheproblem.ParametrIcstatIstIcsare
calledrobuststatIstIcs;theystanduptomuchadversIty.ToastatIstIcIan,robustness
ImplIesthatthemagnItudeoftypeerrorsIsnotserIouslyaffectedbyIllcondItIoneddata.
ParametrIcstatIstIcsaresuffIcIentlyrobustthattheaccuracyofdecIsIonsreachedby
meansofttestsandanalysIsofvarIanceremaInsverycredIble,evenformoderately
severedeparturesfromtheassumptIons.
AnotherpossIbIlItywouldbetousestatIstIcsthatdonotrequIreanyassumptIonsabout
probabIlItydIstrIbutIonsofthepopulatIons.SuchstatIstIcsareknownasnonparametric
tests;theycanbeusedwheneverthereIsveryserIousconcernabouttheshapeofthe
data.NonparametrIcstatIstIcsarealsothetestsofchoIceforordInaldata.ThebasIc
conceptbehIndnonparametrIcstatIstIcsIstheabIlItytorankorordertheobservatIons;
nonparametrIctestsarealsocalledorder statistics.
|ostnonparametrIcstatIstIcsstIllrequIretheuseoftheoretIcalprobabIlItydIstrIbutIons;
thecrItIcalvaluesthatmustbeexceededbytheteststatIstIcaretakenfromthebInomIal,
normal,andchIsquaredIstrIbutIons,dependIngonthenonparametrIctestbeIngused.The
nonparametric sign test, Mann-Whitney rank sum test,andKruskal-Wallis one-way analysis
of varianceareanalogoustothepaIredttest,unpaIredttest,andonewayanalysIsof
varIance,respectIvely.ThecurrentlyavaIlablenonparametrIctestsarenotusedmore
commonlybecausetheydonotadaptwelltocomplexstatIstIcalmodelsandbecausethey
arelessablethanparametrIcteststodIstInguIshbetweenthenullandalternatIve
hypothesesIfthedataare,Infact,normallydIstrIbuted.
Linear Regression
DftenthegoalofanexperImentIstopredIctthevalueofonecharacterIstIcfrom
knowledgeofanothercharacterIstIc;themostcommonlyusedtechnIqueforthIspurposeIs
regressIonanalysIs.ExperImentsforthIspurposecapturedatapaIrs(x, y);thesedata
shouldbedIsplayedInascatterplot.nthesImplesttype,astraIghtlIne(lInear
relatIonshIp)IsassumedbetweentwovarIables;one(y),theresponseordependent
varIable,IsconsIderedafunctIonoftheother(x),theexplanatoryorIndependent
varIable.ThIsIsexpressedasthelInearregressIonequatIony=a+bx;theparametersof
theregressIonequatIonareaandb.TheparameterbIstheslopeofthestraIghtlIne
relatIngxandy;foreach1unItchangeInx,thereIsabunItchangeIny.Theparametera
IstheIntercept(valueofywhenxequals0).EstImatesoftheparametersareobtaIned
fromaleastsquaresmethodthatsetstheslopebvaluetomInImIzethedIstancesfromthe
datapaIrstothe
parameterofgreatestInterestInregressIonIsusuallytheslope,especIallywhetherthe
slopeIsnonzero;azerovaluedslopeImplIesthatxandyarenotrelated.AtteststatIstIc
IsusedtocheckthestatIstIcalsIgnIfIcanceoftheslope.
WhIlethereIsanaddItIonalassumptIon,thesame(x, y)datapaIrsareusuallysubjectedto
correlatIonanalysIs.ThecorrelatIoncoeffIcIentrIsameasureofthecovarIatIonofxand
y;rrangesfrom1to1.ThereIsnocorrelatIonforazerovaluedr.
ThetestofthestatIstIcalsIgnIfIcanceofrIsequIvalenttothetestforthesIgnIfIcanceof
theregressIonslopeb.ThesquaredvalueofrorcoeffIcIentofdetermInatIon(r
2
)hasa
veryusefulInterpretatIon:thefractIonofthevarIatIonofyexplaInedbythevarIatIonof
x.
FegressIonmethodscanbeextendedtodatasetsInwhIchoneresponsevarIableIsthought
tobelInearlyrelatedtomanyexplanatoryvarIables;thIsIscalledmultiple variable linear
regression.ThIsregressIonIncludesmethodsforchoosIngwhIchoftheexplanatory
varIableshaveastatIstIcallysIgnIfIcantregressIonslope.DtherextensIonsofregressIon
IncludethetypIcallysIgmoIdallyshapedregressIonofabInaryoutcome(e.g.,movement)
versusanesthetIcdose.TherearemultIplemethodsforregressIonofbInaryoutcomes,the
mostcommonbeInglogIstIcregressIon.
AresearcherorreadershouldnotbesatIsfIedtoseeonlythestatIstIcalresultsof
regressIonandcorrelatIon.ThestatIstIcIanAnscombe
4
createdfourhypothetIcaldatasets
toIllustratetheImportanceofvIsualInspectIonofdata.Eachdatasethas11paIred(x, y)
observatIons(FIg.91).Forthedata(x
2
, y
2
),therelatIonshIpbetweenxandyIs
curvIlInear;for(x
4
,y
4
),thereIsnorelatIonshIpbetweenxandy;for(x
J
,y
J
),thereIsa
nearperfectcorrelatIonbetweenxandyexceptforone(x, y)paIr.AllregressIonand
correlatIonvaluesofthefourdatasetsIncludIngmeans,S0s,slopes,Intercepts,standard
errorsofregressIonparameters,statIstIcalsIgnIfIcanceofregressIonparameters,and
correlatIoncoeffIcIentsareequal.Yet,theseareclearlyfourdIfferentpatternsthatcan
onlybedetectedbyvIsualInspectIon.EventhIssImplestformoflInearregressIonIsbased
onthestrongassumptIonofanunderlayInglInearrelatIonshIpbetweenxandy;faIlureof
thatassumptIonleadstoerroneousstatIstIcalInference.
Systematic Reviews and Meta-Analyses
FeportsusInganewtypeofresearchmethodthesystematIcrevIew(SF)wIthan
accompanyIngmetaanalysIs(|A)havebecomecommonplaceoverthelast25yearsIn
anesthesIajournals.
5
(AsofNovember2007,alIteraturesearchfor(systematIcrevIew
DFmetaanalysIs)AN0anesthesIaInPub|edattheNatIonalLIbraryof|edIcInereturned
JJ4cItatIonsofatotalofallJ6,026cItatIonsforSFsor|As
a
.)nsystematIcrevIews,a
focusedquestIondrIvestheresearch,forexample,(1)Transient neurologic symptoms (TNS)
following spinal
P.202
anaesthesia with lidocaine versus other local anaesthetics
6
or(2)Ventilation with lower
tidal volumes versus traditional tidal volumes in adults for acute lung injury and acute
respiratory distress syndrome.
7
ThesetItlesrevealsomeoftheresearchdesIgnofa
systematIcrevIew.ThereIsapopulatIonofInterest:(1)patIentshavIngspinal anesthesia
and(2)adults(wIth)acute lung injury and acute respiratory distress syndrome.ThereIsa
comparIsonoftwoInterventIons:(1)lidocaine versus other local anaestheticsand(2)
ventilation with lower tidal volumes versus traditional tidal volumes.ThereIsanoutcome
forchoosIngsuccessorfaIlureoftheInterventIons:(1)occurrenceofTNSand(2)28-day
mortality(lIstedIntext).
Figure 9-1.FourscatterplotsfromtheAnscombedatasets.
4
Foreachdataset,n=11,
[x with bar above]=9.00,SD
x
=J.J1,[Y with bar above]=2.0JSD
y
=2.0J,y=J.00+
0.50x,SE
a
=1.12,SE
b
=0.12,r
2
=0.67,andsoforth.AllstatIstIcsareequaluptothe
fourthdecImalplace.
ToanswertheexperImentalquestIon,dataareobtaInedfromcontrolledtrIals(usually
randomIzed)alreadyInthemedIcallIteratureratherthanfromnewlyconductedclInIcal
trIals;thebasIcunItofanalysIsofthIsobservatIonalresearchIsthepublIshedstudy.The
researchers,alsocalledthereview authors,proceedthroughastructuredprotocol,whIch
IncludesInpart:(1)choIceofstudyInclusIon/exclusIoncrIterIa,(2)explIcItlydefIned
lIteraturesearchIng,(J)abstractIonofdatafromIncludedstudIes,(4)appraIsalofdata
qualIty,(5)systematIcpoolIngofdata,and(6)dIscussIonofInferences.ThIsstructured
protocolIsIntendedtomInImIzebIas.EvenrandomIzedcontrolledtrIalsmayhavesources
ofbIassuchas(1)selectIonbIas:systematIcdIfferencesbetweenthepatIentsreceIvIng
eachInterventIon;(2)performancebIas:systematIcdIfferencesIncarebeInggIvento
studypatIentsotherthanthepreplannedInterventIonsbeIngevaluated;(J)attrItIonbIas:
systematIcdIfferencesInthewIthdrawalofpatIentsfromeachofthetwoInterventIon
groups;and(4)detectIonbIas:systematIcdIfferencesIntheascertaInmentandrecordIng
ofoutcomes.ThemaInfocusofbIasdetectIonInthetrIalsIncorporatedIntoaSFIs(1)the
randomIzatIonprocess,(2)theconcealmentofrandomallocatIon,(J)theuseofblIndIng,
and(4)thereportIng/analysIsofdropouts.
8
8Inaryoutcomes(yes/no,alIve/dead,presence/absence)wIthInastudyareusually
comparedbytherelatIverIsk(rateratIo)statIstIc.fthereIssuffIcIentclInIcalsImIlarIty
amongtheIncludedstudIes,asummaryrelatIverIskoftheoveralleffectofthecomparIson
treatmentsIsestImatedbymetaanalysIs;metaanalysIsIsasetofstatIstIcaltechnIques
forcombInIngresultsfromdIfferentstudIes.
8
ThecalculatIonsforthestatIstIcalanalysesof
ametaanalysIsareunfamIlIartomost,butarenotdIffIcult.TheresultsofametaanalysIs
areusuallypresentInafIgurecalledaforest plot(FIg.92).ThefarleftcolumnIdentIfIes
theIncludedstudIesandtheobserveddata.ThehorIzontallInesanddIamondshapesare
graphIcalrepresentatIonsofIndIvIdualstudyrelatIverIskandsummaryrelatIverIsk,
respectIvely;thefarrIghtcolumnofthefIgurelIststherelatIverIskswIth95Csforthe
IndIvIdualstudIesandthesummarystatIstIcs.TherearealsodescrIptIveandInferentIal
statIstIcsconcernIngthestatIstIcalheterogeneItyofthemetaanalysIsandthesIgnIfIcance
ofthesummarystatIstIcs.
AnexamInatIonofFIgure92showsthatmanyoftheIndIvIdualstudIes(11of14)hadwIde,
nonsIgnIfIcantconfIdenceIntervalsthattouchorcrosstherelatIverIskofIdentIty(FF=1).
However,theoverallrelatIverIskcalculatedfromallstudIeswas7.16wItha95C[4.2,
12.75].ThepowerofsummarystatIstIcstocombIneevIdenceIsclear.TherevIewauthors
concluded:LIdocaInecancausetransIentneurologIcsymptoms(TNS)Ineveryseventh
patIentwhoreceIvesspInalanesthesIa.TherelatIverIskofdevelopIngTNSIsaboutseven
tImeshIgherforlIdocaInethanforbupIvacaIne,prIlocaIne,andprocaIne.ThesepaInful
symptomsdIsappearcompletelybythetenthpostoperatIveday.
6
TheproductIonofSFscomesfromseveralsources.|anycomefromtheIndIvIdual
InItIatIveofresearcherswhopublIshtheIrresultsasstandalonereportsInthejournalsof
medIcIneandanesthesIa.TheAmerIcanSocIetyofAnesthesIologIstshas
P.20J
developedaprocessforthecreatIonofpractIceparametersthatIncludesamongother
thIngsavarIantformofSFs.ThemostpromInentproponentofSFsIstheCochrane
CollaboratIon,Dxford,UnItedKIngdom.TheCochraneCollaboratIonIsanInternatIonal
notforprofItandIndependentorganIzatIon,dedIcatedtomakInguptodate,accurate
InformatIonabouttheeffectsofhealthcarereadIlyavaIlableworldwIde.tproducesand
dIssemInatessystematIcrevIewsofhealthcareInterventIonsandpromotesthesearchfor
evIdenceIntheformofclInIcaltrIalsandotherstudIesofInterventIons.TheCochrane
CollaboratIonwasfoundedIn199Jandnamedafterthe8rItIshepIdemIologIst,ArchIe
Cochrane.
b
Figure 9-2.Forestplot.(|odIfIedfromCraph02/01InZarIc0,ChrIstIansenC,Pace
NL,PunjasawadwongY:TransIentneurologIcsymptoms(TNS)followIngspInal
anaesthesIawIthlIdocaIneversusotherlocalanaesthetIcs(CochraneFevIew).n:The
Cochrane Library,ssueJ.ChIchester,UK,JohnWIleyESons,Ltd.,2004.CopyrIght
CochraneLIbrary,reproducedwIthpermIssIon.)
Therearemorethan50collaboratIverevIewgroupsthatprovIdetheedItorIalcontroland
supervIsIonofSFs;oneofthese,locatedInCopenhagen,
9
produce(s)anddIssemInate
systematIcrevIewsofhealthcareInterventIonsInanesthesIa,perIoperatIvemedIcIne,
IntensIvecaremedIcIne,emergency
P.204
medIcIne,prehospItalmedIcIneandresuscItatIon.
c
TheCochraneCollaboratIonhas
extensIvedocumentatIonandtutorIalsavaIlableelectronIcallyexplaInIngthetechnIquesof
SFsand|A;forthecreatIonofCochraneSFs,software(tItledFev|an)forthe
managementofdataandforthe|AIsfreelyavaIlableanddownloadablefromthe
CochraneCollaboratIonWebsIte.
Interpretation of Results
ScIentIfIcstudIesdonotendwIththestatIstIcaltest.TheexperImentermustsubmItan
opInIonastothegeneralIzabIlItyofhIsorherworktotherestoftheworld.EvenIfthere
IsastatIstIcallysIgnIfIcantdIfference,theexperImentermustdecIdeIfthIsdIfferenceIs
medIcallyorphysIologIcallyImportant.StatIstIcalsIgnIfIcancedoesnotalwaysequatewIth
bIologIcrelevance.ThequestIonsanexperImentershouldaskabouttheInterpretatIonof
resultsarehIghlydependentonthespecIfIcsoftheexperIment.FIrst,evensmall,clInIcally
unImportantdIfferencesbetweengroupscanbedetectedIfthesamplesIzeIssuffIcIently
large.Dntheotherhand,IfthesamplesIzeIssmall,onemustalwaysworrythatIdentIfIed
orunIdentIfIedconfoundIngvarIablesmayexplaInanydIfference;asthesamplesIze
decreases,randomIzatIonIslesssuccessfulInassurInghomogenousgroups.Second,Ifthe
experImentalgroupsaregIventhreeormoredosesofadrug,dotheresultssuggesta
steadIlyIncreasIngordecreasIngdoseresponserelatIonshIp:Supposetheobservedeffect
foranIntermedIatedoseIseIthermuchhIgherormuchlowerthanthatforboththe
hIghestandlowestdose;adoseresponserelatIonshIpmayexIst,butsomeskeptIcIsmabout
theexperImentalmethodsIswarranted.ThIrd,forclInIcalstudIescomparIngdIfferent
drugs,devIces,andoperatIonsonpatIentoutcome,arethepatIents,clInIcalcare,and
studIedtherapIessuffIcIentlysImIlartothoseprovIdedatotherlocatIonstobeofInterest
toawIdegroupofpractItIoners:ThIsIsthedIstInctIonbetweenefficacydoesItwork
underthebest(research)cIrcumstancesandeffectivenessdoesItworkunderthetypIcal
cIrcumstancesofroutIneclInIcalcare:
FInally,IncomparIngalternatIvetherapIes,theconfIdencethataclaImforasuperIor
therapyIstruedependsonthestudydesIgn.ThestrengthoftheevIdenceconcernIng
effIcacywIllbeleastforananecdotalcasereport;nextInImportancewIllbea
retrospectIvestudy,thenaprospectIveserIesofpatIentscomparedwIthhIstorIcal
controls,andfInallyarandomIzed,controlledclInIcaltrIal.Thegreateststrengthfora
therapeutIcclaImIsaserIesofrandomIzed,controlledclInIcaltrIalsconfIrmIngthesame
hypothesIs.ThereIsnowconsIderableenthusIasmfortheformalsynthesIsandcombInIngof
resultsfromtwoormoretrIalsInasystematIcrevIew.
Conclusions
Guidelines for Reading Journal Articles
ThousandsofwordsarewrItteneachyearInjournalartIclesrelevanttoanesthesIa.Noone
canreadthemall.HowshouldtheclInIcIandetermInewhIchartIclesareuseful:AllthatIs
possIbleIstolearntorapIdlyskIpovermostartIclesandconcentrateonthefewselected
fortheIrImportancetothereader.ThosefewshouldbechosenaccordIngtotheIr
relevanceandcredIbIlIty.FelevanceIsdetermInedbythespecIfIcsofone'sanesthetIc
practIce.CredIbIlItyIsafunctIonofthemerItsoftheresearchmethods,theexperImental
desIgn,andthestatIstIcalanalysIs;themoreprofIcIentone'sstatIstIcalskIlls,themore
rapIdlyonecanacceptorrejectthecredIbIlItyofaresearchartIcle.
SIxeasIlyrememberedappraIsalcrIterIaforclInIcalstudIescanbefashIonedfromthe
wordsWHY,HDW,WHD,WHAT,HDW|ANY,andSDWHAT:(1)WHY:sthebIologIc
hypothesIsclearlystated:(2)HDW:WhatIstheresearchdesIgn:(J)WHD:sthetarget
populatIonclearlydefIned:(4)WHAT:HowwasthetherapyadmInIsteredandthedata
collected:(5)HDW|ANY:AretheteststatIstIcsconvIncIng:(6)SDWHAT:sItclInIcally
relevanttomypatIents:AlthoughthestatIstIcalknowledgeofmostphysIcIansIslImIted,
theseskIllsofcrItIcalappraIsalofthelIteraturecanbelearnedandcantremendously
IncreasetheeffIcIencyandbenefItofjournalreadIng.
Statistical Resources
AccompanyIngtheexponentIalgrowthofmedIcalInformatIonsInceWorldWarhasbeen
thecreatIonofawealthofbIostatIstIcalknowledge.TextbooksorIentedtowardmedIcal
statIstIcsandwIthexposItIonsofbasIc,IntermedIate,andadvancedstatIstIcs
abound.
10,11,12,1J,14,15
TherearenewjournalsofbIomedIcalstatIstIcs,IncludIngClinical
Trials, Statistics in Medicine,andStatistical Methods in Medical Research,whoseaudIences
arebothstatIstIcIansandbIomedIcalresearchers.SomemedIcaljournals,forexample,the
British Medical Journal,regularlypublIshexposItIonsofbothbasIcandneweradvanced
statIstIcalmethods.ExtensIventernetresourcesIncludIngelectronIctextbooksofbasIc
statIstIcalmethods,onlInestatIstIcalcalculators,standarddatasets,revIewsofstatIstIcal
software,andsooncanbeeasIlyfound.
Statistics and Anesthesia
DneIntentofthIschapterIstopresentthebasIcscopeofsupportthatthedIscIplIneof
statIstIcscanprovIdetoanesthesIaresearch.JournalsofanesthesIanowIncludemany
newermethodsthathavenotbeendescrIbed.TomentIonjustfour:(1)studIesofthe
pharmacokInetIcsandpharmacokInetIcsofadrugoracombInatIonofdrugstypIcallyuse
lInearmIxedeffectsorgeneralIzedlInearmIxedeffectsmodels,(2)technIquesofsurvIval
analysIsareapplIedtohospItaldIschargetImesorpostoperatIvemorbIdIty/mortalIty
outcomes,(J)methodsofInterImanalysIsorsequentIaltrIaldesIgnareusedInrandomIzed
controlledtrIalstostopfutIleordangeroustreatments,and(4)propensItyanalysIsreduces
thepossIblebIasesInepIdemIologyresearch.
AlthoughanIntuItIveunderstandIngofcertaInbasIcprIncIplesIsemphasIzed,thesebasIc
prIncIplesarenotnecessarIlysImpleandhavebeendevelopedbystatIstIcIanswIthgreat
mathematIcalrIgor.AcademIcanesthesIaneedsmoreworkerstoImmersethemselvesIn
thesestatIstIcalfundamentals.HavIngdoneso,thesestatIstIcallyknowledgeableacademIc
anesthesIologIstswIllbepreparedtoImprovetheIrownresearchprojects,toassIsttheIr
colleaguesInresearch,toeffIcIentlyseekconsultatIonfromtheprofessIonalstatIstIcIan,to
strengthentheedItorIalrevIewofjournalartIcles,andtoexpoundtotheclInIcalreader
thewhysandwhereforesofstatIstIcs.TheclInIcalreaderalsoneedstoexpendhIsorher
ownefforttoacquIresomebasIcstatIstIcalskIlls.JournalsareIncreasInglydIffIcultto
understandwIthoutsomebasIcstatIstIcalunderstandIng.SomeclInIcalproblemscanbe
bestunderstoodwIthaperspectIvebasedonprobabIlIty.FInally,understandIngprIncIples
ofexperImentaldesIgncanpreventprematureacceptancesofnewtherapIesfromfaulty
studIes.
P.205
References
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lIgatIonbyadoubleblIndtechnIc.NEnglJ|ed1959;260:1115
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methodologIcalqualItyassocIatedwIthestImatesoftreatmenteffectsIncontrolled
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ntensIveCare.EdItedby|ollerA,PedersenT,CracknellJ.NewYork,CambrIdge
UnIversItyPress,2006,pp46
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FevIewCroup,EvIdence8asedAnaesthesIaandntensIveCare.EdItedby|ollerA,
PedersenT,CracknellJ.NewYork,CambrIdgeUnIversItyPress,2006,pp77
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ntervalsandStatIstIcalCuIdelInes.NewYork,JohnWIleyESons,2000
11.Campbell|J,|achIn0:|edIcalStatIstIcs:ACommonsenseApproach.NewYork,
JohnWIleyESons,1999
12.0awson8,TrappFC,TrappF:8asIcEClInIcal8IostatIstIcs.NewYork,|cCrawHIll
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1J.FIffenburghFH:StatIstIcsIn|edIcIne.San0Iego,AcademIcPress,2005
14.ClantzSA:PrImerof8IostatIstIcs.NewYork,|cCrawHIll|edIcal,2005
15.FennIe0,CuyattC:Users'CuIdestothe|edIcalLIterature:A|anualforEvIdence
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AmerIcan|edIcalAssocIatIon,2002
Stock, M. Christine
TableofContentsSectIonAnatomyandPhysIologyChapter10CardIovascularAnatomyandPhysIology
Chapter10
Cardiovascular Anatomy and Physiology
John P. Kampine
David F. Stowe
Paul S. Pagel
Key Points
1. The left ventricle (LV) is capable of tolerating large increases in
arterial pressure without a substantial reduction in stroke volume,
but the right ventricle may acutely decompensate with even modest
increases in pulmonary vascular resistance.
2. Atrial contraction establishes final ventricular stroke volume at end-
diastole and normally contributes between 15 and 20% of this
volume.
3. Diastolic dysfunction may independently cause heart failure, even in
the presence of relatively normal contractile function. This heart
failure with normal systolic function has been increasingly
recognized as a major underlying cause for as many as 50% of
patients admitted to the hospital with congestive heart failure.
4. According to Starling's law, the force of LV contraction and volume of
blood ejected from the chamber during systole (stroke volume) is
directly related to the end-diastolic myofilament length, and hence,
the end-diastolic volume.
5. The distensibility of the aorta, the resistance of the peripheral arterial
vasculature, and the actions of reflected waves on the central aortic
circulation are the principle determinants of afterload. Systemic
vascular resistance (the ratio of pressure to cardiac output, P/Q) is
the most commonly used nonparametric expression of peripheral
resistance and is primarily affected by autonomic nervous system
activity.
6. The primary determinant of myocardial oxygen consumption is heart
rate because the heart completes an entire cycle with each beat, and
hence, the more frequently the heart performs pressure-volume
work, the more oxygen must be consumed.
7. The fundamental contractile unit of cardiac muscle is the sarcomere.
The myofilaments within each sarcomere are arranged in parallel
cross-striated bundles of thin (containing actin, tropomyosin, and the
troponin complex) and thick (primarily composed of myosin and its
supporting proteins) fibers. Sarcomeres are connected in series,
thereby producing characteristic shortening and thickening of the
long and short axes of each myocyte, respectively, during
contraction.
8. Attachment of myosin to its binding site on the actin molecule
releases the phosphate anion from the myosin head, thereby
producing a molecular conformation within this cross-bridge structure
that generates tension in both myofilaments. Release of adenosine
diphosphate (ADP) and the stored potential energy from this
activated conformation produce rotation of the cross-bridge (power
stroke) at the hinge point separating the helix tail region from the
globular myosin head and its associated light chain proteins.
9. The QRS complex records potentials at the body surface when the
wave of depolarization is distributed throughout ventricular
myocardium. The QRS complex is much larger in magnitude than the
P wave because ventricular mass is greater than the atrial mass.
Rapid conduction through the His-Purkinje system spreads the wave
of depolarization quickly to the ventricles.
P.210
11. Short-duration regulation of mean arterial pressure occurs through
the arterial, and to a lesser extent, intracardiac baroreceptors.
Arterial baroreceptors are located at the bifurcation of the common
carotid arteries and in the aortic arch.
12. Blood supply to the LV is directly dependent on the difference
between the aortic pressure and LV end-diastolic pressure (coronary
perfusion pressure) and inversely related to the vascular resistance
to flow, which varies to the fourth power of the radius of the vessel
(Poiseuille's law).
13. Metabolic factors are the major physiological determinants of
coronary vascular tone and, hence, myocardial perfusion.
14. Myocardial infarction may occur without evidence of major coronary
thromboses, emboli, or stenosis. This form of infarction is caused by
excessive metabolic demands resulting from severe LV hypertrophy
(e.g., critical aortic stenosis) or vasoactive drug ingestion (e.g.,
amphetamines, cocaine) or it may also result from coronary artery
vasospasm.
15. The lung is richly innervated by the parasympathetic and sympathetic
nervous system, but the dominant effect of the autonomic nervous
system occurs primarily at the level of alveolar and bronchial smooth
muscle.
16. Cerebral blood flow remains relatively constant when mean arterial
pressure varies between 50 and 150 mm Hg in healthy subjects. This
autoregulation of cerebral blood flow is shifted to the right in patients
with chronic, poorly controlled essential hypertension.
17. Arterial CO
2
tension is a major regulator of cerebral blood flow within
the physiologic range of arterial CO
2
tension. Cerebral blood flow
linearly increases 1 to 2 mL/100 g/min for each 1 mm Hg increase in
Paco
2
. Below an arterial CO
2
tension of 25 mm Hg, the cerebral blood
flow response to Paco
2
is attenuated.
Functional Anatomy of the Heart
TheleftandrIghtatrIaconsIstoftwo,thInoverlyIngsheathsofmuscleorIentedatrIght
anglestoeachother.ThetwothIckerwalledventrIclesconsIstofthreeInterdIgItatIng
musclelayers:thedeepsInospIral,thesuperfIcIalsInospIral,andthesuperfIcIalbulbospIral
muscles(FIg.101).ThetwooutermusclelayersareorIentedoblIquelyfromthebaseof
thehearttotheapex.ConstrIctIonofthesefIbersshortensthelongItudInalaxIsoftheleft
ventrIcle(L7)bymovIngthebasetowardtheapex.ThecIrcumferentIaldeepsInospIral
musclesreducetheL7dIameter(FIg.102).Thus,synchronouscontractIonoftheL7
musclesshortensthelongaxIsoftheheart,decreasesthecIrcumferenceoftheL7
chamber,andlIftstheapextowardtheanterIorchestwall.ThIslatteractIonproducesthe
famIlIarpalpablepoIntofmaxImumImpulse,whIchIsnormallylocatedInthefIfthorsIxth
IntercostalspaceInthemIdclavIcularlIne.
1,2
TheL7pumpsbloodfromthelowpressure
venousIntothehIghpressurearterIalsystem.TherIghtventrIcle(F7)receIvesvenous
bloodfromtherIghtatrIumvIathesuperIorandInferIorvenacavaeatlowpressure(2to
10mmHg)andoxygensaturatIon(60to75).TheF7IscrescentshapedandcontaIns
embryologIcallydIstantInflowandoutflowtractsthatcontractInaperIstaltIcsequenceto
propelbloodIntothepulmonaryarterIaltree.8loodflowthroughthepulmonary
cIrculatIonfunctIonsprImarIlyasagasexchanger,provIdIngfortheelImInatIonofcarbon
dIoxIde(CD
2
;amajorproductofcellularmetabolIsm)andtheuptakeofoxygen(D
2
).The
pulmonaryvasculatureIscharacterIzedbylowerpressurethanthesystemIccIrculatIonand
hasshorter,largerborebloodvesselswIthrelatIvelythInnerwallsthansystemIcresIstance
vessels.Thus,thepulmonarycIrculatIonIsalowpressure,lowresIstancesystemInto
whIchtheF7transfersblood.TheL7IscapableoftoleratInglargeIncreasesInarterIal
pressurewIthoutasubstantIalreductIonInstrokevolume;theF7mayacutely
decompensatewIthevenmodestIncreasesInpulmonaryvascularresIstance.TheF7free
walloccupIesamorerIghtsIded,anterIorposItIonwIthInthemedIastInumcomparedwIth
theposItIonofthethIckerwalledL7thatIslocatedInaleftsIded,posterIororIentatIon
(FIg.10J,Aand8).0urIngcontractIon,theF7movestowardtheInterventrIcularseptum
wIthabellowslIkeactIon.TheatrIoventrIcular(A7)groove
P.211
separatIngtherIghtatrIumandF7shortenstowardtheapexdurIngcontractIon.ThIs
anatomIcconfIguratIonpermItsthemoreflexIbleF7walltoejectalargevolumeofblood
wIthamInImalamountofshortenIng.TheechocardIographIcdepIctIonofventrIcular
contractIonIsshownInFIgure10J.
Figure 10-1.ComponentsofthemyocardIum.Theoutermusclelayerspulltheapexof
thehearttowardthebase.TheInnercIrcumferentIallayersconstrIctthelumen,
partIcularlyoftheleftventrIcle.(FeproducedwIthpermIssIonfromFushmerFF:
CardIovascular0ynamIcs.PhIladelphIa,W8Saunders,1976,FIg.J2,p78.)
Figure 10-2.7entrIcularvolumeejectIon.ContractIoncharacterIstIcsandmodesof
emptyIng.ThevolumesejectedbyeachventrIcleIsequalbuttheleftventrIcle
requIresamorecIrcumferentIalmuscularwalltoejectItsvolumeatapressurethatIs
approxImately4to5tImesgreaterthanthatIntherIghtventrIcle.(FeproducedwIth
permIssIonfromFushmerFF:CardIovascular0ynamIcs.PhIladelphIa,W8Saunders,
1976,FIg.J12,p92.)
Figure 10-3.TransesophagealechocardIographydemonstratesthethIcknessand
motIonofatrIalandventrIcularwallsmIdesophagealfIvechamberandtwochamber
vIews(AandBrespectIvely).
TheL7hasacylIndrIcalendocardIalborder,andthIsanatomIcconfIguratIonprovIdesa
mechanIcaladvantageovertheF7IngeneratIngstrokeworkandpowerbecausea
reductIonInthecrosssectIonalareaofthecylIndera(functIonofthesquareoftheradIus)
IspartIallyresponsIbleforL7strokevolume.TheL7alsoprovIdesasplIntagaInstwhIch
theouterwalloftheF7IspulleddurIngcontractIon.TheD
2
contentandsaturatIonof
bloodwIthIntheL7(D
2
20mL/dLand98,respectIvely)IsveryhIghcomparedwIthblood
IntheF7.LeftventrIcularD
2
saturatIonIsIncompletebecauseasmallquantItyofcoronary
venousreturnthroughthebesIanveInsemptIesdIrectlyIntotheleftsIdeoftheheart.
0urIngcontractIon,L7pressureIncreasesfromenddIastolIcvaluesof10to12mmHgtoa
peakpressureof120to140mmHgdurIngsystole.ThepeakpressuresgeneratedbytheL7
reflecttherequIrementtocIrculatebloodthroughthehIghresIstancesystemIccIrculatIon
thatIscomposedofthIckerbloodvesselscontaInInglargerquantItIesofvascularsmooth
musclethantheIrcounterpartsInthepulmonaryarterIaltree.FesIstancetobloodflowIs
especIallyhIghInsmallarterIolesandprecapIllaryvessels,andbloodflowInthesevessels
requIresthattheL7generatehIgherperfusIonpressurethantheF7.Thevolumeofblood
pumpedbyF7andL7IsIdentIcal(strokevolume),butthepressurevolumework(stroke
work)performedbytheL7Is5to7tImesgreaterthanthatoftheF7.LeftventrIcular
ejectIonIsassocIatedwIthawalltensIongradIentfromtheapextothebaseoftheheart
(aortIcoutflowtract),therebyproducIngtheIntraventrIculargradIentrequIredtotransfer
strokevolumefromtheL7Intotheaorta.
EffIcIentpumpIngactIonoftheheartrequIrestwopaIrsofunIdIrectIonalvalves.DnepaIr
IslocatedattheoutletsoftheF7andL7(pulmonIcandaortIcvalves,respectIvely).These
threeleafletvalvesoperatepassIvelywIthchangesInpressuregradIents.TheaortIcvalve
leafletsdonotflattenagaInsttheaortIcwalldurIngL7ejectIonbecauseamodestdIlatIon
oftheaortIcrootlocatedImmedIatelydIstaltoeachleafletestablIshesaneddycurrentof
bloodflow.ThesedIlatedregIonsaretermedthesinuses of ValsalvaandpermItbloodflow
throughtherIghtandleftmaIncoronaryarterIeswhoseopenIngsarelocatedIntheaortIc
walldIrectlybehIndthevalvecusps.TheA7valvesseparatIngtheatrIafromtheventrIcles
arethetrIcuspIdandmItralvalveontherIghtandleftsIdesoftheheart,respectIvely.The
mItralvalveIstheonlycardIacvalvewIthtwoleaflets.8othtrIcuspIdandmItralvalves
arethIn,fIbrousstructuresthataresupportedbychordaetendInaeattachmentsto
papIllarymusclesthatarepartoftheventrIcularmusculatureandcontractdurIngsystole.
ThetrIcuspIdandmItralvalvesopenandclosewIthalternatIonsInthepressuregradIents
betweenthecorrespondIngatrIalandventrIcularchambers.
TheF7andL7arethemajorcardIacpumpIngchambers,buttheatrIaplaycrItIcally
ImportantsupportIngroles.TheatrIafunctIonasreservoIrs,conduIts,andcontractIle
chambersandfacIlItatethetransItIonbetweencontInuous,lowpressurevenoustophasIc,
hIghpressurearterIalbloodflow.ThenormalatrIalpressurecurvehasthreeposItIve
reflectIons.ShortlyaftertheonsetofatrIaldepolarIzatIon(IndIcatedbythePwaveofthe
electrocardIogram),theatrIacontract,producIngaposItIvepressurewave(theAwave)
lateIndIastole.Attheonsetofsystole,ventrIcularcontractIonproducesanotherpressure
wavethatIstransmIttedthroughtheA7valvestotheatrIa,resultIngIntheCwave.0urIng
theremaInderofsystole,theA7valvesremaInclosed,atrIalfIllIngcontInuesfrom
perIpheralandpulmonaryveIns,andatrIalpressuresrIse,therebyproducIngaposItIve
pressuredeflectIonknownastheV wave(FIg.104).AtrIalcontractIonestablIshesfInal
ventrIcularstrokevolumeatenddIastoleandnormallycontrIbutesbetween15and20of
thIsvolume.WhenatrIalcontractIonIsabsentorIneffectIve(e.g.,atrIalfaIlure,atrIal
fIbrIllatIonorflutter),theheartmaybecapableofcompensatIngforthelossoftheatrIal
contractIlefunctIonandcontInuetofunctIoneffectIvelyunderrestIngcondItIons.
However,durIngIncreasedphysIcalactIvItyorstress,theabsenceoftheatrIalpumpmay
substantIallylImItcardIacoutput,therebycausIngamarkedreductIonInarterIalblood
pressureaccompanIedbysyncope,exertIonaldyspnea,easyfatIgabIlIty,oracuteheart
faIlure.
The Cardiac Cycle
ThecardIaccycleIstradItIonallydefInedbasedoneventsoccurrIngbefore,durIng,and
afterL7contractIon.LeftventrIcularsystoleIscommonlydIvIdedIntothreeparts:
IsovolumIccontractIon,rapIdejectIon,andslowerejectIon.
2,J
ClosureofboththetrIcuspId
andmItralvalvesoccurswhenF7andL7pressuresexceedcorrespondIngatrIalpressure
andIsthesourceofthefIrstheartsound(S
1
;FIg.104).sovolumIc
P.212
contractIonIstheIntervalbetweenclosureofthemItralvalveandtheopenIngofthe
aortIcvalve.LeftventrIcularvolumeremaInsconstantdurIngthIsperIodofthecardIac
cycle.TherateofIncreaseofL7pressure(dP/dt,anIndexofmyocardIalcontractIlIty)
reachesItsmaxImumdurIngIsovolumIccontractIon.TrueIsovolumIccontractIondoesnot
occurIntheF7becausethesequentIalnatureofInflowfollowedbyoutflowtractF7
contractIon.PressureIntheaortIcrootdeclInestoItsmInImumvalueImmedIatelybefore
theaortIcvalveopens.FapIdejectIonoccurswhenL7pressureexceedsaortIcpressureand
theaortIcvalveopens.ApproxImatelytwothIrdsoftheL7enddIastolIcvolumeIsejected
IntotheaortadurIngthIsrapIdejectIonphaseofsystole.AortIcdIlatIonoccursInresponse
tothIsrapIdIncreaseInvolumeasthekInetIcenergyofL7contractIonIstransferredto
thesystemIcarterIalcIrculatIonaspotentIalenergy.ThecomplIanceoftheaortaand
proxImalgreatvesselsdetermInestheamountofpotentIalenergythatcanbestoredand
subsequentlyreleasedtothearterIalvasculaturedurIngdIastole.ThenormalL7end
dIastolIcvolumeIsabout120mL.TheaverageejectedstrokevolumeIs80mL,andthe
normalejectIonfractIonIsapproxImately67.AdecreaseInejectIonfractIonbelow40Is
typIcallyobservedwhenthemyocardIumIsaffectedbyIschemIa,InfarctIon,or
cardIomyopathIcdIseaseprocesses(e.g.,myocardItIs,amyloIdInfIltratIon).ContractIle
dysfunctIonmayalsooccurasaresultofchronIcpressureorvolumeoverload,dIabetes,or
hypothyroIdIsm.AsaortIcpressurepeaksandresIstsfurtherL7ejectIon,transferoffurther
strokevolumeslowsandeventuallystops.0urIngthIsperIodofslowerejectIon,aortIc
pressuremaybrIeflyexceedL7pressure.ThereversalofthepressuregradIentbetweenthe
aortIcrootandtheL7causestheaortIcvalvetoclose,therebyproducIngthesecondheart
sound(S
2
).
Figure 10-4.|echanIcalandelectrIcaleventsofthecardIaccycleshowIngalsothe
ventrIcularvolumecurveandtheheartsounds.NotetheIsovolumIccontractIon(CP)
andtherelaxatIonperIod(FP)durIngwhIchthereIsnochangeInventrIcularvolume
becauseallvalvesareclosed.TheventrIcledecreasesInvolumeasItejectsIts
contentsIntotheaorta.0urIngthefIrstthIrdofsystolIcejectIontherapIdejectIon
perIodthecurveofemptyIngIssteep.ECC,electrocardIogram.(FeproducedwIth
permIssIonfromSmIthJJ,KampIneJP:CIrculatoryPhysIologyTheEssentIals,Jrd
edItIon.8altImore,WIllIamsEWIlkIns,1990,FIg.J5,p40.)
0IastoleIsdIvIdedIntofourphasesIntheL7:IsovolumIcrelaxatIon,earlyfIllIng,dIastasIs,
andatrIalsystole.sovolumIcrelaxatIondefInestheperIodbetweenaortIcvalveclosure
andmItralvalveopenIngdurIngwhIchL7volumeremaInsconstant.L7pressurefalls
precIpItouslyasthemyofIlamentsrelax.WhenL7pressurefallsbelowleftatrIalpressure,
themItralvalveopens,andbloodvolumestoredIntheleftatrIumrapIdlyenterstheL7
drIvenbythepressuregradIentbetweenthesechambers.ThIsearlyfIllIngphaseof
dIastoleaccountsforapproxImately70to75oftotalL7strokevolumeavaIlableforthe
subsequentcontractIon.0elaysInL7relaxatIonoccurasaconsequenceofagIngordIsease
process(e.g.,myocardIalIschemIa)andmayattenuateearlyventrIcularfIllIng.Afterleft
atrIalandL7pressureshaveequalIzed,themItralvalveremaInsopenandpulmonary
venousreturncontInuestoflowthroughtheleftatrIumIntotheL7.ThIsphaseofdIastole
Isknownasdiastasis,durIngwhIchtheleftatrIumfunctIonsasaconduIt.TachycardIa
progressIvelyshortensandmaycompletelyelImInatethIsphaseofdIastole.0IastasIs
accountsfornomorethan5oftotalL7enddIastolIcvolumeundernormalcIrcumstances.
ThefInalphaseofdIastoleIsatrIalsystole.ContractIonoftheleftatrIumcontrIbutesthe
remaInIngbloodvolume(approxImately15to20)usedInthesubsequentL7systole.
0IseaseprocessesknowntoreduceL7complIance(e.g.,myocardIalIschemIa,pressure
overloadhypertrophy)attenuateearlyfIllIngandIncreasetheImportanceofatrIalsystole
tooverallL7fIllIng.Thus,lossofnormalsInusrhythmmayprecIpItatecatastrophIc
decreasesIncardIacoutputInpatIentswIthsymptomatIccoronaryarterydIsease,crItIcal
aortIcstenosIs,orpoorlycontrolledchronIcessentIalhypertensIon.
6
TheImportanceofdIastoletooverallcardIacperformancecannotbeunderstated.The
rateandextentofrelaxatIon,thevIscoelastIcpropertIesofL7myocardIum,the
perIcardIum,andthestructureandfunctIonoftheleftatrIum,pulmonaryvenous
cIrculatIon,andmItralvalvedetermInethetImIng,rate,anddegreeofL7fIllIng.The
abIlItyoftheL7toadequatelycollectbloodfromthelowpressurepulmonaryvenous
cIrculatIonIscrItIcalIndetermInIngthestrokevolumethatcanbetransferredtothe
arterIalcIrculatIondurIngsystole.Thus,dIastolIcdysfunctIonmayIndependentlycause
heartfaIlure,evenInthepresenceofrelatIvelynormalcontractIlefunctIon.ThIsheart
faIlurewIthnormalsystolIcfunctIonhasbeenIncreasInglyrecognIzedasamajor
underlyIngcauseforasmanyas50ofpatIentsadmIttedtothehospItalwIthcongestIve
heartfaIlure.
8,9
Determinants of Cardiac Output
CardIacoutputIstheamountofbloodpumpedbytheheartpermInute.tIstheproductof
heartrateandstrokevolumeandmaybenormalIzedtothebodysurfacearea(cardIac
Index).CardIacoutput(Q)IsdIrectlyrelatedtopressure(P)andInverselyrelatedto
perIpheralvascularresIstance(F)usInganequatIonanalogoustoDhm'slaw:Q=P/F.
CardIacoutputIsafunctIonofpreload,afterload,myocardIal
P.21J
contractIlIty(InotropIcstate),andheartrate.PreloadIsdefInedbyL7enddIastolIc
volumeIntheIntactheartandreflectsthestretchofventrIcularmyofIlamentsproduced
bythIsenddIastolIcvolumeImmedIatelybeforetheonsetofcontractIon.AccordIngto
StarlIng'slaw,theforceofL7contractIonandvolumeofbloodejectedfromthechamber
durIngsystole(strokevolume)IsdIrectlyrelatedtotheenddIastolIcmyofIlamentlength,
andhence,theenddIastolIcvolume.
10,11
Thus,theventrIcularmyocardIumbehaves
sImIlartoskeletalmuscleInthatanIncreaseInInItIalstretchdetermInesthesubsequent
forceofcontractIon.AfterloadmaybesImplIstIcallyrepresentedastheaortIcpressure
agaInstwhIchtheL7mustpropelblood.ThedIstensIbIlItyoftheaorta,theresIstanceof
theperIpheralarterIalvasculature,andtheactIonsofreflectedwavesonthecentral
aortIccIrculatIonaretheprIncIpledetermInantsofafterload.SystemIcvascularresIstance
(theratIoofpressuretocardIacoutput,P/Q)IsthemostcommonlyusednonparametrIc
expressIonofperIpheralresIstanceandIsprImarIlyaffectedbyautonomIcnervoussystem
actIvIty.Forexample,anIncreaseInsympathetIcnervoussystemtoneproduces
vasoconstrIctIonofperIpheralresIstancearterIolesthroughactIvatIonof
1
adrenoceptors
Invascularsmoothmuscle,therebyaugmentIngafterload.AbrIef,largeIncreaseIn
afterloadmaycauseatransIentdecreaseInstrokevolume,butacompensatoryIncreaseIn
preloaddurIngsuccessIvecardIaccyclesrestorescardIacoutputbyIncreasIngL7forceof
contractIon.
notropIcstateIstheIntrInsIcforceofmyocardIalcontractIonIndependentofchangesIn
preload,afterload,orheartrate.ThenumberofcrossbrIdgesbetweenthecontractIle
elementsandtherelatIvesensItIvItyofthecontractIleelementstoactIvatorCa
2+
play
ImportantrolesIndetermInIngInotropIcstate.ntheIntactheart,aposItIveInotropIc
effectIsreflectedbyanIncreaseInpressurevolumeworkateachenddIastolIcvolume.
SuchanIncreaseInInotropIcstatemayoccurInresponsetoanIncreaseIncardIac
sympathetIcnerveactIvItythroughstImulatIonof
1
adrenoceptors.PharmacologIc
IncreasesIncontractIlItymaybeproducedbydrugsthatactIvate
1
adrenoceptors(e.g.,
dobutamIne)orbythosethatpreventmetabolIsmoftheIntracellularsecondmessenger
cyclIcadenosInemonophosphate(cA|P;e.g.,mIlrInone).CardIacoutputIsalsoInfluenced
byheartrate.TheprImarydetermInantofmyocardIaloxygenconsumptIonIsheartrate
becausetheheartcompletesanentIrecyclewItheachbeat,andhence,themore
frequentlytheheartperformspressurevolumework,themoreoxygenmustbeconsumed.
TheupperandlowerlImItsofheartratemayInfluencecardIacoutput.Atlowheartrates
(exceptIntraInedathletes),theresImplymaynotbeadequatecardIacoutputtomeetthe
body'soxygenrequIrements,delIversubstratesformetabolIsm,orremoveproductsof
cellularmetabolIsm.ncontrast,athIghheartrates,partIcularlyInpatIentswIthheart
dIsease,theremaynotbeadequatedIastolIcfIllIngtImetomaIntaIncardIacoutputand
coronaryarteryperfusIon,thelatterofwhIchIspartIcularlydependentonduratIonof
dIastole.Thus,shorteneddIastolIctImedurIngprofoundtachycardIamayreducestroke
volumeandcardIacoutput,contrIbutetohypotensIon,anddecreasetheduratIonof
coronaryperfusIon.SucheventsmaycauseacutemyocardIalIschemIaorInfarctIon.
Measures of Cardiac Function
ClInIcalIndIcatorsofcontractIleperformanceIncludecardIacoutput,ejectIonfractIon,
fractIonalshortenIngorareachangeoftheL7shortaxIs,andL7systolIcwallthIckenIng.
TheseIndIcesofcontractIlItyareheartrate,preload,andafterloaddependent,but
neverthelessmaybemeasuredwIthreasonablerelIabIlItyusIngechocardIographIc
technIquesandremaInusefulIndIcesofcontractIleperformance,especIallyInthe
presenceofchronIcheartdIsease,durIngrecoveryafteranacuteIschemIcevent,andIn
patIentsundergoIngcardIacsurgery.|oresophIstIcatedmethodsofassessIngmyocardIal
contractIlItyInvIvo,IncludIngtheL7endsystolIcpressurevolumerelatIonsandpreload
recruItablestrokework,requIreInvasIvemeasurementofcontInuousL7pressureand
volume.
10,12,1J,14,15,16
PreloadrecruItablestrokeworkandtheeffectsofIsofluraneare
shownInFIgure105.ThesetechnIquesareusuallyassessedonlyInalaboratorysettIng,
butmayalsobeobtaInedusIngechocardIography(automatedborderdetectIon)combIned
wIthInvasIvedetermInatIonofcontInuousL7pressuredurIngcardIaccatheterIzatIon.
0IscussIonofIndIcesofcontractIlestatederIvedfrompressurevolumerelatIonsare
beyondthescopeofthecurrentchapter.
Figure 10-5.PreloadrecruItablestrokework(PFSW)relatIonshIpforcontrol(C)and
1.5and2mInImalalveolarconcentratIons(|AC)ofIsoflurane.PFSWIsplottedagaInst
enddIastolIclength(E0L).TheInsetdepIctsPFSWdoneataconstantenddIastolIc
lengthof20mm(PFSW
20
)andIsrepresentedasapercentofcontrol.*SIgnIfIcantly(p
0.05)dIfferentthancontrol;
sIgnIfIcantly(p0.05)dIfferentthan1.5|ACIsoflurane;
sIgnIfIcantly(p0.05)dIfferentslopethancontrol.(FeproducedwIthpermIssIonfrom
PagelPS,KampIneJP,SchmelIngWT,WarltIer0C:ComparIsonofendsystolIc
pressurelengthrelatIonsandpreloadrecruItablestrokeworkasIndIcesofmyocardIal
contractIlItyIntheconscIousandanesthetIzed,chronIcallyInstrumenteddog.
AnesthesIology1990;7J:278.)
Cellular and Molecular Biology of Cardiac Muscle Contraction
Ultrastructure of the Cardiac Myocyte
TheheartcontractsandrelaxesnearlyJbIllIontImesdurInganaveragelIfetIme,basedon
aheartrateof70beatspermInuteandalIfeexpectancyof75years.ArevIewofcardIac
myocyteultrastructureprovIdesImportantInsIghtsIntohowtheheartaccomplIshesthIs
astonIshIngperformance.ThesarcolemmaIstheexternalmembraneofthecardIacmuscle
cell.ThesarcolemmacontaInsIonchannels(e.g.,Na
+
,K
+
,Ca
2+
),Ionpumpsandexchangers
(e.g.,Na
+
K
+
ATPase,Ca
2+
ATPase,Na
+
Ca
2+
orH
+
exchangers),CproteIncoupledand
otherreceptors(e.g.,
1
adrenergIc,adenosIne,opIoId),andtransporterenzymesthat
regulateIntracellularIonconcentratIons,facIlItatesIgnaltransductIon,andprovIde
metabolIcsubstrates
P.214
requIredforenergyproductIon.0eepInvagInatIonsofthesarcolemma,knownas
transverse(T)tubules,penetratetheInternalstructureofthemyocyteatregular
Intervals,therebyassurIngrapId,unIformtransmIssIonofthedepolarIzIngImpulsesthat
InItIatecontractIontobesImultaneouslydIstrIbutedthroughoutthecell.UnlIkethe
skeletalmusclecell,thecardIacmyocyteIsdenselypackedwIthmItochondrIa,whIchare
responsIbleforgeneratIonofthelargequantItIesofhIghenergyphosphates(e.g.,
adenosInetrIphosphate[ATP])requIredfortheheart'sphasIccycleofcontractIonand
relaxatIon.ThefundamentalcontractIleunItofcardIacmuscleIsthesarcomere.The
myofIlamentswIthIneachsarcomerearearrangedInparallelcrossstrIatedbundlesofthIn
(contaInIngactIn,tropomyosIn,andthetroponIncomplex)andthIck(prImarIlycomposed
ofmyosInandItssupportIngproteIns)fIbers.SarcomeresareconnectedInserIes,thereby
producIngcharacterIstIcshortenIngandthIckenIngofthelongandshortaxesofeach
myocyte,respectIvely,durIngcontractIon.
Figure 10-6.SchematIcIllustratIonofthemyosInmoleculedemonstratIngdoublehelIx
taIl,globularheadsthatformcrossbrIdgeswIthactIndurIngcontractIon,twopaIrsof
lIghtchaIns,andhInges(cleavagesItesofproteolytIcenzymes)thatdIvIdethe
moleculeIntomeromyosInfragments(seetext).(FeproducedwIthpermIssIonfrom
KatzA|:PhysIologyoftheHeart,4thedItIon.PhIladelphIa,LIppIncottWIllIamsE
WIlkIns,2006,FIg.41,p104.)
ThestructureofeachsarcomereIsdescrIbedbasedonobservatIonsfromlIghtandelectron
mIcroscopy.TheareaofoverlapofthIckandthInfIberscharacterIzestheAband.ThIs
bandlengthensasthesarcomereshortensdurIngcontractIon.Thebandrepresentsthe
regIonofthesarcomerethatcontaInsthInfIlamentsalone,andthIsbandIsreducedIn
wIdthasthecellcontracts.EachbandIsbIsectedbyaZ(fromtheCermanzuckung
[twItch])lIne,whIchdelIneatestheborderbetweentwoadjacentsarcomeres.Thus,the
lengthofeachsarcomerecontaInsacompleteAbandandtwoonehalfbandunIts
locatedbetweenZlInes.Acentral|bandIsalsopresentwIthIntheAbandandIs
composedofthIckfIlamentsspatIallyconstraInedInacrosssectIonalhexagonalmatrIxby
myosInbIndIngproteInC.AnextensIvelyIntertwInednetworkofsarcoplasmIcretIculum
(SF)InvestseachbundleofcontractIleproteInsandfunctIonsasaCa
2+
reservoIr,thereby
assurInghomogenousdIstrIbutIonandreuptakeofactIvatorCa
2+
throughoutthe
myofIlamentsdurIngcontractIonandrelaxatIon,respectIvely.Thesubsarcolemmal
cIsternaeoftheSFarespecIalIzedstructureslocatedImmedIatelyadjacentto,butnot
contInuouswIth,thesarcolemmalandtransversetubularmembranesandcontaInlarge
numbersofryanodInereceptorsthatfunctIonastheprImaryCa
2+
releasechannelforthe
SF.ThecontractIlemachIneryandthemItochondrIathatpowerItoccupy80,whereas
thecytosolandnucleusfIll15,ofthetotalvolumeofthecardIacmyocyte.tIs
abundantlyclearbasedonthIssImpleobservatIonthatcontractIonandrelaxatIon,andnot
newproteInsynthesIs,arethepredomInantfunctIonsofthecardIacmyocyte.ntercalated
dIscsmechanIcallyconnectadjacentmyocytesthroughthefascIaadherensand
desmosomes,whIchlInkactInandotherproteInsbetweencells,respectIvely.The
IntercalateddIscsalsoprovIdeaseamlesselectrIcalconnectIonbetweenmyocytesvIa
large,nonspecIfIcIonchannelsknownasgap junctionsthatfacIlItateIntercellularcytosolIc
dIffusIonofIonsandsmallmolecules.
Proteins of the Contractile Apparatus
|yosIn,actIn,tropomyosIn,andthethreeproteIntroponIncomplexcomposethesIxmajor
componentsofthecontractIleapparatus.|yosIn(molecularweIghtofapproxImately500
k0a;length,0.17m)contaInstwoInterwovenchaInhelIceswIthtwoglobularheadsthat
bIndtoactInandtwoaddItIonalpaIrsoflIghtchaIns.EnzymatIcdIgestIonofmyosIndIvIdes
thestructureIntolIght(contaInIngthetaIlsectIonofthecomplex)andheavy(composedof
theglobularheadsandthelIghtchaIns)meromyosIn.TheelongatedtaIlsectIonofthe
myosIncomplexfunctIonsasthearchItecturalsupportofthemolecule(FIg.106).The
globularheadsofthemyosIndImercontaIntwohIngeslocatedatthejunctIonofthe
dIstallIghtchaInsandthetaIlhelIxthatplayacrItIcalroleInmyofIlamentshortenIng
durIngcontractIon.TheseglobularstructuresbIndtoactIn,therebyactIvatInganATPase
thatplaysacentralroleInhIngerotatIonandreleaseofactIndurIngcontractIonand
relaxatIon,respectIvely.ThemaxImumvelocItyofsarcomereshortenInghasbeenshown
tobedependentontheactIvItyofthIsactInactIvatedmyosInATPase.Notably,adultand
neonatalatrIalandventrIcularmyocardIumcontaInseveraldIfferentmyosInATPase
IsoformsthataredIstInguIshedbytheIrrelatIveATPaseactIvIty.ThemyosInmoleculesare
prImarIlyarrangedInserIesalongthelengthofthethIckfIlament,butareabuttedtaIlto
taIlInthecenterofthethIckfIlament.ThIsorIentatIonfacIlItatesshortenIngofthe
dIstancebetweenZlInesdurIngcontractIonasthethInfIlamentsaredrawnprogressIvely
towardthecenterofthesarcomere.
ThelIghtchaInscontaInedwIthInthemyosIncomplexserveeItherregulatoryor
essentIalroles.FegulatorymyosInlIghtchaInsmayfavorablymodulatemyosInactIn
InteractIonthroughCa
2+
dependentproteInkInasephosphorylatIon,whereasessentIallIght
chaInsserveanasyetundefInedoblIgatefunctIonInmyosInactIvIty,astheIrremoval
denaturesthemyosInmolecule.0IscussIonofmyosInlIghtchaInIsoformsIsbeyondthe
scopeofthecurrentchapter,butIsoformswItchesfromventrIculartoatrIalformshave
beenobservedInleftventrIcularhypertrophythatmaycontrIbutetocontractIle
dysfunctIon.
17
naddItIontomyosInandItsbIndIngproteIn,thIckfIlamentscontaIntItIn,a
longelastIcproteInthatattachesmyosIntotheZlInes.TItInhasbeenpostulatedtobea
lengthsensorsImIlartoabIdIrectIonalsprIngthatestablIshesprogressIvelygreater
passIverestorIngforcesassarcomerelengthapproaches
P.215
ItsmaxImumormInImum.
18
CompressIonandstretchIngoftItInoccurdurIngdecreasesand
IncreasesInmuscleload,therebyresIstIngfurthersarcomereshortenIngandlengthenIng,
respectIvely.Thus,tItInIsathIrdImportantelastIcelement(InaddItIontoactInand
myosIn)thatcontrIbutestothestressstraInbIomechanIcalpropertIesofcardIacmuscle.
19
Figure 10-7.CrosssectIonalschematIcIllustratIondemonstratIngthestructural
relatIonshIpbetweenthetroponIntropomyosIncomplexandactInunderrestIng
condItIons(left)andafterCa
2+
bIndIngtotroponInC(right;seetext).(Feproduced
wIthpermIssIonfromKatzA|:PhysIologyoftheHeart,4thedItIon.PhIladelphIa,
LIppIncottWIllIamsEWIlkIns,2006,FIg.415,p117.)
ActInIsthemajorcomponentofthethInfIlament.ActInIsa42k0a,ovoIdshaped,
globularproteIn(Cform;5.5nmIndIameter)thatexIstsInapolymerIzedfIlamentous
(F)formIncardIacmuscle.FactInbIndsadenosInedIphosphate(A0P)andadIvalent
catIon(Ca
2+
or|g
2+
),butunlIkemyosIn,themoleculedoesnotdIrectlyhydrolyzehIgh
energynucleotIdessuchasATP.FactInIswoundIndoublestrandedhelIcalchaInsofC
actInmonomersthatresembletwoIntertwInedstrandsofpearls(eachCactInmonomer;
FIg.106).AsInglecompletehelIcalrevolutIonoffIlamentousactInIsapproxImately77nm
InlengthandcontaIns14CactInmonomers.ActInderIvesItsnamefromItsfunctIonasthe
actIvatorofmyosInATPasethroughItsreversIblebIndIngwIthmyosIn.ThehydrolysIsof
ATPbythIsactInmyosIncomplexprovIdesthechemIcalenergyrequIredtoproducethe
conformatIonalchangesInthemyosInheadsthatdrIvethecycleofcontractIonand
relaxatIonwIthInthesarcomere.TropomyosInIsoneoftwomajorInhIbItorsofactIn
myosInInteractIon.TropomyosIn(lengthof40nm;weIghtbetween68and72k0a)IsarIgId
doublestrandedhelIxproteInlInkedbyasIngledIsulfIdebond.HumantropomyosIn
contaInsbothandIsoforms(J4andJ6k0a,respectIvely)andmaybepresentaseIthera
homoorheterodImer.
20
TropomyosInstIffensthethInfIlamentthroughItsposItIonwIthIn
thelongItudInalcleftbetweenIntertwInedFactInpolymers(FIg.107),butItsCa
2+
dependentInteractIonwIthtroponIncomplexproteInsIsthemechanIsmthatlInks
sarcolemmalmembranedepolarIzatIontoactInmyosInInteractIonInthecardIacmyocyte
(excItatIoncontractIoncouplIng).ThethInfIlamentsareanchoredtoZlInesby
cytoskeletalproteInsIncludIngandactInInandnebulette.
21,22
Figure 10-8.SchematIcIllustratIondemonstratIngthelocatIonoftropomyosIn
InterlacedwIthInthegrooveformedbytwoFactInchaIns.(FeproducedwIth
permIssIonfromKatzA|:PhysIologyoftheHeart,4thedItIon.PhIladelphIa,LIppIncott
WIllIamsEWIlkIns,2006,FIg.416,p108.)
ThetroponInproteInsservecomplementarybutdIstInctrolesascrItIcalregulatorsofthe
contractIleapparatus.
2J
ThetroponIncomplexesarearrangedat40nmIntervalsalongthe
lengthofthethInfIlament.TroponInC(sonamedbecausethIsmoleculebIndsCa
2+
)exIsts
InahIghlyconserved,sIngleIsoformIncardIacmuscle.TroponInCIscomposedofacentral
nIneturnahelIxseparatIngtwoglobularregIonsthatcontaInfourdIscreteamInoacId
sequencescapableofbIndIngdIvalentcatIonsIncludIngCa
2+
and|g
2+
.DfthIsquartetof
amInoacIdcatIonbIndIngsequences,two(termedsites IandII)areCa
2+
specIfIc,thereby
allowIngthetroponInCmoleculetorespondtotheacutechangesInIntracellularCa
2+
concentratIonthataccompanycontractIonandrelaxatIon.TroponIn(InhIbItor)Isa2J
k0aproteInthatexIstsInasIngleIsoformIncardIacmuscle.TroponInaloneweakly
preventstheInteractIonbetweenactInandmyosIn,butwhencombInedwIthtropomyosIn,
thetroponIntropomyosIncomplexbecomesthemajorInhIbItorofactInmyosInbIndIng.
ThetroponInmoleculecontaInsaserIneresIduethatmaybephosphorylatedbyproteIn
kInaseA(PKA)vIatheIntracellularsecondmessengercA|P,therebyreducIngtroponInC
Ca
2+
bIndIngandenhancIngrelaxatIondurIngadmInIstratIonofadrenoceptoragonIsts
(e.g.,dobutamIne)orphosphodIesterasefractIonInhIbItors(e.g.,mIlrInone).TroponInT
(sodenotedbecauseItbIndsothertroponInmoleculesandtropomyosIn)Isthelargestof
thetroponInproteInsandexIstsInfourmajorIsoformsInhumancardIacmuscle.TroponIn
TanchorstheothertroponInmoleculesandmayalsoInfluencetherelatIveCa
2+
sensItIvIty
ofthecomplex.
24
Calcium-Myofilament Interaction
8IndIngofCa
2+
totroponInCprecIpItatesaserIesofconformatIonalchangesInthe
troponIntropomyosIncomplexthatleadtotheexposureofthemyosInbIndIngsIteonthe
actInmolecule.0urIngcondItIonsInwhIchIntracellularCa
2+
concentratIonIslow(10
7
|;
dIastole),verylIttleCa
2+
IsboundtotroponInC,andeachtropomyosInmoleculeIs
constraInedtotheouterregIonofthegroovebetweenFactInfIlamentsbyatroponIn
complex(FIg.108).ThIsstructuralconfIguratIonpreventsmyosInactInInteractIonby
effectIvelyblockIngcrossbrIdgeformatIon.Thus,anInhIbItorystateproducedbythe
troponIntropomyosIncomplexexIstsIncardIacmuscleunderrestIngcondItIons.A100fold
IncreaseInIntracellularCa
2+
concentratIon(10
5
|;systole)occursasaconsequenceof
sarcolemmaldepolarIzatIon,whIchopensLandTtypesarcolemmalCa
2+
channels,
therebyallowIngCa
2+
InfluxIntothemyocytefromtheextracellularcompartmentand
stImulatIngCa
2+
dependentCa
2+
releasefromtheSFvIaItsryanodInereceptors.When
Ca
2+
IsboundtotroponInCunderthesecondItIons,theshapeofthetroponInCproteIn
becomeselongatedandItsInteractIonswIthtroponInandTareenhanced.TheseCa
2+
InducedallosterIcrearrangementsIntroponIncomplexstructureweakentheInteractIon
betweentroponInandactIn,allowreposItIonIngofthetropomyosIn
P.216
moleculealongtheFactInfIlaments,andreversethebaselIneInhIbItIonofactInmyosIn
bIndIngbytropomyosIn.
25
nthIsway,Ca
2+
bIndIngtotroponInCmaybedIrectlylInkedto
aserIesofchangesInregulatoryproteInchemIcalstructurethatblockInhIbItIonofthe
bIndIngsIteformyosInontheactInmoleculeandallowcrossbrIdgeformatIonand
contractIontooccur.ThIsantagonIsmofInhIbItIonIsfullyreversIble,asrelaxatIonIs
facIlItatedbydIssocIatIonofCa
2+
fromtroponInCconcomItantwIthrapIdrestoratIonof
theorIgInalconformatIonofthetroponIntropomyosIncomplexonFactIn.
|ostCa
2+
IonsareremovedfromthemyofIlamentsandthecytosolaftermembrane
repolarIzatIonbyaCa
2+
ATPaselocatedIntheSFmembrane(sarcoendoplasmIcretIculum
Ca
2+
ATPase,SEFCA).ThIsCa
2+
Isstored(concentratIonofapproxImately10
J
|)IntheSF
boundtocalsequestrInandcalretIculInuntIlthesubsequentsarcolemmaldepolarIzatIonIs
InItIated.TheNa
+
/Ca
2+
exchangerandaCa
2+
ATPaselocatedwIthInthesarcolemmal
membranealsoremoveasmallquantItyofCa
2+
,sImIlartothatwhIchorIgInallyentered
themyocytefromtheextracellularspacedurIngdepolarIzatIon.PhospholambanIsasmall
proteIn(6k0a)locatedIntheSFmembranethatpartIallyInhIbItstheactIvItyofthe
domInantform(type2a)ofcardIacSEFCAunderbaselInecondItIons.However,
phosphorylatIonofthIsproteInbyPKAblocksthIsInhIbItIonandenhancestherateof
SEFCAuptakeofCa
2+
IntotheSF,
26
therebyIncreasIngtherateandextentofrelaxatIon
(posItIvelusItropIceffect)andaugmentIngtheamountofCa
2+
storedforthenextcycleof
contractIon(posItIveInotropIceffect).Thus,SEFCAactIvItyIsregulatedbyacA|P
dependentPKAthatIsresponsIvetoadrenoceptorstImulatIonorphosphodIesterase
fractIonInhIbItIon.naddItIontoPKAmedIatedphosphorylatIonoftroponInthat
facIlItatesCa
2+
releasefromtroponInC,theseobservatIonsexplaInwhyposItIveInotropIc
drugssuchasdobutamIneandmIlrInonealsoaugmentrelaxatIon.
Myosin-Actin Contraction Biochemistry
ThebIochemIstryofcardIacmusclecontractIonIsmostoftendescrIbedusIngasImplIfIed
fourcomponentmodel(FIg.109).
27
8IndIngofATPwIthhIghaffInItytothecatalytIc
domaInofmyosInInItIatestheserIesofchemIcalandmechanIcaleventsthatcause
contractIonofthesarcomeretooccur.ThemyosInATPaseenzymehydrolyzestheATP
moleculeIntoA0PandInorganIcphosphate,butthesereactIonproductsdonot
ImmedIatelydIssocIatefrommyosIn.nstead,theATPhydrolysIsproductsandmyosInform
anactIvecomplexthatretaInsthechemIcalenergyreleasedfromthereactIonas
potentIalenergy.ntheabsenceofactIn,subsequentdIssocIatIonofA0Pandphosphate
frommyosInIstheratelImItIngstepofmyosInATPaseandthemuscleremaInsrelaxed.
However,theactIvItyofmyosInATPaseIsmarkedlyacceleratedwhenthemyosInA0P
phosphatecomplexIsboundtoactIn,andunderthesecIrcumstances,thechemIcalenergy
obtaInedfromATPhydrolysIsbecomesdIrectlytransferredIntomechanIcalwork.
AttachmentofmyosIntoItsbIndIngsIteontheactInmoleculereleasesthephosphate
anIonfromthemyosInhead,therebyproducIngamolecularconformatIonwIthInthIscross
brIdgestructurethatgeneratestensIonInbothmyofIlaments.
28
FeleaseofA0Pandthe
storedpotentIalenergyfromthIsactIvatedconformatIonproducerotatIonofthecross
brIdge(powerstroke)atthehIngepoIntseparatIngthehelIxtaIlregIonfromtheglobular
myosInheadandItsassocIatedlIghtchaInproteIns.EachcrossbrIdgerotatIongeneratesJ
to410
12
newtonsofforce
29
andmovesmyosInapproxImately11nmalongtheactIn
molecule.CompletIonofmyosInheadrotatIonandA0PreleasedoesnotdIssocIatethe
myosInactIvecomplex,butleavesItInalowenergybound(rIgor)state.SeparatIonof
myosInandactInoccurswhenanewATPmoleculebIndstomyosIn,andtheprocessIs
subsequentlyrepeated,provIdedthatenergysupplyIsadequateandthemyosInbIndIng
sIteonactInremaInsunImpededbytroponIntropomyosInInhIbItIon.
Figure 10-9.SchematIcIllustratIonoftheactInfIlamentsandItsIndIvIdualmonomers
andactIvemyosInbIndIngssItes(m;left panel).ThemyosInheadIsdIssocIatedfrom
actInbybIndIngwIthadenosInetrIphosphate(ATP).SubsequentATPhydrolysIsand
releaseofInorganIcphosphate(P
i
)cockstheheadgroupIntoatensIongeneratIng
confIguratIon.AttachmentofthemyosInheadtoactInallowstheheadtoapply
tensIontothemyosInrodandtheactInfIlament.Theright panelIllustratescalcIum
bIndIngtotroponInC,whIchcausestroponIntodecreaseItsaffInItyforactIn.Asa
resultInaconformatIonalshIftIntropomyosInposItIon(seetext),sevensItesonactIn
monomersarerevealed.
SeveralfactorsmayaffecttheeffIcIencyofcrossbrIdgebIochemIstryandmyocardIal
contractIlItyIndependentofautonomIcnervoussystemtoneoradmInIstratIonof
exogenousvasoactIvedrugs.ThereIsadIrectrelatIonshIpbetweenmyosInATPaseactIvIty
andthemaxImalvelocItyofunloadedmuscleshortenIng(7
max
),andthenormalIncreaseIn
IntracellularCa
2+
concentratIon(from10
7
to10
5
|)thatoccursaftersarcolemmal
depolarIzatIonenhancesbaselInemyosInATPaseactIvItyfIvefoldbeforeItInteractswIth
actIn,therebyIncreasIng7
max
.ContractIleforcedependsonsarcomerelengthImmedIately
beforesarcolemmaldepolarIzatIon.ThIs
P.217
lengthdependentactIvatIon(FrankStarlIngeffect)mayberelatedtoanIncreaseIn
myofIlamentsensItIvItytoCa
2+
,favorablealteratIonsInspacIngbetweenmyofIlaments,or
tItInInducedelastIcrecoIl.AbruptIncreasesInloaddurIngcontractIon(Anrepeffect)or
thosethatoccurafteraprolongedpausebetweenbeats(Woodworthphenomenon)causes
transIentIncreasesIncontractIleforcethroughalengthdependentactIvatIonmechanIsm.
AnIncreaseIncardIacmusclestImulatIonfrequencyalsoaugmentscontractIleforce
(treppephenomenon)vIaenhancedmyofIlamentCa
2+
sensItIvItyandgreaterSFCa
2+
release.
Electrical Properties of the Heart
The Clinical Electrocardiogram
TheclInIcalelectrocardIogram(ECC)consIstsofaregularserIesofdeflectIonsfromthe
IsoelectrIclIne.ThefIrstdeflectIonoftheECCIsthePwave(EInthovenbeganhIs
depIctIonoftheECCInthemIddleofthealphabet).ThePwaveIsaposItIvedeflectIon
thatoccursasaconsequenceofatrIaldepolarIzatIon.TheInItIalelectrIcaleventIs
depolarIzatIonofthesInoatrIal(SA)nodepacemakercellsandIsfollowedalmost
ImmedIatelybyprogressIvedepolarIzatIonofbothatrIa.TheSAnodepacemakeractIvItyIs
notobservedontheECCbecausethenodeIstoosmalltogenerateelectrIcalpotentIal
dIfferenceslargeenoughtoberecordedfromthebodysurface.TheduratIonofthePwave
IsthetImerequIredfordepolarIzatIontospreadovertheatrIaandmaybeprolongedby
atrIalenlargementoraconductIondelay.TheSAnodeIslocatedInthewalloftherIght
atrIumatthejunctIonofthIschamberandthesuperIorvenacava.PropagatIonofthe
depolarIzIngImpulsethroughouttheatrIaIsnotunIform,asaslIghtlyhIgherconductIon
velocItyoccursthroughtheanterIor,mIddle,andposterIorInternodalpathwaysbetween
theSAandtheA7nodes.ActIvatIonanddepolarIzatIonoftheA7nodebegInsdurIngtheP
wavebeforedepolarIzatIonoftheatrIaIscompleted(FIg.1010).
7,J0,J1
ThePwaveIsfollowedbyabrIefIntervalreturnIngtotheIsoelectrIclIne.ThePFInterval
IstheduratIonbetweentheonsetofthePwaveandthebegInnIngofventrIcular
depolarIzatIonsIgnIfIedbytheonsetoftheQFScomplex(FIg.1011).ProlongatIonofthe
PFIntervalusuallyIndIcatesaconductIondelaybetweenatrIalandventrIcularconductIon.
AfterthePwaveIscomplete,theECCbecomesIsoelectrIcbecausechangIngpotentIal
dIfferenceswIthIntheheartarenolongerrecordedatthebodysurfaceasaresultofthe
relatIvelysmallmassoftIssuethatcontInuesthedepolarIzatIonconductIonprocess.0urIng
thIsapparentsIlentIntervalbetweenatrIalandventrIculardepolarIzatIon,thewaveof
depolarIzatIonIsbeIngconductedthroughtheA7node,A7bundle,rIghtandleftbundle
branches,andHIsPurkInjefIbernetwork.TheconductIonvelocItythroughtheA7nodeIs
relatIvelyslow.ncontrast,conductIonvelocItyIsveryrapIdIntheHIsPurkInjesystem(H
InFIg.1011),approachIngthevelocItyobservedInsmallnerves.TheQFScomplexrecords
potentIalsatthebodysurfacewhenthewaveofdepolarIzatIonIsdIstrIbutedthroughout
ventrIcularmyocardIum.TheQFScomplexIsmuchlargerInmagnItudethanthePwave
becauseventrIcularmassIsgreaterthantheatrIalmass.FapIdconductIonthroughtheHIs
PurkInjesystemspreadsthewaveofdepolarIzatIonquIcklytotheventrIcles.0elaysInthIs
conductIondIstaltotheA7nodemostoftenresultfromIntrInsIcmyocardIaldIsease(most
notably,IschemIa)andmayhaveprofoundconsequencesoncardIacrhythmandL7
contractIlesynchrony.
Figure 10-10.TheelectrocardIogram(ECC).|ajorwaves(P,QFS,andT)oftheECC
areIndIcatedaswellasthetImIngoftheactIvatIonofsomeofthekeyconductIve
structures.SA,sInoatrIal.(FeproducedwIthpermIssIonfromKatzA|:PhysIologyof
theHeart,4thedItIon.PhIladelphIa,LIppIncottWIllIamsEWIlkIns,2006,FIg.1510,p
4J6.)
Figure 10-11. Top:ElectrocardIogramrecordedfromthebodysurface.Bottom:
ntracardIacelectrogram.(FeproducedwIthpermIssIonfromKatzA|:PhysIologyof
theHeart,4thedItIon.PhIladelphIa,LIppIncottWIllIamsEWIlkIns,2006,FIg.159,p
4J5.)
TheSTsegmentIstheIntervalbetweentheendoftheQFScomplexandtheTwave.The
STsegmentIsnormallyIsoelectrIcbecausealloftheventrIcularmyocardIumIs
depolarIzed.TheSTsegmentalsoreflectsthelongplateauphaseofthecardIacactIon
potentIal.TheInjurycurrentofanelevatedordepressedSTsegmentobserveddurIng
myocardIalIschemIaorInfarctIonmayoccurasaresultofanabbrevIatedactIonpotentIal
wIthIntheIschemIcregIonorbecausedepolarIzIngcurrentspropagatemoreslowlythrough
theIschemIczone.FepolarIzatIonoftheventrIclesgeneratestheTwave,whIch
correspondstotheendofphase2andallofphaseJofthecardIacactIonpotentIal(see
laterdIscussIon).TheduratIonoftheTwaveIsconsIderablylongerthantheQFScomplex
because,unlIketherapIdlytransmItted,nearlyhomogenousventrIculardepolarIzatIon,
repolarIzatIonoccursmoreslowlyandIslesssynchronous.TheQTIntervalIstheduratIon
betweentheonsetofventrIculardepolarIzatIon(IndIcatedbytheQFScomplex)and
completIonofrepolarIzatIon(assIgnIfIedbytheendoftheTwave).TheQTIntervalvarIes
InverselywIthheartrate,andmayprecIpItatemalIgnantventrIculararrhythmIaswhen
shortenedorprolongedbyadmInIstratIonofvasoactIve
P.218
drugs(e.g.,volatIleanesthetIcs)orInthepresenceofIntrInsIccardIacpathology(e.g.,
prolongedQTsyndrome).
J0,J1
Role of Ion Channels
TheactIonpotentIalsofIndIvIdualgroupsofexcItablecardIacmyocytesarequItedIfferent
(FIg.1012).TheSAandA7nodesandaccessorypacemakercellshaveunstable,
spontaneouslydepolarIzIngpropertIes.TherestIngmembranepotentIalofthesecellsIsnot
90m7,asobservedIntypIcalatrIalandventrIcularmyocytesorHIsPurkInjefIbers.
Spontaneous,phase4slowdepolarIzatIonofSAandA7nodecellsIsInItIatedatmembrane
potentIalsbetween55and66m7.TheSAnode,A7node,andtheremaInIngspecIalIzed
conductIontIssueoftheheartareallcharacterIzedaspotentIalpacemakers,buttheSA
nodeIsthenormalcardIacpacemakerbecauseofItsIntrInsIcallyfasterdIschargerate.
CellswIthIntheSAnodearenothomogenous,andsomeofthesepacemakercellshave
fasterdIschargefrequencIesthanothers.TherestIngmembranepotentIalofcardIac
pacemakercellsIsunstableanddIsplaysaslowdepolarIzatIonofthemembranedurIng
dIastole(FIg.1012).TherateofrIseoftheactIonpotentIalfromthreshold(phase1)Is
relatIvelyslowInSAnodalcellscomparedwIthatrIalandventrIcularmusclecells.The
magnItudeandslopeofspontaneousdepolarIzatIon(alsoknownasautomaticity)ofSA
nodecellsareImportantIntheregulatIonofheartrateanddependontheactIvItyofthe
sympathetIcandvagal(parasympathetIc)neuralInnervatIon.SlowIngtherateof
depolarIzatIonIncreasesthetImetoreachthethresholdpotentIal(TP)anddecreasesheart
rate(SAnoderateofdIscharge;FIg.101J).Theheartratemayalsoslowasaresultofa
shIftInthresholdpotentIaltoahIgherlevel(TP1toTP2)oramorenegatIverestIng
potentIal.
2
TheseeffectsareusuallyobserveddurIngvagalstImulatIonvIa
parasympathetIcnerveoradmInIstratIonofacetylcholIneagonIsts.ncontrast,asharprIse
InthedIastolIcdepolarIzatIonofthepacemakercell(resultIngIntachycardIa)occurs
durIngstImulatIonofthecardIacsympathetIcnervesoradmInIstratIonofexogenous
catecholamInes.TheSAnodepacemakermaybedIsplacedbyalatentpacemaker
elsewhereIntheheartdurIngmyocardIalIschemIabecauseofprImarysuppressIonofthe
SAnodeorbecauseofspontaneousdIschargeofalatentpacemakeratahIgherIntrInsIc
rate.WhenthefrequencyofexcItatIonIshIgherInagroupoflatentpacemakers,therate
offIrIngoftheotherpacemakersIssuppressed.ThIsprocessIsknownasoverdrive
suppression.
Figure 10-12.CardIacactIonpotentIalsthroughouttheconductancesystemfromthe
sInoatrIalnode(SA)throughtheventrIcularmuscledurIngonecardIaccycle.Notethe
automatIcpacemakeractIvIty(slowspontaneousdepolarIzatIon)oftheSAand
atrIoventrIcularnodalcellsandthelackofspontaneousactIvItyofatrIal,PurkInje,
andventrIcularmusclecells.(FeproducedwIthpermIssIonfromLynchC,LakeCL:
CardIovascularanatomyandphysIology,CardIac7ascular,andThoracIcAnesthesIa.
EdItedbyYoungbergJA,LakeCL,FoIzen|F,WIlsonFS.NewYork,ChurchIll
LIvIngstone,1999,p87.)
TheIonchannelsthatareactIveIntheSAnodecellmembranedurIngdepolarIzatIonand
repolarIzatIonaredepIctedInFIgure1014.
7
TwodecreasIngoutwardcurrentsandtwo
IncreasIngInwardcurrentsareobserveddurIngdepolarIzatIon.
P.219
PacemakeractIvItyIspartlyduetodecayofthedelayedrectIfIercurrent(i
K
,anoutward
current),whIchIspermIssIvebyallowIngothercurrentstodepolarIzethepacemaker.An
anomalousrectIfIercurrent(i
k1
,asecondoutwardcurrent)alsopermIssIvelycontrIbutesto
pacemakeractIvIty.ThefIrstInwardcurrentIsi
Ca
.ThIsslowInwardCa
2+
currentIs
prImarIlyresponsIblefortheactIonpotentIalupstrokeInpacemakercells,andIts
contInuatIonafterInItIaldepolarIzatIoncontrIbutestoearlydIastolIcdepolarIzatIon.The
InwardNa
+
current(i
f
)mostlIkelyplaysanImportantroleInthecontrolofheartrateby
theautonomIcnervoussystem.ThIsInwardi
f
currentoccursthroughachannelthat
conductsbothNa
+
andCa
2+
Ions.ThIsforfunnychannelmedIatesautonomIc
dependentmodulatIonofheartrate.
JJ
TheInwardcurrenti
f
IsactIvatedbycA|P.Thus,
1
adrenergIcstImulatIonaccelerates,whereasvagalstImulatIonslows,heartrateby
IncreasInganddecreasIng,respectIvely,theIntracellularcA|PconcentratIonandthe
degreeofactIvatIonofthefchannel.ThefchannelIsthoughttoberesponsIblefor
generatIngspontaneousactIvIty.
Figure 10-13.PacemakerpotentIalsInsInoatrIalnodeIllustratIngtheeffectof
dIastolIcdepolarIzatIonslopesandpotentIalsonheartrate.TheactIonpotentIal
begInswhenthedepolarIzatIonpotentIalreachesthethresholdpotentIal(TP).A
slowIngoftherateofdepolarIzatIonfromatobIncreasesthetImerequIredtoreach
theTP,whereasanIncreaseoftheTPlevel(b,c)oragreaterrestIngpotentIal(d)
slowstheheartrate.(FeproducedwIthpermIssIonfromHoffman8F,CranefIeldPF:
ElectrophysIologyoftheHeart.NewYork,|cCrawHIll.1960,FIg.4.5,p57.)
Figure 10-14.ChangesInfourIonIccurrentsresponsIbleforactIonpotentIal
depolarIzatIonandrepolarIzatIonInasInoatrIalnodalpacemakercell.Twoare
IncreasIngInwardcurrents(i
i
andi
Ca
)andtwoaredecreasIngoutwardcurrents(i
K
,
delayedrectIfIerandi
K1
,InwardrectIfIer).(FeproducedwIthpermIssIonfromKatzA|:
PhysIologyoftheHeart,4thedItIon.PhIladelphIa,LIppIncottWIllIamsEWIlkIns,2006,
FIg.1414,p417.)
P.220
Figure 10-15.|embranepotentIalandcurrentInavoltageclampedventrIcularcell.
NotethattherapIdandtransIentInfluxofNa
+
IonsInducestherapIddepolarIzatIon
(phase0);thIsIsfollowedbyalongerInwardCa
2+
currentthatprolongstheplateau
potentIal(phase1)andthenaslowoutwardK
+
currenttheleadstorepolarIzatIon
(phaseJ).FestIngpotentIalIsphase4.(FeproducedwIthpermIssIonfromKatzA|:
PhysIologyoftheHeart,4thedItIon.PhIladelphIa,LIppIncottWIllIamsEWIlkIns,2006,
FIg.1412,p415.)
AlteratIonsInIoncurrentsIntheventrIcularmyocyteareIllustratedInFIgure1015.The
restIngmembranepotentIalofthemyocyteIs90m7;thIspotentIalcontrolsItsNa
+
channel.AbovethIsthreshold,actIvatIonoftheNa
+
channelproducesasharpIncreaseIn
InwardNa
+
currentthatIsprImarIlyresponsIbleformyocytedepolarIzatIon(phaseD).
TheseNa
+
channelsarerapIdlyInactIvatedbydepolarIzatIon,buttheIrabIlItytoreopen
(reactIvatIon)IsdelayedevenafterthemyocyteIsfullyrepolarIzed.TheInabIlItyofNa
+
channelstorespondtoasecondstImulusafterdepolarIzatIonoccursasaresultofthe
prolongedplateauoftheactIonpotentIalthatpreventsmembranepotentIalfrom
returnIngtotherestInglevelsatwhIchNa
+
channelsmaybereactIvated.TherapId
depolarIzatIonofthemyocyteIsfollowedbyabrIef,rapIdrepolarIzatIonofsmall
magnItude(phase1)causedbyareductIonInNa
+
permeabIlIty,atransIentoutwardK
+
current,andanoutwardCl
current.AdIstInctIvefeatureofventrIcularmyocardIum
depolarIzatIonIstheplateau(phase2)oftheactIonpotentIalthatsIgnIfIesprolonged
stabIlIzatIonofthemyocytenearzeropotentIal(duratIon100ms).AnInwardCa
2+
depolarIzIngcurrentthroughCa
2+
conductancechannelsappearsatthebegInnIngofthe
plateau.ThIsslowInwardCa
2+
currentIsassocIatedwIthopenIngofslowCa
2+
channels
thatareactIvatedatamembranepotentIalof50m7.TheCa
2+
currentactIvatesand
InactIvatesmuchmoreslowlythantheNa
+
current,therebyprovIdInganInwardcurrent
thatmaIntaInsthesarcolemmalmembraneInadepolarIzedstatedurIngtheplateau
phase.PhaseJofthecardIacactIonpotentIalcorrespondstotheTwaveoftheECC.
DutwardrectIfIcatIonandrepolarIzatIonoccurwhenthemembranepassescurrentmost
readIlyIntheoutwarddIrectIon.ThemostImportantoutwardrectIfyIngcurrentIscarrIed
byK
+
.DutwardrectIfyIngcurrentscauserepolarIzatIonbecausemembranepotentIalInthe
depolarIzedcellreturnstoItsrestIngnegatIvelevel.Theoutwardi
k
rectIfyIngcurrent
occursattheendoftheplateauphaseJandIsknownasthedelayed rectifier.TheIon
channelsInventrIcularmyocardIumareenergydependentandregulatedbytheactIvItyof
theautonomIcnervoussystem.
7,J4
Neural Innervation of the Heart and Blood Vessels
Baroreflex Regulation of Blood Pressure
TheheartIsInnervatedbytheparasympathetIcandthesympathetIcnervoussystems.
ParasympathetIcInnervatIonarIsesInthemotornucleusofthevagusandthenucleus
ambIguousInthemedulla.
J5
AsobservedwIthotherparasympathetIcnerves,long
preganglIonIcfIberssynapsewIthshortpostganglIonIcfIberswIthIntheheart.The
postganglIonIcfIbersInnervatepacemakercellsandconductIngpathways.WhenactIvated,
thesefIbersproduceslowIngofpacemakercellsandreduceconductIonvelocIty.AsIde
fromtheIreffectsonheartrate,excItabIlIty,andconductIon,parasympathetIcfIbersdo
notsubstantIallyInfluencecontractIlIty.
J6
AcetylcholIneIstheneurotransmItter
responsIbleforparasympathetIcnervoussystemactIvatIonthroughnIcotInIcand
muscarInIcreceptorsatthepreandpostganglIonIcsynapses,respectIvely,locatedonthe
postganglIonIcneuronandInSAandA7nodepacemakercellsandthecondItIonsystem.
ThesympathetIcInnervatIonoftheheartarIsesfromcellsIntherostralventrolateral
medullawIthdescendIngnervefIbersemergIngfromtheIntermedIolateralcellcolumnof
thespInalcordatC5T6.
J7,J8
ThesepreganglIonIcfIberssynapseprImarIlywIth
postganglIonIcsympathetIcnerveswIthInthestellateganglIon,butmayalsosynapse
wIthInafewganglIalocatedclosertotheheart.CanglIonIctransmIssIonIsmedIatedby
preganglIonIcreleaseofacetylcholIneandbIndIngofacetylcholInewIthnIcotInIc
postganglIonIcreceptors.ActIvatIonofpostganglIonIcsympathetIcnervesInnervatIngthe
heartresultsInreleaseofnorepInephrIne.ThIsendogenouscatecholamInethenstImulates
1
adrenoceptorsInpacemakerandconductIoncellsaswellasatrIalandventrIcular
myocardIum.ActIvatIonofcardIacsympathetIcfIbersproducesposItIvechronotropIc,
dromotropIc,InotropIc,andlusItropIceffects(I.e.,IncreasesInheartrate,conductIon
velocIty,myocardIalcontractIlIty,andtherateofmyofIbrIllarrelaxatIon).
TheafferentInnervatIonoftheheartconsIstsofmechanoreceptorswIthprImarIlyvagal
afferentpathwaysandreceptorswIthspInalafferentpathways.Themechanoreceptors
wIthvagalafferentsarelocatedInventrIcular,andtoalesserextent,atrIalmyocytes.
J6
ActIvatIonoftheventrIcularreceptorsbynocIceptIonorstretch,suchasmayoccurIn
responsetoasuddenIncreaseInventrIcularvolume,causesavagaldepressorresponse
wIthadecreaseInheartrateandmeanarterIalpressure(the8ezoldJarIschreflex).
J9
The
reductIonInheartrateIsmedIatedbyanIncreaseIncardIacvagalefferentactIvIty,In
whIchthedecreaseInmeanarterIalpressureresultsfromwIthdrawalofsympathetIctone
InarterIalresIstanceandvenouscapacItancevessels.ThespInalafferentstraversethe
sympathetIcnervesandserveasnocIceptorsandstretchreceptors.ActIvatIonofthese
receptorsproducesatransIentIncreaseInheartrateandmeanarterIalpressure.SpInal
P.221
afferentmedIatednocIceptorsmaybestImulatedbyeventssuchasacutemyocardIal
IschemIa.8oththecardIacvagalandspInalafferentfIbersprojectcentrallytothenucleus
tractussolItarIus,sImIlartoaortIcandcarotIdbaroreceptorsandchemoreceptors.
ThemajorItyoftheperIpheralvascularsystemderIvesItssympathetIcInnervatIonfrom
thethoracolumbarsectIonofthespInalcord.ncontrast,thesympathetIcInnervatIonof
thecoronaryvasculature,lung,andcerebralcIrculatIonIsderIvedfromthesuperIor
cervIcalandstellateganglIa.AdrenoceptorsmedIatemostsympathetIcnervevascular
responses,butadrenoceptorsunIquelymodulatesympathetIcInnervatIonoftheadrenal
gland,therebycausIngthereleaseofepInephrIneandnorepInephrIne.SympathetIc
InnervatIonofsmallarterIolesandmetarterIolesproducesvasoconstrIctIon,thereby
IncreasIngsystemIcvascularresIstanceandmeanarterIalpressure.SympathetIc
InnervatIonofsmallveInsandvenulescausesconstrIctIonofthesevessels.ThIsactIon
reducesthevolumeofbloodstoredIncapacItancevessels,transIentlyIncreasespreload,
andsubsequentlydecreasesbloodflowInthesplanchnIccIrculatIonand,toalesserextent,
thelowerextremItIes.Thus,actIvatIonofperIpheralsympathetIcnervesIncreasesmean
arterIalpressurebyarterIalvasoconstrIctIoncombInedwIthanIncreaseInpreloaddueto
areductIonInvenouscapacItancewhIlesImultaneouslyIncreasIngheartrateand
myocardIalcontractIlIty.TheseeffectsarecrItIcalcompensatoryresponsestohypovolemIa
resultIngfromacutebloodloss.andadrenoceptorantagonIstsmayattenuate
sympathetIcallymedIatedcardIovasculareffects.
ShortduratIonregulatIonofmeanarterIalpressureoccursthroughthearterIal,andtoa
lesserextent,IntracardIacbaroreceptors.ArterIalbaroreceptorsarelocatedatthe
bIfurcatIonofthecommoncarotIdarterIesandIntheaortIcarch.Thesereceptors,
partIcularlythoseInthecarotIdarterIes,dIsplaytonIcactIvItyundernormalcondItIons.An
acuterIseInarterIalpressureactIvatesbaroreceptorsthroughstretchsensItIveNa
+
channels.FeceptoractIvatIonIncreasesafferentnervetraffIcInthecarotIdsInusnerve,
whIchIscentrallytransmIttedbyaunIquebranchoftheglossopharyngealnervethatfIrst
synapsesInthenucleustractussolItarIus.ThepostsynaptIcneuronsactIvatethevagal
motornucleusandnucleusambIguous,therebycausIngareductIonInheartrate.
J8,40,41
ThepostsynaptIcbaroreceptorneuronsalsosynapsewIthamInobutyrIcacIdmedIated
InhIbItoryneuronsInthecaudalventrolateralmedullathatInnervatemedullary
sympathetIcneuronsandproduceadecreaseInsympathetIcnervoussystemactIvItyvIa
therostralventrolateralmedulla.
J8,41,42
TheresultanteffectIsadecreaseIncardIac
outputandsystemIcvascularresIstanceconcomItantwIthanIncreaseInvascular
capacItance.
TheaortIcbaroreceptorsandcardIacvagalreceptorsproducesImIlarhemodynamIc
effects.CardIacreceptorshavebeentheorIzedtoberesponsIbleforradIocontrastInduced
bradycardIaandhypotensIondurIngcoronaryangIography.Lowpressurebaroreceptors
locatedInthevenacavae,rIghtatrIum,F7,andpulmonaryveInleftatrIaljunctIon
respondtodecreasesInrIghtatrIalfIllIngpressurebyactIvatIngsympathetIctoneInthe
arterIalvasculature.nterestIngly,baroreceptoractIvatIondoesnotInfluenceall
perIpheralvascularbeds.Forexample,thecutaneouscIrculatIondoesnotappearto
respondtobaroreceptorstImulatIonorInhIbItIon.nstead,thecutaneouscIrculatIonIs
prImarIlyaffectedbyperIpheralandcentralthermoregulatorymechanIsmsthatproduce
vasoconstrIctIonorvasodIlatIonInacoldorwarmenvIronmenttopreventorfacIlItate
heatloss,respectIvely.ThermoreceptormedIatedcentralnervoussystemresponses
orIgInateInthesupraoptIcregIonofthehypothalamus.
Other Cardiovascular Reflexes
DtherreflexogenIcareaswIthInthecardIovascularsystemregulatehemodynamIcsthrough
arterIalchemoreceptorsandthecentralnervoussystemresponsetoIschemIa.HIgh
pressuresensItIvereceptorsIntheL7andlowpressureresponsIveelementsIntheatrIa
andF7consIstofstretchInducedmechanoreceptorsthatrespondtopressureorvolume
changes.ThreesetsofreceptorshavebeenIdentIfIed.FIrst,dIscretereceptorsInthe
endocardIumarelocatedatthejunctIonsofthevenacavaewIththerIghtatrIumandthe
pulmonaryveInswIththeleftatrIum.ThesereceptorsactIvatemyelInatedvagalafferent
fIbersthatprojecttothenucleustractussolItarIusandIncreasesympathetIcnerveactIvIty
totheSAnodebutnottotheventrIcles,therebyIncreasIngheartratebutnot
contractIlIty.0IstentIonofthesemechanoreceptorsalsoIncreasesrenalexcretIonoffree
waterbyInhIbItIonofantIdIuretIchormonesecretIonfromtheposterIorlobeofthe
pItuItarygland.
4J
tappearshIghlylIkelythatthe8aInbrIdgereflexmaybemedIatedby
dIstentIonofthesemechanoreceptors.
4
Second,adIffusereceptornetworkIsdIstrIbuted
throughoutthecardIacchambersthatprojectsvIaunmyelInatedvagalafferentneuronsto
thenucleustractussolItarIus.ThesereceptorsbehavelIkethecarotIdandaortIc
mechanoreceptorsandproduceavasodepressorresponseconsIstIngofvagusactIvatIon
concomItantwIthInhIbItIonofsympathetIcInnervatIonoftheheartandperIpheral
cIrculatIon.TheseactIonscausereductIonsInheartrate,InotropIcstate,andsystemIc
vascularresIstanceconcomItantwIthasImultaneousIncreaseInvenouscapacItance.ThIs
IntracardIacreceptornetworkplaysarelatIvelymInorroleInthenormalphysIologIcal
controlofthecardIovascularsystemcomparedwIththearterIalbaroreceptors.Lastly,
sympathetIcafferentfIbersareactIvatedbyreceptorsthatrespondrhythmIcallydurIngthe
cardIaccycle.SomeoftheseneuronsconveyvIsceralpaInsensatIonsandmaybeactIvated
durIngmyocardIalIschemIa.StImulatIonofthesefIbersproducesatransIentIncreaseIn
heartrateandmeanarterIalpressurebyactIvatIngcentralnervoussystemsympathetIc
efferentfIbersInnervatIngtheheartandperIpheralcIrculatIon.
4,44,45
ThearterIalbaroreceptorslocatedInthecarotIdsInusandaortIcarchplaythemajorrole
IncardIovascularhomeostasIs.ArterIalbaroreceptorreflexInducedregulatIonofheart
rateIsInhIbItedbyvolatIleandmanyIntravenousanesthetIcs.
J2,46
ThIsInhIbItIonofhIgh
pressurebaroreceptorreflexesbyanesthetIcsInvolvesseveraldIscretesItesIncludIng
sympathetIcganglIonIctransmIssIon,endorganresponses,andcentralnervoussystem
pathways,andappearstobeespecIallyImportantInshorttermregulatIonofarterIal
pressure.
5,47
ThesereflexesdemonstrateaccommodatIonoradaptatIontothelevelof
arterIalbloodpressureandmayberesetInpatIentswIthhypertensIon.CardIopulmonary
reflexesalsoappeartobeInhIbItedbypotentInhaledanesthetIcsandhaveacrucIalrole
InshorttermregulatIonofarterIalpressure,prImarIlybymodulatIngarterIalbaroreceptor
reflexactIvIty.
J2
TheperIpheralchemoreceptorslocatedInthecarotIdandaortIcbodIes
aresensItIvetoIncreasesInarterIalCD
2
tensIonanddecreasesInpH.ThecarotIdbody
receptorsprojectcentrallythroughHerrIng'snerve,whIchtravelswIththe
glossopharyngealnervetothenucleustractussolItarIus.ncontrast,theaortIcbody
receptorshavevagalafferentfIbersthatalsoprojecttothenucleustractussolItarIus.The
carotIdbodyreflexappearstobemoreImportantthanItsaortIccounterpartInthe
regulatIonofrespIratIonInhumans.ActIvatIonofthecarotIdandaortIcchemoreceptors
producesanIncreaseInrespIratorydrIvemanIfestedbyanIncreaseInrespIratoryrate,
tIdalvolume,andmInuteventIlatIon.ThesechemoreceptorsmayalsocauseactIvatIonof
sympathetIcnervoussystemfIbersIntheheartandperIpheralcIrculatIon,
P.222
therebyIncreasIngheartrateandmeanarterIalpressure.TheperIpheralchemoreceptor
reflexIsanImportantprotectIvemechanIsmInresponsetopathophysIologIcalcondItIons
IncludInghIghaltItudehypoxIa,chronIclungdIsease,andprofoundhypovolemIa.
naddItIontothebaroreceptorresponses,severehypotensIonalsocausesarterIalvaso
andvenoconstrIctIonInresponsetobraInstemhypoxIa.ThIscentralnervoussystem
IschemIcresponsemaybeactIvatedwhenmeanarterIalpressureIsreducedbelow50mm
Hg.AnanalogousmechanIsmmayalsomedIatetheCushIngreflex.ThIssympathetIcally
medIatedhypertensIonoccursInresponsetoanacuteelevatIonofIntracranIalpressure
andaconsequentreductIonIncerebralperfusIonpressure.UnderthesecIrcumstances,
arterIalpressurerIsesprogressIvelyInanefforttoexceedelevatedIntracranIalpressure
andmaIntaIncerebralperfusIonandoxygendelIvery.TheCushIngreflexmayalsobe
actIvatedbybraInstemcompressIon,acutetraumatIcbraInInjury,orIntracranIal
hemorrhageresultIngfromaneurysmrupture.
nanImals,thedIvIngreflexredIstrIbutesbloodflowandoxygendelIverytotheheartand
braInasasurvIvaldefenseofthesubmergedvertebrateagaInstasphyxIa.ThIsreflex
enableswhalestoremaInsubmergedforaslongas2hours.TheresIdualcounterpartofthe
dIvIngreflexInhumansmaybeactIvatedbyImmersIonofthefaceIncoldwater,whIch
producesacomparable,albeItlessIntense,dIvIngresponsecharacterIzedbyrapId
reductIonInheartrateandcutaneousandskeletalmusclebloodflowconcomItantwIthan
IncreaseInarterIalpressure.StImulatIonofreceptorsInthefaceorupperaIrwayInItIates
thedIvIngreflexandcausesapneabyInhIbItIngthemedullaryrespIratorycenter.The
hyperventIlatIonstImulIofhypoxemIaandhypercapnIaarealsosuppressed.The
cardIovascularlImbsofthechemoreceptorreflexarepartIallyretaIned,resultIngIn
generalIzedsystemIcvasoconstrIctIon,exceptInthecoronaryandcerebralcIrculatIons.
ThedIvIngreflexresponseIsdIstInctlydIfferentfromthecoldpressorreflex.ThIslatter
reflexIsactIvatedbycompleteImmersIonofonehandInIcewater.Thecoldpressorreflex
IncreasesheartrateandmeanarterIalpressurebystImulatIngbothpaInandcold
receptors.AcoldenvIronmentdIrectlycausesvasoconstrIctIontopreventheatlossand
alsostImulatesreflexcentralnervoussystemthermoregulatoryreceptorsInthe
hypothalamIcpreoptIcregIon.ThIslattereffectproducessympathetIcallymedIated
vasoconstrIctIon.Awarm,ambIentenvIronmentoranIncreaseInmetabolIcallyInduced
heatproductIonproducesanopposIteresponsetodIssIpateaccumulatedheat.
Figure 10-16.AnterIorvIew(left)showsrIghtcoronaryandleftanterIordescendIng
arterIes.PosterIorvIew(right)showsleftcIrcumflexandposterIordescendIngarterIes.
NotethattherIghtcoronaryorleftcIrcumflexarterymayformthelatterartery.The
anterIorcardIacveInsfromtherIghtventrIcleandthecoronarysInus,whIchdraIn
prImarIlytheleftventrIcle,emptyIntotherIghtatrIum.(FeproducedwIthpermIssIon
fromSmIthJJ,KampIneJP:CIrculatoryPhysIologyTheEssentIals,JrdedItIon.
8altImore,WIllIamsEWIlkIns,1990,FIg.J1,pJ2.)
SomatIcpaInIncreasesheartrateandmeanarterIalpressurebyactIvatIonofsympathetIc
efferentnerves.ncontrast,vIsceralpaInordIstentIonofahollowvIscus(e.g.,small
IntestIne,bladder)mayproducereflexvagalbradycardIaandhypotensIon.The
oculocardIacreflexIsactIvatedbypressureontheocularglobeandcausespronounced
bradycardIaandhypotensIonbyactIvatIonofvagalnervefIbersInnervatIngtheSAnode.
The7alsalvamaneuverconsIstsofforcedexpIratIonagaInstaclosedglottIs.ThIs
maneuverreducesvenousreturntotherIghtheart,decreasescardIacoutputandmean
arterIalpressure,andIncreasesheartrate.ThereflextachycardIaoccursbecauseof
reducedactIvItyofarterIalbaroreceptorsandL7mechanoreceptors.Feleaseoftheforced
expIratIonbyglottIcopenIngacutelyIncreasesvenousreturn,cardIacoutput,andmean
arterIalpressurewhIlesImultaneouslycausIngreflexbradycardIamedIatedbyvagal
InnervatIonoftheSAnodetrIggeredbythearterIalbaroreceptors.
Coronary Circulation
Anatomy of the Coronary Arterial and Venous Systems
TheheartIstheonlyorganthatfurnIshesItsownbloodsupply.TheleftmaInandrIght
coronaryarterIesarIsefromtheaortabehIndtheleftandrIghtaortIcvalveleaflets(FIg.
1016).ThecoronaryostIaremaInpatentthroughoutsystolebecauseeddycurrentsprevent
thevalveleafletsfromcontactIngtheaortIcwalls.TheleftmaIncoronaryarterydIvIdes
almostImmedIatelyIntotheleftanterIordescendIng(LA0)arteryandleftcIrcumflex
coronaryartery(LCCA).TheLA0furtherdIvIdesIntoseveralbranchesalongtheanterIor
InterventrIculargroovetowardtheapexoftheheartwheretheysupplytheanterIorwall
oftheL7andtheanterIortwothIrdsofthe
P.22J
InterventrIcularseptum(FIg.1016).TheLCCAmarksapathwayalongthebaseoftheL7
wIthInthecoronarysulcusandtermInatesIntheleftposterIordescendIngbranch.The
LCCAsupplIestheL7lateralwallandpartoftheL7posterIorwall.TherIghtcoronary
artery(FCA)coursesalongtheA7groovetowardtherIghtchambersoftheheartand
frequentlyextendsalongtheposterIorInterventrIcularsulcustogIverIsetotherIght
posterIordescendIngbranch(FIg.1016).TheFCAsupplIestheanterIorandposterIorwalls
oftheF7exceptfortheapex(supplIedbytheLA0),therIghtatrIumIncludIngtheSAnode,
theupperhalfoftheatrIalseptum,theposterIorthIrdoftheInterventrIcularseptum,the
InferIorwalloftheL7,theA7node,andtheposterIorbaseoftheL7.AbranchoftheLCCA
occasIonallysupplIestheSAnode.8ecauseeIthertheFCAortheLCCAmaysupplythe
posterIordescendIngcoronaryartery,thecoronarycIrculatIonIsdescrIbedasrIghtorleft
domInant,respectIvely,basedonthesourceofthIsvessel'sbloodsupply.
TheproxImalbranchesoftheFCA,LCCA,andLA0arelocatedontheepIcardIalsurfaceof
theheartandgIverIsetomultIpleIntramuralvesselsthatpenetrateperpendIcularlyor
oblIquelydeepIntotheventrIcularwalls.ExceptforthethIntIssuelayeronthe
endocardIalsurface,thenutrItIvebloodsupplyIsalmostentIrelyderIvedfromthesemajor
coronaryarterIes.ThepenetratIngbranchesdIvIdeIntodensecapIllarynetworkslocated
roughlyalongthecoursesofthemyocardIalbundles.ArterIalbrancheswIthdIameters
between50and500mformInterconnectInganastomosesthroughouttheendocardIumof
theventrIcularwalls(FIg.1017,Aand8).AnothernetworkofsubendocardIalvessels
between100and200mIndIameterformsaplexusofdeepanastomoses.Acoronary
collateralcIrculatIonmayalsoarIsefromdIfferentbranchesofthesamecoronaryarteryor
frombranchesoftwodIfferentcoronaryarterIes.FlowthroughsuchcoronarycollateralsIs
usuallyneglIgIblebecausethedrIvIngpressureatthetwoendsoftheanastomosesIsnearly
equal.However,IfthearterysupplyIngonebranchofthIscollateralcIrculatIonbecomes
severelystenotIcoroccluded,thelargepressurereductIonwIlldIvertbloodflowthrough
thepatentarteryandIntothedIstrIbutIonoftheoccludedarterythroughthesecollateral
vessels.Thus,thecoronarycollateralcIrculatIonmaybeespecIallyImportanttopatIents
wIthcoronaryarterydIsease.
48,49,50
|ostofthecoronaryvenoussystemremaInsunnamedwIththeexceptIonofthegreat
cardIacveIn(thatrunsalongtheA7grooveandtheLA0),theanterIorcardIacveIn
(locatedwIththeFCA),andthemIddlecardIacveIn(assocIatedwIththeposterIor
descendIngbranchoftheFCA;FIg.1016).Thus,themaIncoronaryvenousdraInagetends
toretracethecourseofthemajorcoronaryarterIesalongtheA7andInterventrIcular
grooves.ngeneral,therearetwocoronaryveInslocatedalongeIthersIdeofeach
coronaryarterIalbranch.ThecoronaryveInsconvergeandtermInateInthecoronarysInus,
whIchemptIesIntotheposterIoraspectoftherIghtatrIum.ApproxImately85ofthetotal
coronarybloodflowtotheL7draInsIntothecoronarysInus.TheremaInIngbloodflow
emptIesdIrectlyIntotheatrIalandventrIcularcavItIesbythethebesIanveIns.TheF7
veInsdraInIntotheanterIorcardIacveIns;theseemptyIndIvIduallyIntotherIghtatrIum
justabovethetrIcuspIdvalve.
Coronary Microcirculation
ThecoronarycapIllarynetworkhasanorganIzatIonalstructurethatIssImIlartothat
observedInothertIssuebeds.|yocardIumhasaveryhIghdensItyofcapIllarybloodvessels
tomyofIbrIls,approxImately1:1(FIg.1018);thIsIsbecauseoftheexceptIonallyhIgh
metabolIcdemandoftheheart.Dnaverage,adjacentcapIllarIesareseparatedbythe
dIameterofapproxImatelyonemyocyte.ThedIstrIbutIonofcapIllarIesIsquIteunIform
andrangesbetweenJ,000and4,000/mm
2
oftIssue.nterestIngly,capIllarydensItyIs
reducedIntheInterventrIcularseptumandA7nodaltIssue,andthIsobservatIonmay
explaInwhythespecIalIzedconductIngsystemIsmorevulnerabletoIschemIathanthe
myocardIumItself.AsInothercapIllarybeds,coronarycapIllarIesarethesItesfor
exchangeofD
2
,CD
2
,andforthemovementoflargermoleculesacrosstheendothelIalcell
lInIng,whereItIsdevoIdofvascularsmoothmuscle.
Figure 10-17. A.0IagramofthemInutearterIaltoarterIalandvenoustovenous
anastomosesofthecoronaryarterIalsystem,whIchallowsdIversIonofflowIfone
dIstrIbutIonbecomesblocked.(FeproducedwIthpermIssIonfromCuytonAC,HallJE:
HumanPhysIologyand|echanIsmsof0Isease,6thedItIon.PhIladelphIa,W8Saunders,
1997,FIg.184,pp185.)B.0IagramoftheepIcardIalcoronaryvesselslyIngonthe
cardIacmusclesurface,thepenetratIngdeepvessels,andthesubendocardIalarterIal
plexusconnectIngthedeepvessels.(FeproducedwIthpermIssIonfromCuytonAC:
Textbookof|edIcalPhysIology,6thedItIon.PhIladelphIa,W8Saunders,1997,FIg.25
J,p299.)
Mechanics of Coronary Blood Flow
8loodsupplytotheL7IsdIrectlydependentonthedIfferencebetweentheaortIcpressure
andL7enddIastolIcpressure(coronaryperfusIonpressure)andInverselyrelatedtothe
vascularresIstancetoflow,whIchvarIestothefourthpoweroftheradIusofthevessel
(PoIseuIlle'slaw).TwootherdetermInantsofcoronaryflowarevessellengthandvIscosIty
ofthe
P.224
blood,butthesefactorsaregenerallyconstant.FestIngcoronarybloodflowIntheadultIs
approxImately250mL/mIn(1mL/g),representIngapproxImately5ofcardIacoutput.The
changesInaortIcpressureandtheImpedancetoflowduetophysIcalcompressIonofthe
IntramuralcoronaryarterIesdurIngthecontractIonrelaxatIoncycle(FIg.104)governthe
pulsatIlepatternofcoronaryflowIntheL7.AortIcpressureIsslIghtlylessthanL7pressure
durIngsystole.Asaresult,bloodflowIntheL7subendocardIumoccursonlydurIngdIastole
(FIg.1019).DverallcoronaryflowdoesnotceasecompletelydurIngtheearlypartof
systolebecauseofthIsextravascularcompressIon,butmostoftheflowoccursdurIng
dIastolewhenImpedancetoflowIsmInImalandaortIcpressureremaInssuffIcIentto
maIntaInadequatecoronaryperfusIonpressure.
Figure 10-18.0IagramofanelectronmIcrographofcardIacmuscleshowInglarge
numbersofmItochondrIaandtheIntercalateddIskswIthnexI(gapjunctIon),
transversetubules,andlongItudInaltubulessurroundIngcapIllaryendothelIum.
(FeproducedwIthpermIssIonfrom8erneF|,Levy|N:ChapterJ:CardIovascular
PhysIology,8thedItIon.St.LouIs,C7|osby,2000,FIg.J1,p56.)
0urIngsystole,L7subendocardIumIsexposedtoahIgherpressurethanthesubepIcardIal
layer.ndeed,thesystolIcIntraventrIcularpressuremaybehIgherthanthepeakL7
systolIcpressure.8ecauseofthesedIfferencesIntIssuepressure,thesubendocardIallayer
IsmoresusceptIbletoIschemIaInthepresenceofcoronaryarterydIsease,pressure
overloadhypertrophy,orpronouncedtachycardIaconcomItantwIthcompromIsedregIonal
myocardIalperfusIonflow,agreaterIntraventrIcularaortIcpressuregradIent,orreduced
totaldIastolIcflow,respectIvely.CoronarybloodflowIsalsocompromIsedwhenaortIc
dIastolIcpressureIsreduced(e.g.,severeaortIcInsuffIcIency),andthIsobservatIonmay
alsoadverselyaffectperfusIon,partIcularlyInthepresenceofacrItIcalcoronary
stenosIs.
51
ElevatedL7enddIastolIcpressure,asobserveddurIngacuteheartfaIlure,also
reducescoronarybloodflowbecauseofdecreasedcoronaryperfusIonpressure.ncontrast
toleftcoronarybloodflow,FCAflowIscontInuousthroughoutthecardIaccyclebecause
thelowerpressureIntheF7comparedwIththeL7causessubstantIallylessextravascular
compressIon(FIg.1019).CoronarysInus(venous)bloodflowIsmaxImaldurInglatesystole
becauseoftheextravascularcompressIonandthelowrIghtatrIalpressure.
Figure 10-19.SchematIcrepresentatIonofbloodflowIntheleftandrIghtcoronary
arterIesdurIngphasesofthecardIaccycle.Notethatmostleftcoronaryflowoccurs
durIngdIastolewhIlerIghtcoronaryflow(andcoronarysInusflow)occursmostly
durInglatesystoleandearlydIastole.(FeproducedwIthpermIssIonfrom8erneF|,
Levy|N:Chapter10:CardIovascularPhysIology,8thedItIon.St.LouIs,C7|osby,2000,
FIg.10J,p2J1.)
P.225
Regulation of Coronary Blood Flow
ThetwomajordetermInantsofcoronarybloodflow(perfusIonpressureandvascular
resIstance)varysubstantIallydurIngthecardIaccycle(FIg.104).CoronaryperfusIon
pressurecertaInlyvarIeswIthchangesInaortIc,IntramyocardIal,andcoronaryvenous
pressuresdurIngsystoleanddIastole,butthemajorfactorthatregulatescoronaryblood
flowIsthevarIableresIstanceproducedbycoronaryvascularsmoothmuscle.SympathetIc
nervoussystemInnervatIonmodulatesthecontractIlestateofcoronaryvascularsmooth
muscle.naddItIon,smoothmuscletoneIsaffectedbystretchofthemuscle(termedthe
myogenic factor).However,metabolIcfactorsarethemajorphysIologIcaldetermInantsof
coronaryvasculartoneand,hence,myocardIalperfusIon.TheratIoofepIcardIalto
endocardIalbloodflowratIoremaInsnear1.0throughoutthecardIaccycledespItesystolIc
compressIveforcesexertedonthesubendocardIum.ThemorepronouncedresIstanceto
flowInthesubendocardIumIsoffsetbyadrenoceptormedIatedvasodIlatIonandbylocal
metabolIcautocrInefactors(e.g.,adenosInedurInghypoxIa)producedbythemyocardIum
Itself.TherelatIvemaIntenanceofsubendocardIalbloodflowmayalsoberelatedtothe
extensIvenumberofredundantarterIolarandcapIllaryanastomosesInthe
subendocardIum.
1
Oxygen Delivery and Demand
Theheartnormallyextractsbetween75and80ofarterIalD
2
content,byfarthegreatest
D
2
extractIonofallorgans.ThemajorItyofD
2
demandIsderIvedfromthedevelopmentof
L7pressuredurIngIsovolumIccontractIon.DxygenconsumptIonIsalsoaffectedbytherate
ofL7pressuredevelopment(dP/dt)andthedIameteroftheL7(Laplace'slaw).AnIncrease
InmyocardIalcontractIlItyenhancesD
2
consumptIon,butheartrateIstheprImarIly
determInantofD
2
consumptIon.CardIacD
2
extractIonIsnearmaxImalunderrestIng
condItIonsandcannotbesubstantIallyIncreaseddurIngexercIse.Thus,theprImary
mechanIsmbywhIchmyocardIummeetsItsD
2
demandIsthroughenhancedD
2
delIvery,
whIchIsproportIonaltocoronarybloodflowatconstanthemoglobInconcentratIon.
CoronarybloodflowandD
2
consumptIonIncreasefourtofIvefolddurIngstrenuous
physIcalexercIse.ThedIfferencebetweenmaxImalandrestIngcoronarybloodflowIs
knownascoronary reserve.|yocardIalD
2
consumptIonIsamajordetermInantofcoronary
bloodflow.Forexample,coronaryvascularresIstanceIsgreaterIntherested,perfused
heartthanInthecontractIngheart,IndIcatIngthatcoronarybloodflowIncreasesIn
responsetoahIgherrateofD
2
consumptIon.ThemechanIsm(s)responsIbleforthe
correlatIonbetweenmyocardIalwork,D
2
consumptIon,andcoronaryvesseldIlatatIonhas
yettobeprecIselydetermIned.naddItIontometabolIcallyInducedvasodIlatIon,the
factorsresponsIbleforcoronaryautoregulatIon(maIntenanceofcoronarybloodflowwItha
changeInperfusIonpressure)andreactIvehyperemIa(theseveralfoldIncreaseInblood
flowabovebaselIneafterabrIefperIodofIschemIa)arealsonotwellunderstood.
0espItedecadesofIntenseresearchIntothemedIatorsoflocalmetabolIccoronary
vasodIlatIon,surprIsInglylIttleIsknownaboutthedetaIlsofthIsphenomenon.Todate,It
hasbeenestablIshedthatmetabolIccoronaryvasodIlatIonIsatleastpartlytheresultof
actIvatIonofthesympathetIcnervestotheheartandcoronaryvasculaturedurIngan
IncreaseInheartrateandmyocardIalcontractIlIty.SympathetIcnerveactIvatIonproduces
afeedforwardadrenoceptorInducedvasodIlatIon,prImarIlyofsmallcoronary
arterIoles.ThIsfeedforwardmechanIsmoperateswIthoutanerrorsIgnal,IndIcatIngthat
thereIsadIrectandapparentlyunregulatedrelatIonshIpbetweenheartrateandInotropIc
stateandtheactIvatIonofadrenoceptormedIatedvasodIlatIon.
49,50,52
Therealso
appearstobeafeedforward,sympathetIcallymedIated,adrenoceptorInduced
vasoconstrIctIonInlargercoronaryarterIesdurIngexercIse.ThIsvasoconstrIctIonoccurs
upstreamfromcoronarysmallcoronaryarterIolesandservestwoImportantfunctIons:
reductIonofvascularcomplIanceandattenuatIonofsystolIcmInusdIastolIcflow
oscIllatIonsdurIngthecardIaccycle.TheseactIonsassIstInthepreservatIonofbloodflow
tothemorevulnerableL7endocardIumwhenheartrate,contractIlIty,andD
2
consumptIon
areelevated.nterestIngly,cardIacparasympathetIcnerveshaveapromInentroleIn
regulatIngheartrate,butthesenervesappeartohaveaneglIgIbledIrecteffectonthe
regulatIonofcoronarybloodflow.
TheconclusIonsaboutsympathetIcnervoussystemcontrolofthecoronarycIrculatIonare
basedonalteratIonsIntheslopeoftheD
2
consumptIoncoronaryvenousD
2
tensIon
relatIondurInggradedexercIseInthepresenceofexogenousoradrenoceptor
blockade(FIg.1020).ThecurrentevIdenceImplIcatIngtheadrenoceptorIncoronary
vasodIlatIonaccountsforonlyaboutonefourthofthetotalcoronaryvasodIlatIonobserved
durIngexercIseInducedhyperemIa.
5J
Thesedatasuggestthattheotherthreefourthsof
coronaryvasodIlatIondurIngexercIsemaybeproducedbyasyetundefInedlocalmetabolIc
factorsthatactoncoronaryvascularsmoothmusclewIthorwIthouttheInfluenceof
endothelIum.|anymetabolIcfactorshavebeenproposedtoIndIvIduallyorcollectIvely
modulatecoronaryflowatthearterIalorcapIllarylevel,IncludIngadenosIne,nItrIcoxIde,
arterIaloxygenorCD
2
tensIon,pH,osmolarIty,K
+
,Ca
2+
,andprostaglandIns.|anyofthese
factorsexertpredIctabledIrecteffects.Forexample,hypoxIaorIschemIadecreases
arterIaloxygentensIonandpHandIncreasesCD
2
tensIon,adenosIne,K
+
,andCa
2+
concentratIons,andserumosmolarIty.|anyofthesechangesmayIndeedIncrease
coronarybloodflow,butnoneappeartobecrucIaldetermInantsofvasodIlatIondurIng
exercIse.Forexample,adenosInereceptorblockadedoesnotaltercoronarybloodflow
underrestIngcondItIonsordurIngexercIse.SImIlarly,InhIbItIonofnItrIcoxIdeproductIon
orATPsensItIveK
+
(K
ATP
)channelsalsodoesnotaltertheD
2
consumptIoncoronaryvenous
D
2
slopedurInggradedexercIse.Nevertheless,nItrIcoxIdeandK
ATP
channelshavebeen
showntoregulatethebalancebetweenD
2
supplyanddemandunderrestIngcondItIons.
ThereIsverystrongevIdencehowever,thatadenosInereleaseddurInghypoxIaorIschemIa
causescoronaryvasodIlatIonandthatthIseffectIsmedIatedbyactIvatIonofK
ATP
channels.AdenosIneandK
ATP
channelshavealsobeenImplIcateddurIngreactIve
hyperemIaafterIschemIa,butthesemedIatorsdonotappeartoberequIredforcoronary
autoregulatIon.|oreover,theK
ATP
channelprobablymaIntaInsalowervascularsmooth
muscletoneandthus,ahIgherbasalcoronaryflowdurIngrestIngcondItIons.WhIlenot
actIngasalocalmetabolIcvasodIlator,nItrIcoxIdemayreacttoIncreaseddownstream
arterIaldIlatIonbydIlatInglarger,upstreamepIcardIalcoronaryarterIestoprevent
excessIvesheerstressoncoronaryendothelIalcells.
Myocardial Ischemia and Infarction
schemIcheartdIseaseremaInstheleadIngcauseofdeathIntheUnItedStates.Clobal
IschemIaresultsfromInsuffIcIenttotalcoronarybloodflowfortheoverallmetabolIcneeds
oftheheart.
54,55
FegIonalIschemIaresultsfromInsuffIcIentcoronarybloodflowtoa
regIonoftheheartsupplIedbyItsvascularlImb.Alarge,acutecoronaryarteryocclusIon
producesacutemyocardIalIschemIaandoftencontrIbutestothe
P.226
developmentofamalIgnantventrIculararrhythmIabecausebloodflowthroughcoronary
collateralsfaIlstoprovIdesuffIcIentperfusIontotheIschemIczone.
49,51
Thus,many
patIentswIthacutecoronarysyndromesuccumbtosuddencardIacdeathbeforeordurIng
theevolutIonofamyocardIalInfarctIon.fthecoronaryarteryocclusIondevelopsmore
slowly,collateralformatIonInthewatershedregIonmayreducethedegreeofmyocardIal
damageassocIatedwIthacutecoronaryocclusIon.Newcollateraldevelopment(knownas
vasculogenesis)IntotheoccludedvascularbedwIllresultIntheIndependenceofthIs
regIonfromItsorIgInalbloodsupply.
Figure 10-20.Coronaryvenousoxygen(D
2
)tensIonatrestanddurIngthreelevelsof
exercIseplottedasafunctIonofmyocardIalD
2
consumptIonwIthIndIvIdualregressIon
lInesforablockadealoneandwIthblockade.ThesteepslopeofcombIned+
blockadeIndIcatesamodestmatchbylocalmetabolIcfactorsIntheabsenceof
adrenergIcmechanIsms.ThedIfferencesInslopesbetween+blockadeand
blockadedemonstratesadrenergIcmedIatedcoronaryvasodIlatIon,whereasthe
dIfferenceInslopesbetweenblockadeandcontroldemonstratesmedIated
coronaryvasoconstrIctIon.NotethatadrenergIcvasodIlatIonaccountsforonlyabout
25oftheIncreaseIncoronaryflowdurIngexercIse.(FeproducedwIthpermIssIon
fromCorman|W,TuneJ0,FIchmond|W,FeIglED:FeedforwardsympathetIc
coronaryvasodIlatIonInexercIsIngdogs.JApplPhysIol2000;89:1892.)
AnatherosclerotIcplaqueIsthemostfrequentcauseofobstructedbloodflowInlarge,
epIcardIalcoronaryarteryvessels.
56
ThemostcommonsItefordevelopmentofan
atherosclerotIcplaqueIsthefIrstseveralcentImetersofthemajorandcoronaryarterIes
andtheIrprImarybranches.TheposItIonofatherosclerotIcplaquesfacIlItatestheIr
pallIatIonbycoronaryarterybypassgraftsurgery.
57
AtherosclerotIcplaquestypIcally
developveryslowly,eventuallyprotrudIngIntothevesselandpartIallyorcompletely
blockIngflow.TheatherosclerotIcplaquemayalsoprecIpItatethrombusformatIon,whIch
morerapIdlyoccludesthecoronaryartery.Athrombususuallydevelopswhentheplaque
hasbrokenthroughthevascularIntIma,therebyexposIngvascularsmoothmuscleor
adventItIatoclottIngfactorsandplateletscontaInedInblood.WhenfIbrInandplatelets
begIntobedeposIted,bloodcellsbecomeentrappedandformathrombusthatgrows
rapIdlyuntIlItproducesacrItIcalstenosIsorcompleteocclusIonofthecoronaryartery.
ThethrombusmayalsoembolIzebydetachIngfromItsorIgInalsIteofformatIonandflow
toamoreperIpheralbranchofthecoronaryarterIalbed.AtherosclerotIcplaquesare
composedofcholesterolandotherlIpIdsthatbecomedeposItedbeneaththeIntImaand
fIbroustIssue,whIchalsofrequentlybecomescalcIfIed.ThesecalcIumdeposItsarelocated
predomInantlyatthejunctIonoftheIntImalandmedIallayersofthebloodvessel.
AnacuteocclusIonofamajorepIcardIalcoronaryarterycausesalmostImmedIate,
maxImaldIlatIonofexIstIngsmallcollateralvesselssupplyIngbloodflowtotheIschemIc
zone.Unfortunately,bloodflowthroughthesemInutecollateralsIsgenerallyInsuffIcIentto
nourIshallofthemyocardIumthattheysupply.CollateralperfusIonthroughthese
anastomosestemporallyIncreasesandmaydoublewIthIn24hoursafteracutecoronary
occlusIon.Eventually,theaffectedmyocardIumwIllbesupplIedbyanormalquantItyof
bloodflow,albeItfromadIfferentsource.0urIngthegradualdevelopmentofan
atherosclerotIcplaque,collateralvesselsmaydevelopataratesImIlarto,andthereby
compensatefor,theslowocclusIonofthevessellumen.ThIsredIstrIbutIonofmyocardIal
bloodflowfromapartIallyoccludedtoacollateralvascularsupplymaypreventanacute
epIsodeofIschemIawhentheorIgInalcoronaryarterybecomesoccluded.Dnlywhenthe
atherosclerotIcprocessdevelopsmorerapIdlythantheformatIonofanadequatecollateral
bloodsupplywIlltheD
2
demandexceeddelIveryandproducemyocardIaldysfunctIon.ThIs
typeofIschemIccardIomyopathyIsthemostcommoncauseofheartfaIlure.|yocardIal
necrosIsandapoptosIs(programmedcelldeath)occurasaconsequenceofIschemIaand
InfarctIon.However,cellulardemIseusuallywIllnotoccurInaregIonunlesscoronary
bloodflowfallsbelow65ofrestIngvalues.|yocytesInthIsregIonmaybevIable,but
theIrcontractIleabIlItymaybeseverelyImpaIredbecauseofthelackofD
2
andnutrIents.
CrItIcallystenotIcatherosclerotIcplaquesmayproduceapressuregradIentacrossthe
stenosIsand
P.227
substantIallyreducetheperfusIonpressureIndIstalbranchesoftheaffectedvessel.Such
gradIentsareespecIallyImportantwhenstenosesoccurIncoronaryarterIesofsmaller
calIber.TheremaybecompensatoryvasodIlatIonofthecoronarydIstalbed,but
progressIvedImInutIonofdIstalbloodflowmayoccurdespItethIsresponse.
|yocardIalInfarctIonmayalsooccurwIthoutevIdenceofmajorcoronarythromboses,
embolI,orstenosIs.ThIsformofInfarctIonIscausedbyexcessIvemetabolIcdemands
resultIngfromsevereL7hypertrophy(e.g.,crItIcalaortIcstenosIs)orvasoactIvedrug
IngestIon(e.g.,amphetamInes,cocaIne)ormayalsoresultfromcoronaryartery
vasospasm.EItherofthesemechanIsmsmayleadtoIschemIabyadverselyaffectIng
myocardIalD
2
supplydemandrelatIons.Clearly,thepresenceofcoronarystenosesthat
wouldotherwIsebeasymptomatIc(70)mayexacerbateD
2
demandmedIatedmyocardIal
IschemIa.SuchcausesformyocardIalInfarctIonarerelatIvelyuncommon,andcoronary
arterydIseaseremaInstheprImarycauseoftransmuralnecrosIs.SubendocardIalInfarctIon
mayhaveadIfferentetIologythanthetransmuralInfarctIoncausedbyanacutecoronary
occlusIon.SubendocardIalInfarctIonmayoccurwhencoronaryperfusIonpressureIs
adverselyreducedbydeclIneIndIastolIcaortIcpressureorIncreasesInL7enddIastolIc
pressure.Thus,patIentswIthsevereaortIcInsuffIcIencyorendstageheartfaIluremaybe
especIallypronetosubendocardIalInjury.
AlongwIththeseverItyofcoronaryarterystenosIs,themetabolIcactIvItyoftheheart
durIngIschemIaIsacrItIcalfactorIndetermInIngtheextentofcelldeath.fanareaofthe
hearthasreducedbloodsupplyduetoIschemIa,theregIondIstaltothIscoronarystenosIs
IsmaxImallyvasodIlated,andanIncreaseInD
2
demandcausesvasodIlatIonofadjacent
coronaryvesselsthatsupplysurroundIngnormalmyocardIum.ThIsmetabolIcallyInduced
vasodIlatIonmayInadvertentlyredIstrIbutebloodflowawayfromtheIschemIczone
throughcoronarycollateralvessels.ThIsphenomenonIsknownascoronary steal.
58,59
0espIteorIgInalargumentstothecontrary,mostexperImentalandclInIcalevIdence
collectedtodateIndIcatesthatvolatIleanesthetIcsdonotcausecoronarystealunless
profoundhypotensIon(50mmHg)Ispresent.7olatIleanesthetIcsarenotpotent
vasodIlators,unlIkedrugssuchasadenosIneandsodIumnItroprussIdethatareknownto
producecoronarysteal.
ApotentIallylethalcomplIcatIonofacutecoronaryocclusIonIsthedevelopmentof
malIgnantventrIculararrhythmIas(e.g.,ventrIculartachycardIa,fIbrIllatIon).7entrIcular
arrhythmIasaremostlIkelytooccurdurIngthefIrst10mInutesafteranacutecoronary
occlusIon,especIallyIfthecoronarybloodflowtotheconductIonsystembecomes
IschemIc.|yocytesdIstaltooccludedcoronaryarterymaybecomeelectrIcally
dysfunctIonalandfaIltotemporallyrepolarIzewIthsurroundIngnormalmyocardIum.ThIs
repolarIzatIondyssynchronyIsafrequentcauseofarrhythmogenesIsdurIngacute
myocardIalIschemIa.CompensatoryactIvatIonofthesympathetIcnervoussystemIn
responsetomarkedreductIonsIncardIacoutputmayalsocontrIbutetothedevelopment
ofventrIculararrhythmIas.LeftventrIculardIlatatIonorformatIonofanL7aneurysmlate
aftermyocardIalInfarctIonmayalsoprovIdeasubstrateforarrhythmogenesIsby
IncreasIngtheduratIonofImpulseconductIonandcreatIngabnormalconductIonpathways
aroundtheInfarctedzone.TheseconsequencesofInfarctIonmaypredIsposetocIrcuItous
electrIcalactIvItyandresultInanImpulsereenterIngasectIonofthemyocardIumthatIs
stIllrecoverIngfromItsrefractoryperIod,therebyInItIatInganabnormalsubsequentcycle
ofexcItatIonandreentry.
AcentralzoneofmyocardIalnecrosIsdevelopswIthIn1hourafteracutecoronaryartery
occlusIon,whIchIseventuallyreplacedbyscarastheInfarctedmyocardIumheals.A
borderzonecharacterIzedbyprofoundlyreducedcontractIlItyduetoInadequatecoronary
collateralperfusIonsurroundsthIscentralnecrotIczone.SomeofthIsborderzonealso
developsscartIssue;otherregIonssurroundIngthecentralnecrotIcregIonhypertrophyasa
compensatoryresponsetoIncreasedworkload.ThIspostInfarctIonventrIcularhypertrophy
servestomaIntaIncardIacoutput,butmayalsocontrIbutetothelatedevelopmentof
heartfaIlureasaresultofprogressIvedIastolIcdysfunctIon.
1,50,52,60
Pulmonary Circulation
Comparison with the Systemic Circulation
ThepulmonarycIrculatIonreceIvesthebloodpumpedbytheF7.Totalpulmonaryblood
flowIsequIvalenttocardIacoutput.TherearemajordIfferencesInhemodynamIcs
betweenthesystemIcandpulmonarycIrculatIons(FIg.1021).
61
ThereIsagreater
decreaseInmeanpressureacrosssystemIcarterIestoarterIolescomparedwIthvesselsof
sImIlarcalIberInthepulmonarycIrculatIon.TheprecapIllaryandcapIllaryvesselsofthe
pulmonaryvasculaturearelocatedIncloseproxImItytothealveolarmembranes,thereby
facIlItatInggasexchange.ThelungIsrIchlyInnervatedbytheparasympathetIcand
sympathetIcnervoussystem,butthedomInanteffectoftheautonomIcnervoussystem
occursprImarIlyatthelevelofalveolarandbronchIalsmoothmuscle.7agalInnervatIonof
muscarInIcreceptorsInaIrwaysmoothmuscleproducesbronchoconstrIctIonandIsan
ImportantcontrIbutIngfactortobronchospasmInatopIcpulmonarydIsease,pneumonIa,
andInhalatIonofnoxIoussubstances.ThesympathetIcInnervatIonofthelungIsderIved
fromupperthoracIcsympathetIcfIbersthatInnervatebothaIrwayandpulmonaryvascular
smoothmuscle.SympathetIcstImulatIonofaIrwaysmoothmuscleproduces
bronchodIlatIonbyactIvatIonof
2
adrenoceptors.ThesympathetIcInnervatIonofthe
pulmonaryvascularsystemprovIdesaphysIologIcalresponsetogravItatIonaleffectsonthe
IntrapulmonarydIstrIbutIonofbloodflowandpartIallycounteractsalteratIonsInregIonal
ventIlatIon/perfusIon(7/Q)ratIodIfferencesproducedbysuchgravItatIonalforces.
62
Regional Differences in Perfusion and V/Q Matching
The7/QdIstrIbutIonwIthInthelungInanuprIghtposItIonvarIesbecauseoftheeffectof
gravIty(FIg.1022).ntheupperlung(zone1),7/QratIoIs1.0,IndIcatIngthatalveolar
ventIlatIonoccursInexcessofpulmonarybloodflow.8ecause
P.228
partofthIszoneIsventIlatedbutnotperfused,zone1contrIbutestodeadspace
ventIlatIon.nthemIddleregIonofthelung(zone2),the7/QratIoIscloseto1.0,
IndIcatIngabalancebetweenventIlatIonandperfusIon.nthelowerregIonsofthelung
(zoneJ),the7/QratIoIssubstantIallylowerthan1.0.UnderthesecondItIons,ventIlatIon
InadequatelymatchesperfusIonandIntrapulmonaryshuntoccurs.Theoverall7/QratIoof
thelungIsbetween.85and.90.Thus,therearelargegradIentsInventIlatIonandperfusIon
fromthetoptobottomofthelungInstandIngposItIon,andasaresultofgravItatIonal
effects,thebloodvolumeandbloodflowaresubstantIallygreateratthelungbase
comparedwIththeapex.However,ventIlatIonmaybemoreeffectIveInthelungbase
becausethedIaphragmexertsagreaterInfluenceInthIsregIon.
Figure 10-21.ComparIsonofpressuregradIents(InmmHg)alongthehIghpressure
systemIcandlowpressurepulmonarycIrculatIon.(FeproducedwIthpermIssIonfrom
NunnJF:ApplIedFespIratoryPhysIology.London,8utterworth,1971,p21J.)
Figure 10-22.FelatIveventIlatIonandperfusIon(7/Q)dIstrIbutIonIndIfferentareas
ofthelungs(uprIghtposItIon).TheleftsIdeshowsthepercentagedIstrIbutIonofthe
totallungvolumeandtherIghtsIdeshowsthealveolarventIlatIon,pulmonaryblood
flow,and7/QratIoofeachhorIzontalslIceoflungvolume.NotetheupperzoneIs
relatIvelyoverventIlatedandthelowerzoneIsrelatIvelyoverperfused.(Feproduced
wIthpermIssIonfromNunnJF:ApplIedFespIratoryPhysIology.London,8utterworth,
1971,p2J4.)
ThedIstrIbutIonofventIlatIonandperfusIonthroughoutthelungalsoaffectsthe
relatIonshIpsbetweenpulmonaryarterIal,venous,andalveolarpressureswIthIndIfferent
lungzones.ntheupperzone(zone1),pulmonaryarterIalpressureofcompressIblevessels
remaInslessthanthepulmonaryalveolarpressureandIsInsuffIcIenttoopenthevessels,
whIchremaIncollapseddurIngsomeofInspIratIon.nthemIddlezone(zone2),the
pressureatthearterIalendofthecompressIblevesselsexceedspulmonaryvenousand
pulmonaryalveolarpressure;therefore,thebloodflowbecomesdependentonthepressure
gradIentbetweenthepulmonaryarteryandalveolus,bothofwhIchexceedpulmonary
venouspressure.nzoneJ,thepulmonaryvenouspressureexceedspulmonaryalveolar
pressure.Thus,bloodflowdependsonthepressuregradIentbetweenarterIaltovenous
endsofthecapIllarIes,sImIlartothesItuatIonobservedInthesystemIccIrculatIon.As
IntravascularpressuresIncrease,progressIvelylowerresIstancetopulmonarybloodflowIs
observedInthIszone.nthesupIneposItIon,sImIlar7/QdIstrIbutIonsareobservedover
smallerpressuregradIents(comparedwIththeuprIghtposItIon)betweenanterIorand
posterIorthorax.FromthIsdIscussIon,ItIsclearhowpathologIccondItIonsmayreduce
arterIalD
2
tensIon.Forexample,alveolarcollapseInareasofatelectasIsInwhIch
perfusIonpersIstsdespItecompensatoryhypoxIcpulmonaryvasoconstrIctIonmayproduce
profoundhypoxemIaasaresultofIntrapulmonaryshunt.
6J,64
Hypoxic Pulmonary Vasoconstriction
PulmonaryarterIolarvasoconstrIctIontrIggeredbyhypoxIashuntsbloodflowawayfrom
poorlytowellventIlatedregIonsofthelung,therebyImprovIngarterIalD
2
saturatIon.The
mechanIsmbywhIchhypoxIaraIsespulmonaryvascularresIstanceappearstobemedIated
byanD
2
sensorbecauseIsolatedpulmonaryarterIalsmoothmusclecellscontractunder
hypoxIccondItIons.
65,66
TheD
2
sensorhasyettobeIdentIfIed,butmaybemedIatedby
smoothmusclemItochondrIaandpulmonaryvascularendothelIum.PulmonaryarterIal
strIpswIthIntactendothelIumaremoresensItIvetohypoxIathanskInnedfIber
preparatIonsInvItro.HypoxIaalsoInhIbItsanoutwardK
+
current;theresultIng
depolarIzatIonaugmentsaCa
2+
InfluxIntopulmonaryvascularsmoothmuscle,thereby
InItIatIngcontractIon.ThecontractIlemechanIsmofhypoxIcpulmonaryvasoconstrIctIon
appearstobemedIatedbytheCa
2+
calmodulInsystemandcausesphosphorylatIonof
vascularsmoothmusclemyosInlIghtchaIns.ChronIchypoxIacausesprolIferatIonof
vascularsmoothmuscleandthIckensthepulmonaryarterIaltree.ThIsresponseIncreases
pulmonaryvascularresIstanceandmayalsoproduceIrreversIblepulmonaryhypertensIon.
Physiologic Modulation of the Pulmonary Circulation
ThebloodvolumestoredInthepulmonarycIrculatIonIssubstantIal(900mL),andwhen
combInedwIththebloodvolumecontaInedwIthIntheheartandproxImalgreatvessels,
thIspulmonarybloodvolumeprovIdesacrucIal,rapIdlyavaIlablesourceofreserve
IntravascularvolumedurIngacute,massIvehemorrhage.ThemechanIsmsbywhIchblood
volumeIsshIftedtocentralcompartmentsInresponsetohypovolemIaIspoorly
understood,butactIvatIonofregIonalsympathetIcInnervatIonofthevolumecontaInIng
reservoIrs,vasoconstrIctIonofarterIalresIstancevessels,andthesystemIcactIonof
epInephrInereleasedfromtheadrenalglandclearlyplayImportantroles.AngIotensIn,
prostaglandInsandotherarachIdonIcacIdmetabolItes,andnItrIcoxIdearealsocrItIcal
regulatorsofpulmonaryvascularresIstanceandthedIstrIbutIonofbloodflowwIthInthe
lungparenchyma.
67,68,69
NItrIcoxIdehasprovenbenefItsInthetreatmentofacquIredand
congenItalpulmonaryhypertensIon,oftenwIthlIfesavIngresults.Forexample,Inhaled
nItrIcoxIdeIsaselectIvepulmonaryvasodIlatoratdoses40to80partspermIllIon,and
reductIonsInpulmonaryarterIalpressureproducedbythIsdrugareoftenessentIalto
preserveF7functIonInpatIentsundergoIngheartorlungtransplantatIon.
Cerebral Circulation
Anatomy and Cerebral Autoregulation
8loodflowtothebraInIsprovIdedthroughtheInternalcarotIdandvertebralarterIes.The
vertebralarterIesjoIntoformthebasIlarartery,whIch,alongwIthbranchesofthe
InternalcarotIdarterIes,formsthecIrcleofWIllIs.ThebraInIsapproxImately2oftotal
bodyweIght,yetthIsorganreceIvesapproxImately15ofcardIacoutput.ThIsremarkably
largecerebralbloodflow(45to55mL/100g/mIn)reflectsthehIghmetabolIcrateofthe
braIn.CerebraloxygenconsumptIonaveragesJ.5mL/100g/mInandaccountsfor20of
totalbodyoxygenconsumptIonatrest.FegIonalcerebralbloodflowandmetabolIcrate
varysubstantIallythroughoutthebraIn.CerebralbloodflowandmetabolIcrateareclosely
P.229
lInkedandareapproxImately4tImesgreaterIngraycomparedwIthwhItematter.Thus,
thecerebralcortexhasasubstantIallygreaterbloodflowandmetabolIcratethan
subcortIcalregIons.|otoractIvItyorsensorystImulatIonIsassocIatedwIthIncreased
neuronalactIvItyInthecontralateralactIvatedareasofbraInandIscloselycoupledto
regIonalIncreasesInbloodflowandmetabolIcrateIncorrespondIngregIons.
70,71
The
mechanIsmofcouplIngoftheactIvItymetabolIsmbloodflowrelatIonshIpIsmostlIkely
relatedtolocalmetabolIcvasodIlators(e.g.,lactIcacId),alteratIonsInelectrolyte(e.g.,
K
+
,Ca
2+
)concentratIons,andothersubstances(e.g.,adenosIne,released
neurotransmItters).Todate,nosInglecausatIvemoleculehasyetbeenIdentIfIedasthe
prImaryfactorlInkIngregIonalmetabolIcrateandbloodflowtoneuronalactIvIty.
72,7J
Regulation of Cerebral Blood Flow: Hypercarbia, Hypoxia, and
Arterial Pressure
CerebralbloodflowremaInsrelatIvelyconstantwhenmeanarterIalpressurevarIes
between50and150mmHgInhealthysubjects(FIg.102J).ThIsautoregulatIonofcerebral
bloodflowshIftstotherIghtInpatIentswIthchronIc,poorlycontrolledessentIal
hypertensIon.Forexample,theautoregulatIoncurvemayrangebetween80and200mm
HgInapatIentwIthhypertensIon,andreducIngthemeanarterIalpressurebelow80mm
HgmayprecIpItatecerebralIschemIa.ThIsobservatIonemphasIzesthateffectIve
treatmentofhypertensIonreadjuststheautoregulatIoncurvetoItsnormalpressurerange.
CerebralautoregulatIonIsInhIbItedbyhypercarbIaandhIgherendtIdalconcentratIonsof
volatIleanesthetIcs.ncontrast,areductIonInarterIalCD
2
tensIoncounteractsthedIrect
cerebralvasodIlatoractIonsofmanydrugs,IncludIngthoseofvolatIleanesthesIaagents.
74
ArterIalCD
2
tensIonIsamajorregulatorofcerebralbloodflowwIthInthephysIologIc
rangeofarterIalCD
2
tensIons.CerebralbloodflowlInearlyIncreases1to2ml/100g/mIn
foreach1mmHgIncreaseInPaco
2
.8elowanarterIalCD
2
tensIonof25mmHg(FIg.2J),the
cerebralbloodflowresponsetoPaco
2
Isattenuated.ThemechanIsmresponsIbleforthe
cerebralbloodflowarterIalCD
2
tensIonrelatIonshIpIsrelatedtoextracellularH
+
concentratIon.CarbondIoxIderapIdlydIffusesacrossthevascularendothelIum,and
changesInlocalpHaregovernedbytheHendersonHasselbachequatIon.Notably,
alteratIonsIncerebralproducedbychangesInarterIalCD
2
tensIonarenotsustaInedblood
flowbecausebIcarbonateIseventuallytransportedoutofthebraInextracellularfluId,
therebyreturnIngpHtoanormalvalue.ncontrasttotheeffectsofrespIratoryacIdosIson
cerebralbloodflow,theactIonsofmetabolIcacIdosIsaremoregradualbecausetheblood
braInbarrIerIsrelatIvelyImpermeabletoH
+
.HypoxIaInducedIncreasesIncerebralblood
flowoccuratarterIalD
2
tensIonsbelow60mmHg(FIg.102J).TheIncreaseIncerebral
bloodflowatPao
2
levelsbelow60mmHgIsveryrapId.ThemechanIsmofthIshypoxIa
InducedIncreaseIncerebralbloodflowmayberelatedtothevasodIlatoreffectof
neuronalacIdosIs.SeveralothermedIatorsandchemoreceptoractIvatIonhavealsobeen
proposedaspotentIalsIgnalIngmechanIsmsresponsIbleforcerebralvasodIlatIondurIng
hypoxIa.ncontrasttothemarkedIncreasesIncerebralbloodflowobserveddurIng
hypoxIa,lIttlechangeIncerebralbloodflowoccursundernormoxIcorhyperbarIc
condItIons(Pao
2
of60toJ00mmHg).
Figure 10-23.Cerebralbloodflow(C8F)Isautoregulated(relatIvelyunchanged)as
meansystemIcbloodpressurerIsesbetween50to150mmHg.However,flowIsnearly
lInearlyIncreasedwItharIseInPaco
2
andIncreasedIfPao
2
fallsbelow50mmHg.
(|odIfIedandreproducedwIthpermIssIonfrom|IchenfelderJ0:AnesthesIaandthe
braIn,ClInIcal,FunctIonaland7ascularCoordInates.NewYork,ChurchIllLIvIngstone,
1988,pp9411J.)
NeuralcontrolofthecerebralcIrculatIonplaysarelatIvelymInorroleInregulatIonof
cerebralbloodflowdespItetheextensIvesympathetIcnervoussystemInnervatIonof
cerebralbloodvessels.SympathetIcpostganglIonIcneuronsorIgInateInthecervIcal
sympathetIcganglIa,andvasoconstrIctIonproducedbysympathetIcstImulatIonIslargely
exertedonthemedIumtolargersIzedcerebralarterIes.ThIsresponseIsprImarIly
manIfesteddurIngIntensesympathetIcnervoussystemactIvatIonthataccompanIes
profoundhypovolemIa.TheneteffectofthIssympathetIcactIvatIonIsadownwardshIftIn
thecerebralautoregulatIoncurve,IndIcatIngalowercerebralbloodflowthanpredIctedat
agIvenlevelofmeanarterIalpressure.ThecerebralbloodvesselsarealsoInnervatedby
cholInergIcandserotonergIcfIbers.AdmInIstratIonofexogenousvasodIlators(e.g.,sodIum
nItroprussIde,adenosIne,Ca
2+
channelblockers,volatIleanesthetIcs)Increasescerebral
bloodflow.ncontrast,catecholamInessuchasepInephrInedonotsubstantIallyaffect
cerebralbloodflowwhenthesedrugsareusedtoalterasystemIchemodynamIcsunless
cerebralperfusIonpressureIsaffectedattheextremesoftheautoregulatIoncurve.tIs
ImportanttorecognIzethatautoregulatIonofcerebralbloodflowIsnoteffectIveand
cerebralperfusIonbecomespressuredependentInareasofregIonalcerebralIschemIa.
Effects of Increased Intracranial Pressure
AlongwIththebraIn,thecerebralcIrculatIonIsentIrelyconstraInedwIthIntherIgId
cranIalcavIty.ThIsunIqueanatomIcarrangementInfersthatIncreasesIncerebralarterIal
bloodflowmustbematchedbycomparableIncreasesInvenousflowfromtheskullbecause
thevolumeofbloodandextracellularfluIdwIthInthebraInIsrelatIvelyconstant.Thus,an
IntracranIalmass(e.g.,tumor,hematoma)IsInevItablyaccompanIedbyanIncreaseIn
IntracranIalpressure.UnderthesecIrcumstances,theresIstancetocerebralbloodflow
IncreasesandcerebralperfusIonIsnolongerdetermInedbythedIfferencebetweenmean
arterIalpressureandcerebralvenouspressure,butratherthedIfferencebetweenarterIal
pressureandIntracranIalpressure.fIntracranIalpressurecontInuestoIncrease,a
compensatoryIncreaseInarterIalpressureoccurs(CushIngreflex)thatactsasaprotectIve
mechanIsmtomaIntaIncerebralperfusIon.
Renal Circulation
Anatomy of the Renal Circulation: Determinants of Glomerular
Blood Flow
TheprImarybranchesoftherenalarterydIvIdeIntoseveralInterlobararterIesthat
traversetheparenchymaInaradIalfashIonfromthehIlumtothecortIcalmedullary
junctIonthat
P.2J0
separatesthekIdneyIntoanoutercortexandanInnermedullawhereurIneIsprImarIly
concentratedIntherenaltubules.AsanInterlobararteryapproachesthecortIcal
medullaryjunctIon,ItbranchesIntoaserIesofarcuatearterIesthatarelocatedoverthe
basesoftheadjacentmedullarypyramIdsInthezonebetweenthecortexandthemedulla,
butdonotInterconnectwIthadjacentInterlobararterIes.ThIslackofcollateralblood
supplyIndIcatesthatacuteocclusIonofanInterlobararterywIllproduceapyramIdshaped
renalInfarctIon.nterlobularbranchesfromthearcuatearterIestraveltowardthe
capsularsurfaceandformtheafferentarterIalsupplytotheglomerulI.ThekIdneyhas
approxImately1mIllIonglomerulIthatfIlterplasmafromcIrculatIngbloodInto8owman's
capsulethatsurroundeachglomeruluscapIllarytuft.TheafferentarterIoletoeach
glomerulusdIvIdesIntoseveralvesselsthatformdIscretecapIllaryloops.TheproxImaland
dIstallImbsofeachloopareInterconnectedbymanysmallercapIllarIes,therebyformIng
thecapIllarytuft.PlasmafIltratIonoccurswIthInthesecapIllarynetworks.AfterexItIng
thecapIllarynetwork,thedIstalendsofeachcapIllaryloopwIthIntheglomerulusrejoInto
formtheefferentarterIoles.ThedIameterofefferentarterIolesIsusuallysubstantIallyless
thantheafferentarterIole.TheentIreglomerularcapIllarytuftIsenvelopedby8owman's
capsule,whIchcollectstheglomerularfIltrateandtransportsIttotherenaltubuleswhere
urIneIsconcentrated.TheefferentarterIolessubsequentlydIvIdeIntoanothercapIllary
network,theperItubularcapIllarIes,someofwhIchsurroundrelatIvelyshortrenaltubules
locatedalmostentIrelyIntherenalcortex.|ostoftheperItubularcapIllarIesformthe
longhaIrpInloopsofHenleextendIngdeepIntotherenalmedulla.Thesevasarecta
capIllarIesareImportantcomponentsoftherenalcountercurrentexchangemechanIsm
thatIsresponsIbleforurIneconcentratIon.
75
Renal Hemodynamics
ThemeanarterIalpressureIntheglomerularcapIllarIesIsnormallybetween50and60mm
Hg,therebyfavorIngtheoutwardfIltratIonofplasmawateralongtheentIrelengthofthe
capIllaryloop.ApproxImately20oftheplasmawaterthatenterstheglomerular
capIllarIesIsfIlteredInto8owman'scapsule.TheefferentarterIolesprovIdegreatest
vascularresIstanceIntherenalcIrculatIonandreducethepressureIntheperItubular
capIllarIestovaluesbetween10and20mmHg.TheserelatIvelylowpressuresfavorthe
netreabsorptIonofthelargequantItIesoffluIdthatpassfromtherenaltubulesIntothe
InterstItIum.ThepermeabIlItyoftheperItubularcapIllarIesIsalsoconsIderablyhIgher
thanothercapIllarIesInthebody,afeaturethatsubstantIallyfacIlItatestheprImary
dIffusIonfunctIonofthekIdney.FenalbloodflowIsapproxImately20ofcardIacoutput
andIsheavIlybalancedtowardperfusIonoftherenalcortex.TheInnermedullaand
papIllaeusuallyreceIveonlyapproxImatelyonetenthofcortIcalbloodflow.
76
ThekIdneyhasaveryhIghmetabolIcrate,buttheorganextractslessthan10ofD
2
presentInrenalarterIalbloodbecauserenalperfusIonfarexceedsmetabolIc
requIrements.FenalbloodflowIsveryImportantforthedelIveryofthelargevolumesof
bloodtotheglomerulIrequIredforultrafIltratIon.FenalbloodflowremaInsrelatIvely
constantbetweenmeanarterIalpressuresof75and170mmHg,butbecomespressure
dependentbeyondthIsrangeofautoregulatIon.AlteratIonsInafferentarterIoleresIstance
autoregulateglomerularfIltratIonrate(CFF)byconstrIctIngthedIameterofafferent
arterIolesInresponsetoIncreasesIndrIvIngpressure.ThetwoprImarymechanIsmsof
renalautoregulatIonaremyogenIc(vascularsmoothmuscleIntrInsIcallyrespondsto
stretchbyconstrIctIon)andtubularglomerularfeedback.ThIslatermechanIsmIs
medIatedbyafeedbackloopInwhIchanalteratIonInrenaltubularfIltrateflowIs
detectedbythemaculadensaofthejuxtaglomerularapparatus,whIchsIgnalstheafferent
arterIolestorestorebasallevelsofrenalbloodflowandCFF.ThesIgnalthatregulatesthe
calIberoftheafferentarterIolesIntubularglomerularfeedbackhasyettobeprecIsely
defIned,butmanyvasoactIvesubstanceshavebeenImplIcated,IncludIngproductsof
arachIdonIcacIdmetabolIsm,catecholamInes,adenosIne,nItrIcoxIde,andcomponentsof
therenInangIotensInsystem.
77,78,79
TheroleofatrIalnatrIuretIcfactor,a28amInoacId
peptIdewIthpotentdIuretIcandnatrIuretIcpropertIesIntherenalcIrculatIon,hasalso
beenelucIdated.ThIspeptIdeIssynthesIzedandreleasedprImarIlyfromthecardIacatrIa,
anddIstentIonoftheatrIacausesrenalvasodIlatIon,IncreasedfIltratIon,InhIbItIonof
sodIumreabsorptIon,natrIuresIs,andaresultantreductIonofextracellularfluIdvolume.
ThesympathetIcnervoussystemInnervatesthekIdneyandmaycontroltubulartransport
ofNa
+
durIngmodestreductIonsInIntravascularvolume.UndercondItIonsofprofound
hypovolemIa,sympathetIcactIvatIoncausesrenalvasoconstrIctIon,lowersCFF,and
reducesrenalcapIllaryhydrostatIcpressure,therebyproducIngcompensatorywater
retentIonthatIncreasesplasmavolume.AsaresultofthedIstrIbutIonofbloodflowwIthIn
thekIdney,perfusIontocortIcalcomparedwIthmedullarynephronsIsprImaryaffectedby
sympathetIcnervoussystemInducedrenalvasoconstrIctIon.
Splanchnic and Hepatic Circulation
Regulation of Gastrointestinal Blood Flow
ThesplanchnIccIrculatIonIsunIque.ArterIalbranchesoftheabdomInalaortasupplyblood
tothegastroIntestInaltract,spleen,andpancreas,whereasthelIverhasadualblood
supplyconsIstIngoftheportalvenouscIrculatIonandthehepatIcartery.TheIntestInal
cIrculatIonIsweaklyautoregulatedcomparedwIththecerebral,coronary,andrenal
vascularbeds.ntestInalautoregulatIonappearstobeprImarIlymetabolIcInorIgIn.
AdenosIneIsalIkelymedIatorofthIsautoregulatIon,butotherevIdencesuggeststhatK
+
concentratIonandserumosmolalItymayalsoplaycontrIbutIngroles.ThesympathetIc
nervoussystemInnervatesthegastroIntestInaltractandtheconsequencesofsympathetIc
actIvatIonaremedIatedbyadrenoceptors.PronouncedsympathetIcstImulatIondurIng
acutehypovolemIaproducesgastroIntestInalarterIalconstrIctIonandvenoconstrIctIon,
therebyshIftIngbloodfromalargevascularcapacItancebedIntothecentralcIrculatIon.
FoodIngestIonIncreasesgastroIntestInalbloodflowbyseveralmechanIsms,IncludIngthe
releaseofthehormonescholecystokInInandgastrInandabsorptIonofgastroIntestInal
contentsIncludIngglucose,fattyacIds,andpeptIdes.
80
Regulation of Hepatic Blood Flow
ThelIverreceIvesapproxImately25oftotalcardIacoutput,threequartersofwhIchare
derIvedfromtheportalveInthatcontaInsvenousbloodfromthegastroIntestInaltract,
spleen,andpancreas.TheremaInIng25ofhepatIcbloodflowIsprovIdedbythehepatIc
artery,whIchsupplIesthemajorItyofoxygentothelIver.|eanportalvenousandhepatIc
arterIalpressuresare10and90mmHg,respectIvely.
J8,81
ThedownstreamresIstanceIn
thehepatIcsInusoIdsIsrelatIvelylowundernormalcIrcumstances,butmaybeelevatedIn
F7faIlureorhepatIccIrrhosIs.ArIseInsInusoIdalandportalveInpressuresaccompanyIng
thesepathologIc
P.2J1
condItIonsmayproducetransudatIonoffluIdIntotheperItonealspace(ascItes)ordIlate
alternatIveroutesofvenousdraInage,suchasthoselocatedIntheloweresophagealveIns
(esophagealvarIces).8loodflowIntheportalvenousandhepatIcarterIalsystemstendsto
varyrecIprocally,buttheserespectIvehepatIcbloodsupplIesdonotfullyInteract.Thus,a
reductIonofbloodflowIntheportalveInmaybenotfullycompensatedbyanIncreaseIn
hepatIcarterIalflow.ThehepatIcarterIalbutnottheportalvenoussystemIs
autoregulated.ThemostImportantresponseofhepatIcarterIalcIrculatIontosympathetIc
stImulatIonIsconstrIctIonofthepresInusoIdalresIstancevessels.
82
ThelIvercontaIns
about15ofthetotalbodybloodvolumeandIsanImportantvolumereservoIrthatmay
berapIdlymobIlIzedInresponsetosympathetIcnervoussystemactIvatIondurIngacute
hypovolemIa.ThereflexresponsesandresponsetohypoxIaInsmallmesenterIc
capacItancevesselsareInhIbItedbypotentvolatIleanesthetIcs.
8J,84
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Stock, M. Christine
TableofContentsSectIonAnatomyandPhysIologyChapter11FespIratoryFunctIon
Chapter11
Respiratory Function
Michael L. Ault
M. Christine Stock
Key Points
1. In a person with normal lungs, both breathing and coughing can be
performed exclusively by the diaphragm.
2. In the adult, the tip of an orotracheal tube moves an average of 3.8
cm with flexion and extension of the neck, but can travel as much as
6.4 cm. In infants and children, displacement of even 1 cm can move
the tube above the vocal cords or below the carina.
3. The following anatomy should be considered when contemplating the
use of a double-lumen tube. The adult right main stem bronchus is
~2.5 cm long before it branches into lobar bronchi. In 10% of adults,
the right upper lobe bronchus departs from the right main stem
bronchus <2.5 cm below the carina. In 2 to 3% of adults, the right
upper lobe bronchus opens into the trachea, above the carina.
4. When lung compliance is reduced, larger changes in pleural pressure
are needed to create the same tidal volume (V
T
). Patients with low
lung compliance breathe with smaller V
T
and more rapidly, making
spontaneous respiratory rate the most sensitive clinical index of lung
compliance.
5. Carotid and aortic bodies are stimulated by Pao
2
values less than 60
to 65 mm Hg. Thus, patients who depend on hypoxic ventilatory
drive do not have Pao
2
values >65 mm Hg. The peripheral receptors'
response will not reliably increase ventilatory rate or minute
ventilation to herald the onset of hypoxemia during general
anesthesia or recovery.
6. There are three causes of hyperventilation: arterial hypoxemia,
metabolic acidemia, and central etiologies (e.g., intracranial
hypertension, hepatic cirrhosis, anxiety, pharmacologic agents).
7. Increases in dead space ventilation primarily affect CO
2
elimination
(with minimal influence on arterial oxygenation), and physiologic
shunt increase primarily affects arterial oxygenation (with minimal
influence on CO
2
elimination).
8. During spontaneous ventilation, the ratio of alveolar ventilation to
dead space ventilation is 2:1. The alveolar-to-dead space ventilation
ratio during positive-pressure ventilation is 1:1. Thus, minute
ventilation during mechanical ventilatory support must be greater
than that during spontaneous ventilation to achieve the same Paco
2
.
9. Paco
2
PETCO
2
unless the patient inspires or receives exogenous
CO
2
. The difference between Paco
2
and PETCO
2
is because of dead
space ventilation. The most common reason for an acute increase in
dead space ventilation is decreased cardiac output.
10. The best evaluation of the efficiency with which the lungs oxygenate
the arterial blood is the calculation of shunt fraction. It is the only
index of oxygenation that takes into account the contribution of
mixed venous blood to arterial oxygenation.
11. When functional residual capacity is reduced, lung compliance falls
and results in tachypnea, and venous admixture increases, creating
arterial hypoxemia.
12. There is no compelling evidence that defines rules or pa-rameters for
ordering preoperative pulmonary function tests. Rather, they should
be obtained to ascertain the presence of the reversible pulmonary
dysfunction (bronchospasm) or to define the severity of advanced
pulmonary disease.
P.234
14. Smoking patients should be advised to stop smoking at least 2
months prior to an elective operation to decrease the risk of
postoperative pulmonary complications (PPCs).
15. The operative site is one of the most important determinants of the
risk of PPC. The highest risk for PPC is associated with
nonlaparoscopic upper abdominal operations, followed by lower
abdominal and intrathoracic operations.
16. The single most important aspect of postoperative pulmonary care
and prevention of PPC is getting the patient out of bed, preferably
walking.
AnesthesIologIstsdIrectlymanIpulatepulmonaryfunctIon.Thus,asoundandthorough
workIngknowledgeofapplIedpulmonaryphysIologyIsessentIaltothesafeconductof
anesthesIa.ThIschapterdIscussespulmonaryanatomy,thecontrolofventIlatIon,oxygen
andcarbondIoxIdetransport,ventIlatIonperfusIonrelatIonshIps,lungvolumesand
pulmonaryfunctIontestIng,abnormalphysIologyandanesthesIa,theeffectofsmokIngon
pulmonaryfunctIon,andassessIngrIskforpostoperatIvepulmonarycomplIcatIons(PPCs).
Functional Anatomy of the Lungs
ThIssectIonemphasIzesfunctIonallunganatomy,wIthstructuredescrIbedasItapplIesto
themechanIcalandphysIologIcfunctIonofthelungs.
Thorax
ThethoracIccageIsshapedlIkeatruncatedcone,wIthasmallsuperIorapertureanda
largerInferIoropenIngtowhIchthedIaphragmIsattached.ThesternalangleIslocatedIn
thehorIzontalplanethatpassesthroughthevertebralcolumnattheT4orT5level.ThIs
planeseparatesthesuperIorfromtheInferIormedIastInum.0urIngventIlatIon,the
predomInantchangesInthoracIcdIameteroccurIntheanteroposterIordIrectIonInthe
upperthoracIcregIonandInthelateralortransversedIrectIonInthelowerthorax.
Muscles of Ventilation
WorkofbreathIngIstheenergyexpendItureofventIlatorymuscles.LIkeotherskeletal
muscles,theventIlatorymusclesareendurancemusclesthataresubjecttofatIguefrom
InadequateoxygendelIvery,poornutrItIon,IncreasedworksecondarytochronIc
obstructIvepulmonarydIsease(CDP0)wIthgastrappIng,orIncreasedaIrwayresIstance.
TheventIlatorymusclesIncludethedIaphragm,Intercostalmuscles,abdomInalmuscles,
cervIcalstrapmuscles,sternocleIdomastoIdmuscles,andthelargebackandIntervertebral
musclesoftheshouldergIrdle.0urIngbreathIngthedIaphragmperformsmostofthe
musclework.WorkcontrIbutIonfromtheIntercostalmusclesIsmInor.Normally,atrest,
InspIratIonrequIresworkandexhalatIonIspassIve.AsworkofbreathIngIncreases,
abdomInalmusclesassIstwIthrIbdepressIonandIncreaseIntraabdomInalpressureto
facIlItateforcedexhalatIoncausIngthestItchathletesexperIencewhentheyactIvely
exhale.WIthfurtherIncreasesInwork,thecervIcalstrapmuscleshelpelevatethesternum
andupperportIonsofthechest.FInally,durIngperIodsofmaxImalwork,thelargeback
andparavertebralmusclesoftheshouldergIrdlecontrIbutetoventIlatoryeffort.The
musclesoftheabdomInalwall,themostpowerfulmusclesofexpIratIon,areImportantfor
expulsIveeffortssuchascoughIng.
1
WIthnormallungs,bothbreathIngandcoughIngcanbe
performedsolelybythedIaphragm.
8reathIngIsanendurancephenomenonInvolvIngfatIgueresIstantmusclefIbers,
characterIzedbyaslowtwItchresponsetoelectrIcalstImulatIonthatmustcreate
suffIcIentforcetolIfttherIbsandgeneratesubatmospherIcpressureIntheIntrapleural
space.ThesefatIgueresIstantfIberscomprIseapproxImately50ofthetotal
dIaphragmatIcmusclefIbers.ThehIghoxIdatIvecapacItyofthesesfIberscreates
enduranceunIts.
2
FasttwItchmusclefIbers,moresusceptIbletofatIgue,haverapId
responsestoelectrIcalstImulatIonImpartIngstrengthandallowInggreaterforceoverless
tIme.ThecombInatIonoffasttwItchfIbersusefuldurIngbrIefmaxImalventIlatoryeffort
perIods(coughIng,sneezIng)andslowtwItchfIbersprovIdIngendurance(breathIngwIthout
rest)belIeItsunIqueduplIcItousfunctIonasamuscle.
J
AworkIngmusclelIkethedIaphragmmustbefIrmlyanchoredatbothItsorIgInand
InsertIon.However,ItsunIqueInsertIonIsmobIleacentraltendonorIgInatesfromfIbers
attachedtothevertebralbodIesaswellasthelowerrIbsandsternum.0IaphragmatIc
contractIonresultsIndescentofthedIaphragmatIcdomeandexpansIonofthethoracIc
basecreatIngdecreasesInIntrathoracIcandIntrapleuralpressureandanIncreaseInIntra
abdomInalpressure.
ThecervIcalstrapmuscles,actIveevendurIngbreathIngatrest,arethemostImportant
InspIratoryaccessorymuscles.WhendIaphragmfunctIonIsImpaIred,asInpatIentswIth
cervIcalspInalcordtransectIon,theycanbecometheprImaryInspIratorymuscles.
Lung Structures
nanIntactrespIratorysystem,theexpandablelungtIssuefIllsthepleuralcavIty.The
vIsceralandparIetalpleuraeopposeeachother,creatIngapotentIalIntrapleuralspace
wherepressuredecreaseswhenthedIaphragmdescendsandtherIbcageexpands.Atthe
endofInspIratIon,theresultantsubatmospherIcIntrapleuralpressureIsareflectIonofthe
opposIngandequalforcesbetweenthetendencyofthelungtocollapseandthechestwall
musculaturetoremaInexpandedtocreatesubatmospherIcpleuralpressure.Theseequal
andopposIngforcesatendInspIratIonresultInthefunctIonalresIdualcapacIty(FFC),the
volumeofgasInthelungsatpassIveendexpIratIon.AtFFCtheIntrapleuralspace
normallyhasaslIghtlysubambIentpressure(2toJmmHg).|ajordIvIsIonsoftherIght
andleftlungarelIstedInTable111.KnowledgeofthebronchopulmonarysegmentsIs
ImportantforlocalIzInglungpathology,InterpretInglungradIographs,IdentIfyInglung
regIonsdurIngbronchoscopy,andoperatIngonthelung.Eachbronchopulmonarysegment
IsseparatedfromItsadjacentsegmentsbywelldefInedconnectIvetIssueplanesthatoften
anatomIcallyconfIneInItIalprImarylungpathologIes.
ThelungparenchymacanbesubdIvIdedIntothreeaIrwaycategorIesbasedonfunctIonal
lunganatomy(Table112).TheconductIveaIrwaysalloworconductbasIcgastransport
wIthoutgasexchange.ThenextgroupofaIrways,whIchhavesmallerdIameters,are
transItIonalaIrways.TransItIonalaIrwaysarenotonlyconduItsforgasmovement,butalso
allowlImItedgasdIffusIonandexchange.FInally,theprImaryfunctIonofthesmallest
respIratoryaIrwaysIsgasexchange.
ConventIonally,largeaIrwayswIthdIametersof2mmcreate90oftotalaIrway
resIstance.ThenumberofalveolIIncreasesprogressIvelyfromapproxImately24mIllIonat
bIrthtothefInaladultcountofJ00mIllIonattheageof8or9years.ThesealveolIare
assocIatedwIthabout250mIllIon
P.2J5
precapIllarIesand280bIllIoncapIllarysegments,resultIngInasurfaceareaof-70m
2
for
gasexchange.
Table 11-1 Major Divisions of the Lung
LUNG SIDE/LOBE BRONCHOPULMONARY SEGMENT
RIGHT
Upper
ApIcal
AnterIor
PosterIor
|Iddle
|edIal
Lateral
Lower
SuperIor
|edIalbasal
Lateralbasal
AnterIorbasal
PosterIorbasal
LEFT
Upper
ApIcalposterIor
AnterIor
LIngula
SuperIor
nferIor
Lower
SuperIor
PosterIorbasal
AnteromedIalbasal
Lateralbasal
Conductive Airways
ntheadult,thetracheaIsafIbromusculartube-10to12cmlongwIthanoutsIde
dIameterof-20mm.StructuralsupportIsprovIdedby20UshapedhyalInecartIlages,wIth
theopenpartoftheUfacIngposterIorly.ThecrIcoIdmembranetethersthetracheatothe
crIcoIdcartIlageatthelevelofthesIxthcervIcalvertebralbody.Thetracheaentersthe
superIormedIastInumandbIfurcatesatthesternalangle(thelowerborderofthefourth
thoracIcvertebralbody).Normally,halfofthetracheaIsIntrathoracIcandhalfIs
extrathoracIc.8ecausebothendsofthetracheaareattachedtomobIlestructures,the
adultcarInacanmovesuperIorlyasmuchas5cmfromItsnormalrestIngposItIon.
AwarenessofaIrwaymotIonIsessentIaltopropercareoftheIntubatedpatIent.nthe
adult,thetIpofanorotrachealtubemovesanaverageofJ.8cmwIthflexIonand
extensIonoftheneckbutcantravelasfaras6.4cm.
4
nInfantsandchIldren,tracheal
tubemovementwIthrespecttothetracheaIsevenmorecrItIcal:dIsplacementofeven1
cmcanresultInunIntentIonalextubatIonorbronchIalIntubatIon.
ThenextaIrwaygeneratIonIscomposedoftherIghtandleftmaInstembronchI.The
dIameteroftherIghtbronchusIsgenerallygreaterthanthatoftheleft.ntheadult,the
rIghtbronchusleavesthetracheaat-25degreesfromthevertIcaltrachealaxIs,whereas
theangleoftheleftbronchusIs-45degrees.Thus,InadvertentendobronchIalIntubatIon
oraspIratIonofforeIgnmaterIalIsmorelIkelytooccurontherIghtthantheleft.
Furthermore,therIghtupperlobebronchusdIvesalmostdIrectlyposterIorat-90degrees
fromtherIghtmaInbronchusfacIlItatIngaspIratIonofforeIgnbodIesandfluIdIntothe
rIghtupperlobeInthesupInepatIent.nchIldrenyoungerthanJyearsofage,theangles
createdbytherIghtandleftmaInstembronchIareapproxImatelyequal,wIthtakeoff
anglesofabout55degrees.
TheadultrIghtmaInbronchusIs-2.5cmlongbeforeItInItIallybranchesIntolobar
bronchI.However,In10ofadults,therIghtupperlobebronchusdepartsfromtherIght
maInstembronchus2.5cmfromthecarIna.Furthermore,In-2toJofadults,therIght
upperlobebronchusopensIntothetrachea,superIortothecarIna.PatIentswIththese
anomalIesrequIrespecIalconsIderatIonwhenplacIngdoublelumentrachealtubes,
especIallyIfonecontemplatesInsertIngarIghtsIdedendobronchIaltube.AftertherIght
upperandmIddlelobebronchIdIvIdefromtherIghtmaInbronchus,themaInchannel
becomestherIghtlowerlobebronchus.
TheleftmaInbronchusIs-5cmlongbeforeItsInItIalbranchIngpoInttotheleftupperlobe
andthelIngula;ItthencontInuesastheleftlowerlobebronchus.
ThebronchIoles,typIcally1mmIndIameter,aredevoIdofcartIlagInoussupportandhave
thehIghestproportIonofsmoothmuscleIntheIrwalls.DfthethreetofourbronchIolar
generatIons,thefInalgeneratIonIsthetermInalbronchIole,whIchIsthelastaIrway
componentIncapableofgasexchange.
Transitional Airways
TherespIratorybronchIole,whIchfollowsthetermInalbronchIole,IsthefIrstsIteInthe
tracheobronchIaltreewheregasexchangeoccurs.nadults,twoorthreegeneratIonsof
respIratorybronchIolesleadtoalveolarducts,ofwhIchtherearefourtofIvegeneratIons,
eachwIthmultIpleopenIngsIntoalveolarsacs.ThefInaldIvIsIonsofalveolarducts
termInateInalveolarsacsthatopenIntoalveolarclusters.
Respiratory Airways and the AlveolarCapillary Membrane
ThealveolarcapIllarymembranehastwoprImaryfunctIons:transportofrespIratorygases
(oxygenandcarbondIoxIde)andtheproductIonofawIdevarIetyoflocalandhumoral
substances.CastransportIsfacIlItatedbythepulmonarycapIllarybedsthatlogIcallyare
thedensestcapIllarynetworksInthebody.ThIsextensIvevascularbranchIngsystemstarts
wIthpulmonaryarterIolesIntheregIonoftherespIratorybronchIoles.EachalveolusIs
closelyassocIatedwIth-1,000shortcapIllarysegments.
ThealveolarcapIllaryInterfaceIscomplIcatedbutwelldesIgnedtofacIlItategas
exchange.7IewedwIthelectronmIcroscopy,thealveolarwallconsIstsofathIncapIllary
epIthelIalcell,abasementmembrane,apulmonarycapIllaryendothelIalcell,anda
surfactantlInInglayer.Theflattened,squamoustypealveolarcellscover-80ofthe
alveolarsurface.TypecellscontaInflattenednucleIandextremelythIn
P.2J6
cytoplasmIcextensIonsthatprovIdethesurfaceforgasexchange.TypecellsarehIghly
dIfferentIatedandmetabolIcallylImIted,whIchmakesthemhIghlysusceptIbletoInjury.
Whentypecellsaredamagedseverely(durIngacutelungInjuryoradultrespIratory
dIstresssyndrome),typecellsreplIcateandmodIfytoformnewtypecells.
5
Table 11-2 Functional Airway Divisions
TYPE FUNCTION STRUCTURE
ConductIve 8ulkgasmovement TracheatotermInalbronchIoles
TransItIonal
8ulkgasmovement
LImItedgasexchange
FespIratorybronchIoles
Alveolarducts
FespIratory Casexchange
AlveolI
Alveolarsacs
TypealveolarcellsareInterspersedamongtypecells,prImarIlyatalveolarseptal
junctIons.ThesepolygonalcellshavevastmetabolIcandenzymatIcactIvItyand
manufacturesurfactant.TheenzymatIcactIvItyrequIredtoproducesurfactantIsonly50
ofthetotalenzymatIcactIvItypresentIntypealveolarcells.
6
TheremaInIngenzymatIc
actIvItymodulateslocalelectrolytebalance,aswellasendothelIalandlymphatIccell
functIons.8othtypeandtypealveolarcellshavetIghtIntracellularjunctIons,provIdIng
arelatIvelyImpermeablebarrIertofluIds.
Typealveolarcells,alveolarmacrophages,areanImportantelementofImmunologIc
lungdefense.TheIrmIgratoryandphagocytIcactIvItIespermItIngestIonofforeIgn
materIalswIthInalveolarspaces.
7
AlthoughfunctIonalpulmonarymacrophagesreducethe
IncIdenceoflungInfectIon,
8
theyarealsoanIntegralpartoftheorganwIdepulmonary
Inflammatoryresponse.Thus,ItIshIghlycontroversIalwhetherthepresenceofthesecells
IsbenefIcIal(reducIngthesequelaeofInfectIon)orharmful(contrIbutIngtothe
Inflammatoryresponse).
9
Pulmonary Vascular Systems
TwomajorcIrculatorysystemssupplybloodtothelungs:thepulmonaryandbronchIal
vascularnetworks.ThepulmonaryvascularsystemdelIversmIxedvenousbloodfromthe
rIghtventrIcletothepulmonarycapIllarybedvIatwopulmonaryarterIes.Aftergas
exchangeoccursInthepulmonarycapIllarybed,bloodIsreturnedtotheleftatrIumvIa
fourpulmonaryveIns.ThepulmonaryveInsrunIndependentlyalongtheIntralobar
connectIvetIssueplanes.ThepulmonarycapIllarysystemadequatelyprovIdesforthe
metabolIcandoxygenneedsofthealveolarparenchyma.ThebronchIalarterIalsystem
provIdesoxygentotheconductIveaIrwaysandpulmonaryvessels.AnatomIcconnectIons
betweenthebronchIalandpulmonaryvenouscIrculatIonscreateanabsoluteshuntof-2to
5ofthetotalcardIacoutput,andrepresentsnormalshunt.
Lung Mechanics
Lungmovementoccurssecondarytoforcesexternaltothelungs.0urIngspontaneous
ventIlatIon,theexternalforcesareproducedbyventIlatorymuscles.Thelungs'responseIs
governedbytwomaIncategorIes:easeofelastIcrecoIlofthechestwallandbyresIstance
togasflowwIthInaIrways.
Elastic Work
ThenaturaltendencyofthelungsIstocollapsebecauseofelastIcrecoIl;thus,expIratIon
atrestIsnormallypassIveasgasflowsoutofthelungs.ThethoracIccageexertsan
outwarddIrectedforceandthelungsexertanInwarddIrectedforce,andbecausethe
outwardforceofthethoracIccageexceedstheInwardforceofthelung,theoverall
tendencyofthelungwIthInthethoracIccageIstoremaInInflated.FFCrepresentsthegas
volumeInthelungswhentheoutwardandInwardforcesonthelungareequal.
CravItatIonalforcescreateamoresubatmospherIcpressureInnondependentareasofthe
lungthanIndependentareas.ntheuprIghtadult,thedIfferenceInIntrapleuralpressure
fromthetoptothebottomofthelungIs-7cmH
2
D.
SurfacetensIonatanaIrfluIdInterfaceproducesforcesthattendtofurtherreducethe
areaofInterface.ForabubbletoremaInInflatedthegaspressurewIthInabubblethatIs
contaInedbysurfacetensIonmustbehIgherthanthesurroundInggaspressure.AlveolI
resemblebubblesInthIsrespect,butunlIkeabubble,alveolargascommunIcateswIththe
atmospherevIatheaIrways.TheLaplaceequatIondescrIbesthIsphenomenon:P=2T/R,
wherePIsthepressurewIthInthebubble(dynecm
2
),TIsthesurfacetensIonofthe
lIquId(dynecm
1
),andRIstheradIusofthebubble(IncentImeters).
0urIngInspIratIon,thesurfacetensIonofthelIquIdInthelungIncreasesto40mN/m,a
valueclosetothatofplasma.0urIngexpIratIon,thIssurfacetensIonfallsto19mN/m,a
valuelowerthanthatofmostotherfluIds.ThIschangeInsurfacetensIoncreates
hysteresIsofthealveolI,dIfferentpressurevolumerelatIonshIpsofthealveolIdurIng
InspIratIonandexpIratIon.UnlIkeabubble,thepressurewIthInanalveolusdecreasesas
theradIusofcurvaturedecreases,creatInggasflowfromlargertosmalleralveolI,whIch
maIntaInsstructuralstabIlItyandpreventslungcollapse.
ThealveolartransmuralpressuregradIent,ortranspulmonarypressure,IsthedIfference
betweenIntrapleuralandalveolarpressureandIsdIrectlyproportIonaltolungvolume.
ntrapleuralpressurecanbesafelymeasuredwIthapercutaneouslyInsertedcatheter
10
;
however,clInIcIansrarelyperformthIstechnIque.WhenmeasuredwIthanesophageal
balloonInthemIdesophagus,esophagealpressurecanbeusedasareflectIonof
Intrapleuralpressure.
11
CommercIallyavaIlableesophagealpressuremonItorsIncreasethe
easeandaccuracyofmeasurIngesophagealpressureasareflectIonofIntrapleural
pressure.
12
ThesemonItorsareusefulforestImatIngtheelastIcworkperformedbythe
patIentdurIngspontaneousventIlatIon,mechanIcalventIlatIon,oracombInatIonof
spontaneousandmechanIcalventIlatIon.8yestImatIngIntrapleuralpressureonarealtIme
basIs,ItIspossIbletoquantItatethepatIent'sworkofbreathIngandchangessecondaryto
InterventIon.LowlevelsofInspIratorypressuresupportcancompensatefortheworkof
breathIngImposedbytheendotrachealtube.
1J
PhysIologIcworkofbreathIngIncludeselastIcwork(InspIratoryworkrequIredtoovercome
theelastIcrecoIlofthepulmonarysystem)andresIstIvework(worktoovercome
resIstancetogasflowIntheaIrway).ForapatIentInwhombreathIngapparatusIs
employed,theconceptoftotalworkofbreathIngencompassesphysIologIcworkplus
equIpmentImposedventIlatoryworktoovercometheresIstanceImposedbythebreathIng
apparatus;suchasanendotrachealtubeoraventIlatordemandvalve.
fthelungsareslowlyInflatedanddeflated,thepressurevolumecurvedurIngInflatIon
dIffersfromthatobtaIneddurIngdeflatIon.ThetwocurvesformahysteresIsloopthat
becomesprogressIvelybroaderasthetIdalvolumeIsIncreased(FIg.111).ToInflatethe
lungs,pressuregreaterthantherecoIlpressureofdeflatIonIsneeded,whIchmeansthat
thelungacceptsdeformatIonpoorlyand,oncedeformed,reformstoItsorIgInalshape
slowly.ElastIchysteresIsIsImportantforthemaIntenanceofnormallungcomplIancebut
IsnotclInIcallysIgnIfIcant.
ThesumofthepressurevolumerelatIonshIpsofthethoraxandlungresultsInasIgmoIdal
curve(FIg.112).ThevertIcallInedrawnatendexpIratIoncoIncIdeswIthFFC.Normally,
humansbreatheonthesteepestpartofthesIgmoIdalcurve,wherecomplIance(V/P)or
slopeIshIghest.nrestrIctIvepulmonarydIseases,thecomplIancecurveshIftstotherIght,
hasdecreasedslope,orboth.ThIsdecreasedlungcomplIanceresultsInsmallerFFCs.When
lungcomplIanceIsreduced,largerchangesInIntrapleuralpressureareneededtocreate
thesametIdalvolume;thatIs,thethoraxhastoworkhardertogetthesamevolumeof
gasIntothelungs.Thebody,beInganenergyconservIngorganIsm,preferstomovelessgas
wItheachbreathratherthanworkInghardertoachIevethesametIdalvolume.Thus,
patIentswIthrestrIctIvelungdIseasetypIcallybreathewIthsmallertIdalvolumesatmore
rapIdrates,makIngthespontaneousventIlatoryrateoneofthemostsensItIveIndIcesof
P.2J7
lungcomplIance.WhenlungcomplIanceIsdecreased,contInuousposItIveaIrwaypressure
(CPAP)wIllshIftthevertIcallInetotherIght,allowIngthepatIenttobreatheonasteeper,
moreeffIcIentportIonofthevolumepressurecurve,resultIngInaslowerventIlatoryrate
wIthalargertIdalvolume.
Figure 11-1.0ynamIcpressurevolumeloopofrestIngtIdalvolume.QuIet,normal
breathIngIscharacterIzedbyhysteresIsofthepressurevolumeloop.ThelungIsmore
resIstanttodeformatIonthanexpectedandreturnstoItsorIgInalconfIguratIonless
easIlythanexpected.TheslopeofthelIneconnectIngthezenIthandnadIrlung
volumesIslungcomplIance,-500mL/JcmH
2
D=167mL/cmH
2
D.
Attheotherendofthespectrum,patIentswIthdIseasesthatIncreaselungcomplIance
expendlesselastIcworktoInspIrebuthavedecreasedelastIcrecoIlcreatInglargerthan
normalFFC(gastrappIng),andtheIrpressurevolumecurvesshIfttotheleftandsteepen.
ChronIcobstructIvelungdIseaseandacuteasthmaarethemostcommonexamplesof
dIseaseswIthhIghlungcomplIance.flungcomplIanceandFFCaresuffIcIentlyhIghthat
elastIcrecoIlIsmInImal,thepatIentmustuseventIlatorymusclestoactIvelyexhale.The
dIffIcultythesepatIentsexperIenceInemptyIngthelungsIscompoundedbytheIncreased
aIrwayresIstance.
Figure 11-2.PulmonarypressurevolumerelatIonshIpsatdIfferentvaluesoftotallung
capacIty(TLC),IgnorInghysteresIs.Thesolid linedepIctsthenormalpulmonary
pressurevolumerelatIonshIps.HumansnormallybreatheonthelInear,steeppartof
thIssIgmoIdalcurve,wheretheslope,whIchIsequaltocomplIance,Isgreatest.The
vertical lineatzerodefInesfunctIonalresIdualcapacIty(FFC),regardlessofthe
posItIonofthecurveonthegraph.|IldrestrIctIvelungdIsease,IndIcatedbythe
dashed line,shIftsthecurvetotherIghtwIthlIttlechangeInslope.However,wIth
restrIctIvedIsease,thepatIentbreathesonalowerFFC,atapoIntonthecurvewhere
theslopeIsless.SevererestrIctIvepulmonarydIseaseprofoundlydepressestheFFC
anddImInIshestheslopeoftheentIrecurve(dashed-dotted line).DbstructIvedIsease
(dotted line)elevatesbothFFCandcomplIance.
8othcomplIanceandInspIratoryelastIcworkcanbemeasuredforasInglebreathby
measurIngaIrway(Paw),Intrapleural(Ppl)pressures,andtIdalvolume.fesophageal
pressureIsmeasuredcorrectly,theesophagealpressurevaluescanbesubstItutedforPpl
values.LungcomplIance,C
L
,theslopeofthevolumepressurecurve,IsgIvenbythe
equatIon:
whereP
L
Istranspulmonarypressure,PL
I
andPL
e
aretranspulmonarypressureatend
InspIratoryandendexpIratory,7
T
IstIdalvolume,Paw
e
andPaw
I
areexpIratoryand
InspIratoryaIrwaypressures,andPpl
e
andPpl
I
areexpIratoryandInspIratoryIntrapleural
pressures.
ElastIcwork(W
el
)IsperformeddurIngInspIratIononlybecauseexpIratIonIspassIvedurIng
normalbreathIng.TheareawIthInthetrIangleInFIgure112descrIbestheworkrequIred
toInspIre.TheequatIonthatyIeldselastIcwork(andtheareaofthetrIangle)Is:
Resistance to Gas Flow
8othlamInarandturbulentflowsexIstwIthIntherespIratorytract,usuallyInmIxed
patterns.ThephysIcsofeach,however,IssIgnIfIcantlydIfferentandworthconsIderatIon.
Laminar Flow
8elowcrItIcalflowratesthatcreateturbulentflow,gasproceedsthroughastraIghttube
asaserIesofconcentrIccylIndersthatslIdeoveroneanother.Fullydevelopedflowhasa
parabolIcprofIlewIthavelocItyofzeroatthecylInderwallandamaxImumvelocItyat
thecenteroftheadvancIngcone.ThIstypeofstreamlInedflowIsusuallyInaudIble.The
advancIngconIcalfrontmeansthatsomefreshgasreachestheendofthetubebeforethe
tubehasbeencompletelyfIlledwIthfreshgas.Thus,lamInarflowIntheaIrwaysresultsIn
alveolarventIlatIonwhIchcanoccurevenwhenthetIdalvolume(7
T
)IslessthananatomIc
deadspace.ThIsphenomenoncertaInlyhassIgnIfIcantclInIcalImplIcatIons,andasnoted
byFohrer
14
In1915ItallowshIghfrequencyventIlatIontoachIeveadequatealveolar
ventIlatIon.
FesIstancetolamInargasflowsInastraIght,unbranchedtubecanbecalculatedbythe
followIngequatIon:
whereP
8
andP
A
arebarometrIcandalveolarpressures.tIsessentIaltonotethatasradIus
decreasesInnarrowedaIrways,resIstancewIllIncreasebyapoweroffour.7IscosItyIsthe
onlyphysIcalgaspropertythatIsrelevantundercondItIonsoflamInarflow.HelIumhasa
lowdensIty,butItsvIscosItyIsclosetothatofaIr.Therefore,helIumwIllnotImprovegas
flowIftheflowIslamInar.FlowIsusuallyturbulentwhenthereIscrItIcalaIrwaynarrowIng
orabnormallyhIghaIrwayresIstance,makInglowdensItyhelIumusefultherapy(seenext
sectIon).
Turbulent Flow
HIghflowrates,partIcularlythroughbranchedorIrregularlyshapedtubes,dIsruptthe
orderlyflowoflamInargas.When
P.2J8
resIstancetogasflowIssIgnIfIcant,turbulentflowoccursandIsusuallyaudIble.Turbulent
flowusuallypresentswIthasquarefrontsofreshgaswIllnotreachtheendofthetube
untIltheamountofgasenterIngthetubeIsalmostequaltothevolumeofthetube.Thus,
turbulentfloweffectIvelypurgesthecontentsofatube.FourcondItIonsthatwIllchange
lamInarflowtoturbulentflowarehIghgasflows,sharpangleswIthInthetube,branchIng
Inthetube,andadecreaseInthetube'sdIameter.0urInglamInarflow,resIstanceIs
InverselyproportIonaltogasflowrate.Conversely,durIngturbulentflow,resIstance
IncreasessIgnIfIcantlyInproportIontotheflowrate.AdetaIleddescrIptIonofthese
phenomenaIsbeyondthescopeofthIschapter,butthereaderIsreferredtodescrIptIons
byNunn.
15
Increased Airway Resistance
8ronchIolarsmoothmusclehyperreactIvIty(truebronchospasm),mucosaledema,mucous
pluggIng,epIthelIaldesquamatIon,tumors,andforeIgnbodIesallIncreaseaIrway
resIstance.TheconscIoussubjectcandetectsmallIncreasesInInspIratoryresIstance.
16
ThenormalresponsetoIncreasedInspIratoryresIstanceIsIncreasedInspIratorymuscle
effort,wIthlIttlechangeInFFC.
17
EmphysematouspatIentsretaInremarkableabIlItyto
preserveanadequatealveolarventIlatIon,evenwIthgrossaIrwayobstructIon.npatIents
wIthpreoperatIvevaluesofforcedexpIratoryvolumeInthefIrstsecondofexpIratIon
(FE7
1
)thatare1L,Paco
2
IsnormalInmostpatIents.Furthermore,asthmatIcpatIents
compensatewellforIncreasedaIrwayresIstanceandalsokeepthemeanPaco
2
Inthe
lowerendofnormalrange.
18
Thus,anIncreasedPaco
2
InthesettIngofIncreasedaIrway
resIstancewarrantsserIousattentIonasItmaysIgnalthatthepatIent'scompensatory
mechanIsmsarenearlyexhausted.|IldexpIratoryresIstancedoesnotresultInmuscleuse
foractIveexhalatIonInconscIousoranesthetIzedsubjects.nstead,theInItIalworkto
overcomeexpIratoryresIstanceIsperformedbyaugmentIngInspIratoryforceuntIla
suffIcIentlyhIghlungvolumeIsachIevedthatallowselastIcrecoIltoovercomeexpIratory
resIstance.
19
WhenexpIratoryresIstancebecomesexcessIve,accessorymusclesareusedto
forcegasfromthelungs.0urIngacuteIncreasesInexpIratoryresIstance,thIsresponsecan
bewelltoleratedbymostpatIents.However,chronIcuseofaccessorymusclestoexhale
sIgnIfIcantlyIncreasestherIskofventIlatoryfaIlureIfworkofbreathIngIsfurther
Increased.WhenworkofbreathIngexceedsphysIologIcreserves,workofbreathIng
becomesdetrImentaltophysIologIchomeostasIsandImpendIngventIlatoryfaIlure
secondarytoventIlatorymusclefatIguebecomesacuteventIlatoryfaIlureevIdencedbyan
acuteIncreaseInarterIalcarbondIoxIde.Commonly,thIsIsprecIpItatedbypneumonIaor
heartfaIlure.
Physiologic Changes in Respiratory Function Associated With
Aging
PhysIologIcagIngofthelungIsassocIatedwIthdIlatIonofthealveolI,enlargementofthe
aIrspaces,decreaseInexchangesurfacearea,andlossofsupportIngtIssue.
20
ChangesIn
theagInglungandchestwallresultIndecreasedlungrecoIl(elastance),creatIngan
IncreasedresIdualvolumeandFFC.AddItIonally,complIanceofthechestwalldImInIshes,
therebyIncreasIngtheworkofbreathIngcomparedwIthyoungersubjects.FespIratory
musclestrengthdecreaseswIthagIngandIsstronglycorrelatedwIthnutrItIonalstatusand
cardIacIndex.ExpIratoryflowratesdecreasewIthaflowvolumecurvesuggestIveofsmall
aIrwayresIstance.0espItethesechanges,therespIratorysystemIsnormallyableto
maIntaInadequategasexchangeatrestanddurIngexertIonthroughoutlIfe,wIthonly
modestdecrementsInPao
2
andnochangeInPaco
2
.WIthagIng,respIratorycentersInthe
nervoussystemdemonstratedecreasedsensItIvItytohypoxemIaandhypercapnIa,resultIng
InabluntedventIlatoryresponsewhenchallengedbyheartfaIlure,aIrwayobstructIon,or
pneumonIa.
Control of Ventilation
|echanIsmsthatcontrolventIlatIonareextremelycomplex,requIrIngIntegratIonwIth
manypartsofthecentralandperIpheralnervoussystems(FIg.11J).LeCalloIs,
21
who
localIzedtherespIratorycentersInthebraInstemIn1812,demonstratedthatbreathIng
doesnotdependonanIntactcerebrum.Father,breathIngdependsonasmallregIonofthe
medullaneartheorIgInofthevagusnerves.CountlessstudIesInthepasttwocenturIes
havegreatlyIncreasedourknowledgeandunderstandIngoftheanatomIccomponentsof
ventIlatorycontrol.However,experImentalworkperformedInanImalsIsdIffIculttoapply
tohumansbecauseofInterspecIesvarIatIon.
Terminology
8reathIng,ventIlatIon,andrespIratIonareoftenusedInterchangeably.However,ItIs
ImportanttorealIzethatthesetermshavedIstInctmeanIngs.Thetermbreathingrefersto
theactofInspIrIngandexhalIng,whIchrequIresenergyutIlIzatIonformuscleworkand
thusIslImItedbyenergyreserves.Ventilation,ontheotherhand,Isthemovementofgas
Inandoutofthelungs.Whenspontaneous,ventIlatIonrequIresenergyformuscleworkand
Is,thus,breathIng.RespirationoccurswhenenergyIsreleasedfromorganIcmolecules.
SuchenergyreleasedependsonthemovementofgasmoleculessuchascarbondIoxIdeand
oxygenacrossmembranes,whetheralveolarormItochondrIal.Thus,humansbreatheto
ventIlateandventIlatetorespIre.0espItewhatappearstobecleardIstInctIonsIn
termInology,vernacularuseofthesetermsareoftenconfusedIndaIlydIalog.Forexample:
respiratorsareusedtotreatthosewhohavesuccumbedtorespiratoryarrestanddonot
havearespiratoryrate,andresIdentsaresometImesadvIsedtobreathedownapatIent
usIngpotentanesthetIcagent.
Generation of Ventilatory Pattern
FefertoTable11JfordefInItIonsoftermsusedInthIssectIon.Arespiratory centerIsa
specIfIcareaInthebraInthatIntegratesneuraltraffIc,resultIngInspontaneous
ventIlatIon.WIthInthepontIneandmedullaryretIcularformatIons,thereareseveral
dIscreterespIratorycentersthatfunctIonasthecontrolsystem(seeFIg.11J).
nItIaldescrIptIonsofbraInstemrespIratoryfunctIonsarebasedonclassIcablatIonand
electrIcalstImulatIonstudIes.AnothermethodforlocalIzIngrespIratorycentersentaIls
recordIngactIonpotentIalsfromdIfferentareasofthebraInstemwIthmIcroelectrodes.
ThIsmethodIsbasedontheassumptIonthatlocalbraInactIvItythatoccursInphasewIth
respIratoryactIvItyIsevIdencethattheareaunderstudyhasrespIratoryneurons.
22
ThesetechnIquesareImperfectforprecIselylocalIzIngdIscreterespIratorycenters.
Medullary Centers
ThemedullaoblongatacontaInsthemostbasIcventIlatorycontrolcentersInthebraIn.
SpecIfIcmedullaryareasareprImarIlyactIvedurIngInspIratIonordurIngexpIratIon,wIth
manyneuralInspIratoryorexpIratoryInterconnectIons.TheInspIratorycentersthatresIde
InthedorsalrespIratorygroup
P.2J9
(0FC)arelocatedInthedorsalmedullaryretIcularformatIon.The0FCIsthesourceof
elementaryventIlatoryrhythmIcIty
2J,24
andservesasthepacemakerfortherespIratory
system.
25
WhereasrestInglungvolumeoccursatendexpIratIon,theelectrIcalactIvItyof
theventIlatorycentersIsatrestatendInspIratIon.TherhythmIcactIvItyofthe0FC
persIstsevenwhenallIncomIngperIpheralandInterconnectIngnervesaresectIonedor
blockedcompletely.solatIngthe0FCInthIsmannerresultsInataxIc,gaspIngventIlatIon
wIthfrequentmaxImumInspIratoryefforts:apneustIcbreathIng.
Figure 11-3.ClassIccentralnervoussystem(CNS)respIratorycenters.0Iagram
IllustratesmajorrespIratorycenters,neurofeedbackcIrcuIts,prImaryneurohumoral
sensoryInputs,andmechanIcaloutputs.
TheventralrespIratorygroup(7FC),whIchIslocatedIntheventralmedullaryretIcular
formatIon,servesastheexpIratorycoordInatIngcenter.TheInspIratoryandexpIratory
neuronsfunctIonbyasystemofrecIprocalInnervatIon,ornegatIvefeedback.
22
Whenthe
0FCcreatesanImpulsetoInspIre,InspIratIonoccursandthe0FCImpulseIsquenchedbya
recIprocatIng7FCImpulse.ThIs7FCtransmIssIonprohIbItsfurtheruseoftheInspIratory
muscles,thusallowIngpassIveexpIratIontooccur.
Pontine Centers
ThepontInecentersprocessInformatIonthatorIgInatesInthemedulla.TheapneustIc
centerIslocatedInthemIddleorlowerpons.WIthactIvatIon,thIscentersendsImpulses
toInspIratory0FCneuronsandIsdesIgnedtosustaInInspIratIon.ElectrIcalstImulatIonof
thIsarearesultsInInspIratoryspasm.
26
ThemIddleandlowerponscontaInspecIfIcareas
forphasespannIngneurons.
27
TheseneuronsassIstwIththetransItIonbetweenInspIratIon
andexpIratIon,anddonotexertdIrectcontroloverventIlatorymuscles.
ThepneumotaxIcrespIratorycenterIsIntherostralpons.AsImpletransectIonthroughthe
braInstemthatIsolatesthIsportIonoftheponsfromtheupperbraInstemreduces
ventIlatory
P.240
rateandIncreasestIdalvolume.fbothvagusnervesareaddItIonallytransected,apneusIs
results.
28
Thus,theprImaryfunctIonofthepneumotaxIccenterIstolImItthedepthof
InspIratIon.WhenmaxImallyactIvated,thepneumotaxIccentersecondarIlyIncreases
ventIlatoryfrequency.However,thepneumotaxIccenterperformsnopacemakIngfunctIon
andhasnoIntrInsIcrhythmIcIty.
Table 11-3 Definition of Respiratory Pattern Terminology
Word Definition
Eupnea
CoodbreathIng:contInuousInspIratoryandexpIratory
movementwIthoutInterruptIon
Apnea
NobreathIng:cessatIonofventIlatoryeffortatpassIveend
expIratIon(lungvolume=FFC)
ApneusIs CessatIonofventIlatoryeffortwIthlungsfIlledatTLC
ApneustIc
ventIlatIon
ApneusIswIthperIodIcexpIratoryspasms
8Iot
7entIlatorygaspsInterposedbetweenperIodsofventIlatIon
apnea;alsoagonalventIlatIon
FFC,functIonalresIdualcapacIty;TLC,totallungcapacIty.
Higher Respiratory Centers
|anyhIgherbraInstructuresclearlyaffectventIlatorycontrolprocesses.nthemIdbraIn,
stImulatIonoftheretIcularactIvatIngsystemIncreasestherateandamplItudeof
ventIlatIon.
29
ThecerebralcortexalsoaffectsbreathIngpattern,althoughprecIseneural
pathwaysarenotknown.DccasIonally,theventIlatorycontrolprocessbecomessubservIent
tootherregulatorycenters.Forexample,therespIratorysystemplaysanImportantroleIn
thecontrolofbodytemperaturebecauseItsupplIesalargesurfaceareaforheat
exchange.ThIsIsespecIallyImportantInanImalsInwhIchpantIngIsaprImarymeansof
dIssIpatIngheat.Thus,the,ventIlatorypatternIsInfluencedbyneuralInputfrom
descendIngpathwaysfromtheanterIorandposterIorhypothalamustothepneumotaxIc
centeroftheupperpons.
7asomotorcontrolandcertaInrespIratoryresponsesarecloselylInked.StImulatIonofthe
carotIdsInusnotonlydecreasesvasomotortone,butalsoInhIbItsventIlatIon.
AlternatIvely,stImulatIonofthecarotIdbodychemoreceptors(seeChemIcalControlof
7entIlatIon)resultsInanIncreaseInbothventIlatoryactIvItyandvasomotortone.
Reflex Control of Ventilation
FeflexesthatdIrectlyInfluenceventIlatorypatternusuallydosotopreventaIrway
obstructIon.Deglutition,orswallowIng,Involvestheglossopharyngealandvagusnerves.
StImulatIonoftheanterIorandposterIorpharyngealpIllarsoftheposterIorpharynx
InducesswallowIng.0urIngswallowIng,InspIratIonceasesmomentarIly,Isusuallyfollowed
byasInglelargebreath,andbrIeflyIncreasesventIlatIon.
VomitingsIgnIfIcantlymodIfIesnormalventIlatoryactIvIty.
J0
SwallowIng,salIvatIon,
gastroIntestInalreflexes,rhythmIcspasmodIcventIlatorymovements,andsIgnIfIcant
dIaphragmatIcandabdomInalmuscularactIvItymustbecoordInatedoveraverybrIef
Interval.8ecauseoftheobvIousrIskofaspIratInggastrIccontents,ItIsadvantageousto
InhIbItInspIratIondurIngvomItIng.nputIntotherespIratorycentersoccursfromboth
cranIalandspInalcordnerves.
CoughingresultsfromstImulatIonofthetrachealsubepIthelIum,especIallyalongthe
posterIortrachealwallandcarIna.
J1
CoughIngalsorequIrescoordInatIonofbothaIrway
andventIlatorymuscleactIvIty.AneffectIvecoughrequIresdeepInspIratIonandthen
forcedexhalatIonagaInstamomentarIlyclosedglottIstoIncreaseIntrathoracIcpressure,
thusallowInganexpulsIveexpIratorymaneuver.
ProprioceptionInthepulmonarysystem,thequalItatIveknowledgeofthegasvolume
wIthInthelungs,probablyarIsesfromsmoothmusclespIndlereceptors.These
proprIoceptors,whIcharelocatedwIthInthesmoothmuscleofallaIrways,aresensItIveto
pressurechanges.AIrwaystretchreflexescanbedemonstrateddurIngdIstentIonof
IsolatedaIrwayssoaIrwaypressure,ratherthanvolumedIstentIon,appearstobethe
prImarystImulatIon.
J2
ClInIcalcondItIonsInwhIchpulmonaryaIrwaystretchreceptorsare
stImulatedIncludepulmonaryedemaandatelectasIs.
Golgi tendon organs(tendonspIndles),whIchoccurInserIesarrangementswIthIn
ventIlatorymuscles,facIlItateproprIoceptIon.TheIntercostalmusclesarerIchIntendon
spIndles,whereasthedIaphragmhasalImItednumber.Thus,thepulmonarystretchreflex
prImarIlyInvolvestheIntercostalmusclesbutnotthedIaphragm.Whenthelungsarefull
andthechestwallIsstretched,thesereceptorssendsIgnalstothebraInstemthatInhIbIt
furtherInspIratIon.
n1868,HerIngand8reuer
JJ
reportedthatlIghtlyanesthetIzed,spontaneouslybreathIng
anImalswouldceaseordecreaseventIlatoryeffortdurIngsustaInedlungdIstentIon.ThIs
responsewasblockedbybIlateralvagotomy.TheHeringBreuer reflexIspromInentIn
lowerordermammalsandIssuffIcIentlyactIveInlowermammalsthateven5cmH
2
D
CPAPwIllInduceapnea.nhumans,however,thereflexIsonlyweaklypresent,as
evIdencedbythefactthathumanswIllcontInuetobreathespontaneouslywIthCPAPIn
excessof40cmH
2
D.
Chemical Control of Ventilation
Peripheral Chemoreceptors
nasImplIstIcvIewofchemIcalventIlatorycontrol,theperIpheralchemoreceptors
respondprImarIlytolackofoxygen,andthecentralnervoussystem(CNS)receptors
respondprImarIlytochangesInPCD
2
,pH,andacIdbasedIsturbances.
TheperIpheralchemoreceptorsarecomposedofthecarotIdandaortIcbodIes.ThecarotId
bodIes,locatedatthebIfurcatIonofthecommoncarotIdartery,havepredomInantly
ventIlatoryeffects.TheaortIcbodIes,whIcharescatteredabouttheaortIcarchandIts
branches,havepredomInantlycIrculatoryeffects.TheneuraloutputfromthecarotIdbody
reachesthecentralrespIratorycentersvIatheafferentglossopharyngealnerves.Dutput
fromtheaortIcbodIestravelstothemedullarycentersvIathevagusnerve.8othcarotId
andaortIcbodIesarestImulatedbydecreasedPao
2
,butnotbydecreasedSao
2
orCao
2
.
WhenPao
2
fallsto100mmHg,neuralactIvItyfromthesereceptorsbegInstoIncrease.
However,ItIsnotuntIlthePao
2
reaches60to65mmHgthatneuralactIvItyIncreases
suffIcIentlytosubstantIallyaugmentmInuteventIlatIon.Thus,patIentswhodependon
hypoxIcventIlatorydrIvehavePao
2
valuesInthemIddle60s.DncethesepatIents'Pao
2
valuesexceed60to65mmHg,ventIlatorydrIvedImInIshesandPao
2
fallsuntIlventIlatIon
IsagaInstImulatedbyarterIalhypoxemIa.Thus,durIngwIthdrawalofmechanIcal
ventIlatorysupportInthepatIentwhodependsonhypoxIcventIlatorydrIve,thePao
2
must
fallto65mmHgforspontaneousventIlatIontoresume(seeChapter56.)
ThecarotIdbodIesarealsosensItIvetodecreasedpH
a
,butthIsresponseIsmInor.
SImIlarly,changesInPaco
2
donotstImulatethesereceptorssuffIcIentlytoaltermInute
ventIlatIon.ncreasesInbloodtemperature,hypoperfusIonofthecarotIdbodIes
themselves,andsomechemIcalswIllstImulatethesereceptors.SympathetIcganglIon
stImulatIonbynIcotIneoracetylcholInewIllstImulatethecarotIdandaortIcbodIes;thIs
effectIsblockedbyhexamethonIum.8lockadeofthecytochromeelectrontransportsystem
bycyanIdewIllpreventoxIdatIvemetabolIsmandwIllalsostImulatethesereceptors.
7entIlatoryeffectsresultIngfromstImulatIonofthesereceptorsareIncreasedventIlatory
rateandtIdalvolume.HemodynamIcchangesresultIngfromstImulatIonofthesereceptors
IncludebradycardIa,hypertensIon,IncreasesInbronchIolartone,andIncreasesInadrenal
secretIon.ThecarotIdbodychemIcalreceptorshavebeentermedultimum moriens(last
todIe).AlthoughtheresponseofperIpheralreceptorstohypoxemIawasformerly
belIevedtoberesIstanttotheInfluencesofanesthesIa,potentInhaledanesthetIcsappear
todepresshypoxIcventIlatoryresponsebydepressIngcarotIdbodyresponseto
hypoxemIa.
J4
TheresponseoftheperIpheralreceptorsIsnotsuffIcIentlyrobusttorelIably
IncreaseventIlatoryrateormInuteventIlatIontoheraldtheonsetofarterIalhypoxemIa
durInggeneralanesthesIaor
P.241
recoveryfromanesthesIa.Furthermore,flumazenIl,Ina1mgIntravenousdose,only
partIallyreversedthedIazepamInduceddepressIonofhypoxIcventIlatorydrIve.
J5
The
dataof|oraetal.
J5
furthersuggestthathumansmaydeveloptolerancetorespIratory
depressanteffectsofdIazepam.
Central Chemoreceptors
ApproxImately80oftheventIlatoryresponsetoInhaledcarbondIoxIdeorIgInatesInthe
centralmedullarycenters.AcIdbaseregulatIonInvolvIngcarbondIoxIde,H
+
,and
bIcarbonateIsrelatedprImarIlytochemosensItIvereceptorslocatedInthemedullaclose
toorIncontactwIththecerebrospInalfluId(CSF).ThechemosensItIveareasofthe
braInstemareIntheInferolateralaspectsofthemedullaneartheorIgInofcranIalnerves
XandX.TheareajustbeneaththesurfaceoftheventralmedullaIsexquIsItelysensItIve
totheextracellularfluIdH
+
concentratIon.
J6
AlthoughthecentralresponseIsthemajor
factorIntheregulatIonofbreathIngbycarbondIoxIde,carbondIoxIdehaslIttledIrect
stImulatIngeffectonthesechemosensItIveareas.ThesereceptorsareprImarIlysensItIve
tochangesInH
+
concentratIon.CarbondIoxIdehasapotentbutIndIrecteffectbyreactIng
wIthwatertoformcarbonIcacId,whIchdIssocIatesIntohydrogenandbIcarbonateIons.
J7
AnacuteIncreaseInPaco
2
IsamorepotentventIlatorystImulusthananacuteIncreaseIn
arterIalprotonsconcentratIonfromametabolIcsource.CarbondIoxIde,butnotH
+
,passes
readIlythroughthebloodbraInandbloodCSFbarrIers.LocalbufferIngsystems
ImmedIatelyneutralIzeH
+
InarterIalbloodandbodyfluIds.ncontrast,theCSFhas
mInImalbufferIngcapacIty.Thus,oncecarbondIoxIdecrossesIntotheCSF,H
+
arecreated
andtrappedIntheCSF,resultIngInaCSFH
+
concentratIonconsIderablygreaterthanthat
foundIntheblood.8ecausecarbondIoxIdecrossesthebloodbraInbarrIerreadIly,the
Paco
2
valuesIntheCSF,cerebraltIssue,andjugularvenousbloodrIsequIcklyandtothe
samedegreeasthePaco
2
,althoughthecentralvaluesare-10mmHghIgherthanthose
measuredInarterIalblood.
TheventIlatoryresponsetochangesInPaco
2
(Increased7
T
,IncreasedrespIratoryrate)Is
rapIdandpeakswIthIn1to2mInutesafteranacutechangeInPaco
2
.WIththesame,
persIstentlevelofcarbondIoxIdestImulatIon,theresultantIncreaseInventIlatIondeclInes
overaperIodofseveralhours,probablyasaresultofbIcarbonateIonsthatareactIvely
transportedfromthebloodIntotheCSFthroughthearachnoIdvIllI.
J8
ThIsphenomenon
explaInsthedIfferIngeffectsofacutehypercapnIaversuschronIchypercapnIaontheCNS
medIatedventIlatoryresponse.FInally,centralmedullarychemoreceptorsalsorespondto
temperaturechange.ColdCSF(wIthnormalpH)orlocalanesthetIcapplIedtothe
medullarysurfacewIlldepressventIlatIon.
Ventilatory Response to Altitude
7entIlatoryresponseandadaptatIontohIghaltItudearegoodexamplesoftheIntegratIon
ofperIpheralandcentralchemoreceptorcontrolofventIlatIon.ThefollowIngmechanIsm
ofacclImatIzatIonwasproposedbySeverInghausetal.
J9
In196JandhassIncebeen
confIrmed.
FollowIngascentfromsealevelto4,000m,acuteexposuretohIghaltItudeandlowPD
2
resultsInarterIalhypoxemIa.ThIsdecreaseInPao
2
actIvatestheperIpheralhypoxemIc
ventIlatorydrIvebystImulatIngthecarotIdandaortIcbodIes,andcausesIncreasedmInute
ventIlatIon.AsmInuteventIlatIonIncreases,Paco
2
andCSFPco
2
decrease,causIng
concomItantIncreasesInpH
a
andCSFpH.ThealkalIneshIftoftheCSFdecreases
ventIlatorydrIvevIamedullarychemoreceptors,partIallyoffsettInghypoxemIcdrIve.A
temporaryequIlIbrIumIsattaInedwIthInmInutes,wIthPaco
2
only2to5mmHglessthan
normalandPao
2
approxImately45mmHg.ThIsInItIallyprofoundhypoxemIaprobably
causestheacuterespIratorydIstressandotherassocIatedsymptoms(headache,dIarrhea)
assocIatedwIthrapIdascent.However,theCNSIsabletorestoreCSFpHtonormal(7.J26)
bypumpIngbIcarbonateIonsoutoftheCSFover2toJdays.n2toJdays,CSF
bIcarbonateconcentratIondecreasesapproxImately5mEq/LandrestoresCSFpHtowIthIn
0.01pHunItofvaluesatsealevel.Then,centrallymedIatedventIlatorydrIvereturnsto
normal,andhypoxIcdrIveandstImulatIonofperIpheralreceptorscanproceedunopposed.
Thus,afterJdays'exposureto4,000maltItude,ventIlatoryadaptatIonwouldresultIna
newequIlIbrIum,wIthPaco
2
approxImatelyJ0mmHgandPao
2
approxImately55mmHg.
FollowIngdescenttosealevel,thelowCSFbIcarbonateconcentratIonpersIstsforseveral
days,andtheclImberoverbreathesuntIlCSFbIcarbonateandpHvaluesreturnto
normal.
Breath-Holding
|ostadultswIthnormallungsandgasexchangecanholdtheIrbreathfor-1mInutewhen
breathIngroomaIrwIthoutprevIouslyhyperventIlatIng.After1mInuteofbreathholdIng
underthesecIrcumstances,Pao
2
decreasesto-65to70mmHgandPaco
2
Increasesby-12
mmHg.ntheabsenceofsupplementaloxygenandhyperventIlatIon,thebreakpoIntat
whIchnormalpeoplearecompelledtobreatheIsremarkablyconstantataPaco
2
of50mm
Hg.
40,41
However,IftheIndIvIdualbreathes100oxygenprIortobreathholdIng,heorshe
shouldbeabletoholdhIsorherbreathfor2toJmInutes,oruntIlPaco
2
rIsesto60mm
Hg.HyperventIlatIonsuffIcIenttoreducePaco
2
to20mmHgcanlengthentheperIodof
breathholdIngtoJto4mInutes.
42
HyperventIlatIonwIth100oxygenprIortobreath
holdIngshouldextendtheapneIcperIodto6to10mInutes.ThePaco
2
rateofrIseIn
awake,preoxygenatedadultswIthnormallungswhoholdtheIrbreathwIthoutprevIous
hyperventIlatIonIs7mmHg/mInInthefIrst10seconds,2mmHg/mInInthenext10
seconds,and6mmHg/mInthereafter.
41
TheduratIonofvoluntarybreathholdIngIsdIrectlyproportIonaltolungvolumeatonset
andIsprobablyrelatedbothtooxygenstoresInthealveolIandtotherateatwhIchPaco
2
rIses.WIthsmallerlungvolumes,thesameamountofcarbondIoxIdeIsemptIedIntoa
smallervolumedurIngtheapneIcperIod,thusIncreasIngthecarbondIoxIdeconcentratIon
morerapIdlythanoccurswIthlargerlungvolumes.Dfnote,apneIcpatIentsdurInggeneral
anesthesIaactuallybreathholdatFFCratherthanatvItalcapacIty,whIchwouldtend
toacceleratetherateofrIseofcarbondIoxIde.0espItethIsdIfferenceInlungvolume,the
rateofrIseofPaco
2
InapneIcanesthetIzedpatIentsIs12mmHgdurIngthefIrstmInute
andJ.5mmHg/mInthereafter,sIgnIfIcantlylowerthanIntheawakestate.
42,4J
0urIng
anesthesIa,metabolIcrateandcarbondIoxIdeproductIonaresIgnIfIcantlylessthandurIng
ambulatorywakefulness,whIchprobablyaccountsforthedIfferentratesofrIseIncarbon
dIoxIdelevels.
HyperventIlatIonwIthroomaIrprIortoprolongedbreathholdIngdurIngexercIseIs
InadvIsable.0urIngunderwaterswImmIngafterpoolsIdehyperventIlatIon,theurgeto
breatheIsfIrststImulatedbyarIsIngPaco
2
.8ecauseanIncreasedarterIalcarbondIoxIde
tensIonprovIdesthestImulustoInspIre,swImmerswhohyperventIlatewIthroomaIrprIor
toswImmInglongdIstancesfrequentlyloseconscIousnessfromarterIalhypoxemIabefore
thePaco
2
IssuffIcIentlyIncreasedtostImulatetheneedtobreathe.
HyperventIlatIonIsrarelyfollowedbyanapneIcperIodInawakehumans,despItea
markedlydepressedPaco
2
.However,mInuteventIlatIonmaydecreasesIgnIfIcantly.
AggressIveIntermIttentposItIvepressurebreathIngtreatmentsforpatIentswIthCDP0who
contInuetohaveacarbondIoxIdebasedventIlatorydrIvecandepressmInuteventIlatIon
suffIcIentlytocreatearterIalhypoxemIaIftheybreatheroomaIraftercessatIonof
therapy.
44
ncontrast,
P.242
evenmIldhyperventIlatIondurInggeneralanesthesIawIllproduceprolongedapneIc
perIods.
45
Quantitative Aspects of Chemical Control of Breathing
TheventIlatoryresponsestooxygenandcarbondIoxIdecanbeassessedquantItatIvely.
Unfortunately,thequantItatIveIndIcesofhypoxemIcsensItIvItyarenotclInIcallyuseful
becausethenormalrangeIswIdeandconfoundedbymanyenvIronmentalfactors.The
readerIsreferredtoaclassIcdIscussIonofthequantItatIveIndIcesofhypoxemIc
sensItIvIty.
46
7entIlatoryresponsestoPaco
2
changesaremeasuredInseveralways,provIdedthatcarbon
dIoxIdeproductIonremaInsconstant.WhensubjectsvoluntarIlyIncreasemInute
ventIlatIontoaprescrIbedlevel,thePaco
2
decreaseshyperbolIcally.TheplotofmInute
ventIlatIon(IndependentvarIable)andPaco
2
(dependentvarIable)IsthemetabolIc
hyperbola(FIg.114).ThemetabolIchyperbolaIscumbersometoevaluateanddIffIcultto
useclInIcally.
ThecurvemorecommonlyusedIsthePaco
2
ventIlatoryresponsecurve(seeFIg.114).t
descrIbestheeffectofchangIngPaco
2
ontheresultantmInuteventIlatIon.Usually,
subjectsInspIrecarbondIoxIdetoraIsePaco
2
,andtheeffectonmInuteventIlatIonIs
measured.CreatIngthesecurvesandobservInghowtheychangeInvarIouscIrcumstances
allowquantItatIvestudyoffactorsthataffectthechemIcalcarbondIoxIdecontrolof
ventIlatIon.ThecarbondIoxIderesponsecurveapproacheslInearItyIntherangemost
oftenencounteredInlIfe:atPaco
2
valuesbetween20and80mmHg.DncethePaco
2
exceeds80mmHg,thecurvebecomesparabolIc,wIthItspeakventIlatoryresponseata
Paco
2
between100and120mmHg.ncreasIngthePaco
2
tohIgherthan100mmHgallows
carbondIoxIdetoactasaventIlatoryandCNSdepressant,theorIgInofthetermcarbon
dIoxIdenarcosIs,wIth1mInImumalveolarconcentratIonbeIngapproxImately200mmHg.
Figure 11-4.CarbondIoxIdeventIlatoryresponsecurve.ThemetabolIchyperbola,
curveA,IsgeneratedbyvaryIng[7wIthdotabove]
A
/[QwIthdotabove]Eand
measurIngchangesIncarbondIoxIdeconcentratIon.ThehyperbolIcconfIguratIon
makesItcumbersomeforclInIcaluse.ThecarbondIoxIdeventIlatoryresponsecurve,
8,IslInearbetweenapproxImately20and80mmHg.tIsgeneratedbyvaryIngPaco
2
(usuallybycontrollIngInspIredcarbondIoxIdeconcentratIon)andmeasurIngthe
resultant[7wIthdotabove]
A
/[QwIthdotabove]E.ThIsIsthemostcommonlyused
testofventIlatoryresponse.TheslopedefInessensItIvIty;thesetpoInt,orrestIng
Paco
2
,occursattheIntersectIonofthemetabolIchyperbolaandthecarbondIoxIde
ventIlatoryresponsecurve;theapneIcthresholdcanbeobtaInedbyextrapolatIngthe
carbondIoxIdeventIlatoryresponsecurvetothexIntercept.ntheabsenceof
surgIcalstImulatIon,IncreasIngdosesofpotentInhaledanesthesIaoropIoIdswIllshIft
thecurvetotherIghtandeventuallydepresstheslope(dashed lines).PaInful
stImulatIonwIllreversethesechangestovaryIngandunpredIctabledegrees.
TheslopeofthecarbondIoxIderesponsecurveIsconsIderedtorepresentcarbondIoxIde
sensItIvIty.WhenPaco
2
reaches100mmHg,carbondIoxIdesensItIvItyIsatItspeak.The
set point,thepoIntofIntersectIonofthecarbondIoxIderesponsecurveandthemetabolIc
hyperbola,defInesnormalrestIngPaco
2
.ExtrapolatIonofthecarbondIoxIderesponse
curvetothexIntercept(wheremInuteventIlatIonIs0)defInestheapneIcthreshold.n
awake,normaladults,theapneIcthresholdnormallyoccursataPaco
2
of-J2mmHg,
althoughawakeadultsusuallycontInuetobreathewhentheyachIevetheapneIcthreshold
becausethesensatIonofapneaIsdIsturbIng.TheslopeofthecurveIsameasureofthe
responseoftheentIreventIlatorymechanIsmtocarbondIoxIdestImulatIon.
DncePao
2
exceeds100mmHg,ItnolongerInfluencesthecarbondIoxIderesponsecurve.
WhenthePao
2
Isbetween65and100mmHg,ItseffectonthecarbondIoxIderesponse
curveIssmall.However,whenPao
2
fallsto65mmHg,thecarbondIoxIderesponsecurve
shIftstotheleftandItsslopeIncreases,probablyasaresultofIncreasedventIlatorydrIve
stImulatedbytheperIpheralchemoreceptors.Thus,durIngmeasurementsofcarbon
dIoxIdeventIlatoryresponse,thesubjectshouldbreathesupplementaloxygentoprevent
hypoxIcventIlatorydrIveInterference.
ThecarbondIoxIderesponsecurvecanbegeneratedrapIdlybyIncreasIngthefractIonof
InspIredcarbondIoxIde(FCD
2
)byrequIrIngthesubjecttorebreatheexhaledgas.The
resultsobtaInedwIththIstechnIquearelesspurebecausetheFCD
2
Isnotcontrolled.
ThreeclInIcalstatesresultInaleftshIftand/orasteepenedslopeofthecarbondIoxIde
responsecurve.ThesesamethreesItuatIonsaretheonlycausesoftruehyperventIlatIon;
thatIs,anIncreaseInmInuteventIlatIonsuchthatthedecreasedPaco
2
createsrespIratory
alkalemIa(eItherprImaryorcompensatory).ThethreecausesofhyperventIlatIon
(enhancedcarbondIoxIderesponse)arearterIalhypoxemIa,metabolIcacIdemIa,andCNS
etIologIes.ExamplesofcentralcausesthatcausehyperventIlatIonIncludedrug
admInIstratIon,IntracranIalhypertensIon,hepatIccIrrhosIs,andnonspecIfIcarousalstates
suchasanxIetyandfear.AmInophyllIne,doxapram,salIcylates,andnorepInephrIne
stImulateventIlatIonIndependentofperIpheralchemoreceptors.DpIoIdantagonIsts,gIven
IntheabsenceofopIoIds,donotstImulateventIlatIon.However,whengIvenafteropIoId
admInIstratIon,theydoreversetheeffectsofopIoIdsonthecarbondIoxIderesponse
curve.
7entIlatorydepressantsdIsplacethecarbondIoxIderesponsecurvetotherIghtordecrease
Itsslopeorboth.ChangesInphysIologythatdepressventIlatIonIncludemetabolIc
alkalemIa,denervatIonofperIpheralchemoreceptors,normalsleep,anddrugs.0urIng
normalsleep,thecarbondIoxIderesponsecurveIsdIsplacedtotherIght,wIththedegree
ofdIsplacementdependIngonthedepthofsleep.Usually,Paco
2
Increasesupto10mmHg
durIngdeepsleep.HypoxemIcresponsesarenotImpaIredbysleep,whIchIsconvenIentfor
contInuedsurvIvalathIghaltItudewhIlesleepIng.
DpIoIdsdIsplacethecarbondIoxIderesponsecurvetotherIghtwIthlIttlechangeInslope
atsedatIvedoses(seeChapter19.)WIthhIgher,anesthetIcdoses,thecurveshIftsfarther
totherIghtandItsslopeIsdepressed,sImulatIngtheeffectofpotentInhalatIonagentson
thecarbondIoxIderesponsecurve(seeFIg.114).ntheabsenceofotherventIlatory
depressantdrugs,opIoIdsInducepathognomonIcchangesInventIlatorypatterns:a
decreasedventIlatoryratewIthanIncreasedtIdalvolume.NotuntIlopIoIdsnearlyInduce
apneaIstIdalvolumedecreased.LargenarcotIcdosesusuallyresultInapnearesponsIveto
verbalencouragementbeforeconscIousnessIslost.
8arbIturatesInsedatIveorlIghthypnotIcdoseshavelIttleeffectonthecarbondIoxIde
responsecurve.However,IndosesadequatetoallowskInIncIsIon,barbIturatesshIftthe
carbondIoxIderesponsecurvetotherIght.TheventIlatorypattern
P.24J
resultIngfrombarbIturateadmInIstratIonIscharacterIzedbydecreasedtIdalvolumeand
IncreasedventIlatoryrate.PotentInhaledanesthetIcsdIsplacethecarbondIoxIderesponse
curvetotherIghtanddecreasetheslope,thedegreeofwhIchdependsontheanesthetIc
doseandthelevelofsurgIcalstImulatIon.LIkebarbIturates,theventIlatorypattern
followIngadmInIstratIonofpotentInhaledanesthetIcsIsInItIallyrepresentedbya
decreasedtIdalvolumeandIncreasedventIlatoryrate.AsmorepotentanesthetIcagentIs
admInIstered,however,ventIlatoryratedecreasestowardanapneIcendpoInt.ThIs
clInIcalresponseoccurswhenthecarbondIoxIderesponsecurveeventuallybecomes
horIzontal(slope=0),resultIngInessentIallynoventIlatoryresponsetoPaco
2
changes.
PotentInhaledanesthetIcsandopIoIdsdIsplacethesetpoInttotherIght,ImplyIngthatthe
restIng,steadystatePaco
2
IshIgherandmInuteventIlatIonlower.Furthermore,whenthe
carbondIoxIderesponsecurveshIftstotherIght,theapneIcthresholdalsoIncreases(see
FIg.114).SurgIcalstImulatIonreversestheventIlatoryresponsechangesInducedby
InhaledanesthetIcsandopIoIds,butthedegreeofreversalIsnotpredIctable.
Oxygen and Carbon Dioxide Transport
ThIschapterdIscussesonlyexternalrespIratIon,InwhIchoxygenmovesfromtheambIent
envIronmentIntothepulmonarycapIllarIesandcarbondIoxIdeleavesthepulmonary
capIllarIestoentertheatmosphere.ThemovementofgasacrossthealveolarcapIllary
membranedependsontheIntegrItyofthepulmonaryandcardIacsystems.UnlessItIs
otherwIsestated,thereadershouldassumetheventIlatIonandperfusIonofalveolar
capIllaryunItsarenormal.AbnormaldIstrIbutIonofventIlatIonorperfusIonofthelungsIs
dIscussedlater(see7entIlatIonPerfusIonFelatIonshIps).
Bulk Flow of Gas (Convection)
ConvectIon,InwhIchallgasmoleculesmoveInthesamedIrectIon,IstheprImary
mechanIsmresponsIbleforgasflowInlargeandmostsmallaIrways,downtothebronchI
andbronchIolaraIrwaysofthe14thor15thgeneratIon.8ecausethecrosssectIonalareaof
theaIrwaysprogressIvelyIncreasesasgasmovestowardthelungperIphery,theaverage
velocItyofgaspartIclesdecreasesastheytraveltowardthealveolI.8ecauseresIstance
dependsonflow,thegreatestpartofaIrwayresIstanceoccursInthelargeraIrways,where
gasmoleculestravelmorequIckly.0urIngnormalquIetventIlatIon,gasflowwIthIn
convectIveaIrwaysIsmaInlylamInar.
Figure 11-5.0IstrIbutIonofbloodflowIntheIsolatedlung.nzone1,alveolar
pressure(P
A
)exceedspulmonaryarterypressure(P
pa
),andnoflowoccursbecausethe
vesselsarecollapsed.nzone2,arterIalpressureexceedsalveolarpressure,but
alveolarpressureexceedspulmonaryvenouspressure(P
pv
).FlowInzone2Is
determInedbythearterIalalveolarpressuredIfference(P
pa
P
A
),whIchsteadIly
Increasesdownthezone.nzoneJ,pulmonaryvenouspressureexceedsalveolar
pressureandflowIsdetermInedbythearterIalvenouspressuredIfference(P
pa
P
pv
),
whIchIsconstantdownthIspulmonaryzone.However,thepressureacrossthevessel
wallsIncreasesdownthezonesotheIrcalIberIncreases,asdoesflow.(FromWestJ8,
0olleryCT,NaImarkA:0IstrIbutIonofbloodflowInIsolatedlung:FelatIontovascular
andalveolarpressures.JApplPhysIol1964;19:71J,wIthpermIssIon.)
Gas Diffusion
0IffusIonwIthInagasfIlledspaceIsrandommolecularmotIonthatresultsIncomplete
mIxIngofallgases.nthedIstalaIrwaysofthelungbegInnIngwIththetermInal
bronchIoles(16thaIrwaygeneratIon),dIffusIonbecomesthepredomInantmodeofgas
transport.Dncegasreachesthesmallalveolarducts,alveolarsacs,andalveolI,both
dIffusIonandregIonal([7wIthdotabove]
A
/[QwIthdotabove])relatIonshIpsInfluencegas
transport.HIstorIcally,clInIcIansassumeddefectsIngasdIffusIonwereresponsIblefor
arterIalhypoxemIa.However,themostfrequentcauseofarterIalhypoxemIaIsphysIologIc
shunt(see7entIlatIonPerfusIonFelatIonshIps).
47
TheotherusageofdIffusIonreferstothepassIvemovementofmoleculesacrossa
membranethatIsgovernedprImarIlybyconcentratIongradIent.nthIssense,carbon
dIoxIdeIs20tImesmoredIffusIbleacrosshumanmembranesthanIsoxygen;therefore,
carbondIoxIdecrossesalveolIeasIly.Asaresult,hypercapnIaIsnevertheresultof
defectIvedIffusIon;rather,ItIstheresultofInadequatealveolarventIlatIonwIthrespect
tocarbondIoxIdeproductIon.
TruedIffusIondefectsthatcreatearterIalhypoxemIaarerare.Themostcommonreason
forameasureddecreaseIndIffusIngcapacIty(seePulmonaryFunctIonTests)Is
mIsmatchedventIlatIonandperfusIon,whIchfunctIonallyresultsInadecreasedsurface
areaavaIlablefordIffusIon.
Distribution of Ventilation and Perfusion
TheeffIcIencywIthwhIchoxygenandcarbondIoxIdeexchangeatthealveolarcapIllary
levelhIghlydependsonthematchIngofcapIllaryperfusIonandalveolarventIlatIon.AtthIs
level,themarrIagebetweenthelungandthecIrculatorysystemmustbewellmatchedand
IntImate.
Distribution of Blood Flow
8loodflowwIthInthelungIsmaInlygravItydependent.8ecausethealveolarcapIllarybeds
arenotcomposedofrIgIdvessels,thepressureofthesurroundIngtIssuescanInfluencethe
resIstancetoflowthroughtheIndIvIdualcapIllarIes.Thus,bloodflowdependsonthe
relatIonshIpbetweenpulmonaryarterypressure(Ppa),alveolarpressure(PA),and
pulmonaryvenouspressure(Ppv;FIg.115).Westetal.
47
andWestand0ollery
48
createda
lungmodelthatdIvIdesthelungIntothreezones.Zone1condItIonsoccurInthemost
gravItyIndependentpartofthelung.8ecausealveolarpressureIsapproxImatelyequalto
atmospherIcpressure;andpulmonaryarterypressure,
P.244
whIchIsalwaysInexcessofpulmonaryvenouspressure,IssubatmospherIcInzone1,then
zone1IsdescrIbedbythefollowIngrelatIonshIp:P
A
P
pa
P
pv
.nzone1alveolarpressure
thatIstransmIttedtothepulmonarycapIllarIespromotestheIrcollapse,wIthaconsequent
theoretIcalbloodflowofzerotothIslungregIon.Thus,zone1receIvesventIlatIonInthe
absenceofperfusIon.ThIsrelatIonshIpIsalveolardeadspaceventIlatIon.Normally,zone1
areasexIstonlytoalImItedextent.However,IncondItIonsofdecreasedpulmonaryartery
pressuresuchashypovolemIcshock,zone1enlarges.
Zone2occursfromthelowerlImItofzone1totheupperlImItofzoneJ,whereP
pa
P
a
P
pv
.ThepressuredIfferencebetweenpulmonaryarteryandalveolarpressuredetermInes
bloodflowInzone2.PulmonaryvenouspressurehaslIttleInfluence.Wellmatched
ventIlatIonandperfusIonoccurInzone2,whIchcontaInsthemajorItyofalveolI.
FInally,zoneJoccursInthemostgravItydependentareasofthelung,whereP
pa
P
p7
P
A
andbloodflowIsprImarIlygovernedbythepulmonaryarterIaltovenouspressure
dIfference.8ecausegravItyalsoIncreasespulmonaryvenouspressure,thepulmonary
capIllarIesbecomedIstended.Thus,perfusIonInzoneJIslush,resultIngIncapIllary
perfusIonInexcessofventIlatIon,orphysIologIcshunt.
Distribution of Ventilation
AlveolarpressureIsthesamethroughoutthelung;therefore,themorenegatIve
Intrapleuralpressureattheapex(ortheleastgravItydependentarea)resultsInlarger,
moredIstendedapIcalalveolIthanInotherareasofthelung.Thetranspulmonarypressure
(PawPpl),ordIstendIngpressureofthelung,Isgreateratthetopandloweratthe
bottom,whereIntrapleuralpressureIslessnegatIve.0espItethesmalleralveolarsIze,
moreventIlatIonIsdelIveredtodependentpulmonaryareas.ThedecreaseInIntrapleural
pressureatthebaseofthelungsdurIngInspIratIonIsgreaterthanattheapexbecauseof
dIaphragmatIcproxImIty.Thus,becausethedependentareaofthelunggeneratesthe
greatestchangeIntranspulmonarypressure,moregasIssuckedIntodependentareasof
thelung.
VentilationPerfusion Relationships
AsdIscussedprevIously,themajorItyofbloodflowIsdIstrIbutedtothegravItydependent
partofthelung.Also,durIngaspontaneousbreath,thelargestportIonofthetIdalvolume
alsoreachesthegravItydependentpartofthelung.Thus,thenondependentareaofthe
lungreceIvesalowerproportIonofbothventIlatIonandperfusIon,anddependentlung
receIvesgreaterproportIonsofventIlatIonandperfusIon.Nevertheless,ventIlatIonand
perfusIonarenotmatchedperfectly,andvarIous[7wIthdotabove]
A
/[QwIthdotabove]
ratIosresultthroughoutthelung.TheIdeal[7wIthdotabove]
A
/[QwIthdotabove]ratIoof
1IsbelIevedtooccuratapproxImatelythelevelofthethIrdrIb.AbovethIslevel,
ventIlatIonoccursslIghtlyInexcessofperfusIon,whereasbelowthethIrdrIbthe[7wIth
dotabove]
A
/[QwIthdotabove]ratIobecomeslessthan1(FIg.116).
nasImplIfIedmodel,gasexchangeunItscanbedIvIdedIntonormal([7wIthdot
above]
A
/[QwIthdotabove]=1:1),deadspace([7wIthdotabove]
A
/[QwIthdotabove]=
1:0),shunt([7wIthdotabove]
A
/[QwIthdotabove]=0:1),orasIlentunIt([7wIthdot
above]
A
/[QwIthdotabove]=0:0;FIg.117).AlthoughthIsmodelIshelpfulIn
understandIng[7wIthdotabove]
A
/[QwIthdotabove]relatIonshIpsandtheIrInfluenceson
gasexchange,[7wIthdotabove]
A
/[QwIthdotabove]reallyoccursasacontInuum.nthe
lungsofahealthy,uprIght,spontaneouslybreathIngIndIvIdual,themajorItyofalveolar
capIllaryunItsarenormalgasexchangeunIts.The[7wIthdotabove]
A
/[QwIthdotabove]
ratIovarIesbetweenabsoluteshunt(InwhIch[7wIthdotabove]
A
/[QwIthdotabove]=0)
toabsolutedeadspace(InwhIch[7wIthdotabove]
A
/[QwIthdotabove]=).Fatherthan
absoluteshunt,mostunItswIthlow[7wIthdotabove]
A
/[QwIthdotabove]mIsmatch
receIveasmallamountofventIlatIonrelatIvetobloodflow.SImIlarly,mostdeadspace
unItsarenotabsolute,butratherarecharacterIzedbylowbloodflowrelatIveto
ventIlatIon.0urIngacutelungInjuryandadultrespIratorydIstresssyndrome,areasoflow
[7wIthdotabove]
A
/[QwIthdotabove]matchIngcommonlylIeadjacenttoareasofhIgh[7
wIthdotabove]
A
/[QwIthdotabove]matchIng.
49
Thus,thelungzonemodelproposedby
Westandcoworkers
47,48
shouldbeusedtoaIdtheunderstandIngofpulmonaryphysIology
andnotberegardedasanIncontrovertIbleanatomIctruIsm.
Figure 11-6.0IstrIbutIonofventIlatIon,bloodflow,andventIlatIonperfusIonratIoIn
thenormal,uprIghtlung.StraIghtlIneshavebeendrawnthroughtheventIlatIonand
bloodflowdata.8ecausebloodflowfallsmorerapIdlythanventIlatIonwIthdIstance
upthelung,ventIlatIonperfusIonratIorIses,slowlyatfIrst,thenrapIdly.(FromWest
J8:7entIlatIon/8loodFlowandCasExchange,4thed.Dxford,England,8lackwell
ScIentIfIc,1985,wIthpermIssIon.)
HypoxIcpulmonaryvasoconstrIctIonandbronchoconstrIctIonallowthelungstomaIntaIn
optImal[7wIthdotabove]
A
/[QwIthdotabove]matchIng(seeChapter40.)HypoxIc
pulmonaryvasoconstrIctIon,
P.245
stImulatedbyalveolarhypoxIa,severelydecreasesbloodflow.Thus,poorlyventIlated
alveolIalsoreceIvemInusculebloodflow.Furthermore,decreasedregIonalpulmonary
bloodflowresultsInbronchIolarconstrIctIonanddImInIshesthedegreeofdeadspace
ventIlatIon.
50,51
WheneItherphenomenaoccurs,theshuntordeadspaceunItseffectIvely
becomesIlentunItsInwhIchlIttleventIlatIonorperfusIonoccurs.
Figure 11-7.ContInuumofventIlatIonperfusIonrelatIonshIps.CasexchangeIs
maxImallyeffectIveInnormallungunItsandonlypartIallyeffectIveInshuntanddead
spaceeffectunIts.CasexchangeIstotallyabsentInsIlentunIts,absoluteshunt,and
deadspaceunIts.
|anypulmonarydIseasesresultInbothphysIologIcshuntanddeadspaceabnormalItIes.
However,mostdIseaseprocessescanbecharacterIzedasproducIngeItherprImarIlyshunt
ordeadspaceIntheIrearlystages.ncreasesIndeadspaceventIlatIonprImarIlyaffect
carbondIoxIdeelImInatIonandhavelIttleInfluenceonarterIaloxygenatIonuntIldead
spaceventIlatIonexceeds80to90ofmInuteventIlatIon([7wIthdotabove]
E
).SImIlarly,
physIologIcshuntprImarIlyaffectsarterIaloxygenatIonwIthlIttleeffectoncarbondIoxIde
elImInatIonuntIlthephysIologIcshuntfractIonexceeds75to80ofthecardIacoutput.
0efectIvetoabsentgasexchangecanbetheneteffectofeItherabnormalItyInthe
extreme.
Physiologic Dead Space
EachInspIredbreathIscomposedofgasthatcontrIbutestoalveolarventIlatIon(7
A
)and
gasthatbecomesdeadspaceventIlatIon(7
0
).Thus,tIdalvolume(7
T
)=7
A
+7
0
.nthe
normal,spontaneouslybreathIngperson,theratIoofalveolartodeadspaceventIlatIonfor
eachbreathIs2:1.ConvenIently,theruleof1,2,JapplIestonormal,spontaneously
breathIngpersons.Foreachbreath,1mL/lb(leanbodyweIght)becomes7
0
,2mLlb
1
becomes7a,andJmLlb
1
constItutesthe7
T
.
PhysIologIcdeadspaceconsIstsofanatomIcandalveolardeadspace.AnatomIcdeadspace
ventIlatIon,approxImately2mL/kgIdealbodyweIght,accountsforthemajorItyof
physIologIcdeadspace.tarIsesfromventIlatIonofstructuresthatdonotexchange
respIratorygases:theoronasopharynxtothetermInalandrespIratorybronchIoles.ClInIcal
condItIonsthatmodIfyanatomIcdeadspaceIncludetrachealIntubatIon,tracheostomy,
andlargelengthsofventIlatortubIngbetweenthetrachealtubeandtheventIlatorY
pIece.tIsImportanttonotethatventIlatIonoccursbecausegasflowsIntoandoutofthe
alveolI.ncontrast,theInspIratoryorexpIratorylImbofanesthesIacIrclesystemhas
unIdIrectIonalflow,andthereforeIsnotacomponentofanatomIcdeadspaceventIlatIon.
AlveolardeadspaceventIlatIonarIsesfromventIlatIonofalveolIwherethereIslIttleorno
perfusIon.8ecausedIseaseproduceslIttlechangeInanatomIcdeadspace,physIologIcdead
spaceIsprImarIlyInfluencedbychangesInalveolardeadspace.FapIdchangesIn
physIologIcdeadspaceventIlatIonmostoftenarIsefromchangesInpulmonarybloodflow,
resultIngIndecreasedperfusIontoventIlatedalveolI.Themostcommoncauseofacutely
IncreasedphysIologIcdeadspaceIsanabruptdecreaseIncardIacoutput.Another
pathologIccondItIonthatInterfereswIthpulmonarybloodflow,andtherebycreatesdead
space,IspulmonaryembolIsm,whetherduetothrombusortofat,aIr,oramnIotIcfluId.
AlthoughtheremaybeobstructIontobloodflowwIthsometypesofpulmonaryembolI,the
greatestdecreaseInpulmonarybloodflowIsduetovasoconstrIctIonInducedbylocally
releasedvasoactIvesubstancessuchasleukotrIenes.
ChronIcpulmonarydIseasescreatedeadspaceventIlatIonbyIrreversIblychangIngthe
relatIonshIpbetweenalveolarventIlatIonandbloodflow;thIsalteratIonIsespecIally
promInentInpatIentswIthCDP0.Furthermore,acutedIseasessuchasadultrespIratory
dIstresssyndromecancauseanIncreaseIndeadspaceventIlatIonowIngtoIntense
pulmonaryvasoconstrIctIon.FInally,therapeutIcorsupportIvemanIpulatIonssuchas
posItIvepressureventIlatIonorposItIveaIrwaypressuretherapycanIncreasealveolar
deadspacebecausedepressedvenousreturntotherIghtheartwIlldecreasecardIac
output,whIchcanusuallybeovercomebyIntravenousfluIdadmInIstratIon.DccasIonally,
therapeutIcsthatcreateIntrapulmonaryposItIvepressuremayIncreasephysIologIcshunt
whenbloodflowtoaprevIouslysIlentareaof[7wIthdotabove]
A
/[QwIthdotabove]
matchIngnowreceIvesbloodredIstrIbutedbyposItIvepressurefrommorecomplIantareas
ofthelung.
Assessment of Physiologic Dead Space
8ecausethelungreceIvesnearly100ofthecardIacoutput,assessmentofphysIologIc
deadspaceventIlatIonIntheacutesettIngyIeldsvaluableInformatIonaboutpulmonary
bloodflowand,ultImately,aboutcardIacoutput.fpulmonarybloodflowdecreases,the
mostlIkelycauseIsadecreasedcardIacoutput.Thus,ItIsclInIcallyusefultobeableto
readIlyassessthedegreeofphysIologIcdeadspaceventIlatIon.
TherearetwoeasyandseveraldIffIcultwaystoassessdeadspaceventIlatIon.A
comparIsonofmInuteventIlatIonandPaco
2
allowsagrossqualItatIveassessmentof
physIologIcdeadspaceventIlatIon.ThePaco
2
IsdetermInedonlybyalveolarventIlatIon
and[7wIthdotabove]co
2
.f[7wIthdotabove]co
2
remaInsconstant,Paco
2
alsowIll
remaInconstantaslongasmInuteventIlatIonsupplIesthesamedegreeofalveolar
ventIlatIon.fthespontaneouslybreathIngIndIvIdualmustIncreasemInuteventIlatIonto
maIntaInthesamePaco
2
,heorshehasexperIencedanIncreaseIndeadspaceventIlatIon
becauselessofthemInuteventIlatIonIscontrIbutIngtoalveolarventIlatIon.AlternatIvely,
amechanIcallyventIlatedpatIentwIthafIxedmInuteventIlatIonandnoIncreaseIn[7
wIthdotabove]co
2
alsoexperIencesanIncreaseddeadspaceventIlatIonIfthePaco
2
rIses.
Hence,whenPaco
2
InamechanIcallyventIlatedpatIentIncreases,ItIsnecessaryto
determIneIfthecauseIsIncreaseddeadspaceventIlatIonoranIncreased[7wIthdot
above]co
2
.
8ecauseposItIvepressureventIlatIonIncreasesalveolarpressure,themechanIcally
ventIlatedpatIentwIthnormallungshasadeadspacetoalveolarventIlatIonratIo(70/7a)
of1:1(moreWestzone1)ratherthan1:2,asdurIngspontaneousventIlatIon.fmechanIcal
7
T
Is1,000mL,500mLcontrIbutesto7A,and500mLcontrIbutesto70.Atrest,the
requIred[7wIthdotabove]AwIthnormal[7wIthdotabove]co
2
IsapproxImately60
mL/kg/mIn.A70kgmanwouldthenrequIrea[7wIthdotabove]Aof4,200mL/mIn.0urIng
spontaneousbreathIng,therequIred[7wIthdotabove]Ewouldbe6,J00mL/mIn,but
durIngmechanIcalventIlatIon[7wIthdotabove]Ewouldhavetobe8,400mL/mIn.UsIng
thIscalculatIon,Ifa70kgrestIngpatIentrequIres[7wIthdotabove]EmuchInexcessof
8,400mL/mIn,eIther[7wIthdotabove]0or[7wIthdotabove]co
2
IsIncreased.Aruleof
thumbformechanIcallyventIlatedpatIentsIsthatdoublIngbaselInemInuteventIlatIon
decreasesPaco
2
from40toJ0mmHg,andquadruplIngmInuteventIlatIondecreasesPaco
2
from40to20mmHg.
ThePaco
2
wIllbegreaterthanorequaltoendtIdalPaco
2
(PETCD
2
)unlessthepatIent
InspIresorreceIvesexogenouscarbondIoxIde(e.g.,fromperItonealInsufflatIon).The
dIfferencebetweenPETCD
2
andPaco
2
IsbecauseofdeadspaceventIlatIon.Themost
commonreasonforanacuteIncreaseIndeadspaceventIlatIonIsdecreasedcardIac
output.|easurementofthIsdIfferencewhIchIssImple,readIlyobtaInable,andfaIrly
InexpensIveyIeldsrelIableInformatIonrelatIvetothedegreeofdeadspaceventIlatIon.
ClInIcalsItuatIonsthatchangepulmonarybloodflowsuffIcIentlytoIncreasedeadspace
ventIlatIoncanbedetectedbycomparIngPETCD
2
wIthtemperaturecorrectedPaco
2
.
YamanakaandSue
52
foundthatthePETCD
2
InventIlatedpatIentsvarIedlInearlywIththe
deadspacetotIdalvolumeratIo(70/7
T
)andthatPETCD
2
correlatedpoorlywIthPaco
2
.
Thus,InthecrItIcallyIll,mechanIcallyventIlatedpatIent,andInanesthetIzedpatIents,
monItorIngPETCD
2
gIvesfarmoreInformatIonaboutventIlatoryeffIcIencyordeadspace
ventIlatIonthanItdoesabouttheabsolutevalueofPaco
2
.
P.246
AnesthesIologIstscommonlymeasurePETCD
2
todetectvenousaIrembolIsmdurIng
anesthesIa.AloweredcardIacoutputalone,IntheabsenceofvenousaIrembolIsm,may
suffIcIentlydecreasepulmonaryperfusIonsodeadspaceventIlatIonIncreasesandPETCD
2
falls.Thus,adepressedPETCD
2
IssensItIvefordecreasedcardIacoutputbutnonspecIfIc
pulmonaryembolIsm.AIrInthepulmonaryarterIesmechanIcallyInterfereswIthbloodflow
andalsocausespulmonaryarterIalconstrIctIon,furtherdecreasIngpulmonarybloodflow.
AdecreasedPETCD
2
suggeststhataphysIologIcallysIgnIfIcantaIrembolIsmhasoccurred.
ThesamephysIologIcconsIderatIonsapplytodetectIngpulmonarythromboembolIsm.
SomeclInIcIansusethedIvergenceofPETCD
2
fromPaco
2
asareflectIonofpulmonary
bloodflowforotherapplIcatIons.0urIngIntentIonalpharmacologIcorsurgIcal
manIpulatIonofpulmonarybloodflow,thedIfferencebetweenPaco
2
andPETCD
2
servesas
ausefulphysIologIcmonItoroftheeffectIvenessoftheseInterventIons.Furthermore,
PETCD
2
asareflectIonofpulmonaryperfusIonIsausefultoolforstudyIngandmonItorIng
theeffectIvenessofresuscItatIoneffortsandmayprovIdeamarkerforsurvIvalafter
resuscItatIon.
5J
ThemostquantItatIvetechnIqueusedtomeasurephysIologIcdeadspaceusesa
modIfIcatIonofthe8ohrequatIon:
wherePco
2
IsthePco
2
fromthemIxtureofallexpIredgasesovertheperIodoftIme
durIngwhIchmeasurementsaremade.ThIscalculatIonestImatesthefractIonofeach
breaththatdoesnotcontrIbutetogasexchange.nspontaneouslybreathIngpatIents,
normal7
0
/7
T
Isbetween0.2and0.4,or-0.JJ.npatIentsreceIvIngposItIvepressure
ventIlatIon,7
0
/7
T
becomes-0.5.ThemajorlImItatIonofperformIngthIscalculatIonIsthe
dIffIcultyIncollectIngexhaledgasforPco
2
measurement.Exhaledgases,collectedIn
cumbersome50Lbags,caneasIlybecontamInatedwIthInspIredaIrorsupplemental
oxygen.ThemeasurementwIllalsobeInaccurateIfthepatIentdoesnotmaIntaInasteady
ventIlatorypattern.Therefore,extremecaremustbetakentoensureallmeasurements
areperformedaccurately.npractIce,thIsmeasurementIsrarelyperformed.
P.247
Physiologic Shunt
WhereasphysIologIcdeadspaceventIlatIonapplIestoareasofthelungthatareventIlated
butpoorlyperfused,physIologIcshuntoccursInlungthatIsperfusedbutpoorlyventIlated.
ThephysIologIcshunt([QwIthdotabove]SP)IsthatportIonofthetotalcardIacoutput([Q
wIthdotabove]T)thatreturnstotheleftheartandsystemIccIrculatIonwIthoutreceIvIng
oxygenInthelung.WhenpulmonarybloodIsnotexposedtoalveolIorwhenthosealveolI
aredevoIdofventIlatIon,theresultIsabsolute or true shunt,InwhIch[7wIthdot
above]
A
/[QwIthdotabove]=0.Shunt effect,orvenous admixture,Isthemorecommon
clInIcalphenomenonandoccursInareaswherealveolarventIlatIonIsdefIcIentcompared
wIththedegreeofperfusIon:0[7wIthdotabove]
A
/[QwIthdotabove]1.
8ecausebloodpassIngthroughareasofabsoluteshuntreceIvesnooxygen,arterIal
hypoxemIaresultIngfromabsoluteshuntIsmInImallyreversedwIthsupplementaloxygen.
AlternatIvely,supplementaloxygensupplIedtopatIentswItharterIalhypoxemIadueto
venousadmIxturewIllIncreasethePao
2
.AlthoughventIlatIontothesealveolIIsdefIcIent,
theydocarryasmallamountofoxygentothecapIllarybed.Thus,assessmentofarterIal
oxygenresponsIvenesstosupplementaloxygenadmInIstratIonIsahelpfuldIagnostIctool.
AsmallpercentageofvenousbloodnormallybypassestherIghtventrIcleandemptIes
dIrectlyIntotheleftatrIum.ThIsanatomIc,absolute,ortrueshuntarIsesfromthevenous
returnfromthepleural,bronchIolar,andthebesIanveIns.ThIsvenousdraInageaccounts
for2to5oftotalcardIacoutputandexplaInsthesmallshuntthatnormallyoccurs.
AnatomIcshuntsofgreatestmagnItudeareusuallyassocIatedwIthcongenItalheartdIsease
thatcausesrIghttoleftshunt.ntrapulmonaryanatomIcshuntscanalsocauseanatomIc
shunt.Forexample,thearterIalhypoxemIaassocIatedwIthadvancedhepatIcfaIlure
(hepatopulmonarysyndrome)IspartlyduetoarterIovenousmalformatIons.
54,55
0Iseases
thatmaycauseabsoluteortrueshuntIncludeacutelobaratelectasIs,extensIveacutelung
Injury,advancedpulmonaryedema,andconsolIdatedpneumonIa.0IseaseentItIesthat
tendtoproducevenousadmIxtureIncludemIldpulmonaryedema,postoperatIve
atelectasIs,andCDP0.
Assessment of Arterial Oxygenation and Physiologic Shunt
ThesImplestassessmentofoxygenatIonIsqualItatIvecomparIsonofthepatIent'sFD
2
and
Pao
2
.ThehIghestpossIblePao
2
foranygIvenFD
2
(andPaco
2
)canbecalculatedfromthe
alveolargasequatIon:
wherePAD
2
andPACD
2
arealveolarPo
2
andPco
2
,PH
2
oIswatervaporpressureat100
saturatIonandJ7`C,P
b
IsbarometrIcpressure,andFIsrespIratoryquotIent.AssumIngone
makesthecalculatIonforawellperfusedalveolus,thealveolarandarterIalPco
2
are
equal.Therefore,Paco
2
canbesubstItutedforPACD
2
.FespIratoryquotIent(F)IstheratIo
ofD
2
consumed([7wIthdotabove]o
2
)toCD
2
produced([7wIthdotabove]co
2
):
DxygentensIonbasedIndIcesdonotreflectmIxedvenouscontrIbutIontoarterIal
oxygenatIonandcanbemIsleadIng.
56
EvenIfvenousadmIxtureIssmall,mIxedvenous
bloodwIthverylowoxygencontentwIllmagnIfytheeffectofasmallshunt.Dxygen
tensIonbasedIndIces,forexample,Pao
2
/FD
2
,alveolartoarterIalPo
2
dIfference(P
(Aa)
D
2
),
andratIoPao
2
/PAD
2
,donottakeIntoaccounttheInfluenceofCv_o
2
onarterIal
oxygenatIon.Therefore,IncrItIcallyIllpatIentswhoarehypoxemIc,theInsertIonofa
pulmonaryarterycathetertoassessshuntandtomeasurecardIacoutputmaybeessentIal
tounderstandIngtheInfluenceofcardIacfunctIononarterIaloxygenatIon.
P
(Aa)
D
2
IsausefulquantItatIveassessmentofarterIaloxygenatIonmaInlywhenarterIal
hemoglobInIswellsaturatedwhennormal0Aao
2
Is5mmHg.WhenPao
2
Is150mmHg
(andcertaInlywhenItIs100mmHg),therelatIonshIpbetweenoxygencontentand
oxygentensIonIsnonlInear,thusmakIng0Aao
2
moredIffIculttoInterpret.
TheassessmentofarterIaloxygenatIonrequIres,atleast,knowledgeofFD
2
andeIther
Pao
2
orSao
2
.DxygentensIonbasedIndIcesofoxygenatIonareuseful,buttheydonottake
IntoaccountthecontrIbutIonofmIxedvenousbloodtoarterIaloxygenatIon.|Ixedvenous
bloodcanbecomeextremelydesaturatedInthecrItIcallyIllpatIentowIngtoInadequate
cardIacoutput,anemIa,arterIalhypoxemIa,orIncreased[7wIthdotabove]o
2
.Thebest
knowledgeoftheeffIcIencywIthwhIchthelungsoxygenatethearterIalbloodcanbe
obtaInedonlybycalculatIngshuntfractIonorventIlatIonperfusIonIndex(7Q).
Physiologic Shunt Calculation
TheclInIcalreferencestandardforthecalculatIonofphysIologIcshuntfractIonIsderIved
fromatwocompartmentpulmonarybloodflowmodelwhereonecompartmentperforms
IdealgasexchangeandcontaInsperfectlymarrIedalveolarcapIllaryunIts.Theother
compartmentIstheshuntcompartmentandcontaInspulmonarycapIllarIesthathaveno
exposuretoventIlatedalveolI.UsIngtheFIckrelatIonshIp,thefollowIngequatIoncanbe
derIved:
where[QwIthdotabove]SP/[QwIthdotabove]TIstheshuntfractIon,[QwIthdotabove]
SPIsbloodflowthroughthephysIologIcshuntcompartment,[QwIthdotabove]TIstotal
cardIacoutput,andCco
2
andC
v
D
2
areendcapIllaryandmIxedvenousoxygencontents,
respectIvely.NormalIntrapulmonaryshuntIsapproxImately5.8ecausethIsequatIonIs
basedonanartIfIcIaltwocompartmentmodel,theabsolutevalueIsphysIcally
meanIngless.Acalculated[QwIthdotabove]
SP
/[QwIthdotabove]
T
of25meansthatIf
thelungexIstedIntwocompartments,25ofthecardIacoutputwouldtravelthroughthe
shuntcompartment.8ecausethelungdoesnotexIstIntwocompartments,thIsequatIon
onlygrosslyestImatespulmonaryoxygenexchangedefects.Nevertheless,ItremaInsour
besttoolforclInIcallyevaluatIngtheeffIcIencywIthwhIchthelungsoxygenatearterIal
blood.DbservIngshuntfractIonchangewIththerapeutIcInterventIonorwIththeprogress
ofdIseaseIsmorevaluablethanknowIngtheabsolutevalueperse.
8ecausehemoglobInconcentratIonIsunIformthroughoutthevascularsystem,theoxygen
contentsIntheshuntequatIonaredetermInedprImarIlybyoxyhemoglobInsaturatIon.
Thus,theshuntequatIoncanbeapproxImatedbysubstItutIngsaturatIonvaluesforeach
term;thenewvalue,calledventilationperfusion ratio(7Q),
55
IsdetermInedasfollows:
fthepatIentIsneItherbreathIngahypoxIcgasmIxturenorhasamethemoglobInor
carboxyhemoglobInvalueInexcessof5to6,Sco
2
mustequal1becausethemodel
requIresaperfectalveolarcapIllaryInterface.ThIssubstItutIonresultsInthefInal
expressIonIntheprevIousequatIon.Theabsolutevaluesof7QaremeanIngless,although
normalshouldbe0to4.LIke[QwIthdotabove]SP/[QwIthdotabove]T,the
ImportanceofthesevalueslIesIntheIrtrendasdIseaseandtreatmentprogress.
Sao
2
andSvo
2
canbeestImatedcontInuouslywIthpulseoxImetryandbyusInga
pulmonaryarterycatheterwIthoxImetrycapabIlIty.8yInterfacIngtheoutputsofthese
twodevIceswIthacomputer,7QcanbecalculatedcontInuously.Thegreatestadvantage
ofcalculatIng[QwIthdotabove]SP/[QwIthdotabove]Tor7QtoassessarterIal
oxygenatIoneffIcIencyIsthatthesevaluesIncludethecontrIbutIonofmIxedvenousblood.
Pulmonary Function Testing
AnesthesIologIstsfrequentlycareforpatIentswIthsIgnIfIcantpulmonarydysfunctIon(see
Chapter2J).tIsImportantfortheanesthesIologIsttobeabletoInterprettestsof
pulmonaryfunctIonIntellIgentlyandtoknowwhIchtestswIllhelpdefInedysfunctIonIfthe
patIent'shIstoryandphysIcalaresuggestIveofdIsease.ThIssectIondIscusseslungvolumes,
testsofpulmonarymechanIcs,anddIffusIngcapacIty.
Lung Volumes and Capacities
Known,reproducIblepulmonarygasvolumesandcapacItIesprovIdearelIablebasIsfor
comparIsonbetweennormalandabnormalmeasurements.
57
8ecausenormal
measurementsvarywIthsIze,heIghtIsmostfrequentlyusedtodefInenormal.Lung
capacItIesarecomposedoftwoormorelungvolumes.LungvolumesandcapacItIesare
schematIcallyIllustratedInFIgure118.
Tidal volumeIsthevolumeofgasthatmovesInandoutofthelungsdurIngquIetbreathIng
andIs-6to8mL/kg.TIdalvolumefallswIthdecreasedlungcomplIanceorwhenthe
patIenthasreducedventIlatorymusclestrength.
Vital capacityIsusually-60mL/kgbutmayvaryasmuchas20fromnormalInhealthy
IndIvIduals.7ItalcapacItycorrelateswellwIththecapabIlItyfordeepbreathIngand
effectIvecoughIng.tIsdecreasedbyrestrIctIvepulmonarydIseasesuchaspulmonary
edemaoratelectasIs.7ItalcapacItymayalsobereducedbythemechanIcallyInduced
extrapulmonaryrestrIctIonseenInpleuraleffusIon,pneumothorax,pregnancy,large
ascItes,orventIlatorymuscleweakness.
Theinspiratory capacityIsthelargestvolumeofgasthatcanbeInspIredfromtherestIng
expIratorylevelandIsfrequentlydecreasedInthepresenceofsIgnIfIcantextrathoracIc
aIrwayobstructIon.ThIsmeasurementIsoneofthefewsImpleteststhatcandetect
extrathoracIcaIrwayobstructIon.|ostroutInepulmonaryfunctIontestsmeasureonly
exhaledflowsandvolumes,whIchmayberelatIvelyunaffectedbyextrathoracIc
obstructIonuntIlItIssevere.ChangesIntheabsolutevolumeofInspIratorycapacIty
usuallyparallelchangesInvItalcapacIty.Expiratory reserve volumeIsnotofgreat
dIagnostIcvalue.
Functional residual capacity(FFC)IsthevolumeofgasremaInIngInthelungsatpassIve
endexpIratIon.Residual volumeIsthatgasremaInIngwIthInthelungsattheendofforced
maxImalexpIratIon.TheFFCservestwoprImaryphysIologIcfunctIons.tdetermInesthe
poIntonthe
P.248
pulmonaryvolumepressurecurveforrestIngventIlatIon(seeFIg.112).Thetangent
defInedbythemIdportIonpulmonaryvolumepressurecurveatFFCdefIneslung
complIance.Thus,FFCdetermInestheelastIcpressurevolumerelatIonshIpswIthInthe
lung.Furthermore,FFCIstherestIngexpIratoryvolumeofthelungandIstheprImary
determInantofoxygenreserveInhumanswhenapneaoccurs.Assuch,ItgreatlyInfluences
ventIlatIonperfusIonrelatIonshIpswIthInthelung.WhenFFCIsreduced,venousadmIxture
(low[7wIthdotabove]
A
/[QwIthdotabove])IncreasesandresultsInarterIalhypoxemIa
(seeDxygenandCarbon0IoxIdeTransportandLung|echanIcs).
Figure 11-8.LungvolumesandcapacItIes.ThedarkestbaronthefarrIghtdepIctsthe
fourbasIclungvolumesthatsumtocreatetotallungcapacIty(TLC).Dtherlung
capacItIesarecomposedoftwoormorelungvolumes.TheoverlyIngspIrographIc
tracIngorIentsthereadertotherelatIonshIpbetweenthelungvolumesandcapacItIes
andthespIrogram.EF7,expIratoryreservevolume;FFC,functIonalresIdualcapacIty;
C,InspIratorycapacIty;F7,InspIratoryreservevolume;F7,resIdualvolume;7C,
vItalcapacIty;T7,tIdalvolume.
Further,theFFCmaybeusedtoquantIfythedegreeofpulmonaryrestrIctIon.0Isease
processesthatreduceFFCandlungcomplIanceIncludeacutelungInjury,pulmonary
edema,pulmonaryfIbrotIcprocesses,andatelectasIs.|echanIcalfactorsalsoreduceFFC;
examplesIncludepregnancy,obesIty,pleuraleffusIon,andposture.TheFFCdecreases10
whenahealthysubjectlIesdown.7entIlatorymuscleweaknessorparalysIswIllalso
decreaseFFC.ncontrast,patIentswIthCDP0haveexcessIvelycomplIantlungsthatrecoIl
lessforcIbly.TheIrlungsretaInanabnormallylargevolumeattheendofpassIve
expIratIon,aphenomenoncalledgas trapping.
Functional Residual Capacity Measurement
TheFFCandresIdualvolumemustbemeasuredIndIrectlybecauseresIdualvolumecannot
beremovedfromthelung.ThemultIplebreathnItrogenwashouttestIsperformedby
havIngthesubjectbreathe100oxygenforseveralmInutessoalveolarnItrogenIs
graduallywashedout.WItheachbreath,thevolumeofgasandtheconcentratIonof
nItrogenIntheexhaledgasaremeasured.ArapIdnItrogenanalyzercoupledtoa
spIrometerorpneumotachometerprovIdesabreathbybreathanalysIsofnItrogen
washout.ElectronIcsIgnalsproportIonaltonItrogenconcentratIonsandexhaledvolumes
(orflow,IfapneumotachometerIsused)areIntegratedtoderIvetheexhaledvolumeof
nItrogenforeachbreath.ThenthevaluesforallbreathsaresummedtoprovIdeatotal
volumeofnItrogenwashedoutofthelungs.ThetestproceedsuntIlthealveolarnItrogen
concentratIonIsreducedto7,usuallyrequIrIng7to10mInutes.FFCIscalculatedusIng
theequatIon:
where[N
2
]
I
and[N
2
]
f
arethefractIonalconcentratIonsofalveolarnItrogenatthebegInnIng
andendofthetest,respectIvely.
Pulmonary Function Tests
Forced Vital Capacity
TheforcedvItalcapacIty(F7C)IsthevolumeofgasthatcanbeexpIredasforcefullyand
rapIdlyaspossIbleaftermaxImalInspIratIon.Normally,F7CIsequaltovItalcapacIty.
8ecauseforcedexpIratIonsIgnIfIcantlyIncreasesIntrapleuralpressuresbutchangesaIrway
pressurelIttle,bronchIolarcollapse,obstructIvelesIons,andgastrappIngareexaggerated.
Thus,F7CmaybereducedInchronIcobstructIvedIseasesevenwhenthevItalcapacIty
appearsnearnormal.F7CIsnearlyalwaysdecreasedbyrestrIctIvedIseases.F7Cvalues
15mL/kgareassocIatedwIthanIncreasedIncIdenceofPPCs,probablybecausepatIentsIn
thIscondItIoncoughIneffectIvely.
58
F7CreducedtothIslevelrepresentsaprofound
defect,mostcommonlyseenInquadrIplegIcpatIentsorpatIentswIthsevere
neuromusculardIsease.FInally,F7CIslargelydependentonpatIenteffortand
cooperatIon.
Forced Expiratory Volume
FE7
T
IstheforcedexpIratoryvolumeofgasoveragIventImeIntervaldurIngtheF7C
maneuver.TheInterval,descrIbedbythesubscrIptT,IsthetImeelapsedInsecondsfrom
theonsetofexpIratIon.8ecauseFE7
T
recordsavolumeofgasexpIredovertIme,ItIs
actuallyameasureofflow.8ymeasurIngexpIratoryflowatspecIfIcIntervals,theseverIty
ofaIrwayobstructIoncanbeascertaIned.0ecreasedFE7
T
valuesarecommonInboth
obstructIveandrestrIctIvedIseasepatterns.ThemostImportantapplIcatIonofFE7
T
IsIts
comparIsonwIththepatIent'sF7C.NormalsubjectscanexpIreatleastthreefourthsofF7C
wIthInthefIrstsecondoftheforcedexpIratorymaneuver.TheFE7
1
,themostfrequently
employedvalue,Isnormally75oftheF7C,orFE7
1
/F7C0.75.
Normally,anIndIvIdualcanexpIre50to60ofF7CIn0.5second,75to85In1second,
94In2seconds,and97InJseconds.CooperatIvepatIentswIthobstructIvedIseasewIll
exhIbItareducedFE7
1
/F7CInmostcases.However,patIentswIthrestrIctIvedIsease
usuallyhavenormalFE7
1
/F7CratIos.ThevalIdItyoftheevaluatIonoftheFE7
1
/F7CIs
hIghlydependentonpatIentcooperatIonandeffort.tIspossIbletodelIberatelyproduce
anartIfIcIallylowFE7
1
/F7C.
Forced Expiratory Flow
FEF
2575
IstheaverageforcedexpIratoryflowdurIngthemIddlehalfoftheFE7maneuver.
ThIstestIsalsocalledmaximum midexpiratory flow rate.ThelengthoftImerequIredfora
subjecttoexpIrethemIddlehalfoftheF7CIsdIvIdedInto50oftheF7C.ThespIrogram
InFIgure119markstheplacefrom25to75ofF7C,constItutIngthemIddle50ofF7C.
ThestraIghtlIneconnectIngthe25and75volumeshasaslopeapproxImatelyequalto
averageflow.Anormalvalueforahealthy70kgmanIsapproxImately4.7L/sec(or280
mL/mIn).Normally,boththeabsolutevalueandthepercentageofpredIctedvalueforthe
IndIvIdualbeIngstudIedarerecorded.AnormalvalueIs10025ofpredIctedvalue.
0ecreasedflowratesfromthIsmIddle50ofF7CanatomIcallyrepresentflowInmedIum
sIzedaIrways,andwhendecreased,thereIsobstructIvedIseaseofmedIumsIzedaIrways.
ThIsvalueIstypIcallynormalInrestrIctIvedIseases.ThIstestIsfaIrlysensItIveIntheearly
stagesofobstructIveaIrwaydIsease.0ecreasedFE7
2575
frequentlywIllbeobserved
P.249
beforeotherobstructIvemanIfestatIonsoccur.Althoughsomewhateffortdependent,the
testIsmuchmorerelIableandreproducIblethanFE7
1
/F7C.
Figure 11-9.ForcedexpIratoryflow,25to75(FEF
2575
).ThespIrogramdepIctsa4L
forcedvItalcapacIty(F7C)onwhIchthepoIntsrepresentIng25and75F7Care
marked.TheslopeofthelIneconnectIngthesepoIntsIstheFEF
2575
.
Maximum Voluntary Ventilation
|axImumvoluntaryventIlatIon(|77)IsthelargestvolumeofgasthatcanbebreathedIn
1mInutebyvoluntaryeffort.The|77IsmeasuredbyhavIngthesubjectbreatheasdeeply
andasrapIdlyaspossIblefor10,12,or15seconds.Theresultsareextrapolatedto1
mInute.ThesubjectIsInstructedtosethIsorherownventIlatoryrateandmovemore
thantIdalvolumebutlessthanvItalcapacItyIneachbreath.
|77measurestheenduranceoftheventIlatorymusclesandIndIrectlyreflectslungthorax
complIanceandaIrwayresIstance.|77IsthebestventIlatoryendurancetestthatcanbe
performedInthelaboratory.7aluesthatvarybyasmuchasJ0frompredIctedvalues
maybenormal,soonlylargereductIonsIn|77aresIgnIfIcant.Healthy,youngadults
average-170L/mIn.7aluesarelowerInwomenanddecreasewIthageInbothsexes.
8ecausethIsmaneuverexaggeratesaIrtrappIngandexertstheventIlatorymuscles,|77Is
decreasedgreatlyInpatIentswIthmoderatetosevereobstructIvedIsease.|77Isusually
normalInpatIentswIthrestrIctIvedIsease.
FlowVolume Loops
TheflowvolumeloopgraphIcallydemonstratestheflowgenerateddurIngaforced
expIratorymaneuverfollowedbyaforcedInspIratorymaneuver,plottedagaInstthe
volumeofgasexpIred(FIg.1110;seeChapter40).Thesubjectforcefullyexhales
completely,thenImmedIatelyandforcefullyInhalestovItalcapacIty.TheexpIredand
InspIredvolumesareplottedontheabscIssaandflowIsplottedontheordInate.Although
varIousnumberscanbegeneratedfromtheflowvolumeloop,theconfIguratIonofthe
loopItselfIsprobablythemostInformatIvepartofthetest.
FlowvolumeloopswereformerlyusefulInthedIagnosIsoflargeaIrwayandextrathoracIc
aIrwayobstructIonprIortotheavaIlabIlItyofprecIseImagIngtechnIques.magIng
technIquessuchasmagnetIcresonanceImagInggIvemoreprecIseandusefulInformatIon
InthedIagnosIsofupperaIrwayandextrathoracIcobstructIonandsupersededtheuseof
flowvolumeloopsfordIagnosIsofthesecondItIons.Therefore,ItIsrarethatflowvolume
loopsareusefulforpreoperatIvepulmonaryevaluatIonInthemoderneraofImagIng.
Figure 11-10.Flowvolumeloop.ThefIguredepIctsanormallyconfIguredadultflow
volumeloop.TheslopeoftheloopafterthesubjectreachespeakexpIratoryflowIs
nearlylInear.
Carbon Monoxide Diffusing Capacity
8ecausePD
2
InthepulmonarycapIllarybloodvarIeswIthtImeasItmovesthroughthe
pulmonarycapIllarybed,oxygencannotbeusedtoassessdIffusIngcapacIty.AgasmIxture
contaInIngcarbonmonoxIdeIsthetradItIonaldIagnostIcgasusedtomeasuredIffusIng
capacIty.tspartIalpressureInthebloodIsnearlyzero,andItsaffInItyforhemoglobInIs
200tImesthatofoxygen.
59
CarbonmonoxIdedIffusIngcapacIty(0
LCD
)collectIvely
measuresallthefactorsthataffectthedIffusIonofgasacrossthealveolarcapIllary
membrane.The0
LCD
IsrecordedInmLCD/mIn/mmHgatSTP0(standardtemperatureand
pressure,dry).npersonswIthnormalhemoglobInconcentratIonsandnormal[7wIthdot
above]
A
/[QwIthdotabove]matchIng,themaInfactorlImItIngdIffusIonIsthealveolar
capIllarymembrane.SmallamountsofcarbondIoxIdeandInspIredgascanproduce
measurablechangesIntheconcentratIonofInspIredgascomparedwIthexpIredgas.There
areseveralmethodsfordetermInIng0
LCD
,butallmethodsmeasuredIffusIngcapacIty
accordIngtotheequatIon:
TheaveragevalueforrestIngsubjectswhenthesInglebreathmethodIsusedIs25mL
CD/mIn/mmHg.0
LCD
valuescanIncreaseto2orJtImesnormaldurIngexercIse.
The0LD
2
maybeestImatedfromthe0
LCD
bymultIplyIng0
LCD
by1.2J,althoughthe0
LCD
Is
usuallythereportedvalue.0LCDcanbedIvIdedbythelungvolumeatwhIchthe
measurementwasmadetoobtaInanexpressIonofdIffusIngcapacItyperunItlungvolume.
SomeoftheotherfactorsthatcanInfluence0
LCD
areasfollows:
1. HemoglobInconcentratIon:decreasedhemoglobInconcentratIondecreasesthe0
LCD
.
2. AlveolarPco
2
:anIncreasedPACD
2
raIses0
LCD
.
J. 8odyposItIon:thesupIneposItIonIncreases0
LCD
.
4. PulmonarycapIllarybloodvolume.
0IffusIngcapacItyIsdecreasedInalveolarfIbrosIsassocIatedwIthsarcoIdosIs,asbestosIs,
beryllIosIs,oxygentoxIcIty,andpulmonaryedema.ThesestatesarefrequentlycategorIzed
asdiffusion defects,butlow0
LCD
Isprobablymorecloselyrelatedtolossoflungvolumeor
capIllarybedperfusIon.0
LCD
IsdecreasedInobstructIvedIseasebecauseofthedecreased
alveolarsurfacearea,lossofcapIllarybed,theIncreaseddIstancefromthetermInal
bronchIoletothealveolarcapIllarymembrane,and[7wIthdotabove]
A
/[QwIthdot
above]mIsmatchIng.nshort,fewdIseasestatestrulyInhIbItoxygendIffusIonacrossthe
alveolarcapIllarymembrane.
Practical Application of Pulmonary Function Tests
AlthoughwehaveahostofpulmonaryfunctIontestsfromwhIchtochoose,spIrometryIs
themostuseful,costeffectIve,andcommonlyusedtest.
60
ScreenIngspIrometryyIelds
vItalcapacIty(7C),F7C,andFE7
1
.Fromthesevalues,twobasIctypesofpulmonary
dysfunctIoncanbeIdentIfIedandquantItated:obstructIvedefectsandrestrIctIvedefects.
TheprImarycrIterIonforaIrflowobstructIonIsdecreasedFE7
1
/FC7ratIo.Dther
measurementssuchasFEF
2575
canbeusedtosupport
P.250
thedIagnosIsofanobstructIvedefectortoassIstInmakIngdecIsIons(e.g.,whetherto
InstItutebronchodIlatIon).ArestrIctIvedefectIsaproportIonaldecreaseInalllung
volumes;thus,7C,F7C,andFE7
1
allarereduced,butFE7
1
/F7CremaInsnormal.When
thereIsaquestIonaboutwhetheradecreased7CIsduetorestrIctIon,totallungcapacIty
shouldbemeasured.FeducedtotallungcapacItydefInesarestrIctIvedefectbutIsnot
necessaryunless7ConscreenIngspIrometryIsreduced.TheAmerIcanThoracIcSocIety
publIshedanexperts'consensusconcernIngInterpretatIonoflungfunctIontests.
61
Table11
4summarIzesthedIstInctIonbetweenpulmonaryfunctIonresultsobtaInedfromthosewIth
restrIctIveandobstructIvedefects.FefertoPulmonaryFunctIonPostoperatIvelyfora
dIscussIonoftheuseofpulmonarytestIng.
Table 11-4 Pulmonary Function Tests in Restrictive and Obstructive Lung
Disease
Value Restrictive Disease Obstructive Disease
0efInItIon
ProportIonaldecreasesInall
lungvolumes
SmallaIrwayobstructIonto
expIratoryflow
F7C NormalorslIghtly
FE7
1
NormalorslIghtly
FE7
1
/F7C
Normal
FEF
2575
Normal
FFC NormalorIfgastrappIng
TLC NormalorIfgastrappIng
F7C,forcedvItalcapacIty;,=largedecreaseorIncrease,respectIvely;,
=small/moderatedecreaseorIncrease,respectIvely;FE7,forcedexpIratory
volume;FFC,functIonalresIdualcapacIty;TLC,totallungcapacIty.
Preoperative Pulmonary Assessment
|arkedlyImpaIredpulmonaryfunctIonIslIkelyInpatIentswhohavethefollowIng:
1. AnychronIcdIseasethatInvolvesthelung
2. SmokInghIstory,persIstentcough,and/orwheezIng
J. ChestwallandspInaldeformItIes
4. |orbIdobesIty
5. FequIrementforsInglelunganesthesIaorlungresectIon
6. SevereneuromusculardIsease
PreoperatIvepulmonaryevaluatIonmustIncludehIstoryandphysIcalexamInatIonandmay
IncludechestradIograph,arterIalbloodgasanalysIs,andscreenIngspIrometry,dependIng
onthepatIent'shIstory.AhIstoryofsputumproductIon,wheezIngordyspnea,exercIse
Intolerance,orlImIteddaIlyactIvItIesmayyIeldmorepractIcalInformatIonthandoes
formaltestIng.ArterIalbloodanalysIs,whIchshouldbesampledwhIlethepatIentbreathes
roomaIr,addsInformatIonregardInggasexchangeandacIdbasebalance.ArterIalblood
gassamplIngIsprImarIlyusefulIfthepatIent'shIstorysuggeststhatheorshemaybe
chronIcallyhypoxemIcormayretaInCD
2
(I.e.,apatIentwIthachronIc,compensated
arterIalacIdemIa)andbeusedtoguIdeventIlatorymanagementgoals.
ThegoalsonemIghthopetoachIevethroughpreoperatIvepulmonaryfunctIonwouldbeto
predIctthelIkelIhoodofpulmonarycomplIcatIons,obtaInquantItatIvebaselIne
InformatIonconcernIngpulmonaryfunctIonthatguIdesdecIsIonmakIng,andIdentIfy
patIentswhomaybenefItfromtherapytoImprovepulmonaryfunctIonpreoperatIvely.For
patIentswhowIllhavelungresectIons,pulmonaryfunctIontestIngdoesprovIdesome
predIctIvebenefIt.
62
ForallotherpatIents,however,overwhelmIngevIdencesuggeststhat
preoperatIvepulmonaryfunctIontestIngdoesnotpredIctorassIgnrIskforPPCs.
6J,64
n2002,theAmerIcanSocIetyofAnesthesIologIsts'TaskForceonPreanesthetIcEvaluatIon
publIshedapractIceadvIsory
65
whereIntheyrecommendedthatthereIsInsuffIcIent
evIdencetoIdentIfyexplIcItdecIsIonparametersorrulesfororderIngpreoperatIvetests
onthebasIsofspecIfIcclInIcalcharacterIstIcs.FevIewofthelIterature
66
alsorevealsthat
specIfIcmeasurementsoflungfunctIondonotpredIctPPCs.Father,theyshouldbe
obtaInedtoascertaInthepresenceofreversIblepulmonarydIsease(bronchospasm)orto
defInetheseverItyofadvancedpulmonarydIsease.nstead,theclInIcIanobtaInsmore
InformatIonfromthepatIent'shIstory.naserIesof272adultsundergoIngnonthoracIc
surgery,|cAlIsteretal.
67
foundthatthefollowInghIstorIcalfactorsIndependently
IncreasedtherIskofPPC:age65years,smokIng40packyears,CDP0,asthma,productIve
cough,andexercIsetoleranceoflessthanoneflIghtofstaIrs.
TheneedtoobtaInbaselInepulmonaryfunctIondatashouldbereservedforthosepatIents
wIthseverelyImpaIredpreoperatIvepulmonaryfunctIon,suchastetraplegIcsor
myasthenIcs,soassessmentforlIberatIonfrommechanIcalventIlatIonand/ortracheal
extubatIonmIghtbebasedonthepatIent'sbaselInepulmonaryfunctIon.
ArterIalbloodgasesarenotIndIcatedunlessthepatIent'shIstorysuggestsarterIal
hypoxemIaorsevereenoughCDP0thatonesuspectsCD
2
retentIon.ThenthearterIalblood
gasfIndIngshouldbeusedInessentIallythesamemannerasonemIghtusepreoperatIve
pulmonaryfunctIontests:tolookforreversIbledIseaseortodefInetheseverItyofthe
dIseaseatItsbaselIne.0efInIngbaselInePao
2
andPaco
2
IspartIcularlyImportantIfone
antIcIpatespostoperatIvelyventIlatIngapatIentwhohassevereCDP0.Table115
summarIzestherespIratoryphysIologyformulasdIscussedInthIschapter.
Anesthesia and Obstructive Pulmonary Disease
PatIentswIthmarkedobstructIvepulmonarydIseaseareatIncreasedrIskforboth
IntraoperatIveandPPCs.Forexample,patIentswIthreducedFE7
1
/F7Correduced
mIdexpIratoryflownotonlysufferaIrwayobstructIon,butalsousuallyexhIbItIncreased
aIrwayreactIvIty.8ecauseofthehazardofprovokIngreflexbronchoconstrIctIondurIng
laryngoscopyandtrachealIntubatIon,patIentswIthCDP0orasthmashouldreceIve
aggressIvebronchodIlatortherapypreoperatIvely.
P.251
HIghalveolarconcentratIonsofmostpotentInhalatIonalanesthetIcswIllbluntaIrway
reflexesandreflexbronchoconstrIctIon,butrequIreafaIrlyrobustcardIovascularsystem.
AdjunctIveIntravenousadmInIstratIonofopIoIdsandlIdocaIneprIortoaIrway
InstrumentatIonwIlldecreaseaIrwayreactIvItybydeepenInganesthesIa.Furthermore,a
sIngledoseofcortIcosteroIdsmayhelppreventpostoperatIveIncreasesInaIrway
resIstance.
Table 11-5 Respiratory Formulas
Formula
Normal Values (70
kg)
AlveolaroxygentensIon 110mmHg
PAD
2
=(P847)FD
2
;(PACD
2
/F) (FD
2
=0.21)
AlveolararterIaloxygengradIent 10mmHg
(AaD
2
)=PAD
2
PaD
2
(FD
2
=0.21)
ArterIaltoalveolaroxygenratIo,PaD
2
/PAD
2
ratIo
0.75
ArterIaloxygencontent
20mL/100mL
blood
Cao
2
=(Sao
2
)(Hb1.J4)+Pao
2
(0.00J1)
|Ixedvenousoxygencontent
15mL/100mL
blood
C[vwIthbarabove]D
2
=(S[vwIthbarabove]o
2
)(Hb1.J4)+
P[vwIthbarabove]o
2
(0.00J1)
ArterIalvenousoxygencontentdIfference
46mL/100
mLblood
C(a[vwIthbarabove])D
2
=Cao
2
C[vwIthbarabove]o
2
ntrapulmonaryshunt 5
[QwIthdotabove]sp/[QwIthdotabove]T=(Cco
2
Cao
2
)/(Cco
2
C[vwIthbarabove]o
2
)
whereCco
2
=(Hb1.J4)+(PAD
2
0.00J1)
PhysIologIcdeadspace 0.JJ
70/7
T
=(PaCD
2
Pco
2
)/PaCD
2
DxygenconsumptIon 250mL/mIn
[7wIthdotabove]D
2
=CD(Cao
2
C[vwIthbarabove]o
2
)
Dxygentransport 1,000mL/mIn
0o
2
=CD(Cao
2
)
FespIratoryquotIent 0.8
[7wIthdotabove]CD
2
/[7wIthdotabove]o
2
=F
PAD
2
,alveolaroxygentensIon;P8,barometrIcpressure;FD
2
,fractIonInspIred
oxygen;PACD
2
,alveolarcarbondIoxIdetensIon;F,respIratoryquotIent;Pao
2
,
arterIaloxygentensIon;Cao
2
,arterIaloxygencontent;Sao
2
,arterIaloxygen
saturatIon;Hb,hemoglobInconcentratIon;CvD
2
,mIxedvenousoxygencontent;
Svo
2
,mIxedvenousoxygensaturatIon;Pvo
2
,mIxedvenousoxygentensIon;[Q
wIthdotabove]SP/[QwIthdotabove]T,Intrapulmonaryshunt;Cco
2
,end
pulmonarycapIllaryoxygencontent;70,deadspacegasvolume;7
T
,tIdalvolume;
PaCD
2
,arterIalcarbondIoxIdetensIon;PCD
2
,mIxedexpIredcarbondIoxIde
tensIon;[7wIthdotabove]D
2
,oxygenconsumptIon(mL/mIn);CD,cardIacoutput;
[7wIthdotabove]CD
2
,carbondIoxIdeproductIon(mL/mIn);0o
2
,oxygen
transport.
SpontaneousventIlatIondurInggeneralanesthesIaInpatIentswIthsevereobstructIve
dIseaseIsmorelIkelytoresultInhypercapnIathanInpatIentswIthnormalpulmonary
functIon.
68
PreoperatIveFE7
1
reductIoncorrelateswIththePaco
2
IncreasedurIng
anesthesIa.SlowerratesofmechanIcalventIlatIon(8to10breathsmIn
1
)shouldbeused
toallowtImeforexhalatIon.LowventIlatoryratesnecessItatelargertIdalvolumeIfone
desIresanormalPaco
2
,butlarger7
T
andresultanthIgherpeakaIrwaypressuremay
predIsposethepatIenttopulmonarybarotrauma.TIdalvolumeandInspIratoryflowsshould
beadjustedtokeeppeakaIrwaypressurelessthan40cmH
2
D,
69,70
IfpossIble.HIgher
InspIratoryflowsproduceashorterInspIratorytImeand,usually,ahIghpeakaIrway
pressure.Thus,abalancethatavoIdshIghpeakaIrwaypressureandexcessIvelylarge7
T
thatallowsthelongestpossIbleexpIratorytImeshouldbesought.
deally,dependIngontheprocedureandtheduratIonofanesthesIa,onewouldextubate
thepatIent'stracheaattheendoftheoperatIon.TheIrrItatIngtrachealtubeIncreases
bothaIrwayresIstanceandreflexbronchoconstrIctIon,lImItstheabIlItyofthepatIentto
clearsecretIonseffectIvely,andIncreasestherIskofIatrogenIcInfectIon.Forsome
patIentswIthobstructIvedIsease(e.g.,theyoungasthmatIcpatIent),manyadvocate
trachealextubatIondurIngdeepanesthesIaattheconclusIonoftheoperatIon.
Anesthesia and Restrictive Pulmonary Disease
FestrIctIvedIseaseIscharacterIzedbyproportIonaldecreasesInalllungvolumes.The
decreasedFFCproduceslowlungcomplIanceandalsoresultsInarterIalhypoxemIa
becauseoflow[7wIthdotabove]
A
/[QwIthdotabove]mIsmatchIng.PatIentswIththIs
dIseasetypIcallybreatherapIdlyandshallowly.
PosItIvepressureventIlatIonofpatIentswIthrestrIctIvedIseaseIsfraughtwIthhIghpeak
aIrwaypressuresbecausemorepressureIsrequIredtoexpandstIfflungs.LowermechanIcal
tIdalvolumesatmorerapIdratesreducetherIskofbarotraumabutaugmentventIlatIon
InducedcardIovasculardepressIonandIncreasethechancesofdevelopIngatelectasIs.
LargertIdalvolumesshouldbeavoIdedbecauseoftheIncreasedrIskofbothbarotrauma
71
andvolutrauma.
72
7arIouslungprotectIvestrategIeshavebeendevelopedtoventIlate
patIentswIthprofoundrestrIctIvelungdIsease(seeChapter56).
8ecausetheFFCIsreduced,aloweroxygenstoreIsavaIlabledurIngapneIcperIods.Even
preoxygenatIonwIthanFD
2
of1.0canresultInarterIalhypoxemIasecondsafterthe
cessatIonofbreathIngordIsconnectIonfromaventIlatorcIrcuIt.PatIentswIthsevere
restrIctIvedIseasestolerateapneapoorly.8ecausearterIalhypoxemIadevelopssorapIdly,
transportatIonofthesepatIentswIthInthehospItalshouldbeperformedwIthapulse
oxImeter.
P.252
EvenhealthyIndIvIdualsdevelopmIldrestrIctIvedefectsdurInganesthesIa.FFCdecreases
10to15whenhealthy,spontaneouslybreathIngIndIvIdualslIesupIne.TrachealIntubatIon
furtherreducesFFConlyslIghtly.CeneralanesthesIaconsIstentlydecreasesFFCbya
further5to10,
7J
whIchusuallyresultsIndecreasedlungcomplIance.
74
TheFFCreaches
ItsnadIrwIthInthefIrst10mInutesofanesthesIa
7J,75,76
andIsIndependentofwhether
ventIlatIonIsspontaneousorcontrolled.ThedImInIshedFFCpersIstsInthepostoperatIve
perIodbutmayberestoredpostoperatIvelybytheuseofposItIveendexpIratorypressure
orCPAP.
7J,77,78
However,onceposItIveaIrwaypressureIsremoved,FFCplummetsto
prevIouslydImInIshedlevels,whIchreachapostoperatIvenadIr12hoursafteroperatIon.
79
Effects of Cigarette Smoking on Pulmonary Function
SmokIngaffectspulmonaryfunctIonInmanyways(seeChapter2J).TheIrrItantsmoke
decreasescIlIarymotIlItyandIncreasessputumproductIon.Thus,thesepatIentshavea
hIghvolumeofsputumanddecreasedabIlItytoclearIteffectIvely.AssmokInghabIts
persIst,aIrwayreactIvItyandthedevelopmentofobstructIvedIseasebecomeproblematIc.
StudIesofthepathogenesIsofCDP0suggestthatsmokIngresultsInanexcessofpulmonary
proteolytIcenzymes,whIchdIrectlycausedamagetothelungparenchyma.
80
Exposureto
smokeIncreasessynthesIsandreleaseofelastolytIcenzymesfromalveolarmacrophages
cellsInstrumentalInthegenesIsofCDP0fromsmokIng.FurtherdamagetothelungtIssue
IsprobablycausedbyreactIvemetabolItesofoxygen,suchashydroxylradIcalsand
hydrogenperoxIde,whIchareusuallyusedbythemacrophagestokIllmIcroorganIsms.The
ImmunoregulatoryfunctIonofthemacrophagesIsalsochangedbycIgarettesmokIng,wIth
changesoccurrIngInthepresentatIonofantIgensandInteractIonwIthTlymphocytes.
81
DtherdIrecteffectsonlungtIssuecausedbysmokIngIncludeIncreasedepIthelIal
permeabIlIty
82
andchangedpulmonarysurfactant.
8J
TheaIrwayIrrItatIonorsmallaIrway
reactIvItyevokedbyInhalIngcIgarettesmokeIstheresultofactIvatIonofsensoryendIngs
locatedInthecentralaIrways,whIchIsprImarIlycausedbynIcotIne.
84
EarlyInthedIsease,mIld[7wIthdotabove]
A
/[QwIthdotabove]mIsmatch,bronchItIc
dIsease,andaIrwayhyperreactIvItyareprImaryproblems.Later,theseproblemsare
accompanIedbythehallmarksofCDP0:gastrappIng,flatteneddIaphragmatIc
confIguratIon(whIchdecreasestheeffIcIencywIthwhIchthedIaphragmfunctIons),and
barrelchestdeformIty.LungcomplIanceIncreasessIgnIfIcantlysolImItedelastIcrecoIl
preventscompletepassIveemptyIng.Asaresult,manypatIentsexhaleforcIblytoreduce
gastrappIng.
WIthgastrappIng,ventIlatIonandperfusIonbecomeIncreasInglymIsmatched.Largeareas
ofdeadspaceventIlatIonandvenousadmIxtureoccur.CarbondIoxIdeelImInatIonIs
IneffIcIentbecauseofdeadspaceventIlatIon.ThetypIcalmInuteventIlatIonforpatIents
wIthadvancedobstructIvelungdIseasecanbe1.5to2tImesnormal.naddItIon,venous
admIxtureproducesarterIalhypoxemIathatIsexquIsItelysensItIvetolowconcentratIons
ofsupplementaloxygen.CasexchangeIsfurtherImpaIredbytheIncreased
carboxyhemoglobInconcentratIonthatresultsfromInspIrIngsmoke.Normal
carboxyhemoglobInconcentratIonInnonsmokersIsapproxImately1;Insmokers,however,
ItcanbeashIghas8to10.CessatIonofsmokIng,evenfor12to24hourspreoperatIvely,
candecreaseCDconcentratIontonearnormal.
SmokIngIsoneofthemaInandmostprevalentrIskfactorsassocIatedwIthpostoperatIve
morbIdIty.
85
CDP0patIentswhosmokehaveatwotosIxfold
86
rIskofdevelopIng
postoperatIvepneumonIacomparedwIthnonsmokers.Further,smokers'relatIverIskofPPC
Isdoubled,evenIftheydonothaveevIdenceofclInIcalpulmonarydIseaseorabnormal
pulmonaryfunctIon.
87
TheIncIdenceofPPCInsmokerscanbereducedbyabstInencefrom
smokIng,althoughthereIsnoconsensusonthemInImaloroptImalduratIonof
preoperatIvesmokIngabstInence.
88,89,90
Warneretal.
85
studIed200patIentsundergoIng
coronaryarterybypassgraftIngandfoundthatpatIentswhocontInuedtosmokeorstopped
8weeksbeforetheoperatIonhadacomplIcatIonratenearly4tImesthatofpatIentswho
hadquItsmokIngmorethan8weekspreoperatIvely.Thesedatafurtherdemonstratedthat
thosewhoquItsmokIng8weekspreoperatIvelyhadahIgherrateofcomplIcatIonthan
thosewhocontInuedtosmoke.NormalIzatIonofmucocIlIaryfunctIonrequIres2toJweeks
ofabstInencefromsmokIng,durIngwhIchtImesputumIncreases.Severalmonthsof
smokIngabstInenceIsrequIredtoreturnsputumclearancetonormal.
91
nastudyof
bupropIonassIstedsmokIngcessatIon,Hurtetal.
92
demonstrateddecreasedrIskof
postoperatIvecomplIcatIonsevenafter4weeksofabstInencefromsmokIng.
Nonetheless,PublIcHealthServIceguIdelInespublIshedIn2000emphasIzethe
responsIbIlItyofhealthcarefacIlItIestocoordInateInterventIonsaImedattobacco
dependencetreatment.naddItIontotheguIdelInesnotIngthattobaccodependenceoften
necessItatesrepeatedInterventIons,everypatIentwhousestobaccoshouldbeofferedat
leastbrIeftreatmentasbrIeftobaccodependencetherapyhasbeenshowntobe
effectIve.TheseguIdelInesrecognIzefIvefIrstlInepharmacologIcadjunctsthatIncrease
smokIngcessatIonsuccess:bupropIonSF,nIcotInegum,nIcotIneInhaler,nIcotInenasal
sprayandnIcotInepatch.AddItIonally,clonIdIneandnortrIptylInewereIdentIfIedas
secondlInepharmacologIcadjuncts.
9J
FollowIngpublIcatIonofthese2000guIdelInes,arandomIzedcontrolledtrIalusIngthe
partIalnIcotInIcacetylcholIneagonIst,varenIclIne,showedImprovedsmokIngabstInence
ratesatalltImesevaluateddurIngthestudywhencomparedwIthbupropIonSF
treatment.
94
8asedonthIsInformatIon,theutIlIzatIonofvarenIclIneInasmokIng
cessatIonprogramshouldbeconsIdered.
Smokerswhodecrease,butdonotstop,cIgaretteconsumptIonwIthouttheaIdofnIcotIne
replacementtherapycontInuetoacquIreequalamountsofnIcotInefromfewercIgarettes
bychangIngtheIrtechnIqueofsmokIngtomaxImIzenIcotIneIntake.
95
Levelsofserum
nIcotIneandcotInIneandurInarymutagenesIslevelsremaInunchanged.Thus,reductionIn
thenumberofcIgarettessmokedwIlllIkelyhavelIttleeffectontherIskofdevelopIng
PPCs.
86
SmokIngpatIentsshouldbeadvIsedtostopsmokIng2monthsprIortoelectIve
operatIonstomaxImIzetheeffectofsmokIngcessatIon,
85
orforatleast4weekstobenefIt
fromImprovedmucocIlIaryfunctIonandsomereductIonInPPCrate.fpatIentscannot
stopsmokIngfor4to8weekspreoperatIvely,ItIscontroversIalwhethertheyshouldbe
advIsedtostopsmokIng24hourspreoperatIvely.A24hoursmokIngabstInencewouldallow
carboxyhemoglobInlevelstofalltonormalbutmayIncreasetherIskofPPC.
Pulmonary Function Postoperatively
Risk of Postoperative Pulmonary Complications
Postoperative Pulmonary Function
ThechangesInpulmonaryfunctIonthatoccurpostoperatIvelyareprImarIlyrestrIctIve,
wIthproportIonaldecreasesInalllungvolumesandnochangeInaIrwayresIstance.The
decreaseInFFC,however,IstheyardstIckbywhIchtheseverItyofthe
P.25J
restrIctIvedefectIsgauged.ThIsdefectIsgeneratedbyabdomInalcontentsthatImpInge
onandpreventnormalmovementofthedIaphragmandbyanabnormalrespIratory
patterndevoIdofsIghsandcharacterIzedbyshallow,rapIdrespIratIons.Thenormal
restIngrespIratoryrateforadultsIs12breathspermInute,whereasthepostoperatIve
patIentusuallybreathesapproxImately20breathspermInute.Furthermore,most(butnot
all)factorsthattendtomaketherestrIctIvedefectworsearealsothoseassocIatedwItha
hIgherrIskofPPCs.
TheoperatIvesIteIsoneofthesInglemostImportantdetermInantsofthedegreeof
pulmonaryrestrIctIonandtherIskofPPCs.NonlaparoscopIcupperabdomInaloperatIons
causethemostprofoundrestrIctIvedefect,precIpItatInga40to50decreaseInFFC
comparedwIthpreoperatIvelevels,whenconventIonalpostoperatIveanalgesIaIs
employed.LowerabdomInalandthoracIcoperatIonscausethenextmostseverechangeIn
pulmonaryfunctIon,wIthdecreasesInFFCtoJ0ofpreoperatIvelevels.|ostother
operatIvesItesIntracranIal,perIpheralvascular,otolaryngologIchaveapproxImatelythe
sameeffectonFFC,wIthreductIonsto15to20ofpreoperatIvelevels.
Postoperative Pulmonary Complications
TwoproblemsconfoundInterpretatIonofthelIteratureexamInIngPPCs(seeChapter65).
FIrst,thereIsnocleardefInItIonofwhatconstItutesaPPC.Forexample,someclInIcal
studIesIncludeonlypneumonIa,whereasothersaddatelectasIsand/orventIlatoryfaIlure.
Thus,toInterpretdataconcernIngratesofPPCs,ItIsImportanttodIscernwhat
complIcatIonsarespecIfIcallybeIngaddressed.Second,thecrIterIabywhIchthedIagnosIs
ofpostoperatIvepneumonIaoratelectasIsIsmadevaryfromstudytostudy.ForthIs
dIscussIon,PPCsIncludeatelectasIsandpneumonIaonly.Feasonable,wellaccepted
dIagnostIccrIterIaforthesedIagnosesIncludechangeInthecolorandquantItyofsputum,
oraltemperatureexceedIngJ8.5`C,andanewInfIltrateonchestradIograph.
TheoperatIvesIteIsanImportantrIskfactorforthedevelopmentofPPCs.
NonlaparoscopIcupperabdomInaloperatIonsIncreaserIskforPPCatleasttwofold,
89
wIth
ratesofoccurrencevaryIngfrom20to70.
95
.LowerabdomInalandIntrathoracIc
operatIonsareassocIatedwIthslIghtlylessrIsk,butstIllhIgherrIskthanextremIty,
IntracranIal,andhead/neckoperatIons.
PatIentswIthCDP0areatrIskforPPC.TheIrrIskscanbemInImIzedbyensurIngtheydo
nothaveanactIvepulmonaryInfectIonandanyIncreasedresIstanceassocIatedwIth
reactIveaIrwaysdIseaseIsmInImIzedbytheuseofbronchodIlatortherapy.nterestIngly,
thosewIthasthmaarenotatIncreasedrIskforatelectasIsorpneumonIa.However,
exacerbatIonofasthmaInthepostoperatIveperIodcanbeproblematIc.CarefulattentIon
mustbegIventoensurIngthecontInuatIonofbronchodIlatIngregImensandsteroId
admInIstratIon(eItherInhaledorsystemIc)throughtheperIoperatIveperIod.
ThereareseveralstrategIesbywhIchItIspossIbletoreducerIskofPPC:theuseoflung
expandIngtherapIespostoperatIvely,choIceofanalgesIa,
96
andcessatIonofsmokIng.After
upperabdomInaloperatIons,whIchareassocIatedwIththehIghestIncIdenceofPPCs,FFC
recoversoverJto7days.WIththeuseofIntermIttentCPAPbymask,FFCwIllrecover
wIthIn72hours.
97
PatIentscorrectlyuseIncentIvespIrometersonly10ofthetImeunless
therapyIssupervIsed.
98
StIrupregImensareaseffectIveasIncentIvespIrometryat
preventIngPPCs
99
andtheyarelessexpensIvethansupervIsedIncentIvespIrometry;thus,
theyarepreferredoverIncentIvespIrometrytherapy.
AftermedIansternotomyforcardIacoperatIons,FFCdoesnotreturntonormalforseveral
weeks,regardlessofpostoperatIvepulmonarytherapy.
100
ThepersIstentlylowFFCInthIs
populatIonIsprobablyduetomechanIcalfactorssuchasawIdenedmedIastInum,
IntrapleuralfluId,andalteredchestwallcomplIance.ThesInglemostImportantaspectof
postoperatIvepulmonarycareIsgettIngthepatIentoutofbed,preferablywalkIng.
ThechoIceofanesthetIctechnIqueforIntraoperatIveanesthesIadoesnotchangetherIsk
forPPCIndependentoftheoperatIvesIteorduratIonoftheoperatIon.DperatIons
exceedIngJhoursareassocIatedwIthahIgherrateofPPC.ChoIceofpostoperatIve
analgesIastronglyInfluencestherIskofPPC.
89
TheuseofpostoperatIveepIduralanalgesIa,
partIcularlyforabdomInalandthoracIcoperatIons,markedlydecreasestherIskofPPCand
appearstodecreaselengthofstayInthehospItal.
AlthoughobesItyIsassocIatedwIthmarkedrestrIctIvedefects,somestudIesdemonstrate
thatobesItydoesnotIndependentlyIncreasetherIskofPPC,whereasothersdo
demonstrateIncreasedIndependentrIskforPPCsIntheobesepopulatIon.
101
However,
therearedatatosupport
101
advancedageasanIndependentrIskfactorforPPCs.
SeveralauthorshaveattemptedtoassesstheInfluenceofoverallhealthonPPCrIsk.The
useofIndIcesthatweIghtandscorevarIousaspectsofphysIologyandhealthshowsthat
patIentswhoareInapoorstateofhealthpreoperatIvelytendtobeathIgherrIskofPPC.
90
PatIentswIthobstructIveaIrwaydIseaseanddecreasedexpIratoryflowsmaybenefItfrom
preoperatIvebronchodIlatortherapyandformalpulmonarytoIlet.
102
HIghrIskpatIents
wIthCDP0whoreceIvebronchodIlatIon,chestphysIcaltherapy,deepbreathIng,forced
oralfluIds(JL/day),andpreoperatIveInstructIonInpostoperatIverespIratorytechnIques,
aswellasthosewhostopsmokIngformorethan2monthspreoperatIvely,experIencea
PPCrateapproxImatelyequaltothatobservedInnormalpatIents.
10J
nterestIngly,
althougharegImenofthIsnaturesIgnIfIcantlyreducestheIncIdenceofPPCs,
104
aIrway
obstructIonandarterIalhypoxemIaarenotmeasurablyreverseddurIngthe48to72hours
ofpreoperatIvetherapy.
105
tIspossIblethatthereducedcomplIcatIonrateresultsfrom
theaddItIonalattentIonthatthesepatIentsreceIveratherthanfromthespecIfIcregImen
employed.
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Stock, M. Christine
TableofContentsSectIonAnatomyandPhysIologyChapter12mmuneFunctIonandAllergIcFesponse
Chapter12
Immune Function and Allergic Response
Jerrold H. Levy
Key Points
1. Anesthesiologists routinely manage patients during their
perioperative medical care during which they are exposed to foreign
substances, including drugs (antibiotics, anesthetic agents,
neuromuscular-blocking agents [NMBAs], sedative/hypnotics),
polypeptides (e.g., protamine, aprotinin), blood products, and
environmental antigens (e.g., latex).
2. Antibodies are specific proteins called immunoglobulins that can
recognize and bind to a specific antigen.
3. Cytokines are inflammatory cell activators that are synthesized to act
as secondary messengers and activate endothelial cells and white
cells.
4. Immune competence during surgery can be affected by direct and
hormonal effects of anesthetic drugs, by immunologic effects of other
drugs used, by the surgery, by coincident infection, and by
transfused blood products.
5. More than 90% of the allergic reactions evoked by intravenous drugs
occur within 5 minutes of administration. In the anesthetized patient,
the most common life-threatening manifestation of an allergic
reaction is circulatory collapse, reflecting vasodilation with resulting
decreased venous return.
6. Many diverse molecules administered during the perioperative period
release histamine in a dose-dependent, nonimmunologic fashion.
7. A plan for treating anaphylactic reactions must be established before
the event. Airway maintenance, 100% oxygen administration,
intravascular volume expansion, and epinephrine are essential to
treat the hypotension and hypoxia that result from vasodilation,
increased capillary permeability, and bronchospasm. Vasopressin
should be considered for refractory shock.
8. After an anaphylactic reaction, it is important to identify the
causative agent to prevent readministration.
9. Health care workers and children with spina bifida, urogenital
abnormalities, or certain food allergies have been recognized as
people at increased risk for anaphylaxis to latex.
10. NMBAs have several unique molecular features that make them
potential antigens.
AllergIcreactIonsrepresentanImportantcauseofperIoperatIvecomplIcatIons.
AnesthesIologIstsroutInelymanagepatIentsdurIngtheIrperIoperatIvemedIcalcaredurIng
whIchtheyareexposedtoforeIgnsubstances,IncludIngdrugs(I.e.,antIbIotIcs,anesthetIc
agents,neuromuscularblockIngagents[N|8As],sedatIvehypnotIcs),polypeptIdes
(protamIne,aprotInIn),bloodproducts,andenvIronmentalantIgens(I.e.,latex).
AnesthesIologIstsmustbeabletorapIdlyrecognIzeandtreatanaphylaxIs,themostlIfe
threatenIngformofanallergIcreactIon.
1
TheallergIcresponserepresentsjustonelImbofthepathologIcresponsethattheImmune
systemcanmountagaInstforeIgnsubstances.AspartofnormalhostsurveIllance
mechanIsms,aserIesofcellularandhumoralelementsoverseesforeIgnstructurescalled
antigenstoprovIdehostdefense.TheseforeIgnsubstances(antIgens)consIstofmolecular
arrangementsfoundoncells,bacterIa,vIruses,proteIns,orcomplexmacromolecules.
1,2,J,4
mmunologIcmechanIsms(1)InvolveantIgenInteractIonwIthantIbodIesorspecIfIc
effectorcells;(2)arereproducIble;and(J)arespecIfIcandadaptIve,dIstInguIshIngforeIgn
substancesandamplIfyIngreactIvItythroughaserIesofInflammatorycellsandproteIns.
TheImmunesystemservestoprotectthebodyagaInstexternalmIcroorganIsmsand
toxIns,aswellasInternalthreatsfromneoplastIccells;however,Itcanrespond
InapproprIatelytocausehypersensItIve(allergIc)reactIons.LIfethreatenIngallergIc
reactIonstodrugsandotherforeIgnsubstancesobservedperIoperatIvelymayrepresent
dIfferentexpressIonsoftheImmuneresponse.
1,2
P.257
Basic Immunologic Principles
HostdefensecanbedIvIdedIntocellularandhumoralelements.
1,2,J,4
Thehumoralsystem
IncludesantIbodIes,complement,cytokInes,andothercIrculatIngproteIns,whereas
cellularImmunItyIsmedIatedbyspecIfIclymphocytesoftheTcellserIes.Lymphocytes
havereceptorsthatdIstInguIshbetweenantIgensofhostandforeIgnorIgIn.When
lymphocytesreactwIthforeIgnantIgens,theyrespondtoorchestrateImmunosurveIllance,
regulateImmunospecIfIcantIbodysynthesIs,anddestroyforeIgnInvaders.ndIvIdual
aspectsoftheImmuneresponseandtheIrImportanceareconsIderedseparately.
Antigens
|oleculesstImulatInganImmuneresponse(antIbodyproductIonorlymphocyte
stImulatIon)arecalledantigens.
4
DnlyafewdrugsusedbyanesthesIologIsts,suchas
polypeptIdes(protamIne)andotherlargemacromolecules(dextrans),arecomplete
antIgens(Table121).|ostcommonlyuseddrugsaresImpleorganIccompoundsoflow
molecularweIght(around1,000daltons).Forsuchasmallmoleculetobecome
ImmunogenIc,ItmustformastablebondwIthcIrculatIngproteInsortIssuemIcromolecules
toresultInanantIgen(haptenmacromolecularcomplex).SmallmolecularweIght
substancessuchasdrugsordrugmetabolItesthatbIndtohostproteInsorcellmembranes
tosensItIzepatIentsarecalledhaptens.HaptensarenotantIgenIcbythemselves.Dften,a
reactIvedrugmetabolIte(e.g.,penIcIlloylderIvatIveofpenIcIllIn)IsbelIevedtobIndwIth
macromoleculestobecomeantIgens,butformostdrugsthIsphenomenonhasnotbeen
proved.
Thymus-Derived (T-Cell) and Bursa-Derived (B-Cell)
Lymphocytes
ThethymusofthefetusdIfferentIatesImmaturelymphocytesIntothymusderIvedcells(T
cells).TcellshavereceptorsthatareactIvatedbybIndIngwIthforeIgnantIgensand
secretemedIatorsthatregulatetheImmuneresponse.ThesubpopulatIonsofTcellsthat
exIstInhumansIncludehelper,suppressor,cytotoxIc,andkIllercells.
5
Thetwotypesof
regulatoryTcellsarehelpercells(DKT4)andsuppressorcells(DKT8).Helpercellsare
Importantforkeyeffectorcellresponses,whereassuppressorcellsInhIbItImmune
functIon.nfectIonofhelperTcellswItharetrovIrus,thehumanImmunodefIcIencyvIrus,
producesaspecIfIcIncreaseInthenumberofsuppressorcells.CytotoxIcTcellsdestroy
mycobacterIa,fungI,andvIruses.Dtherlymphocytes,callednatural killer cells,donot
needspecIfIcantIgenstImulatIontosetuptheIrrole.8oththecytotoxIcTcellsandnatural
kIllercellstakepartIndefenseagaInsttumorcellsandIntransplantrejectIon.Tcells
producemedIatorsthatInfluencetheresponseofothercelltypesInvolvedInthe
recognItIonanddestructIonofforeIgnsubstances.
Figure 12-1.8asIcstructuralconfIguratIonoftheantIbodymoleculerepresentIng
humanImmunoglobulInC.mmunoglobulInsarecomposedoftwoheavychaInsandtwo
lIghtchaInsboundbydIsulfIdelInkages(representedbycrossbars).PapaIncleavesthe
moleculeIntotwoFabfragmentsandoneFcfragment.AntIgenbIndIngoccursonthe
Fabfragments,whereastheFcsegmentIsresponsIbleformembranebIndIngor
complementactIvatIon.(FeprIntedwIthpermIssIonfromLevyJH:AnaphylactIc
FeactIonsInAnesthesIaandntensIveCare,2ndedItIon.8oston,8utterworth
HeInemann,1992.)
8cellsrepresentaspecIfIclymphocytecelllInethatcandIfferentIateIntospecIfIcplasma
cellsthatsynthesIzeantIbodIes,astepcontrolledbybothhelperandsuppressorTcell
lymphocytes.
5
8cellsarealsocalledbursa-derived cellsbecauseInbIrds,thebursaof
FabrIcIusIsImportantInproducIngcellsresponsIbleforantIbodysynthesIs.
Antibodies
AntIbodIesarespecIfIcproteInscalledimmunoglobulins(g)thatcanrecognIzeandbIndto
aspecIfIcantIgen.
6
ThebasIcstructureoftheantIbodymoleculeIsIllustratedInFIgure12
1.EachantIbodyhasatleasttwoheavychaInsandtwolIghtchaInsthatarebound
togetherbydIsulfIdebonds.TheFabfragmenthastheabIlItytobIndantIgen,andtheFc,
orcrystallIzable,fragmentIsresponsIblefortheunIquebIologIcalpropertIesofthe
dIfferentclassesofImmunoglobulIns(cellbIndIngandcomplementactIvatIon).AntIbodIes
functIonasspecIfIcreceptormoleculesforImmunecellsandproteIns.WhenantIgenbInds
covalentlytotheFabfragments,theantIbodyundergoes
P.258
conformatIonalchangestoactIvatetheFcreceptor.TheresultsofantIgenantIbody
bIndIngdependonthecelltype,whIchcausesaspecIfIctypeofactIvatIon(e.g.,
lymphocyteprolIferatIonanddIfferentIatIonIntoantIbodysecretIngcells,mastcell
degranulatIon,andcomplementactIvatIon).
Table 12-1 Agents Administered During Anesthesia That Act as Antigens
HAPTENS MACROMOLECULES
PenIcIllInandItsderIvatIves
AprotInIn
8loodproducts
AnesthetIcdrugs(:)
ChymopapaIn
ColloIdvolumeexpanders
NeuromuscularblockIngagents
ProtamIne
Latex
Table 12-2 Biological Characteristics of Immunoglobulins (Igs)
IgG IgM IgA IgE IgD
HeavychaIn A
|olecular
weIght
160,000 900,000 170,000 188,000 184,000
Subclasses 1,2,J,4 1,2 1,2
Serum
concentratIon
(mg/dL)
614 0.51.5 1J
0.5
10
J
0.1
Complement
actIvatIon
AllbutgC
4
+
Placental
transfer
+
Serumhalf
lIfe(days)
2J 5 6 15 28
|astcells
CellbIndIng
(gC
4
)
NeutrophIls
Lymphocytes
|ononuclear
cells
Platelets
Lymphocytes
|ast
cells
8asophIls
NeutrophIls
Lymphocytes
|odIfIedfromLevyJH:AnaphylactIcFeactIonsInAnesthesIaandntensIveCare,2nd
edItIon.8oston,8utterworthHeInemann,1992.
FIvemajorclassesofantIbodIesoccurInhumans:gC,gA,g|,g0,andgE.Theheavy
chaIndetermInesthestructureandthefunctIonofeachmolecule.ThebasIcpropertIesof
eachantIbodyarelIstedInTable122.
Effector Cells and Proteins of the Immune Response Cells
|onocytes,neutrophIls(polymorphonuclearleukocytes[P|Ns]),andeosInophIlsrepresent
ImportanteffectorcellsthatmIgrateIntoareasofInflammatIonInresponsetospecIfIc
chemotactIcfactors,IncludInglymphokInes,cytokInes,andcomplementderIved
medIators.ThedeposItIonofantIbodyorcomplementfragmentsonthesurfaceofforeIgn
cellsIscalledopsonization,aprocessthatpromoteskIllIngforeIgncellsbyeffectorcells.n
addItIon,lymphokInesandcytokInesproducechemotaxIsofotherInflammatorycellsIna
mannerdescrIbedInthefollowIngsectIons.
Monocytes and Macrophages
|acrophagesregulateImmuneresponsesbyprocessIngandpresentIngantIgenstoeffect
Inflammatory,tumorIcIdal,andmIcrobIcIdalfunctIons.|acrophagesarIsefromcIrculatIng
monocytesormaybeconfInedtospecIfIcorganssuchasthelung.TheyarerecruItedand
actIvatedInresponsetomIcroorganIsmsortIssueInjury.|acrophagesIngestantIgens
beforetheyInteractwIthreceptorsonthelymphocytesurfacetoregulatetheIractIon.
|acrophagessynthesIzemedIatorstofacIlItateboth8lymphocyteandTlymphocyte
responses.
Polymorphonuclear Leukocytes (Neutrophils)
ThefIrstcellstoappearInacuteInflammatoryreactIonareneutrophIlsthatcontaInacId
hydrolases,neutralproteases,andlysosomes.DnceactIvated,theyproducehydroxyl
radIcals,superoxIde,andhydrogenperoxIde,whIchaIdInmIcrobIalkIllIng.
Eosinophils
TheexactfunctIonoftheeosInophIlInhostdefenseIsunclear;however,Inflammatory
cellsrecruIteosInophIlstocollectatsItesofparasItIcInfectIons,tumors,andallergIc
reactIons.
1
Basophils
8asophIlscomprIse0.5to1ofcIrculatInggranulocytesIntheblood.
1
Thesurfaceof
basophIlscontaIngEreceptors,whIchfunctIonsImIlarlytothoseonmastcells.
Mast Cells
|astcellsareImportantcellsforImmedIatehypersensItIvItyresponses.TheyaretIssue
fIxedandlocatedIntheperIvascularspacesoftheskIn,lung,andIntestIne.
1
Thesurfaceof
mastcellscontaIngEreceptors,whIchbIndtospecIfIcantIgens.DnceactIvated,these
cellsreleasephysIologIcallyactIvemedIatorsImportanttoImmedIatehypersensItIvIty
responses(seegE|edIatedPathophysIology).|astcellscanbeactIvatedbyaserIesof
bothImmuneandnonImmunestImulI.
Proteins
Cytokines/Interleukins
CytokInesareInflammatorycellactIvatorsthataresynthesIzedbymacrophagestoactas
secondarymessengersandactIvateendothelIalcellsandwhItecells.
7
nterleukIn1and
tumornecrosIsfactorareexamplesofcytokInesconsIderedtobeImportantmedIatorsof
thebIologIcalresponsestoInfectIonandotherInflammatoryreactIons.LIberatIonof
InterleukIn1andtumornecrosIsfactorproducesfever,neuropeptIderelease,endothelIal
cellactIvatIon,IncreasedadhesIonmoleculeexpressIon,neutrophIlprImIng,hypotensIon,
myocardIalsuppressIon,andacatabolIcstate.
7
TheterminterleukinwascoInedfora
groupofcytokInesthatpromotescommunIcatIonbetweenandamong(Inter)leukocytes
(leukIn).nterleukInsareagroupofdIfferentregulatoryproteInsthatacttocontrol
manyaspectsoftheImmuneandInflammatoryresponses.TheInterleukInsare
polypeptIdessynthesIzedInresponsetocellularactIvatIon;theyproducetheIr
InflammatoryeffectsbyactIvatIngspecIfIcreceptorsonInflammatorycellsand
vasculature.TcelllymphocytesInfluencetheactIvItyofotherImmunologIcand
nonImmunologIccellsbyproducInganarrayofInterleukInsthattheysecrete.0Ifferent
InterleukInsofthIsclasshavebeenIsolatedandcharacterIzed;theyfunctIonasshort
rangeorIntracellularsolublemedIatorsoftheImmuneandInflammatoryresponses.The
InterleukInfamIlyofcytokIneshasbeenrapIdlygrowIngInnumberbecauseofadvancesIn
geneclonIng.
Complement
TheprImaryhumoralresponsetoantIgenandantIbodybIndIngIsactIvatIonofthe
complementsystem.
8
ThecomplementsystemconsIstsofaround20dIfferentproteInsthat
bIndtoactIvatedantIbodIes,othercomplementproteIns,andcellmembranes.The
complementsystemIsanImportanteffectorsystemofInflammatIon.Complement
actIvatIoncanbeInItIated
P.259
bygCorg|bIndIngtoantIgen,byplasmInthroughtheclassIcpathway,byendotoxIn,or
bydrugsthroughthealternate(properdIn)pathway
8
(FIg.122).SpecIfIcfragments
releaseddurIngcomplementactIvatIonIncludeCJa,C4a,andC5a,whIchhaveImportant
humoralandchemotactIcpropertIes(seeNongE|edIatedFeactIons).Themajor
functIonofthecomplementsystemIstorecognIzebacterIabothdIrectlyandIndIrectlyby
attractIngphagocytes(chemotaxIs),aswellastheIncreasedadhesIonofphagocytesto
antIgens(opsonIzatIon),andcelllysIsbyactIvatIonofthecompletecascade.
Figure 12-2.0IagramofcomplementactIvatIon.ComplementsystemcanbeactIvated
byeIthertheclassIcpathway(ImmunoglobulIn[g]C,g|antIgenInteractIon)orthe
alternatepathway(endotoxIn,drugInteractIon).SmallpeptIdefragmentsofCJandC5
calledanaphylatoxins(CJa,C5a)thatarereleaseddurIngactIvatIonarepotent
vasoactIvemedIators.FormatIonofthecompletecomplementcascadeproducesa
membraneattackunItthatlysescellwallsandmembranes.AnInhIbItorofthe
complementcascade,theC1esteraseInhIbItor,ensuresthecomplementsystemIs
turnedoffmostofthetIme.
AserIesofInhIbItorsregulatesactIvatIontoensureregulatIonofthecomplementsystem.
HeredItary(autosomaldomInant)oracquIred(assocIatedwIthlymphoma,lymphosarcoma,
chronIclymphocytIcleukemIa,andmacroglobulInemIa)angIoneurotIcedemaIsanexample
ofadefIcIencyInanInhIbItoroftheC1complementsystem(C1esterasedefIcIency).ThIs
syndromeIscharacterIzedbyrecurrentIncreasedvascularpermeabIlItyofspecIfIc
subcutaneousandserosaltIssues(angIoedema),whIchproduceslaryngealobstructIonand
respIratoryandcardIovascularabnormalItIesaftertIssuetraumaandsurgery,oreven
wIthoutanyobvIousprecIpItatIngfactor.
9
DneoftheImportantpathologIcmanIfestatIons
ofcomplementactIvatIonIsacutepulmonaryvasoconstrIctIonassocIatedwIthprotamIne
admInIstratIon.
1
Effects of Anesthesia on Immune Function
AnesthesIaandsurgerydepressnonspecIfIchostresIstancemechanIsms,IncludIng
lymphocyteactIvatIonandphagocytosIs.
6
mmunecompetencedurIngsurgerycanbe
affectedbydIrectandhormonaleffectsofanesthetIcdrugs,byImmunologIceffectsof
otherdrugsused,bythesurgery,bycoIncIdentInfectIons,andbytransfusedblood
products.8loodrepresentsacomplexofhumoralandcellularelementsthatmayalter
ImmunomodulatIontovarIousantIgens.AlthoughmultIplestudIesdemonstrateInvItro
changesofImmunefunctIon,nostudIeshaveeverprovedtheIrImportance.
6
8esIdes,suchchangesarelIkelyofmInorImportancecomparedwIththehormonalaspects
ofstressresponses.
Hypersensitivity Responses (Allergy)
Celletal.
J
fIrstdescrIbedaschemeforclassIfyIngImmuneresponsestounderstand
specIfIcdIseasesmedIatedbyImmunologIcprocesses.TheImmunepathwayfunctIonsasa
protectIvemechanIsm,butcanalsoreactInapproprIatelytoproduceahypersensItIvItyor
allergIcresponse.TheydefInedfourbasIctypesofhypersensItIvIty,typesto7.tIsuseful
fIrsttorevIewallfourmechanIsmstounderstandthedIfferentImmunereactIonsthat
occurInhumans.
Figure 12-3.TypeImmedIatehypersensItIvItyreactIons(anaphylaxIs)Involve
ImmunoglobulInE(gE)antIbodIesbIndIngtomastcellsorbasophIlsbywayoftheIrFc
receptors.DnencounterIngImmunospecIfIcantIgens,thegEbecomescrosslInked,
InducIngdegranulatIon,IntracellularactIvatIon,andreleaseofmedIators.ThIs
reactIonIsIndependentofcomplement.
Type I Reactions
TypereactIonsareanaphylactIcorImmedIatetypehypersensItIvItyreactIons(FIg.12J).
PhysIologIcallyactIvemedIatorsarereleasedfrommastcellsandbasophIlsafterantIgen
bIndIngtogEantIbodIesonthemembranesofthesecells.TypehypersensItIvItyreactIons
IncludeanaphylaxIs,extrInsIcasthma,andallergIcrhInItIs.
Type II Reactions
TypereactIonsarealsoknownasantibody-dependent cell-mediated cytotoxic
hypersensitivityorcytotoxic reactions(antIbodydependentcellmedIatedcytotoxIc;FIg.
124).ThesereactIonsaremedIatedbyeIthergCorg|antIbodIesdIrected
P.260
agaInstantIgensonthesurfaceofforeIgncells.TheseantIgensmaybeeItherIntegralcell
membranecomponents(Aor8bloodgroupantIgensInA8DIncompatIbIlItyreactIons)or
haptensthatabsorbtothesurfaceofacell,stImulatIngtheproductIonofantIhapten
antIbodIes(autoImmunehemolytIcanemIa).ThecelldamageIntypereactIonsIs
producedby(1)dIrectcelllysIsaftercompletecomplementcascadeactIvatIon,(2)
IncreasedphagocytosIsbymacrophages,or(J)kIllerTcelllymphocytesproducIng
antIbodydependentcellmedIatedcytotoxIceffects.ExamplesoftypereactIonsIn
humansareA8DIncompatIbletransfusIonreactIons,drugInducedImmunehemolytIc
anemIa,andheparInInducedthrombocytopenIa.
Figure 12-4.TypeorcytotoxIcreactIons.AntIbodyofanImmunoglobulIn(g)Cor
g|classIsdIrectedagaInstantIgensonanIndIvIdual'sowncells(targetcell).The
antIgensmaybeIntegralmembranecomponentsorforeIgnmoleculesthathavebeen
absorbed.ThIsphysIologIcchoIcemayleadtocomplementactIvatIon,IncludIngcell
lysIs(upper figure)ortocytotoxIcactIonbykIllerTcelllymphocytes(lower figure).
Figure 12-5.TypeImmunecomplexreactIons.AntIbodIesofanImmunoglobulIn(g)
Corg|typebIndtotheantIgenInthesolublebaseandaresubsequentlydeposItedIn
themIcrovasculature.ComplementIsactIvated,resultIngInchemotaxIsand
actIvatIonofpolymorphonuclearleukocytesatthesIteofantIgenantIbodycomplexes
andsubsequenttIssueInjury.
Type III Reactions (Immune Complex Reactions)
TypereactIonsresultfromcIrculatIngsolubleantIgensandantIbodIesthatbIndtoform
InsolublecomplexesthatdeposItInthemIcrovasculature(FIg.125).ComplementIs
actIvated,andneutrophIlsarelocalIzedtothesIteofcomplementdeposItIontoproduce
tIssuedamage.TypereactIonsIncludeclassIcserumsIcknessobservedaftersnake
antIseraorantIthymocyteglobulIn,andImmunecomplexvascularInjury,andmayoccur
throughmechanIsmsofprotamInemedIatedpulmonaryvasoconstrIctIon.
1
Type IV Reactions (Delayed Hypersensitivity Reactions)
Type7reactIonsresultfromtheInteractIonsofsensItIzedlymphocyteswIthspecIfIc
antIgens(FIg.126).0elayedhypersensItIvItyreactIonsaremaInlymononuclear,manIfest
In18to24hours,peakat40to80hours,anddIsappearIn72to96hours.AntIgen
lymphocytebIndIngproduceslymphokInesynthesIs,lymphocyteprolIferatIon,generatIonof
cytotoxIcTcells,andattractsmacrophagesandotherInflammatorycells.CytotoxIcTcells
areproducedspecIfIcallytokIlltargetcellsthatbearantIgensIdentIcalwIththosethat
trIggeredthereactIon.ThIsformofImmunItyIsImportantIntIssuerejectIon,graftversus
hostreactIons,contactdermatItIs(e.g.,poIsonIvy),andtuberculInImmunIty.
Figure 12-6.Type7ImmunecomplexreactIons(delayedhypersensItIvItyorcell
medIatedImmunIty).AntIgenbIndstosensItIzedTcelllymphocytestorelease
lymphokInesafterasecondcontactwIththesameantIgen.ThIsreactIonIs
IndependentofcIrculatIngantIbodyorcomplementactIvatIon.LymphokInesInduce
InflammatoryreactIonsandactIvate,aswellasattract,macrophagesandother
mononuclearcellstoproducedelayedtIssueInjury.
Intraoperative Allergic Reactions
ntraoperatIveallergIcreactIonsoccuronceInevery5,000to25,000anesthetIcs,wItha
J.4mortalItyrate.
10,11
|orethan90oftheallergIcreactIonsevokedbyIntravenous
drugsoccurwIthIn5mInutesofadmInIstratIon.ntheanesthetIzedpatIent,themost
commonlIfethreatenIngmanIfestatIonofanallergIcreactIonIscIrculatorycollapse,
reflectIngvasodIlatIonwIthresultIngdecreasedvenousreturn(Table12J).Theonly
manIfestatIonofanallergIcreactIonmayberefractoryhypotensIon.
12
PortIerandFIchet
1J
fIrstusedthewordanaphylaxis(fromana,agaInst,andprophylaxis,protectIon)to
descrIbetheprofoundshockandresultIngdeaththatsometImesoccurredIndogs
ImmedIatelyafterasecondchallengewIthaforeIgnantIgen.WhenlIfethreatenIngallergIc
reactIonsmedIatedbyantIbodIesoccur,theyaredefInedasanaphylactIc.Althoughthe
termanaphylactoidhasbeenusedInthepasttodescrIbenonImmunologIcreactIons,thIs
termIsnowrarelyused.
14
Anaphylactic Reactions
IgE-Mediated Pathophysiology
AntIgenbIndIngtogEantIbodIesInItIatesanaphylaxIs(FIg.127).PrIorexposuretothe
antIgenortoasubstanceofsImIlarstructureIsneededtoproducesensItIzatIon,although
anallergIchIstorymaybeunknowntothepatIent.Dnreexposure,bIndIngoftheantIgen
tobrIdgetwoImmunospecIfIcgEantIbodIesfoundonthesurfacesofmastcellsand
basophIlsreleasesstoredmedIators,IncludInghIstamIne,tryptase,andchemotactIc
factors.
15,16,17
ArachIdonIcacIdmetabolItes(leukotrIenesandprostaglandIns),kInIns,and
cytokInesaresubsequentlysynthesIzedandreleasedInresponsetocellularactIvatIon.
18
ThereleasedmedIatorsproduceasymptomcomplexofbronchospasmandupperaIrway
edemaIntherespIratorysystem,vasodIlatIonandIncreasedcapIllarypermeabIlItyInthe
cardIovascularsystem,andurtIcarIaInthecutaneoussystem.0IfferentmedIatorsare
releasedfrommastcellsandbasophIlsafteractIvatIon.
Chemical Mediators of Anaphylaxis
HIstamInestImulatesH
1
,H
2
,andH
J
receptors.H
1
receptoractIvatIonreleases
endothelIumderIvedrelaxIngfactor(nItrIcoxIde)fromvascularendothelIum,Increases
capIllarypermeabIlIty,andcontractsaIrwayandvascularsmooth
P.261
muscle.
1,19,20
H
2
receptoractIvatIoncausesgastrIcsecretIon,InhIbItsmastcellactIvatIon,
andcontrIbutestovasodIlatIon.
19
WhenInjectedIntoskIn,hIstamIneproducestheclassIc
wheal(IncreasedcapIllarypermeabIlItyproducIngtIssueedema)andflare(cutaneous
vasodIlatIon)responseInhumans.
21
HIstamIneundergoesrapIdmetabolIsmInhumansby
theenzymeshIstamIneNmethyltransferaseanddIamIneoxIdasefoundInendothelIal
cells.
1
Table 12-3 Recognition of Anaphylaxis During Regional and General
Anesthesia
SYSTEMS SYMPTOMS SIGNS
FespIratory
0yspnea CoughIng
ChestdIscomfort
WheezIng
SneezIng
Laryngealedema
0ecreasedpulmonarycomplIance
FulmInantpulmonaryedema
AcuterespIratoryfaIlure
CardIovascular
0IzzIness 0IsorIentatIon
|alaIse 0IaphoresIs
Fetrosternal
oppressIon
LossofconscIousness
HypotensIon
TachycardIa
0ysrhythmIas
0ecreasedsystemIcvascular
resIstance
CardIacarrest
PulmonaryhypertensIon
Cutaneous
tchIng UrtIcarIa(hIves)
8urnIng FlushIng
TInglIng PerIorbItaledema
PerIoraledema
FeprIntedwIthpermIssIonfromLevyJH:AnaphylactIcFeactIonsInAnesthesIaand
ntensIveCare,2ndedItIon.8oston,8utterworthHeInemann,1992.
Figure 12-7.0urInganaphylaxIs(typeImmedIatehypersensItIvItyreactIon),(1)
antIgenentersapatIentdurInganesthesIathroughaparenteralroute.(2)tbrIdges
twoImmunoglobulInEantIbodIesonthesurfaceofmastcellsorbasophIls.na
calcIumdependentandenergydependentprocess,cellsreleasevarIoussubstances
hIstamIne,eosInophIlIcchemotactIcfactorofanaphylaxIs(ECFA),leukotrIenes,
prostaglandIns,andkInIns.(3)ThesereleasedmedIatorsproducethecharacterIstIc
effectsInthepulmonary,cardIovascular,andcutaneoussystems.Themostsevereand
lIfethreatenIngeffectsofthevasoactIvemedIatorsoccurIntherespIratoryand
cardIovascularsystems..7.,Intravenous;.|.,Intramuscular.(FeprIntedwIth
permIssIonfromLevyJH:dentIfIcatIonandTreatmentofAnaphylaxIs:|echanIsmsof
ActIonandStrategIesforTreatmentUnderCeneralAnesthesIa.ChIcago,SmIth
LaboratorIes,198J.)
Peptide Mediators of Anaphylaxis
FactorsarereleasedfrommastcellsandbasophIlsthatcausegranulocytemIgratIon
(chemotaxIs)andcollectIonatthesIteoftheInflammatorystImulus.
18
EosInophIlIc
chemotactIcfactorofanaphylaxIs(ECFA)IsasmallmolecularweIghtpeptIdechemotactIc
foreosInophIls.
22
AlthoughtheexactroleofECFAortheeosInophIlInacuteallergIc
responseIsunclear,
P.262
eosInophIlsreleaseenzymesthatcanInactIvatehIstamIneandleukotrIenes.
18
naddItIon,
aneutrophIlIcchemotactIcfactorIsreleasedthatcauseschemotaxIsandactIvatIon.
18,2J
NeutrophIlactIvatIonmayberesponsIbleforrecurrentmanIfestatIonsofanaphylaxIs.
Table 12-4 Biological Effects of Anaphylatoxins
Biological Effects C32 C52
HIstamInerelease + +
SmoothmusclecontractIon + +
ncreasedvascularpermeabIlIty + +
ChemotaxIs +
LeukocyteandplateletaggregatIon +
nterleukInrelease + +
Arachidonic Acid Metabolites
LeukotrIenesandprostaglandInsarebothsynthesIzedaftermastcellactIvatIonfrom
arachIdonIcacIdmetabolIsmofphospholIpIdcellmembranesthrougheItherlIpoxygenase
orcyclooxygenasepathways.
24,25
TheclassIcslowreactIngsubstanceofanaphylaxIsIsa
combInatIonofleukotrIenesC
4
,0
4
,andE
4
.
25
LeukotrIenesproducebronchoconstrIctIon
(moreIntensethanthatproducedbyhIstamIne),IncreasedcapIllarypermeabIlIty,
vasodIlatIon,coronaryvasoconstrIctIon,andmyocardIaldepressIon.
25
ProstaglandInsare
potentmastcellmedIatorsthatproducevasodIlatIon,bronchospasm,pulmonary
hypertensIon,andIncreasedcapIllarypermeabIlIty.
18,25
ProstaglandIn0
2
,themajor
metabolIteofmastcells,producesbronchospasmandvasodIlatIon.
25
Elevatedplasma
levelsofthromboxane8
2
(themetabolIteofthromboxaneA
2
),alsoaprostaglandIn
synthesIzedbymastcellsaswellasbyP|Ns,havebeendemonstratedafterprotamIne
reactIonsassocIatedwIthpulmonaryhypertensIon.
26,27
Kinins
SmallpeptIdescalledkininsaresynthesIzedInmastcellsandbasophIlstoproduce
vasodIlatIon,IncreasedcapIllarypermeabIlIty,andbronchoconstrIctIon.
18,28
KInInscan
stImulatevascularendothelIumtoreleasevasoactIvefactors,IncludIngprostacyclIn,and
endothelIalderIvedrelaxIngfactorssuchasnItrIcoxIde.
1
Platelet-Activating Factor
PlateletactIvatIngfactor(PAF),anunstoredlIpIdsynthesIzedInactIvatedhumanmast
cells,IsapotentbIologIcalmaterIal,producIngphysIologIceffectsatconcentratIonsaslow
as10
10
|.
18
PAFaggregatesandactIvateshumanplatelets,andperhapsleukocytes,to
releaseInflammatoryproducts.PAFcausesanIntensewhealandflareresponse,smooth
musclecontractIon,andIncreasedcapIllarypermeabIlIty.
18
Recognition of Anaphylaxis
TheonsetandseverItyofthereactIonrelatetothemedIator'sspecIfIcendorganeffects.
AntIgenIcchallengeInasensItIzedIndIvIdualusuallyproducesImmedIateclInIcal
manIfestatIonsofanaphylaxIs,buttheonsetmaybedelayed2to20mInutes.
29,J0
The
reactIonmayIncludesomeorallthesymptomsandsIgnslIstedInTable12J.ndIvIduals
varyIntheIrmanIfestatIonsandcourseofanaphylaxIs.
J1,J2
AspectrumofreactIonsexIsts,
rangIngfrommInorclInIcalchangestothefullblownsyndromeleadIngtodeath.
J1,JJ
The
enIgmaofanaphylaxIslIesIntheunpredIctabIlItyofwhenIthappens,theseverItyofthe
attack,andthelackofaprIorallergIchIstory.
NonIgE-Mediated Reactions
DtherImmunologIcandnonImmunologIcmechanIsmsreleasemanyofthemedIators
prevIouslydIscussed,IndependentofgE,creatIngaclInIcalsyndromeIdentIcalwIth
anaphylaxIs.SpecIfIcpathwaysImportantInproducIngthesameclInIcalmanIfestatIonsare
consIderedlater.
Complement Activation
ComplementactIvatIonfollowsbothImmunologIc(antIbodymedIated;I.e.,classIc
pathway)ornonImmunologIc(alternatIve)pathwaystoIncludeaserIesofmultImolecular,
selfassemblIngproteInsthatreleasebIologIcallyactIvecomplementfragmentsofCJand
C5.
10,J4
CJaandC5aarecalledanaphylatoxinsbecausetheyreleasehIstamInefrommast
cellsandbasophIls,contractsmoothmuscle,IncreasecapIllarypermeabIlIty,andcause
InterleukInsynthesIs(Table124).C5aInteractswIthspecIfIchIghaffInItyreceptorson
P|Nsandplatelets,causIngleukocytechemotaxIs,aggregatIon,andactIvatIon.
J5
AggregatedleukocytesembolIzetovarIousorgans,producIngmIcrovascularocclusIonand
lIberatIonofInflammatoryproductssuchasarachIdonIcacIdmetabolItes,oxygenfree
radIcals,andlysosomalenzymes(FIg.128).AntIbodIesofthegCclassdIrectedagaInst
antIgenIcdetermInantsorgranulocytesurfacescanalsoproduceleukocyteaggregatIon.
J6
These
P.26J
antIbodIesarecalledleukoagglutinins.nvestIgatorshaveassocIatedcomplement
actIvatIonandP|NaggregatIonInproducIngtheclInIcalexpressIonoftransfusIon
reactIons,
J6,J7
pulmonaryvasoconstrIctIonafterprotamInereactIons,
27
adultrespIratory
dIstresssyndrome,
J6
andseptIcshock.
J8
Table 12-5 Drugs Capable of Nonimmunologic Histamine Release
AntIbIotIcs(vancomycIn,pentamIdIne)
8asIccompounds
HyperosmotIcagents
|usclerelaxants(dtubocurarIne,metocurIne,atracurIum,mIvacurIum,
doxacurIum)
DpIoIds(morphIne,meperIdIne,codeIne)
ThIobarbIturates
Figure 12-8.SequenceofeventsproducInggranulocyteaggregatIon,pulmonary
leukostasIs,andcardIopulmonarydysfunctIon.(FeprIntedfromLevyJH:AnaphylactIc
FeactIonsInAnesthesIaandntensIveCare,2ndedItIon.8oston,8utterworth
HeInemann,1992.)
Nonimmunologic Release of Histamine
|anydIversemoleculesadmInIstereddurIngtheperIoperatIveperIodreleasehIstamIneIn
adosedependent,nonImmunologIcfashIon
J9,40,41,42,4J
(Table125andFIg.129).The
mechanIsmsInvolvedInnonImmunologIchIstamInereleasearenotwellunderstood,but
representselectIvemastcellandnotbasophIlactIvatIon.
4J,44
(FIg.1210).Human
cutaneousmastcellsaretheonlycellpopulatIonthatreleaseshIstamIneInresponseto
bothdrugsandendogenousstImulI(neuropeptIdes).
1
NonImmunologIchIstamInerelease
mayInvolvemastcellactIvatIonthroughspecIfIccellsIgnalIngactIvatIon.
40
(FIg.1211).
0IfferentmolecularstructuresreleasehIstamIneInhumans,whIchsuggeststhatdIfferent
mechanIsmsareInvolved.HIstamInereleasedoesnotdependonthereceptorbecause
fentanylandsufentanIl,themostpotentreceptoragonIstsclInIcallyavaIlable,donot
releasehIstamIneInhumanskIn.
J9
Althoughthenewermusclerelaxantsmaybemore
potentattheneuromuscularjunctIon,drugsthataremastcelldegranulatorsareequally
capableofreleasInghIstamIne.
J9,40
DnanequImolarbasIs,atracurIumIsaspotentasd
tubocurarIneormetocurIneInItsabIlItytodegranulatemastcells.
40
AtclInIcally
recommendeddoses,neweramInosteroIdalagents(suchasrocuronIumandrapacuronIum)
havemInImaleffectsonhIstamInerelease.
44,45
Figure 12-9.ExampleofananaphylactIcreactIonafterrapIdvancomycIn
admInIstratIonInapatIent.HypotensIonIsassocIatedwIthanIncreasedcardIacoutput
anddecreasedcalculatedsystemIcvascularresIstance.PlasmahIstamInelevels1
mInuteafterthevancomycInadmInIstratIonwere2.4ng/mLandsubsequently
decreasedtozero.ThepatIentwasgIvenephedrIne,5mg,andbloodpressure
returnedtobaselInevalues.AP,arterIalpressure;PAP,pulmonaryarterIalpressure;
CD,cardIacoutput;HF,heartrate;C7P,centralvenouspressure;S7F,systemIc
vascularresIstance.(FeprIntedfromLevyJH,KettlekampN,CoertzP,HermensJ,
HIrshmanCA:HIstamInereleasebyvancomycIn:AmechanIsmforhypotensIonInman.
AntIhIstamInepretreatmentbeforeadmInIstratIonofdrugsthatareknowntorelease
hIstamIneInhumansdoesnotInhIbIthIstamInerelease;rather,theantIhIstamInes
competewIthhIstamIneatthereceptorandmayattenuatedecreasesInsystemIcvascular
resIstance.
1
However,theeffectofanydrugonsystemIcvascularresIstancemaydepend
onotherfactorsInaddItIontohIstamInerelease.
46,47
Treatment Plan
AplanfortreatInganaphylactIcreactIonsmustbeestablIshedbeforetheevent.AIrway
maIntenance,100oxygenadmInIstratIon,IntravascularvolumeexpansIon,and
epInephrIneareessentIaltotreatthehypotensIonandhypoxIathatresultfrom
vasodIlatIon,IncreasedcapIllarypermeabIlIty,andbronchospasm.
1
Table126lIstsa
protocolformanagInganaphylaxIsdurInggeneralanesthesIa,wIthrepresentatIvedosesfor
a70kgadult.ThetreatmentplanIsthesameforlIfethreatenInganaphylactIcor
anaphylactoIdreactIons.TherapymustbetItratedtoneededeffectswIthcareful
monItorIng.
1
SeverereactIonsneedaggressIvetherapyandmaybeprotracted,wIth
persIstenthypotensIon,pulmonaryhypertensIon,lowerrespIratoryobstructIon,or
laryngealobstructIonthatmaypersIst5toJ2hoursdespItevIgoroustherapy.
48
AllpatIents
whohaveexperIencedananaphylactIcreactIonshouldbeadmIttedtoanIntensIvecare
unItfor24hoursofmonItorIngbecausemanIfestatIonsmayrecuraftersuccessful
treatment.
Figure 12-10.ElectronmIcrographofhumancutaneousmastcellafterInjectIonof
dynorphIn,aopIoIdagonIst.ThecelloutlIneIsroundedandmostofthecytoplasmIc
granulesareswollen,exhIbItIngvaryIngdegreesofdecreasedelectrondensItyand
flocculenceconsIstentwIthongoIngdegranulatIon.TheperIgranularmembranesofthe
adjacentgranulesattheperIpheryofthecellarefusedtoeachotherandtoplasma
membrane.DrIgInalmagnIfIcatIon72,000.(FeprIntedwIthpermIssIonfromCasaleT8,
8owmanS,KalIner|:nductIonofhumancutaneousmastcelldegranulatIonby
opIatesandendogenousopIoIdpeptIdes:EvIdenceforopIateandnonopIatereceptor
partIcIpatIon.JAllergyClInmmunol1984;7J:778781.)
P.264
Initial Therapy
AlthoughItmaynotbepossIbletostoptheadmInIstratIonofantIgen,lImItIngantIgen
admInIstratIonmaypreventfurthermastcellandbasophIlactIvatIon.
Maintain Airway and Administer 100% Oxygen
ProfoundventIlatIonperfusIonabnormalItIesproducInghypoxemIacanoccurwIth
anaphylactIcreactIons.
49
AlwaysadmInIster100oxygen,wIthventIlatorysupportas
needed.ArterIalbloodgasvaluesmaybeusefultofollowdurIngresuscItatIon(seeChapter
59).
Figure 12-11.0IfferentmechanIsmsofmedIatorreleasefromhumancutaneousmast
cellsstImulatedImmunologIcallybyantIImmunoglobulIn(g)EandbynonImmunologIc
stImulIwIthsubstanceP.AntIgEstImulatIon,lIkeantIgenstImulatIon,InItIatesthe
releaseofhIstamIne,prostaglandIn0
2
(PC0
2
),orleukotrIeneC
4
(LTC
4
)byamechanIsm
thattakes5mInutestoreachcompletIonandrequIrestheInfluxofIntracellular
calcIum.NonImmunologIcactIvatIonwIthdrugsorsubstancePreleaseshIstamInebut
notPC0
2
orLTC
4
byamechanIsmthatIscompletewIthIn15secondsandusescalcIum
mobIlIzedfromIntracellularsources.(FeprIntedwIthpermIssIonfromCaulfIeldJP,El
LatIS,ThomasC,Church|K:0IssocIatedhumanforeskInmastcellsdegranulateIn
responsetoantIgEandsubstanceP.Labnvest1990;6J:502510.)
Discontinue All Anesthetic Drugs
nhalatIonalanesthetIcdrugsarenotthebronchodIlatorsofchoIcetotreatbronchospasm
durInganaphylaxIs,especIallyIfthepatIentIshypotensIve.
P.265
ThesedrugsInterferewIththebody'scompensatoryresponsetocardIovascularcollapse,
andhalothanesensItIzesthemyocardIumtoepInephrIne.
Table 12-6 Management of Anaphylaxis During General Anesthesia
INITIAL THERAPY
1. StopadmInIstratIonofantIgen.
2. |aIntaInaIrwayandadmInIster100D
2
.
J. 0IscontInueallanesthetIcagents.
4. StartIntravascularvolumeexpansIon(24LofcrystalloId/colloIdwIth
hypotensIon).
5. CIveepInephrIne(510g7boluswIthhypotensIon,tItrateasneeded;0.11.0
mg7wIthcardIovascularcollapse).
SECONDARY TREATMENT
1. AntIhIstamInes(0.51mg/kgdIphenhydramIne)
2. CatecholamIneInfusIons(startIngdoses:epInephrIne,48g/mIn;
norepInephrIne,48g/mIn;orIsoproterenol,0.51g/mInasanInfusIon;
tItratedtodesIredeffects)
J. 8ronchodIlators:Inhaledalbuterol,terbutalIne,and/orantIcholInergIcagents
wIthpersIstentbronchospasm)
4. CortIcosteroIds(0.251ghydrocortIsone;alternatIvely,12g
methylprednIsolone)
a
5. SodIumbIcarbonate(0.51mEq/kgwIthpersIstenthypotensIonoracIdosIs)
6. AIrwayevaluatIon(beforeextubatIon)
7. 7asopressInforrefractoryshock
7,Intravenous(ly).
a
|ethylprednIsolonemaybethedrugofchoIceIfthereactIonIssuspectedtobe
medIatedbycomplement.
ntensIveCare,2ndedItIon,8oston,8utterworthHeInemann,1992;p162.
Provide Volume Expansion
HypovolemIarapIdlydevelopsdurInganaphylactIcshock.
50
FIsher
50
reportedupto40loss
ofIntravascularfluIdIntotheInterstItIalspacedurIngreactIons.Therefore,volume
expansIonandepInephrIneareImportantIncorrectIngtheacutehypotensIon.nItIally,2
to4LoflactatedFIngersolutIon,colloId,ornormalsalIneshouldbeadmInIstered,keepIng
InmIndthatanaddItIonal25to50mL/kgmaybenecessaryIfhypotensIonpersIsts.
FefractoryhypotensIonafterIntravascularvolumeandepInephrIneadmInIstratIonrequIres
addItIonalhemodynamIcmonItorIng.TheuseoftransesophagealechocardIographyfor
rapIdassessmentofIntraventrIcularvolumeandventrIcularfunctIon,andtodetermIne
otheroccultcausesofacutecardIovasculardysfunctIon,canbeImportantforaccurate
assessmentofIntravascularvolumeandguIdanceofratIonaltherapeutIcInterventIons.
51
FulmInantnoncardIogenIcpulmonaryedemawIthlossofIntravascularvolumecanoccur
afteranaphylaxIs.ThIscondItIonrequIresIntravascularvolumerepletIonwIthcareful
hemodynamIcmonItorInguntIlthecapIllarydefectImproves.ColloIdvolumeexpansIonhas
notprovedtobemoreeffectIvethancrystalloIdvolumeexpansIonfortreatIng
anaphylactIcshock.
Administer Epinephrine
EpInephrIneIsthedrugofchoIcewhenresuscItatIngpatIentsdurInganaphylactIcshock.
EpInephrIne'sadrenergIceffectsvasoconstrIcttoreversehypotensIon;
2
receptor
stImulatIonbronchodIlatesandInhIbItsmedIatorreleasebyIncreasIngcyclIcadenosIne
monophosphateInmastcellsandbasophIls.
52,5J,54
TherouteofepInephrIneadmInIstratIon
andthedosedependonthepatIent'scondItIon.FapIdandtImelyInterventIonIsImportant
whentreatInganaphylaxIs.Furthermore,patIentsundergeneralanesthesIamayhave
alteredsympathoadrenergIcresponsestoacuteanaphylactIcshock,whereaspatIentsunder
spInalorepIduralanesthesIamaynotbeabletomounttheapproprIatevasoconstrIctIve
sympathetIcresponseandmayneedevenlargerdosesofcatecholamInes.
nhypotensIvepatIents,5to10gIntravenousdosesofepInephrIneshouldbe
admInIsteredIncrementallytorestorebloodpressure.AddItIonalvolumeandIncrementally
IncreaseddosesofepInephrIneshouldbeadmInIstereduntIlhypotensIonIscorrected.
nfusIonIsanIdealmethodofadmInIsterIngepInephrIne;ItIsbesttoInfuseepInephrIne
throughcentralIntravenousaccesslInesdurIngacutevolumeresuscItatIon.f
cardIovascularcollapseensues,IntravenouscardIopulmonaryresuscItatIvedosesof
epInephrIne,0.1to1.0mg,shouldbeadmInIsteredandrepeateduntIlhemodynamIc
stabIlItyresumes.PatIentswIthlaryngealedemawIthouthypotensIonshouldreceIve
subcutaneousepInephrIne.ntravenousepInephrIneshouldnotbeadmInIsteredtopatIents
wIthnormalbloodpressures.
Secondary Treatment
Antihistamines
8ecauseH
1
receptorsmedIatemanyoftheadverseeffectsofhIstamIne,theIntravenous
admInIstratIonof0.5to1mg/kgofanH
1
antagonIstsuchasdIphenhydramInemaybe
usefulIntreatIngacuteanaphylaxIs.AntIhIstamInesdonotInhIbItanaphylactIcreactIons
orhIstamInerelease,butcompetewIthhIstamIneatreceptorsItesafterItIsreleased.H
1
antagonIstsareIndIcatedInallformsofanaphylaxIs.TheH
1
antagonIstsavaIlablefor
parenteraladmInIstratIonmayhaveantIdopamInergIceffectsandshouldbegIvenslowlyto
preventprecIpItoushypotensIonInpotentIallyhypovolemIcpatIents.
1
TheIndIcatIonsfor
admInIsterInganH
2
antagonIstonceanaphylaxIshasoccurredremaInunclear.
Catecholamines
EpInephrIneInfusIonsmaybeusefulInpatIentswIthpersIstenthypotensIonor
bronchospasmafterInItIalresuscItatIon.
1
EpInephrIneInfusIonsshouldbestartedat0.05to
0.1g/kg/mIn(5to10g/mIn)andtItratedtocorrecthypotensIon.NorepInephrIne
InfusIonsmaybeneededInpatIentswIthrefractoryhypotensIonduetodecreasedsystemIc
vascularresIstance.tmaybestartedat0.05to0.1g/kg/mInandadjustedtocorrect
hypotensIon.
51
Bronchodilators
nhaledadrenergIcagents,IncludIngInhaledalbuterolorterbutalIne,IfbronchospasmIs
amajorfeature.
54
nhaledIpratropIummaybeespecIallyusefulfortreatmentof
bronchospasmInpatIentsreceIvIngadrenergIcblockers.
54
SpecIaladaptersallow
admInIstratIonofbronchodIlatorsthroughtheendotrachealtube(seeChapter2).
Corticosteroids
CortIcosteroIdshaveaserIesofantIInflammatoryeffectsmedIatedbymultIple
mechanIsms,IncludIngalterIngtheactIvatIonandmIgratIonofotherInflammatorycells
(e.g.,P|Ns)afteranacutereactIon.
5J,54
DneshouldconsIderInfusInghIghdose
cortIcosteroIdsearlyInthecourseoftherapy,althoughbenefIcIaleffectsaredelayedat
least4to6hours.
54
0espItetheIrunprovenusefulnessIntreatIngacutereactIons,
cortIcosteroIdsareoftenadmInIsteredasadjunctstotherapywhenrefractory
bronchospasmorrefractoryshockoccursafterresuscItatIvetherapy.
55
Althoughtheexact
cortIcosteroIddoseandpreparatIonareunclear,InvestIgatorshaverecommended0.25to1
gIntravenouslyofhydrocortIsoneIngEmedIatedreactIons.Alternately,1to2gof
methylprednIsolone(J0toJ5mg/kg)IntravenouslymaybeusefulInreactIonsbelIevedto
becomplementmedIated,suchascatastrophIcpulmonaryvasoconstrIctIonafter
protamInetransfusIonreactIons.
56
AdmInIsterIngcortIcosteroIdsafterananaphylactIc
reactIonmayalsobeImportantInattenuatIngthelatephasereactIonsreportedtooccur
12to24hoursafteranaphylaxIs.
48
Bicarbonate
AcIdosIsdevelopsrapIdlyInpatIentswIthpersIstenthypotensIon.ThIsacIdemIareduces
theeffectofepInephrIneontheheartandsystemIcvasculature.Therefore,wIthrefractory
hypotensIonoracIdemIa,sodIumbIcarbonate,0.5to1mEq/kg,maybegIvenandrepeated
every5mInutesorasdIctatedbyarterIalbloodgasvalues.
Airway Evaluation
8ecauseprofoundlaryngealedemacanoccur,theaIrwayshouldbeevaluatedbefore
extubatIonofthetrachea.
29
PersIstentfacIaledemasuggestsaIrwayedema.Thetrachea
ofthesepatIentsshouldremaInIntubateduntIltheedemasubsIdes.0evelopInga
sIgnIfIcantaIrleakafterendotrachealtubecuffdeflatIonandbeforeextubatIonofthe
tracheaIsusefulInassessIngaIrwaypatency.fthereIsanyquestIonofaIrwayedema,
dIrectlaryngoscopyshouldbeperformedbeforethetracheaIsextubated.
Refractory HypotensionVasopressin
7asopressInIsanImportantdrugforrefractoryshock,IncludIngvasodIlatoryshock
assocIatedwIthanaphylaxIs.7asodIlatoryshockIscharacterIzedbyhypotensIonassocIatIon
wIthahIghcardIacoutput,andIsthoughttobeduetothemultIpleactIvatIonof
vasodIlatormechanIsmsandtheInabIlItyofadrenergIcmechanIsmstocompensate.
51
StartIngdosestoconsIderare0.01unIts/mInasanInfusIon,althoughbolusadmInIstratIon
IspartofAdvancedCardIopulmonaryLIfeSupportguIdelInes.7asopressInmayattenuate
pathologIcInducedvasodIlatIon.Further,addItIonalmonItorIng,IncludIng
echocardIographyandpreferablytransesophageal,shouldbeconsIderedInpatIentswIth
refractoryhypotensIontobetterevaluatecardIacfunctIonorhypovolemIa.
P.266
Perioperative Management of the Patient with Allergies
AllergIcdrugreactIonsaccountfor6to10ofalladversereactIons.
57
0eSwarte
58
suggestedthattherIskofanallergIcdrugreactIonoccurrIngIsapproxImately1toJfor
mostdrugs,andthataround5ofadultsIntheUnItedStatesmaybeallergIctooneor
moredrugs.Unfortunately,patIentsoftenrefertoadversedrugeffectsasbeIngallergIcIn
nature.Forexample,opIoIdadmInIstratIoncanproducenausea,vomItIng,orevenlocal
releaseofhIstamInealongtheveInofadmInIstratIon.PatIentswIllsaytheyareallergIc
toaspecIfIcdrugwhen,Infact,theIradversereactIonIsIndependentofallergy.Nearly
15ofadultsIntheUnItedStatesbelIevetheyareallergIctospecIfIcmedIcatIon(s)and
thereforemaybedenIedtreatmentwIthanIndIcateddrug.TounderstandallergIc
reactIons,thespectrumofadversereactIonstodrugsneedstobeconsIdered.
PredIctableadversedrugreactIonsaccountforabout80ofadversedrugeffects.Theyare
oftendosedependent,relatedtoknownpharmacologIcactIonsofthedrug,andtypIcally
occurInnormalpatIents.|ostserIous,predIctableadversedrugreactIonsaretoxIcand
aredIrectlyrelatedtothedrugInthebody(overdosage)ortoanunIntentIonalrouteof
admInIstratIon(e.g.,unIntendedIntravenousbupIvacaIneInducedseIzuresand
cardIovascularcollapse).SIdeeffectsarethemostcommonadversedrugreactIonsandare
undesIrablepharmacologIcactIonsofthedrugsoccurrIngatusualprescrIbeddosages.|ost
anesthetIcdrugspresentmultIplesIdeeffectsthatcanproduceprecIpItoushypotensIon.
Forexample,morphInedIlatesthevenouscapacItancebed,therebydecreasIngpreload;
releaseshIstamInefromcutaneousmastcells,therebyproducIngarterIalandvenous
dIlatIon;slowstheheartrate;anddecreasessympathetIctone.However,theneteffectsof
morphIneonbloodpressureandmyocardIalfunctIondependonthepatIent'sbloodvolume,
sympathetIctone,andventrIcularfunctIon.HypotensIonrapIdlydevelopsInavolume
depletedtraumapatIentInpaInwhoIsgIvenmorphIne.0rugInteractIonsalsorepresent
ImportantpredIctableadversedrugreactIons.ntravenousfentanyladmInIstratIontoa
patIentwhohasjustreceIvedIntravenousbenzodIazepInesorothersedatIvehypnotIc
drugsmayproduceprecIpItoushypotensIonthatresultsfromdecreasedsympathetIctone
ordIrectvasodIlatIonfrompropofoladmInIstratIon.
59
ThIsphenomenonrepresentsadose
dependent,predIctableadversedrugreactIonthatIsIndependentofallergy.
UnpredIctableadversedrugreactIonsareusuallydoseIndependentandusuallynotrelated
tothedrug'spharmacologIcactIons,butareoftenrelatedtotheImmunologIcresponse
(allergy)oftheIndIvIdual.DnoccasIon,adversereactIonscanberelatedtogenetIc
dIfferences(I.e.,IdIosyncratIc)InasusceptIbleIndIvIdualwhohasanIsolatedgenetIc
enzymedefIcIency.nmostallergIcdrugreactIons,anImmunologIcmechanIsmIspresent
or,moreoften,presumed.ProvIdIngthatthecausaleventInvolvesareactIonbetweenthe
drugordrugmetabolIteswIthdrugspecIfIcantIbodIesorsensItIzedTlymphocytesIsoften
ImpractIcal.WIthoutdIrectImmunologIcevIdence,attrIbutesthatmaybehelpfulIn
dIstInguIshInganallergIcreactIonfromotheradversereactIonsInclude(1)allergIc
reactIonsoccurInonlyasmallpercentageofpatIentsreceIvIngthedrug,and(2)the
clInIcalmanIfestatIonsdonotresembleknownpharmacologIcactIons.ntheabsenceof
prIordrugexposure,allergIcsymptomsrarelyappearafter1weekofcontInuous
treatment.AftersensItIzatIon,thereactIondevelopsrapIdlyonreexposuretothedrug.n
general,drugsthathavebeenadmInIsteredwIthoutcomplIcatIonsforseveralmonthsor
longerarerarelyresponsIbleforproducIngdrugallergy.ThetImespanbetweenexposure
tothedrugandnotIcedmanIfestatIonsIsoftenthemostvItalInformatIonIndecIdIng
whIchdrugsadmInIsteredwerethecauseofasuspectedallergIcreactIon.
AlthoughthereactIonmayproducealIfethreatenIngresponseInthecardIopulmonary
system(anaphylaxIs),varIouscutaneousmanIfestatIons,fever,andpulmonaryreactIons
havebeenattrIbutedtodrughypersensItIvIty.Usually,thereactIonmaybereproducedby
smalldosesofthesuspecteddrugorotheragentshavIngsImIlarorcrossreactIngchemIcal
structures.DnoccasIon,drugspecIfIcantIbodIesorlymphocyteshavebeenIdentIfIedthat
reactwIththesuspecteddrug,althoughtherelatIonshIpIsseldomdIagnostIcallyusefulIn
practIce.EvenwhenanImmuneresponsetoadrugIsdemonstrated,Itmaynotbe
assocIatedwIthaclInIcalallergIcreactIon.AswIthadversedrugreactIonsIngeneral,the
reactIonusuallysubsIdeswIthInseveraldaysofdIscontInuatIonofthedrug.
Immunologic Mechanisms of Drug Allergy
0IfferentImmunologIcresponsestoanyantIgencanoccur.0rugshavebeenassocIatedwIth
alltheImmunologIcmechanIsmsproposedbyCelletal.
J
Althoughmorethanone
mechanIsmmaycontrIbutetoapartIcularreactIon,anyonecanoccur.PenIcIllInmay
producedIfferentreactIonsIndIfferentpatIentsoraspectrumofreactIonsInthesame
patIent.nonepatIent,penIcIllIncanproduceanaphylaxIs(typereactIon),hemolytIc
anemIa(typereactIon),serumsIckness(typereactIon),andcontactdermatItIs(type
7reactIon).
58
Therefore,anyoneantIgenhastheabIlItytoproduceadIffusespectrumof
allergIcresponsesInhumans.WhysomepatIentshavelocalIzedrashesorangIoneurotIc
edemaInresponsetopenIcIllInwhereasotherssuffercompletecardIopulmonarycollapseIs
unknown.|ostanesthetIcdrugsandagentsadmInIsteredperIoperatIvelyhavebeen
reportedtoproduceanaphylactIc
reactIons.
J1,J9,40,41,42,4J,44,45,60,61,62,6J,64,65,66,67,68,69,70,71,72,7J,74,75,76,77,78,79,80,81
|uscle
relaxantsarethemostcommondrugsresponsIbleforevokIngIntraoperatIveallergIc
reactIons.
67
nthIsregard,thereIscrosssensItIvItybetweensuccInylcholIneandthe
nondepolarIzIngmusclerelaxants.UnexplaInedIntraoperatIvecardIovascularcollapsehas
beenattrIbutedtoanaphylaxIstrIggeredbylatex(naturalrubber),andcertaInpatIents,
IncludIngthosewIthahIstoryofspInabIfIda,areatagreaterrIskforreactIons.
1,68
Even
vasculargraftmaterIalhasbeenreportedasacauseofIntraoperatIveallergIcreactIons.
69
LIfethreatenIngallergIcreactIonsaremorelIkelytooccurInpatIentswIthahIstoryof
allergy,atopy,orasthma.Nevertheless,becausetheIncIdenceIslow,thehIstoryIsnota
relIablepredIctorthatanallergIcreactIonwIlloccuranddoesnotmandatethatsuch
patIentsshouldbeInvestIgatedorpretreated,orthatspecIfIcdrugsbeselectedor
avoIded.
60
AlthoughdIfferentmechanIsmshavebeenproposed,noonetheoryhasbeen
proved.
1
ThedrugsandforeIgnsubstanceslIstedInTable127mayhavebothImmunologIc
andnonImmunologIcmechanIsmsforadversedrugreactIonsInhumans.
Evaluation of Patients With Allergic Reactions
dentIfyIngthedrugresponsIbleforasuspectedallergIcreactIonstIlldependson
cIrcumstantIalevIdence,suggestIngthetemporalsequenceofdrugadmInIstratIon.
ConventIonalin vivoandin vitromethodsofdIagnosIngallergIcreactIonstomost
anesthetIcdrugsareunavaIlableornotapplIcable.The
P.267
mostImportantfactorIndIagnosIsIstheawarenessofthephysIcIanthatanuntoward
eventmayberelatedtoadrugthepatIentreceIved.ThephysIcIanmustalwaysbeaware
ofthecapacItyofanydrugtoproduceanallergIcreactIon.ThehIstoryIsImportantwhen
evaluatIngwhetheranadversedrugreactIonIsallergIcandwhetherthedrugcanbe
readmInIstered.AlthoughaprIorallergIcreactIontothedrugInquestIonIsImportant,It
wIllrarelybeconclusIve.0IrectchallengeofapatIentwIthatestdoseofdrugIstheonly
waytoproveareactIon,butthIsIspotentIallydangerousandnotrecommended.Although
theanesthesIologIstcommonlygIvessmalltestdosesofanesthetIcdrugs,theseare
pharmacologIctestdosesandhavenothIngtodowIthImmunologIcdosages.The
demonstratIonofdrugspecIfIcgEantIbodIesIsacceptedasevIdencethepatIentmaybe
atrIskforanaphylaxIsIfthedrugIsadmInIstered.
58
0IfferentclInIcaltestsareavaIlableto
confIrmordIagnosedrugallergy;severalareconsIderedInthefollowIngsectIon.
Table 12-7 Agents Implicated in Allergic Reactions During Anesthesia
ANESTHETIC AGENTS
nductIonagents(cremophorsolubIlIzeddrugs,barbIturates,etomIdate,propofol)
LocalanesthetIcs(paraamInobenzoIcesteragents)
|usclerelaxants(succInylcholIne,gallamIne,pancuronIum,dtubocurarIne,
metocurIne,atracurIum,vecuronIum,mIvacurIum,doxacurIum)
DpIoIds(meperIdIne,morphIne,fentanyl)
OTHER AGENTS
AntIbIotIcs(cephalosporIns,penIcIllIn,sulfonamIdes,vancomycIn)
AprotInIn
8loodproducts(wholeblood,packedcells,freshfrozenplasma,platelets,
cryoprecIpItate,fIbrInglue,globulIn)
8onecement
ChymopapaIn
CortIcosteroIds
CyclosporIn
0rugaddItIves(preservatIves)
FurosemIde
nsulIn
|annItol
|ethylmethacrylate
NonsteroIdalantIInflammatorydrugs
ProtamIne
FadIocontrastdye
Latex(naturalrubber)
StreptokInase
7asculargraftmaterIal
7ItamInK
ColloIdvolumeexpanders(dextrans,proteInfractIons,albumIn,hydroxyethyl
starch)
ntensIveCare,2ndedItIon.8oston,8utterworthHeInemann,1992.
Testing for Allergy
AfterananaphylactoIdreactIon,ItIsImportanttoIdentIfythecausatIveagenttoprevent
readmInIstratIon.WhenonepartIculardrughasbeenadmInIsteredandthereIsaclear
correlatIonbetweenthetImeofadmInIstratIonandtheoccurrenceofareactIon,testIng
maybeunnecessary,andgeneralavoIdanceofthedrugshouldbeInstItuted.However,
whenpatIentshavesImultaneouslyreceIvedmultIpledrugs(e.g.,anopIoId,muscle
relaxant,hypnotIc,andantIbIotIc),ItIsoftendIffIculttoprovewhIchpartIculardrug
causedthereactIon.Further,thereactIonmIghthavebeencausedbythevehIcleorby
oneofthepreservatIves.ForpatIentswhowanttoknowwhIchdrugwasresponsIbleand
forpatIentsscheduledforsubsequentprocedures,somedegreeofallergyevaluatIonshould
beundertakentoevaluatethedrugatrIsk.Unfortunately,fewlaboratorytestsexIstfor
anesthetIcdrugs;therefore,theavaIlableallergytestsaredIscussed.
Leukocyte Histamine Release
LeukocytehIstamInereleaseIsperformedbyIncubatIngthepatIent'sleukocyteswIththe
offendIngdrugandmeasurInghIstamInereleaseasamarkerforbasophIlactIvatIon,
althoughfalseposItIveresultscanoccur.
J1
ThIstestIsnoteasytoperform,although
varIatIonsallowtheuseofwholebloodInsteadofIsolatedP|Ns,andIsgenerallynot
avaIlable.
76,82
Radioallergosorbent Test
TheradIoallergosorbenttest(FAST)allowslaboratorydetectIonofspecIfIcgEdIrected
towardpartIcularantIgens.
8J
nthIstest,antIgensarelInkedtoInsolublematerIaltomake
anImmunoabsorbent.
8J,84
WhenIncubatedwIththeserumInquestIon,antIbodIesof
dIfferentclassesdIrectedtowardtheantIgenbIndtoIt.AfterwashIng,theantIgen
antIbodycomplexontheImmunoabsorbentIsIncubatedwIthradIolabeledantIbodIes
dIrectedagaInsthumangEandcountedInascIntIllatIoncounter.TheconcentratIonof
specIfIcgEInthepatIent'sserumdIrectedtowardtheallergenIsmeasured.TheFASTIs
morequantItatIvethanskIntestsandavoIdsthepotentIalofreexposure.
84
FASTtestIng
hasbeenusedtodetectthepresenceofantIbodIestomeperIdIne,
49
succInylcholIne,
85
and
thIopental.
86
Twomajor
P.268
lImItatIonstothIstestIncludethecommercIalavaIlabIlItyofthedrugpreparedasan
antIgenandfalseposItIvetestresultsInpatIentswIthhIghgElevels.
87
Enzyme-Linked Immunosorbent Assay
TheenzymelInkedImmunosorbentassay(ELSA)measuresantIgenspecIfIcantIbodIes.The
basIsoftheELSAIssImIlartothatoftheFAST;however,ImmunospecIfIcgEdIrected
agaInsttheantIgenInquestIonIsdetermInedbyaddInganantIgEcoupledtoanenzyme
suchasperoxIdasethatactsasachromogen.
5
AcolorlesssubstrateIsactedonby
peroxIdasetoproduceacoloredbyproduct.TheELSAhasbeenusedtoprovegE
antIbodIestochymopapaInandprotamIne,andhasbeendevelopedtoscreenforother
antIbodIestodIverseagents.
Intradermal Testing (Skin Testing)
SkIntestIngIsthemethodmostoftenusedInpatIentsafteranaphylactIcreactIonto
anesthetIcdrugsafterthehIstoryhassuggestedtherelevantantIgensfortestIng.
88,89
WIthInmInutesafterantIgenIntroductIon,hIstamInereleasedfromcutaneousmastcells
causesvasodIlatIon(flare)andlocalIzededemafromIncreasedvascularpermeabIlIty
(wheal).FIsherand|unro
67
andFIsher
88
suggestedthatthIsIsasImple,safe,anduseful
methodofestablIshIngadIagnosIsInmostcasesofanaphylactIcreactIonsoccurrIngInthe
perIoperatIveperIod.fthestrIctprotocolsestablIshedbyFIsher
88
areused,Intradermal
reactIonsarehelpful.ntradermaltestIngIsofnovalueInreactIonstocontrastmedIaor
colloIdvolumeexpanders.CrosssensItIvItybetweendrugsofsImIlarstructurescanoften
beevaluatedbasedonskIntestIng.SkIntestIngtolocalanesthetIcsIsconsIderedadIrect
challengeorprovocatIvedosetestIng.
90
LocalanesthetIcdrugsareInjectedInIncreasIng
quantItIesundercontrolledcIrcumstances.ThIstestIngdecIdesIfthepersoncansafely
receIveamIdederIvatIves(e.g.,lIdocaIne)andcanalsobeusedtodecIdeIfthepersonIs
sensItIvetotheparaamInobenzoIcesteragents(e.g.,procaIne,tetracaIne).
Agents Implicated in Allergic Reactions
|ultIpleagentsIncludIngantIbIotIcs,InductIonagents,musclerelaxants,nonsteroIdal
antIInflammatorydrugs,protamIne,colloIdvolumeexpanders,andbloodproductsare
theetIologIcagentsoftenresponsIbleforanaphylaxIsInsurgIcalpatIents.
1
However,any
agentthepatIentreceIvesasanInjectIon,InfusIon,orenvIronmentalantIgenhasthe
potentIaltoproduceanallergIcreactIon.
1
AlmosteverythInghasbeenreportedtoproduce
anallergIcreactIonatsometIme,butusuallyfromacasereportorsmallserIes.The
agentsmostoftenImplIcatedIncludeantIbIotIcs,bloodproducts,colloIdvolume
expanders,latex,polypeptIdes,andN|8As.fpatIentsareallergIctoamusclerelaxant,
thereIsapotentIalforcrossreactIvItybecauseofthesImIlarItyoftheactIvesIte,a
quaternaryammonIummolecule,amongthedIfferenttypesofrelaxants,andalternatIves
cannotbechosenwIthoutsomedegreeofImmunologIctestIng.8ecauseoftheubIquItyof
latexasaperIoperatIveenvIronmentalantIgen,latexallergyIsconsIderedseparately.
Latex Allergy
FortheanesthesIologIst,latexrepresentsanenvIronmentalagentoftenImplIcatedasan
ImportantcauseofperIoperatIveanaphylaxIs.
91,92,9J,94,95,96,97,98,99
LatexIsthemIlkysap
derIvedfromthetreeHevea brasiliensistowhIchmultIpleagents,IncludIngpreservatIves,
accelerators,andantIoxIdantsareaddedtomakethefInalrubberproduct.LatexIspresent
InavarIetyofdIfferentproducts.n|arch1991,theU.S.Foodand0rugAdmInIstratIon
alertedhealthcareprofessIonalsaboutthepotentIalofsevereallergIcreactIonsto
medIcaldevIcesmadeoflatex.ThefIrstcaseofanallergIcreactIonbecauseoflatexwas
reportedIn1979andwasmanIfestedbycontacturtIcarIa.n1989,thefIrstreportsof
IntraoperatIveanaphylaxIsbecauseoflatexwerereported.
HealthcareworkersandchIldrenwIthspInabIfIda,urogenItalabnormalItIes,orcertaIn
foodallergIeshavealsobeenrecognIzedaspeopleatIncreasedrIskforanaphylaxIsto
latex.
91,92,9J,94,95,96,97,98,99
8rownetal.
95
reporteda24IncIdenceofIrrItantorcontact
dermatItIsanda12.5IncIdenceoflatexspecIfIcgEposItIvItyInanesthesIologIsts.DfthIs
group,10wereclInIcallyasymptomatIc,althoughgEposItIve.AhIstoryofatopywasalso
asIgnIfIcantrIskfactorforlatexsensItIzatIon.8rownetal.
95
suggestedthatthesepeople
areIntheIrearlystagesofsensItIzatIonandtheIrprogressIontosymptomatIcdIseasemay
bepreventedbyavoIdInglatexexposure.PatIentsallergIctobananas,avocados,andkIwIs
havealsobeenreportedtohaveantIbodIesthatcrossreactwIthlatex.
96,97
|ultIple
attemptsarebeIngmadetoreducelatexexposuretobothhealthcareworkersand
patIents.flatexallergyoccurs,thenstrIctavoIdanceoflatexfromglovesandother
sourcesneedstobeconsIdered,followIngrecommendatIonsasreportedbyHolzman.
91
8ecauselatexIssuchacommonenvIronmentalantIgen,thIsrepresentsadauntIngtask.
|oreImportant,anesthesIologIstsmustbepreparedtotreatthelIfethreatenIng
cardIopulmonarycollapsethatoccursafteranaphylaxIs,asprevIouslydIscussed.Themost
ImportantpreventIvetherapyIstoavoIdantIgenexposure;althoughclInIcIanshaveused
pretreatmentwIthantIhIstamIne(dIphenhydramIneandcImetIdIne)andcortIcosteroIds,
therearenodataInthelIteraturetosuggestthatpretreatmentpreventsanaphylaxIsor
decreasesItsseverIty.
1
TwopatIentsInaserIesreportedbyColdetal.
9J
werepretreated,
yetstIllhadlIfethreatenIngreactIonstolatex.PatIentsInwhomlatexallergyIssuspected
shouldbereferredtoanallergIstforproperevaluatIonandpotentIalInvItrotestIng(FAST)
fordefInItIvedIagnosIs.WhenthIsIsnotpossIble,patIentsshouldbetreatedasIfthey
werelatexallergIc,andtheantIgenavoIded.PatIentswIthadocumentedhIstoryoflatex
allergyshouldwear|edIcAlertbracelets.
Muscle Relaxants
N|8AshaveseveralunIquemolecularfeaturesthatmakethempotentIalallergens.All
N|8AsarefunctIonallydIvalentandarethuscapableofcrosslInkIngcellsurfacegEand
causIngmedIatorreleasefrommastcellsandbasophIlswIthoutbIndIngorhaptenatIngto
largercarrIermolecules.N|8AshavealsobeenImplIcatedInepIdemIologIcstudIesof
anesthetIcdrugInducedanaphylaxIs.EpIdemIologIcdatafromFrancesuggestthatN|8As
areresponsIblefor62to81ofreactIons,dependIngontheperIod
evaluated.
100,101,102,10J,104,105
nmorerecentyears,N|8As,especIallysteroIdderIvedagents,havebeenreportedas
potentIalcausatIveagentsofanaphylactIcreactIonsdurInganesthesIa.Thedata
assocIatIngN|8AsInthemostrecentreportsfromFrancearemaInlybasedonskIntestIng;
however,studIeshaveprevIouslyreportedthesteroIdalderIvedN|8Asandother
moleculesproducefalseposItIveskIntests(I.e.,whealandflare).Dneofthemajor
problemsIsthatanaphylaxIstoN|8AsIsrareIntheUnItedStates,buthasbeenreported
moreoftenInEurope.
105,106,107
AlthoughsuggestIonshavebeenmadethatthIsIsbecause
ofunderreportIng,theseverItyofanaphylaxIsandItssequelaetoproduceadverse
outcomesclearlymakethIsunlIkelybasedonthecurrentmedIcolegalclImatethatexIstsIn
theUnItedStates.DneoftheonlywaystoexplaInthIswIdelydIvergentperspectIveIsto
understandhowthedIagnosIsIsmadebecausetherecommendedthresholdtest
concentratIonshavenotbeendefIned,resultIngInunrelIableresults.
WeprevIouslyreportedInseveralstudIesthatsteroIdderIvedagentscouldInduceposItIve
whealandflareresponses
P.269
IndependentofmastcelldegranulatIon,evenatlowconcentratIons,followIngIntradermal
InjectIon.ThIseffectIslIkelybecauseofadIrecteffectonthecutaneousvasculaturethat
occursformostN|8AsatconcentratIonsaslowas10
5
|usIngIntradermalskIntestsInJ0
volunteers.
106
AposItIvecutaneousreactIonwIthoutevIdenceofmastcelldegranulatIon
wasnotedatlowconcentratIons(100g/mL)ofrocuronIumInalmostallthevolunteers.
Levyetal.
106
haveusedIntradermalInjectIonstocomparecutaneouseffectsofanesthetIc
andotheragents.
DtherInvestIgatorshavealsoreportedsImIlarresults.8ecauseprIcktestsareoftenused
forauthentIcatIngN|8AsascausatIvedrugs,0honneuretal.
105
evaluatedJ0volunteers,
usIngprIcktestIng.EachsubjectreceIved10prIcktests(50L)onbothforearms.The
InvestIgatorsstudIedthewhealandflareresponsestoprIcktestswIthrocuronIumand
vecuronIum,usIngfourdIlutIons(1/1,000,1/100,1/10,and1)andtwocontrols,and
measuredwhealandflareImmedIatelyafterandat15mInutes.Theynoted50and40of
thesubjectshadaposItIveskInreactIontoundIlutedrocuronIumandvecuronIum,
respectIvely.
105
ToavoIdfalseposItIveresults,theysuggestedthatprIcktestIngwIth
rocuronIumandvecuronIumshouldbeperformedInsubjectswhohaveexperIenceda
hypersensItIvItyreactIondurInganesthesIa,wIthconcentratIonsbelowthatcommonly
InducIngposItIvereactIonsInanesthesIanaIve,healthysubjects(I.e.,formenInadIlutIon
of1/10andforwomenInadIlutIonof1/100).CuIdelInesforprIcktestIngthatare
InternatIonallyagreedonneedtobeestablIshed.|anyofthesedIfferencesmayexplaIn
thevarIousIncIdencesofallergytoN|8AsamongcountrIes.ConcentratIonskInresponse
curvestorocuronIumandvecuronIumhaveshowedthatprIcktestsshouldbeperformed
wIthdIlutIonofthecommercIallyavaIlablepreparatIon.FemalevolunteerssIgnIfIcantly(p
01)reactedtolowervecuronIumandrocuronIumconcentratIonsthanmalevolunteers.n
femalesubjects,posItIveskInreactIonswerereportedwIthdIlutIonsof1/100ofboth
relaxants.nmalesubjects,posItIveskInreactIonswerenotedwIththeundIluted
concentratIon,exceptforonevolunteerwhoreactedtorocuronIum(1/10dIlutIon).
Summary
AlthoughtheImmunesystemfunctIonstoprovIdehostdefense,Itcanrespond
InapproprIatelytoproducehypersensItIvItyorallergIcreactIons.AspectrumoflIfe
threatenIngallergIcreactIonstoanydrugoragentcanoccurIntheperIoperatIve
perIod.
100
TheenIgmaofthesereactIonslIesIntheIrunpredIctablenature.CertaIn
patIentsundergoInghIghrIskprocedureswIthmulItplebloodproductexposuresarealsoat
hIgherrIsk.
52
However,ahIghIndexofsuspIcIon,promptrecognItIon,andapproprIateand
aggressIvetherapycanhelpavoIdadIsastrousoutcome.
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107.LevyJH:AnaphylactIcreactIonstoneuromuscularblockIngdrugs:ArewemakIng
thecorrectdIagnosIs:AnesthAnalg2004;98:881
Stock, M. Christine
TableofContentsSectIonAnatomyandPhysIologyChapter1JnflammatIon,WoundHealIngandnfectIon
Chapter1J
Inflammation, Wound Healing and Infection
Harriet W. Hopf
C. Richard Chapman
Amalia Cochran
Michael B. Dorrough
Randal O. Dull
Key Points
1. The most crucial component of infection prevention is frequent and
effective hand hygiene.
2. The ideal hand hygiene agent kills a broad spectrum of microbes, has
antimicrobial activity that persists for at least 6 hours after
application, is simple to use, and has few side effects.
3. Wearing gloves does not reduce the need for hand hygiene.
4. Antibiotic prophylaxis has become standard for surgeries in which
there is more than a minimum risk of infection. The most commonly
used antibiotic for surgical prophylaxis is cefazolin, a first-generation
cephalosporin, as the potential pathogens for most surgeries are
Gram-positive cocci from the skin.
5. The exact timing for the administration of the antibiotic, ideally within
30 minutes to 1 hour of incision, depends on the pharmacology and
half-life of the drug. Prophylactic antibiotics should be discontinued
by 24 hours following surgery if postoperative dosing is selected at
all. Prolonging the course of prophylactic antibiotics does not reduce
the risk of infection but does increase the risk of adverse
consequences of antibiotic administration, including resistance,
Clostridium difficile infection, and sensitization.
6. Anesthesiologists should work in consultation with the surgeon to use
guidelines determined by the local infection control committee to take
initiative for administering prophylactic antibiotics because they have
access to the patient during the 60 minutes prior to incision and can
optimize timing of administration.
7. The standard teaching that oxygen delivery depends more on
hemoglobin-bound oxygen (oxygen content) than on arterial PO
2
may be true of working muscle, but it is not true of wound healing.
8. Although oxygen consumption is relatively low in wounds, it is
consumed by processes that require oxygen at a high concentration.
9. High oxygen tensions (>100 mm Hg) can be reached in wounds but
only if perfusion is rapid and arterial PO
2
is high.
10. Peripheral vasoconstriction, which results from central sympathetic
control of subcutaneous vascular tone, is probably the most frequent
and clinically the most important impediment to wound oxygenation.
11. Prevention or correction of hypothermia and blood volume deficits
has been shown to decrease wound infections and increase collagen
deposition in patients undergoing major abdominal surgery.
12. Modifiable risks include smoking, malnutrition, hyperglycemia,
hypercholesterolemia, and hypertension. These should be assessed
and corrected when possible prior to surgery.
13. Maintenance of a high room temperature or forced air warming
before, during, and after the operation is significantly more effective
than other methods of warming, such as circulating water blankets
placed under the patient and humidification of the breathing circuit.
14. Optimizing the volume of perioperative fluid administration to
minimize morbidity and mortality remains a significant and
controversial challenge.
15. Current best recommendations for volume management include
replacing fluid losses based on standard recommendations for the
type of surgery, replacement of blood loss, and replacement of other
ongoing fluid losses (e.g., high urine output due to diuretic or dye
administration, hyperglycemia, or thermoregulatory
vasoconstriction).
16. Wounds are most vulnerable in the first few hours after surgery.
17. All vasoconstrictive stimuli must be corrected simultaneously to allow
optimal healing.
18. Local perfusion is not assured until patients have a normal blood
volume, are warm and pain-free, and are receiving no
vasoconstrictive drugs; that is, until the sympathetic nervous system
is inactivated.
19. Urine output is a poor, often misleading guide to peripheral perfusion.
20. Physical examination of the patient is a better guide to hypovolemia
and vasoconstriction.
P.272
22. Administration of supplemental oxygen via face mask or nasal
cannulae increases safety in patients receiving systemic opioids. As a
side benefit, it may also improve wound healing, although this has
not been formally studied. Pain control also appears important since
it favorably influences both pulmonary function and vascular tone.
23. In patients with moderate to high risk of surgical site infection,
anesthesiologists have the opportunity to enhance wound healing
and reduce the incidence of wound infections by simple, inexpensive,
and readily available means.
0espItemajoradvancesInthemanagementofpatIentsundergoIngsurgeryIncludIng
aseptIctechnIque,prophylactIcantIbIotIcs,andadvancesInsurgIcalapproachessuchas
laparoscopIcsurgerysurgIcalwoundInfectIonandwoundfaIlureremaIncommon
complIcatIonsofsurgery(FIg.1J1).WoundcomplIcatIonsareassocIatedwIthprolonged
hospItalIzatIon,IncreasedresourceconsumptIon,andevenIncreasedmortalIty.|orethan
J00,000surgIcalsIteInfectIons(SSs;Table1J1)occureachyearIntheUnItedStatesatan
estImatedcostofmorethanS1bIllIon.
1
AgrowIngbodyoflIteraturesupportstheconcept
thatpatIentfactorsareamajordetermInantofwoundoutcomefollowIngsurgery.
ComorbIdItIessuchasdIabetesandcardIacdIseaseclearlycontrIbute,butenvIronmental
stressorsaswelltheIndIvIdualresponsetostressmaybeequallyImportant.npartIcular,
woundsareexquIsItelysensItIvetohypoxIa,whIchIsbothcommonandpreventable.
PerIoperatIvemanagementcanbeadaptedtopromotepostoperatIvewoundhealIngand
resIstancetoInfectIon.AlongwIthaseptIctechnIqueandprophylactIcantIbIotIcs,
maIntaInIngperfusIonandoxygenatIonofthewoundIsparamount.ThIschapterdIscusses
howknowledgeoftheprIncIplesofInfectIoncontrolandthebIologyandphysIologyof
woundrepaIrandresIstancetoInfectIoncanImproveoutcomes.
Infection Control
Hand Hygiene
PerhapsthemostcrucIalcomponentofInfectIonpreventIonIsfrequentandeffectIvehand
hygIene.n1847gnazSemmelweIsmadetheobservatIonthatwomenwhodelIveredtheIr
babIesIntheFIrstClInIcattheCeneralHospItalof7Ienna,staffedbymedIcalstudentsand
physIcIans,hadamortalItyrateof5to15,largelytheresultofpuerperalInfectIons;thIs
wassubstantIallyhIgherthanthe2rateofwomenwhodelIveredatClInIc2,whIchwas
staffedbymIdwIfestudentsandmIdwIves.
2
StudentsandphysIcIansatClInIc1usually
startedthedayperformIngautopsIes(IncludIngonpatIentswhodIedofpuerperalfever)
andthenmovedontotheClInIc,wheretheyperformedexamInatIonsonwomenInlabor.
SemmelweIsmadetheconnectIon,andalthoughgermtheorywassomeyearsoff,he
InsIstedthatphysIcIansandmedIcalstudentswashtheIrhandsInachlorInatedsolutIon
whenleavIngthepathologylaboratory.ThIsreducedtherateofpuerperalfevertothe
samerateasatClInIc2.Soon,SemmelweIsIdentIfIedcasesoftransmIssIonfroman
InfectedtoanunInfectedpatIent,andInstItutedtheuseofchlorInatedsolutIonhand
washIngbetweencasesaswell.HealsodemonstratedthatthechlorInatedsolutIonwas
moreeffectIvethansoapandwater.Unfortunately,hIsInnovatIonwasnotwIdelyadopted,
resultIngfromacombInatIonofhIsdelayInpublIshInghIsresults,thereluctanceofhIs
colleaguestoacceptthattheymIghtberesponsIblefortransmIttIngdIsease,andhIslack
oftactIntryIngtoconvIncehealthcareworkerstoadopthIsmeasures.0espIteourcurrent
knowledgeofgermtheory,handhygIeneremaInsanInexplIcablyneglectedcomponentof
InfectIoncontrol:studIesconsIstentlydemonstrateabouta40rateofadherence(range,5
to81)tohandhygIeneguIdelInes.
J
Figure 13-1.8rennanetal.
148
revIewedtherecordsorJ0,121patIentsat51acute
carehospItalsInNewYorkStateIn1984andfoundthatsurgIcalsIteInfectIonwasthe
mostcommonadversesurgIcalevent(andthesecondmostcommonadverseevent
overall).nfect.,InfectIon;Tech.comp.,technIquecomplIcatIon;0Iag.,dIagnosIs;
Therap,therapeutIc;Proc.,procedure.From8rennanTA,LeapeLL,LaIrdN|,etal.
ncIdenceofadverseeventsandneglIgenceInhospItalIzedpatIents.Fesultsofthe
Harvard|edIcalPractIceStudy.NEJ|1991;J24:J70,wIthpermIssIon.
8acterIaareresIdentIntheskInandcanneverbecompletelyelImInated.
J
FesIdentflora
areembeddedInthedeeperfoldsoftheskInandaremoreresIstanttoremoval,butare
alsoInfrequentlypathogenIc.CoagulasenegatIvestaphylococcIanddIphtheroIdsarethe
mostcommon.TransIentfloracolonIzethesuperfIcIallayersoftheskInandthusareeasIer
toremovewIthhandhygIene.TransIentfloraarealsothesourceofmosthealthcare
assocIatedInfectIons,ashealthcareworkerskIncanbecomecontamInatedfrompatIent
contactorcontactwIthcontamInatedsurfaces.ContamInatIonfromsurfacesIsmost
commonlywIthorganIsmssuchasstaphylococcIandenterococcI,whIchareresIstantto
dryIng.EvencleanactIvItIessuchastakIngapatIent'spulseorapplyIngmonItorscan
leadtohandcontamInatIon:100to1,000colonyformIngunItsofKlebsiellaspecIeswere
measuredonnurses'handsfollowIngsuchactIvItIesInonestudy.
4
NostudIeshaverelated
handcontamInatIontoactualtransmIssIonofInfectIontopatIents;however,numerous
studIes,startIngwIththoseofSemmelweIs,havedemonstratedareductIonInhealthcare
assocIatedInfectIonsfollowIngInstItutIonofhandhygIeneorImprovedadherencetohand
hygIene.
J
AnumberofproductsareavaIlableforhandhygIene.TheIdealagentkIllsabroad
spectrumofmIcrobes,hasantImIcrobIalactIvItythatpersIstsforatleast6hoursafter
applIcatIon,IssImpletouse,andhasfewsIdeeffects.Themostcommonlyusedand
effIcacIousagentsarerevIewedhere.
PlaIn(notantIseptIc)soapandwateraregenerallytheleasteffectIveatreducInghand
contamInatIon.
5
AlthoughobvIousdIrtIsremovedbythedetergenteffectofsoapandthe
mechanIcalactIonofwashIng,bacterIalloadIsnotgreatlyreduced.Further,soapand
waterhandhygIeneIsassocIatedwIthhIghratesofskInIrrItatIonanddryIng,bothofwhIch
arerIskfactorsforanIncreasedbacterIalload.Soapandwaterare,however,themost
effectIveatremovIngspores,andthereforeshouldbeusedwhencontamInatIonwIth
Clostridium difficileorBacillus anthracisIsaconcern.
J
Table 13-1 Criteria for Defining a Surgical Site Infection (SSI)
Superficial Incisional SSI
nfectIonoccurswIthInJ0daysaftertheoperatIon
and
nfectIonInvolvesonlyskInorsubcutaneoustIssueoftheIncIsIon
and
AtleastoneofthefollowIng:
1. PurulentdraInage,wIthorwIthoutlaboratoryconfIrmatIon,fromthe
superfIcIalIncIsIon
2. DrganIsmsIsolatedfromanaseptIcallyobtaInedcultureoffluIdortIssuefrom
thesuperfIcIalIncIsIon
J. AtleastoneofthefollowIngsIgnsorsymptomsofInfectIon:paInor
tenderness,localIzedswellIng,redness,orheatandsuperfIcIalIncIsIonIs
delIberatelyopenedbythesurgeon,unlessIncIsIonIsculturenegatIve
4. 0IagnosIsofsuperfIcIalIncIsIonalSSbythesurgeonorattendIngphysIcIan
0onotreportthefollowIngcondItIonsassuperfIcIalIncIsIonalSS:
1. StItchabscess(mInImalInflammatIonanddIschargeconfInedtothepoIntsof
suturepenetratIon)
2. nfectIonofanepIsIotomyornewborncIrcumcIsIonsIte
J. nfectedburnwound
4. ncIsIonalSSthatextendsIntothefacIalandmusclelayers(see0eep
ncIsIonalSS)
Note:SpecIfIccrIterIaareusedforIdentIfyIngInfectedepIsIotomyand
cIrcumcIsIonsItesandburnwounds
Deep Incisional SSI
nfectIonoccurswIthInJ0daysaftertheoperatIonIfnoImplantIsleftInplace
orwIthIn1yearIfImplantIsInplaceandtheInfectIonappearstoberelatedto
theoperatIon
and
nfectIonInvolvesdeepsofttIssues(e.g.,fascIalandmusclelayers)ofthe
IncIsIon
and
1. PurulentdraInagefromthedeepIncIsIonbutnotfromtheorgan/space
componentofthesurgIcalsIte
2. AdeepIncIsIonspontaneouslydehIscesorIsdelIberatelyopenedbyasurgeon
whenthepatIenthasatleastoneofthefollowIngsIgnsorsymptoms:fever
(J8`C),localIzedpaIn,ortenderness,unlesssIteIsculturenegatIve
J. AnabscessorotherevIdenceofInfectIonInvolvIngthedeepIncIsIonIsfound
ondIrectexamInatIon,durIngreoperatIon,orbyhIstopathologIcorradIologIc
examInatIon
4. 0IagnosIsofadeepIncIsIonalSSbyasurgeonorattendIngphysIcIan
Notes:
1. FeportInfectIonthatInvolvesbothsuperfIcIalanddeepIncIsIonsItesasdeep
IncIsIonalSS
2. Feportanorgan/spaceSSthatdraInsthroughtheIncIsIonasadeepIncIsIonal
SS
Organ/Space SSI
nfectIonoccurswIthInJ0daysaftertheoperatIonIfnoImplantIsleftInplace
orwIthIn1yearIfImplantIsInplaceandtheInfectIonappearstoberelatedto
theoperatIon
and
nfectIonInvolvesanypartoftheanatomy(e.g.,organsorspaces),otherthan
theIncIsIon,whIchwasopenedormanIpulateddurInganoperatIon
and
1. PurulentdraInagefromadraInthatIsplacedthroughastabwoundIntothe
organ/space
2. DrganIsmsIsolatedfromanaseptIcallyobtaInedcultureoffluIdortIssueIn
theorgan/space
J. AnabscessorotherevIdenceofInfectIonInvolvIngtheorgan/spacethatIs
foundondIrectexamInatIon,durIngreoperatIon,orbyhIstopathologIcor
radIologIcexamInatIon
4. 0IagnosIsofanorgan/spaceSSbyasurgeonorattendIngphysIcIan
From|angramAJ,HoranTC,Pearson|L,etal:CuIdelIneforpreventIonof
surgIcalsIteInfectIon,1999.Centersfor0IseaseControlandPreventIon(C0C)
HospItalnfectIonControlPractIcesAdvIsoryCommIttee.AmJnfectControl
1999;27:97,wIthpermIssIon.
P.27J
AlcoholbasedrInsesandgelsdenatureproteIns,andthIsconferstheIrantImIcrobIal
actIvIty.
J
EthanolIsmostcommonlyusedbecauseIthasmoreantIvIralactIvItythan
Isopropanol.AntIseptIcscontaInIng60to95ethanolwIthawaterbasearegermIcIdaland
effectIveagaInstCramposItIveandCramnegatIvebacterIa,lIpophIlIcvIrusessuchas
herpessImplex,humanImmunodefIcIency,Influenza,respIratorysyncytIal,andvaccInIa
vIruses,andhepatItIs8andCvIruses.TheyhavelIttlepersIstentactIvIty,although
regrowthofbacterIadoesoccurslowlyafteruseofalcoholbasedproducts.CombInatIon
wIthlowdosesofotheragentssuchaschlorhexIdIne,quaternaryammonIumcompounds,or
trIclosancanconferpersIstentactIvIty.EffIcacydependsonvolumeapplIed(JmLIs
superIorto1mL)andduratIonofcontact(Ideally,J0seconds).
ChlorhexIdIneIsacatIonIcbIsbIguanIdethatdIsruptscytoplasmIcmembranes,resultIngIn
precIpItatIonofcellularcontents.
J
tIsgermIcIdalagaInstCramposItIvebacterIaand
lIpophIlIcvIruses,wIthsomewhatlessactIvItyagaInstCramnegatIvebacterIaandfungI,
andmInImalagaInsttuberclebacIllI.thassubstantIalpersIstenceontheskIn,andthe
Centersfor0IseaseControlandPreventIon(C0C)hasIdentIfIedItasthetopIcalagentof
choIceforskInpreparatIonIncentralvenouscatheterInsertIon.tmaycausesevere
cornealdamage
P.274
afterdIrectcontactwIththeeye,ototoxIcItyafterdIrectcontactwIththeInnerormIddle
ear,andneurotoxIcItyafterdIrectcontactwIththebraInormenInges.Therearereports
ofbacterIathathaveacquIredreducedsusceptIbIlItytochlorhexIdIne,buttheseareof
questIonableclInIcalpertInencesIncetheconcentratIonsatwhIchresIstancewasfound
weresubstantIallylowerthanthatofcommercIallyavaIlableproducts.
odIneandIodophors(IodInewIthapolymercarrIer)penetratethecellwallandImpaIr
proteInsynthesIsandcellmembranefunctIon.
J
TheyarebacterIcIdalagaInstCram
posItIve,CramnegatIve,andsomesporeformIngbacterIaIncludIngclostrIdIaandBacillus
specIes,althoughInactIveagaInstspores.TheyalsohaveactIvItyagaInstmycobacterIa,
vIruses,andfungI.TheIrpersIstenceIsgenerallyfaIrlypoor.Theycausemorecontact
dermatItIsthanothercommonlyusedagents,andallergIestothIsclassoftopIcalagentare
common.odophorsgenerallycausefewersIdeeffectsthanIodIneagents.
ThechoIceofanantIseptIcdependsontheexpectedpathogens,acceptabIlItybyhealth
careworkers,andcost.ngeneral,antIseptIcscostaboutS1perpatIentday,farlessthan
thecostofhealthcareassocIatedInfectIons.nnInestudIesthatexamInedtheeffectof
ImprovedhandhygIeneadherenceonhealthcareassocIatedInfectIons,themajorIty
demonstratedthatashandhygIenepractIcesImproved,InfectIonratesdecreased.
J
8arrIerstohandhygIeneIncludeskInIrrItatIonandfearofskInIrrItatIon,InaccessIbIlIty,
tIme,andhealthcareworkeracceptance(largelyrelatedtotheotherfactorsmentIoned).
AlthoughalcoholbasedagentshavelongbeenbelIevedtocausemoreskInIrrItatIon,
severalrecenttrIalshavedemonstratedlessskInIrrItatIonandbetteracceptancewIth
emollIentcontaInIng,alcoholbasedhandrubscomparedwItheItherantImIcrobIalor
nonantImIcrobIalsoap.TheuseofapproprIate(glovecompatIble)lotIonstwIceadayalso
reducesskInIrrItatIonaswellasleadIngtoa50IncreaseInhandhygIenefrequencyIn
onestudy.
J
AlcoholbasedgelsarealsogenerallymoreaccessIblethanantIseptIcsoapand
water,asthedIspensermaybepocketsIzedorplacedconvenIentlynearsItesofpatIent
care.thasbeenestImatedthatalcoholbasedgelsrequIreonlyabout25ofthetImeof
goIngtoasInktowashone'shands.However,soapandwatershouldbeusedtoremove
partIculatematterIncludIngbloodandotherbodyfluIdsorafterfIvetotenapplIcatIonsof
alcoholbasedagent.
AdherencetohandhygIeneguIdelInes(Tables1J2,1JJand1J4)generallydecreasesas
thefrequencyofIndIcatedhandwashIngIncreases,astheworkloadIncreases,andas
staffIngdecreases.nanIntensIvecareunIt(CU),handhygIenefornursesIsgenerally
IndIcatedabout20tImesperhour,ascomparedwIthanormalwardwherethIsnumber
decreasesto8perhour.
J
ntheoperatIngroom(DF),frequentpatIentcontactbythe
anesthesIologIstrequIresfrequenthandhygIene,probablyataboutthelevelofnursesIn
theCU,whIleaccessIbIlItyIsoftenquItelImIted.SInksareavaIlableonlyoutsIdetheDF.
Therefore,alcoholbasedagentsshouldbeavaIlablewIthInhand'sreachoftheanesthesIa
machIne.Loftusetal.
6
studIedbacterIalcontamInatIonoftheanesthesIaworkarea
(adjustablepressurelImItIngvalvecomplexandagentflowmeter)andcrosscontamInatIon
ofthesterIleanesthesIastopcockdurIng61fIrstcasesIntheIroperatIngroom.Theyfound
anaverageIncreaseInbacterIalcontamInatIonoftheworkareaof115colonIesper
surfaceareasampleddurIngcases(95confIdenceInterval:62169;p0.001).TransmIssIon
ofbacterIafromtheworkareatothesterIlestopcockInthepatIents'IntravenoustubIng
occurredInJ2ofcases,IncludIngtransmIssIonofmethIcIllInresIstantStaphylococcus
aureus(|FSA)IntwocasesandvancomycInresIstantEnterococcusInonecase.AhIghlevel
ofcontamInatIonoftheworkarea(100colonIespersurfaceareasampled)Increasedthe
rIskofstopcockcontamInatIon4.7fold(95confIdenceInterval:1.4215.42;p=0.011).
Thus,transmIssIonofbacterIalcontamInatIonbytheanesthesIaprovIderappearstobe
common,
P.275
apotentIalsourceofnosocomIalInfectIons,andlargelypreventable.
6
Table 13-2 Indications for Hand Hygiene
WhenhandsarevIsIblydIrtyorcontamInatedwIthproteInaceousmaterIalorare
vIsIblysoIledwIthbloodorotherbodyfluIds,washhandswItheIthera
nonantImIcrobIalsoapandwateroranantImIcrobIalsoapandwater.
fhandsarenotvIsIblysoIled,useanalcoholbasedhandrubforroutInely
decontamInatInghands.AlternatIvely,washhandswIthanantImIcrobIalsoap
andwater.
0econtamInatehandsbeforehavIngdIrectcontactwIthpatIents.
0econtamInatehandsbeforedonnIngsterIlegloveswhenInsertIngacentral
Intravascularcatheter.
0econtamInatehandsbeforeInsertIngIndwellIngurInarycatheters,perIpheral
vascularcatheters,orotherInvasIvedevIcesthatdonotrequIreasurgIcal
procedure.
0econtamInatehandsaftercontactwIthapatIent'sIntactskIn(e.g.,applyIng
monItors,movIngpatIent).
0econtamInatehandsaftercontactwIthbodyfluIdsorexcretIons,mucous
membranes,nonIntactskIn,andwounddressIngsIfhandsarenotvIsIblysoIled.
0econtamInatehandsIfmovIngfromacontamInatedbodysIte(e.g.,mouth
durIngtrachealIntubatIon)toacleanbodysIte(e.g.,adjustInggasflow,turnIng
onventIlator,startIng7)durIngpatIentcare.
0econtamInatehandsaftercontactwIthInanImateobjects(IncludIngmedIcal
equIpment)IntheImmedIatevIcInItyofthepatIent.Takecaretoreduce
contamInatIonoftheanesthesIamachIne(e.g.,aftertrachealIntubatIon)as
well!
0econtamInatehandsafterremovInggloves.
8eforeeatIngandafterusIngarestroom,washhandswIthanonantImIcrobIal
soapandwaterorwIthanantImIcrobIalsoapandwater.
AntImIcrobIalImpregnatedwIpes(I.e.,towelettes)maybeconsIderedasan
alternatIvetowashInghandswIthnonantImIcrobIalsoapandwater.8ecause
theyarenotaseffectIveasalcoholbasedhandrubsorwashInghandswIthan
antImIcrobIalsoapandwaterforreducIngbacterIalcountsonthehandsof
HCWs,theyarenotasubstItuteforusInganalcoholbasedhandrubor
antImIcrobIalsoap.
7,Intravenous(tube);HCW,healthcareworker.
|odIfIedfrom8oyceJ|,PIttet0:CuIdelIneforhandhygIeneInhealthcare
settIngs.FecommendatIonsoftheHealthcarenfectIonControlPractIcesAdvIsory
CommItteeandtheHPAC/SHEA/APC/0SAHandHygIeneTaskForce.AmJnfect
Control2002;J0(8):S1.
Table 13-3 Hand Hygiene Technique
WhendecontamInatInghandswIthanalcoholbasedhandrub,applythe
recommendedvolumeofproducttopalmofonehandandrubhandstogether,
coverIngallsurfacesofhandsandfIngers,untIlhandsaredry.
WhenwashInghandswIthsoapandwater,wethandsfIrstwIthwater,applyan
amountofproductrecommendedbythemanufacturertohands,andrubhands
togethervIgorouslyforatleast15seconds,coverIngallsurfacesofthehands
andfIngers.FInsehandswIthwateranddrythoroughlywIthadIsposabletowel.
Usetoweltoturnoffthefaucet.AvoIdusInghotwaterbecauserepeated
exposuretohotwatermayIncreasetherIskofdermatItIs.
LIquId,bar,leaflet,orpowderedformsofplaInsoapareacceptablewhen
washInghandswIthanonantImIcrobIalsoapandwater.WhenbarsoapIsused,
soapracksthatfacIlItatedraInageandsmallbarsofsoapshouldbeused.
WearIngglovesdoesnotreducetheneedforhandhygIene.AlthoughglovesprovIde
protectIon,bacterIalflorafrompatIentsmaybeculturedfromuptoJ0ofhealthcare
workerswhowearglovesdurIngpatIentcontact.
J
Therefore,handhygIeneshouldbe
practIcedbothbeforeputtIngonglovesandImmedIatelyafterremoval.|oreover,gloves
shouldberemovedorchangedImmedIatelyaftereachprocedure,IncludIngvascular
access,IntubatIon,andneuraxIalanesthesIa,becauseglovesbecomecontamInatedby
patIentcontactjustashandsdo.
ArtIfIcIalandlongfIngernaIls,aswellaschIppedfIngernaIlpolIsh,areassocIatedwIth
hIgherconcentratIonsofbacterIaonthehandsofhealthcareworkers.ArtIfIcIalnaIlshave
beenIdentIfIedasasourceInseveralhospItalassocIatedoutbreaksofInfectIonwIthCram
negatIvebacIllIandyeast,andC0CguIdelInesdIscouragewearIngofartIfIcIalnaIlsby
healthcareworkersInhIghrIsksettIngs;manyhospItalshavebannedwearIngofartIfIcIal
naIlsbyanyemployeewhohasdIrectpatIentcontact.
J
tmayalsobeapproprIateto
counselpatIentsscheduledforsurgerythatartIfIcIalnaIlsmayIncreasetheIrrIskof
InfectIon,althoughthIshasnotbeenInvestIgated.LargequantItIesofbacterIaare
typIcallytrappedunderthefIngernaIls,and2002C0CguIdelInesrecommendthathealth
careworkerskeeptheIrnaIltIpstrImmedtolessthanInch.
J
8acterIamaybeculturedathIgherconcentratIonsfromtheskInbeneatharIng.Dnthe
otherhand,wearIngarIngdoesnotIncreaseoverallbacterIallevelsmeasuredonthe
handsofhealthcareworkers.Therefore,ItremaInsunclearwhethertransmIssIonof
InfectIoncouldbereducedbyprohIbItInghealthcareworkersfromwearIngrIngs.
J
Table 13-4 Skin Care
ProvIdehealthcareworkerswIthhandlotIonsorcreamstomInImIzethe
occurrenceofIrrItantcontactdermatItIsassocIatedwIthhandantIsepsIsor
handwashIng.
SolIcItInformatIonfrommanufacturersregardInganyeffectsthathandlotIons,
creams,oralcoholbasedhandantIseptIcsmayhaveonthepersIstenteffectsof
antImIcrobIalsoapsbeIngusedIntheInstItutIon,aswellasongloveIntegrIty.
SelectacombInatIonofproductsthatmInImIzestheseeffects.
Antisepsis
|askshavelongbeenadvocatedaspreventIngsurgIcalsIteInfectIon,andareusedalmost
unIversallyInU.S.operatIngrooms.Tunevall
7
studIedtherateofwoundInfectIonsInJ,088
patIentsover115weeks.nalternatIngweeks,DFpersonneleItherworemasksordIdnot
(personnelwIthactIverespIratoryInfectIonscontInuedtowearmasks).Therewasno
dIfferenceIntherateofsurgIcalwoundInfectIons(4.7vs.J.5,respectIvely)Inthetwo
groups,norInbacterIalspecIesculturedfromthewounds.FrIbergetal.
8
demonstrated
comparableaIrandsurfacecontamInatIondurIngshamsurgeryInahorIzontallamInaraIr
flowunItwhetherDFpersonnelworeanonsterIlehoodandmaskorasterIlIzedhelmet
aspIratorsystem.WhentheheadcoverIngbutnotthemaskwasomItted,however,
contamInatIonIncreasedthreetofIvefold.ThesedatasuggestthatwearIngaheadcover
IsusefulforpreventIngSS,whIlewearIngamaskIsnot.Nonetheless,thestudyby
TunevallIsasmallone,andmosthospItalpersonnelcontInuetorequIreamaskIntheDF
whIlesurgIcalInstrumentsareopen.|oreover,themaskdoesservethepurposeof
protectIngthehealthcareprovIder,partIcularlywhencombInedwItheyeprotectIon,and
thusshouldmostlIkelybeuseddurIngtrachealIntubatIonandatothertImeswhen
protectIonfrombodyfluIdsIsapproprIate.
AlthoughthepreponderanceofpostoperatIvesurgIcalInfectIonsIscausedbyflorathatare
endogenoustothepatIent,envIronmentalandaIrbornecontamInantsmayalsoplaya
causatIverole.AnImportant,butfrequentlyoverlooked,consIderatIonIstherolethat
traffIcpatternsIntoanDFcanplayInpatIentexposuretoaIrborneorganIsms.Arecent
sraelIstudyofrIskfactorsforsurgIcalInfectIonaftertotalkneereplacement
demonstratedatrendtowardIncreasedInfectIonrateswIthInIncreasednumberof
orthopaedIcsurgeonsoranesthetIstspresentIntheDF.
9
ThIsstudyreconfIrmedaprIor
studyshowIngatrendtowardIncreasedIncIdenceofsurgIcalsIteInfectIonasthenumber
ofpeopleIntheoperatIngsuIteIncreases.
10
However,IthasbeennotedInoneaudItthat
physIcIansandnursesdIdlIttletolImItthenumberofpeoplethroughDFsdurIng
procedures.
11
CurrentrecommendedpractIcesarethattraffIcpatternsshouldlImItthe
flowofpeoplethroughanDFthatIsInuse,andthatnomorepeoplethannecessaryshould
beInanDFdurIngaprocedure.
12
TheanesthesIologIstIsclearlyInaposItIontoplaya
leadershIproleIncontrollInghumantraffIcthroughtheDF.
|ermeletal.
1J
In1991demonstratedthatcentralvenouslInesplacedbythe
anesthesIologIstIntheDFbecameInfectedmoreoften(relatIverIsk[FF],2.1;p=0.0J)
thanthoseplacedbysurgeonsorotherprovIders,whetherInoroutoftheDF.ContrIbutIng
factorsappearedtobesIteofplacementandthestrIngencyofaseptIctechnIque.nternal
jugularveInInsertIonhasagreaterrIskofInfectIon(FF,4.J;p0.01)comparedwIth
subclavIanveIn,althoughItsotherbenefItsmayoutweIghthIsrIsk.Faadetal.
14
demonstratedthatuseofamaxImalsterIlebarrIer
P.276
technIqueversussterIleglovesandsmallsterIledrapesledtoasIgnIfIcantreductIonIn
centralvenouscatheterrelatedInfectIonfrom7.2to2.2(p=0.0J).Therefore,gownIng
andglovIng,carefulaseptIctechnIque,anduseofawIdesterIlefIeldshouldberoutIne.
15
nanesthetIzedpatIents,thecentrallIneIsIdeallyplacedbeforethesurgIcalsIteIsdraped
InordertoavoIdcontamInatIonofthewIreontheundersIdeofthesurgIcaldrape.
EpIduralabscessformatIonIsanextremelyrarebutpotentIallycatastrophIccomplIcatIon
ofneuraxIalanesthesIaandepIduralcatheterplacement.Therefore,carefulattentIonto
aseptIctechnIqueandInfectIoncontrolIsrequIred.ThemostImportantconsIderatIonIsto
preventcontamInatIonoftheneedleandcatheter.Thus,handwashIng,skInpreparatIon,
drapIng,andmaIntenanceofasterIlefIeldshouldbecarefullyobserved.CownIngand
wearIngamask,however,areunlIkelytoreducetherIskofInfectIon.FInally,epIdurals
shouldprobablybeavoIdedInpatIentsknownorsuspectedtohavebacteremIaordeferred
untIlafterapproprIateantIbIotIcsareadmInIstered.
P.277
Antibiotic Prophylaxis
AfterantIbIotIcscameIntowIdespreaduseInthe1940sand1950s,therewasmuchdebate
overthepossIbIlItythatantIbIotIcprophylaxIsmIghtpreventSS.n1957|Ilesetal.
16
used
aguIneapIgmodelfortheproofofprIncIplethatadmInIstratIonofanantIbIotIcprIorto
contamInatIon(IncIsIon)couldreducetherIskofsurgIcalsIteInfectIon.WhenapproprIate
antIbIotIcsweregIvenwIthIn2hoursbeforeorafterIntradermalInjectIonofbacterIathey
wereeffectIveInpreventIngInvasIveInfectIonandnecrosIs.WhengIvenoutsIdethIs
wIndow,theywerenoteffectIve.ThIsgaverIsetotheconceptofadecIsIveperIodIn
whIchantIbIotIcswIllbeeffectIve,whIchremaInsaguIdIngprIncIpleofantIbIotIc
prophylaxIs.|Ilesetal.alsodemonstratedthatInjectIonofepInephrIneIntradermally
prIortoadmInIstratIonofantIbIotIcsledtoantIbIotIcfaIlure,asdemonstratedInan
IncreasedwoundInfectIonrate.ThIsdemonstratedthecrucIalroleoflocalperfusIonIn
delIverIngantIbIotIcstothesIte.KnIghtonetal.,
17
usIngthesamemodel,demonstrated
thatIncreasedInspIredoxygenwasequallyaseffectIveasantIbIotIcsInpreventIng
InfectIon,andthatthetwoeffectswereaddItIve(FIg.1J2).KnIghtonetal.
18
alsodelayed
theadmInIstratIonofoxygenforupto6hoursafterInoculatIonanddemonstratedno
reductIonIneffect.Thus,thedecIsIveperIodforoxygenIsconsIderablylongerthanthatof
antIbIotIcs.
TwosurgeonsatWashIngtonUnIversItyInSt.LouIs,Harvey8ernardandWIllIamCole,
19
reportedonthefIrstcontrolledclInIcaltrIaloftheeffIcacyofantIbIotIcprophylaxIsIn1964
anddemonstratedabenefItInabdomInaloperatIons.Thereafter,numerousclInIcaltrIals
wereperformedwIthsomewhatvarIableresults.EventuallytheseservedtodefInethe
tImIngandpopulatIonInwhIchprophylactIcantIbIotIcswork.8ythe1970santIbIotIc
prophylaxIsforhIghrIsksurgerymeanIngcleancontamInatedandcontamInatedcases
wasbecomIngwellacceptedandwIdelyused,althoughsomeskeptIcsremaIned.n1992,
Classenetal.
20
publIshedtheIrprospectIveserIesIncludIng2,847patIentsundergoIngclean
orcleancontamInatedsurgIcalproceduresatL0SHospItalInSaltLakeCIty,UT(FIg.1JJ).
TheydemonstratedthatthedecIsIveperIodforSSInhumansundergoIngsurgerywas
essentIallythesameasforexperImentalInfectIonsInguIneapIgs.ThatIs,theyfoundthe
lowestInfectIonratewhenantIbIotIcsweregIvenwIthIn2hoursbeforeorafterIncIsIon
andarapIdIncreaseInSSratewhentheyweregIvenoutsIdethatrange.Thebestresults,
thoughonlybyasmallmargInandnotstatIstIcallysIgnIfIcant,werewIthIn0to60mInutes
ofsurgery,andthIssubsequentlybecametheclInIcalstandard.
Figure 13-2.Theeffectofoxygenand/orantIbIotIcsonlesIondIameterafter
IntradermalInjectIonofbacterIaIntoguIneapIgs.Notethatateverylevel,oxygen
addstotheeffectofantIbIotIcsandthatIncreasIngoxygenInthebreathIngmIxture
from12to20orfrom20to45exertsaneffectcomparabletothatofapproprIately
tImedantIbIotIcs.(FromFabkInJ,HuntTK:nfectIonandoxygen,Problemwounds:
TheFoleofDxygen.EdItedby0avIsJ,HuntTK.NewYork,ElsevIer,1988,pp1,wIth
permIssIon.)
Figure 13-3.ThefIguredemonstratesratesofsurgIcalwoundInfectIoncorrespondIng
tothetemporalrelatIonbetweenantIbIotIcadmInIstratIonandthestartofsurgery.
ThenumberofInfectIonsandthenumberofpatIentsforeachhourlyIntervalappear
asthenumeratoranddenomInator,respectIvely,ofthefractIonforthatInterval.The
trendtowardhIgherratesofInfectIonforeachhourthatantIbIotIcadmInIstratIonwas
delayedafterthesurgIcalIncIsIonwassIgnIfIcant(zscore=2.00;p0.05bythe
WIlcoxontest).(FromClassen0,EvansF,PestotnIKS,etal:ThetImIngofprophylactIc
admInIstratIonofantIbIotIcsandtherIskofsurgIcalwoundInfectIon.NEJ|
1992:J26;281,wIthpermIssIon.)
AntIbIotIcprophylaxIshasnowbecomestandardforsurgerIesInwhIchthereIsmorethana
mInImumrIskofInfectIon.AlthoughnoteverysurgeryandsItuatIonhasbeenstudIed,a
strongratIonalefortheapproachtoprophylactIcantIbIotIcshasemerged.Severalgroups
separatelydevelopedguIdelInesforuse,culmInatIngInrecommendatIonspublIshedIn2004
bytheNatIonalSurgIcalnfectIonPreventIonProject.
21
TheseguIdelInesemphasIzetImIng
andchoIceofapproprIateagents.CuIdelInesgenerallydonotspecIfyantIbIotIcagents,
althoughtheygIveratIonalesforvarIouschoIces.
21
TheagentforantIbIotIcprophylaxIs
mustcoverthemostlIkelyspectrumofbacterIapresentedInthesurgIcalfIeld(seeTable
1J5).ThemostcommonlyusedantIbIotIcforsurgIcalprophylaxIsIscefazolIn,afIrst
generatIoncephalosporIn,asthepotentIalpathogensformostsurgerIesareCramposItIve
coccIfromtheskIn.
21,22
8ydefInItIon,prophylactIcantIbIotIcsaregIvenpreorIntraoperatIvely.TheexacttImIng
fortheadmInIstratIonoftheantIbIotIcdependsonthepharmacologyandhalflIfeofthe
drug.deally,admInIstratIonoftheprophylaxIsshouldbewIthInJ0mInutesto1hourof
IncIsIon.
16,20,22,2J
ThIsIsuncomplIcatedforantIbIotIcsthatcanbegIvenasabolusdose
(e.g.,cephalosporIns)orasanInfusIonoverafewmInutes(e.g.,clIndamycIn)andthus
provIdetIssuelevelswIthInmInutes.FordrugslIkevancomycInthatrequIreInfusIonover
anhour,coordInatIonofadmInIstratIonIsmorecomplex.ngeneral,ItIsconsIdered
acceptableIftheInfusIonIsstartedprIortoIncIsIon.WhenatournIquetIsused,the
InfusIonmustbecompleteprIortoInflatIonofthetournIquet.AnapproprIatedosebased
onbodyweIghtandvolumeofdIstrIbutIonshouldbegIven.0ependIngonthehalflIfe,
antIbIotIcsshouldberepeateddurInglongoperatIonsoroperatIonswIthlargebloodloss.
24
Forexample,cefazolInIsnormallydosedevery8hoursbutthedoseshouldberepeated
every4hoursIntraoperatIvely.
24
FInally,prophylactIcantIbIotIcsshouldbedIscontInuedby
24hoursfollowIngsurgeryIfpostoperatIvedosIngIsselectedatall.ProlongIngthecourse
ofprophylactIcantIbIotIcsdoesnotreducetherIskofInfectIonbutdoesIncreasetherIsk
ofadverseconsequencesofantIbIotIcadmInIstratIon,
21
IncludIngresIstance,Clostridium
difficileInfectIon,andsensItIzatIon.
Unfortunately,|FSAIsbecomIngamorecommonpathogen.AlthoughItvarIesbycountry,
regIon,andhospItal,about60ofS. aureusare|FSA.ndependentrIskfactorsIdentIfIed
for|FSAInfectIonIncludeprolongeduseofprophylaxIs,useofdraInsformorethan24
hours,andIncreasIngnumberofproceduresperformedonthepatIent.HandhygIeneIs
amongthemosteffectIvemeansofpreventIngdevelopmentof|FSAsIncealcoholbased
gelusedproperlykIllsover99.9ofalltransIentpathogensIncludIng|FSA.Theredoesnot
appeartobeajustIfIcatIonforusIngantIbIotIcseffectIveagaInst|FSAforprophylaxIsIn
mostclInIcalsettIngs.
8ecausetheyhaveaccesstothepatIentdurIngthe60mInutesprIortoIncIsIonandcan
optImIzetImIngofadmInIstratIon,anesthesIologIstsshouldworkInconsultatIonwIththe
surgeontouseguIdelInesdetermInedbythelocalInfectIoncontrolcommItteetotake
InItIatIveforadmInIsterIngprophylactIcantIbIotIcs.nthIsway,anesthesIologIstscan
makeamajorcontrIbutIontopreventIngsurgIcalsIteInfectIon.TheCentersfor|edIcare
and|edIcaIdServIceshasIdentIfIedtImelyandapproprIateantIbIotIcprophylaxIs
admInIstratIonasacornerstoneofsurgIcalsIteInfectIonpreventIon.PhysIcIanandhospItal
reImbursementsareIncreasInglytIedtosuchperformancemeasures,meanIng
anesthesIologIstsalsohaveaneconomIcInterestInensurIngadherencetoguIdelInes.
Mechanisms of Wound Repair
WoundhealIngIsacomplexprocess,requIrIngacoordInatedrepaIrresponseIncludIng
InflammatIon,matrIxproductIon,angIogenesIs,epIthelIzatIon,andremodelIng(FIg.1J4).
|anyfactorsmayImpaIrwoundhealIng.SystemIcfactorssuchasmedIcalcomorbIdItIes,
nutrItIon,
25,26
sympathetIcnervoussystemactIvatIon,
27
andage
28,29,J0
haveasubstantIal
effectontherepaIrprocess.LocalenvIronmentalfactorsInandaroundthewound
IncludIngbacterIalload,
J1
degreeofInflammatIon,moIsturecontent,
J2
oxygentensIon,
JJ
andvascularperfusIon
J4
alsohaveaprofoundeffectonhealIng.Althoughallofthese
factorsareImportant,perhapsthemostcrItIcalelementIsoxygensupplytothewound.
WoundhypoxIaImpaIrseachofthecomponentsofhealIng.
J5
AlthoughtheroleofoxygenIsusuallythoughtofIntermsofaerobIcrespIratIonandenergy
productIonvIaoxIdatIvephosphorylatIon,InwoundhealIngoxygenIsrequIredasa
cofactorforenzymatIcprocessesandforcellsIgnalIngmechanIsms.DxygenIsarate
lImItIngcomponentInleukocytemedIatedbacterIalkIllIngandcollagenformatIonbecause
specIfIcenzymesrequIreoxygenatapartIalpressureofatleast40mmHg.
J6,J7
The
mechanIsmsbywhIchtheotherprocessesareoxygendependentarelessclear,butthese
processesalsorequIreoxygenataconcentratIonmuchabovethatrequIredforcellular
respIratIon.
J8,J9,40,41
The Initial Response to Injury
AsurgIcalIncIsIondIsruptstheskInbarrIer,creatInganacutewound,andaneffectIve
InItIalresponsetoInjurydependsontheabIlItytocleanforeIgnmaterIalandtoresIst
InfectIon.ThIsresponseInItIatesasequenceofeventsthatstartswIthanysourceofInjury
thatdIsruptshomeostasIsInthelocalenvIronmentandeventuallyleadstohealIng.
WoundhealInghastradItIonallybeendescrIbedInfourseparatephases:hemostasIs,
InflammatIon,prolIferatIon,andremodelIng.
42
ConsIderableoverlapexIstsbetweeneach
ofthesephases,anddIfferentIatIngprecIselywhenonephaseendsandthenextbegInsIs
vIrtuallyImpossIble.EachphaseIscomposedofcomplexInteractIonsbetweenhostcells,
contamInants,cytokInesandotherchemIcalmedIatorsthat,whenfunctIonIngproperly,
leadtorepaIrofInjury.TheseprocessesarehIghlyconservedacrossspecIes,
4J
IndIcatIng
thecrItIcalImportanceoftheInflammatoryresponsethatdIrectstheprocessof
cellular/tIssuerepaIr.WhenanycomponentofhealIngIsdIsturbedandInterruptsthe
orderlyprogressIonofrepaIr,woundfaIluremayresult.
44
njurydamagesthelocalcIrculatIonandcausesplateletstoaggregateandreleasea
varIetyofsubstances,IncludIngchemoattractantsandgrowthfactors.
42
TheInItIalresultIs
coagulatIon,whIchpreventsexsanguInatIonbutalsowIdenstheareathatIsnolonger
perfused.PlateletdegranulatIonreleasesplateletderIvedgrowthfactor,transformIng
growthfactorbeta(TCF),epIdermalgrowthfactor,andInsulInlIkegrowthfactor1(CF
1),whIchconjoIntlyInItIatetheInflammatoryprocess.
42
8radykInIn,complement,and
hIstamInereleasedbymastcellscausevasodIlatIonandIncreasedvascularpermeabIlIty.
PolymorphonuclearleukocytesarrIveatthewoundalmostImmedIatelyandarefollowed
bymacrophagesat24to48hours.TheseInflammatorycellsactIvateInresponseto
endothelIalIntegrIns,selectIns,celladhesIonmolecules,cadherIns,fIbrIn,lactate,
hypoxIa,foreIgnbodIes,InfectIousagents,andgrowthfactors.
42
nturn,macrophagesand
lymphocytesproducemorelactate
45
andgrowthfactors,IncludIngCF1,leukocytegrowth
factor,InterleukIns(Ls)1and2,TCF,andvascularendothelIalgrowthfactor(7ECF).
46
ThIsearlyInflammatoryphase
P.278
P.279
IscharacterIzedbyerythemaandedemaofthewoundedges.
Table 13-5 UCSF Guidelines for Prophylactic Antibiotics in Adult Patients
to Reduce Surgical Site Infection
DRUG DOSE TIMING
ADDITIONAL
DOSE
Hip and Knee Arthroplasty, Extradural Ortho and Neuro Spine, Cardiothoracic,
Vascular Surgery and Kidney Transplantation
CefazolIn*
80
kg:1
gm
80
kg:2
gm
60mInbeforeIncIsIonasabolusoverJ5
mIn;wIthbolusdose,tIssuelevelsare
adequateInafewmInutes
Q4
hours
Exclude
KIdney
Tx
Neurosurgery (Cranial and Intradural Spine)
80
kg:1
CeftrIaxone*
gm
80
kg:2
gm
mIn
Q12
hours
Liver Transplantation
CeftrIaxone*
80
kg:1
gm
80
kg:2
gm
mIn
Q12
hours
*For Significant Beta Lactam Allergy (anaphylaxis to penicillins)
7ancomycIn
or
1gm
StartInfusIononarrIvalInDF(once
monItorsareattached);InfuseoverJ060
mIn
Q12
hours
ClIndamycIn
100
kg:
600
mg
100
kg:
900
mg
60mInbeforeIncIsIonasInfusIonover10
15mIn
Q6
hours
Colon Surgery
Cefotetan*
80
kg:1
gm
80
kg:2
gm
mIn
Q6
hours
*For significant Beta Lactam Allergy (anaphylaxis to penicillins)
CIprofloxacIn 400 60mInbeforeIncIsIonasInfusIonoverJ0 Q6
and mg mIn hours
|etronIdazole
500
mg

Vaginal and Abdominal Hysterectomy
CefazolIn
or
80
kg:1
gm
mIn
Q4
hours
Cefotetan(If
bowel
Involved)
80
kg:2
gm
Q6
hours
*For Significant Beta Lactam Allergy (anaphylaxis to penicillins)
CIprofloxacIn
and
400
mg
60mInbeforeIncIsIonasInfusIonoverJ0
mIn
Q6
hours
|etronIdazole
or
500
mg

ClIndamycIn
and
600
mg
60mInbeforeIncIsIonasInfusIonover10
15mIn
Q6
hours
CentamIcIn
1.5
mg/kg

Pediatric PatientsSuggested Dosing
Drug Dose
CefazolIn 20J0mg/kg
CeftrIaxone 25mg/kg
Cefotetan 20J0mg/kg
CefuroxIme 50mg/kg
7ancomycIn 15mg/kg(asanInfusIonoverJ060mIn)
CentamIcIn 2mg/kg
ClIndamycIn 15mg/kg
|etronIdazole 10mg/kg
CIprofloxacIn Notrecommended
NDTES:
AlwaysconfIrmwIthsurgeonsattheTImeDutorearlIer;Insomecasestheymay
wIshtodelayantIbIotIcsuntIlafterculture.
|akesuredoseIsInbeforetournIquetgoesup.
AddItIonalIntraoperatIvedoseshouldalsobegIvenIncIrcumstancesof
sIgnIfIcantbloodloss.
UsedwIthpermIssIonfromtheUnIversItyofCalIfornIa,SanFrancIsco0epartment
ofAnesthesIaandPerIoperatIveCare.
Figure 13-4.SchematIcoftheprocessesofwoundhealIng.(FromHuntT:
FundamentalsofwoundmanagementInsurgery,WoundHealIng:0IsordersofFepaIr.
SouthPlaInfIeld,NJ,ChIrugecom,nc,1976,wIthpermIssIon.)
ActIvatedneutrophIlsandmacrophagesalsoreleaseproteases,IncludIngneutrophIl
elastase,neutrophIlcollagenase,matrIxmetalloproteInase,andmacrophage
metalloelastase.
42
TheseproteasesdegradedamagedextracellularmatrIxcomponentsto
allowtheIrreplacement.ProteasesalsodegradethebasementmembraneofcapIllarIesto
enableInflammatorycellstomIgrateIntothewound.
nwounds,localbloodsupplyIscompromIsedatthesametImethatmetabolIcdemandIs
Increased.Asaresult,thewoundenvIronmentbecomeshypoxIcandacIdotIcwIthhIgh
lactatelevels.
47,48
ThIsrepresentsthesumofthreeeffects:(1)decreasedoxygensupply
duetovasculardamageandcoagulatIon,(2)IncreasedmetabolIcdemandduetothe
heIghtenedcellularresponse(anaerobIcglycolysIs),and(J)aerobIcglycolysIsby
Inflammatorycells.
49,50
LeukocytescontaInfewmItochondrIaandthereforeacquIreenergy
fromglucose,prImarIlybyproductIonoflactateandevenInthepresenceofadequate
oxygensupply.
50
nactIvatedneutrophIls,therespIratoryburst,InwhIchoxygenand
glucoseareconvertedtosuperoxIde,hydrogenIon,andlactate,accountsforupto98of
oxygenconsumptIon;InthesettIngofInjury,thIsactIvItyIncreasesbyupto50foldover
baselIne.
51,52
LocalhypoxIaIsanormalandInevItableresultoftIssueInjury.
5J,54
HypoxIaactsasa
stImulustorepaIr,
55
butalsoleadstopoorhealIng
JJ
andIncreasedsusceptIbIlItyto
InfectIon.
56,57
NumerousexperImentalmodels
16,56,57,58,59
aswellashumanclInIcal
experIence
60,61,62
haveledtotheconclusIonthatwoundhealIngIsdelayedInhypoxIc
wounds.ThepartIalpressureofoxygenIndermalwoundsIsheterogeneous,rangIngfrom0
to10mmHgInthecentral(deadspace)portIonofthewound,to80to100mmHg(near
arterIal)adjacenttoperfusedarterIolesandcapIllarIes
5J
(FIg.1J5).ThePD
2
ofagIven
areadependsondIffusIonofoxygenfromperfusedcapIllarIes,andthuswoundPD
2
depends
oncapIllarydensIty,arterIalPD
2
,andthemetabolIcactIvItyofthecells,wIthsome
contrIbutIonfromshIftsIntheoxyhemoglobIndIssocIatIoncurveassocIatedwIthwoundpH
andtemperature.
Resistance to Infection
AfteradIsruptIonofthenormalskInbarrIer,successfulwoundhealIngrequIrestheabIlIty
toclearforeIgnmaterIalandresIstInfectIon.NeutrophIlsprovIdenonspecIfIcImmunIty
andpreventInfectIon.LeukocytesmIgrateIntIssuetowardthesIteofInjuryvIa
chemotaxIs,defInedaslocomotIonorIentedalongachemIcalgradIent.
42
ChemIcal
gradIentscanbeproducedbothexogenouslyandendogenously.ExogenousgradIentsresult
frombacterIalproductspresentIncontamInatedtIssues.EndogenousmedIatorsInclude
componentsofthecomplementsystem(C5a),productsoflIpoxygenasepathway
(leukotrIene84),andcytokInes(L1,8),alongwIthlactate.
6J
P.280
Together,thesechemIcalmedIatorshelptoorganIzeandcontrolleukocyteInvasIon,
bacterIalkIllIng,necrotIctIssueremoval,andtheInItIatIonofangIogenesIsandmatrIx
productIon.ntheabsenceofInfectIon,neutrophIlsdIsappearbyabout48hours.
NonspecIfIcphagocytosIsandIntracellularkIllIngarethemajorImmunepathways
actIvatedInwounds.
64
Figure 13-5.ThevaryIngoxygentensIonInthewoundmodule.CrosssectIonofthe
woundmoduleInarabbItearchamberIsInleftuppercorneroffIgure.NotethatPD
2
,
depIctedgraphIcallyabovethecrosssectIon,IshIghestnexttothevessels,wItha
gradIentdowntozeroatthewoundedge.NotealsothelactategradIent,hIghInthe
deadspaceandlower(butstIllaboveplasma)towardthevasculature.Hydrogen
peroxIdeIspresentatfaIrlyhIghconcentratIonsandIsalsoamajorstImulustowound
repaIr.
7J
7ECF,vascularendothelIalgrowthfactor.(|odIfIedversIonreprIntedfromA
SIlver:ThephysIologyofwoundhealIng,FundamentalsofWound|anagement.EdIted
byTKHunt,JE0unphy.NewYork,AppletonCenturyCrofts,1980,pJ0,wIth
permIssIon.)
NeutrophIlsaretheprImarycellresponsIblefornonspecIfIcImmunIty,andtheIrfunctIon
dependsonahIghpartIalpressureofoxygen.
J6,65
ThIsIsbecausereactIveoxygenspecIes
arethemajorcomponentofthebacterIcIdaldefenseagaInstwoundpathogens.
64
PhagocytosIsofthepathogenactIvatesthephagosomaloxIdase(alsoknownastheprImary
oxIdaseornIcotInamIdeadenInedInucleotIdephosphateoxIdase[NA0PH]lInked
oxygenase),presentInthephagocytIcmembrane,whIchusesoxygenasthesubstrateto
catalyzetheformatIonofsuperoxIde.SuperoxIdeItselfIsbacterIcIdal,butmore
ImportantlyItInItIatesaserIesofcascadesthatproduceotheroxIdantswIthInthe
phagosomethatIncreasebacterIalkIllIngcapacIty(FIg.1J6).Forexample,Inthepresence
ofsuperoxIdedIsmutase,superoxIdeIsreducedtohydrogenperoxIde(H
2
D
2
).H
2
D
2
combInes
wIthchlorIdeandInthepresenceofmyeloperoxIdaseformsthebacterIcIdalhypochlorous
acId,morecommonlyrecognIzedastheactIveIngredIentInbleach.
65,66
.8ecause
IntraphagosomaloxIdantproductIondependsonconversIonofoxygentosuperoxIde,the
processIsexquIsItelysensItIvetothepartIalpressureofoxygenInthetIssue.TheK
m
(half
maxImalvelocIty)forthephagosomaloxIdaseusIngoxygenasasubstrateIs40to80mm
Hg.
J6
ThIsmeansthatresIstancetoInfectIonIscrItIcallyImpaIredbywoundhypoxIaand
becomesmoreeffIcIentasPD
2
IncreaseseventoveryhIghlevels(500to1,000mmHg).
J6
SuchlevelsdonotoccurnaturallyIntIssue,butcanbeachIevedbytheadmInIstratIonof
hyperbarIcoxygen.
67,68,69,70
ThIsIsonemechanIsmfortheproposedbenefItofhyperbarIc
oxygentherapyasanadjunctIvetreatmentfornecrotIzIngInfectIonsandchronIc
refractoryosteomyelItIs.
71,72
Figure 13-6.SchematIcofsuperoxIdeandotheroxIdantproductIonwIthInthe
phagosome.NA0PH,nIcotInamIdeadenInedInucleotIdephosphateoxIdase;NA0P,
nIcotInamIdeadenInedInucleotIdephosphate;SD0,superoxIdedIsmutase;|P,
myeloperoxIdase.(FromHuntTK,HopfHW:WoundhealIngandwoundInfectIon.What
surgeonsandanesthesIologIstscando.SurgClInNorthAm1997;77(J):587,wIth
permIssIon.)
DxIdantsproducedbyInflammatorycellshaveadualroleInwoundrepaIr.Notonlyare
theycentraltoresIstancetoInfectIon,buttheyalsoplayamajorroleInInItIatIngand
dIrectIngthehealIngprocess.DxIdants,andInpartIcular
P.281
hydrogenperoxIdeproducedvIatherespIratoryburst,IncreaseneovascularIzatIonand
collagendeposItIonInvItroandInvIvo.
7J
Proliferation
TheprolIferatIvephasenormallybegInsapproxImately4daysafterInjury,concurrentwIth
awanIngoftheInflammatoryphase.tconsIstsofgranulatIontIssueformatIonand
epIthelIzatIon.CranulatIonInvolvesneovascularIzatIonandsynthesIsofcollagenand
connectIvetIssueproteIns.
Neovascularization
NewbloodvesselsmustreplacetheInjuredmIcrocIrculatIon.NeovascularIzatIonInwounds
proceedsbothbyangIogenesIsandvasculogenesIs.AngIogenesIsIsthephenomenonofnew
vesselgrowthvIabuddIngfromexIstIngvessels.nthesettIngofwounds,newvesselsgrow
frommaturevessels,usuallyIntact,postcapIllaryvenulesIntheundamagedtIssue
ImmedIatelyadjacenttothesIteofInjury.Normally,theoxygentensIonInadjacenttIssue
IssuffIcIenttosupportthIsprocess.ThenewvesselgrowthextendsandentersIntothe
damagedareasthataretypIcallyhIghInlactateandhavealowpartIalpressureofoxygen.
|atureextracellularmatrIxIsrequIredforIngrowthofmaturevessels.
74
nvasculogenesIs,bonemarrowderIvedendothelIalprecursorcells(EPCs)populatethe
tIssueanddIfferentIateandgrowIntonewvesseltubules.nwounds,thesetubulesappear
InthedamagedareabeforeanydIrectanastomosIswIthpreexIstIngvesselsIsmade.
ThesetubulesmustconnectwIthexIstIngvasculaturetoestablIshanIntactbloodsupplyIn
thewound.AngIogenesIshaslongbeenheldtobetheprImarymechanIsmfornewblood
vesselgrowthIngranulatIontIssue.Fecentresearch,however,hasdemonstratedthatas
manyas15to20ofnewbloodvesselsInwoundsarederIvedfromhematopoIetIcstem
cells.
74,75,76
AngIogenesIsandvasculogenesIsbothoccurInresponsetosImIlarstImulI,consIstIngof
somecombInatIonofredoxstress,hypoxIa,andlactate.However,thespecIfIcmechanIsms
bywhIchtheyproceedappeartodIffersomewhat.AngIogenesIsInvolvesthemovementof
endothelIalcellsInresponsetothreewavesofgrowthfactors.ThefIrstwaveofgrowth
factorscomeswIththereleasebyplateletsofplateletderIvedgrowthfactor,TCF,CF
1,andothersdurIngtheInflammatoryphase.ThesecondwavecomesfromfIbroblast
growthfactorreleasedfromnormalbIndIngsItesonconnectIvetIssuemolecules.ThethIrd
anddomInantwavecomesfrom7ECF,delIveredlargelybymacrophagesstImulatedby
fIbrInopeptIdes,hypoxIa,andlactate.
77
AlthoughItIsusuallypresent,hypoxIaIsnot
requIredforgranulatIonbecauseofconstItutIve(aerobIc)lactateproductIonby
InflammatorycellsandfIbroblasts.ToolIttlelactateleadstoInadequategranulatIon,
whIlelevelsInexcessofabout15m|usuallyassocIatedwIthInflammatIonorInfectIon
delaygranulatIon.
78
ThecapIllaryendothelIalresponsetoangIogenIcagentsrequIres
oxygensothatangIogenesIsprogressesInproportIontobloodperfusIonandarterIalPD
2
.
79
7asculogenesIsoccursInresponsetosImIlarstressorsasangIogenesIs.EPCsaremobIlIzed
fromthebonemarrowIntothecIrculatIonvIaanItrIcoxIdemedIatedmechanIsm.TIssue
hypoxIaInducesreleaseof7ECFA,whIchactIvatesbonemarrowstromalnItrIcoxIde
synthase.ncreasedbonemarrownItrIcoxIdeleadstoreleaseofEPCsIntothecIrculatIon.
ThesecIrculatIngEPCshometothewoundvIatIssuehypoxIaInducedupregulatIonof
stromalcellderIvedfactor1.WIthInthewound,EPCsundergodIfferentIatIonand
partIcIpateIntheformatIonofnewbloodvessels.
75
Collagen and Extracellular Matrix Deposition
NewbloodvesselsgrowIntothematrIxthatIsproducedbyfIbroblasts.AlthoughfIbroblasts
replIcateandmIgratemaInlyInresponsetogrowthfactorsandchemoattractants,
productIonofmaturecollagenrequIresoxygen.
J7,80,81
Lactate,hypoxIa,andsomegrowth
factorsInducecollagenmFNAsynthesIsandprocollagenproductIon.PosttranslatIonal
modIfIcatIonbyprolylandlysylhydroxylasesIsrequIredtoallowcollagenpeptIdesto
aggregateIntotrIplehelIces.CollagencanonlybeexportedfromthecellwhenItIsInthIs
trIplehelIcalstructure.ThehelIcalconfIguratIonIsalsoprImarIlyresponsIblefortIssue
strength.TheactIvItyofthehydroxylasesIscrItIcallydependentonvItamInCandtIssue
oxygentensIon,wIthaK
m
foroxygenofabout25mmHg.
J7,80,81,82
Woundstrength,whIch
resultsfromcollagendeposItIon,IsthereforehIghlyvulnerabletowoundhypoxIa.
JJ
NeovascularIzatIonandextracellularmatrIx(prImarIlycollagen)productIonareclosely
lInked.FIbroblastscannotproducematurecollagenIntheabsenceofmaturebloodvessels
thatdelIveroxygentothesIte.NewbloodvesselscannotmaturewIthoutastrongcollagen
matrIx.|IcekeptInahypoxIcenvIronmentof1JInspIredoxygendevelopsomenew
bloodvesselsInatestwoundwIththeaddItIonofexogenous7ECForlactate,butthese
vesselsareImmaturewIthlIttlesurroundIngmatrIxanddemonstratefrequentareasof
hemorrhage.
41
Epithelization
EpIthelIzatIonIscharacterIzedbyreplIcatIonandmIgratIonofepIthelIalcellsacrossthe
skInedgesInresponsetogrowthfactors.CellmIgratIonmaybegInfromanysItethat
contaInslIvIngkeratInocytes,IncludIngremnantsofhaIrfollIcles,sebaceousglands,Islands
oflIvIngepIdermIs,orthenormalwoundedge.nacutewoundsthatareprImarIlyclosed,
epIthelIzatIonIsnormallycompletedIn1toJdays.nopenwoundshealIngbysecondary
IntentIon,epIthelIzatIonIsthefInalphaseofhealIngandcannotprogressuntIlthewound
bedIsfullygranulated.LIkeImmunItyandgranulatIon,epIthelIzatIondependsongrowth
factorsandoxygen.SIlver
8J
and|edawar
40
demonstratedInvIvothattherateof
epIthelIzatIondependsonlocaloxygen.TopIcaloxygenapplIedInamannerthatdoesnot
dryoutepIthelIalcellshasbeenadvocatedasamethodtoIncreasetherateof
epIthelIzatIon.
84
Ngoetal.
85
demonstratedoxygendependentdIfferentIatIonandcell
growthInhumankeratInocyteculture.ncontrast,D'Tooleetal.
86
demonstratedthat
hypoxIaIncreasesepIthelIalmIgratIonInvItro.ThIsmaybeexplaIned,atleastInpart,by
thedependenceofepIthelIzatIononthepresenceofabedofhealthygranulatIontIssue,
whIchIsknowntobeoxygendependent.
Maturation and Remodeling
ThefInalphaseofwoundrepaIrIsmaturatIon,whIchInvolvesongoIngremodelIngofthe
granulatIontIssueandIncreasIngwoundtensIlestrength.AsthematrIxbecomesdenser
wIththIcker,strongercollagenfIbrIls,ItbecomesstIfferandlesscomplIant.FIbroblastsare
capableofadaptIngtochangIngmechanIcalstressandloadIng.FIbroblastsmIgrate
throughoutthematrIxtohelpmoldthewoundtonewstresses.|atrIxmetalloproteInases
andotherproteaseshelpwIthfIbroblastmIgratIonandcontInuedmatrIxremodelIngIn
responsetomechanIcalstress.SomefIbroblastsdIfferentIateIntomyofIbroblastsunderthe
InfluenceofTCF,resultIngIncontractIlecells.AsthemyofIbroblastscontract,the
collagenousmatrIxcrosslInksIntheshortenedposItIon.ThIshelpstostrengthenthe
matrIxandmInImIzescarsIze.ContractIonIsInhIbItedbytheuseofhIghdosesof
cortIcosteroIds.
87
EvensteroIdsgIven
P.282
severaldaysafterInjuryhavethIseffect.nthosewoundswherecontractIonIs
detrImental,thIseffectcanbeusedforbenefIt.
NetcollagensynthesIscontInuesforatleast6weeksandupto6monthsafterwoundIng.
DvertIme,theInItIalcollagenthreadsarereabsorbedanddeposItedalongstresslInes,
conferrInggreatertensIlestrength.CollagenfoundIngranulatIontIssueIsbIochemIcally
dIfferentfromcollagenofunInjuredskIn,andascarneverachIevesthetensIlestrengthof
unInjuredskIn.HydroxylatIonandglycosylatIonoflysIneresIduesIngranulatIontIssue
collagenleadtothInnercollagenfIbers.At1week,awoundclosedbyprImaryIntentIon
hasonlyreachedJofthetensIlestrengthofnormalskIn.8yJweeksItIsatJ0,andIt
onlyreaches80afterJto6months.
Somewoundshealtoexcess.HypertrophIcscarandkeloIdarecommonformsofabnormal
scarduetoabnormalresponsestohealIng.HypertrophIcscarrIngmaybethoughtofas
exuberantscarrIngInwhIchtheInflammatoryprocessthatallowswoundhealIngremaIns
excessIvelyactIve,resultIngInstIff,rubbery,nonmobIlescartIssue.HypertrophIcscarsare
mostcommonlyseenfollowIngburnsandarethoughttocorrelatewIththelengthoftIme
requIredtoclosethewound,althoughotherfactorsarealsobelIevedtoplayaroleandare
beIngactIvelyexplored.KeloIdsarescarsthatoutgrowtheboundarIesoftheInItIalscar,
andaremosttypIcallyseenfollowIngsurgIcalIncIsIons.KeloIdformatIonIsmostlIkelydue
toagenetIcpredIsposItIon,althoughexogenousInflammatoryfactorsmayalsoplayarole.
Wound Perfusion and Oxygenation
ComplIcatIonsofwoundsIncludefaIluretoheal,InfectIon,andexcessIvescarrIngor
contracture.FapIdrepaIrhastheleastpotentIalforInfectIonandexcessscarrIng.The
perIoperatIvephysIcIan'sgoals,therefore,aretoavoIdcontamInatIon,ensurerapIdtIssue
synthesIs,andoptImIzetheImmuneresponse.AllsurgIcalproceduresleadtosomedegree
ofcontamInatIonthatmustbecontrolledbylocalhostdefenses.TheInItIalhoursafter
contamInatIonrepresentadecIsIveperIoddurIngwhIchInadequatelocaldefensesmay
allowanInfectIontobecomeestablIshed.
Normally,woundsontheextremItIesandtrunkhealmoreslowlythanthoseontheface.
ThemajordIfferenceInthesewoundsIsthedegreeoftIssueperfusIonandthusthewound
tIssueoxygentensIon.Asarule,repaIrproceedsmostrapIdlyandImmunItyIsstrongest
whenwoundoxygenlevelsarehIgh,andthIsIsonlyachIevedbymaIntaInIngperfusIonof
InjuredtIssue.
88
schemIcorhypoxIctIssue,ontheotherhand,IshIghlysusceptIbleto
InfectIonandhealspoorly,Ifatall.WoundtIssueoxygenatIonIscomplexanddependson
theInteractIonofbloodperfusIon,arterIaloxygentensIon,hemoglobIndIssocIatIon
condItIons,carryIngcapacIty,masstransferresIstances,andlocaloxygenconsumptIon.
WoundoxygendelIverydependsonvascularanatomy,thedegreeofvasoconstrIctIon,and
arterIalPD
2
.
ThestandardteachIngthatoxygendelIverydependsmoreonhemoglobInboundoxygen
(oxygencontent)thanonarterIalPD
2
maybetrueofworkIngmuscle,butItIsnottrueof
woundhealIng.nmuscle,IntercapIllarydIstancesaresmallandoxygenconsumptIonIs
hIgh.ncontrast,IntercapIllarydIstancesarelargeandoxygenconsumptIonIsrelatIvely
lowInsubcutaneoustIssue.
J8
nwounds,wherethemIcrovasculatureIsdamaged,dIffusIon
dIstancesaresubstantIallyIncreased.PerIpheralvasoconstrIctIonfurtherIncreases
dIffusIondIstance.
5J
ThedrIvIngforceofdIffusIonIspartIalpressure.Hence,ahIghPD
2
Is
neededtoforceoxygenIntoInjuredandhealIngtIssues,partIcularlyInsubcutaneous
tIssue,fascIa,tendon,andbone,thetIssuesmostatrIskforpoorhealIng.
AlthoughoxygenconsumptIonIsrelatIvelylowInwounds,ItIsconsumedbyprocessesthat
requIreoxygenatahIghconcentratIon.nflammatorycellsuselIttleoxygenfor
respIratIon,producIngenergylargelyvIathehexosemonophosphateshunt.
J6
|ostofthe
oxygenconsumedInwoundsIsusedforoxIdantproductIon(bacterIalkIllIng),wItha
sIgnIfIcantcontrIbutIonaswellforcollagensynthesIs,angIogenesIs,andepIthelIzatIon.The
rateconstants(K
m
)foroxygenforthesecomponentsofrepaIrallfallwIthInthephysIologIc
rangeof25to100mmHg.
J6,J7,40,65,80,89
8ecauseofthehIghrateconstantsforoxygensubstrateforthecomponentsofrepaIr,the
rateatwhIchrepaIrproceedsvarIesaccordIngtotIssuePD
2
fromzerotoatleast250mm
Hg.nvItrofIbroblastreplIcatIonIsoptImalataPD
2
ofabout40to60mmHg.NeutrophIls
losetheIrabIlItytokIllbacterIaInvItrobelowaPD
2
ofabout40mmHg.
90,91
TheseInvItro
observatIonsareclInIcallyrelevant.NormalsubcutaneousPD
2
,measuredIntestwounds
InunInjured,euthermIc,euvolemIcvolunteersbreathIngroomaIr,Is657mmHg.
92
Thus,
anyreductIonInwoundPD
2
mayImpaIrImmunItyandrepaIr.nsurgIcalpatIents,therate
ofwoundInfectIonsIsInverselyproportIonal
56
andcollagendeposItIonIsdIrectly
proportIonal
JJ
topostoperatIvesubcutaneouswoundtIssueoxygentensIon.
HIghoxygentensIons(100mmHg)canbereachedInwoundsbutonlyIfperfusIonIsrapId
andarterIalPD
2
IshIgh.
JJ,88
ThIsIsbecausesubcutaneoustIssueservesareservoIr
functIon,sothereIsnormallyflowInexcessofnutrItIonalneedsandwoundcellsconsume
relatIvelylIttleoxygen,about0.7mL/100mLofbloodflowatanormalperfusIonrate.
J8,J9
WhenarterIaloxygentensIon(Pao
2
)IshIgh,thIssmallvolumecanbecarrIedbyplasma
alone.ContrarytopopularbelIef,therefore,oxygencarryIngcapacIty,thatIs,hemoglobIn
concentratIon,IsnotpartIcularlyImportanttowoundhealIng,provIdedthatperfusIonIs
normal.
9J,94
WoundPD
2
andcollagensynthesIsremaInnormalInIndIvIdualswhohave
hematocrItlevelsaslowas15to18provIdedtheycanapproprIatelyIncreasecardIac
outputandvasoconstrIctIonIsprevented.
94,95
PerIpheralvasoconstrIctIon,whIchresultsfromcentralsympathetIccontrolof
subcutaneousvasculartone,IsprobablythemostfrequentandclInIcallythemost
ImportantImpedImenttowoundoxygenatIon.SubcutaneoustIssueIsbothareservoIrto
maIntaIncentralvolumeandamajorsIteofthermoregulatIon.ThereIslIttlelocal
regulatIonofbloodflow,exceptbylocalheatIng.
96,97
Therefore,subcutaneoustIssueIs
partIcularlyvulnerabletovasoconstrIctIon.SympathetIcallyInducedperIpheral
vasoconstrIctIonIsstImulatedbycold,paIn,fear,andbloodvolumedefIcIt,
98,99
andby
varIouspharmacologIcagentsIncludIngnIcotIne,
92
adrenergIcantagonIsts,and
1
agonIsts,allcommonlypresentIntheperIoperatIveenvIronment.PerIoperatIve
hypothermIaIscommonandresultsfromanesthetIcdrugs,exposuretocold,andredIstrI
butIonofbodyheatfromthecoretotheperIphery.
100
8loodlossandIncreasesInInsensIble
lossesIncreasefluIdrequIrementsIntheperIoperatIveperIod,therebyleavIngthepatIent
vulnerabletoInadequatefluIdreplacement.Thus,vasomotortoneIs,toalargedegree,
undertheperIoperatIvephysIcIan'scontrol.
98,99
PreventIonorcorrectIonofhypothermIa
101
andbloodvolumedefIcIts
102
havebeenshown
todecreasewoundInfectIonsandIncreasecollagendeposItIonInpatIentsundergoIng
majorabdomInalsurgery.PreoperatIvesystemIc(forcedaIrwarmer)orlocal(warmIng
bandage)warmInghavealsobeenshowntodecreasewoundInfectIons,evenInclean,low
rIsksurgerIessuchasbreastsurgeryandInguInalhernIarepaIr.
10J
SubcutaneoustIssue
oxygentensIonIssIgnIfIcantlyhIgherInpatIentswIthgoodpaIncontrolthanthosewIth
poorpaIncontrolafter
P.28J
arthroscopIckneesurgery.
104
StressalsocauseswoundhypoxIaandsIgnIfIcantlyImpaIrs
woundhealIngandresIstancetoInfectIon.
105,106
TheseeffectsareclearlymedIated,In
largepart,bychangesInthepartIalpressureofoxygenIntheInjuredtIssue.
CreIfetal.
107
demonstratedInarandomIzed,controlled,doubleblIndtrIalIncludIng500
patIentsthatInwarm,volumerepletepatIentswIthgoodpaIncontrolundergoIngmajor
colonsurgery,admInIstratIonof80versusJ0oxygenIntraoperatIvelyandforthefIrst2
postoperatIvehourssIgnIfIcantlyreducedthewoundInfectIonrateby50.8eldaetal.
108
replIcatedtheseresults(sIgnIfIcant40reductIonInsurgIcalsIteInfectIon)Ina
randomIzed,controlled,doubleblIndtrIalInJ00colonsurgerypatIentsrandomIzedto80
versusJ0oxygenIntraoperatIvelyanddurIngthefIrst6postoperatIvehours.SurgIcaland
anesthetIcmanagementwerestandardIzedandIntendedtosupportoptImalperfusIon.
|ylesetal.
109
demonstratedasIgnIfIcantreductIonInmajorpostoperatIvecomplIcatIons,
aswellasspecIfIcallywoundInfectIonsIn2,050majorsurgerypatIentsrandomIzedto80
oxygenversusJ0oxygenIn70nItrousoxIdeIntraoperatIvely.Asmaller(n=165)
randomIzed,controlledstudybyPryoretal.,
110
demonstratedadoublIngofsurgIcalsIte
InfectIonInpatIentsrandomIzedto80versusJ5oxygenIntraoperatIvely.Therewerea
numberofmethodologIcflawsInthestudy,but,moreImportantly,thetwogroupsof
patIentswerenotequIvalent,whIchlIkelyexplaInedtheIncreaseInInfectIonsseenInthe
80oxygengroup.Thus,thepreponderanceofevIdenceIndIcatesthatuseofhIghInspIred
oxygenIntraoperatIvelyandprovIdIngsupplementaloxygenpostoperatIvelyInwell-
perfusedpatIentsundergoIngmajorabdomInalsurgerywIllreducetherIskofwound
InfectIon.
0elIveryofantIbIotIcsalsodependsonperfusIon.ParenteralantIbIotIcsgIvensothathIgh
levelsarepresentInthebloodatthetImeofwoundIngclearlydImInIshbutdonot
elImInatewoundInfectIons.
20
naboutonethIrdofallwoundInfectIons,thebacterIa
culturedfromthewoundaresensItIvetotheprophylactIcantIbIotIcgIventothepatIent,
evenwhentheantIbIotIcsweregIvenaccordIngtostandardprocedure.
20
Thevulnerable
thIrdofpatIentsappeartobethehypoxIcandvasoconstrIctedgroup.WhenantIbIotIcsare
presentInthewoundatthetImeofInjury,theyaretrappedInthefIbrInclotatthewound
sItewheretheymayhaveeffIcacyagaInstcontamInatIngorganIsms.AntIbIotIcsdIffuse
poorlyIntothefIbrInclot,however,sothatlateradmInIstratIon,whethermorethan2
hoursafterInjuryorInresponsetowoundInfectIon,wIllhavelIttleeffect.Dntheother
hand,oxygendIffuseseasIlythroughthefIbrInclotsandIseffectIveeven6hoursafter
contamInatIon.
18
Role of Dysregulation in Impaired Wound Healing
HumanbeIngschallengedbyadversephysIcalorpsychosocIaleventsmountacoordInated,
adaptIvereactIoncharacterIzedbyphysIologIcalarousal.ThIsresponseIsoftenassocIated
psychologIcallywIththeexperIenceofthreatorothernegatIveaffect.Thetermforsuch
anarousalreactIonIsstress response,andanyeventthattrIggerssucharesponseIsa
stressor.ThemajormechanIsmsofthestressresponsearethehypothalamopItuItary
adrenocortIcal(HPA)axIsandthesympathoadrenomedullary(SA|)axIs.
111
PsychosocIal
stressorsevokecognItIveresponsessuchasappraIsal,memory,expectatIon,andthe
attrIbutIonofmeanIng.TheseendogenousprocessesheavIlyInvolvetheprefrontaland
frontalcortIcesofthebraIn,andthesecortIcesexertcontroloveraspectsofthe
hypothalamus,IncludIngtheperIventrIcularnucleus(P7N).TheP7NInItIatestheHPAstress
responseandcontrolsItthroughnegatIvefeedbackmechanIsms.TheP7NtrIggersfurther
stressresponseIntheSA|axIsbyrecruItIngcatecholamInergIccellsIntherostral
ventrolateralmedulla.ThIsstructureIsacardIovascularregulatoryareaInvolved,
togetherwIththesolItarynucleus,Inthecontrolofbloodpressure.Therostral
ventrolateralmedullaactIvatesthesolItarynucleusand,togetherwIthIt,provIdestonIc
excItatorydrIvetosympathetIcvasoconstrIctornervesthatmaIntaInrestIngblood
pressurelevels.AnormalstressresponseInvolvesacomplexpatternofautonomIcarousal
thatIncludesIncreasedbloodpressurefollowedbyaperIodofrecoverywhenblood
pressureandotheraspectsofarousalreturntonormal.
HumanlIfeIscomplexandoftenInvolvesrepetItIvestressorsoraserIesofstressors.When
theHPAaxIsmustmountanewstressresponsebeforetheprevIousstressresponsehas
fullyrecovered,ItIncursrIskofsystemdysregulatIon.ThatIs,processesnormallyself
regulatIngthroughnegatIvefeedbackbecomeunregulatedanddysfunctIonal,wIth
maladaptIveconsequences.SA|dysregulatIon,whIchmayInvolvealteredmedullary
CA8AergIcneurotransmIssIon,
112
canresultInabnormalbloodflowofIndefInIteduratIon.
ThIs,Inturn,cancompromIseoxygenatIonofthehealIngwound.
Patient Management
Preoperative Preparation
CIvenknowledgeofthephysIologyofwoundhealIng,whatarethebeststrategIestoensure
optImalhealIng:WoundInfectIon,healIngfaIlure,anddehIscencearedreaded
complIcatIonsofsurgery.TothedegreetheyarepredIctable,InterventIonscanbe
targetedatthosepatIentsmostatrIsk(Table1J6).
TheC0C,IntheStudyoftheEffectofNosocomIalnfectIonControl(SENC),
11J
developed
aremarkablyusefulandsImplepredIctIvetoolbasedonascoreof0or1foreachofthe
followIngfourpatIentfactors:anabdomInaloperatIon,anoperatIonthatlasts2hoursor
more,asurgIcalsItethatIscontamInatedorInfected,andapatIentwhowIllhavethreeor
moredIagnosesatdIscharge,exclusIveofwoundInfectIon.TherIskofInfectIonwItha
scoreof0Is1,wIthascoreof1IsJ.6,wIthascoreof2Is9,wIthascoreofJIs17,
andwIthascoreof4Is27.ThesepercentagesmayseemhIgh,butthIsIndexwas
constructedonJoftheAmerIcansurgIcalpatIentsIn19751976and198J,andtheoverall
resultsare
P.284
consIstentwIthnumerousotherstudIes.|orerecentrIskanalysesbythesamegroup,
basedonsImplerpredIctors(e.g.,AmerIcanSocIetyofAnesthesIologIstsPhysIcalStatus
ClassIfIcatIon)haveyIeldedlesssensItIvIty,butaboutthesameoverallInfectIonrate.
114
Table 13-6 Preoperative Checklist
AssessandoptImIzecardIopulmonaryfunctIon.CorrecthypertensIon.
TreatvasoconstrIctIon:Attendtobloodvolume,thermoregulatory
vasoconstrIctIon,paIn,andanxIety.
AssessrecentnutrItIonandtreatasapproprIate.
TreatexIstIngInfectIon.AmongotheractIons,cleanandtreatskInInfectIons.
AssesswoundrIskbySENC
a
scoreInordertodecIdeontheextenttowhIch
prophylactIcmeasuresshouldbetaken.
StartvItamInAoranabolIcsteroIdsInpatIentstakIngprednIsone.
mproveormaIntaInbloodsugarcontrol.
a
Seetextandreference11J.
FromHuntTK,HopfHW:WoundhealIngandwoundInfectIon.Whatsurgeonsand
anesthesIologIstscando.SurgIcalClInIcsofNorthAmerIca1997;77:587,wIth
permIssIon.
|odIfIablerIsksIncludesmokIng,malnutrItIon,hyperglycemIa,hypercholesterolemIa,and
hypertensIon.TheseshouldbeassessedandcorrectedwhenpossIbleprIortosurgery.The
decIsIontodelaysurgerymusttakeIntoaccountboththeurgencyofthesurgeryandthe
severItyoftherIsk.
StressdysregulatIonalsopredIsposestopoorwoundhealIng.HumanandmurInestudIesare
consIstentInshowIngthatexposIngasubjecttoastressordelayswoundrepaIr.AnImal
stressmodelstypIcallyInvolverestraIntorsocIaldIsruptIon,whIlehumanmodelsusually
employapublIcspeakIngchallenge.
115
LaboratorystressIsshorttermandassocIatedwIth
IncreasedcortIsolandcortIcosteronelevelsthatdownregulatetheearlyInflammatory
response.ThIsdIrectlyImplIcatestheHPAaxIs,butthebackgroundprocessesaremore
extensIve.HumanstudIescanalsotakeadvantageofnaturallyoccurrIngstressorssuchas
academIcexamInatIonormarItaldIscord.SuchstudIescomparestressedandnonstressed
populatIonsInrateofhealIngfollowIngapunchbIopsyorInducedblIster.ThIsapproach
allowsInvestIgatorstostudychronIccondItIonsassocIatedwIthdysregulatIonsuchas
depressIon.
ThemechanIsmsbehIndwoundhealIngaremoreextensIvethanalteredHPAaxIsfunctIon
alone,andsonegatIveclInIcaloutcomescantakemultIpleforms.Thenervous,endocrIne,
andImmunesystemsoperateInterdependentlythroughacommonchemIcallanguage
composedofneurotransmItters,hormones,cytokInes,peptIdes,andendocannabInoIds.
111
SImplestresscanslowwoundhealIng,butstressInduceddysregulatIoncanleadto
endurIngdysfunctIonInautonomIcnervoussystem,endocrInefunctIon,and/orImmune
functIon.mmunecomplIcatIonsIncludeImpaIredbacterIalclearanceatthewound,
105
the
sIcknessresponsesassocIatedwIthproInflammatorycytokInes,
116
andsystemIcImbalance
IntheThelper1/Thelper2(Th1/Th2)cytokIneprofIle.ThIsprofIlerepresentsbalanceIn
thecontrIbutIonsofhelperTcellsubsets:Th1IsproInflammatoryandTh2antI
Inflammatory.Th1domInantImbalanceIndIcatesexcessIveInflammatIonwIthresultant
fatIgue,achIngjoInts,andlossofappetIte.SurgerysometImescreatesaTh2Imbalance,
whIchputsthepatIentatrIskforsepsIs,edema,andothercomplIcatIonssuchaspoor
sleep.Th1/Th2balancenormallyrecoversaftersurgery,butsomepatIentscometosurgery
alreadychronIcallydysregulatedIncytokIneprofIle,whIchmaypredIsposethemtopoor
woundhealIngandothernegatIveoutcomes.
AdversepsychosocIalcIrcumstancesatthetImeofsurgerymayputpatIentsatrIskforpoor
woundhealIng.KIecoltClaseretal.
117
studIedtheImpactofhostIlemarItalInteractIonson
thehealIngofexperImentalblIsterwounds.HIghhostIlecouplesproducedmore
proInflammatorycytokInesandhealedmoreslowlythanlowhostIlecouples.UsIngatape
strIppIngmodel,|uIzzuddInetal.
118
InvestIgatedtheeffectofmarItaldIssolutIononskIn
barrIerrecoveryandfoundthathIghstresswasassocIatedwIthslowerrecovery.8oschand
colleagues
119
studIedthehealIngofacIrcularwoundontheoralhardpalateInsubjects
whovarIedIndepressIonand/ordysphorIa.HIghdysphorIcIndIvIdualshadhIgherwound
sIzesfromday2onwardanddepressIvesymptomspredIctedslowerwoundhealIng.
CollectIvely,thesestudIespoInttolInksbetweenpsychosocIaldIstress,dysregulatIonat
thesystemlevel,andImpaIredcapacItyforwoundhealIng.tseemslIkelythatstress
reductIontechnIqueswIllreducewoundcomplIcatIons,andwelldesIgnedclInIcaltrIalsare
neededInthIsarea.
Intraoperative Management
CarefulsurgIcaltechnIqueIsfundamentaltooptImalwoundhealIng(Table1J7).0elIcate
handlIngofthetIssue,adequatehemostasIs,andsurgeonexperIenceleadtohealthIer
wounds.ncIsIonsshouldbeplannedwIthregardtobloodsupply,partIcularlywhen
operatIngnearorInoldIncIsIons.|echanIcalretractorsshouldbereleasedfromtImeto
tImetoallowperfusIontothewoundedges.JudIcIousantIbIotIcIrrIgatIonofcontamInated
areasmaybeeffectIve.8ecausedrIedwoundsloseperfusIon,woundsshouldbekeptmoIst,
especIallydurInglongoperatIons.NotallwoundscanbeanatomIcallyclosed.Edema,
obesIty,thepossIbIlItyofunacceptablerespIratorycompromIse,orneedtodebrIdegrossly
contamInatedornecrotIcsofttIssuescanallInterferewIthclosureofthewound.
AstheoperatIonproceeds,newwoundsaremadeandcontamInatIoncontInues.All
anesthetIcagentstendtocausehypothermIafIrst,bycausIngvasodIlatIon,whIch
redIstrIbutesheatfromcoretoperIpheryInprevIouslyvasoconstrIctedpatIents,and
secondlybyIncreasIngheatlossanddecreasIngheatproductIon.
100
7asoconstrIctIonIs
uncommonIntraoperatIvely,asthethresholdforthermoregulatoryvasoconstrIctIonIs
decreased,butIsoftensevereIntheImmedIatepostoperatIveperIodwhenanesthesIaIs
dIscontInuedandthethermoregulatorythresholdreturnstonormalInthefaceofcore
hypothermIa.TheonsetofpaInwIthemergencefromanesthesIaaddstothIs
vasoconstrIctIonbecauseoftheassocIatedcatecholamInerelease.
104
FapIdrewarmIng
usIngaforcedaIrwarmerforhypothermIcpatIentsInthepostanesthesIacareunIt(PACU)
doesappeartobeeffectIve,
120
althoughpreventIonofhypothermIaIsclearlythegoal.
101
|aIntenanceofahIghroomtemperatureorforcedaIrwarmIngbefore,durIng,andafter
theoperatIonIssIgnIfIcantlymoreeffectIvethanothermethodsofwarmIngsuchas
cIrculatIngwaterblanketsplacedunderthepatIentandhumIdIfIcatIonofthebreathIng
cIrcuIt.
121
Volume Management
SurgIcalstressresultsInIncreasedIntravenousfluIdrequIrements.TheIncreasedfluId
requIrementmaybepartlyduetosubstanceslIkeL6,TNF,substanceP,andbradykInIn,
whIcharereleasedInresponseto,andInproportIonto,surgIcalstress.
122
These
InflammatorymedIatorscausebothvasodIlatIonandan
P.285
IncreaseInvascularpermeabIlIty.
12J
ThIslossoffunctIonalIntravascularvolumeIsIn
addItIontootherknowncausesofperIoperatIvehypovolemIaorfluIdloss.TheseInclude
preoperatIvemechanIcalbowelpreparatIon,lackoforalIntake,fever,preexIstIng
medIcalcondItIons,andmedIcatIonssuchasdIuretIcs,aswellsurgIcalfluIdlosses,whIch
IncludeevaporatIonandbloodloss.
Table 13-7 Intraoperative Management
ApproprIateprophylactIcantIbIotIcsshouldbegIvenatthestartofany
procedureInwhIchInfectIonIshIghlyprobableand/orhaspotentIallydIsastrous
consequences.|aIntaInantIbIotIclevelsdurInglongoperatIons.
KeeppatIentswarm.
DbservegentlesurgIcaltechnIquewIthmInImaluseoftIesandcautery.
KeepwoundsmoIst.
AntIbIotIcIrrIgatIonIncontamInatedcases.
ElevatePao
2
.
0elayedclosureforheavIlycontamInatedwounds.
UseapproprIatesutures(andskIntapes).
UseapproprIatedressIngs.
permIssIon.
ThereareknownserIouscomplIcatIonsofbothhypervolemIaandhypovolemIa,
partIcularlyIntheperIoperatIveperIod.ThemajorcomplIcatIonsassocIatedwIthhyper
volemIaIncludepulmonaryedema,congestIveheartfaIlure,edemaofgutwIthprolonged
Ileus,andpossIblyanIncreaseIncardIacarrhythmIas.
124
ThemajorcomplIcatIonsofhypo
volemIa,asIdefromhemodynamIcInstabIlIty,IncludedecreasedoxygenatIonofsurgIcal
wounds(whIchpredIsposestowoundInfectIon),
JJ,56,88,125,126,127
decreasedcollagen
formatIon,
JJ,102
ImpaIredwoundhealIng,andIncreasedwoundbreakdown.
DptImIzIngthevolumeofperIoperatIvefluIdadmInIstratIontomInImIzemorbIdItyand
mortalItyremaInsasIgnIfIcantandcontroversIalchallenge.EstImatesofbloodloss,thIrd
spacefluIdlosses,andmaIntenancerequIrementsarenotorIouslyInaccurateandmaylead
toeItheroverorunderreplacementIfusedasguIdes.Currently,mostpractItIonersrelyon
clInIcalacumen,vItalsIgnssuchasheartrateandbloodpressure,andurIneoutputto
manageperIoperatIvefluIds.SurgIcalpatIentscanbemarkedlyhypovolemIcwIthouta
changeInanyoneofthesevarIablesbecauseofthecompensatoryactIonofperIpheral
vasoconstrIctIon,
JJ,88,127
Unfortunately,thIsshuntsbloodawayfromskIn,Increaseswound
hypoxemIa,andIncreasestherIskofsurgIcalwoundInfectIon.
56
Kabonetal.
128
performed
arandomIzed,controlledtrIaltocomparestandard(8mL/kg/hr)versushIgh(16to18
mL/kg/hr)volumeadmInIstratIonIn25JpatIentsundergoIngelectIvecolonresectIon.They
foundatrendtowardreducedwoundInfectIonsInthegroupthatreceIvedhIghvolume(8.5
vs.11.J),whIchwouldbeaclInIcallysIgnIfIcantreductIon.Unfortunately,thestudywas
termInatedearly,soIthadInadequatepower.PatIentsathIghrIskforheartfaIlureorwIth
endstagerenaldIseasewereexcluded,sothestudyalsohaslImItedgeneralIzabIlIty.
Anumberofmethods,bothInvasIveandmInImallyInvasIve,havebeenInvestIgatedas
moresensItIvemeasuresofvolumestatus.Hartmannetal.
102
usedsubcutaneousPD
2
to
guIdeperIoperatIvevolumemanagementInarandomIzedcontrolledtrIalInabdomInal
surgerypatIents.PatIentsrandomIzedtotheInterventIongroup(vs.usualmanagement)
receIvedmorefluId,hadsIgnIfIcantlyhIgherwoundoxygentensIon,anddeposItedmore
collagenInatestwound.
PulmonaryarterIalcathetershavealsobeenusedInanattempttooptImIzevolume
management,generallywIthlIttlesuccess.|ostofthesestudIeswereperformedInanCU
settIng,ratherthandurIngsurgery.nonestudyIn4,059patIentsundergoIngabdomInal
surgery,
12J
thosewhoreceIvedapulmonaryartery(PA)catheterhadworseoutcomesthan
thosewhodIdnot.nfact,therateofmajorpostoperatIvecardIaceventswas15.4Inthe
PAcathetergroupversusJ.6Inthecontrolgroup.ThIscouldbepartlyduetothe
observatIonthatmanyclInIcIansmIsInterpretPAdata.
129
WIthrecentstudIes
demonstratIngalackofpatIentbenefItwIthPAcathetersandtheIncreaseInuseand
avaIlabIlItyoflessInvasIvemonItorslIkeechocardIography,thefutureofthesecathetersIs
uncertaIn.
1J0
ntraoperatIvetransesophagealechocardIography(TEE)hasbeenadvocatedasamore
usefulmonItorofIntraoperatIvevolumestatus.|ythenandWebb
1J1
usedTEEtooptImIze
IntraoperatIvevolumemanagementIn60cardIacpatIentsanddemonstratedthatthe
patIentswIthTEEmanagementreceIvedmoreIntravenous(7)fluIdandhaddecreasedgut
hypoperfusIon(7vs.56)comparedwIthtradItIonalmanagement.Therewerealsofewer
majorcomplIcatIons(0vs.6),althoughthestudywastoosmalltoachIevestatIstIcal
sIgnIfIcance.SInclaIretal.
1J2
randomIzed40patIentsundergoIngsurgIcalrepaIrof
proxImalfemoralfracturestoTEEguIdedvolumemanagementortradItIonalmanagement.
ThepatIentswIththeTEEmanagementhadfasterrecoverIesandmorerapIdhospItal
dIscharge.Thus,TEEshowspromIseforguIdIngvolumemanagementInbothcardIacand
noncardIacsurgerIes.dentIfIcatIonoftheapproprIatemarkersandInterventIons,
however,remaInsInadequatelystudIed.
AfInaltopIcofdebateIswhethercolloIdsorcrystalloIdsarepreferableforIntraoperatIve
fluIdadmInIstratIon.SynthetIccolloIdshavebeenassocIatedwIthcoagulopathywhenlarge
volumesaredelIvered,whIchappearstobeInlargepartmedIatedbydIlutIonof
coagulatIonfactors.
1JJ
CrystalloIds,ontheotherhand,maycauseahypercoagulable
state.
1J4
TheIntravascularhalflIfeofcolloIds,eItheralbumInorsynthetIccolloIds,Is
muchlongerthanthatofcrystalloIds,allowIngthetotalvolumeoffluIdadmInIsteredtobe
reducedbyIncludIngcolloIdsInsurgIcalfluIdresuscItatIon.
1J5
EdemaformatIonmayalso
bedecreased.AnumberofstudIes
124,1J5,1J6
purporttoevaluateIntraoperatIveor
postoperatIvefluIdadmInIstratIonIntermsofrestrIctIveversustradItIonalfluId
management.7IrtuallyallhavecomparedcolloId(restrIctIvegroup)wIthcrystalloId
(tradItIonalgroup)admInIstratIon.Thus,therestrIctedvolumegrouplIkelyreceIveda
largeramountofeffectIveIntravascularvolumethanthetradItIonalorlIberalgroup.n
general,thesestudIeshavedemonstratedImprovedoutcomes(reductIonInSS,earlIer
returnofbowelfunctIon)forthecolloIdgroup.ThemechanIsmforthebenefItIsunclear,
however,asonthebasIsofeffectIveIntravascularvolumedelIvered,thecrystalloIdgroups
mIghtactuallyhavebeenlesswellvolumereplacedthanthecolloIdgroups.
CurrentbestrecommendatIonsIncludereplacIngfluIdlossesbasedonstandard
recommendatIons(Table1J8)forthetypeofsurgery,replacementofbloodloss,and
replacementofotherongoIngfluIdlosses(e.g.,hIghurIneoutputduetodIuretIcordye
admInIstratIon,hyperglycemIa,orthermoregulatoryvasoconstrIctIon).|aIntenanceof
normothermIaIs
P.286
alsocrItIcaltooptImalvolumemanagement.WarmpatIentsareunlIkelytodevelop
pulmonaryedemawIthahIghrateoffluIdadmInIstratIonbecausetheyhaveexcess
capacItanceduetovasodIlatIon.ColdpatIents,ontheotherhand,arehIghlysusceptIbleto
pulmonaryedemaevenafterrelatIvelysmallfluIdboluses.Thermoregulatory
vasoconstrIctIonIncreasesafterload,causIngIncreasedcardIacwork.|oreover,
admInIsteredfluIdcannotopenupconstrIctedvesselsuntIlthehypothermIcstImulusIs
removed;thus,thereIsvIrtuallynoexcesscapacItanceInthesystem.
Table 13-8 Standard Volume Management Guidelines for Surgical Patients
FluIdFequIrement=0efIcIt+|aIntenance(baselIneplusreplacement)+estImated
bloodlossandothersensIblefluIdlosses
0efIcIt=|aIntenance(1.5mL/kg/hr)hoursNPD
Adjustforfever,hIghNCoutput,bowelpreparatIon,andothersourcesofongoIng
preoperatIveIncreasedfluIdloss
FeplaceE8LJ:1wIthcrystalloId,1:1wIthcolloId
|aIntenancerequIrementsfordIfferentsurgerIes:
SuperfIcIalsurgIcaltrauma:12mL/kg/hr
PerIpheralsurgery
|InImalSurgIcalTrauma:J4mL/kg/hr
Headandneck,hernIa,kneesurgery
|oderateSurgIcalTrauma:56mL/kg/hr
|ajorsurgerywIthoutexposedabdomInalcontents
SeveresurgIcaltrauma:810mL/kg/hr(ormore)
|ajorabdomInal,especIallywIthexposedabdomInalcontents
NPD,nothIngbymouth;NC,nasogastrIc;E8L,estImatedbloodloss.
PaIncontrolshouldbeaddressedIntraoperatIvelysothatpatIentsdonothaveseverepaIn
onemergence.AchIevIngthegoalIsmoreImportantthanthetechnIqueusedtodoso.
AlthoughregIonalanesthesIaandanalgesIamayprovIdesuperIorpaInrelIef,theeffectsof
specIfIcanalgesIcregImensonwoundoutcomehavenotyetbeenadequatelystudIed.
Postoperative Management
WoundsaremostvulnerableInthefIrstfewhoursaftersurgery(Table1J9).Although
antIbIotIcslosetheIreffectIvenessafterthefIrsthours,oxygenmedIatednaturalwound
ImmunItylastslonger.
17
EvenashortperIodofvasoconstrIctIondurIngthefIrstdayIs
suffIcIenttoreduceoxygensupplyandIncreaseInfectIonrIsk.
56
CorrectIonandpreventIon
ofvasoconstrIctIonInthefIrst24to48hoursaftersurgerywIllhavesIgnIfIcantbenefIcIal
effects.
56
StrIctglycemIccontrolIsalsoImportant,
1J7
althoughthebestmethodtoachIeve
thIsInthenonCUsettInghasnotyetbeenestablIshed.
AllvasoconstrIctIvestImulImustbecorrectedsImultaneouslytoallowoptImalhealIng.
7olumeIsthelasttobecorrectedbecausevasoconstrIctIonforotherreasonsInduces
dIuresIsandrendersthepatIentrelatIvelyhypovolemIc(perIpherally,notcentrally).These
measuresarepartIcularlyImportantInanypatIentsathIghrIskforwoundcomplIcatIons
forotherreasons(e.g.,malnutrItIon,steroIduse,dIabetes),orwhenvasoconstrIctIvedrugs
suchasbetablockersandagonIstsarerequIredforotherreasons.
LocalperfusIonIsnotassureduntIlpatIentshaveanormalbloodvolume,arewarmand
paInfree,andarereceIvIngnovasoconstrIctIvedrugs;thatIs,untIlthesympathetIc
nervoussystemIsInactIvated.WarmIngshouldcontInueuntIlpatIentsarethoroughly
awakeandactIveandcanmaIntaIntheIrownthermalbalance.AftermajoroperatIons,
warmIngmaybeusefulformanyhoursorevendays.ThegoalIstoachIevewarmthatthe
skIn;woundvasoconstrIctIonduetocoldsurroundIngsoftencoexIstswIthcore
hyperthermIa.|oderatehyperthermIaIsnot,Itself,aproblem.WhenextensIvewoundsare
leftopen,warmthshouldbecontInued,andheatlossesduetoevaporatIonshouldbe
preventedtoavoIdvasoconstrIctIonandtomInImIzecalorIclosses.
Table 13-9 Postoperative Management
KeeppatIentswarm.
ProvIdeanalgesIatokeeppatIentscomfortable,IfnotpaInfree.PatIentreport
andtheabIlItytomovefreelyarethebestsIgnsofadequatepaInrelIef.
DnlyonemoredoseofantIbIotIcunlessanInfectIonIspresentorcontamInatIon
contInues.
KeepupwIththIrdspacelosses.FememberthatfeverIncreasesfluIdlosses.
AssessperfusIonandreacttoabnormalItIes.
AvoIddIuresIsuntIlpaInIsgoneandpatIentIswarm.
Assesslosses(IncludIngthermallosses)IfwoundIsopen.
AssessneedforparenteralorenteralnutrItIonandrespond.
ContInuetocontrolhypertensIonandhyperglycemIa.
permIssIon.
AssessIngperfusIon,especIallyInthePACU,IscrItIcal.Unfortunately,urIneoutputIsa
poor,oftenmIsleadIngguIdetoperIpheralperfusIon.
126
|arkedlylowoutputmayIndIcate
decreasedrenalperfusIon,butnormalorevenhIghurIneoutputhaslIttlecorrelatIonto
woundortIssuePD
2
.|anyfactorscommonlypresentIntheperIoperatIveperIod,IncludIng
hyperglycemIa,dyeadmInIstratIon,thermoregulatoryvasoconstrIctIon,adrenal
InsuffIcIency,andvarIousdrugs,maycauseInapproprIatedIuresIsInthefaceofmIld
hypovolemIa.
PhysIcalexamInatIonofthepatIentIsabetterguIdetohypovolemIaandvasoconstrIctIon.
AssessvasoconstrIctIonbyacapIllaryreturntImeof2toJsecondsattheforeheadand5
secondsoverthepatella.EyeturgorIsanothergoodmeasureofvolumestatus.FInally,
patIentscanusuallydIstInguIshthIrstfromadrymouth.SkInshouldbewarmanddry.
AftermajorabdomInalsurgery,thIrdspacelossescontInueforabout12to24hours,sothat
IncreasedfluIdrequIrementscontInue.ngeneral,forlargeabdomInalcases,2toJ
mL/kg/hrof7fluIdsIssuffIcIentforthefIrst12to24postoperatIvehours.Afterthat
perIod,the7rateshouldbedecreasedbelowcalculatedmaIntenancelevelsbecause
edemafluIdbegInstobemobIlIzed,thusIncreasIngcIrculatIngIntravascularvolume.
WhenexcessIvetIssuefluIdshaveaccumulated,dIuresIsshouldbeundertakengentlyso
thattranscapIllaryrefIllcanmaIntaInbloodvolume.ThIsapplIestopatIentswhoneed
renaldIalysIsaswell.TheaveragedIalysIspatIentvasoconstrIctssuffIcIentlytolower
tIssuePD
2
byJ0ormoredurIngdIalysIsandneedsabout24hourstoreturnvasomotor
toneandwoundandtIssuePD
2
tonormal.
1J8
FluIdlossesfromthevascularsystemarenot
necessarIlyreplacedfromthetIssuesasrapIdlyastheyaresustaIned.TIssueedemamaybe
theprIcepaIdforadequateIntravascularvolume.EdemaIncreasesIntracapIllarydIstance,
sothattheremaybeadelIcatebalancebetweenexcessIveedemaandperIpheral
vasoconstrIctIon(whIchworsensthehypoxIacausedbyedema).
7asoconstrIctIvedrugsshouldbeavoIded.ThemostcommonandmostavoIdableIs
nIcotIneIntheformofcIgarettes.8etablockersshouldbeusedonlywhenclearly
medIcallyIndIcated.
1J9
8othareknowntoreducewoundandtIssuePD
2
.ClonIdIneIsan
alternatIvedrugforheartratecontrol
140,141,142
thatalsoInducesvasodIlatIonandmay
IncreasewoundPD
2
.
14J
HIghdoseadrenergIcagonIstsorothervasopressorsmaycause
harmbydecreasIngtIssuePD
2
,butInalImItedexperIencewehavefoundthatlowerdoses
havelIttleornoeffectonwound/tIssuePD
2
.tIsImportanttorememberthatdecreasIng
cardIacoutputmayalsoreducewoundperfusIon.Thus,abalancemustbemaIntaIned
betweenmInImIzInguseofvasopressorsandmaIntaInIngadequatecardIacoutput.
|aIntenanceoftIssuePD
2
requIresattentIontopulmonaryfunctIonpostoperatIvely.
AdmInIstratIonofsupplementaloxygenvIafacemaskornasalcannulaeIncreasessafetyIn
patIentsreceIvIngsystemIcopIoIds.
144
AsasIdebenefItItmayalsoImprovewoundhealIng,
althoughthIshasnotbeenformallystudIed.PaIncontrolalsoappearsImportantsInceIt
favorablyInfluencesbothpulmonaryfunctIonandvasculartone.ThIsIspartIcularlytrueIn
patIentsathIghrIskforpulmonarycomplIcatIonspostoperatIvely,suchasmorbIdlyobese
patIentsandthosewIthpulmonarydIsease.
145
EpIduralanalgesIamay
P.287
betherouteofchoIceInthesepatIents.thasseveraladvantagesoverparenterally
admInIsteredopIoIdsInthatItgenerallyachIeveslowerpaInscoreswIthlesssedatIon.
Nonetheless,opIoIdInducedprurItusIsmorecommonwIthepIduraladmInIstratIon,andIn
somepatIentsmaybesevereenoughtocounteractthebenefItsofpaIncontrol.
PatIentcontrolledanalgesIaIsalsoquIteeffectIveatachIevInglowpaInscores.talsohas
thebenefItofgIvIngcontroltothepatIent,leadIngtopatIentsatIsfactIonashIghaswIth
epIduralanalgesIaInmanycases.
146
NurseadmInIstered,asneededdosesof7or
IntramuscularopIoIdsshouldbeavoIdedasInadequatepaIncontroloftenexceeds50
usIngthIsapproach.
147
ThekeytopaIncontrolIsrecognItIonoftheneedforanalgesIaand
attentIontothepatIent'scomplaIntsofpaIn.DpIoIdrequIrementsvaryenormouslyandare
notalwayspredIctable,buteventolerantpatIents(7drugabusersorthosewIthcancer
paIn)canbegIvenadequatepaInrelIefwIthsuffIcIentattentIon.
Summary
npatIentswIthmoderatetohIghrIskofsurgIcalsIteInfectIon,anesthesIologIstshavethe
opportunItytoenhancewoundhealIngandreducetheIncIdenceofwoundInfectIonsby
sImple,InexpensIve,andreadIlyavaIlablemeans.ntraoperatIvely,approprIateantIbIotIc
use,preventIonofvasoconstrIctIonthroughvolumeandwarmIng,andmaIntenanceofa
hIghPaD
2
(J00to500mmHg)arekey.PostoperatIvely,thefocusshouldremaInon
preventIonofvasoconstrIctIonthroughpaInrelIef,warmIng,andadequatevolume
admInIstratIonInthePACU.TheaddItIonofmeasurestoreduceandpreventthestress
responseIslIkelytobeeffectIveaswell,althoughfurtherstudyIsrequIred.
Areas for Future Research
WhenandwhyshouldamaskbewornIntheDF:
Should7sbeplacedusIngsterIletechnIque:AlInes:
sdelayofantIbIotIcsforculturejustIfIed:
CanyoumodulatemorethanthesympathetIcnervoussystem:
PsychologIcalpreparatIonandInterventIoncanmodulatebothHPAaxIsandSA|axIs
aspectsofthestressresponse.WIllthIsreducewoundcomplIcatIons:
0ononsteroIdalantIInflammatoryagentsIncreaserIskofwoundcomplIcatIons:
0oesdexamethasoneforpostoperatIvenauseaandvomItIngprophylaxIsIncreasetherIsk
ofwoundcomplIcatIons:
0oepIduralsreducetherIskofSS:AretheycosteffectIve(vs.tImeandrIsk):
WhoshouldgetahIghFD
2
:stherepotentIaltoxIcIty:
0oespostoperatIveoxygenreducewoundcomplIcatIons:HowlongshouldpatIents
receIvesupplementaloxygenpostoperatIvely:
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Stock, M. Christine
TableofContentsSectIonAnatomyandPhysIologyChapter14FluIds,Electrolytes,andAcId8asePhysIology
Chapter14
Fluids, Electrolytes, and Acid-Base Physiology
Donald S. Prough
J. Sean Funston
Christer H. Svensn
Scott W. Wolf
Key Points
1. The Henderson-Hasselbalch equation describes the relationship
between pH, Paco
2
, and serum bicarbonate. The Henderson equation
defines the previous relationship but substitutes hydrogen
concentration for pH.
2. The pathophysiology of metabolic alkalosis is divided into generating
and maintenance factors. A particularly important maintenance factor
is renal hypoperfusion, often due to hypovolemia.
3. The addition of iatrogenic respiratory alkalosis to metabolic alkalosis
can produce severe alkalemia.
4. Metabolic acidosis occurs as a consequence of the use of bicarbonate
to buffer endogenous organic acids or as a consequence of external
bicarbonate loss. The former causes an increase in the anion gap
(Na
+
- [Cl
-
+ [HCO
3
-
]]).
5. When substituting mechanical ventilation for spontaneous ventilation
in a patient with severe metabolic acidosis, it is important to maintain
an appropriate level of ventilatory compensation, pending effective
treatment of the primary cause for the metabolic acidosis.
6. Sodium bicarbonate, never proved to alter outcome in patients with
lactic acidosis, should be reserved for those patients with severe
acidemia.
7. Tight control of blood glucose in critically ill surgical patients has been
associated with substantial improvements in mortality.
8. In patients undergoing moderate surgical procedures, generous
administration of fluids is associated with fewer minor complications,
such as nausea, vomiting, and drowsiness.
9. In patients undergoing colon surgery, careful perioperative fluid
restriction has been associated with lower mortality and better wound
healing.
10. Homeostatic mechanisms are usually adequate for the maintenance
of electrolyte balance. However, critical illnesses and their treatment
strategies can cause significant perturbations in electrolyte status,
possibly leading to worsened patient outcome.
11. Disorders of the concentration of sodium, the principal extracellular
cation, depend on the total body water concentration and can lead to
neurologic dysfunction. Disorders of potassium, the principal
intracellular cation, are influenced primarily by insults that result in
increased total body losses of potassium or changes in distribution.
12. Calcium, phosphorus, and magnesium are all essential for
maintenance and function of the cardiovascular system. In addition,
they also provide the milieu that ensures neuromuscular
transmission. Disorders affecting any one of these electrolytes may
lead to significant dysfunction and possibly result in cardiopulmonary
arrest.
AsaconsequenceofunderlyIngdIseasesandoftherapeutIcmanIpulatIons,surgIcalpatIents
developpotentIallyharmfuldIsordersofacIdbaseequIlIbrIum,Intravascularand
extravascularvolume,andserumelectrolytes.PrecIseperIoperatIvemanagementofacId
basestatus,fluIds,andelectrolytesmaylImItperIoperatIvemorbIdItyandmortalIty.
FecentdataprovIdeprovocatIveInsIghtsregardIngapproprIateperIoperatIvefluId
managementInpatIentsundergoIngbothambulatoryandmajorInpatIentsurgeryorthe
possIbIlItyofchronIchypercapnIa.
Acid-Base Interpretation and Treatment
|anagementofperIoperatIveacIdbasedIsturbancesrequIresanunderstandIngofthefour
sImpleacIdbasedIsordersmetabolIcalkalosIs,metabolIcacIdosIs,respIratoryalkalosIs,
andrespIratoryacIdosIsaswellasmorecomplexcombInatIonsofdIsturbances.ThIs
sectIonwIllrevIewthepathogenesIs,major
P.291
complIcatIons,physIologIccompensatorymechanIsms,andtreatmentofcommon
perIoperatIveacIdbaseabnormalItIes.
Overview of Acid-Base Equilibrium
ConventIonally,acIdbaseequIlIbrIumIsdescrIbedusIngtheHendersonHasselbalch
equatIon:
where6.1=thepK
a
ofcarbonIcacIdand0.0JIsthesolubIlItycoeffIcIentInbloodofcarbon
dIoxIde(CD
2
).WIthInthIscontext,pHIsthedependentvarIablewhIlethebIcarbonate
concentratIon[HCD
J
]andPaco
2
areIndependentvarIables;therefore,metabolIcalkalosIs
andacIdosIsaredefInedasdIsturbancesInwhIch[HCD
J
]IsprImarIlyIncreasedor
decreasedandrespIratoryalkalosIsandacIdosIsaredefInedasdIsturbancesInwhIchPaco
2
IsprImarIlydecreasedorIncreased.pH,thenegatIvelogarIthmofthehydrogenIon
concentratIon([H
+
]),defInestheacIdItyoralkalInItyofsolutIonsorblood.ThesImpler
HendersonequatIon,afterconversIonofpHto[H
+
],alsodescrIbestherelatIonshIpbetween
thethreemajorvarIablesmeasuredorcalculatedInbloodgassamples:
ToapproxImatethelogarIthmIcrelatIonshIpofpHto[H
+
],assumethat[H
+
]Is40mmol/Lat
apHof7.4;thatanIncreaseInpHof0.10pHunItsreduces[H
+
]to0.8thestartIng[H
+
]
concentratIon;thatadecreaseInpHof0.10pHunItsIncreasesthe[H
+
]byafactorof1.25;
andthatsmallchanges(I.e.,0.05pHunIts)producerecIprocalIncreasesordecreasesof
approxImately1.0mmol/LIn[H
+
]foreach0.01decreaseorIncreasepHunIts.
ThealternatIveStewartapproachtoacIdbaseInterpretatIondIstInguIshesbetweenthe
IndependentvarIablesanddependentvarIablesthatdetermInepH.
1,2
TheIndependent
varIablesarePaco
2
,thestrong(I.e.,hIghlydIssocIated)IondIfference,andthe
concentratIonofproteIns,whIchusuallyarenotstrongIons.ThestrongIonsIncludesodIum
(Na
+
),potassIum(K
+
),chlorIde(Cl
),andlactate.ThestrongIondIfference,calculatedas
(Na
+
+K
+
Cl
),undernormalcIrcumstancesIsapproxImately42mEq/L.ngeneral,the
StewartapproachprovIdesmoreInsIghtIntothemechanIsmsunderlyIngacIdbase
dIsturbances,IncontrasttothemoredescrIptIveHendersonHasselbalchapproach.
However,theclInIcalInterpretatIonortreatmentofcommonacIdbasedIsturbancesIs
rarelyhandIcappedbythesImplerconstructsoftheconventIonalHendersonHasselbalchor
HendersonequatIons.
Metabolic Alkalosis
|etabolIcalkalosIs,characterIzedbyhyperbIcarbonatemIa(27.0mEq/L)andusuallybyan
alkalemIcpH(7.45),occursfrequentlyInpostoperatIvepatIentsandcrItIcallyIllpatIents.
FactorsthatgeneratemetabolIcalkalosIsIncludevomItInganddIuretIcadmInIstratIon
(Table141).
J
|aIntenanceofmetabolIcalkalosIsdependsonacontInuedstImulus,suchas
renalhypoperfusIon,hypokalemIa,hypochloremIaorhypovolemIa,fordIstaltubular
reabsorptIonof[HCD
J
](Table142).
J
|etabolIcalkalosIsIsassocIatedwIthhypokalemIa,IonIzedhypocalcemIa,secondary
ventrIculararrhythmIas,IncreaseddIgoxIntoxIcIty,andcompensatoryhypoventIlatIon
(hypercarbIa),althoughcompensatIonrarelyresultsInPaco
2
55mmHg(Table14J).
AlkalemIamayreducetIssueoxygenavaIlabIlItybyshIftIngtheoxyhemoglobIndIssocIatIon
curvetotheleftandbydecreasIngcardIacoutput.0urInganesthetIcmanagement,
InadvertentaddItIonofIatrogenIcrespIratoryalkalosIstopreexIstIngmetabolIcalkalosIs
mayproduceseverealkalemIaandprecIpItatecardIovasculardepressIon,dysrhythmIas,
hypokalemIa,andthecomplIcatIons.
npatIentsInwhomarterIalbloodgaseshavenotyetbeenobtaIned,serumelectrolytes
andahIstoryofmajorrIskfactors,suchasvomItIng,nasogastrIcsuctIon,orchronIc
dIuretIcuse,cansuggestmetabolIcalkalosIs.TotalCD
2
(usuallyabbrevIatedonelectrolyte
reportsasCD
2
)shouldbeabout1.0mEq/Lgreaterthan[HCD
J
]onsImultaneouslyobtaIned
arterIalbloodgases.feIthercalculated[HCD
J
]onthearterIalbloodgasesorCD
2
onthe
serumelectrolytesexceedsnormal(24and25mEq/L,respectIvely)by4.0mEq/L,eIther
thepatIenthasaprImarymetabolIcalkalosIsorhasconservedbIcarbonateInresponseto
chronIchypercarbIa.FecognItIon
P.292
ofhyperbIcarbonatemIaonthepreoperatIveserumelectrolytesjustIfIesarterIalbloodgas
analysIsandshouldalerttheanesthesIologIsttothelIkelIhoodoffactorsthatgenerateor
maIntaInmetabolIcalkalosIs(seeTables141and142).
Table 14-1 Generation of Metabolic Alkalosis
GENERATION EXAMPLES
.LossofacIdfromextracellularspace
A.LossofgastrIcfluId(HCl) 7omItIng
8.AcIdlossIntheurIne:IncreaseddIstal
NadelIveryInpresenceof
hyperaldosteronIsm
PrImaryaldosteronIsmplusdIuretIc
C.AcIdshIftsIntocells PotassIumdefIcIency
0.LossofacIdIntostool CongenItalchlorIdelosIngdIarrhea
.ExcessIveHCD
J
loads
A.Absolute
1)DralorparenteralHCD
J
|IlkAlkalIsyndrome
2)|etabolIcconversIonofthesaltsof
organIcacIdstoHCD
Lactate,acetate,orcItrate
admInIstratIon
8.FelatIve
NaHCD
J
dIalysIs
.PosthypercapnIcstates
CorrectIon(e.g.,bymechanIcal
ventIlatorysupport)ofchronIc
hypercapnIa
|odIfIedfromKhannaA,KurtzmanNA:|etabolIcalkalosIs.JNephrol2006;
19(Suppl9):S86,wIthpermIssIon.
Table 14-2 Factors that Maintain Metabolic Alkalosis
FACTOR PROPOSED MECHANISM
0ecreasedCFF
ncreasesfractIonalHCD
J
reabsorptIonandpreventsthe
elevatedplasma[HCD
J
]fromexceedIngTm
7olume
contractIon
StImulatesproxImaltubularHCD
J
reabsorptIon
HypokalemIa
0ecreasesCFFandIncreasesproxImaltubularHCD
J
reabsorptIon;stImulatesNaIndependent/Kdependent(low)
secretIonInCCT.
HypochloremIa
a
ncreasesrenIn,decreasesCFF,anddecreasesdIstalchlorIde
delIvery(protonsecretIonIn|CT)
PassIve
backfluxof
CreatesafavorableconcentratIongradIentforpassIveHCD
J
HCD
J
movementfromproxImaltubularlumentoblood
Aldosterone
ncreasesNadependentprotonsecretIonInCCTandNa
IndependentprotonsecretIonInCCTand|CT
AllfactorsdecreaseurInaryHCD
J
excretIonInvIvo.
CFF,glomerularfIltratIonrate;CCT,cortIcalcollectIngtubule;|CT,medullary
collectIngtubule.
a
AnImalmodelsareassocIatedwIthhypokalemIa;thus,theprecIseroleofchlorIde
InhumansIsnotclearlyunderstood.
|odIfIedfromKhannaA,KurtzmanNA:|etabolIcalkalosIs.JNephrol2006;
19(Suppl9):S86S96,wIthpermIssIon.
TreatmentofmetabolIcalkalosIsconsIstsofetIologIcandnonetIologIctherapy.EtIologIc
therapyconsIstsofmeasuressuchasexpansIonofIntravascularvolumeorthe
admInIstratIonofpotassIum.nfusIonof0.9salInewIlldosedependentlyIncreaseserum
[Cl
]anddecreaseserum[HCD
J
].
4
NonetIologIctherapyIncludesadmInIstratIonof
acetazolamIde(acarbonIcanhydraseInhIbItorthatcausesrenalbIcarbonatewastIng),
InfusIonof[H
+
]IntheformofammonIumchlorIde,argInInehydrochlorIde,or0.1N
hydrochlorIcacId(100mmol/L),ordIalysIsagaInstahIghchlorIde/lowbIcarbonate
dIalysate.
J
DftheprevIouslymentIonedfactors,0.1NhydrochlorIcacIdmostrapIdly
correctslIfethreatenIngmetabolIcalkalosIsbutmustbeInfusedIntoacentralveIn;
perIpheralInfusIonwIllcauseseveretIssuedamage.
Metabolic Acidosis
|etabolIcacIdosIs,characterIzedbyhypobIcarbonatemIa(21mEq/L)andusuallybyan
acIdemIcpH(7.J5),canbeInnocuousorreflectalIfethreatenIngemergency.|etabolIc
acIdosIsoccursasaconsequenceofbufferIngbybIcarbonateofendogenousorexogenous
acIdloadsorasaconsequenceofabnormalexternallossofbIcarbonate.
5,6,7
ApproxImately70mmolofacIdmetabolItesareproduced,buffered,andexcreteddaIly;
theseIncludeabout25mmolofsulfurIcacIdfromamInoacIdmetabolIsm,40mmolof
organIcacIds,andphosphorIcandotheracIds.ExtracellularvolumeIna70kgadult
contaInsJJ6mmolofbIcarbonatebuffer(24mEq/L14Lofextracellularvolume).
ClomerularfIltratIonofplasmavolumenecessItatesreabsorptIonof4,500mmolof
bIcarbonatedaIly,ofwhIch85IsreabsorbedIntheproxImaltubule,10InthethIck
ascendInglImb,andtheremaInderIstItratedbyprotonsecretIonInthecollectIngduct.
Table 14-3 Respiratory Compensation in Response to Metabolic Alkalosis
and Metabolic Acidosis
|etabolIcalkalosIs
1. PaD
2
Increases-0.50.6mmHgper1.0mEq/LIncreaseIn[HCD
J
]
2. ThelasttwodIgItsofthepHshouldapproxImatethe[HCD
J
]+15
|etabolIcacIdosIs
1. PaCD
2
-[HCD
J
]1.5+8
2. PaCD
2
decreases1.2mmHgper1.0mEq/LIn[HCD
J
]toamInImumof1015mm
Hg
J. ThelasttwodIgItsofthepH-[HCD
J
]+15
CalculatIonoftheanIongap[(Na
+
([Cl
]+[HCD
J
])]dIstInguIshesbetweentwotypesof
metabolIcacIdosIs(Table144).
8
TheanIongapIsnormal(1JmEq/L)InsItuatIonssuchas
dIarrhea,bIlIarydraInage,andrenaltubularacIdosIs
P.29J
InwhIchbIcarbonateIslostexternally.TheanIongapalsoIsnormalorreducedIn
hyperchloremIcacIdosIsassocIatedwIthperIoperatIveInfusIonofsubstantIalquantItIesof
0.9salIne.
4,9
|etabolIcacIdosIsassocIatedwIthahIghanIongap(1JmEq/L)occurs
becauseofexcessproductIonordecreasedexcretIonoforganIcacIdsorIngestIonofoneof
severaltoxIccompounds(Table144).nmetabolIcacIdosIsassocIatedwIthahIghanIon
gap,bIcarbonateIonsareconsumedInbufferInghydrogenIons,whIletheassocIatedanIon
replacesbIcarbonateInserum.8ecausethreequartersofthenormalanIongapconsIstsof
albumIn,thecalculatedanIongapshouldbecorrectedforhypoalbumInemIabyaddIngto
thecalculatedanIongapthedIfferencebetweenmeasuredserumalbumInandanormal
albumInconcentratIonof4.0g/dLmultIplIedby2.0to2.5.
10
ngeneral,anIncreaseInthe
albumIncorrectedanIongap(AC)shouldbeapproxImatelymatchedbyadecreaseInthe
serum[HCD
J
](HCD
J
).
11
AratIoofAC:HCD
J
thatIs0.8or1.2shouldprompt
consIderatIonofamIxedacIdbasedIsturbance.
Table 14-4 Differential Diagnosis of Metabolic Acidosis
ELEVATED ANION GAP
a
NORMAL ANION GAP
b
Three0Iseases
1.UremIa 1.FenaltubularacIdosIs
2.KetoacIdosIs 2.0Iarrhea
J.LactIcacIdosIs J.CarbonIcanhydraseInhIbItIon
ToxIns 4.UreteraldIversIons
1.|ethanol 5.EarlyrenalfaIlure
2.Ethyleneglycol 6.HydronephrosIs
J.SalIcylates 7.HCladmInIstratIon
4.Paraldehyde 8.SalIneadmInIstratIon
a
CorrectIonoftheanIongapforhypoalbumInemIaIsessentIalforeffectIve
perIoperatIveuse.
b
TocorrecttheanIongapforhypoalbumInemIa,addtothecalculatedanIongap
twIcethedIfferencebetweennormalserumalbumIn(4.0g/L)andactualserum
albumIn.
SuffIcIentreductIonsInpHmayreducemyocardIalcontractIlIty,Increasepulmonary
vascularresIstance,anddecreasesystemIcvascularresIstance.tIspartIcularlyImportant
tonotethatfaIlureofapatIenttoapproprIatelyhyperventIlateInresponsetometabolIc
acIdosIsIsphysIologIcallyequIvalenttorespIratoryacIdosIsandsuggestsclInIcal
deterIoratIon.fapatIentwIthmetabolIcacIdosIsrequIresmechanIcalventIlatIon,for
example,durInggeneralanesthesIa,everyattemptshouldbemadetomaIntaInan
approprIatelevelofventIlatorycompensatIon(seeTable14J)untIltheprImaryprocess
canbecorrected.Table145IllustratesfaIluretomaIntaIncompensatoryhyperventIlatIon.
TheanesthetIcImplIcatIonsofmetabolIcacIdosIsareproportIonaltotheseverItyofthe
underlyIngprocess.AlthoughapatIentwIthhyperchloremIcmetabolIcacIdosIsmaybe
relatIvelyhealthy,thosewIthlactIcacIdosIs,ketoacIdosIs,uremIa,ortoxIcIngestIonswIll
bechronIcallyoracutelyIll.PreoperatIveassessmentshouldemphasIzevolumestatusand
renalfunctIon.fshockhascausedmetabolIcacIdosIs,dIrectarterIalpressuremonItorIng
andpreloadmayrequIreassessmentvIaechocardIographyorpulmonaryarterIal
catheterIzatIon.ntraoperatIvely,oneshouldbeconcernedaboutthepossIbIlItyof
exaggeratedhypotensIveresponsestodrugsandposItIvepressureventIlatIon.nplannIng
IntravenousfluIdtherapy,consIderthatbalancedsaltsolutIonstendtoIncrease[HCD
J
]
(e.g.,bymetabolIsmoflactatetobIcarbonate)andpHand0.9salInetendstodecrease
[HCD
J
]andpH.
ThetreatmentofmetabolIcacIdosIsconsIstsofthetreatmentoftheprImary
pathophysIologIcprocess,thatIs,hypoperfusIon,hypoxIa,andIfpHIsseverelydecreased,
admInIstratIonofNaHCD
J
.HyperventIlatIon,althoughanImportantcompensatory
responsetometabolIcacIdosIs,IsnotdefInItIvetherapyformetabolIcacIdosIs.TheInItIal
doseofNaHCD
J
canbecalculatedas:
where0.J=theassumeddIstrIbutIonspaceforbIcarbonateand24mEq/LIsthenormal
valuefor[HCD
J
]onarterIalbloodgasdetermInatIon.ThecalculatIonmarkedly
underestImatesdosageInseveremetabolIcacIdosIs.nInfantsandchIldren,acustomary
InItIaldoseIs1.0to2.0mEq/kgofbodyweIght.
8othevIdenceandopInIonsuggestthatNaHCD
J
shouldrarelybeusedtotreatacIdemIa
InducedbymetabolIcacIdosIs.
5,6,12
ncrItIcallyIllpatIentswIthlactIcacIdosIs,therewere
noImportantdIfferencesbetweenthephysIologIceffects(otherthanchangesInpH)of0.9
|NaHCD
J
and0.9|sodIumchlorIde.
1J
mportantly,NaHCD
J
dIdnotImprovethe
cardIovascularresponsetocatecholamInesandactuallyreducedplasmaIonIzedcalcIum.
1J
AlthoughmanyclInIcIanscontInuetoadmInIsterNaHCD
J
topatIentswIthpersIstentlactIc
acIdosIsandongoIngdeterIoratIon,neItherNaHCD
J
nordIchloroacetate
14
hasImproved
outcome.ThebufferTHA|(trishydroxymethylamInomethane)effectIvelyreduces[H
+
],
doesnotIncreaseplasma[Na
+
],doesnotgenerateCD
2
asabyproductofbufferIng,and
doesnotdecreaseplasma[K+]
15
;however,thereIsnogenerallyacceptedIndIcatIonfor
THA|.
Respiratory Alkalosis
FespIratoryalkalosIs,alwayscharacterIzedbyhypocarbIa(Paco
2
J5mmHg)andusually
characterIzedbyanalkalemIcpH(7.45),resultsfromanIncreaseInmInuteventIlatIon
thatIsgreaterthanthatrequIredtoexcretemetabolIcCD
2
productIon.8ecause
respIratoryalkalosIsmaybeasIgnofpaIn,anxIety,hypoxemIa,centralnervoussystem
dIsease,orsystemIcsepsIs,thedevelopmentofspontaneousrespIratoryalkalosIsIna
prevIouslynormocarbIcpatIentrequIrespromptevaluatIon.ThehyperventIlatIon
syndrome,adIagnosIsofexclusIon,IsmostoftenencounteredIntheemergency
department.
16
FespIratoryalkalosIs,lIkemetabolIcalkalosIs,mayproducehypokalemIa,hypocalcemIa,
cardIacdysrhythmIas,bronchoconstrIctIon,andhypotensIon,andmaypotentIatethe
toxIcItyofdIgoxIn.naddItIon,bothbraInpHandcerebralbloodflowaretIghtlyregulated
andrespondrapIdlytochangesInsystemIcpH.
17
0oublIngmInuteventIlatIonreducesPaco
2
to20mmHgandhalvescerebralbloodflow;conversely,halvIngmInuteventIlatIon
doublesPaco
2
anddoublescerebralblood
P.294
flow.Therefore,acutehyperventIlatIonmaybeusefulInneurosurgIcalproceduresto
reducebraInbulkandtocontrolIntracranIalpressure(CP)durIngemergentsurgeryfor
noncranIalInjurIesassocIatedwIthacuteclosedheadtrauma.nthosesItuatIons,
IntraoperatIvemonItorIngofarterIalbloodgases,correlatedwIthcapnography,wIll
documentadequatereductIonofPaco
2
.AcuteprofoundhypocapnIa(20mmHg)may
produceelectroencephalographIcevIdenceofcerebralIschemIa.fPaco
2
IsmaIntaInedat
abnormallyhIghorlowlevelsfor8to24hours,cerebralbloodflowwIllreturntoward
prevIouslevels,assocIatedwIthareturnofcerebrospInalfluId[HCD
J
]towardnormal.
Table 14-5 Failure to Maintain Appropriate Ventilatory Compensation for
Metabolic Acidosis
a

Spontaneous
ventilation

Mechanical
hypoventilation
ArterIal pH 7.29 7.1J
blood
gases
PaCD
2
(mm
Hg)
29

49
[HCD
J
]
(mEq/L)
14 16
a
nthepresenceofmetabolIcacIdosIs,anotherwIsemodestIncreaseInPaCD
2
may
createalIfethreatenIngdecreaseInpH.
TreatmentofrespIratoryalkalosIsperseIsoftennotrequIred.ThemostImportantsteps
arerecognItIonandtreatmentoftheunderlyIngcause.
16
ForInstance,correctIonof
hypoxemIaorhypoperfusIonInducedlactIcacIdosIsshouldresultInresolutIonofthe
assocIatedIncreasesInrespIratorydrIve.PreoperatIverecognItIonofchronIc
hyperventIlatIonnecessItatesIntraoperatIvemaIntenanceofasImIlarPaco
2
.
Respiratory Acidosis
FespIratoryacIdosIs,alwayscharacterIzedbyhypercarbIa(Paco
2
45mmHg)andusually
characterIzedbyalowpH(7.J5),occursbecauseofadecreaseInmInutealveolar
ventIlatIon(7
A
),anIncreaseInproductIonofcarbondIoxIde(7
CD2
)orboth,fromthe
equatIon:
whereK=constant(rebreathIngofexhaled,carbondIoxIdecontaInInggasmayalso
IncreasePaco
2
).FespIratoryacIdosIsmaybeeItheracute,wIthoutcompensatIonbyrenal
[HCD
J
]retentIon,orchronIc,wIth[HCD
J
]retentIonoffsettIngthedecreaseInpH(Table
146).AreductIonIn7
A
maybeduetoanoveralldecreaseInmInuteventIlatIon(7
E
)orto
anIncreaseIntheamountofwastedventIlatIon(7
0
),accordIngtotheequatIon:
Table 14-6 Changes of [HCO
3
-
] and pH in Response to Acute and Chronic
Changes in Paco
2
0ecreasedPaCD
2
1. pHIncreases0.10per10mmHgdecreaseInPaCD
2
2. [HCD
J
]decreases2mEq/Lper10mmHgdecreaseInPaCD
2
J. pHwIllnearlynormalIzeIfhypocarbIaIssustaIned
4. [HCD
J
]wIlldecrease5to6mEq/Lper10mmHgchronIcInPaCD
2
a
ncreasedPaCD
2
1. pHwIlldecrease0.05peracute10mmHgIncreasePaCD
2
2. [HCD
J
]wIllIncrease1.0mEq/Lper10mmHgIncreasePaCD
2
J. pHwIllreturntowardnormalIfhypercarbIaIssustaIned
4. [HCD
J
]wIllIncrease45mEq/LperchronIc10mmHgIncreaseInPaCD
2
a
HospItalIzedpatIentsrarelydevelopchronIccompensatIonforhypocarbIabecause
ofstImulIthatenhancedIstaltubularreabsorptIonofsodIum.
0ecreasesIn7
E
mayoccurbecauseofcentralventIlatorydepressIonbydrugsorcentral
nervoussystemInjurybecauseofIncreasedworkofbreathIng,orbecauseofaIrway
obstructIonorneuromusculardysfunctIon.ncreasesIn7
0
occurwIthchronIcobstructIve
pulmonarydIsease,pulmonaryembolIsm,andmostacuteformsofrespIratoryfaIlure.7
CD2
maybeIncreasedbysepsIs,hIghglucoseparenteralfeedIng,orfever.
PatIentswIthchronIchypercarbIaduetoIntrInsIcpulmonarydIseaserequIrecareful
preoperatIveevaluatIon.TheventIlatoryrestrIctIonImposedbyupperabdomInalor
thoracIcsurgerymayaggravateventIlatoryInsuffIcIencyaftersurgery.AdmInIstratIonof
narcotIcsandsedatIves,evenInsmalldoses,maycausehazardousventIlatorydepressIon.
PreoperatIveevaluatIonshouldconsIderdIrectarterIalpressuremonItorIngandfrequent
IntraoperatIvebloodgasdetermInatIons,aswellasstrategIestomanagepostoperatIve
paInwIthmInImaldosesofsystemIcopIoIds.ntraoperatIvely,apatIentwIthchronIcally
compensatedhypercapnIashouldbeventIlatedtomaIntaInanormalpH.nadvertent
restoratIonofnormal7
A
mayresultInprofoundalkalemIa.PostoperatIvely,prophylactIc
ventIlatorysupportmayberequIredforselectedpatIentswIthchronIchypercarbIa.
EpIduralnarcotIcadmInIstratIonrepresentsonepotentIalalternatIvethatmayprovIde
adequatepostoperatIveanalgesIawhIlelImItIngdepressIonofventIlatorydrIve.
ThetreatmentofrespIratoryacIdosIsdependsonwhethertheprocessIsacuteorchronIc.
AcuterespIratoryacIdosIsmayrequIremechanIcalventIlatIonunlessasImpleetIologIc
factor(I.e.,narcotIcoverdosageorresIdualmuscularblockade)canbetreatedquIckly.
8IcarbonateadmInIstratIonrarelyIsIndIcatedunlessseveremetabolIcacIdosIsIsalso
presentorunlessmechanIcalventIlatIonIsIneffectIveInreducIngacutehypercarbIa.n
contrast,chronIcrespIratoryacIdosIsIsrarelymanagedwIthventIlatIonbutratherwIth
effortstoImprovepulmonaryfunctIon.npatIentsrequIrIngmechanIcalventIlatIonfor
acuterespIratoryfaIlure,ventIlatIonwIthalungprotectIvestrategymayresultIn
hypercapnIa,whIchoccasIonallymayrequIreadmInIstratIonofbufferstoavoIdexcessIve
acIdemIa.
18
Practical Approach to Acid-Base Interpretation
FapIdInterpretatIonofapatIent'sacIdbasestatusInvolvestheIntegratIonofthreesetsof
data:arterIalbloodgases,electrolytes,andhIstory.AsystematIc,sequentIalapproach
facIlItatesInterpretatIon(Table147).AcIdbaseassessmentusuallycanbecompleted
beforeInItIatIngtherapy;however,InspectIonofarterIalbloodgasdatamaydIsclose
dIsturbances(e.g.,respIratoryacIdosIsormetabolIcacIdosIswIthpH7.1)thatrequIre
ImmedIateattentIon.
ThesecondstepIstodetermInewhetherapatIentIsacIdemIc(pH7.J5)oralkalemIc(pH
7.45).ThepHstatuswIllusuallyIndIcatethepredomInantprImaryprocess,thatIs,
acIdosIsproducesacIdemIa;andalkalosIsproducesalkalemIa.NotethatthesuffIxosIs
IndIcatesaprImaryprocessthat,Ifunopposed,wIllproducethecorrespondIngpHchange.
ThesuffIxemIareferstothepH.AcompensatoryprocessIsnotconsIderedanosIs.Df
course,apatIentmayhavemIxedoses,thatIs,morethanoneprImaryprocess.
ThethIrdstepIstodetermInewhethertheentIrearterIalbloodgaspIctureIsconsIstent
wIthasImpleacuterespIratoryalkalosIsoracIdosIs(seeTable146).Forexample,a
patIentwIthacutehypocapnIa(Paco
2
J0mmHg)wouldhaveapHIncreaseof0.10unItsto
apHof7.50andadecreaseofcalculated[HCD
J
]to22mEq/L.
Asthefourthstep,IfchangesInPaco
2
,pH,and[HCD
J
]arenotconsIstentwIthasImple
acuterespIratorydIsturbance,chronIcrespIratoryacIdosIs(24hours)
P.295
ormetabolIcacIdosIsoralkalosIsshouldbeconsIdered.nchronIcrespIratoryacIdosIs,pH
returnstonearlynormalasbIcarbonateIsretaInedbythekIdneys(Table146),usuallyata
ratIoof4to5mEq/Lper10mmHgchronIcIncreaseInPaco
2
.
19
Forexample,chronIc
hypoventIlatIonataPaco
2
of60mmHgwouldbeassocIatedwIthanIncreaseIn[HCD
J
]of
8to10mEq/Lsothat[HCD
J
]wouldbeexpectedtorangefromJ2toJ4mEq/LandpH
wouldbeexpectedtobewIthInthelownormalrange(7.J5to7.J8).fneItheranacutenor
chronIcrespIratorychangeappearstoexplaInthearterIalbloodgasdata,thenametabolIc
dIsturbancemustalsobepresent.
Table 14-7 Sequential Approach to Acid-Base Interpretation
1. sthepHlIfethreatenIng,requIrIngImmedIateInterventIon:
2. sthepHacIdemIcoralkalemIc:
J. CouldtheentIrearterIalbloodgaspIcturerepresentonlyanacuteIncreaseor
decreaseInPaCD
2
:
4. ftheanswertoquestIonJIsNo,IsthereevIdenceofachronIcrespIratory
dIsturbanceorofanacutemetabolIcdIsturbance:
5. fanacutemetabolIcdIsturbanceIspresent,IsItaccompanIedbyapproprIate
respIratorycompensatorychanges:
6. sananIongappresent:
7. AretheclInIcaldataconsIstentwIththeproposedInterpretatIon:
ThefIfthquestIonaddressesrespIratorycompensatIonformetabolIcdIsturbances.
FespIratorycompensatIonformetabolIcdIsturbancesoccursmorerapIdlythanrenal
compensatIonforrespIratorydIsturbances(Table14J).SeveralgeneralrulesdescrIbe
compensatIon.FIrst,overcompensatIonIsrare.Second,InadequateorexcessIve
compensatIonsuggestsanaddItIonalprImarydIsturbance.ThIrd,hypobIcarbonatemIa
assocIatedwIthanIncreasedanIongapIsnevercompensatory.
ThesIxthquestIon,whetherananIongapIspresent,shouldbeassessedevenIfthearterIal
bloodgasesappearstraIghtforward.ThesImultaneousoccurrenceofmetabolIcalkalosIs
andmetabolIcacIdosIsmayresultInanunremarkablepHand[HCD
J
];therefore,the
combInedabnormalItymayonlybeapprecIatedbyexamInIngtheanIongap(Ifthecauseof
themetabolIcacIdosIsIsassocIatedwIthahIghanIongap).AsnotedprevIously,correct
assessmentoftheanIongaprequIrescorrectIonforhypoalbumInemIa.
10
|etabolIcacIdoses
assocIatedwIthIncreasedanIongapsrequIrespecIfIctreatments,thusnecessItatInga
correctdIagnosIsanddIfferentIatIonfromhyperchloremIcmetabolIcacIdosIs.ForInstance,
IfmetabolIcacIdosIsresultsfromadmInIstratIonoflargevolumesof0.9salIne,nospecIfIc
treatmentofmetabolIcacIdosIswouldusuallybenecessary.
TheseventhandfInalquestIonIswhethertheclInIcaldataareconsIstentwIththe
proposedacIdbaseInterpretatIon.FaIluretoIntegrateclInIcalfIndIngswItharterIalblood
gasandplasmaelectrolytedatamayleadtoserIouserrorsInInterpretatIonand
management.
Examples
ThefollowIngtwohypothetIcalcasesIllustratetheuseofthealgorIthmandrulesofthumb
prevIouslydIscussed.
Example Number 1
A65yearoldwomanhasundergone12hoursofanexpected16hourradIcalneck
dIssectIonandflapconstructIon.EstImatedbloodlossIs1,000mL.ShehasreceIvedthree
unItsofpackedredbloodcellsandsIxLof0.9salIne.Herbloodpressureandheartrate
haveremaInedstablewhIleanesthetIzedwIth0.5to1.0IsofluraneIn70:J0nItrousoxIde
andoxygen.UrInaryoutputIsadequate.ArterIalbloodgaslevelsareshownInTable148.
Table 14-8 Hyperchloremic Metabolic Acidosis During Prolonged Surgery
ArterIalbloodgases
pH 7.40
PaCD
2
J2mmHg
[HCD
J
] 19mEq/L
Electrolytes
[Na
+
] 140mEq/L
[Cl
] 114mEq/L
CD
2
20mEq/L
AnIongap 8mEq/L
SerumalbumIn J.0g/dL
ThestepbystepInterpretatIonIsasfollows:
1. ThepHrequIresnoImmedIatetreatment.
2. ThepHIsnormal.
J. ThearterIalbloodgasescannotbeadequatelyexplaInedbyacutehypocarbIa.The
predIctedpHwouldbe7.48andthepredIcted[HCD
J
]wouldbe22mEq/L(seeTable14
6).
4. AmetabolIcacIdosIsappearstobepresent.
5. PatIentsundergeneralanesthesIawIthcontrolledmechanIcalventIlatIoncannot
compensateformetabolIcacIdosIs.However,spontaneoushypocapnIaofthIsmagnItude
wouldrepresentslIghtovercompensatIonformetabolIcacIdosIs(seeTable14J)and
wouldsuggestthepresenceofaprImaryrespIratoryalkalosIs.
6. |etabolIcacIdosIsoccurrIngdurIngprolongedanesthesIaandsurgerycouldsuggestlactIc
acIdosIsandpromptaddItIonalfluIdtherapyorotherattemptstoImproveperfusIon.
However,serumelectrolytesrevealananIongapthatIsslIghtlylessthannormal(Table
148),IndIcatIngthatthemetabolIcacIdosIsIsprobablytheresultofdIlutIonofthe
extracellularvolumewIthahIghchlorIdefluId.CorrectIonoftheanIongapforthe
serumalbumInofJ.0g/dLonlyIncreasestheanIongapto10to11mEq/L,agaIn
consIstentwIthhyperchloremIcmetabolIcacIdosIs.AfterdIfferentIatIonfromhIghanIon
gapmetabolIcacIdoses,hyperchloremIcacIdosIssecondarytoInfusIonofhIghchlorIde
fluIdusuallyrequIresnotreatment.ThearterIalbloodgasesandserumelectrolytesare
compatIblewIththeclInIcalpIcture.
Example Number 2
AJ5yearoldman,Jdaysafterappendectomy,developsnauseawIthrecurrentemesIs
persIstIngfor48hours.AnarterIalbloodgasrevealstheresultsshownInthemIddle
columnofTable149.
1. ThepHof7.50requIresnoImmedIateInterventIon.
2. ThepHIsalkalemIc,suggestIngaprImaryalkalosIs.
J. AnacutePaco
2
of46mmHgwouldyIeldapHofapproxImately7.J7;therefore,thIsIs
notsImplyanacuteventIlatorydIsturbance.
4. ThepatIenthasaprImarymetabolIcalkalosIsassuggestedbythe[HCD
J
]ofJ5mEq/L.
5. ThelImItsofrespIratorycompensatIonformetabolIcalkalosIsarewIdeanddIffIcultto
predIctforIndIvIdualpatIents.Therulesofthumb,summarIzedInTable14J,suggest
that[HCD
J
]+15shouldequalthelasttwodIgItsofthepHandthatthePaco
2
should
Increase5to6mmHg
P.296
forevery10mEq/LchangeInserum[HCD
J
],thatIs,apHof7.50andaPaco
2
of46mm
HgarewIthIntheexpectedrange.
6. TheanIongapIs10mEq/L.
7. ThedIagnosIsofaprImarymetabolIcalkalosIswIthcompensatoryhypoventIlatIonIs
consIstentwIththehIstoryofrecurrentvomItIng.ConsIderhowthearterIalbloodgases
couldchangeIfvomItIngweresuffIcIentlyseveretoproducehypovolemIcshockand
lactIcacIdosIs(thIrdcolumn,Table149).
Table 14-9 Metabolic Alkalosis Secondary to Nausea and Vomiting with
Subsequent Lactic Acidosis Secondary to Hypovolemia
NORMAL
METABOLIC
ALKALOSIS
METABOLIC
ACIDOSIS
8loodgases
PH 7.40 7.50 7.40
PaCD
2
(mmHg)
40 46 40
[HCD
J
](mEq/L) 24 J5 24
Serum
electrolytes
[Na
+
](mEq/L) 140 140 140
[Cl
](mEq/L) 105 94 94
CD
2
(mEq/L)
25 J6 25
AnIongap
(mEq/L)
10 10 21
ThIssequenceIllustratestheImportantconceptthatthefInalpH,Paco
2
and[HCD
J
]
representtheresultofallofthevectorsoperatIngonacIdbasestatus.ComplexortrIple
dIsturbancescanonlybeInterpretedusIngathorough,stepwIseapproach.
Fluid Management
Physiology
Body Fluid Compartments
AccuratereplacementoffluIddefIcItsnecessItatesanunderstandIngoftheexpected
dIstrIbutIonspacesofwater,sodIum,andcolloId.ThesumofIntracellularvolume(C7),
whIchconstItutes40oftotalbodyweIght,andextracellularvolume(EC7),whIch
constItutes20ofbodyweIght,comprIsestotalbodywater(T8W),whIchtherefore
approxImates60oftotalbodyweIght.Plasmavolume(P7),equalsaboutonefIfthofEC7,
theremaInderofwhIchIsInterstItIalfluIdvolume(F7).Fedcellvolume,approxImately2
L,IspartofC7.
ThedIstrIbutIonvolumeofsodIumfreewaterIsT8W.ThedIstrIbutIonvolumeofInfused
sodIumIsEC7,whIchcontaInsequalsodIumconcentratIons([Na
+
])IntheP7andF.Plasma
[Na
+
]IsapproxImately140mEq/L.ThepredomInantIntracellularcatIon,potassIum,hasan
IntracellularconcentratIon([K
+
])approxImatIng150mEq/L.AlbumIn,themostImportant
oncotIcallyactIveconstItuentofEC7,IsunequallydIstrIbutedInP7(-4g/dL)andF7(-1
g/dL).TheF7concentratIonofalbumInvarIesgreatlyamongtIssues;however,EC7Isthe
dIstrIbutIonvolumeforcolloIdsolutIons.
Distribution of Infused Fluids
ConventIonally,clInIcalpredIctIonofplasmavolumeexpansIonafterfluIdInfusIonassumes
thatbodyfluIdspacesarestatIc.KInetIcanalysIsofplasmavolumeexpansIonreplacesthe
statIcassumptIonwIthadynamIcdescrIptIon.AsanexampleofthestatIcapproach,
assumethata70kgpatIenthassufferedanacutebloodlossof2,000mL,approxImately
40ofthepredIcted5Lbloodvolume.TheformuladescrIbIngtheeffectsofreplacement
wIth5dextroseInwater(05W),lactatedFIngersolutIon,or5or25humanserum
albumInIsasfollows:
FearrangIngtheequatIonyIeldsthefollowIng:
TorestorebloodvolumeusIng05W,assumIngadIstrIbutIonvolumeforsodIumfreewater
ofT8W,requIres28L:
where2LIsthedesIredP7Increment,42L=T8WIna70kgperson,andJLIsthenormal
estImatedP7.
TorestorebloodvolumeusInglactatedFIngersolutIonrequIres9.1L:
where14L=EC7Ina70kgperson.
f5albumIn,whIchexertscolloIdosmotIcpressuresImIlartoplasma,wereInfused,the
InfusedvolumeInItIallywouldremaInIntheP7,perhapsattractIngaddItIonalInterstItIal
fluIdIntravascularly.TwentyfIvepercenthumanserumalbumIn,aconcentratedcolloId,
expandsP7byapproxImately400mLforeach100mLInfused.
However,thesestatIcanalysesaresImplIstIc.nfusedfluIddoesnotsImplyequIlIbrate
throughoutanassumeddIstrIbutIonvolumebutIsaddedtoahIghlyregulatedsystemthat
attemptstomaIntaInIntravascular,InterstItIal,andIntracellularvolume.Amore
comprehensIvekInetIcmodelwasproposedbySvensenandHahn.
20
KInetIcmodelsof
IntravenousfluIdtherapyallowclInIcIanstopredIctmoreaccuratelythetImecourseof
volumechangesproducedbyInfusIonsoffluIdsofvarIouscomposItIons.KInetIcanalysIs
permItsestImatIonofpeakvolumeexpansIonandratesofclearanceofInfusedfluIdand
complementsanalysIsofpharmacodynamIceffects,suchaschangesIncardIacoutputor
cardIacfIllIngpressures.
UsIngakInetIcapproachtofluIdtherapypermItsanalysIsoftheeffectsofcommon
physIologIcandpharmacologIcInfluencesonfluIddIstrIbutIonInexperImentalanImalsor
humans.Forexample,InchronIcallyInstrumentedsheep,IsofluraneanesthesIaandthe
conscIousstatewereassocIatedwIthsImIlarkInetIcsofP7expansIonafterfluIdInfusIon,
butreducedurInaryoutputInanesthetIzedsheepdemonstrated
P.297
thatexpansIonofextravascularvolumewasrelatIvelygreaterdurInganesthesIa
21
;
subsequentexperImentsdemonstratedthatthIseffectwasattrIbutabletoIsofluraneand
nottomechanIcalventIlatIondurInganesthesIa.
22
AlsoInchronIcallyInstrumentedsheep,
admInIstratIonofcatecholamIneInfusIonsbeforeanddurIngfluIdInfusIonsprofoundly
alteredIntravascularfluIdretentIon,wIthphenylephrInedImInIshIngandIsoproterenol
enhancIngIntravascularfluIdretentIon(FIg.141).
2J
Figure 14-1. A.8loodhemoglobIn(meanSE|)sampledatthreebaselIneperIods
durIngaJ0mInutecatecholamIneInfusIonandforJhoursafterstartInga20mInute
0.9NaClbolusof24mL/kg.CatecholamIneprotocolsaredopamIne(0opa,open
diamonds),Isoproterenol(so,closed circles),phenylephrIne(Phen,open triangles),
andnodrugcontrol(Control,closed squares).The0.9NaClbolusdecreased
hemoglobInInallprotocolsattheendofthe20mInute0.9NaCLInfusIonandInall
protocolsexceptthePhenprotocolthereafter.PostInfusIonprotocoldIfferenceswere
Phen0opa=Controlso.B.Calculatedbloodvolume(meanSE|)atthree
baselIneperIodsdurIngacatecholamIneInfusIonandforJhoursafterstartInga20
mInute0.9NaClbolusof24mL/kg.The0.9NaClbolusIncreasedbloodvolumeInall
protocolsatT20andInallprotocolsexceptthePhenprotocolthereafter.PostInfusIon
protocoldIfferenceswereso0opa=ControlPhen.NS,normalsalInebolus.(From
7aneLA,Prough0S,KInsky|A,WIllIamsCA,CradyJJ,KramerCC:EffectsofdIfferent
catecholamInesonthedynamIcsofvolumeexpansIonofcrystalloIdInfusIon.
AnesthesIology2004;101:11J61144,wIthpermIssIon).
Regulation of Extracellular Fluid Volume
TotalbodywatercontentIsregulatedbytheIntakeandoutputofwater.WaterIntake
IncludesIngestedlIquIdsplusanaverageof750mLIngestedInsolIdfoodandJ50mLthatIs
generatedmetabolIcally.nsensIblelossesarenormally1L/dayandgastroIntestInallosses
are100to150mL/day.ThIrst,theprImarymechanIsmofcontrollIngwaterIntake,Is
trIggeredbyanIncreaseInbodyfluIdtonIcItyorbyadecreaseInextracellularvolume.
FeabsorptIonoffIlteredwaterandsodIumIsenhancedbychangesmedIatedbythe
hormonalfactorsantIdIuretIchormone(A0H),atrIalnatrIuretIcpeptIde(ANP),and
aldosterone.FenalwaterhandlInghasthreeImportantcomponents:(1)delIveryoftubular
fluIdtothedIlutIngsegmentsofthenephron,(2)separatIonofsoluteandwaterInthe
dIlutIngsegment,and(J)varIablereabsorptIonofwaterInthecollectIngducts.nthe
descendIngloopofHenle,waterIsreabsorbedwhIlesoluteIsretaInedtoachIeveafInal
osmolalItyoftubularfluIdofapproxImately1,200mDsm/kg(FIg.142).ThIsconcentrated
fluIdIsthendIlutedbytheactIvereabsorptIonofelectrolytesIntheascendInglImbofthe
loopofHenleandInthedIstaltubule,bothofwhIcharerelatIvelyImpermeabletowater.
AsfluIdexItsthedIstaltubuleandentersthecollectIngduct,osmolalItyIsapproxImately
50mDsm/kg.WIthInthecollectIngduct,waterreabsorptIonIsmodulatedbyA0H(also
calledvasopressin).7asopressInbIndsto7
2
receptorsalongthebasolateralmembraneof
thecollectIngductcells,thenstImulatesthesynthesIsandInsertIonoftheaquaporIn2
waterchannelIntothelumInalmembraneofcollectIngductcells.
24
PlasmahypotonIcItysuppressesA0Hrelease,resultIngInexcretIonofdIluteurIne.
HypertonIcItystImulatesA0HsecretIon,whIchIncreasesthepermeabIlItyofthecollectIng
ducttowaterandenhanceswaterreabsorptIon.nresponsetochangIngplasma[Na
+
],
changIngsecretIonofA0HcanvaryurInaryosmolalItyfrom50to1,200mDsm/kgand
urInaryvolumefrom0.4to20L/day(FIg.14J).
25
DtherfactorsthatstImulateA0H
secretIon,althoughnoneaspowerfullyasplasmatonIcIty,IncludehypotensIon,
hypovolemIa,andnonosmotIcstImulIsuchasnausea,paIn,andmedIcatIons,IncludIng
opIates.
TwopowerfulhormonalsystemsregulatetotalbodysodIum.ThenatrIuretIcpeptIdes,ANP,
braInnatrIuretIcpeptIde,andCtypenatrIuretIcpeptIde,defendagaInstsodIum
overload
26,27,28
andtherenInangIotensInaldosteroneaxIsdefendsagaInstsodIum
depletIonandhypovolemIa.ANP,releasedfromthecardIacatrIaInresponsetoIncreased
atrIalstretch,exertsvasodIlatoryeffectsandIncreasestherenalexcretIonofsodIumand
water.ANPsecretIonIsdecreaseddurInghypovolemIa.EvenInpatIentswIthchronIc
(nonolIgurIc)renalInsuffIcIency,InfusIonofANPInlow,nonhypotensIvedosesIncreased
sodIumexcretIonandaugmentedurInarylossesofretaInedsolutes.
29
AldosteroneIsthefInalcommonpathwayInacomplexresponsetodecreasedeffectIve
arterIalvolume,whetherdecreasedeffectIvearterIalvolumeIstrueorrelatIve,asIn
edematousstatesorhypoalbumInemIa.nthIspathway,decreasedstretchInthe
baroreceptorsoftheaortIcarchandcarotIdbodyandstretchreceptorsInthegreatveIns,
pulmonaryvasculature,andatrIaresultInIncreasedsympathetIctone.ncreased
sympathetIctone,IncombInatIonwIthdecreasedrenalperfusIon,leadstorenInrelease
andformatIonofangIotensInfromangIotensInogen.AngIotensInconvertIngenzyme(ACE)
convertsangIotensIntoangIotensIn,whIchstImulatestheadrenalcortextosynthesIze
andreleasealdosterone.
J0
ActIngprImarIlyInthedIstaltubules,hIghconcentratIonsof
aldosteronecausesodIumreabsorptIonandmayreduceurInaryexcretIonofsodIumnearly
tozero.ntrarenalphysIcalfactorsarealsoImportantInregulatIngsodIumbalance.
SodIumloadIngdecreasescolloIdosmotIcpressure,therebyIncreasIngtheglomerular
fIltratIonrate(CFF),decreasIngnetsodIumreabsorptIonandIncreasIngdIstalsodIum
delIvery,whIch,Inturn,suppressesrenInsecretIon.
P.298
Figure 14-2.FenalfIltratIon,reabsorptIon,andexcretIonofwater.Open arrows
representwaterandsolid arrowsrepresentelectrolytes.Waterandelectrolytesare
fIlteredbytheglomerulus.ntheproxImaltubule(1),waterandelectrolytesare
absorbedIsotonIcally.nthedescendIngloopofHenle(2),waterIsabsorbedto
achIeveosmotIcequIlIbrIumwIththeInterstItIumwhIleelectrolytesareretaIned.The
numbers(J00,600,900,and1200)betweenthedescendIngandascendInglImbs
representtheosmolalItyoftheInterstItIumInmIllIosmolesperkIlogram.ThedelIvery
ofsoluteandfluIdtothedIstalnephronIsafunctIonofproxImaltubularreabsorptIon;
asproxImaltubularreabsorptIonIncreases,delIveryofsolutetothemedullary(Ja)
andcortIcal(Jb)dIlutIngsItesdecreases.nthedIlutIngsItes,electrolytefreewaterIs
generatedthroughselectIvereabsorptIonofelectrolyteswhIlewaterIsretaInedInthe
tubularlumen,generatIngadIlutetubularfluId.ntheabsenceofvasopressIn,the
collectIngduct(4a)remaInsrelatIvelyImpermeabletowaterandadIlutedurIneIs
excreted.WhenvasopressInactsonthecollectIngducts(4b),waterIsreabsorbedfrom
thesevasopressInresponsIvenephronsegments,allowIngtheexcretIonofa
concentratedurIne.(FromFrIedLF,PalevskyP|:HyponatremIaandhypernatremIa,
The|edIcalClInIcsofNorthAmerIca.Fenal0Isease.EdItedbySaklayen|C.
PhIladelphIa,W8SaundersCompany,1997,pp585609,wIthpermIssIon.)
Figure 14-3. Left.ThesIgmoIdrelatIonshIpbetweenplasmavasopressIn(7P)and
urInaryosmolalIty.0atawereobtaIneddurIngwaterloadIngandfluIdrestrIctIonIna
groupofhealthyadults.|axImumurInaryconcentratIonIsachIevedbyplasma7P
valuesofJto4pmol/L.Right.ThelInearrelatIonshIpbetweenplasmaosmolalItyand
plasma7P.ncreasesIn7PInresponsetohypertonIcItyInducedbyInfusIonof855
mmol/LsalIneInagroupofhealthyadults.Theshadedarearepresentsthereference
rangeresponse.L0representsthelImItofdetectIonofthe7Passay,0.Jpmol/L.(From
8allSC:7asopressInanddIsordersofwaterbalance:thephysIologyand
pathophysIologyofvasopressIn.AnnClIn8Iochem2007;44:4174J1,wIthpermIssIon.)
P.299
Fluid Replacement Therapy
Maintenance Requirements for Water, Sodium, and Potassium
CalculatIonofmaIntenancefluIdrequIrementsIsoflImItedvalueIndetermInIng
IntraoperatIvefluIdrequIrements.However,calculatIonofmaIntenancefluIdrequIrements
(Table1410)IsusefulforestImatIngwaterandelectrolytedefIcItsthatresultfrom
preoperatIverestrIctIonoforalfoodandfluIdsandforestImatIngtheongoIng
requIrementsforpatIentswIthprolongedpostoperatIveboweldysfunctIon.nhealthy
adults,suffIcIentwaterIsrequIredtobalancegastroIntestInallossesof100to200mL/day,
InsensIblelossesof500to1,000mL/day(halfofwhIchIsrespIratoryandhalfIscutaneous),
andurInarylossesof1,000mL/day.UrInarylossesexceedIng1,000mL/daymayrepresent
anapproprIatephysIologIcresponsetoEC7expansIonorpathophysIologIcInabIlItyto
conservesaltorwater.
0aIlyadultrequIrementsforsodIumandpotassIumareapproxImately75and40mEq/kg,
respectIvely,althoughwIderrangesofsodIumIntakethanpotassIumIntakeare
physIologIcallytoleratedbecauserenalsodIumconservatIonandexcretIonaremore
effIcIentthanpotassIumconservatIonandexcretIon.Therefore,healthy,70kgadults
requIre2,500mL/dayofwatercontaInInga[Na
+
]ofJ0mEq/Landa[K
+
]of15to20mEq/L.
ntraoperatIvely,fluIdscontaInIngsodIumfreewater(I.e.,[Na
+
]1J0mEq/L)arerarely
usedInadultsbecauseofthenecessItyforreplacIngIsotonIclossesandtherIskof
postoperatIvehyponatremIa.
Dextrose
TradItIonally,glucosecontaInIngIntravenousfluIdshavebeengIvenInanefforttoprevent
hypoglycemIaandlImItproteIncatabolIsm.However,becauseofthehyperglycemIc
responseassocIatedwIthsurgIcalstress,onlyInfantsandpatIentsreceIvIngInsulInordrugs
thatInterferewIthglucosesynthesIsareatrIskforhypoglycemIa.atrogenIchyperglycemIa
canlImIttheeffectIvenessoffluIdresuscItatIonbyInducInganosmotIcdIuresIsand,In
anImals,mayaggravateIschemIcneurologIcInjury.
J1
AlthoughassocIatedwIthworsened
outcomeaftersubarachnoIdhemorrhage
J2
andtraumatIcbraInInjury
JJ
Inhumans,
hyperglycemIamayalsoconstItuteahormonallymedIatedresponsetomoresevereInjury.
ncrItIcallyIllpatIents,someevIdencesuggeststhattIghtcontrolofplasmaglucose
(maIntenanceofplasmaglucosebetween80and110mg/dL)IsassocIatedwIthreduced
mortalItyandmorbIdIty,butotherevIdencedoesnot.
J4,J5,J6,J7
EvIdencealsosuggeststhat
tIghtglucosecontrolImprovesoutcomeInsurgIcalpatIents.
J8
Surgical Fluid Requirements
Water and Electrolyte Composition of Fluid Losses
SurgIcalpatIentsrequIrereplacementofP7andEC7lossessecondarytowoundorburn
edema,ascItes,andgastroIntestInalsecretIons.WoundandburnedemaandascItIcfluId
areproteInrIchandcontaInelectrolytesInconcentratIonssImIlartoplasma.Although
gastroIntestInalsecretIonsvarygreatlyIncomposItIon,thecomposItIonofreplacement
fluIdneednotbecloselymatchedIfEC7IsadequateandrenalandcardIovascular
functIonsarenormal.SubstantIallossofgastroIntestInalfluIdsrequIresmoreaccurate
replacementofelectrolytes(I.e.,potassIum,magnesIum,phosphate).ChronIcgastrIclosses
mayproducehypochloremIcmetabolIcalkalosIsthatcanbecorrectedwIth0.9salIne;
chronIcdIarrheamayproducehyperchloremIcmetabolIcacIdosIsthatmaybepreventedor
correctedbyInfusIonoffluIdcontaInIngbIcarbonateorbIcarbonatesubstrate(e.g.,
lactate).fcardIovascularorrenalfunctIonIsImpaIred,moreprecIsereplacementmay
requIrefrequentassessmentofserumelectrolytes.
Table 14-10 Hourly and Daily Maintenance Water Requirements
WEIGHT (kg) WATER (mL/kg/hr) WATER (mL/kg/day)
110 4 100
1120 2 50
21n
+
1 20
Influence of Perioperative Fluid Infusion Rates on Clinical
Outcomes
ConventIonally,IntraoperatIvefluIdmanagementhasIncludedreplacementoffluIdthatIs
assumedtoaccumulateextravascularlyInsurgIcallymanIpulatedtIssue.UntIlrecently,
perIoperatIveclInIcalpractIceIncluded,InaddItIontomaIntenancefluIdsandreplacement
ofestImatedbloodloss,4to6mL/kg/hrforproceduresInvolvIngmInImaltIssuetrauma,6
to8mL/kg/hrforthoseInvolvIngmoderatetrauma,and8to12mL/kg/hrforthose
InvolvIngextremetrauma.
However,recentclInIcaltrIalsstronglylInkperIoperatIvefluIdmanagementtopotentIally
ImportantalteratIonsofbothmInorandmajormorbIdIty.|oreover,theInfluenceoffluId
volumemaybespecIfIctothetypeofsurgeryandtothetypesoffluIdused.|aharajet
al.
J9
randomIzed80ASApatIentsscheduledforgynecologIclaparoscopyeIthertolarge
volume,defInedas2.0mL/kg/hroffastIngover20mInutespreoperatIvely(e.g.,1,440
mL/60kgInapatIentwhohadbeenfastIngfor12hours)orsmallvolume,defInedastotal
fluIdofJ.0mL/kgover20mInutespreoperatIvely.npatIentsreceIvIngthehIgherdose,
postoperatIvenauseaandvomItIngandpaInweresIgnIfIcantlyreduced(FIg.144).
J9
Holte
etal.
40
randomIzed48ASApatIentsundergoInglaparoscopIccholecystectomyto
receIveeIther15or40mL/kgoflactatedFIngersolutIonIntraoperatIvely;thehIgherdose
offluIdwasassocIatedwIthImprovedpostoperatIvepulmonaryfunctIonandexercIse
capacIty,reducedneurohumoralstressresponse,andImprovementsInnausea,general
senseofwellbeIng,thIrst,dIzzIness,drowsIness,fatIgue,andbalancefunctIon.Holteet
al.
41
randomIzed48ASApatIentsundergoIngfasttrackelectIvekneearthroplasty
underIntraoperatIveepIdural/spInalanesthesIaandpostoperatIveepIduralanalgesIato
eItherlIberalorrestrIctedfluIds.|edIanIntravenousfluIdadmInIsteredIntraoperatIvely
andInthepostanesthesIacareunItIntherestrIctIvegroupwas1,740mL(range,1,100to
2,165mL)oflactatedFIngersolutIonandInthelIberalgroupwasJ,275mL(range,2,400to
4,000mL).FestrIctIvefluIdadmInIstratIonwasassocIatedwIthahIgherIncIdenceof
vomItIngbutlesshypercoagulabIlItyandnodIfferenceInshorttermpostoperatIvemobIlIty
orIleus.Therefore,fluIdrestrIctIonappearstobelesswelltoleratedthanmorelIberal
fluIdtherapyInpatIentsundergoIngsurgeryoflImItedscope,butperhapsattheexpenseof
hypercoagulabIlIty.
npatIentsundergoIngmajorIntraabdomInalsurgery,recentrandomIzedcontrolledtrIals
alsosuggestthatrestrIctIvefluIdadmInIstratIonIsassocIatedwIthacombInatIonof
posItIveandnegatIveeffects.8randstrupetal.
42
randomIzed172electIvecolonsurgery
patIentstoeItherrestrIctIveperIoperatIvefluIdmanagementorstandardperIoperatIve
fluIdmanagement,wIththeprImarygoalofmaIntaInIngpreoperatIvebodyweIghtInthe
fluIdrestrIctedgroup.8ydesIgn,thefluIdrestrIctedgroupreceIvedlessperIoperatIvefluId
and
P.J00
acutelygaIned1kgIncontrasttoJkgInthestandardtherapygroup.|oreImportantly,
cardIopulmonarycomplIcatIons,tIssuehealIngcomplIcatIons,andtotalpostoperatIve
complIcatIonsweresIgnIfIcantlyfewerInthefluIdrestrIctedgroup.n152patIents
undergoIngIntraabdomInalsurgery,IncludIngcolonsurgery,NIsanevIchetal.
4J
reported
lesspromptreturnofgastroIntestInalfunctIonandlongerhospItalstaysInpatIents
receIvIngconventIonalfluIdtherapy(10mL/kg/hroflactatedFIngersolutIon)thanIn
patIentsreceIvIngrestrIctedfluIdtherapy(4.0mL/kg/hr).nasmallclInIcaltrIal
comparInggastrIcemptyIngInpatIentsrandomIzedtoreceIvepostoperatIvefluIdsata
restrIcted(2.0L/dayofwater;77mEq/day)orlIberalregImen(J.0L/dayofwater;154
mEq/day),gastrIcemptyIngtImeforbothlIquIdsandsolIdswassIgnIfIcantlyreducedIn
patIentsreceIvIngrestrIctedfluIds(FIg.145).
44
Khooetal.
45
randomIzed70ASA
patIentsundergoIngelectIvecolorectalsurgerytoconventIonalperIoperatIve
management,IncludIngIntraoperatIvefluIdmanagementatthedIscretIonofthe
anesthesIologIst,ortomultImodalperIoperatIvemanagement,IncludIngIntraoperatIve
fluIdrestrIctIon,unrestrIctedpostoperatIveoralIntake,prokInetIcagents,early
ambulatIon,andpostoperatIveepIduralanalgesIa.|ultImodalperIoperatIvemultImodal
managementwasassocIatedwIthareducedmedIanstay(5vs.7days)andfewer
cardIorespIratoryandanastomotIccomplIcatIons,butmorehospItalreadmIssIons.Holteet
al.
46
randomIzedJ2ASApatIentsundergoIngfasttrackcolonresectIonunder
combInedepIdural/generalanesthesIatoIntraoperatIvefluIdadmInIstratIonusIngeIthera
restrIctIve(medIan,1,640mL;range,9J5to2,250mL)orlIberal(medIan,5,050mL;range,
J,56Jto8,050mL)regImen.FluIdrestrIctedpatIentshadsIgnIfIcantlyImproved
postoperatIveforcedvItalcapacItyandfewer,lesssevereepIsodesofoxygensaturatIon
butattheexpenseofIncreasedstressresponses(aldosterone,antIdIuretIchormoneand
angIotensInmeasurements)andastatIstIcallyInsIgnIfIcantlyIncreasednumberof
complIcatIons.
Figure 14-4. Top.|eanpostoperatIveverbalanalogscale(7AS)nauseascoresIneach
groupoverthefIrst72postoperatIvehours.|ean7ASnauseascoresweresIgnIfIcantly
lowerInthegroupthatreceIvedthelargevolumeIntravenousfluIdInfusIoncompared
wIththecontrolgroupat1,4,24,and72hourspostoperatIvely.Bottom.|ean
postoperatIve7ASpaInscoresIneachgroupoverthefIrst72postoperatIvehours.
|ean7ASpaInscoresweresIgnIfIcantlylowerInthegroupthatreceIvedthelarge
volumeIntravenousfluIdInfusIoncomparedwIththecontrolgroupat0,1,24,and72
hourspostoperatIvely.*SIgnIfIcantlyhIgher(p0.05,ttestpostanalysIsofvarIance)
7ASscorecomparedwIththelargevolumegroup.PACU,postanesthesIacareunIt.
(From|aharajCH,KallamSF,|alIkA,HassettP,Crady0,LaffeyJC:PreoperatIve
IntravenousfluIdtherapydecreasespostoperatIvenauseaandpaInInhIghrIsk
patIents.AnesthAnalg2005;100:675682,wIthpermIssIon.)
CrItIcallyIllpatIentswIthacutelungInjuryrepresentanImportantgroupthatmaybenefIt
fromcarefulregulatIonoffluIdIntake.TheAF0SClInIcalTrIalsNetwork
47
randomIzed
P.J01
1,000patIentswIthacutelungInjurytoa7daytrIalcomparIngaconservatIvefluId
strategywIthalIberalfluIdstrategy.DverthecourseofthetrIaltheconservatIvestrategy
grouphadacumulatIvenetfluIdbalancethatwasslIghtlynegatIveIncomparIsontoa
meannetcumulatIvefluIdbalanceInthelIberalgroupofnearly7.0L.Althoughoverall
mortalItywasnodIfferentInthetwogroups,theconservatIvefluIdgrouphadImproved
oxygenatIonandrequIredfewerdaysofmechanIcalventIlatIonandIntensIvecare.0espIte
achIevInganegatIvefluIdbalance,theconservatIvestrategygrouphadnogreater
IncIdenceofacuterenalfaIlure.
Figure 14-5.SolIdandlIquIdphasegastrIcemptyIngtImes(T
50
)after4daysof
standardorrestrIctedIntravenouspostoperatIvefluIdtherapy.SolIdlInesaremedIans,
shadedareasInterquartIleranges,andwhIskersrepresentextremevalues.0Ifferences
betweenmedIansforsolIdandlIquIdphaseT
50
were56mInutes(95confIdence
Interval:12to1J2mInutes)and52mInutes(9to95mn),respectIvely.(FeprIntedwIth
permIssIonfromLobo0N,8ostockKA,NealKF,PerkInsAC,Fowlands8J,AllIsonSP:
EffectofsaltandwaterbalanceonrecoveryofgastroIntestInalfunctIonafterelectIve
colonIcresectIon:arandomIsedcontrolledtrIal.Lancet2002;J59:1812).
Colloids, Crystalloids, and Hypertonic Solutions
Physiology and Pharmacology
DsmotIcallyactIvepartIclesattractwateracrosssemIpermeablemembranesuntIl
equIlIbrIumIsattaIned.TheosmolarityofasolutIonreferstothenumberofosmotIcally
actIvepartIclesperliterofsolvent;osmolality,ameasurementofthenumberof
osmotIcallyactIvepartIclesperkilogram,canbeestImatedasfollows:
whereosmolalItyIsexpressedInmmol/kg,[Na
+
]IsexpressedInmEq/L,serumglucoseIs
expressedInmg/dL,and8UNIsbloodureanItrogenexpressedInmg/dL.Sugars,alcohols,
andradIographIcdyesIncreasemeasuredosmolalIty,generatInganIncreasedosmolal
gapbetweenthemeasuredandcalculatedvalues.
AhyperosmolarstateoccurswhenevertheconcentratIonofosmotIcallyactIvepartIclesIs
hIgh.8othuremIa(Increased8UN)andhypernatremIa(IncreasedserumsodIum)Increase
serumosmolalIty.However,becauseureadIstrIbutesthroughoutT8W,anIncreaseIn8UN
doesnotcausehypertonicity.SodIum,largelyrestrIctedtotheEC7,causeshypertonIcIty,
thatIs,osmotIcallymedIatedredIstrIbutIonofwaterfromC7toEC7.ThetermtonicityIs
alsousedcolloquIallytocomparetheosmotIcpressureofaparenteralsolutIontothatof
plasma.
AlthoughonlyasmallproportIonoftheosmotIcallyactIvepartIclesInbloodconsIstof
plasmaproteIns,thosepartIclesareessentIalIndetermInIngtheequIlIbrIumoffluId
betweentheInterstItIalandplasmacompartmentsofEC7.ThereflectIoncoeffIcIent()
descrIbesthepermeabIlItyofcapIllarymembranestoIndIvIdualsolutes,wIth0
representIngfreepermeabIlItyand1.0representIngcompleteImpermeabIlIty.The
reflectIoncoeffIcIentforalbumInrangesfrom0.6to0.9InvarIouscapIllarybeds.8ecause
capIllaryproteInconcentratIonsexceedInterstItIalconcentratIons,theosmotIcpressure
exertedbyplasmaproteIns(termedcolloid osmotic pressureoroncotic pressure)IshIgher
thanInterstItIaloncotIcpressureandtendstopreserveP7.ThefIltratIonrateoffluIdfrom
thecapIllarIesIntotheInterstItIalspaceIsthenetresultofacombInatIonofforces,
IncludIngthegradIentfromIntravasculartoInterstItIalcolloIdosmotIcpressuresandthe
hydrostatIcgradIentbetweenIntravascularandInterstItIalpressures.ThenetfluId
fIltratIonatanypoIntwIthInasystemIcorpulmonarycapIllaryIsrepresentedbyStarlIng's
lawofcapIllaryfIltratIon,asexpressedIntheequatIon:
whereQ=fluIdfIltratIon,k=capIllaryfIltratIoncoeffIcIent(conductIvItyofwater),A=the
areaofthecapIllarymembrane,P
c
=capIllaryhydrostatIcpressure,P
i
=InterstItIal
hydrostatIcpressure,=reflectIoncoeffIcIentforalbumIn,
i
=InterstItIalcolloIdosmotIc
pressure,and
c
=capIllarycolloIdosmotIcpressure.
TheF7IsdetermInedbytherelatIveratesofcapIllaryfIltratIonandlymphatIcdraInage.
P
c
,themostpowerfulfactorpromotIngfluIdfIltratIon,IsdetermInedbycapIllaryflow,
arterIalresIstance,venousresIstance,andvenouspressure.fcapIllaryfIltratIonIncreases,
theratesofwaterandsodIumfIltratIonusuallyexceedproteInfIltratIon,resultIngIn
preservatIonof
c
,dIlutIonof
i
,andpreservatIonoftheoncotIcpressuregradIent,the
mostpowerfulfactoropposIngfluIdfIltratIon.WhencoupledwIthIncreasedlymphatIc
draInage,preservatIonoftheoncotIcpressuregradIentlImItsthe
P.J02
accumulatIonofF.fP
c
IncreasesatatImewhenlymphatIcdraInageIsmaxImal,thenF7
accumulates,formIngedema.
Clinical Implications of Choices Between Alternative Fluids
fmembranepermeabIlItyIsIntact,colloIdssuchasalbumInorhydroxyethylstarch
preferentIallyexpandP7ratherthanF7.ConcentratedcolloIdcontaInIngsolutIons(e.g.,
25albumIn)exertsuffIcIentoncotIcpressuretotranslocatesubstantIalvolumesofF7
IntotheP7,therebyIncreasIngP7byavolumethatexceedstheorIgInalInfusedvolume.
P7expansIonunaccompanIedbyF7expansIonoffersapparentadvantages:lowerfluId
requIrements,lessperIpheralandpulmonaryedemaaccumulatIon,andreducedconcern
aboutthecardIopulmonaryconsequencesoflaterfluIdmobIlIzatIon(Table1411).
However,exhaustIveresearchhasfaIledtoestablIshthesuperIorItyofeIthercolloId
contaInIngorcrystalloIdcontaInIngfluIdsforeItherIntraoperatIveorpostoperatIveuse.
|orettIetal.
48
reportedthatpatIentswhowererandomIzedtoreceIve6hetastarchhad
lesspostoperatIvenauseaandvomItIngthanthosewhoreceIvedlactatedFIngersolutIon
wIthoutcolloId.naddItIon,colloIdadmInIstratIonappearstohavebeenanessentIal
componentofperIoperatIvemanagementstrategIesthatdemonstratedImprovedmorbIdIty
aftercolonsurgery
42
andaftermajorsurgeryInconjunctIonwIthgoaldIrectedfluId
challenges.
49,50
ncrItIcallyIllpatIentsandpatIentsundergoIngmoreextensIvesurgery,systematIc
revIewsofavaIlablecomparIsonsofcolloIdversuscrystalloId
51
andalbumInversus
crystalloId
52
suggestedthatthechoIceoffluIddIdnotInfluencemortalIty.Arecent
randomIzedcontrolledtrIalcomparIng4albumInwIth0.9salIneforfluIdmaIntenanceIn
6,997crItIcallyIllpatIentssupportstheconclusIonthatchoIceofcolloIdorcrystalloIddoes
notInfluencemortalIty.
5J
8aselIneserumalbumInconcentratIondIdnotalterthelackof
effectofalbumInmanagementonoutcome.
54
However,subgroupanalysessuggestedthat
crystalloIdtreatmentcouldbesuperIorInpatIentsaftertraumaandthatcolloIdcouldbe
superIorInpatIentswIthseveresepsIs.
5J
Subsequent2yearfollowupofasubsetof460
patIentswIthtraumatIcbraInInjury(ClasgowComaScalescore1J)demonstratedanearly
twofoldIncreasedrIskofdeathInpatIentsreceIvIngcolloIdfluIdmanagement.
55
Althoughhydroxyethylstarch,themostcommonlyusedsynthetIccolloId,IslessexpensIve
thanalbumIn,largedoses(exceedIng20mL/kg/day)producelaboratoryevIdenceof
coagulopathy.
56
Fecently,anewhydroxyethylstarchformulatIonhasbeenIntroducedthat
contaInsadIfferentmIxofmolecularsIzesandIsdIssolvedInabaseconsIstIngofa
balancedsaltsolutIonratherthan0.9salIne.ProposedadvantagesofthenewformulatIon
IncludelessrIskofInducIngcoagulopathyandofhyperchloremIcmetabolIcacIdosIs.
57
However,lowermolecularweIghthetastarchformulatIonsappeartoInfluencecoagulatIon
less.
56
FurtherrefInementIslIkelytooccurInthedIstInctIonsamongvarIousclInIcally
avaIlablecolloIds.
58
Implications of Crystalloid and Colloid Infusions on Intracranial
Pressure
8ecausethecerebralcapIllarymembrane,thebloodbraInbarrIer,IshIghlyImpermeable
tosodIum,abruptchangesInserumosmolalItyproducedbychangesInserumsodIum,
producerecIprocalchangesInbraInwater.nanesthetIzedrabbIts,reducIngplasma
osmolalItyfrom295to282mDsm/kg(whIchdecreasesplasmaosmotIcpressureby-250mm
Hg)IncreasedcortIcalwatercontentandCP;IncontrastreducIngcolloIdosmotIcpressure
from20to7mmHgproducednosIgnIfIcantchangeIneIthervarIable.
59
SImIlar
IndependenceofbraInwaterandCPfromcolloIdosmotIcpressurehasbeendemonstrated
wIthprolongedhypoalbumInemIa
60
andInanImalsafterforebraInIschemIa
61
andfocal
cryogenIcInjury.
62
AlthoughratshadreducedbraInwaterafterfluIdpercussIontraumatIc
braInInjuryIfcolloIdoncotIcpressurewasIncreasedwIthhetastarch,
6J
theseobservatIons
mustbebalancedagaInsttheapparentIncreaseInmortalItyIntraumatIcbraInInjury
patIentsmanagedwIthalbumInratherthan0.9salInedurIngIntensIvecare.
55
Clinical Implications of Hypertonic Fluid Administration
AnIdealalternatIvetoconventIonalcrystalloIdandcolloIdfluIdswouldbeInexpensIve,
wouldproducemInImalperIpheralorpulmonaryedema,wouldgeneratesustaIned
hemodynamIceffects,andwouldbeeffectIveevenIfadmInIsteredInsmallvolumes.
HypertonIc,hypernatremIcsolutIons,wIthorwIthoutaddedcolloId,appeartofulfIllsome
ofthesecrIterIa(Table1412).
CurrententhusIasmforhypertonIcresuscItatIonwasstImulatedbytheworkof7elascoet
al.,
64
whosuccessfullyusedsmallvolumes(6.0mL/kg)of7.5hypertonIcsalIneasthesole
resuscItatIvemeasureIndogsafterseverehemorrhage.HypertonIcsolutIonsexert
favorableeffectsoncerebralhemodynamIcs,InpartbecauseoftherecIprocalrelatIonshIp
P.J0J
betweenplasmaosmolalItyandbraInwater.
59
CPIncreaseddurIngresuscItatIonfrom
hemorrhagIcshockwIthlactatedFIngersolutIonbutremaInedunchangedIf7.5salInewas
InfusedInasuffIcIentvolumetocomparablyImprovesystemIchemodynamIcs.
65
However,
ImprovementsInCPgraduallyarelost.0elayedIncreasesInCPwerereportedafter
hypertonIcresuscItatIonfromhypovolemIcshockaccompanIedbyanIntracranIalmass
lesIon.
66
naddItIon,systemIchemodynamIcImprovementproducedbyhypertonIc
resuscItatIonIsshortlIved.
65
StrategIestoprolongthetherapeutIceffectsbeyondJ0to60
mInutesIncludecontInuedInfusIonofhypertonIcsalIne,subsequentInfusIonofbloodor
conventIonalfluIds,oraddItIonofcolloIdtohypertonIcresuscItatIon.
Table 14-11 Claimed Advantages and Disadvantages of Colloid Versus
Crystalloid Intravenous Fluids
SOLUTION ADVANTAGES DISADVANTAGES
ColloId
SmallerInfusedvolume Creatercost
ProlongedIncreaseIn
plasmavolume
Coagulopathy(dextranHES)
LessperIpheraledema
Pulmonaryedema(capIllaryleak
states)
0ecreasedCFF
DsmotIcdIuresIs(lowmolecular
weIghtdextran)
CreaterduratIonofexcessIvevolume
expansIon
CrystalloId
Lowercost
TransIentIncreaseInIntravascular
volume
CreaterurInaryflow TransIenthemodynamIcImprovement
nterstItIalfluId
replacement
PerIpheraledema(proteIndIlutIon)
Pulmonaryedema(proteIndIlutIon
plushIghPADP)
HES,hydroxyethylstarch;CFF,glomerularfIltratIonrate;PADP,pulmonary
arterIalocclusIonpressure.
Table 14-12 Hypertonic Resuscitation Fluids: Advantages and
Disadvantages
SOLUTION ADVANTAGES DISADVANTAGES
HypertonIccrystalloId
nexpensIve HypertonIcIty
PromotesurInary
flow
Subdural
hemorrhage
SmallInItIal
volume
TransIenteffect
ArterIolardIlatIon
PotentIalrebound
IntracranIal
hypertensIon
Feduced
perIpheraledema
LowerIntracranIal
pressure
HypertonIccrystalloIdpluscolloId(In
comparIsontohypertonIccrystalloId
alone)
SustaIned
hemodynamIc
response
Feduced
subsequent
volume
requIrements
Addedexpense
DsmotIcdIuresIs
HypertonIcIty
FromPrough0S,JohnstonWE:FluIdresuscItatIonInseptIcshock:NosolutIonyet.
AnesthAnalg1989;69:699704,wIthpermIssIon.
0espIteconcernsaboutcentralnervoussystemdysfunctIonduetohypertonIcItyand
hypernatremIaassocIatedwIthhypertonIcsalIne,acuteIncreasesInserumsodIumto155
to160mEq/LproducednoapparentharmInhumansresuscItatedwIthhypertonIcsalIne.
67
CentralpontInemyelInolysIs,whIchfollowsrapIdcorrectIonofsevere,chronIc
hyponatremIa,hasnotbeenobservedInclInIcaltrIalsofhypertonIcresuscItatIon.0espIte
theoretIcalconsIderatIonsfavorIngtheuseofhypertonIcsalIneInresuscItatIonofpatIents
wIthtraumatIcbraInInjury,arecentrandomIzedtrIalfaIledtodemonstratean
ImprovementInoutcome.
68
WIllclInIcIansroutInelyusehypertonIcorcombInatIonhypertonIc/hyperoncotIcfluIdsfor
resuscItatIonInthefuture:PendIngfurtherpreclInIcalwork,thetheoretIcaladvantagesof
suchfluIdsappearmostattractIveIntheacuteresuscItatIonofhypovolemIcpatIentswho
havedecreasedIntracranIalcomplIance.
69
Fluid Status: Assessment and Monitoring
FormostsurgIcalpatIents,conventIonalclInIcalassessmentoftheadequacyof
IntravascularvolumeIsapproprIate.ForhIghrIskpatIents,goaldIrectedhemodynamIc
managementmaybesuperIor.
Conventional Clinical Assessment
ClInIcalquantIfIcatIonofbloodvolumeandEC7begInswIthrecognItIonofdefIcIt
generatIngsettIngssuchasbowelobstructIon,preoperatIvebowelpreparatIon,chronIc
dIuretIcuse,sepsIs,burns,andtrauma.PhysIcalsIgnsthatsuggesthypovolemIaInclude
olIgurIa,supInehypotensIon,andaposItIvetIlttest.DlIgurIaImplIeshypovolemIa,
althoughhypovolemIcpatIentsmaybenonolIgurIcandnormovolemIcpatIentsmaybe
olIgurIcbecauseofrenalfaIlureorstressInducedendocrIneresponses.
70
SupIne
hypotensIonImplIesabloodvolumedefIcItexceedIngJ0,althougharterIalbloodpressure
wIthInthenormalrangecouldrepresentrelatIvehypotensIonInanelderlyorchronIcally
hypertensIvepatIent.
nthetIlttest,aposItIveresponseIsdefInedasanIncreaseInheartrate20beatsper
mInuteandadecreaseInsystolIcbloodpressure20mmHgwhenthesubjectassumesthe
uprIghtposItIon.However,young,healthysubjectscanwIthstandacutelossof20ofblood
volumewhIleexhIbItIngonlyposturaltachycardIaandvarIableposturalhypotensIon.n
contrast,orthostasIsmayoccurIn20toJ0ofelderlypatIentsdespItenormalblood
volume.nvolunteers,wIthdrawalof500mLofblood
71
wasassocIatedwIthagreater
IncreaseInheartrateonstandIngthanbeforebloodwIthdrawal,butwIthnosIgnIfIcant
dIfferenceIntheresponseofbloodpressureorcardIacIndex.
LaboratoryevIdencethatsuggestshypovolemIaorEC7depletIonIncludesazotemIa,low
urInarysodIum,metabolIcalkalosIs(IfhypovolemIaIsmIld),andmetabolIcacIdosIs(If
hypovolemIaIssevere).HematocrItIsvIrtuallyunchangedbyacutehemorrhageuntIlfluIds
areadmInIsteredoruntIlfluIdshIftsfromtheInterstItIaltotheIntravascularspace.8UN,
normally8.0to20mg/dL,IsIncreasedbyhypovolemIa,hIghproteInIntake,
gastroIntestInalbleedIng,oracceleratedcatabolIsmanddecreasedbyseverehepatIc
dysfunctIon.SerumcreatInIne(SCr),aproductofmusclecatabolIsm,maybemIsleadIngly
lowInelderlyadults,females,anddebIlItatedormalnourIshedpatIents.ncontrast,In
muscularoracutelycatabolIcpatIents,SCrmayexceedthenormalrange(0.5to1.5
mg/dL)becauseofgreatermuscleproteInmetabolIsm.AratIoof8UNtoSCrexceedIngthe
normalrange(10to20)suggestsdehydratIon.nprerenalolIgurIa,enhancedsodIum
reabsorptIonshouldreduceurInary[Na
+
]to20mEq/LandenhancedwaterreabsorptIon
shouldIncreaseurInaryconcentratIon(I.e.,urInaryosmolalIty400,urIne/plasma
creatInIneratIo40:1).However,thesensItIvItyandspecIfIcItyofmeasurementsofurInary
varIablesmaybemIsleadIng.AlthoughhypovolemIadoesnotgeneratemetabolIcalkalosIs,
EC7depletIonIsapotentstImulusforthemaIntenanceofmetabolIcalkalosIs.Severe
hypovolemIamayresultInsystemIchypoperfusIonandlactIcacIdosIs.
Intraoperative Clinical Assessment
7IsualestImatIon,thesImplesttechnIqueforquantIfyIngIntraoperatIvebloodloss,assesses
theamountofbloodabsorbedbygauzesquaresandlaparotomypadsandaddsanestImate
of
P.J04
bloodaccumulatIononthefloorandsurgIcaldrapesandInsuctIoncontaIners.8oth
surgeonsandanesthesIaprovIderstendtounderestImatelosses.
AssessmentoftheadequacyofIntraoperatIvefluIdresuscItatIonIntegratesmultIple
clInIcalvarIables,IncludIngheartrate,bloodpressure,urInaryoutput,arterIal
oxygenatIon,andpH.TachycardIaIsanInsensItIve,nonspecIfIcIndIcatorofhypovolemIa.
npatIentsreceIvIngpotentInhalatIonalagents,maIntenanceofasatIsfactoryblood
pressureImplIesadequateIntravascularvolume.PreservatIonofbloodpressure,
accompanIedbyaC7Pof6to12mmHg,morestronglysuggestsadequatereplacement.
0urIngprofoundhypovolemIa,IndIrectmeasurementsofbloodpressuremaysIgnIfIcantly
underestImatetruebloodpressure.npatIentsundergoIngextensIveprocedures,dIrect
arterIalpressuremeasurementsaremoreaccuratethanIndIrecttechnIquesandprovIde
convenIentaccessforobtaInIngarterIalbloodsamples.AnaddItIonaladvantageofdIrect
arterIalpressuremonItorIngmayberecognItIonofIncreasedsystolIcbloodpressure
varIatIonaccompanyIngposItIvepressureventIlatIonInthepresenceofhypovolemIa.
72,7J
UrInaryoutputusuallydeclInesprecIpItouslydurIngmoderatetoseverehypovolemIa.
Therefore,IntheabsenceofglycosurIaordIuretIcadmInIstratIon,aurInaryoutputof0.5
to1.0mL/kghrdurInganesthesIasuggestsadequaterenalperfusIon.ArterIalpHmay
decreaseonlywhentIssuehypoperfusIonbecomessevere.CardIacoutputcanbenormal
despIteseverelyreducedregIonalbloodflow.|IxedvenoushemoglobIndesaturatIon,a
specIfIcIndIcatorofpoorsystemIcperfusIon,reflectsaverageperfusIonInmultIpleorgans
andcannotsupplantregIonalmonItorssuchasurInaryoutput.
ApromIsIngtechnIqueforassessIngtheadequacyofcardIacpreloaddurInghIghrIsk
surgIcalproceduresIstheuseofesophageal0opplerthatmeasuresbloodflowInthe
descendIngthoracIcaortaandthatalsomeasurestheduratIonofaortIcsystole,whIch,If
correctedforheartrate,correlateswIthleftventrIcularpreload.
74,81
ngeneral,a
correctedflowtIme0.J5secondsuggeststhatvolumeexpansIonshouldImprovecardIac
output,whIleacorrectedflowtIme0.40secondsuggeststhatfurthervolumeexpansIon
wIllbeIneffectIve.
Oxygen Delivery as a Goal of Management
NoIntraoperatIvemonItorIssuffIcIentlysensItIveorspecIfIctodetecthypoperfusIonInall
patIents.DnekeyvarIablethathasbeenassocIatedwIthImprovedoutcomeInhIghrIsk
surgIcalpatIentsandcrItIcallyIllpatIentsIsasystemIcoxygendelIvery(0o
2
)600mL
D
2
/m
2
mIn(equIvalenttoacardIacIndex[C]ofJ.0L/m
2
mIn,a[Hgb]of14g/dL,and98
oxyhemoglobInsaturatIon).Atpresent,avaIlabledataareconsIstentwIthtwoInferences.
FIrst,thereIsnoapparentbenefItforpatIentsotherthansurgIcalpatIents
75
andpatIents
undergoIngInItIalresuscItatIonfromseptIcshockIntheemergencydepartment.
76
n
surgIcalpatIents,earlyInItIatIonofgoaldIrectedresuscItatIonIsassocIatedwIthbetter
outcomethandelayedInItIatIon.
77
Second,outcomemaybestronglyInfluencedbythe
choIceofmethodstoIncreaseoxygendelIvery,thatIs,thechoIceoffluIdadmInIstratIonor
varIousInotropIcagents.Loboetal.
78
randomIzed50hIghrIskpatIents,defInedaselderly
patIentswIthcoexIstentpathologIeswhowereundergoIngmajorelectIvesurgery,togoal
dIrectedhemodynamIctherapyeItherwIthfluIdsaloneorwIthfluIdsplusdobutamIne.
HemodynamIcgoalsIntraoperatIvelyandforthefIrst24hourspostoperatIvelyconsIstedof
0D
2
600mLD
2
/m
2
mIn.PostoperatIvecardIovascularcomplIcatIonsoccurredsIgnIfIcantly
morefrequentlyInthegroupreceIvIngfluIdsalone(1J/25,52,vs.4/25,16;relatIverIsk,
J.25;95C,1.228.60;p0.05)andmortalItywasgreater,butnotstatIstIcally
sIgnIfIcantlygreaterInthIssmallserIes.ncreasedfluIdgIvenaspartofgoalorIented
resuscItatIonhasbeenassocIatedwIthanIncreasedIncIdenceofabdomInalcompartment
syndromeIntraumapatIents.
79
WIlsonetal.
80
randomIzed1J8patIentsundergoIngmajor
electIvesurgeryIntothreegroups.DnegroupreceIvedroutIneperIoperatIvecare;one
receIvedfluIdanddopexamInepreoperatIvely,IntraoperatIvely,andpostoperatIvelyto
maIntaInoxygendelIvery600mLD
2
/m
2
mIn;andthethIrdreceIvedfluIdplusepInephrIne
preoperatIvely,IntraoperatIvely,andpostoperatIvelytoachIevethesameendpoInts.n
thetwogroupsInwhIchoxygendelIverywassupported,onlyJof92dIed,comparedwIth8
of46controlpatIents.However,thecomplIcatIonratewassIgnIfIcantlylowerInthe
dopexamInegroupthanIntheepInephrInegroup.
Fecently,severalstudIeshavereportedImprovedoutcomebasedonadjustmentof
perIoperatIvefluIdsthroughtheuseofanesophageal0opplermonItor.
81
UsIngthe
esophageal0opplertoguIdeadmInIstratIonofcolloIdboluses,7ennetal.
49
andCanet
al.
50
havereportedshortenedlengthofhospItalstayafterhIpsurgeryandmajorsurgery,
respectIvely.Dfnote,HorowItzandKumar
82
speculatedthattheInfusIonofcolloIdrather
thanthemonItordrIvenalgorIthmwasresponsIblefortheImprovedresults.
Electrolytes
Sodium
Physiologic Role
SodIum,theprIncIpalextracellularcatIonandsolute,IsessentIalforgeneratIonofactIon
potentIalsInneurologIcandcardIactIssue.0Isorders(pathologIcIncreasesordecreases)of
total body sodiumareassocIatedwIthcorrespondIngIncreasesordecreasesofEC7andP7.
0IsordersofsodIumconcentration,thatIs,hyponatremIaandhypernatremIa,usuallyresult
fromrelatIveexcessesordefIcIts,respectIvely,ofwater.FegulatIonoftotalbodysodIum
and[Na
+
]IsaccomplIshedprImarIlybytheendocrIneandrenalsystems(Table141J).
SecretIonofaldosteroneandANPcontroltotal body sodium.A0H,whIchIssecretedIn
responsetoIncreasedosmolalItyordecreasedbloodpressure,prImarIlyregulates[Na
+
].
Therefore,prImaryhyperaldosteronIsmIsassocIatedwIthhypervolemIaandwIth
hypertensIon,butnotwIthabnormal[Na
+
].
8J,84
Hyponatremia
HyponatremIa,defInedas[Na
+
]1J0mEq/L,IsthemostcommonelectrolytedIsturbance
InhospItalIzedpatIents.nthemajorItyofhyponatremIcpatIents,totalbodysodIumIs
normalorIncreased.ThemostcommonclInIcalscenarIosassocIatedwIthhyponatremIa
IncludethepostoperatIvestate,acuteIntracranIaldIsease,malIgnantdIsease,
medIcatIons,andacutepulmonarydIsease.HyponatremIaIsassocIatedwIthIncreased
mortalIty,bothasadIrecteffectofhyponatremIaandbecauseoftheassocIatIonbetween
hyponatremIaandseveresystemIcdIsease.
ThesIgnsandsymptomsofhyponatremIadependonboththerateandseverItyofthe
decreaseInplasma[Na
+
].SymptomsthatcanaccompanyseverehyponatremIa([Na
+
]120
mEq/L)IncludelossofappetIte,nausea,vomItIng,cramps,weakness,alteredlevelof
conscIousness,coma,andseIzures.
AcutecentralnervoussystemmanIfestatIonsofhyponatremIaresultfrombraIn
overhydratIon.8ecausethebloodbraInbarrIerIspoorlypermeabletosodIumbutfreely
permeabletowater,arapIddecreaseInplasma[Na
+
]promptlyIncreasesboth
extracellularandIntracellularbraIn
P.J05
water.8ecausethebraInrapIdlycompensatesforchangesInosmolalIty,acute
hyponatremIaproducesmoreseveresymptomsthanchronIchyponatremIa.Thesymptoms
ofchronIchyponatremIaprobablyrelatetodepletIonofbraInelectrolytes.DncebraIn
volumehascompensatedforhyponatremIa,rapIdIncreasesIn[Na
+
]mayleadtoabrupt
braIndehydratIon.
Table 14-13 Regulation of Total Body Electrolyte Mass and Plasma
Concentrations
ELECTROLYTE REGULATED BY
SodIum
TotalbodysodIumregulatedbyaldosterone,ANP,[Na
+
]alteredby
A0H
PotassIum
TotalbodypotassIumregulatedbyaldosterone,IntrInsIcrenal
mechanIsms;[K
+
]regulatedbyepInephrIne,InsulIn
CalcIum 8othtotalbodycalcIumand[Ca
++
]regulatedbyPTH,vItamIn0
Phosphate
8othtotalbodyphosphateand[HPD
4
]regulatedprImarIlybyrenal
mechanIsmswIthamInorcontrIbutIonfromPTH
|agnesIum
8othtotalbodymagnesIumand[|g
++
]regulatedprImarIlybyrenal
mechanIsmswIthamInorcontrIbutIonfromPTHandvItamIn0
ANP,atrIalnatrIuretIcpeptIde;[Na
+
],sodIumconcentratIon;A0H,antIdIuretIc
hormone;PTH,parathyroIdhormone.
nhyponatremIcpatIents,serumosmolalItymaybenormal,hIghorlow(FIg.146).
HyponatremIawIthanormalorhIghserumosmolalItyresultsfromthepresenceofa
nonsodIumsolute,suchasglucoseormannItol,whIchholdswaterwIthIntheextracellular
spaceandresultsIndIlutIonalhyponatremIa.ThepresenceofanonsodIumsolutemaybe
InferredIfmeasuredosmolalItyexceedscalculatedosmolalItyby10mDsm/kg.For
example,plasma[Na
+
]decreasesapproxImately2.4mEq/Lforeach100mg/dLrIseIn
glucoseconcentratIonwIthperhapsevengreaterdecreasesasglucoseconcentratIon400
mg/dL.
85
nanesthesIapractIce,acommoncauseofhyponatremIaassocIatedwItha
normalosmolalItyIstheabsorptIonoflargevolumesofsodIumfreeIrrIgatIngsolutIons
(contaInIngmannItol,glycerIne,orsorbItolasthesolute)durIngtransurethralresectIonof
theprostate.
86
NeurologIcsymptomsaremInImalIfmannItolIsusedbecausetheagent
doesnotcrossthebloodbraInbarrIerandIsexcretedwIthwaterIntheurIne.ncontrast,
asglycIneorsorbItolIsmetabolIzed,hyposmolalItywIllgraduallydevelopandcerebral
edemamayappearasalatecomplIcatIon,thatIs,hypoosmolalItyIsmoreImportantIn
generatIngsymptomsthanhyponatremIaperse.
86
HyponatremIawIthanormalorelevated
serumosmolalItyalsomayaccompanyrenalInsuffIcIency.8UN,IncludedInthecalculatIon
oftotalosmolalIty,dIstrIbutesthroughoutbothEC7andC7.CalculatIonofeffective
osmolalIty(2[Na
+
]+glucose/18)excludesthecontrIbutIonofureatotonIcItyand
demonstratestruehypotonIcIty.
HyponatremIawIthlowserumosmolalItymaybeassocIatedwIthahIgh,low,ornormal
totalbodysodIumandP7.Therefore,hyponatremIawIthhyposmolalIty(FIg.146)Is
evaluatedbyassessIngtotalbodysodIumcontent,8UN,SCr,urInaryosmolalIty,and
urInary[Na
+
].HyponatremIawIthIncreasedtotalbodysodIumIscharacterIstIcof
edematousstates,thatIs,congestIveheartfaIlure,cIrrhosIs,nephrosIs,andrenalfaIlure.
AquaporIn2,thevasopressInregulatedwaterchannel,IsupregulatedInexperImental
congestIveheartfaIlure,
87
andcIrrhosIs
88
anddecreasedbychronIcvasopressIn
stImulatIon.
89
npatIentswIthrenalInsuffIcIency,reducedurInarydIlutIngcapacItycan
leadtohyponatremIaIfexcessfreewaterIsgIven.ngeneral,dIseasesthatprompt
hospItalIzatIongeneratenumerousstImulIforsecretIonofargInInevasopressIn(A7P),
whIchhaspromptedsomeexpertstosuggestthathyponatremIcfluIdsrarelybegIvento
hospItalIzedpatIents.
90
TheunderlyIngmechanIsmofhypovolemIchyponatremIaIssecretIonofA7Psynonymous
wIthA0HInresponsetovolumecontractIonInassocIatIonwIthongoIngoralorIntravenous
IntakeofhypotonIcfluId.
91
AngIotensInalsodecreasesrenalfreewaterclearance.
ThIazIdedIuretIcs,unlIkeloopdIuretIcs,promotehypovolemIchyponatremIabyInterferIng
wIthurInarydIlutIonInthedIstaltubule.
91
HypovolemIchyponatremIaassocIatedwItha
urInary[Na
+
]20mmol/LsuggestsmIneralocortIcoIddefIcIency,especIallyIfserum[K
+
],
8UN,andSCrareIncreased.
91
ThecerebralsaltwastIngsyndromeIsanoftensevere,symptomatIcsaltlosIngdIathesIs
thatappearstobemedIatedbybraInnatrIuretIcpeptIdeandInwhIch,Incontrasttothe
syndromeofInapproprIateantIdIuretIchormonesecretIon(SA0H),secretIonofargInIne
vasopressInIsappropriate
91
;patIentsatrIskforthecerebralsaltwastIngsyndromeInclude
thosewIthcerebrallesIonsduetotrauma,subarachnoIdhemorrhage,tumors,and
InfectIon.npatIentsaftersubarachnoIdhemorrhage,admInIstratIonofhydrocortIsone
1,200mg/daypreventedthecerebralsaltwastIngsyndrome.
92
EuvolemIchyponatremIamostcommonlyIsassocIatedwIthnonosmotIcvasopressIn
secretIon,forexample,glucocortIcoIddefIcIency,hypothyroIdIsm,thIazIdeInduced
hyponatremIa,SA0H,andtheresetosmostatsyndrome.TotalbodysodIumandEC7are
relatIvelynormalandedemaIsrarelyevIdent.SA0HmaybeIdIopathIcbutalsoIs
assocIatedwIthdIseasesofthecentralnervoussystemandwIthpulmonarydIsease(Table
1414).EuvolemIchyponatremIaIsusuallyassocIatedwIthexogenousA7PadmInIstratIon,
pharmacologIcpotentIatIonofA7PactIon,drugsthatmImIctheactIonofA7PIntherenal
tubules,orexcessIveectopIcA7PsecretIon.TIssuesfromsomesmallcelllungcancers,
duodenalcancers,andpancreatIccancersIncreaseA7PproductIonInresponsetoosmotIc
stImulatIon.
91
Atleast4.0ofpostoperatIvepatIentsdevelopplasma[Na
+
]1J0mEq/L.Although
neurologIcmanIfestatIonsusuallydonotaccompanypostoperatIvehyponatremIa,sIgnsof
hypervolemIaareoccasIonallypresent.|uchlessfrequently,postoperatIvehyponatremIa
IsaccompanIedbymentalstatuschanges,seIzuresandtranstentorIalhernIaton,
9J
attrIbutableInparttoIntravenousadmInIstratIonofhypotonIcfluIds,secretIonofA7P,and
otherfactors,IncludIngdrugsandalteredrenalfunctIon,thatInfluenceperIoperatIve
waterbalance.
P.J06
Womenappeartobemorevulnerablethanmenandpremenopausalwomenappeartobe
morevulnerablethanpostmenopausalwomentobraIndamagesecondarytopostoperatIve
hyponatremIa.
94
PostoperatIvehyponatremIacandevelopevenwIthInfusIonofIsotonIc
fluIdsIfA7PIspersIstentlyIncreased.Twentyfourhoursaftersurgery,meanplasma[Na
+
]
In22women(meanage,42years)undergoInguncomplIcatedgynecologIcsurgeryhad
decreasedfrom1401to1J60.5mEq/L.
95
AlthoughthepatIentsretaInedsodIum
perIoperatIvely,theyretaInedproportIonatelymorewater(anaverageof1.1Lof
electrolytefreewater).CarefulpostoperatIveattentIontofluIdandelectrolytebalance
maymInImIzetheoccurrenceofsymptomatIchyponatremIa.
Figure 14-6.AlgorIthmbywhIchhyponatremIacanbeevaluated.SA0H,syndromeof
InapproprIateantIdIuretIchormonesecretIon;F/D,ruleout;CHF,congestIveheart
faIlure.
fboth[Na
+
]andmeasuredosmolalItyarebelowthenormalrange,hyponatremIaIsfurther
evaluatedbyfIrstassessIngvolumestatususIngphysIcalfIndIngsandlaboratorydata.n
hypovolemIcpatIentsoredematouspatIents,theratIoof8UNtoSCrshouldbe20:1.
UrInary[Na
+
]Isgenerally15mEq/LInedematousstatesandvolumedepletIonand20
mEq/LInhyponatremIasecondarytorenalsaltwastIngorrenalfaIlurewIthwater
retentIon.
ThecrIterIaforthedIagnosIsofSA0HarelIstedInTable1415.UrInary[Na
+
]shouldbe20
mEq/LunlessfluIdshavebeenrestrIcted.ArIeff
96
hasarguedthatthedIagnosIsofSA0H
maybeInaccuratelyapplIedtofunctIonallyhypovolemIcpostoperatIvepatIents,Inwhom,
bydefInItIon,A7PsecretIonwouldbeapproprIate.
TreatmentofhyponatremIaassocIatedwIthanormalorhIghserumosmolalItyrequIres
reductIonoftheelevatedconcentratIonsoftheresponsIblesolute,forexample,ureaor
mannItol.UremIcpatIentsaretreatedbyfreewaterrestrIctIonordIalysIs.Treatmentof
edematous(hypervolemIc)patIentsnecessItatesrestrIctIonofbothsodIumandwater,
usuallyaccompanIedbyeffortstoImprovecardIacoutputandrenalperfusIonandtouse
dIuretIcstoInhIbItsodIumreabsorptIon(FIg.147).nhypovolemIc,hyponatremIcpatIents,
bloodvolumemustberestored,usuallybyInfusIonof0.9salIne,andexcessIvesodIum
lossesmustbecurtaIled.CorrectIonofhypovolemIausuallyresultsInremovalofthe
stImulusforA7Prelease,accompanIedbyarapIdwaterdIuresIs.
ThecornerstoneofSA0HmanagementIsfreewaterrestrIctIonandelImInatIonof
precIpItatIngcauses.Water
P.J07
restrIctIon,suffIcIenttodecreaseT8Wby0.5to1.0Lperday,decreasesEC7evenIf
excessIveA7PsecretIoncontInues.TheresultantreductIonInCFFenhancesproxImal
tubularreabsorptIonofsaltandwater,therebydecreasIngfreewatergeneratIon,and
stImulatesaldosteronesecretIon.Aslongasfreewaterlosses(I.e.,renal,skIn,
gastroIntestInal)exceedfreewaterIntake,plasma[Na
+
]wIllIncrease.0urIngtreatmentof
hyponatremIa,IncreasesInplasma[Na
+
]aredetermInedbothbythecomposItIonofthe
InfusedfluIdandbytherateofrenalfreewaterexcretIon.
97
FreewaterexcretIoncanbe
IncreasedbyadmInIsterIngfurosemIde.
Table 14-14 Common Associations with the Syndrome of Inappropriate
Antidiuretic Hormone Secretion
Neoplastic disease
CarcInoma(e.g.,lung)
Thymoma
|esothelIoma
Lymphoma,leukemIa
EwIngsarcoma
CarcInoId
8ronchIaladenoma
Neurologic disorders
HeadInjury,neurosurgery
8raInabscessortumor
|enIngItIs,encephalItIs
Cerebralhemorrhage
CuIllaIn8arrsyndrome
Hydrocephalus
Alcohol withdrawal
PerIpheralneuropathy
SeIzures
Subduralhematoma
Chest disorders
PneumonIa
TuberculosIs
Empyema
CystIcfIbrosIs
Pneumothorax
AspergIllosIs
Drugs
Sulphonylureas
DpIates
ThIazIdesandloopdIuretIcs
0opamIneantagonIsts
AntIconvulsants
TrIcyclIcantIdepressants
SSFs
Miscellaneous
dIopathIc
PsychosIs
PorphyrIa
SSF,selectIveserotonInreuptakeInhIbItor.
|odIfIedfrom8allSC:7asopressInanddIsordersofwaterbalance:ThephysIology
andpathophysIologyofvasopressIn.AnnClIn8Iochem2007;44:4174J1,wIth
permIssIon.
Fecently,vasopressInreceptorblockIngagentshavebeendevelopedthatInhIbIttheactIon
ofA7PontherenalcollectIngducts.
98,99,100,101
nphaseJclInIcaltrIals,theseagentshave
proventobesafeandeffIcacIousInhyponatremIcpatIents,appearIngtohavepartIcular
valueInpatIentswIthhypervolemIchyponatremIasecondarytocongestIveheartfaIlure.
98
ConIvaptan,whIchInhIbItsboth7
1
and7
2
receptors,hasbeenapprovedfortreatmentof
normovolemIcandhypervolemIchyponatremIcpatIents.
100
However,potentIaldecreases
InbloodpressureassocIatedwIth7
1
receptorblockadenecessItatecautIonInpatIents
wIthborderlInelowbloodpressure.
101
Tolvaptan,aselectIve7
2
receptorantagonIst,also
hasproveneffectIveInclInIcaltrIals.
102
WIthInafewyears,vaptanswIlllIkelybecomea
maInstayoftherapyfornormovolemIcandhypervolemIchypernatremIa.
101
Table 14-15 Diagnostic Criteria for Syndrome of Inappropriate Antidiuretic
Hormone Secretion
HyponatremIawIthapproprIatelylowplasmaosmolalIty
UrInaryosmolalItygreaterthanplasmaosmolalIty
FenalsodIumexcretIon20mmol/L
AbsenceofhypotensIon,hypovolemIa,andedematousstates
NormalrenalandadrenalfunctIon
AbsenceofdrugsthatdIrectlyInfluencerenalwaterandsodIumhandlIng
|odIfIedfrom8allSC:7asopressInanddIsordersofwaterbalance:ThephysIology
andpathophysIologyofvasopressIn.AnnClIn8Iochem2007;44:4174J1,wIth
permIssIon.
NeurologIcsymptomsorprofoundhyponatremIa([Na
+
]115to120mEq/L)requIresmore
aggressIvetherapy.HypertonIc(J)salIneIsmostclearlyIndIcatedInpatIentswhohave
seIzuresorpatIentswhoacutelydevelopsymptomsofwaterIntoxIcatIonsecondaryto
IntravenousfluIdadmInIstratIon.nsuchcases,JsalInemaybeadmInIsteredatarateof
1to2mL/kg/hr,toIncreaseplasma[Na
+
]by1to2mEq/L/hr;however,thIstreatment
shouldnotcontInueformorethanafewhours.ThreepercentsalInemayonlytransIently
Increaseplasma[Na
+
]becauseEC7expansIonresultsInIncreasedurInarysodIumexcretIon.
ntravenousfurosemIde,combInedwIthquantItatIvereplacementofurInarysodIumlosses
wIth0.9orJ.0salIne,canrapIdlyIncreaseplasma[Na
+
],InpartbyIncreasIngfreewater
clearance.
TherateoftreatmentofhyponatremIacontInuestogeneratecontroversy,extendIngfrom
toofast,toosoontotooslow,toolate.AlthoughdelayedcorrectIonmayresultIn
neurologIcInjury,InapproprIatelyrapIdcorrectIonmayresultInabruptbraIndehydratIon
(FIg.148)orpermanentneurologIcsequelae(I.e.,osmotIcdemyelInatIonsyndrome),
10J
cerebralhemorrhage,orcongestIveheartfaIlure.ThesymptomsoftheosmotIc
demyelInatIonsyndromevaryfrommIld(transIentbehavIoraldIsturbancesorseIzures)to
severe(IncludIngpseudobulbarpalsyandquadrIparesIs).
P.J08
P.J09
TheprIncIpaldetermInantsofneurologIcInjuryappeartobethemagnItudeandchronIcIty
ofhyponatremIaandtherateofcorrectIon.TheosmotIcdemyelInatIonsyndromeIsmore
lIkelywhenhyponatremIahaspersIsted48hours.|ostpatIentsInwhomtheosmotIc
demyelInatIonsyndromeIsfatalhaveundergonecorrectIonofplasma[Na
+
]ofmorethan
20mEq/L/day.DtherrIskfactorsforthedevelopmentoftheosmotIcdemyelInatIon
syndromeIncludealcoholIsm,poornutrItIonalstatus,lIverdIsease,burns,and
hypokalemIa.
Figure 14-7.HyponatremIaIstreatedaccordIngtotheetIologyofthedIsturbance,the
levelofserumosmolalIty,andaclInIcalestImatIonoftotalbodysodIum.
Figure 14-8.8raInwaterandsoluteInconcentratIonsInhyponatremIa.fnormal
plasmasodIum(Na;A)suddenlydecreased,theIncreaseInbraInwatertheoretIcally
wouldbeproportIonaltothedecreaseInplasmaNa(B).However,becauseofadaptIve
lossofcerebralIntracellularsolute,cerebraledemaIsmInImIzedInchronIc
hyponatremIa(C).DnceadaptatIonhasoccurred,arapIdreturnofplasmaNa
concentratIontowardanormallevelresultsInbraIndehydratIon(D).(FromSternsFH:
7IgnettesInclInIcalpathophysIology.NeurologIcaldeterIoratIonfollowIngtreatment
forhyponatremIa.AmJKIdney0Is1989;X:4J44J7,wIthpermIssIon.)
TheclInIcIanfacesformIdabledIffIcultIesInpredIctIngtherateatwhIchplasma[Na
+
]wIll
IncreasebecauseIncreasesInplasma[Na
+
]aredetermInedbothbythecomposItIonofthe
InfusedfluIdandbytherateofrenalfreewaterexcretIon.TheexpectedchangeInplasma
[Na
+
]resultIngfrom1LofselectedInfusatecanbeestImatedusIngthefollowIng
equatIon
104
:
where[Na
+
]
s
=thechangeInthepatIent'sserum[Na
+
],[Na
+
]
Inf
=[Na
+
]oftheInfusate,
[Na
+
]
s
=thepatIent'sserum[Na
+
],T8W=thepatIent'sestImatedtotalbodywaterInlIters,
and1=afactoraddedtotakeIntoaccountthevolumeofInfusate.
TreatmentshouldbeInterruptedorslowedwhensymptomsImprove.Frequent
determInatIonsof[Na
+
]areImportanttopreventcorrectIonatarate1to2mEq/LInany
1hourand8mEq/LIn24hours.
105
nItIally,plasma[Na
+
]maybeIncreasedby1to2
mEq/L/hr;however,therateofcorrectIonshouldthenbeslowedtoavoIdexcessIvely
rapIdcorrectIon.HypernatremIashouldbeavoIded.Dnceplasma[Na
+
]exceeds120to125
mEq/L,waterrestrIctIonaloneIsusuallysuffIcIenttonormalIze[Na
+
].Asacute
hyponatremIaIscorrected,centralnervoussystemsIgnsandsymptomsusuallyImprove
wIthIn24hours,although96hoursmaybenecessaryformaxImalrecovery.
ForpatIentswhorequIrelongtermpharmacologIctherapyofhyponatremIa,
demeclocyclIneIscurrentlythedrugofchoIce.
106
AlthoughbettertoleratedthanlIthIum,
demeclocyclInemayInducenephrotoxIcIty,apartIcularconcernInpatIentswIthhepatIc
dysfunctIon.HemodIalysIsIsoccasIonallynecessaryInseverelyhyponatremIcpatIentswho
cannotbeadequatelymanagedwIthdrugsorhypertonIcsalIne.DncehyponatremIahas
Improved,carefulfluIdrestrIctIonIsnecessarytoavoIdrecurrenceofhyponatremIa.nthe
future,oralreceptorantagonIstsmaybeusedtotreatchronIchyponatremIa.
Figure 14-9.SeverehypernatremIaIsevaluatedbyfIrstseparatIngpatIentsInto
hypovolemIc,euvolemIc,andhypervolemIcgroupsbasedonassessmentof
extracellularvolume(EC7).Next,potentIaletIologIcfactorsaredIagnostIcally
assessed.[Na
+
],serumsodIumconcentratIon;U
Na
,urInarysodIumconcentratIon;U
DSm
,
urInaryosmolalIty.
Hypernatremia
HypernatremIa([Na
+
]150mEq/L)IndIcatesanabsoluteorrelatIvewaterdefIcIt.
Normally,slIghtIncreasesIntonIcItyor[Na
+
]stImulatethIrstandA7PsecretIon.
Therefore,severe,persIstenthypernatremIaoccursonlyInpatIentswhocannotrespondto
thIrstbyvoluntaryIngestIonoffluId,thatIs,obtundedpatIents,anesthetIzedpatIents,and
Infants.
HypernatremIaproducesneurologIcsymptoms(IncludIngstupor,coma,andseIzures),
hypovolemIa,renalInsuffIcIency(occasIonallyprogressIngtorenalfaIlure),anddecreased
urInaryconcentratIngabIlIty.8ecausehypernatremIafrequentlyresultsfromdIabetes
InsIpIdus(0)orosmotIcallyInducedlossesofsodIumandwater,manypatIentsare
hypovolemIcorbearthestIgmataofrenaldIsease.PostoperatIveneurosurgIcalpatIents
whohaveundergonepItuItarysurgeryareatpartIcularrIskofdevelopIngtransIentor
prolonged0.PolyurIamaybepresentforonlyafewdayswIthInthefIrstweekofsurgery,
maybepermanent,ormaydemonstrateatrIphasIcsequence:early0,returnofurInary
concentratIngabIlIty,thenrecurrent0.
107
TheclInIcalconsequencesofhypernatremIaaremostserIousattheextremesofageand
whenhypernatremIadevelopsabruptly.CerIatrIcpatIentsareatIncreasedrIskof
hypernatremIabecauseofdecreasedrenalconcentratIngabIlItyanddecreasedthIrst.8raIn
shrInkagesecondarytorapIdlydevelopInghypernatremIamaydamagedelIcatecerebral
vessels,leadIngtosubduralhematoma,subcortIcalparenchymalhemorrhage,
subarachnoIdhemorrhage,andvenousthrombosIs.PolyurIamaycausebladderdIstentIon,
hydronephrosIs,andpermanentrenaldamage.AlthoughthemortalItyofhypernatremIaIs
40to55,ItIsunclearwhetherhypernatremIacontrIbutestomortalItyorIssImplya
markerofsevereassocIateddIsease.
SurprIsIngly,Ifplasma[Na
+
]IsInItIallynormal,moderateacuteIncreasesInplasma[Na
+
]
donotappeartoprecIpItatecentralpontInemyelInolysIs.However,largeraccIdental
IncreasesInplasma[Na
+
]haveproducedsevereconsequencesInchIldren.nexperImental
anImals,acuteseverehypernatremIa(acuteIncreasefrom146to170mEq/L)caused
neuronaldamageat24hours,suggestIveofearlycentralpontInemyelInolysIs.
108
8ydefInItIon,hypernatremIaIndIcatesanabsoluteorrelatIvewaterdefIcItandIsalways
assocIatedwIthhypertonIcIty.HypernatremIacanbegeneratedbyhypotonIcfluIdloss,as
Inburns,gastroIntestInallosses,dIuretIctherapy,osmotIcdIuresIs,renaldIsease,
mIneralocortIcoIdexcessordefIcIency,andIatrogenIccausesorcanbegeneratedby
Isolatedwaterloss,asIncentralornephrogenIc0.TheacquIredformof
P.J10
nephrogenIc0IsmorecommonandusuallylessseverethanthecongenItalform.As
chronIcrenalfaIlureadvances,mostpatIentshavedefectIveconcentratIngabIlIty,
resultIngInresIstancetoA7PassocIatedwIthhypotonIcurIne.8ecausehypovolemIa
accompanIesmostpathologIcwaterloss,sIgnsofhypoperfusIonalsomaybepresent.n
manypatIents,beforethedevelopmentofhypernatremIa,anIncreasedvolumeof
hypotonIcurInesuggestsanabnormalItyInwaterbalance.Althoughuncommonasacause
ofhypernatremIa,IsolatedsodIumgaInoccasIonallyoccursInpatIentswhoreceIvelarge
quantItIesofsodIum,suchastreatmentofmetabolIcacIdosIswIth8.4sodIum
bIcarbonate,InwhIch[Na
+
]IsapproxImately1,000mEq/L,orperIoperatIveorprehospItal
treatmentwIthhypertonIcsalIneresuscItatIonsolutIons.
HypernatremIcpatIentscanbeseparatedIntothreegroups,basedonclInIcalassessmentof
EC7(FIg.149).Notethatplasma[Na
+
]doesnotreflecttotalbodysodIum,whIchmustbe
estImatedseparatelybasedonsIgnsoftheadequacyofEC7.PolyurIc,hypernatremIc
patIentsmaybeundergoIngsolutedIuresIsormayhave0.|easurementofurInarysodIum
andosmolalItycanhelptodIfferentIatethevarIouscauses.AurInaryosmolalIty150
mDsm/kgInthesettIngofhypertonIcItyandpolyurIaIsdIagnostIcof0.
TreatmentofhypernatremIaproducedbywaterlossrequIresrepletIonofwateraswellof
assocIateddefIcItsIntotalbodysodIumandotherelectrolytes(Table1416).Common
errorsIntreatInghypernatremIaIncludeexcessIvelyrapIdcorrectIonaswellasfaIlIngto
apprecIatethemagnItudeofthewaterdefIcItandfaIlIngtoaccountforongoIng
maIntenancerequIrementsandcontInuedfluIdlossesInplannIngtherapy.
ThefIrststepIntreatInghypernatremIaIstoestImatetheT8WdefIcIt,whIchcanbe
accomplIshedbyInsertIngthemeasuredplasma[Na
+
]IntotheequatIon:
where140IsthemIddleofthenormalrangefor[Na
+
].Adrogueand|adIas
109
proposedan
equatIon(seeEq.1412)thatcanbeusedInhypernatremIcpatIentsasItcanbeIn
hyponatremIcpatIentstopredIcttheexpecteddecreaseInserum[Na
+
]producedby
InfusIonof1LofInfusate.
104
TheaccuracyofthIsequatIonhasrecentlybeenvalIdatedIna
largeclInIcalserIesofhypernatremIcandhyponatremIcpatIents.
110
Table 14-16 Hypernatremia: Acute Treatment
Sodium depletion (hypovolemia)
HypovolemIacorrectIon(0.9salIne)
HypernatremIacorrectIon(hypotonIcfluIds)
Sodium overload (hypervolemia)
EnhancesodIumremoval(loopdIuretIcs,dIalysIs)
FeplacewaterdefIcIt(hypotonIcfluIds)
Normal total body sodium (euvolemia)
FeplacewaterdefIcIt(hypotonIcfluIds)
ControldIabetesInsIpIdus
CentraldIabetesInsIpIdus:
00A7P,1020gIntranasally;24gSC
AqueousvasopressIn,5Uq24hr|orSC
NephrogenIcdIabetesInsIpIdus:
FestrIctsodIum,waterIntake
ThIazIdedIuretIcs
00A7P,desmopressIn.
Figure 14-10. A.TheconcentratIonofsodIumIsreflectedIntheIntensItyofthe
stIpplIng:theupperfIgure,representIngextracellularvolume(smallercIrcle)and
Intracellularvolume(largercIrcle),IsmoreheavIlystIppled,thatIs,serumsodIumIs
hIgher.B.nresponsetoanacuteIncreaseInserumsodIumresultIngfromwaterloss,
bothIntracellularandextracellularvolumesubstantIallydecrease.ThebraIn
(schematIcallyIllustrated)shrInksInproportIontothereductIonInIntracellular
volumeInothertIssues.C.However,owIngtotheproductIonofIdIogenIcosmoles,the
braInrapIdlyrestoresItsIntracellularvolume,despItethepersIstentreductIonIn
IntracellularvolumeInothertIssuesandInextracellularvolume.D.WIthexcessIvely
rapIdcorrectIonofhypernatremIa(thereductIonInserumsodIumIsreflectedInthe
decreaseIntheIntensItyofstIpplIng),thebraInexpandstogreaterthanItsorIgInal
sIze.TheresultIngIncreaseIncerebraledemaandIntracranIalpressurecancause
severeneurologIcdamage.(|odIfIedfromFeIgPU:HypernatremIaandhypertonIc
syndromes.|edClInNorthAm1981;65:271290,wIthpermIssIon.)
HypernatremIamustbecorrectedslowlybecauseoftherIskofneurologIcsequelaesuchas
seIzuresorcerebraledema(FIg.1410).Atthecellularlevel,restoratIonofcellvolume
occursremarkablyquIcklyaftertonIcItyIsaltered;asaconsequence,acutetreatmentof
hypertonIcItymayresultInovershootIngtheorIgInal,normotonIccellvolume.Thewater
defIcItshouldbereplacedover24to48hours,andtheplasma[Na
+
]shouldnotbereduced
bymorethan1to2mEq/L/hr.FeversIbleunderlyIngcausesshouldbetreated.
HypovolemIashouldbecorrectedpromptlywIth0.9salIne.Althoughthe
P.J11
[Na
+
]of0.9salIneIs154mEq/L,thesolutIonIseffectIveIntreatIngvolumedefIcItsand
wIllreduce[Na
+
]thatexceeds154mEq/LInhypovolemIchypernatremIcpatIents.Dnce
hypovolemIaIscorrected,watercanbereplacedorallyorwIthIntravenoushypotonIc
fluIds,dependIngontheabIlItyofthepatIenttotolerateoralhydratIon.ntheoccasIonal
sodIumoverloadedpatIent,sodIumexcretIoncanbeacceleratedusIngloopdIuretIcsor
dIalysIs.
ThemanagementofhypernatremIasecondaryto0varIesaccordIngtowhetherthecause
IscentralornephrogenIc(seeTable1416).ThetwomostsuItableagentsforcorrectIng
central0(anA7PdefIcIencysyndrome)aredesmopressIn(00A7P)andaqueous
vasopressIn.00A7P,gIvensubcutaneouslyInadoseof1to4gorIntranasallyInadoseof
5to20gevery12to24hours,IseffectIveInmostpatIents.00A7PIspreferredbecauseIt
hasalongerduratIonofactIonthanA7PandlacksvasoconstrIctoreffects.
111
ncomplete
A7PdefIcIts(partIal0)oftenareeffectIvelymanagedwIthpharmacologIcagentsthat
stImulateA7PreleaseorenhancetherenalresponsetoA7P.ChlorpropamIde,whIch
potentIatestherenaleffectsofvasopressIn,andcarbamazepIne,whIchenhances
vasopressInsecretIon,havebeenusedtotreatpartIalcentral0,butareassocIatedwIth
clInIcallyImportantsIdeeffects.nnephrogenIc0,saltandwaterrestrIctIonorthIazIde
dIuretIcsInducecontractIonofEC7,therebyenhancIngfluIdreabsorptIonIntheproxImal
tubules.flessfIltratepassesthroughIntothecollectIngducts,lesswaterwIllbeexcreted.
Potassium
Physiologic Role
PotassIumplaysanImportantroleIncellmembranephysIology,especIallyInmaIntaInIng
restIngmembranepotentIalsandIngeneratIngactIonpotentIalsInthecentralnervous
systemandheart.PotassIumIsactIvelytransportedIntocellsbyaNa/KadenosIne
trIphosphatase(ATPase)pump,whIchmaIntaInsanIntracellular[K
+
]thatIsatleastJ0fold
greaterthanextracellular[K
+
].ntracellularpotassIumconcentratIon([K
+
])Isnormally150
mEq/LwhIletheextracellularconcentratIonIsonlyJ.5to5.0mEq/L.Serum[K
+
]measures
about0.5mEq/LhIgherthanplasma[K
+
]becauseofcelllysIsdurIngclottIng.Totalbody
potassIumIna70kgadultIsapproxImately4,256mEq,ofwhIch4,200mEqIsIntracellular;
ofthe56mEqIntheEC7,only12mEqIslocatedIntheP7.TheratIoofIntracellularto
extracellularpotassIumcontrIbutestotherestIngpotentIaldIfferenceacrosscell
membranesandthereforetotheIntegrItyofcardIacandneuromusculartransmIssIon.The
prImarymechanIsmthatmaIntaInspotassIumInsIdecellsIsthenegatIvevoltagecreated
bythetransportofthreesodIumIonsoutofthecellforeverytwopotassIumIons
transportedIn.8othInsulInandagonIstspromotepotassIumentryIntocells.
112,11J
|etabolIcandrespIratoryacIdosIstendstoshIftpotassIumoutofcells,whIlemetabolIc
andrespIratoryalkalosIsfavorsmovementIntocells.
UsualpotassIumIntakevarIesbetween50and150mEq/day.FreelyfIlteredatthe
glomerulus,mostpotassIumexcretIonIsurInary,wIthsomefecalelImInatIon.|ostfIltered
potassIumIsreabsorbed;usually,excretIonIsapproxImatelyequaltodaIlyIntake.Aslong
asCFFIs8mL/mIn,dIetarypotassIumIntake,unlessgreaterthannormal,canbe
excreted.AssumIngaplasma[K
+
]of4.0mEq/LandanormalCFFof180L/day,720mEqof
potassIumIsfIltereddaIly,ofwhIch85to90IsreabsorbedIntheproxImalconvoluted
tubuleandloopofHenle.TheremaInIng10to15reachesthedIstalconvolutedtubule,
whIchIsthemajorsIteatwhIchpotassIumexcretIonIsregulated.ExcretIonofpotassIum
IonsIsafunctIonofopenpotassIumchannelsandtheelectrIcaldrIvIngforceInthecortIcal
collectIngduct.
ThetwomostImportantregulatorsofpotassIumexcretIonareplasma[K
+
]and
aldosterone.PotassIumsecretIonIntothedIstalconvolutedtubulesandcortIcalcollectIng
ductsIsIncreasedbyhyperkalemIa,aldosterone,alkalemIa,IncreaseddelIveryofNa
+
to
thedIstaltubuleandcollectIngduct,hIghurInaryflowrates,andthepresenceInlumInal
fluIdofnonreabsorbableanIonssuchascarbenIcIllIn,phosphates,andsulfates.AssodIum
reabsorptIonIncreases,theelectrIcaldrIvIngforceopposIngreabsorptIonofpotassIumIs
Increased.AldosteroneIncreasessodIumreabsorptIonbyInducIngamoreopen
confIguratIonoftheepIthelIalsodIumchannel;potassIumsparIngdIuretIcs(amIlorIdeand
trIamterene)andtrImethoprImblocktheepIthelIalsodIumchannel,therebyIncreasIng
potassIumreabsorptIon.|agnesIumdepletIoncontrIbutestorenalpotassIumwastIng.
Hypokalemia
Uncommonamonghealthypersons,hypokalemIa([K
+
]J.5mEq/L)Isafrequent
complIcatIonoftreatmentwIthdIuretIcdrugsandoccasIonallycomplIcatesotherdIseases
andtreatmentregImens(Table1417).Plasma[K
+
]poorlyreflects
P.J12
totalbodypotassIum;hypokalemIamayoccurwIthnormal,low,orhIghtotalbody
potassIum.However,asageneralrule,achronIcdecrementof1.0mEq/LIntheplasma
[K
+
]correspondstoatotalbodydefIcItofapproxImately200toJ00mEq.nuncomplIcated
hypokalemIa,thetotalbodypotassIumdefIcItexceedsJ00mEqIfplasma[K
+
]IsJ.0mEq/L
and700mEqIfplasma[K
+
]Is2.0mEq/L.
Table 14-17 Causes of Renal Potassium Loss
Drugs Bicarbonaturia
0IuretIcs 0IstalrenaltubularacIdosIs
ThIazIdedIuretIcs
TreatmentofproxImalrenaltubular
acIdosIs
LoopdIuretIcs CorrectIonphaseofmetabolIcalkalosIs
DsmotIcdIuretIcs Magnesium deficiency
AntIbIotIcs Other less common causes
PenIcIllInandpenIcIllIn
analogues
CIsplatIn
AmphoterIcIn8 CarbonIcanhydraseInhIbItors
AmInoglycosIdes LeukemIa
Hormones 0IuretIcphaseofacutetubularnecrosIs
Aldosterone Intrinsic renal transport defects
ClucocortIcoIds 8artersyndrome
CItelmansyndrome
|odIfIedfromWeIner0,WIngoCS:HypokalemIaconsequences,causes,and
correctIon.JAmSocNephrol1997;8:11791188,wIthpermIssIon.
ThesymptomsandsIgnsofhypokalemIaprImarIlyrelatetoneuromuscularand
cardIovascularfunctIon.HypokalemIacausesmuscleweaknessand,whensevere,mayeven
causeparalysIs.WIthchronIcpotassIumloss,theratIoofIntracellulartoextracellular[K
+
]
remaInsrelatIvelystable;Incontrast,acuteredIstrIbutIonofpotassIumfromthe
extracellulartotheIntracellularspacesubstantIallychangesrestIngmembranepotentIals.
CardIacrhythmdIsturbancesareamongthemostdangerouscomplIcatIonsofpotassIum
defIcIency.AcutehypokalemIacauseshyperpolarIzatIonofthecardIaccellandmayleadto
ventrIcularescapeactIvIty,reentrantphenomena,ectopIctachycardIas,anddelayed
conductIon.npatIentstreatedwIthdIgoxIn,hypokalemIaIncreasestoxIcItybyIncreasIng
myocardIaldIgoxInbIndIngandpharmacologIceffectIveness.HypokalemIacontrIbutesto
systemIchypertensIon,especIallywhencombInedwIthahIghsodIumdIet.ndIabetIc
patIents,hypokalemIaImpaIrsInsulInsecretIonandendorgansensItIvItytoInsulIn.
AlthoughnoclearthresholdhasbeendefInedforalevelofhypokalemIabelowwhIchsafe
conductofanesthesIaIscompromIsed,[K
+
]J.5mEq/LIncardIacsurgIcalpatIentshas
beenassocIatedwIthanIncreasedIncIdenceofperIoperatIvedysrhythmIas,especIally
atrIalfIbrIllatIon/flutter.
114
PotassIumdepletIonalsoInducesdefectsInrenalconcentratIngabIlIty,resultIngIn
polyurIaandareductIonInCFF.PotassIumreplacementImprovesCFF,althoughthe
concentratIngdefIcItmaynotImproveforseveralmonthsaftertreatment.fhypokalemIa
IssuffIcIentlyprolonged,chronIcrenalInterstItIaldamagemayoccur.nexperImental
anImals,hypokalemIawasassocIatedwIthIntrarenalvasoconstrIctIonandapatternof
renalInjurysImIlartothatproducedbyIschemIa.
115
Figure 14-11.AdIagnostIcflowchartforhypokalemIawIthahIghrateofK
+
excretIon.ECF,extracellularfluId.(FromLInSH,HalperIn|L:HypokalemIa:a
practIcalapproachtodIagnosIsandItsgenetIcbasIs.Curr|edChem2007;14:1551
1565,wIthpermIssIon.)
HypokalemIamayresultfromchronIcdepletIonoftotalbodypotassIumorfromacute
redIstrIbutIonofpotassIumfromtheEC7totheC7.FedIstrIbutIonofpotassIumIntocells
occurswhentheactIvItyofthesodIumpotassIumATPasepumpIsacutelyIncreasedby
extracellularhyperkalemIaorIncreasedIntracellularconcentratIonsofsodIum,aswellas
byInsulIn,carbohydrateloadIng(whIchstImulatesreleaseofendogenousInsulIn),
2
agonIsts,andaldosterone.8othmetabolIcandrespIratoryalkalosIsleadtodecreasesIn
plasma[K
+
].
CausesofchronIchypokalemIaIncludethoseetIologIesassocIatedwIthrenalpotassIum
conservatIon(extrarenalpotassIumlosses;lowurInary[K
+
])andthosewIthrenalpotassIum
wastIng(FIg.1411).
116
AlowurInary[K
+
]suggestsInadequatedIetaryIntakeorextrarenal
depletIon(IntheabsenceofrecentdIuretIcuse).0IuretIcInducedurInarypotassIumlosses
arefrequentlyassocIatedwIthhypokalemIa,secondarytoIncreasedaldosteronesecretIon,
alkalemIa,andIncreasedrenaltubularflow.AldosteronedoesnotcauserenalpotassIum
wastIngunlesssodIumIonsarepresent;thatIs,aldosteroneprImarIlycontrolssodIum
reabsorptIon,notpotassIumexcretIon.FenaltubulardamageduetonephrotoxInssuchas
amInoglycosIdesoramphoterIcIn8mayalsocauserenalpotassIumwastIng.
nItIalevaluatIonofhypokalemIaIncludesamedIcalhIstory(e.g.,dIarrhea,vomItIng,
dIuretIcorlaxatIveuse),physIcal
P.J1J
examInatIon(e.g.,hypertensIon,cushIngoIdfeatures,edema),measurementofserum
electrolytes(e.g.,magnesIum),arterIalpHassessment,andevaluatIonofthe
electrocardIogram(ECC).|easurementof24hoururInaryexcretIonofsodIumand
potassIummaydIstInguIshextrarenalfromrenalcauses.|agnesIumdefIcIency,assocIated
wIthamInoglycosIdeandcIsplatIntherapy,cangeneratehypokalemIathatIsresIstantto
replacementtherapy.PlasmarenInandaldosteronelevelsmaybehelpfulInthe
dIfferentIaldIagnosIsofhypokalemIaofunclearorIgIn,especIallyIfprImary
hyperaldosteronIsmIssuspected.
117
CharacterIstIcelectrocardIographIcchangesassocIated
wIthhypokalemIaIncludeflatorInvertedTwaves,promInentUwaves,andSTsegment
depressIon.
Table 14-18 Hypokalemia: Treatment
Correct precipitating factors
ncreasedpH
0ecreased[|g
2+
]
0rugs
Mild hypokalemia([K
+
]2.0mEq/L)
ntravenousKClInfusIon10mEq/hr
Severe hypokalemia([K
+
]2.0mEq/L,paralysIsorECCchanges)
ntravenousKClInfusIon40mEq/hr
ContInuousECCmonItorIng
flIfethreatenIng,56mEqbolus
ECC,electrocardIographIc.
ThetreatmentofhypokalemIaconsIstsofpotassIumrepletIon,correctIonofalkalemIa,and
removalofoffendIngdrugs(Table1418).HypokalemIasecondaryonlytoacute
redIstrIbutIon(e.g.,secondarytoacutealkalemIa)maynotrequIretreatment.ThereIsno
urgentneedforpotassIumreplacementtherapyInmIldtomoderatehypokalemIa(JtoJ.5
mEq/L)InpatIentswhohavenosymptoms.ftotalbodypotassIumIsdecreased,oral
potassIumsupplementatIonIspreferabletoIntravenousreplacement.PotassIumIsusually
replacedasthechlorIdesaltbecausecoexIstIngchlorIdedefIcIencymaylImIttheabIlItyof
thekIdneytoconservepotassIum.
ntravenouspotassIumrepletIon,whennecessary,mustbeperformedcautIously(I.e.,
usuallyatarate10to20mEq/hr)becausethemagnItudeofpotassIumdefIcItsIs
unpredIctable.Theplasma[K
+
]andtheECCmustbemonItoreddurIngrapIdrepletIon(10
to20mEq/hr)toavoIdhyperkalemIccomplIcatIons.Theplasma[K
+
]andECCshouldbe
monItoredtodetectInadvertenthyperkalemIa.PartIcularcareshouldbetakenInpatIents
whohaveconcurrentacIdemIa,type7renaltubularacIdosIs,dIabetesmellItus,orIn
thosepatIentsreceIvIngnonsteroIdalantIInflammatoryagents,ACEInhIbItors,or
2
blockers,allofwhIchdelaymovementofextracellularpotassIumIntocells.8eta
1
blockers
donotdelaymovementofextracellularpotassIumIntocellsorpredIsposepatIentsto
hyperkalemIa.
118
However,InpatIentswIthlIfethreatenIngdysrhythmIassecondarytohypokalemIa,serum
[K
+
]mustberapIdlyIncreased.AssumIngthatP7Ina70kgadultIsJ.0L,admInIstratIonof
6.0mEq/LofpotassIumIn1.0mInutewIllacutelyIncreaseserum[K
+
]bynomorethan2.0
mEq/LbecauseredIstrIbutIonIntoInterstItIalfluIdandIntracellularvolumewIlldecrease
thequantItyremaInIngIntheplasmavolume.
HypokalemIaassocIatedwIthhyperaldosteronemIa(e.g.,prImaryaldosteronIsm,CushIng
syndrome)usuallyrespondsfavorablytoreducedsodIumIntakeandIncreasedpotassIum
Intake.HypomagnesemIa,Ifpresent,aggravatestheeffectsofhypokalemIa,ImpaIrs
potassIumconservatIon,andshouldbetreated.PotassIumsupplementsorpotassIum
sparIngdIuretIcsshouldbegIvencautIouslytopatIentswhohavedIabetesmellItusorrenal
InsuffIcIency,whIchlImItcompensatIonforacutehyperkalemIa.npatIentssuchasthose
whohavedIabetIcketoacIdosIs,whoarebothhypokalemIcandacIdemIc,potassIum
admInIstratIonshouldprecedecorrectIonofacIdosIstoavoIdaprecIpItousdecreaseIn
plasma[K
+
]aspHIncreases.
npatIentswIthnormalserumpotassIumaccompanIedbysymptomsofpotassIumdepletIon
(e.g.,musclefatIgue),hIstoryofpotassIumlossorInsuffIcIentIntake,orInpatIentsIn
whompotassIumdepletIonmaybeofspecIalthreat(e.g.,patIentsondIuretIcs,dIgItalIs,or
2
agonIsts),musclebIopsywIthmeasurementofmusclepotassIumconcentratIonmaybea
usefulproceduretodetectandquantIfypotassIumdepletIon.
Hyperkalemia
ThemostlethalmanIfestatIonsofhyperkalemIa([K
+
]5.0mEq/L)InvolvethecardIac
conductIngsystemandIncludedysrhythmIas,conductIonabnormalItIes,andcardIacarrest.
nanesthesIapractIce,theclassIcexampleofhyperkalemIccardIactoxIcItyIsassocIated
wIththeadmInIstratIonofsuccInylcholInetoparaplegIc,quadrIplegIcorseverelyburned
119
patIents.fplasma[K
+
]Is6.0mEq/L,cardIaceffectsareneglIgIble.AstheconcentratIon
Increasesfurther,theelectrocardIogramshowstall,peakedTwaves,especIallyInthe
precordIalleads.WIthfurtherIncreases,thePFIntervalbecomesprolonged,followedbya
decreaseIntheamplItudeofthePwave.FInally,theQFScomplexwIdensIntoapattern
resemblIngasInewave,asapreludetocardIacstandstIll(FIg.1412).
112
HyperkalemIc
cardIotoxIcItyIsenhancedbyhyponatremIa,hypocalcemIa,oracIdosIs.8ecause
progressIontofatalcardIotoxIcItyIsunpredIctableandoftenswIft,thepresenceof
hyperkalemIcECCchangesmandatesImmedIatetherapy.ThelIfethreatenIngcardIac
effectsusuallyrequIremoreurgenttreatmentthanothermanIfestatIonsofhyperkalemIa.
However,ascendIngmuscleweaknessappearswhenplasma[K
+
]approaches7.0mEq/L,and
mayprogresstoflaccIdparalysIs,InabIlItytophonate,andrespIratoryarrest.
ThemostImportantdIagnostIcIssuesaremedIcalhIstory,emphasIzIngrecentdrug
therapy,andassessmentofrenalfunctIon.AlthoughtheECCmayprovIdethefIrst
suggestIonofhyperkalemIaInsomepatIents,anddespItethewelldescrIbedeffectsof
hyperkalemIaoncardIacconductIonandrhythm,theECCIsanInsensItIveandnonspecIfIc
methodofdetectInghyperkalemIa.fhyponatremIaIsalsopresent,adrenalfunctIonshould
beevaluated.
HyperkalemIamayoccurwIthnormal,hIgh,orlowtotalbodypotassIumstores.A
defIcIencyofaldosterone,amajorregulatorofpotassIumexcretIon,leadstohyperkalemIa
InadrenalInsuffIcIencyandhyporenInemIchypoaldosteronIsm,astateassocIatedwIth
dIabetesmellItus,renalInsuffIcIency,andadvancedage.8ecausethekIdneysexcrete
potassIum,severerenalInsuffIcIencycommonlycauseshyperkalemIa.PatIentswIthchronIc
renalInsuffIcIencycanmaIntaInnormalplasma[K
+
]despItemarkedlydecreasedCFF
becauseurInarypotassIumexcretIondependsontubularsecretIonratherthanglomerular
fIltratIonIfCFFexceeds8mL/mIn.
0rugsarenowthemostcommoncauseofhyperkalemIa,especIallyInelderlypatIents.
0rugsthatmaylImItpotassIumexcretIonIncludenonsteroIdalantIInflammatorydrugs,
ACEInhIbItors,cyclosporIn,andpotassIumsparIngdIuretIcssuchastrIamterene.0rug
InducedhyperkalemIamostcommonlyoccursInpatIentswIthotherpredIsposIngfactors,
suchasdIabetesmellItus,renalInsuffIcIency,advancedage,orhyporenInemIc
hypoaldosteronIsm.ACEInhIbItorsare
P.J14
partIcularlylIkelytoproducehyperkalemIaInpatIentswhohavecongestIveheart
faIlure.
120
Figure 14-12.ElectrocardIographIc(ECC)manIfestatIonsofhyperkalemIa.(FromSood
||,SoodAF,FIchardsonF:Emergencymanagementandcommonlyencountered
outpatIentscenarIosInpatIentswIthhyperkalemIa.|ayoClInProc2007;82:155J
npatIentswhohavenormaltotalbodypotassIum,hyperkalemIamayaccompanyasudden
shIftofpotassIumfromtheC7totheEC7becauseofacIdemIa,IncreasedcatabolIsm,or
rhabdomyolysIs.|etabolIcacIdosIsandrespIratoryacIdosIstendtocauseanIncreaseIn
plasma[K
+
].However,organIcacIdoses(I.e.,lactIcacIdosIs,ketoacIdosIs)havelIttleeffect
on[K
+
],whereasmIneralacIdscausesIgnIfIcantcellularshIfts.nresponsetoIncreased
hydrogenIonactIvItybecauseofaddItIonofacIds,potassIumwIllIncreaseIftheanIon
remaInsIntheextracellularvolume.NeItherlactatenorketoacIdsremaInInthe
extracellularfluId.Therefore,hyperkalemIaInthesecIrcumstancesreflectstIssueInjuryor
lackofInsulIn.PseudohyperkalemIa,whIchoccurswhenpotassIumIsreleasedfromcellsIn
bloodcollectIontubes,canbedIagnosedbycomparIngserumandplasmaK
+
levelsfrom
thesamebloodsample.HyperkalemIausuallyaccompanIesmalIgnanthyperthermIa.
ThetreatmentofhyperkalemIaIsaImedatelImInatIngthecause,reversIngmembrane
hyperexcItabIlIty,andremovIngpotassIumfromthebody(FIg.141J).
112,11J,120,121
|IneralocortIcoIddefIcIencycanbetreatedwIth9fludrocortIsone(0.025to0.10
mg/day).HyperkalemIasecondarytodIgItalIsIntoxIcatIonmayberesIstanttotherapy
becauseattemptstoshIftpotassIumfromtheEC7totheC7areoftenIneffectIve.nthIs
sItuatIon,useofdIgoxInspecIfIcantIbodIeshasbeensuccessful.
EmergentmanagementofseverehyperkalemIaIsdescrIbedIndetaIlInTable1419.
|embranehyperexcItabIlItycanbeantagonIzedbytranslocatIngpotassIumfromtheEC7
totheC7,removIngexcesspotassIum,or(transIently)byInfusIngcalcIumchlorIdeto
depressthemembranethresholdpotentIal.PendIngdefInItIvetreatment,rapIdInfusIonof
calcIumchlorIde(1gofCaCl
2
overJmInutes,ortwotothreeampulesof10calcIum
gluconateover5mInutes)maystabIlIzecardIacrhythm(Table1419).CalcIumshouldbe
gIvencautIouslyIfdIgItalIsIntoxIcatIonIslIkely.nsulIn,InadosedependentfashIon,
causescellularuptakeofpotassIumbyIncreasIngtheactIvItyofthesodIum/potassIum
ATPasepump.nsulInIncreasescellularuptakeofpotassIumbestwhenhIghInsulInlevels
areachIevedbyIntravenousInjectIonof5to10unItsofregularInsulIn,accompanIedby50
mLof50glucose.
112,120
2
AdrenergIcdrugssuchassalbutamolandalbuterolalsoIncrease
potassIumuptakebyskeletalmuscleandreduceplasma[K
+
],anactIonthatmayexplaIn
hypokalemIawIthsevere,acuteIllness.Salbutamol,aselectIve
2
agonIst,decreases
serumpotassIumacutelyby1mEq/LormorewhengIvenbyInhalatIonorIntravenously,
althoughcardIacdysrhythmIasmayoccasIonallycomplIcatetreatmentwIthselectIve
2
agonIsts.
112
AlthoughadmInIstratIonofsodIumbIcarbonatehaslongbeenconsIderedapart
ofthetreatmentofhyperkalemIa,bIcarbonate,whenusedalone,IsrelatIvelyIneffectIve
andIsnolongerfavored.
120
PotassIummayberemovedfromthebodybytherenalorgastroIntestInalroutes.
FurosemIdepromoteskalIuresIsInadosedependentfashIon.SodIumpolystyrenesulfonate
resIn(Kayexalate),whIchexchangessodIumforpotassIum,canbegIvenorally(J0g)oras
aretentIonenema(50gIn200mLof20sorbItol).However,sodIumoverloadand
hypervolemIaarepotentIalrIsks.Farely,whentemporIzIngmeasuresareInsuffIcIent,
emergencyhemodIalysIsmayremove25to50mEq/hr.PerItonealdIalysIsIslesseffIcIent.
Calcium
Physiologic Role
CalcIumIsadIvalentcatIonfoundprImarIlyIntheextracellularfluId.ThefreecalcIum
concentratIon[Ca
2+
]InEC7IsapproxImately1m|,whereasthefree[Ca
2+
]IntheC7
approxImates100m|,agradIentof10,000to1.CIrculatIngcalcIumconsIstsofaproteIn
boundfractIon(40to50),afractIonboundtoInorganIcanIons(10to15),andanIonIzed
fractIon(45to50),whIchIsthephysIologIcallyactIveandhomeostatIcallyregulated
component.AcuteacIdemIaIncreasesandacutealkalemIadecreasesIonIzedcalcIum.
122
P.J15
8ecausemathematIcalformulaethatcorrecttotalcalcIummeasurementsforalbumIn
concentratIonareInaccurateIncrItIcallyIllpatIents,
12J
IonIzedcalcIumshouldbedIrectly
measured.
Figure 14-13.AlgorIthmIcmanagementofhyperkalemIa.ECC,electrocardIographIc;
7,Intravenous;K,potassIum;ECF,extracellularfluId;CF,IntracellularfluId;|0,
metereddoseInhaler;NaCl,sodIumchlorIde.(FromSood||,SoodAF,FIchardsonF:
EmergencymanagementandcommonlyencounteredoutpatIentscenarIosInpatIents
wIthhyperkalemIa.|ayoClInProc2007;82:155J1561,wIthpermIssIon.)
ngeneral,calcIumIsessentIalforallmovementthatoccursInmammalIansystems.
EssentIalfornormalexcItatIoncontractIoncouplIng,calcIumIsalsonecessaryforproper
functIonofmuscletIssue,cIlIarymovement,mItosIs,neurotransmItterrelease,enzyme
secretIon,andhormonalsecretIon.CyclIcadenosInemonophosphate(cA|P)and
phosphoInosItIdes,whIcharemajorsecondmessengersregulatIngcellularmetabolIsm,
functIonprImarIlythroughtheregulatIonofcalcIummovement.ActIvatIonofnumerous
IntracellularenzymesystemsrequIrescalcIum.CalcIumIsImportantbothforgeneratIon
P.J16
ofthecardIacpacemakeractIvItyandforgeneratIonofthecardIacactIonpotentIaland
thereforeIstheprImaryIonresponsIblefortheplateauphaseoftheactIonpotentIal.
CalcIumalsoplaysvItalfunctIonsInmembraneandbonestructure.
Table 14-19 Severe Hyperkalemia
a
Treatment
Feversemembraneeffects
CalcIum(10mLof10calcIumchlorIde7over10mIn)
Transferextracellular[K
+
]Intocells
ClucoseandInsulIn(010W+510UregularInsulInper2550gglucose)
SodIumbIcarbonate(50100mEqover510mIn)
2
AgonIsts
FemovepotassIumfrombody
0IuretIcs,proxImalorloop
PotassIumexchangeresIns(sodIumpolystyrenesulfonate)
HemodIalysIs
|onItorECCandserum[K
+
]level
7,Intravenous;010W,10dextroseInwater;ECC,electrocardIogram.
a
PotassIumconcentratIon([K
+
])7.0mEq/LorelectrocardIographIcchanges.
Serum[Ca
2+
]IsregulatedbymultIplefactors(FIg.1414),
124
IncludIngacalcIum
receptor
124,125
andseveralhormones.ParathyroIdhormone(PTH)andcalcItrIol,themost
ImportantneurohumoralmedIatorsofserum[Ca
2+
],
126
mobIlIzecalcIumfrombone,
IncreaserenaltubularreabsorptIonofcalcIum,andenhanceIntestInalabsorptIonof
calcIum.7ItamIn0,afterIngestIonorcutaneousmanufactureunderthestImulusof
ultravIoletlIght,Is25hydroxylatedtocalcIdIolInthelIverandthenIs1hydroxylatedto
calcItrIol,theactIvemetabolIte,InthekIdney.EvenIntheabsenceofdIetarycalcIum
Intake,PTHandvItamIn0canmaIntaInanormalcIrculatIng[Ca
2+
]bymobIlIzIngcalcIum
frombone.naddItIontothekeyrolesplayedbyPTHandcalcItrIolInregulatIngserum
[Ca
2+
],otherrecentlydescrIbedpathwaysplaykeymolecularrolesInboneresorptIon.The
receptoractIvatorofnuclearfactor8(FANK),FANKlIgand(FANKL),and
osteoprotegenerInplaykeymolecularroles;bIndIngofFANKLtoFANKstImulates
osteoclastactIvIty,whereasbIndIngofFANKLtoosteoprogenerIn,asolubledecoy
receptor,dIsruptsbIndIngtoFANK.
127
Figure 14-14.SchematIcrepresentatIonoftheregulatorysystemmaIntaInIngCa
2+
homeostasIs.Thesolid arrowsandlinesdelIneateeffectsofparathyroIdhormone
(PTH)and1,25(DH)
2
0
J
(dIhydroxyvItamIn0)ontheIrtargettIssues;dashed arrowsand
linesshowexamplesofhowextracellularCa
2+
orphosphateIonsactdIrectlyontIssues
regulatIngmIneralIonmetabolIsm.Ca,calcIum;PD
4
,phosphate;ECF,extracellular
fluId;cA|P,cyclIcadenosInemonophosphate;25(DH)0=25hydroxyvItamIn0;
negatIvesIgnsIndIcateInhIbItoryactIonsandplussIgnsIndIcatestImulatoryeffects.
(FeprIntedwIthpermIssIonfrom8rownE|,Pollak|,HebertSC:Theextracellular
calcIumsensIngreceptor:ItsroleInhealthanddIsease.AnnFev|ed1998;49:1529).
Hypocalcemia
HypocalcemIa(IonIzed[Ca
2+
]4.0mg/dLor1.0mmol/L)occursasaresultoffaIlureof
PTHorcalcItrIolactIonorbecauseofcalcIumchelatIonorprecIpItatIon,notbecauseof
calcIumdefIcIencyalone.PTHdefIcIencycanresultfromsurgIcaldamageorremovalof
theparathyroIdglandsorfromsuppressIonoftheparathyroIdglandsbyseverehypoor
hypermagnesemIa.8urns,sepsIs,andpancreatItIsmaysuppressparathyroIdfunctIonand
InterferewIthvItamIn0actIon.7ItamIn0defIcIencymayresultfromlackofdIetary
vItamIn0orvItamIn0malabsorptIonInpatIentswholacksunlIghtexposure.
HyperphosphatemIaInducedhypocalcemIa
P.J17
mayoccurasaconsequenceofoverzealousphosphatetherapy,fromcelllysIssecondaryto
chemotherapy,orasaresultofcellulardestructIonfromrhabdomyolysIs.PrecIpItatIonof
CaHPD
4
complexesoccurswIthhyperphosphatemIa.However,IonIzed[Ca
2+
]onlydecreases
approxImately0.019m|foreach1.0m|IncreaseInphosphateconcentratIon.nmassIve
transfusIon,cItratemayproducehypocalcemIabychelatIngcalcIum;however,decreases
areusuallytransIentandproduceneglIgIblecardIovasculareffects,unlesscItrate
clearanceIsdecreased(e.g.,byhepatIcorrenaldIseaseorhypothermIa)orblood
transfusIonexceeds5unItsofpackedredbloodcells.
128
AlkalemIaresultIngfrom
hyperventIlatIonorsodIumbIcarbonateInjectIoncanacutelydecrease[Ca
2+
].
Table 14-20 Hypocalcemia: Clinical Manifestations
Cardiovascular
0ysrhythmIas
0IgItalIsInsensItIvIty
ECCchanges
HeartfaIlure
HypotensIon
Neuromuscular
Tetany
|usclespasm
PapIlledema
SeIzures
Weakness
FatIgue
Respiratory
Apnea
Laryngealspasm
8ronchospasm
Psychiatric
AnxIety
0ementIa
0epressIon
PsychosIs
ThehallmarkofhypocalcemIaIsIncreasedneuronalmembraneIrrItabIlItyandtetany
(Table1420).EarlysymptomsIncludesensatIonsofnumbnessandtInglIngInvolvIng
fIngers,toes,andthecIrcumoralregIon.nfranktetany,tonIccontractIonofrespIratory
musclesmayleadtolaryngospasm,bronchospasm,orrespIratoryarrest.Smoothmuscle
spasmcanresultInabdomInalcrampIngandurInaryfrequency.|entalstatusalteratIons
IncludeIrrItabIlIty,depressIon,psychosIs,anddementIa.HypocalcemIamayImpaIr
cardIovascularfunctIonandhasbeenassocIatedwIthheartfaIlure,hypotensIon,
dysrhythmIas,InsensItIvItytodIgItalIs,andImpaIredadrenergIcactIon.
FeducedionizedserumcalcIumoccursInasmanyas88ofcrItIcallyIllpatIents,66of
lessseverelyIllIntensIvecareunItpatIentsand26ofhospItalIzednonIntensIvecareunIt
patIents.
129
PatIentsatpartIcularrIskIncludepatIentsaftermultIpletraumaand
cardIopulmonarybypass.nmostsuchpatIents,IonIzedhypocalcemIaIsclInIcallymIld
([Ca
2+
]0.8to1.0mmol/L).
nItIaldIagnostIcevaluatIonshouldconcentrateonhIstoryandphysIcalexamInatIon,
laboratoryevaluatIonofrenalfunctIon,andmeasurementofserumphosphate
concentratIon.LatenthypocalcemIacanbedIagnosedbytappIngonthefacIalnerveto
elIcItChvosteksIgnorbyInflatIngasphygmomanometerto20mmHgabovesystolIc
pressure,whIchproducesradIalandulnarnerveIschemIaandcausescarpalspasmknown
asTrousseau sign.ThedIfferentIaldIagnosIsofhypocalcemIacanbeapproachedby
addressIngfourIssues:ageofthepatIent,serumphosphateconcentratIon,generalclInIcal
status,andduratIonofhypocalcemIa.
1J0
LowornormalphosphateconcentratIonsImply
vItamIn0ormagnesIumdefIcIency.AnotherwIsehealthypatIentwIthchronIc
hypocalcemIaprobablyIshypoparathyroId.HIghphosphateconcentratIonssuggestrenal
faIlureorhypoparathyroIdIsm.nrenalInsuffIcIency,reducedphosphorusexcretIonresults
InhyperphosphatemIa,whIchdownregulatesthe1hydroxylaseresponsIblefortherenal
conversIonofcalcIdIoltocalcItrIol.ThIs,IncombInatIonwIthdecreasedproductIonof
calcItrIolsecondarytoreducedrenalmass,causesreducedIntestInalabsorptIonofcalcIum
andhypocalcemIa.
126
ChronIcallyIlladultswIthhypocalcemIaoftenhavedIsorderssuchas
malabsorptIon,osteomalacIa,orosteoblastIcmetastases.
Table 14-21 Hypocalcemia: Acute Treatment
AdmInIstercalcIum
7:10mL10calcIumgluconate
a
over10mIn,followedbyelementalcalcIum
0.J2.0mg/kg/hr
Dral:500100mgelementalcalcIumq6hr
Administer vitamin D
ErgocalcIferol,1,200g/day(T
1/2
=J0days)
0Ihydrotachysterol,200400g/day(T
1/2
=7days)
1,25dIhydroxycholecalcIferol,0.251.0g/day(T
1/2
=1day)
|onItorelectrocardIogram
7,Intravenous;T
1/2
.halflIfe.
a
CalcIumgluconatecontaIns9JmgelementalcalcIumper10mlvIal.
ThedefInItIvetreatmentofhypocalcemIanecessItatesIdentIfIcatIonandtreatmentofthe
underlyIngcause(Table1421).SymptomatIchypocalcemIausuallyoccurswhenserum
IonIzed[Ca
2+
]Is0.7m|.
UnnecessaryoffendIngdrugsshouldbedIscontInued.HypocalcemIaresultIngfrom
hypomagnesemIaorhyperphosphatemIaIstreatedbyrepletIonofmagnesIumorremoval
ofphosphate.TreatmentofapatIentwhohastetanyandhyperphosphatemIarequIres
coordInatIonoftherapytoavoIdtheconsequencesofmetastatIcsofttIssue
calcIfIcatIon.
1J1
PotassIumandotherelectrolytesshouldbemeasuredandabnormalItIes
shouldbecorrected.HyperkalemIaandhypomagnesemIapotentIatehypocalcemIaInduced
cardIacandneuromuscularIrrItabIlIty.ncontrast,hypokalemIaprotectsagaInst
hypocalcemIctetany;therefore,correctIonofhypokalemIawIthoutcorrectIonof
hypocalcemIamayprovoketetany.
|Ild,IonIzedhypocalcemIashouldnotbeovertreated.ForInstance,InmostpatIentsafter
cardIacsurgery,admInIstratIonofcalcIumonlyIncreasesbloodpressureandactually
attenuatestheadrenergIceffectsofepInephrIne.nnormocalcemIcdogs,calcIum
chlorIdeprImarIlyactsasaperIpheralvasoconstrIctor,wIthtransIentreductIonof
myocardIalcontractIlIty;InhypocalcemIcdogs,calcIumInfusIonsIgnIfIcantlyImproves
contractIleperformanceandbloodpressure.
1J2
Therefore,calcIumInfusIonsshouldbeof
lImItedvalueInsurgIcalpatIentsunlessthereIsdemonstrableevIdenceofIonIzed
hypocalcemIa.CalcIumsaltsappeartoconfernobenefIttopatIentsalreadyreceIvIng
InotropIcorvasoactIveagents.
ThecornerstoneoftherapyforconfIrmed,symptomatIc,IonIzedhypocalcemIa([Ca
2+
]0.7
m|)IscalcIumadmInIstratIon.npatIentswhohaveseverehypocalcemIaorhypocalcemIc
symptoms,calcIumshouldbeadmInIsteredIntravenously.nemergencysItuatIons,Inan
averagedsIzedadult,theruleof10sadvIsesInfusIonof10mLof10calcIumgluconate
(9JmgelementalcalcIum)over10mInutes,followedbyacontInuousInfusIonofelemental
calcIum,0.Jto2mg/kg/hr(I.e.,Jto16mL/hrof10calcIumgluconatefora70kgadult).
CalcIumsaltsshouldbedIlutedIn50to100mL05W(tolImItvenousIrrItatIonand
thrombosIs),shouldnotbemIxedwIthbIcarbonate(topreventprecIpItatIon),andmustbe
gIvencautIouslytodIgItalIzedpatIentsbecausecalcIumIncreasesthetoxIcItyof
P.J18
dIgoxIn.ContInuousECCmonItorIngdurIngInItIaltherapywIlldetectcardIotoxIcIty(e.g.,
heartblock,ventrIcularfIbrIllatIon).0urIngcalcIumreplacement,theclInIcIanshould
monItorserumcalcIum,magnesIum,phosphate,potassIum,andcreatInIne.Dncethe
IonIzed[Ca
2+
]IsstableIntherangeof4to5mg/dL(1.0to1.25m|),oralcalcIum
supplementscansubstItuteforparenteraltherapy.UrInarycalcIumshouldbemonItoredIn
anattempttoavoIdhypercalcIurIa(5mg/kgper24hours)andurInarytractstone
formatIon.
WhensupplementatIonfaIlstomaIntaInserumcalcIumwIthInthenormalrange,orIf
hypercalcIurIadevelops,vItamIn0orvItamIn0analogsmaybeadded.Althoughthe
prIncIpaleffectofvItamIn0IstoIncreaseenterIccalcIumabsorptIon,osseouscalcIum
resorptIonIsalsoenhanced.WhenrapIdchangesIndosageareantIcIpatedoranImmedIate
effectIsrequIred(e.g.,postoperatIvehypoparathyroIdIsm),shorteractIngcalcIferolssuch
asdIhydrotachysterolmaybepreferable.8ecausetheeffectofvItamIn0Isnotregulated,
thedosagesofcalcIumandvItamIn0shouldbeadjustedtoraIsetheserumcalcIumInto
thelownormalrange.
AdversereactIonstocalcIumandvItamIn0IncludehypercalcemIaandhypercalcIurIa.f
hypercalcemIadevelops,calcIumandvItamIn0shouldbedIscontInuedandapproprIate
therapygIven.ThetoxIceffectsofvItamIn0metabolItespersIstInproportIontotheIr
bIologIchalflIves(ergocalcIferol,20to60days;dIhydrotachysterol,5to15days;calcItrIol,
2to10days).ClucocortIcoIdsantagonIzethetoxIceffectsofvItamIn0metabolItes.
Hypercalcemia
AlthoughIonIzed[Ca
2+
]mostaccuratelydefIneshypercalcemIa(IonIzed[Ca
2+
]1.5mmol/L
ortotalserumcalcIum10.5mg/dL),hypercalcemIacustomarIlyIsdIscussedIntermsof
totalserumcalcIum.nhypoalbumInemIcpatIents,totalserumcalcIumcanbeestImated
(albeItInaccurately)byassumInganIncreaseof0.8mg/dLforevery1g/dLofalbumIn
concentratIonbelow4.0g/dL.PatIentsInwhomtotalserumcalcIumIs11.5mg/dLare
usuallyasymptomatIc.PatIentswIthmoderatehypercalcemIa(totalserumcalcIum11.5to
1Jmg/dL)mayshowsymptomsoflethargy,anorexIa,nausea,andpolyurIa.Severe
hypercalcemIa(totalserumcalcIum1Jmg/dL)IsassocIatedwIthmoresevere
neuromyopathIcsymptoms,IncludIngmuscleweakness,depressIon,ImpaIredmemory,
emotIonallabIlIty,lethargy,stupor,andcoma.ThecardIovasculareffectsof
hypercalcemIaIncludehypertensIon,arrhythmIas,heartblock,cardIacarrest,anddIgItalIs
sensItIvIty.SkeletaldIseasemayoccursecondarytodIrectosteolysIsorhumoralbone
resorptIon.
HypercalcemIaImpaIrsurInaryconcentratIngabIlItyandrenalexcretorycapacItyfor
calcIumbyIrreversIblyprecIpItatIngcalcIumsaltswIthIntherenalparenchymaandby
reducIngrenalbloodflowandCFF.nresponsetohypovolemIa,renaltubularreabsorptIon
ofsodIumenhancesrenalcalcIumreabsorptIon.EffectIvetreatmentofsevere
hypercalcemIaIsnecessarytopreventprogressIvedehydratIonandrenalfaIlureleadIngto
furtherIncreasesIntotalserumcalcIum,becausevolumedepletIonexacerbates
hypercalcemIa.
1JJ
HypercalcemIaoccurswhencalcIumenterstheEC7morerapIdlythan
thekIdneyscanexcretetheexcess.ClInIcally,hypercalcemIamostcommonlyresultsfrom
anexcessofboneresorptIonoverboneformatIon,usuallysecondarytomalIgnantdIsease,
hyperparathyroIdIsm,hypocalcIurIchypercalcemIa,thyrotoxIcosIs,ImmobIlIzatIon,and
granulomatousdIseases.CranulomatousdIseasesproducehypercalcIurIaand
hypercalcemIabecauseofconversIonbygranulomatoustIssueofcalcIdIoltocalcItrIol.
126
|alIgnancymayproducehypercalcemIaeItherthroughbonedestructIonorsecretIonby
malIgnanttIssueofhormonesthatpromotehypercalcemIa.ExamplesofmalIgnancy
assocIatedhormonaleffectsIncludesecretIonbysolIdtumorsofparathormonelIkepeptIdes
andderangementoftheFANKL/osteoprogenerInsystemInmultIplemyeloma.
1J4
PrImary
hyperparathyroIdIsmIsassocIatedwIthweakness,weIghtloss,andanemIa,symptomsthat
suggestmalIgnancybutmayresultsImplyfromhyperparathyroIdIsm.HypercalcemIa
assocIatedwIthgranulomatousdIseases(e.g.,sarcoIdosIs)resultsfromtheproductIonof
calcItrIolbygranulomatoustIssue.TocompensateforIncreasedgutabsorptIonorbone
resorptIonofcalcIum,renalexcretIoncanreadIlyIncreasefrom100tomorethan400
mg/day.FactorsthatpromotehypercalcemIamaybeoffsetbycoexIstIngdIsorders,suchas
pancreatItIs,sepsIs,orhyperphosphatemIa,thatcausehypocalcemIa.
AlthoughdefInItIvetreatmentofhypercalcemIarequIrescorrectIonofunderlyIngcauses,
temporIzIngtherapymaybenecessarytoavoIdcomplIcatIonsandtorelIevesymptoms.
TotalserumcalcIumexceedIng14mg/dLrepresentsamedIcalemergency.Ceneral
supportIvetreatmentIncludeshydratIon,correctIonofassocIatedelectrolyte
abnormalItIes,removalofoffendIngdrugs,dIetarycalcIumrestrIctIon,andIncreased
physIcalactIvIty.8ecauseanorexIaandantagonIsmbycalcIumofA0HactIonInvarIably
leadtosodIumandwaterdepletIon,InfusIonof0.9salInewIlldIluteserumcalcIum,
promoterenalexcretIon,andcanreducetotalserumcalcIumby1.5toJmg/dL.UrInary
outputshouldbemaIntaInedat200toJ00mL/hr.AsCFFIncreases,sodIumIonsIncrease
calcIumexcretIonbycompetIngwIthcalcIumIonsforreabsorptIonIntheproxImalrenal
tubulesandloopofHenle.
FurosemIdefurtherenhancescalcIumexcretIonbyIncreasIngtubularsodIum.PatIentswho
haverenalImpaIrmentmayrequIrehIgherdosesoffurosemIde.0urIngsalIneInfusIonand
forceddIuresIs,carefulmonItorIngofcardIopulmonarystatusandelectrolytes,especIally
magnesIumandpotassIum,IsrequIred.ntensIvedIuresIsandsalIneadmInIstratIoncan
achIevenetcalcIumexcretIonratesof2,000to4,000mgper24hours,arate8tImes
greaterthansalInealone,butstIllsomewhatlessthanthe6,000mgevery8hoursthatcan
beremovedbyhemodIalysIs.PatIentstreatedwIthphosphatesforhypercalcemIashouldbe
wellhydrated.
8oneresorptIon,theprImarycauseofhypercalcemIa,canbemInImIzedbyIncreasIng
physIcalactIvItyandInItIatIngdrugtherapywIthbIphosphonates,calcItonIn,
glucocortIcoIds,orcalcImetrIcs.
1J5
8Isphosphonates,currentlythefIrstlInetherapyfor
acutehypercalcemIa,InhIbItosteoclastfunctIonandvIabIlIty.8Isphosphonatesarethe
prIncIpaldrugsforthemanagementofhypercalcemIamedIatedbyosteoclastIcbone
resorptIon.
1J4
PamIdronate,unlIkeearlIerbIphosphonates,doesnotappeartoworsenrenal
InsuffIcIency.|orerecentlyreleasedbIphosphonatesIncludealendronate,rIsedronate.and
zoledronate.FIsedronatehasbeenassocIatedwIthlessgastroIntestInalmorbIdItythan
alendronate.
1J6,1J7
ZoledronatehasthemostrapIdonsetofactIonamongthe
bIphosphonatesandprolongstheduratIonbeforerelapseofhypercalcemIa;however,
zoledronatehasbeenassocIatedwIthcompromIsedrenalfunctIon.
1J5
8Iphosphonatesalso
areusedtocontrolosteoporosIsInbothmenandwomen.
1J8,1J9
CalcItonIn,usuallyreservedasasecondarytreatmentforlIfethreatenInghypercalcemIa,
lowersserumcalcIumwIthIn24to48hoursandIsmoreeffectIvewhencombInedwIth
glucocortIcoIds.
1J4,1J5
UsuallycalcItonInreducestotalserumcalcIumbyonly1to2mg/dL.
AlthoughcalcItonInIsrelatIvelynontoxIc,morethan25ofpatIentsmaynotrespond.
Thus,calcItonInIsunsuItableasafIrstlInedrugdurInglIfethreatenInghypercalcemIa.
HydrocortIsoneIseffectIveIntreatInghypercalcemIcpatIentswIthlymphatIc
malIgnancIes,vItamIn0orAIntoxIcatIon,anddIseasesassocIatedwIthproductIonby
tumororgranulomasof1,25(DH)
2
0orosteoclastactIvatIngfactor.ClucocortIcoIdsrarely
ImprovehypercalcemIasecondarytomalIgnancyorhyperparathyroIdIsm.
P.J19
nthenearfuture,calcImetIcsmaybecomethetreatmentofchoIceforsuppressIng
prImary,secondary,andtertIaryhyperparathyroIdIsm.WIththefIrstagent,cInacalcet,
recentlyreleasedforclInIcaluseIntheUnItedStatesandothersundergoIngclInIcaltrIals,
calcImetIcagentsalsoreduceInorganIcphosphateconcentratIon(PI)andthecalcIum
phosphateproduct.
140,141,142
AlthoughhyperparathyroIdectomyremaInsthetreatmentof
choIceforprImaryhyperparathyroIdIsm,calcImetIcsrepresentanalternatIveforpatIents
whoarenotacceptablecandIdatesforsurgery.
142
nhyperparathyroIdIsmsecondaryto
chronIcrenalfaIlure,conventIonaltreatmentwIthcalcIumsupplements,phosphate
bInders,andvItamIn0analogsreducestheassocIatedsecondaryhyperparathyroIdIsmbut
alsogenerateundesIrablesIdeeffects,IncludInghypercalcemIa.
140
neffect,suchpatIents
developavarIatIonofthemIlkalkalIsyndrome.
14J
nchronIcrenalfaIlurepatIents,
calcImetIcsreduceserumcalcIum,PIandthecalcIumphosphateproductbysensItIzIng
theparathyroIdcalcIumreceptortocalcIum.
141
naddItIon,calcImetIcsappeartobe
effectIveIntertIaryhyperparathyroIdIsm,whIchdevelopsafterrenaltransplantatIonIn25
to50ofrenalallograftrecIpIents.
142
PhosphateslowerserumcalcIumbycausIngdeposItIonofcalcIumInboneandsofttIssue.
8ecausetherIskofextraskeletalcalcIfIcatIonoforganssuchasthekIdneysand
myocardIumIslessIfphosphatesaregIvenorally,theIntravenousrouteshouldbereserved
forpatIentswIthlIfethreatenInghypercalcemIaandthoseInwhomothermeasureshave
faIled.
Phosphate
Physiologic Role
Phosphorus,IntheformofInorganIcphosphate(PI),IsdIstrIbutedInsImIlarconcentratIons
throughoutIntracellularandextracellularfluId.Dftotalbodyphosphorus,90exIstsIn
bone,10IsIntracellular,andtheremaInder,1,IsfoundIntheextracellularfluId.
PhosphatecIrculatesasthefreeIon(55),complexedIon(JJ),andInaproteInbound
form(12).8loodlevelsvarywIdely:thenormaltotalPIrangesfrom2.7to4.5mg/dLIn
adults.
ControlofPIIsachIevedbyalteredrenalexcretIonandredIstrIbutIonwIthInthebody
compartments.AbsorptIonoccursIntheduodenumandjejunumandIslargelyunregulated.
PhosphatereabsorptIonInthekIdneyIsprImarIlyregulatedbyPTH,dIetaryIntake,and
InsulInlIkegrowthfactor.PhosphateIsfreelyfIlteredattheglomerulusandIts
concentratIonIntheglomerularultrafIltrateIssImIlartothatofplasma.ThefIltered
phosphateIsthenreabsorbedIntheproxImaltubulewhereItIscotransportedwIthsodIum.
ProxImaltubularreabsorptIonofphosphorusoccursbypassIvecotransportwIthsodIum.
CotransportIsregulatedbyphosphorusIntakeandPTH.PhosphateexcretIonIsIncreasedby
volumeexpansIonanddecreasedbyrespIratoryalkalosIs.
PhosphatesprovIdetheprImaryenergybondInATPandcreatInephosphate.Therefore,
severephosphatedepletIonresultsIncellularenergydepletIon.PhosphorusIsanessentIal
elementofsecondmessengersystems,IncludIngcA|PandphosphoInosItIdes,andamajor
componentofnucleIcacIds,phospholIpIds,andcellmembranes.Aspartof2,J
dIphosphoglycerate,phosphatepromotesreleaseofoxygenfromthehemoglobInmolecule.
PhosphorusalsofunctIonsInproteInphosphorylatIonandactsasaurInarybuffer.
Hypophosphatemia
HypophosphatemIaIscharacterIzedbylowlevelsofphosphatecontaInIngcellular
components,IncludIngATP,2,JdIphosphoglycerate,andmembranephospholIpIds.SerIous
lIfethreatenIngorgandysfunctIonmayoccurwhentheserumPIfallsbelow1mg/dL.
NeurologIcmanIfestatIonsofhypophosphatemIaIncludeparesthesIas,myopathy,
encephalopathy,delIrIum,seIzures,andcoma.
144
HematologIcabnormalItIesInclude
dysfunctIonoferythrocytes,platelets,andleukocytes.8ecausehypophosphatemIalImIts
thechemotactIc,phagocytIc,andbacterIcIdalactIvItyofgranulocytes,assocIatedImmune
dysfunctIonmaycontrIbutetothesusceptIbIlItyofhypophosphatemIcpatIentstosepsIs.
145
|uscleweaknessandmalaIsearecommon.FespIratorymusclefaIlureandmyocardIal
dysfunctIonarepotentIalproblemsofpartIcularconcerntoanesthesIologIsts.
FhabdomyolysIsIsacomplIcatIonofseverehypophosphatemIa.
CommonInpostoperatIveandtraumatIzedpatIents,hypophosphatemIa(PI2.5mg/dL)Is
causedbythreeprImaryabnormalItIesInPIhomeostasIs:anIntracellularshIftofPI,an
IncreaseInrenalPIloss,andadecreaseIngastroIntestInalPIabsorptIon.Carbohydrate
InducedhypophosphatemIa(therefeedIngsyndrome),
146
medIatedbyInsulInInduced
cellularPIuptake,IsthetypemostcommonlyencounteredInhospItalIzedpatIents.
HypophosphatemIamayalsooccurascatabolIcpatIentsbecomeanabolIcanddurIng
medIcalmanagementofdIabetIcketoacIdosIs.AcutealkalemIa,whIchmayreduceserum
PIto1to2mg/dL,IncreasesIntracellularconsumptIonofPIbyIncreasIngtherateof
glycolysIs.HyperventIlatIonsIgnIfIcantlyreducesPIand,Importantly,theeffectIs
progressIveaftercessatIonofhyperventIlatIon.
147
AcutecorrectIonofrespIratoryacIdemIa
mayalsoresultInseverehypophosphatemIa.FespIratoryalkalosIsprobablyexplaInsthe
hypophosphatemIaassocIatedwIthCramnegatIvebacteremIaandsalIcylatepoIsonIng.
ExcessIverenallossofPIexplaInsthehypophosphatemIaassocIatedwIth
hyperparathyroIdIsm,hypomagnesemIa,hypothermIa,dIuretIctherapy,andrenaltubular
defectsInPIabsorptIon.ExcessgastroIntestInallossofPIIsmostcommonlysecondaryto
theuseofPIbIndIngantacIdsortomalabsorptIonsyndromes.
|easurementofurInaryPIaIdsIndIfferentIatIonofhypophosphatemIaduetorenallosses
fromthatareduetoexcessIvegastroIntestInallossesorredIstrIbutIonofPIIntocells.
ExtrarenalcausesofhypophosphatemIacauseavIdrenaltubularPIreabsorptIon,reducIng
urInaryexcretIonto100mg/day.
PatIentswhohavesevere(1mg/dL)orsymptomatIchypophosphatemIarequIre
IntravenousphosphateadmInIstratIon(Table1422).
144,147
nchronIcallyhypophosphatemIc
patIents,0.2to0.68mmol/kg(5to16mg/kgelementalphosphorus)shouldbeInfusedover
12hours.FormoderatelyhypophosphatemIcadultpatIentssufferIngfromcrItIcalIllness,
theuseof15mmolboluses(465mg)mIxedwIth100mLof0.9sodIumchlorIdeandgIven
overa2hourperIodsafelyrepletesphosphate.
148
ThedosageIsthenadjustedasIndIcated
bytheserumPIlevelbecausethecumulatIvedefIcItcannotbepredIctedaccurately.Dral
therapycanbesubstItutedforparenteralPIoncetheserumPIlevelexceeds2.0mg/dL.
ContInuedtherapywIthPIsupplementsIsrequIredfor5to10daysInordertoreplenIsh
bodystores.
Table 14-22 Hypophosphatemia: Acute Treatment
Parenteralphosphate,0.2m|to0.68m|/kg(516mg/kg)over12hr
PotassIumphosphate(9Jmg/mLofphosphate)
SodIumphosphate(9Jmg/mLofphosphate)
P.J20
PhosphateshouldbeadmInIsteredcautIouslytohypocalcemIcpatIentsbecauseoftherIsk
ofprecIpItatIngmoreseverehypocalcemIa.nhypercalcemIcpatIents,PImaycausesoft
tIssuecalcIfIcatIon.PhosphorusmustbegIvencautIouslytopatIentswIthrenal
InsuffIcIencybecauseofImpaIredexcretoryabIlIty.0urIngtreatment,closemonItorIngof
serumPI,calcIum,magnesIum,andpotassIumIsessentIaltoavoIdcomplIcatIons.
Hyperphosphatemia
TheclInIcalfeaturesofhyperphosphatemIa(PI5.0mg/dL)relateprImarIlytothe
developmentofhypocalcemIaandectopIccalcIfIcatIon.HyperphosphatemIaIscausedby
threebasIcmechanIsms:InadequaterenalexcretIon,IncreasedmovementofPIoutof
cells,andIncreasedPIorvItamIn0Intake.FapIdcelllysIsfromchemotherapy,
rhabdomyolysIs,andsepsIscancausehyperphosphatemIa,especIallywhenrenalfunctIonIs
ImpaIred.FenalfaIlureIsthemostcommoncauseofhyperphosphatemIa.
FenalexcretIonofPIremaInsadequateuntIltheCFFfallsbelow20to25mL/mIn.
AccumulatIonofPIInpatIentswIthchronIcrenalfaIluremerItstheInclusIonofPIasa
uremIctoxIn.
149
|easurementsof8UN,creatInIne,CFF,andurInaryPIarehelpfulInthedIfferentIal
dIagnosIsofhyperphosphatemIa.NormalrenalfunctIonaccompanIedbyhIghPIexcretIon
(1,500mg/day)IndIcatesanoversupplyofPI.Anelevated8UN,elevatedcreatInIne,and
lowCFFsuggestImpaIredrenalexcretIonofPI.NormalrenalfunctIonandPIexcretIon
1,500mg/daysuggestIncreasedPIreabsorptIon(I.e.,hypoparathyroIdIsm).
HyperphosphatemIaIscorrectedbyelImInatIngthecauseofthePIelevatIonandcorrectIng
theassocIatedhypocalcemIa.CalcIumsupplementatIonofhypocalcemIcpatIentsshouldbe
delayeduntIlserumphosphatehasfallenbelow2.0mmol/L(6.0mg/dL).
126
Theserum
concentratIonofPIIsreducedbyrestrIctIngIntake,IncreasIngurInaryexcretIonwIthsalIne
andacetazolamIde(500mgevery6hours),andIncreasInggastroIntestInallossesbyenterIc
admInIstratIonofalumInumhydroxIde(J0to45mLevery6hours).
AlthoughcalcImetIcsmayreplacePIbIndersformanagInghyperphosphatemIaInpatIents
wIthchronIcrenalfaIlure,severalremaInIncommonuse.CalcIumbasedbIndersmay
contrIbutetohypercalcemIa,sevelamerhydrochlorIdebIndsbIleacIds,andlanthanum
carbonateofferstheadvantageofrequIrIngpatIentstoIngestfewerpIlls.
150
HemodIalysIs
andperItonealdIalysIsareeffectIveInremovIngPIInpatIentswhohaverenalfaIlure.
Magnesium
Physiologic Role
|agnesIumIsanImportant,multIfunctIonal,dIvalentcatIonlocatedprImarIlyInthe
Intracellularspace.ApproxImately50ofthetypIcaladult's24gofmagnesIumIslocatedIn
bone,12gIslocatedIntracellularly(approxImatelyonehalfor6gInmuscle),and1
(240mg)oftotalbodymagnesIumcIrculatesIntheserum.
151
DfthenormalcIrculatIng
totalmagnesIumconcentratIon(1.5to1.9mEq/Lor0.75to0.95mmol/Lor1.5to1.9
mg/dL),therearethreecomponents:proteInbound(J0),anIonbound(15),andIonIzed
(55),ofwhIchonlyIonIzedmagnesIumIsactIve.
|agnesIumIsnecessaryforenzymatIcreactIonsInvolvIng0NAandproteInsynthesIs,
energymetabolIsm,glucoseutIlIzatIon,andfattyacIdsynthesIsandbreakdown.
152
Asa
prImaryregulatororcofactorInmanyenzymesystems,magnesIumIsImportantforthe
regulatIonofthesodIumpotassIumpump,CaATPaseenzymes,adenylcyclase,proton
pumps,andslowcalcIumchannels.|agnesIumhasbeencalledanendogenous calcium
antagonistbecauseregulatIonofslowcalcIumchannelscontrIbutestomaIntenanceof
normalvasculartone,preventIonofvasospasm,andperhapsthepreventIonofcalcIum
overloadInmanytIssues.8ecausemagnesIumpartIallyregulatesPTHsecretIonandIs
ImportantforthemaIntenanceofendorgansensItIvItytobothPTHandvItamIn0,
abnormalItIesInIonIzedmagnesIumconcentratIon([|g
2+
])mayresultInabnormalcalcIum
metabolIsm.|agnesIumfunctIonsInpotassIummetabolIsmprImarIlythroughregulatIng
sodIumpotassIumATPase,anenzymethatcontrolspotassIumentryIntocells,especIallyIn
potassIumdepletedstates,andcontrolsreabsorptIonofpotassIumbytherenaltubules.n
addItIon,magnesIumfunctIonsasaregulatorofmembraneexcItabIlItyandservesasa
structuralcomponentInbothcellmembranesandtheskeleton.
8ecausemagnesIumstabIlIzesaxonalmembranes,hypomagnesemIadecreasesthe
thresholdofaxonalstImulatIonandIncreasesnerveconductIonvelocIty.|agnesIumalso
InfluencesthereleaseofneurotransmIttersattheneuromuscularjunctIonbycompetItIvely
InhIbItIngtheentryofcalcIumIntothepresynaptIcnervetermInals.TheconcentratIonof
calcIumrequIredtotrIggercalcIumreleaseandtherateatwhIchcalcIumIsreleasedfrom
thesarcoplasmIcretIculumareInverselyrelatedtotheambIentmagnesIumconcentratIon.
Thus,theneteffectofhypomagnesemIaIsmusclethatcontractsmoreInresponseto
stImulIandIstetanyprone.
|agnesIumIswIdelyavaIlableInfoodsandIsabsorbedthroughthegastroIntestInaltract,
althoughdIetaryconsumptIonappearstohavedecreasedoverseveraldecades.
152
Seventy
percentofplasmamagnesIumIsfIlteredthroughtheglomerularmembrane;ofthefIltered
magnesIum,J0IsabsorbedIntheproxImaltubule,60InthethIckascendIngloopof
Henle,and10to15InthedIstaltubule.
151
WhIlebothmagnesIumandPIareprImarIly
regulatedbyIntrInsIcrenalmechanIsms,PTHexertsagreatereffectonrenallossofPI.
|agnesIumhasbeenusedtohelpmanageanImpressIvearrayofclInIcalproblemsIn
patIentswhoarenothypomagnesemIc.TherapeutIchypermagnesemIaIsusedtotreat
patIentswIthprematurelabor,preeclampsIa,andeclampsIa.8ecausemagnesIumblocks
thereleaseofcatecholamInesfromadrenergIcnervetermInalsandtheadrenalglands,
magnesIumhasbeenusedreducetheeffectsofcatecholamIneexcessInpatIentswIth
tetanusandpheochromocytoma.
15J
npatIentsawaItInglIvertransplantatIon,onestudy
showedthatadmInIstratIonofmagnesIumsIgnIfIcantlyreversedhypocoagulabIlIty.
154
AlthoughclInIcaldataareInconsIstent,magnesIumalsomayexertananalgesIceffecton
postoperatIvepaIn,
15J,155
perhapsInpartduetomagnesIum'santagonIsmoftheNmethyl
0aspartateglutamatereceptor.
15J
|agnesIumhasbeenproposedaspartofan
antIvasospasmregImenaftersubarachnoIdhemorrhage,butItseffIcacymaybelImItedby
InductIonofIncreasIngmagnesIumlevelsofhypocalcemIa,whIchInturncouldaggravate
cerebralvasospasm.
156
SurprIsIngly,redIstrIbutIonofmagnesIumaftersubarachnoId
hemorrhagehasbeencorrelatedwIthECCchanges.
157
|agnesIumadmInIstratIonmayInfluencedysrhythmIasbydIrecteffectsonmyocardIal
membranes,byalterIngcellularpotassIumandsodIumconcentratIons,byInhIbItIng
cellularcalcIumentry,byImprovIngmyocardIaloxygensupplyanddemand,byprolongIng
theeffectIverefractoryperIod,bydepressIngconductIon,byantagonIzIngcatecholamIne
actIonontheconductIngsystem,andbypreventIngvasospasm.AdmInIstratIonof
magnesIumreducestheIncIdenceofdysrhythmIasaftermyocardIalInfarctIonandIn
patIentswIthcongestIveheartfaIlure.
158
nhumanswIthIschemIcmyocardIum,
magnesIumpreventedIschemIcIncreasesInactIonpotentIalduratIonandmembrane
repolarIzatIon.
159
P.J21
AfteracutemyocardIalInfarctIon,IntravenousmagnesIumadmInIstratIondecreasedshort
termmortalIty.
160
naddItIon,magnesIummaybeusefulastreatmentfortorsadesde
poIntes,evenInnormomagnesemIcpatIents.
161
TreatmentofhypomagnesemIadurIng
cardIopulmonarybypassdecreasedtheIncIdenceofpostoperatIveventrIculartachycardIa
fromJ0to7andIncreasedthefrequencyofcontInuoussInusrhythmfrom5toJ4.
162
Hypomagnesemia
TheclInIcalfeaturesofhypomagnesemIa([|g
2+
]1.8mg/dL),lIkethoseofhypocalcemIa,
arecharacterIzedbyIncreasedneuronalIrrItabIlItyandtetany(Table142J).
151
Symptoms
arerarewhentheserum[|g
2+
]Is1.5to1.7mg/dL;InmostsymptomatIcpatIentsserum
[|g
2+
]Is1.2mg/dL.PatIentsfrequentlycomplaInofweakness,lethargy,musclespasms,
paresthesIas,anddepressIon.Whensevere,hypomagnesemIamayInduceseIzures,
confusIon,andcoma.CardIovascularabnormalItIesIncludecoronaryarteryspasm,cardIac
faIlure,dysrhythmIas,andhypotensIon.SeverehypomagnesemIamayreducetheresponse
ofadenylatecyclasetostImulatIonofthePTHreceptor.
16J
HypomagnesemIacanaggravate
dIgoxIntoxIcItyandcongestIveheartfaIlure.
FarelyresultIngfromInadequatedIetaryIntake,hypomagnesemIamostcommonlyIs
causedbyInadequategastroIntestInalabsorptIon,excessIvemagnesIumlosses,orfaIlureof
renalmagnesIumconservatIon.HypomagnesemIaIspartIcularlyfrequentInalcoholIc
patIents.
151
DfalcoholIcpatIentsadmIttedtothehospItal,J0arehypomagnesemIc.
164
ExcessIvelossofmagnesIumIsassocIatedwIthprolongednasogastrIcsuctIonIng,
gastroIntestInalorbIlIaryfIstulas,andIntestInaldraIns.nabIlItyoftherenaltubulesto
conservemagnesIumcomplIcatesavarIetyofsystemIcandrenaldIseases,although
advancedrenaldIseasewIthadecreasedCFFmayleadtomagnesIumretentIon.PolyurIa,
whethersecondarytoEC7expansIonortopharmacologIcorpathologIcdIuresIs,mayresult
InexcessIveurInarymagnesIumexcretIon.7arIousdrugs,IncludIngamInoglycosIdes,cis
platInum,cardIacglycosIdes,anddIuretIcs,enhanceurInarymagnesIumexcretIon.
ntracellularshIftsofmagnesIumasaresultofthyroIdhormoneorInsulInadmInIstratIon
mayalsodecreaseserum[|g
2+
].
8ecausethesodIumpotassIumpumpIsmagnesIumdependent,hypomagnesemIaIncreases
myocardIalsensItIvItytodIgItalIspreparatIonsandmaycausehypokalemIaasaresultof
renalpotassIumwastIng.AttemptstocorrectpotassIumdefIcItswIthpotassIum
replacementtherapyalonemaynotbesuccessfulwIthoutsImultaneousmagnesIum
therapy.|agnesIumIsImportantIntheregulatIonofpotassIumchannels.The
InterrelatIonshIpsofmagnesIumandpotassIumIncardIactIssuehaveprobablythegreatest
clInIcalrelevanceIntermsofdysrhythmIas,dIgoxIntoxIcIty,andmyocardIalInfarctIon.
8othseverehypomagnesemIaandhypermagnesemIasuppressPTHsecretIonandcancause
hypocalcemIa.SeverehypomagnesemIamayalsoImpaIrendorganresponsetoPTH.
HypomagnesemIaIsassocIatedwIthhypokalemIa,hyponatremIa,hypophosphatemIa,and
hypocalcemIa.ThereportedprevalenceofhypomagnesemIaInhospItalIzedandcrItIcally
IllpatIentsvarIesfrom11to61,wIththevarIabIlItyattrIbutabletodIfferencesIn
measurementtechnIque.
165
FecentdevelopmentofaspecIfIcelectrodetomeasureIonIzed
[|g
2+
]hasdemonstratedanassocIatIonbetweenhypomagnesemIa,useof
P.J22
dIuretIcs,anddevelopmentofsepsIs.
165
PatIentswhodevelophypomagnesemIawhIleIn
IntensIvecarehaveanIncreasedmortalIty.
165
Serum[|g
2+
]maynotreflectIntracellular
magnesIumcontent.PerIpherallymphocytemagnesIumconcentratIoncorrelateswellwIth
skeletalandcardIacmagnesIumcontent.
Table 14-23 Manifestations of Altered Serum Magnesium Concentrations
MAGNESIUM LEVEL
MANIFESTATION
mg/dL mEq/L mmol/L
1.2 1 0.5
Tetany
SeIzures
ArrhythmIas
1.21.8 1.01.5 0.50.75
NeuromuscularIrrItabIlIty
HypocalcemIa
HypokalemIa
1.82.5 1.52.1 0.751.05 NormalmagnesIumlevel
2.55.0 2.14.2 1.052.1 TypIcallyasymptomatIc
5.07.0 4.25.8 2.12.9
Lethargy
0rowsIness
FlushIng
NauseaandvomItIng
0ImInIsheddeeptendonreflex
7.012 5.810 2.95
Somnolence
Lossofdeeptendonreflexes
HypotensIon
ECCchanges
12 10 5
Completeheartblock
CardIacarrest
Apnea
ParalysIs
Coma
FeprIntedfromTopfJ|,|urrayPT:HypomagnesemIaandhypermagnesemIa.Fev
Endocr|etab0Isord200J;4:195206,wIthpermIssIon.
Table 14-24 Hypomagnesemia: Acute Treatment
ntravenous|g
a
:816mEq(12g|gSD
4
)bolusover1hr,followedby24mEq/hr
(250500mg/hr|gSD
4
)ascontInuousInfusIon
ntramuscular|g
a
:10mEqq46hr
a
|gSD
4
:1g=8mEq/mg;|gCl
2
:1g=10mEq/mg.
|easurementof24hoururInarymagnesIumexcretIonIsusefulInseparatIngrenalfrom
nonrenalcausesofhypomagnesemIa.NormalkIdneyscanreducemagnesIumexcretIonto
1to2mEq/dayInresponsetomagnesIumdepletIon.HypomagnesemIaaccompanIedby
hIghurInaryexcretIonofmagnesIum(Jto4mEq/day)suggestsarenaletIology.nthe
magnesIumloadIngtest,urInary[|g
2+
]excretIonIsmeasuredfor24hoursafteran
IntravenousmagnesIumload.
166
|agnesIumdefIcIencyIstreatedbytheadmInIstratIonofmagnesIumsupplements(Table
1424).DnegramofmagnesIumsulfateprovIdesapproxImately4mmol(8mEq,or98mg)
ofelementalmagnesIum.|IlddefIcIencIescanbetreatedwIthdIetalone.Feplacement
mustbeaddedtodaIlymagnesIumrequIrements(0.Jto0.4mEq/kg/day).SymptomatIcor
severehypomagnesemIa([|g
2+
]1.0mg/dL)shouldbetreatedwIthparenteralmagnesIum:
1to2g(8to16mEq)ofmagnesIumsulfateasanIntravenousbolusoverthefIrsthour,
followedbyacontInuousInfusIonof2to4mEq/hr.TherapyshouldbeguIdedsubsequently
bytheserummagnesIumlevel.TherateofInfusIonshouldnotexceed1mEq/mIn,evenIn
emergencysItuatIons,andthepatIentshouldreceIvecontInuouscardIacmonItorIngto
detectcardIotoxIcIty.8ecausemagnesIumantagonIzescalcIum,bloodpressureandcardIac
functIonshouldbemonItored,althoughbloodpressureandcardIacoutputusuallychange
lIttledurIngmagnesIumInfusIon.
0urIngrepletIon,patellarreflexesshouldbemonItoredfrequentlyandmagnesIumwIthheld
Iftheybecomesuppressed.PatIentswhohaverenalInsuffIcIencyhaveadImInIshedabIlIty
toexcretemagnesIumandrequIrecarefulmonItorIngdurIngtherapy.FepletIonofsystemIc
magnesIumstoresusuallyrequIres5to7daysoftherapy,afterwhIchdaIlymaIntenance
dosesofmagnesIumshouldbeprovIded.|agnesIumcanbegIvenorally,usuallyInadose
of60to90mEq/dayofmagnesIumoxIde.HypocalcemIc,hypomagnesemIcpatIentsshould
receIvemagnesIumasthechlorIdesaltbecausethesulfateIoncanchelatecalcIumand
furtherreducetheserum[Ca
2+
].
Hypermagnesemia
|ostcasesofhypermagnesemIa([|g
2+
]2.5mg/dL)areIatrogenIc,resultIngfromthe
admInIstratIonofmagnesIumInantacIds,enemas,orparenteralnutrItIon,especIallyto
patIentswIthImpaIredrenalfunctIon.DtherrarercausesofmIldhypermagnesemIaare
hypothyroIdIsm,AddIsondIsease,lIthIumIntoxIcatIon,andfamIlIalhypocalcIurIc
hypercalcemIa.HypermagnesemIaIsrarelydetectedInroutIneelectrolyte
determInatIons.
151
HypermagnesemIaantagonIzesthereleaseandeffectofacetylcholIne
attheneuromuscularjunctIon.TheresultIsdepressedskeletalmusclefunctIonand
neuromuscularblockade.|agnesIumpotentIatestheactIonofnondepolarIzIngmuscle
relaxantsanddecreasespotassIumreleaseInresponsetosuccInylcholIne.TheclInIcal
featuresofprogressIvehypermagnesemIaarelIstedInTable142J.
151
TheneuromuscularandcardIactoxIcItyofhypermagnesemIacanbeacutely,but
transIently,antagonIzedbygIvIngIntravenouscalcIum(5to10mEq)tobuytImewhIle
moredefInItIvetherapyIsInstItuted.
151
AllmagnesIumcontaInIngpreparatIonsmustbe
stopped.UrInaryexcretIonofmagnesIumcanbeIncreasedbyexpandIngEC7andInducIng
dIuresIswIthacombInatIonofsalIneandfurosemIde.nemergencysItuatIonsandIn
patIentswIthrenalfaIlure,magnesIummayberemovedbydIalysIs.
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Stock, M. Christine
TableofContentsSectIonAnatomyandPhysIologyChapter15AutonomIcNervousSystem
Chapter15
Autonomic Nervous System
Joel O. Johnson
Loreta Grecu
Noel W. Lawson
Key Points
1. The autonomic nervous system (ANS) includes that part of the
central and peripheral nervous system concerned with involuntary
regulation of cardiac muscle, smooth muscle, glandular, and visceral
functions.
2. The sympathetic and parasympathetic nervous systems (SNS, PNS)
affect cardiac pump function in three ways: (1) by changing the rate
(chronotropism), (2) by changing the strength of contraction
(inotropism), and (3) by modulating coronary blood flow.
3. SNS nerves are by far the most important regulators of the
peripheral circulation.
4. The ANS can be pharmacologically subdivided by the
neurotransmitter secreted at the effector cell: acetylcholine (ACh)
released by the PNS and the catecholamines epinephrine (EPI) and
norepinephrine (NE) are considered the mediators of peripheral SNS
activity.
5. An agonist is a substance that interacts with a receptor to evoke a
biologic response. An antagonist is a substance that interferes with
the evocation of a response at a receptor site by an agonist.
6. The adrenergic receptors are termed adrenergic or noradrenergic,
depending on their responsiveness to epinephrine or norepinephrine.
7. The numbers and sensitivity of adrenergic receptors can be
influenced by normal, genetic, and developmental factors.
8. The autonomic nervous system reflex has (1) sensors, (2) afferent
pathways, (3) central nervous system integration, and (4) efferent
pathways to the receptors and efferent organs.
9. The clinical application of ANS pharmacology is based on knowledge
of ANS anatomy, physiology, and molecular pharmacology.
10. Clinically, anticholinesterase drugs may be divided into two types: the
reversible and nonreversible cholinesterase inhibitors.
11. The net physiologic effect of a sympathomimetic is usually defined by
the relative actions on the , , and dopamine receptors.
12. Dexmedetomidine is a more selective
2
agonist than clonidine.
13. Drugs that bind selectively to -adrenergic receptors block the action
of endogenous catecholamines or moderate the effects of exogenous
adrenergics.
14. Calcium channel blockers are not true pharmacologic antagonists of
calcium. They interact with the cell membrane to control the
intracellular concentration of calcium.
Anesthesia and the Autonomic Nervous System
AnesthesIologyIsthepractIceofautonomIcmedIcIne.0rugsthatproduceanesthesIaalso
producepotentautonomIcsIdeeffects.ThegreaterpartofourtraInIngandpractIceIs
spentacquIrIngskIllsInavertIngorusIngtheautonomIcnervoussystem(ANS)sIdeeffects
ofanesthetIcdrugsunderavarIetyofpathophysIologIccondItIons.Thesuccessofany
anesthetIcdependsonhowwellhomeostasIsIsmaIntaIned.ThenumbersthatwefaIthfully
recorddurIngthecourseofanesthesIareflectANSfunctIon.
P.J27
TheANSIncludesthatpartofthecentralandperIpheralnervoussystemconcernedwIth
InvoluntaryregulatIonofcardIacmuscle,smoothmuscle,glandular,andvIsceralfunctIons.
ANSactIvItyreferstovIsceralreflexesthatfunctIonbelowtheconscIouslevel.TheANSIs
alsoresponsIvetochangesInsomatIcmotorandsensoryactIvItIesofthebody.The
physIologIcevIdenceofvIsceralreflexesasaresultofsomatIceventsIsabundantlyclear.
TheANSIsthereforenotasdIstInctanentItyasthetermsuggests.NeIthersomatIcnorANS
actIvItyoccursInIsolatIon.
1
TheANSorganIzesvIsceralsupportforsomatIcbehavIorand
adjustsbodystatesInantIcIpatIonofemotIonalbehavIororresponsestothestressof
dIsease(I.e.,fIghtorflIght).
AfferentfIbersfromvIsceralstructuresarethefIrstlInkInthereflexarcsoftheANS
whetherrelayIngvIsceralpaInorchangesInvesselstretch.|ostANSefferentfIbersare
accompanIedbysensoryfIbersthatarenowcommonlyrecognIzedascomponentsofthe
ANS.However,theafferentcomponentsoftheANScannotbeasdIstInctIvelydIvIded,as
cantheefferentnerves.ANSvIsceralsensorynervesareanatomIcallyIndIstInguIshable
fromsomatIcsensorynerves.TheclInIcalImportanceofvIsceralafferentfIbersIsmore
closelyassocIatedwIthchronIcpaInmanagement.
Functional Anatomy
TheANSfallsIntotwodIvIsIonsbyanatomy,physIology,andpharmacology.Langley
dIvIdedthIsnervoussystemIntotwopartsIn1921.HeretaInedthetermsympathetic
nervoussystem(SNS)IntroducedbyWIllIsIn1665forthefIrstpartandIntroducedtheterm
parasympathetic(parasympathetIcnervoussystem,PNS)forthesecond.Theterm
autonomic nervous systemwasadoptedasacomprehensIvenameforboth.Table151lIsts
thecomplementaryeffectsofSNS(adrenergIc,sympathetIc)andPNS(cholInergIc,
parasympathetIc)actIvItyoforgansystems.
Central Autonomic Organization
PurecentralANSorsomatIccentersarenotknown.ntegratIonofANSactIvItyoccursat
alllevelsofthecerebrospInalaxIs.EfferentANSactIvItycanbeInItIatedlocallyandby
centerslocatedInthespInalcord,braInstem,andhypothalamus.ThecerebralcortexIsthe
hIghestlevelofANSIntegratIon.FaIntIngatthesIghtofbloodIsanexampleofthIshIgher
levelofsomatIcandANSIntegratIon.ANSfunctIonhasalsobeen
P.J28
successfullymodulatedthroughconscIous,IntentIonaleffortsdemonstratIngthatsomatIc
responsesarealwaysaccompanIedbyvIsceralresponsesandvIceversa.
Table 15-1 Homeostatic Balance Between Adrenergic and Cholinergic
Effects
ORGAN SYSTEM
RESPONSE
ADRENERGIC CHOLINERGIC
HEAFT
SInoatrIalnode TachycardIa 8radycardIa
AtrIoventrIcular
node
ncreasedconductIon
0ecreased
conductIon
HIsPurkInje
ncreasedautomatIcItyand
|InImal
conductIonvelocIty
|yocardIum
ncreasedcontractIlIty,conductIon
velocIty,automatIcIty
|InImaldecreaseIn
contractIlIty
Coronaryvessels
ConstrIctIon(
1
)anddIlatIon(
1
)
0IlatIonand
constrIctIon:
a
8LDD07ESSELS
SkInandmucosa ConstrIctIon 0IlatIon
Skeletalmuscle
ConstrIctIon(
1
)dIlatIon(
2
)
0IlatIon
Pulmonary ConstrIctIon :0IlatIon
8FDNCHAL
S|DDTH|USCLE
FelaxatIon ContractIon
CASTFDNTESTNALTFACT
Callbladderand
ducts
FelaxatIon ContractIon
CutmotIlIty 0ecreased ncreased
SecretIons 0ecreased ncreased
SphIncters ConstrIctIon FelaxatIon
8LA00EF
0etrusor Felaxes Contracts
TrIgone Contracts Felaxes
CLAN0S
Nasal
7asoconstrIctIonandreduced
secretIon
StImulatIonof
secretIons
LacrImal
ParotId
SubmandIbular
CastrIc
PancreatIc
SWEATCLAN0S 0IaphoresIs(cholInergIc) None
APDCFNE
CLAN0S
ThIck,odIferoussecretIon None
EYE
PupIl |ydrIasIs |IosIs
CIlIarymuscle FelaxatIonforfarvIsIon
ContractIonfornear
vIsIon
a
SeenteractIonofAutonomIcNervousSystemFeceptors.
Figure 15-1.SchematIcdIstrIbutIonofthecranIosacral(parasympathetIc)and
thoracolumbar(sympathetIc)nervoussystems.ParasympathetIcpreganglIonIcfIbers
passdIrectlytotheorganthatIsInnervated.TheIrpostganglIonIccellbodIesare
sItuatednearorwIthIntheInnervatedvIscera.ThIslImIteddIstrIbutIonof
parasympathetIcpostganglIonIcfIbersIsconsIstentwIththedIscreteandlImItedeffect
ofparasympathetIcfunctIon.ThepostganglIonIcsympathetIcneuronsorIgInateIn
eItherthepaIredsympathetIcganglIaoroneoftheunpaIredcollateralplexuses.Dne
preganglIonIcfIberInfluencesmanypostganglIonIcneurons.ActIvatIonofthe
sympathetIcnervoussystemproducesamoredIffusephysIologIcresponseratherthan
dIscreteeffects.
TheprIncIpalsIteofANSorganIzatIonIsthehypothalamus.SNSfunctIonsarecontrolledby
nucleIIntheposterolateralhypothalamus.StImulatIonofthesenucleIresultsInamassIve
dIschargeofthesympathoadrenalsystem.PNSfunctIonsaregovernedbynucleIInthe
mIdlIneandsomeanterIornucleIofthehypothalamus.TheanterIorhypothalamusIs
InvolvedwIthregulatIonoftemperature.ThesupraoptIchypothalamIcnucleIregulate
watermetabolIsmandareanatomIcallyandfunctIonallyassocIatedwIththeposterIorlobe
ofthepItuItary(seenteractIonofAutonomIcNervousSystemFeceptors).ThIs
hypothalamIcneurohypophysealconnectIonrepresentsacentralANSmechanIsmthat
affectsthekIdneybymeansofantIdIuretIchormone.Longtermbloodpressurecontrol,
reactIonstophysIcalandemotIonalstress,sleep,andsexualreflexesareregulatedthrough
thehypothalamus.
Themedulla oblongataandponsarethevItalcentersofacuteANSorganIzatIon.Together
theyIntegratemomentaryhemodynamIcadjustmentsandmaIntaInthesequenceand
automatIcItyofventIlatIon.ntegratIonofafferentandefferentANSImpulsesatthIs
centralnervoussystem(CNS)levelIsresponsIbleforthetonIcactIvItyexhIbItedbythe
ANS.TonIcItyholdsvIsceralorgansInastateofIntermedIateactIvItythatcaneItherbe
dImInIshedoraugmentedbyalterIngtherateofnervefIrIng.Thenucleustractus
solItarIus,locatedwIthInthemedulla,IstheprImaryareaforrelayofafferent
chemoreceptorandbaroreceptorInformatIonfromtheglossopharyngealandvagusnerves.
ncreasedafferentImpulsesfromthesetwonervesInhIbItsperIpheralSNSvasculartone,
producIngvasodIlatIonandIncreasIngvagaltone,producIngbradycardIa.StudIesof
patIentswIthhIghspInalcordlesIonsshowthatanumberofreflexchangesaremedIated
atthespInalorsegmentallevel.ANShyperreflexIaIsanexampleofspInalcordmedIatIon
ofANSreflexeswIthoutIntegratIonoffunctIonfromhIgherInhIbItorycenters.
1
Peripheral Autonomic Nervous System Organization
TheperIpheralANSIstheefferent(motor)componentoftheANSandconsIstsofthesame
twocomplementaryparts,theSNSandthePNS.|ostorgansreceIvefIbersfromboth
dIvIsIons(FIg.151).ngeneral,actIvItIesofthetwosystemsproduceopposItebut
complementaryeffects(Table151).AfewtIssues,suchassweatglandsandspleen,are
InnervatedonlybySNSfIbers.AlthoughtheanatomyofthesomatIcandANSsensory
pathwaysIsIdentIcal,themotorpathwaysarecharacterIstIcallydIfferent.Theefferent
somatIcmotorsystem,lIkesomatIcafferents,IscomposedofasIngle(unIpolar)neuron
wIthItscellbodyIntheventralgraymatterofthespInalcord.tsmyelInatedaxonextends
dIrectlytothevoluntarystrIatedmuscleunIt.ncontrast,theefferent(motor)ANSIsa
twoneuron(bIpolar)chaInfromtheCNStotheeffectororgan.ThefIrstneuronofboththe
SNSandPNSorIgInateswIthIntheCNSbutdoesnotmakedIrectcontactwIththeeffector
organ.nstead,ItrelaystheImpulsetoasecondstatIonknownasanANS ganglion,whIch
contaInsthecellbodyofthesecondANS(postganglIonIc)neuron.tsaxoncontactsthe
effectororgan.Thus,themotorpathwaysofbothdIvIsIonsoftheANSareschematIcallya
serIal,twoneuronchaInconsIstIngofapreganglIonIcneuronandapostganglIonIceffector
neuron(FIg.152).
PreganglIonIcfIbersofbothsubdIvIsIonsaremyelInatedwIthdIametersofJmm.
1
mpulsesareconductedataspeedofJto15m/s.ThepostganglIonIcfIbersare
unmyelInatedandconductImpulsesatslowerspeedsof2m/s.TheyaresImIlar
P.J29
tounmyelInatedvIsceralandsomatIcafferentCfIbers(Table152).ComparedwIththe
myelInatedsomatIcnerves,theANSconductsImpulsesatspeedsthatprecludeIts
partIcIpatIonIntheImmedIatephaseofasomatIcresponse.
Figure 15-2.SchematIcdIagramoftheefferentautonomIcnervoussystem.Afferent
ImpulsesareIntegratedcentrallyandsentreflexlytotheadrenergIcandcholInergIc
receptors.SympathetIcfIbersendIngIntheadrenalmedullaarepreganglIonIc,and
acetylcholIne(ACh)IstheneurotransmItter.StImulatIonofthechromaffIncells,actIng
aspostganglIonIcneurons,releasesepInephrIne(EP)andnorepInephrIne(NE).
Sympathetic Nervous System
TheefferentSNSIsreferredtoasthethoracolumbar nervous system.FIgure151
demonstratesthedIstrIbutIonoftheSNSandItsInnervatIonofvIsceralorgans.The
preganglIonIcfIbersoftheSNS(thoracolumbardIvIsIon)orIgInateIntheIntermedIolateral
graycolumnofthe12thoracIc(T1throughT12)andthefIrstthreelumbarsegments(L1
throughLJ)ofthespInalcord.ThemyelInatedaxonsofthesenervecellsleavethespInal
cordwIththemotorfIberstoformthewhIte(myelInated)communIcatIngramI(FIg.15J).
TheramIenteroneofthepaIred22sympathetIcganglIaattheIrrespectIvesegmental
levels.DnenterIngtheparavertebralganglIaofthelateralsympathetIcchaIn,the
preganglIonIcfIbermayfollowoneofthreecourses:(1)synapsewIthpostganglIonIcfIbers
InganglIa
P.JJ0
atthelevelofexIt,(2)courseupwardordownwardInthetrunkoftheSNSchaInto
synapseInganglIaatotherlevels,or(J)trackforvarIabledIstancesthroughthe
sympathetIcchaInandexItwIthoutsynapsIngtotermInateInanoutlyIng,unpaIred,SNS
collateralganglIon(FIg.15J).TheadrenalglandIsanexceptIontotherule.PreganglIonIc
fIberspassdIrectlyIntotheadrenalmedullawIthoutsynapsIngInaganglIon(FIg.152).
ThecellsofthemedullaarederIvedfromneuronaltIssueandareanalogousto
postganglIonIcneurons.
Table 15-2 Classification of Nerve Fibers
Figure 15-3.ThespInalreflexarcofthesomatIcnervesIsshownontheleft.The
dIfferentarrangementsofneuronsInthesympathetIcsystemareshownontherIght.
PreganglIonIcfIberscomIngoutthroughwhIteramImaymakesynaptIcconnectIons
followIngoneofthreecourses:(1)synapseInganglIaatthelevelofexIt,(2)courseup
ordownthesympathetIcchaIntosynapseatanotherlevel,or(J)exItthechaIn
wIthoutsynapsIngtoanoutlyIngcollateralganglIon.
ThesympathetIcpostganglIonIcneuronalcellbodIesarelocatedInganglIaofthepaIred
lateralSNSchaInorunpaIredcollateralganglIaInmoreperIpheralplexuses.Collateral
ganglIa,suchasthecelIacandInferIormesenterIcganglIa(plexus),areformedbythe
convergenceofpreganglIonIcfIberswIthmanypostganglIonIcneuronalbodIes.SNSganglIa
arealmostalwayslocatedclosertothespInalcordthantotheorganstheyInnervate.The
sympathetIcpostganglIonIcneuroncanthereforeorIgInateIneItherthepaIredlateral
paravertebralSNSganglIaoroneoftheunpaIredcollateralplexus.TheunmyelInated
postganglIonIcfIbersthenproceedfromtheganglIatotermInatewIthIntheorgansthey
Innervate.|anyofthepostganglIonIcfIberspassfromthelateralSNSchaInbackIntothe
spInalnerves,formIngthegray(unmyelInated)communIcatIngramIatalllevelsofthe
spInalcord(FIg.152).TheyaredIstrIbuteddIstallytosweatglands,pIlomotormuscle,and
bloodvesselsoftheskInandmuscle.ThesenervesareunmyelInatedCtypefIbers(Table
152)andarecarrIedwIthInthesomatIcnerves.ApproxImately8ofthefIbersInthe
averagesomatIcnervearesympathetIc.
ThefIrstfourorfIvethoracIcspInalsegmentsgeneratepreganglIonIcfIbersthatascendIn
thenecktoformthreespecIalpaIredganglIa.ThesearethesuperIorcervIcal,mIddle
cervIcal,andcervIcothoracIcganglIa.ThelastIsknownasthestellate ganglionandIs
actuallyformedbythefusIonoftheInferIorcervIcalandfIrstthoracIcSNSganglIa.These
ganglIaprovIdesympathetIcInnervatIonofthehead,neck,upperextremItIes,heart,and
lungs.AfferentpaInfIbersalsotravelwIththesenerves,accountIngforchest,neck,or
upperextremItypaInwIthmyocardIalIschemIa.
ActIvatIonoftheSNSproducesadIffusedphysIologIcresponse(massreflex)ratherthan
dIscreteeffects.SNSpostganglIonIcneuronsoutnumberthepreganglIonIcneuronsInan
averageratIoof20:1toJ0:1.
2
DnepreganglIonIcfIberInfluencesalargernumberof
postganglIonIcneurons,whIcharedIspersedtomanyorgans.
Parasympathetic Nervous System
ThePNS,lIketheSNS,hasbothpreganglIonIcandpostganglIonIcneurons.The
preganglIonIccellbodIesorIgInateInthebraInstemandsacralsegmentsofthespInalcord.
PNSpreganglIonIcfIbersarefoundIncranIalnerves(oculomotor),7(facIal),X
(glossopharyngeal),andX(vagus).ThesacraloutfloworIgInatesIntheIntermedIolateral
grayhornsofthesecond,thIrd,andfourthsacralnerves.FIgure151showsthedIstrIbutIon
ofthePNSdIvIsIonandItsInnervatIonofvIsceralorgans.
Thevagus(cranIalnerveX)nervehasthemostextensIvedIstrIbutIonofallthePNS,
accountIngformorethan75ofPNSactIvIty.ThepaIredvagusnervessupplyPNS
InnervatIontotheheart,lungs,esophagus,stomach,smallIntestIne,proxImalhalfofthe
colon,lIver,gallbladder,pancreas,andupperportIonsoftheureters.ThesacralfIbers
formthepelvIcvIsceralnerves,ornervIerIgentes.ThesenervessupplytheremaInderof
thevIscerathatarenotInnervatedbythevagus.TheysupplythedescendIngcolon,
rectum,uterus,bladder,andlowerportIonsoftheureters,andareprImarIlyconcerned
wIthemptyIng.7arIoussexualreactIonsarealsogovernedbythesacralPNS.ThePNSIs
responsIbleforpenIleerectIon,butSNSstImulatIongovernsejaculatIon.
ncontrasttotheSNSdIvIsIon,PNSpreganglIonIcfIberspassdIrectlytotheorganthatIs
Innervated.ThepostganglIonIccellbodIesaresItuatednearorwIthIntheInnervated
vIsceraandgenerallyarenotvIsIble.TheproxImItyofPNSganglIatoorwIthInthevIscera
provIdesalImIteddIstrIbutIonofpostganglIonIcfIbers.TheratIoofpostganglIonIcto
preganglIonIcfIbersInmanyorgansappearstobe1:1toJ:1comparedwIththe20:1found
IntheSNSsystem.Auerbach'splexusInthedIstalcolonIstheexceptIon,wItharatIoof
8,000:1.ThefactthatPNSpreganglIonIcfIberssynapsewIthonlyafewpostganglIonIc
neuronsIsconsIstentwIththedIscreteandlImItedeffectofPNSfunctIon.Forexample,
vagalbradycardIacanoccurwIthoutaconcomItantchangeInIntestInalmotIlItyor
salIvatIon.|assreflexactIonIsnotacharacterIstIcofthePNS.Theeffectsoforgan
responsetoPNSstImulatIonareoutlInedInTable151.
Autonomic Innervation
Heart
TheheartIswellsupplIedbytheSNSandPNS.ThesenervesaffectcardIacpumpfunctIon
Inthreeways:(1)bychangIngtherate(chronotropIsm),(2)bychangIngthestrengthof
contractIon(InotropIsm),and(J)bymodulatIngcoronarybloodflow.ThePNScardIacvagal
fIbersapproachthestellateganglIaandthenjoIntheefferentcardIacSNSfIbers;
therefore,thevagusnervetotheheartandlungsIsamIxednervecontaInIngbothPNSand
SNSefferentfIbers.ThePNSfIbersaredIstrIbutedmaInlytothesInoatrIaland
atrIoventrIcular(A7)nodesandtoalesserextenttotheatrIa.ThereIs
P.JJ1
lIttleornodIstrIbutIontotheventrIcles.Therefore,themaIneffectofvagalcardIac
stImulatIontotheheartIschronotropIc.7agalstImulatIondecreasestherateofsInoatrIal
nodedIschargeanddecreasesexcItabIlItyoftheA7junctIonalfIbers,slowIngImpulse
conductIontotheventrIcles.AstrongvagaldIschargecancompletelyarrestsInoatrIal
nodefIrIngandblockImpulseconductIontotheventrIcles.
J
ThephysIologIcImportanceofthePNSonmyocardIalcontractIlItyIsnotaswellunderstood
asthatoftheSNS.CholInergIcblockadecandoubletheheartrate(HF)wIthoutalterIng
contractIlItyoftheleftventrIcle.7agalstImulatIonoftheheartcanreduceleft
ventrIcularmaxImumrateoftensIondevelopment(dP/dT)anddecreasecontractIleforce
byasmuchas10to20.However,PNSstImulatIonIsrelatIvelyunImportantInthIsregard
comparedwIthItspredomInanteffectonHF.TheSNShasthesamesupraventrIcular
dIstrIbutIonasthePNS,butwIthstrongerrepresentatIontotheventrIcles.SNSefferentsto
themyocardIumfunnelthroughthepaIredstellateganglIa.TherIghtstellateganglIon
dIstrIbutesprImarIlytotheanterIorepIcardIalsurfaceandtheInterventrIcularseptum.
FIghtstellatestImulatIondecreasessystolIcduratIonandIncreasesHF.Theleftstellate
ganglIonsupplIestheposterIorandlateralsurfacesofbothventrIcles.Leftstellate
stImulatIonIncreasesmeanarterIalpressureandleftventrIcularcontractIlItywIthout
causIngasubstantIalchangeInHF.NormalSNStonemaIntaInscontractIlItyapproxImately
20abovethatIntheabsenceofanySNSstImulatIon.
4
Therefore,thedomInanteffectof
theANSonmyocardIalcontractIlItyIsmedIatedprImarIlythroughtheSNS.ntrInsIc
mechanIsmsofthemyocardIum,however,canmaIntaIncIrculatIonquItewellwIthoutthe
ANS,asevIdencedbythesuccessofcardIactransplants(seeChapter54).Early
InvestIgatIons,performedInanesthetIzed,openchestanImals,demonstratedthatcardIac
ANSnervesexertonlyslIghteffectsonthecoronaryvascularbed;however,morerecent
studIesonchronIcallyInstrumented,Intact,conscIousanImalsshowconsIderableevIdence
forastrongSNSregulatIonofthesmallcoronaryresIstanceandlargerconductance
vessels.
5,6
0IfferentsegmentsofthecoronaryarterIaltreereactdIfferentlytovarIousstImulIand
drugs.Normally,thelargeconductancevesselscontrIbutelIttletooverallcoronary
vascularresIstance(seeChapter10).FluctuatIonsInresIstancereflectchangesInlumen
sIzeofthesmall,precapIllaryvessels.8loodflowthroughtheresIstancevesselsIs
regulatedprImarIlybythelocalmetabolIcrequIrementsofthemyocardIum.Thelarger
conductancevessels,however,canconstrIctmarkedlybecauseofneurogenIcstImulatIon.
NeurogenIcInfluencealsoassumesagreaterroleIntheresIstancevesselswhenthey
becomehypoxIcandloseautoregulatIon.
Peripheral Circulation
TheSNSnervesarebyfarthemostImportantregulatorsoftheperIpheralcIrculatIon.The
PNSnervesplayonlyamInorroleInthIsregard.ThePNSdIlatesvessels,butonlyIn
lImItedareassuchasthegenItals.SNSstImulatIonproducesbothvasodIlatIonand
vasoconstrIctIon,wIthvasoconstrIctoreffectspredomInatIng.TheSNSeffectonthe
vascularbedIsdetermInedbythetypeofreceptorsonwhIchtheSNSfIbertermInates(see
AdrenergIcFeceptors).SNSconstrIctorreceptorsaredIstrIbutedtoallsegmentsofthe
cIrculatIon.8loodvesselsIntheskIn,kIdneys,spleen,andmesenteryhaveanextensIve
SNSdIstrIbutIon,whereasthoseIntheheart,braIn,andmusclehavelessSNSInnervatIon.
8asalvasomotortoneIsmaIntaInedbyImpulsesfromthelateralportIonofthevasomotor
centerInthemedullaoblongatathatcontInuallytransmItsImpulsesthroughtheSNS,
maIntaInIngpartIalarterIolarandvenularconstrIctIon.CIrculatIngepInephrIne(EP)from
theadrenalmedullahasaddItIveeffects.ThIsbasalANStonemaIntaInsarterIolar
constrIctIonatanIntermedIatedIameter.ThearterIole,therefore,hasthepotentIalfor
eItherfurtherconstrIctIonordIlatIon.fthebasaltonewerenotpresent,theSNScould
onlyeffectvasoconstrIctIonandnotvasodIlatIon.
7
TheSNStoneInthevenulesproduces
lIttleresIstancetoflowcomparedwIththearterIolesandthearterIes.TheImportanceof
SNSstImulatIonofveInsIstoreduceorIncreasetheIrcapacIty.8yfunctIonIngasa
reservoIrforapproxImately80ofthetotalbloodvolume,smallchangesInvenous
capacItanceproducelargechangesInvenousreturnand,thus,cardIacpreload.
Lungs
ThelungsareInnervatedbyboththeSNSandPNS.PostganglIonIcSNSfIbersfromthe
upperthoracIcganglIa(stellate)passtothelungstoInnervatethesmoothmusclesofthe
bronchIandpulmonarybloodvessels.PNSInnervatIonofthesestructuresIsvIathevagus
nerve.SNSstImulatIonproducesbronchodIlatIonandpulmonaryvasoconstrIctIon.
8
LIttle
elsehasbeenprovenconclusIvelyaboutthevasomotorcontrolofthepulmonaryvessels
otherthanthattheyadjusttoaccommodatetheoutputoftherIghtventrIcle.Theeffect
ofstImulatIonofthepulmonarySNSnervesonpulmonaryvascularresIstanceIsnotIdeal
butmaybeImportantInmaIntaInInghemodynamIcstabIlItydurIngstressandexercIseby
balancIngrIghtandleftventrIcularoutput.StImulatIonofthevagusnerveproducesalmost
novasodIlatIonofthepulmonarycIrculatIon.HypoxIcpulmonaryvasoconstrIctIonIsalocal
phenomenoncapableofprovIdIngafasteradjustmenttotheorganIsmneeds.
8oththeSNSandthevagusnerveprovIdeactIvebronchomotorcontrol.SNSstImulatIon
causesbronchodIlatIon,whereasvagalstImulatIonproducesconstrIctIon.PNSstImulatIon
mayalsoIncreasesecretIonsofthebronchIalglands.7agalreceptorendIngsInthealveolar
ductsalsoplayanImportantroleInthereflexregulatIonoftheventIlatIoncycle.Thelung
hasImportantnonventIlatoryactIvItyaswell.tservesasametabolIcorganthatremoves
localmedIatorssuchasnorepInephrIne(NE)fromthecIrculatIonandconvertsothers,such
asangIotensIn1,toactIvecompounds.
9
Autonomic Nervous System Transmission
TransmIssIonofexcItatIonacrossthetermInaljunctIonalsItes(synaptIcclefts)ofthe
perIpheralANSoccursthroughthemedIatIonoflIberatedchemIcals(FIg.154).
TransmIttersInteractwIthareceptorontheendorgantoevokeabIologIcresponse.The
ANScanbepharmacologIcallysubdIvIdedbytheneurotransmIttersecretedattheeffector
cell.
PharmacologIcparlancedesIgnatestheSNSandPNSasadrenergIcandcholInergIc,
respectIvely.ThetermInalsofthePNSpostganglIonIcfIbersreleaseacetylcholIne(ACh).
WIththeexceptIonofsweatglands,NEIsconsIderedtheprIncIpalneurotransmItter
releasedatthetermInalsofthesympathetIcpostganglIonIcfIbers(seeFIg.152).
CotransmIssIonofadenosInetrIphosphate(ATP),neuropeptIdeY,andNEhasbeen
demonstratedatvascularsympathetIcnervetermInalsInanumberofdIfferenttIssues
IncludIngmuscle,IntestIne,kIdney,andskIn(seeSympathetIcNervousSystem
NeurotransmIssIon).ThepreganglIonIcneuronsofbothsystemssecreteACh.
ThetermInatIonsofthepostganglIonIcfIbersofbothANSsubdIvIsIonsareanatomIcallyand
physIologIcallysImIlar.ThetermInatIonsarecharacterIzedbymultIplebranchIngscalled
terminal effector plexuses,orretIculae.ThesefIlamentssurroundtheelementsofthe
effectorunItlIkeameshstockIng.
7
Thus,oneSNSpostganglIonIcneuron,forexample,
canInnervate-25,000effectorcells(e.g.,vascularsmoothmuscle).
P.JJ2
ThetermInalfIlamentsendInpresynaptIcenlargementscalledvaricosities.EachvarIcosIty
contaInsvesIcles,-500mIndIameter,InwhIchtheneurotransmIttersarestored(FIg.15
4).TherateofsynthesIsdependsonthelevelofANSactIvItyandIsregulatedbylocal
feedback.ThedIstancebetweenthevarIcosItyandtheeffectorcell(synaptIcorjunctIonal
cleft)varIesfrom100mInganglIaandarterIolestoasmuchas20,000mInlarge
arterIes.ThetImefordIffusIonIsdIrectlyproportIonaltothewIdthofthesynaptIcgap.
0epolarIzatIononthenervereleasesthevesIcularcontentsIntothesynaptIccleftby
exocytosIs.
Figure 15-4.TheanatomyandphysIologyofthetermInalpostganglIonIcfIbersof
sympathetIcandparasympathetIcfIbersaresImIlar.
Parasympathetic Nervous System Transmission
Synthesis
AChIsconsIderedtheprImaryneurotransmItterofthePNS.AChIsformedInthe
presynaptIctermInalbyacetylatIonofcholInewIthacetylcoenzymeA.ThIsstepIs
catalyzedbycholIneacetyltransferase(FIg.155).AChIsthenstoredInaconcentrated
formInpresynaptIcvesIcles.AcontInualreleaseofsmallamountsofACh,calledquanta,
occursdurIngtherestIngstate.EachquantumresultsInsmallchangesIntheelectrIcal
potentIalofthesynaptIcendplatewIthoutproducIngdepolarIzatIon.Theseareknownas
mInIatureendplatepotentIals.ArrIvalofanactIonpotentIalcausesasynchronousrelease
ofhundredsofquanta,resultIngIndepolarIzatIonoftheendplate.FeleaseofAChfrom
thevesIclesdependsonInfluxofcalcIum(Ca
2+
)fromtheInterstItIalspace.AChIsnot
reusedlIkeNE;therefore,ItmustbesynthesIzedconstantly.
Figure 15-5.SynthesIsandmetabolIsmofacetylcholIne.
Metabolism
TheabIlItyofareceptortomodulatefunctIonofaneffectororgandependsonrapId
recoverytoItsbaselInestateafterstImulatIon.ForthIstooccur,theneurotransmItter
mustbequIcklyremovedfromthevIcInItyofthereceptor.AChremovaloccursbyrapId
hydrolysIsbyacetylcholInesterase(FIg.155).ThIsenzymeIsfoundInneurons,atthe
neuromuscularjunctIon,andInvarIousothertIssuesofthebody.AsImIlarenzyme,
pseudocholInesteraseorplasmacholInesterase,Isalsofoundthroughoutthebodybutonly
toalImItedextentInnervoustIssue.tdoesnotappeartobephysIologIcallyImportantIn
termInatIonoftheactIonofACh.8othacetylcholInesteraseandpseudocholInesterase
hydrolyzeAChaswellasotheresters(suchastheestertypelocalanesthetIcs),andthey
maybedIstInguIshedbyspecIfIcbIochemIcaltests.
J
Sympathetic Nervous System Transmission
TradItIonally,thecatecholamInesEPandNEareconsIderedthemedIatorsofperIpheral
SNSactIvIty.NEIsreleasedfromlocalIzedpresynaptIcvesIclesofnearlyallpostganglIonIc
sympathetIcnerves.7ascularSNSnervetermInals,though,alsoreleaseATP.Thus,ATPand
NEareconeurotransmItters.TheyarereleaseddIrectlyIntothesItewheretheyact.TheIr
postjunctIonaleffectsappeartobesynergIstIcIntIssues.
TheSNSfIbersendIngIntheadrenalmedullaarepreganglIonIc,andAChIsthe
neurotransmItter(seeFIg.152).tInteractswIththechromaffIncellsIntheadrenal
medulla,causIngreleaseofEPandNE.ThechromaffIncellstaketheplaceofthe
postganglIonIcneurons.StImulatIonofthesympathetIcnervesInnervatIngtheadrenal
medulla,however,causesthereleaseoflargequantItIesofamIxtureofEPandNEInto
thecIrculatIon.ThegreaterportIonofthIshormonalsurgeIsnormallyEP.Nevertheless,
EPandNE,whenreleasedIntothecIrculatIon,areclassIfIedashormonesInthattheyare
synthesIzed,stored,andreleasedfromtheadrenalmedullatoactatdIstantsItes.
HormonalEPandNEhavealmostthesameeffectsoneffectorcellsasthosecausedby
localdIrectsympathetIcstImulatIon;however,thehormonaleffects,althoughbrIef,last
about10tImesaslongasthosecausedbydIrectstImulatIon.EPhasagreatermetabolIc
effectthanNE.tcanIncreasethemetabolIcrateofthebodyasmuchas100.talso
IncreasesglycogenolysIsInthelIverandmusclewIthglucosereleaseIntotheblood.These
functIonsareallnecessarytopreparethebodyforfIghtorflIght.
Figure 15-6.ThechemIcalconfIguratIonsofthreeendogenouscatecholamInesare
comparedwIththoseoftwosynthetIccatecholamInes.SympathomImetIcdrugsdIffer
IntheIrhemodynamIceffectslargelybecauseofdIfferencesInsubstItutIonofthe
amInegrouponthecatecholnucleus.
P.JJJ
Catecholamines: The First Messenger
AcatecholamIneIsanycompoundofacatecholnucleus(abenzenerIngwIthtwoadjacent
hydroxylgroups)andanamInecontaInIngsIdechaIn.ThechemIcalconfIguratIonoffIveof
themorecommoncatecholamInesInclInIcaluseIsdemonstratedInFIgure156.The
endogenouscatecholamInesInhumansaredopamIne(0A),NE,andEP.0AIsa
neurotransmItterpresentIntheCNS.tIsprImarIlyInvolvedIncoordInatIngmotoractIvIty
InthebraIn.tIstheprecursorofNE.NEIssynthesIzedandstoredInnerveendIngsof
postganglIonIcSNSneurons.tIsalsosynthesIzedIntheadrenalmedullaandIsthe
chemIcalprecursorofEP.StoredEPIslocatedchIeflyInchromaffIncellsoftheadrenal
medulla.EIghtytoeIghtyfIvepercentofthecatecholamInecontentoftheadrenal
medullaIsEPand1520IsNE.ThebraIncontaInsbothnoradrenergIcanddopamInergIc
receptors,butcIrculatIngcatecholamInesdonotcrossthebloodbraInbarrIer.The
catecholamInespresentInthebraInaresynthesIzedthere.
CatecholamInesareoftenreferredtoasadrenergIcdrugsbecausetheIreffectoractIons
aremedIatedthroughreceptorsspecIfIcfortheSNS.SympathomImetIcscanactIvatethese
samereceptorsbecauseoftheIrstructuralsImIlarIty.Forexample,clonIdIneIsa
2
receptoragonIstthatdoesnotpossessacatecholnucleusandevenhastworIngsystems
thatareaplanartoeachother.However,clonIdIneenjoysaremarkablespatIalsImIlarIty
toNEthatallowsIttoactIvatethereceptor.0rugsthatproducesympathetIclIkeeffects
butlackthebasIccatecholamInestructurearedefInedassympathomImetIcs.AllclInIcally
usefulcatecholamInesaresympathomImetIcs,butnotallsympathomImetIcsare
catecholamInes.TheeffectsofendogenousorsynthetIccatecholamInesonadrenergIc
receptorscanbedIrectorIndIrectndIrectactIngcatecholamInes(I.e.ephedrIne)have
lIttleIntrInsIceffectonadrenergIcreceptorsbutproducetheIreffectsbystImulatIng
releaseofthestoredneurotransmItterfromSNSnervetermInals.SomesynthetIcand
endogenouscatecholamInesstImulateadrenergIcreceptorsItesdIrectly,whereasothers
haveamIxedmodeofactIon.TheactIonsofdIrectactIngcatecholamInesareIndependent
ofendogenousNEstores;however,theIndIrectactIngcatecholamInesaretotally
dependentonadequateneuronalstoresofendogenousNE.
Figure 15-7.SchematIcofthesynthesIsofcatecholamInes.TheconversIonoftyrosIne
to0DPAbytyrosInehydroxylaseIsInhIbItedbyIncreasednorepInephrInesynthesIs.
EpInephrIneIsshownInthesestepsbutIsprImarIlysynthesIzedIntheadrenalmedulla.
Synthesis
ThemaInsIteofNEsynthesIsIsInornearthepostganglIonIcnerveendIngs.SomesynthesIs
doesoccurInvesIclesnearthecellbodythatpasstothenerveendIngs.PhenylalanIneor
tyrosIneIstakenupIntotheaxoplasmofthenervetermInalandsynthesIzedIntoeItherNE
orEP.FIgure157demonstratesthIssynthesIscascade.TyrosInehydroxylasecatalyzesthe
conversIonoftyrosInetodIhydroxyphenylalanIne.ThIsIstheratelImItIngstepatwhIchNE
synthesIsIscontrolledthroughfeedbackInhIbItIon.0opamIne(0A)synthesIsoccursInthe
cytoplasmoftheneuron.ThevesIclesofperIpheralpostganglIonIcneuronscontaInthe
enzymedopamInebhydroxylase,whIchconverts0AtoNE.Theadrenalmedulla
addItIonallycontaInsphenylethanolamIneNmethyltransferase,whIchconvertsNEtoEP.
ThIsreactIontakesplaceoutsIdethemedullaryvesIcles,andthenewlyformedEPthen
entersthevesIcleforstorage(FIg.158).AlltheendogenouscatecholamInesarestoredIn
presynaptIcvesIclesandreleasedonarrIvalofanactIonpotentIal.ExcItatIonsecretIon
couplIngInsympathetIcneuronsIsCa
2+
dependent.
P.JJ4
Figure 15-8.SchematIcofthesynthesIsanddIsposItIonofnorepInephrIne(NE)In
adrenergIcneurotransmIssIon.(1)SynthesIsandstorageInneuronalvesIcles;(2)actIon
potentIalpermItscalcIumentrywIth(J)exocytosIsofNEIntosynaptIcgap.(4)
FeleasedNEreactswIthreceptoroneffectorcell.NE(5)mayreactwIthpresynaptIc
2
receptortoInhIbItfurtherNEreleaseorwIthpresynaptIcreceptortoenhance
reuptakeofNE(6;uptake1).Extraneuronaluptake(uptake2)absorbsNEIntoeffector
cell(7)wIthoverflowoccurrIngsystemIcally(8).Tyr,tyrosIne;0DPA,
dIhydroxyphenylalanIne;0A,dopamIne;|AD,monoamIneoxIdase;CD|T,catecholO
methyltransferase.
Regulation
ncreasedSNSnervousactIvIty,asIncongestIveheartfaIlureorchronIcstress,stImulates
thesynthesIsofcatecholamInes.ClucocortIcoIdsfromtheadrenalcortexstImulatean
IncreaseInphenylethanolamIneNmethyltransferasethatmethylatesNEtoEP.
ThereleaseofNEdependsondepolarIzatIonofthenerveandanIncreaseIncalcIumIon
permeabIlIty.ThIsreleaseIsInhIbItedbycolchIcIneandprostaglandInE
2
,suggestInga
contractIlemechanIsm.NEInhIbItsItsownreleasebystImulatIngpresynaptIc
(prejunctIonal)
2
receptors.PhenoxybenzamIneandphentolamIne,receptor
antagonIsts,IncreasethereleaseofNEbyblockIngInhIbItorypresynaptIc
2
receptors(FIg.
159).DtherreceptorsarealsoImportantInNEregulatIon.
Inactivation
ThecatecholamInesareremovedfromthesynaptIccleftbythreemechanIsms(FIg.158).
ThesearereuptakeIntothepresynaptIctermInals,extraneuronaluptake,anddIffusIon.
TermInatIonofNEattheeffectorsIteIsalmostentIrelybyreuptakeofNEIntothe
termInalsofthepresynaptIcneuron.ThIsIsanactIve,energyrequIrIng,andtemperature
dependentprocess.ThereuptakeofNEInthepresynaptIctermInalsIsalsoastereospecIfIc
process.StructurallysImIlarcompounds(guanethIdIne,metaramInol)mayenterthe
vesIclesanddIsplacetheneurotransmItter.TrIcyclIcantIdepressantsandcocaIneInhIbIt
thereuptakeofNE,resultIngInhIghsynaptIcNEconcentratIonsandaccentuatedreceptor
response.naddItIon,evIdencesuggeststhatNEreuptakeIsmedIatedbyapresynaptIc
adrenergIcmechanIsmbecausebetablockadecausesmarkedelevatIonsofEPandNE
10
(seeFIgs.158and159).ExtraneuronaluptakeIsamInorpathwayforInactIvatIngNE.
EffectorcellsandotherextraneuronaltIssuestakeupNE.TheNEthatIstakenupbythe
extraneuronaltIssueIsmetabolIzedbymonoamIneoxIdase(|AD)andbycatecholD
methyltransferasetoformvanIllylmandelIcacId.ThemInuteamountofcatecholamIne
thatescapesthesetwomechanIsmsdIffusesIntothecIrculatIon,whereItIsmetabolIzed
bythelIverandkIdney.ThesameenzymesInactIvateEP.FeuptakeIsthepredomInant
pathwayforInactIvatIonoftheendogenouscatecholamInes,whIlemetabolIsmbythelIver
andkIdneyIsthepredomInantpathwayforcatecholamInesgIvenexogenously.ThIs
accountsforthelongerduratIonofactIonoftheexogenouscatecholamInesthanthat
notedatthelocalsynapse.
ThefInalmetabolIcproductofthecatecholamInesIsvanIllylmandelIcacId.
7anIllylmandelIcacIdconstItutesthemajormetabolIte(80to90)ofNEfoundIntheurIne.
Lessthan5ofreleasedNEappearsunchangedIntheurIne.ThemetabolIcproducts
excretedIntheurIneprovIdeagrossestImateofSNSactIvItyandcanfacIlItatetheclInIcal
dIagnosIsofpheochromocytoma(seeEndocrIneFunctIon).
Figure 15-9.ThIsschematIcdemonstratesjustafewofthepresynaptIcadrenergIc
receptorsthoughttoexIst.AgonIstandantagonIstdrugsareclInIcallyavaIlablefor
thesereceptors(seeTable155).The
2
receptorsserveasanegatIvefeedback
mechanIsmwherebynorepInephrIne(NE)stImulatIonInhIbItsItsownrelease.
PresynaptIcstImulatIonIncreasesNEuptake,augmentIngItsavaIlabIlIty.PresynaptIc
muscarInIc(|USC)receptorsrespondtoacetylcholIne(ACh)dIffusIngfromnearby
cholInergIctermInals.TheyInhIbItNEreleaseandcanbeblockedbyatropIne.
Receptors
AnagonIstIsasubstancethatInteractswIthareceptortoevokeabIologIcresponse.ACh,
NE,EP,0A,andATParethemajoragonIstsoftheANS.AnantagonIstIsasubstancethat
InterfereswIththeevocatIonofaresponseatareceptorsItebyanagonIst.Feceptorsare
thereforeregardedastargetsItesthat,whenactIvatedbyanagonIst,wIllleadtoa
responsebytheeffectorcell.FeceptorsareproteInmacromoleculesandarelocatedInthe
plasmamembrane.SeveralthousandreceptorshavebeendemonstratedInasInglecell.
TheenormItyofthIsnetworkIsrealIzedwhenItIsconsIderedthat-25,000sInglecellscan
beInnervatedbyasIngleneuron.
Cholinergic Receptors
AChIstheneurotransmItterforthreedIstInctclassesofreceptors.Thesereceptorscanbe
dIfferentIatedbytheIranatomIc
P.JJ5
locatIonandtheIraffInItytobIndvarIousagonIstsandantagonIsts.AChmedIatesthefIrst
messengerfunctIonoftransmIttIngImpulseswIthInthePNS,theganglIaoftheSNS,and
theneuroeffectorjunctIonofstrIated,voluntarymuscle(FIg.152).CholInergIcreceptors
arefurthersubdIvIdedIntomuscarInIcandnIcotInIcreceptorsbecausemuscarIneand
nIcotInestImulatethemselectIvely.
J
However,bothmuscarInIcandnIcotInIcreceptors
respondtoACh(seeCholInergIc0rugs).|uscarIneactIvatescholInergIcreceptorsatthe
postganglIonIcPNSjunctIonsofcardIacandsmoothmusclethroughoutthebody.|uscarInIc
stImulatIonIscharacterIzedbybradycardIa,decreasedInotropIsm,bronchoconstrIctIon,
mIosIs,salIvatIon,gastroIntestInalhypermotIlIty,andIncreasedgastrIcacIdsecretIon
(Table151).|uscarInIcreceptorscanbeblockedbyatropInewIthouteffectonnIcotInIc
receptors(seeCholInergIc0rugs).|uscarInIcreceptorsareknowntoexIstInsItesother
thanPNSpostganglIonIcjunctIons.TheyarefoundonthepresynaptIcmembraneof
sympathetIcnervetermInalsInthemyocardIum,coronaryvessels,andperIpheral
vasculature(FIg.159).Thesearereferredtoasadrenergic muscarinic receptorsbecauseof
theIrlocatIon;however,AChstImulatesthemalso.StImulatIonofthesereceptorsInhIbIts
releaseofNEInamannersImIlarto
2
receptorstImulatIon.|uscarInIcblockaderemoves
InhIbItIonofNErelease,augmentIngSNSactIvIty.AtropIne,theprototypIcalmuscarInIc
blocker,mayproducesympathomImetIcactIvItyInthIsmanneraswellasvagalblockade.
NeuromuscularblockIngdrugsthatcausetachycardIaarethoughttohaveasImIlar
mechanIsmofactIon.AChactIngonpresynaptIcadrenergIcmuscarInIcreceptorsIsa
potentInhIbItorofNErelease.
10
TheprejunctIonalmuscarInIcreceptormayplayan
ImportantphysIologIcrolebecauseseveralautonomIcallyInnervatedtIssues(e.g.,the
heart)possessANSplexusesInwhIchtheSNSandPNSnervetermInalsareclosely
assocIated.ntheseplexuses,ACh,releasedfromthenearbyPNSnervetermInals(vagus
nerve),canInhIbItNEreleasebyactIvatIonofpresynaptIcadrenergIcmuscarInIcreceptors
(FIg.159).
NIcotInIcreceptorsarefoundatthesynaptIcjunctIonsofbothSNSandPNSganglIa.
8ecausebothjunctIonsarecholInergIc,AChorAChlIkesubstancessuchasnIcotInewIll
excItepostganglIonIcfIbersofbothsystems(seeFIg.152).LowdosesofnIcotIneproduce
stImulatIonofANSganglIa,whereashIghdosesproduceblockade.ThIsdualIsmIsreferred
toasthenicotinic effect(seeCanglIonIc0rugs).NIcotInIcstImulatIonoftheSNSganglIa
produceshypertensIonandtachycardIabycausIngthereleaseofEPandNEfromthe
adrenalmedulla.AdrenalhormonereleaseIsmedIatedbyAChInthechromaffIncells,
whIchareanalogoustopostganglIonIcneurons(FIg.152).AfurtherIncreaseInnIcotIne
concentratIonproduceshypotensIonandneuromuscularweakness,asItbecomesa
ganglIonIcblocker.ThecholInergIcneuroeffectorjunctIonofskeletalmusclealsocontaIns
nIcotInIcreceptors,althoughtheyarenotIdentIcaltothenIcotInIcreceptorsInANS
ganglIa.
Adrenergic Receptors
TheadrenergIcreceptorsaretermedadrenergicornoradrenergic,dependIngontheIr
responsIvenesstoEPorNE.ThedIssImIlarItIesofthesetwodrugsledAhlquIstIn1948to
proposetwotypesofopposIngadrenergIcreceptors,termedalpha()andbeta().The
developmentofnewagonIstsandantagonIstswIthrelatIvelyselectIveactIvItyallowed
subdIvIsIonthereceptorsInto
1
and
2
.FeceptorsweresubsequentlydIvIdedInto
1
and
2
,andlaterfurthersubdIvIdedusIngmolecularclonIng.ThesympathomImetIc
adrenergIcdrugsIncurrentusedIfferfromoneanotherIntheIreffectslargelybecauseof
dIfferencesInsubstItutIonontheamInegroup,whIchInfluencestherelatIveoreffect
(FIg.156).
AnothermajorperIpheraladrenergIcreceptorspecIfIcfor0AIstermedthedopaminergic
receptor.FurtherstudIeshaverevealednotonlysubsetsoftheandreceptorsbutalso
the0Areceptor.These0AreceptorshavebeenIdentIfIedIntheCNSandInrenal,
mesenterIc,andcoronaryvessels.ThephysIologIcImportanceofthesereceptorsIsa
matterofcontroversybecausetherearenoIdentIfIableperIpheral0Aneurons.0A
measuredInthecIrculatIonIsassumedtoresultfromspIlloverfromthebraIn.
ThefunctIonof0AIntheCNShaslongbeenknown,buttheperIpheral0Areceptorhas
beenelucIdatedonlywIthInthepast25years.ThepresenceoftheperIpheral0Areceptor
wasobscuredbecause0Adoesnotaffectthe0AreceptorexclusIvely.talsostImulates
andreceptorsInadoserelatedmanner.However,0AreceptorsfunctIonIndependently
oforblockadeandaremodIfIedby0AantagonIstssuchashaloperIdol,droperIdol,and
phenothIazInes.Thus,thereIsanecessItyfortheaddItIonofthe0AreceptorandIts
subsets(0A
1
and0A
2
).
ThedIstrIbutIonofadrenergIcreceptorsInorgansandtIssuesIsnotunIformandtheIr
functIondIffersnotonlybytheIrlocatIonbutalsoIntheIrnumbersand/ordIstrIbutIon.
AdrenergIcreceptorsarefoundIntwolocIInthesympathetIcneuroeffectorjunctIon.They
arefoundInboththepresynaptIc(prejunctIonal)andpostsynaptIc(postjunctIonal)sItesas
wellasextrasynaptIcsItes(FIg.1510).Table15JIsarevIewofthefunctIonandsynaptIc
locatIonofsomeoftheclInIcallyImportantreceptorsandtheIrsubtypes.
Alpha-Adrenergic Receptors
TheadrenergIcreceptorshavebeenfurthersubdIvIdedIntotwoclInIcallyImportant
classes
1
and
2
.ThIsclassIfIcatIonIsbasedontheIrresponsetotheantagonIsts
yohImbIneandprazosIn.PrazosInIsamorepotentantagonIstof
1
receptors,whereas
2
receptorsaremoresensItIvetoyohImbIne.Fecently,thepharmacologIcexperImentshave
demonstratedtheexIstenceoftwosubtypeswIthInthe
1
group,namely
1A
and
18
,and
atleasttwosubtypeswIthInthe
2
,respectIvely
2A
,and
28.
TheImportanceofthese
subsetsIsstIllemergIngwIthevIdencethatthespleen,andlIvercontaInmaInly
18
receptors,andtheheart,neocortex,kIdney,vasdeferns,andhIppocampuscontaInIng
equalamountsof
1A
and
18
receptors.The
1
adrenergIcreceptorsarefoundInthe
smoothmusclecellsoftheperIpheralvasculatureofthecoronaryarterIes,skIn,uterus,
IntestInalmucosa,andsplanchnIcbeds
11
(Table154).The
1
receptorsserveas
postsynaptIcactIvatorsofvascularandIntestInalsmoothmuscleaswellasofendocrIne
glands.TheIractIvatIonresultsIneItherdecreasedorIncreasedtone,dependIngonthe
effectororgan.TheresponseInresIstanceandcapacItancevesselsIsconstrIctIon,whereas
IntheIntestInaltractItIsrelaxatIon.ThereIsnowalargebodyofevIdencedocumentIng
thepresenceofpostjunctIonal
1
adrenoreceptorsInthemammalIanheart.
1
AdrenergIc
receptorshavebeenshowntohaveaposItIveInotropIceffectoncardIactIssuesfrommost
mammalsstudIed,IncludInghumans.ExperImentalworkstronglysupportstheconceptthat
enhancedmyocardIal
1
responsIvenessplaysaprImaryroleInthegenesIsofmalIgnant
arrhythmIasInducedbycatecholamInesdurIngmyocardIalIschemIaandreperfusIon.0rugs
possessIngpotent
1
antagonIstactIvItysuchasprazosInandphentolamIneprovIde
sIgnIfIcantantIarrhythmIcactIvIty.TheclInIcalmechanIsmandsIgnIfIcanceofthese
fIndIngsarenotyetclear.However,thereIsnodoubtthat
1
adrenergIcantagonIsts
preventcatecholamIneInducedventrIculararrhythmIas.
12
ncontrast,studIesofthe
effectsofantagonIstsInexperImentalandclInIcalmyocardIalInfarctIonhaveprovIded
conflIctIngresults.
ThedIscoveryofpresynaptIcadrenoreceptorsandtheIrroleInthemodulatIonofNE
transmIssIonprovIdedthestImulusforthesubclassIfIcatIonofreceptorsInto
1
and
2
subtypes.
P.JJ6
PresynaptIc
1
receptorshavenotbeenIdentIfIedandtheyappearconfInedonlytothe
postsynaptIcmembrane.Dntheotherhand,
2
receptorsarefoundonbothpresynaptIc
andpostsynaptIcmembranesoftheadrenergIcneuroeffectorjunctIon.Table154revIews
thesesItes.PostsynaptIcmembranescontaInanearequalmIxof
1
and
2
receptors.
Figure 15-10.LocIofseveralknownadrenergIcreceptors.ThepresynaptIc
2
and
dopamIne(0A)receptorsserveasanegatIvefeedbackmechanIsm,whereby
stImulatIonofnorepInephrIne(NE)InhIbItsItsownrelease.PresynaptIc
2
stImulatIon
IncreasesNEuptake,augmentIngItsavaIlabIlIty.PostsynaptIc
2
and
2
receptorsare
extrasynaptIcandareconsIderednonInnervatedhormonalreceptors.
The
2
adrenoreceptorsmaybesubdIvIdedevenfurtherIntoasmanyasfourpossIble
subtypes.ThepostsynaptIc
2
receptorshavemanyactIons,whIchIncludearterIaland
venousvasoconstrIctIon,plateletaggregatIon,InhIbItIonofInsulInrelease,InhIbItIonof
bowelmotIlIty,stImulatIonofgrowthhormonerelease,andInhIbItIonofantIdIuretIc
hormonerelease.
2
FeceptorscanbefoundIncholInergIcpathwaysaswellasInadrenergIcpathways.They
cansIgnIfIcantlymodulateparasympathetIcactIvItyaswell.CurrentresearchImplIesthat
2
stImulatIonoftheparasympathetIcpathwaysplaysaroleInthemodulatIonofthe
baroreceptorreflex(IncreasedsensItIvIty),vagalmedIatIonofHF(bradycardIa),
bronchoconstrIctIon,andsalIvatIon(drymouth).However,cholInergIcreceptorscanalso
befoundInadrenergIcpathways;thus,muscarInIcandnIcotInIcreceptorshavebeenfound
InpresynaptIcandpostsynaptIclocatIons,whereInturntheymodulatesympathetIc
actIvIty(FIg.159).ThereIsspeculatIonthatthefeaturesthataresodesIrabletothe
anesthesIologIst,suchassedatIon,anxIolysIs,analgesIa,andhypnosIs,aremedIated
throughthIssIte.
StImulatIonofpresynaptIc
2
receptorsmedIatesInhIbItIonofNEreleaseIntothesynaptIc
cleft,servIngasanegatIvefeedbackmechanIsm.ThecentraleffectsareprImarIlyrelated
toareductIonInsympathetIcoutflowwIthaconcomItantlyenhancedparasympathetIc
outflow(e.g.,enhancedbaroreceptoractIvIty).TheseresultsInadecreasedsystemIc
vascularresIstance,decreasedcardIacoutput(CD),decreasedInotropIcstateInthe
myocardIum,anddecreasedHF.TheperIpheralpresynaptIc
2
effectsaresImIlar,andNE
releaseIsInhIbItedInpostganglIonIcneurons.However,stImulatIonofpostsynaptIc
2
receptors,lIkethe
1
postsynaptIcreceptor,affectsvasoconstrIctIon.NEactsonboth
1
and
2
receptors.Thus,NEnotonlyactIvatessmoothmusclevasoconstrIctIon(postsynaptIc
1
and
2
receptors)butalsostImulatespresynaptIc
2
receptorsandInhIbItsItsown
release.SelectIvestImulatIonofthepresynaptIc
2
receptorcouldproduceabenefIcIal
reductIonofperIpheralvascularresIstance.Unfortunately,mostknownpresynaptIc
2
agonIstsalsostImulatethepostsynaptIc
2
receptors,causIngvasoconstrIctIon.8lockadeof
2
presynaptIcreceptors,however,ablatesnormalInhIbItIonofNE,causIng
vasoconstrIctIon.7asodIlatIonoccurswIththeblockadeofpostsynaptIc
1
and
2
receptors.
Alpha-Adrenergic Receptors in the Cardiovascular System
PostsynaptIc
1
and
2
receptorsInthemammalIanmyocardIumandcoronaryarterIes
medIateanumberofresponses.
Coronary Arteries
ThepresenceofpostsynaptIc
1
and
2
receptorsInmammalIanmodelshasbeen
demonstrated.SympathetIcnervescausecoronaryvasoconstrIctIon,whIchIsmedIated
morebypostsynaptIc
2
than
1
receptors.ThelargerepIcardIalarterIespossessmaInly
1
receptors,whereas
2
receptorsandsome
1
receptorsarepresentInthesmallcoronary
arteryresIstancevessels.
1J
EpIcardIalvesselscontrIbuteonly5tothetotalresIstanceof
thecoronarycIrculatIon;therefore,
1
agonIstssuchasphenylephrInehavelIttleInfluence
oncoronaryresIstance.
14,15
|yocardIalIschemIahasbeenshowntoIncrease
2
receptor
densItyInthecoronaryarterIes.schemIahasalsobeenshowntocauseareflexIncreaseIn
sympathetIcactIvItymedIatedbymechanIsms.ThIscascademayfurtherIncrease
coronaryconstrIctIon.PostsynaptIc
1
receptorsdonotrelyuponextracellularCa
2+
to
constrIctthevessel,whereasthe
2
constrIctorresponseIshIghlydependenton
extracellularInfluxandexquIsItelysensItIvetocalcIumchannelInhIbItors.
16
Myocardium
TheroleofreceptorsInmedIatIngcatecholamIneInducedInotropIsmand
arrhythmogenesIsIswellknown(see8etaAdrenergIcFeceptors).StudIeshaveshownthe
presenceofpostsynaptIcmyocardIal
1
receptors,
P.JJ7
P.JJ8
whIchalsoexertamajor,facIlItory,posItIveInotropIceffectonthemyocardIumofseveral
specIesofmammalsIncludInghumans.TheIrcontrIbutIontomalIgnantreperfusIon
arrhythmogenesIshasalsobeenrecognIzed.
Table 15-3 Adrenergic Receptors: Order of Potency of Agonists and Antagonists
RECEPTOR
AGONISTS
a
ANTAGONISTS LOCATION ACTION
1
++++
+++
++
+
NorepInephrIne
EpInephrIne
0opamIne
soproterenol
PhenoxybenzamIne
b
PhentolamIne
b
ErgotalkaloIds
b
PrazosIn
Smoothmuscle
(vascular,IrIs,
radIal,ureter,
pIlomotor,
uterus,trIgone,
gastroIntestInal,
andbladder
sphIncters)
ContractIon
7asoconstrIctIon
TolazolIne
b
8raIn NeurotransmIssIon
Labetalol
b
Smoothmuscle
(gastroIntestInal)
FelaxatIon
Heart ClycogenolysIs
SalIvaryglands
ncreasedforce,
glycolysIs
AdIposetIssue
SecretIon(K
H
2
D)
Sweatglands
(localIzed)
ClycogenesIs
KIdney(proxImal
tubule)
SecretIon
CluconeogenesIs
Na
+
reabsorptIon
++++ ClonIdIne YohImbIne
AdrenergIcnerve
endIngs
nhIbItIon
norepInephrIne
release
+++ NorepInephrIne PIperoxan PresynaptIcCNS
++ EpInephrIne PhentolamIne
b
2
++ NorepInephrIne PhenoxybenzamIne
b
Platelets
AggregatIon,
granulerelease
+ PhenylephrIne TolazolIne
b
Labetalol
b
AdIposetIssue
EndocrIne
pancrease
7ascularsmooth
muscle:
KIdney
8raIn
nhIbItIon
lypolysIs
nhIbItIonInsulIn
release
ContractIon
nhIbItIonrenIn
dIsease
NeurotransmIssIon
1
++++ soproterenol
b
Acebutolol Heart
ncreasedrate,
contractIlIty,
conductIon
velocIty
+++ EpInephrIne Practolol
++ NorepInephrIne Propranolol
b
Coronary
vasodIlatIon
+ 0opamIne
Alprenolol
b
|etoprolol
Esmolol
AdIposetIssue LIpolysIs
2
++++ soproterenol
a
Propranolol
b
LIver
ClycogenolysIs,
gluconeogenesIs
+++ EpInephrIne 8utoxamIne
+++ NorepInephrIne Alprenolol
Esmolol Skeletalmuscle
ClycogenolysIs,
lactaterelease
Nadolol
+ 0opamIne
TImolol
Labetalol
Smoothmuscle
(bronchI,uterus,
vascular,
gastroIntestInal,
detrusor,spleen
capsule)
FelaxatIon
EndocrIne
pancreas
nsulInsecretIon
SalIvaryglands AmylasesecretIon
0A
1
++++ Fenoldopam
7ascularsmooth
muscle
7asodIlatIon
++ 0opamIne HaloperIdol
Fenaland
mesentery
+ EpInephrIne 0roperIdol
+ |etaclopramIde PhenothIazInes
0A
2
++
+
0opamIne
0omperIdone
8romocrIptIne
PresynaptIc
adrenergIcnerve
endIngs
nhIbIts
norepInephrIne
release
0A,dopamIne.
a
LIstedIndecreasIngorderofpotency.
b
NonselectIve.
C
1
adrenergIcresponsesaregreater.
PlusesIndIcatestrengthofpotency.
Table 15-4 Adrenergic Receptors
RECEPTOR SYNAPTIC SITE ANATOMIC SITE ACTION
LV FUNCTION
AND STROKE
VOLUME
1
PostsynaptIc
PerIpheral
vascularsmooth
muscle
ConstrIctIon 0ecreased
Fenalvascular
smoothmuscle
ConstrIctIon
Coronary
arterIes,
epIcardIal
ConstrIctIon
|yocardIum
PosItIve
InotropIsm
mproved
J040ofrestIngtone
Fenaltubules AntIdIuresIs
2
PresynaptIc
PerIpheral
vascularsmooth
musclerelease
nhIbItNE
Secondary
vasodIlatIon
mproved
CoronarIes
CNS
:
nhIbItIonofCNS
actIvIty
SedatIon
0ecrease|AC
PostsynaptIc
CoronarIes,
endocardIal
CNS
ConstrIctIon
nhIbItIonof
InsulInrelease
0ecreasedbowel
motIlIty
nhIbItIonof
antIdIuretIc
hormone
AnalgesIa
0ecreased
Fenaltubule
PromotesNa
2+
andH
2
D
excretIon
1
PostsynaptIc
NEsensItIve
|yocardIum
PosItIve
InotropIsmand
chronotropIsm
mproved
SInoatrIal(SA)
node
7entrIcular
conductIon

KIdney FenInrelease
CoronarIes FelaxatIon
2
PresynaptIc
NEsensItIve
|yocardIum
SAnode
ventrIcular
conductIon
vessels
AcceleratesNE
release
DpposIteactIon
topresynaptIc
2
agonIsm
ConstrIctIon
mproved
PostsynaptIc
(extrasynaptIc)
(EPsensItIve)
|yocardIum
PosItIve
InotropIsmand
chronotropIsm
7ascularsmooth
muscle
FelaxatIon mproved
8ronchIalsmooth
muscle
FelaxatIon mproved
Fenalvessels FelaxatIon mproved
PostsynaptIc
8loodvessels
(renal,
mesentery,
coronary)
7asodIlatIon mproved
0A
1
Fenaltubules
NatrIuresIs
0IuresIs
Juxtaglomerular
cells
FenInrelease
(modulates
dIuresIs)
SympathetIc
ganglIa
|InorInhIbItIon
0A
2
PresynaptIc
PostganglIonIc
sympathetIc
nerves
nhIbItNE
release
mproved

Secondary
vasodIlatIon
PostsynaptIc
Fenaland
mesenterIc
vasculature
:
7asoconstrIctIon
L7,leftventrIcular;NE,norepInephrIne;|AC,EP,epInephrIne;0A,dopamIne.
PhenylephrIne,an
1
agonIst,canIncreasemyocardIalcontractIlItytwotothreefold
comparedwIthasIxtosevenfoldIncreaseproducedbyIsoproterenol,apureagonIst.
|yocardIalpostsynaptIc
1
receptorsmedIateperhapsasmuchasJ0to50ofthebasal
InotropIctoneofthenormalheart.
PostsynaptIcmyocardIal
1
receptorsplayamorepromInentInotropIcroleInthefaIlIng
heartbyservIngasareservetothenormallypredomInant
1
receptors.Althoughthe
P.JJ9
responsetoboth
1
and
1
agonIstsIsreducedInthefaIlIngmyocardIum,theInteractIon
betweenthetworeceptorsIsmoreapparent.ChronIcheartfaIlureIsknowntoproducea
reduceddensIty(downregulatIon)ofmyocardIal
1
receptorsasaresultofhIghlevelsof
cIrculatIngcatecholamInes.However,thereIsnoevIdenceofdownregulatIonofeIther
1
or
2
receptorsduetocardIacfaIlure.TheIncreaseIndensItyofmyocardIal
1
adrenoreceptorsshowsarelatIveIncreasewIthfaIlureandmyocardIalIschemIa.
17
Thus,
enhancedmyocardIal
1
receptornumbers,andsensItIvIty,maycontrIbutetoposItIve
InotropIsmseendurIngIschemIaaswellastothemalIgnantarrhythmIasthatoccurwIth
reperfusIon.ntracellularmobIlIzatIonofcytosolIcCa
2+
bytheactIvated
1
myocardIal
receptorsdurIngIschemIaappearstocontrIbutetothesearrhythmIas.The
1
receptoralso
IncreasesthesensItIvItyofthecontractIleelementstoCa
2+
.0rugspossessIngpotent
1
antagonIsmsuchasprazosInandphentolamInehavebeenshowntopossesssIgnIfIcant
antIarrhythmIcactIvIty,althoughoflImItedusefulnessbecauseofhypotensIon.Enhanced
1
actIvItywIthmyocardIalIschemIamayexplaInwhytheantIarrhythmIcbenefItsof
antagonIstsInpatIentswIthacutemyocardIalInfarctIonarefarfromcertaIn.The
contrIbutIonofreceptorstoposItIveInotropIsmandarrhythmogenesIsdurIngIschemIa
andreperfusIonmaybeovershadowedbythereceptorsdurIngacutefaIlureand
IschemIa.
Peripheral Vessels
ActIvatIonofthepresynaptIc
2
vascularreceptorsproducesvasodIlatIon,whereasthe
postsynaptIc
1
and
2
vascularreceptorssubservevasoconstrIctIon.PresynaptIcvascular
2
receptorsInhIbItNErelease.ThIsrepresentsanegatIvefeedbackmechanIsmbywhIch
NEInhIbItsItsownreleasevIatheprejunctIonalreceptor.PresynaptIc
2
agonIsts,suchas
clonIdIne,InhIbItNEreleaseattheneurosympathetIcjunctIonproducIngvasodIlatatIon.
TheeffectofselectIvepresynaptIc
2
receptoragonIststoamelIoratecoronary
vasoconstrIctIonInhumansIsunclear.ExcItatIonoftheInhIbItorypresynaptIc
2
receptors
byendogenousorsynthetIccatecholamInesalsoInhIbItsNErelease.However,most
sympathomImetIcsarenonselectIveagonIststhatwIllexcIteequallypresynaptIc
2
vasodIlatorsandvasoconstrIctIvepostsynaptIc
1
and
2
receptors.PostsynaptIc
1
and
2
receptorscoexIstInboththearterIalandvenoussIdesofthecIrculatIonwIththerelatIve
dIstrIbutIonof
2
receptorsbeInggreateronthevenoussIde.
11
ThIsmayexplaInwhypure
1
agonIsts,suchasmethoxamIne,producelIttlevenoconstrIctIon,whereasmany
nonselectIveagonIstssuchasphenylephrIneproducesIgnIfIcantvenoconstrIctIon.NEIsthe
mostpotentvenoconstrIctorofallthecatecholamInes.ClInIcally,venoconstrIctIonwould
havetheeffectofpreloadIngbyshIftIngvenouscapacItancecentrally,whereasstImulatIon
ofarterIalpostsynaptIc
1
and
2
receptorswouldeffectafterloadIngbyIncreasIngarterIal
resIstance.
Alpha-Adrenergic Receptors in the Central Nervous System
Allsubtypesofthe,,and0AreceptorshavebeenfoundInvarIousregIonsofthebraIn
andspInalcord.ThefunctIonalroleofthecerebralandreceptorssuggestsaclose
assocIatIonwIthbloodpressureandHFcontrol.CerebralandspInalcordpresynaptIc
2
receptorsarealsoInvolvedInInhIbItIonofpresynaptIcNErelease.AlthoughthebraIn
contaInsadrenergIcanddopamInergIcreceptors,cIrculatIngcatecholamInesdonotcross
thebloodbraInbarrIer.ThecatecholamInesInthebraInaresynthesIzedthere.|any
actIonshavebeenattrIbutedtothecerebralpostsynaptIc
2
receptor.ThIsIncludes
InhIbItIonofInsulInrelease,InhIbItIonofbowelmotIlIty,stImulatIonofgrowthhormone
release,andInhIbItIonofantIdIuretIchormonerelease.CentralneuraxIsInjectIonof
2
agonIsts,suchasclonIdIne,InducesanalgesIa,sedatIon,andcardIovasculardepressIon.The
IncreasedduratIonofepIduralorIntrathecalanesthesIabytheaddItIonofnonselectIve
agonIststothelocalanesthetIcmayproduceaddItIonalanalgesIathroughthIsmechanIsm.
Alpha Receptors in the Kidney
ThekIdneyhasanextensIveandexclusIveadrenergIcInnervatIonoftheafferentand
efferentglomerulararterIoles,proxImalanddIstalrenaltubules,ascendIngloopofHenle,
andjuxtaglomerularapparatus.ThegreatestdensItyofInnervatIonIsInthethIck
ascendIngloopofHenle,followedbythedIstalconvolutedtubulesandproxImaltube.8oth
1
and
2
subtypesarefoundInthekIdneywIththe
2
receptordomInatIng.The
1
receptorIspredomInantIntherenalvasculatureandelIcItsvasoconstrIctIon,whIch
modulatesrenalbloodflow.Tubular
1
receptorsenhancesodIumandwaterreabsorptIon,
leadIngtoantInatrIuresIs,whereastubular
2
receptorspromotesodIumandwater
excretIon.
Beta-Adrenergic Receptors
TheadrenergIcreceptors,lIkethereceptor,havebeendIvIdedIntosubtypes.Theyare
desIgnatedasthe
1
and
2
subtypes.Fecently,molecularclonInghasdemonstratedthe
exIstenceofathIrdsubtype,namely
J
receptor.ActIvatIonofallthesereceptorssubtypes
InducestheactIvatIonofadenylylcyclaseandIncreasedconversIonofATPtocyclIc
adenosIneJ,5monophosphate(cA|P).
1
receptorspredomInateInthemyocardIum,the
sInoatrIalnode,andtheventrIcularconductIonsystem.The
1
receptorsalsomedIatethe
effectsofthecatecholamInesonthemyocardIum.ThesereceptorsareequallysensItIveto
EPandNE,whIchdIstInguIshesthemfromthe
2
receptors.Effectsof
1
stImulatIonare
outlInedInTable154,whIchIncludestheIreffectsspecIfIcallyonthecardIovascular
system.
The
2
receptorsarelocatedInthesmoothmusclesofthebloodvesselsIntheskIn,
muscle,mesentery,andInbronchIalsmoothmuscle.StImulatIonproducesvasodIlatIonand
bronchIalrelaxatIon.The
2
receptorsaremoresensItIvetoEPthanNE.Feceptorsare
foundInbothpresynaptIcandpostsynaptIcmembranesoftheadrenergIcneuroeffector
junctIon(Table154).
1
FeceptorsaredIstrIbutedtopostsynaptIcsItesandhavenotbeen
IdentIfIedonthepresynaptIcmembrane.PresynaptIcreceptorsareofthe
2
subtype.
TheeffectsofactIvatIonofthepresynaptIc
2
receptoraredIametrIcallyopposedtothose
ofthepresynaptIc
2
receptor.ThepresynaptIc
2
receptoracceleratesendogenousNE
release,whereasblockadeofthIsreceptorwIllInhIbItNErelease.AntagonIsmofthe
presynaptIc
2
receptorsproducesaphysIologIcalresultsImIlartoactIvatIonofthe
presynaptIc
2
receptor.ThepostsynaptIc
1
receptorsarelocatedonthesynaptIc
membraneandrespondprImarIlytoneuronalNE.ThepostsynaptIc
2
receptors,lIkethe
postsynaptIc
2
receptor,respondprImarIlytocIrculatIngEP.
Beta Receptors in the Cardiovascular System
Myocardium
|yocardIalreceptorswereorIgInallyclassIfIedas
1
receptors.ThoseInthevascularand
bronchIalsmoothmusclewerecalledthe
2
subtype.However,studIeshaveconfIrmedthe
coexIstenceof
1
and
2
receptorsInthemyocardIum.
18
8oth
1
and
2
receptorsare
functIonallycoupledtoadenylatecyclase,suggestIngasImIlarInvolvementInthe
regulatIonofInotropIsmandchronotropIsm.PostsynaptIc
1
receptorsaredIstrIbuted
predomInantlytothemyocardIum,thesInoatrIalnode,andtheventrIcularconductIon
system.The
2
receptorshavethesamedIstrIbutIonbutarepresynaptIc.ActIvatIonofthe
presynaptIc
2
receptoracceleratesthereleaseofNEIntothesynaptIccleft.The
2
receptorapproxImates20toJ0ofthereceptorsIntheventrIcularmyocardIumandup
to40ofthereceptorsIntheatrIum.
TheeffectofNEonInotropIsmInthenormalheartIsmedIatedentIrelythroughthe
postsynaptIc
1
receptor,whereastheInotropIceffectsofEParemedIatedthroughboth
the
1
and
P.J40
2
myocardIalreceptors.The
2
receptorsmayalsomedIatethechronotropIcresponsesto
EP,whIchexplaInswhyselectIve
1
antagonIstsarelesseffectIveInsuppressIngInduced
tachycardIathanthenonselectIve
1
antagonIstpropranolol.
Peripheral Vessels
ThepostsynaptIcvascularreceptorsarevIrtuallyallofthe
2
subtype.The
2
receptors
arelocatedInthesmoothmuscleofthebloodvesselsoftheskIn,muscle,mesentery,and
bronchI.StImulatIonofthepostsynaptIc
2
receptorproducesvasodIlatIonandbronchIal
relaxatIon.|odestvasoconstrIctIonoccurswhensubjectedtoblockadebecausetheactIons
ofthevascularpostsynaptIc
2
receptorsnolongeropposetheactIonsofthe
1
and
postsynaptIcreceptors.
Beta Receptors in the Kidney
ThekIdneycontaInsboth
1
and
2
receptors,wIththe
1
beIngpredomInant.FenInrelease
fromthejuxtaglomerularapparatusIsenhancedbystImulatIon.The
1
receptorevokes
renInreleaseInhumans.Fenal
2
receptorsalsoappeartoregulaterenalbloodflowatthe
vascularlevel.TheyhavebeenIdentIfIedpharmacologIcallyandmedIateavasodIlatory
response.
Dopaminergic Receptors
0A,synthesIzedIn1910,wasrecognIzedIn1959notonlyasavasopressorandtheprecursor
ofNEandEP,butalsoasanImportantcentralandperIpheralneurotransmItter.0A
receptorshavebeenlocalIzedIntheCNS,onbloodvessels,andpostganglIonIcsympathetIc
nerves(Table154).TwoclInIcallyImportanttypesof0AreceptorshavebeenrecognIzed
0A
1
and0A
2,
whIleothersubtypeslIke0A
4,
and0A
5
,arestIllbeIngInvestIgated.The0A
1
receptorsarepostsynaptIc,whereasthe0A
2
receptorsarebothpresynaptIcand
postsynaptIc.ThepresynaptIc0A
2
receptors,lIkethepresynaptIc
2
receptor,InhIbItNE
releaseandcanproducevasodIlatatIon.ThepostsynaptIc0A
2
receptormaysubserve
vasoconstrIctIonsImIlartothatofthepostsynaptIc
2
receptor.ThIseffectIsopposIteto
thatofthepostsynaptIc0A
1
renalvascularreceptor.Thezonaglomerulosaoftheadrenal
cortexalsocontaIns0A
2
receptors,whIchInhIbItthereleaseofaldosterone.
Myocardium
0efInIngspecIfIcdopamInergIcreceptorshasbeendIffIcultbecause0Aalsoexertseffects
ontheandreceptors.0AreceptorshavenotbeendescrIbedInthemyocardIum.Effects
of0AarethoserelatedtoactIvatIonof
1
receptors,whIchpromoteposItIveInotropIsm
andchronotropIsm.
2
ActIvatIonwouldproducesomesystemIcvasodIlatatIon.
Peripheral Vessels
Thegreatestnumbersof0A
1
postsynaptIcreceptorsarefoundonvascularsmoothmuscle
cellsofthekIdneyandmesentery,butarealsofoundIntheothersystemIcarterIes
IncludIngcoronary,cerebral,andcutaneousarterIes.Thevascularreceptorsare,lIkethe
2
receptors,lInkedtoadenylatecyclaseandmedIatesmoothmusclerelaxatIon.
ActIvatIonofthesereceptorsproducesvasodIlatatIon,IncreasIngbloodflowtothese
organs.ConcurrentactIvatIonofvascularpresynaptIc0A
2
receptorsalsoInhIbItsNErelease
atpresynaptIc
2
receptors,whIchmayalsocontrIbutetoperIpheralvasodIlatatIon.HIgher
dosesof0AcanmedIatevasoconstrIctIonvIathepostsynaptIc
1
and
2
receptors.The
constrIctIveeffectIsrelatIvelyweakInthecardIovascularsystemwheretheactIonof0A
onadrenergIcreceptorsIs1/J5and1/50aspotentasthatofEPandNE,respectIvely.
19,20
Central Nervous System
0AreceptorshavebeenIdentIfIedInthehypothalamuswheretheyareInvolvedIn
prolactInrelease.TheyarealsofoundInthebasalganglIawheretheycoordInatemotor
functIon.0egeneratIonofdopamInergIcneuronsInthesubstantIanIgraIsthesourceof
ParkInsondIsease.AnothercentralactIonof0AIstostImulatethechemoreceptortrIgger
zoneofthemedulla,producIngnauseaandvomItIng.0AantagonIstssuchashaloperIdol
anddroperIdolareclInIcallyeffectIveIncounterIngthIsactIon.
Kidney and Mesentery
ApartfromtheIreffectonthevesselsofthekIdneyandmesentery,0Areceptorsonthe
smoothmuscleoftheesophagus,stomach,andsmallIntestIneenhancesecretIon
productIonandreduceIntestInalmotIlIty.
19,20
|etoclopramIde,a0AantagonIst,Isuseful
foraspIratIonprophylaxIsbypromotInggastrIcemptyIng.ThedIstrIbutIonof0Areceptors
IntherenalvasculatureIswellknown,but0AreceptorshaveotherfunctIonswIthInthe
kIdney.0A
1
receptorsarelocatedonrenaltubules,whIchInhIbItsodIumreabsorptIonwIth
subsequentnatrIuresIsanddIuresIs.ThenatrIuresIsmaybetheresultofacombInedrenal
vasodIlatatIon,ImprovedCD,andtubularactIonofthe0A
1
receptors.Juxtaglomerular
cellsalsocontaIn0A
1
receptors,whIchIncreaserenInreleasewhenactIvated.ThIsactIon
modulatesthedIuresIsproducedby0A
1
actIvatIonofthetubules.
0AhasunIqueautonomIceffectsbyactIvatIngspecIfIcperIpheraldopamInergIcreceptors,
whIchpromotenatrIuresIsandreduceafterloadvIadIlatatIonoftherenalandmesenterIc
arterIalbeds.PerIpheraldopamInergIcactIvItyservesasanaturalantIhypertensIve
mechanIsm.tsactIonsareovershadowedbytheopposIteeffectofItsmaInbIologIc
partner,NE.PlasmaNElevelsareknowntoIncreasewIthagIng,lIkelytheresultof
reducedclearance,whIleperIpheraldopamInergIcactIvItyIsknowntodImInIsh.Subtle
changesInthe0ANEbalancewIthagIngmayaccountforthedImInIshedabIlItyoftheaged
kIdneytoexcreteasaltload.
Other Receptors
Adenosine Receptors
AdenosIneproducesInhIbItIonofNErelease.TheeffectofadenosIneIsblockedbycaffeIne
andothermethylxanthInes.ThephysIologIcfunctIonofthesereceptorsmaybethe
reductIonofsympathetIctoneunderhypoxIccondItIonswhenadenosIneproductIonIs
enhanced.AsaconsequenceofreducedNErelease,cardIacworkwouldbedecreasedand
oxygendemandreduced.AdenosInehasbeeneffectIvelyusedtoproducecontrolled
hypotensIon.
21
Serotonin
SerotonIn(5hydroxytryptamIne)depressestheresponseofIsolatedbloodvesselstoSNS
stImulatIonanddecreasesreleaseoflabeledNEInthesepreparatIons.FaIsIngtheexternal
calcIumIonconcentratIonantagonIzesthIsInhIbItoryactIonofserotonIn.Thus,serotonIn
mayInhIbItneuronalNEreleasebyamechanIsmthatlImItstheavaIlabIlItyofcalcIumIons
atthenervetermInal.
Prostaglandin E2, Histamine, and Opioids
ProstaglandInE
2
,hIstamIne,andseveralopIoIdshavebeenreportedtoacton
prejunctIonalreceptorsItestoInhIbItNEreleaseIncertaInsympathetIcallyInnervated
tIssue.However,theseInhIbItoryreceptorsareunlIkelytoplayaphysIologIcroleIn
lImItIngNEreleasesIncetheIrdIrectantagonIsts,compoundslIkeInhIbItorsofcyclo
oxygenase,hIstamIneantagonIsts,andnaloxonedonotIncreaseaNErelease.
HIstamIneactsInamannersImIlartotheneurotransmIttersoftheSNS.Cellmembranehas
specIfIcreceptorsforhIstamIne,wIththeIndIvIdualresponsebeIngdetermInedbythetype
ofcellbeIngstImulated(seeChapter1J).Two
P.J41
receptorsforhIstamInehavebeendetermIned.ThesehavebeendesIgnatedH
1
andH
2
,for
whIchIthasbeenpossIbletodevelopspecIfIcagonIstsandantagonIsts.StImulatIonofthe
H
1
receptorsproducesbronchoconstrIctIonandIntestInalcontractIon.Themajorroleof
theH
2
receptorsIsrelatedtoacIdproductIonbytheparIetalcellsofthestomach;
however,hIstamIneIspresentInrelatIvelyhIghconcentratIonsInthemyocardIumand
cardIacconductIngtIssue,whereItexertsposItIveInotropIcandchronotropIceffectswhIle
depressIngdromotropIsm.TheposItIveInotropIcandchronotropIceffectsofhIstamIneare
H
2
receptoreffectsthatarenotblockedbyantagonIsm.TheseeffectsareblockedbyH
2
antagonIsts,suchascImetIdIne,whIchaccountsfortheoccasIonalreportofcardIovascular
collapsefollowIngtheuseofcImetIdIne.ThenegatIvedromotropIceffectandthatof
coronaryspasmcausedbyhIstamIneareH
1
receptoreffects.
Adrenergic Receptor Numbers and Sensitivity
Feceptors,oncethoughttobestatIcentItIes,arenowthoughttobedynamIcallyregulated
byavarIetyofcondItIonsandtobeInaconstantstateofflux.FeceptorsaresynthesIzed
InthesarcoplasmIcretIculumoftheparentcell,wheretheymayremaInextrasynaptIcor
externalIzetothesynaptIcmembraneswheretheymaycluster.|embranereceptorsmay
beremovedorInternalIzedtoIntracellularsItesforeItherdehydratIonorrecyclIng.
ThenumbersandsensItIvItyofadrenergIcreceptorscanbeInfluencedbynormal,genetIc,
anddevelopmentalfactors.ChangesInthenumberofreceptorsaltertheresponseto
catecholamInes.AlteratIonInthenumber,ordensIty,ofreceptorsIsreferredtoaseIther
up-regulationordown-regulation.Asarule,thenumberofreceptorsIsInversely
proportIonaltotheambIentconcentratIonofthecatecholamInes.Extendedexposureof
receptorstotheIragonIstsmarkedlyreduces,butdoesnotablate,thebIologIcresponseto
catecholamInes.Forexample,IncreasedadrenergIcactIvItyoccursInresponsetoreduced
perfusIonasaresultofacuteorchronIcmyocardIaldysfunctIon.PlasmacatecholamInes
areIncreased.Subsequently,themyocardIalpostsynaptIc
1
receptorsdownregulate
(seeChapter6).ThIsIsthoughttoexplaInthedImInIshedInotropIcandchronotropIc
responseto
1
agonIstsandexercIseInpatIentswIthchronIcheartfaIlure.However,
calcIumInducedInotropIsmIsnotImpaIredbecause
2
receptor(extrasynaptIc)numbers
remaInrelatIvelyIntact.The
2
receptorsmayaccountforupto40oftheInotropIsmof
thefaIlIngheartcomparedwIth20Inthenormalheart.
17,22
TachyphylaxIstoInfused
catecholamInesIsalsothoughttobetheresultofacutedownregulatIonofreceptor
numbers.ThereappearstobeareductIonInnumbersorsensItIvItyofreceptorsIn
hypertensIvepatIentswhoalsohaveelevatedplasmacatecholamInes.0ownregulatIonIs
thepresumptIveexplanatIonforthelackofcorrelatIonbetweenplasmacatecholamIne
levelsandthebloodpressureelevatIonInpatIentswIthpheochromocytoma.ChronIcuseof
agonIstssuchasterbutalIne,Isoproterenol,orEPforthetreatmentofasthmacanresult
IntachyphylaxIsbecauseofdownregulatIon.Evenshorttermuse(1to6hours)of
agonIstsmaycausedownregulatIonofreceptornumbers.0ownregulatIonIsreversIbleon
termInatIonoftheagonIst.ChronIctreatmentofanImalswIthnonselectIvebetablockade
causesa100IncreaseInthenumberofreceptors.ThIsaccountsforthepropranolol
wIthdrawalsyndromeInwhIchtheacutedIscontInuatIonoftheantagonIstleavesthe
receptorsunopposedplusanIncreasednumberofreceptors.ClonIdInewIthdrawalcanbe
explaInedbythesamemechanIsm.UpordownregulatIonofreceptornumbersmaynot
altersensItIvItyofthereceptor.LIkewIse,sensItIvItymaybeIncreasedordecreasedInthe
presenceofnormalnumbersofreceptors.ThepharmacologIcfactorsaffectIngupor
downregulatIonoftheandreceptorsaresImIlar.
Autonomic Nervous System Reflexes and Interactions
TheANSreflexhasbeencomparedtothecomputercIrcuIt.ThIscontrolsystem,asInall
reflexsystems,has(1)sensors,(2)afferentpathways,(J)CNSIntegratIon,and(4)efferent
pathwaystothereceptorsandefferentorgans.FIneadjustmentsaremadeatthelocal
levelaccordIngtoposItIveandnegatIvefeedbackmechanIsms.ThebaroreceptorIsan
example.ThevarIabletobecontrolled(bloodpressure)Issensed(carotIdsInus),
Integrated(medullaryvasomotorcenter),andadjustedthroughspecIfIceffectorreceptor
sItes.0rugsordIseasecanInterruptthIscIrcuItatanypoInt.8etablockersmayattenuate
theeffectorresponse,whereasanagonIstsuchasclonIdInemayalterboththeeffector
andtheIntegratorfunctIonsofbloodpressurecontrol.
Baroreceptors
ThereareseveralreflexesInthecardIovascularsystem,whIchhelpcontrolarterIalblood
pressure,CD,andHF.TheaImofthecIrculatIonIstoprovIdebloodflowtoallthebody
organs(seeChapter10).Yet,themostImportantcontrolledvarIabletowhIchthesensors
areattunedIsbloodpressure,aproductofthebloodflowandvascularresIstance.EtIenne
|areynotedIn1859thatthepulserateIsInverselyproportIonaltothebloodpressure,and
thIsIsknownasMarey's law.Subsequently,HerIng,Koch,andothersdemonstratedthatthe
alteratIonsInHFevokedbychangesInbloodpressuredependonbaroreceptorslocatedIn
theaortIcarchandthecarotIdsInuses.ThesepressuresensorsreacttoalteratIonsIn
stretchcausedbybloodpressure.mpulsesfromthecarotIdsInusandaortIcarchreachthe
medullaryvasomotorcenterbytheglossopharyngealandvagusnerves,respectIvely.
ncreasedsensorytraffIcfromthebaroreceptors,causedbyIncreasedbloodpressure,
InhIbItsSNSeffectortraffIc.TherelatIveIncreaseInvagaltoneproducesvasodIlatIon,
slowIngoftheHF,andalowerIngofbloodpressure.FealIncreasesInvagaltoneoccur
whenbloodpressureexceedsnormallImIts.The7alsalvamaneuvercanbestdemonstrate
thearterIalbaroreceptorreflex(FIg.1511).The7alsalvamaneuver
P.J42
raIsestheIntrathoracIcpressurebyforcedexpIratIonagaInstaclosedglottIs.ThearterIal
bloodpressurerIsesmomentarIlyastheIntrathoracIcbloodIsforcedIntotheheart
(preload).SustaInedIntrathoracIcpressuredImInIshesvenousreturn,reducestheCD,and
dropsthebloodpressure.FeflexvasoconstrIctIonandtachycardIaensue.8loodpressure
returnstonormalwIthreleaseoftheforcedexpIratIon,butthenbrIeflyovershoots
becauseofthevasoconstrIctIonandIncreasedvenousreturn.AslowIngoftheHF
accompanIestheovershootInpressure.ThecardIovascularresponsestothe7alsalva
maneuverrequIreanIntactANScIrcuItfromperIpheralsensortoperIpheraladrenergIc
receptors.The7alsalvamaneuverhasbeenusedtoIdentIfypatIentsatrIskforanesthesIa
becauseofANSInstabIlIty(FIg.1511).ThIswasonceamajorconcernInpatIentsreceIvIng
drugsthatdepletedcatecholamInes,suchasreserpIne.0ysfunctIonoftheSNSIsImplIcated
IfexaggeratedandprolongedhypotensIondevelopsdurIngtheforcedexpIratIonphase(50
fromrestIngmeanarterIalpressure).naddItIon,theovershootattheendofthe7alsalva
maneuverIsabsent.0ysfunctIonofthePNScanbeassumedIftheHFdoesnotrespond
approprIatelytothebloodpressurechanges.
Figure 15-11. A.Thenormalbloodpressureresponsetothe7alsalvamaneuverIs
demonstrated.PulseratemovesInarecIprocaldIrectIonaccordIngto|arey'slawof
theheart.B.Anabnormal7alsalvaresponseIsshownInapatIentwIthC5
quadrIplegIa.
7enousbaroreceptorsmaybemoredomInantInthemomenttomomentregulatIonofCD.
8aroreceptorsIntherIghtatrIumandgreatveInsproduceanIncreaseInHFwhen
stretchedbyIncreasedrIghtatrIalpressure.FeducedvenouspressuredecreasesHF.UnlIke
thearterIalbaroreceptors,venoussensorsarenotthoughttoaltervasculartone;however,
venoconstrIctIonIspostulatedtooccurwhenatrIalpressuresdeclIne.Stretchofthevenous
receptorsproduceschangesInHFopposItethoseproducedwhenthearterIalpressure
sensorsarestImulated.ThearterIalandvenouspressurereceptorsareseparately
monItorIngtwoofthefourmajordetermInantsofCD,afterloadandpreload,respectIvely.
7enousbaroreceptorssamplepreloadbystretchoftheatrIum.ArterIalbaroreceptors
surveyresIstance,orafterload,asreflectedInthemeanarterIalpressure.Afterloadand
preloadproduceopposIteeffectsonCD;thus,oneshouldnotbesurprIsedthatthevenous
andarterIalbaroreceptorsproduceeffectsopposItethoseofasImIlarstretchstImulus,
pressure.
8aInbrIdgedescrIbedthevenousbaroreceptorreflexanddemonstratedthatItcanbe
abolIshedbyvagalresectIon.NumerousInvestIgatorshaveconfIrmedtheacceleratIonof
theHFInresponsetovolume.However,themagnItudeanddIrectIonoftheHFresponse
dependontheprevaIlIngHFatthetImeofstImulatIon.Thedenervated,transplanted
mammalIanheartalsoacceleratesInresponsetovolumeloadIng.HF,lIkeCD,can
apparentlybeadjustedtothequantItyofbloodenterIngtheheart.The8aInbrIdgereflex
relatestothecharacterIstIcbutparadoxIcalslowIngoftheheartseenwIthspInal
anesthesIa.8lockadeoftheSNSlevelsofT1T4ablatestheefferentlImbofthecardIac
acceleratornerves.ThIssourceofcardIacdeceleratIonIsobvIous,asthevagusnerveIs
unopposed.However,bradycardIadurIngspInalanesthesIaIsmorerelatedtothe
developmentofarterIalhypotensIonthantotheheIghtoftheblock.TheprImarydefectIn
thedevelopmentofspInalhypotensIonIsadecreaseInvenousreturn.TheoretIcally,the
arterIalhypotensIonshouldreflexlyproduceatachycardIathroughthearterIal
baroreceptors.nstead,bradycardIaIsmorecommon.8rIdenbaughetal.
2J
suggestthat,In
theunmedIcatedperson,thevenousbaroreceptorsaredomInantoverthearterIal.A
reducedvenouspressure,therefore,slowsHF.ncontrast,humorallymedIatedtachycardIa
IstheusualresponsetohypotensIonoracIdosIsfromothercauses.
Denervated Heart
FeflexmodulatIonoftheadrenergIcagonIstsIsbestseenInthedenervatedtransplant
heart,whIchretaInstherecIpIent'sInnervatedsInoatrIalnodeandthedonor'sdenervated
sInoatrIalnode
24
(seeChapter54).NEInfusIonInthetransplantedheartproducesaslowIng
oftherecIpIent'satrIalratethroughvagalfeedbackasthebloodpressurerIses.nthe
unmodulateddonorheart,atrIalrateIncreases.Thebaroreceptorsarethereforenot
operantInthetransplantedheart.soproterenol,apureagonIst,IncreasesthedIscharge
rateofboththerecIpIentanddonornodebydIrectactIon,wIththedonorratenear
doublIngthatoftherecIpIentnode.AtropIneacceleratestherecIpIent'satrIalrate,
whereasnoeffectIsseenonthedonorrate,whIchnowcontrolsHF.
8etablockadeproducescomparableslowIngofthesInoatrIalnodeofbothrecIpIentand
donor.TheexercIsecapabIlItyofthedenervatedheartIsconspIcuouslyreducedbybeta
blockade,presumablybecauseofItsrelIanceoncIrculatIngcatecholamInes.Propranolol
hasalsobeendemonstratedtoreducetheresponsetochronotropIceffectsofNEand
IsoproterenolInthetransplantedheart.TheCDofthetransplantedheartvarIes
approprIatelywIthchangesInpreloadandafterload.
Interaction of Autonomic Nervous System Receptors
StrongInteractIonshavebeennotedbetweenSNSandPNSnervesInorgansthatreceIve
dual,antagonIstIcInnervatIon.FeleaseofNEatthepresynaptIctermInalIsmodIfIedbythe
PNS.Forexample,vagalInhIbItIonofleftventrIcularcontractIlItyIsaccentuatedasthe
levelofSNSactIvItyIsraIsed.ThIsInteractIonIstermedaccentuated antagonismandIs
medIatedbyacombInatIonofpresynaptIcandpostsynaptIcmechanIsms.Thecoronary
arterIespresentanexampleofthIsphenomenonanddeservespecIalattentIon.
ThemyocardIumandcoronaryvesselsareabundantlysupplIedwIthadrenergIcand
cholInergIcfIbers.StrongactIvItyofbothandreceptorshasbeendemonstratedInthe
coronaryvascularbed.SelectIvestImulatIonofboththe
1
andpostsynaptIc
2
receptors
IncreasescoronaryvascularresIstance,whereasselectIveblockadeelImInatesthIs
effect.Therefore,both
1
and
1
adrenoreceptorsarepresentoncoronaryarterIesand
accessIbletoNEreleasedbysympathetIcnerves.
5,14
ThepresynaptIcadrenergIctermInalsofthemyocardIumandcoronaryvessels,lIkeall
bloodvesselsexamIned,contaInmuscarInIcreceptors.
10
FecentobservatIonsconfIrmthat
muscarInIcagentsandvagalstImulatIon,actIngonthepresynaptIc,SNSmuscarInIc
receptor,InhIbItthereleaseofNEInamannersImIlartothatofthepresynaptIc
2
and
0A
2
receptors(FIg.159).Conversely,blockadeofthemuscarInIcreceptorswIthatropIne
markedlyaugmentstheposItIveInotropIcresponsestocatecholamInes.
5
SuppressIonofNE
releaseexplaIns,Inpart,vagalInducedattenuatIonoftheInotropIcresponsetostrongSNS
stImulatIon(accentuatedantagonIsm)andonlyaweaknegatIveInotropIceffectofvagal
stImulatIonwhenthereIslowbackgroundSNSactIvIty.ThIsmayalsoexplaInwhyvagal
actIvItyreducesthevulnerabIlItyofthemyocardIumtofIbrIllatIondurIngInfusIonsofNE.
AChmaycausecoronaryspasmdurIngperIodsofhIghSNStone.
5
nhIbItIonofNEreleaseby
presynaptIcadrenergIcmuscarInIcreceptorsofthesmoothmuscleofcoronaryvessels
wouldlessenthecoronaryrelaxatIonnormallyproducedbyNEonthe
1
receptor(FIg.15
9).nanesthetIzeddogs,therateofNEoutflowIntothecoronarysInusblood,evokedby
cardIacSNSstImulatIon,IsmarkedlydImInIshedbysImultaneousvagalefferent
stImulatIon.
25
ThIsactIonIsknowntobepreventedbyatropIne,whIchalsocauses
coronaryvasodIlatIon.
Interaction with Other Regulatory Systems
TheANSIsIntegrallyrelatedtoseveralendocrInesystemsthatultImatelysummateto
controlbloodpressureandregulatehomeostasIs.TheseIncludetherenInangIotensIn
system,
P.J4J
antIdIuretIchormone,glucocortIcoIds,andInsulIn(seeChapter49).8othandreceptors
havebeenfoundIntheendocrInepancreasandmodulateInsulInrelease(Table154).
StImulatIonIncreasesInsulInrelease,whereasstImulatIondecreasesIt.Theoverall
ImportanceofthIsInteractIonIsnotentIrelyclear,butdecreasedtolerancetoglucoseand
potassIumhasbeennotedInsubjectstakIngbetablockIngdrugs.TherenInangIotensIn
systemIsacomplexendocrInesystemthatmodulatesbothbloodpressureandwater
electrolytehomeostasIs(FIg.1512).FenInIsaproteolytIcenzymecontaInedwIthInthe
cellsofthejuxtaglomerularapparatusoftherenalcortex.Whenreleased,Itactson
plasmaangIotensInogentoformangIotensIn.AngIotensInIsthenconvertedto
angIotensInbyconvertIngenzymeInthelung.AngIotensInIsapowerfuldIrectarterIal
vasoconstrIctor.talsoactsontheadrenalcortextoreleasealdosteroneandonthe
adrenalmedullatoreleaseEP.naddItIontoItsdIrecteffectsonvascularsmoothmuscle,
angIotensInaugmentsNEreleasevIapresynaptIcreceptors,thusenhancIngperIpheral
SNStone.CaptoprIl,enalaprIl,andlIsInoprIlInhIbIttheactIonofconvertIngenzyme,thus
preventIngtheconversIonofangIotensIntoangIotensIn.FenInIsreleasedInresponse
tohyponatremIa,decreasedrenalperfusIonpressure,andANSstImulatIonvIareceptors
onjuxtaglomerularcells.ChangesInsympathetIctonemaythusalterrenInreleaseand
affecthomeostasIsInavarIetyofways.TheANSIsalsoIntImatelyrelatedto
adrenocortIcalfunctIon.AsprevIouslyoutlIned,glucocortIcoIdreleasemodulates
phenylethanolamIneNmethyltransferaseformatIonandthussynthesIsofEP.
ClucocortIcoIdsarealsoImportantInregulatIngtheresponseofperIpheraltIssuesto
changesInSNStone.Thus,theANSIsIntImatelyrelatedtootherhomeostatIcmechanIsms.
Figure 15-12.TheInteractIonsoftherenInangIotensInandsympathetIcnervous
systemInregulatInghomeostasIsareshownschematIcallyalongwIththephysIologIc
varIablesthatmodulatetheIrfunctIon.ArrowswIthaplussIgn(+)represent
stImulatIon,andthosewIthamInussIgn()representInhIbItIon.
Clinical Autonomic Nervous System Pharmacology
TheclInIcalapplIcatIonofANSpharmacologyIsbasedonknowledgeofANSanatomy,
physIology,andmolecularpharmacology.0rugsthatmodIfyANSactIvItycanbeclassIfIed
bytheIrsIteofactIon,mechanIsmofactIon,orpathologyforwhIchtheyaremost
commonlyused.AntIhypertensIvedrugsareanexampleofthethIrdcategory.ThIs
classIfIcatIonIsamatterofdegreebecauseconsIderablefunctIonaloverlapoccurs.An
exampleofclassIfIcatIonbysIterelatestotheganglIonIcagonIstsorblockIngagents.ANS
drugscanbefurthercategorIzedasthosethatactattheprejunctIonalmembraneand
thoseactIngpostjunctIonally.TheycanthenbemorespecIfIcallyclassIfIedbythe
predomInantreceptororreceptorsonwhIchtheyact.
Mode of Action
ANSdrugsmaybebroadlyclassIfIedbymodeofactIonaccordIngtotheIrmImetIcorlytIc
actIons.ThIsmayalsobetermedagonistorantagonist.AsympathomImetIc,suchas
ephedrIne,mImIcsSNSsympathetIcactIvItybystImulatIonofadrenergIcreceptorsItes
bothdIrectlyandIndIrectly.SympatholytIcdrugscausedIssolutIonofSNSactIvItyatthese
samereceptorsItes.FeceptorblockersareexamplesofsympatholytIcdrugs.Several
modesofANSdrugactIonbecomeevIdentwhenonefollowsthecascadeof
neurotransmIssIon.0rugsthatactonprejunctIonalmembranesmaytherefore(1)Interfere
wIthtransmIttersynthesIs(methylparatyrosIne),(2)InterferewIthtransmItterstorage
(reserpIne),(J)InterferewIthtransmItterrelease(clonIdIne),(4)stImulatetransmItter
release(ephedrIne),or(5)InterferewIthreuptakeoftransmItter(cocaIne).0rugsmayalso
(6)modIfymetabolIsmoftheneurotransmItterInthesynaptIccleft(antIcholInesterase).
0rugsactIngatpostjunctIonalsItesmay(7)dIrectlystImulatepostjunctIonalreceptorsand
(8)InterferewIthtransmItteragonIstatthepostjunctIonalreceptor.
TheultImateresponseofaneffectororgantoanagonIstorantagonIstdependson(1)the
drug,(2)ItsplasmaconcentratIon,(J)thenumberofreceptorsIntheeffectororgan,(4)
bIndIngbythereceptor,(5)theconcurrentactIvItIesofotherdrugsandhormones,(6)the
cellularmetabolIcstatus,and(7)reflexadjustmentsbytheorganIsm.
Ganglionic Drugs
SNSandPNSganglIaarepharmacologIcallysImIlarInthattransmIssIonthroughtheseANS
ganglIaIseffectedbyACh(FIg.152).|ostganglIonIcagonIstsandantagonIstsarenot
P.J44
selectIveandaffectSNSandPNSganglIaequally.ThIsnonselectIvepropertycreatesmany
undesIrableandunpredIctablesIdeeffects,whIchhavelImItedtheclInIcalusefulnessof
thIscategoryofdrug.
Agonists
ThereareessentIallynoclInIcallyusefulganglIonIcagonIsts.NIcotIneIstheprototypIcal
ganglIonIcagonIst.nlowdoses,ItstImulatesANSganglIaandtheneuromuscularjunctIon
ofstrIatedmuscle.HIghdosesproduceganglIonIcandneuromuscularblockade.The
proteansIdeeffectsofnIcotInIcstImulatIonrenderItusefulonlyasanInvestIgatIvetool.
Antagonists
0rugsthatInterferewIthneurotransmIssIonatANSganglIaareknownasganglionic blocking
agents.NIcotIneInhIghdosesIstheprototypIcalganglIonIcblockIngagentalso;however,
earlystImulatorynIcotInIcactIvItycanbeblockedbothattheganglIaandmuscleend
plateswIthotherganglIonIcblockersandmusclerelaxants,respectIvely,wIthoutblockIng
muscarInIceffects.CanglIonIcblockersproducetheIrnIcotInIceffectsbycompetIng,
mImIckIng,orInterferIngwIthAChmetabolIsm.HexamethonIum,trImethaphan,and
pentolInIumproduceaselectIvenondepolarIzIngblockadeofneurotransmIssIonatANS
ganglIawIthoutproducIngnIcotInIcneuromuscularblockade.TheycompetewIthAChInthe
ganglIawIthoutstImulatIngthereceptors.TheIntroductIonofdrugsthatproduce
vasodIlatIondIrectlyorbyactIonontheSNSvasomotorcenterhasmadetheganglIonIc
blockersobsolete.dTubocurareproducesacompetItIvenondepolarIzIngblockofboth
motorendplatesandANSganglIa.TheactIonofmotorparalysIspredomInates,butthe
concomItantganglIonIcblockadeathIgherdosesexplaInspartofthehypotensIveeffect
oftenseenwIththeuseofdtubocurareformusclerelaxatIon.AntIcholInesterasedrugs
mayproducenIcotInIctypeganglIonIcblockadebycompetItIonwIthAChaswellasby
persIstentdepolarIzatIonvIaaccumulatedACh.
TrImethaphanproducesblockadebycompetItIonwIthAChforreceptors,thusstabIlIzIng
thepostsynaptIcmembrane.However,sIdeeffectsandrapIdonsettachyphylaxIshave
markedlyreducedItsuseInanesthesIa.
26
ThepatIent'spupIlsbecomefIxedanddIlated
durIngadmInIstratIon,whIchobscureseyesIgns,anImportantconsIderatIonfor
neurosurgery.nthIsregard,ItIsdIstInctlyInferIortonItroprussIde.Themajoradvantage
oftrImethaphanIsItsshortduratIonofactIon,whIchIstheresultofpseudocholInesterase
hydrolysIs.
Cholinergic Drugs
Muscarinic Agonists
ThecholInomImetIcmuscarInIcdrugsactatsItesInthebodywhereAChIsthe
neurotransmItterofthenerveImpulse.ThesedrugsmaybedIvIdedIntothreegroups,the
fIrsttwoofwhIcharedIrectmuscarInIcagonIsts.ThethIrdgroupactsIndIrectly.These
groupsarecholIneesters(ACh,methacholIne,carbamylcholIne,bethanechol),alkaloIds
(pIlocarpIne,muscarIne),andantIcholInesterases(physostIgmIne,neostIgmIne,
pyrIdostIgmIne,edrophonIum,echothIophate).
Direct Cholinomimetics
AChhasvIrtuallynotherapeutIcapplIcatIonsbecauseofItsdIffuseactIonandrapId
hydrolysIsbycholInesterase(seeFIg.155).DnemayencountertheuseoftopIcalACh(1)
dropsdurIngcataractextractIonwhenarapIdmIosIsIsdesIred.SystemIceffectsarenot
usuallyseenbecauseoftherapIdItyofAChhydrolysIs.0erIvatIvesofACh,othercholIne
estershavebeensynthesIzed,whIchpossessmoreselectIvemuscarInIcactIvItythanACh.
TheydIfferfromAChInbeIngmoreresIstanttoInactIvatIonbycholInesteraseandthus
havIngamoreprolongedandusefulactIon.TheyalsodIfferfromAChIntheIrrelatIve
muscarInIcandnIcotInIcactIvItIes.ThebeststudIedofthesedrugsaremethacholIne,
bethanechol,andcarbamylcholIne.ThechemIcalstructuresofAChandthesecholIne
estersareshownInFIgure151J.TheIrpharmacologIcactIonsarecomparedwIththoseof
AChInTable155.ThesearenotImportantdrugsInanesthesIologypractIcebut
anesthesIologIstsmayencounterpatIentswhoarereceIvIngthem.
Figure 15-13.ChemIcalstructuresofdIrectactIngcholInomImetIcestersand
alkaloIds.
AChIsaquaternaryammonIumcompoundthatInteractswIthpostsynaptIcreceptors,
causIngconformatIonalmembranechanges.ThIsresultsInIncreasedpermeabIlItytosmall
Ionsand,thus,depolarIzatIon.AllthereceptorstranslatethereversIblebIndIngofAChInto
openIngsofdIscretechannelsInexcItablemembranes,allowIngNa+andK+Ionstoflow
alongtheIrelectrochemIcalgradIents.StructureactIvItyrelatIonshIpspoInttothe
presenceoftwoImportantbIndIngsItesonthereceptor,anesteratIcsItethatbIndsthe
esterendofthemoleculeandanIonIcsItethatbIndsthequaternaryamIneportIon(FIg.
155).SubtlechangesInthestructureofthecompoundcanmarkedlyaltertheresponses
amongdIfferenttIssuegroups.ThedegreeofmuscarInIcactIvItyfallsIftheacetylgroupIs
replaced,butthIsconfersaresIstancetoenzymatIchydrolysIs.8ethanecholIsresIstantto
hydrolysIsbutpossessesmaInlymuscarInIcactIvIty.|ethylsubstItutIonproduces
methacholIne,whIchIslessresIstanttohydrolysIsandIsprImarIlyamuscarInIcagonIst.
|ethacholIneslowstheheartanddIlatesperIpheralbloodvessels.tIsusedtotermInate
supraventrIculartachydysrhythmIas,especIallyparoxysmaltachycardIa,whenother
measureshavefaIled.talsoIncreasesIntestInaltone.|ethacholIneshouldnotbegIvento
patIentswIthasthma.HypertensIvepatIentsmayalsodevelopmarkedhypotensIon.SIde
effectsarethoseofPNSstImulatIonsuchasnausea,vomItIng,andflushedsweatIng.
DverdoseIstreatedwIthatropIne.8ethanecholIsrelatIvelyselectIveforthe
P.J45
gastroIntestInalandurInarytracts.nusualdosesItdoesnotslowtheheartorlowerthe
bloodpressure.8ethanecolIsofvalueIntreatIngpostoperatIveabdomInaldIstentIon
(nonobstructIveparalytIcIleus),gastrIcatonyfollowIngbIlateralvagotomy,congenItal
megacolon,nonobstructIveurInaryretentIon,andsomecasesofneurogenIcbladder.
Table 15-5 Comparative Muscarinic Actions of Direct Cholinomimetic
Agents

SYSTEMIC
ACETYL-
CHOLINE
METHA-
CHOLINE
CARBAMYL-
CHOLINE
BETHANECHOL PILOCARPINE
Esterase Hydrolysis +++ + 0 0 0
Eye (Topical)
rIs ++ ++ +++ +++ +++
CIlIary ++ ++ +++ +++ ++
Heart
Fate - - :
ContractIlIty
ConductIon -
Smooth Muscle
7ascular -
8ronchIal ++ ++ + + ++
CastroIntestInal
motIlIty
++ ++ +++ +++ ++
CastroIntestInal
sphIncters
- - ++
8IlIary ++ ++ +++ +++ ++
8ladder
0etrusor ++ ++ +++ +++ ++
SphIncter - -
Exocrine Glands
FespIratory +++ ++ +++ ++ ++++
SalIvary ++ ++ ++ ++ +++++
Pharyngeal ++ ++ ++ ++ ++++
LacrImal ++ ++ ++ ++ ++++
Sweat ++ ++ ++ ++ +++++
CastroIntestInalacId
andsecretIons
++ ++ ++ ++ ++++
Nicotinic Actions +++ + +++ +++
+,stImulatIon;,InhIbItIon.
0IrectactIngcholInomImetIcalkaloIdsIncludemuscarIneandpIlocarpIne.Theyactatthe
samesItesasACh,andtheIreffectsaresImIlartothoseofAChasdescrIbedInTable155.
TherearenousesforthesedrugsInanesthesIology.PIlocarpIneIstheonlydrugofthIs
groupusedtherapeutIcallyIntheUnItedStates.tssoleuseIsforthetreatmentof
glaucoma,forwhIchItIsthestandard.tIsusedasatopIcalmIotIcdrugInophthalmologIc
practIcetoreduceIntraocularpressureInglaucoma.
|uscarInIcagonIstsarepartIcularlydangerousInpatIentswIthmyasthenIagravIs(whoare
receIvIngantIcholInesterases),bulbarpalsy,cardIacdIsease,asthma,peptIculcer,
progressIvemuscularatrophy,ormechanIcalIntestInalobstructIonorurInaryretentIon
becausetheyIntensIfythesecondItIons.
Indirect Cholinomimetics
TheIndIrectactIngcholInomImetIcdrugsareofgreaterImportancetotheanesthesIologIst
thanarethedIrectactIngdrugs.ThesedrugsproducecholInomImetIceffectsIndIrectlyas
aresultofInhIbItIonorInactIvatIonoftheenzymeacetylcholInesterase,whIchnormally
destroysAChbyhydrolysIs.Theyarereferredtoascholinesterase inhibitorsor
anticholinesterases.|ostofthesedrugsInhIbItbothacetylcholInesteraseand
pseudocholInesterase.nhIbItIonofacetylcholInesterasepermItstheaccumulatIonofACh
transmItterInthesynapse,resultIngInIntensePNSactIvItysImIlartothatofthedIrect
cholInomImetIcagents.TheaccumulatIonofAChbytheantIcholInesterasespotentIallycan
produceallofthefollowIng:(1)stImulatIonofmuscarInIcreceptorsatANSeffectorgans,
(2)stImulatIonfollowedbydepressIonofallANSganglIaandskeletalmuscle(nIcotInIc),
and(J)stImulatIonwIthlaterdepressIonofcholInergIcreceptorsItesIntheCNS.Allof
theseeffectsmaybeseenwIthlethaldosesofantIcholInesterasedrugs,buttherapeutIc
dosesonlyproducethefIrsttwo.
ActIonsoftherapeutIcsIgnIfIcanceoftheantIcholInesterasedrugstotheanesthesIologIst
concerntheeye,theIntestIne,andtheneuromuscularjunctIon.Theeffectsof
antIcholInesterasesareusefulInthetreatmentofmyasthenIagravIs,glaucoma,andatony
ofthegastroIntestInalandurInarytracts.AntIcholInesterasedrugsareusedroutInelyIn
anesthesIatoreversenondepolarIzIngneuromuscularblock.ThemostpromInent
pharmacologIceffectsoftheantIcholInesterasedrugsaremuscarInIc.TheIrmostuseful
actIonsaretheIrnIcotInIceffects.|uscarInIcactIvItyIsevokedbylowerconcentratIonsof
AChthanarenecessarytoproducethedesIrednIcotInIceffect.Forexample,the
antIcholInesteraseneostIgmInereversesneuromuscularblockadebyIncreasIngACh
concentratIonatthemuscleendplate,anIcotInIcreceptor.NIcotInIcreversalof
neuromuscularblockadecanusuallybeproducedsafelyonlywhenthepatIenthasbeen
protectedbyatropIneorothermuscarInIc
P.J46
blockers.ThIspreventstheuntowardmuscarInIceffectsofbradycardIa,hypotensIon,
bronchospasm,orIntestInalspasm.FeversalofneuromuscularblockadeInpatIentswho
havehadbowelanastomosIswasatonetImeamajorcontroversy(seeNeuromuscular
8lockers).SomethoughtthatthemuscarInIceffectsofantIcholInesterasedrugs
(hypermotIlIty)IncreasedtherIskofanastomotIcleakagewhereasothersfoundno
assocIatIonbetweentheIruseandsubsequentbreakdown.NatIonalexperIencehasfavored
thelatteropInIon.
ClInIcally,antIcholInesterasedrugsmaybedIvIdedIntotwotypes:thereversIbleand
nonreversIblecholInesteraseInhIbItors.
26
FeversIblecholInesteraseInhIbItorsdelaythe
hydrolysIsofAChfrom1to8hours.NonreversIbledrugsaresonamedbecausetheIr
InhIbItoryeffectsmaylastfromdaystoweeks.ThedIfferencesInduratIonofvarIous
antIcholInesterasesapparentlydependonwhethertheyInhIbIttheanIonIcoresteratIcsIte
ofacetylcholInesterase.Therefore,theantIcholInesterasedrugshavealsobeen
pharmacologIcallysubdIvIded.0rugsthatInhIbIttheanIonIcsItearecalledcompetitive
inhibitors.TheIractIonIsduetocompetItIonbetweentheantIcholInesteraseandAChfor
theanIonIcsIte.ThesedrugstendtobeshortactIng.EdrophonIumIsanexampleofthIs
type.0rugsthatInhIbIttheesteratIcsItearecalledacid-transferring inhibitors.These
drugsIncludethelongeractIngneostIgmIne,pyrIdostIgmIne,andphysostIgmIne.
|ostofthereversIblecholInesteraseInhIbItorsarequaternaryammonIumcompoundsand
donotcrossthebloodbraInbarrIer.PhysostIgmIneIsatertIaryamInethatreadIlypasses
IntotheCNS(FIg.1514).tproducescentralmuscarInIcstImulatIonand,thus,Isnotused
toreverseneuromuscularblockadebutcanbeusedtotreatatropInepoIsonIng.
Conversely,atropIneIsusedtotreatphysostIgmInepoIsonIng.PhysostIgmInehasalsobeen
foundtobeaspecIfIcantIdoteInthetreatmentofpostoperatIvedelIrIum(seeCentral
AntIcholInergIcSyndrome).
J
Table 15-6 Comparison of Antimuscarinic Drugs

DURATION
CNS
GI
TONE
GASTRIC
ACID
AIRWAY
SECRETIONS
a
HEART
RATE
IV IM
AtropIne
15J0
mIn
24
hr
++ +++
C
ScopolamIne
J060
mIn
46
hr
+++
b
0
C
Clycopyrrolate 24hr
68
hr
0 +0
7,Intravenous;|,Intramuscular;C,gastroIntestInal.
a
SecretIonsmaybereducedbyInspIssatIon.
b
CNSeffectoftenmanIfestassedatIonbeforestImulatIon.
c
|aydecelerateInItIally.
Table 15-7 Antimuscarinic Compounds Associated with Central
Anticholinergic Syndrome
Belladonna Alkaloids
AtropInesulfate
ScopolamInehydrobromIde
Synthetic and Natural Tertiary Amine Compounds
0IcyclomIneantIspasmodIcwIthlocalanesthetIcactIvIty
ThIphenamIlantIspasmodIcwIthlocalanesthetIcactIvIty
ProcaIne
CocaIne
CyclopentolatemydrIatIc
Quaternary Derivatives of Belladonna Alkaloids
|ethscopolamInebromIdeantIspasmodIc
HomatropInemethylbromIdesedatIve,antIspasmodIc
HomatropInehydrobromIdeophthalmIcsolutIonmydrIatIc
Synthetic Quaternary Compounds
|ethanthelInebromIde
PropanthelInebromIde
Antihistamines
ChlorphenIramIne
0IphenhydramIne
Plants
0eadlynIghtshade(atropIne)
8Ittersweet
Potatoleavesandsprouts
JImsonorlocoweed
Cocaplant(cocaIne)
Over-the-Counter
Asthma0oratropInelIke
CompozscopolamInesedatIon
SleepEzescopolamInesedatIon
SomInexscopolamInesedatIon
Antiparkinson Drugs
8enztropIne
TrIhexphenIdyl
8IperIden
EthopropazIne
ProcyclIdIne
Antipsychotic Drugs
ChlorpromazIne
ThIorIazIne
HaloperIdol
0roperIdol
PromethazIne
Tricyclic Antidepressants
AmItrIptylIne
mIpramIne
0esIpramIne
Synthetic Opioids
|eperIdIne
|ethadone
Figure 15-14.StructuralformulasofclInIcallyusefulreversIbleantIcholInesterase
drugs.PhysostIgmIneIsatertIaryamIneandcrossesthebloodbraInbarrIer.tIsuseful
IntreatIngthecentralantIcholInergIcsyndrome.
TheIrreversIblecholInesteraseInhIbItorsaremostlyorganophosphatecompounds.The
organophosphatecompoundsarehIghlylIpIdsoluble,readIlypassIntotheCNS,andare
rapIdlyabsorbedthroughtheskIn.TheyareusedastheactIveIngredIentInpotent
InsectIcIdesandchemIcalwarfareagentsknownasnerve gases(seeChapter60).Theonly
therapeutIcdrugofthIsgroupIsechothIophate,whIchIsavaIlableIntheformoftopIcal
dropsforthetreatmentofglaucoma.tsprImaryadvantageIsItsprolongedduratIonof
actIon.TopIcalabsorptIonIsvarIablebutconsIderable.EchothIophatecanremaIn
effectIvefor2orJweeksfollowIngcessatIonoftherapy.AhIstoryofuseofechothIophate
IsImportantInavoIdIngprolongedactIonofsuccInylcholIne,whIchrequIres
pseudocholInesteraseforItshydrolysIs.DrganophosphatepoIsonIngmanIfestsallthesIgns
andsymptomsofexcessACh.TheantIdotecartrIdgesdIspensedtotroopstocounterthe
effectsofantIcholInesterasenervegasescontaInonlyatropIne,whIchwouldeffectIvely
counterthemuscarInIceffectsofthegas;however,atropInedoeslIttletocounterthe
hIghdosenIcotInIcmuscleparalysIsorthecentralventIlatIondepressIonthatcontrIbutes
todeathfromnervegases.TreatmentrequIreshIghdosesofatropIne,J5to70mg/kg
Intravenously(7)everyJto10mInutesuntIlmuscarInIcsymptomsabate.Lowerdosesat
lessfrequentIntervalsmayberequIredforseveraldays.CentralventIlatorydepressIonand
weaknessrequIrerespIratorysupportandspecIfIctherapyofthecholInesteraselesIon.
PralIdoxImehasbeenreportedtoreactIvatecholInesteraseactIvItybyhydrolysIsofthe
phosphateenzymecomplex.tIspartIcularlyeffectIvewIthparathIonpoIsonIngandIsthe
onlycholInesterasereactIvatoravaIlableIntheUnItedStates.
26
Muscarinic Antagonists
Muscarinic antagonistreferstoaspecIfIcdrugactIonforwhIchthetermanticholinergicIs
wIdelyused.AnydrugthatInterfereswIththeactIonofAChasatransmIttercanbe
consIderedanantIcholInergIcagent.ThetermantIcholInergIcreferstoabroader
classIfIcatIonthatalsoIncludesthenIcotInIcantagonIsts.
Atropine-Like Drugs
AtropIne,scopolamIne,andglycopyrrolatearethemostcommonlyusedmuscarInIc
antagonIstsusedInanesthesIa(FIg.1515).TheactIonsofthesedrugsIncludeInhIbItIonof
salIvary,bronchIal,pancreatIc,andgastroIntestInalsecretIonsandantagonIsmthe
muscarInIcsIdeeffectsofantIcholInesterasesdurIngreversalofmusclerelaxants.
HIstorIcally,atropInewasIntroducedtoanesthesIapractIcetopreventexcessIve
secretIonsdurIngetheranesthesIaandtopreventvagalbradycardIadurIngthe
admInIstratIonofchloroform.
26
AntImuscarInIcagentsdonotInhIbIttransmIssIonequally,
andtherearemarkedvarIatIonsInsensItIvItyatdIfferentmuscarInIcsItesowIngto
dIfferencesInpenetratIonandaffInItIesofthevarIousreceptors.0IfferencesInrelatIve
potencybetweenthedIfferentantImuscarInIcsareoutlInedInTable156.AtropIneand
scopolamInearetertIaryamInes(FIg.1515)andeasIlypenetratethebloodbraInbarrIer
andplacenta.ClycopyrrolateIsaquaternaryamInethat,lIkethereversIble
antIcholInesterasedrugs,doesnoteasIlypenetratethesebarrIers.Clycopyrrolate,a
synthetIcantImuscarInIc,hasgaInedpopularItybecauseItavoIdsthecentraleffectsofthe
othertwodrugs.AtropIneandscopolamInehavenotableCNSeffectsthataredIssImIlar.
ScopolamInedIffersfromatropInemaInlyInItscentraldepressanteffects,whIchproduce
P.J47
sedatIon,amnesIa,andeuphorIa.SuchpropertIesarewIdelyusedforpremedIcatIonfor
cardIacpatIentsIncombInatIonwIthmorphIneandamajortranquIlIzer.talsohasbeen
usedtoInduceamnesIaInpatIentswhohaveahIghrIskforIntraoperatIveawareness,such
astraumavIctImswhoarehemodynamIcallyunstableandcannotreceIveadequate
anesthesIa.AtropIne,asapremedIcant,hasslIghteffectsontheCNS,IncludIngmIld
stImulatIon.HIgherdosessuchasthosegIvenforreversalofmusclerelaxants(1to2mg)
mayproducerestlessness,dIsorIentatIon,hallucInatIons,anddelIrIum(seeCentral
AntIcholInergIcSyndrome).
Figure 15-15.StructuralformulasoftheclInIcallyusefulantImuscarInIcdrugs.
AtropIneIsusefulInIncreasIngCDwhensInusbradycardIaduetovagalstImulatIonIs
present.AtropIneandscopolamInearenotedtoproduceaparadoxIcalbradycardIawhen
gIvenInlowdoses.ScopolamIne(0.1to0.2mg)usuallycausesmoreslowIngthanatropIne
butalsoproduceslesscardIacacceleratIonathIgherdoses.TheusualIntramuscular
premedIcantdosesofscopolamInecauseeItheradecreaseornochangeInHF.AtropIne
mayalsoproducesympathomImetIceffectsbyblockIngpresynaptIcmuscarInIcreceptors
foundonadrenergIcnervetermInals.
27
AChstImulatIonofthesereceptorsInhIbItsNE
release,andblockadebyatropInereleasesthIsInhIbItIon(seeCholInergIcFeceptors:
|uscarInIc).AtropInelIkedrugsthatcrossthebloodbraInbarrIeralsoproducedIlatIonof
thepupIl(mydrIasIs)andparalysIsofaccommodatIon(cycloplegIa).AtropInelIkedrugsare
wIdelyusedInophthalmologyasmydrIatIcsandcycloplegIcs.AtropIneIscontraIndIcatedIn
patIentswIthnarrowangleglaucoma(seeChapter51).PupIllarydIlatIonthIckensthe
perIpheralpartoftheIrIs,whIchnarrowstheIrIdocornealangle.ThIsleadstoImpaIred
draInageofaqueoushumorandIncreaseoftheIntraocularpressure.0osesofatropIneused
forpremedIcatIonhavelIttleeffectInthIsregard,whereasequaldosesofscopolamIne
causemydrIasIs.PrudencewoulddIctateavoIdanceofeItheragentInpatIentswIth
narrowangleglaucoma.TheneedforantImuscarInIcpremedIcatIonIsquestIonableInthIs
sItuatIon.
AtropIneandscopolamInealsopossessantIemetIcactIon.AtropIne,however,reducesthe
openIngpressureoftheloweresophagealsphIncter,whIchtheoretIcallyIncreasestherIsk
ofpassIveregurgItatIon.ThebelladonnaalkaloIds(atropIneandscopolamIne)alsoblock
AChtransmIssIontosweatglands,whIch,althoughtheyarecholInergIc,areInnervatedby
theSNS.AntImuscarInIcagentsproduceantInIcotInIcactIonsathIgherdosesandresultIn
ImportantactIonsonCNStransmIssIonthatarepharmacologIcallysImIlartothe
postganglIonIccholInergIcfunctIon.AtropIneIsbestavoIdedwheretachycardIawouldbe
harmful,asmayoccurInthyrotoxIcosIs,pheochromocytoma,orobstructIvecoronary
arterydIsease.AtropIneshouldbeavoIdedInhyperpyrexIalpatIentsbecauseItInhIbIts
sweatIng.
Central Anticholinergic Syndrome
ThebelladonnaalkaloIdshavelongbeenknowntoproduceundesIrablesIdeeffectsrangIng
fromstupor(scopolamIne)todelIrIum(atropIne).ThIssyndromehasbeencalled
postoperative delirium,atropine toxicity,andthecentral anticholinergic syndrome.
8IochemIcalstudIeshavedemonstratedabundantmuscarInIcAChreceptorsInthebraIn
thatcanbeaffectedbyanydrugpossessIngantImuscarInIcactIvItyandcapableofcrossIng
thebloodbraInbarrIer.HundredsofdrugsexIstthatmeetthesecrIterIawIthwhIchthIs
syndromehasbeenassocIated.Table157lIstssomeofthosedrugs.
J
HIghdosesof
atropInIcalkaloIdsrapIdlyproducedrynessofthemouth,blurredvIsIonwIthphotophobIa
(mydrIasIs),hotanddryskIn(flushed),andfever.|entalsymptomsrangefromsedatIon,
stupor,andcomatoanxIety,restlessness,dIsorIentatIon,hallucInatIons,anddelIrIum.
ConvulsIonsmayoccurIflethalpoIsonInghasoccurred.AlthoughanalarmIngreactIonmay
occur,fatalItIesarerare.ntoxIcatIonIsusuallyshortlIvedandfollowedbyamnesIa.
ThesereactIonscanbecontrolledbytheIntravenousInjectIonofphysostIgmIne.
PhysostIgmIneIsanantIcholInesterasethat,byvIrtueofbeIngatertIaryamIne,readIly
passesIntotheCNStocounterantImuscarInIcactIvIty.tshouldbegIvenslowlyIn1mg
doses,
P.J48
notexceedIngJmg,toavoIdproducIngperIpheralcholInergIcactIvIty.NeostIgmIne,
pyrIdostIgmIne,andedrophonIumarenoteffectIvebecausetheycannotpassIntotheCNS.
TheduratIonofphysostIgmIneactIonmaybeshorterthanthatoftheoffendIng
antImuscarInIcagentandrequIrerepeatedInjectIonIfsymptomsrecur.PhysostIgmIne
appearssafewhenusedwIthIndoserecommendatIonsandwhenIndIcatIonsare
establIshed.CentraldIsorIentatIonalonedoesnotestablIshadIagnosIs.PerIpheralsIgnsof
antImuscarInIcactIvItyshouldbepresentInaddItIontoacentralantIcholInergIcsyndrome.
PhysostIgmInehasbeenreportedtoreversetheCNSeffectsofmanyofthedrugslIstedIn
Table157,IncludIngantIhIstamInes,trIcyclIcantIdepressants,andtranquIlIzers.Feversal
ofthesedatIveeffectsofopIoIdsandbenzodIazepIneshasalsobeenreported.
28
However,
antIcholInesteraseagentspotentIatecholInergIcsynaptIctransmIssIonandIncrease
neuronalactIvIty,evenIfnoreceptorantagonIstIspresent.Thus,arousalmaynotbea
functIonIndependentofItscholInesteraseactIvIty,andclaImsthatphysostIgmIneIsa
nonspecIfIcCNSstImulantmaynotbewarrantedandcould,Infact,bedangerous.These
consIderatIons,InassocIatIonwIthpossIblesIgnIfIcantbradycardIa,madetheuseof
physostIgmInefaIrlyrareInthemodernrecoveryrooms.
Sympathomimetic Drugs
TheselectIonofvasoactIvedrugsrequIresknowledgeofboththehemodynamIc
dIsturbanceandpharmacologyoftheavaIlabledrugs.ThecatecholamInesand
sympathomImetIcdrugscontInuetobethepharmacologIcmaInstayofcardIovascular
supportforthelowflowstate.SustaInedInterestInthecatecholamInesIsrelatedtotheIr
predIctablepharmacodynamIcsandfavorablepharmacokInetIcprofIles.ThehalflIfeof
mostIsshort,rangIngfrom2toJmInutes.UndesIrablesIdeeffectsdIssIpatewIthIn
mInutesoflowerIngorstoppIngtheInfusIon.SympathomImetIcs,asagroup,producea
wIderangeofhemodynamIceffectsandcanbeusedIncombInatIontoachIeveayetwIder
spectrumofeffects.Asaresult,oneneedstobecomefamIlIarwIthonlyafewagentsto
managemostclInIcalsItuatIons(Table158).
ThegoalformanagIngthelowoutputorhIghoutputshocksyndromeIstoestablIshand
maIntaInadequatetIssueperfusIon.SympathomImetIcsarenotasubstItuteforvolume,
andaretobeusedInhypotensIveemergencIes,Inordertopreservecerebralandcoronary
bloodflow,thatmaybeduetoseverehemorrhage,spInalcordInjury,antIhypertensIve
overdose,orcentralnervoussystemdepressantmedIcatIon,justtonameafew
cIrcumstances.Therefore,whIleIntravascularvolumeIsoptImIzed,avasoactIvedrugmay
berequIredtosustaInCD.AggressIvefluIdtherapywIllsuffIceInmostInstances.f,onthe
otherhand,adequatefluIdresuscItatIonhasbeenachIevedandhemodynamIcstatusstIll
requIressympathomImetIcstomaIntaInanormalarterIalbloodpressure,onemust
consIderalternatIvecausesforhypotensIonsuchasseptIcshock,andseekthemost
adequatetherapy.TheterminodilatorhasenteredourlexIcondurIngtheearly1990sto
supplantthemorearchaIctermvasopressor.ThIsneologIsmreflectsachangeInphIlosophy
InmanagInglowflowstates,partIcularlythosecharacterIzedbyheartfaIlure.Thenew
synthetIcsympathomImetIcshavebeenchemIcallyengIneeredtoobtaInInotropIsmand
P.J49
P.J50
vasodIlatIonratherthanforpressoreffects.ThepotentIalforbenefItorharmcanbestbe
understoodIntermsofreceptorcharacterIstIcs.Forexample,actIvatIonoftheInotropIc
1
and
2
receptorsresultsInposItIveInotropIsmandchronotropIsm.SelectIvestImulatIonof
thevascular
2
receptorscausesvasodIlatatIon.LeftventrIcularoutflowmayImproveasa
functIonofafterloadreductIonandInotropIsm.However,chronotropIsmmaynotbea
desIrablefeatureInapatIentwIthmItral(valvular)stenosIsorcoronaryarterydIsease.
Table 15-8 Dose Schedule and Hemodynamic Effects of the Adrenergic Agonists
DRUG DOSAGES SITE OF ACTIVITY
LISTED FROM TO IV PUSHADULTS
IV INFUSION
a
1A
1V
2
50100g
a.10
mg/250mL

b.40g/mL
PhenylephrIne
c.0.150.75
g/kg/mIn

d.0.15
g/kg/mIn
++++ +++++ 0 0
NorepInephrIne
N/Fa.4
mg/250mL

b.16g/mL
c.0.010.1
g/kg/mIn

d.0.1
g/kg/mIn
+++ +++ ++++ :+
EpInephrIne
0.J0.5mL
1:1000
a.1mg/250
mL

(0.J0.5
mg)
b.4g/mL
SC
Asthma
0.010.0J
g/kg/mIn
+ + ++++
7
AnaphylaxIs
c.
0.0J0.15
g/kg/mIn
+++ +++ ++++

0.150.J0
g/kg/mIn
+++++ +++++
5mL
1:10,000
d.0.015
g/kg/mIn
+ + ++++
(0.5mg)
cardIac
arrest

every5mIn
EphedrIne 510mg N/F ++ +++ +++ ++++
0opamIne
C
N/F
a.200
mg/250mL

b.800
g/mL
+++
0.055
g/kg/mIn

c.210
g/kg/mIn
++
10
g/kg/mIn
b

d.2
g/kg/mIn

0obutamIne
C
N/F
a.250
mg/250mL
++++
b.1,000
g/mL
+ ++++ +++
c.2
J0g/kg/mIn
+++++ ++++ +++++
d.5
g/kg/mIn
++++
0.004mg
a.1mg/250
mL

(0.2mLof
0.2
b.4g/mL +++++
soproterenol
mg/mL
solutIon)
c.0.15
g/kg/mIn
to

ThIrd
degree
heart
desIred
effect
0+ : ++++
block
d.0.015
g/kg/mIn

7,Intravenous;0A,dopamIne;CD,cardIacoutput;notrop,contractIlIty;HF,heartrate;7F,venousreturn(preload);TPF,perIpheralresIstance
(afterload);F8F,renalbloodflow;N/F,notrecommended.
a
a.|Ixture
b.ConcentratIong/mL.
c.0oserangeg/kg/mIn.
d.StandardrateInfusIon.
b
FuleofsIx.
C
0opamIneanddobutamIneemploythesamedoses.0osageofeIthermayquIcklybecalculatedbymultIplyIngpatIent'sweIght(kg)6=mgadded
to100mL05W.ThenumberofdropsdelIveredthroughacalIbratedInfusor(60drops=1mL)Isthenumberofg/kg/mInInfusedIntothepatIent.
Example:70kg6=420;420mg/100mL=4,200g/kgor70ggtt;5g/kg/mIn=5gtt/mIn.
FromLawsonNW,WallfIschHK:CardIovascularpharmacology:Anewlookatthepressors,AdvancesInAnesthesIa.EdItedbyStoeltIngFK,8arash
PC,CallagherTJ.ChIcago,Year8ook|edIcalPublIshers,1986,p195,wIthpermIssIon.
Table 15-9 Actions of Adrenergic Agonists
SYMPATHO-MIMETICS
RECEPTORS
DOSE
DEPENDENCE (,
, or DA)
1
2
DA
1
DA
2
PhenylephrIne +++++ : 0 0 ++
NorepInephrIne +++++ +++++ +++ 0 0 +++
EpInephrIne +++++ +++ ++++ ++ 0 ++++
EphedrIne ++ : +++ ++ 0 ++
0opamIne
+to
+++++
: ++++ ++ +++ : +++++
0obutamIne 0to+ : ++++ ++ 0 ++
soproterenol 0 0 +++++ +++++ 0 0
0A,dopamIne.
Catecholamine Receptor-Effector Coupling
ThenetphysIologIceffectofasympathomImetIcIsusuallydefInedasthealgebraIcsumof
ItsrelatIveactIonsonthe,,and0Areceptors.|ostadrenergIcdrugsactIvateorblock
thesereceptorstovaryIngdegrees.EachcatecholamInehasadIstInctIveeffect,
qualItatIvelyandquantItatIvely,onthemyocardIumandperIpheralvasculature.Table15
9demonstratestherelatIvepotencyoftheadrenergIcamInesonthevarIousmyocardIal
andvascularreceptors.ThIsrelatIvepotencyIsalsodoserelated,addIngyetanother
varIable.Formanyyears,theemphasIsoncatecholamIneswasfocusedalmostentIrelyon
theIractIonsonthemyocardIumandonarterIolarresIstancevessels.ChangesInvenous
resIstancecontrIbutelIttletototalvascularresIstanceandbloodpressure.However,small
changesInvenouscapacItanceresultInlargechangesInvenousreturnbecause60to70
ofthecIrculatIngbloodvolumeIsthevenouscIrculatIon.
4
Theeffectofthe
sympathomImetIcamInesonthevenouscIrculatIonappearstobedIstrIbutIveInthatacute
venularconstrIctIonIncreasesthecentralbloodvolume(preload),whereasdIlatatIon
decreasesvenousreturnbythepromotIonofperIpheralpoolIng.
4
ThedIstrIbutIveeffectof
acatecholamInemaybeasImportantasItsInotropIcactIonandmoreImportantthanIts
arterIolareffect.
10
FurtherdefInItIonshouldelucIdatesomeofthecomplexandconfusIng
dataInthelIteraturegeneratedwhenclInIcalobservatIonsarelImItedsolelytoadrenergIc
effectsonthemyocardIumandarterIolarvasculature.
ntravenousandIntraarterIalInfusIonsofEPInhumanshavebeenshowntocausemarked
constrIctIonoftheveIns.ArterIolarvasoconstrIctIonmayormaynotprecede
venoconstrIctIon;however,strokevolumedoesnotIncreaseuntIltheonsetof
venoconstrIctIon.TheInItIalIncreaseInCDseenwIththeInfusIonofEPIsmoreaneffect
ofIncreasedpreloadthananarterIolarordIrectcardIaceffect.NEproducesasImIlar
effect,buttheonsetofvenoconstrIctIonIsslower.TheperIpheralreceptorsofboth
resIstanceandcapacItancevesselssubservevasoconstrIctIon,butwIthdIvergenteffectson
afterloadandpreload;therefore,the
1
receptorshavebeensubdIvIdedInto
1
arterIal
(
1a
)and
1
venous(
1v
).0AhaspotentvenoconstrIctor(
1v
)effectatdosesatwhIchfew
1a
or
1
effectsarenoted.
Adverse Effects
ThemajoradverseeffectsofthesympathomImetIcamInesarerelatedtoexcessIveor
actIvIty.ThepotentIalforharmcanbeunderstoodIntermsofreceptorcharacterIstIcs.
ExcessIve
1
actIvItymayIncreasecontractIlItybutIncreaseHFandmyocardIaloxygen
consumptIonbeyondsupply.SeveredysrhythmIasareafrequentcompanIonofexcess
1
actIvItyasaresultofIncreasedconductIonvelocIty,automatIcIty,andIschemIa.The
2
actIvItyhasthepotentIaltoIncreaseCDbyreducIngresIstance(afterload)whIlereducIng
bloodpressure.AnexcessIvedecreaseIndIastolIcpressure,however,reducescoronary
perfusIonpressureandmayfurtheraggravatemyocardIalIschemIa.Unfortunately,ItIs
dIffIculttoseparatetheInotropIc,dromotropIc,andchronotropIceffectsIntheclInIcal
settIng.ThecharacterIstIcsoftheIdealposItIveInotropIcagentarelIstedInTable159for
comparIsonwItheachdrugasItIsdIscussed.
0rugswIthpromInent
1
agonIsteffectsmayproduceanIncreaseInbloodpressurebutat
thesametImecanreducetotalflowduetoIncreasesInarterIolarresIstance(afterload).A
morepromInent
1
venousconstrIctIonmayImproveCDbyIncreasIngpreloador
precIpItatefaIlureIfpreloadexceedsthecontractIlelImItsofthemyocardIum.ngeneral,
theeffectsofthesympathomImetIcsareofbenefItonlywhenusedforspecIfIc
IndIcatIonssuchassIgnIfIcantvasodIlatIonduetodIfferentmechanIsms.Dthermeasures
lIkefluIdresuscItatIonareusuallymoreeffectIveInImprovIngflowandareIndIcated
beforeapressorshouldbeused.CardIopulmonaryresuscItatIonIstheprImaryexample
whereapressoreffectIsnecessarytocreatedIastolIccoronaryperfusIondurIngclosedor
openheartmassage.AnydrugwIthstrongagonIstpropertIesseemsequallyeffectIveIn
thIsregard.EP,wIthItsaddedpropertIes,hasbeenthefIrstlIneagentforthIssItuatIon.
7asopressInhasrecentlybeenaddedasanImportantagentIncardIopulmonary
resuscItatIon.
29
Adrenergic Agonists
Phenylephrine
Tables158and159lIstadrenergIcagonIststobedIscussedInthIssectIon.PhenylephrIne,
IsconsIderedapuredrug,IncreasesbothvenousconstrIctIonandarterIalconstrIctIonIn
adoserelatedmanner.7enousconstrIctIonmaybeItsmostredeemIngfeaturewhen
comparedwIththepurelyarterIolareffectofmethoxamIne.DnecannotdIscountthe
possIbIlItyofanInotropIceffectnowthat
1
receptorsareknowntoexIstInthe
myocardIum.Acutely,venoconstrIctIonfavors
P.J51
venousreturn(preload),andeventhougharterIalresIstance(afterload)alsoIncreases,one
mayobservearIseInthearterIalbloodpressure.8ecausephenylephrInedoesIncreasethe
venousreturnandstrokevolume,butatthesametImeInducesreflexbradycardIa
secondarytoavagalreflex,onemustbeawarethatCDIsnotIncreased.PhenylephrIne
doesnotchangeCDInnormalIndIvIdualsbutcancauseadecreasedoutputInpatIentswIth
IschemIcheartdIsease.
J0
PhenylephrIneIsusefulInreversIngrIghttoleftshuntIn
tetralogyofFallotwhenpatIentsarehavIngspellsdurInganesthesIa.PhenylephrInehas
contInuedtobefavoredInoperatIngroomstoIncreasebloodpressuredurIng
cardIopulmonarybypassaswellasdurIngIntracranIal,vascularproceduresandtoreverse
sIgnIfIcantvasodIlatorystatesrelatedtoregIonalblockslIkespInalandepIduralanalgesIa.
tseffIcacy,thefactthatItcanbeusedeItherasabolus,orasaperIpheralInfusIon,made
thIsdrugoneofthemostcommonlyusedmedIcatIonsIntheoperatIngroomtoreverse
anesthetIchypotensIonfromamultItudeofcauses.naddItIon,ItcanbeusedInprImary
vasodIlatorycondItIons,suchasIncIpIentphasesofseptIcshock.
J1
Norepinephrine
NEIsthenaturallyoccurrIngmedIatoroftheSNSandtheImmedIateprecursorofEP.t
producesdIrectactInghemodynamIceffectsontheandreceptorsInadoserelated
mannerwhengIvenbyInfusIon.NEproducesIncreasedCDandbloodpressurewhengIven
Inlowdoses(Table158).HIgherdosesreduceflowbecausearterIolarconstrIctIon
supersedestheeffects.FeflexbaroreceptormedIatedbradycardIamayoccurdespIte
actIvestImulatIon.ncreasedplasmalevelsoftheendogenouscatecholamInesNEandEP
arethesympathetIcmIlIeuInwhIchexogenoussympathomImetIcsareordInarIlygIven.NE
IsthecatecholamInestandardagaInstwhIchothercatecholamInesarecompared.
ntravenousNEhasreceIvedanunseemlyreputatIonovertheyearsthatIsnotmerIted.
StudIesIndIcatethatNEwasbeIngusedIndosesthatareordersofmagnItudegreaterthan
thatnecessarytoobtaInItsbestresponse.ComplIcatIonssuchastIssuenecrosIsmaybe
expectedwhenNEIsused.AresurgenceofInterestInthIsagentIsnotedandIthas
remaInedclInIcallyusefulbecauseItseffectsarepredIctable,prompt,andpotent.
DbjectIonstotheuseofNEforthetreatmentofcardIogenIcshockarebasedontwo
consIderatIons:(1)vasoconstrIctIonIncreasesthepressureworkoftheleftventrIcle,wIth
anadverseeffectontheoxygeneconomyoftheIschemIcpump,and(2)thesedrugscause
furthervasoconstrIctIonandorganIschemIaInasyndromeInwhIchIntenseconstrIctIon
mayalreadyhaveoccurred.FormanagementofcardIogenIcshock,otherdrugsaremore
approprIate(dobutamIneandmIlrInone).However,thepredIctabIlItyofNEpharmacologIc
effectsmakesItoneofthemostusefuldrugswhenIntenseactIvItyIsIntended.Feduced
vasculartonestateswIthorwIthoutcardIogenIcshock,IncludIngseparatIonfrom
cardIopulmonarybypass,orsItuatIonswhenothervasopressorssuchasphenylephrInefaIl
tomaIntaInasteadyhemodynamIcstate,renderNEoneofthemostcommonlyused
drugs.
10,J2
AddItIonalundesIrableeffectsassocIatedwIthNEIncluderenalarterIolar
constrIctIonandolIgurIa.TheseeffectsaresecondarytopersIstentanduntreated
hypovolemIa.Fecently,clInIcIanswhomanageolIgurIaInIntensIvecareunIts,after
adequatefluIdresuscItatIontocontrolprerenalcauses,douseNEtomaIntaInrenal
perfusIonpressure,especIallyIncasesofvasodIlatedhypotensIon.
JJ
NEshouldonlybeadmInIsteredInacentrallyplaced7toavoIdtIssuenecrosIsfrom
extravasatIon.tcanbeusedforItsInotropIceffectatlowdosesandtItratedtoeffect
whIlemonItorIngCD.|onItorIngofbloodpressurealone,ortItratIngtoapredetermIned
effect,IsoftendetrImentaltoCD.8loodpressureIncreasesareusuallyduetoIncreasesIn
systemIcvascularresIstance,andexcessIveIncreasesoftheafterloadcandImInIshforward
flowandcontrIbutetocardIacfaIlure.EvenmoderatedosesofNEmayhaveadetrImental
effectonendorganperfusIon,whIchhasgIventhedruganIllgottenreputatIonwhenused
totItratetopressureratherthanflow.However,InthoseclInIcalcondItIonscharacterIzed
byhIghouput,lowtonestateswIthalowperfusIonpressure,NEhasbeenshownto
ImproverenalandsplanchnIcbloodflowbyIncreasIngpressure,provIdedthepatIenthas
beenvolumeresuscItated.
Epinephrine
EPIstheprototypIcalendogenouscatecholamIne.tIssynthesIzed,stored,andreleased
fromtheadrenalmedullaandIsthekeyhormonalelementInthefIghtorflIghtresponse.
tIsthemostwIdelyusedcatecholamIneInmedIcIneand,todate,ItremaInsthedrugof
choIceIncasesofcardIacarrest.tIsusedtotreatasthma,anaphylaxIs,cardIacarrest,
bleedIng,andtoprolongregIonalanesthesIa.ThecardIovasculareffectsofEP,whengIven
systemIcally,resultfromItsdIrectstImulatIonofbothandreceptors.ThIsIsdose
dependentandIsoutlInedInTable158.
TheeffectofEPontheperIpheralvasculatureIsmIxed.thaspredomInantly
stImulatIngeffectsInsomebeds(skIn,mucosa,andkIdney)andstImulatIngactIonsIn
others(skeletalmuscle).Theseeffectsarealsodosedependent.AttherapeutIcdoses,
adrenergIceffectspredomInateIntheperIpheralvessels,andtotalresIstancemaybe
reduced.However,constrIctIonIsmaIntaInedIntherenalandcutaneousareasbecauseof
ItsdomInanteffectIntheseareas.AnIncreaseInCDwIthEPmaybeduetoa
redIstrIbutIonofbloodtolowresIstancevesselsInthemuscle,butwIthfurtherreductIon
InflowtovItalorgans.CardIacdysrhythmIasareapromInenthazard,andthestrong
chronotropIceffectsofEPhavelImItedItsuseInthetreatmentofcardIogenIcshock.
EPIscommonlyusedIntheperIoperatIveperIodInanesthesIa.tIsoftenusedtoproduce
abloodlessfIeldIndentIstry,otolaryngology,andskIngraftIngeIthertopIcallyorInlocal
andfIeldblocks.AnesthesIologIstsoftenuseIttoprolongregIonalanesthesIa(seeChapter
21).TheaddItIonofEPtoarthroscopIcInfusIonstoattaInabloodlessfIeldIsanotherarea
ofIncreasedEPusagewIththedevelopmentofthesetechnIques.TheseInfusIonsare
usuallysafeInmaIntaInIngadryoperatIvefIeldbecausethesolutIonsareverydIluteat
around1:J,000,000.However,thelargevolumesInfused,theunpredIctableabsorptIonof
theEP,especIallyIndenudedcancellousbone,offerstheopportunItyofexposureofthe
patIenttoanexcessIveamountofEPoverashortperIoddespItethedIlutIon.Thedoseof
submuscoallyInjectedEPnecessarytoproduceventrIcularcardIacdysrhythmIaIn50of
patIentsanesthetIzedwItha1.25mInImalalveolarconcentratIon(|AC)ofavolatIle
anesthetIcwas10.9,10.9,and6.7g/kgdurIngadmInIstratIonofhalothane,enflurane,and
Isoflurane,respectIvely.
J4
TheIncIdenceofcardIacdysrhythmIaIselImInatedwhenthIs
doseIshalvedInpatIentsanesthetIzedwIthhalothaneorIsoflurane.ncontrastwIth
adults,chIldrenseemtotoleratehIgherdosesofsubcutaneousEPwIthoutdevelopIng
cardIacdysrhythmIa.
J5
EPInfusIonmaIntaInsposItIvechronotropIsmIncIrcumstancesof
symptomatIcbradycardIawhensIngledosesofatropInedonotsuffIce.
J6
Atlowdoses,the
useofEPInfusIonmayalsoInduceabenefIcbronchodIlatIoneffectsduetoItseffecton
2
receptors.Nevertheless,EPcanbeusedathIgherdoses,whIchInducesasIgnIfIcant
IncreaseInthearterIalbloodpressureandCD.Unfortunately,theserelatIvehIghdosesof
EPcanbefollowedbyIncreasesInarrhythmogenIcpropertIes,IncludIngsupraventrIcular
andtachycardIa,whIchImposeanIncreaseInthemyocardIaloxygenconsumptIon;
therefore,manyclInIcIansfIndotheralternatIves.
J6
P.J52
Table 15-10 Comparison of Relative
1
Catecholamine Responses on
Peripheral Resistance and Capacitance Vessels
a

VASOCONSTRICTION
1
ARTERIAL (
1
a
)
1
VENOUS (
1v
)
NorepInephrIne +++++ +++++
PhenylephrIne ++++ +++++
EpInephrIne 0/++++
b
0/++++
b
0opamIne 0/++++
C
+++
EphedrIne ++ +++
0obutamIne +/0 :
soproterenol 0 0
a
0rugsarelIstedIndescendIngorderofpotencywIthIneachvascularregIon.
b
0osedependent;effectsofepInephrInepredomInateatlowdoses.
c
0osedependent;dopamIneandeffectspredomInateatlowdoses.
FeprIntedwIthpermIssIonfromLawsonNW,WallfIschHK:CardIovascular
pharmacology:Anewlookatthepressors,AdvancesInAnesthesIa.EdItedby
StoeltIngFK,8arashPC,CallagherTJ.ChIcago,Year8ook|edIcalPublIshers,
1986,p195.
Ephedrine
EphedrIneIsoneofthemostcommonlyusednoncatecholamInesympathomImetIcagents.
tIsusedextensIvelyfortreatInghypotensIonfollowIngspInalorepIduralanesthesIa.
EphedrInestImulatesbothandreceptorsbydIrectandIndIrectactIons.tIs
predomInantlyanIndIrectactIngpressor,producIngItseffectsbycausIngNErelease.
TachyphylaxIsdevelopsrapIdlyandIsprobablyrelatedtothedepletIonofNEstoreswIth
repeatedInjectIon.ThecardIovasculareffectsofephedrIne(Table158)arenearly
IdentIcaltothoseofEP,butarelesspotent.tseffectsaresustaInedabout10tImeslonger
thanthoseofEP.EphedrIneremaInsthepressorofchoIceInobstetrIcsbecauseuterIne
bloodflowImproveslInearlywIthbloodpressure(seeChapter4J).
2J
ThIseffectIsprobably
notrelatedtoItsarterIolarvasoconstrIctIonbutrathertoItsvenoconstrIctIveactIon.
EphedrIneIsaweak,IndIrectactIngsympathomImetIcagentthatproduces
venoconstrIctIontoagreaterdegreethanarterIolarconstrIctIon(Table1510).ThIsmaybe
ItsmostImportantandunapprecIatedeffect.tcausesaredIstrIbutIonofbloodcentrally,
Improvesvenousreturn(preload),IncreasesCD,andrestoresuterIneperfusIon.ThemIld
actIonrestoresHFsImultaneouslywIthImprovedvenousreturn.AnIncreasedblood
pressureIsnotedasaresultratherthanacauseoftheseevents.|Ild
1
arterIolar
constrIctIondoesoccur,buttheneteffectofImprovIngvenousreturnandHFIsIncreased
CD.UterInebloodflowIsspared.ThIsresponse,however,dependsonthepatIent'sstateof
hydratIon.
Isoproterenol
soproterenolIsapotentbalanced
1
and
2
receptoragonIstwIthnovasoconstrIctor
effects.tIncreasesHFandcontractIlItywhIledecreasIngsystemIcvascularresIstance.
AlthoughItcanIncreaseCD,ItIsnotusefulInshockbecauseItredIstrIbutesbloodto
nonessentIalareasbyItspreferentIaleffectonthecutaneousandmuscularvessels.Asa
result,ItproducesvarIableandunpredIctableresultsonCDandbloodpressure.
soproterenolIsapotentdysrhythmogenIcdrugandextendsmyocardIalIschemIcareas.
0eleterIouseffectsonanevolvIngcardIacIschemIcprocessIncludecardIacdysrhythmIas,
tachycardIa,andreduceddIastolIccoronaryperfusIonpressureandtIme.ncreased
myocardIaloxygendemandmakesItanunattractIvedrugforpatIentsIncardIogenIcshock.
However,IsoproterenolIshelpfulInmanagIngcardIacfaIlureassocIatedwIthbradycardIa,
asthma,andcorpulmonale.tIsalsoausefulchemIcalpacemakerInthIrddegreeheart
blockuntIlanartIfIcIalpacemakercanbeInsertedorthecausecanberemoved,andmay
beoneofthemostImportantdrugsusedfordenervatedheartIncasesofsIgnIfIcant
bradycardIa(seeChapter54).soproterenolmIghtbeusefulIntreatIngbothIdIopathIcand
secondarypulmonaryhypertensIon.thasalsobeenreportedasusefulInImprovIngthe
forwardflowInpatIentswIthregurgItantaortIcvalvulardIsease,butItshouldnotbeused
IfthereIsanaccompanyIngstenosIs.
Dobutamine
0obutamIne(08T)IsasynthetIccatecholamInemodIfIedfromtheclassIcInodIlator
Isoproterenol.soproterenolwas,Inturn,synthesIzedfrom0A.7arIatIonsandsImIlarItIes
InstructurecanbeseenInFIgure156.08ThasclearadvantagesoverIsoproterenoland0A
InmanyclInIcalsItuatIons.tactsdIrectlyon
1
receptorsbutexertsmuchweaker
2
stImulatIonthanIsoproterenol.tdoesnotcauseNEreleaseorstImulate0Areceptors.08T
possessesweak
1
agonIsm,whIchcanbeunmaskedbybetablockadeasapromptand
dramatIcIncreaseInbloodpressure.08TIncreasesHFmorethanEPforagIvenIncrease
InCD.
J2,J7
08TmaydecreasedIastolIccoronaryfIllIngpressurebecauseofItsvasodIlatIon.However,
ItappearstoproducecoronaryvasodIlatIonIncontrasttotheconstrIctIonproducedby0A.
0obutamInehasbeenusedeffectIvelytoImprovecoronaryflowtodIfferentIate,by
echocardIography,responsIveorunresponsIveareasofdyskInesIaInpatIentsfollowIng
myocardIalInfarctIon.08TdoesnothaveanyclInIcallyImportantvenoconstrIctoractIvIty,
Incontrastto0A,InwhIchanIncreaseInventrIcularfIllIngpressurecanbenotedatlow
doses.ClInIcalstudIessuggestthat08TIslesslIkelytoIncreaseHFthan0AforagIven
dose,amajorconcernInthepatIentwIthcoronaryarterydIsease.08TIsacoronaryartery
dIlator,whereas0AIsnot.A0AInducedtachycardIa,however,maybeoflessconcernIn
theseptIcpatIentwhocommonlyhasamaldIstrIbutIonofvolume,lowvascularresIstance,
apreexIstIngrefractorytachycardIa,buta
P.J5J
prevIouslyhealthyheart.TheempIrIcpreferenceof0AInsurgIcalunItsand08TIn
coronaryunItshasbeenobservedandIsperhapswellfounded.0Aand08Talsohave
contrastIngeffectsonthepulmonaryvasculature.0AhasbeennotedtoIncrease
pulmonaryarterypressureanddoesnotInhIbItthepulmonaryhypoxIcresponse.tIsnot
recommendedforpatIentsInrIghtheartfaIlure.08TdoesvasodIlatethepulmonary
vasculatureandIshelpfulIntreatIngrIghtheartfaIlureandcorpulmonale.
J8,J9
08TIs
hIghlycontrollable,wIthahalflIfeof2mInutes.TachyphylaxIsIsrarebutmaybenotedIf
gIvenover72hours.ThenethemodynamIceffectsof08TIncludeanIncreaseInCD,a
decreaseInleftventrIcularfIllIngpressure,andadecreaseInsystemIcvascularresIstance
wIthoutasIgnIfIcantIncreaseInchronotropIsmatlowerdoses.
40
Table 15-11 Autonomic Effects of Calcium Entry Blockers in Intact Humans
VERAPAMIL DILTIAZEM NIFEDIPINE
NegatIveInotropIc + 0/+ 0
NegatIvechronotropIc + 0/+ 0
NegatIvedromotropIc ++++ +++ 0
CoronaryvasodIlatIon ++ +++ ++++
SystemIcvasodIlatIon ++ ++ ++++
8ronchodIlatIon 0/+ 0/+
Dopamine
0AoffersadvantagesovermanysympathomImetIcsIntreatIngthelowoutputsyndrome.t
IsadoserelatedagonIsttoallthreetypesofadrenoceptors,andthedesIredactIoncanbe
selectedbychangIngtheInfusIonrate.The0AreceptorsaremostsensItIvefollowedbythe
,andthenreceptors.0AdosageregImenshavebeentradItIonally,andarbItrarIly,
dIvIdedIntolow,medIum,andhIghdosesaccordIngtoItsdosereceptorsensItIvIty(Table
1511).FenalandmesenterIcvasculardIlatatIonandtubularcellnatrIuresIsaremedIated
throughthe0AreceptorsatlowdoseInfusIonratesof0.5to2.0g/kg.ThIsIsoften
referredtoasrenal dose0Abecauseofthepurportedenhancedrenalbloodflowand
dIuresIs.However,theconceptofrenaldose0AmaybemoreImagInedthanreal,andIs
nowconsIderedoutdated.
41,42
ThehemodynamIceffectsoflowdose0AareprImarIly
relatedtovasodIlatatIonbyactIvatIonofthe0A
1
and0A
2
receptors.ActIvatIonof
presynaptIc0A
2
adrenoceptorsaddstothevasodIlatIngeffectofthe0A
1
receptorsby
InhIbItIngpresynaptIcNEreleaseIntherenalandmesenterIcvessels.ThereductIonof
totalsystemIcvascularresIstancewouldbesIgnIfIcantwhenoneconsIdersthat25ofthe
CDgoestothekIdneysalone.AreduceddIastolIcbloodpressureIsoftennotedwIthaslIght
reflexIncreaseInHF.ncreasIngtheInfusIonrateof0Ato2to5g/kg/mInbegInsto
actIvatereceptorsIncreasIngtheCDbyIncreasIngchronotropIsmandcontractIlItywIth
earlyvenoconstrIctIon(preload)andsystemIcvasodIlatatIon(afterloadreductIon).8lood
pressuremaynotIncreasedespItesIgnIfIcantIncreasesInCD.ThIsdoserangewould
appearoptImalformanagIngcongestIveheartandlungfaIlurebecauseItcombInes
InotropIsmandafterloadreductIonwIthpossIbledIuresIs,butforthIsspecIfIcreason,
InotropeswIthoutactIvItyarebetterused.FurtherIncreasesIndoseactIvate
receptors,whIchwIllIncreasevascularresIstanceandbloodpressure,butfurther
ImprovementsInCDmaybeattenuated.nfusIonratesofgreaterthan10g/kg/mIn
produceIntenseactIvIty,whIchmayoverrIdeanybenefIcIal0AorvasodIlatIoneffect
ontotalflow.HIghdose0AbehavesmuchlIkeNEand,Infact,causesNEreleaseatthIs
doserange.
0espItetheapparentdoseresponsedIvIsIonsof0A,awIdevarIabIlItyofIndIvIdual
responseshasbeennoted.TheadrenergIceffectscanbeseenInsomeIndIvIdualsIn
dosesaslowas5g/kg/mIn,whereasdosesashIghas20g/kg/mInmayberequIredto
obtaInthIseffectInshockedpatIents.ThIswIdevarIatIonIndoseresponsehasledtoare
examInatIonof0AasaprImaryadrenergIcforpatIentsIncardIogenIcshockorfaIlure.
ncreasedvenousreturnmaynotbedesIrableInthIssItuatIon,but0A'shemodynamIc
versatIlItycontInuestobeusefulIncardIogenIcshockwhencombInedwIthother
complementarycatecholamInessuchas08T.ThevenoconstrIctIon,ordIstrIbutIveeffects,
of0AareusefulInsurgIcalpatIentsInwhomthIrdspaceedemaandsepsIsarethemost
commonabnormalItIes.0AIncreasesmeanpulmonaryarterIalpressureandIsnot
recommendedforsolesupportInpatIentswIthrIghtheartfaIlure,adultrespIratorydIstress
syndrome,orpulmonaryhypertensIon.
Combination Therapy
ThestudIeduseofadrenergIccombInatIonsInpatIentswIthcardIacfaIlurehasbeen
proposedbecausepathophysIologycannotbeapproachedwIththeattItudethatagonIsm
IsallgoodandagonIsmIsallbad.TheobjectIveIstoIncreasecoronaryperfusIonandCD
whIledecreasIngafterload.NosInglevasoactIveagentcanachIevethIs,butthese
condItIonscanbeapproachedwIthcombInatIontherapy.8ecauseofreceptorsummatIon
durIngcombInatIontherapy,standardratesofInfusIon(asoutlInedInTable158)nolonger
apply.nvasIvehemodynamIcmonItorIngIsmandatoryforsuccess;otherwIse,IatrogenIc
dIsasterscanbeexpected.DthercondItIonsnecessaryforsuccesswIthvasoactIvedrugs
alsorequIrethatthefaIlIngmyocardIumorvasculaturemusthavefunctIonalreserve,the
reservecanbestImulated,andperfusIoncanbemaIntaIned.TheadrenergIceffectsof
combInedsympathomImetIcs,lIkethesolodrugs,alsoappeartobeaddItIveand
competItIveforreceptorsItes.SummatIonIsmoreconsIstentwIthcurrentreceptor
pharmacologyandcanbeusedtoadvantageInavoIdIngunwantedsIdeeffectsofonedrug
whIlesupplementIngItsdesIredattrIbuteswIthanother.ThesummatIonprIncIpleobvIates
thenecessItyofknowIngalargenumberofdrugs.DneneedonlybecomefamIlIarwItha
fewagentstomanagemostclInIcalsItuatIons.8ecauseofsummatIon,manycombInatIons
ofvasoactIvedrugshavebeenfoundusefulInmakIngfInehemodynamIcadjustmentsInthe
crItIcallyIll.TheavaIlablesympathomImetIcagentsprovIdeawIderangeofhemodynamIc
effectspartIcularlywhencombInedwIthvasodIlators.Forexample,IfalargerposItIve
InotropIcactIonandlessvasoconstrIctIonaredesIred,08Tcouldbeaddedto0A.Also,
nItroprussIdecouldbeaddedto0AorcombInedwIthanyotherapproprIateInodIlator.
4J
0Aand08TaretwoofthemostpopularInodIlatorsInusetoday.AcomparIsonofthese
twodrugswIllunderscoretheImportanceoftheextracardIacsIdeeffectsInselectInga
drugeItherforusealoneorIncombInatIon.
J9,44,45,46
ThIscomparIsonIspartIcularly
approprIatebecause0Aand08TareconsIdered
P.J54
equIpotentInotropIcagents,andareeffectIveInthesamedoserangeof2to15
g/kg/mIn.TheIrdIfferencescanbecomparedatlow(0.5to4g/kg/mIn),medIum(5to9
g/kg/mIn),andhIgh(10to15g/kg/mIn)doses.ThIscomparIsonwIllIllustratethe
dIvergenteffectsoftwodrugsonpreloadandafterloadwhIlesharIngthepropertyof
InotropIsm.AlthoughtheyshareseveralclInIcalIndIcatIons,thesedrugsare
pharmacologIcallydIstInctandnotInterchangeable.TheIrdIvergentpropertIes,however,
makethempartIcularlyvaluablewhenadmInIsteredIncombInatIon.Althoughfrequently
combInedprevIously,thIscombInatIontherapyIsfallIngoutoffavorsIncetheyactonthe
samereceptorsandtheyhavesomanysImIlarItIesofactIon.Therefore,mostclInIcIans
nowcombIneanInotrope,suchas08TormIlrInone,wIththemorepotentagonIsts
phenylephrIne,NE,orevenEPInfusIons,InordertocompensateforthevasodIlatIon
InducedbytheInotropes,andtomaIntaInanadequateperfusIonpressure.08TIsadIrect
actIngcatecholamInethatproducesaposItIveInotropIc
1
effectbutwIthmInImalchanges
In
2
HForvascularresIstance(
2
,
1
counteractIon).Thus,08Tmaynotalterblood
pressureeventhoughCDIsmarkedlyImproved(seeChapter10).
08Tand/ormIlrInonearethemaInstayforthetreatmentofdecompensatedcardIac
faIlure.AlthoughtheseagentsdoImprovetheCD,theIruseIsassocIatedwIthIncreaseIn
thecardIacoxygenconsumptIon,cardIacarrhythmIas,andevenmortalIty.Therefore,for
patIentswIthnormalbloodpressureandnoevIdenceofhypoperfusIon,thereIslIttlerole
fortheInotropIctherapy.Nevertheless,InpatIentswIthevIdenceofImpaIredorgan
perfusIon(hypotensIon,decreasedrenalfunctIon)andlowoutputstate,wIthorwIthout
congestIonorpulmonaryedemarefractorytodIuretIcsandvasodIlatorsatoptImaldoses,
thereIsarolefortheseagents,atleastforshorttermstabIlIzatIon.Fecently,anewclass
ofdrugswasdeveloped,namelycalcIumsensItIzIngagents(levosImendan).Thesedrugsare
aunIqueclassofposItIveInotropIcagentsthatIncreasethesensItIvItyofthe
cardIomyocytecontractIleapparatustoIntracellularcalcIum.Thesemayprovetobe
benefIcIaleItheraloneorIncombInatIonwIththeclassIcInotropesInmanagementof
decompensatedheartfaIlure,butmorestudIesarenecessarytoevaluatetheIroverall
benefItandlongtermoutcome.
45,46
Fenoldopam
Fenoldopam,abenzazepInederIvatIve,IsaselectIve0A
1
agonIstwIthnoorreceptor
actIvItycomparedto0A
41
(seeChapter56).ntravenousfenoldopamhasdIrectnatrIuretIc
anddIuretIcpropertIesandpromotesanIncreaseIncreatInIneclearance.toffers
advantagesIntheacuteresolutIonofseverehypertensIoncomparedtosodIum
nItroprussIde,partIcularlyIfthepatIenthaspreexIstIngrenalImpaIrment.
47
PreservatIon
oraugmentatIonofrenalbloodflowdurIngbloodpressurereductIonpresentsapotentIal
forusedurIngseveralsItuatIonsIntheperIoperatIveperIod.Fenoldopamhasan
elImInatIonhalflIfeof5mInutes.ThIspropertymIghtwelllendItselfIntheproducIng
hypotensIveanesthesIawhIlepreservIngrenalfunctIon.HumanstudIeshavedemonstrated
thatfenoldopamIsapotentdIrectrenalvasodIlator.ntravenousfenoldopammayproveto
beIdealfortreatIngcondItIonsInwhIchrenalvasoconstrIctIonIsanexpected
complIcatIon.SInceIthasrenalvasodIlatoryeffectsandItpromotesIncreasedurIne
output,fenoldopamhasbeenemployedInvascularanesthesIaasarenalprotector,
especIallyIncaseswhenrenalarterIeshavebeentemporarIlyclamped.tsroleIn
preventIngdevelopmentofrenaldysfunctIonIsstIlldebatablebecausethereare
conflIctIngresultsIndIfferentstudIes.Therefore,Stoneetal.
48
andZacharIasetal.
49
show
InaJ15patIentpopulatIonthatfenoldopamIsnotusefulInpreventIngfurther
deterIoratIonoftherenalfunctIonaftercontrastadmInIstratIon.AlargemetaanalysIs
concludedthatthereIsnopharmacologIcInterventIonthatIseffectIveIntreatmentof
patIentswIthacuterenalInjury.Dntheotherhand,LandonIetal.,
50
Inamorerecentand
completemetaanalysIs,suggestthatfenoldopamreducestherIskofacutetubular
necrosIs,theneedforrenalreplacementtherapy,andoverallmortalItyInpatIentswIth
acutekIdneyInjury.tIsobvIousthatInsuchcIrcumstancesofconflIctIngresults,large
randomIzedstudIesarenecessarytoreachavalIdconclusIon.
TheonsetofactIonwIth7fenoldopamIsabout5mInutes,reachIngasteadystateIn
about20mInutes.ThedrugIsrapIdlymetabolIzedInthelIverandexcretedIntheurIne.
TheelImInatIonhalflIfeIsabout5mInutes.TherehasbeennoevIdenceoftoleranceIn
reducIngbloodpressureforupto24hours.NoreboundonwIthdrawalhasbeennoted.The
mostcommonadverseeffectsoffenoldopamarerelatedtovasodIlatIon,whIchInclude
hypotensIon,flushIng,dIzzIness,headache,andIncreasesInHF,nausea,andhypokalemIa
haveoccurred.tshouldbeusedcautIouslyInpatIentswIthglaucomaasItcanIncrease
Intraocularpressure.NosIgnIfIcantdrugInteractIonshavebeenreported.ConcomItantuse
wIthbetablockerswIllreducetheeffectIvedoseoffenoldopam.
FenoldopamIsdIlutedInnormalsalIneor5dextroseIsgIvenbycontInuousInfusIon
wIthoutabolusdose.TheeffectIvedosagerangeIs0.1to1.6g/kg/mIn.Areflex
tachycardIamaybeproduced.ThedosageIstItratedupwardevery15mInutesaccordIngto
patIentresponse.AnychangeInInfusIonrateshouldbedetectablewIthIn15mInutes.
Clonidine
ClonIdIneIsacentrallyactIngselectIvepartIal
2
adrenergIcagonIst(220:1
2
to
1
).tIs
anantIhypertensIvedrugbecauseofItsabIlItytodecreasecentralsympathetIcoutflow.
StImulatIonof
2
receptorsInthevasomotorcentersofthemedullaoblongataIsthought
toproducethIseffect.
51
tIsnotclearwhetherthesearepreorpostsynaptIcreceptors;
however,theendresultIsdecreasedSNStoneandenhancedvagaltone.PerIpherally,
thereIsdecreasedplasmarenInactIvItyaswellasdecreasedEPandNElevels.ThIsdrug
hasbeenproventobeeffectIveInthetreatmentofseverehypertensIonandrenIn
dependenthypertensIvedIsease.
ClonIdIneIsnotavaIlablefor7use.TheusualdaIlyadultoraldoseIs0.2to0.Jmg.A
transdermalclonIdInepatchIsavaIlableforuseonaweeklybasIsforsurgIcalpatIents
unabletotakeoralmedIcatIon.ClonIdIneIsclInIcallyusefulInanesthesIologyInother
ways.thasbeenfoundtoproducedosedependentanalgesIawhenIntroducedIntothe
epIduralorsubarachnoIdspaceIndosesof150to450g(seeChapter57).ClonIdInecanbe
addedtolocalanesthetIcsforepIdural,spInal,orregIonalblocks,andthereforeIntensIfIes
theanesthesIa.tcanalsobeusedpostoperatIvelyasItreducesthedoseofotherregIonal
anesthetIccomponents,andsubsequentlythepossIblesIdeeffects.Dnemustbeawarethat
clonIdInecanproducehypotensIon,bradycardIa,andsedatIon.
52
DralclonIdIne(5g/kg)
whenusedasapremedIcantenhancesthepostoperatIveanalgesIaprovIdedbyIntrathecal
morphInewIthoutaddIngtothesIdeeffectsofthemorphIne.DtheraddItIonalbenefIts
notedfromaclonIdInepremedIcatIonInclude(1)bluntedreflextachycardIaforIntubatIon,
(2)reductIonofvasomotorlIabIlIty,(J)decreasedplasmacatecholamInes,and(4)dramatIc
decreasesIn|ACforInhaledgasesorInjecteddrugs.
ClonIdIneIsrapIdlyabsorbedbymouthandreachespeakplasmalevelswIthIn60to90
mInutes.TheelImInatIonhalflIfeIsbetween9and12hours.tIsequallyexcretedInthe
lIverandkIdneys.TheduratIonofthehypotensIveeffectafterasIngledoseIsabout8
hours.ThetransdermaladmInIstratIonofclonIdInerequIresabout48hourstoachIeve
therapeutIclevels.ThedecreaseInsystolIcbloodpressureIsmorepromInentthanthe
decreaseIndIastolIcbloodpressure.ThereseemstobenoeffectonglomerularfIltratIon
rate.TheperIoperatIveadmInIstratIon
P.J55
ofclonIdIneeItherasanoraldosesorasapatchfortotalof4days,hassIgnIfIcantly
reducedtheIncIdenceofmyocardIalIschemIaandmortalItyupto2yearspostoperatIvely.
ThemostcommonsIdeeffectsaresedatIonandadrymouth.However,skInrashesare
frequentwIthchronIcuse.mpotencemaybeseenoccasIonally,andorthostatIc
hypotensIonIsrare.DneofthemoreworrIsomecomplIcatIonsofchronIcclonIdIneuseIsa
wIthdrawalsyndromeonacutedIscontInuatIonofthedrug.ThIsusuallyoccursabout18
hoursafterdIscontInuatIon.ThesymptomsarehypertensIon,tachycardIa,InsomnIa,
flushIng,headache,apprehensIon,sweatIng,andtremulousness.ThIscondItIonlastsfor24
to72hoursandIsmostlIkelytooccurInpatIentstakIngmorethan1.2mg/dayof
clonIdIne.ThewIthdrawalsyndromehasbeennotedpostoperatIvelyInpatIentswhowere
wIthdrawnfromclonIdInebeforesurgery.tcanbeconfusedwIthanesthesIaemergence
symptoms,partIcularlyInapatIentwIthuncontrolledhypertensIon.
5J
Absentthe
avaIlabIlItyoftheoralrouteInthesurgIcalpatIent,wIthdrawalcanbetreatedwIth
clonIdInetransdermallyormorerapIdlywIthrectalclonIdIne.
Dexmedetomidine
0exmedetomIdIneIsamoreselectIve
2
agonIstthanclonIdIne(seeChapter56).
54
ts
potent
2
agonIsmIs1,620:1
2
to
1
.ComparedwIthclonIdIne,dexmedetomIdIneIs7
tImesmoreselectIvefor
2
receptorsandhasashorterhalflIfeof1.5hours.TheloadIng
dose(1g/kg)IsgIvenover10mInutesorlonger.ThenanInfusIonIsbegunat0.2to0.7
g/kg/hr.8ecauseofhemodynamIcsIdeeffects,somecentersomIttheloadIngdoseand
startthecontInuousInfusIon.thasamorerapIdonsetofactIon(5mInutes).ThetImeto
peakeffectIs15mInutes.tcanbegIvenIntravenouslyandhasmanyusesIn
anesthesIology.tprovIdesexcellentsedatIon,reducesbloodpressure,HF,andprofoundly
decreasesplasmacatecholamInes.LIttlerespIratorydepressIonaccompanIesweanIngfrom
mechanIcalventIlatIon.tcanbeadmInIsteredasapremedIcantIncasesofdIffIcult
IntubatIonswhereawakefIberoptIcIntubatIonIsemployed.ntheIntensIvecareunItthe
useofclonIdIneIsemployedbecauseofItssedatIngandanalgesIceffectswIthoutthe
respIratorydepressIveactIonsofotheragents.ThereIsconcernforpossIblerebound
hypertensIon,reboundhyperexcItabIlIty,andarrhythmIasInInfusIonslongerthan24hours;
ultImately,clInIcaltrIalsarerequIredtoclarIfythesequestIons.
55
ArecentmetaanalysIs
demonstratedatrendtowardImprovedcardIacoutcomesInnoncardIacsurgIcalpatIents
whohavebeentreatedperIoperatIvelywIthdexmedetomIdIne.
56
0exmedetomIdInehas
beenshowntobeaneffectIveanxIolytIcandsedatIvewhenusedaspremedIcatIon.
PretreatmentwIthdexmedetomIdIne,lIkeclonIdIne,attenuateshemodynamIcresponsesto
IntubatIon.LIkewIse,Itdecreasesthe|ACforvolatIleanesthetIcsfromJ5to50but
IncreasesthelIkelIhoodofhypotensIon.0exmedetomIdIne,lIkeclonIdIne,Increasesthe
rangeoftemperaturesnottrIggerIngthermoregulatorydefenses.tIslIkelytopromote
perIoperatIvehypothermIa,butalsoIseffectIveagaInstshIverIng.
Nonadrenergic Sympathomimetic Agents
NonadrenergIcsympathomImetIcdrugsalsoactIndIrectlybyInfluencIngthecA|PcalcIum
cascade,exclusIveofthereceptors(FIg.1510).ThefunctIonofthesecondmessenger
(Ca
2+
)nearlyalwaysgoestogether.ThIsconceptreInforcestherecentapprecIatIonofthe
homogeneItyofactIonofawIdevarIetyofdrugsprevIouslythoughttobeunrelated.
SympathomImetIcshavemorepharmacologIcsImIlarItIesthandIfferences.
Vasopressin
7asopressIn,andItscongener(desmopressIn)areexogenouspreparatIonsofthe
endogenousantIdIuretIchormone(A0H).A0HandoxytocInarethetwoprIncIplehormones
secretedbytheposterIorpItuItary.TargetsItesforA0HaretherenalcollectIngducts,
vascularsmoothmuscle,andcardIacmyocytes.WaterabsorptIonIspassIvelyreabsorbed
fromrenalcollectIngductsIntoextracellularfluId.NonrenalactIonsIncludeInotropIsm
andIntensevasoconstrIctIonaccountIngforItsalternatIvedesIgnatIonasvasopressIn.
57
ArgInInevasopressInIsthemostactIveformofA0H.HIstorIcally,vasopressInhasbeenused
for(1)treatmentofdIabetesInsIpIdus,(2)dIagnosIsofdIabetesInsIpIdus,(J)abdomInal
dIstentIon,and(4)asanadjunctInthetreatmentofgastroIntestInalhemorrhageand
esophagealvarIces.Fecently,threenewIndIcatIonsfortheuseofvasopressInhave
emerged:(1)pressuresupportforseptIcshock,(2)cardIacarrestsecondarytoventrIcular
fIbrIllatIon/ventrIculartachycardIa,or(J)pulselesselectrIcalactIvIty/asystole.
58,59,60,61
AnImalstudIeshaveshown,bothInopenandclosedchestmodels,vasopressIncaused
largerIncreasesInsystemIcvascularresIstance,cerebralperfusIonpressure,andcoronary
perfusIonpressurethanEP.7asopressInIsamoreeffectIvevasoconstrIctorthanEPInthe
presenceofhypoxIaandacIdosIs.ncontrasttoEP,vasopressIndoesnotseemtoIncrease
myocardIaloxygenconsumptIonorlactateproductIon.
61,62
The2005guIdelInesfor
AdvancedCardIacLIfeSupport(ACLS)oftheAmerIcanHeartAssocIatIonrecommendthat
vasopressInmaybeusedtoreplacethefIrstorseconddoseofEPdurIngthepulseless
arrestalgorIthm
6J
(seeChapter59).EPIsclassbrecommendatIon,andvasopressIn,
whIchdIdnotshowanyImprovementInsurvIvalwhencomparedwIthEP,maybeused
InsteadofthefIrstortheseconddoseofEPandIsconsIderedclassIndetermInate
J6
(see
Chapter59).7asopressInadmInIsteredforcardIacarrestIsknownasvasopressin injection
USP.ThedoseIncardIacarrestIs40UIn40mL7asasIngledoseInaperIpheral7lIne.
ExtravasatIonmaycauselocaltIssuenecrosIs.tsuseInvasodIlatedsepsIsIsbyInfusIon
pumpstartIngat0.04U/mIn.TherearesuggestIonsthatvasopressInmaybeusefulIn
addItIontopotentagonIstsfortreatmentofshock,especIallyfromrelatIvesparIngofthe
mesenterIcvessels;thesedataaresupportedbyratstudIes.
64
0espIteatheoretIcal
advantageofusIngvasopressIntodecreasethecatecholamInesdosageInseptIcpatIents,
theuseofvasopressInfaIledtodecreasemortalItywhencomparedwIthNE.
58
nsuch
cIrcumstancesItseemsthattImIngofInItIatIonoftherapyIsthemostImportant
parameterforsurvIval.
65,66
Adenosine
AdenosIne,avaIlableformorethan50years,hasbeenrecognIzedrecentlyasaclInIcally
usefuldrug.tIsanendogenousnucleotIdeandIsfoundIneverycellInthebody.tIs
composedofadenIneandapentosesugar.ProductIoncanbeIncreasedbystImulIsuchas
hypoxIaandIschemIa.ThIsubIquItousnucleotIdehaspotentelectrophysIologIcaleffectsIn
addItIontohavIngamajorroleInregulatIonofvasomotortone.AdenosIneIsbelIevedto
haveacardIoprotectIveeffectbyregulatIngoxygensupplyanddemand(seeChapter59).
ThereceptorsInthemyocardIalconductIonsystemarethemostsensItIveandmedIate
sInoatrIalnodeslowIngandA7nodalconductIondelay.AdenosInehyperpolarIzesatrIal
myocytesanddecreasestheIractIonpotentIalduratIonvIaanIncreaseInoutwardK
+
current.ThesearetheAChregulatedK
+
channels.
AdenosInemImIcstheeffectsofAChInmanyways,IncludInganextremelyshortplasma
halflIfeofmereseconds.AdenosInealsoantagonIzestheInwardCa
2+
currentproducedby
catecholamInes.ThIsantIdysrhythmIcmechanIsmofCa
2+
channelblockadeIsthoughttobe
anIndIrecteffectandImportantonlywhenstImulatIonIspresent.TheprImary
antIdysrhythmIceffectofadenosIneIstoInterruptreentrantA7nodaltachycardIa,whIch
mostlIkelyrelatestoItsK
+
current,ratherthanCa
2+
currenteffects.ThechIefIndIcatIon
foradenosIneIsparoxysmalsupraventrIculartachycardIa,whIchItmaytermInateIna
matterofseconds,adenosInebeIngtherecommended
P.J56
asfIrstlIneoftreatement.
J6,67
AdenosIneIstobeusedonlycautIouslyInpatIentswIth
WolffParkInsonWhItesyndromewIthnarrowcomplextachycardIa,andshouldbeavoIded
InWolffParkInsonWhItesyndromewIthatrIalfIbrIllatIonasItsusemayIncreasethe
conductIonvIatheatrIoventrIcularnodeandInduceventrIcularfIbrIllatIon.Dnemayuse
adenosIneforreentranttachycardIasInvolvIngtheA7node,aswellasrIghtventrIcular
tachycardIa.
68
ThesamecharacterIstIcsthatmakeadenosIneaneffectIvetherapeutIc
agentmayalsomakeItanIdealagentfordIagnosIngothertypesofdysrhythmIa.The
IncIdenceofIncorrectdIagnosIsofsupraventrIculardysrhythmIahasbeenreportedtobeas
hIghas15usIngconventIonalmeans.ApproxImately10ofsupraventrIculartachycardIas
donotInvolveA7nodalreentry.AdenosInewIllneverthelessslowA7nodalconductIonIn
thesecases,decreasetheventrIcularrate,andallowInspectIonofPwaves.Thus,
adenosInemaybeusefulInunmaskIngatrIalfIbrIllatIonorflutterwhenfastventrIcular
responsesarenoted.
AnumberofsIdeeffectshavebeenreportedwIththeuseofadenosIne,IncludIngflushIng,
headache,dyspnea,bronchospasm,andchestpaIn.ThemajorItyofthesearebrIef
(seconds)andnotclInIcallysIgnIfIcant.TransIentnewdysrhythmIas(65)wIllbenotedat
thetImeofcardIoversIon,butthesedIsappeardurIngthehalflIfeofthedrug.|ajor
hemodynamIcchangesarerarebutconsIstofhypotensIonandbradycardIa.AdenosIne
shouldbegIvenbymeansofarapId7boluswIthflushbecauseofItsextremelyshorthalf
lIfeof10seconds.TheInItIaladultdoseIs6mg(100to150g/kgforpedIatrIcs),whIch
canbefollowedby12mgwIthIn1to2mInutesIftheInItIaldoseIswIthouteffect.
51
The
12mgdosemayberepeatedonce.TheantIdysrhythmIceffectofadenosIneoccursassoon
asthedrugreachestheA7node.AlthoughbothadenosIneandverapamIlareaseffectIve
IntreatIngtheparoxysmalsupraventrIculartachycardIa,onemustbeawareofsIdeeffects
beforechoosIngoneversustheother.Nevertheless,adenosIneseemstobeabetterchoIce
becauseoffewersIdeeffects,avIewthatIsrecommendedbytherecentACLS
CuIdelInes
J6,69
(seeChapter59).
Phosphodiesterase Inhibitors
PhosphodIesteraseInhIbItorshavepharmacologIcpropertIesapproachIngthe
characterIstIcsoftheIdealInotropIcagent.
70,71,72
TheydonotrelyonstImulatIonof
and/orreceptors.ThesedrugscombIneposItIveInotropIsmwIthvasodIlatoractIvItyby
selectIvelyInhIbItIngphosphodIesterase(P0E).P0EandhydrolyzeallcyclIc
nucleotIdes,whereasP0EactsspecIfIcallyoncA|P.TheP0EInhIbItorsInteractwIth
P0EatthecellmembraneandImpedethebreakdownofcA|P.cA|PlevelsIncreaseand
proteInkInaseIsactIvatedtopromotephosphorylatIon.ncardIacmuscle,phosphorylatIon
IncreasestheslowInwardmovementofcalcIumcurrent,promotIngIncreasedIntracellular
calcIumstores.Thus,InotropIsmIncreases.nvascularsmoothmuscle,IncreasedcA|P
actIvItyaccountsforthevasodIlatIon,decreasedperIpheralvascularresIstance,and
lusItropIsm.AmrInone(currentlytermedinamrinone)IstheprototypIcalP0EInhIbItor,
andlIkenItroprussIdeandnItroglycerIn,promotesdIastolIcrelaxatIon,whIchpromotes
ventrIcularfIllIng.
7J
|IlrInoneIscurrentlythemostpopularP0EInhIbItorreleasedfor
clInIcaluseIntheUnItedStates.ThedegreeofhemodynamIceffectofthesedrugsdepends
onthedose,degreeofInotropIcreserve,andstateofcA|PdepletIon.
Milrinone
|IlrInoneIsaderIvatIveofamrInone.(nmostcentersmIlrInonehasreplacedamrInone;In
general,theIrhemodynamIcactIonsaresImIlar.)thasnearly20tImestheInotropIc
potencyoftheparentcompound.|IlrInoneIsactIvebothIntravenouslyandorallyandhas
benefIcIalshorttermhemodynamIceffectsInpatIentswIthsevererefractorycongestIve
heartfaIlure.mprovementofCDappearstoresultfromacombInatIonofenhanced
myocardIalcontractIlItyandperIpheralvasodIlatIon.TreatmentwIthoralmIlrInoneforup
to11monthshasbeeneffectIveandwelltoleratedwIthoutevIdenceoffever,
thrombocytopenIa,orgastroIntestInaleffects.|IlrInonehasbeenapprovedforshortterm
7therapyofcongestIveheartfaIlure.
70,71,72
tIsadmInIsteredwIthaloadIngdoseof50
g/kgover10mInutes.ThemaIntenance7InfusIonraterangesfromamInImumof0.J75
g/kg/mIntoamaxImumof0.75g/kg/mIn(nottoexceed1.1Jg/kg/day).0osagemust
beadjustedInrenalfaIlurepatIentsasmIlrInoneIsexcretedIntheurIne,prImarIlyIn
unconjugatedform.PeakresponsewIthan7doseoccursafter5mInutesandrevealsno
evIdenceoftoleranceovershorttermtrIals(24hours);ItIscompatIblewIthother
adrenergIcagonIsts.tIsaneffectIveInotropIcagentInpatIentsreceIvIngbetablockers.
tseffIcacyInthepatIentwhohasbeendIgItalIzedhasbeendemonstrated.|IlrInoneand
08ThavebecomethemaInstayoftreatmentfordecompensatedheartfaIlurepatIentswho
requIre7vasodIlatorsandposItIveInotropIcagents.Nevertheless,theuseofsuchagents
sIgnIfIcantlyIncreasesmortalIty
74
andonemustbeawarethatthesedrugsmayIncrease
therIskofarrhythmIasInthesepatIentswhomayInfactrequIreImplantablecardIoverter
defIbrIllators.
75
Glucagon
ClucagonIsasInglechaInpolypeptIdeof29amInoacIdsthatIssecretedbypancreatIc
cellsInresponsetohypoglycemIa(seeChapter49).ThelIverandkIdneyareresponsIblefor
ItsdegradatIon.KnowneffectsofthIshormoneInhumansIncludethefollowIng:(1)
InhIbItIonofgastrIcmotIlIty,(2)enhancedurInaryexcretIonofInorganIcelectrolytes,(J)
IncreasedInsulInsecretIon,(4)hepatIcglycogenolysIsandgluconeogenesIs,(5)anorexIa,
(6)InotropIcandchronotropIccardIaceffects,and(7)relaxatIonofsmoothmuscle(bIlIary,
I.e.,sphIncters).
76
LIttleattentIonwasgIventoglucagonuntIl1968,whenItwas
demonstratedtoproduceposItIveInotropIcandchronotropIceffectsInthecanIneheart.
ClucagonenhancestheactIvatIonofadenylcyclaseInamannersImIlartothatofNE,EP,
andIsoproterenol.ThesecardIacactIonsofglucagonarenotblockedbyblockadeor
catecholamInedepletIon.Clucagon,IncontrasttothexanthInes,rarelycauses
dysrhythmIa,evenInthefaceofIschemIcheartdIsease,hypokalemIa,anddIgItalIs
toxIcIty.ClucagonmaypossessantIdysrhythmIcactIvItyIndIgItalIstoxIcItybecauseIthas
beenshowntoenhanceA7nodalconductIonInpatIentswIthvaryIngdegreesofA7block.
An7doseof1to5mgofglucagonIncreasescardIacIndex,meanarterIalpressure,and
ventrIcularcontractIlIty,evenInthepresenceofdIgItalIstherapy.Afterabolusdose,Its
actIondIssIpatesInapproxImatelyJ0mInutes.NauseaandvomItIngarecommonsIde
effectsIntheawakepatIent,especIallyfollowIngabolusdose.HypokalemIa,
hypoglycemIa,andhyperglycemIaarealsoseen.ClucagonIsalsousefulIntreatIngInsulIn
InducedhypoglycemIa.
0espItetheobvIousbenefItsofglucagonIncardIacpatIents,Itsusehasnotbecome
popular.ThIspancreatIchormonemaybeofhemodynamIcbenefItwhenmore
conventIonalapproacheshaveprovedrefractoryInthefollowIngsettIngs:(1)lowCD
syndromefollowIngcardIopulmonarybypass,(2)lowCDsyndromewIthmyocardIal
InfarctIon,(J)chronIccongestIveheartfaIlure,and(4)excessIveadrenergIcblockade.n
casesofanaphylactIcshockwIthsIgnIfIcantandrefractoryhypotensIon,glucagonIs
extremelyusefulalternatIveagentInreversIngthedecreasedbloodpressure.
77
Digitalis Glycosides
ThemostImportantactIonsofthedIgItalIsglycosIdesarethoseaffectIngmyocardIal
contractIlIty,conductIon,andrhythm.TheglycosIdemostlIkelytobeusedbythe
anesthesIologIstIsdIgoxIn.TheprIncIpalusesof
P.J57
dIgoxInareforthetreatmentofcongestIveheartfaIlureandtocontrolsupraventrIcular
cardIacdysrhythmIasuchasatrIalfIbrIllatIon.0IgoxInIsoneofthefewposItIveInotropes
thatdoesnotIncreaseHF.0IgoxInenhancesmyocardIalInotropIsmandautomatIcItybut
slowsImpulsepropagatIonthroughtheconductIontIssues.
51
0espItenearlytwocenturIesof
use,ItsmechanIsmofactIonIsonlymodestlycertaIn.0IgItalIsrecIprocallyfacIlItates
calcIumentryIntothemyocardIalcellbyblockIngtheNa
+
,K
+
adenosInetrIphosphatase
pump.ThIscalcIumInfluxmayaccountforItsposItIveInotropIcactIonbecausethIs
InotropIcresponseIsnotcatecholamIneorreceptordependent,andIstherefore
effectIveInpatIentstakIngblockIngdrugs.TheInhIbItIonofthIsenzymetransport
mechanIsmalsoresultsInanetK
+
lossfromthemyocardIalcell.ThIscontrIbutesto
dIgItalIstoxIcItywIthhypokalemIa.CalcIumpotentIatesthetoxIceffectsofdIgItalIs.
ExtremecautIonshouldbeobservedwhencalcIumIsgIventoapatIenttakIngdIgItalIsor
whendIgItalIsadmInIstratIonIscontemplatedInthepatIentwIthhypercalcemIa.0IgItalIs
hasbeenoflIttleuseIncardIogenIcshockandhasprovedpotentIallyInjurIousInpatIents
wIthuncomplIcatedmyocardIalInfarctIonbecauseofItsvasoconstrIctIvepropertIesand
effectsonmyocardIaloxygenconsumptIonIntheabsenceofcardIomegaly.Caremustbe
takentoruleoutcondItIonsInwhIchtheuseofdIgItalIsIsofnobenefItandIspotentIally
harmful.TheseIncludemItralstenosIswIthnormalsInusrhythmandconstrIctIve
perIcardItIswIthtamponade.SIgnsandsymptomsofIdIopathIchypertrophIcsubaortIc
stenosIsareoftenexacerbatedbydIgItalIs.WIthIncreasedstrengthofcontractIon,the
muscularobstructIoncanbemarkedlyIncreased.ThesameIstruefortheuseofdIgItalIsIn
patIentswIthInfundIbularpulmonIcstenosIs,asoccurswIthtetralogyofFallot.Any
augmentatIonofcontractIlItymayfurtherreduceanalreadydImInIshedpulmonaryblood
flow.8ewareofdIgItalIstoxIcreactIonsIntheolderagegroupandInpatIentssufferIng
fromarterIalhypoxemIa,acIdosIs,renalcompromIse,hypothyroIdIsm,hypokalemIa,or
hypomagnesemIa,aswellasInpatIentsreceIvIngquInIdIneorcalcIumchannelblockers.
WhenentertaInIngthepossIbIlItyofperIoperatIvedIgItalIsadmInIstratIon,thefollowIng
poIntsmustbeconsIdered.
1. |yocardIaloxygenconsumptIonIsIncreasedInthenonfaIlIng,nondIlatedheart.
2. ThetherapeutIctotoxIcratIoofdIgItalIsIsnarrow.
J. notropIcdrugsthatarelesstoxIcandreversIblearereadIlyavaIlable.
4. 7erapamIlorbetablockersaremoreeffIcacIousforsupraventrIculartachydysrhythmIas
notInItIatedbyheartfaIlure.
5. 0IgItalIsmaycauseserIousdysrhythmIaIntheunstablepatIent.
6. SerumpotassIumconcentratIonsmayfluctuateInthesurgIcalpatIent.
7. AnycardIacdysrhythmIathatoccursInthepresenceofdIgItalIsmustbeconsIdereda
toxIcphenomenon.
8. 0IgItalIsInducedcardIacdysrhythmIasaredIffIculttotreat.
9. FenalcompromIsewIllresultIntoxIceffectswIthstandardmaIntenancedoses.
10. CardIoversIonmaybedangerousafterdIgItalIsadmInIstratIon.
11. AfterInItIatIonofdIgItalIstherapy,theadmInIstratIonofalternatIvedrugsbecomes
morecomplIcated.
0IgoxIn,betablockers,andcalcIumchannelblockerssuchasdIltIazemandverapamIlmay
beusedInpatIentswIthheartfaIlureandnormalejectIonfractIontocontroltheHF,
especIallyIfpatIentsdohavesupraventrIculartachyarrhythmIassuchasatrIalfIbrIllatIon.
Nevertheless,dIgoxInIsnotrecommendedforpatIentswIthheartfaIlure,butwIthnormal
ejectIonfractIon,asItmayIncreasetheleftventrIcularfIllIngpressure,andsubsequently
aggravatetheIrheartfaIlure.
78
Calcium Salts
CalcIumIsofgreatImportanceInthegenesIsofthecardIacactIonpotentIalandIsthekey
tocontrollIngIntracellularenergystorageandutIlIzatIon.|ovementofextracellular
calcIumacrossmembranesalsogovernsthefunctIonofuterInesmoothmuscleaswellas
thesmoothmuscleofthebloodvessels.ThesympathomImetIcdrugspromotethe
transmembraneInfluxofcalcIum,whereasthebetablockersandcalcIumchannelblockers
InhIbItsuchmovement.TheAmerIcanHeartAssocIatIonhasrecommendedagaInsttheuse
ofcalcIumdurIngcardIacarrestexceptwhenhyperkalemIa,hypocalcemIa,orcalcIum
channelblockertoxIcItyIspresent.
79
Subsequently,theIndIcatIonsforcalcIumusearenow
lImItedtoonlyfewclInIcalapplIcatIons(seeChapter59).CalcIumchlorIdeIsoftengIvenat
thetermInatIonofcardIopulmonarybypasstooffsetthemyocardIaldepressIonassocIated
wIthhypothermIcpotassIumcardIoplegIa.
80
ThereIsnewerevIdencethattheuseof
calcIumIntheearlypostbypassperIodmayInducespasmofthecoronarIes,IncludIngthe
newlygraftedInternalmammaryartery,alsocauseshypercontractureoftheheartcells,
andthereforeIncreasestherIskformyocardIalIschemIa,reperfusIonInjury,andeven
myocardIalInfarctIon.
81,82,8J
TheuseofcalcIumsaltsIsclearlyIndIcateddurIngrapIdor
massIvetransfusIonsofcItratedblood.
80
CItratebIndscalcIum,andrapIdInfusIonratesofcItratedbloodresultInmyocardIal
depressIonthatIsreversIblebycalcIum.TwoformsofcalcIumsaltsarecommonly
avaIlable:calcIumchlorIdeandcalcIumgluconate.TradItIonally,calcIumgluconatehas
beenpreferredInpedIatrIcpatIentsandcalcIumchlorIdeInadultpatIents.PrevIousdata
heldthatcalcIumchlorIdeproducedconsIstentlyhIgherandmorepredIctablelevelsof
IonIzedcalcIum.
84
StudIeshaveshown,however,thatIonIzatIonofanyofthepreparatIons
IsImmedIateandequallyeffectIve(seeChapter14).CalcIumchlorIdeproducesonly
transIentIncreasesInCDandbloodpressure.8olusdosesof2to10mg/kg(1.5mg/kg/mIn)
ofcalcIumchlorIdecanproducemoderateImprovementIncontractIlIty.TherapId
admInIstratIonofcalcIumsalts,IftheheartIsbeatIng,canproducebradycardIaandmust
beusedcautIouslyInthepatIentwhoIsdIgItalIzedbecauseofthehazardofproducIng
toxIceffects.CalcIumsaltswIllprecIpItateascalcIumcarbonateIfmIxedwIthsodIum
bIcarbonate.
Antidepressant Drugs
Monoamine Oxidase Inhibitors
|onoamIneoxIdaseInhIbItors(|ADs)andthetrIcyclIcantIdepressantsareusedtotreat
psychotIcdepressIon.ThesedrugsarenotusedInthepractIceofanesthesIabutarea
sourceofpotentIallyserIousanesthetIcInteractIonsInpatIentswhoaretakIngthem
chronIcally(seeChapter2J).TheIruseIsrapIdlydeclInIngasthenontrIcyclIc
antIdepressantssuchasProzacaremoreeffIcacIousandproducefewersIdeeffects.Fewof
the|ADsortrIcyclIcantIdepressantswIllbeencounteredInananesthesIapractIcetoday,
wIththeexceptIonsofphenelzIne(NardIl)andamItrIptylIne(AmItrIl,ElavIl).TheIr
pharmacologIcactIonsandsIdeeffectsareadIrectresultoftheIreffectonthecascadeof
catecholamInemetabolIsm.|ADsblocktheoxIdatIvedeamInatIonofendogenous
catecholamInesIntoInactIvevanIllylmandelIcacId.TheydonotInhIbItsynthesIs.Thus,
blockadeof|ADwouldproduceanaccumulatIonofNE,EP,0A,and5hydroxytryptamIne
InadrenergIcallyactIvetIssues,IncludIngthebraIn.TheactIonofsympathomImetIc
amInesIspotentIatedInpatIentstakIng|ADs.ndIrectactIng
P.J58
sympathomImetIcs(ephedrIne,tyramIne)produceanexaggeratedresponseastheytrIgger
thereleaseofaccumulatedcatecholamInes.FoodscontaInIngahIghtyramInecontentsuch
ascheese,redtalIanwIne,andpIckledherrIngcanalsoprecIpItatehypertensIvecrIses.
26
|eperIdInehasbeenreportedtoproducehypertensIvecrIsIs,convulsIons,andcomawIth
|ADs.HepatotoxIcItyhasbeenreportedthatdoesnotseemtoberelatedtodosageor
duratIonoftreatment.tsIncIdenceIslowbutremaInsafactorInselectInganesthesIa.
TheanesthetIcmanagementofpatIentstakIng|ADsremaInscontroversIal.Currently,
recommendatIonsformanagementIncludedIscontInuatIonofthedrugsforatleast2weeks
beforesurgery;however,thIsrecommendatIonIsnotbasedoncontrolledstudIesbut
ratherIstheresultoflImItedcasereportsthatsuggestpotentdrugInteractIons.
Tricyclic Antidepressants
ThIsgroupofantIdepressantdrugsIsreferredtoastricyclic antidepressantsbecauseof
theIrstructure.Thesedrugshavealmostreplacedthe|ADsbecauseoffewersIdeeffects.
AlloftheseagentsblockuptakeofNEIntoadrenergIcnerveendIngs.JustaswIththe
|ADs,hIghdosesofthetrIcyclIcantIdepressantscanInduceseIzureactIvItythatIs
responsIvetodIazepam.NeuroleptIcdrugsmaypotentIatetheeffectsoftrIcyclIc
antIdepressantsbycompetItIonwIthmetabolIsmInthelIver.ChronIcbarbIturateuse
IncreasesmetabolIsmofthetrIcyclIcantIdepressantsbymIcrosomalenzymeInductIon.
DthersedatIves,however,potentIatethetrIcyclIcantIdepressantsInamannersImIlarto
thatoccurrIngwIththe|ADs.AtropInealsohasanexaggeratedeffectbecauseofthe
antIcholInergIceffectoftrIcyclIcantIdepressants.ProlongedsedatIonfromthIopentalhas
beenreported.KetamInemayalsobedangerousInpatIentstakIngtrIcyclIcantIdepressants
byproducIngacutehypertensIonandcardIacdysrhythmIa.0espItetheseserIous
InteractIons,dIscontInuatIonofthesedrugsbeforesurgeryIsprobablynotnecessary.The
latencyofonsetofthesedrugsIsfrom2to5weeks;however,theexcretIonoftrIcyclIc
antIdepressantsIsrapId,wIthapproxImately70ofadoseappearIngIntheurInedurIng
thefIrst72hours.ThelonglatencyperIodforresumptIonoftreatmentmIlItatesagaInst
Interruptedtreatment.AthoroughknowledgeofthepossIbledrugInteractIonsand
autonomIccountermeasuresnowavaIlableobvIatespostponement.
Selective Serotonin Reuptake Inhibitors
ThemechanIsmofactIonofselectIveserotonInreuptakeInhIbItorsappearstobethe
selectIveInhIbItIonofneuronaluptakeofserotonIn.ThIspotentIatesthebehavIoral
changesInducedbytheserotonInprecursor,5hydroxytryptophan.
85
TheavaIlabIlItyof
sympathetIcantagonIstsforpossIblesIdeeffectsdurInganesthesIaweIghsInfavorof
contInuatIonoftherapyversustherIskofexacerbatIonofaseveredepressIon.Prozac
(fluoxetIne)IsapopularoralnontrIcyclIcantIdepressant.UnlIkedesyrel,theelImInatIon
halflIfeofProzacIs1toJdaysandcanleadtosIgnIfIcantaccumulatIonofthedrug.
Prozac'smetabolIsm,lIkethatofothercompoundsIncludIngtrIcyclIcantIdepressants,
phenobarbItal,ethanol,andpentothal,InvolvestheP45006system.Therefore
concomItanttherapywIthdrugsalsometabolIzedbythIsenzymesystemmayleadtodrug
InteractIonsandprolongatIonofeffectofthebenzodIazepInes.8uproprIonIsusedasan
antIdepressant,whereasasustaInedreleasedrugIsmarketedasanonnIcotIneaIdto
smokIngcessatIon.TheneurochemIcalmechanIsmoftheantIdepressanteffectof
bupoprIonIsnotknown.tdoesnotInhIbItmonoamIneoxIdaseandIsaweakblockerofthe
neuronaluptakeofserotonInandNE.talsoInhIbItstheneuronaluptakeof0Atosome
extent.NosystematIcdatahavebeencollectedontheInteractIonsofbupropIonandother
drugs.
Sympatholytics Drugs
Alpha Antagonists
0rugsthatbIndselectIvelytoadrenergIcreceptorsblocktheactIonofendogenous
catecholamInesormoderatetheeffectsofexogenousadrenergIcs.Theresultanteffects
maybeascrIbedtogethertheblockadeeffecttoadrenergIcagonIstsortounopposed
adrenergIcreceptoractIvIty.TheeffectIssmoothmusclerelaxatIon.Theresponsetothe
vasculaturemayvaryoverawIderangeInasInglevascularbed,dependIngonItsIntrInsIc
stateofconstrIctIon.7esselswIthhIgherInItIaltonehaveagreaterresponseto
blockade.PromInentclInIcaleffectsofblockersIncludehypotensIon,orthostatIc
hypotensIon,tachycardIaandmIosIs,nasalstuffIness,dIarrhea,andInhIbItIonof
ejaculatIon.TheblockersmaybeclassIfIedaccordIngtobIndIngcharacterIstIcs.
PhenoxybenzamIneIsanoralblockerthatproducesandIrreversIbleblockade.tIsa
relatIvelynonselectIveblocker.PhentolamIne,tolazolIne,andprazosInare
characterIzedbyreversIblebIndIngandantagonIsm.WhenpatIentsaretakIngthesedrugs
chronIcally,oneshouldkeepInmIndthatthenormalautonomIcresponsetostress,
InhalatIonanesthetIcs,orextensIveregIonalanesthesIamaybeblunted.ElevatIonsof
catecholamIneswIllnotreflexlyIncreaseperIpheralvascularresIstanceandmayactually
decreaseIfvascularreceptorsareunopposed.8lockersareoftenusedIncombInatIon
wIthdIuretIcsandotherantIhypertensIves.7olumedepletIonmaynotbeevIdenton
preoperatIveexamInatIonbutbecomeunmaskedwIththeInductIonofanesthesIa,
resultIngIntheonsetofamarkedhypotensIon.ThIshypotensIonIsusuallyresponsIveto
volumerepletIonandthetemporaryuseofadIrectactIngagonIstsuchasneosynephrIne.
ThereIsnocausefordIscontInuatIonofthesedrugsbeforesurgerybutpreloadIngwIth7
fluIdsIssuggestedtoensureadequatecentralvolume.
Phentolamine
PhentolamIneIsusedalmostexclusIvelyInthepresurgIcaltreatmentof
pheochromocytoma(seeChapter49).tIsacompetItIveantagonIstat
1
and
2
receptors.
PhentolamInemayalsohavesomeantIhIstamInIcandcholInomImetIcactIvIty.The
cholInomImetIcactIvItymayresultInabdomInalcrampInganddIarrhea,bothofwhIchare
blockedbyatropIne.TachycardIaandhypotensIonarealsocommonsIdeeffects.
ntravenously,phentolamIneproducesperIpheralvasodIlatatIonandadecreaseInsystemIc
bloodpressurewIthIn2mInutesandlastIngfrom10to15mInutes.8loodpressurereductIon
elIcItsbaroreceptorreflexesandNErelease.CardIacarrhythmIasandangInapectorIsmay
accompanyphentolamIneadmInIstratIon.tcanbegIvenIndosesofJ0to70g/kg7to
produceatransIentdecreaseInbloodpressure.tcanalsobeusedasacontInuousInfusIon
tomaIntaInbloodpressuredurIngresectIonofapheochromocytoma.
Phenoxybenzamine
PhenoxybenzamIneactsasanonselectIveadrenergIcantagonIst(seeChapter49).
8lockadeIs100tImesmorepotentonpostsynaptIc
1
receptorsthanat
2
receptors.
PreoperatIvelyInpreparatIonforremovalofapheochromocytoma,thedugIsadmInIstered
orallystartIngat10mgtwIcedaIly.
86
TheonsetofblockadeIsslow.ThIsIsrelatedtothe
tImerequIredforstructuralmodIfIcatIonofthephenoxybenzamInemoleculetobecome
actIve.TheelImInatIonhalflIfeIsabout24hours.DrthostatIchypotensIonIspromInent,
especIallyInthepresenceofpreexIstInghypertensIonorhypovolemIa.CDIsoften
IncreasedandrenalbloodflowIsnotgreatlyalteredexceptInpreexIstIngrenal
P.J59
vasoconstrIctIonorstenosIs.CoronaryandcerebralvascularresIstanceIsnotchanged.
Prazosin
PrazosInIsrelatIvelyselectIvefor
1
receptors,leavIngtheInhIbItIngeffectof
2
receptor
actIvItyonNEreleaseIntact.Asaresult,ItIslesslIkelythannonselectIveantagonIststo
evokereflextachycardIa.TheInItIaloraldoseIs1mgtwIcedaIly,thentItratedtoeffect.
PrazosIndIlatesbotharterIolesandveIns.CardIovasculareffectsIncludetotalbody
reductIonsInsystemIcvascularresIstanceandvenousreturn.WhencombInedwItha
dIuretIcItIsaneffectIveantIhypertensIvedrug.tshouldnotbeusedwIthclonIdIneor
methyldopa,asItappearstodecreasetheIreffectIveness.PrazosInmayalsocause
bronchodIlatIon.
Dral
1
blockershavebeenfoundusefulforbenIgnprostatIchypertrophyandhypertensIon.
TheanesthesIologIstmayencounterpatIentstakIngthesemedIcatIonsonachronIcbasIs
andmustbeawareoftheIrpossIbleInteractIonswIthanesthetIcs(seeChapter2J).
0oxazosInIsalongactIngselectIve
1
blockerusedfortreatIngbenIgnprostate
hyperplasIaandhypertensIon.ThemostcommonsIdeeffect,aswIthallblockers,Is
orthostatIchypotensIonanddIzzIness.TamsulosInIsanotherblockerthatIsusedfor
benIgnprostatehyperplasIa.tIsnotIndIcatedforhypertensIonbutItIscapableof
producIngorthostatIchypotensIon.
Beta Antagonists
AdrenergIcblockerswereIntroducedInthe1960s.ThesesympatholytIcagentshave
domInatedcardIovascularpharmacology.TheyareamongthemostcommondrugsusedIn
thetreatmentofcardIacdIseaseandhypertensIon.AvarIetyofdrugsareavaIlablewIth
blockIngactIvItythatmaybedIstInguIshedbydIfferIngpharmacokInetIcand
pharmacodynamIcpropertIes.ExamplesofsomeofthedrugsavaIlableandtheIrdIversIty
ofactIonsarelIstedInTable1512.8etablockerscanbeclassIfIedaccordIngtowhether
theyareselectIveornonselectIveonthe
1
or
2
receptorandwhethertheypossess
IntrInsIcsympathomImetIcactIvIty.Forexample,abetablockerwIthselectIvepropertIes
forthe
1
receptorwouldbIndtothecardIacreceptors,whereasanonselectIvebeta
blockerwouldbIndtoboth
1
(cardIac)and
2
(vascular,bronchIalsmoothmuscleand
metabolIc)receptors.NonselectIveantagonIstsarereferredtoasfirst-generation beta-
blockers.TheseIncludepropranolol,nadolol,sotalol,andtImolol.SecondgeneratIondrugs
arethoseconsIderedselectIvefor
1
adrenergIcblockade.TheseIncludeatenolol,esmolol,
andmetoprolol.Dverthepastdecade,andbecauseoftheIrselectIvIty,theuseofbeta
blockershasexpandedtoIncludethetreatmentofcongestIveheartfaIlure.Fecently,a
newbetablockersubcategoryhasbeendeveloped,respectIvely,betablockerwIth
vasodIlatorypropertIes,suchasInanewbetablocker,nebIvolol.
87
8etablockersareanImportantclassofagentsthatareIndIcatedfortreatmentofcoronary
arterydIsease,hypertensIon,heartfaIlure,andtachyarrhythmIas.TheyhaveaprImary
roleIntreatmentofpatIentsafteramyocardIalInfarctIon.
88
8etablockershaveadIrect
effectonreducIngthemortalItyInpatIentswIthheartfaIlureduetoleftventrIcular
systolIcdysfunctIon(bIsoprolol,carvedIlol,andmetoprolol).Fecently,afourthagenthas
beenusedwIthsImIlarfavorableresults,andthIsIsnebIvolol.
89,90
NebIvololIsabeta
blockerwIthanexcellentselectIvIty,andendothelIumdependentvasodIlatIonsecondary
toLargInIne/nItrIcoxIdepathway.Therefore,thIsnoveldrughashemodynamIc
advantagesandabetterprofIleforsIdeeffects.FecenttrIalsdemonstratedareduced
morbIdItyandmortalItyInelderlypatIentswIthchronIcheartfaIlure,whIchmakesthIs
drugaveryInterestIngoptIonforthefuturetreatmentofcardIacdIseasebecauseItIs
currentlyonlyavaIlableInEurope.
87,91
8etablockersreducetheIncIdenceofperIoperatIve
myocardIalInfarctIon;thereIsanIncreasedInterestInusIngtheseagentsperIoperatIvely
InhIghrIskpatIentsundergoIngvascularandotherhIghrIsksurgIcalprocedures
92
(see
Chapter42).
SelectIveblockadeIsofgreatbenefItIntreatmentofpatIentswIthobstructIveaIrway
dIsease,dIabetes,orperIpheralvasculardIsease.However,ItmustbeemphasIzedthat
specificityIsarelatIvetermandnotabsolute.NonselectIveblockIngeffectsmaybeseenIn
alltIssuesIfhIgherbloodlevelsarereachedwIthselectIvedrugs.Forexample,theuse
of
1
selectIveblockersInpatIentswIthobstructIveorreactIveaIrwaydIseaseremaIns
controversIal.PatIentswIthreactIveaIrwaydIseasemaydevelopserIousreductIonsIn
ventIlatoryfunctIonevenwIth
1
selectIveantagonIsts,butthesecIrcumstancesarerare,
sothesedrugscanbeemployedforlargecategorIesofpatIents.DtherdrugsareavaIlable
fortreatmentofsupraventrIculararrhythmIasandhypertensIonInasthmatIcpatIents.
SympathetIcactIvatIongenerallyresultsInIncreasedcIrculatIngglucoselevelssecondary
toenhancedglycogenolysIs,lIpolysIs,andgluconeogenesIs.AdmInIstratIonof
2
blockersto
InsulIndependentdIabetIcsreducestheIrabIlItytorecoverfromhypoglycemIcepIsodes
(seeChapter49).
npatIentsreceIvIngchronIcbetablockertherapy,thedrugshouldbecontInued
throughouttheperIoperatIveandpostoperatIveperIod
92
(seeChapter42).Acute
wIthdrawalofantagonIstsmayproduceahemodynamIcwIthdrawalsyndromeandInduce
tachycardIa.
26
HFIsamajordetermInantofmyocardIaloxygendemands.TachycardIaIs
knowntoIncreasetherIskofpooroutcomeInpatIentswIthIschemIcheartdIsease;
therefore,hemodynamIccontrolofHFandbloodpressure(work)IsImportantInreducIng
perIoperatIverIsk.SeveralstudIeshaveshownthebenefItsofprophylactIcblockadewIth
atenololInpatIentsatrIskforIschemIccardIacdIsease.
9J
ThereductIonInperIoperatIve
morbIdItyandmortalItyInthesegroupsofpatIentswassIgnIfIcant.
94,95,96,97,98,99
Fecent
datasuggestthattheuseofbetablockeraloneIsnoteffectIve,unlesstIghtHFcontrolIs
present(80beatspermInuteperIoperatIvely).ForthIspurposeacombInatIonofdrugs
mayberequIred;furtherstudIesareunderwaythatmayIndeedestablIshthebestclInIcal
practIce.
95,97,100,101,102,10J,104
SeveraloftheblockerslIstedInTable1512alsohavealocalanesthetIclIkeeffecton
myocardIalmembranesathIghdoses.ThIseffectIssImIlartothatofquInIdIneInthat
phase0ofthecardIacactIonpotentIalIsdepressedslowIngconductIon.ThIsmembrane
stabIlIzIngactIvItyIscausedbythe0Isomer,whereastheLIsomerIsresponsIblefor
blockIngactIvIty.TheclInIcalsIgnIfIcanceofmembranestabIlIzIngactIvItyIsunclear.
Propranolol
PropranololIstheprototypIcalblockIngdrugagaInstwhIchallothersarecompared.tIs
nonselectIveandhasnoIntrInsIcsympathomImetIcactIvItybutdoeshavemembrane
stabIlIzIngactIvItyathIgherdoses.tIsavaIlableInboth7andoralforms.The7doseIs
usually0.5to1mgrepeatedevery5mInutesuptoatotalof5mgwIthcarefultItratIonto
effect.
51
tIshIghlylIpophIlIcandIsmetabolIzedbythelIvertomorewatersoluble
metabolItes,oneofwhIch,17DHpropranolol,hasweakblockIngactIvIty.ThereIsa
sIgnIfIcantfIrstpasseffectbythelIverafteroraladmInIstratIonofthedrug.tIshIghly
proteInbound,andthefreedruglevelmaybealteredbyotherhIghlybounddrugs.The
elImInatIonhalflIfeIsapproxImately4hours,butthepharmacologIchalflIfeIsaround10
hours.HemodynamIceffectsIncludedecreasedHFandcontractIlIty.Themajorfactors
contrIbutIngtothedecreaseInbloodpressurebypropranololaredecreasedCDandrenIn
release.SystemIcvascularresIstancemayIncreaseonacuteadmInIstratIonowIngto
blockadeof
2
receptorsIntheperIpheralvasculature.WIthchronIcadmInIstratIon,
however,perIpheralvascularresIstancedecreases.ThIsIsthoughttobesecondaryto
decreasedrenInreleaseand,possIbly,decreased
P.J60
P.J61
centralSNSoutflow.ComplIcatIonswIththeuseofpropranololIncludebradycardIa,heart
block,worsenIngofcongestIveheartfaIlure,bronchospasm,andsedatIon.
105
0urIng
anesthesIawIthhalothane,ItmaycauseseverebradydysrrhythmIas.8ecauseItIsnot
cardIoselectIve,mostclInIcIansaremovIngawayfromusIngpropranolol,andInsteadare
usIngtheselectIvealternatIvessuchasmetoprolol,oratenolol.
Table 15-12 -Adrenergic Blocking Drugs
DRUG
RELATIVE
1
SELECTIVITY
MEMBRANE-
STABILIZING
ACTIVITY
INTRINSIC
SYMPATHOMIMETIC
ACTIVITY
PLASMA
HALF-
LIFE(hr)
ORAL
AVAILABILITY
(%)
LIPID
SOLUBILITY
Propranolol 0 + 0 J4 J6 +++
|etoprolol ++ 0 0 J4 J8 +
Atenolol ++ 0 0 69 57 0
Esmolol ++ 0 0 016 :
TImolol 0 0 0 45 50 +
F8C,redbloodcells.
a
PrImarIlyhepatIc,butactIvemetabolItesareformedthatmustberenallyexcreted.
Metoprolol
|etoprololIsarelatIvelyselectIveblockIngdrugwIthblockIngeffectsatmoderateand
hIghdoses.thasneItherIntrInsIcsympathomImetIcactIvItynormembranestabIlIzIng
actIvIty.thasapossIbleadvantageInpatIentswIthreactIveaIrwaydIseaseatoraldoses
upto100mg/day.TheInItIal7doseIs1.255mgevery6to12hours.FormyocardIal
InfarctIonthedoseIs2to5mgevery2mInutesforthreedoses,followedby50mgorally
every6hours,wIthcarefulmonItorIngoftheheartratewhIletheloadIngdoseIsbeIng
admInIstered.
51
tIsmostlymetabolIzedInthelIver,wIthonlyabout5excreted
unchangedIntheurIne.TheelImInatIonhalflIfeIsJ.5hours.tIsavaIlableIn7aswellas
oralform;therefore,ItIscommonlyrecommendedprIortosurgeryandanesthesIa.
89
Atenolol
AtenololIssImIlartometoprololInthatItIsrelatIvelycardIoselectIveandhasnoIntrInsIc
sympathomImetIcactIvItyormembranestabIlIzIngactIvIty.tIslesslIpophIlIc,however,
andIselImInatedprImarIlybyrenalexcretIon.ThestartIngdoseIs5mgover5mInutes7,
and25to50mg/dayoraladmInIstratIon.
51
TheelImInatIonhalflIfeIs6to7hours.The
lackoffIrstpassmetabolIsmresultsInmorepredIctablebloodlevelsafteroraldosIng.The
maInadvantageofthIsdrugIsItsonceadaydosIng.
9J,106
Esmolol
EsmololhasseveralusesIntheperIoperatIveperIod.
107
ThemostunIquefeatureofthe
drugIstheesterfunctIonIncorporatedIntothephenoxypropanolamInestructure.ThIs
allowsforrapIddegradatIonbyesterasesIntheredbloodcellsandaresultant
pharmacologIchalflIfeof10to20mInutes.EsmololIscardIoselectIveandappearstohave
lIttleeffectonbronchIalorvasculartoneatdosesthatdecreaseHFInhumans.thasbeen
usedsuccessfullyInlowdosesInpatIentswIthasthmabutcautIonIsagaInadvIsedwhen
usIngbetablockersInthesepatIents.The7bolusdoseIs0.25to0.5mg/kg,anda
contInuousInfusIonloadIngdoseIs500g/kg/mInover1to2mInutes,wIthamaIntenance
doseof50to200g/kg/mIn.
51
EsmololIsmetabolIzedrapIdlyInthebloodbyanesteraselocatedIntheredbloodcell
cytoplasm.tIsdIfferentfromtheplasmacholInesteraseandIsnotInhIbItedtoa
sIgnIfIcantdegreebyphysostIgmIneorechothIophatebutIsmarkedlyInhIbItedbysodIum
fluorIde.TherearenoapparentImportantclInIcalInteractIonsbetweenesmololandother
estercontaInIngdrugs.AtthehIghestInfusIonrates(500g/kg/mIn),esmololdoesnot
prolongneuromuscularblockadebysuccInylcholIne.EsmololhasproventobeusefulInthe
perIoperatIveperIodbecauseofItscapabIlItytobeadmInIsteredIntravenouslyandIts
shorthalflIfe.ThIsfeaturepermItsatrIalofblockadeIndoubtfulsItuatIons.Esmololhas
beenshowntoblunttheresponsetoIntubatIonofthetracheaandIsmoderatelyeffectIve
IntreatIngpostoperatIvehypertensIon.
108,109,110
|ostreportedstudIesInhumanshave
useddosesof50to500g/kg/mIn.ThemostbenefIcIalapproachseemstobealoadIng
doseof500g/kgoverJ0seconds,followedbycontInuousInfusIonof50toJ00g/kg/mIn.
PeakblockadeappearstooccurwIthIn5mInutes.DndIscontInuatIonoftheInfusIon,serum
levelsdeclInewIthanelImInatIonhalflIfeof9mInutes.
Timolol
TImololIsalsononcardIoselectIvewIthlIttleIntrInsIcsympathomImetIcactIvItyandno
membranestabIlIzIngactIvIty.tIstheonlybetablockerusedastheLIsomerratherthan
theracemIcmIxture.tIs5to10tImesaspotentaspropranolol.HepatIcmetabolIsm
accountsforapproxImately66ofItselImInatIon,andanother20IsfoundunchangedIn
theurIne.TheelImInatIonhalflIfeIs5.6hours,andthepharmacologIchalflIfeIs
approxImately15hours.twasfIrstusedtopIcallyfortreatmentofglaucomabutIsnow
usedInhypertensIonandhasbeenshowntodecreasetherIskofreInfarctIonanddeath
followIngmyocardIalInfarctIon.tshemodynamIceffectsandsIdeeffectsaresImIlarto
thoseofotherbetablockers.TheanesthesIologIstshouldalsobeawarethattImololeye
dropsmaybeabsorbedsystemIcallyandcausebradycardIaandhypotensIonthatare
refractorytotreatmentwIthatropIne.
111
Other Beta-Blockers
DtherbetablockersIncludedrugssuchasnadolol(noncardIoselectIvebetablocker),
acebutolol(cardIoselectIvebetablockerwIthIntrInsIcsympathomImetIcactIvItyand
membranestabIlIzIngactIvIty),pIndolol(nonselectIvebetablockerwIthmembrane
stabIlIzIngactIvItyandIntrInsIcsympathomImetIcactIvIty),betaxolol(cardIacselectIve),
penbutolol(nonselectIvewIthsomeIntrInsIcsympathetIcactIvIty),carteolol(nonselectIve)
areusedfortreatmentofhypertensIonorHFcontrol.
Mixed Antagonists
Labetalol
LabetalolIsanantIhypertensIvedrugwIthblockIngactIvItyatbothandreceptors.The
relatIve/blockIngeffectsdependontherouteofadmInIstratIon.Afteroral
admInIstratIon,theratIoof/effectIvenessIs1:J;however,whengIvenIntravenously,It
Is1:7.TheeffectsareprImarIlyon
1
receptors,whereastheeffectsonnonselectIve.
HemodynamIceffectsconsIstprImarIlyofdecreasedperIpheralresIstanceanddecreasedor
unchangedHFwIthlIttlechangeInCD.SerumrenInactIvItyIsdecreased.|aIntenanceof
lowerHFsInthepresenceofdecreasedsystemIcbloodpressureIsbenefIcIalIncontrollIng
themyocardIaloxygensupply/demandratIoandIsamajorbenefItoflabetalolInpatIents
wIthcoronaryarterydIsease.
LabetalolIselImInatedbyhepatIcglucuronIdeconjugatIon.TheelImInatIonhalflIfeafter
7admInIstratIonIs5.5hoursand6to8hoursafteroraluse.ElImInatIonIsnotmarkedly
prolongedInpatIentswIthhepatIcorrenalfaIlure.AnotheradvantageofthedrugIsthe
abIlItytoconvertfrom7tooralformsofthesamedrugafterthepatIentIsstable.For
treatmentofhypertensIonwhenusedasabolus,theInItIaldoseIs2.5to10mg7over2
mInutes,thenrepeatevery10mInutestoatotalofJ0mg.WhenusedasacontInuous
InfusIon,ItIsusuallystartedat0.5to2.0mg/mInandtItratedtoeffect.8ecausethereIs
anenhancedeffectbyInhalatIonanesthetIcs,thesedosesshouldbedecreasedwhenused
IntraoperatIvely.
ComplIcatIonsandcontraIndIcatIonsaresImIlartothoseforthebetablockers.Labetalol
shouldbeusedwIthcautIonInpatIentswIthcompromIsedmyocardIalfunctIonbecauseIt
mayworsenheartfaIlure.Also,owIngtoblockIngactIvIty,thedrugmayInduce
bronchospasmInasthmatIcs.AswIthotherbetablockers,abruptwIthdrawalIsnot
recommended.LabetalolIsoneofthefavorItesofmanyanesthesIologIstsforuseInthe
perIoperatIveperIodbecauseItrapIdlydecreasesbothbloodpressure,andtosomeextent,
alsotheHF,Itcanbeusedasabolus,andultImatelyachIevesnormotensIonwIthInafew
mInutesofInItIaladmInIstratIon.
112,11J
Calcium Channel Blockers
CalcIumIsregardedastheunIversalmessengerIncellsandplaysacrItIcalroleIna
numberofbIologIcprocesses.tIs
P.J62
InvolvedInbloodcoagulatIon,abroadarrayofenzymatIcreactIons,themetabolIsmof
bone,neuromusculartransmIssIon,theelectrIcalactIvatIonofvarIousexcItable
membranes,aswellasendocrInesecretIonandmusclecontractIon.CalcIumInItIates
severalphysIologIceventsInthespecIalIzedautomatIcandconductIngcellsIntheheart.t
IsInvolvedInthegenesIsofthecardIacactIonpotentIalandItlInksexcItatIonto
contractIonandcontrolsenergystoresandutIlIzatIon.|ovementofextracellularcalcIum
acrossmembranesalsogovernsthefunctIonofsmoothmuscleInbronchIandIncoronary,
pulmonary,andsystemIcarterIoles.tsrolesInadrenergIceffectorresponsehavebeen
outlInedIndetaIl(seeAdrenergIcFeceptors).|embranecalcIumchannelsareknownto
provIdeapathwayforcalcIumInfluxacrosscellmembranesthatdIfferfromcalcIumefflux
movementsassocIatedwIthactIvepumpsorexchange.TheInwardcalcIumchannel
exhIbItstwodIstInguIshIngpropertIes:(1)selectIvItyInthattheyhavetheabIlItyto
dIstInguIshbetweenIonspecIes,and(2)excItabIlItyInthattheyhavethepropertyof
respondIngtochangesInmembranepotentIal.Separate,IonspecIfIcchannelsforsodIum
andcalcIumInfluxexIst.ThestatusofthesechannelscanvarytoproducethreekInetIc
states:restIng,actIvated,andInactIvated.
Figure 15-16.StructuralformulasofthecalcIumentryblockersdemonstrate
dIssImIlarstructuresconsIstentwIththeIrdIssImIlarelectrophysIologIcand
pharmacologIcpropertIes.TheyalsosharesomesImIlarItIesbutcannotbeconsIdered
therapeutIcallyInterchangeable.NIfedIpIneandnItrendIpInearestructurallysImIlar
andarebothpotentvasodIlators.
ClassIfIcatIonofcalcIumchannelblockershasbeendIffIcultsIncetheIrdIscovery.They
wereInItIallythoughttobeadrenergIcblockIngdrugsbecauseoftheIrsympatholytIc
actIon.Latertheywerecalledcalcium antagonists.tIsclear,however,thatthesedrugs
arenottruepharmacologIcantagonIstsofcalcIum.nstead,theyInteractwIththecell
membranetocontroltheIntracellularconcentratIonofcalcIum.ThecorrecttermInology
forthIsgroupofdrugsappearstobecalcium channel blockers.Themolecularstructuresof
threeclInIcallyusefulcalcIumentryblockersareseenInFIgure1516.Thesedrugsproduce
vasodIlatatIon,depresscardIacconductIonvelocIty(dromotropIsm),depresscontractIlIty
(InotropIsm),anddecreaseHF(chronotropIsm).AllcalcIumchannelblockersdothIs,but
wIthvaryIngdegreesofpotencyIntheIntacthumanandInvItro(Table1511).Thus,
despItetheIrsImIlarItIes,thesedrugscannotbeconsIderedtherapeutIcally
Interchangeable.TheusefulpharmacologIceffectsofthecalcIumchannelblockershave
beenconfInedalmostsolelytothecardIovascularsystem.
99
ThedrugsareallabsorbedvIa
thegastroIntestInaltract,buttheextensIvefIrstpasshepatIcextractIonofverapamIl
lImItsItsbIoavaIlabIlItyorally(Table151J).DnsetofactIonIsequIvalentforallthree
P.J6J
drugsandIsconsIstentwIthrapIdmembranetransport.AllthreedrugsareextensIvely
proteInboundandsubjecttotheeffectofchangesInplasmaproteInconcentratIonand
competItIonfromotherproteInbounddrugsandmetabolItes,butfInalelImInatIonof
verapamIlandnIfedIpIneIsprImarIlyrenal.
Table 15-13 Comparative Pharmacology of Calcium Entry Blockers
VERAPAMIL DILTIAZEM NIFEDIPINE
Dose
Dral 80160mgtId 6090mgtId 1020mgtId
7 75150g/kg 75150g/kg 515g/kg
Absorption
Dral() 90 90 90
8IoavaIlabIlIty
Dral() 20 :20 6070
a
Dnset
Dral 1520mIn 20J0mIn 1520mIn
7 1mIn : 1mIn
SublIngual JmIn
Peak Effect
Dral 5hr J0mIn 12hr
7 5J0mIn : 1Jhr
Elimination
half-life
27hr 4hr 45hr
Plasma protein
binding
90 80 90
Metabolism
70
FIrstpasshepatIc
0eacetylated 80tolactone
Elimination
Fenal 75 J5 70
CastroIntestInal
(lIver)
15 75 15
Side effects
ConstIpatIon,
headache,vertIgo,
hypotensIon,
atrIoventrIcular
conductIon
dIsturbances
Headache,
dIzzIness,flushIng,
atrIoventrIcular
conductIon
dIsturbances,
constIpatIon
Headache,
hypotensIon,
flushIng,
dIgItal
dysesthesIas,
legedema
7,Intravenous.
a
LIghtsensItIve.
Verapamil
7erapamIlIsacalcIumchannelblockerthatIsadmInIsteredIntravenouslyfortermInatIng
supraventrIculartachydysrhythmIas.NearlyallformsofsupraventrIcular
tachydysrhythmIasarecausedbyreentryusIngeItherthesInoatrIalortheA7nodeaspart
ofthecIrcuIt.7erapamIltermInatesthesecardIacdysrhythmIasbydecreasIngnodal
conductIvItyandconvertIngtheunIdIrectIonalblockofreentrytoabIdIrectIonalblock.
7erapamIldoesnotaltertheactIonpotentIalupstrokeInfIberswhoserestIngmembrane
potentIalIsmorenegatIvethan60m7,thatIs,fastactIonpotentIals.(tdoesslowor
preventdepolarIzatIonIncardIactIssuewItharestIngmembranepotentIalthatIsless
negatIvethan50m7,thatIs,calcIumdependentupstroke.)7erapamIl,therefore,has
profoundeffectsonpacemakercells,whIchdependonthecalcIumcurrentfor
depolarIzatIon.tdepressestherateofsInusdIscharge,reducesconductIonvelocIty,and
IncreasesrefractorInessoftheA7node.AdosedependentIncreaseInthePFIntervaland
A7IntervalIsproducedontheelectrocardIogram.ThIshasbeendescrIbedasa
quInIdInelIkeeffectsImIlartothatproducedbyclassAantIdysrhythmIcdrugs(e.g.,
procaInamIde),whIcharealsoeffectIveforsupraventrIculardysrhythmIa.ncontrastto
procaInamIde,verapamIldoesnotIncreasetheQFSorQTIntervalbecauseItlacksactIvIty
onthesodIumdependentactIonpotentIals.
7erapamIlIsafIrstlInedrugfortreatmentofsupraventrIculartachydysrhythmIas(Table
1511)(seeChapter59).TheIncIdenceofsuccessfultermInatIonofparoxysmalatrIal
tachycardIawIthverapamIlInadultshasapproached90.tIsalsoeffectIveIntreatIng
atrIalfIbrIllatIonandatrIalflutterbyeItherconvertIngtoasInusrhythmorslowIngthe
ventrIcularresponse.TheventrIcularratewIllslowasaresultofdecreasedconductIon
velocItythroughtheA7nodeevenwhenconversIonIsnotproduced.CautIonmustbe
exercIsedIntreatIngpatIentswhentheunderlyIngcauseoftheatrIaltachycardIa,atrIal
fIbrIllatIon,oratrIalflutterIstheWolffParkInsonWhItesyndrome.
J6
7erapamIlmay
termInatethetachydysrhythmIabyItsspecIfIcdepressanteffectsontheA7node,whIchIs
onelImbofthereentrantpathway.tmayalsoIncreaseconductIonvelocItyInthe
accessorytract,InwhIchcasetheHFmayactuallyIncrease.7erapamIlhasnoadverse
effectsonbronchIalasthmaorobstructIvelungdIseaseandmaybeselectedover
propranololInpatIentswIththesecondItIons.tshouldbeavoIdedInpatIentswIthsIck
sInussyndrome,A7block,andthepresenceofheartfaIlure,unlesstheheartfaIlureIsthe
resultofasupraventrIculartachycardIa.7erapamIlhasbeeneffectIveIntermInatIng
ventrIculartachycardIasandprematuredepolarIzatIonsInabouttwothIrdsofthe
treatmenttrIalswhenotherdrugshavefaIled,andcanbeusedalsoasan
antIhypertensIve.
78,114
TheImportantsIdeeffectsofverapamIlaredIrectlyrelatedtoItspredomInant
pharmacologIcactIon(Table1511).tmayproduceunwantedA7conductIondelaysand
bradycardIa,resultIngIncardIovascularcollapse.7erapamIlmustbeusedcarefully,Ifat
all,Inthepresenceofpropranolol.ThecombInedeffecthasproducedcompleteheart
blockInanImalsandhumans.tmustbeusedcarefullyIndIgItalIzedpatIentsforthesame
reason.NosuchInteractIonsexIstwIthnIfedIpIne.ThecombInatIonofblockadeand
nIfedIpInemaybebenefIcIalInpatIentswIthIschemIcheartdIseasebecausethereflex
tachycardIaseenwIthnIfedIpInecanbecounteredwIthblockade.
Nifedipine
NIfedIpIneIsthemostpotentcalcIumentryblockerwhentestedInIsolatedtIssue
preparatIons.tIsanequIpotentcardIacdepressantandvasodIlator.0epressIonof
InotropIsmandcardIacconductIon,however,IsnotevIdentIntheIntacthuman.tdoes
notaffectbaroreflexmechanIsmsand,asaresult,themarkedvasodIlatIonIsaccompanIed
byIncreasedSNStoneandafterloadreductIon(Table1511).
26
AcompensatorytachycardIa
mayresult,andCDmayactuallyIncreaseasaresultoftheafterloadreductIon.Themost
specIfIctherapeutIcapplIcatIonfornIfedIpIneIscoronaryvasospasm(varIantof
PrInzmetal'sangIna;seeChapter41).thasbeenmoresuccessfulthannItroglycerInforthIs
purposebecauseItproducesamoreprofoundandpredIctablecoronaryvasodIlatIon.thas
alsobeenextremelyusefulInothertypesofIschemIcheartdIseaserangIngfromunstable
angInatomyocardIalInfarctIon.ThedecreaseInmyocardIaloxygendemandthatresults
fromthereducedafterloadandreducedleftventrIcularvolumeappearstobethe
mechanIsmfortherelIefofangIna.CoronaryvasodIlatIonIsanotherfactor,butItIsnot
knownIfthIsIstheantIangInaleffectInpatIentswIthcoronaryarterydIsease.ThedIlatIng
effectmaylastonly5mInutes,buttheantIangInaleffectmaylastmorethan1hour.Asan
antIhypertensIvetheusualdosageIsoraladmInIstratIonof10to20mg/day.
51
Diltiazem
ThehemodynamIceffectsofdIltIazemlIesomewherebetweenthoseofverapamIland
nIfedIpIne.tIslesspotentthaneItherofthesetwoagents.0IltIazemIsagoodcoronary
arterydIlatorbutapoorperIpheralvasodIlator.toftenproducesbradycardIaanddelayed
conductIon,andreflextachycardIaIsnotaproblem.tappearstobeaneffectIveoraldrug
forthetreatmentofcoronarydIseaseInwhIchcardIacdysrhythmIasaretroublesome.
CardIacdysrhythmIasarenotIceablyapartoftheclInIcalpIctureInpatIentssufferIngfrom
coronaryspasm.ntravenousadmInIstratIonofdIltIazemIseffectIvetherapyfor
supraventrIculartachycardIasIncludIngparoxysmalsupraventrIculartachycardIa,atrIal
fIbrIllatIon,atrIalflutter,andreentranttachycardIas.LIkeverapamIl,dIltIazemactsby
prolongIngA7nodalconductIon.TheperIpheralvasculareffectsofdIltIazem,though,are
lesssevere,makIngItamoredesIrabletherapeutIcchoIceInmostcases.Abolusdoseof
0.25mg/kgIsadmInIsteredover2mInutesandmayberepeatedat0.J5mg/kgIfnecessary
after15mInutes.AnInfusIonof5to15mg/hrmaybenecessarytomaIntaInthereductIon
ofHFThenew2005ACLSCuIdelInesrecommendsuseofcalcIumchannelblockersfora
varIetyofsupraventrIculararrhythmIas,andbecauseofdImInIshedperIpheral
vasodIlatIon,whIchImplIeslImItedeffectonthearterIalbloodpressure,dIltIazemappears
tobeoneofthebestoptIonsformanagementoftachyarrhythmIas
J6
(seeChapter59).
Nicardipine
NIcardIpInehydrochlorIdeIsacalcIumchannelblockerthatcanbeadmInIsteredorallyand
Intravenously.tIstheonlycalcIumchannelblockerthatcanbetItratedIntravenouslyto
beusedasanantIhypertensIveagent,theusualdosebeIng1to2g/kg/mInor5mg/hr.
51
NIcardIpIneIsasmoothmusclerelaxantproducIngvasodIlatIonofperIpheralandcoronary
arterIes.thasarapIdonsetofactIon,andthemajoreffectslast10to15mInutes.ToxIc
metabolIcproductsarenotproduced.thasmInImalcardIodepressanteffectsanddoesnot
decreasetherateofthesInusnodepacemakerorslowconductIonthroughtheA7node,
butoneshoulduseItcautIouslyInpatIentshavIngacutemyocardIalIschemIa.FenalfaIlure
doesnotaffectthedosage,butthedosageshouldbereducedIntheelderlyandthosewIth
hepatIcdysfunctIon.tIscompatIblewIthmost
P.J64
crystalloIdsolutIons.SIdeeffectsofnIcardIpIneIncludeheadache,lIghtheadedness,
flushIng,andhypotensIon.FeflextachycardIaIsnotafrequentfIndIngwIthnIcardIpIne,as
IsthecasewIthnItroprussIde,hydralazIne,ornIfedIpIne.
112,11J,115
Nimodipine
NImodIpIneIshIghlylIpophIlIc.thasagreatervasodIlatIngeffectoncerebralarterIesthan
onvesselselsewherebecauseofItslIpophIlIsm,whIchpromotescrossIngthebloodbraIn
barrIer.ClInIcalstudIesdemonstrateafavorableeffectontheseverItyofneurologIc
defIcItscausedbycerebralvasospasmfollowIngsubarachnoIdhemorrhage.However,no
radIographIcevIdencehasbeenpresentedthatnImodIpIneeItherpreventsorrelIeves
spasmofthesearterIes.ThemechanIsmforclInIcalImprovementIsnotknown.tIsanoral
drugthatIsrapIdlyabsorbed,wIthaTtermInalhalflIfeofapproxImately8to9hours.The
usualdoseIs60mgevery4hoursfor21days.
51
EarlIerelImInatIonratesaremuchmore
rapId,whIchresultsInaneedtoredoseevery4hours.ThebIoavaIlabIlItyofanoraldoseIs
only1J.0osageshouldbereducedInpatIentswIthhepatIcdysfunctIon.TheprImary
IndIcatIonfornImodIpIneIsfortheImprovementofneurologIcdefIcItscausedby
vasospasmfollowIngsubarachnoIdhemorrhagefromarupturedcerebral
aneurysm.
112,11J,116
Calcium Channel Blockers and Anesthesia
EvIdenceIndIcatesthathalothanedepressesslowchannelkInetIcs.Allofthepotent
InhalatIonanesthetIcsbehaveInasImIlarfashIonInthattheydepressmyocardIal
contractIlItyandvasculartoneInadoserelatedmanner.|oststudIesIndIcatethatthe
calcIumentryblockersandInhalatIonanesthetIcsexertaddItIveeffectsontheInward
calcIumcurrent.
117
DpIoIdanesthetIcsdonotappeartoaddanythIngtotheeffectsofthe
calcIumentryblockers.CalcIumchannelblockersappeartoaugmenttheeffectsofboth
depolarIzIngandnondepolarIzIngmusclerelaxants.
118
TheseobservatIonsserveasaword
ofcautIonbecausetheIrclInIcalsIgnIfIcancehasnotbeendefIned.Prolongedapneaand
relaxatIonhavebeenreportedwhenverapamIlwasusedtotreatasupraventrIcular
tachycardIaInapatIentwIth0uchenne'smusculardystrophy.
119
Dnemustbeawarethat
calcIumchannelblockersmayhavesIdeeffectssuchashypotensIon,Incasesof
overdosage,headaches,facIalflushIng,dIzzIness,ankleedema,constIpatIon,andmay
evenInduceangIna;therefore,theIradmInIstratIonInperIoperatIveperIod,when
dehydratIonIsacommonoccurrence,shouldbecloselymonItored.
120
CalcIumentry
blockersshouldbecontInueduntIlthetImeofsurgerytomaIntaIncontrolofangIna
pectorIs,hypertensIon,orcardIacdysrhythmIa.
101
naddItIon,theuseofcalcIumchannel
blockersIntheperIoperatIveperIodappearstoInduceabenefIcIaleffectofdecreasIng
cardIaccomplIcatIonsunrelatedtocardIacsurgIcalprocedures
121
(seeChapter2J).
7erapamIlmayIncreasethetoxIcItyofdIgoxIn,thebenzodIazepInes,carbamazepIne,oral
hypoglycemIcs,andpossIblyquInIdIneandtheophyllIne.
122
CardIacfaIlure,A7conductIon
dIsturbances,andsInusbradycardIamaybemorefrequentwIthconcurrentuseofbeta
blockers,andseverehypotensIonandbradycardIamayoccurwIthbupIvacaIne.0ecreased
lIthIumeffectandlIthIumneurotoxIcItyhavebothbeenreportedwIththeconcurrentuse
ofverapamIl.
12J
TheeffectsofverapamIlmayalsobeIncreasedbycImetIdIne.
Vasodilators
|ostantIhypertensIvedrugsblunttheANSorItseffectororgansorcausereflexIncreasesIn
ANSoutflow.AnesthetIcagentsmayalsoInhIbItANStonetosomedegreeandmIght
thereforehaveaddItIveeffectswIthantIhypertensIvedrugs.naddItIon,patIentswIth
hypertensIonmayexhIbItgreaterlabIlItyInbloodpressureIntraoperatIvelyandrebound
hypertensIonInthepostoperatIveperIod.AratIonalapproachtotheIrperIoperatIveuse
IncludesdecIsIonsastoholdIngorcontInuIngthempreoperatIvely,possIbleInteractIons
wIthanesthetIcdrugs,andresumptIonoftreatmentpostoperatIvely.
Angiotensin-Converting Enzyme Inhibitors
TherenInangIotensInsystemIsIntegrallyrelatedtotheANSIncontrollIngbloodpressure
(FIg.1512;seeChapter49).ThecentralroleoftherenInangIotensInaldosteronesystem
IntheregulatIonoffluIdbalanceandhemodynamIcswasnotfullyapprecIateduntIlthe
dIscoveryandclInIcalapplIcatIonofInhIbItorsoftheangIotensInconvertIngenzyme(ACE).
CaptoprIl,enalaprIl,andlIsInoprIlInhIbItconvertIngenzymeandtherebypreventthe
conversIonofangIotensIntotheactIveangIotensIn.ThesedrugshavebeenhIghly
effectIveInthetreatmentofalllevelsofessentIalhypertensIonaswellasrenovascular
andmalIgnanthypertensIon.ThecardIovasculareffectsnormallyInvolveonlydecreased
perIpheralvascularresIstance.CDmayremaInnormalorIncreasewhIlethefIllIngpressure
remaInsunchanged.Thus,thesedrugshavebeeneffectIveInthemanagementof
congestIveheartfaIlureaswell.
40
ThereIsusuallynoIncreaseInSNStoneInresponseto
theloweredbloodpressure.ACEInhIbItIongenerallyresultsInreductIonsInangIotensIn
aldosterone,NE,andplasmaantIdIuretIchormone.ThIssuppressIonIsaccompanIedbya
decreaseInaldosteroneandanImprovementIncumulatIveplasmapotassIumlevels,whIch
arebenefIcIalInbothcongestIveheartfaIlureandhypertensIon.tcanbeconcludedthat
themajorhumoralresponsestochronIccongestIveheartfaIlure,evenoverlookIngthe
effectsofthedIuretIcs,areaffectedbythereleaseofangIotensIn,aldosterone,and
IncreasedSNStone.CaptoprIl,thefIrstorallyactIvecompound,hasprovenhIghlyeffectIve
InthetreatmentofalllevelsofhypertensIonandcongestIveheart.EnalaprIlIsasecond
generatIon(nonsulfhydryl)ACEInhIbItor.TheomIssIonofthesulfhydrylgrouppossIbly
dImInIshessIdeeffects.8othcaptoprIlandenalaprIlcombIneahIghdegreeofclInIcal
effIcacywIthalowrateofsIdeeffects.8othareelImInatedvIarenalexcretIonandshould
begIvenInreduceddosesInpatIentswIthrenaldysfunctIon.CaptoprIlhasashorterhalf
lIfeandrequIresmorefrequentdosIngthanenalaprIl.EnalaprIlhastobeconvertedby
esteraseInthelIverandothertIssuesIntotheactIvecompoundenalaprIlat.LIsInoprIlIs
oneoftheseACEInhIbItorsthatIsabsorbedastheactIveformandIsverylongactIng.
TheACEInhIbItorsareassocIatedwIthfewsIdeeffectsandarepopularIntreatIng
hypertensIon.CaptoprIlmayproducereversIbleneutropenIa,dermatItIs,andangIoedema.
EnalaprIlproducessyncope,headache,anddIzzInessInabout1ofelderlypatIents.All
ACEInhIbItorsmaycausehypotensIonInpatIentswhoarehypovolemIcandtakIngdIuretIc
therapy.ThehypotensIveeffectsarealsoenhancedbytheconcomItantuseofcalcIum
channelblockers.TheACEInhIbItorsbluntthehypokalemIceffectsofthIazIdedIuretIcs
andmaymagnIfythepotassIumsparIngeffectsofspIronolactone,trIamterene,and
amIlorIde.naddItIon,nonsteroIdalantIInflammatorydrugs,IncludIngaspIrIn,may
magnIfythepotassIumretaInIngeffectsofACEInhIbItors.ACEIsnowamaInstayIn
treatmentofpatIentswIthheartfaIlureanddecreasedejectIonfractIon,sInceItIncreases
theIrsurvIval.
74
ForpatIentswIthheartfaIlureandnormalleftventrIcularejectIon
fractIon,thefIrstlIneoftreatmentIsloopdIuretIcsIncombInatIonwIthbetablockersand
(ACE)InhIbItors.
99
ntheperIoperatIveperIod,theACEInhIbItorshavebeenassocIated
wIthsIgnIfIcanthypotensIon,whIchattImessuchaswhenseparatIngfromcardIopulmonary
P.J65
bypassrequIresaddItIonalvasopressorstosustaInsystemIcbloodpressure.
124
Anewclassofdrugs,namelyangIotensInreceptorblockers,wasdevelopedbyInhIbItIng
dIrectlytheeffectsofthehormoneangIotensIn.ThesemedIcatIonshavebeendeveloped
wIththehopethat,beIngsImIlartoanACEInhIbItor,onecouldexpectthesame
effectIveness,wIthfewersIdeeffectssuchascough,angIoneurotIcedema,andrash.
125
AlternatIvely,therearedatathatthIsclassofdrugsmayhavesomebenefIcIaleffectson
decreasIngtherenaldeterIoratIonIndIabetIcpatIents.
126
Hydralazine
HydralazIneIsthemostcommonlyusedvasodIlatorandcanbegIvenbytheIntramuscular,
Intravenous,andoralroutestoachIeveanoptImumbloodpressurecontrol.trelaxes
smoothmuscletonedIrectly,wIthoutInteractIngwIthadrenergIcorcholInergIcreceptors.
ThemechanIsmofactIonIsunknown.tIsmostpotentIncoronary,splanchnIc,renal,and
cerebralvessels,causIngIncreasedbloodflowIneachoftheseorgans.ThedecreaseIn
cardIacafterloadIsbenefIcIal,but,unfortunately,thereIsusuallyaconcomItantreflex
tachycardIathatmaybesevere.tIscommonlycombInedwIthabetablockersuchas
propranolol.HydralazIneIsmetabolIzedbyhepatIcacetylatIon,andoralbIoavaIlabIlIty
maybelowowIngtofIrstpassmetabolIsm.TheelImInatIonhalflIfeIsabout4hours,but
thepharmacologIchalflIfeIsmuchlongerasaresultofavIdbIndIngofthedrugtosmooth
muscle.TheeffectIvehalflIfeIsapproxImately100hours.SIdeeffectsIncludealupuslIke
syndrome,drugfever,skInrash,pancytopenIa,andperIpheralneuropathy.The7dosefor
perIoperatIveuseIs5to10mgInan7bolusevery15to20mInutesuntIlbloodpressure
controlIsachIeved.tmayalsobegIven10to40mgIntramuscularly,buttheresponseIs
slower.
78,112,127
Sodium Nitroprusside
SodIumnItroprussIdeIsanextremelypotentvasodIlatorthatIsavaIlableonlyfor7
admInIstratIon(seeChapter41).tactsdIrectlyonsmoothmuscle,causIngbotharterIal
andvenousdIlatIon.TheactIonofsodIumnItroprussIdeonbothvenousandarterIalsIdes
ofthecIrculatIoncausesdecreasesIncardIacpreloadaswellasafterload.
99,128
ThIsresults
IndecreasedcardIacwork;however,IthasbeensuggestedthatsodIumnItroprussIdemay
furthercompromIseIschemIcmyocardIumInthepresenceofocclusIvecoronaryartery
dIseasebyshuntIngbloodawayfromtheIschemIczone.
129
DtherpotentIalanddeleterIous
sIdeeffectsIncludepulmonaryvasodIlatIonwIthanIncreasedventIlatIonperfusIon
mIsmatchandwIthresultanthypoxIa,andtemporarydecreaseInplateletfunctIon.
51,1J0
SodIumnItroprussIdeIsusefuldurIngtheperIoperatIveperIod.tlowersbloodpressure
wIthIn1to2mInutes,wIththeeffectdIssIpatIngwIthIn2mInutesafterInfusIonIsstopped.
tIsextremelypotentandshouldbeadmInIsteredthroughacentralvenouslInebyInfusIon
pumpwhIlecontInuouslymonItorIngarterIalpressure.ThestartIngdoseIs0.25to0.5
g/kg/mIn.tcanbeIncreasedslowlyasneededtocontrolbloodpressure,butchancesfor
toxIcItyaregreaterIfthedoseof2g/kg/mInIsexceeded.ThedoserequIredforsteady
stateInducedhypotensIonIsvarIable.ThehypotensIveeffectsofsodIumnItroprussIdemay
bepotentIatedbyInhalatIonanesthetIcsandbloodloss;therefore,closeperIoperatIve
monItorIngIsessentIal.tIscommonlyusedtoInducehypotensIonfordecreasIngbloodloss
InpatIentspredIsposedtomajorhemorrhage.
112
ChemIcally,sodIumnItroprussIdeconsIstsofaferrousIronatomboundwIthfIvecyanIde
moleculesandonenItrIcgroup.TheferrousIronreactswIthsulfhydrylgroupsInredblood
cellsandreleasescyanIde.CyanIdeIsreducedtothIocyanateInthelIverandexcretedIn
theurIne.ThehalflIfeofthIocyanateIs4days,andItaccumulatesInthepresenceof
renalfaIlure.
AdmInIstratIonofhIghdosesofsodIumnItroprussIdecanresultIncyanIdetoxIcIty.The
cyanIdemoleculebIndstocytochromeoxIdase,InterferIngwIthelectrontransportand
causIngcellularhypoxIa.ToxIcItycanberecognIzedbythetrIadoftachyphylaxIs
(IncreasIngtolerancetothedrugdose),elevatedmIxedvenousPao
2
,andmetabolIc
acIdosIs.ThepossIbletreatmentsofcyanIdetoxIcItyconsIstof(1)admInIstratIonofamyl
nItrate(byInhalatIonordIrectlyIntotheanesthesIacIrcuIt),(2)InfusIonofsodIumnItrIte,
and(J)admInIstratIonofsodIumthIosulfate.
Nitroglycerin
NItroglycerIn,orglyceryltrInItrate,IsavenodIlatorusedtotreatmyocardIalIschemIa(see
Chapter41).tspredomInantactIonIsonvenules,causIngIncreasedvenouscapacItance
anddecreasedcardIacpreload.EffectsonthearterIalsIdearemInImalexceptatveryhIgh
doses.Theusual7doseIs1toJg/kg/mIn.Dn7admInIstratIon,effectscanbeseen
wIthIn2mInutes,andtheyusuallyresolvewIthIn5mInutesofdIscontInuIngthedrug.SIde
effectsaremInImal,andthereIsnopotentIalforcyanIdetoxIcItyaswIthnItroprussIde.
UseofnItroglycerInforcontrolofperIoperatIvehypertensIonhasbeenreportedbut
becauseofItsrelatIvelyweakarterIolaractIonItIsnotasusefulasotherdrugsasan
antIhypertensIveagent.
99,128
nobstetrIcpatIentswIthpreeclampsIa,however,Itmaybe
chosenovernItroprussIdetocIrcumventpotentIalcyanIdetoxIcItytothefetus.
1J1
Nesiritide
NesIrItIdeIsarecombInantformofahuman8typenatrIuretIcpeptIde.tIsIdentIcalwIth
theendogenoushormonelIberatedbytheventrIclesInsItuatIonscharacterIzedbyvolume
overloadandIncreasedwalltensIon.NesIrItIdeactsonguanylatecyclasesImIlartonItrIc
oxIde,andthereforeInducesbenefIcIaleffectsonhemodynamIcsbyvenousandarterIal
vasodIlatIon,IncludIngcoronaryvasodIlatIon.tIsmoreeffectIvethannItroglycerInIn
decreasIngtherIghtatrIalpressure,pulmonarycapIllarywedgepressure,systemIcvascular
resIstance,andultImatelyImprovestheCD.ThepossIblesIdeeffectsIncludehypotensIon,
headache,andrenaldysfunctIon.ThedoseIs2g/kgbolus,contInuedwIthcontInuous
InfusIonof0.01g/kg/mInthatmaybeIncreasedtoamaxImumof0.0Jg/kg/mIn,wIth
themostsIgnIfIcantsIdeeffectbeInghypotensIon.ThebIologIceffectslastlongerthan
expectedfromthedrug'shalflIfe.NesIrItIdeIsbenefIcIalforrapIdImprovementof
dyspnea,andcanbeusedInpatIentswIthdecompensatedheartfaIlure,InaddItIonto
dIuretIctherapyforrapIdImprovementofsymptoms;butagaInthepossIbIlItyofworsenIng
renalfunctIon,togetherwIthpossIbleworsenIngJ0daymortalItyInarecentstudy,made
ItssafetyquestIonable.
J1,40,128
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TableofContentsSectIonAnatomyandPhysIologyChapter16HemostasIsandTransfusIon|edIcIne
Chapter16
Hemostasis and Transfusion Medicine
John C. Drummond
Charise T. Petrovitch
Thomas A. Lane
Key Points
1. In terms of transfusion-transmitted infectious diseases, the American
blood supply has never been safer than it is today.
2. Clerical and patient identification errors are the most common causes
of ABO incompatibility and a large fraction of these errors typically
occur in the operating theater.
3. The three leading causes of transfusion-related death in the United
States are ABO incompatibility, transfusion-related acute lung injury,
and sepsis caused by bacterial infections.
4. In the setting of massive transfusion, assuming maintenance of
isovolemia and the absence of a consumptive coagulopathy, critical
dilution of clotting factors and platelets is likely to occur after an
average replacement of 140% and 230% of blood volume,
respectively.
5. With the possible exception of trauma resuscitation, coagulation
factor and platelet replacement should be determined by laboratory
assessment and/or observation of clinical coagulopathy and not
estimated blood loss-driven formulas.
6. The red blood cell (RBC) transfusion trigger for most patients will lie
between hemoglobin values of 7 and 10 g/dL.
7. Platelet administration thresholds relevant to anesthesiologists
usually will lie between 50,000 and 100,000/uL.
8. Normal coagulation can be achieved with clotting factor levels of 20
to 30% of normal. Those levels can usually be achieved by
administration of 10 to 15 mL/kg of fresh-frozen plasma.
9. Recipient or donor unit identification errors will result in an acute
hemolytic transfusion reaction for one of every three packed RBC
(PRBC) units mistransfused.
10. A patient who has received 10 to 12 units of group O RBCs should
not be switched back to his or her own ABO group until testing has
been performed to confirm that significant titers of anti-A or anti-B
antibodies are not present.
11. The classic, dual-cascade (intrinsic and extrinsic pathway) model of
coagulation is an inadequate representation of coagulation, as it
occurs in vivo.
12. In vivo, coagulation is initiated principally by contact of factor VII
with extravascular tissue factor leading first to platelet activation
followed by the generation of large amounts of thrombin by activated
clotting factors acting on the phospholipid surface provided by
activated platelets.
13. Under normal conditions, plasmin is generated only at the site of clot
formation and is destroyed rapidly once released into the circulation.
This localization process fails at times of accelerated fibrinolysis
(disseminated intravascular coagulation, primary fibrinolysis).
14. von Willebrand disease is the most common hereditary bleeding
disorder. Some form of the disease, which may be subclinical prior to
surgery, is present in approximately 1% of the population.
P.370
16. Factors II, VII, IX, and X and proteins C and S depend on vitamin K
for their synthesis. Vitamin K deficiency occurs frequently in
hospitalized patients because of dietary insufficiency, gut sterilization,
and malabsorption. A high index of suspicion for vitamin K deficiency
should be maintained.
17. As many as 5% of patients who receive heparin therapy for 5 days
will develop heparin-induced thrombocytopenia/ thrombosis. The
clinical manifestations are more often the result of thrombosis and
thromboembolism than thrombocytopenia.
ntheyear2004,14.2mIllIonunItsofpackedredbloodcells(PF8Cs),9.9mIllIonunItsof
platelets(84ofwhIchwereapheresIsunIts),and4.1mIllIonunItsoffreshfrozenplasma
(FFP)wereadmInIsteredIntheUnItedStates.
1
AttheUnIversItyofCalIfornIa,San0Iego
(UCS0)|edIcalCenter,approxImately40ofalltransfusedunItsareadmInIsteredto
surgIcalpatIentsbyanesthesIapersonnel.AnextrapolatIonofthesenumberssuggeststhat
anesthesIaprovIdersmaybeInvolvedInasmanyas8.JmIllIondonorunItexposuresper
yearIntheUnItedStates.AccordIngly,nospecIaltygroup,savethosewhocollect,process,
anddelIverbloodproducts,hasagreaterIncentIvetohaveabroadgraspoftheprIncIples
oftransfusIonmedIcIne.
ThIschapterbegInswItharevIewoftherIsksassocIatedwIththeadmInIstratIonofblood
products,followedbyadIscussIonofthefactorsthatdetermInethenecessItyforthe
admInIstratIonofthethreemostcommonlyusedcomponents,F8Cs,FFP,andplatelets,
andthenadIscussIonofconservatIontechnIquesformInImIzIngthenecessItyfor
transfusIon.TheremaInderofthechapterpresentsadescrIptIonofthepreparatIonof
bloodproducts,adIscussIonofthephysIologyofhemostasIs,adescrIptIonoftestsofthe
hemostatIcmechanIsm,andfInallyarevIewofcommonbleedIngdIsorders,IncludInga
dIscussIonoftheeffectsofpharmacologIcagentsonhemostasIs.
The Risks of Blood Product Administration
TherecognItIonthatthehumanImmunodefIcIencyvIrus(H7)IstransmIssIblebyblood
generatedpublIcfearoftransfusIonandledtodramatIcchangesIntransfusIonpractIces
(seeChapter1J).WhIlethetransfusIonrelatedtransmIssIonofH7IsnowvanIshInglyrare,
thereremaInnumerousotherhazardsassocIatedwIthbloodproducts.TherIskscanbe
subdIvIdedIntothoseofInfectIousandnonInfectIousetIologIes.TransfusIontransmIssIble
InfectIons,InpartIcularvIralInfectIons,havegeneratedthegreatestconcernandwIll
thereforebeaddressedfIrst.However,InrealIty,themorbIdItyandmortalItyassocIated
wIthnonvIralhazardsarefargreaterconcerns.
Infectious Risks Associated with Blood Product Administration
ThepotentIallytransmIttabledIseases/agentsInbloodarenumerous.TheyIncludeseveral
vIruses(hepatItIsA,8,C,0,E),thehumanTcelllymphotropIcvIruses(HTL71,HTL72),
thehumanImmunodefIcIencyvIruses1and2,cytomegalovIrus(C|7),WestNIlevIrus
(WN7),theEpsteIn8arrvIrus,humanherpesvIrus8(theagentofKaposIsarcoma),
parvovIrus819,theC87CvIrus(alsocalledhepatItIsC),transfusIontransmIttedvIrus,and
theSENvIrus.DtherdIseases/agentsIncludeprIons(CreutzfeldtJakobdIsease[CJ0]and
varIantCreutzfeldtJakobdIsease[vCJ0]),LymedIsease,contamInatIngbacterIa,parasItes
(malarIa,Chagas'dIsease,ehrlIchIosIs,babesIosIs),andsyphIlIs.
2,J
SeveralofthesewIllnot
beconsIderedfurther.AlthoughC87C,transfusIontransmIttedvIrus,andSENvIrusare
transmIttedbytransfusIon,theydonotappeartocauseclInIcaldIsease;therateof
transmIssIonofparvovIrus819IsverylowandclInIcaldIseaseIsextremelyInfrequent
2
;
therehavebeennoreportedInstancesoftransfusIontransmIttedLymedIseaseandonly
oneInstanceofehrlIchIosIs.
4
EstImatesofthefrequencyofInfectIousagentsIntheNorthAmerIcanbloodsupplyare
presentedInTable161.TherateofvIralInfectIvItyhasdecreaseddramatIcallyInthelast
2decades.TheadventofunIversal(IntheUnItedStates)nucleIc
P.J71
acIdtestIng(NAT)forH7andhepatItIsC(HC7)hasreducedthefrequencyoftransmIssIon
ofthoseagentstoverylowlevels,approxImately1In1.7mIllIonunItstransfused.HepatItIs
8(H87)remaInsthegreatestrIsk,currentlywIthabout1/269,000donorexposures.
5
Allof
theseestImatesarederIvedfromtheobservedratesofseroposItIvItyamongdonorsand
thestatIstIcallIkelIhoodofadmInIstratIonofbloodfromdonorswhoseInfectIonIsInthe
wIndowperIodbetweencontractIngthevIrusanddetectabIlItybytheavaIlableassays.
ThewIndowperIodsfromInfectIontodetectIonby16unItmInIpoolNATtestIngforH7and
HC7areestImatedtobe9and7.4days,respectIvely.
6
|InIpooltestIngentaIlsanalysIsof
pooledalIquotsfrom6to24unIts.tIsestImatedthatthemoreexpensIveIndIvIdualdonor
testIngcouldreducethewIndowperIodforH7andHC7to5.6and4.9days,respectIvely.
6
ForH87,usInghepatItIs8surfaceantIgentestIng,thewIndowperIodIsJ8days.
7
ANAT
testforH87IsavaIlable.However,whenperformedonmInIpoolsratherthanonIndIvIdual
donatIons,ItwIllprobablyaddlIttletothedetectIonsensItIvItyachIevedwIththe
combInatIonofhepatItIs8surfaceantIgenandtheantIhepatItIs8coreantIgen.
7,8,9
Table 16-1 Estimates of The Rate (Per Donor Exposure) of Transfusion-
Transmitted Infectious Disease in North America
DISEASE RATE
HepatItIs8(H87) 1/269,000
HepatItIsC(HC7) 1/1,600,000
HumanImmunodefIcIencyvIrus(H7) 1/1,780,000
HumanTcelllymphotrophIcvIrus(HTL7) 1/2,900,000
WestNIle7Irus(WN7)
ndetermInate/very
low
CytomegalovIrus(C|7)Nonleukoreducedrandom
donor
7
Leukoreducedrandomdonor 24
C|7seronegatIvedonor 12
EpsteIn8arrvIrus(E87) 05
Chagas';malarIa;otherparasItes 1/1,000,000
8acterIalsepsIs
Platelets(apheresIs,culturetested) 1/50,000
Platelets(wholebloodderIved,surrogatetested) 1/JJ,000
Platelets(untested) 1/2,5001J,400
0ataderIvedfromseveralsources(Fefs.5,7,14,17,18,19,52,and276).
ntermsoftransfusIontransmIttedInfectIousdIseases,theNorthAmerIcanbloodsupply
hasneverbeensaferthanItIstoday.
Hepatitis C
ThesIgnIfIcanceofHC7Isthat,despIteItscommonlymIldInItIalpresentatIon,It
progressestoachronIcstateIn85wIthsIgnIfIcantassocIatedmorbIdItyandmortalItyof
patIents.TwentypercentofchronIccarrIersdevelopcIrrhosIsand1to5develop
hepatocellularcarcInoma.
10,11
Hepatitis B
tIsestImatedthatonlyJ5ofH87exposedpatIentswIlldevelopacutedIsease,
12
althoughapproxImately1wIlldevelopfulmInantacutehepatItIs.napproxImately85of
patIents,thedIseaseresolvesspontaneously,9developchronIcpersIstenthepatItIs,J
developchronIcactIvehepatItIs,1developcIrrhosIswIthorwIthoutchronIcactIve
hepatItIs,and1develophepatocellularcarcInoma.
Hepatitis A
TransmIssIonofhepatItIsAvIrus(HA7)bytransfusIonhasbeenveryrare.8loodbanks
screenforHA7byhIstoryonlyandthereIsnocarrIerstateforthIsvIrus.TheInfectIous
perIodIslImItedto1to2weeks.ThedIagnosIsdependsonhepatItIsantIbody
seroconversIon.
Human Immunodeficiency Virus
H7IsaretrovIrus,socalledbecauseItspropagatIonrequIrestranslatIonofFNAto0NA.
CurrentscreenIngtestsaredIrectedatbothH71andH72,thoughthelatterhasbeenan
extremelyInfrequentcauseofhumandIsease.TheIncIdenceoftransfusIonrelatedH7
InfectIonhasdecreaseddramatIcally.AsatestImonIaltotheeffectIvenessofourblood
delIverysystem'sresponsetotheemergenceofH7,therIskoftransfusIonrelated
transmIssIon,whIchwasapproxImately1:100Intheearly1980sand1:400,000In1997,
1J
Is
currentlyapproxImately1per1.7mIllIondonorexposures.
Human T-Cell Lymphotropic Virus
HTL71andHTL72belongtothesameretrovIrusfamIlyasH7.TheIncIdenceofclInIcal
dIseaseresultIngfromtransmIttedvIrusappearstobeverylow.TheyareassocIatedwIth
TcellleukemIaandlymphomaratherthanthegeneralIzedImmunodefIcIencyofthe
acquIredImmunedefIcIencysyndrome(A0S).ntheUnItedStates,alldonorunItsare
screenedforthepresenceofantIbodytoHTL7andHTL72.
Cytomegalovirus
TransfusIonassocIatedC|7InfectIonsareusuallybenIgnandselflImIted.However,C|7
maycauseserIous,evenfatal,InfectIonsInImmunocompromIsedpatIents.PatIentsatrIsk
Includeprematureneonates,C|7seronegatIvebonemarrowtransplantrecIpIents,
pregnantfemales,andthosepatIentswIthseverelydepressedImmunefunctIon.
LeukoreductIonand/ortheuseofbloodfromC|7seronegatIvedonorsreduce,butdonot
prevent,C|7transmIssIon.
14
FestrIctIonofImmunocompromIsedpatIentstoleukoreduced
bloodfromC|7seronegatIvedonorsIsstandardInmanycenters.
West Nile Virus
WN7IsamosquItoborneflavIvIrus(asIsdenguefever)thatbecameepIdemIcIn
mIdwesternstatesIn2002andhassInceoccurrednatIonwIde.AlthoughthemajorItyof
InfectedIndIvIdualsareeItherasymptomatIcordeveloponlyamIldIllness,
encephalItIs/menIngItIscanoccurandthedeathrateamongconfIrmedcasesIs5to
10.
15,16
TransmIssIonbytransfusIonandorgantransplantatIonhasbeenconfIrmed.
Fortunately,thewIndowperIodbetweenInfectIonandclInIcalsymptomsIsshort,
approxImatelyJdays,andtheperIodofInfectIvItyalsoappearstoberelatIvelybrIef.
UnIversalmInIpoolNATtestIngforWN7beganIn200J,wIthdIscretIonaryselectIve
IndIvIdualdonorNATtestIngInareasofhIghIncIdence.
17
TransfusIontransmIssIonhas
subsequentlybeenveryInfrequent.
17
Parasitic Diseases
TransfusIontransmIttedmalarIaIsrelatIvelycommonInregIonswherethedIseaseIs
endemIcbuthasbeenrareIntheUnItedStates.
J
8ecausetheparasIteresIdeswIthInthe
redcell,thehazardIsassocIatedalmostexclusIvelywIthF8CtransfusIon.Chagas'dIsease
Iscausedbyaprotozoan(Trypanosoma cruzi)thatIsendemIctoSouthandCentral
AmerIca(IncludIng|exIco).SIgnIfIcantclInIcaldIseasehasbeenrareInNorthAmerIcaand
hasoccurredalmostexclusIvelyInImmunocompromIsedtransfusIonrecIpIents.0onor
screenIngforChagas'dIseasebyImmunoassayIsnowstandardInallFedCrosscollectIon
centersandIsIncreasIngamongotherU.S.agencIes,especIallyInthesouthwestand
FlorIda.
J
Bacterial Contamination of Blood Components
8acterIalcontamInatIonoccursatamuchhIgherfrequency(Table161)thananyofthe
otherInfectIonsdIscussedInthIssectIonandIsassocIatedwIthsubstantIalmortalIty.
18,19
TheIncIdenceofsepsIsIssubstantIallygreaterwIthplateletthanF8CadmInIstratIon
becausetheformerarestoredatroomtemperature.TherIskIslesswIthapheresIs
platelets(obtaInedfromasIngledonorwIthonevenIpuncture)thanwIthwholeblood
derIvedplateletadmInIstratIon,whIchentaIlspoolsderIvedfromsIxtotenseparatedonor
unIts.ThesourceofthebacterIacanbedonorskInflora,donorbacteremIa,or
contamInantsIntroduceddurIngcollectIon,processIng,andstorage.NumerousCram
posItIveandnegatIveorganIsmscanoccurInplateletsIncludIngStaphylococcus aureus,
Klebsiella pneumoniae,Serratia marcescens,andStaphylococcus epidermidis.
12
Dnlya
lImItednumberofbacterIa,IncludIngYersinia enterocoliticaandcertaInSerratiaand
PseudomonasspecIescangrowatF8Cstoragetemperatures.
2
FatalsepsIsIsusuallythe
resultofCramnegatIveorganIsms,andY. enterocoliticaIsthemostfrequentlyImplIcated.
ThereIsconsIderablecurrentattentIonbeInggIventothepreventIonofplatelet
transmIttedbacterIalInfectIon.CarefulskInpreparatIonIsthenormandsomecollectIon
centersdIvert
P.J72
anddIscardthefIrstfewmIllIlItersofthedraw.n2004,bacterIaltestIngofallplatelets
becamearequIrementforachIevIngAA88(formerly,theAmerIcanAssocIatIonof8lood
8anks)certIfIcatIon,andthemajorItyofagencIesnowcultureapheresIsunIts.However,
cultureIsnotpractIcalforwholebloodderIvedpools,andlesssensItIvesurrogatemethods
(basedonmeasurementsofpH,glucose,PD
2
,orassayforbacterIalFNA
20
)areemployed.
ThesemeasureshavereducedbutnotelImInatedtransfusIonofcontamInatedunIts(Table
161).
18,19,21
ThepatIentwhoreceIvescontamInatedbloodtransfusIonwIllrapIdlyexperIencesome
combInatIonoffever,chIlls,tachycardIa,dyspnea,emesIs,shock,andmaydevelop
dIssemInatedIntravascularcoagulatIon(0C)andacuterenalfaIlure.ThereactIonsare
varIableInseverIty,andanIndexofsuspIcIonshouldbemaIntaInedInordertodIstInguIsh
thesereactIonsfromothermajorandmInortransfusIonreactIons.ThetransfusIonshould
bestoppedImmedIately,bloodculturesobtaIned,andthepatIenttreatedwIthbroad
spectrumantIbIotIcs.ThebloodbankshouldbenotIfIedImmedIatelyInorderthatItmay
InterdIctadmInIstratIonofothercomponentsmadefromthesamedonatIonandperform
dIagnostIctestIng(CramstaInandunItculture).
Prion-Related Diseases
PrIonsarethecausatIveagentsofCJ0andvCJ0.ThelatterIsthehumandIseasecausedby
theagentresponsIbleforbovInespongIformencephalItIs.Allthreearefatal,degeneratIve
neurologIcdIseasescausedbyanabnormallyfoldedvarIantofaproteInthatIs
constItutIvelypresent.SIncetheemergenceofbovInespongIformencephalItIsInEngland
In1984,approxImately200casesofvCJ0hadbeenreported,wIththelargemajorIty
occurrIngIntheUnItedKIngdom.
22
TherIskoftransfusIonrelatedvCJ0IsundefIned.CJ0
hasneverbeenknowntohavebeentransmIttedbytransfusIonbuttherehavebeenthree
reportedcasesofapparentlytransfusIonrelatedvCJ0.
22
TheIncubatIonperIodofvCJ0
maybeaslongas6years.AccordIngly,thetruetransmIssIonratemayasyetbe
underrecognIzed.NATtestIngIsnotfeasIble(prIonshavenonucleIcacIds)andthereareno
knownantIgenIcorImmuneresponsemarkers.Therefore,ItmustbehopedthatchangesIn
anImalhusbandrypractIcescombInedwIthexclusIonofdonorswhohavespenttImeIn
hIghrIskareaswIllmInImIzewhateverrIskexIsts.
Other Infectious Risks
|anyaddItIonalmIcrobIalagentscanbetransmIttedbybloodcomponents.TheyInclude
Borrelia,Babesia,dengue,thevIralagentofsevereacuterespIratorysyndrome,andother
herpesvIruses.TransmIssIonoftheseagentsIsapparentlyextremelyrare.However,the
recentexperIencewIthWN7reveals,onceagaIn,thepotentIalfornewagentstobecomea
suddenthreattothebloodsupplyandservesasaremInderofthecontInuIngneedto
admInIsterbloodcomponentsonlywhenabsolutelyIndIcated.
Noninfectious Risks Associated with Blood Product
Administration
ThenonInfectIousrIsksassocIatedwIthbloodproductadmInIstratIon,themajorItyofwhIch
areImmunologIcallymedIated,andtheIrapproxImateIncIdencesarepresentedInTable
162.
Table 16-2 The Noninfectious Adverse Reactions Associated with Blood
Product Administration, in the Approximate Order of Their Average
Frequencies in the Published Literature
a
ADVERSE REACTION INCIDENCE COMMENT
TF| 100
nflammatoryresponse (:)100 ncreaseswIthduratIonofstorage
AlloImmunIzatIon
F8Cs 0.5
Plts 10 FeducedbyleukoreductIon
25
|InorallergIcreactIons
(urtIcarIa,flushIng)
0.54 PltsandFFPF8Cs
FebrIlereactIons 0.12 ProbablyreducedbyleukoreductIon
0HTF 1/2,000
|ostoftenKell,KIdd,andFhesus(E)
antIbodIes
TFAL 1/5,000
AllplasmacontaInIngproducts;
FFPandPltsPF8Cs
AnaphylactIc/toId
reactIons
1/25,000
PltsPF8Cs
gAdefIcIencyIncreasesrIsk
AHTF 1/25,000
UsuallypatIent0error;2mortalIty;
PlasmaIncompatIblePltsarearare
cause
C7H0 Fare
mmunocompromIsedpatIents,
especIallymarrowtransplantrecIpIents
TF|,transfusIonrelatedImmunomodulatIon;F8Cs,redbloodcells;Plts,
platelets;FFP,freshfrozenplasma;0HTF,delayedhemolytIctransfusIonreactIon;
TFAL,transfusIonrelatedacutelungInjury;PF8Cs,packedF8Cs;gA,
ImmunoglobulInA;AHTF,acutehemolytIctransfusIonreactIon;0,IdentIfIcatIon;
C7H0,graftversushostdIsease.
a
ThefrequencIesarepresentedaspercentageswhen0.1andotherwIseasratIos.
ThIstabledrawsextensIvelyfromInformatIonpresentedbyEderetal.
26
andKleIn
etal.
277
aswellasothersources.
24
,
278
P.J7J
Immunologically Mediated Transfusion Reactions
FeactIonstotransfusedbloodproductscanoccurasaresultofthepresenceofantIbodIes
thatareconstItutIve(e.g.,antIA,antI8)orthathavebeenformedasaresultofexposure
todonorF8Cs,whItebloodcells,plateletsand/orproteIns,orasaconsequenceofthe
effectsoftransfusedwhItecells.
Reactions to RBC Antigens
Acute Hemolytic Transfusion Reactions
ThemosthazardousoftheImmunereactIonsIstheImmedIateacutehemolytIctransfusIon
reactIon(AHTF)agaInstforeIgnF8Cs.HemolysIsofdonorF8Cscanleadtoacuterenal
faIlureand0C.ThemortalItyrateIs2.
2J
TherearemorethanJ00antIgensonhumanred
cells,butmostareweakImmunogensthatusuallydonotelIcItaclInIcallydetectable
antIbodyresponse.TheantIbodIesthatfIxcomplementandcommonlyproduceImmedIate
IntravascularhemolysIsIncludethoseagaInstA,8,Kell,KIdd,0uffy,andSsantIgens.Fh
antIbodIes(I.e.,antI0,antICc,andantIEe),althoughtypIcallynotcomplementbIndIng,
arealsocapableofcausIngserIousacutehemolytIcreactIons.TransfusIonofIncompatIble
FFPtoA,8,orA8patIents,resultIngInhemolysIsofrecIpIentredcells,hasalsobeena
rarecauseofAHTFs.
2J
A8DIncompatIbIlIty,IncompanywIthtransfusIonrelatedacutelungInjury(TFAL)and
bacterIalcontamInatIon,IsamongthethreeleadIngcausesoftransfusIonrelateddeathsIn
theUnItedStates.ClerIcalandpatIentIdentIfIcatIonerrorsarethemostcommoncausesof
A8DIncompatIbIlItyandalargefractIonoftheseerrorstypIcallyoccurIntheoperatIng
theater.tIsanuncomfortableIronythatoneofprIncIpalhazardsoftransfusIonresIdes
notInthebloodsupplyperse,butratherIntheprocesswherebyItIsdelIveredtothe
patIent.
WhenIncompatIblebloodIsadmInIstered,antIbodIesandcomplementInrecIpIentplasma
attackthecorrespondIngantIgensondonorF8Cs.HemolysIsensues.ThehemolytIc
reactIonwIlltakeplaceIntheIntravascularspaceandItmayalsooccurextravascularly
wIthIntheretIculoendothelIalsystem(spleen,lIver,bonemarrow).TheantIgenantIbody
complexesactIvateHagemanfactor(factorX),whIchInturnactsonthekInInsystemto
producebradykInIn(seeChapter1J).ThereleaseofbradykInInIncreasescapIllary
permeabIlItyanddIlatesarterIoles,bothofwhIchcontrIbutetohypotensIon.ActIvatIonof
thecomplementsystemresultsInthereleaseofhIstamIneandserotonInfrommastcells,
resultIngInbronchospasm.ThIrtyto50ofpatIentsdevelop0C.
HemolysIsreleaseshemoglobIn(Hb)Intotheblood.nItIallyItIsboundtohaptoglobInand
albumIn.WhenthosebIndIngsItesaresaturated,ItcIrculatesunbounduntIlItIsexcreted
bythekIdneys.Fenaldamageoccursforseveralreasons.8loodflowtothekIdneysIs
reducedInthepresenceofsystemIchypotensIonandrenalvasoconstrIctIon.FreeHbInthe
formofacIdhematInorredcellstromamaydamagerenaltubules.AntIgenantIbody
complexesmaybedeposItedIntheglomerulI.fthepatIentdevelops0C,fIbrInthrombI
wIllalsobedeposItedIntherenalvasculature,furthercompromIsIngperfusIonand/or
causIngacutecortIcalnecrosIs,whIchIsfrequentlyIrreversIble.
ThesIgnsandsymptomsofahemolytIctransfusIonreactIonIncludefever,chIlls,nausea
andvomItIng,dIarrhea,andrIgors.ThepatIentIshypotensIveandtachycardIc(bradykInIn
effects)andmayappearflushedanddyspneIc(hIstamIne).ChestandbackpaInsoccurand
havebeenattrIbutedtocytokInerelease.ThepatIentIsoftenrestless,hasaheadache,
andasenseofImpendIngdoom.HemoglobInurIawIlloccurIfplasmaHbrIsesabovethe
renalthreshold(about25mg/dL).0IffusebleedIngoccurswIththedevelopmentof0C.
WIthrenalfaIlure,olIgurIadevelops.0urInggeneralanesthesIa,manyofthesIgnsare
masked.HypotensIonandmIcrovascularbleedIngmaybetheonlyInItIalcluesthata
hemolytIctransfusIonreactIonhasoccurred,andthedIagnosIsmaynotbesuspecteduntIl
hemoglobInurIaIsobserved.AreasonableIndexofsuspIcIonshouldbemaIntaIneddurIng
admInIstratIonofF8CstoanesthetIzedpatIentsInordertoavoIdcrItIcaldelayIn
dIagnosIs.
fareactIonIssuspected,thetransfusIonshouldbestoppedandtheIdentItyofthepatIent
andthelabelIngofthebloodrechecked.ExamInatIonofthepatIent'splasmaafterbrIef
centrIfugatIonforthepInkIshdIscoloratIoncausedbyfreeHbIsasImple,rapIdscreenIng
testwhenahemolytIctransfusIonreactIonIssuspected.HemolysIscanbeduetoother
causes,butshouldbeassumedtoIndIcateahemolytIctransfusIonreactIonuntIlproven
otherwIse.|anagementhasthreemaInobjectIves:maIntenanceofsystemIcblood
pressure,preservatIonofrenalfunctIon,andthepreventIonof0C.SystemIcblood
pressureshouldbesupportedbyadmInIstratIonofvolume,pressors,andInotropesas
requIred.UrIneoutputshouldbepromotedbyadmInIstratIonoffluIdsandtheuseof
dIuretIcs,eIthermannItolorfurosemIde,orboth.SodIumbIcarbonatecanbeadmInIstered
toalkalInIzetheurIne.ThereIscurrentlynospecIfIctherapytopreventthedevelopment
of0C.However,preventInghypotensIonandsupportIngcardIacoutputtopreventstasIs
andhypoperfusIon,bothofwhIchcontrIbutetotheevolutIonof0C,areImportant.
TheresponseshouldIncludeImmedIatenotIfIcatIonofthebloodbank,towhIchthe
suspectedunItofbloodshouldbereturned,aseptIcallysealed,alongwIthaposttransfusIon
E0TAbloodspecImen.ThebloodbankwIlldetermInewhethertheunItofbloodhadbeen
correctlyreleasedtothepatIent.mmedIatetestsontheposttransfusIonspecImenwIll
Include(1)avIsualcheckforhemoglobInemIaand(2)adIrectantIglobulIn(Coombs)test.
ThedIrectantIglobulIntestexamInesrecIpIentF8Csforthepresenceofsurface
ImmunoglobulInsandcomplement.fposItIve,anacutehemolytIcreactIonmayhave
occurredandaddItIonaltestIngIsIndIcatedtoascertaInthecause,IncludIngrepeat
A8D/Fhtype,antIbodyscreen,crossmatchIng,andothertestsasIndIcated.Serum
haptoglobInlevel,plasma,andurIneHbandbIlIrubInassaysareusuallyperformed.
However,theseareevIdenceofhemolysIsonly,notspecIfIcallyofanImmunereactIon.
TheunItshouldbeculturedIfbacterIalsepsIs,usuallyassocIatedwIthtemperature
elevatIon,IsInthedIfferentIaldIagnosIs.LaboratoryteststoestablIshbaselInecoagulatIon
statusIncludIngplateletcount,prothrombIntIme(PT),actIvatedpartIalthromboplastIn
tIme(aPTT),thrombIntIme(TT),fIbrInogenlevel,andfIbrIndegradatIonproductsshould
beperformed,asshouldbaselInestudIesofrenalfunctIon.
Delayed Hemolytic Transfusion Reactions
NumerousInstanceshavebeenreportedInwhIchtransfusedredcellsarerapIdly
elImInatedfromthecIrculatIonatashortInterval(days)afteranapparentlycompatIble
crossmatch.ThesedelayedhemolytIctransfusIonreactIonscanbetheresultofadonor
F8CantIgentowhIchtherecIpIenthasbeenprevIouslyexposedbyeIthertransfusIonor
pregnancy.DvertIme,therecIpIentantIbodIesfalltolevelstoolowtobedetectedby
compatIbIlItytestIng.WIthreexposure,ananamnestIcresponseresultsInantIbodythat
eventuallylysestheforeIgnF8Cs.notherInstances,denovoalloImmunIzatIonmaybe
responsIble.TypIcally,theantIbodycoatedF8CIssequesteredextravascularlyandlysIs
occursInthespleenandretIculoendothelIalsystem.8ecausetheF8CdestructIonoccurs
extravascularly,symptomsarelesssevereandthereactIonIsunlIkelytobefatal.UnlIke
AHTFs,whIchusuallyInvolveantIbodIesIntheA8Dsystem,delayedhemolytIctransfusIon
reactIonscommonlyInvolveantIbodIesagaInstKell,KIdd,andFhesusantIgens.
24
WhIle
alloImmunIzatIonandthe
P.J74
appearanceofnewantIbodIesoccurswIthapproxImately1per200unItstransfused,
clInIcallydetectabledelayedhemolytIcreactIonsoccuratarateofonly1per2,000to
2,500transfusIons
24
(Table162).
EvIdenceofhemolysIsIsusuallydetectedbythefIrstorsecondweekfollowIngtransfusIon.
ThereactIonshouldbesuspectedIntheeventofalowgradefever,IncreasedIndIrect
bIlIrubInwIthorwIthoutmIldjaundIce,and/oranunexplaInedreductIonInHb
concentratIon.SerumhaptoglobInmayalsobedecreased.ThedIagnosIsIsconfIrmedbya
posItIvedIrectantIglobulIntest(Coombstest)andtheIdentIfIcatIonofanewantIbodyIn
thepatIent'splasma.ThereactIonIstypIcallymIldandselflImItIngandtheclInIcal
manIfestatIonsresolveasthetransfusedcellsareremovedfromthecIrculatIon.SupportIve
careIncludesmonItorIngofHb,maIntenanceofhydratIon,andprovIsIonofcompatIble
bloodIfnecessary.
Reactions to Donor Proteins
Minor Allergic Reactions
AllergIcreactIonstoproteInsIndonorplasmacauseurtIcarIalreactIonsIn0.5to4ofall
transfusIons.
2,2J
ThereactIonIsmostfrequentlyassocIatedwIththetransfusIonofFFPor
platelets.ThepatIentmayhaveItchIng,swellIng,andarash(hIstamInerelease).These
mIldsymptomscanbetreatedwIthdIphenhydramIne(Chapter12).|ostmIldurtIcarIal
reactIonsareIsolatedeventsthatdonotrecur.PatIentswhoexperIencerepeated
reactIonsorasInglesevereurtIcarIalreactIonmaybenefItfromtheuseofsalInewashed
redcells.ThewashIngofplateletsIsgenerallyIneffectIve,andsusceptIblepatIentswho
requIreplateletsorFFPcanbemanagedbyadmInIstratIonofantIhIstamIneandsteroIds
(e.g.,prednIsone,1mg/kgorequIvalent)1hourprIortotransfusIon.
Anaphylactic Reactions
nfrequently,moresevere,anaphylactIcreactIonsIncludIngdyspnea,bronchospasm,
angIoedema,andhypotensIonmayoccur(Chapter12).ClassIcally,theseoccurwhen
patIentswIthheredItaryImmunoglobulIn(g)AdefIcIencywhohavebeensensItIzedby
prevIoustransfusIonsorpregnancyareexposedtobloodwIthforeIgngAproteIn.However,
otherplasmaproteInpolymorphIsms(e.g.,haptoglobIn)maycausesImIlarreactIons.
TreatmentconsIstsofdIscontInuatIonofthetransfusIonandadmInIstratIonofepInephrIne
andmethylprednIsolone.Washedredcells,frozendeglycerolIzedredcells,orIn
approprIatecases,redcellsfromgAdefIcIentdonorsshouldsubsequentlybeusedfor
thesepatIents.PlateletandFFPtransfusIonmaybemanagedwIthpretransfusIon
admInIstratIonofprednIsone(seeprevIousdIscussIon),carefulmonItorIng,andepInephrIne
atthebedsIde.
White Cell-Related Transfusion Reactions
Febrile Reactions
PatIentswhoreceIvemultIpletransfusIonsofF8Csorplateletscommonlydevelop
antIbodIes(alloImmunIzatIon)tothehumanleukocyteantIgens(HLAs)onthepassenger
leukocytesIntheseproducts.0urIngsubsequentF8CtransfusIons,febrIlereactIonsmay
occurasaresultofantIbodyattackondonorleukocytes.ThesefebrIleresponsesoccurIn
upto2ofplatelet,FFP,andF8CtransfusIons(Table162).TypIcally,thepatIent
experIencesatemperatureIncreaseofmorethan1`CwIthIn4hoursofabloodtransfusIon
anddefervesceswIthIn48hours.ThefeverIssometImesaccompanIedbychIlls,respIratory
dIstress,anxIety,headache,myalgIas,nausea,andanonproductIvecough.FebrIle
reactIonscanbetreatedwIthacetamInophen.AleukocytemedIatedfebrIletransfusIon
reactIonshouldbedIstInguIshedfromahemolytIctransfusIonreactIon(dIrectCoombs
test).LeukoreductIon(seelater)reducesorpreventsthesereactIons.
25
Transfusion-Related Acute Lung Injury
TFALIsanoncardIogenIcformofpulmonaryedemaoccurrIngafterbloodproduct
admInIstratIon(seeChapter12).thasbeenassocIatedwIthallplasmacontaInIngblood
components,wIthplateletconcentratesandFFPbeIngImplIcatedmuchmorecommonly
thanPF8Csorotherproducts.
26,27
TheIncIdence(Table162)IsfrequentlyestImatedtobe
1:5,000unItstransfused,althoughIthasbeenrecentlyreportedtobeashIghas1per1,271
transfusedunItsInacarefullyobserved,atrIskIntensIvecareunIt(CU)patIent
populatIon.
28
tIslIkelythatTFAL,whIchcarrIesamortalItyofatleast5,
29
has
hIstorIcallybeenbothunderrecognIzedandunderreported.AwarenessIsIncreasIng,and
accordIngtoareportbyHolnessandEpsteIn,TFALwasresponsIblefor46.5ofdeaths
reportedtotheFoodand0rugAdmInIstratIon(F0A)InthefIrsthalfof2006.
J0
0etaIledrevIewsofTFALareavaIlable.
29,J1
nmostInstances(90),TFALoccurswhen
medIatorspresentIntheplasmaphaseofdonorbloodactIvateleukocytesInthehost.
ThosemedIatorsareusuallyantIHLA(ClassorClass)orantIgranulocyteantIbodIesIn
donorplasmaformedasaresultofprevIoustransfusIonorpregnancy.nasmall
percentageofInstances,theInversereactIon,aggregatIonofdonorleukocytesbyrecIpIent
antIbodIes,maybethecausewhentherecIpIenthasbeenalloImmunIzedagaInstleukocyte
antIgens.neIthercIrcumstance,theactIvatedleukocytesaresequestratedInthelungand
themedIatorstheyreleasecausecapIllaryendothelIaldamageandIncreasedpermeabIlIty.
8ecauseantIleukocyteantIbodIescannotbedemonstratedInallInstancesofTFAL,It
seemscertaInthatothermechanIsmsaresometImesoperatIve.AdoubleInsult,ortwo
hIt,theoryproposesthatthehumoralresponsetovarIousphysIologIcstresses(e.g.,
trauma,surgery,sepsIs,systemIcInflammatoryresponse)mayfIrstprImenatIve
granulocytes,causIngtheappearanceofsurfaceadhesIonsItes,whIchInturnresultsIn
lungsequestratIon.TransfusIonIsproposedtobethewIelderofthesecondhIt.The
medIatorsarethoughttobebIologIcallyactIvelIpIds,sometImesreferredtoasbiological
response modifiers(8F|s)thataccumulateasaresultofthebreakdownofmembranesof
thecellularelementsInstoredbloodproducts.tIsthe8F|s,notablyvarIous
lysophosphatIdylcholInes,thatactIvatethesequesteredleukocytes.ConsIstentwIththIs
theoryIsthatTFALhasbeenreportedtobemorelIkelytooccurwIthlongerproduct
storagetImes.
J2
AmergIngofthesetwotheorIesmayoccur,IfforInstanceItIs
demonstratedthatthecombInatIonofantIbodIesand8F|sIndonorbloodcollaborateIn
somewaytoeffectthetwohIts.
TheclInIcalappearanceIsverysImIlartothatofacutelungInjuryofotheretIologIes,
althoughthemortalItyrateshouldbesubstantIallyless.8egInnIngwIthIn6hoursof
transfusIon,andoftenmorerapIdly,thepatIentdevelopsdyspnea,chIlls,fever,and
noncardIogenIcpulmonaryedema.8othhypotensIonandhypertensIonmayoccur.Chestx
rayrevealsbIlateralInfIltrates.SeverepulmonaryInsuffIcIencycandevelop.SpecIfIc
dIagnostIccrIterIaforthedIagnosIsofTFALhavebeenestablIshed(Table16J).
JJ
TreatmentIslargelysupportIve.ThetransfusIonshouldbestoppedIfthereactIonIs
recognIzedIntIme.TransfusIonassocIatedcIrculatoryoverload(TACDInthevernacular
ofbloodbankers)shouldbeconsIderedandruledout.SupplementaloxygenandventIlatory
supportshouldbeprovIdedasnecessary,IdeallyusIngthesamelowtIdalvolumelung
protectIvestrategIesthatareemployedIntheacuterespIratorydIstresssyndrome.
J4
The
pulmonaryedemaIsnoncardIogenIc.AccordIngly,dIuretIcsarenonwarranted.
ClucocortIcoIdshavebeenadmInIsteredbuttherearenodatatosupportthepractIce.
TherearepreventIvestandardsatthetImeofthIswrItIng(AprIl2008).tIsantIcIpated
thatunIversalleukoreductIon
P.J75
wIlldecreasethepresenceofantIleukocyteantIbodIesInbothdonorsandrecIpIents.
J5
|ultIparousfemaledonorshavebeenIdentIfIedasthemostcommonsourceofthe
antIleukocyteantIbodIesInTFALfatalItIes.
2J
8egInnIngIn200J,theUnItedKIngdom
substantIallyrestrIctedtheuseofplasmacontaInIngproductsfromthIsdonorsubgroup.A
programtosImIlarlylImItthepreparatIonofhIghplasmavolumecomponents(FFP,TP,
FP24,orplasmafrozenwIthIn24hoursafterphlebotomy[seelaterdIscussIon],apheresIs
platelets,wholeblood)fromdonorsknowntobeleukocytealloImmunIzedoratIncreased
rIskofleukocytealloImmunIzatIon(pregnancyorprIortransfusIon),ortoperformHLA
antIbodytestIng,IsIntheprocessofImplementatIonIntheUnItedStates.
1
Table 16-3 Diagnostic Criteria for Transfusion-Related Acute Lung Injury
1. AcuteonsetofhypoxemIa(wIthIn6hoursofconclusIonoftransfusIon)
2. 8IlateralCXFInfIltratesconsIstentwIthAL
J. AbsenceofevIdenceofleftatrIalhypertensIon
4. AbsenceofothertemporallyrelatedcausesofAL
CXF,chestxray;AL,acutelungInjury.
FromKleInmanS,CaulfIeldT,ChanP,etal:TowardanunderstandIngof
transfusIonrelatedacutelungInjury:statementofaconsensuspanel.TransfusIon
2004;44:1774wIthpermIssIon.
Graft-versus-Host Disease
PF8CsandplateletsbothcontaInasIgnIfIcantnumberofvIabledonorlymphocytes.When
transfusedIntoImmunocompromIsedpatIents,thedonorlymphocytesmaybecome
engrafted,prolIferate,andestablIshanImmuneresponseagaInsttherecIpIent(see
Chapter54).nessence,theengraftedlymphocytesrejectthehost.
J6
PatIentsatrIskforgraftversushostdIsease(C7H0)IncludeorgantransplantrecIpIents,
neonateswhohaveundergoneabloodexchangetransfusIon,andpatIents
ImmunocompromIsedbymanyotherdIseaseprocesses(butnotA0S;Table164).C7H0
typIcallyprogressesrapIdlytopancytopenIa.ThefatalItyrateIsveryhIgh.TransfusIon
assocIatedC7H0hasalsobeenreportedInapparentlyImmunocompetentpatIentswhena
genetIcrelatIonshIpexIstsbetweenthedonorandtherecIpIent.nthesecIrcumstances,
therecIpIentmayshareHLAantIgenhaplotypeswIththedonorlymphocytes.ThepatIents,
althoughImmunologIcallycompetent,faIltorejectthetransfusedcellsbecausetheydo
notrecognIzethemasforeIgn.Thetransfuseddonorlymphocytes,however,recognIzethe
hostasforeIgnandaC7H0reactIontakesplace.
Table 16-4 Irradiation of Cellular Blood Products for Patients at Risk of
Graft-Versus-Host Disease
WIdelyrecommended:
8onemarrowtransplantrecIpIents
TransfusIonfromconsanguIneousdonor
HodgkIn'sdIsease
ntrauterInetransfusIons
HLAmatchedplateletorgranulocytestransfusIon
DngoIngtreatmentwIthpurIneanalogantImetabolItes
SeverecombInedImmunodefIcIencysyndrome
LesserrIsk/practIcesvarywIthIntensItyofImmunosuppressIon:
AcuteleukemIas
NonHodgkIn'slymphoma
SolIdtumors
SolIdorgantransplantrecIpIents
|odIfIedfromSchroeder|L:TransfusIonassocIatedgraftversushostdIsease.8rJ
Haematol2002;117:275.
C7H0hasbeenreportedonlyafterthetransfusIonofcellularbloodcomponents.thasnot
occurredfollowIngtransfusIonofFFPorcryoprecIpItate.TheAA88recommendsthatHLA
matchedplateletsanddIrecteddonatIonsfromfIrstdegreerelatIvesbeIrradIatedto
InactIvatedonorlymphocytes.
a
LeukoreductIonmayreducetheIncIdenceofC7H0,butIt
doesnotpreventIt
2
orreducethemortalItyIfItoccurs.rradIatIonremaInstheonly
effectIvemeansforpreventIngC7H0.
J7
AnesthesIologIstswIllencounterpatIentsIn
operatIngroomsandCUswhoareatrIskforC7H0;theyshouldbepreparedtoask,
ShouldthebloodweadmInIstertothIspatIentbegammaIrradIated:
The three leading causes of transfusion-related death in the United States are TRALI, ABO
incompatibility, and sepsis caused by bacterial contamination.
Transfusion-Related Immunomodulation (TRIM)
AllogeneIctransfusIonhaslongbeenknowntocausealteratIonofImmuneresponsIveness.
TheInItIalobservatIonswereofdecreasedratesoftransplantrejectIon
J8
anddecreased
ratesofspontaneousabortIonamongpatIentswhohadreceIvedallogeneIctransfusIons.
ThatsomemodIfIcatIonofImmunesurveIllanceoccursseemsInescapable,andthe
occurrenceofnumeroustransfusIonassocIatedchangesInImmunerelatedprocesses,
IncludIngTlymphocytehelper/suppressorratIo,thefunctIonofkIllerTcells,lymphocyte
responsIveness,anddelayedhypersensItIvItyhasbeendemonstrated.
J9
WhIletransfused
mononuclearwhItecellsarethoughttobeprIncIpallyresponsIble,othermechanIsmsmay
beInvolved.
J9
Numerousadverseeffects,presumedtoreflectthIsattenuatIonof
Immunocompetence,havebeenreported,IncludIngIncreasedmortalIty,accelerated
recurrenceofmalIgnancy,IncreasedratesofInfectIon,andmorerapIdprogressIonof
H7/A0S.AlthoughmanyofthetypIcalobservatIonalstudIeshaveleftItlessthan
absolutelyclearwhethertransfusIonwasthecauseoftheadverseoutcomeormerelya
reflectIonoftheconcomItantprocessesthatnecessItatedbloodproductadmInIstratIon,
theweIghtoftheaccumulatedInvestIgatIons,IncludIngsomethathavecontrolled
carefullyforconfoundIngvarIables,
40,41,42,4J
arguethattheadverseeffectoftransfusIon
onInfectIonratesandmortalItyIsarealoneInatleastsomecontexts.
44
DneInvestIgatIon
IspartIcularlyrevealIng.Hebertetal.
45
prospectIvelycomparedtransfusIonstrategIes
basedonalIberal(10g/dL)versusarestrIctIve(7g/dL)transfusIonthresholdInanCU
populatIonInwhomthepotentIalconfounderswerebalancedatthetImeofpatIent
enrollment.TheyobservedlesserseverItyofmultIpleorgandysfunctIon,reducedlengthof
CUandhospItalstay,andreducedmortalItyatallfollowupIntervalsIntherestrIctIve
group.AlthoughthIsInvestIgatIonIsstronglysuggestIveofanadverseeffectofallogeneIc
bloodandfurthersupportstheImportanceofavoIdIngunnecessarytransfusIon,Itshouldbe
acknowledgedthatthereIsnocertaIntythattheadverseeffectwasentIrelyafunctIonof
Immunesuppression(seenextsectIon).
P.J76
Transfusion-Induced Inflammatory Response
tseemsprobablethat,InaddItIontoanyTF|effect,transfusIonInducesanInflammatory
responseIntherecIpIent.(NotethatTF|IsnowsometImesusedtoencompassboththe
ImmunesuppressantandproInflammatoryeffectsoftransfusIon.)
NumerousbIoactIvesubstances,IncludIngcytokInes,membranelIpIdbreakdownproducts,
andcomplement,accumulatedurIngbloodproductstorageandaresuspectedof
contrIbutIngtoanInflammatoryresponseIntherecIpIentandtotheprogressIonof
multIorgandysfunctIon.
J9,46,47
tIspossIblethatsomeoftheadverseeffectsoftransfusIon
onmortalItyareafunctIonofaproInflammatoryratherthananImmunesuppressant
effect.8ecausetheconcentratIonsofthesemedIatorsIncreasedurIngstorage,several
InvestIgatIonshavesoughttodetermInewhethertheduratIonofstoragehasanyrelatIon
tooutcome.AcorrelatIonbetweentheageoftransfusedPF8CsandtheseverItyof
multIorganfaIlureIntraumapatIents,
48
lIfethreatenIngoutcomesandmortalItyInanCU
populatIon,
49
andmortalIty,renaldysfunctIon,andlengthofstayIncardIacsurgIcal
patIents
50,51
havebeenreported.ftheseresultsareborneoutbylargerprospectIvetrIals,
ItwIllbrIngpressureonourblooddelIverysystemtoachIeveshortershelftImes(whIch
currentlyaverageabout20days
52
),atleastforpatIentsInthemorecrItIcalcIrcumstances.
Leukoreduction
ThesuspIcIonthattransfusedleukocytesarethemedIatorsoftheImmunItyattenuatIng
effectsoftransfusIonmentIonedprevIouslyledtothedevelopmentandprogressIve
applIcatIonoftechnIquesforleukocytedepletIonofdonorbloodproducts.fleukocytesare
responsIbleforTF|,leukoreductIonshouldattenuatetheadverseeffects.However,meta
analysIsofstudIescomparIngwhItebloodcell(W8C)reducedandnonW8Creducedblood
hasrevealedareductIonofmortalItythatIsevIdentonlyInthecontextofcardIac
surgery.
5J
ArecentretrospectIvecomparIsonofpatIentswhoreceIvedallogeneIcblood
aftertheonsetofacutelungInjurysubsequentlyreportedIncreasedmortalItyamong
patIentswhoreceIvednonleukoreducedblood.
4J
ThatstudywaslImItedbysome
noncurrencyoftheleukoreducedandnonleukoreducedgroups.FurthermetaanalysIs,
lImItedtothemostcarefullyperformedInvestIgatIons,alsorevealedaneffectontherate
ofpostoperatIveInfectIons.
5J
However,whentheImpactofleukoreductIononthe
progressIonofH7/A0SwasstudIedInablIndedprospectIvemanner,noeffectwas
IdentIfIed.
54
AlbeItthattheextenttowhIchwhItecellsareresponsIblefortheadverseImmunologIc
effectsoftransfusIonIsnotabsolutelyclear,forthatandotherreasons,manycountrIes
IncludIngCanada,France,Portugal,andtheUnItedKIngdomandcertaInstatesand
regIonswIthIntheUnItedStateshavealreadyadoptedthepractIceofleukoreductIonof
100oftheIrbloodsupplIes.TheentIreUnItedStatesIsmovIngtowardsthatobjectIve.At
present(2008),about70ofplateletsand40to50ofFFPandPF8Csareleukoreduced.
ThereareseveralotherwellconfIrmedbenefItsofleukoreductIon
25
IncludIngreductIonIn
thedevelopmentofalloImmunIzatIonandplateletrefractorIness,reductIonInthe
IncIdenceoffebrIlenonhemolytIctransfusIonreactIons,andreductIonIn(butnot
preventIonof
14
)thetransmIssIonofC|7.However,Ithasbeenarguedthat(less
expensIve)selectIveleukoreductIoncouldreadIlybeapplIedforthepatIentstowhom
thesebenefItsarerelevant.TheadvocacyofunIversalleukoreductIonIsbasedonthe
premIsethatItmIghtservetoaccomplIshthevarIousunconfIrmedbenefItslIstedInTable
165,and/orthatselectIveleukocytereductIonmIghtresultInmanypatIentsreceIvIng
nonleukoreducedbloodbeforetheIndIcatIonforleukocytereductIonbecameapparent
e.g.,aseverelyanemIc,undIagnosed,acuteleukemIcpatIent.nIndIvIdualInstItutIons
wIthdualInventorIes,ItwIllbetheresponsIbIlItyoftheclInIcIanatthebedsIdetorequest
leukoreducedbloodwhenheorsheperceIvesIttobeInthepatIent'sbestInterest.
Table 16-5 The Benefits of Leukoreduction
ConfIrmedbenefIts
0ecreasedalloImmunIzatIon/plateletrefractorInessInmultIplytransfused
leukemIcs
PreventIonoffebrIlereactIonstoF8CtransfusIons
FeductIonofC|7transmIssIon
FeducedInflammatorymedIatoraccumulatIondurIngstorage
FeportedbutunconfIrmedbenefIts:
ShortenedhospItalIzatIon
0ecreasedpostoperatIvemortalItyIncardIacsurgery
0ecreasedpostoperatIveInfectIons
PreventIonoftransfusIonrelatedIncreaseIntumorrecurrence
SuggestedbutunconfIrmed:
FeducedIncIdenceofC7H0
F8C,redbloodcell;C|7,cytomegalovIrus;C7H0,graftversushostdIsease.
WhIlemanyoftheputatIvebenefItsareunconfIrmed,addItIonalreportsofbenefIts
attrIbutedtoleukoreductIonarebeIngaddedtothelIterature.
55,56
AlthoughskeptIcIsm
persIsts,thecommonvIewIsthat,InspIteoftheassocIatedcosts,becausethehazardsof
leukoreductIonaremInImal,thepossIblebenefItsjustIfyproceedIngwIthunIversal
leukoreductIon.UnIversalleukoreductIon,whenfullyImplemented,wIllemployprestorage
depletIonratherthanbedsIdeleukoreductIonfIltersatthetImeofadmInIstratIon.
PrestoragedepletIonavoIdstheaccumulatIonofcytokInesreleasedbyW8CsdurIng
storage.ClInIcIansshouldalsobeattentIvetothepossIbIlItyofsevere,apparently
bradykInInmedIatedhypotensIonInpatIentswhoreceIvebedsIdefIlteredblood.The
reactIonappearstooccurmorefrequently,althoughnotexclusIvely,InpatIentsreceIvIng
angIotensInconvertIngenzymeInhIbItors(whIchreducebreakdownofbradykInIn).
57
Other Noninfectious Risks Associated with Transfusion
Massive Transfusion
TherapIdtransfusIonoflargevolumesofstoredbloodcanhaveseveralconsequences
(Table166).SomeofthesearefunctIonsofpropertIesofthebloodItself,someofthe
agentsusedtopreserveandantIcoagulateIt,andsomeofthebIochemIcalreactIonsthat
occurdurIngstorage(seeChapterJ6).DthercomplIcatIonsarenotunIquetoblood
transfusIons,butmayoccurwIththerapIdtransfusIonoflargevolumesofanyfluId.
Hypothermia
HypothermIaslowshemostasIs(asItdoesallenzymatIcallymedIatedprocesses)andcauses
sequestratIonofplatelets.TheadmInIstratIonofoneunItofPF8Csat4`CwIllreducethe
coretemperatureofa70kgpatIentapproxImately0.25`C.At29`C(thetemperatureat
whIchtherIskofcardIacdysrhythmIasIscrItIcal),PTandaPTTwIllIncreaseapproxImately
50overnormothermIcvalues,andplateletcountwIlldecreasebyapproxImately40.
58
0ysrhythmIasmaybeseenathIghercoretemperaturesIfunwarmedbloodIsadmInIstered
P.J77
rapIdly;InpartIcular,throughcentralcatheters.WIthdecreasIngbodytemperature,
cardIacoutputdeclInes,tIssueperfusIonIsImpaIred(asaconsequenceofboth
vasoconstrIctIonandaleftshIftoftheoxygenhemoglobIn[D
2
Hb]dIssocIatIoncurve),and
metabolIcacIdosIsmaydevelop.ShIverIngonemergencecanIncreaseoxygenconsumptIon
by400.
Table 16-6 Hazards Associated with Massive Transfusion
HypothermIa
7olumeoverload
0IlutIonalcoagulopathy
FeducedoxygencarryIngcapacIty(decreased2,J0PC)
|etabolIcacIdosIs
HyperkalemIa
CItrateIntoxIcatIon
2,J0PC,2,JdIphosphoglycerate.
AmetaanalysIsconcludedthatevenmIldhypothermIaIncreasesbloodloss.
59
HypothermIa,afterattemptIngtocorrectforcovarIates,IsanIndependentpredIctorof
mortalItyIntraumapatIents.
60,61
HypothermIahasbeenassocIatedwIthIncreased
postoperatIvemorbIdItyandmortalItyIncludIngIncreasedratesofpostoperatIve
InfectIon.
62
However,InstudIesofthIsnature,ItIsdIffIculttoseparatetheeffectsofthe
commonclInIcalconcomItantsofhypothermIa(e.g.,acIdosIs,shock,massIvetransfusIon,
massIvetIssueInjury)fromthoseofhypothermIaperse.Furthermore,thesIgnIfIcanceof
hypothermIamaylIeIntheInteractIonwIthothervarIablesassuggestedbythe
observatIonthattemperaturesofJJ`ChavebeenusedextensIvelyInelectIveneurosurgery
wIthoutclInIcallyapparentcoagulopathy.Nonetheless,hypothermIashouldbecarefully
avoIdedandaggressIvelycorrectedInthepatIentreceIvIngmassIvetransfusIon.
AccordIngly,transfusIonsadmInIsteredrapIdlyorInsubstantIalvolumeshouldbewarmed.
Volume Overload
CIrculatoryvolumeoverloadoccurswhenbloodorfluIdIstransfusedtoorapIdlyfor
compensatoryfluIdredIstrIbutIontotakeplace.
nthesettIngofmassIvetransfusIon,assumIngmaIntenanceofIsovolemIaandtheabsence
ofaconsumptIvecoagulopathy,crItIcaldIlutIonofclottIngfactorsandplateletsIslIkelyto
occurafteranaveragereplacementof140and2J0ofbloodvolume,respectIvely.
Dilutional Coagulopathy
AdmInIstratIonoflargevolumesoffluIddefIcIentInplateletsandclottIngfactorswIll
resultInacoagulopathyasaconsequenceofdIlutIon.ncontemporarypractIce,InwhIch
patIentsreceIveprIncIpallyPF8CswIthonlyverylImItedamountsofresIdualplasma,
factordefIcIencIesdevelopbeforethrombocytopenIa.WIthlargevolumeIsovolemIc
dIlutIon,clInIcallysIgnIfIcantdIlutIonoffIbrInogen,factors,7,and7,andplatelets
wouldbeexpectedtooccuraftervolumeexchangesofapproxImately140,200to2J0
and2J0(I.e.,1.4,2,and2.Jbloodvolumes),respectIvely.
6J
However,fIbrInogenIsan
acutephasereactant,andlevelswIlloftenbegreaterthanwouldbepredIctedbydIlutIon
calculatIons.FesuscItatIonfromhypovolemIawIllresultInreachIngthesethresholdsat
smallerpercentagevolumeexchanges.NotethatcalculatIonsofthIsnatureshouldnotbe
usedasaguIdetobloodproductadmInIstratIonbutmerelyasameansofantIcIpatIng
clInIcallyrelevantoccurrences.ThedecIsIontoadmInIsterFFPorplateletswIlldependon
clInIcalandlaboratoryevIdenceofcoagulopathy,orfrequentlyontheuncertaIntIes
assocIatedwIthrapIdandongoIngbloodloss.nthesettIngoftrauma,PT/InternatIonal
normalIzedratIo(NF)hasbeenshowntorevealfactordefIcIencIeswIthgreatersensItIvIty
thanaPTT.
64
ThIsIsprobablybecausetheaPTTassayIsveryF7sensItIve,andF7,lIke
fIbrInogen,IsanacutephasereactantthatIsoftenIncreasedInthesettIngoftrauma.The
mostcommonInItIalfactordefIcIencIesInthesettIngoftraumaareF7andFX.
64
WIththepossIbleexceptIonoftraumaresuscItatIon,coagulatIonfactorandplatelet
replacementshouldbedetermInedbylaboratoryassessmentand/orobservatIonofclInIcal
coagulopathyandnotestImatedbloodlossdrIvenformulas.
Decreases in 2,3-Diphosphoglycerate
StorageofF8CsIsassocIatedwIthaprogressIvedecreaseInIntracellularATPand2,J
dIphosphoglycerate(2,J0PC)wItharesultantleftshIftoftheD
2
HbdIssocIatIoncurve.
AccordIngly,transfusIonofthe2,J0PCdepletedblood,whIleIncreasIngthepatIent'sHb
value,wIllresultInlesseffIcIentoxygendelIverythanwouldoccurwIthnatIveHbatthe
samehematocrIt.AftertransfusIon,2,J0PClevelsreturntowardnormalover12to24
hours.
65
Acid-Base Changes
WhencItratephosphatedextrose(CP0)solutIonIsaddedtoaunItoffreshlydrawnblood,
pHdecreasestoapproxImately7.0to7.1(seeChapter14).FurtherreductIonofpHwIll
occurdurIngstorageasaconsequenceofongoIngmetabolIsmofglucosetolactate.Atthe
endof21days,thepHmaybeaslowas6.9,butmuchofthIsIstheresultoftheproductIon
ofCD
2
thatIsrapIdlyelImInatedfollowIngthetransfusIon.WhetherrapIdInfusIonofthIs
acIdIcbankbloodleadstometabolIcacIdosIsIsdebated.WhenthelIverIsadequately
perfused,cItratefromtheCP0solutIonIsmetabolIzedtobIcarbonateandanyacIdbase
dIsturbanceshouldthereforebeselfcorrectIng.ClInIcally,IntheInjuredpatIentwhoIs
hypotensIve,poorlyperfused,andhasInadequatetIssueoxygenatIon,ItwIllbedIffIcultto
dIfferentIatewhatportIonofthemetabolIcacIdosIsIsduetorapIdtransfusIon,andwhat
portIonIsduetotheproductIonoflactIcacId.TheapproprIatecourseIstobase
bIcarbonatetherapyonbloodgasanalysIs.
Hyperkalemia
0urIngstorage,potassIummovesoutoftheF8Cs,InparttomaIntaInelectrochemIcal
neutralItyashydrogenIonsgenerateddurIngstorageredIstrIbute.ThepotassIum
concentratIonInplasmamayreachlevelsvarIouslyreportedtobebetween19andJ5
mEq/LInbloodstoredfor21days.HazardexIstsIflargevolumesofstoredbloodare
admInIsteredrapIdly.WhIlethereareonly20to60mLofplasmaInaunItofPF8Cs,
contemporaryInfusIondevIcesallowbloodtobetransfusedatratesof500to1,000
mL/mIn.AttheseInfusIonrates,crItIcalhyperkalemIacanoccurandIntraoperatIvearrests
havebeendocumented.
66
PrematureneonatesareespecIallysusceptIbletohyperkalemIa,
andtypIcallythereforereceIveeItherfresh(8dayold),plasmareduced,orwashedPF8Cs
IfrapIdtransfusIon(10to15mL/kgper2hours)IsrequIred.
Citrate Intoxication
Whenlargevolumesofstoredblood(morethanonebloodvolume)areadmInIstered
rapIdly,thecItratecancauseatemporaryreductIonInIonIzedcalcIumlevels.CItrateIs
normallymetabolIzedeffIcIentlybythelIveranddecreasedIonIzedcalcIumlevelsshould
notoccurunlesstherateoftransfusIonexceeds1mL/kgpermInuteorabout1unItof
bloodper5mInutesInanaveragesIzedadult.ThenowcommonaddItIvesolutIonblood
preservatIveshaveamuchsmallercItratecontentthancItratephosphatedextrose
adenIne(CP0A).ThIsshouldfurtherreducethehazardof
P.J78
cItrateIntoxIcatIonwIthPF8CadmInIstratIon.However,mostofthecItrateadmInIstered
durIngmassIvetransfusIonIsIntheFFPratherthanthePF8Cs.mpaIredlIverfunctIonor
perfusIonwIlllowertheratethresholdfordevelopIngcItrateIntoxIcatIon.Notealsothat
crItIcalcardIacconsequencesthatoccurbeforehypocalcemIahavesIgnIfIcantImplIcatIons
forcoagulatIon.SIgnsofcItrateIntoxIcatIon(hypocalcemIa)IncludehypotensIon,narrow
pulsepressure,andelevatedIntraventrIcularenddIastolIcpressureandcentralvenous
pressure,prolongedQTInterval,wIdenedQFScomplexes,andflattenedTwaves.
Microaggregate Delivery
StoredbloodcontaInsmIcroaggregates.PlateletaggregatesformdurIngthesecondtofIfth
dayofstorageandafterapproxImately10days,largeraggregatescomposedoffIbrIn,
degeneratedwhItecells,andplateletsappear.|acroaggregatesofF8Csalsodevelop.
StandardfluIdadmInIstratIonsetscontaIn170mIcronfIlters,whIchwIllremovethese
largeraggregates,andareapproprIateforF8Cs,FFP,cryoprecIpItate,andplatelet
admInIstratIon.|IcroaggregateshavebeensuspectedInthepathogenesIsofpulmonary
InsuffIcIencyafterlargevolumetransfusIon.However,concomItantphysIologIc
dIsturbances(hypotensIon,sepsIs,tIssueInjury)maybetheactualcauses,andsomeof
whathasbeenattrIbutedtomIcroaggregatesmayInfactbeTFAL.|IcroporefIlters,
typIcallywItha40mIcronporesIze,wereonceadvocatedforF8CadmInIstratIonbutwere
ofnodemonstratedbenefIt(wIththeexceptIonofthearterIalcannulaofthe
cardIopulmonarybypass[CP8]cIrcuIt).
F8CsarefrequentlydIlutedwIthcrystalloIdsolutIonstoIncreasetherateatwhIchthe
bloodcanbetransfused.ntheIdealsItuatIon,normalsalIne,Normosol,orotherdIluents
acceptedbytheF0AandAA88shouldbeusedInpreferencetolactatedFIngersolutIon
(LF).nfact,theamountofcItratepresentInstoredbloodIsmorethansuffIcIenttobInd
thesmallamountsofcalcIumInthe100toJ00mLofLFtypIcallyusedfordIlutIon.
67
There
IsnoevIdencethatanyclInIcallysIgnIfIcantsequelaehaveresultedfromtheuseofLFas
anF8CdIluent.
68
Blood Products and Transfusion Thresholds
Red Blood Cells
ThequestIonofwhathemoglobIn/hematocrIt(Hb/Hct)leveljustIfIestherIsksassocIated
wIththeadmInIstratIonofbloodhasbeenwIdelydIscussed.TheonceallbutInvIolable10
J0rulehasbeenabandoned.ExperIencewIthseveralpatIentsubpopulatIons(renal
faIlure,mIlItarycasualtIes,Jehovah'sWItnesses)andsystematIcstudyhasrevealedthat
consIderablegreaterdegreesofanemIacanbewelltoleratedandthat,InmanysItuatIons,
morbIdItyandmortalItyratesdIdnotIncreaseuntIlHblevelsfellbelow7g/dL.
45,69
As
sIgnIfIcantastheIdentIfIcatIonofa7g/dLthresholdforIncreasedmorbIdItywasthe
observatIonthatstablegeneralmedIcalsurgIcalmanagedtoatargetHbof10g/dLfared
lesswellthanaparallelgroupmanagedwIthatransfusIontrIggerof7g/dL.
45
That
observatIonImplIesanadverseeffectoftransfusIon(seeTransfusIonFelated
mmunomodulatIon).AccordIngly,thecontemporarytransfusIontrIggerforstablegeneral
medIcalsurgIcalpatIentsIs21/7.0g/dL(Hb/Hct).However,thereIsevIdencethatthe
thresholdforpatIentswIthcardIacdIseaseshouldbehIgher.
45
ThatevIdenceIncludesan
InvestIgatIonsupportIngathresholdofJ0/10g/dL(Hb/Hct)InpatIentswhohavesuffered
arecentacutemyocardIalInfarctIon(|),
70
andanobservatIonalstudysuggestsbetter
outcomesInpatIentswIthseveralcardIacdIagnoses(cardIacandvascularsurgery,
IschemIcheartdIsease,dysrhythmIas)aboveathresholdof9.5g/dL
71
(seeChapter42).The
Practice Guidelines for Blood Component TherapydevelopedbytheAmerIcanSocIetyof
AnesthesIologIsts(ASA)statethatredbloodcelltransfusIonIsrarelyIndIcatedwhenthe
hemoglobInconcentratIonIsgreaterthan10g/dLandIsalmostalwaysIndIcatedwhenItIs
lessthan6g/dL.TheIndIcatIonsforautologoustransfusIonmaybemorelIberalthanfor
allogeneIc(homologous)transfusIon.
72
TheclInIcIan'sresponsIbIlItyIstoantIcIpate,onapatIentbypatIentbasIs,themInImum
Hblevel(probablyIntherangeof7to10g/dL)thatwIllavoIdorgandamageduetooxygen
deprIvatIon.0etermInIngthIsIndIvIdualtransfusIontrIggerrequIresreferencetothe
manyelementsofpatIentcondItIonthatdetermInedemandforthedelIveryofoxygenand
thephysIologIcreserve(Table167),
7J
IncludIngongoIngbloodlossandthepotentIalfor
suddenbloodloss.UltImately,thedecIsIontotransfuseF8CsshouldbemadeonthebasIs
oftheclInIcaljudgmentthattheoxygencarryIngcapacItyofthebloodmustbeIncreased
topreventoxygenconsumptIonfromoutstrIppIngoxygendelIvery.ThatjudgmentIsbased
onanunderstandIngofthephysIologIcmechanIsmsthatcompensateforanemIaandthe
lImItsofthosemechanIsms.
TheF8CtransfusIontrIggerformostpatIentswIlllIebetweenhemoglobInvaluesof7and
10g/dL.
Table 16-7 Conditions that May Decrease Tolerance for Anemia and
Influence the Red Blood Cell Transfusion Threshold
ncreasedoxygendemand
HyperthermIa
HyperthyroIdIsm
SepsIs
Pregnancy
LImItedabIlItytoIncreasecardIacoutput
CoronaryarterydIsease
|yocardIaldysfunctIon(InfarctIon,cardIomyopathy)
AdrenergIcblockade
nabIlItytoredIstrIbutecardIacoutput
LowS7Fstates
SepsIs
PostcardIopulmonarybypass
DcclusIvevasculardIsease(cerebral,coronary)
LeftshIftoftheD
2
Hbcurve
AlkalosIs
HypothermIa
AbnormalhemoglobIns
PresenceofrecentlytransfusedHb(decreased2,J0PC)
HbS(sIcklecelldIsease)
a
AcuteanemIa(lImIted2,J0PCcompensatIon)
mpaIredoxygenatIon
PulmonarydIsease
HIghaltItude
DngoIngorImmInentbloodloss
TraumatIc/surgIcalbleedIng
PlacentaprevIaoraccreta,abruptIon,uterIneatony
ClInIcalcoagulopathy
S7F,systemIcvascularresIstance;D
2
Hb,oxygenhemoglobIn;2,J0PC,2,J
dIphosphoglycerate.
a
TotalHbshouldnotbeIncreasedto10g/dLunlessHbSJ0.
7J
P.J79
Compensatory Mechanisms During Anemia
WhenanemIadevelops,butbloodvolumeIsmaIntaIned(IsovolemIchemodIlutIon),four
compensatorymechanIsmsservetomaIntaInoxygendelIvery:(1)anIncreaseIncardIac
output,(2)aredIstrIbutIonofbloodflowtoorganswIthgreateroxygenrequIrements,(J)
IncreasesIntheextractIonratIosofsomevascularbeds,and(4)alteratIonofoxygenHb
bIndIngtoallowtheHbtodelIveroxygenatloweroxygentensIons.
1. ncreasedcardIacoutput.
WIthIsovolemIchemodIlutIon,cardIacoutputIncreasesprImarIlybecauseofanIncrease
InstrokevolumebroughtaboutbyreductIonsInsystemIcvascularresIstance(S7F).The
twoprIncIpaldetermInantsofS7FarevasculartoneandbloodvIscosIty.
74
AsHct
decreases,reductIonofbloodvIscosItydecreasesS7F.ThIsdecreaseInS7FIncreases
strokevolumeandconsequentlycardIacoutputandbloodflowtothetIssues.Dvera
wIderangeofHcts,IsovolemIchemodIlutIonIsselfcorrectIng.LIneardecreasesInthe
oxygencarryIngcapacItyofthebloodarematchedbyImprovementsInoxygentransport.
8ecauseoxygentransportIsoptImalatHctsofJ0,oxygendelIverymayremaInconstant
betweentheHctsof45andJ0.
74
FurtherreductIonsInHctareaccompanIedby
IncreasesIncardIacoutput,whIchreach180ofcontrolastheHctapproaches20.The
exactHbvalueatwhIchcardIacoutputrIsesvarIesamongIndIvIdualsandIsInfluenced
byageandwhethertheanemIaIsacuteordevelopsslowly.
2. FedIstrIbutIonofcardIacoutput.
WIthIsovolemIchemodIlutIon,bloodflowtothetIssuesIncreases,butthIsIncreasedflow
IsnotdIstrIbutedequallytoalltIssuebeds.DrganswIthhIgherextractIonratIos(braIn
andheart)receIvedIsproportIonatelymoreoftheIncreaseInbloodflowthanorgans
wIthlowextractIonratIos(muscle,skIn,vIscera).8ecausebasalextractIonratIo(EF)Is
alreadyhIghInthecoronarycIrculatIon(seenextparagraph),Increasedflowmustbethe
prIncIpalmeansbywhIchthehealthyheartcompensatesforanemIa.
74
Coronaryblood
flowcanIncreasebyasmuchas500.
75
WhentheheartcanachIevenofurtherIncrease
IncardIacoutputandcoronarybloodflow,thelImItsofIsovolemIchemodIlutIonhave
beenreached.Thereafter,furtherdecreasesInoxygendelIverywIllresultInmyocardIal
Injury.AcuteIsovolemIcHbreductIonsto5g/dLcanoccurwIthoutImpaIrmentoftotal
bodyoxygendelIveryInhealthy,otherwIseunstressedadults.
76
However,Inthesame
experImentalparadIgm(acuteIsovolemIcreductIon),reversIbleImpaIrmentofcognItIve
functIonoccurredwhenHbconcentratIonsfellbelow7.0g/dL.
77
ThelatterobservatIon
servesasaremInderthatmeasuresofglobaloxygendelIverymayconcealcrItIcal
occurrencesInIndIvIdualcIrculatorybeds.
J. ncreasedoxygenextractIon.
ncreasIngoxygenEFIsacrItIcalcompensatorymechanIsmwhenHctdropsbelow25.As
IsovolemIcHctdecreasesto15,thewholebodyoxygenEFIncreasesfromJ8to60,
andthemIxedvenousoxygensaturatIondecreasesfrom70to50orless.
68
Someorgans
(braInandheart)alreadyhavehIghEFsunderbasalcondItIons,andhavealImIted
capacItytofurtherIncreaseoxygendelIverybythIsmechanIsm.Theheart,underbasal
condItIons,extractsbetween55and70oftheoxygendelIvered.
78,79
ThebraIn'sEFIsJ0
toJ5.ThIscontrastswIthEFsof7toJ0,InmostothertIssues.nclInIcalpractIce,the
measurementoftheEFsofIndIvIdualorgansIsusuallynotfeasIble.8ecausetheheart
hasthehIghestEF,ItIscommonlysaIdtobetheorganatgreatestrIskundercondItIons
ofIsovolemIcanemIa(althoughtheworkofWeIskopfetal.
76,77
cItedIntheprevIous
paragrapharguesthatItmayInfactbethebraIn).
4. ChangesInoxygenhemoglobInaffInIty.
ThesIgmoIdD
2
HbdIssocIatIoncurvedescrIbestherelatIonshIpbetweenthepartIal
pressureofoxygen(PD
2
)InthebloodandthepercentagesaturatIonoftheHbmolecule
(seeChapter11).TheP50,thePD
2
atwhIchtheHbmoleculeIs50saturatedwIth
oxygenatJ7`CandapHof7.4,Is27mmHg.WhenthecurveIsshIftedtotheleft
(hypothermIa,alkalosIs),theP50Isreduced.TheHbmoleculeIsmorestIngyand
requIreslowerPD
2
toreleaseoxygentothetIssues;thatIs,theHbmoleculedoesnot
release50ofItsoxygenuntIlanambIentPD
2
27mmHgIsreached.ThIsmayImpaIr
tIssueoxygenatIon.FIghtshIftIngofthecurve(Increasedtemperature,acIdosIs)results
InanIncreaseofP50,decreasedHbaffInItyfortheoxygenmoleculesandreleaseof
oxygentotIssuesathIgherpartIalpressuresofoxygen.
WhenanemIadevelopsslowly,theaffInItyofHbforoxygenmaybedecreased,thatIs,
thecurveIsrIghtshIftedasaresultoftheaccumulatIonof2,J0PCInF8Cs.SynthesIsof
supranormallevelsof2,J0PCbegInsataHbof9g/dL.StoredF8Csbecomedepletedof
2,J0PC.TemperaturereductIonandstoragerelatedpHdecreasesalsoreducetheP
50
of
storedblood.Thesechanges,however,arereversedInvIvo,buttheresynthesIsof2,J
0PCbyF8CswIllrequIrefrom12to24hours.
Isovolemic Anemia Versus Acute Blood Loss
AlthoughthesamecompensatorymechanIsmsareoperatIveInacuteandchronIcanemIas,
theyhavedIfferentdegreesofImportanceandoccuratdIfferentHbconcentratIons.n
chronIcallyanemIcpatIents,theaccumulatIonof2,J0PCIntheF8Cs,therebyIncreasIng
theP
50
ofHb,IstheImportantfIrstmechanIsmforcompensatIon.CardIacoutputIncreases
asHbdecreasestoapproxImately7to8g/dL.WIthacutebloodloss,vasoconstrIctIon
occursandcardIacoutputdoesnotIncrease.FedIstrIbutIonandIncreasedextractIonare
thecompensatorymechanIsms.
Platelets
WhIlepublIshedguIdelInesforplateletadmInIstratIonareavaIlable,thereIsonceagaIna
substantIalrequIrementforclInIcIanjudgment.TheIndIcatIonsforplateletadmInIstratIon
presentedInTable168areanamalgamofrecommendatIonspresentedbytheASAIn1996
and2006,the8rItIshCommItteeforStandardsInHaematologyIn200Jand2006,andthe
FrenchSafetyAgencyforHealthProductsIn200J.
27,72,80,81,82
Table168makesItapparentthattheplateletadmInIstratIonthresholdsthatwIllmost
oftenberelevanttoanesthesIologIstswIlllIebetween50,000and100,000/uL.
8J,84
The
thresholdwIthInthatrangeatwhIchplateletsareadmInIsteredshouldbebasedonthe
lIkelIhoodoftheIntendedproceduretocausebleedIng,thehazardofbleedIngshouldIt
occur(e.g.,IntracranIalneurosurgeryperIpheralorthopaedIcs),andthepresenceor
possIbIlItyofaddItIonalcausesofcoagulatIondIsturbance(e.g.,recentadmInIstratIonof
antIplateletagents,CP8,0C,dIlutIonduetolargevolumeadmInIstratIon).8leedIng
manIfestatIonscanvarysubstantIallyfrompatIenttopatIentInthefaceofsImIlarplatelet
counts.ThIsoccursbecausesomeplateletsaremoreeffectIvethanothers.When
thrombocytopenIaresultsfromperIpheraldestructIonofplatelets,thebonemarrow
contInuestoproducenormal,young,largeplateletsthatarehemostatIcallyveryeffectIve.
ApatIentwIththeseplateletsmayhavemoreeffectIveprImaryhemostasIsthanapatIent
wIththesameplateletcountbutwhoseplateletswereproducedbyalessactIve,less
healthybonemarrow.
P.J80
Table 16-8 Indications, Expressed as Platelet Count Thresholds or Target
Levels, Commonly Warranting the Administration of Platelets
NonbleedIngpatIentswIthoutotherabnormalItIesofhemostasIs
25
10,000/L
Lumbarpuncture,epIduralanesthesIa,
a
centrallIneplacement,
endoscopywIthbIopsy,lIverbIopsyorlaparotomyInpatIents
wIthoutotherabnormalItIesofhemostasIs,vagInaldelIvery
50,000/L
TomaIntaInplateletcountdurIngongoIngbleedIngandtransfusIon
notlessthan
50,000/L
TomaIntaInplateletcountdurIng0CwIthongoIngbleedIngnot
lessthan
50,000/L
TomaIntaInplateletsdurIngmanagementofmassIvebloodloss 75,000/L
ntendedproceduresInwhIchclosedcavItybleedIngmIghtbe
especIallyhazardous(e.g.,neurosurgery)
100,000/L
|IcrovascularbleedIngattrIbutedtoplateletdysfunctIonsuchas
uremIa,
b
postcardIopulmonarybypass,orInassocIatIonwIth
massIvetransfusIon.
ClInIcIan
judgment
0C,dIssemInatedIntravascularcoagulatIon.
a
TheFrenchSafetyAgencyforHealthProductsrecommends50,000/LforspInal
and80,000/LforepIduralanesthesIa.
82
b
AfteratrIalof00A7P,IfpermIttedbytheclInIcalsItuatIon.
8J
,
84
PlateletadmInIstratIonthresholdsrelevanttoanesthesIologIstswIlllIeusuallybetween
50,000and100,000/L.
AplateletconcentratederIvedfromasIngleunItofdonorbloodwIllIncreasetheplatelet
countofa70kgrecIpIentby5,000to10,000/L.However,themajorItyofplatelets(70)
arenowobtaInedbyapheresIs(seeCollectIonandPreparatIonof8loodProducts).Dne
apheresIsunItwIllIncreaseplateletcountbyJ0,000to60,000/L.AcommonpractIceIsto
admInIstereItheroneunItofapheresIsplateletstoanadultoroneunItofplatelet
concentrate/10kgofbodyweIght.TheIncreaseInplateletcountmustbeverIfIedby
plateletcount,especIallyInpatIentswhomayhavebeenalloImmunIzedbyfrequent
plateletadmInIstratIon.
Fresh-Frozen Plasma
nspIteofthefactthatover2,000,000unItsofFFPareadmInIsteredannuallyIntheUnIted
States,thereIsremarkablylIttlesystematIcallyderIvedevIdenceofeffIcacy.
85
Nonetheless,theuseofFFPtorestorecoagulatIonfactorlevelsIsInevItablyvalIdInmany
clInIcalcIrcumstances.TheIndIcatIonsforFFPadmInIstratIonpresentedInTable169are
anamalgamofrecommendatIonspresentedbytheASAIn1996and2006,andthe8rItIsh
CommItteeforStandardsInHaematologyIn2004.
72,80,86
EffectIvecoagulatIoncanusually
occurwIthclottIngfactorlevelsof20toJ0ofnormal.LevelsthatareJ0ofnormalcan
usuallybeachIevedbyadmInIstratIonof10to15mL/kgofFFP.
80
Fresh-Frozen Plasma/Thawed Plasma in Trauma Resuscitation
tIsthetradItIonaldogmathatadmInIstratIonofbloodproducts,InpartIcularFFPand
platelets,shouldnotbeformuladrIven,butshouldoccurInresponsetoaclInIcal
coagulopathy,IdeallywIthlaboratorydemonstratIonofabnormalIty.However,thereIsan
evolvIngsentImentIntheareaoftraumaresuscItatIonthatthIsapproachresultsInfallIng
behIndInthestruggleagaInstthetIghtenIngspIralofbleedIng,hypotensIon,stasIs,
acIdosIs,hypothermIa,and0C
87,88,89
(seeChapterJ6).8ecauseoftheveryhIghIncIdence
ofcoagulopathyInmultIpletraumavIctIms,
87,88,90
empIrIcapproachesthatInvolvethe
oncetabooformulas(e.g.,twounItsofFFPor
P.J81
thawedplasma[TP;seelaterfordescrIptIonofTP]wItheveryfIveunItsofPF8C)when
massIvetransfusIonIsantIcIpatedorongoIngarealreadyInroutIneuse.
87,88,91
AnF8Cto
plasmaratIoof1:1hasbeenadvocatedandreportedeffectIveInmIlItarytrauma.
89
FormuladrIvenadmInIstratIonofplateletsIsalsooccurrIng.However,platelet
admInIstratIonmaybelessurgentbecause,asHoandcolleagues
88
haveobserved,
thrombocytopenIaIsnotacentralelementoftheInsIdIousspIraljustmentIoned,andIt
maybeeasIertocatchupfromtheconsequencesofalowplateletcountthanfrom
coagulopathydrIvenbleedIngandtheassocIatedhypovolemIa.
Table 16-9 Indications for the Administration of Fresh-Frozen Plasma
CorrectIonofmultIplecoagulatIonfactordefIcIencIes(e.g.,0C)wIthevIdence
ofmIcrovascularbleedIngandPTand/oraPTT1.5tImesnormal
CorrectIonofmIcrovascularbleedIngdurIngmassIvetransfusIon(morethanone
bloodvolume)whenPT/aPTTcannotbeobtaInedInatImelymanner
UrgentreversalofwarfarIntherapy
a
HeparInresIstance(antIthrombIn[AT]defIcIency)InapatIentrequIrIng
heparInwhenATconcentrateIsnotavaIlable
ThrombotIcthrombocytopenIcpurpuraorhemolytIcuremIcsyndrome
CorrectIonofsInglecoagulatIonfactordefIcIencIesforwhIchspecIfIc
concentratesarenotavaIlable(prIncIpallyfactor7)
:Formulamanagementoftrauma/massIvebloodloss(seetext)
0C,dIssemInatedIntravascularcoagulatIon;PT,prothrombIntIme;aPTT,
actIvatedpartIalthromboplastIntIme.
a
ProthrombIncomplexconcentrate(,7,X,X)IsanalternatIvethathasbeen
reportedtobemoreeffectIvethanfreshfrozenplasma.
Table 16-10 Indications for the Administration of Cryoprecipitate
|IcrovascularbleedIngwhenthereIsadIsproportIonatedecreaseInfIbrInogen,
suchas0CandverymassIvetransfusIon,
a
wIthfIbrInogen80100mg/dL(or
assayresultnotavaIlable)
FIbrInsealant(IfvIrusInactIvatedconcentrateIsunavaIlable)
8leedIngduetouremIathatIsunresponsIveto00A7P
ProphylaxIsbeforesurgeryortreatmentofbleedIngInhemophIlIaAandvW0(If
vIrusInactIvatedconcentratesareunavaIlableorIneffectIve)
ProphylaxIsbeforesurgeryortreatmentofbleedIngInpatIentswIthcongenItal
dysfIbrInogenemIas
FXdefIcIency
0C,dIssemInatedIntravascularcoagulatIon;vW0,vonWIllebranddIsease.
a
FreshfrozenplasmaIsthefIrstlInecomponentforthefactordepletIon
assocIatedwIthmassIvetransfusIon.
NormalcoagulatIoncanbeachIevedwIthclottIngfactorlevelsof20toJ0ofnormal.
ThoselevelscanusuallybeachIevedbyadmInIstratIonof10to15mL/kgofFFP.
Cryoprecipitate
CryoprecIpItatecontaInsfactor7,thevonWIllebrandfactor(vWF),fIbrInogen,
fIbronectIn,andfactorX.7IrallyInactIvatedfactor7concentrates,someofwhIch
contaInclInIcallyeffectIveconcentratIonsofvWF(e.g.,HaemateP,Alphanate)arenow
avaIlable.Asaresult,hemophIlIaAandvonWIllebranddIsease(vW0)areusuallytreated
(InconsultatIonwIthahematologIst)wIththoseconcentrates
92
ratherthan
cryoprecIpItate,whIchIsnowgenerallyusedforfIbrInogendefIcIentstates.TheremaInIng
IndIcatIonsforcryoprecIpItatearepresentedInTable1610.
Blood Conservation Strategies
8ecauseofthemanyhazardsofbloodproductadmInIstratIon,numeroustechnIquesand
alternatIveshavebeenexplored(Table1611).
Autologous Donation
PreoperatIvedonatIonandperIoperatIvesalvageofautologousbloodhavebeenused
extensIvelyaspartofprogramstoreduceallogeneIcbloodadmInIstratIon.Autologous
bloodmaybecollecteddaystoweeksprIortosurgery(predonatIon);Itmaybecollected
ImmedIatelyprIortosurgery(IsovolemIchemodIlutIon);orItmaybesalvagedfromthe
surgIcalfIeldorwounddraInsandreInfused(bloodsalvage).nspIteofthedemonstratIon
ofmodesteffIcacy,
9J
enthusIasmformanyoftheseapproacheshasdeclInedparIpassuwIth
theprogressIvereductIonoftherIskoftransfusIontransmIttedInfectIons.
Table 16-11 Blood Conservation Techniques
PreoperatIveautologousdonatIon
AcutenormovolemIchemodIlutIon
ntraoperatIvebloodsalvage
PostoperatIvebloodsalvage
PharmacologIcagents
ErythropoIetIn
8loodsubstItutes(hemoglobInandnonhemoglobInbased)
00A7P
AntIfIbrInolytIcs
Preoperative Autologous Donation
PreoperatIvedonatIonofautologousblood(PA0)hasbeenapplIedprIncIpallyInpatIents
undergoIngmajororthopaedIcprocedures(totalhIpandkneereplacement,scolIosIs
procedures)andprostatIcandcardIacsurgery.However,wIthlImItedexceptIon,
94
the
systematIcexperIencehasgenerallyfaIledtodemonstrateareductIonInallogeneIcblood
exposure.
95
EffectIvenesshasprobablybeenlImItedbecausethepatIents'erythropoIetIc
responseIsoftennotvIgorous,InwhIchcasetheprocessmaysImplyresultInananemIaat
thetImeofsurgery.Furthermore,thePA0procedureIsmoreexpensIvethanthecollectIon
ofallogeneIcblood,andIfautologousbloodIsnottransfusedItIsusuallydIscarded.The
wastageratewas59In2004.
1
NotealsothatthetransfusIonofautologousblooddoesnot
elImInatethechanceofhumanerrordurIngbloodcollectIon,processIng,andreInfusIonor
therIskofbacterIalcontamInatIonortheadverseeffectsofthestoragelesIon(bIoactIve
lIpIds,cytokInes).TheuseofPA0hasdecreasedsubstantIallysIncetheInItIalenthusIasm
forthetechnIque.
95,96,97
PA0nonethelessmaybeausefulalternatIveInalloImmunIzed
patIentsforwhomcompatIbleallogeneIcbloodIsdIffIculttoobtaIn.
ThemedIcalcondItIonofthepatIentmustbeconsIderedprIortorecommendIngPA0.
SevereaortIcstenosIs,sIgnIfIcantcoronarydIseaseormyocardIaldysfunctIon,lowInItIal
Hctandbloodvolume(bodyweIght50kg)arerelatIvecontraIndIcatIonstoPA0.fthe
patIent'sHblevel,cardIacstatus,andgeneralcondItIonpermIt,bloodcanbedonatedat
weeklyIntervalsprIortosurgery.FourunItsIstypIcallythemaxImumdonatIonbecauseof
theshelflIfeofthefIrstunItcollected.PatIentsmakIngPA0shouldreceIvesupplemental
Iron(e.g.,2mg/kg/dayforJweeks).naddItIon,PA0canbesupplementedwIth
admInIstratIonofrecombInanterythropoIetIn(Epo).
Erythropoietin
TheeffectIvenessofEpoInhastenIngrecoveryofHctInconjunctIonwIthPA0andIn
ImprovIngHctInpatIentsnotsubmIttedtoPA0hasbeen
demonstrated.
98,99,100,101,102,10J,104
However,thepractIcehasnotbecomewIdespreadIn
partbecauseoftheexpenseoftheagentandInpartbecauseofthenecessItyforfrequent
(e.g.,weeklyInjectIonsforJweeksandtwoaddItIonalInjectIonsInthefInalweek)
parenteral(subcutaneousorIntravenous)admInIstratIon.AdmInIstratIonofEpoto
P.J82
presurgIcalpatIentshasresultedInreductIonInallogeneIcbloodadmInIstratIon,
105
and
selectIveadmInIstratIontoanemIcpatIentshasbeenmoreobvIouslyeffectIve
106,107
than
hasadmInIstratIontoallcomers.
108,109
Epo,arecombInantproduct,Isoftenacceptedby
Jehovah'sWItnesses,andItseffIcacyInthatpopulatIonhasbeendemonstrated.
110,111
The
demonstratIonofthereductIonbyEpooftransfusIonrequIrementsIncrItIcallyIll
patIents
112
mayIncreaseawarenessandencourageItssystematIcuseInanemIcelectIve
surgIcalpatIents.ErythropoIetIcagentswIthlongerhalflIves(e.g.,darbepoetInalpha)are
underdevelopmentandmayservetoovercomeoneofthelogIstIclImItatIons(frequent
parenteraladmInIstratIon)tothepreoperatIveuseofEpo.
11J
Acute Normovolemic Hemodilution
AcutenormovolemIchemodIlutIon(ANH)entaIlswIthdrawalofthepatIent'sbloodearlyIn
theIntraoperatIveperIodwIthsImultaneousadmInIstratIonofcrystalloIdsorcolloIdsto
maIntaInnormovolemIa.TheratIonaleIsthatdurIngtheensuIngsurgery,thepatIentwIll
losebloodoflowHct,andthewIthdrawnbloodwIllbeavaIlableforreInfusIonattheend
oftheoperatIon.TheendpoIntfortheInItIalwIthdrawalIsaHctof27toJJ,dependIng
onthepatIent'scardIovascularandrespIratoryreserve.SelectIonforthIstechnIqueshould
relyoncarefulevaluatIonofthepatIentforcoronaryorcerebralvasculardIsease.ANH
evolvedIntheantIcIpatIonthatItwouldreducetotalredcelllossandallogeneIcblood
admInIstratIon.However,bothmathematIcalmodelIngandempIrIcexperIencehave
revealedonlyamodestbenefIt.
114
8ywayofexample,Coodnough
115
calculatedthat,Ina
100kgpatIentfromwhomthreeunItsofbloodIswIthdrawnandreplacedbyasanguInous
fluId,IfthesubsequentbloodlossIs2,800mL,215mLofF8Cs(aboutoneunIt)wIllbe
saved.ForpatIentsoflImItedbodysIze,lowstartIngHct,orbloodloss70ofoneblood
volume,
116
avoIdanceofallogeneIcbloodmIghtbedIffIculttoachIeve.Arecentmeta
analysIsreportedthatANHdoesnotachIevecompleteavoIdanceofallogeneIcblood,but
thatwhentransfusIonIsnecessarytheamounttransfusedIsreducedbyonetotwounIts
perpatIent.TheauthorsconcludedthatwIdespreadadoptIonofANHcannotbe
encouraged.
114
Nonetheless,therearereportsoffavorableexperIencesInlIverresectIon,
prostatectomy,totalhIparthroplasty,andabdomInalaortIcsurgery.
101,117,118,119,120
tIs
possIblethatInthefuturetheeffIcacyofANHwIllbeenhancedbyadmInIstratIonof
preoperatIveerythropoIetIcsand/orbytheuseofeItherHbbasedoxygencarryIng
compoundsorperfluorocarbonemulsIonstopermItwIthdrawaloflargervolumesofblood.
ANHhasalsobeenemployedforthepurposeofmakIngfreshautologousbloodavaIlableat
theendofproceduresInwhIcheItheradIlutIonalorCP8relatedcoagulopathymayoccur.
TheeffIcacyInthIscontexthasnotbeenconfIrmedbysystematIcstudy.8loodcollected
andreInfusedforthIspurposeshouldnotbepassedthrougha40mIcronfIlterInorderto
avoIdplateletelImInatIon.
Perioperative Blood Salvage
PerIoperatIvebloodsalvagereferstotherecoveryofshedbloodfromthesurgIcalfIeldor
wounddraInsandreadmInIstratIontothepatIent.nmostInstances,theprocessInvolves
washIngofthesalvagedmaterIalwIthreturnofonlytheF8Ccomponentofblood.n
someInstances,usuallythoseInvolvIngwounddraInage,bloodIsreturnedfIlteredbut
otherwIseunprocessed.
Intraoperative Blood Salvage
ntraoperatIvebloodsalvage(8S)IsemployedwIthmanysurgIcalproceduresthathavethe
potentIaltorequIreallogeneIctransfusIon.ContemporarycellsalvagedevIces
antIcoagulatethesalvagedbloodasItleavesthesurgIcalfIeld,separatetheF8Csfrom
otherlIquIdandcellularelementsbycentrIfugatIon,andthenwashthesalvagedF8Cs
extensIvelywIthsalIne.TheF8CsaretypIcallyreturnedtothepatIentsuspendedInsalIne
InalIquotsof125or225mLwIthaHctof45to65.
121
HIgherHctscanbeachIevedatthe
expenseoftheaddItIonaltImerequIredforslowerfIllIngofthecentrIfugechamber.
8ShasbeenusedcommonlydurIngcardIovascularsurgIcalprocedures,aortIc
reconstructIon,spInalInstrumentatIon,joIntarthroplasty,lIvertransplantatIon,resectIon
ofarterIovenousmalformatIons,
122
andoccasIonallyInthemanagementoftrauma
patIents.
12J
TherehavebeennumerousdemonstratIonsthat8Scanreducetotalbloodloss
and/ortheuseofallogeneIcF8Cs.
124,125,126
ThepresenceofInfectIon,malIgnantcells,
urIne,bowelcontents,andamnIotIcfluIdIntheoperatIvefIeldhavebeenvIewedas
contraIndIcatIons.However,althoughmalIgnantcellsareknowntoberetaInedwIthF8Cs
afterthewashIngprocess,8ShasbeenapplIedInthemanagementofhepatIcandurologIc
malIgnancIeswIthoutevIdenceofmetastasIs.
127,128
Atleastone8SwashIngdevIcehas
alsobeenshowntoremovethecrItIcalprocoagulantfactorspresentInamnIotIcfluId
129
and8ShasbeenemployedsuccessfullyIncesareansectIon.
1J0
However,thesafetyof8S
useInthatcontextIsunconfIrmedandshouldnotberoutIne.
1J1
ThepotentIalcomplIcatIonsof8SarelargelyafunctIonofthereInfusIonofmaterIalsthat
mIghtremaInafterthewashIngprocess.TheseIncludefat,mIcroaggregatessuchas
plateletsandleukocytes,aIr,redcellstroma,freeHb,heparIn,bacterIa,anddebrIsfrom
thesurgIcalfIeld.|ostoftheseareremovedquIteeffIcIentlybycontemporarycellsalvage
equIpment.8acterIaaretheexceptIon,andcontamInatIonofcellsalvagereturnwIthskIn
organIsmsIsrelatIvelycommon.
124
LeukocytereductIonfIltershavebeenshowntoremove
mostbacterIa
1J2
andmayberelevanttotheuseof8SIntraumaandcesareansectIon.
|assIveaIrembolIsmhasoccurredasaresultofusererror.0Irectreturnfromthecell
salvageapparatushasnowbeenlargelyabandonedInfavorofreturnvIaanIntermedIary
bagunderthecontroloftheanesthesIologIst.CareshouldstIllbetakenIntheeventthat
pressureInfuserdevIcesareapplIedtothesebags.
AdIlutIonalcoagulopathyInassocIatIonwIthlargevolume8SIstobeexpectedbecause
essentIallyallclottIngfactorsandmostplateletsareremovedbythewashIngprocess.A
0ClIkecoagulopathywasonceassocIatedwIth8S;however,ItseemslIkelythatthIs
syndromewastheresultofInadequatepreparatIonofbloodbyoldercellsalvagedevIces.
Unwashed,salvagedbloodhasbeenshowntocontaInnumerousconstItuentsthatInfluence
thecoagulatIonprocess:thromboplastIcmaterIal,InterleukIns,complement,fIbrIn
degradatIonproducts,andfactorsreleasedfromactIvatedleukocytesandplatelets
122
and
toactIvatethecoagulatIonprocessInrecIpIents.
1JJ
ThemajorItyofthesearequIte
effIcIentlyremovedbycontemporary8SprocessIngdevIces.However,theIrpresenceIs
usedasanargumentagaInstthereturnofunprocessedbloodfromwounddraIns(see
PostoperatIve8loodSalvage).
1J4
SImIlarelements,IncludInglIpIdsandcytokInes,In
bloodshedIntothemedIastInumdurIngCP8aresuspectedofcontrIbutIngtopostprocedure
morbIdIty,IncludIngcognItIvedysfunctIon.
1J5
AccordIngly,ItIsanIncreasInglycommon
practIcetoreturnmedIastInalbloodtothepatIentvIa8SdevIcesratherthantheCP8
reservoIr.
AnaddItIonalcoagulopathyrIskarIseswIththeuseofthrombInandmIcrofIbrIllarcollagen
orcelluloseproductsIn
P.J8J
thesurgIcalfIeld.
1J6
TheseagentsarenotrelIablyremovedbythewashIngprocess,and
suctIonIngofbloodIntothe8SdevIceshouldbedIscontInueddurIngtheuseofthese
agentsandresumedafterthefIeldhasbeenIrrIgated.
TheclInIcIanshouldapprecIatethattheeffIcIencyoftherecoveryofshedF8Csbythe8S
processIsontheorderof50.AllogeneIcbloodwIllthereforefrequentlybenecessaryIn
spIteofthe8S,andbloodandfluIdreplacementcalculatIonsshouldtakethIsInto
account.
1J7,1J8
TheeffIcIencyofF8CrecoveryIsImprovedbypromptrecoveryofblood
fromthesurgIcalfIeld(I.e.,beforeclottIngoccurs)bylImItIngthenegatIvepressureused,
andbymInImIzIngthemechanIcalaIrbloodInterfacedurIngsuctIonIng.
1J9
Postoperative Blood Salvage
PostoperatIverecoveryofbloodfrommedIastInalchesttubesandwounddraInsafterhIp
andkneereplacementwIthImmedIatereInfusIonoftheunwashedbloodhasbeen
employedquItecommonly.ThemanysubstancespresentIntheunprocessedblood(see
prevIoussectIon)suggestthatcoagulatIondysfunctIonmIghtresult,andmanyareskeptIcal
regardIngthewIsdomofthIspractIce
121,1J4
(wIthoneedItorIalIstgoIngsofarasto
characterIzethetechnIqueasrepugnant
140
).However,therehavebeenseveralreports
ofeffIcacyInreducIngallogeneIcbloodexposurewIthoutapparentadverse
effects,
141,142,14J
andonlyoccasIonalreportsofapparentadverseconsequences.
144
ThIs
mayreflectthefactthatthereInfusedvolumesareusuallysmall.
Hemoglobin-Based Oxygen-Carrying Solutions
HemoglobInbasedoxygencarryIngsolutIonswouldoffernumerousadvantages:longshelf
lIve,mInImalInfectIonhazard,absenceofalloImmunIzatIon,ImmedIateavaIlabIlIty(no
typIng),lIttlelIkelIhoodofTF|,andnostoragelesIon/Inflammatoryresponse.However,
whIlenumerouspolymerIzedHbproductshavebeenstudIed,onlyone,Hemopure(8Iopure
ncEvanstonL),Isapprovedforhumanuse(InSouthAfrIca)andonlyone,PolyHeme
(NorthfIeldLaboratorIesCambrIdge,|A)IscurrentlyInphasetrIalIntheUnIted
States.
145
DneaddItIonalproductIsatthephasetrIalstage(Hemospan,Sangart,San
0Iego,CA).ThemanyproductsstudIedhaveusedbovIne,outdatedhuman,orrecombInant
HbthathasbeenentIrelyseparatedfromredcellmembranes(stroma)andpolymerIzedto
IncreasehalflIfe.TheInItIaldIffIcultIeswIthrenalfaIlurecausedbyresIdualstromaand
excessIvefreeHbhavebeenovercome.However,thereareseveralremaInIngdIffIcultIes
wIthwhIchclInIcIanswIllprobablyhavetocontendIncludIngmethemoglobInemIa,
InterferencewIthsomecalorImetrIcallybasedlaboratoryassays(IncludIngcreatInIne,total
bIlIrubIn,andlactatedehydrogenase),somedegreeofvasoconstrIctIoncausedbynItrIc
oxIdebIndIngbyfreeHb,andarelatIvelyshorthalflIfe.ThenItrIcoxIdeeffectIsprobably
thebasIsforthefaIlureoftheseveralproductsthathavebeenwIthdrawnfromclInIcal
trIals.PolymerIzatIonIncreaseshalflIfeto18toJ6hoursbutthatperIodIssuffIcIently
shortsuchthatoxygencarryIngcapacItywIllusuallybecomeInadequatebeforenatIve
retIculocytosIscancompensate.
146
PerfluorocarbonemulsIons
146
appeartobefurtherfrom
potentIalclInIcalapplIcatIonthanhemoglobInbasedoxygencarryIngsolutIonsandwIllnot
bedIscussedhere.
Jehovah's Witnesses
ngeneral,onthebasIsofNewTestamentadmonItIons(Acts15:20,29),Jehovah's
WItnesseswIllacceptneItheradmInIstratIonofmostallogeneIcbloodproductsnorthe
readmInIstratIonofautologousproductsthathaveleftthecIrculatIon.AccordIngtoa
recentJehovah'sWItnesspublIcatIon,theyrejectalltransfusIonsInvolvIngwholebloodor
thefourprImarycomponentsredcells,plasma,whItecells,andplatelets.Asforthe
varIousfractIons,derIvedfromthosecomponentsandproductsthatcontaInsuchfractIons
the8Ibledoesnotcommentonthese.ThereforeeachWItnessmakeshIsownpersonal
decIsIononsuchmatters.
147
AccordIngly,thewIshesofeachpatIentmustbeclarIfIed
carefully.FewwIllpermIttheadmInIstratIonofPF8Cs,FFP,platelets,orgranulocytes,but
othercomponentsandfractIonsmaybeacceptable.ThemajorItywIlldeclInePA0.
However,manywIllacceptproceduresthatmaIntaInextracorporealbloodIncontInuIty
wIththecIrculatIon.TheacceptabIlItyofCP8,acutenormovolemIchemodIlutIon,and
perIoperatIvecellsalvagemustbeclarIfIedwItheachpatIentIndIvIdually.|ostwIll
permItadmInIstratIonofEpo.
Collection and Preparation of Blood Products for Transfusion
Red Blood Cells
WholebloodIsfIrstcollectedInbagscontaInIngCP0AorCP0solutIon.ThecItratechelates
thecalcIumpresentInbloodandpreventscoagulatIon.SequentIalcentrIfugatIonat
varIousspInspeedsandduratIonsIsusedtoseparatewholebloodIntocomponents
IncludIngPF8Cs,plateletconcentrates,cryoprecIpItate,andcellfreeplasma.Thetwo
commonPF8CpreparatIonsultImatelydelIveredtotheclInIcIanhaveeItherCP0Aorso
calledaddItIvesolutIonasthepreservatIve.CP0AbloodhasanHctofabout70to75,
contaIns50to70mLofresIdualplasmaInatotalvolumeof250to275mL,andhasashelf
lIfeofJ5days.WIththeaddItIvesolutIonpreparatIon,theorIgInalpreservatIveandmost
oftheplasma(10to15mLremaIns)IsremovedandreplacedwIth100mLofaddItIve
solutIon.ThIsresultsInalowerHct(60)Inatotalvolumeof250toJ50mL,lesscItrate
perunIt,75to80fewermIcroaggregates,andalongershelflIfe(42days).AddItIve
solutIonF8Csarethoughttoregenerate2,J0PCmorerapIdly.ThepHandK+contentof
thetwopreparatIonsaresImIlar.ThesmallerplasmavolumeInaddItIvesolutIonblood
resultsInsmalleramountsofcoagulatIonfactorsInPF8CsbutalsoapotentIallylesserrIsk
ofmInorallergIcreactIonsandTFAL(Table162).
TherearealternatIveF8CpreparatIonsthatelImInatethevarIouspassengers.SalIne
washedF8CsmaybeusedforpatIentswhoexperIencereactIonstoforeIgnproteIns.F8Cs
canbefrozenandstoredIndefInItely.PreservatIvestopreventfreezethawassocIated
damagemustbeaddedandsubsequentlyremovedbeforeadmInIstratIon,whIchmustoccur
wIthIn24hoursofthawIng.TheprocessIsexpensIveandthereforenotwIdelyused.
LymphocytescanberenderedIncapableofdIvIsIon(andthereforeunabletoInduceC7H0)
byIrradIatIon.
TheadmInIstratIonofoneunItofPF8CswIllIncreasetheHbandHctofa70kgadultby
approxImately1g/dLandJ,respectIvely.However,boththefreezethawprocessand
washIngtoreduceallergIcreactIonsresultInanF8Cwastageofatleast20.
Compatibility Testing
CompatIbIlItytestIngInvolvesthreeseparateprocedures:A8DFhesusbloodtype
IdentIfIcatIon,antIbodyscreenIngofdonorandrecIpIentplasma,andthedonor/recIpIent
crossmatch.
P.J84
ABO, Rhesus Typing
ThefIrststepIstodetermInetheA8DbloodgrouptypeandtheFhstatusofbothdonorand
recIpIentblood.ThIsIsacrItIcalstepbecausemostofthefatalhemolytIctransfusIon
reactIonsresultfromthetransfusIonofA8DIncompatIbleblood.8loodtypesaredefIned
accordIngtotheantIgenspresentonthesurfaceoftheF8Cs.PatIentswIthtypeAblood
havetypeAantIgensonthesurfaceoftheIrredcells.Type8bloodhas8antIgens.When
bothantIgensarepresentthepatIentIssaIdtohavetypeA8blood,andwhenbothare
lackIngthepatIentIshastypeDblood.8y6to12monthsofage,theserumconstItutIvely
contaInsantIbodIestotheAand8antIgensthatarelackIngontheF8C.PatIentswIthtype
AbloodhaveantIbodIesagaInstthe8antIgenandvIceversa.PatIentswIthnoantIgenson
theIrcells,typeDblood,wIllhavebothantIAandantI8antIbodIesIntheplasma.
PatIentswIththe0antIgenoftheFhesusgroupofantIgensaresaIdtobeFhposItIve.
ApproxImately85ofthepopulatIonIsFhposItIve.ncontrasttotheAand8bloodgroups,
antI0antIbodIesarenotconstItutIvelypresentIntheserumofanFhnegatIvepatIent.
However,60to70ofFhnegatIvepatIentsexposedtodonorFhposItIveF8CswIlldevelop
antI0antIbodIes.ThereIsalatencybeforetheseantIbodIesaresynthesIzed.Asa
consequence,thereactIonbetweentheFhposItIvedonorcellsandtheantI0evolves
slowlyandmaynotbeclInIcallyapparentonfIrstexposure.ThIsprocesswherebyaforeIgn
antIgenstImulatesthesynthesIsofthecorrespondIngantIbodyIstermedalloimmunization.
SubsequentexposureoftheseFhnegatIveIndIvIdualstoFhposItIvecellsmayresultInan
AHTF.
AHTFsaremostoftencausedbyantIbodIesInrecIpIentplasmadIrectedagaInstA,8,or0
antIgensondonorF8Cs.TheantIbodyantIgenInteractIonactIvatescomplementandleads
toIntravascularhemolysIs.DposItIverecIpIents(typeD,Fh[0]posItIve)wIllhaveboth
antIAandantI8antIbodIes,butnottheantI0antIbodyIntheIrplasma.ThesepatIents
mustnotreceIvetypeA,type8,ortypeA8blood.TheymustreceIvetypeDblood,butIt
maybeFhposItIveorFhnegatIve.ncontrast,patIentswIthbloodtypeA8negatIve(type
A8,FhnegatIve)wIlllackboththeAand8antIbodIesIntheIrplasmaandmayormaynot
havetheantI0antIbodyIntheIrplasma.TheycanreceIveA,8,A8,orDblood.
ndIvIdualswIththegreatestnumberofantIgensontheIrF8Cs(I.e.,typeA8posItIve)have
thefewestconstItutIveantIbodIesIntheIrplasmaandcanreceIveallbloodtypes(types
A+,A,8+,8,A8+,A8,D+,andD)andarereferredtoasuniversal recipients.ndIvIduals
wIththefewestantIgensontheIrcells(typeD)havethegreatestnumberofantIbodIesIn
theIrplasma.TypeDnegatIveF8CscanbeadmInIsteredtoallA8D,Fhtypesandthese
IndIvIdualsarereferredtoasuniversal donors.ThedIstrIbutIonofA,8,D,and0
phenotypesIntheU.S.populatIonIspresentedInTable1612.AderIvatIveofthose
dIstrIbutIonsIsthat,assumIngthesamerepresentatIonamongdonorsandrecIpIents(and
theabsenceofsuperImposedalloImmunIzatIonthatwouldcompoundtherIsk),random
admInIstratIonofblood(orrecIpIentIdentIfIcatIonerrors)wIllresultInanAHTFwIthone
ofeverythreePF8CunItsadmInIstered.
Table 16-12 Major Red Blood Cell Surface Antigen Incidence (%) in the U.S.
Population
GROUP WHITES BLACKS
D 45 49
A 40 27
8 11 20
A8 4 4
Fh(0) 85 92
The Antibody Screen
TheantIbodyscreen,anIndIrectCoombstest,IsperformedtoIdentIfyrecIpIentantIbodIes
agaInstF8CantIgens.CommercIallysupplIedF8Cs,selectedforstrongexpressIonof25to
J0potentIallyhemolytIcantIgens,aremIxedwIthrecIpIentserum.Dnlyabout4In1,000
potentIalrecIpIentsdemonstrateunexpectedantIbodIes.ThelIkelIhoodthattheantIbody
screenwIllmIssapotentIallydangerousantIbodyhasbeenestImatedtobemuchlessthan
1In10,000.ftherecIpIentplasmascreenIsposItIve,theantIbodymustbeIdentIfIedand
approprIateantIgennegatIvedonorunItsselected.TheantIbodyscreenIngofrecIpIent
plasmashouldberepeatedatJdayIntervalsIfthepatIentIsreceIvIngongoIngtransfusIon.
The Crossmatch
ThepredIctIvepowerofanegatIveantIbodyscreenIssuchthatmosthospItalsperformno
furthercrossmatchproceduresInpatIentswhohavenohIstoryofantIbodyformatIon.n
InstItutIonswIthvalIdatedbloodbankcomputersystems,elIgIblepatIentsmayreceIve
bloodsolelyonthebasIsofanelectronIc[computerdatabase]crossmatchofthe
recIpIentandtheavaIlableunIts.AlternatIvely,someInstItutIonsperformanImmedIate
spIn(J0secondsatroomtemperature)crossmatchofrecIpIentplasmaanddonorF8Csand
examIneforgrossagglutInatIon,whIchIspredIctIveofA8DIncompatIbIlIty.TherequIsIte
tImeforA8D/FhtypIngandantIbodyscreen,fromsamplearrIvalInthebloodbankto
bloodrelease,IsJ0to45mInuteswhentheantIbodyscreenIsnegatIve.
AformalcrossmatchIsperformedIfanantIbodyIsIdentIfIed,IfthepatIenthasahIstoryof
antIbodyformatIon,orIfthepatIentIsdeemedtobeathIghrIskforalloImmunIzatIon.
Currentprocedures,whIchuseavarIetyofenhancementtechnIques(e.g.,lowIonIc
strengthsolutIons,polyethyleneglycol,gels,orsolIdphasetechnology)allowantIbody
screensand/orcrossmatchestobeaccomplIshedInapproxImately20mInutes.ThevarIous
IncubatIonphasesthatwereonceused,necessItatIng2hoursforacompletecrossmatch,
arenolongerperformedInthemajorItyofInstItutIons.Crossmatchproceduresvary,butat
amInImumwIllentaIlIncubatIonofrecIpIentplasmawIthdonorF8CsatJ7`Cfor10to15
mInutesfollowedbyanIndIrectantIglobulIntestandexamInatIonforagglutInatIon.
npatIentswhohavebeentransfusedprevIouslyorwhomayhavebeenexposedtoforeIgn
F8CantIgensdurIngpregnancy,therateofdevelopmentofanantIF8CantIbodytoother
thantheA,8antIgensIsabout1per200exposures(andIscumulatIvewIthmultIple
exposures).
24
0etermInIngtheA8DandFhstatusaloneIssuffIcIenttoassurethatthe
transfusIonwIllbecompatIbleIn99.8ofpatIentswhohavenotprevIouslybeentransfused
orpregnant(I.e.,thelIkelIhoodofIncompatIbletransfusIonIsabout1In1,000).Thatlatter
ratewIllrIseInproportIontothenumberofprIordonorexposuresorpregnancIes.The
addItIonoftheJ0to45mInuteantIbodyscreenfurtherIncreasesthelIkelIhoodofa
compatIbletransfusIon(to99.9InUCS0|edIcalCenter'sexperIencewIth50,000
transfusedunIts).ThesedatarevealthattheadmInIstratIon,InemergencysItuatIons,of
typespecIfIc,uncrossmatchedbloodtopatIentswIthnohIstoryofpregnancyortransfusIon
shouldentaIlrelatIvelylIttlerIsk.
Type and Screen Orders
WhenbloodIsorderedpreoperatIvelyforsurgIcalcasesInwhIchItIsunlIkelythatthe
bloodwIllactuallybetransfused,theordersshouldbefortypeandscreenonly.TheA8D,
P.J85
FhstatusofthepatIentIsdetermInedandtheantIbodyscreen(seeprevIousdIscussIon)Is
performedtodetermInethepresenceofantIbodIesotherthanA8DInthepotentIal
recIpIent'splasma.ftheantIbodyscreenIsnegatIve,typespecIfIcotherwIse
uncrossmatchedbloodwIllresultInahemolytIcreactIonIn1/50,000unIts.fthescreenIs
posItIve,thebloodbankwIllproceedtoIdentIfyapoolofpotentIallycompatIbleunIts.
Emergency Transfusions
TheexsanguInatIngpatIentmayrequIreF8CsbeforecompletecompatIbIlItytestIngcanbe
performed.ftestIngIstobeabbrevIated,thereIsapreferredorderforselectIngpartIally
testedblood(seeChapterJ6).ThefIrstchoIceIstotransfusetypespecIfIcpartIally
crossmatchedbloodortypespecIfIcuncrossmatchedblood(althoughverIfIcatIonofblood
typebyanalysIsoftwoseparatelydrawnspecImensmustbeperformedbeforereleasIng
anyuncrossmatchedblood).nurgentsItuatIonsInwhIchthepatIent'sA8DandFhtypeIs
unknown,groupDF8CsshouldbeadmInIstereduntIlthereIstImetocompleteA8DandFh
testIng.FhnegatIvebloodIspreferable,partIcularlyIfthepatIentIsawomanofchIld
bearIngage.fFhnegatIvebloodIsnotavaIlableforacrItIcallyIll,bleedIngFhnegatIve
patIent,FhposItIvebloodIsfrequentlyused.fanongroupDpatIentreceIvesalarge
volumeofgroupDredcells,thecombInedamountofantIAand/orantI8presentInsmall
amountsIntheresIdualplasmaofeachPF8CunItmayreactwIththepatIent'sownA,8,or
A8redcellsandcausesomehemolysIs.ForthIsreason,anongroupDpatIentwhohas
receIvedgroupDredcellsapproxImatIngonepatIentbloodvolume(10to12unIts)durIng
theperIodofacutebloodlossshouldnotbeswItchedbacktohIsorherownA8Dgroup
untIltestInghasbeenperformedtoconfIrmthatsIgnIfIcanttItresofantIAorantI8
antIbodIesarenotpresent.ThattestIngIstypIcallyperformedautomatIcallyby
contemporarybloodbanks.WhenFFPorTP(seelaterdIscussIon)areadmInIsteredprIorto
A8DtypIng,typeA8plasmaIspreferable,
90
althoughsometImesnotfeasIblebecauseof
lImItedsupply(Table1612).
Platelets
PlateletsareseparatedfromplasmabycentrIfugatIon.
25
|orethan70oftheplatelets
usedIntheUnItedStatesarenowderIvedbyapheresIs.AsIngleapheresIsunIt(referredto
asapheresis platelets),whIchIsobtaInedfromasIngledonoratasInglesessIon,supplIesJ
10
11
plateletsInavolumeof200to400mL.AnapheresIsunItsupplIestheequIvalentof
theplateletsderIvedbyconcentratIngplateletsfromsIxtoeIghtIndIvIdualdonorunItsof
wholeblood.Thelatter,whencombIned,arereferredtoasplateletpacksorconcentrates.
TheuseofapheresIsplateletssubstantIallyreducesdonorexposureswIththeattendant
rIsksofalloImmunIzatIonandInfectIon(vIralandbacterIal).PlateletvIabIlItyIsoptImalat
22`C.AlthoughplateletsarepotentIallyvIableforaslongas10days(thenormalInvIvo
lIfespan),byF0Amandate,storageIslImItedto5daysbecauseofthetImerelatedrIskof
bacterIalgrowth.
25
PlateletsshouldbedelIveredthroughthestandard170mIcronbloodset
fIlter.AmIcroporefIltershouldnotbeused.
PlateletsbearA8D,HLA,andotherplateletspecIfIcantIgens.A8DcompatIbIlItyIsIdeal,
althoughnotabsolutelyrequIred.A8DIncompatIbIlItyreducesplateletsurvIval.n
addItIon,ItappearstoIncreaseImmuneresponsIvenesstoHLAandotherplateletsurface
antIgens,therebyIncreasIngtheIncIdenceofalloImmunIzatIon.
25
A8D/HLAmatched
platelets,crossmatchedplatelets,andHLAantIgennegatIveplateletscanbeusedfor
patIentswhobecomerefractorytorandomdonorplatelets.PlateletsdonotcarrytheFh
antIgen.However,admInIstratIonofplateletsfromanFhposItIvedonortoanFhnegatIve
femaleofchIldbearIngageshouldbeavoIdedIfdelaydoesnotImposehazardInorderto
preventsensItIzatIonasaresultofpassengerF8CsIntheplateletpreparatIon.The
sensItIzatIonrIskIssmallbecauseoftheverylImItednumberofF8CsIncontemporary
plateletpreparatIonsandIseffectIvelypreventedbyFhImmuneglobulIn,whIchshouldbe
admInIstered.A8DcompatIbIlItyofplateletsIsalsodesIrablebecausetheantIbodIes
presentIntheplasmaphasecancausehemolysIsofrecIpIentF8Cs.
148
HemolytIcevents
haveInvarIablyInvolvedadmInIstratIonofDtypeplateletstoanonDrecIpIent,andblood
bankprocedurestypIcallyavoIdlargevolumeadmInIstratIonofthosepaIrIngs.
148
Fresh-Frozen Plasma/Thawed Plasma
PlasmaIsseparatedfromtheF8CcomponentofwholebloodbycentrIfugatIon.DneunIt
hasavolumeof200to250mL.twIllcontaInthepreservatIveaddedatthetImeof
collectIon,usuallyCP0A.TopreservethetwolabIleclottIngfactors(7and7),FFPIs
frozenpromptlyandthawedonlyImmedIatelyprIortoadmInIstratIon.FFPmustbeA8D
compatIble.AvoIdIngFhposItIveplasmaInFhnegatIvepatIentsseemsunnecessary
becausetherehasbeennoreportedInstanceofalloImmunIzatIonInover40years.
TPIsbeIngevermorewIdelyusedInlIeuofFFP,especIallyInthemanagementoftrauma.
(|anyofthereadersofthIschaptermaydIscoverthattheyhavealreadybeen
admInIsterIngTP.)tIsobtaInedfromthawedFFPthatIsmaIntaInedat6`CforamaxImum
of5days.tsadvantageIsImmedIateavaIlabIlIty(andreductIonofwastageofthawedFFP
notadmInIsteredwIthIn24hours).LevelsofF7andF7declInedurIngstorage.However,
ItIsbelIevedthatthereIssuffIcIentresIdualF7evenafter5daystoachIeveF7levelsof
25toJ0readIly.Factor7IsanacutephasereactantthatIsusuallypresentInsuffIcIent
amountsIntraumavIctIms.TPcanbeusedInterchangeablywIthFFPInmostsItuatIons,
wIththeexceptIonofpatIentswIthspecIfIcdefIcIencIesofF7orF7,In0C,andIn
neonates.SomeclInIcIanswIllencounterFP24(plasmafrozenwIthIn24hoursafter
phlebotomy),whIchIstypIcallyusedInterchangeablywIthFFP.
Solvent Detergent Plasma
DneoftheprIncIpalhazardsofFFPadmInIstratIonhasbeenvIrustransmIssIon.Three
procedurespasteurIzatIon,photochemIcaltreatment,andsolventdetergent(S0)
treatmenthavebeenusedtoInactIvatevIruses.TheS0technIqueIshIghlyeffectIveIn
InactIvatIngallofthelIpIdencapsulatedvIruses(I.e.,H7,HC7,H87,andHTL7).The
dIsadvantageoftheS0technIqueIsthattheprocessInvolvespoolIngoflargenumbersof
sIngleFFPunIts(1,000)andIsnoteffectIveagaInstnonlIpIdenvelopedvIruses(HA7,
parvovIrus)ortheagentofCJ0.TheconcernwIthS0plasmaIsthatthepoolIngprocess
mIghtresultInwIdedIssemInatIonofanInfectIousagent.TheIncIdenceofparvovIrus
vIremIaamongdonorsIsestImatedtobenearly1.0.
149
ParvovIrus819InfectIonhasbeen
reportedasaconsequenceoftransfusIon.WhIlethedIseaseIsusuallyselflImIted,
sIgnIfIcantmorbIdIty,suchasredcellaplasIaand/ormenIngItIs,especIallyIn
ImmunocompromIsedpatentscanoccur.
150
S0plasmaIsnowtestedfor819andHA7andIs
wIdelyusedInEuropebutIsnolongeravaIlableIntheUnItedStates.
P.J86
Cryoprecipitate
CryoprecIpItateIstheprecIpItatethatremaInswhenFFPIsthawedslowlyat4`C.tIsa
concentratedsourceofF7,FX,vWF,andfIbrInogen.DneunItofcryoprecIpItate(the
yIeldfromoneunItofFFP)contaInssuffIcIentfIbrInogentoIncreasefIbrInogenlevelsby5
to7mg/dL.
151
AccordIngly,ItIsusuallyprovIdedInbagsthatcontaIn10or20unIts.A8D
compatIbIlItyIsnotessentIalbecauseofthelImItedantIbodycontentoftheassocIated
plasmavehIcle(10to20mL).7IrusescanbetransmIttedwIthcryoprecIpItate.tIsstored
at20`CandthawedImmedIatelyprIortouse.
Factor VIII and IX
FecombInantandvIrallyInactIvatedplasmaderIvedF7andFXconcentratesare
avaIlable.
152
Antithrombin III
7IrustreatedantIthrombIn(AT)concentratesareavaIlable.TheycanbeusedInthe
treatmentofcongenItalandacquIredATdefIcIencIes,IncludIngheparInresIstance,0C,
andfulmInanthepatIcfaIlure.
15J,154,155
The Hemostatic Mechanism
NormalhemostasIsInvolvesaserIesofphysIologIcchecksandbalancesthatassurethat
bloodremaInsInvarIablyInalIquIdstateasItcIrculatesthroughoutthebodybut,oncethe
vascularnetworkIsvIolated,transformsrapIdlytoasolIdstate.ThattransformatIontoa
solIdstate(I.e.,coagulatIon)mustInevItablybecomplementedbyprocessesfor
elImInatIngclotthatIsnolongerneededforhemostasIs.ThelatterIsaccomplIshedby
fIbrInolysIs.
The Nomenclature of Coagulation
ThenomenclatureofcoagulatIonIsunfortunatelycomplex.ThefIrst4ofthe12orIgInally
IdentIfIedfactorsareusuallyreferredtobytheIrcommonnamesfIbrInogen,prothrombIn,
tIssuefactor(TF),andcalcIumandnotbytheIrFomannumerals.F7nolongerexIsts;It
provedtobeactIvatedF7.ThemorerecentlydIscoveredclottIngfactors(e.g.,
prekallIkreInandhIghmolecularweIghtkInInogen)havenotbeenassIgnedFoman
numerals.Somefactorshavemorethanonename(Table161J).
The Coagulation Mechanism
TheclassIcdualcascade(IntrInsIcandextrInsIcpathway)modelofcoagulatIon(FIg.161)
IsnowrecognIzedtobeanInadequaterepresentatIonofInvIvocoagulatIon.tfaIlsto
explaInseveralclInIcalphenomena.FIrst,personslackIngFX,prekallIkreIn,orhIgh
molecularweIghtkInInogendonotbleedabnormally,suggestIngthatcontactactIvatIonIs
notcrItIcalforInvIvohemostasIs.Second,patIentswIthonlytracequantItIesofFX
wIthstandmajortraumawIthoutunusualbleedIng,andthosecompletelylackIngfactorX
(hemophIlIaC)haveonlyamIldhemorrhagIcdIsorder.FXthereforeappearstohavea
moremInorroleIncoagulatIonthanascrIbedtoItbyclassIctheory.Next,defIcIencIesof
F7andFX(bothIntrInsIcpathwayfactors)leadtohemophIlIaAand8,respectIvely.
However,theclassIcdescrIptIonoftwopathwaysofcoagulatIonleavesItunclearclear
whyeIthertypeofhemophIlIaccouldnotsImplyclotvIatheunaffectedpathway.|ost
Importantly,ItIsnowapprecIatedthatwhIletheclassIctheorIesmayprovIdeareasonable
modelofInvItrocoagulatIontests(I.e.,theaPTTandPT),theyfaIltoIncorporatethe
centralroleofcellbasedsurfacesIntheInvIvocoagulatIonprocess.Thethreestagesof
thatprocessthathavebeenthoroughlydefInedanddescrIbedbyHoffmanand
P.J87
|onroe
156
aresummarIzedInthefollowIngsectIonsandInFIgure162.
Table 16-13 Factor Nomenclature and Half-Lives
FACTOR SYNONYMS
IN VIVO HALF-LIFE
(hours)
FIbrInogen 100150
ProthrombIn 5080
TIssuefactor,thromboplastIn
7 CalcIumIon
7 ProaccelerIn,labIlefactor 24
7
SerumprothrombInconversIonaccelerator,
stablefactor
6
7 AntIhemophIlIcfactor(AHF),AHFA,factor7:C 12
vWF vonWIllebrandfactor 24
X ChrIstmasfactor,AHF8 24
X
StuartProwerfactor,Stuartfactor,
AutoprothrombIn
2560
X PlasmathromboplastInantecedent,AHFC 4080
X Hagemanfactor,contactfactor 5070
X FIbrInstabIlIzIngfactor 150
PrekallIkreIn Fletcherfactor J5
H|W
kInInogen
FItzgerald,Flaujeac,orWIllIamsfactor;contact
actIvatIoncofactor
150
H|W,hIghmolecularweIght.
Figure 16-1.TheclassIcIntrInsIcandextrInsIcpathwaysofcoagulatIon.ntrInsIc
pathway(left).AcascadeInItIatedbycontactwIthaforeIgnsurface(contact
actIvatIon)leadstotheformatIonoffIbrIn(a).ExtrInsIcpathway(right).ThIs
pathway,alsoleadIngtofIbrInformatIon,IsdepIctedasItwasorIgInallythoughtto
occur,thatIs,largelyextravascularlyandIndependentoftheclassIcIntrInsIcpathway
(cf:FIg.162).Thedotted arrowsIndIcatetheoccurrenceofanenzymatIcally
medIatedconversIonofanInactIvefactortoItsactIveform.Theshaded spheroids
representtheprocoagulantsurfacesprovIdedIntheextrInsIcpathwaybothInvIvoand
InvItrobytIssuefactor(TF)and,IntheIntrInsIcpathway,byphospholIpIdsInvItro
andplateletsInvIvo.
Activation
ActIvatIonofthecoagulatIonprocessbegInswhenabreachInthevascularendothelIum
exposesbloodtoTF.TFIsamembraneboundproteIn,wIthadjacentmembrane
phospholIpIds,thatIsconstItutIvelyexpressedInextravasculartIssue,prIncIpallyon
fIbroblasts(FIg.162A).TFalsoappearsonthesurfaceofvascularendothelIumand
cIrculatIngmonocytesInresponsetomechanIcalInjuryorInflammatIon.
157
TFactIvates
F7(FIg.1628)toyIeldacomplexofTFandactIvatedF7(F7a)onthephospholIpId
surface.TheTF7aInturnactIvatesFX,yIeldIngacomplexofTF7aXa(FIg.162C).The
FXa,stIllonthephospholIpIdsurface,thenbIndswIthF7atoformtheprothrombInase
complex.TheF7athatpartIcIpatesInthIsreactIonIslIberatedfromthealphagranulesof
plateletsthatwereactIvatedatthesIteofInjuryasaresultofbIndIngtosubendothelIal
vWF(FIgs.162Eand16J).TheprothrombInasecomplexcatalyzestheconversIonof
prothrombIn(F)tothrombIn(Fa;FIg.162E).However,generatIonofabythIspathway
IslImItedbytIssuefactorpathwayInhIbItor(TFP).TFP,aproteInthatIsconstItutIvely
presentInendothelIumandplatelets,
158
bIndstoandInhIbItstheXacomponentoftheTF
7aXacomplexand,oncebound,InhIbItsadjacentTF7acomplexesfromfurther
actIvatIonofFX
158
(FIg.1620).Asaconsequence,onlyverylImItedamountsofthrombIn
canbegeneratedbythIsmechanIsm(whIchexplaInswhyhemophIlIacsbleedInspIteofan
IntactIntrInsIcpathway).8utthIsInItIalformatIonofsmallamountsofthrombInIs
suffIcIenttoadvancethecoagulatIonprocesstothemoreeffIcIentamplIfIcatIonphase
thatfollows.
Amplification
WhIleItwasthesurfaceprovIdedbymembraneboundTFandadjacentphospholIpIdthat
InItIatedthecoagulatIonprocess,ItIsnowthephospholIpIdsurfaceprovIdedbyplatelets
thatservestoperpetuateIt.ThebreachInthevasculartreethat
P.J88
begantheactIvatIonprocessalsoexposedplateletstocollagentowhIchtheybecome
boundvIavWFandtheCPbreceptorontheplateletsurface(FIg.164).ThatbIndIng
resultsInplateletsurfacechanges,mostnotablytheappearanceoftheCPb/areceptor,
andInthereleaseofthecontentsofalphaanddenseplateletgranules(FIg.16J).
159
The
lattercontaInnumeroussubstancesthatcontrIbutetoaddItIonalplateletactIvatIon
(adenosInedIphosphate[A0P],Ca++,serotonIn),plateletaggregatIon(vWF,fIbronectIn,
thrombospondIn,fIbrInogen),clotformatIonandstabIlIzatIon(calcIum,fIbrInogen,factors
7,XandX,plasmInogenactIvatorInhIbItor[PA1]),andtoadhesIonandactIvatIonof
addItIonalplatelets.ThethrombInjustgeneratedbytheTFboundprothrombInase
complexsupportstheamplIfIcatIonofthecoagulatIonprocessInfourways.FIrst,
thrombIn,aserIneprotease,furtheractIvatestheadjacentplatelets(FIg.162F)vIa
proteaseactIvatedsurfacereceptors.
160
ThrombIn'ssecondeffectIstopromotethe
actIvatIonF7InplasmatoF7a(FIg.162F).ThIrd,thrombInreleasescIrculatIngF7from
ItscarrIermolecule(vWF)andactIvatesIt(FIg.162C).Fourth,thrombInactIvatesFX.
FXaInturnactIvatesFX(FIg.162H).NotethatsomeFXawasalsogeneratedbytheTF
7adurIngtheactIvatIonphase(FIg.162C).ThIsmayexplaInwhyFXdefIcIencyresultsIn
suchamInorcoagulatIondIsturbance.ThenetresultofthIsamplIfIcatIonstageIsthe
avaIlabIlItyofaddItIonalactIvatedplateletsandactIvatedFactors7,7,andX.
Figure 16-2.ThecoagulatIonmechanIsm.SeetextfordetaIls.TF,membranebound
tIssuefactoronaextravascularcellsurface;TFP,tIssuefactorpathwayInhIbItor;
vWF7:C,cIrculatIngfactor7boundtoItscarrIerproteIn,thevonWIllebrand
factor.
Figure 16-3.PlateletreleasereactIon.PlateletsundergoareleasereactIonIn
responsetoadherencetothesubendothelIumortophysIologIcagonIstsIncludIng
epInephrIne,adenosInedIphosphate(A0P),andthrombIn.Thenumeroussubstances
releasedfromthealphaanddensegranulesofplateletscontrIbutetoaddItIonal
plateletactIvatIon(A0P,Ca++,serotonIn),plateletaggregatIon(vonWIllebrandfactor
[vWF],fIbronectIn,thrombospondIn,fIbrInogen),andclotformatIon(calcIum,
fIbrInogen,factors7,XandX,plasmInogenactIvatorInhIbItor[PA1]).ATP,
adenosInetrIphosphate;TFP,tIssuefactorpathwayInhIbItor;CP,glycoproteIn;EC,
endothelIalcell.
Figure 16-4.PlateletadhesIonandaggregatIon.WhentheendothelIumIsdenuded,
plateletsadheretothecollagenInthesubendothelIumvIatheIrglycoproteIn
glycoproteIn(CP)1breceptorsandvonWIllebrandfactor,presentInbothplasmaand
thesubendothelIalmatrIx.PlateletsaggregatetooneanotherbycrosslInkIngvIa
fIbrInogen(orvonWIllebrandfactor,notshown)betweenCPlb/areceptors
expressedontheplateletsurfacedurIngtheprocessofplateletactIvatIon.
Propagation
TheplateletthenprovIdesthephospholIpIdsurfaceonwhIchtwocoagulatIonfactor
complexesformandacttoproducetheexplosIvegeneratIonofthrombIn.FIrst,F7aand
FXaformthetenasecomplex,whIchactIvatesFX(FIg.162H).TheresultantFXaforms
addItIonalprothrombInasecomplex(Xa7a),andlargeamountsofthrombInareelaborated
(FIg.162J).(FormnemonIcpurposesItIseIghtnIneandnIckeldImethattogetherare
responsIbleforthethrombInburst.)ThrombIn(Fa)catalyzestheformatIonoffIbrInfrom
fIbrInogen,andfIbrInactstocrosslInktheplatelets,largelyvIatheb/areceptors(FIg.
164),toreInforcethefrIableplateletplug.ThrombInalsoactIvatesFX(FIgs.162Kand
165)andthrombInactIvatablefIbrInolysIsInhIbItor(TAF;FIg.165).FIbrIn
P.J89
monomersInItIallyaggregaterelatIvelylooselytoformclotcomposedoffIbrInS(soluble),
whIchIsheldtogetheronlybyhydrogenbonds.FX(fIbrInstabIlIzIngfactor)medIatesthe
formatIonofcovalentpeptIdebondsbetweenthefIbrInmonomers.FXmaybean
underapprecIatedcauseofclInIcalcoagulatIondIsturbance.
161
TAFfunctIonstoprevent
lysIsofthenewlyformedclot(FIg.165).nthepresenceofsubnormalamountsof
thrombIn,althoughfIbrInclotcanform,ItmaynotachIevenormalstrengthandstabIlIty
162
andmaynotbeprotectedbyadequateconcentratIonsofTAF.
16J
Figure 16-5.TheformatIonandlysIsoffIbrIn.FIbrInIsformedfromfIbrInogenbythe
actIonofthrombIn(Fa).ThrombInalsoconvertsfactorX(FX)toactIvatedfactor
X(FXa),whIchInturnstabIlIzestheevolvIngfIbrInclotbycrosslInkage.
CIrculatIngplasmInogenbIndstofIbrInandIsconvertedtoplasmInbytIssue
plasmInogenactIvator(tPA)releasedfromnormalendothelIumInareasremotefrom
sItesofvascularInjury.PlasmIndIgestsfIbrIntoItsvarIousdegradatIonproducts
(F0Ps).TheactIonoftPAcanbeInhIbItedbyplasmInogenactIvatorInhIbItor(PA1)
releasedbyendothelIumandplatelets.TheactIonofplasmInIsalsoInhIbItedby
thrombInactIvatedfIbrInolysIsInhIbItor(TAF).
nvIvo,coagulatIonIsInItIatedprIncIpallybycontactoffactor7wIthextravascularTF
leadIngfIrsttothegeneratIonofsmallamountsofthrombIn.Thereafter,actIvatedclottIng
factors,actIngIntravascularlyonthephospholIpIdsurfaceprovIdedbyactIvatedplatelets,
leadtothegeneratIonoflargeamountsofthrombIn.
Additional Principles of Coagulation
AfewaddItIonalfactswIllaIdInachIevIngabroaderunderstandIngofcoagulatIon.
1. |ostclottIngfactorscIrculateInanInactIveproenzyme,orzymogen,form.0urIngthe
processofcoagulatIon,aportIonofthemoleculeIscleavedoff,resultIngInactIve
enzymes(desIgnatedbytheaddItIonofalowercaseaaftertheFomannumeral,e.g.,
Xa),mostofwhIchareserIneproteases.
2. |ostclottIngfactorsaresynthesIzedbythelIver.TheprobableexceptIonIsfactor7,
whIchprobablyalsohassomeextrahepatIcsynthesIs.
J. Factor7Isactuallyalarge,twomoleculecomplex(vWFandcoagulantfactor7).
Factor7cIrculatesasaverylargecomplexoftwodIstInctproteIncomponents.The
hIghmolecularweIghtportIon(7F:Ag)encompassesboththeF7antIgenandvWF.
ThevWFportIonservesasacarrIerproteInforthesecondandsmallercomponentofthIs
macromolecularcomplex,7C,whIchcontaInsthefactor7coagulantactIvIty.The
vWFhasasecondfunctIon.0urIngtheprocessofprImaryhemostasIs,whenthe
endothelIallInInghasbeendenuded,vWFInthesubendothelIalmatrIxmedIates
adhesIonofplateletstocollagen.AbsenceofthesmallerportIonofthefactor7
complex(7:C),resultsInhemophIlIaA.vWFdefIcIencycausestwohemostatIc
abnormalItIes:(1)adefectInprImaryhemostasIsbecauseofafaIlureofplatelet
adhesIontothesItesofvascularInjury,and(2)theclInIcalequIvalentofhemophIlIaA
becauseofdefIcIencyofcIrculatIngfactor7:C.FestoratIonofvWFlevelsrestores
normalhemostasIs.SynthesIsofthevWFoccursInendothelIalcellsandmegakaryocytes.
ThesIteofsynthesIsofthecoagulantportIonoffactor7Isunknownbutmaybe
locatedInthehepatIcsInusoIdalendothelIalcells.
4. FourclottIngfactorsarevItamInKdependent.Factors,7,X,andXrequIrevItamInK
forcompletIonoftheIrsynthesIsInthelIver.EachundergoesafInalenzymatIcaddItIon
ofacarboxylgroupthatrequIresthepresenceofvItamInK.Thecarboxylgroupenables
thesefactorstobInd(usIngcalcIumasacofactor)tophospholIpIdsurfaces.WIthout
vItamInK,factors,7,X,andXareproducedInnormalamountsbutare
nonfunctIonal.
TheantIcoagulantactIonofvItamInKantagonIstsIstheresultoftheIrabIlItytoInhIbIt
thIsfInalcarboxylatIonstep.ThewarfarInlIkedrugscompetewIthvItamInKforbIndIng
sItesonthehepatocyte.WIthsuffIcIentwarfarInadmInIstratIon,vItamInKIsdIsplaced
andthevItamInKdependentfactorsarenotcarboxylated.DfthefourvItamInK
dependentfactors,factor7hastheshortesthalflIfe.tIsthefIrstclottIngfactorto
dIsappearfromthecIrculatIonwhenapatIentIsgIvenwarfarInorbegInstodevelop
vItamInKdefIcIency.
5. Factors7and7haveshortstoragehalflIves.Factors7and7arealsoreferredtoas
thelabile factorsbecausetheIrcoagulantactIvItyIsnotdurableInstoredblood.WhIle
PF8CscontaInsomeresIdualplasmawIthclottIngfactors,massIvetransfusIonwIth
storedbloodwIllnonethelessleadtoadIlutIonalcoagulopathybecauseofdImInIshed
actIvItyoffactors7and7.
Fibrinolysis
FIbrInolysIsservestodIssolveorremodelfIbrInclotsandtherebyrecanalIzevesselsthat
havebeenoccludedbythrombosIs.
The Formation of Plasmin
PlasmInogenIstheInactIveformofthefIbrInolytIcenzymeplasmIn.ConversIonof
plasmInogentoplasmInIsaccomplIshedprIncIpallybytIssueplasmInogenactIvator(tPA;
FIg.165).PlasmInIsrapIdlydegradedbycIrculatIngantIplasmInsandthereforecannot
cIrculatefreely.PlasmInogen,however,cancIrculate.tbIndstofIbrInoncontactandIs
IncorporatedIntheevolvIngfIbrInclotwhereItIsconvertedtoplasmInbytPA.WhIle
boundplasmInIsprotectedfromattackbycIrculatIngantIplasmIns,anyplasmInthatIs
releasedfromtheclotIsImmedIatelyneutralIzedbycIrculatIng
2
antIplasmIn.Thus,lIke
thecoagulatIoncascade,thefIbrInolytIcsystemrelIesonsurfacemedIatedreactIonsthat
lImItbothplasmInformatIonandfIbrInolysIstothesIteofvascularInjury.
Plasminogen Activation
TheprIncIpalactIvatorofplasmInIstPA.tPAIssynthesIzedbyvascularendothelIalcells.
ntheeventofclotformatIon(whIchrequIresthepresenceofthrombIn),thrombInformsa
complexwIththrombomodulIn(presentonthevascularendothelIalsurface)thatactIvates
proteInC.ActIvatedproteInC(APC)stImulatesthereleaseoftPA.tPAIsalsoreleased
fromtheendothelIumInresponsetovenousocclusIon,physIcalactIvIty,stress,or
vasoactIvedrugs(suchasepInephrIne,vasopressIn,and00A7P).
164
tPAbIndstothe
adjacentfIbrInandconvertsplasmInogentoplasmIn(FIg.165).ThIsmechanIsmservesto
localIzefIbrInolysIstothesIteofvascularInjury,therebypreventIngvascularInjuryata
sInglelocatIonfromInItIatIngwIdespreadfIbrInolysIs.Asafurthercheckonthe
fIbrInolytIcprocess,thevascularendothelIumandplateletsalsosynthesIzeanInhIbItorof
tPA,PA1,whIchreducestheamountofplasmInformedandservestoslowthefIbrInolytIc
process(FIg.165).SomepatIentswIththrombotIcdIsordershavebeenfoundtohave
IncreasedlevelsofthIsInhIbItor.
164
AsImIlarInhIbItorIsfoundInplacentaltIssue,andIt
maybethattheprogressIvehypercoagulablestateassocIatedwIthpregnancyIsrelatedto
IncreasedlevelsofthIstPAInhIbItor.
164
ThereareotherplasmInogenactIvators.UrokInaseIspresentInprostatIctIssueandurIne
butnotIncIrculatIngblood.PhysIologIcactIvatorsofthefIbrInolytIcsystemInclude
vIgorousexercIse,anoxIa,andstress.ExogenousplasmInogenactIvatorsInclude
streptokInase,urokInase,andrecombInanttPA.ThesefIbrInolytIcagentsalldIfferwIth
respecttotheIractIon,clotspecIfIcIty,systemIcfIbrInolytIceffect,antIgenIceffect,and
effIcacy.ProteInsderIvedfromstreptococcIandstaphylococcIhavealsobeenfoundtobe
actIvatorsofthefIbrInolytIcsystem.ThetherapeutIcfIbrInolytIcagents,streptokInaseand
urokInase,dIfferfromtPAInthattheywIllactIvatecIrculatIngplasmInogen.Theseleadto
morewIdespreadfIbrInolysIs.FIbrInolytIctherapyhasbeenusedInthetreatmentof
unstable
P.J90
angIna,acutethrombotIcstroke,acuteperIpheralarterIalocclusIons,deepveIn
thrombosIs,pulmonaryembolIsm(PE),andoccludedIndwellIngcathetersand
arterIovenousshunts.
Plasmin Inactivation/Inhibition
UndernormalcIrcumstances,freeplasmInIsrapIdlyInactIvatedbyantIplasmIns.nthe
eventofdefIcIencyof
2
antIplasmInorwhenantIplasmIncapacItyIsexceededInprImary
fIbrInolysIsor0C,plasmIncIrculates.CIrculatIngplasmInwIllcontrIbutetothebleedIng
dIathesIsbecauseplasmIn,InaddItIontodegradIngfIbrIn,IsaserIneproteasethatcanalso
degradeothercoagulatIonprocesscomponentsIncludIngfIbrInogen,F7,F7,FX,vWF,
andtheCPbplateletreceptor.
164
Fibrin Degradation Products
ThestructureoftheproductsoffIbrInbreakdown,calledfibrin degradation products(F0Ps)
orfibrin split products(FSPs),varIesaccordIngtowhetherplasmIncleavesfIbrInogen,
fIbrInthatIscrosslInked,orfIbrInthatIsnotcrosslInked.F0Psareremovedfromthe
bloodbythelIver,kIdney,andretIculoendothelIalsystem.ftheyareproducedatarate
thatexceedstheIrnormalclearance,theywIllaccumulate.nhIghconcentratIons,F0Ps
ImpaIrplateletfunctIon,InhIbItthrombIn,andpreventthecrosslInkIngoffIbrInstrands.
ThedefectIvepolymerIzatIonofthefIbrInmonomersresultsInaclotthatIsmorereadIly
degradedbyplasmIn.
164
UndernormalcondItIons,plasmInIsgeneratedonlyatthesIteofclotformatIonandIs
destroyedrapIdlyoncereleasedIntothecIrculatIon.ThIslocalIzatIonprocessfaIlsattImes
ofacceleratedfIbrInolysIs(0C,prImaryfIbrInolysIs).
Control of CoagulationThe Checks and Balances
CoagulatIonmustbeprecIselyregulatedtopreventrampant,uncontrolledclottIng,suchas
thatwhIchoccurswIth0C.SeveralmechanIsmsregulateandcontrolcoagulatIon.
Endothelial Inhibition
ThefIrstlIneofdefenseIsthevascularendothelIum.TheIntactendothelIumhas
antIthrombotIcpropertIesthatservetolImItbothplateletaggregatIonandcoagulatIon
andtoInducefIbrInolysIsshouldaclotbegIntoformonnormalendothelIum.These
propertIesaresummarIzedInTable1614.
Table 16-14 Endothelial Control of Platelet Aggregation, Coagulation, and
Fibrinolysis
EndothelIalcontrolofplateletaggregatIon
SynthesIsofprostacyclIn
SynthesIsofA0PasesandnItrIcoxIde
EndothelIalInhIbItIonofcoagulatIon
SynthesIsofthrombomodulIn
SynthesIsofheparansulfate
EndothelIalcontroloffIbrInolysIs
SynthesIsoftPA
A0Pase,adenosInedIphosphatase;tPA,tIssueplasmInogenactIvator.
1. ThethromboxaneprostacyclInbalance.PrImaryhemostasIsIs,Inpart,controlledbythe
balancebetweentheeffectsoftwoprostaglandIns,thromboxaneA
2
(TxA
2
)and
prostacyclIn.TxA
2
IssynthesIzedatthesIteofvasculardamagebyactIvatedplatelets.
TxA
2
hastwohemostatIceffects:(1)ItIsapotentvasoconstrIctorthatlImItsflowtothe
sIteofInjury,and(2)ItstImulatesaddItIonalA0Preleasefromplatelets,thereby
recruItIngaddItIonalplatelets.FemotefromthesIteofvasculardamage,normal
endothelIalcellssynthesIzeprostacyclIn(FIg.166).ProstacyclInhasactIonsopposIte
thoseofTxA
2
.ProstacyclInInhIbItsplateletactIvatIon,secretIon,andaggregatIonandIs
apotentvasodIlatorandtherebyservestopreventplateletaggregatIonandclot
formatIonontheendothelIalsurfacebeyondthesIteofInjury.
2. NItrIcoxIdeandadenosInedIphosphatase(A0Pase).TheeffectsofprostacyclInare
potentIatedbynItrIcoxIde,whIchIsconstItutIvelysynthesIzedbynormalendothelIum
andwhIchalsohasvasodIlatoryandplateletantIaggreganteffects(FIg.166).Asan
addItIonalmeansofpreventIngclotformatIononthesurfaceofnormalendothelIum,
A0PasesareexpressedontheoutermembraneofendothelIalcellsandservetodegrade
surplusA0PthatmIghtotherwIseInItIateplateletaggregatIononnormalsurfaces.
J. Heparansulfate.DneoftheconstItuentsofthemucopolysaccharIdeglycocalyxthat
coversnormalendothelIumIsanaturallyoccurrIngheparInlIkesubstance,heparan
sulfate(FIg.166).LIkeheparIn,heparanhastheabIlItytoacceleratethebIndIngofAT
tothrombInandtheotheractIvatedclottIngfactorsoftheclassIcIntrInsIcpathway.ThIs
heparansulfateIswellposItIonedbecauseItIsatthIsbloodendothelIalInterfacethat
actIvatedfactorsofthecoagulatIoncascadearebeInggenerated.
Figure 16-6.FIveantIthrombotIcmechanIsms.FIvemechanIsmsthatserveto
preventunrestraInedcoagulatIonaredepIcted.1.TIssuefactorpathwayInhIbItor
(TFP)InhIbItstheInItIalactIvatIonoffactorXbytheextrInsIcpathway.2.A
complexofthrombomodulIn(T|)andthrombIn(a)actIvatesproteInC,whIch,wIth
proteInS(ProtS)asacofactor,InhIbItsactIvatedfactors7and7.J.ntact
vascularendothelIumreleasesseveralsubstancesthathaveaplateletInhIbItIngor
clotlysIngeffect,IncludIngnItrIcoxIde(eND),prostacyclIn(Pg2),adenosIne
dIphosphatase(A0Pase),andtIssueplasmInogenactIvator(tPA).4.naddItIonto
T|,othercoagulatIonInhIbItIngsubstancesIncludIngheparansulphateand
dermatansulphate(latternotshown)arepresentIntheIntactglycocalyx.5.
AntIthrombInbInds,andtherebyInhIbIts,severalactIvatedclottIngfactors(Xa,
Xa,Xa,Xa,anda).
P.J91
5. ThrombIn,thrombomodulIn,andproteInsCandS.ThrombIn,InanegatIvefeedback
process,candecreaseItsownsynthesIsbyInhIbItIonoffactors7and7.ThatInhIbItIon
IsaccomplIshedvIaproteInC.ProteInCcIrculatesInplasmaasanInactIveprecursor.
ThrombomodulInIsaglycoproteInlocatedonthevascularendothelIalcellsurface(FIg.
166).ThebIndIngofthrombIntothrombomodulInaltersthethrombInmoleculesuch
thatItcannolongerdIrectlyactIvateclottIngfactors7and7orcatalyzethe
conversIonoffIbrInogentofIbrIn.naddItIon,thethrombInthrombomodulIncomplex
rapIdlyconvertsproteInCtoactIvatedproteInC(APC).APC,wIthproteInSasa
cofactor,cleavesandInactIvatesfactors7aand7a(FIg.166).LIkeproteInC,proteIn
SIsvItamInKdependent.WheretheendothelIumIsIntact,thethrombomodulIn
thrombInproteInCInteractIonwIllInhIbItcoagulatIonandmaIntaInthe
nonthrombogenIcpropertyoftheendothelIallInIng.WheretheendothelIumhasbeen
strIppedawayordamaged,thIsantIcoagulantmechanIsmwIllbeabsentandclottIngcan
contInueunopposed.
6. EndothelIalsynthesIsoftPA.EndothelIalsynthesIsoftPAIsoneofseveralmechanIsmsby
whIchthenormalendothelIalsurfaceIsmaIntaInedInanonthrombogenIcstate(FIg.16
6).ShouldclotbegIntoformonthenormalendothelIalsurface,theassocIatedthrombIn
InducesthereleaseoftPA,whIch,IntheabsenceofotherpromotersofcoagulatIon,
leadsrapIdlytodIssolutIonoftheIncIpIentclot.
Other Modulators of Coagulation
SeveraladdItIonalfactorsservetolImItandlocalIzeclotformatIon.FIrst,theclottIng
factorsthemselvescIrculateInanInactIveform.DnceactIvatedatanInjurysIte,normal
bloodflowdIlutestheIrconcentratIonandclearsthemawayfromsItesofInjury,lImItIng
clotformatIon.ActIvatedclottIngfactorsarepreferentIallyremovedfromthecIrculatIon
bythelIverandtheretIculoendothelIalsystem.FInally,mostoftheInteractIonsofthe
coagulatIonpathwayrequIrethepresenceofaphospholIpIdsurface,whIchlocalIzesclot
formatIontothosesurfaces(TF,actIvatedplatelets).SeveralspecIfIccoagulatIon
InhIbItIngsystemsareoperatIve.FIveofthemaredepIctedInFIgure166.TFPandATare
descrIbedlater.TheothershavebeenprevIouslydescrIbedInEndothelIalnhIbItIon.
1. TIssueFactorPathwaynhIbItor(TFP).SuperfIcIally,thedescrIptIonofthecellbased
coagulatIonmechanIsmstIllleavesInplaceoneoftheInadequacIesoftheclassIc
cascadetheorIesofcoagulatIon,thatIs,IfactIvatedfactorX,andsubsequently
thrombIn,canbeformedvIathedIrectactIonofthe7a/TFcomplex,whyIsItthat
hemophIlIacsbleed:Whydotheyappeartobedependentonfactors7andXto
produceactIvatedfactorX:TheanswerlIesInafeedbackInhIbItoroftheextrInsIc
pathwayknownasTFP(FIgs.162and166).TFP,theprecursormoleculeofactIvated
TFP(TFPa),IsconstItutIvelypresentontheendothelIalsurfaceandboundtocIrculatIng
lIpoproteIns.
158
tIsactIvatedbycontactwIththeXa7aTFcomplex,thatIs,ItIsnot
actIvateduntIlcoagulatIonhasbeenInItIated.tInactIvatesfactorXaandcauses
InternalIzatIonofmembranebound7a/TFcomplexes.
158
nthepresenceofTFP,
extensIveactIvatIonoffactorXappearstorequIrethereactIonsequencesoftheclassIc
IntrInsIcpathway.TheTFpathwaycanInItIatethefIrstflurryofthrombIngeneratIon
enoughtoactIvateplateletsandstImulatecofactors7and7.Thereafter,contInued
thrombInproductIonappearstorequIretheactIonoffactors7aandXa.
165
2. AntIthrombIn(AT).ATIsacIrculatIngserIneproteaseInhIbItorthatbIndstothrombIn
andtherebyInactIvatesIt.ATcanbIndandInactIvateeachoftheactIvatedclottIng
factorsoftheclassIcIntrInsIccoagulatIoncascadefactorsXa,Xa,Xa,andXa(see
FIg.166).TheATmoleculehastwocrItIcalbIndIngsItes,oneofwhIchreactswIth
thrombInandtheotheractIvatedclottIngfactorsandasecondtowhIchheparIncan
bInd(seeChapter41).ntheabsenceofheparIn,AThasarelatIvelylowaffInItyfor
thrombIn.HeparInbIndIngtoATIncreasestheeffIcIencyofbIndIngofATtothrombIn
andtheotherfactorsdramatIcally.CongenItalATdefIcIency(levels40to50ofnormal)
canleadtoaprothrombotIcdIathesIs.AcquIredATdefIcIencycanoccurwIthlIver
dIsease,prolongedheparInadmInIstratIon,nephrotIcsyndrome,0C,sepsIs,pre
eclampsIa,fattylIverofpregnancy,oralcontraceptIveuse,anddurIngCP8.
166,167
AT
concentrateshavebeenusedInATdefIcIencystates,IncludIngheparIn
resIstance.
167,168,169
J. ThrombInActIvatableFIbrInolysIsnhIbItor(TAF).AnaddItIonalfeedbackmechanIsmto
preventexcessIvefIbrInolysIsandprematureclotbreakdownexIstsIntheformofTAF
(FIg.165).TAFIsactIvatedbylowconcentratIonsofthrombInwhenthrombomodulInIs
presentordIrectlybygreaterconcentratIons.TAF'sroleInabnormalItIesofhemostasIs
IsnotwelldefIned.
16J
The Complexities of the Hemostatic Mechanism
|anymechanIsmsInteracttomaIntaInthelIquIdstateofthebloodundernormal
cIrcumstancesandtotransformbloodIntoasolIdclotwhenInjuryoccurs.These
mechanIsmsIncludenumerousfeedbackprocesses.ThecomplexItyIsrevealedbythe
exIstenceofdoubleagents,whIchactatsometImesasprocoagulantsandatothertImes
asantIcoagulants.ChIefamongthemIsthrombIn.ThrombInIsprImarIlyaprocoagulant.t
promotesprImaryhemostasIsbyactIvatIngplatelets,andpromotescoagulatIonbydIrect
actIvatIonoffactors7,7,andX.ThrombIn,InthefInalstepofthecoagulatIon
cascade,cleavesfIbrInogentofIbrIn.However,ItalsohasantIcoagulanteffects.tInhIbIts
coagulatIonthroughItsInteractIonwIththrombomodulInandproteInC.APCstImulatesthe
releaseoftPAfromendothelIalcells,andbythIsmechanIsmthrombInhasafIbrInolytIc
effectwhIlesImultaneouslyactIvatIngthefIbrInolysIsInhIbItorTAF.AccordIngly,thrombIn
throughItseffectsatmanystagesofthefeedbackcontrolledhemostasIsprocess,functIons
asplateletproaggregant,aprocoagulant,anantIcoagulant,aprofIbrInolytIc,andanantI
fIbrInolytIc.
The Hemostatic Mechanism: Summary
UndernormalcIrcumstances,thehemostatIcmechanIsmIsquIescentwIthmanyofthe
potentIalpartIcIpantscIrculatIngInanInactIveform.DnlywhentheendothelIallInIngIs
breachedIsthehemostatIcmechanIsmsetInmotIon.WIthcollagenandTFexposed,the
IntertwInedprocessesofplateletmedIatedprImaryhemostasIsandfactormedIated
coagulatIonbegIn.7ascularInjuryIssealedrapIdlybyaplateletmassIntowhIchare
IncorporatedfIbrInogen,thrombIn,plasmInogen,andtPA.ThecompletIonofthe
coagulatIonprocessconvertsfIbrInogenIntofIbrInandtheplateletplugIstransformedInto
afIbrInclot.SImultaneously,severalpropertIesofadjacentIntactendothelIum
(elaboratIonofA0Pases,prostacyclIn,thrombomodulIn,heparans,andtPA)serveto
preventextensIonoftheclotbeyondthesIteofInjury.WIthIntheclot,plasmIn,generated
bytheactIonoftPAonthetrappedplasmInogen,begInstheprocessoffIbrInolysIs.Dver
tIme,theentIrefIbrInclotdIssolves,newendothelIalcellslInethevessel,andflowIs
restored.
P.J92
Laboratory Evaluation of the Hemostatic Mechanism
Laboratory Evaluation of Primary Hemostasis
Platelet Count
AplateletcountshouldbethefIrsttestorderedIntheevaluatIonofprImaryhemostasIs.
TheplateletcountIsquIck,accurate,andreproducIble.However,Itrevealsonlyplatelet
numbersandgIvesnoInformatIonregardIngtheIrfunctIon.Normalplateletcountsrange
between150,000and440,000/mm
J
.Countsbelow150,000/mm
J
aredefInedas
thrombocytopenia.SpontaneousbleedIngIsunlIkelyInpatIentswIthplateletcounts
10,000to20,000/mm
J
.WIthcountsfrom40,000to70,000/mm
J
,bleedIngInducedby
surgery,maybesevere.AdetaIledrevIewofthemanymethodsfortestIngplatelet
functIonIsavaIlable.
170
DnlythemorewIdelyusedmethodsarementIonedhere.
Bleeding Time
ThevybleedIngtIme(8T)IsthemostwIdelyacceptedclInIcaltestofplateletfunctIon.A
bloodpressurecuffIsplacedaroundtheupperarmandInflatedto40mmHg.AcutIsmade
onthevolarsurfaceoftheforearmandthewoundblottedatJ0secondIntervalsuntIl
bleedIngstops.TheSImplate8leedIngTIme(DrganonTelenIkaCorp.,0urham,NC)devIce,
whIchusesasprIngloadedlancet,standardIzesthesIzeanddepthofthecut.Thenormal
rangeIs2to9mInutes.7arIatIonsInvenouspressure,blottIngtechnIque,andpatIent
cooperatIonresultInalackofprecIsIonandreproducIbIlItythatmakethIstestsomewhat
lessrelIablethanothercoagulatIontests.The8TIspurportedtoevaluatethetIme
necessaryforaplateletplugtoformfollowIngvascularInjury.ThIsrequIresanormal
numberofcIrculatIngplatelets,plateletswIthnormalfunctIon(whIchcanadhereand
aggregate),andanapproprIateplateletInteractIonwIththebloodvesselwall.A
prolongatIonofthe8Tmaybebecauseof(1)thrombocytopenIa,(2)plateletdysfunctIon
(adhesIon,aggregatIon),and(J)vascularabnormalItIessuchasscurvyortheEhlers0anlos
syndrome.8TsareprolongedInpatIentswIthmanycondItIonsthatcauseplatelet
dysfunctIon(e.g.,useofaspIrIn,uremIa).However,prolonged8Tshavebeenobserved
wIthnumerousdIsordersthatarenotassocIatedwIthplateletdysfunctIon,suchasvItamIn
KdefIcIencyofthenewborn,amyloIdosIs,congenItalheartdIsease,thepresenceoffactor
7InhIbItors,oranemIa.
171
Whetherornotthe8TtestrepresentsaspecIfIcmeasureofIn
vIvoplateletfunctIonIsmuchdebated.ThetestIsunpleasantforthepatIentandleavesa
smallscar.nspIteofthecorrelatIonof8TwIthcondItIonsknowntoInfluenceplatelet
functIon,andInspIteof8TquIterelIablybecomIngprogressIvelyprolongedasplatelet
countfallsbelow80,000/L,therearenoconvIncIngdatatoconfIrmthat8TIsarelIable
predIctorofthebleedIngthatwIlloccurInassocIatIonwIthsurgIcalprocedures.
Platelet Aggregometry
PlateletaggregometryquantIfIesplateletaggregatIoneItherspectrophotometrIcallyorby
ImpedancechangesInresponsetostImulatIonwIthA0P,epInephrIne,collagen,arachIdonIc
acId,orrIstocetIn.ThetestsaresuffIcIentlywellstandardIzedtoallowdIstInctIonsamong
normalfunctIon,drugrelatedImpaIrmentoffunctIon,andIntrInsIcplateletdefects.
However,thetestsaretImeconsumIngandrequIreabsolutelyfreshblood,andare
thereforenotwIdelyusedInacutepatIentmanagement.
170
The Platelet Function Analyser
ThePFA100(0ade8ehrIng,|arburg,Cermany)IsapoIntofcare,flowcytometrydevIce.
ThetestIsbasedonthetImetoocclusIonasthespecImenpassesthroughasmallaperture
ImpregnatedwIthplateletactIvators(e.g.,collagen,A0P).noneInvestIgatIon,Itproved
lesssensItIvetotheeffectofaspIrInthanaggregometry.
172
ThePFA100hasalsobeen
reportedtobeveryInsensItIvetotheplateletInhIbItIngeffectofclopIdogrel.
172,17J
ts
predIctIvevaluehasnotbeenwellconfIrmed,andareportbythePlateletPhysIology
SubcommItteeoftheScIentIfIcandStandardIzatIonCommItteeofthenternatIonalSocIety
onThrombosIsandHemostasIsofferedtheopInIonthat,AlthoughthePFA100closure
tImeIsabnormalInsomeformsofplateletdIsorders,thetestdoesnothavesuffIcIent
sensItIvItyorspecIfIcItytobeusedasascreenIngtoolforplateletdIsorders.
174
Clot Retraction
ClotretractIonIsanotherfunctIonofplateletsthatcanbeassessedgrosslyandby
thromboelastography.WhenmaIntaInedatJ7`C,aclotshouldbegIntoretractwIthIn2to
4hours.ThIstestIsdIffIculttoquantIfyandonlyqualItatIveresults(retractIonvs.no
retractIon)areusuallyreported.
Laboratory Evaluation of Coagulation
WhenbloodIsplacedInaglasstesttube,clotformatIonoccursInresponsetocontactwIth
theforeIgnsurface.NoexogenousreagentsarerequIredbecauseallofthefactors
necessaryforcontactInItIatedcoagulatIonareIntrInsIctoblood.ThetImetoformatIon
ofaclotvIathIspathwaycanbeprolongedbydefIcIencIesofanyfactorsIntheclassIc
IntrInsIcpathway.However,theobservatIonthat,evenInhemophIlIacs,theaddItIonof
thromboplastIn(nowmorecommonlycalledTF)tothetesttubecouldshortenthetImeto
clotformatIonsuggestedthepresenceofanalternatIvepathwayoffIbrInformatIon.That
pathwayrequIredtheaddItIonofsomethIngextrInsIctobloodanddIdnotrequIrethe
presenceoffactors7orX.n19J6,whenQuIckIntroducedtheprothrombIntIme(PT)to
clInIcalmedIcIne,suffIcIentthromboplastInwasusedtoyIeldaclotformatIontImeof
approxImately12seconds.UnderthesecIrcumstances,evenpatIentslackIngfactors7or
XshowednormalclotformatIontImes.
175
However,whendIlute(partIal)
thromboplastIn,whIchlackedtheTFequIvalentactIvItynecessarytoactIvateF7,was
usedInlIeuofthe12secondreagent,hemophIlIacsshowedmuchlongerclottIngtImes
thandIdhealthycontrols.ThetwodIfferentpathwayscouldbetestedIndIvIdually.WIth
completethromboplastIn,coagulatIonproceedsvIareactIonsthatareIndependentof
factors7aandXa.WIthpartIalthromboplastIn,coagulatIonmustproceedvIaa
sequenceofreactIonsthatrequIresfactors7andX.Forbothtests,calcIumIsadded
becauseofthechelatIngagentInthebloodspecImencontaIner.ThetImetofIbrInstrand
formatIonIsthenmeasured.
Prothrombin Time
ThePTmeasuresthetImetofIbrInstrandformatIonvIaashortsequenceofreactIons
InvolvIngonlyTF,factors7,X,7,(prothrombIn)and(fIbrInogen),thatIs,theclassIc
extrInsIccoagulatIonpathway(FIg.161).ThenormalPTIs10to12secondsandwIllbe
prolongedbydefIcIencIes,abnormalItIes,orInhIbItorsoffactors7,X,7,,or.ThePT
haslImItatIons.FIrst,ItIsnotverysensItIvetodefIcIencIesofanyofthesefactors.The
coagulantactIvItyofthesefactorsmustdroptoJ0ofnormalbeforethePTIsprolonged.
ThePTIsmost
P.J9J
sensItIvetoadecreaseInF7andleastsensItIvetochangesInprothrombIn(F).When
prothrombInlevelsareonly10ofnormal,theIncreaseInthePTmaybeonly2seconds.
PTwIllnotbeprolongeduntIlthefIbrInogenlevelIsbelow100mg/dL.ftheaPTT(see
laterdIscussIon)Isnormal,thenaprolongedPTIsmostlIkelytorepresentadefIcIencyor
abnormalItyoffactor7.8ecauseF7hastheshortesthalflIfeamongtheclottIngfactors
synthesIzedInthelIver,ItIsthefactorthatfIrstbecomesdefIcIentwIthlIverdIsease,
vItamInKdefIcIency,orwarfarIntherapy.ProlongatIonofthePTmayalsobedueto
defIcIencIesofmultIplefactors.However,whenmultIplefactordefIcIencIesoccur,the
aPTTIsusuallyalsoprolonged.
International Normalized Ratio
ThevarIatIonInthromboplastInreagentsusedresultedInwIdevarIatIonInnormalvalues
andmadecomparIsonofPTresultsbetweenlaboratorIesdIffIcult.TheNFwasIntroduced
tocIrcumventthIsdIffIculty.
176
EachthromboplastInIscomparedwIthanInternatIonally
acceptedstandardthromboplastInandassIgnedannternatIonalSensItIvItyndex.PTtest
tImesobtaInedwIthIndIvIdualreagentscantherebybenormalIzedandreportedasan
NF.
177
Activated Partial Thromboplastin Time
TheaPTTassessesthefunctIonoftheclassIcIntrInsIcandfInalcommonpathways(FIg.16
1).PatIentbloodIscombInedwIththreereagents.naddItIontocalcIum,thereIsa
contactactIvator(e.g.,dIatomaceousearth,kaolIn,celIte,andellagIcacId)onthebasIsof
whIchthetestIscalledanactivatedPTT;andapartial thromboplastin(oftena
phospholIpIdextractedfromrabbItbraInorhumanplacenta),whIchsubstItutesforthe
phospholIpIdsurfaceprovIdedbyplateletsInvIvo.TheaPTTwIllrevealdefIcIencIes,
abnormalItIes,orInhIbItorsofoneormorecoagulatIonfactors:hIghmolecularweIght
kInInogen(H|WK),prekallIkreIn,X,X,X,7,X,7,,and.SurfaceactIvatIonInthe
laboratoryparallelsthe(clInIcallyrelatIvelyunImportant)contactactIvatIonphase
InvolvIngfactorsXandX,prekallIkreIn,andH|WKthatInItIatestheIntrInsIcpathwayIn
vIvo.NormalaPTTvaluesarebetween25andJ5seconds.TheaPTTIsprolongedwhen
thereIsadefIcIency,abnormalIty,orInhIbItoroffactorsX,X,X,7,X,7,,and(I.e.,
allfactorsexcept7andX).TheaPTTIsmostsensItIvetodefIcIencIesoffactors7and
X,but,asIsthecasewIththePT,levelsofthesefactorsmustbereducedto
approxImatelyJ0ofnormalvalues,beforethetestIsprolonged.TheassayIsalsovery
sensItIvetoInhIbItIonofthrombIn(e.g.,byunfractIonatedheparInanddIrectthrombIn
InhIbItors).HeparInInItIallyprolongstheaPTT,butwIthhIghlevelswIllalsoprolongPT.As
wIththePT,theleveloffIbrInogenmustbereducedto100mg/dLbeforetheaPTTIs
prolonged.FXdefIcIency,whIchIsarelatIvelycommoncauseofaPTTprolongatIon,does
notcauseaclInIcalcoagulopathy.FXdefIcIency,whIchisassocIatedwIthasIgnIfIcant
bleedIngdIathesIs,doesnotalteraPTT(oranyothercommoncoagulatIontest).aPTT
results(lIkethoseofthePT)varyfromlaboratorytolaboratorybecauseof
nonstandardIzatIonofthephospholIpIdsandactIvators.
Activated Clotting Time
TheactIvatedclottIngtIme(ACT)IssImIlartotheaPTTInthatItdependsonfactorsthat
areallIntrInsIctoblood(theclassIcIntrInsIcpathwayofcoagulatIon;seeChapter41).
FreshwholebloodIsaddedtoatesttubethatcontaInsapartIculatesurfaceactIvatorof
factorsXandX.ThetImetoclotformatIonIsmeasured.NeItherpartIalthromboplastIn
norphospholIpIdsubstItuteIsadded.CoagulatIonthereforedependsonadequateamounts
ofplateletphospholIpIdbeIngpresentInthebloodsample.TheautomatedACTIswIdely
usedtomonItorheparIntherapyIntheoperatIngroom.NormalvaluesareIntherangeof
90to120seconds.TheACTIslesssensItIvethantheaPTTtofactordefIcIencIesInthe
classIcIntrInsIccoagulatIonpathway.
Thrombin Time
TT,alsocalledthrombin clotting time,IsameasureoftheabIlItyofthrombIntoconvert
fIbrInogentofIbrIn.ThIstest,whIchIsperformedbyaddIngexogenousthrombIntocItrated
plasma,bypassesalltheprecedIngreactIons.TTmaybeprolongedbycondItIonsthat
affecteItherthesubstrate,fIbrInogen,ortheactIonoftheenzyme,thrombIn.TTIs
prolongedwhenthereIsanInadequateamountoffIbrInogen(100mg/dL)orfIbrInogenIs
abnormal(dysfIbrInogenemIa),asInadvancedlIverdIsease.ThrombIn'senzymatIcfunctIon
canbeInhIbItedbyheparIn(complexedtoantIthrombIn),dIrectthrombInInhIbItors(see
laterdIscussIon),F0Ps(seeprevIousdIscussIon),orbyInhIbItorsthatmayoccurInpatIents
wIthplasmacellmyelomaandotherImmunoprolIferatIvecondItIons.
178
ThenormalTTIs
10to15seconds.
Reptilase Time
WhenTTIsprolonged,thereptIlasetImecanbeusedtodIfferentIatebetweentheeffects
ofheparInandF0Ps.FeptIlase,whIchIsderIvedfromsnakevenom,convertsfIbrInogento
fIbrIn.TheactIonofreptIlaseIsunaffectedbyheparInbutIsInhIbItedbyF0Ps.Aprolonged
TTandanormalreptIlasetImesuggestthepresenceofheparIn.ProlongatIonofbothTT
andreptIlasetImewIlloccurInthepresenceofF0Ps,orwhenfIbrInogenlevelIslow.The
normalreptIlasetImeIs14to21seconds.
Ecarin Clotting Time
0IrectthrombInInhIbItors(0Ts)suchashIrudIn,lepIrudIn,argatroban,andbIvalIrudInare
frequentlyusedInpatIentswIthheparInInducedthrombocytopenIa/thrombosIs(HT/T).At
low0TconcentratIons,TT,aPTT,andACTprovIdereasonablecorrelatIonswIth0T
concentratIon,andonthelImItedoccasIonswhenmonItorIngIsdeemednecessary(most
oftenpatIentsInrenalfaIlure),theaPTTIscommonlyused.8utwIththelevelsrequIred
forCP8,thecorrelatIonbecomespoorandtherIskofoverdosewIththeseagents,for
whIchtherearenoantagonIsts,becomessIgnIfIcant.TheecarInclottIngtImeprovIdesa
bettercorrelatIonandcanbeusedformonItorIngInthatcontext.
179
Thetestemploysthe
venomofthesawscaled(alsoknownassawtooth)vIper(Echis carinatus).A
metalloproteaseInthevenomconvertsnormalprothrombIntoaform(meIzothrombIn)
thatIsstIllcapableofconvertIngfIbrInogentofIbrInbutthatIsInhIbItedby0TsIna
relIablydosedependentmanner.
180
AthromboelastographIcmethodInwhIchecarInIsused
toInItIatecoagulatIonhasalsobeenreportedtoprovIdeamuchbettercorrelatIonwIth
bIvalIrudInlevelsthantheACT.
181
Anti-Xa Activity Assay
TheantIXaactIvItyassayIsusedtomonItortheeffectsoflowmolecularweIghtheparIns,
IndIrectXaInhIbItorsandoccasIonallyunfractIonatedheparIn.PatIentplasmaIsmIxed
wIthareagentcontaInIngaknownamountofXaandexcessantIthrombIn.AchromogenIc
substrateofXaIsadded,andacolorchangereactIonoccursInproportIontotheXanot
boundbyantIXaactIvItyInthepatIent'sserum.
Fibrinogen Level
NormalfIbrInogenvaluesarebetween160andJ50mg/dL.8elow100mg/dL,fIbrInogen
maybeInadequate.FIbrInogenIsrapIdlydepleteddurIng0C.AmarkedIncreaseIn
fIbrInogen
P.J94
mayoccurInresponsetostress,IncludIngsurgeryandtrauma.LevelsInexcessof700
mg/dLmayoccur.8ecauseofthIsIncrease,InspIteofrapIdfIbrInogenconsumptIondurIng
ahypercoagulablestatesuchas0C,thefIbrInogenlevelmaystIllappeartobenormal.
Evaluation of Fibrinolysis-Fibrin Degradation Products and D-
Dimer
TheF0PtestIdentIfIesthebreakdownproductsoffIbrIn(crosslInkedoruncrosslInked)and
fIbrInogen.The0dImerassayIsspecIfIcforbreakdownproductsofcrosslInkedfIbrIn.F0Ps
wIllbeIncreasedInanystateofacceleratedfIbrInolysIs,IncludIngadvancedlIverdIsease,
fIbrInolysIsassocIatedwIthCP8,exogenousthrombolytIcs(e.g.,streptokInase),and0C.0
dImerIsspecIfIctocondItIonsInwhIchextensIvelysIsofthecrosslInkedfIbrInofamature
thrombusIsoccurrIng,asoccursIn0C,butalsowIthdeepveInthrombosIs(07T)andPE.
The Thromboelastogram
ThromboelastographyprovIdesameasureofthemechanIcalpropertIesofevolvIngclotas
afunctIonoftIme.AprIncIpaladvantageIsthattheprocessesItmeasuresrequIrethe
IntegratedactIonofalltheelementsofthehemostatIcprocess:plateletaggregatIon,
coagulatIon,andfIbrInolysIs.ThethromboelastogramIsobtaInedbyplacIngaspecImenof
bloodInarotatIngcuvettecontaInIngacontactactIvatorandcalcIum.(HeparInasecan
alsobeaddedtoelImInateheparIneffect.)ApIstonIsloweredIntothecuvette.Asclot
formatIonbegIns,thepIstonrotatesasafunctIonoftheadherenceoftheevolvIngfIbrIn
clottothepIston.TherotatIonofthepIstonresultsInatoandfroexcursIonofastylus,
theamplItudeofwhIchIsproportIonaltothespeedofpIstonrotatIon.
FIgure167depIctsanormalthromboelastogram.SeveralparametersarederIvedfromthe
thromboelastogram.ThemostcommonlyusedonesandtheIrInterpretatIonareas
follows.
182
F,thereactIontIme,IstheIntervaluntIlInItIalclotformatIon.trequIres
thrombInformatIon,andprolongatIonIsusuallyIndIcatIveofanIntrInsIcpathwayfactor
defIcIency.K,theclotformatIontIme,IstheIntervalrequIredafterFforthe
thromboelastogramtoachIeveawIdthof20mm.ProlongatIonoccurswIthdefIcIencIesof
thrombInformatIonorgeneratIonoffIbrInfromfIbrInogen.Thealphaangle,lIkeK,Isa
measureofthespeedofclotformatIon.AdecreaseofthealphaanglehassImIlar
sIgnIfIcancetoaprolongatIonofK.|A,themaxImumamplItude,Isameasureofthe
strengthofthefullyformedclot.treflectsprImarIlyplateletnumberandfunctIon,
althoughItalsorequIresproperfIbrInformatIontoachIevenormalvalues.|AtypIcally
occursbetweenJ0and60mInutes.The(|A+x)/|A,IstheratIooftheamplItudeata
specIfIctImeInterval(x)after|AdIvIdedby|A,Isusedasameasureoftherateof
fIbrInolysIs.The(|A+60)/|AratIohasbeenusedmostwIdely.
18J
AratIoof0.85Is
evIdenceofabnormalfIbrInolysIs.
184
nclInIcalpractIce,partIcularlyInlIver
transplantatIon,anonquantItatIveapprecIatIonofthetypIcalteardropshape(FIg.168)Is
usedmoreoftentosupportadIagnosIsofIncreasedfIbrInolysIsthanarespecIfIcnumerIcal
values.F,theIntervalfrom|AtoreturntoazeroamplItude,Isameasureoftherateof
fIbrInolysIs.FIssuffIcIentlylongInnormalsubjectssothatthetestIsusuallytermInated
beforethIstImeelapses.
Figure 16-7.ThenormalthromboelastogramandthevarIablescommonlyderIved
fromIt.SeetextfordetaIls.(FromKangY,LewIsJH,NavalgundA,etal:EpsIlon
amInocaproIcacIdfortreatmentoffIbrInolysIsdurInglIvertransplantatIon.
AnesthesIology1987;66:766,wIthpermIssIon.)
Figure 16-8.ThromboelastogrampatternsseenInnormalsubjectsandInsubjectswIth
fourabnormalItIesofhemostasIs.(FromKangY:|onItorIngandtreatmentof
coagulatIon,HepatIcTransplantatIon:AnesthetIcandPerIperatIve|anagement.
EdItedbyWInterK,KangY.NewYork,Praeger,1986,pp151,wIthpermIssIon.)
ThethromboelastogramhasbeenemployedIncardIacsurgery,majortrauma,andhepatIc
transplantatIon.tIsInthelatterthatItIsusedmostfrequently.Commonly,Inthat
context,anIncreasedFpromptstheadmInIstratIonofFFP,adecreased|Aleadsto
plateletadmInIstratIon,andtheteardropconfIguratIonoffIbrInolysIsleadstothe
admInIstratIonofantIfIbrInolytIcs.TheuseofthethromboelastogramtoguIdetransfusIon
InlIvertransplantatIonhasbeenshowntodecreasetheamountsofF8CsandFFP
admInIstered.
185
Interpretation of Tests of the Hemostatic Mechanism
AneffectIveapproachtotheInterpretatIonofcoagulatIontestsIstoapprecIateInadvance
theconstellatIonoftestresults(thecoagulatIonprofIle)thatIslIkelytooccurwItheach
ofthecommonbleedIngdIsorders(Table1615).ThemostcommonlyorderedcoagulatIon
testsaretheplateletcount,PT,aPTT,andoccasIonally8T.WhenagreaterdIsruptIonof
thehemostatIcmechanIsmIssuspected,furthertestsIncludIngfIbrInogen,TT,andassays
forF0Psand0dImermaybeordered.NotethatsomesIgnIfIcantclInIcalbleedIng
dIatheses,IncludIngdefIcIencIesofFXand
2
antIplasmInandmIlddegreesofvW0,wIll
notberevealedbyroutInecoagulatIontestIng.
8ecausethecoagulatIondefectsthatappearmostoftenarerevealedbyabnormalvalues
ofPTand/oraPTT,FIgure169provIdesanalgorIthmfortheevaluatIonofthose
abnormalItIes.
Common Coagulation Profiles
1.Plateletcountdecreased(normalaPTTandPT).0IfferentIaldIagnosIs:decreased
plateletproductIon(seelaterdIscussIon),excessconsumptIon,plateletdestructIon,or
sequestratIonInthespleen(seebleedIngdIsorders,thrombocytopenIa).
Figure 16-9.AnapproachtotheevaluatIonofprolongedprothrombIntIme(PT)
and/oractIvatedpartIalthromboplastIntIme(aPTT).TT,thrombIntIme;Fbg,
fIbrInogen;00,0dImers;APA,antIphospholIpIdantIbody(e.g.,lupusantIcoagulant,
antIcardIolIpIn,andantI82CPantIbodIes);0C,dIssemInatedIntravascular
coagulatIon.(|odIfIedfrom8ombelIT,Spahn0F:UpdatesInperIoperatIve
coagulatIon:physIologyandmanagementofthromboembolIsmandhaemorrhage.8rJ
Anaesth2004;9J:275,wIthpermIssIon.)
P.J95
P.J96
2.Prolonged8T(normalplateletcount,aPTT,PT).0IfferentIaldIagnosIs:antIplateletdrug
IngestIon(e.g.,nonsteroIdalantIInflammatorydrugs,acetylsalIcylIcacId,clopIdogrel),
uremIa,vW0(althoughfactor7:ClevelsmaybedecreasedwIthvW0[type1],only25to
J0of7:CcoagulantactIvItyIsnecessarytoproduceanormalaPTT).
J.ProlongedaPTT(normalplateletcountandPT).0IfferentIaldIagnosIs:heparIn,thelupus
antIcoagulantorotherantIphospholIpIdantIbodIessuchasantIcardIolIpInandantI82CP
antIbodIes,
186
defIcIencyofFX,H|WK,orprekallIkreIn,hemophIlIaAor8,vW0,
acquIredfactorInhIbItors,andpoorcollectIontechnIque.
0IsordersthatproducethIscombInatIonaffectfactorsoftheIntrInsIcpathway
(prekallIkreIn,H|WK,factorsX,X,X,and7)and/orthecommonpathway(X,7,,and
).WIthheparIntherapy,InItIallyonlytheaPTTIsprolonged.AthIgherdosesboththeaPTT
andPTareprolonged.NotethatsomecommoncausesofaprolongedaPTTarenot
assocIatedwIthableedIngdIathesIs.TheaPTTprolongatIoncausedbythelupus
antIcoagulantandotherantIphospholIpIdantIbodIesIstheresultofthebIndIngofthe
phospholIpIdusedtosupportcoagulatIonInvItro.ThesepatIentsactuallyhavea
prothrombotIctendency.0efIcIencIesofFX,H|WK,orprekallIkreIn,InpartIcularFX,
arealsocommoncausesofaPTTprolongatIon.TheyarenotusuallyassocIatedwItha
sIgnIfIcantclInIcalhemostatIcdefect.CollectIontechnIquecanprolongtheaPTTeItherby
heparIncontamInatIonorbecausefactors7and7,thelabIlefactors,maybeconsumedIf
thebloodbecomespartIallyclottedprIortodelIverytothelaboratory.TheaPTTIsvery
sensItIvetofactor7defIcIency.WhentheaPTTIsprolongedInIsolatIon,IsItlesslIkely
tobeduetoableedIngdIsorderthatInvolvesmultIplefactordefIcIencIes(suchaslIver
dIsease,vItamInKdefIcIency,theadmInIstratIonofwarfarIn,orthecoagulopathy
assocIatedwIthmassIvetransfusIonor0C).HeparIntherapyorcongenItaldIsordersof
hemostasIsaremoreprobable.
4.ProlongedPT(normalplateletcountandaPTT).0IfferentIaldIagnosIs:vItamInK
defIcIency,warfarInadmInIstratIon,earlylIverdysfunctIon,F7defIcIency,andacquIred
coagulatIonfactorInhIbItors.
8ecausefactor7hastheshortesthalflIfeamongthevItamInKdependentfactors,
depletIonofthevItamInKdependentfactorswIllfIrstprolongthePTandonlylaterthe
aPTT.SImIlarly,thedevelopmentoflIverdIseasewIllleadtodefIcIencIesoffactor7fIrst
andInItIalprolongatIonofonlythePT.WIthfurtherdeterIoratIonoflIverfunctIon,both
thePTandtheaPTTwIllbeprolonged.AdvancedlIverdIseasecanalsoleadto
thrombocytopenIaandplateletdysfunctIon.
84
AcquIredcoagulatIonfactorInhIbItorsare
rarebutcanoccurInpatIentswIthlymphomaorcollagenvasculardIsease.
5.ProlongedPTandaPTT(normalplateletcount).0IfferentIaldIagnosIs:vItamInK
defIcIency,warfarIn,andheparIn.
6.ProlongedPT,aPTT,andTT(normalplateletcount).0IfferentIaldIagnosIs:heparIn,
0Ts,F0Ps,hypofIbrInogenemIa,anddysfIbrInogenemIa.
AlthoughadvancedlIverdIseasecanalsoproducemultIplefactordefIcIencIesandthIs
pattern,theplateletcountIsusuallydecreased.F0PswIllalsobeelevated(seelater
dIscussIon).
SImultaneousprolongatIonoftheTTmakesthedIagnosIsofsImplevItamInKdefIcIencyor
warfarIntherapyunlIkely.TTIssensItIvetomInutelevelsofheparIn.AddItIonof
protamIneorareptIlasetImewIllIdentIfyheparIn.F0PsmaybeelevatedwIthfIbrInolytIc
therapy,0C,orlIverdIsease.0CandlIverdIseaseusuallyresultInthrombocytopenIaas
well.AnormalplateletcountmakesheparInorextensIvefIbrInolysIsmorelIkely.
7.ProlongedPT,aPTT,TT,decreasedplateletcount.0IfferentIaldIagnosIs:0C,dIlutIonby
massIvetransfusIon,lIverdIsease,andheparIntherapy.
Table 16-15 Interpretation of Coagulation Tests
PLATELET
COUNT
BLEEDING
TIME
apTt PT TT FIBRINOGEN FDPs POSSIBLE CAUSE EXAMPLE
Nor N N N N N
ProductIon
sequestratIon
ConsumptIon
mmune
destructIon
FadIatIon,
chemotherapy
Splenomegaly
ExtensIve
tIssuedamage
H..T.
N N N N N N
Platelet
dysfunctIon
0rugs:ASA,
NSA0s,
ClopIdogrel,
b/a
InhIbItors;
uremIa;mIld
vW0
N N N N N
SeverevWF
defIcIency
vW0
N N N N N N
Factor
defIcIency
Factor
InhIbItIon
AntIphospholIpId
antIbody
HemophIlIaA
or8
Lowdose
heparIn,
L|WH
a
Poor
collectIon
technIque
Lupus
antIcoagulant
N N N N N N
Factor7
defIcIency
EarlylIver
dIsease
EarlyvItamIn
KdefIcIency
Early
CoumadIn
therapy
N N N N
|ultIplefactor
defIcIencIes
LatevItamIn
KdefIcIency
Late
CoumadIn
therapy
HeparIn
therapy
b
N
0IlutIonof
factorsand
platelets
|assIve
transfusIon

Hypercoagulable
state
productIonof
factors
0C
c
Advanced
lIverdIsease
,Increased;,decreased;N,normal;ASA,aspIrIn;aPTT,actIvatedpartIal
thromboplastIntIme;PT,prothrombIntIme;TT,thrombIntIme;F0Ps,fIbrIndegradatIon
products;HT,heparInInducedthrombocytopenIa;vWF,vonWIllebrandfactors;vW0,
vonWIllebrand'sdIsease;L|WH,lowmolecularweIghtheparIn;NSA0s,nonsteroIdal
antIInflammatorydrugs;0C,dIssemInatedIntravascularcoagulatIon;H..T.,heparIn
InducedthrombocytopenIa.
a
aPTTprolongatIonIsmorelIkelytooccurwIthL|WHswIthlowerXa/aeffectratIos,
forexample,tInzaparIn,thanwIthgreaterratIos,forexample,enoxaparIn.
b
8leedIngtImemayalsobeprolongedInassocIatIonwIthamarkedaPTTIncrease.
c
0CmaybedIstInguIshedbythepresenceof0dImers.
F0Psand0dImerareelevatedIn0CandallowdIfferentIatIonfromdIlutIonaleffectsand
excessheparIn.HeparIncausesthrombocytopenIaonlywhenprolongedexposureresultsIn
HT/T.F0Ps,butnot0dImer,areelevatedInseverelIverdIsease.
TheInterpretatIonofcoagulatIontestsmaybemademoredIffIcultbythefactthat
patIentswhodevelopableedIngdIathesIsIntheperIoperatIveperIodmayhavemorethan
onebleedIngdIsorder(e.g.,0CandcoagulopathyrelatedtomassIvetransfusIon)andmay
alsohaveasurgIcalcauseforbleedIng.
Disorders of Hemostasis: Diagnosis and Treatment
ThehemostatIcmechanIsmInvolvesanIntrIcatebalancethatservestolImItbloodlossIn
theeventofvascularInjurywhIlemaIntaInIngthelIquIdcharacterofbloodatothertImes.
UndernormalcIrcumstances,anequIlIbrIumbetweenclottIngandbleedIngIsmaIntaIned
wIththehelpofmultIpleactIvators,InhIbItors,cofactors,andfeedbackloops,both
posItIveandnegatIve.UnderpathologIccIrcumstances,thatequIlIbrIummaybelost,
leadIngtoeItherhemorrhagIcorthrombotIccomplIcatIons.AccordIngly,dIsordersof
hemostasIscanbebroadlyclassIfIedIntothosethatleadtoabnormalbleedIngandthose
thatleadtoabnormalclottIng.ThedIsordersmaybefurthercategorIzedaccordIngto
whethertheyInvolveplatelets,clottIngfactors,and/orthepresenceorabsenceof
InhIbItors(suchasF0Ps).FInally,dIsordersmaybeheredItaryoracquIred.Treatmentmay
requIreadmInIstratIonofhemostatIcbloodproducts(plateletsand/orclottIngfactors)or
pharmacologIcagents.Thelattermaybechosenforeffectsonplatelets(desmopressIn,
antIplateletdrugs),onclottIngfactors(vItamInK,warfarIn,heparIn),oronnaturally
occurrIngInhIbItors(antIfIbrInolytIcagents,protamIne,fIbrInolytIcs).
ThepreoperatIvehIstoryIsInvaluable.AbnormalItIesofprImaryhemostasIs,usuallycaused
byreducedplateletnumberorfunctIon,wIllberevealedbyevIdenceofsuperfIcIal(skIn
andmucosal)bleedIngIncludIngeasybruIsIng,petechIae,prolongedbleedIngfrommInor
skInlaceratIons,recurrentepIstaxIs,andmenorrhagIa(seeChapter2J).CoagulatIon
abnormalItIesareassocIatedwIthdeepbleedIngeventsIncludInghemarthrosesor
hematomasafterblunttrauma.
Hereditary Disorders of Hemostasis
Inherited Platelet Disorders
The8ernardSoulIersyndromeInvolvesvarIousabnormalItIesoftheCPbreceptorand
thereforeresultsIndefIcIencIesofplateletadhesIon(FIg.16J).nClanzmann's
thrombasthenIa,abnormalItIesoftheCPbareceptorcomplexresultIndefectIve
plateletaggregatIon(FIg.164).8othareextremelyrare.Thereareotherevenless
commonabnormalItIesaffectIngvIrtuallyeveryphaseofplateletfunctIonIncludIng
synthesIsofTXA
2
,synthesIsandreleaseofthecontentsofalphaanddensegranules(FIg.
16J),andreceptor(A0P,TXA
2
)morphologyandfunctIon.
187
von Willebrand Disease
vW0IsthemostcommonheredItarybleedIngdIsorder.SomeformofthedIseaseIspresent
InapproxImately1ofthegeneralpopulatIon,althoughItIsovertlysymptomatIcInonly
about10ofthoseafflIcted.
188
vW0IstheresultofthesynthesIsofanabnormalvWFor
normalvWFInreducedamount.ThevWFIsaproteInsynthesIzedbyendothelIalcells,
P.J97
megakaryocytes,andplatelets.tIsImportantforbothprImaryhemostasIs,thatIs,the
bIndIngofplateletstosItesofvascularInjury,andforcoagulatIon,thelatterthroughIts
roleasacarrIerproteIn/stabIlIzerforF7.vWFhasseveraldIstInctbIndIngdomaIns
responsIbleforItsseveralhemostatIcfunctIons.ThosedomaInsIncludesItesthatare
specIfIcforcollagen(foradherencetothesubendothelIum),fortheplateletCPbreceptor
(forplateletadhesIontocollagen),fortheplateletCPb/areceptor(forplatelet
aggregatIon),andforfactor7:C(forvWF'scarrIerproteInfunctIon).Thereareatleast50
genetIcvarIatIonsofvW0,whIchaccountsforItsphenotypIcheterogeneIty.Thereare
threeprIncIpalsubtypes.Type1,whIchcomprIses70to80ofvW0,IsaquantItatIve
defect.vWFIspresentbutIssecretedInreducedamount.PatIentswIthtype1vW0present
wIthapatternofbleedIngthatIscharacterIstIcofabnormalItIesofprImaryhemostasIs.
Type2vW0,whIchcomprIses20toJ0ofpatIentswIthvW0,IncludesahostofqualItatIve
defectsofvWF.SomemutatIonsaffecttheplateletInteractIonsofvWFandothersthe
factor7InteractIon.Type2IssubdIvIdedIntofoursubtypes.Type28IscharacterIzedby
avarIantofthevWFthatcausesabnormalaggregatIonofplateletsandthrombocytopenIa.
TheabnormalvWFhasahIghaffInItyfortheplateletCPbreceptor.ThebleedIngdIathesIs
IsprobablytheresultofformatIonandclearanceofvWFplateletcomplexesandthe
resultantthrombocytopenIa.nthe2N(Normandy)subtype,thevWFhasamarkedly
reducedaffInItyforfactor7.ThesepatIentsdemonstratenormalplateletfunctIon,but
bleedbecauseofdecreasedfactor7coagulantactIvIty.ThesepatIentsarereadIly
mIsdIagnosedashavIngmIldhemophIlIaA.TypeJvW0,whIchIsveryrare,entaIlsa
completeabsenceofvWF,resultIngInasevereabnormalItyofbothprImaryhemostasIs
andcoagulatIon.
The Role of vWF in Hemostasis
vWFIsessentIalforplateletplugformatIon.tmedIatesplateletadhesIontothe
subendothelIalsurfaceofbloodvessels.AfterbIndIngtothesubendothelIum,vWF
undergoesaconformatIonalchangethatonlythenallowsplateletstoadherevIatheIr
glycoproteInCPbreceptors.TheantIbIotIc,rIstocetIn,canInducetheplateletCPbvWF
InteractIonand,accordIngly,IsthebasIsforonelaboratorytestofplateletfunctIon.vWF
alsopartIcIpatesInplatelettoplateletaggregatIon.PlateletaggregatIonoccursbybIndIng
ofvWFmoleculestotheCPb/areceptorsonthesurfaceofseveralplatelets.ThevWF
alsoactsasacarrIerproteInforthecoagulantactIvItyoffactor7,referredtoasVIII:C,
wIthwhIchItcIrculatesInacomplexedformthatprolongsthecIrculatIontImeof7:C.
Diagnosis and Treatment of vWD
HIstorywIllcommonlyrevealabnormalbleedIngfrommucosalsurfaces.SIxtypercentof
thepatIentswIllreportepIstaxIs,50wIllreportmenorrhagIa,andJ5wIllacknowledge
gIngIvalbleedIng,easybruIsIng,andhematomas.
189
vW0shouldbeconsIderedInpatIents
whogIveahIstoryofunexplaInedpostoperatIvebleedIng,partIcularlyfollowIng
tonsIllectomyordentalextractIon.AlthoughvW0IsaheredItarydIsease,aclearfamIly
hIstoryIsnotalwaysevIdentbecausedIseaseseverItyvarIessubstantIally.
SpecIalIzedlaboratorytests,IdeallydIrectedbyahematologIst,mayberequIredto
confIrmthedIagnosIsandtypeofvW0.DneormorevWFmarkers,IncludIngvWFfactor
antIgen(vWF:Ag),vWFrIstocetIncofactoractIvIty(vWF:FCo),and/orvWFcollagenbIndIng
actIvIty(vWF:C8)wIllbedImInIshedorabsent.8ecausevW0IsacarrIerproteIn/stabIlIzer
ofF7,F7halflIfeIsdImInIshed,andF7levelsarecharacterIstIcallyalsodecreased.
WhatIsImportantfortheanesthesIologIsttoapprecIateIsthattheresultsofthemost
commonlyorderedcoagulatIontests,theplateletcount,theaPTT,andthePT,maybe
normalInthepatIentwIthvW0.AlthoughthehalflIfeof7:CIsdImInIshedInvW0,there
IsusuallysuffIcIent7:CtoyIeldanormalaPTTInbasalcondItIons.
ThetwoestablIshedtreatmentsforvW0are00A7P(1deamIno80argInInevasopressIn)
andfactorconcentrates.
190,191
00A7P,whIchpromotesreleaseofvWF,IseffectIvefIrst
lInetherapyforthelargemajorIty(approxImately80)ofpatIentswIthvW0,IncludIng
thosewIthtype1andtype2AdIsease.
192
However,therecognItIonofsubtype28(see
prevIousdIscussIon)IsImportantbecause00A7PwIllcausethrombocytopenIaInthese
patIents.
19J
00A7P,gIvenIntravenouslyInadoseof0.Jg/kg,Increasesfactor7:Cand
vWFtwotofIvefoldInmostpatIents.tseffectIsmaxImalafterJ0mInutes,andelevated
levelspersIstfor6to8hours
189,192
(seePharmacologIcTherapy:0esmopressIn).Forthe
20ofpatIentswhodonotrespondadequatelyto00A7P,vIrallyInactIvatedfactor
concentrates(e.g.,HaemateP)wIllbeapproprIate.TheIreffIcacyIswellconfIrmed.
194,195
AntIfIbrInolytIcagents,amInocaproIcacId(EACA)andtranexamIcacId(TXA),are
sometImesusedIncombInatIonwIth00A7PtomanagethesepatIentsdurIngthe
perIoperatIveperIod.
19J
ThesedrugsmaybegIvenIntravenouslyororally.Theyhavealso
beenadmInIsteredtopIcally,asmouthwashes,InpatIentswIthvW0undergoIngdental
extractIons.DralcontraceptIves(estrogens)havebeenusedtotreatpatIentswIthvW0
whohavemenorrhagIa,orwhoareundergoIngelectIvesurgery.
19J
ThemechanIsmof
actIonoftheestrogensIsnotwellunderstood,althoughaconnectIonwIthvWFsynthesIsIs
suspected.AntIplateletdrugsshouldbeavoIdedInpatIentswIthvW0.
The Hemophilias
HemophIlIaAresultsfrommutatIonsthatleadtoeItherdefIcIentorfunctIonallydefectIve
factor7:C.HemophIlIa8(ChrIstmasdIsease)andhemophIlIaCarecausedbydefIcIency
orabnormalItyoffactorsXandX,respectIvely.
196
TherelatIvefrequencIesofthethree
hemophIlIasarefactor7:C,85;factorX,14;andfactorX,1.FareInherIted
defIcIencIesoffactors,7,7,andXalsooccur.
196
8othhemophIlIaAand8aresexlInked
recessIvedIsorders,whIchthereforeoccuralmostexclusIvelyInmales.HemophIlIaCIsan
autosomalrecessIvedIsorderthatoccursalmostexclusIvelyInAshkenazIJews.
196
About
50ofoperatIonsInhemophIlIacsareorthopaedIcproceduresrequIredfortreatmentof
thearthrItIcconsequencesofhemarthroses.
Hemophilia A
Factor7:CcIrculatesboundtoandprotectedbyvWF.nhemophIlIaA,patIentshave
normallevelsofvWFbuthavereducedordefectIvefactor7:C.HemophIlIaAoccursIn
approxImately1In10,000males.HemophIlIacsexperIencedeeptIssuebleedIng,
hemarthroses,andhematurIamostcommonly.PatIentswIthmIlddIseasehavefactor
levelsof5toJ0ofnormalandusuallybleedabnormallyonlyfollowIngtrauma.PatIents
wIthmoderatedIseasehavefactorlevelsof1to5andoccasIonallybleedspontaneously.
ThegreatmajorItyofhemophIlIacshavethesevereformofthedIsease.Factor7:C
levelsare1ofnormalandtheyfrequentlyexperIencespontaneousbleedIngepIsodes.
TheseverItyofclInIcalsymptomsusuallycorrelateswIththelevelofclottIngfactor
actIvIty.LIkethepatIentwIthvW0,hemophIlIacsshouldavoIdaspIrInandotherplatelet
InhIbItIngagents.
Diagnosis and Treatment
PatIentswIthhemophIlIaAwIllcommonlyreportahIstorythatrevealstheXlInked
recessIvepatternofdIseaseInherItance.0IagnosIsIsmadeonthebasIsofaprolonged
aPTTandspecIfIcfactorassaysdemonstratIngadefIcIencyoffactor7coagulantactIvIty
wIthnormallevelsofvWF,factorX,andfactorX.PTand8TwIllbe
P.J98
normal.HemophIlIaAIstreatedwIthplasmaderIved,vIrallyattenuatedconcentratesor
wIthrecombInantfactor7.
196
ntheeventofanepIsodeofspontaneousbleedIng(mostoftenahemarthrosIs),a
procoagulantlevelof25Isacommontarget.ForelectIvesurgIcalprocedures,thelevel
offactor7:CactIvItyIsusuallyraIsedto50to100ofnormalbyadmInIstratIonofvIrally
InactIvatedfactorconcentrate.|anyhemophIlIacsdevelopInhIbItorstofactor7:C,
whIchIncreasestheamountofconcentratethatwIllberequIred.FecombInantactIvated
F7a(seelaterdIscussIon)maybenecessaryforthepatIentwIthInhIbItors.
00A7PwIllalsoIncreaseplasmafactor7:CandvWFconcentratIonsandIsofteneffectIve
InmIldhemophIlIaA.TheeffectmaybepartlytheresultofprotectIonofavaIlableF7
byIncreasedconcentratIonsofthecarrIermolecule,vWF.However,00A7PIsalsothought
tocausethereleaseoffactor7:CfromlIverendothelIalcells.
197
ThereIsalarge
varIatIonInpatIentresponseto00A7P,andItIsmosteffectIveInpatIentswIthfactor
7:Clevels5.
8J,192,198
tIsgIvenIntravenouslyInadoseof0.Jg/kgIn50mLofsalIne
over15toJ0mInutes.tcausesapromptIncreaseInfactor7:C.However,tachyphylaxIs
doesdevelop,whIchlImItsItsusefulness.TheantIfIbrInolytIcsEACAandTXAhavebeen
usedtotreathemophIlIacpatIentsprIortodentalprocedures.Theagentsare
contraIndIcatedInbleedIngepIsodesInvolvIngjoIntsortheurInarytractbecausetheclots
thatdoformmaynotbelysedforalongperIodoftIme.
Hemophilia B
FactorXdefIcIencyIsalsoanXlInkedrecessIvedIsorder,occurrIngInapproxImately
1/25,000males.
196
tproducesableedIngdIathesIsthatIsclInIcallyIndIstInguIshablefrom
hemophIlIaA.TypIcally,mInorhemorrhageIsmanagedbyachIevIngFXlevelsof20toJ0
ofnormal.Levelsof50to100aresoughtformoreseverehemorrhageandInantIcIpatIon
ofsurgery.FecombInantandvIrallyattenuatedFXfactorconcentratesareavaIlableand
arethepreferredtreatment.
Protein C and Protein S Deficiency
HeredItarydefIcIencIesofproteInCandproteInSareassocIatedwIththromboembolIc
eventsorIgInatIngonthevenoussIdeofthecIrculatIon(e.g.,07T,PE,andparadoxIcal
embolIzatIoncausIngstroke).ThecompleteabsenceofproteInCIsassocIatedwIthdeath
InInfancy.PatIentswhoexperIencethromboembolIceventsandhavedecreasedlevelsof
proteInCorproteInSshouldremaInonantIcoagulanttherapyIndefInItely.
Acquired Disorders of Hemostasis
FormnemonIcpurposes,ItIshelpfultoclassIfybleedIngdIsordersaccordIngtowhIchof
thethreehemostatIcprocessesIsInvolved:prImaryhemostasIs(plateletdIsorders),
coagulatIon(clottIngfactordIsorders),fIbrInolysIs(productIonofInhIbItorssuchasF0Ps),
orsomecombInatIonofthethree.SImIlarly,ItIsusefultousetheresultsofcoagulatIon
teststodetermInewhethertheclInIcalproblemInvolvesprImaryhemostasIs(e.g.,
decreasedplateletcount,Increased8T),coagulatIon(e.g.,prolongedPTandaPTT,
decreasedfactorlevels),fIbrInolysIs(IncreasedF0Ps,Increased0dImer),orsome
combInatIonofthethree.UltImately,therapeutIcdecIsIons(e.g.,admInIstratIonof
platelets,FFP,oranantIfIbrInolytIcagent)wIllsImIlarlybeorIentedtotreatmentofone
ormoreoftheseprocesses.
Acquired Disorders of Platelets
TheclInIcalcondItIonsthatcauseanIsolateddIsorderofprImaryhemostasIstypIcally
InvolveabnormalItIesofeItherplateletnumberorfunctIon.
Thrombocytopenia
PlateletsarederIvedfrommegakaryocytesInthebonemarrowInresponseto
thrombopoIetIn,whIchIssynthesIzedbythelIver.ThecausesofthrombocytopenIamaybe
categorIzedas(1)InadequateproductIonbythebonemarrow,(2)IncreasedperIpheral
consumptIonordestructIon(nonImmunemedIated),(J)IncreasedperIpheraldestructIon
(ImmunemedIated),(4)dIlutIonofcIrculatIngplatelets,and(5)sequestratIon.
1. 8onemarrowproductIonofplateletscanbeImpaIredInmanyways.PhysIcaland
chemIcalagents(radIatIonandchemotherapy),varIousdrugs(thIazIdedIuretIcs,
sulfonamIdes,dIphenylhydantoIn,alcohol),InfectIousagents(hepatItIs8,T8,
overwhelmIngsepsIs),andchronIcdIseasestates(uremIa,lIverdIsease)canallcause
bonemarrowsuppressIon.nfIltratIonofthebonemarrowbycancercellsorreplacement
byfIbrosIswIllalsoresultInInadequateplateletproductIon.
2. AcceleratednonImmunologIcallymedIatedconsumptIoncanoccurInmanycondItIons
thatcauseextensIveactIvatIonofcoagulatIonwIthorwIthouttheoccurrenceof0C.
AfterextensIvetIssuedamage(e.g.,burns,crushInjurIes),whIchdenudevascular
endothelIum,thenormalprocessofhemostasIsactIvatesplateletsandleadstotheIr
consumptIonandtothrombocytopenIa.nasImIlarfashIon,theInteractIonofplatelets
wIthnonendothelIalIzedstructuressuchaslargevasculargraftscanalsoleadtoa
transIentthrombocytopenIa.PlateletsareconsumedInpatIentswIthanextensIve
vasculItIssuchasoccurswIthtoxemIaofpregnancy.ThemanycondItIonsthatcause0C
(seelaterdIscussIon)wIllalsocauseplateletstobeconsumedordestroyedmorerapIdly
thantheycanbeproduced.
J. mmunologIcallymedIatedconsumptIoncanbecausedbyvarIousdrugs(heparIn,
quInIdIne,cephalosporIns,vancomycIn)andautoImmunedIsorders(systemIclupus
erythematosus,rheumatoIdarthrItIs,thrombotIcthrombocytopenIcpurpura).
AlloImmunIzatIonresultIngfromprevIoustransfusIonsorpregnancycancause
refractorInesstoplatelettransfusIons.
4. 0IlutIonofplateletswIlloccurInthecontextofmassIvetransfusIon(seelaterdIscussIon
and|assIveTransfusIon).
5. UndernormalcondItIons,approxImatelyonethIrdofplateletsaresequesteredInthe
spleen.Whenthespleenenlarges,anIncreasIngnumberofplateletsaresequesteredand
thrombocytopenIamayresult.ThIsmayoccurwIththesplenomegalyassocIatedwIth
myelodysplastIcsyndromesandcIrrhosIsofthelIver,althoughInthelattercondItIon,
decreasedproductIonalsocontrIbutestothrombocytopenIa.
Disorders of Platelet Function
Uremia
PlateletdysfunctIonIscommonInuremIa.ThoroughrevIewsareavaIlable.
84,199
The
accumulatIonofseveralmetabolItesIsthoughttoInterferewIthvWFformatIonand
releaseandtocauseabnormalfunctIonoftheCPbareceptor.SynthesIsofprostacyclIn
andnItrIcoxIdesynthesIs,bothofwhIchhaveplateletInhIbItoryeffects,IsIncreasedIn
uremIa.0IalysIsfrequentlyImprovesthehemostatIcdefect.Thereareseveralother
potentIaltreatmentmodalItes.
84,200
CryoprecIpItate(asourceofvWF)wasonceusedfor
uremIcbleedIngbuthasnowbeensupplantedby00A7P,whIchInducesImmedIaterelease
ofvWFfromendothelIalcellsandrapIdlyImprovesplateletadhesIveness.SevereanemIa,
perse,contrIbutestobleedIngbecauseInthelowervIscosItystate,plateletshavea
reducedtendencytotravelIntheperIpheryofthebloodcolumn,alongtheendothelIal
surface.mprovementofthehemostatIcdefectassocIatedwIthuremIahasbeenobserved
wIthadmInIstratIonoferythropoIetIn(probablybycorrectIonofanemIa
201
)andconjugated
estrogens
84
(perhapsbyreductIonofnItrIcoxIdeformatIon).
P.J99
WhenlIfethreatenIngbleedIngoccursIntheuremIcpatIent,plateletconcentratesshould
beadmInIstered.
Antiplatelet Agents
NumerousmedIcatIonsareadmInIsteredexpresslyforthepurposeofplateletInhIbItIonto
reducetherIskof|,stroke,andotherthromboembolIccomplIcatIons.TheyInduce
plateletdysfunctIonbyseveralmechanIsms,whIchIncludeInhIbItIonofcyclooxygenase
(Cox),InhIbItIonofphosphodIesterase,A0PreceptorantagonIsm,andblockadeoftheCP
b/areceptor.
Cyclo-oxygenase Inhibitors
AspIrInIstheprototype.AspIrInproducesIrreversIbleInhIbItIonofplateletCox,whIch
preventssynthesIsofTxA
2
,apotentplateletproaggregantandvasoconstrIctor.n
moderatedoses,thereIsselectIvesparIngofthesynthesIsofprostacyclIn(antIaggregant,
vasodIlator),whIchresultsIntIltIngthebalancesubstantIallyInfavorofplatelet
InhIbItIon.TheplateletInhIbItIngeffectIvenessofaspIrInvarIessubstantIally.ncreased
ratesofnewplateletsynthesIs,sImultaneousadmInIstratIonofotherdrugsthat
temporarIlybIndandtherebyprotectCox1(e.g.,Ibuprofen),andpolymorphIsmsofthe
Cox1enzymemayberesponsIble.
202
ndomethacIn,phenylbutazone,andallthenonsteroIdalantIInflammatoryagents(e.g.,
Naprosyn,Ibuprofen)alsoInhIbItCox.However,unlIkeaspIrIn,theIrInhIbItIonIspromptly
reversIblewIthclearanceofthedrug.ThemorerecentCox2InhIbItorsselectIvelyInhIbIt
Cox2,theIsoformresponsIbleforgeneratIngthemedIatorsofpaInandInflammatIon,
whIlesparIngCox1,theInhIbItIonofwhIchcausesbothgastrIcdamageanddecreased
renalbloodflowandInhIbItIonofplateletTxA
2
.AccordIngly,plateletfunctIonshouldnot
beImpaIred.However,IthasbecomeapparentthatCox2InhIbItorsreduceprostacyclIn
generatIonbyvascularendothelIalcellsandmaytherebytIltthenaturalbalancetoward
plateletaggregatIon.ThatprocoagulanteffectIsnotunIformamongCox2InhIbItors.
CelecoxIbsImultaneouslydecreasesendothelIalexpressIonofTFandmaytherebyproduce
acompensatorycountertIlt.
20J
AnIncreasedrateofmyocardIalIschemIceventsresulted
InthewIthdrawalofsomeCox2InhIbItorsfromthemarketIn2004.
Phosphodiesterase Inhibitors
CyclIcadenosInemonophosphateIsanInhIbItorofplateletaggregatIon,andlevelsare
IncreasedbyInhIbItIonofphosphodIesterase.0IpyrIdamole,whIchIsusedforstroke
prophylaxIs(usuallyIncombInatIonwIthaspIrIn),andcIlostazolappeartoactprImarIlyby
thIsmechanIsm.CaffeIne,amInophyllIne,andtheophyllInewIllalsosImIlarlyproducemIld,
reversIbleplateletInhIbItIon.
ADP Receptor Antagonists
ActIvatIonoftheplateletA0PreceptorleadstosurfaceexpressIonoftheb/areceptor.
ClopIdogrel,whIchIsadmInIsteredforpreventIonofstentocclusIonaswellasstrokeand
|prophylaxIs,blockstheA0PreceptorInanoncompetItIveandIrreversIblemanner.
Glycoprotein IIb/IIIa Receptor Antagonists
TheCPb/aplateletsurfacereceptor,bywhIchfIbrInogencrosslInksplatelets,Isthe
fInalcommonpathwayforplateletaggregatIon.Theb/aantagonIstshavebeenused
prIncIpallyforthemanagementofacutecoronarysyndromes.TheyIncludeabcIxImab
(FeoPro),amonoclonalantIbody,tIrofIban(Aggrastat),andeptIfIbatIde(ntegrIlIn).These
agentsallrequIreIntravenousadmInIstratIon.TheIreffectIsreversIble.ThehalflIvesare
approxImately2.5hoursfortIrofIbanandeptIfIbatIde(bothIncreasedwIthrenal
dysfunctIon)and12hoursforabcIxImab.
204
However,abcIxImabhasarelatIvelyhIgh
affInItyfortheb/areceptor,andplateletdysfunctIonlastslonger(approxImately48
hours)thanImplIedbyhalflIfe.AlloftheseagentshavealsobeenassocIatedwIth
thrombocytopenIa,theIncIdenceofwhIchhasbeengreaterforabcIxImab(2.5)than
tIrofIbanandeptIfIbatIde(0.5).
205
ThethrombocytopenIacausedbyabcIxImabcanbe
eItherdelayed(antIbodymedIated)orImmedIate.
174
Notethattheseagentscause
prolongatIonoftheACT.
204
Herbal Medications and Vitamins
SeveralherbalmedIcatIonsmaycauseInhIbItIonofplateletfunctIon
84
(seeChapter22).
AmongthemorecommonagentsIdentIfIedbytheASAPractIceAdvIsoryarefeverfew,
flaxseedoIl,garlIc,gInger,gIngkobIloba,grapeseedextract,andsawpalmetto.
80
8ecause
theactualrIsksarenotwelldefIned,theyshouldbedIscontInuedbeforesurgery,andIn
partIcular,beforecardIac,neurologIc,andcosmetIcsurgIcalprocedures.7ItamInEand
gInsengarealsoplatelet/coagulatIonInhIbItorsandshouldsImIlarlybedIscontInued.
206,207
Other Conditions
|yeloprolIferatIveandmyelodysplastIcsyndromescanproduceIntrInsIcdefectsIn
platelets.nthesedIsorders,theplateletsmaybeabnormalInbothmorphologyand
functIon.PlateletdysfunctIonoccursInconjunctIonwIthcondItIonsthatalsocauseother
hemostatIcabnormalItIes(lIverdIsease,fIbrInolytIcstatesIncludIng0C,storagedefects),
whIcharedIscussedInthefollowIngsectIon.
Acquired Disorders of Clotting Factors (Including
Anticoagulant Therapy)
Vitamin K Deficiency
HepatIcsynthesIsofclottIngfactors,7,X,andXaswellasproteInCandproteInS
requIresthepresenceofvItamInK.7ItamInKIsnecessaryfortheenzymatIccarboxylatIon
ofthesefactors.ThecarboxylgroupenablesbIndIngtophospholIpIdsurfacesdurIngthe
coagulatIonprocess.WIthvItamInKdefIcIency,thesefactorsaredepletedInanorder
determInedbytheIrhalflIves.Factor7hastheshortesthalflIfeandIsthefIrsttobe
depleted,followedbyFX,FX,andfInallyF(prothrombIn).7ItamInKdefIcIencyoccurs
frequentlyInhospItalIzedpatIentsbecauseofdIetaryInsuffIcIency,gutsterIlIzatIon,and
malabsorptIon.AhIghIndexofsuspIcIonshouldbemaIntaIned.
7ItamInKoccursnaturallyIntwoforms.
206
7ItamInK
1
(phylloquInone)IsfoundInleafy
greenvegetables.ThegreatestconcentratIonsoccurInbrusselssprouts.7ItamInK
2
(menaquInone)IssynthesIzedbythenormalIntestInalflora.tIsuncommonforpatIentsto
developvItamInKdefIcIencysolelybecauseofdIetarydefIcIency,butItmayoccurIn
patIentswhoarereceIvIngparenteralnutrItIonwIthoutvItamInKsupplementatIon,and
whoarebeIngtreatedconcurrentlywIthbroadspectrumantIbIotIcsthatdestroythegut
flora.8ecausethebodyhasnoapprecIablestoresofvItamInK,defIcIencIescandevelopIn
aslIttleas7days.Newborns,whohaveasterIlegutatbIrth,havebeennotedtodevelop
vItamInKdefIcIency.7ItamInKIsfatsolubleandthereforerequIresbIlesaltsfor
absorptIonfromthejejunum.8IlIaryobstructIon,malabsorptIonsyndromes,
gastroIntestInalobstructIon,orrapIdgastroIntestInaltransItcanresultInvItamInK
defIcIencybecauseofInadequateabsorptIon.
Diagnosis and Treatment of Vitamin K Deficiency
7ItamInKdefIcIencywIllcauseprolongatIonofthePT.PTIsanF7sensItIveassayand
wIthvItamInKdefIcIency,F7IsthefIrstfactortobedepleted.WIthmoreprolonged
defIcIency,aPTT(averyFXsensItIveassay)wIllalsoIncrease.PlateletcountwIllbe
normal.7ItamInKmaybeadmInIsteredorally,Intramuscularly,orIntravenously.Urgent
treatmentofvItamInKdefIcIencyIsbestaccomplIshedbytheIntramuscularorIntravenous
admInIstratIonofvItamInK(Aquamephyton),
P.400
usuallyIndosesof1to5mg.7ItamInKshouldbeadmInIsteredslowlytoavoIdthe
occurrenceofhypotensIon.mprovementofthecoagulatIondIsturbancewIllbegIntobe
apparentIn6to8hours.
Warfarin Therapy
WarfarInIsadmInIsteredforthepreventIonof07TandPEandtopatIentswIthatrIal
fIbrIllatIon,someprosthetIcheartvalves,andventrIcularmuralthrombIInthesettIngof
acute|.PatIentswIthproteInSorproteInCdefIcIencymayalsobetreatedwIthlong
termantIcoagulatIonwIthwarfarIn.WarfarInproducesItsantIcoagulanteffectby
competItIonwIthvItamInKforthecarboxylatIonbIndIngsItesandleadstothedepletIonof
factors,7,X,X,proteInC,andproteInS.AswIthvItamInKdefIcIency(prevIous
paragraph),F7IsthefIrstfactortobedepletedandInItIallyonlythePTwIllbe
prolonged.WIthhIgherdoses,FXlevelswIlldecreaseandtheaPTTwIllIncrease.WarfarIn
therapyIsadjustedaccordIngtotheNF(seeTestsoftheHemostatIc|echanIsm).The
prImaryuntowardeffectofwarfarIntherapyIsbleedIng.FapIdreversal(12to24hours)of
warfarIneffect
208
canbeaccomplIshedbyIntravenousadmInIstratIonofvItamInK.0oses
of5to10mgIntravenouslyarerecommendedforurgentsItuatIons.
209
Smallerdoses,0.5to
Jmg,andtheoralrouteshouldbeusedInlessurgentsItuatIonswhentheobjectIveIsto
reduceratherthannormalIzeNF.NFshouldberecheckedat6hourIntervals.7ItamInK
admInIstratIonmayhavetoberepeatedat12hourIntervals.nsItuatIonsofgreater
urgency,FFP,TP(whIchIsImmedIatelyavaIlableInfacIlItIesthatprovIdeIt),or
prothrombIncomplexconcentrate(PCC)wIllallprovIdetherelevantfactorsandcanbe
employed.npatIentswhomIghtnottoleratetherequIsItevolumeofFFPorTP(15
mL/kg),PCC,whIchcontaInsF,F7,FX,andFX,IsanalternatIve.PCCdosIng
recommendatIonsvary.However,15U/kgwhenNFIs5andJ0U/kgforNF5appear
reasonable.
210
FecombInantF7a(rF7a;seelaterdIscussIon)hasalsobeenusedto
achIeverapIdnormalIzatIonofNF.
211
Note,however,thattheactIonofrF7arequIres
thepartIcIpatIonofFXandF(prothrombIn),bothofwhIcharedepletedatgreater
degreesofwarfarIneffect(aswItnessedbyaPTTprolongatIon).nthIscIrcumstance,rF7a
maynotprovIdeeffectIvereversalofantIcoagulatIon.PCCcontaInsF,7,FX,andFX
andIsmorelIkelytobeeffectIve.
212
ThrombotIceventshaveoccurredwIththe
admInIstratIonofbothPCCandrF7a.
212,21J
fFFP,TP,PCC,orrF7aareadmInIsteredfor
rapIdreversalandsustaInedreversalIsdesIred,vItamInKshouldbeadmInIstered
sImultaneously
209
becauseoftheshorthalflIfeofF7(6hoursfornatIveF7,2hoursfor
rF7a).
Heparin Therapy
UnfractIonatedheparIn(UFH)IsusedwIdelyforantIcoagulatIonInvascularsurgeryandIn
proceduresrequIrIngCP8.tInhIbItscoagulatIonprIncIpallythroughItsInteractIonwIthAT
(seeChapter41).UFHbIndstoAT,andInsodoIngcausesaconformatIonalchangethat
greatlyIncreasesAT'sInhIbItoryactIvIty.nspIteofItsname,antIthrombIn,ATalso
InhIbItsseveralactIvatedfactorsIncludIng,InaddItIontoa(thrombIn),Xa,Xa,Xa,and
Xa(FIg.166).tIsmostactIveagaInstthrombInandXa.UFHalsoIncreasestheactIvItyof
asecondnatIveantIthrombIn,heparIncofactor.HeparIncofactorInhIbItsthrombInand
nottheotheractIvatedfactors.tscontrIbutIontotheclInIcaleffectsofUFHIsnotclear.
FesIstancetoUFHcanoccurInpatIentswhoaredefIcIentInAToneItheraheredItaryor
anacquIredbasIs.ThelattermayoccurInpatIentsonsustaInedUFHtherapy,Inthe
presenceofdepletIonbyaconsumptIvecoagulopathyordurIngCP8.UFHresponsIveness
canberestoredbyadmInIstratIonofATconcentrates
168,169
orFFP.
Low-Molecular-Weight Heparin
LowmolecularweIghtfractIonsofheparIn(L|WH)havebeenemployedprIncIpallyfor07T
prophylaxIsandtreatment,andaresupplantIngsubcutaneousUFHandwarfarInforthese
IndIcatIons.
214
ThereareseveralavaIlableagentsIncludIngcertoparIn,dalteparIn,
enoxaparIn,revIparIn,andtInzaparIn.TheseagentsdonotappeartodIfferIntheIr
effIcacy,
215
andenoxaparInIsusedmostwIdelyIntheUnItedStates.L|WHs,whIchalso
actvIaAT,havegreateractIvItyagaInstFXathanthrombIn(Fa).However,theratIoof
thatactIvItyvarIesamongtheagents(e.g.,enoxaparIn,J.8:1;tInzaparIn,1.9:1).
216
AccordIngly,theeffectoftheseagentsonstandardcoagulatIontestswIllvary(mInImalfor
enoxaparIn
217
)aswIlltheeffectofprotamIneneutralIzatIon,whIchIsveryIncompletefor
enoxaparIn.|onItorIngIsusuallynotrequIredorperformed.fItIsdeemednecessary
(e.g.,renalfaIlure,extremeobesIty),theantIXaactIvItylevel(seeprevIousdIscussIon)Is
theapproprIatetest.TheL|WHscauselessplateletInhIbItIonandareassocIatedwItha
lesserIncIdenceofHT/TthanUFH.
218
WhIletwIcedaIlydosIngwIthenoxaparInhasbeen
commonInNorthAmerIca,oncedaIlyregImensareusuallysuffIcIent.8ecauseofthe
relatIvelylonghalflIfeofenoxaparIn,twIcedaIlydosIngposesaproblemwIthrespectto
removalofepIduralcathetersbecausethereIsnoantIcoagulantnadIr(seeChapter5J.)
Heparin Induced Thrombocytopenia/Thrombosis (HIT/T)
DnetofIvepercentofpatIentswhoreceIveUFHtherapyfor5dayswIlldevelop
thrombocytopenIaasaresultofantIbodIes(usuallygC)dIrectedagaInstplateletfactor4
(PF4)heparIncomplexesontheplateletsurface.
219,220
DnsetrequIresseveraldaysInthe
heparInnaIvepatIentbutcanoccurmuchmorequIckly(10to12hours)Inthosewhohave
beenexposedwIthIntheprecedIng100days.DccurrenceappearstobedoserelatedandIs
morecommonwIthbovInethanporcIneheparIn.HT/TIsrelatIvelyuncommonwIthL|WH
andrequIreslongerperIodsofexposure.
218,221
WhenL|WHdoesInduceantIbodIes,they
aremorecommonlyoftheg|orgAtypeandoftendonotcausethrombocytopenIa.
However,patIentswhohavedevelopedgCantIbodIesandHT/TInresponsetoUFHwIll
frequentlydevelopHT/TonexposuretoL|WH.
218
AlthoughHT/TIsmostoftenIdentIfIed
becauseofthrombocytopenIa,notallpatIentsbecomemarkedlythrombocytopenIc.
ThrombotIcandthromboembolIceventsIncludIng07T,PE,lImboracralIschemIa,|,or
strokefrequentlyrevealtheoccurrenceofHT/T.0IagnosIsIscomplIcatedbythefactthat
notallpatIentswhodevelopantIplateletantIbodIeshaveclInIcalHT/T.AhematologIst
shouldbeconsulted.
TreatmententaIlswIthdrawalofheparInandadmInIstratIonofanonheparInantIcoagulant.
The0Ts(lepIrudIn,argatroban,andbIvalIrudIn)andtheIndIrectXaInhIbItordanaparoId
areapprovedforthIsuseInvarIouscountrIes(althoughdanaparoIdIsnotavaIlableInthe
UnItedStates).SeveralotherantIcoagulantsareunderdevelopment,IncludIngorally
admInIstered0TsanddIrectInhIbItorsofFXaandFXa.
222
AL|WHIsnotapproprIate.
FondaparInux(anIndIrectXaInhIbItor;seelaterdIscussIon)hasaneglIgIble(perhapszero)
IncIdenceofantIheparIn/PF4crossreactIvItybutIsnotformallyapproved.WarfarInIs
contraIndIcatedbecausethecombInatIonofproteInCandSInhIbItIonbywarfarInInthe
faceofongoIngplateletclumpIngmayaggravatethrombosIs.PlateletssImIlarlyshouldnot
beadmInIsteredunlessthrombocytopenIaIsextreme.
Cardiac Surgery and HIT/T
SeveralalternatIveshavebeenemployedforthepatIentwIthHT/TwhorequIresCP8
180
(seeChapter41).
P.401
Themostcommon,whenantIheparIn/PF4antIbodIesarestIllpresent,Istheuseof
nonheparInantIcoagulants,usuallya0T(seelaterdIscussIon).AnalternatIveIstoprovIde
profoundInhIbItIonofplateletactIvatIonwItheItherIloprost(synthetIcprostacyclIn)ora
b/aInhIbItor(tIrofIbanatUCS0)durIngCP8andproceedwIthUFHadmInIstratIon,
protamInereversal,andanonheparInantIcoagulantInthepostoperatIveperIod.
22J
When
antIheparIn/PF4antIbodIeshavedecreasedtoundetectablelevelsInapatIentwItha
hIstoryofHT/T,heparInmaybeemployeddurIngCP8,althoughItmustberIgIdlyavoIded
durIngtheremaInderofthehospItalIzatIon.AntIbodygeneratIonrequIres5daysbywhIch
tImeheparInwIllbeabsent.
219
Asmanyas5ofpatIentswhoreceIveUFHtherapyfor5dayswIlldevelopheparInInduced
thrombocytopenIa/thrombosIs.TheclInIcalmanIfestatIonsaremoreoftentheresultof
thrombosIsandthromboembolIsmthanthrombocytopenIa.
Heparin in Cardiopulmonary Bypass
AcomprehensIvedIscussIonofthIstopIcIsbeyondthescopeofthIschapter.ExtensIve
revIewsareavaIlable
224
(seeChapter41).nbrIef,thecommonpractIceIstomaIntaInACT
480to500secondsfortheduratIonofbypass.ThereIssubstantIalvarIatIonIntheUFH
ACTdoseresponserelatIonshIp,probablybecauseofvarIabIlItyInUFHbIndIngtomany
natIvesurfacesIncludIngplatelets,W8Cs,endothelIum,andplasmaproteInsIncludIngthe
vWFandAT.
224
ThereIshazard,IntermsofactIvatIonofbothplateletsandcoagulatIon,In
allowIngACTtobeonthelowsIde.PlateletandcoagulatIonactIvatIoncanbe
demonstratedatACTlevelsof400seconds.
225
EvIdenceofactIvatIonIslessapparentwhen
longerACTsaremaIntaIned.
226
ProtamIneIsadmInIsteredforreversalofUFHeffect.|any
clInIcIansemployamIllIlIterformIllIlItertechnIque.However,amorecarefultItratIon
ofprotamIneagaInstACTIsIdealtoavoIdexcessIveadmInIstratIonofprotamIne,whIch
hasInherentantIcoagulanteffectsIncludIngplateletInhIbItIon,stImulatIonoftPArelease
fromendothelIum,andInhIbItIonoffIbrInogencleavagebythrombIn.
227
Direct Thrombin Inhibitors
0TsproducetheIrantIcoagulanteffectbydIrectlybIndIngtothrombIn.
180
HIrudInIsa
naturallyoccurrIngcompound;lepIrudInIsItsrecombInantequIvalent.Argatrobanand
bIvalIrudInaresynthetIc.8ycontrastwIthUFH,L|WH,andfondaparInux,allofwhIchact
vIaATtoInhIbItonlyunboundthrombIn,0TsInhIbItbothunboundandfIbrInbound
thrombIn.0TsthereforeInhIbItallofthrombIn'snumerouseffectsonhemostasIs(FIgs.16
2and165).ClotboundthrombIncancontInuetopromotecoagulatIonbyactIvatIonof
platelets,byactIvatIonofF7,F7,FX,andFX,andbyconversIonoffIbrInogento
fIbrIn.
228
ThereIsnoantIdotetotheantIcoagulanteffectof0Ts.TermInatIonoftheeffect
ofhIrudInandlepIrudIn(halflIfe,80mInutes)dependsonrenalelImInatIon.Argatroban
(halflIfe,40to50mInutes)IsmetabolIzedbythelIver.8IvalIrudIn(halflIfe,25mInutes)Is
largelyclearedbyproteolysIsbyplasmaproteaseswIthsomecontrIbutIonbyrenal
clearance.
0TsdonotbIndtoPF4andarewIdelyusedtoantIcoagulatepatIentswIthHT/T,In
partIcularthosewhorequIreCP8.Forthelatter,bIvalIrudInIsthemostwIdelyusedagent
becauseofItsrelatIveIndependenceofhepatIcandrenalclearanceandarelatIvelyshort
halflIfe.|onItorIngofantIcoagulatIonIsproblematIc.AsnotedInthesectIonLaboratory
EvaluatIonofCoagulatIon,wIththegreaterdegreesofantIcoagulatIonrequIredforCP8,
thecorrelatIonbetweenACTand0TserumlevelIspoor,andunnecessaryoverdosecan
occureasIly.TheecarInclottIngtIme(seeprevIousdIscussIon)Isthepreferredtest.
However,ItIsnotwIdelyavaIlable.FIxeddosageregImenshavethereforebeenemployed
(e.g.,loadIngdose,1.0to1.5mg/kg;InfusIon,2.5mg/kg/hr).
229,2J0
ACTshouldbe400.
NotethattherelatIvelyshorthalflIfeandenzymatIcdegradatIonmeanthatbloodthatIs
statIc(CP8orcellsalvagereservoIrs)mayclot.ThetechnIquehastobeadjusted
accordIngly.nthepatIentwIthrenalfaIlureorInurgentsItuatIons,elImInatIoncanbe
accomplIshedbydIalysIsorhemofIltratIon.
2J1
XImelagatranIsadIrectthrombInInhIbItor.thasbeenwIthdrawnfromthemarketonthe
basIsofhepatotoxIcIty.
Indirect Inhibitors of Xa
FondaparInuxandIdraparInuxaresynthetIcagentsthatactvIaATtoproduceahIghly
specIfIcInhIbItIonofFXa.
2J2
FondaparInuxIsanIncreasInglypopularalternatIvefor07T
prophylaxIs,InpartbecauseofItsverypredIctableuptake(afteroncedaIlysubcutaneous
admInIstratIon)andkInetIcsthatmakemonItorInganddosageadjustmentunnecessary.
FondaparInuxcanformacomplexwIthPF4.However,heparIn/PF4antIbodIesdonotreact
wIththatcomplexInamannerthatproducesplateletactIvatIonandHT/T.
2JJ
Nonetheless,fondaparInuxIsnotyetapprovedforuseInHT/T.Theseagentshavelong
halflIves(fondaparInux,17hours;IdraparInux,80hours),andthereIsnoantIdote.
ExcretIonIsvIathekIdneys.WIththerapeutIcdosesPT,aPTT,andACTremaInwIthInthe
normalrange.
0anaparoId,whIchIsnotavaIlableIntheUnItedStates,IsamIxtureofthree
glycosamInoglycans(heparansulphate,dermatansulfate,andchondroItInsulfate)derIved
fromporcIneIntestIne.AntIXatoantIaactIvItyoccursInaratIoof22:1.HalflIfeIs25
hours.ElImInatIonIsrenal.PTandaPTTareunaffectedbytherapeutIcdoses.Cross
reactIvItywIthheparIn/PF4antIbodIesoccursInfrequently,anddanaparoIdIsapprovedfor
useInHT/T.
180
Acquired Combined Disorders of Platelets and Clotting Factors
with Increased Fibrinolysis
Liver Disease
ChronIclIverdIseaseIsassocIatedwIthabnormalItIesofallthreephasesofhemostasIs:
prImaryhemostasIs,coagulatIon,andfIbrInolysIs.Table1616provIdesanovervIewof
theseabnormalItIes.
Table 16-16 The Etiology of Hemostatic Abnormalities in Liver Disease
ThrombocytopenIa
0ecreasedproductIon
HypersplenIsm
ncreasedconsumptIon(0C)
mpaIredplateletfunctIon
0ecreasedF0Pclearance
0ecreasedfactorsynthesIs
0ecreasedhepatocytefunctIon
7ItamInKdefIcIency(dIet,malabsorptIon)
ncreasedfactorconsumptIon
0ecreasedclearanceofactIvatedfactors
0ecreasedsynthesIsofInhIbItors(proteInC,proteInS)
ncreasedfIbrInolysIs
0ecreasedsynthesIsof
2
antIplasmIn
0ecreasedclearanceoftPA
0ecreasedsynthesIsofPA1
0C,dIssemInatedIntravascularcoagulatIon;F0P,fIbrIndegradatIonproduct;tPA,
tIssueplasmInogenactIvator;PA1,plasmInogenactIvatorInhIbItor1.
P.402
Impaired Primary Hemostasis
mpaIredprImaryhemostasIsoccursasaresultofboththrombocytopenIaandImpaIred
plateletfunctIon.TheformerIslargelytheresultofdecreasedproductIon,whIchInturnIs
probablytheresultofdecreasedthrombopoIetInsecretIonbythelIver.HypersplenIsmmay
alsocontrIbute,butItsrolehasbeenoveremphasIzed.PlateletdysfunctIoncanoccurwhen
lIverdIseaseIssuffIcIentlyadvancedthatclearanceofF0PsIsImpaIred,orwhen0C
complIcatesthecoagulatIondIsturbance.TheF0PscoatthesurfaceofplateletsandImpaIr
aggregatIon.
84
EthanolcanalsodIrectlycontrIbutetoplateletdysfunctIonbyInhIbItIonof
thesynthesIsofA0P,ATP,andTxA
2
.
84
AccordIngly,whenfacedwIthapatIentwIthlIver
dIseasewhoIsbleedIng,anormalplateletcountcannotbeassuranceofIntactprImary
hemostasIs.00A7Pmaybehelpful,buttransfusIonofplateletconcentratesmaybe
necessary.
Disturbances of Coagulation
WIthlIverdIsease,factorproductIondecreasesandconsumptIonIncreases.ThelIver
synthesIzesalloftheclottIngfactors(wIththeprobableexceptIonoffactor7).AswIth
vItamInKdefIcIency,hepatIcdIseasefIrstleadstoadefIcIencyoffactor7asIthasthe
shortesthalflIfe.Thereafter,defIcIencIeswIlldevelopInfactorsX,X,and.0Ietary
defIcIencyofvItamInK,asmayoccurInalcoholIcs,combInedwIthdImInIshedsecretIonof
bIlesaltsleadIngtomalabsorptIon,wIllexaggeratethesedefIcIencIes.fImpaIred
coagulatIonIstheresultofvItamInKdefIcIencyandnothepatIcdamage,thenparenteral
vItamInKmaybehelpfulInrestorIngfactorlevelsof,7,X,andX.Further
deterIoratIonofhepatIcfunctIonwIllaffecttheremaInIngfactors,,7,X,X,andX.
mpaIredlIverfunctIoncanalsocauseathrombotIctendency,whIchleadstoIncreased
consumptIonofclottIngfactors.ThIsoccursfortworeasons.FIrst,synthesIsofthenatural
antIcoagulants,AT,proteInC,andproteInS,maybedImInIshed,therebyalterIngthe
balanceofproandantIcoagulantforces.Second,clearanceofactIvatedclottIngfactors
fromthecIrculatIonmaybeImpaIred,therebyallowIngpersIstentactIvatIonofthe
coagulatIoncascade.
Increased Fibrinolysis
ncreasedfIbrInolysIsoccursasaresultofdecreasedclearanceoftPAfromthecIrculatIon
bytheImpaIredlIveranddecreasedhepatIcsynthesIsof
2
antIplasmIn.ProductIonofthe
naturalInhIbItoroftheplasmInsystem,PA1,IsalsodImInIshed.
2J4
ThecombInatIonof
acceleratedcoagulatIonandIncreasedfIbrInolysIsInpatIentswIthadvancedlIverdIsease
canleadtoapersIstent,lowgrade0C.ThereleaseIntothecIrculatIonofthebreakdown
productsofnecrotIchepatocytesmaycontrIbutetothedevelopmentof0C.
2J5
Diagnosis and Treatment of Coagulation Abnormalities Associated with Liver
Disease
TheInItIallaboratoryevaluatIonshouldIncludeplateletcount,PT,aPTT,fIbrInogenlevel,
and0dImer.ntheeventofthrombocytopenIaandclInIcalbleedIngorpendIngsurgery,
platelettransfusIonmaybeapproprIate.fthePTIsprolonged(1.5tImescontrol),
vItamInKshouldbeadmInIsteredspeculatIvely.ntheabsenceofaresponsetovItamInK
(whIchrequIresamInImumof8hours),factordefIcIencIesshouldbetreatedwIthFFP,wIth
attentIontothepossIbIlItyofvolumeoverload.CryoprecIpItateIsapproprIateIntheevent
ofhypofIbrInogenemIa(fIbrInogen100to125g/dL).WhIleantIfIbrInolytIcshavebeen
applIedInthecontextoflIvertransplantatIon,theyshouldnototherwIsebeusedfor
bleedIngassocIatedwIthlIverdIseasebecauseofthecatastrophIcconsequencesof
admInIsterIngtheseagentsInthefaceofanunrecognIzed0C.However,makIngthe
dIagnosIsof0C(seelaterdIscussIon)IsoftendIffIcultbecausethelaboratorytestsusedto
IdentIfy0CarealreadyabnormalInpatIentswIthlIverdysfunctIon.ThrombocytopenIa,
prolongedPTandaPTT,decreasedfIbrInogenlevel,andcIrculatIngF0PswIllcommonly
occurIntheabsenceof0C.Elevated0dImerIssomewhatmorespecIfIcforthe
occurrenceof0C.
DIC
0etaIledrevIewsof0CareavaIlable.
2J6,2J7,2J8
0CIscharacterIzedbyexcessIvedeposItIon
offIbrInthroughoutthevasculartree,wIthsImultaneousdepressIonofthenormal
coagulatIonInhIbItorymechanIsmsandImpaIredfIbrIndegradatIon(seeChapter56).tIs
trIggeredbytheappearanceofprocoagulantmaterIal(TForequIvalent)InthecIrculatIon
InamountssuffIcIenttooverwhelmthemechanIsmsthatnormallyrestraInandlocalIze
clotformatIon.ThatappearancemaybetheresultofeItherextensIveendothelIalInjury,
whIchexposesTF,orthereleaseofTFIntothecIrculatIonasoccurswIthamnIotIcfluId
embolus,extensIvesofttIssuedamage,severeheadInjury,oranycauseofasystemIc
Inflammatoryresponse.ThenatIvepathwaysthatInhIbItcoagulatIonareeItherInhIbIted
oroverwhelmed:ATlevelsaredepletedbyexcessthrombInformatIon,asreflectedby
elevatedlevelsofthrombInATcomplexes;thrombomodulInexpressIonInvascular
endothelIumIsreducedInresponsetoInflammatIontherebyreducIngproteInCformatIon;
andthecapacItyofTFPtorestraIntheTFdrIvenextrInsIcpathwaymaybeexceeded
becauseofexcessIveTF.
2J8
TheacceleratedprocessofclotformatIoncausesbothtIssue
IschemIaand,ultImately,crItIcaldepletIonofplateletsandfactors.SImultaneously,the
fIbrInolytIcsystemIsactIvated,andplasmInIsgeneratedtolysetheextensIvefIbrInclots.
F0PsappearInthecIrculatIon.F0PsstImulatereleaseofPA1fromtheendothelIum,and
thrombolysIsbecomesImpaIred.TheF0PsalsoInhIbItplateletaggregatIonandpreventthe
normalcrosslInkIngoffIbrInmonomers.0epletedofplateletsandclottIngfactorsand
InhIbItedbyF0Ps,thecoagulatIonsystemfaIlsandthepatIentbleeds.SImultaneously,the
mIcrovascularocclusIonbyfIbrIncausesbothcutaneous(purpurafulmInans)anddeep
tIssueIschemIa,wIththelattercontrIbutIngtomultIorganfaIlure.
Table1617lIststhenumerousclInIcalcondItIonsthathavebeenassocIatedwIth0C.t
revealsthatseveralclInIcalentItIesthatareencounteredfrequentlyInanesthetIcand
crItIcal
P.40J
carepractIceareassocIatedwIththedevelopmentof0C.SepsIsIsthemostcommon.
EndotoxInsorlIpopolysaccharIdebreakdownproductsfromCramnegatIveandposItIve
bacterIa,respectIvely,IncIteanInflammatoryresponsethatIncludesthegeneratIonof
cytokInes(tumornecrosIsfactor,varIousInterleukIns).ThesecytokInesInturnstImulate
thereleaseorexpressIonofTFbyendothelIalcellsandmonocytes,andthe0CsequenceIs
InItIated.
Table 16-17 Clinical Conditions Associated with Disseminated Intravascular
Coagulopathy
SepsIs(CramposItIveornegatIve)
7IremIas
DbstetrIccondItIons
AmnIotIcfluIdembolus
FetaldeathInutero
AbruptIoplacentae
PreeclampsIa
ExtensIvetIssuedamage
8urns
Trauma
LIverfaIlure
ExtensIvecerebralInjury
HeadInjury
Stroke
ExtensIvevascularendothelIaldamage
7asculItIs
PreeclampsIa
HemolytIctransfusIonreactIons
|etastatIcmalIgnancIes
LeukemIa
Snakevenoms
SeveralobstetrIccondItIonscancause0C.AmnIotIcfluIdembolIsm,placentalabruptIon,
andfetaldeathInuteroresultInthedIrectreleaseofTFequIvalentmaterIalIntothe
cIrculatIon.PreeclampsIaIscharacterIzedbyasystemIcvasculItIs.TheassocIated
endothelIaldamagecausesanInItIallylowgrade0CthatacceleratesasvasculItIsrelated
damageleadstoreleaseofTFfromIschemIctIssues,InpartIcular,placenta.
Largeburns,extensIvetraumatIcsofttIssueInjurIes,severebraInInjury,andhemolytIc
transfusIonreactIonscanalsolIberateTFequIvalentmaterIalIntothecIrculatIonand
IncIte0C.CertaInmalIgnancIes,mostnotablypromyelocytIcleukemIaand
adenocarcInomas,areassocIatedwIth0C.However,wIthmalIgnancyassocIated0C,
thrombotIcmanIfestatIonsaremorelIkelytoappearfIrst,whereaswIththeothers
mentIonedhere,thehemorrhagIcdIathesIsIsoftenthefIrstclInIcalmanIfestatIon.
AfewgeneralcondItIonssuchasacIdosIs,shock,andhypoxIaareassocIatedwIth0C.
ShockpromotescoagulatIonbecauseoneofthecontrolmechanIsms(rapIdbloodflow)Is
compromIsed.ClearanceofactIvatedclottIngfactorsIsreducedwhenbloodflowIs
decreased.AcIdosIsandhypoxIamaycontrIbutetobothtIssueandendothelIaldamage.
TheclInIcalmanIfestatIonsof0CareaconsequenceofboththrombosIsandbleedIng.
8leedIngIsamorecommonclInIcalpresentatIonInpatIentswIthacute,fulmInant0C.
PetechIae,ecchymoses,epIstaxIs,gIngIval/mucosalbleedIng,hematurIa,andbleedIng
fromwoundsandpuncturesItesmaybeevIdent.WIththechronIcformsof0C,thrombotIc
manIfestatIonsaremorelIkely.DrganswIththegreatestbloodflow(e.g.,kIdneyandbraIn)
typIcallysustaInthegreatestdamage.PulmonaryfunctIonmaydeterIorateasa
consequenceofmIcrothrombusaccumulatIon.
Diagnosis of DIC
ThereIsnoabsolutelyconsIstentconstellatIonoflaboratoryfIndIngsamongroutInetests.
ncreasedPT,aPTT,thrombocytopenIa,decreasedfIbrInogenlevel,andthepresenceof
F0Psand0dImermayallbenoted.TheperIpheralsmearmayrevealschIstocytes
(fragmentedF8CsreflectIngthemIcroangIopathythatoccursasaconsequenceof
wIdespreadfIbrIndeposItIon).ThrombocytopenIa(100,000/L)IsnotalwaysevIdentearly
Intheprocess,buttrue0CwIthoutsequentIalreductIonInplateletcountIsveryunlIkely.
PTandaPTTmayremaInnormalInspIteofdecreasIngfactorlevelsbecauseofthe
presenceofhIghlevelsofactIvatedfactorsIncludIngthrombInandXa.FIbrInogenlevels
maynotbedecreased,thatIs,100mg/dL,InItIally.FIbrInogenIsanacutephase
reactantthatIncreasesInresponsetostress,andtheearlyconsumptIonoffIbrInogenmay
sImplyreduceItslevelstonormal.F0PsareasensItIvemeasureoffIbrInolytIcactIvIty
althoughtheyarenotspecIfIcfor0C.0dImer(abreakdownproductofthecrosslInked
fIbrInInamatureclot)IssomewhatmorespecIfIcfor0C,butnotentIrelyso,andshould
bemeasuredwhenthatdIagnosIsIssuspected.TheJP(plasmaprotamIne
paracoagulatIon)testIsarelatIvelyspecIfIc,althoughnotverysensItIve,assaysometImes
usedtoconfIrmadIagnosIsof0C.ttestsforthepresenceofsolublecomplexescomposed
offIbrInmonomers(generatedbyexcessthrombIn)andF0Ps.TheaddItIonofprotamIne
desolublIzesthesecomplexesresultIngInaprecIpItate.
7arIousotherlaboratoryassayshavebeenemployedtosupportadIagnosIsof0C
2J6
but
shouldprobablynotbeconsIderedpartoftheanesthesIologIst'sroutIne.TheyInclude
levelsofprothrombInfragmentsF1+F2(amarkerofprothrombInconversIontothrombIn
Increased),thrombInATcomplexes(Increased),AT(decreased),
2
antIplasmIn(decreased
bybIndIngtoexcessplasmIn),proteInC(decreased),plasmInogen(decreased),andfactor
7(decreasedIn0CbutnormalwIthhepatIcfaIlurewIthout0C).
Treatment of DIC
TreatmentshouldfocusonmanagementoftheunderlyIngcondItIon.SeptIcemIawIll
requIreantIbIotIctherapy.TheobstetrIccondItIonsarefrequentlyselflImIted,although
evacuatIonoftheuterusorhysterectomymaybewarranted.HypovolemIa,acIdosIs,and
hypoxemIashouldbecorrectedtopreventtheIrcontrIbutIontothe0Cprocess.When
bleedIngIsormaybecomelIfethreatenIng,theconsumptIvecoagulopathymustbe
treated.PlateletswIllberequIredforthrombocytopenIa(e.g.,50,000/mm
J
).FFPwIll
replacetheclottIngfactordefIcIencIes.FIbrInogenlevelshouldberaIsedto100mg/dL.
WhenhypofIbrInogenemIaIssevere(50mg/dL),cryoprecIpItatemayberequIred.SIxunIts
ofcryoprecIpItatewIllIncreasefIbrInogenlevelbyapproxImately50mg/dLIna70kg
patIent.
2J9
HeparInhasbeenadvocated.However,thecontemporarypractIceIstorestrIctItsuseto
onlythosesItuatIonswherethrombosIsIsclInIcallyproblematIc,prIncIpally0CassocIated
wIthmalIgnancIes.ThereIsnoprovenbenefItInsItuatIonsInwhIchbleedIngIsthe
predomInantmanIfestatIon.AdmInIstratIonofantIfIbrInolytIcsInthefaceofwIdespread
thrombosIsIspotentIallydIsastrous,andtheyshouldnotbeused.ATconcentrateshave
beenadmInIstered.ThehopeIsthatItsadmInIstratIonwIllservetoslowtherunaway
coagulatIonprocess.However,abenefIcIaleffectonoutcomefrom0Chasnotbeen
confIrmed(seedatarevIewbyLevI
2J7
),andItsuseshouldbevIewedasexperImental.An
InsuffIcIencyIntheproteInCendogenouscoagulatIonInhIbItIonsystemIsthoughtto
contrIbutetotheprothrombotIcstateIn0C(seeprevIousdIscussIon).APChasbeenshown
todecreasemortalItyandorganfaIlureInpatIentswIthseveresepsIs,andthat
ImprovementIsalsoevIdentamongpatIentswIthsepsIswIthovert0C.
240
tsuseshouldbe
consIderedInanysustaInedepIsodeof0C.
240
Cardiopulmonary Bypass and Coagulation
LImItedmentIonofthIstopIchasbeenmadeIntheearlIersectIonsHeparInIn
CardIopulmonary8ypass,CardIacSurgery,andHT/Tand0IrectThrombInnhIbItors.
ThemanagementofantIcoagulatIonandpostCP8bleedIngIsaddressedIndetaIlInChapter
41.
Pharmacologic Therapy
Recombinant Factor VIIa
FecombInantF7a(rF7a)(NovoSeven)wasdevelopedforthetreatmentofpatIentswIth
hemophIlIaAor8andInhIbItorstoexogenousF7orFXpreparatIons.Theonlycurrent
onlabelIndIcatIonsforrF7aIntheUnItedStatesarethosetwocondItIonsplus
congenItalF7defIcIency.Clanzmann'sthrombasthenIaIsanapprovedIndIcatIonInsome
othercountrIes.However,rF7ahasbecomeahemostatIcagentoflast(andsometImes
earlIer)resortInmanyclInIcalsItuatIons.tsusehasbeenreportedIntrauma,hepatIc
faIlure,gastroIntestInalbleedIng,obstetrIchemorrhage,acuteIntracerebralhemorrhage,
andIncardIac,prostatIc,hepatIc,spInal,neurologIc,andhepatIctransplantatIonsurgery.
thasbeenusedtoreversetheantIcoagulanteffectofwarfarIn,
P.404
L|WHs,andselectIveXaInhIbItors.thasbeenadmInIsteredtopatIentswIthvW0,FX
defIcIency,thrombocytopenIa,andwIthbothcongenItal(8ernardSoulIersyndrome,
Clanzmann'sthrombasthenIa)andacquIred(uremIa,aspIrIn,A0Pandb/aantagonIsts)
plateletabnormalItIes.
211,241,242
However,mostoftheseusesaresupportedbyonly
anecdotalreports,amongwhIchtheremaybesIgnIfIcantpublIcatIonbIas;thatIs,apparent
successIsreportedmoreoftenthanobvIousfaIlure.DftheofflabelapplIcatIons,onlythe
useInprostatesurgery,trauma,cardIacsurgery(averysmallserIes),andIntracerebral
hemorrhagearesupportedbyrandomIzed,blIndedprospectIvetrIals.
24J,244,245,246
ThemechanIsmofactIonIsmorethananaugmentatIonofthenatIvefunctIonsofF7.
Werethatthecase,rF7awouldnotbeeffectIveInhemophIlIa(FIg.162).tseems
probablethatrF7adIrectlyactIvatesFXonplateletsurfacesandtherebyeffects,wIthout
thepartIcIpatIonoffactors7,X,andX,thegeneratIonofthelargeamountsof
thrombInnecessarytoproduceafIrmfIbrInclot.
247
WhIlethepreferredlIgandofF7aIs
TF,ItalsoundergoeslowaffInItybIndIngtoactIvatedplatelets.TheserumconcentratIons
achIevedbytypIcalrF7adosIngareseveralhundredtImesthosethatoccur
physIologIcallyandareprobablysuffIcIenttoactIvateFXontheplateletsurface.
nasurveyofexperIencewIthtraumapatIents,ItwasreportedthatacIdosIs(pH7.20)
appearedtodecreasetheeffIcacyofrF7abutthatmoderatehypothermIadIdnot.
248
NotethatwhIleseveralreportsspeaktotheeffIcacyofrF7aInreversIngtheeffectsof
warfarIn,L|WH,andfondaparInux,productIonofthefIbrInburstInresponsetorF7a
requIrestheavaIlabIlItyofsomeFX.WarfarIn,L|WH,andfondaparInux,alleItherInhIbIt
thesynthesIsortheactIvItyofFX.tseemsreasonabletoexpectthatInsevereoverdoses,
rF7amaynotbeeffectIve.
TheapproprIatedosIngofthIsexpensIveagent(approxImatelyUSS1permIcrogramat
UCS0)IsnotwelldefIned.ThedoseusedmostoftenInhemophIlIahasbeen90g/kgand
thatdosehaswIdely,andarbItrarIly,wethInk,beenadoptedInotherclInIcalsItuatIons.
0osesaslowas20g/kghavebeeneffectIveInsomereportsIncludIngtheprostatesurgery
InvestIgatIonjustmentIoned
24J
andthereversalofwarfarIneffect.
249
ntheprospectIve
traumaInvestIgatIonby8offardetal.,
244
theInItIaldosewas200g/kg,althoughothers
havereportedapparenteffIcacyIntraumapatIentswIthdosesof75g/kg.
250
tseems
reasonablethattheapproprIatedosagemayvarywIththeclInIcIan'sperceptIonofthe
severItyofthephysIologIcdIsturbanceandtheurgencyofthesItuatIon.AoneunItper
hourgastroIntestInalbleedandanexsanguInatIngtraumapatIentwIthescalatIngacIdosIs
andhypothermIamaywarrantdIfferentdoses.Thecurrent,somewhatarbItrary,algorIthm
InplaceatUCS0provIdesfortheadmInIstratIonof60g/kgforprofusebleedIngthatIs
unresponsIvetoconventIonaltherapy.ThatdoseIsroundedtothenearest1,200gIn
recognItIonthattheagentIssupplIedInvIalsof1.2mg.AU.S.consensuspanel
recommended20to40g/kgfornonemergentreversaland41to90g/kgforallother
scenarIos.
251
ThehalflIfeIsapproxImately2hoursandrepeatdosIngatthatIntervalmay
berequIred.
8ecauser7aIsanactIveprocoagulantonlywhenItIsIncontactwIthTForactIvated
platelets,thrombosIsInlocatIonsremotefromsItesofvesseldIsruptIonhasbeen
Infrequent.However,thrombotIccomplIcatIons,somefatal,havebeenreported,
21J
and
theuseofrF7ashouldbeundertakenwIthanawarenessofthathazard.Whenthe
exIgencIesoftheclInIcalsItuatIonpermIt,modestInItIaldosesof20to40g/kgwIth
supplementarydosesat15mInuteIntervalsaswarrantedbyclInIcalresponseseem
prudent.rF7ashouldprobablybevIewedasrelatIvelycontraIndIcatedInclInIcalstatesIn
whIchTFmaybewIdelyexposedorcIrculatIngfreely,thatIs,InmostofthecondItIons
assocIatedwIth0C.
TheeffectIvenessofavaIlablelaboratorytestsInmonItorIngtheclInIcaleffectofrF7aIs
uncertaIn.
241
thasnotbeenconfIrmedthattheeffectofhIghserumconcentratIonsof
rF7aonInvItrotests(PT,PTT)wIllreflecteffectsoncoagulatIonInvIvo.Furthermore,
theuseofnormalvaluesasacomparatorforpostrF7aaPTTvaluesmayhavelIttle
meanIngIf,InvItro,rF7adIrectlyactIvatesFXonthephospholIpIdreagent,andthereby
bypassescontactactIvatIonandalltheearlIerstepsoftheIntrInsIcpathway(FIg.161).
Desmopressin
0esmopressIn,1deamIno80argInInevasopressIn(00A7P),IsasynthetIcanalogueofthe
naturalhormonevasopressIn.
192,197
TheactIonsofvasopressInaremedIatedbytwo
generalclassesofreceptors:71,whIchmedIatesmoothmusclecontractIonInthe
perIpheralvasculature,and72,whIchregulatewaterreabsorptIonInthecollectIngducts
ofthenephron.00A7PIsactIveonlyat72receptors.AccordIngly,ItIsapotent
antIdIuretIcwIthnovasoconstrIctoreffect.00A7PwasusedprImarIlyforclInIcal
condItIonssuchasdIabetesInsIpIdusuntIlItshemostatIceffectswererecognIzed.00A7P
causesrapIdreleaseofvWFandtPAfromvascularendothelIumvIastImulatIonof
endothelIal72receptors.00A7PalsocausesIncreasesInserumlevelsofF7,perhapsby
releasefromhepatIcsInusoIdalendothelIalcells,
197
andIncreasedexpressIonofplatelet
surfaceCP1breceptors.
252
nvW0,the00A7PInducedIncreasesInF7levelaremedIated
InpartbyIncreasedserumlIfeofF7becauseoftheavaIlabIlItyofItsprotectIvecarrIer
proteInvWF.nmIldhemophIlIaA,00A7PcanIncreasethecIrculatIngfactor7:C
concentratIontwotosIxfold.00A7PIncreasesplateletadhesIvenessandshortensthe8T.
Indications
00A7PIseffectIvetreatmentfortypeandsometypevarIantsofvW0andformIld
hemophIlIaA(seevonWIllebrand0IseaseandHemophIlIaA).00A7Phasbeenshownto
reduce8TInseveralcondItIonsassocIatedwIthplateletdysfunctIon,IncludInguremIa(see
UremIa)andadvancedlIverdIsease.
84
00A7Palsodecreasestheprolonged8Tscausedby
manydrugsIncludIngaspIrIn,nonsteroIdalantIInflammatorydrugs,dextran,tIclopIdIne,
andheparIn.tIseffectIveforsomecongenItalplateletabnormalItIes,IncludIngthe
8ernardSoulIersyndrome(butnotClanzmann'sthrombasthenIa).
192
8ecauseplateletdysfunctIonandthrombocytopenIaarecommonIncardIacsurgery,studIes
ofprophylactIcadmInIstratIonof00A7Phavebeenperformed.Thosethathaverevealed
decreasedbloodlossorbloodproductadmInIstratIonhaveInvolvedprIncIpallypatIents
whowerepredIsposedtobloodloss(e.g.,thosehavIngrepeatprocedures
25J,254,255,256
)and
patIentsreceIvIngaspIrIn.
257
thasnotproveneffectIveatreducIngbloodlossIn
unselectedsurgIcalpopulatIons.
258
Dosage
00A7P,whengIvenforItsprocoagulanteffect,IsusuallyadmInIsteredIntravenouslyIna
doseof0.Jg/kg.(NotethatthIsdoseIsnotapproprIateforthemanagementofacute
centraldIabetesInsIpIdus,forwhIchthetotalInItIalIntravenousdoseshouldbe0.2to0.4
g.)AdmInIstratIonoverJ0mInutesIsrecommendedbecause00A7PInducesendothelIal
releaseofnItrIcoxIde,andmIlddegreesofhypotensIonmayoccur.Peaklevelsoffactor
7:CandvWFareachIevedwIthInJ0to60mInutes,andtheeffectlastsforseveralhours.
00A7PadmInIstratIonmayberepeatedafter8to12hours.WhenusedIncardIacsurgery,
thedrugshouldbeadmInIsteredaftertermInatIonofCP8.Waterbalanceshouldbe
monItored.However,whIlecongestIvecardIacfaIlureand
P.405
hyponatremIaandseIzuresInchIldrenhavebeenreported,clInIcallysIgnIfIcantwater
retentIonIsrelatIvelyuncommon.
Antifibrinolytics
AntIfIbrInolytIcagentshavebeenusedfrequentlyInsItuatIonsInwhIchexaggerated
fIbrInolysIsIssuspectedofcontrIbutIngtoIntraoperatIvebleedIng.ThesItuatIonsInwhIch
favorableeffectsonbloodlossandreplacementhavebeenreportedIncludeCP8
procedures,hepatIctransplantatIon,scolIosIssurgery,totaljoIntreplacement,and
prostatesurgery
259,260,261,262
(seeChapter41).TheuseofantIfIbrInolytIcmouthwashesIn
thecontextofdentalproceduresInpatIentswIthhemophIlIahasbeenmentIoned
elsewhereInthIschapter.ThreeantIfIbrInolytIcshavebeenwIdelyemployed:thelysIne
analogues,EACA,andTXA,andtheserIneproteaseInhIbItoraprotInIn(AP).APwas
wIthdrawnfromthemarketInNovember2007becauseofreportsofrenaldysfunctIonand
IncreasedmortalItyafterCP8.
105,26J,264
SomedIscussIonofAPhasbeenIncludedIncase
thewIthdrawalIsonlytemporary,asantIcIpatedbythemanufacturer.
-Aminocaproic Acid and Tranexamic Acid
EACAandTXAbIndtoproduceastructuralchangeInbothplasmInogenandplasmIn.That
structuralchangepreventstheconversIonofplasmInogentoplasmInandalsoprevents
plasmInfromdegradIngfIbrInogenandfIbrIn.ThedualactIonoftheseagentsresultsIntwo
effectsonthehemostatIcmechanIsm.FIrst,decreasedconversIonofplasmInogento
plasmInresultsInreducedfIbrInolysIs.Thesecondeffect,theInactIvatIonofplasmIn,
decreasestheformatIonofdegradatIonproductsoffIbrInogenandfIbrIn.F0Pshave
antIcoagulanteffects,IncludIngtheInhIbItIonofplateletaggregatIonandtheInhIbItIonof
thecrosslInkIngoffIbrInstrands,whIcharetherebyavoIded.TheIreffectIvenessIn
reducIngbloodlossInthewIdevarIetyofsurgIcalsItuatIonsprevIouslymentIonedIswell
confIrmed.
261
Aprotinin
APproducesItsantIfIbrInolytIceffectbyadIfferentmechanIsm.tIsanInhIbItorof
numerousserIneproteaseenzymesIncludIngplasmInandkallIkreIn.ThelatterpartIcIpates
IntheprocessofcontactactIvatIonoffactorX.AsaconsequenceofItsInhIbItIonof
plasmIn,AP,lIkeEACAandTXA,preventsdegradatIonoffIbrInogenandfIbrIn.AsIsthe
casewIthEACAandTXA,thereductIonInF0PsshouldImprovebothplateletand
coagulatIonfunctIon.However,APIsbelIevedtohaveaddItIonalbenefIcIaleffectsonthe
InflammatoryresponsetoCP8Ingeneral,andonplateletsInpartIcular.
265,266
The
mechanIsmoftheseeffectsIsnotknownwIthcertaInty.However,thrombInIsaserIne
proteasethatcanactIvateplateletsvIaaproteaseactIvatedreceptorontheplatelet
surface.
267
8etterpreservatIonoftheCP1breceptor(whIchIsnecessaryforInItIalplatelet
adhesIontovasculardefects)hasbeenreporteddurIngCP8InpatIentswhoreceIvedAP.
268
APalsoappearstoreduceneutrophIlactIvatIonandtransmIgratIonacrosscapIllary
endothelIum,perhapsvIaaneffectonanendothelIalproteaseactIvatedreceptor,and
maythereforealsoblunttheneutrophIlmedIatedcomponentoftheresponseto
endothelIalInjury.
266
Use of Antifibrinolytics in Cardiac Surgery
|etaanalysesofthemanystudIesperformedInthecontextofCP8confIrmthatbloodloss
andtheadmInIstratIonofallogeneIcbloodaredImInIshedbytheuseofallthree
agents.
259,261,269,270
ConcernhasbeenexpressedthatantIfIbrInolysIsmIghtleadtoan
IncreasedrateofgraftocclusIon,|,andrenalfaIlure.WhIlemetaanalysIshadnotborne
outanyofthoseconcerns,
261,269,270
asprevIouslynoted,IncreasedrenaldysfunctIonand
mortalItyhaverecentlybeenattrIbutedtoAP.
26J,264,271
ThemechanIsmoftherenal
dysfunctIonremaInsamatterofspeculatIon,andconcernaboutselectIonbIasInthose
InvestIgatIons(I.e.,sIckerpatIentsweremorelIkelytoreceIveAP)hasbeen
expressed.
266
Asaresult,atleastthreeotherretrospectIverevIewsofexIstIngdatabases,
wIthattemptstocontrolforcovarIates,havebeenperformed.TwodIdnotprovIdesupport
foranadverseeffect.Furnaryetal.
272
reportednoeffectofAPonrenalfunctIon,and
0IetrIchetal.
27J
reportedtheabsenceofanydoserelatedeffectofAPonrenalfunctIon.
However,SchneeweIssetal.
274
comparedJJ,517patIentswhoreceIvedAPwIth44,682who
receIvedEACA,andreportedanadverseeffectofAPonbothmortalItyandrenalfunctIon.
APIsnotcurrentlyavaIlable.
ThereIsnotaclearconsensusastowhIchoftheremaInIngtwoagentsIsmostapproprIate
InthecontextofCP8.|etaanalysIshasrevealedbothtobeeffectIve.
269
However,there
IsmoreevIdenceInsupportofTXA,andatleastonestudyreportedgreaterreductIonof
bloodlosswIthTXAthanEACA.
275
ThepatternsofuseofantIfIbrInolytIcagentsIncardIacsurgeryvarysubstantIallyamong
InstItutIons.FewappeartousetheseagentsforallCP8procedures.|ostreservethemfor
sItuatIonsmorelIkelytobeassocIatedwIthpostCP8bleedIng(e.g.,repeatandcIrculatory
arrestprocedures).StIllothersappeartoreserveantIfIbrInolytIcsforrefractorybleedIng
postCP8.ThelatterseemslesslogIcalbecausemuchoftheactIvatIonofthehemostatIc
mechanIsmoccursdurIngCP8.
Use of Antifibrinolytics in Liver Transplantation
AcceleratedfIbrInolysIsoccurscommonlydurInghepatIctransplantatIon.ThIsIsprobably,
Inpart,theconsequenceofdecreasedclearanceofactIvatedclottIngfactorsbythe
dIseasedlIver.|oreImportantly,hepatIcclearanceceasesentIrelydurIngtheanhepatIc
phase.naddItIon,wIthreperfusIonofthedonorlIver,thereIsareleaseoftPAIntothe
systemIccIrculatIon.Allthreeagentshaveallbeenused,andmetaanalysIsconfIrms
reducedbloodlosswIthAPandTXA,wIthtoolIttleInformatIontodrawconclusIonsabout
EACA.
262
SomeadvocateprophylactIcadmInIstratIontoallpatIents,whIleothers
admInIstertheseagentsonlyInresponsetothedemonstratIon,typIcallyby
thromboelastography,ofhyperfIbrInolysIs.
Use of Antifibrinolytics in Orthopaedic and Other Surgery
TherehavebeennumerousInvestIgatIonsoftheeffectofTXAandEACAonbloodlossand
transfusIonrequIrementInscolIosIsandjoIntreplacementsurgery.AmetaanalysIs
confIrmedtheeffIcacyofTXA,butnotEACA,InthosecIrcumstances.
260
Conclusions
TheapproachtothebleedIngpatIentrequIresaknowledgeofthebasIchemostatIc
mechanIsmandofcommonbleedIngdIsorders,anabIlItytoInterpretcoagulatIontests,
andanapprecIatIonoftherIsksInherenttobloodcomponenttherapy.ThehemostatIc
balanceIsdelIcateandcomplex,andItIstheresponsIbIlItyoftheanesthesIologIstto
antIcIpate,prevent,andtreatdIsturbancesofthatbalance.PreoperatIveevaluatIonmust
IdentIfythosepatIentswhoseInherItedoracquIredmedIcalcondItIonsorwhosecurrent
medIcatIonsmayInfluencetheseprocesses.WIthrespecttomedIcatIons,therearea
rapIdlyIncreasIngnumberofagentsthatareadmInIsteredspecIfIcallyforthepurposeof
alterIngthehemostatIcbalance,suchasclopIdogrel,tPA,andL|WH.AsthepatIent
proceedsthroughtheperIoperatIveperIod,theanesthesIologIstmustdetermInewhether
bleedIngIssurgIcalInnatureorIstheresultofapreexIstIngorevolvInghemostatIcdefect
thatwIllrequIrethetransfusIonofhemostatIcbloodcomponentsplatelets,FFP,or
cryoprecIpItateortheadmInIstratIonofpharmacologIcagents.
P.406
Acknowledgment
Theauthorsaregratefulto0zungLe,|0,ProfessorofPathology,UCS0Schoolof|edIcIne,
fortImespentIndIscussIonofcoagulatIonmechanIsmsandtestIng.
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Stock, M. Christine
TableofContentsSectIon7AnesthetIcAgents,Adjuvants,and0rugnteractIonChapter17nhaledAnesthetIcs
Chapter17
Inhaled Anesthetics
Thomas J. Ebert
Phillip G. Schmid
Key Points
1. At equilibrium, the CNS partial pressure of inhaled anesthetics equals
their arterial partial pressure, which in turn equals their alveolar
partial pressure if cardiopulmonary function is normal.
2. Isoflurane is the most potent of the volatile anesthetics in clinical
use, desflurane is the least soluble, and sevoflurane is the least
irritating to the airways.
3. The inspired concentration and the blood:gas solubility of an inhaled
anesthetic are the major determinants of the speed of induction.
Solubility alone determines the rate of elimination, provided there is
normal cardiopulmonary function.
4. Nitrous oxide can expand a pneumothorax to double or triple its size
in 10 to 30 minutes, and washout of nitrous oxide can lower alveolar
concentrations of oxygen and carbon dioxide, a phenomenon called
diffusion hypoxia.
5. Minimum alveolar concentration (MAC) is the alveolar concentration
of an inhaled anesthetic at one atmosphere that prevents movement
in response to a surgical stimulus in 50% of patients. Concentrations
of inhaled anesthetics that provide loss of awareness and recall are
about 0.4 to 0.5 MAC.
6. Excluding data in patients <1 year of age (where MAC is lower than
in older children), MAC decreases approximately 6% per decade.
7. Volatile anesthetics depress cerebral metabolic rate and increase
cerebral blood flow (CBF) in a dose-dependent manner. The latter
effect may increase intracranial pressure in patients with a mass-
occupying lesion of the brain.
8. Hypocapnia may blunt or abolish volatile anesthetic-induced
increases in CBF depending on when the hypocapnia is produced and
the nature of the cerebral disease process.
9. Volatile anesthetics produce dose-dependent depression of the
electroencephalogram, sensory-evoked potentials, and motor-evoked
potentials.
10. Volatile anesthetics in current use decrease arterial blood pressure,
systemic vascular resistance, and myocardial function comparably
and in a dose-dependent fashion.
11. Volatile anesthetics decrease tidal volume, decrease ventilatory
response to hypercarbia and hypoxia, increase respiratory rate, and
relax airway smooth muscle in a dose-dependent fashion.
P.414
13. Unlike halothane, volatile anesthetics in current use have minimal
adverse effects on the liver and might afford some protection for
hepatocytes from ischemic and/or hypoxic injury.
14. Volatile anesthetics are potent triggers for malignant hyperthermia in
genetically susceptible patients, while nitrous oxide is only a weak
trigger.
15. CO
2
absorbents degrade sevoflurane, desflurane, and isoflurane to
carbon monoxide when the normal water content of the absorbent
(13 to 15%) is markedly decreased (<5%).
nhalatIonanesthetIcsarethemostcommondrugsusedfortheprovIsIonofgeneral
anesthesIa.AddIngonlyafractIonofavolatIleanesthetIctotheInspIredoxygenresultsIn
astateofunconscIousnessandamnesIa.WhencombInedwIthIntravenousadjuvants,such
asopIoIdsandbenzodIazepInes,abalancedtechnIqueIsachIevedthatresultsInanalgesIa,
furthersedatIon/hypnosIs,andamnesIa.ThepopularItyoftheInhaledanesthetIcsfor
surgIcalproceduresIsbecauseoftheIreaseofadmInIstratIonandtheabIlItytorelIably
monItortheIreffectswIthbothclInIcalsIgnsandendtIdalconcentratIons.naddItIon,the
volatIleanesthetIcgasesarerelatIvelyInexpensIveIntermsoftheoverallcost.
ThemostpopularpotentInhaledanesthetIcsusedInadultsurgIcalproceduresare
sevoflurane,desflurane,andIsoflurane(FIg.171).npedIatrIccases,sevofluraneIsmost
commonlyemployed.AlthoughtherearemanysImIlarItIesIntermsoftheoveralleffectsof
thevolatIleanesthetIcs(e.g.,theyallhaveadosedependenteffecttodecreaseblood
pressure),therearesomeunIquedIfferencesthatmIghtInfluencetheclInIcIan'sselectIon
processdependIngonthepatIent'shealthandthesurgIcalprocedure.0IscussIonofthe
threemostpopularInhaledanesthetIcsprovIdesthemajoremphasIsofthIschapter.For
thesakeofcompletenessandforhIstorIcalperspectIverelatedtometabolIsmandtoxIcIty,
commentsonhalothane,enflurane,andmethoxyfluranealsoareIncluded.
Figure 17-1.ChemIcalstructureofInhaledanesthetIcs.HalothaneIsanalkane,a
halogensubstItutedethanederIvatIve.tIsnolongeravaIlablecommercIally.
sofluraneandenfluraneareIsomersthataremethylethylethers.0esfluranedIffers
fromIsofluraneInthesubstItutIonofafluorIneforachlorIneatomandsevofluraneIs
amethylIsopropylether.
Pharmacokinetic Principles
Kety
1
In1950wasthefIrsttoexamInethepharmacokInetIcsofInhaledagentsIna
systematIcfashIon.Eger
2
accomplIshedmuchoftheearlyresearchInthefIeld,leadIngto
hIslandmarktextonthesubjectIn1974.TheInhaledanesthetIcsdIffersubstantIallyfrom
nearlyallotherdrugsbecausetheyaregasesgIvenvIaInhalatIon.ThIsmakestheIr
pharmacokInetIcsunIqueaswell,andthusdIscussIonofpharmacokInetIcprIncIplesof
currentlyusedagentsIsnecessaryforunderstandIngandpredIctIngtheIreffects.
0rugpharmacologyIsclassIcallydIvIdedIntotwodIscIplInes,pharmacodynamIcsand
pharmacokInetIcs.PharmacodynamicscanbedefInedaswhatdrugsdotothebody.t
descrIbesthedesIredandundesIredeffectsofdrugs,aswellasthecellularandmolecular
changesleadIngtotheseeffects.PharmacokineticscanbedefInedaswhatthebodydoesto
drugs.tdescrIbeswheredrugsgo,howtheyaretransformed,andthecellularand
molecularmechanIsmsunderlyIngtheseprocesses.
TIssuesareoftengroupedIntohypothetIcalcompartmentsbasedonperfusIon.An
ImportantImplIcatIonofdIfferentcompartmentsandperfusIonratesIstheconceptof
redIstrIbutIon.AfteragIvenamountofdrugIsadmInIstered,ItreacheshIghlyperfused
tIssuecompartmentsfIrst,whereItcanequIlIbraterapIdlyandexertItseffects.WIthtIme,
however,compartmentswIthlowerperfusIonratesreceIvethedrugandaddItIonal
equIlIbrIaareestablIshedbetweenbloodandthesetIssues.AsthetIssueswIthlower
perfusIonabsorbdrug,maIntenanceofequIlIbrIathroughoutthebodyrequIresdrug
transferfromhIghlyperfusedcompartmentsbackIntothebloodstream.ThIslowerIngof
drugconcentratIonInonecompartmentbydelIveryIntoanothercompartmentIscalled
redistribution.
ndIscussIonsoftheInhaledanesthetIcs,theabsorptIonphaseIsusuallycalleduptake,the
metabolIcphaseIsusuallycalledbiotransformation,andtheexcretIonphaseIsusually
calledelimination.
Unique Features of Inhaled Anesthetics
Speed, Gas State, and Route of Administration
TheInhaledanesthetIcsareamongthemostrapIdlyactIngdrugsInexIstence,andwhen
admInIsterIngageneralanesthetIc,thIsspeedprovIdesamargInofsafety.TheabIlItyto
quIcklyIncreaseordecreaseanesthetIclevelsasnecessarycanmeanthedIfference
betweenananesthetIcstateandananesthetIcmIsadventure.SpeedalsomeanseffIcIency.
FapIdInductIonandrecoverymayleadtofasteroperatIngroomturnovertImes,shorter
recoveryroomstays,andearlIerdIschargestohome.
TechnIcally,oftheInhaledanesthetIcsonlynItrousoxIdeandxenonaretruegases,whIle
thesocalledpotent agentsarethevaporsofvolatIlelIquIds.8utforsImplIcIty,allofthem
arereferredtoasgasesbecausetheyareallInthegasphasewhenadmInIsteredvIathe
lungs.Asgases,nonedevIatesIgnIfIcantlyfromIdealgasbehavIor.Theseagentsareall
nonIonIzedandhavelowmolecularweIghts.ThIsallowsthemtodIffuserapIdlywIthout
theneedforfacIlItateddIffusIonoractIve
P.415
transportfrombloodstreamtotIssues.TheotheradvantageofgasesIsthattheycanbe
delIveredtothebloodstreamvIaaunIquerouteavaIlableInallpatIents:thelungs.
Table 17-1 Physiochemical Properties of Volatile Anesthetics
Property SEVOFLURANE DESFLURANE ISOFLURANE ENFLURANE HALOTHANE N
2
O
8oIlIngpoInt
(`C) 59 24 49 57 50 88
7apor
pressureat
20`C(mm
Hg)
157 669 2J8 172 24J J8,770
|olecular
weIght(g)
200 168 184 184 197 44
DIl:gas
partItIon
coeffIcIent
47 19 91 97 224 1.4
8lood:gas
partItIon
coeffIcIent
0.65 0.42 1.46 1.9 2.50 0.46
8raIn:blood
solubIlIty
1.7 1.J 1.6 1.4 1.9 1.1
Fat:blood
solubIlIty
47.5 27.2 44.9 J6 51.1 2.J
|uscle:blood
solubIlIty
J.1 2.0 2.9 1.7 J.4 1.2
|ACInD
2
J060yr,at
J7`CP
8
760
()
1.8 6.6 1.17 1.6J 0.75 104
|ACIn60
70N
2
D()
0.66 2.J8 0.56 0.57 0.29
|AC,65yr
()
1.45 5.17 1.0 1.55 0.64
PreservatIve No No No No Thymol No
StableIn
moIstCD
2
absorber
No Yes Yes Yes No Yes
FlammabIlIty
()(In70
N
2
D/J0D
2
)
10 17 7 5.8 4.8
Fecovered
as
metabolItes
()
25 0.02 0.2 2.4 20
|AC,mInImumalveolarconcentratIon;N
2
D,nItrousoxIde.
Speed,gaseousstate,andthelungrouteofadmInIstratIoncombInetoformthemajor
benefIcIalfeatureoftheInhaledanesthetIcs:theabIlItytodecreaseplasmaconcentratIons
aseasIlyandasrapIdlyastheyareIncreased.
Physical Characteristics of Inhaled Anesthetics
ThephysIcalcharacterIstIcsofInhaledanesthetIcsareshownInTable171.Thegoalof
delIverIngInhaledanesthetIcsIstoproducetheanesthetIcstatebyestablIshIngaspecIfIc
concentratIonofanesthetIcmoleculesInthecentralnervoussystem(CNS).ThIsIsdoneby
establIshIngthespecIfIcpartIalpressureoftheagentInthelungs,whIchultImately
equIlIbrateswIththebraInandspInalcord.AtequIlIbrIum,CNSpartIalpressureequals
bloodpartIalpressure,whIchInturnequalsalveolarpartIalpressure:
wherePIspartIalpressure.EquIlIbratIonIsaresultofthreefactors:
1. nhaledanesthetIcsaregasesrapIdlytransferredbIdIrectIonallyvIathelungstoandfrom
thebloodstreamandsubsequentlytoandfromCNStIssuesaspartIalpressures
equIlIbrate.
2. PlasmaandtIssueshavealowcapacItytoabsorbtheInhaledanesthetIcsrelatIvetothe
amountwecandelIvertothelungs,allowIngustoquIcklyestablIshorabolIsh
anesthetIzIngconcentratIonsofanesthetIcInthebloodstreamandultImatelytheCNS.
J. |etabolIsm,excretIon,andredIstrIbutIonoftheInhaledanesthetIcsaremInImalrelatIve
totherateatwhIchtheyaredelIveredorremovedfromthelungs.ThIspermItseasy
maIntenanceofbloodandCNSconcentratIons.
Thesocalledpermanent gases,suchasoxygenandnItrogen,exIstonlyasgasesatambIent
temperatures.CasessuchasnItrousoxIdecanbecompressedIntolIquIdsunderhIgh
pressureatambIenttemperature.|ostpotent volatile anestheticsarelIquIdsatambIent
temperatureandpressure.fthesystemInwhIchthevolatIlelIquIdresIdesIsaclosed
contaIner,moleculesofthesubstancewIllequIlIbratebetweenthelIquIdandgasphases.
AtequIlIbrIum,thepressureexertedbymolecularcollIsIonsofthegasagaInstthe
contaInerwallsIsthevapor pressure.DneImportantpropertyofvaporpressureIsthatas
longasanylIquIdremaInsInthecontaIner,thevaporpressureIsIndependentofthe
volumeofthatlIquId.AswIthanygas,however,vaporpressureIsproportIonalto
temperature.
Forallofthepotentagents,at20`CthevaporpressureIsbelowatmospherIcpressure.f
thetemperatureIsraIsed,thevaporpressureIncreases.Theboiling pointofalIquIdIsthe
temperatureatwhIchItsvaporpressureexceedsatmospherIcpressureInanopen
contaIner.0esfluraneIsbottledInaspecIalcontaInerbecauseItsboIlIngpoIntof2J.5`C
makesItboIlattypIcalroomtemperatures.8oIlIngdoesnotoccurwIthInthebottle
becauseItIscounteredbybuIldupofvaporpressurewIthInthebottle,butonceopenedto
aIr,thedesfluranewouldquIcklyboIlaway.ThebottleIsdesIgnedtoallowtransferof
desfluranefrombottletovaporIzerwIthoutexposuretotheatmosphere.
Gases in Mixtures
ForanymIxtureofgasesInaclosedcontaIner,eachgasexertsapressureproportIonalto
Itsfractional mass.ThIsIsItspartial
P.416
pressure.ThesumofthepartIalpressuresofeachgasInamIxtureofgasesequalsthetotal
pressureoftheentIremIxture(0alton'slaw).
AnotherwaytostatethIsIsthateachgasInamIxtureofgasesatagIvenvolumeand
temperaturehasapartIalpressurethatIsthepressureItwouldhaveif it aloneoccupIed
thevolume.TheentIremIxturebehavesjustasIfItwereasInglegasaccordIngtothe
Idealgaslaw.
Gases in Solution
PartIalpressureofagasInsolutIonIsabItcomplexbecausepressurecanonlybemeasured
Inthegasphase,whIleInsolutIontheamountofgasIsmeasuredasaconcentratIon.
PartIalpressureofagasInsolutIonreferstothepressureofthegasInthegasphase(IfIt
werepresent)InequIlIbrIumwIththelIquId.tIsImportanttotalkofpartIalpressures,
however,becausegasesequIlIbratebasedonpartIalpressures,notconcentratIons.
CasmoleculeswIthInalIquIdInteractwIthsolventmoleculestoamuchlargerextentthan
domoleculesInthegasphase.SolubilityIsthetermusedtodescrIbethetendencyofagas
toequIlIbratewIthasolutIon,hencedetermInIngItsconcentratIonInsolutIon.Henry'slaw
expressestherelatIonshIpofconcentratIonofagasInsolutIontothepartIalpressureof
thegaswIthwhIchthesolutIonIsInequIlIbrIum:
whereC
g
IsconcentratIonofgasInsolutIon,kIsasolubIlItyconstant,andP
g
IsthepartIal
pressureofthegas.FromEquatIon17JonecanseethatdoublIngthepressureofagas
doublesItsconcentratIonInsolutIon.AmoreclInIcallyusefulexpressIonofsolubIlItyIsthe
solubIlItycoeffIcIent,:
whereV=volume.ThIsequatIonstatesthatforanygasInequIlIbrIumwIthalIquId,a
certaInvolumeofthatgasdIssolvesInagIvenvolumeoflIquId.
TheprIncIplesofpartIalpressuresandsolubIlItyapplyInmIxturesofgasesInsolutIon.That
Is,theconcentratIonofanyonegasInamIxtureofgasesInsolutIondependsontwo
factors:(1)ItspartIalpressureInthegasphaseInequIlIbrIumwIththesolutIon,and(2)Its
solubIlItywIthInthatsolutIon.
TheImplIcatIonsofthesepropertIesarethatanesthetIcgasesadmInIsteredvIathelungs
dIffuseIntoblooduntIlthepartIalpressuresInalveolIandbloodareequal.The
concentratIonofanesthetIcIntheblooddependsonthepartIalpressureatequIlIbrIumand
thebloodsolubIlIty.LIkewIse,transferofanesthetIcfrombloodtotargettIssuesalso
proceedstowardequalIzIngpartIalpressures,butatthIsInterfacethereIsnogasphase.A
partIalpressurestIllexIststoforceanesthetIcmoleculesoutofsolutIonandIntoagas
phasebutthereIsnogasphasebecauseblood(outsIdethelungs)andtIssuesarelIke
closed,lIquIdfIlledcontaIners.FemembertheprIncIple:thepartIalpressureofagasIn
solutIonrepresentsthepressurethatthegasInequIlIbrIumwIththelIquIdwould haveIfa
gasphaseexIstedIncontactwIththelIquIdphase.
TheconcentratIonofanesthetIcIntargettIssuedependsonthepartIalpressureat
equIlIbrIumandthetargettIssuesolubIlIty.8ecauseInhaledanesthetIcsaregases,and
becausepartIalpressuresofgasesequIlIbratethroughoutasystem,monitoring the alveolar
concentration of inhaled anesthetics provides an index of their effects in the brain.
nsummary:
1. nhaledanesthetIcsequIlIbratebasedontheIrpartIalpressuresIneachtIssue(ortIssue
compartment),notbasedontheIrconcentratIons.
2. ThepartIalpressureofagasInsolutIonIsdefInedbythepartIalpressureInthegas
phasewIthwhIchItIsInequIlIbrIum.WherethereIsnogasphasethepartIalpressure
reflectsaforcetoescapeoutofsolutIon.
J. TheconcentratIonofanesthetIcInatIssuedependsonItspartIalpressureandtIssue
solubIlIty.
FInally,thepartIculartermInologyusedwhenreferrIngtogasesInthegasphaseor
absorbedInplasmaortIssuesIsImportant.nspIredconcentratIonsorfractIonalvolumesof
InhaledanesthetIcaretypIcallyusedratherthanpartIalpressure.PartIalpressureIs
expressedInmIllImetersofmercury(mmHg)ortorr(1torr=1mmHg)orkIlopascals(kPa).
Formostdrugs,concentratIonIsexpressedasmass(mIllIgram[mg])pervolume(mIllIlIter
[mL]),butItcanalsobeexpressedInpercentbyweIghtorvolume.8ecausevolumeofa
gasInthegasphaseIsdIrectlyproportIonaltomassaccordIngtotheIdealgaslaw,ItIs
easIertoexpressthIsfractIonalconcentratIonasapercentbyvolume.nthegasphase,
fractIonalconcentratIonIsequaltothepartIalpressuredIvIdedbyambIentpressure,
usuallyatmospherIc,or:
Anesthetic Transfer: Machine to Central Nervous System
WhenthefreshgasflowandthevaporIzerareturnedon,freshgaswIthafIxedfractIonal
concentratIonofanesthetIcleavesthefreshgasoutletandmIxeswIththegasInthe
cIrcuItthebag,tubIng,absorbentcanIster,andpIpIng.tIsImmedIatelydIlutedtoa
lowerfractIonalconcentratIon,thenslowlyrIsesasthIscompartmentequIlIbrateswIththe
freshgasflow.WIthspontaneouspatIentventIlatIonbymask,theanesthetIcgaspasses
fromcIrcuIttoaIrways.ThefractIonalconcentratIonofanesthetIcleavIngthecIrcuItIs
desIgnatedasF
(fractIonInspIred).nthelungsthegascomprIsIngthedeadspaceInthe
aIrways(trachea,bronchI)andthealveolIfurtherdIlutesthecIrcuItgas.ThefractIonal
concentratIonofanesthetIcpresentInthealveolIIsF
A
(fractIonalveolar).TheanesthetIc
thenpassesacrossthealveolarcapIllarymembraneanddIssolvesInpulmonaryblood
accordIngtothepartIalpressureofthegasandItsbloodsolubIlIty.tIsfurtherdIlutedand
travelsvIabulkbloodflowthroughoutthevasculartree.TheanesthetIcthenpassesvIa
sImpledIffusIonfrombloodtotIssuesaswellasbetweentIssues.
ThevascularsystemdelIversbloodtothreephysIologIctIssuegroups;thevesselrIchgroup
(7FC),themusclegroup,andthefatgroup.The7FCIncludesthebraIn,heart,kIdney,
lIver,dIgestIvetract,andglandulartIssues.ThepercentofbodymassandperfusIonof
eachgroupareshownInTable172.TheCNStIssuesofthe7FCarereferredtoastissues
of desired effect.TheothertIssuesofthe7FCthatcomprIsethecompartmentare
referredtoastissues of undesired effects.ThetIssuesofthemuscleandfatgroups
comprIsethetissues of accumulation.
AnesthetIcIsdelIveredmostrapIdlytothe7FCbecauseofhIghbloodflow.HereItdIffuses
accordIngtopartIalpressuregradIents.CNStIssuetakesIntheanesthetIcaccordIngtothe
tIssuesolubIlIty,andatahIghenoughtIssueconcentratIon,unconscIousnessandanesthesIa
areachIeved.ncreasIngCNStIssueconcentratIonscauseprogressIvelydeeperstagesof
anesthesIa.AsthIsIsoccurrIng,anesthetIcIsalsodIstrIbutIngtoother7FCtIssues.Also
coIncIdentwIthdelIverytothe
P.417
CNS,anesthetIcIsbeIngdelIveredalbeItmoreslowlybecauseoflowerperfusIonto
muscleandfat,whereItaccumulatesandmayaffectthespeedofemergencefromthe
anesthetIc.nrealIty,thefatsolubIlItIesprovIdelIttleInfluenceonemergenceIncases
lastIng4hourssIncethedelIveryofanesthetIctofattIssueIsextremelyslowasaresult
oflowbloodflow.TheconcentratIonofInhaledanesthetIcInagIventIssueatapartIcular
tImedurIngtheadmInIstratIondependsnotonlyontIssuebloodflow,butalsoontIssue
solubIlIty,whIchgovernshowtheInhaledanesthetIcspartItIonthemselvesbetweenblood
andtIssue.PartItIonIngdependsontherelatIvesolubIlItIesoftheanesthetIcforeach
compartment.TheserelatIvesolubIlItIesareexpressedbyapartItIoncoeffIcIent,,whIch
IstheratIoofdIssolvedgas(byvolume)IntwotIssuecompartmentsatequIlIbrIum.Some
ofthepartItIoncoeffIcIentsfortheInhaledanesthetIcsareshownInTable171.
Table 17-2 Distribution of Cardiac Output by Tissue Group
GROUP % BODY MASS % CARDIAC OUTPUT PERFUSION (mL/min/100 g)
7esselrIch 10 75 75
|uscle 50 19 J
Fat 20 6 J
Uptake and Distribution
F
A
/F
I
AsImple,commonwaytoassessanesthetIcuptakeIstofollowtheratIooffractIonal
concentratIonofalveolaranesthetIctoInspIredanesthetIc(F
A
/F
)overtIme.
ExperImentallyderIveddataforF
A
/F
versustImedurIngInductIonareshownInFIgure17
2.ThefasterF
A
rIsesrelatIvetoF
,thefasterthespeedofInductIonsInceF
A
Is
proportIonaltoP
A
(F
A
=P
A
/P
barometrIc
)andP
A
=P
blood
=P
CNS
;thatIs,thealveolarfractIonIs
dIrectlyproportIonaltothepartIalpressureofanesthetIcIntheCNS.
AsfreshgascarryInganesthetIcbegInstoflowIntotheaIrfIlledcIrcuIt(assumIngcomplete
mIxIng),theconcentratIonInthecIrcuIt(F
)wIllrIseaccordIngtofIrstorderkInetIcs:
F
FCD
IsthefractIonofInspIredanesthetIcInthegasleavIngthefreshgasoutlet(I.e.,the
vaporIzersettIng),TIstIme,andIsatImeconstant.ThetImeconstantIssImplythe
volumeorcapacItyofthecIrcuIt(V
C
)dIvIdedbythefreshgasflow(FCF)or=V
C
/FCF.
Forexample,Ifthebag,tubIng,absorbentcanIster,andpIpIngcomprIse8L,andthefresh
gasflowIs2L,thetImeconstant=
8
/
2
=4.DneofthecharacterIstIcsoffIrstorder
kInetIcsIsthat95ofmaxImumIsreachedafterthreetImeconstantsInthIscase,J4=
12mInutes.
8ecause12mInutesIsrelatIvelylong,startIngwIthahIgherF
FCD
canIncreasetherateof
rIseofF
.UsIngtheearlIerexamplewIth=4,byfIrstorderkInetIcs6JofmaxImumIs
reachedafteronetImeconstant,or4mInutes.ToattaInanF
of2at4Insteadof12
mInutes,theF
FCD
canbesettoJ.2(2dIvIdedby0.6J)andthenloweredto2atthe4
mInutemark.
DtherwaystospeedtheIncreaseInF
IncludeIncreasIngthefreshgasflow,thus
decreasIng.Furthermore,therebreathIngbagcanbecollapsedprIortostartIngthefresh
gasflow,suchthatthecapacItyInthecIrcuIt(V
C
)Isless,whIchalsodecreases.FInally,
athIghflows(4L/mIn)thereIsfarlessmIxIngbecausefreshgaspushesoldgasoutof
thecIrcuItvIathepopoffvalvebeforecompletemIxIngoccurs,causIngF
toIncreaseata
greaterrate;thIsIsthemostImportantfactorInrapIdlyIncreasIngF
tothedesIred
concentratIon.
Figure 17-2.TherIseInalveolar(F
A
)anesthetIcconcentratIontowardtheInspIred(F
)
concentratIonIsmostrapIdwIththeleastsolubleanesthetIcs,nItrousoxIde(N
2
D),
desflurane,andsevoflurane.trIsesmostslowlywIththemoresolubleanesthetIcs,
suchashalothane.AlldataarefromhumanstudIes.(AdaptedfromYasudaN,Lockhart
SH,EgerE,etal:ComparIsonofkInetIcsofsevofluraneandIsofluraneInhumans.
AnesthAnalg1991;72:J16;andYasudaN,LockhartSH,EgerE,etal:KInetIcsof
desflurane,Isoflurane,andhalothaneInhumans.AnesthesIology1991;74:489.)
DnefactorthatdelaystherateofrIseofF
IsthatCD
2
absorbentcanadsorband
decomposetheInhaledanesthetIcs.FromapractIcalstandpoInt,thIsdoesnotaffectthe
rateofrIseInF
toasIgnIfIcantextentcomparedwIthotherfactors.Anotherfactorthat
delaystherateofrIseofF
IssolubIlItyoftheInhaledanesthetIcsInsomeoftheplastIc
andrubberpartsoftheanesthesIacIrcuIt.ThIsabsorptIonhasbeenquantIfIed,butplays
onlyasmallroleIndecreasIngtherateofrIseofF
.
Rise in F
A
in the Absence of Uptake
TherateofrIseInF
dIscussedearlIerassumesthatnoanesthetIcIsmIxIngwIthgasInthe
patIent'slungs.nrealIty,cIrcuItgasmIxeswIthexhaledgasesfromthelungwItheach
breath,thuslowerIngF
wIthInthecIrcuIt.fhIghfreshgasflows(4L/mIn),whIchproduce
ahIghvolumeofgasatthedesIredconcentratIon,areused,lIttlemIxIngwIthexhaledaIr
occursandF
IsrelatIvelyfIxed.nthIssItuatIon,cIrcuItgasentersthelungswhereItmIxes
wIthalveolargas.ftherewerenobloodflowtothelungs,F
A
wouldrIseInafashIon
analogoustoF
;thatIs:
nthIsequatIon,IsthetImeconstantforalveolarrIseInanesthetIcconcentratIonand
equalsthefunctIonalresIdualcapacIty(FFC)ofthepatIent'slungsdIvIdedbymInute
ventIlatIon,[7wIthdotabove]
A
.TherearetwowaystospeedtheequIlIbratIonofF
A
wIth
F
,thatIs,todecrease.DnewayIstoIncreasemInuteventIlatIon,
P.418
andtheotherIstodecreaseFFC.8othofthesemethodscanbeusedtospeedInductIonby
mask:thepatIentcanexhaledeeplybeforeapplyIngthemask(todecreasetheInItIalFFC),
andthepatIentcanbreathedeeplyandrapIdly(toIncrease)afterthemaskIsapplIed.
mportantly,hIghalveolarventIlatIonrelatIvetouptakefromthelungstothebloodstream
generatestheInItIalhIghslopetothecurvesshownInFIgure172.
Table 17-3 Factors that Increase or Decrease the Rate of Rise of F
A
/F
I
INCREASE DECREASE
Low
8
HIgh
8
Thelowertheblood:gassolubIlIty,thefastertherIseInF
A
/F
LowQ HIghQ
ThelowerthecardIacoutput,thefastertherIseInF
A
/F
HIgh
7.
A
Low
7.
A
ThehIgherthemInuteventIlatIon,thefastertherIseInF
A
/F
HIgh
(P
A
P
v
)
Low
(P
A
P
v
)
AtthebegInnIngofInductIon,P
v
IszerobutrIsesrapIdly(thus
[P
A
P
v
]fallsrapIdly)andF
A
/F
IncreasesrapIdly.LaterdurIng
InductIonandmaIntenanceP
v
rIsesmoreslowlysoF
A
/F
rIses
moreslowly.
8
=bloodsolubIlIty;Q=cardIacoutput;7.=mInuteventIlatIon;P
A
,P
7
=
pulmonaryarterIalandvenousbloodpartIalpressure.
DneofthereasonsthatpedIatrIcInductIonsbyspontaneousbreathIngofInhaled
anesthetIcsaresomuchquIckerthanadultInductIonsIsthatthelowFFCrelatIveto[7
wIthdotabove]
A
ofchIldrenmakesforalowtImeconstant,andhenceamorerapId
IncreaseInF
A
/F
.DneImportantcaveatabouttherelatIonshIpofF
A
toFFCIsthatFFC
IncludesaIrwaydeadspace;thus,InrealIty,F
A
byEquatIon177Isnotjustthe
concentratIonofInhaledanesthetIcInthealveolIbutalsotheconcentratIonIntheentIre
lung.However,ItIssImplycalledthealveolarconcentratIonbecausethedeadspaceInthe
aIrwaysIsrelatIvelyInsIgnIfIcantandonlythealveolargasIsexchangInganesthetIcwIth
theblood.
Rise in F
A
in the Presence of Uptake
AnesthetIcsaresolubleIntIssues,thusuptakeofanesthetIcfromalveolItobloodIsagaIn
characterIzedbyfIrstorderkInetIcs:
Here,P
8
IsthebarometrIcpressureandthetImeconstant,,equalscapacIty(volumeof
anesthetIcdIssolvedInbloodatthedesIredalveolarpartIalpressure)dIvIdedbyflow
(volumeofanesthetIcdelIveredperunIttIme).ForanygIvenflowofanesthetIcIntothe
system,thIscapacItyforthemoresolublehalothaneIsgreaterthanthecapacItyforthe
lesssolubledesflurane;thus,forhalothaneIsgreaterthanthatfordesflurane.Themore
solubletheInhaledanesthetIc,thelargerthecapacItyofthebloodandtIssuesforthat
anesthetIc,andthelongerIttakestosaturateatanygIvendelIveryrate.
ThemostImportantfactorIntherateofrIseofF
A
/F
IsuptakeofanesthetIcfromthe
alveolIIntothebloodstream.TherateofrIseofF
A
/F
(especIallytheposItIonofthe
kneesInthecurvesofFIgure172)reflectsthespeedatwhIchalveolaranesthetIc(F
A
)
equIlIbrateswIththatbeIngdelIveredtothelungs(F
).SIncethereIsuptakefromalveolI
toblood,F
A
IsnotsolelyafunctIonofF
andtIme.Thegreatertheuptake,theslowerthe
rateofrIseofF
A
/F
,andvIceversa.SInceuptakeIsproportIonaltotIssuesolubIlIty,the
lesssolubletheanesthetIc(suchasdesflurane),thelesserItsuptakeandthefasterIt
reachesequIlIbrIum,P
A
=P
blood
=P
CNS
.
ConsIderahypothetIcalexample.SupposethathalothaneanddesfluranearesolubleIn
blood,butInsolubleInallothertIssues.SupposefurtherthattotallungcapacItyandblood
volumewereboth5L.fafIxedvolumeofanesthetIcIsdelIveredtothelungs(byaskIng
thepatIenttotakeonedeepbreathandholdIt),accordIngtotheblood:gaspartItIon
coeffIcIentsforhalothane(2.5)anddesflurane(0.42),71.4ofthedelIveredhalothanewIll
betransferredtothebloodwhIle28.6remaInsInthealveolI(71.4/28.6=2.5).ncontrast,
29.6ofthedesfluranewIllbetransferredtothebloodwhIle70.4remaInsInthealveolI
(29.6/70.4=0.42).Therefore,2.4tImes(71.4/29.6)morehalothanethandesflurane(by
volumeornumberofmolecules)wIllbetransferredfromalveolItobloodstreambefore
partIalpressuresequIlIbrate.AtequIlIbrIum,thealveolarpartIalpressuresofhalothane
anddesfluraneare28.6and70.4oftheIrInhaledvalues,respectIvely.ThIsmeansthat
F
A
rIsesfasterwIthdesfluranethanhalothane,asdoesF
A
/F
.
8looduptakeofanesthetIcIsexpressedbytheequatIon:
where[7wIthdotabove]
8
Isblooduptake,
b/g
Istheblood:gaspartItIoncoeffIcIent,QIs
cardIacoutput,P
A
IsalveolarpartIalpressureofanesthetIc,P
v
IsmIxedvenouspartIal
pressureofanesthetIc,andP
8
IsbarometrIcpressure.ThIsIstheFIckequatIonapplIedto
blooduptakeofInhaledanesthetIcs.The greater the value of V.
B
, the greater the uptake
from alveoli to blood, and the slower the rise in F
A
/F
I
.
FromtheprecedIngparagraphs,theparametersthatIncreaseordecreasetherateofrIse
InF
A
/F
durIngInductIoncannowbeclearlydelIneatedandtheseImportantfactorshave
beensubstantIatedInexperImentalmodels(Table17J).
Distribution (Tissue Uptake)
ThemaxImumF
A
/F
atagIvenInspIredconcentratIonofanesthetIc,cardIacoutput,and
mInuteventIlatIondependsentIrelyonthesolubIlItyofthatdrugInthebloodas
characterIzedbytheblood:gaspartItIoncoeffIcIent
b/g
.ThIscanbeseenInthetIme
curvesfortherIseInF
A
/F
durIngInductIonforthevarIousInhalatIonanesthetIcsshownIn
FIgure172.ThefIrstkneeIneachcurveInFIgure172representsthepoIntatwhIchthe
rapIdrIseInP
v
begInstotaperoff;thatIs,whensIgnIfIcantInhaledanesthetIc
concentratIonsbegIntobuIldupInthebloodstreambecauseofdIstrIbutIontoand
equIlIbratIonwIththevarIoustIssuecompartments.
P.419
AsbloodIsequIlIbratIngwIthalveolargas,ItalsobegInstoequIlIbratewIththe7FC,
muscle,and,moregradually,thefatcompartmentsbasedonperfusIon.|uscleIsnotthat
dIfferentfromthe7FC,havIngpartItIoncoeffIcIentsthatrangefrom1.2(nItrousoxIde)to
J.4(halothane),justunderathreefolddIfference;andforeachanesthetIcexceptnItrous
oxIde,themusclepartItIoncoeffIcIentIsapproxImatelydoublethatforthe7FC.Although
both7FCandmuscleareleantIssues,themusclecompartmentequIlIbratesfarmore
slowlythanthe7FC.TheexplanatIoncomesInpartduetothemassofthecompartments
relatIvetoperfusIon.TheperfusIonofthe7FCIsabout75mL/mIn/100goftIssue,whereas
ItIsonlyJmL/mIn/100goftIssueInthemuscle(Table172).ThIs25folddIfferenceIn
perfusIonbetween7FC(especIallybraIn)andmusclemeansthatevenIfthepartItIon
coeffIcIentswereequal,themusclewouldstIlltake25tImeslongertoequIlIbratewIth
blood.
FatIsperfusedtoalesserextentthanmuscleandItstImeforequIlIbratIonwIthbloodIs
consIderablyslowerbecausethepartItIoncoeffIcIentsaresomuchgreater.Allofthe
potentagentsarehIghlylIpIdsoluble.PartItIoncoeffIcIentsrangefrom27(desflurane)to
51(halothane).Dnaverage,thesolubIlItyfortheseagentsIsabout25tImesgreaterInfat
thanInthe7FCgroup.Thus,fatequIlIbratesfarmoreslowlywIththebloodanddoesnot
playasIgnIfIcantroleIndetermInIngspeedofInductIon.AfterlonganesthetIcexposures
(4hours),thehIghsaturatIonoffattIssuemayplayaroleIndelayIngemergence.
NItrousoxIderepresentsanexceptIon.tspartItIoncoeffIcIentsarefaIrlysImIlarIneach
tIssue:ItdoesnotaccumulatetoanygreatextentandIsnotaverypotentanesthetIc.ts
utIlItylIesasanadjuncttothepotentagents,andasavehIcletospeedInductIon.
Metabolism
0atasuggestthatenzymesresponsIbleforbIotransformatIonofInhaledanesthetIcsbecome
saturatedatlessthananesthetIzIngdosesofthesedrugs,suchthatmetabolIsmplayslIttle
roleInopposIngInductIon.tmay,however,havesomesIgnIfIcancetorecoveryfrom
anesthesIa,asdIscussedlater.
Overpressurization and the Concentration Effect
ThereareseveralwaystospeeduptakeandInductIonofanesthesIawIththeInhaled
anesthetIcs.ThefIrstIsoverpressurization,whIchIsanalogoustoanIntravenousbolus.
ThIsIstheadmInIstratIonofahIgherpartIalpressureofanesthetIcthanthealveolar
concentratIon(F
A
)actuallydesIredforthepatIent.nspIredanesthetIcconcentratIon(F
)
canInfluencebothF
A
andtherate of riseofF
A
/F
.ThegreatertheInspIredconcentratIon
ofanInhaledanesthetIc,thegreatertherateofrIse.ThIsconcentratIoneffecthastwo
components:theconcentratIngeffectandanaugmentedgasInfloweffect.
Forexample,consIdertheadmInIstratIonof10anesthetIc(10partsanesthetIcand90
partsothergas)toapatIentInwhom50oftheanesthetIcInthealveolIIsabsorbedby
theblood.nthIscase,fIveparts(0.510)anesthetIcremaInInthealveolI,fIveparts
entertheblood,and90partsremaInasotheralveolargas.ThealveolarconcentratIonIs
now5/(90+5)=5.J.ConsIdernextadmInIsterIng50anesthetIcwIththesame50
uptake.Now25partsanesthetIcremaInInalveolI,25partspassIntoblood,and50parts
remaInasotheralveolargas.ThealveolarconcentratIonbecomes25/(50+25)=JJ.
CIvIng5tImesasmuchanesthetIchasledtoaJJ/5.J=6.2tImesgreateralveolar
concentratIon.ThehIghertheF
,thegreatertheeffect.ThusnItrousoxIde,typIcallygIven
InconcentratIonsof50to70,hasthegreatestconcentratIngeffect.ThIsIswhytheF
A
/F
versustImecurveInFIgure172rIsesthemostquIcklywIthnItrousoxIde,eventhough
desfluranehasaslIghtlylowerblood:gassolubIlIty.
ThIsIsnotthecompletepIcture;thereIsyetanotherfactortoconsIder.AsgasIsleavIng
thealveolIfortheblood,newgasattheorIgInalF
IsenterIngthelungstoreplacethat
whIchIstakenupbytheblood.ThIsotheraspectoftheconcentratIoneffecthasbeen
calledaugmented gas inflow.AgaIn,taketheexampleof10anesthetIcdelIveredwIth50
uptakeIntothebloodstream.ThefIvepartsanesthetIcabsorbedbythebloodstreamare
replacedbygasInthecIrcuItthatIsstIll10anesthetIc.ThefIvepartsanesthetIcand90
partsothergasleftInthelungsmIxwIthfIvepartsreplacementgas,or50.10=0.5parts
anesthetIc.NowthealveolarconcentratIonIs(5+0.5)/(100)=5.5(ascomparedto5.J
wIthoutaugmentedInflow).For50anesthetIcand50uptake,25partsofanesthetIc
removedfromthealveolIarereplacedwIth25partsof50anesthetIc,gIvInganew
alveolarconcentratIonof(25+12.5)/(100)=J7.5(ascomparedtoJJwIthoutaugmented
Inflow).Thus,5tImestheF
leadstoJ7.5/5.5=6.8tImesgreaterF
A
(comparedto6.2tImes
wIthoutaugmentedgasInflow).Dfcourse,thIscycleofabsorbedgasbeIngreplacedby
freshgasInflowIscontInuousandhasafInIterate,soourexampleIsasImplIfIcatIon.
Second Gas Effect
AspecIalcaseofconcentratIoneffectapplIestoadmInIstratIonofapotentanesthetIcwIth
nItrousoxIdethatIs,twogasessImultaneously.AlongwIththeconcentratIonofpotent
agentInthealveolIvIaItsuptake,thereIsfurtherconcentratIonvIatheuptakeofnItrous
oxIde,aprocesscalledthesecond gas effect.TheprIncIpleIssImple(FIgs.17Jand174).
ConsIder,
P.420
forexample,admInIsterIng2ofapotentanesthetIcIn70nItrousoxIdeand28oxygen.
nthIscase,nItrousoxIde,wIthItsextremelyhIghpartIalpressure(despItelowsolubIlIty),
partItIonsIntothebloodmorerapIdlythanthepotentanesthetIc,decreasIngthealveolar
N
2
D(nItrousoxIde)concentratIonbysomeamount(e.g.,by50).gnorInguptakeofthe
potentanesthetIc,theuptakeofN
2
DIsJ5parts,leavIngJ5partsN
2
D,28partsD
2
,andtwo
partspotentagentInthealveolI.TheanesthetIcgasIsnowpresentInthealveolIata
concentratIonof2/(2+J5+28)=J.1.ThepotentagenthasbeenconcentratedandF
A
Is
Increased.
Figure 17-3.TheconcentratIoneffectIsdemonstratedInthetophalfofthegraph
fromdogsreceIvIngnItrousoxIde(N
2
D).AdmInIstratIonof70nItrousoxIdeproducesa
morerapIdrIseIntheF
A
/F
ratIoofnItrousoxIdethanadmInIstratIonof10nItrous
oxIde.ThesecondgaseffectIsdemonstratedInthelowergraphs.TheF
A
/F
ratIofor
0.5halothanerIsesmorerapIdlywhengIvenwIth70nItrousoxIdethanwhengIven
wIth10nItrousoxIde.(AdaptedfromEpsteInF,FackowH,SalanItreE,etal:
nfluenceoftheconcentratIoneffectontheuptakeofanesthetIcmIxtures:Thesecond
gaseffect.AnesthesIology1964;25:J64.)
Figure 17-4.AgraphIcandrelatIveequatIontodemonstratethesecondgaseffect.n
thIshypothetIcalexample,thesecondgasIssetat2ofapotentanesthetIcandthe
modelIssetfor50uptakeofthefIrstgas(nItrousoxIde[N
2
D])InthefIrstInspIred
breath.ThesecondgasIsconcentratedbecauseoftheuptakeofN
2
D(middle panel).
DnreplenIshIngtheInspIredsecondgas(F
=2)Inthenextbreath,thesecondgashas
beenconcentratedtobe2.7becauseoftheuptakeofN
2
DIntheprevIousbreath.
Ventilation Effects
AsIndIcatedbyFIgure172andTable17J,InhaledanesthetIcswIthverylowtIssue
solubIlItyhaveanextremelyrapIdrIseInF
A
/F
wIthInductIon.ThIssuggeststhatthereIs
verylIttleroomtoImprovethIsratebyIncreasIngordecreasIngventIlatIon,whIchIs
consIstentwIththeexperImentalevIdenceshownInFIgure175.ThegreaterthesolubIlIty
ofanInhaledanesthetIc,themorerapIdlyItIsabsorbedbythebloodstream,suchthat
anesthetIcdelIverytothelungsmayberatelImItIngtotherIseInF
A
/F
.Therefore,for
moresolubleanesthetIcs,augmentatIonofanesthetIcdelIverybyIncreasIngmInute
ventIlatIonalsoIncreasestherateofrIseInF
A
/F
.
SpontaneousmInuteventIlatIonIsnotstatIc,however,andtotheextentthattheInhaled
anesthetIcsdepressspontaneousventIlatIonwIthIncreasIngInspIredconcentratIon,[7wIth
dotabove]
A
wIlldecreaseandsowIlltherateofrIseofF
A
/F
.ThIsIsdemonstratedIn
FIgure175.ThIsnegatIvefeedbackshouldnotbeconsIderedadrawbackoftheInhaled
anesthetIcsbecausetherespIratorydepressIonproducedathIghanesthetIcconcentratIons
essentIallyslowstherIseInF
A
/F
.ThIsmIghtarguablyaddamargInofsafetyInpreventIng
anoverdose.ControlledventIlatIondoesnotofferthIsmargInofsafety.
Perfusion Effects
AswIthventIlatIon,cardIacoutputIsnotstatIcdurIngthecourseofInductIon.Fortheless
solubleagents,changesIncardIacoutputdonotaffecttherateofrIseofF
A
/F
toagreat
extent,butforthemoresolubleagentstheeffectIsnotIceable,asseenInFIgure176.
However,asInspIredconcentratIonIncreases,greatercardIovasculardepressIonreduces
anesthetIcuptakeandactuallyIncreasestherateofrIseofF
A
/F
.ThIsposItIvefeedback
canrapIdlyleadtoprofoundcardIovasculardepressIon.FIgure176presentsexperImental
dataInwhIchlowercardIacoutputsleadtoamuchmorerapIdrIseInF
A
/F
when[7wIth
dotabove]
A
Isheldconstant.ThIsmorerapIdrIseIsgreaterthancanbeaccountedforjust
byconcentratIoneffect.
Figure 17-5.TheF
A
/F
ratIorIsesmorerapIdlyIfventIlatIonIsIncreasedfrom2to8
L/mIn.SolubIlItymodIfIesthIsImpactofventIlatIon;forexample,theeffectIs
greatestwIththeleastsolubleanesthetIc,nItrousoxIde(N
2
D;top three lines),and
leastwIththemoresolubleanesthetIc,halothane.(AdaptedfromEgerE:
7entIlatIon,cIrculatIonanduptake,AnesthetIcUptakeandActIon.8altImore,WIllIams
EWIlkIns,1974,pp122.)
P.421
Figure 17-6.fventIlatIonIsfIxed,anIncreaseIncardIacoutputfrom2to18L/mIn
wIlldecreasethealveolaranesthetIcconcentratIonbyaugmentInguptake,thereby
slowIngtherIseoftheF
A
/F
ratIo.ThIseffectIsmostpromInentwIththemoresoluble
anesthetIcs(halothane)thanwIththelesssolubleanesthetIcs(nItrousoxIde[N
2
D]).
(AdaptedfromEgerE:7entIlatIon,cIrculatIonanduptake,AnesthetIcUptakeand
ActIon.8altImore,WIllIamsEWIlkIns,1974,p1J1.)
VentilationPerfusion Mismatching
7entIlatIonandperfusIonarenormallyfaIrlywellmatchedInhealthypatIentssuchthatP
A
(alveolarpartIalpressure)/P
andP
a
(arterIalpartIalpressure)/P
arethesamecurve.
However,IfsIgnIfIcantIntrapulmonaryshuntoccurs,asInthecaseofInadvertentbronchIal
IntubatIon,therateofrIseofalveolarandarterIalanesthetIcpartIalpressurescanbe
affected.Theeffects,however,dependonthesolubIlItyoftheanesthetIc,asseenIn
FIgure177.7entIlatIonoftheIntubatedlungIsdramatIcallyIncreasedwhIleperfusIon
IncreasesslIghtly.ThenonIntubatedlungreceIvesnoventIlatIon,whIleperfusIondecreases
slIghtly.ForthelesssolubleanesthetIcs,IncreasedventIlatIonoftheIntubatedlungcannot
apprecIablyIncreasealveolarpartIalpressurerelatIvetoInspIredconcentratIononthat
sIde,butalveolarpartIalpressureonthenonIntubatedsIdeIsessentIallyzero.Pulmonary
mIxedvenousblood,therefore,comprIsesnearlyequalpartsbloodcontaInIngnormal
amountsofanesthetIcandbloodcontaInIngnoanesthetIc;thatIs,dIlutedrelatIveto
normal.ThustherateofrIseInP
a
relatIvetoP
IssIgnIfIcantlyreduced.ThereIslesstotal
anesthetIcuptake,sotherateofrIseofP
A
relatIvetoP
IncreaseseventhoughInductIonof
anesthesIaIsslowedbecauseCNSpartIalpressureequIlIbrateswIthP
a
.Forthemore
solubleanesthetIcs,IncreasedventIlatIonoftheIntubatedlungdoesIncreasethealveolar
partIalpressurerelatIvetoInspIredconcentratIononthatsIde.Pulmonaryvenousblood
fromtheIntubatedsIdecontaInsahIgherconcentratIonofanesthetIcthatlessensthe
dIlutIonbybloodfromthenonIntubatedsIde.ThustherateofrIseofP
a
/P
Isnotas
depressedasthatforthelesssolubleanesthetIcs,andInductIonofanesthesIaIsless
delayedrelatIvetonormal.
Elimination
Percutaneous and Visceral Loss
AlthoughthelossofInhaledanesthetIcsvIatheskInIsverysmall,Itdoesoccurandtheloss
IsthegreatestfornItrousoxIde.TheseanesthetIcsalsopassacrossgastroIntestInalvIscera
andthepleura.0urIngopenabdomInalorthoracIcsurgerythereIssomeanesthetIclossvIa
theseroutes.FelatIvetolossesbyallotherroutes,lossesvIapercutaneousandvIsceral
routesareInsIgnIfIcant.
Diffusion Between Tissues
UsIngmoreelaboratemathematIcalmodelIngofInhaledanesthetIcpharmacokInetIcsthan
presentedhere,severallaboratorIeshavederIvedafIvecompartmentmodelthatbest
descrIbestIssuecompartments.ThesecompartmentsarethealveolI,the7FC,themuscle,
thefat,andoneaddItIonalcompartment.CurrentopInIonIsthatthIsfIfthcompartment
representsadIposetIssueadjacenttoleantIssuethatreceIvesanesthetIcvIaIntertIssue
dIffusIon.ThIstransferofanesthetIcIsnotInsIgnIfIcant,andmayaccountforuptoone
thIrdofuptakedurInglongadmInIstratIon.
Exhalation and Recovery
FecoveryfromanesthesIa,lIkeInductIon,dependsonanesthetIcsolubIlIty,cardIacoutput,
andmInuteventIlatIon.SolubIlItyIstheprImarydetermInantoftherateoffallofF
A
P.422
(FIg.178).ThegreaterthesolubIlItyofInhaledanesthetIc,thelargerthecapacItyfor
absorptIonInthebloodstreamandtIssues.ThereservoIrofanesthetIcInthebodyatthe
endofadmInIstratIondependsontIssuesolubIlIty(whIchdetermInesthecapacIty)andthe
doseandduratIonofanesthetIc(whIchdetermInehowmuchofthatcapacItyIsfIlled).
FecoveryfromanesthesIa,orwashout,IsusuallyexpressedastheratIoofexpIred
fractIonalconcentratIonofanesthetIc(F
A
)totheexpIredconcentratIonattImezero(F
A0
)
whentheanesthetIcwasdIscontInued(orF
A
/F
A0
).ElImInatIoncurvesoflowandhIgh
solubleanesthetIcsareshownInFIgure179.ThelongertheduratIonofahIghlysoluble
anesthetIc,thegreaterthereservoIrofanesthetIcInthebody,andthehIgherthecurve
seenIntherIghthalfofFIgure179.ThIseffectIsnearlyabsentwIthlowsolubleagents
suchasnItrousoxIde,desflurane,andsevoflurane.
J
Figure 17-7.WhennoventIlatIon/perfusIonabnormalItIesexIst,thealveolar(P
A
)or
endtIdal(P
ET
)andarterIal(P
a
)anesthetIcpartIalpressuresrIsetogether(blue lines)
towardtheInspIredpartIalpressure(P
).When50ofthecardIacoutputIsshunted
throughthelungs,therateofrIseoftheendtIdalpartIalpressure(orange lines)Is
acceleratedwhIletherateofrIseofthearterIalpartIalpressure(green lines)Is
slowed.ThegreatesteffectofshuntIngIsfoundwIththeleastsolubleanesthetIcs.
(AdaptedfromEgerE,SeverInghausJW:EffectofunevenpulmonarydIstrIbutIonof
bloodandgasonInductIonwIthInhalatIonanesthetIcs.AnesthesIology1964;25:620.)
Figure 17-8.ElImInatIonofanesthetIcgasesIsdefInedastheratIoofendtIdal
anesthetIcconcentratIon(F
A
)tothelastF
A
durIngadmInIstratIonandImmedIately
beforethebegInnIngofelImInatIon(F
A0
).0urIngthe120mInuteperIodafterendIng
theanesthetIcdelIvery,theelImInatIonofsevofluraneanddesfluraneIs2to2.5tImes
fasterthanIsofluraneorhalothane(notelogarIthmIcscalefortheordInate).(Adapted
fromYasudaN,LockhartSH,EgerE,etal:ComparIsonofkInetIcsofsevofluraneand
IsofluraneInhumans.AnesthAnalg1991;72:J16;andYasudaN,LockhartSH,EgerE,
etal:KInetIcsofdesflurane,Isoflurane,andhalothaneInhumans.AnesthesIology1991;
74:489.)
Figure 17-9.8othsolubIlItyandduratIonofanesthesIaaffectthedecreaseofthe
alveolarconcentratIon(F
A
)fromItsvalueImmedIatelyprecedIngthecessatIonof
anesthetIcadmInIstratIon(F
A0
).AlongeranesthetIctIme(from15mInutesto240
mInutes)onlyslIghtlyslowsthedecreasewIthlowsolubleanesthetIcs(left graph).An
agentwIthahIgherbloodandtIssuesolubIlIty(right graph)slowstheelImInatIonof
theanesthetIcandenhancestheeffectofduratIon.(AdaptedfromStoeltIngFK,Eger
E:TheeffectsofventIlatIonandanesthetIcsolubIlItyonrecoveryfromanesthesIa:
AnInvIvoandanaloganalysIsbeforeandafterequIlIbrIum.AnesthesIology1969;J0:
290.)
TherearetwomajorpharmacokInetIcdIfferencesbetweenrecoveryandInductIon.FIrst,
whereasoverpressurIzatIoncanIncreasethespeedofInductIon,thereIsno
underpressurIzatIon.8othInductIonandrecoveryratesdependontheP
A
toP
v
gradIent,
andP
A
canneverfallbelowzero.Second,whereasalltIssuesbegInInductIonwIthzero
anesthetIc,eachbegInsrecoverywIthquItedIfferentanesthetIcconcentratIons.The7FC
tIssuesbegInrecoverywIththesameanesthetIcpartIalpressureasthatInalveolI,sInce
P
CNS
=P
blood
=P
alveolI
.ThepartIalpressuresInmuscleandfatdependontheInspIred
concentratIondurInganesthesIa,theduratIonofadmInIstratIon,andtheanesthetIctIssue
solubIlItIes.AslongasanarterIaltotIssuepartIalpressuregradIentexIsts,thesetIssues
wIllabsorbanesthetIcespecIallyfat,sInceItIsahugepotentIalreservoIrwhose
anesthetIcpartIalpressuresaretypIcallylowafterhoursofanesthesIa.After
dIscontInuatIonofanesthesIa,muscleandfatmaycontInuetoabsorbanesthetIc,even
hourslater.TheredIstrIbutIoncontInuesuntIlblood/alveolaranesthetIcpartIalpressure
fallsbelowtIssuepartIalpressure.ThIsredIstrIbutIoncausestheearlyrateofdeclIneIn
alveolaranesthetIcconcentratIondurIngrecoverytoexceedItsearlyrateofIncrease
durIngInductIon.
8ecause7FCtIssuesarehIghlyperfusedandwashoutofanesthetIcIsmostlyvIa
elImInatIonfromthesetIssuesearlyInrecovery,allanesthetIcs,regardlessofduratIonof
admInIstratIon,haveapproxImatelythesamerateofelImInatIonto50ofF
A0
.
Unfortunately,halvIngtheCNSconcentratIonofanesthetIcIsrarelysuffIcIentforwakIng
thepatIent.|orecommonly,80to90ofInhaledanesthetIcmustbeelImInatedbefore
emergence.Attheseamountsofwashout,themoresolubleanesthetIcsareelImInated
moreslowlythanlesssolubleagents.
Diffusion Hypoxia
0urIngrecoveryfromanesthesIa,washoutofhIghconcentratIonsofnItrousoxIdecanlower
alveolarconcentratIonsofoxygenandcarbondIoxIde,aphenomenoncalleddiffusion
hypoxia.TheresultIngalveolarhypoxIacancausehypoxemIa,andalveolarhypocarbIacan
depressrespIratorydrIve,whIchmayexacerbatehypoxemIa.tIsthereforeapproprIateto
InItIaterecoveryfromnItrousoxIdeanesthesIawIth100oxygenratherthanless
concentratedD
2
/aIrmIxtures.
P.42J
Clinical Overview of Current Inhaled Anesthetics
Isoflurane
sofluraneIsahalogenatedmethylethyletherthatIsaclear,nonflammablelIquIdatroom
temperatureandhasahIghdegreeofpungency.tIsthemostpotentofthevolatIle
anesthetIcsInclInIcaluse,hasgreatphysIcalstabIlIty,andundergoesessentIallyno
deterIoratIondurIngstorageforupto5yearsoronexposuretosunlIght.thasbecomethe
goldstandardanesthetIcsInceItsIntroductIonInthe1970s.TherewasabrIefperIodof
controversyconcernIngtheuseofIsofluraneInpatIentswIthcoronarydIseasebecauseof
thepossIbIlItyforcoronarystealarIsIngfromthepotenteffectsofIsofluraneoncoronary
vasodIlatIon.nclInIcaluse,however,thIshasbeen,atmost,arareoccurrence.
Desflurane
0esfluraneIsafluorInatedmethylethyletherthatdIffersfromIsofluranebyjustoneatom:
afluorIneatomIssubstItutedforachlorIneatomontheethylcomponentofIsoflurane
(FIg.171).TheprocessofcompletefluorInatIonoftheethermoleculehasseveraleffects.
tdecreasesbloodandtIssuesolubIlIty(theblood:gassolubIlItyofdesfluraneequalsthatof
nItrousoxIde),andItresultsInalossofpotency(the|ACofdesfluraneIs5tImeshIgher
thanIsoflurane).|oreover,fluorInatIonofthemethylethermoleculeresultsInahIgh
vaporpressureowIngtodecreasedIntermolecularattractIon.Thus,anewvaporIzer
technologywasdevelopedtodelIveraregulatedconcentratIonofdesfluraneasagas.tIs
aheated,pressurIzedvaporIzerrequIrIngelectrIcalpowerandmorefrequentservIcIng.
DneoftheadvantagesofdesfluraneIsthenearabsentmetabolIsmtoserum
trIfluoroacetate.ThIsmakesImmunemedIatedhepatItIsarareoccurrence.0esfluraneIs
themostpungentofthevolatIleanesthetIcs,andIfadmInIsteredvIathefacemaskresults
IncoughIng,salIvatIon,breathholdIng,andlaryngospasm.nextremelydryCD
2
absorbers,
desflurane(andtoalesserextentIsoflurane,enflurane,andsevoflurane)degradestoform
carbonmonoxIde.0esfluranehasthelowestblood:gassolubIlItyofthepotentvolatIle
anesthetIcs;moreover,ItsfatsolubIlItyIsroughlyhalfofthatoftheothervolatIle
anesthetIcs.Thus,desfluranerequIreslessdownwardtItratIonInlongsurgIcalprocedures
toachIevearapIdemergencebyvIrtueofdecreasedtIssuesaturatIon.0esfluranehasbeen
assocIatedwIthtachycardIa,hypertensIon,and,Inselectcases,myocardIalIschemIawhen
usedInhIghconcentratIonsorrapIdlyIncreasIngtheInspIredconcentratIon(wIthoutusIng
opIoIdadjuvantstopreventsucharesponse).
Sevoflurane
SevofluraneIsasweetsmellIng,completelyfluorInatedmethylIsopropylether(FIg.171).
tsvaporpressureIsroughlyonefourththatofdesfluraneandItcanbeusedIna
conventIonalvaporIzer.Theblood:gassolubIlItyofsevofluraneIssecondonlytodesflurane
IntermsofpotentvolatIleanesthetIcs.SevofluraneIsapproxImatelyhalfaspotentas
Isoflurane,andsomeofthepreservatIonofpotency,despItefluorInatIon,Isbecauseofthe
bulkypropylsIdechaInontheethermolecule.SevofluranehasmInImalodor,nopungency,
andIsapotentbronchodIlator.TheseattrIbutesmakesevofluraneanexcellentcandIdate
foradmInIstratIonvIathefacemaskonInductIonofanesthesIaInbothchIldrenandadults.
SevofluraneIshalfaspotentacoronaryvasodIlatorasIsoflurane,butIs10to20tImes
morevulnerabletometabolIsmthanIsoflurane.ThemetabolIsmofsevofluraneresultsIn
InorganIcfluorIde;theIncreaseInplasmafluorIdeaftersevofluraneadmInIstratIonhasnot
beenassocIatedwIthrenalconcentratIngdefects.UnlIkeotherpotentvolatIleanesthetIcs,
sevofluraneIsnotmetabolIzedtotrIfluoroacetate;rather,ItIsmetabolIzedtoanacyl
halIde(hexafluoroIsopropanol).ThIsdoesnotstImulateformatIonofantIbodIes.
SevofluranecanformcarbonmonoxIdedurIngexposuretodryCD
2
absorbents,andan
exothermIcreactIonIndryabsorbenthasresultedIncanIsterfIres.NewgenerIcversIonsof
sevofluranehavethepotentIaltobreakdowntohydrogenfluorIdewhenexposedtometal
compoundsbecauseoftheIrlackofadequatewaterIntheformulatIon.Sevofluranealso
breaksdownInthepresenceofthecarbondIoxIdeabsorbertoformavInylhalIdecalled
compound A.CompoundAhasbeenshowntobeadosedependentnephrotoxInInrats,but
hasnotbeenassocIatedwIthrenalInjuryInhumanvolunteersorpatIents,wIthorwIthout
renalImpaIrment,evenwhenfreshgasflowsare1L/mInorless.
Xenon
XenonIsanInertgas.0IffIculttoobtaIn,andhenceextremelyexpensIve,IthasreceIved
consIderableInterestInthelastfewyearsbecauseIthasmanycharacterIstIcsapproachIng
thoseofanIdealInhaledanesthetIc,
4,5
althoughItcantrIggermalIgnanthyperthermIa.
tsblood:gaspartItIoncoeffIcIentIs0.14,andunlIketheotherpotentvolatIleanesthetIcs
(exceptmethoxyflurane),xenonprovIdessomedegreeofanalgesIa.The|ACofxenonIn
humansIs71,whIchmIghtprovetobealImItatIon.tIsnonexplosIve,nonpungent,and
odorless,andthuscanbeInhaledwIthease.naddItIon,ItdoesnotproducesIgnIfIcant
myocardIaldepressIon.
4
8ecauseofItsscarcItyandhIghcost,newanesthetIcsystemsneed
tobedevelopedtoprovIdeforrecyclIngofxenon.fthIsprovestobetoodIffIcultfrom
eItheratechnIcalorpatIentsafetystandpoInt,ItmaybenecessarytouseItInaverylow,
orclosed,freshgasflowsystemtoreducewastage.
Nitrous Oxide
NItrousoxIdeIsasweetsmellIng,nonflammablegasoflowpotency(|AC=104)andIs
relatIvelyInsolubleInblood.tIsmostcommonlyadmInIsteredasananesthetIcadjuvant
IncombInatIonwIthopIoIdsorvolatIleanesthetIcsdurIngtheconductofgeneral
anesthesIa.Althoughnotflammable,nItrousoxIdewIllsupportcombustIon.UnlIkethe
potentvolatIleanesthetIcsInclInIcaluse,nItrousoxIdedoesnotproducesIgnIfIcant
skeletalmusclerelaxatIon,butItdoeshavedocumentedanalgesIceffects.0espItealong
trackrecordofuse,controversyhassurroundednItrousoxIdeInfourareas:ItsroleIn
postoperatIvenauseaandvomItIng,ItspotentIaltoxIceffectsoncellfunctIonvIa
InactIvatIonofvItamIn8
12
,ItsadverseeffectsrelatedtoabsorptIonandexpansIonInto
aIrfIlledstructuresandbubbles,andlastly,ItseffectonembryonIcdevelopment.Theone
concernthatseemsmostvalIdandmostclInIcallyrelevantIstheabIlItyofnItrousoxIdeto
expandaIrfIlledspacesbecauseofItsgreatersolubIlItyInbloodcomparedtonItrogen.
Severalclosedgasspaces,suchasthebowelandmIddleear,exIstInthebodyandother
spacesmayoccurasaresultofdIseaseorsurgery,suchasapneumothorax.8ecause
nItrogenInaIrfIlledspacescannotberemovedreadIlyvIathebloodstream,nItrousoxIde
delIveredtoapatIentdIffusesfrom
P.424
thebloodIntotheseclosedgasspacesquIteeasIly.|ovementofnItrousoxIdeIntothese
spacescontInuesuntIlthepartIalpressureequalsthatofthebloodandalveolI.ComplIant
spaceswIllcontInuetoexpanduntIlsuffIcIentpressureIsgeneratedtoopposefurther
nItrousoxIdeflowIntothespace.ThehIghertheInspIredconcentratIonofnItrousoxIde,
thehIgherthepartIalpressurerequIredforequIlIbratIon.
SeventyfIvepercentnItrousoxIdecanexpandapneumothoraxtodoubleortrIpleItssIze
In10andJ0mInutes,respectIvely.AIrfIlledcuffsofpulmonaryarterycathetersand
endotrachealtubesalsoexpandwIththeuseofnItrousoxIde,possIblycausIngtIssue
damagevIaIncreasedpressureInthepulmonaryarteryortrachea,respectIvely.
6,7
na
rabbItmodel,thevolumeofanaIrembolusresultIngIncardIovascularcompromIseIsless
durIngcoadmInIstratIonofnItrousoxIde.
8
AccumulatIonofnItrousoxIdeInthemIddleear
candImInIshhearIngpostoperatIvely
9
andIsrelatIvelycontraIndIcatedfortympanoplasty
becausetheIncreasedpressurecandIslodgeatympanIcgraft.
Neuropharmacology of Inhaled Anesthetics
Minimum Alveolar Concentration
ThepharmacodynamIceffectsofInhaledanesthetIcsmustbebasedonadose,andthIs
doseIstheminimum alveolar concentrationor|AC.|ACIsthealveolarconcentratIonof
ananesthetIcatoneatmospherethatpreventsmovementInresponsetoasurgIcal
stImulusIn50ofpatIents.tIsanalogoustotheE0
50
expressedforIntravenousdrugs.A
varIetyofsurgIcalstImulIhavebeenusedtoestablIshthe|ACforeachInhaledanesthetIc,
buttheclassIc,defInIng,noxIousstImulusIsIncIsIonoftheabdomen.LIkewIse,skeletal
musclemovementIsthedefInIngpatIentresponse,butotherresponseshavebeenusedto
establIsh|ACaswell.ExperImentallydetermIned|ACvaluesforhumansfortheInhaled
anesthetIcsareshownInTable171.
The95confIdencerangesfor|ACareapproxImately25ofthelIsted|ACvalues.
|anufacturer'srecommendatIonsandclInIcalexperIenceestablIsh1.2to1.JtImes|ACas
adosethatconsIstentlypreventspatIentmovementdurIngsurgIcalstImulI.Lossof
conscIousnesstypIcallyprecedestheabsenceofstImulusInducedmovementbyawIde
margIn.Although1.2to1.J|ACvaluesdonotabsolutelyensurethedefInIngcrIterIafor
braInanesthesIa(theabsenceofselfawarenessandrecall),vastclInIcalexperIence
suggestsItIsextremelyunlIkelyforapatIenttobeawareof,ortorecall,thesurgIcal
IncIsIonattheseanesthetIcconcentratIonsunlessothercondItIonsexIstsuchthat|ACIs
IncreasedInthatpatIent(Table174).
ConcentratIonsofInhaledanesthetIcsthatprovIdelossofselfawarenessandrecallare
about0.4to0.5|AC.SeverallInesofreasonIngleadtothIsconclusIon.FIrst,mostpatIents
receIvIngonly50nItrousoxIde(approxImately0.4to0.5|AC)asInatypIcaldentIst's
offIcewIllhavenorecalloftheIrproceduredurIngN
2
DadmInIstratIon.Second,varIous
studIeshaveshownthatashIftInelectroencephalogram(EEC)domInancetotheanterIor
leads,thatIs,theshIftfromselfawaretononselfaware,accompanIeslossof
conscIousness,andInprImates,theEECshIftandlossofconscIousnessoccurat0.5|AC.
10
ThIrd,Indogs,lossofconscIousnessaccompanIesasuddennonlInearfallIncerebral
metabolIcrate(C|F)atapproxImately0.5|AC(FIg.1710).
Table 17-4 Factors that Increase Minimum Alveolar Concentration
ncreasedcentralneurotransmItterlevels(monoamIneoxIdaseInhIbItors,acute
dextroamphetamIneadmInIstratIon,cocaIne,ephedrIne,levodopa)
HyperthermIa
ChronIcethanolabuse(determInedInhumans)
HypernatremIa
Figure 17-10.TheeffectsofhalothaneoncerebralmetabolIcrateofoxygen
consumptIon(C|FD
2
)asapercentageofcontrol(awake).C|FD
2
Isplottedversus
endtIdalIsofluraneconcentratIon.FegressIonlInesforchangesInC|FD
2
aredrawn
foreachelectroencephalogramdetermInedarea.ThepatterndepIctedhereIs
characterIstIcofalloftheanesthetIcsexamIned(enflurane,halothane,and
Isoflurane).|AC,mInImumalveolarconcentratIon.(AdaptedfromStullkenEHJr,
|IldeJH,|IchenfelderJ0,etal:ThenonlInearresponsesofcerebralmetabolIsmto
lowconcentratIonsofhalothane,enflurane,IsofluraneandthIopental.AnesthesIology
1977;46:28.)
|ACvaluescanbeestablIshedforanymeasurableresponse.|ACawake,orthealveolar
concentratIonofanesthetIcatwhIchapatIentopenshIsorhereyestocommand,varIes
from0.15to0.5|AC.
11
nterestIngly,transItIonfromawaketounconscIousandback
typIcallyshowssomehysteresIsInthatItquIteconsIstentlytakes0.4to0.5|ACtolose
conscIousness,butlessthanthat(aslowas0.15|AC)toregaInconscIousness.ThIsmaybe
becauseofthespeedofalveolarwashInversuswashout.
12
|AC8AF,orthealveolar
concentratIonofanesthetIcthatbluntsadrenergIcresponsestonoxIousstImulI,has
lIkewIsebeenestablIshedandIsapproxImately50hIgherthanstandard|AC.
1J
|ACalso
hasbeenestablIshedfordIscreetlevelsofEECactIvIty,suchasonsetofburstsuppressIon
orIsoelectrIcIty.
Standard|ACvaluesareroughlyaddItIve.AdmInIsterIng0.5|ACofapotentagentand0.5
|ACofnItrousoxIdeIsequIvalentto1|ACofpotentagentIntermsofpreventIngpatient
movement,althoughthIsdoesnotholdovertheentIrerangeofN
2
Ddoses.|ACeffectsfor
otherresponseparametersarenotnecessarIlyaddItIve.8ecause|ACmovementprobably
dIffersfrom|ACforvarIoussecondarysIdeeffects(suchhypothetIcalsItuatIonsas|AC
dysrhythmIa,|AChypotensIon,or|ACtachycardIa),combInatIonsofapotentagent
andnItrousoxIdemaydecreaseorIncreasethesesecondaryeffectsrelatIvetopotent
agentalone.Forexample,combInIng0.6|ACofnItrousoxIdewIth0.6|ACofIsoflurane
produceslesshypotensIonthan1.2|ACofIsofluranealonebecauseIsofluraneIsamore
potentvasodIlatorandmyocardIaldepressantatequIvalent|ACthanN
2
D.
P.425
Table 17-5 Factors that Decrease Minimum Alveolar Concentration
ncreasIngage
|etabolIcacIdosIs
HypoxIa(PaD
2
,J8mmHg)
nducedhypotensIon(meanarterIalpressure50mmHg)
0ecreasedcentralneurotransmItterlevels(methyldopa,reserpIne,chronIc
dextroamphetamIneadmInIstratIon,levodopa)
2
AgonIsts
HypothermIa
HyponatremIa
LIthIum
HypoosmolalIty
Pregnancy
AcuteethanoladmInIstratIon
a
KetamIne
PancuronIum
a
PhysostIgmIne(10tImesclInIcaldoses)
NeostIgmIne(10tImesclInIcaldoses)
LIdocaIne
DpIoIds
DpIoIdagonIstantagonIstanalgesIcs
8arbIturates
a
ChlorpromazIne
a
0Iazepam
a
HydroxyzIne
a
9TetrahydrocannabInol
7erapamIl
AnemIa(4.JmLD
2
/dLblood)
a
0etermInedInhumans.
7arIousfactorsIncrease(Table174)ordecrease(Table175)|AC.Unfortunately,nosIngle
mechanIsmexplaInsthesealteratIonsIn|AC,supportIngthevIewthatanesthesIaIsthe
netresultofnumerousandwIdelyvaryIngphysIologIcalteratIons.ngeneral,thosefactors
thatIncreaseCNSmetabolIcactIvItyandneurotransmIssIon,IncreaseCNSneurotransmItter
levels,andupregulateofCNSresponsestochronIcallydepressedneurotransmItterlevels
(asInchronIcalcoholIsm)alsoseemtoIncrease|AC.Conversely,thosefactorsthat
decreaseCNSmetabolIcactIvIty,neurotransmIssIon,andCNSneurotransmItterlevels,and
downregulateCNSresponsestochronIcallyelevatedneurotransmItterlevelsseemto
decrease|AC.|anynotablefactorsdonotalter|AC,IncludIngduratIonofInhaled
anesthetIcadmInIstratIon,gender,typeofsurgIcalstImulatIon,thyroIdfunctIon,hypoor
hypercarbIa,metabolIcalkalosIs,hyperkalemIa,andmagnesIumlevels.However,there
maybeagenetIccomponentInfluencIng|AC.FedhaIredfemaleshavea19IncreaseIn
|ACcomparedwIthdarkhaIredfemales.
14
ThesedatasuggestInvolvementofmutatIonsof
theMCIRallele.7arIantsoftheMCIRallelealsohavebeenImplIcatedInalterInganalgesIc
responsestoaopIoId.
15
|ACalsocanvaryInrelatIonshIptogenotypeandchromosomal
substItutIonsasshownInrats.
16
The Effect of Age on MAC
The|ACforeachofthepotentanesthetIcgasesshowsaclear,agerelatedchange(FIg.
1711).|ACdecreaseswIthageandtherearesImIlarItIesbetweenagentsInthedeclIneIn
|ACandage.ExcludIngdataInpatIents1yearofage(where|ACcanbelower
17
),there
IsalInearmodelthatdescrIbesachangeIn|ACofapproxImately6perdecade,a22
decreaseIn|ACfromage40toage80,anda27decreaseIn|ACfromage1to40
years.
18
Figure 17-11.EffectofageonmInImumalveolarconcentratIon(|AC)Isplotted.
FegressIonlInesarefIttedtopublIshedvaluesfromseparatestudIes.0ataarefrom
patIentsages1to80years.(Adaptedfrom|aplesonWW:Effectofageon|ACIn
humans:ametaanalysIs.8rJAnaesth1996;76:179.)
Other Alterations in Neurophysiology
Thethreecurrent,wIdelyused,potentagentsIsoflurane,desflurane,andsevofluraneall
havereasonablysImIlareffectsonawIderangeofparametersIncludIngcerebralmetabolIc
rate,theEEC,cerebralbloodflow(C8F),andflowmetabolIsmcouplIng.Therearenotable
dIfferencesIneffectsonCP,cerebrospInalfluId(CSF)productIonandresorptIon,CD
2
vasoreactIvIty,C8FautoregulatIon,andcerebralprotectIon.NItrousoxIdedepartsfrom
thepotentagentsInseveralImportantrespects,andIsthereforedIscussedseparately.
Cerebral Metabolic Rate and Electroencephalogram
AllofthepotentagentsdepressC|FtovaryIngdegreesInanonlInearfashIon.Dnce
spontaneouscortIcalneuronalactIvItyIsabsent(anIsoelectrIcEEC),nofurtherdecreases
InC|Faregenerated.
sofluranecausesalarger|ACdependentdepressIonofC|Fthanhalothane.8ecauseof
thIsgreaterdepressIonInneuronalactIvIty,IsofluraneabolIshesEECactIvItyatdosesused
clInIcallyandcanusuallybetoleratedfromahemodynamIcstandpoInt.
19
0esfluraneand
sevofluranebothcausedecreasesInC|FsImIlartoIsoflurane.
20,21
nterestIngly,whIleboth
desfluraneandsevofluranedepresstheEECandabolIshactIvItyatclInIcallytolerated
dosesofapproxImately2|AC,
20,21
IndogsdesfluraneInducedIsoelectrIcEECrevertsto
contInuousactIvItywIthtImedespIteanunchangIng|AC,apropertyunIqueto
desflurane.
21
AtnormalCD
2
andbloodpressure,noevIdenceofsevofluranecerebraltoxIcItyexIsts.
22
WIthextremehyperventIlatIontodecreasecerebralbloodflowbyhalf,braInlactatelevels
Increase,butsIgnIfIcantlylessthanwIthhalothane.ThereareconflIctIngdataasto
whethersevofluranehasaproconvulsanteffect.
20,2J
HIgh,longlastIngconcentratIonsof
sevoflurane(1.5to2.0|AC),asuddenIncreaseIncerebralsevoflurane
P.426
concentratIons,andhypocapnIacantrIggerEECabnormalItIesthatoftenareassocIated
wIthIncreasesInheartrateInbothadultsandchIldren.
24,25
ThIshasraIsedthequestIonas
totheapproprIatenessofsevofluraneInpatIentswIthepIlepsy.
26
Figure 17-12.Cerebralbloodflow(andvelocIty)measuredInthepresenceof
normocapnIaandIntheabsenceofsurgIcalstImulatIonInvolunteersreceIvIng
halothaneorIsoflurane.AtlIghtlevelsofanesthesIa,halothane(butnotIsoflurane)
Increasedcerebralbloodflow.At1.6mInImumalveolarconcentratIon(|AC),
IsofluranealsoIncreasedcerebralbloodflow.(AdaptedfromEgerE:soflurane
(Forane):AcompendIumandreference.|adIson,DhIo|edIcalProducts,1985.)
CerebralbloodflowvelocItymeasuredbeforeanddurIngsevofluraneanddesflurane
anesthesIaupto1.5|ACshowednochangeIncerebralbloodflowandvelocIty.
(Adaptedfrom8edforthN|,HardmanJC,Nathanson|H:CerebralhemodynamIc
responsetotheIntroductIonofdesflurane:AcomparIsonwIthsevoflurane.Anesth
Analg2000;91:152.)
Cerebral Blood Flow, FlowMetabolism Coupling, and
Autoregulation
AllofthepotentagentsIncreaseC8FInadosedependentmanner.soflurane,sevoflurane,
anddesfluranecausefarlesscerebralvasodIlatIonper|ACmultIplethanhalothane(FIg.
1712).nhumanstudIes,IsofluraneproducesInsIgnIfIcantornochangesInC8F.
27
0esfluraneandsevofluranebothInfluenceC8FInafashIonsImIlartoIsoflurane.
20,21
Allof
theseInhaledanesthetIcagentsaffectC8FInatImedependentaswellasdosedependent
manner.nanImals,anInItIaldosedependentIncreaseInC8FwIthhalothaneand
IsofluraneadmInIstratIonrecoverstopreInductIonlevelsapproxImately2to5hoursafter
InductIon.ThemechanIsmofthIsrecoveryIsunclear.
TheIncreaseInC8FwIthIncreasIngdosecausedbythepotentagentsoccursdespIte
decreasesInC|F.ThIsphenomenonhasbeencalleduncoupling,butfromamechanIstIc
standpoInt,trueuncouplIngofflowfrommetabolIsmmaynotoccur.ThatIs,asC|FIs
depressedbythevolatIleanesthetIcs,therestIllIsacoupleddeclIneInC8Fopposedbya
coIncIdentdIrectvasodIlatoryeffectonthecerebralbloodvessels.Theneteffectonthe
cerebralvesselsdependsonthesumofIndIrectvasoconstrIctInganddIrectvasodIlatIng
Influences.
AutoregulatIonIstheIntrInsIcmyogenIcregulatIonofvasculartone.nnormalbraIn,the
mechanIsmsofautoregulatIonofC8FoverarangeofmeanarterIalpressuresfrom50to
150mmHgareIncompletelyunderstood.8ecausethevolatIleanesthetIcsaredIrect
vasodIlators,allareconsIderedtodImInIshautoregulatIonInadosedependentfashIon
suchthatathIghanesthetIcdosesC8FIsessentIallypressurepassIve.Sevoflurane
preservesautoregulatIonuptoapproxImately1|AC.
20
At1.5|AC,thedynamIcrateof
autoregulatIon(changeInmIddlecerebralarterybloodflowafterarapIdtransIent
decreaseInbloodpressure)IsbetterpreservedwIthsevofluranethanIsoflurane(FIg.17
1J).ThIsmaybearesultoflessofadIrectvasodIlatoreffectofsevoflurane,preservIngthe
abIlItyofthevesseltorespondtochangesInbloodpressureat1.5|AC.8asedonasImIlar
modelbutaseparatestudyofdynamIcautoregulatIonofcerebralbloodflow,0.5|AC
desfluranereducedautoregulatIonandIsofluranedIdnot.At1.5|AC,bothanesthetIcs
substantIallyreducedautoregulatIon(FIg.171J).
Figure 17-13.0ynamIcrateofautoregulatIon(thechangeInmIddlecerebralartery
bloodflowafterarapIdtransIentdecreaseInbloodpressure)durIngawake(or
fentanylandN
2
DbaselIne),0.5,and1.5mInImumalveolaranesthetIcconcentratIon
(|AC)anesthesIa.7aluesaremeanSE(S0forsevoflurane).*P0.05versusbaselIne,
**P0.001versusbaselIneandsevoflurane.(AdaptedfromSummorsAC,CuptaAK,
|atta8F:0ynamIccerebralautoregulatIondurIngsevofluraneanesthesIa:A
comparIsonwIthIsoflurane.AnesthAnalg1999;88:J41J45;andStrebelS,LamA,
|atta8,etal:0ynamIcandstatIccerebralautoregulatIondurIngIsoflurane,
desflurane,andpropofolanesthesIa.AnesthesIology1995;8J:6676.)
Intracerebral Pressure
ProbablytheareaofgreatestclInIcalInteresttotheanesthesIologIstIstheeffectof
volatIleanesthesIaonIntracerebralpressure(CP).ngeneral,CPwIllIncreaseordecrease
InproportIontochangesInC8F.sofluraneIncreasesCPmInImallyInanImalsbothwIth
andwIthoutbraInpathology,IncludIngthosewIthanalreadyelevatedCP.
28
nhuman
studIesthereusuallyaremIldIncreasesInCPwIthIsofluraneadmInIstratIonthatare
blockedorbluntedbyhyperventIlatIonorbarbIturatecoadmInIstratIon.
29
Therearesome
contradIctorydata,however.nonehumanstudy,hypocapnIadIdnotpreventelevatIons
InCPwIthIsofluraneadmInIstratIonInpatIentswIthspaceoccupyIngbraInlesIons.
J0
However,IsofluraneInducedIncreasesInCPtendtobeofshortduratIon,Inonestudyonly
J0mInutes.
J1
LIkeIsoflurane,bothsevofluraneanddesflurane1|ACproducemIldIncreasesInCP,
parallelIngtheIrmIldIncreasesInC8F.
20,21,J2,JJ
DnepotentIaladvantageofsevofluraneIs
thatItslowerpungencyandaIrwayIrrItatIonmaylessentherIskofcoughIngandbuckIng
andtheassocIatedrIseInCPascomparedwIthdesfluraneorIsoflurane.nfact,
IntroductIonofdesfluraneafterpropofolInductIonofanesthesIahasledtosIgnIfIcant
IncreasesInheartrate,meanarterIalpressure,andmIddlecerebralarterybloodflow
velocItythatwerenotnotedInpatIentsgIvensevoflurane.
J4
ThIsmayrelatetotheaIrway
IrrItanteffectsofdesfluraneratherthanaspecIfIcalteratIonIn
P.427
neurophysIology.However,severalstudIesInbothchIldrenandadultssuggestthat
IncreasesInCPfromdesfluraneareslIghtlygreaterthanfromeItherIsofluraneor
sevoflurane.
J5,J6
ThebottomlIneIsthatallthreepotentagentsmaybeusedat
approprIatedoses,especIallywIthadjunctIveandcompensatorytherapIes,Injustabout
anyneurosurgIcalprocedure.
Cerebrospinal Fluid Production and Resorption
sofluranedoesnotappeartoalterCSFproductIon,
J1
butmayIncrease,decrease,orleave
unchangedtheresIstancetoresorptIondependIngondose.Sevofluraneat1|ACdepresses
CSFproductIonupto40.
J7
0esfluraneat1|ACleavesCSFproductIonunchangedor
Increased.
J5,J8
ngeneral,anesthetIceffectsonCPvIachangesInCSFdynamIcsare
clInIcallyfarlessImportantthananesthetIceffectsonC8F.
Cerebral Blood Flow Response to Hypercarbia and Hypocarbia
SIgnIfIcanthypercapnIaIsassocIatedwIthdramatIcIncreasesInC8Fwhetherornot
volatIleanesthetIcsareadmInIstered.AsdIscussedearlIer,hypocapnIacanbluntorabolIsh
volatIleanesthetIcInducedIncreasesInC8FdependIngonwhenthehypocapnIaIs
produced.ThIsvasoreactIvItytoCD
2
maybesomewhatalteredbythevolatIleanesthetIcs
ascomparedwIthnormal.CD
2
vasoreactIvItyunderdesfluraneanesthesIaIsnormalupto
1.5|AC,
28
andCD
2
vasoreactIvItyforsevofluraneIspreservedat1|AC.
J9
Cerebral Protection
nonestudy,cerebralhypoperfusIonsecondarytohypotensIonfromIsofluranewas
assocIatedwIthbettertIssueoxygencontentthandurInghypotensIonbyothermeans,
consIstentwIththeprofounddecreaseIncerebralmetabolIcrateofoxygenconsumptIon
(C|FD
2
)seenwIthIsoflurane.
40
8othsevofluraneanddesfluranehavebeenshownto
ImproveneurologIcoutcomeIncomparIsontoN
2
DfentanylafterIncompletecerebral
IschemIaInaratmodel.
41,42
npIgletsundergoInglowflowcardIopulmonarybypass,
desfluraneImprovedneurologIcoutcomecomparedwIthafentanyl/droperIdolbased
anesthetIc.
4J
nhumans,desfluranehasbeenshowntoIncreasebraIntIssuePD
2
durIng
admInIstratIon,andtomaIntaInPD
2
toagreaterextentthanthIopentaldurIngtemporary
cerebralarteryocclusIondurIngcerebrovascularsurgery.
44
HumanneuroprotectIon
outcomestudIesforsevofluraneanddesfluranehavenotbeenpublIshed.
Processed Electroencephalograms and Neuromonitoring
AllofthevolatIleanesthetIcsproducedosedependenteffectsontheEEC,sensoryevoked
potentIals(SEPs)andmotorevokedpotentIals(|EPs).EECsrecordedonthescalpcanbe
processedtoquantIfytheamountofactIvItyIneachoffourfrequencybands:delta(0toJ
Hz),theta(4to7Hz),alpha(8to1JHz),andbeta(1JHz).Allthreecurrentlyusedagents
at1|ACandN
2
DatJ0to70canproduceshIftstoIncreasIngfrequencIes.8etween1and
2|ACthepotentagentsproduceshIftstodecreasIngfrequencIesandIncreasesIn
amplItude.At2|AC,allofthepotentagentscanproduceburstsuppressIonorelectrIcal
sIlence.TheseareImportantfactorstorememberbecauseEECchangesdurIng
admInIstratIonofgeneralanesthesIacanalsobecausedbyhypoxIa,hypercarbIa,and
hypothermIa.TheEECmustalwaysbeInterpretedwIthIntheapproprIateclInIcalcontext.
AllofthevolatIleagentscauseadosedependentIncreaseInlatencyanddecreaseIn
amplItudeInallcortIcalSEPmodalItIes.nsubcortIcalmodalItIes,suchasbraInstem
audItoryevokedpotentIals,theseagentsareassocIatedwIthneglIgIbleeffects.ngeneral,
vIsualevokedpotentIalsaresomewhatmoresensItIvetotheeffectsofthevolatIle
anesthetIcsthansomatosensoryevokedpotentIals.LIkeEECs,theseeffectsfrom
anesthetIcsmustbekeptInmIndwhenchangesdurIngSEPsoccur,andapproprIatedosesof
thevolatIleagentsmustbeused.SuddenchangesIntheanesthetIcregImen(0.5|AC)also
seemtohavegreatereffectsonSEPsthanmoregradualchanges.
|EPsevaluatethefunctIonalIntegrItyofdescendIngmotorpathways.Theevokedresponse
IsmostcommonlyrecordedasamusclepotentIaloraperIpheralnervesIgnal.ThetrIgger
IstypIcallytransosseousactIvatIonvIaelectrIcalormagnetIcstImulatIon.|EPsare
exquIsItelysensItIvetodepressIonbyvolatIleanesthetIcs,whIchareusuallyavoIdedIn
thesecases.
Nitrous Oxide
TheeffectsofnItrousoxIdeoncerebralphysIologyarenotclear.8oththe|ACforN
2
Dand
ItseffectsonC|FvarywIdelydependIngonspecIes.ThedIfferenceInC|FeffectsmayIn
partbeaccountedforbydIfferencesIn|AC,but|ACequIvalenteffectsonC|Falso
dIffer.SeveralstudIesIndogs,goats,andswInefoundthatN
2
DIncreasesC|FD
2
andC8F,
whIleInrodentsnosuchIncreasesoronlyslIghtIncreasesoccur.nhumanstudIes,N
2
D
admInIstratIonpreservedC8FbutdecreasedC|FD
2
.
19
AnotherproblemIsthefactthatN
2
DIsacoanesthetIcusedtosupplementpotentagents,
notacompleteanesthetIcInItself,andC|FeffectsmaydIfferdependIngonpresenceor
absenceofpotentagentaswellasthepartIcularagentanddose.AddItIonofN
2
Dto1or
2.2|ACIsofluranedoesnotalterC|FD
2
,butItdoesIncreaseC8Fat1|ACbutnot2.2
|AC.
8arbIturates,narcotIcs,oracombInatIonofthetwoappeartodecreaseorelImInatethe
IncreasesInC|FandC8FproducedbyN
2
D.TheeffectofpentobarbItal/N
2
DIsdose
dependent,wIthpreservedIncreasesInC|FbyN
2
DatlowdosepentobarbItal,andno
changesInC|FathIghdosepentobarbItal.
45
N
2
DandbenzodIazepInecoadmInIstratIonIs
partIcularlyconfusIng.|Idazolam/N
2
DIndogsIncreasedC8FbutdIdnotalterC|FD
2
,
46
whIletheopposItewastrueInrats,
47
andbothC8FandC|FD
2
declInedInratsgIven
dIazepam/N
2
D.N
2
DadmInIstratIonIncreasesCP,butasIsthecaseforC|FandC8F,
changesInCParedecreasedorelImInatedbyavarIetyofcoanesthetIcsand,more
Importantly,byhypocapnIa.
N
2
DappearstohaveanantIneuroprotectIveeffect,asaddItIonofN
2
DtoIsofluranedurIng
temporaryIschemIaIsassocIatedwIthgreatertIssuedamageandworsenedneurologIc
outcome.
47
nastudyInmIce,survIvaltImeafterahypoxIceventwasdecreasedby
addItIonofN
2
D.
48
CIventheconflIctIngdataontheeffectsofN
2
DonC|F,C8F,CP,and
theapparentantIneuroprotectIveeffectofthIsagent,avoIdanceordIscontInuatIonofIts
useshouldbeconsIderedInsurgIcalcaseswIthahIghlIkelIhoodofelevatedCPor
sIgnIfIcantcerebralIschemIa.
The Circulatory System
Hemodynamics
ThecardIac,vascular,andautonomIceffectsofthevolatIleanesthetIcshavebeen
carefullydefInedthroughanumberofstudIescarrIedoutInhumanvolunteersnot
undergoIngsurgery.
49,50,51,52,5J,54
ngeneral,theInformatIonfromthesevolunteer
P.428
studIeshastranslatedwelltothepatIentpopulatIoncommonlyexposedtothese
anesthetIcsdurIngelectIveandemergentsurgerIes.
Figure 17-14.Heartrateandbloodpressurechanges(fromawakebaselIne)In
volunteersreceIvInggeneralanesthesIawIthhalothane(H),enflurane(E),Isoflurane
(),desflurane(0),orsevoflurane(S).HalothaneandsevofluraneproducedlIttleorno
changeInheartrateat1.5mInImumalveolarconcentratIon.AllanesthetIcscaused
sImIlardecreasesInbloodpressure.(Adaptedfrom|alanTPJr,0INardoJA,snerFJ,
etal:CardIovasculareffectsofsevofluranecomparedwIththoseofIsofluraneIn
volunteers.AnesthesIology1995;8J:918;WeIskopfF8,Cahalan|K,EgerE,etal:
CardIovascularactIonsofdesfluraneInnormocarbIcvolunteers.AnesthAnalg1991;7J:
14J;andCalverleyFK,SmIthNT,PrysFobertsC,etal:CardIovasculareffectsof
enfluraneanesthesIadurIngcontrolledventIlatIonInman.AnesthAnalg1978;57:619.)
AcommoneffectofthepotentvolatIleanesthetIcshasbeenadoserelateddecreaseIn
arterIalbloodpressure,wIthessentIallynodIfferencesnotedbetweenthevolatIle
anesthetIcsatsteadystate,equIanesthetIcconcentratIons(FIg.1714).TheIrprImary
mechanIsmtodecreasebloodpressurewIthIncreasIngdoseIsrelatedtotheIrpotent
effectstolowerregIonalandsystemIcvascularresIstance(FIg.1715).
nvolunteers,sevofluraneuptoabout1|ACresultsInmInImal,Ifany,changesInsteady
stateheartratewhIleenflurane,Isoflurane,anddesfluraneIncreaseIt5to10from
baselIne(FIg.1714).8othdesfluraneand,toalesserextent,Isofluranehavebeen
assocIatedwIthtransIentandsIgnIfIcantIncreasesInheartratedurIngrapIdIncreasesIn
theInspIredconcentratIonofeItheranesthetIc.
55,56
ThemechanIsm(s)underlyIngthese
transIentheartratesurgesIslIkelyduetotherelatIvepungencyoftheseanesthetIcs,
whIchstImulatesaIrwayreceptorstoelIcItareflextachycardIa.
57
ThetachycardIacanbe
lessenedwIthfentanyl,alfentanIl,orclonIdInepretreatment.
58,59,60
Figure 17-15.CardIacIndex,centralvenouspressure(orrIghtatrIalpressure),and
systemIcvascularresIstancechanges(fromawakebaselIne)InvolunteersreceIvIng
generalanesthesIawIthhalothane(H),enflurane(E),Isoflurane(),desflurane(0),or
sevoflurane(S).ncreasesIncentralvenouspressurefromhalothaneanddesflurane
mIghtbeduetodIfferentmechanIsms.WIthhalothane,theIncreasemIghtbedueto
myocardIaldepressIon,whereaswIthdesflurane,theIncreaseIsmorelIkelydueto
venoconstrIctIon.(Adaptedfrom|alanTPJr,0INardoJA,snerFJ,etal:
CardIovasculareffectsofsevofluranecomparedwIththoseofIsofluraneInvolunteers.
AnesthesIology1995;8J:918;WeIskopfF8,Cahalan|K,EgerE,etal:CardIovascular
actIonsofdesfluraneInnormocarbIcvolunteers.AnesthAnalg1991;7J:14J;and
CalverleyFK,SmIthNT,PrysFobertsC,etal:CardIovasculareffectsofenflurane
anesthesIadurIngcontrolledventIlatIonInman.AnesthAnalg1978;57:619.)
Myocardial Contractility
|yocardIalcontractIlItyIndIceshavebeendIrectlyevaluatedInanImalsandIndIrectly
evaluatedInhumansdurIngtheadmInIstratIonofeachofthevolatIleanesthetIcs.Human
studIeswIthIsoflurane,sevoflurane,anddesfluranehavenotdemonstratedsIgnIfIcant
changesInechocardIographIcdetermInedIndIcesofmyocardIalfunctIon,IncludIngthe
morenoteworthymeasurementofthevelocItyofcIrcumferentIalfIbershortenIng(FIg.17
16).|oreprecIseIndIcesofmyocardIalcontractIlItyhavebeenobtaInedforsevoflurane,
Isoflurane,anddesfluraneInchronIcallyInstrumenteddogs
P.429
afterautonomIcdenervatIonoftheheart.soflurane,desflurane,andsevofluraneresulted
InadosedependentdepressIonofmyocardIalfunctIonwIthnodIfferencesbetweenthe
threeanesthetIcs(FIg.1717).
Figure 17-16.NonInvasIveassessmentofmyocardIalcontractIlItywIth
echocardIographydurInganesthesIaInvolunteers.Sevoflurane,desflurane,and
IsofluranedIdnotcausechangessuggestIveofmyocardIaldepressIon.(Adaptedfrom
|alanTPJr,0INardoJA,snerFJ,etal:CardIovasculareffectsofsevoflurane
comparedwIththoseofIsofluraneInvolunteers.AnesthesIology1995;8J:918;
WeIskopfF8,Cahalan|K,EgerE,etal:CardIovascularactIonsofdesfluraneIn
normocarbIcvolunteers.AnesthAnalg1991;7J:14J;andCalverleyFK,SmIthNT,Prys
FobertsC,etal:CardIovasculareffectsofenfluraneanesthesIadurIngcontrolled
ventIlatIonInman.AnesthAnalg1978;57:619.)
Other Circulatory Effects
|ostofthevolatIleanesthetIcshavebeenstudIeddurIngbothcontrolledandspontaneous
ventIlatIon.
51,61,62
TheprocessofspontaneousventIlatIonreducesthehIghIntrathoracIc
pressuresfromposItIvepressureventIlatIon.ThenegatIveIntrathoracIcpressuredurIng
theInspIratoryphaseofspontaneousventIlatIonaugmentsvenousreturnandcardIacfIllIng
andImprovescardIacoutputand,hence,bloodpressure.SpontaneousventIlatIonIs
assocIatedwIthhIgherPaCD
2
,causIngcerebralandsystemIcvascularrelaxatIon.ThIs
contrIbutestoanImprovedcardIacoutputvIaafterloadreductIon.Thus,spontaneous
ventIlatIondecreasessystemIcvascularresIstanceandIncreasesheartrate,cardIac
output,andstrokevolumeascontrastedtoposItIvepressureventIlatIon.thasbeen
suggestedthatspontaneousventIlatIonmIghtImprovethesafetyofInhaledanesthetIc
admInIstratIonbecausetheconcentratIonofavolatIleanesthetIcthatproduces
cardIovascularcollapseexceedstheconcentratIonthatresultsInapnea.
6J
AcurIousobservatIonwIththepotentvolatIleanesthetIcshasbeenanalteratIonInthe
cardIovasculareffectsdurIngprolongedanesthetIcexposures,notedasasmallIncreaseIn
heartrateandcardIacIndex,agradualdecreaseInsystemIcvascularresIstance,andno
changeInmyocardIalIndIces.
51,52
ThemechanIsm(s)ofthIseffectarenotclear.
NItrousoxIdeIscommonlycombInedwIthpotentvolatIleanesthetIcstomaIntaIngeneral
anesthesIa.NItrousoxIdehasunIquecardIovascularactIons.tIncreasessympathetIc
nervoussystemactIvItyandvascularresIstancewhengIvenIna40concentratIon.
49,64
WhennItrousoxIdeIscombInedwIthvolatIleanesthetIcsandcomparedwIthequIpotent
concentratIonsofthevolatIleanesthetIcwIthoutnItrousoxIde,thereIsanIncreased
systemIcvascularresIstanceandanImprovedarterIalpressurewIthlIttleeffectoncardIac
output.
51,65
TheseeffectsmIghtnotbeduesolelytosympathetIcactIvatIonfromnItrous
oxIdeperse,butmaybepartIallyattrIbutedtoadecreaseIntheconcentratIonofthe
coadmInIsteredpotentvolatIleanesthetIcrequIredtoachIevea|ACequIvalentwhen
usIngnItrousoxIde.
DxygenconsumptIonIsdecreasedapproxImately10to15durInggeneralanesthesIa.
66
The
dIstrIbutIonofcardIacoutputalsoIsalteredbyanesthesIa.8loodflowtolIver,kIdneys,
andgutIsdecreased,partIcularlyatdeeplevelsofanesthesIa.ncontrast,bloodflowto
thebraIn,muscle,andskInIsIncreasedornotchangeddurInggeneralanesthesIa.
67
n
humans,IncreasesInmusclebloodflowarenotedwIthIsoflurane,desflurane,and
sevofluranewIthverysmalldIfferencesbetweenanesthetIcsatequIpotent
concentratIons.
68
soflurane,sevoflurane,anddesfluranedonotpredIsposepatIentstoventrIcular
arrhythmIas,norsensItIzethehearttothearrhythmogenIceffectsofepInephrIne(FIg.17
18).SomeofthedIfferencesbetweenvolatIleanesthetIcsIntheIrabIlItytopromoteother
arrhythmIascanbeattrIbutedtotheIrdIrecteffectsoncardIacpacemakercellsand
conductIonpathways.
69
SInoatrIalnodedIschargerateIsslowedbythevolatIle
anesthetIcs
70
andconductIonIntheHIsPurkInjesystemand
P.4J0
conductIonpathwaysIntheventrIclealsoIsprolongedbythevolatIleanesthetIcs.
69
Figure 17-17.|yocardIalcontractIlItyIndIcesfromchronIcallyInstrumenteddogs.For
thesemeasurements,pharmacologIcblockadeoftheautonomIcnervoussystemwas
establIshedtoelImInateneuralorcIrculatInghumoralInfluencesontheInotropIcstate
oftheheart.TheconscIouscontroldatawereassIgned100,andsubsequent
reductIonsIntheInotropIcstatearedepIctedforboth1and1.5mInImumalveolar
anesthetIcconcentratIonsofsevoflurane,desflurane,andIsoflurane.Therewereno
dIfferencesbetweenthesethreevolatIleanesthetIcs.|
w
,slopeoftheregIonalpreload
recruItablestrokeworkrelatIonshIp;dP/dt
50
,changeInpressureperunItoftIme.
(AdaptedfromPagelPS,KampIneJP,SchmelIngWT,etal:nfluenceofvolatIle
anesthetIcsonmyocardIalcontractIlItyInvIvo:0esfluraneversusIsoflurane.
AnesthesIology1991;74:900;andHarkInCP,PagelPS,KerstenJF,etal:0Irect
negatIveInotropIcandlusItropIceffectsofsevoflurane.AnesthesIology1994;81:156.)
Figure 17-18.ThedoseofepInephrIneassocIatedwIthcardIacarrhythmIasInanImal
andhumanmodelswasleastwIthhalothane.TheetheranesthetIcsIsoflurane,
desflurane,andsevofluranerequIredthreetosIxfoldgreaterdosesofepInephrIneto
causearrhythmIas.(AdaptedfromNavarroF,WeIskopfF8,|oore|A,etal:Humans
anesthetIzedwIthsevofluraneorIsofluranehavesImIlararrhythmIcresponseto
epInephrIne.AnesthesIology1994;80:545;WeIskopfF8,EgerE,Holmes|A,etal:
EpInephrIneInducedprematureventrIcularcontractIonsandchangesInarterIalblood
pressureandheartratedurIng65J,Isoflurane,andhalothaneanesthesIaInswIne.
AnesthesIology1989;70:29J;HayashIY,SumIkawaK,TashIroC,etal:ArrhythmogenIc
thresholdofepInephrInedurIngsevoflurane,enflurane,andIsofluraneanesthesIaIn
dogs.AnesthesIology1988;69:145;and|oore|A,WeIskopfF8,EgerE,etal:
ArrhythmogenIcdosesofepInephrInearesImIlardurIngdesfluraneorIsoflurane
anesthesIaInhumans.AnesthesIology199J;79:94J.)
Coronary Steal
soflurane(andmostotherpotentvolatIleanesthetIcs)Increasescoronarybloodflowmany
tImesbeyondthatofthemyocardIaloxygendemand,therebycreatIngpotentIalfor
steal.StealIsthedIversIonofbloodfromamyocardIalbedwIthlImItedorInadequate
perfusIontoabedwIthmoreadequateperfusIon;especIallyonethathasaremaInIng
elementofautoregulatIon.WorkInachronIcallyInstrumented,canInemodelof
multIvesselcoronaryarteryobstructIon,hasshownthatneItherIsoflurane,sevoflurane,or
desfluraneatconcentratIonsupto1.5|ACresultedInabnormalcollateralcoronaryblood
flowredIstrIbutIon(steal),whereasadenosIne,apotentcoronaryvasodIlator,clearly
resultedInabnormalflowdIstrIbutIon.
71,72,7J,74
nterestIngly,sevofluranefavorably
Increased(ratherthandecreased)collateralcoronarybloodflowInthIsInstrumented
anImalmodelwhenaortIcpressurewasheldconstantbypharmacologIcsupportofblood
pressure.
7J
Myocardial Ischemia and Cardiac Outcome
NotsurprIsIngly,theclInIcalrelevanceofcoronarystealwIthIsofluranehasbeendebated
andIsgenerallythoughttobemInImal.
75
DutcomestudIeshavefaIledtoassocIatetheuse
ofIsofluraneInpatIentsundergoIngcoronaryarterybypassoperatIonswIthanIncreased
IncIdenceofmyocardIalInfarctIonorperIoperatIvedeath.
75,76,77
|oststudIeswould
suggestthatdetermInantsofmyocardIaloxygensupplyanddemand,ratherthanthe
anesthetIc,areoffargreaterImportancetopatIentoutcomes.
SeveralstudIeshaveevaluatedsevofluraneanddesfluraneInreferencetocomparator
anesthetIcs,IntermsofmyocardIalIschemIaandoutcomeInpatIentswIthcoronaryartery
dIseaseeItherundergoIngnoncardIacorcoronaryarterybypassgraftsurgery.
78,79
nboth
populatIons,sevofluraneappearstobeessentIallyequIvalenttoIsofluraneIntermsofthe
IncIdenceofmyocardIalIschemIaandadversecardIacoutcomes.0esfluraneappearsto
resultInsImIlaroutcomeeffectsasIsofluraneIncardIacpatIentshavIngcoronaryartery
bypassgraftIng
80
wIthoneexceptIon.nastudyInwhIchdesfluranewasgIvenwIthout
opIoIdstopatIentswIthcoronaryarterydIseaserequIrIngcoronaryarterybypassgraft
surgery,sIgnIfIcantIschemIamandatIngtheuseofbetablockerswasnoted.
81
0esflurane
hasnotbeenevaluatedIntermsofIschemIaandoutcomeInapatIentpopulatIonwIth
coronarydIseaseundergoIngnoncardIacsurgery.
Cardioprotection from Volatile Anesthetics
AprecondItIonIngstImulussuchasbrIefcoronaryocclusIonandIschemIaInItIatesa
sIgnalIngcascadeofIntracellulareventsthatreducesIschemIaandreperfusIonmyocardIal
Injury.ThereIsamemoryeffectfromanIschemIcstImulusthatoffers2toJhoursof
protectIon.ThevolatIleanesthetIcsmImIcIschemIcprecondItIonIngandtrIggerasImIlar
cascadeofIntracellulareventsresultIngInmyocardIalprotectIonthatlastsbeyondthe
elImInatIonoftheanesthetIc.
82
NumerousfactorsmaybeInvolvedInprecondItIonIng,
IncludIngthesodIum:hydrogenexchanger,theadenosInereceptor(partIcularly
1
and
2
subtypes),InhIbItoryCproteIns,proteInkInaseC,tyrosInekInase,andpotassIum(K
ATP
)
channelopenIng.PharmacologIcblockadeofthesefactors(e.g.,wIthadenosIneblockers,
delta1opIoIds,pertussIstoxIn,orglIbenclamIde)reducesorelImInatesthe
cardIoprotectIveeffectofIschemIcorvolatIleanesthetIcprecondItIonIng.
82,8J
AlternatIvely,admInIstratIonofcertaIndrugscanmImIcIschemIcorvolatIleanesthetIc
precondItIonIng.TheseIncludeadenosIne,opIoIdagonIsts,andK
ATP
channelopeners.n
contrasttotheInhalatIonofvolatIleanesthetIcs,thesecardIoprotectIvedrugsmustbe
delIveredIntoacoronaryarterybecausesystemIcadmInIstratIoncanhaveserIoussIde
effects.
LIpophIlIcvolatIleanesthetIcsdIffusethroughmyocardIalcellmembranesandalter
mItochondrIalelectrontransport,leadIngtoreactIveoxygenspecIesformatIon.
8J
ThIsmay
bethetrIggerforprecondItIonIngviaproteInkInaseCactIvatIonofK
ATP
channel
openIng.
84,85
ApproxImatelyJ0to40ofthecardIoprotectIonfromthevolatIleanesthetIcs
appearstoberelatedtoareducedloadIngofcalcIumIntothemyocardIalcellsdurIng
IschemIa.PrecondItIonedheartsmaytolerateIschemIafor10mInuteslongerthan
noncondItIonedhearts.
86
WhIletheseevolvIngdatagenerallyderIvefromanImalmodels,therenowIsIncreasIng
evIdenceIncardIacpatIentpopulatIonsthatanesthetIccardIoprotectIonlessens
myocardIaldamage(basedontroponInlevels)durIngonandoffpumpcardIac
surgery.
87,88
ThIseffectseemstobecommontoallcurrentpotentvolatIleanesthetIcs,and
mayfavorablyInfluenceIntensIvecareunItlengthofstayaftercoronarysurgery.
89
SulfonylureaoralhyperglycemIcdrugscloseK
ATP
channels,abolIshInganesthetIc
precondItIonIng.TheyshouldbedIscontInued24to48hoursprIortoelectIvesurgeryIn
hIghrIskpatIents.
82
8uthyperglycemIaalsopreventsprecondItIonIng,soInsulIntherapy
shouldbestartedwhenholdIngoralagents.
90
FecentevIdencesuggeststhatvolatIle
anesthetIcsmayprotectotherorgansfromIschemIcInjuryIncludIngkIdney,lIver,and
braIn.
91,92,9J
P.4J1
Figure 17-19.SummarydataofthebaroreflexregulatIonofheartrate(FFInterval)
InresponsetoadecreasIngpressurestImulus(sodIumnItroprussIde)orInresponseto
anIncreasIngpressurestImulus(phenylephrIne).ThesedatawereacquIredInhealthy
volunteerswhowererandomIzedtoreceIveIsoflurane,desflurane,orsevoflurane.
WIthIncreasIngmInImumalveolaranesthetIcconcentratIon,eachofthevolatIle
anesthetIcsledtoaprogressIvereductIonInthecardIacbaroslope(anIndexof
baroreflexsensItIvItyderIvedbyrelatIngchangesInmeanpressuretochangesInFF
Interval).TherewerenostatIstIcaldIfferencesbetweenanesthetIcs.(Adaptedfrom
EbertTJ,HarkInCP,|uzI|:CardIovascularresponsestosevoflurane:ArevIew.
AnesthAnalg1995;81:S11.)
Autonomic Nervous System
StudIesthathavefocusedontheefferentactIvItyoftheparasympathetIcandsympathetIc
nervoussystemsIndIcatethatthevolatIleanesthetIcsdepresstheIractIvItyInadose
dependentfashIon.
94,95
However,becausetheautonomIcnervoussystemIsImportantly
modulatedbybaroreceptorreflexmechanIsms,theeffectsoftheanesthetIconthe
efferentsystemcannotbereportedwIthouttakIngIntoaccounttheIreffectsondIfferent
componentsofthebaroreflexarc.Thus,althoughbothlImbsoftheautonomIcnervous
systemhavebeenshowntobeattenuatedbytheanesthetIcs,theafferentactIvItyfrom
thearterIalbaroreceptorshasbeenfoundtobeIncreasedwIthsomeoftheanesthetIcs,
suchasIsoflurane.
96
ThIsIncreaseddIschargeofthebaroreceptorsactuallycontrIbutesto
thedepressIonoftheentIrebaroreflexarcbytonIcallylowerIngtheoveralllevelof
outflowofthesympathetIcnervoussystem.FromtheperspectIveofclInIcalrelevance,
studIeshaveexamInedthebehavIorofthearterIalbaroreflexsystemdurIngahypotensIve
orhypertensIvestImulusbyevaluatIngchangesInheartrateandsympathetIcnerve
actIvIty.ThearterIalbaroreflexIsthemostrapIdlyrespondIngsystemtobloodpressure
perturbatIons.EarlyInvestIgatIonsfocusedprImarIlyontheregulatIonofheartrate,whIch
reflectsaprImarIlyvagalmedIatedendpoInt.sofluranereduces,Inadosedependent
fashIon,arterIalbaroreflexcontrolofheartrate.
97
SImIlareffectsonthereflexcontrolof
heartratehaverecentlybeendemonstratedwIthsevofluraneanddesflurane(FIg.17
19).
98,99,100
ThereIsgreaterdIffIcultyInevaluatIngthesympathetIccomponentofthebaroreflexarc
Inhumans,butatechnIquecalledsympathetic microneurographyhasbeenusedtodIrectly
recordvasoconstrIctorImpulsesdIrectedtobloodvesselsInhumans.
50,55
ThereIsadose
dependentdepressIonofthereflexcontrolofsympathetIcoutflowthatappearstobe
relatIvelyequIvalentforIsoflurane,sevoflurane,anddesflurane(FIg.1720).mportantly,
atlowlevelsofanesthesIa(e.g.,0.5|AC),thereIslIttleIfanydepressIonofreflex
functIonandthIsmIghthaveImportantImplIcatIonsInthecompromIsedpatIent
populatIon.DpIoIdandbenzodIazepIneadjuvantshaveonlymInImaleffectsonreflex
functIonandcombInIngthesewIthlowlevelsofpotentanesthetIcsmIghtpreservereflex
functIon.
101,102
AnotherImportantobservatIonhasbeenthemorerapIdreturnof
baroreflexfunctIonwIththelesssolubleanesthetIcsevofluraneversusIsoflurane.
10J
ThIs
mIghtaddtohemodynamIcstabIlItyInthepostoperatIveperIodwhentIssueconcentratIons
ofthevolatIleanesthetIcsaredeclInIng.
0esfluranehasaunIqueandpromInenteffectonsympathetIcoutflowInhumans,whIchIs
notapparentInanImalmodels.WIthIncreasIngsteadystateconcentratIonsofdesflurane,
thereIsaprogressIveIncreaseInrestIngsympathetIcnervoussystemactIvItyandplasma
norepInephrInelevels.
50,55,104
0espItethIsIncreaseIntonIcsympathetIcoutflow,blood
pressuredecreasessImIlarlytosevofluraneandIsoflurane.ThIsraIsesthequestIonasto
whetherdesfluranehastheabIlItytouncoupleneuroeffectorresponses.naddItIon,
desfluranecancausemarkedactIvatIonofthesympathetIcnervoussystemwhenthe
InspIredconcentratIonIsIncreased,especIallyto
P.4J2
concentratIonsabove5to6(FIg.1721).
50,55,104
ThereIsatransIentsurgeInsympathetIc
outflowleadIngtobothhypertensIonandtachycardIa.naddItIon,theendocrIneaxIsIs
actIvatedasevIdencedby15to20foldIncreasesInplasmaantIdIuretIchormoneand
epInephrIneandnorepInephrIne(FIg.1722).ThehemodynamIcresponsepersIstsfor4to5
mInutesandtheendocrIneresponsepersIstsfor15to25mInutes.AdequateconcentratIons
ofopIoIdsorclonIdInegIvenprIortoIncreasIngtheconcentratIonofdesfluranehavebeen
showntoattenuatetheseresponses.
58,59,60
ThesourceoftheneuroendocrIneactIvatIon
hasbeenactIvelysought,andItwouldappearthattherearereceptorsInboththeupper
andtheloweraIrways,and/orperhapsInahIghlyperfusedtIssueneartheaIrways,that
InItIatesthesympathetIcactIvatIon.
57
Figure 17-20.ThesympathetIcbaroreflexfunctIonofhealthyvolunteersrandomIzed
toreceIveIsoflurane,desflurane,orsevoflurane.Theslope(sensItIvIty)Isthe
relatIonshIpbetweendecreasIngdIastolIcpressureandIncreasIngefferentsympathetIc
nerveactIvIty.ThereflexregulatIonofsympathetIcoutflowwasfaIrlywellpreserved
at0.5and1.0mInImumalveolaranesthetIcconcentratIon(|AC)ofanesthetIc.At1.5
|AC,therewasa50decreaseIntheslopewIthallanesthetIcs.(AdaptedfromEbert
TJ,HarkInCP,|uzI|:CardIovascularresponsestosevoflurane:ArevIew.Anesth
Analg1995;81:S11.)
Figure 17-21.ConsecutIvemeasurementsofsympathetIcnerveactIvIty(SNA;mean
SE)fromhumanvolunteersdurIngInductIonofanesthesIawIthpropofolandthe
subsequentmaskadmInIstratIonofsevofluraneordesfluranefora10mInuteperIod.
TheInspIredconcentratIonoftheseanesthetIcswasIncreasedat1mInuteIntervals
begInnIngafterpropofoladmInIstratIon(0.41|ACofsevofluraneanddesflurane).n
bothgroups,propofolreducedSNAandmeanarterIalpressure.0esfluraneresultedIn
sIgnIfIcantIncreasesInSNAthatpersIstedthroughoutthe10mInutemask
admInIstratIonperIod.(AdaptedfromEbertTJ,|uzI|,LopatkaCW:NeurocIrculatory
responsestosevofluraneInhumans.AcomparIsontodesflurane.AnesthesIology1995;
8J:88.)
The Pulmonary System
General Ventilatory Effects
AllvolatIleanesthetIcsdecreasetIdalvolumeandIncreaserespIratoryratesuchthatthere
areonlymInoreffectsondecreasIngmInuteventIlatIon(FIg.172J).TheventIlatory
effectsaredosedependent,wIthhIgherconcentratIonsofvolatIleanesthetIcsresultIngIn
greaterdecreasesIntIdalvolumeandgreaterIncreasesInrespIratoryrate,wIththe
exceptIonofIsoflurane,whIchdoesnotIncreaserespIratoryrateabove1|AC.TheIrnet
effectofagradualdecreaseInmInuteventIlatIonhasbeenassocIatedwIthIncreasIng
restIngPaco
2
.TherespIratorydepressIoncanbepartIallyantagonIzeddurIngsurgIcal
stImulatIonwhererespIratoryrateandtIdalvolumehavebeenshowntoIncrease,resultIng
InadecreaseInthePaco
2
(FIg.1724).N
2
DIncreasesrespIratoryrateasmuchormorethan
theInhaledanesthetIcs.WhenN
2
DIsaddedtosevofluraneordesflurane,restIngPaco
2
decreasesrelatIvetoequI|ACconcentratIonsofsevofluraneordesfluraneInD
2
.The
degreeofrespIratorydepressIonfromInhaledanesthetIcsIsreducedwhenanesthesIa
admInIstratIonexceeds5hours.
105
Figure 17-22.StresshormoneresponsestoarapIdIncreaseInanesthetIc
concentratIon,from4to12InspIred.7olunteersgIvendesfluraneshowedalarger
IncreaseInplasmaepInephrIneandnorepInephrIneconcentratIonsthanwhengIven
Isoflurane.0ataaremeanSE.A=awakevalue;8=valueafterJ2mInutesof0.55
mInImumalveolarconcentratIon;tImerepresentsmInutesafterthefIrstbreathof
IncreasedanesthetIcconcentratIon.(AdaptedfromWeIskopfF8,|oore|A,EgerE,
etal:FapIdIncreaseIndesfluraneconcentratIonIsassocIatedwIthgreatertransIent
cardIovascularstImulatIonthanwIthrapIdIncreaseInIsofluraneconcentratIonIn
humans.AnesthesIology1994;80:10J5.)
Ventilatory Mechanics
FFCIsdecreaseddurInggeneralanesthesIa;thIshasbeenexplaInedbyanumberof
mechanIsmsIncludIngadecreaseIntheIntercostalmuscletone,alteratIonIndIaphragm
posItIon,
P.4JJ
changesInthoracIcbloodvolume,andtheonsetofphasIcexpIratoryactIvItyofrespIratory
muscles.About40ofthemuscularworkofbreathIngIsvIaIntercostalmusclesandabout
60IsfromthedIaphragm.ThedIaphragmatIcmusclefunctIonIsrelatIvelysparedwhen
contrastedtotheparasternalIntercostalmuscles.However,InspIratoryrIbcageexpansIon
IsreasonablywellmaIntaIneddurInganesthesIabecauseofpreservedactIvItyofthe
scalenemuscles.ExpIratIonIsgenerallyconsIderedapassIvefunctIonmedIatedbythe
elastIcrecoIlofthelung.TheprocessofapplyIngaresIstanceorloadtoexpIratIon
typIcallyresultsInaslowIngofrespIratIon,butunderanesthesIa,addItIonalresponses
IncludeasubstantIalasynchronyofthethoracIcmovementswIthrespIratIon.ThIssuggests
thatInpatIentswIthpulmonarydIseaseassocIatedwIthIncreasedexpIratoryresIstance,
theactofspontaneousventIlatIondurInggeneralanesthesIamIghtbepoorlytolerated.
Figure 17-23.ComparIsonofmeanchangesInrestIngPaco
2
,tIdalvolume,respIratory
rate,andmInuteventIlatIonInpatIentsanesthetIzedwItheItherhalothane,
Isoflurane,enflurane,sevoflurane,desflurane,ornItrousoxIde(N,N
2
D).AnesthetIc
InducedtachypneacompensatesInpartfortheventIlatorydepressIoncausedbyall
volatIleanesthetIcs(decreaseInmInuteventIlatIonandtIdalvolume,and
concomItantIncreaseInPaco
2
).0esfluraneresultsInthegreatestIncreaseInPaco
2
wIthcorrespondIngreductIonsIntIdalvolumeandmInuteventIlatIon.soflurane,lIke
allotherInhaledagents,IncreasesrespIratoryrate,butdoesnotresultIndose
dependenttachypnea.(AdaptedfromLockhartSH,FampIlJ,YasudaN,etal:
0epressIonofventIlatIonbydesfluraneInhumans.AnesthesIology1991;74:484;0oI|,
kedaK:FespIratoryeffectsofsevoflurane.AnesthAnalg1987;66:241;FourcadeHE,
StevensWC,LarsonCPJr,etal:TheventIlatoryeffectsofForane,anewInhaled
anesthetIc.AnesthesIology1971;J5:26;andCalverleyFK,SmIthNT,JonesCW,etal:
7entIlatoryandcardIovasculareffectsofenfluraneanesthesIadurIngspontaneous
ventIlatIonInman.AnesthAnalg1978;57:610.)
Figure 17-24.TheeffectofsurgIcalstImulatIonontheventIlatorydepressIonof
InhaledanesthesIawIthIsofluraneInthepresenceandabsenceofnItrousoxIde(N
2
D).
SurgIcalstImulatIonIncreasedalveolarventIlatIonanddecreasedPaco
2
atalldepths
ofanesthesIaexamIned.(AdaptedfromEgerE2nd,0olanW|,StevensWC,etal:
SurgIcalstImulatIonantagonIzestherespIratorydepressIonproducedbyForane.
AnesthesIology1972;J6:544.)
Response to Carbon Dioxide and Hypoxemia
nawakehumans,thecentralchemoreceptorsrespondvIgorouslytochangesInarterIal
carbondIoxIdetensIonsuchthatmInuteventIlatIonIncreasesJL/mInpera1mmHg
IncreaseInPaco
2
.AlloftheInhaledanesthetIcsproduceadosedependentdepressIonof
theventIlatoryresponsetohypercarbIa(FIg.1725).TheaddItIonofnItrousoxIdetoa
volatIleanesthetIchadbeenthoughttodImInIshPaco
2
responseslessthananequI|AC
doseoftheanesthetIcalone,however,thIsdoesnotappeartobethecasefordesflurane
(FIg.1725).npatIentswIthchronIcobstructIvepulmonarydIsease,thereIsanImpaIred
responsetoIncreasedPaco
2
underanesthesIa.
ThethresholdatwhIchbreathIngstops,calledtheapneic threshold,canbedetermIned
durInganesthesIawIthspontaneousventIlatIon.tIsgenerally4to5mmHgbelowthe
prevaIlIngrestIngPaco
2
andunrelatedtotheslopeoftheco
2
responsecurvesortothe
leveloftherestIngPaco
2
.TheclInIcal
P.4J4
relevanceofthIsthresholdmayberecognIzedwhenassIstIngventIlatIonInan
anesthetIzedpatIentwhoIsbreathIngspontaneously.ThIsonlyservestolowerthePaco
2
to
approachthatoftheapneIcthreshold,thereforemandatIngmorecontrolofventIlatIon.
Figure 17-25.AllInhaledanesthetIcsproducesImIlardosedependentdecreasesInthe
ventIlatoryresponsetocarbondIoxIde(CD
2
).N
2
D,nItrousoxIde.(AdaptedfromEgerE
:0esflurane.AnesthFev199J;20:87;and0oI|,kedaK:FespIratoryeffectsof
sevoflurane.AnesthAnalg1987;66:241.)
nhaledanesthetIcs,IncludIngnItrousoxIde,produceadosedependentattenuatIonofthe
ventIlatoryresponsetohypoxIa.ThIsactIonappearstodependontheperIpheral
chemoreceptors.nfact,evensubanesthetIcconcentratIonsofvolatIleanesthetIcs(0.1
|AC)elIcItanywherefroma15to75depressIonoftheventIlatorydrIvetohypoxIa(FIg.
1726).ThemechanIsmofthIsdepressIonstIllremaInspoorlyunderstood.StudIeshave
suggestedthathypoxIamaydecreasetheprobabIlItythatpotassIumchannelsareopen,
thuscausIngmembranedepolarIzatIon,anInfluxofcalcIumIons,andareleaseof
neurotransmItters.
106
DnetheoryIsthatthepotassIumchannelsarerespondIngtoreactIve
oxygenspecIes.DnestudyfoundtheadmInIstratIonofantIoxIdantsprIortothe
admInIstratIonofavolatIleanesthetIcpreventedthedepressIonofthehypoxIc
response.
107
TheextremesensItIvItyofthevolatIleanesthetIcstoInhIbItventIlatory
responsestohypoxIahasImportantclInIcalImplIcatIons.FesIdualeffectsofvolatIle
anesthetIcsmayImpaIrtheventIlatorydrIveofpatIentsIntherecoveryroom.nthIs
regard,theshortactInganesthetIcs(sevofluraneanddesflurane)mayproveadvantageous
becauseoftheIrmorerapIdwashoutandtheIrmInImaleffectonhypoxIcsensItIvItyat
subanesthetIcconcentratIons(FIg.1726).TheeffectsofthevolatIleanesthetIcsonhypoxIc
drIvemayplayanevenmoreImportantroleInpatIentswhorelyonhypoxIcdrIvetoset
theIrlevelofventIlatIon,suchasthosewIthchronIcrespIratoryfaIlureorpatIentswIth
obstructIvesleepapnea.
Bronchiolar Smooth Muscle Tone
8ronchoconstrIctIonunderanesthesIaoccursbecauseofdIrectstImulatIonofthelaryngeal
andtrachealareas,fromtheadmInIstratIonofadjuvantdrugsthatcausehIstamIne
release,andfromnoxIousstImulIactIvatIngvagalafferentnerves.Thereflexresponseto
thesestImulImaybeenhancedInlIghtlyanesthetIzedpatIents.
108
Theresponsesalsoare
enhancedInpatIentswIthknownreactIveaIrwaydIsease,IncludIngthoserequIrIng
bronchodIlatortherapyorthosewIthchronIcsmokInghIstorIes.AIrwaysmoothmuscle
extendsasfardIstallyasthetermInalbronchIolesandIsundertheInfluenceofboth
parasympathetIcandsympathetIcnerves.TheparasympathetIcnervesmedIatebaselIne
aIrwaytoneandreflexbronchoconstrIctIonvIa|2and|JmuscarInIcreceptorsonthe
aIrwaysmoothmuscle,whIchInItIateIncreasesInIntracellularcyclIcguanosIne
monophosphate.AdrenergIcreceptorsalsoarelocatedonbronchIalsmoothmuscle,and
the
2
receptorsubtypeplaysthepredomInantroleInpromotIngbronchIolarmuscle
relaxatIonthroughanIncreaseInIntracellularcyclIcadenosInemonophosphate.The
volatIleanesthetIcsrelaxaIrwaysmoothmuscleprImarIlybydIrectlydepressIngsmooth
musclecontractIlItyandIndIrectlyInhIbItIngthereflexneuralpathways.
109
0Irecteffects
ofthevolatIleanesthetIcspartIallydependonanIntactbronchIalepIthelIum,suggestIng
thatepIthelIaldamageorInflammatIonsecondarytoasthmamaylessentheIr
bronchodIlatIngeffect.ThevolatIleanesthetIcsalsomayhaveprotectIveeffectsbyactIng
onthebronchIalepIthelIumvIaanonadrenergIc,noncholInergIcmechanIsm,possIbly
InvolvIngthenItrIcoxIdepathway.
110
0esfluraneadmInIstratIonshortlyafterthIopental
InductIonandtrachealIntubatIonresultsInatransIentIncreaseInrespIratorysystem
resIstance(bronchoconstrIctIon),andthIshasbeenattrIbutedtoadIrecteffectofthe
pungencyandaIrwayIrrItabIlItyofdesflurane(FIg.1727).ThIseffectIsworsenedIn
patIentswIthanactIvesmokInghIstory.
111
7olatIleanesthetIcshavebeenusedeffectIvely
totreatstatusasthmatIcuswhenotherconventIonaltreatmentshavefaIled.
112,11J
AlthoughhalothanehasbeenhIstorIcallyusedInthesesItuatIons,ItIsnolongeravaIlable
commercIally.SevofluranemaybeabetterchoIcebecauseofItsquIckonset,lackof
pungency,lackofcardIovasculardepressIon,andlowerrIskofcardIacarrhythmIas
comparedwIthhalothane.
P.4J5
Figure 17-26.nfluenceof0.1mInImumalveolarconcentratIon(|AC)offIvevolatIle
anesthetIcagentsontheventIlatoryresponsetoastepdecreaseInendtIdaloxygen
concentratIon.7aluesaremeanS0.SubanesthetIcconcentratIonsofthevolatIle
anesthetIcs,exceptdesfluraneandsevoflurane,profoundlydepresstheresponseto
hypoxIa.(AdaptedfromSartonE,0ahanA,TeppemaL,etal:AcutepaInandcentral
nervoussystemarousaldonotrestoreImpaIredhypoxIcventIlatoryresponsesdurIng
sevofluranesedatIon.AnesthesIology1996;85:295.)
Figure 17-27.ChangesInrespIratorysystemresIstanceexpressedasapercentageof
thebaselInerecordedaftertrachealIntubatIonbutprIortoadmInIstratIonof
sevofluraneordesfluranetotheInspIredgasmIxture.AIrwayresIstanceresponsesto
sevofluraneweresIgnIfIcantlydIfferentfromdesflurane(*p0.05).(AdaptedfromCoff
|J,AraInSF,FIcke0J,etal:AbsenceofbronchodIlatIondurIngdesfluraneanesthesIa:
AcomparIsontosevofluraneandthIopental.AnesthesIology2000;9J:404.)
Mucociliary Function
CIlIatedrespIratoryepIthelIumextendsfromthetracheatothetermInalbronchIoles.Cells
andglandsInthetracheobronchIaltreesecretemucusthatcapturessurfacepartIclesfor
transportvIacIlIaryactIon.ThereareanumberoffactorsInvolvedIndImInIshed
mucocIlIaryfunctIon,partIcularlyInthemechanIcallyventIlatedpatIentInwhomdrIed,
InspIredgasesImpaIrcIlIarymovement,thIckentheprotectIvemucus,andreducethe
abIlItyofmucocIlIaryfunctIontotransportsurfacepartIclesoutoftheaIrway.7olatIle
anesthetIcsandnItrousoxIdereducecIlIarymovementandalterthecharacterIstIcsof
mucus.talsoIsknownthatsmokershaveImpaIredmucocIlIaryfunctIoncomparedwIth
nonsmokers,andthecombInatIonofavolatIleanesthetIcInasmokerwhoIsmechanIcally
ventIlatedsetsupascenarIoforInadequateclearIngofsecretIons,mucuspluggIng,
atelectasIs,andhypoxemIa.
Pulmonary Vascular Resistance
AlthoughvascularsmoothmuscleIsclearlyaffectedbythevolatIleanesthetIcs,the
pulmonaryvascularrelaxatIonfromclInIcallyrelevantconcentratIonsofInhaled
anesthetIcsIsmInImal.naddItIon,ananesthetIcrelateddecreaseIncardIacoutputtends
tooffsetthedIrectvasodIlatoractIonoftheanesthetIc,resultIngInlIttleornochangeIn
pulmonaryarterypressuresandpulmonarybloodflow.EvennItrousoxIde,whIchhaslIttle
effectoncardIacoutputandpulmonarybloodflow,hasatbestasmalleffecttoIncrease
pulmonaryvascularresIstance.However,theeffectofnItrousoxIdemaybemagnIfIedIn
patIentswIthrestIngpulmonaryhypertensIon.
114
PerhapsmoreImportantIntermsofvolatIleanesthetIcsandpulmonarybloodflowIstheIr
potentIaltoattenuatehypoxIcpulmonaryvasoconstrIctIon(HP7).0urIngperIodsof
hypoxemIa,HP7reducesbloodflowtounderventIlatedareasofthelung,therebydIvertIng
bloodflowtoareasofthelungwIthgreaterventIlatIon.TheneteffectIstoImprovethe
7/QmatchIng,resultIngInareducedamountofvenousadmIxtureandImprovedarterIal
oxygenatIon.AlthoughalloftheInhaledanesthetIcsInhIghconcentratIonshavebeen
showntoattenuateHP7InanImalmodels,thesItuatIonIslessclearInpatIentstudIes.ThIs
mayreflectthemultIfactorIaleffectsofthevolatIleanesthetIcsonfactorsInvolvedIn
pulmonarybloodflow,IncludIngtheIrcardIovascular,autonomIc,andhumoralactIons.
Furthermore,nonpharmacologIcvarIablesImpaIrHP7,IncludIngsurgIcaltrauma,
temperature,pH,Paco
2
,sIzeofthehypoxIcsegment,andIntensItyofthehypoxIcstImulus.
DnelungventIlatIon(DL7)servesasamodelwhereHP7shouldlessentheexpected
decreaseInPao
2
andIntrapulmonaryshuntfractIon(Qs/Qt).npatIentsundergoIngDL7
durIngthoracIcsurgery,volatIleanesthetIcshavehadmInImaleffectsonPao
2
andQs/Qt
whenchangIngfromtwolungtoDL7(FIg.1728).
115,116
TheeffIcacyofHP7tolessenshunt
fractIonvarIesInverselywIthpulmonarybloodflow(andcardIacoutput).soflurane,
sevoflurane,anddesfluranepreservecardIacoutputandhavemInImaltomodesteffects
onshuntfractIondurIngDL7.PropofolappearstobenomorebenefIcIalonshuntfractIon
durIngDL7comparedwIthsevoflurane.
117
Hepatic Effects
PostoperatIvelIverdysfunctIon,tovaryIngdegrees,hasbeenassocIatedwIthallofthe
volatIleanesthetIcsIncurrentuse.TherearetwodIstInctmechanIsmsbywhIch
anesthetIcshavecausedhepatItIs.DneIsmorecommonandrelatedtohepatocyte
toxIcIty.tIsrelatIvelymIld,doesnotrequIreaprevIousexposure,andhasalow
morbIdIty.ThesecondIsassocIatedwIthrepeatexposureandprobablyrepresentsan
ImmunereactIontooxIdatIvelyderIvedmetabolItesofanesthetIcs.thasbeenassocIated
wIthseverelIverdamageandfulmInanthepatIcfaIlureandIsdIscussedlaterInthe
chapter.
Figure 17-28.ShuntfractIon(top panel)andthealveolararterIaloxygengradIent
(bottom)ImmedIatelybefore,durIng,andafteronelungventIlatIon(DL7)InpatIents
anesthetIzedwIthdesfluraneorIsoflurane.0ataaremeans.(AdaptedfromPagelPS,
FuJL,0amask|C,etal:0esfluraneandIsofluraneproducesImIlaralteratIonsIn
systemIcandpulmonaryhemodynamIcsandarterIaloxygenatIonInpatIents
undergoIngonelungventIlatIondurIngthoracotomy.AnesthAnalg1998;87:800.)
P.4J6
Figure 17-29.Changes(,meanSE)InhepatIcbloodflowdurIngadmInIstratIonof
Isofluraneorhalothane.0ecreasesInportalveInbloodflowproducedby2mInImum
alveolarconcentratIon(|AC)IsofluraneareoffsetbyIncreasesInhepatIcarteryblood
flow(autoregulatIon).HalothaneresultedIndecreasesInbothportalveInandhepatIc
arterybloodflow,therebysIgnIfIcantlycompromIsIngtotalhepatIcarterybloodflow.
(AdaptedfromCelmanS,FowlerKC,SmIthLF:LIvercIrculatIonandfunctIondurIng
IsofluraneandhalothaneanesthesIa.AnesthesIology1984;61:726.)
HypoxIcInjurytohepatocytescanbeasIgnIfIcantcontrIbutortopostoperatIvehepatIc
Injury.ThelIverhastwobloodsupplIes.DneIsthewelloxygenatedbloodfromthehepatIc
arteryandthesecondIsthepoorlyoxygenatedbloodfromtheportalveIn.AposItIve
attrIbuteoftheetherbasedanesthetIcs(Isoflurane,sevoflurane,anddesflurane)IstheIr
abIlItytomaIntaInorIncreasehepatIcarterybloodflowwhIledecreasIng(ornotchangIng)
portalveInbloodflow(FIg.1729).
118
SurgeryIntheareaofthelIver(orelsewhereInthe
abdomInalcavIty)thatmIghtcompromIsehepatIcbloodflowputspatIentsatrIskfor
hepatIccellInjury.naddItIon,hepatIcenzymeInductIon,whIchIncreasesoxygendemand,
enhancesthevulnerabIlItyofpatIents.Furthermore,patIentswhoarecrItIcallydependent
onoxygensupplyforsurvIvalofremaInInglIvertIssue,suchasthecIrrhotIcpatIent,areat
ahIgherrIskforfurtherhepatIcInjurythannoncIrrhotIcIndIvIduals.AlteredlIverfunctIon
testshavebeenusedasanIndexofhepatIcInjurydurInganesthesIa.TransIentIncreasesIn
plasmaalanIneamInotransferaseactIvItydonotoccurInhumanvolunteersadmInIstered
desflurane,Isoflurane,orsevoflurane,
118,119,120
norfollowIngsevofluraneordesflurane
anesthesIaInpedIatrIcpatIents.
121
ncreasesInthealanIneamInotransferaseoraspartate
amInotransferasemaynotaccuratelyreflecttheextentofhepatIcInjuryandarenot
unIquelyspecIfIctothelIver.ThecentrIlobularareaofthelIverIsmostsusceptIbleto
hypoxIa.Therefore,amoresensItIvemeasureofInjurymaybeglutathIoneStransferase
(CST),sInceItIsdIstrIbutedprImarIlyInthecentrIlobularhepatocytes.npatIentstudIes,
IsofluranedIdnotIncreaseCST.
122
nelderlypatIentswIthnopreexIstInglIverdIseaseand
havIngperIpheralsurgeryundersevofluraneordesflurane,abrIefImpaIrmentof
splanchnIcbloodflowwasdemonstratedandthIsledtoIncreasesInCSTthatresolvedIn24
hours.
12J
ThepossIbIlItythattheorganprotectIonfromsevofluranewouldlessenhepatIc
dIsturbancesafterCA8CsurgerywIthcardIopulmonarybypasswhencomparedwIth
propofolwasexploredInaprospectIverandomIzedstudyofJ20patIents.PostoperatIve
bIochemIcalmarkersofhepatIcdysfunctIonwerelowerafterthesevofluranebased
anesthetIc.
9J
Thus,IntermsofhepatocytehypoxIa,themoderndayvolatIleanesthetIcs
havemInImaladverseeffectsandmIghtevenaffordprotectIonfromIschemIc/hypoxIc
Injurytocells.
Neuromuscular System and Malignant Hyperthermia
TheInhaledanesthetIcshavetwoImportantactIonsonneuromuscularfunctIon.They
dIrectlyrelaxskeletalmuscleandtheypotentIatetheactIonofneuromuscularblockIng
drugs.
124,125
ncontrast,nItrousoxIdedoesnotrelaxskeletalmuscles.ThedIrecteffectsof
volatIleanesthetIcstorelaxskeletalmusclearemostpromInentabove1|ACandcanbe
furtherenhanced,by40,InpatIentswIthmyasthenIagravIs.
126
7olatIleanesthetIcpotentIatIonofneuromuscularblockadehasbeenwelldocumented.For
example,theInfusIonrateofrocuronIumrequIredtomaIntaInneuromuscularblockadeIs
J0to40lessdurIngIsoflurane,desflurane,andsevofluranecomparedwIthpropofol.
127
A
sImIlarleftshIftInthedoseresponserelatIonshIphasbeenobservedwIthcIsatracurIum
durIngvolatIleanesthetIcadmInIstratIonversusdurIngIntravenousanesthesIa.
125
WhIle
themechanIsmofvolatIleanesthetIcpotentIatIonoftheneuromuscularblockIngdrugsIs
notentIrelyclear,ItappearstobelargelybecauseofapostsynaptIceffectatthenIcotInIc
acetylcholInereceptorlocatedattheneuromuscularjunctIon.SpecIfIcally,atthereceptor
level,thevolatIleanesthetIcsactsynergIstIcallywIththeneuromuscularblockIngdrugsto
enhancetheIractIon.
128
ThedegreeofenhancementIsrelatedtotheIraqueous
concentratIonsothatatequI|ACconcentratIons,thelesspotentanesthetIcs(e.g.,
desfluraneandsevofluranevs.Isoflurane)shouldhaveagreaterInhIbItoryeffecton
neuromusculartransmIssIon.SupportforthIsconceptcomesfromaclInIcalstudy
demonstratIng20lowerrequIrementforvecuronIumtomaIntaInastabletwItch
depressIondurIng1.25desfluranecomparedwIth1.25Isoflurane.
129
However,desflurane
andIsoflurane(andsevoflurane)atequIpotentconcentratIonsactedsImIlarlytoenhance
theeffectofcIsatracurIumonneuromuscularfunctIon.
125
ThIsmayrelatetostructural
dIfferencesofthebenzylIsoquInolInesversusamInosteroIdneuromuscularblockIngdrugs.
AllofthepotentvolatIleanesthetIcsserveastrIggersformalIgnanthyperthermIa(|H)In
genetIcallysusceptIblepatIents.
1J0,1J1
ncontrast,nItrousoxIdeIsonlyaweaktrIggerfor
|H.
1J2
TheaugmentatIonofcaffeIneInducedcontracturesbynItrousoxIdeIs1.Jfold,by
IsofluraneIsJfold,andbyhalothane,11fold.
1J2
AlthoughdesfluraneIsaweaktrIggerfor
|H,IthasbeenassocIatedwIthanunusualdelayedonsetofsymptomsof|HInanImals
andhumans.
1J1,1JJ
Genetic Effects, Obstetric use, and Effects on Fetal
Development
ThepotentIalforgenetIctoxIcItyfromvolatIleanesthetIcsseemsmInImal.TheAmestest
IdentIfIeschemIcalsthatactasmutagensandcarcInogensandhasbeennegatIvefor
P.4J7
Isoflurane,desflurane,sevoflurane,andnItrousoxIde.
1J4,1J5
ApossIblegenotoxIceffectof
desfluranehasbeendetectedInfemalepatIentswIthacytogenetIcassaythatdetects
sIsterchromatIdexchanges(SCE)InlymphocytesfromperIpheralblood.0esflurane
transIentlyIncreasedthefrequencyofSCE,whereasInchIldren,sevofluranedIdnot
IncreaseSCE.
1J6,1J7
TheclInIcalImplIcatIonsofthesefIndIngsarenotclearInrelatIonto
thenegatIveAmestest.
7olatIleanesthetIcscanbeteratogenIcInanImals,
1J8
butnonehavebeenshowntobe
teratogenIcInhumans.AnImalstudIeshaveIndIcatedthatnItrousoxIdeexposureInthe
earlyperIodsofgestatIonmayresultInadverseeffects,IncludInganIncreasedIncIdenceof
fetalresorptIon.
1J9
ThesamevulnerabIlItydoesnotexIstdurIngtheadmInIstratIonofthe
potentvolatIleanesthetIcs.
1J9
NItrousoxIdedecreasestheactIvItyofvItamIn8
12
dependentenzymes,methIonIne
synthetaseandthymIdylatesynthetase.ThemechanIsmappearstobeanIrreversIble
oxIdatIonofthecobaltatomofvItamIn8
12
bynItrousoxIde.When70nItrousoxIdeIs
admInIsteredtopatIents,thetImeto50InactIvatIonofmethIonInesynthetaseIs46
mInutes.TheconcernthatthesechangesmIghthaveaneffectonarapIdlydevelopIng
embryo/fetusseemsapproprIatebecausemethIonInesynthetaseandthymIdylate
synthetaseareInvolvedIntheformatIonofmyelInandtheformatIonof0NA,respectIvely.
nhIbItIonoftheseenzymescouldmanIfestasdepressIonofbonemarrowfunctIonand
neurologIcdIsturbances.nfact,megaloblastIcchangesInbonemarrowareconsIstently
observedInpatIentsexposedtonItrousoxIdefor24hours,and4daysofexposureto
nItrousoxIdehasresultedInagranulocytosIs.Furthermore,anImalsexposedto15nItrous
oxIdeforseveralweeksdevelopedneurologIcchangesIncludIngspInalcordandperIpheral
nervedegeneratIonandataxIa.AsensorymotorpolyneuropathythatIsoftencombIned
wIthsIgnsofposterIorlateralspInalcorddegeneratIonhasbeendescrIbedInhumanswho
chronIcallyInhalenItrousoxIdeforrecreatIonaluse.
140
TheseeffectshavebeenattrIbuted
toreducedactIvItyofthevItamIn8
12
dependentenzymes.
UterInesmoothmuscletoneIsdImInIshedbyvolatIleanesthetIcsInsImIlarfashIontothe
effectsofvolatIleanesthetIcsonvascularsmoothmuscle.ThereIsadosedependent
decreaseInspontaneousmyometrIalcontractIlItythatIsconsIstentamongthevolatIle
anesthetIcs.
141,142
0esfluraneandsevofluranealsoInhIbItthefrequencyandamplItudeof
myometrIalcontractIonsInducedbyoxytocInInadosedependentmanner.
141
UterIne
relaxatIon/atonycanbecomeproblematIcatconcentratIonsofvolatIleanesthesIa1|AC,
andmIghtdelaytheonsettImeofnewbornrespIratIon.
14J
Consequently,acommon
technIqueusedtoprovIdegeneralanesthesIaforurgentcesareansectIonsIstoadmInIster
lowconcentratIonsofthevolatIleanesthetIc,suchas0.5to0.75|AC,combInedwIth
nItrousoxIde.ThIsdecreasesthelIkelIhoodofuterIneatonyandbloodloss,especIallyata
tImeafterdelIverywhenoxytocInresponsIvenessoftheuterusIsessentIal.
14J
nsome
sItuatIons,uterInerelaxatIonmaybedesIrable,suchastoremovearetaInedplacenta.n
thIscase,abrIef,hIghconcentratIonofavolatIleanesthetIcmaybeadvantageous.
TherehasbeenanongoIngconcernabouttheIncIdenceofspontaneousabortIonsIn
operatIngroompersonnelchronIcallyexposedtotraceconcentratIonsofInhaled
anesthetIcs,especIallynItrousoxIde.
144
EarlyepIdemIologIcstudIessuggestedthat
operatIngroompersonnelhadanIncreasedIncIdenceofspontaneousabortIonsand
congenItalabnormalItIesInoffsprIng.However,subsequentanalysIsofthedatasuggests
InaccuratestudydesIgn,confoundIngvarIables,andnonrespondersmIghthaveledto
flawedconclusIons.
145
nprospectIvestudIes,nocausalrelatIonshIphasbeenshown
betweenexposuretowasteanesthetIcgases,regardlessofthepresenceorabsenceof
scavengIngsystems,andadversehealtheffects.0espItetheunprovenInfluenceoftrace
concentratIonsofthevolatIleanesthetIcsonfetaldevelopmentandspontaneous
abortIons,concernsforanadverseInfluencehaveresultedIntheuseofscavengIngsystems
toremoveanesthetIcgasesfromtheoperatIngroomandtheestablIshmentofstandards
forwastegasexposure.TheNatIonalnstItuteforDccupatIonalSafetyandHealthhas
recommendedexposurelevelsfornItrousoxIdeIs25partspermIllIon(ppm)asatIme
weIghtedaverageover8hours.The1hourexposurelImItforhalogenatedanesthetIcs
wIthoutnItrousoxIdeexposureIs2ppm,andwIthnItrousoxIdeIs0.5ppm.
ntermsofneonataleffectsfromgeneralanesthesIa,ApgarscoresandacIdbasebalance
arenotaffectedbyanesthetIctechnIque,suchasspInalversusgeneral.
146
|oresensItIve
measuresofneurologIcandbehavIoralfunctIon,suchastheScanlonEarlyNeonatal
NeurobehavIoralScaleandtheNeurologIcandAdaptIveCapacItIesScore(NACS)IndIcate
sometransIentdepressIonofscoresfollowInggeneralanesthesIathatresolvesat24hours
afterdelIvery.
146,147
Anesthetic Degradation by Carbon Dioxide Absorbers
Compound A
SevofluraneundergoesbasecatalyzeddegradatIonIncarbondIoxIdeabsorbentstoforma
vInylethercalledcompound A.TheproductIonofcompoundAIsenhancedInlowflowor
closedcIrcuItbreathIngsystemsandbywarmorverydryCD
2
absorbents.
148,149
8arIum
hydroxIdelImeproducesmorecompoundAthansodalImeandthIscanbeattrIbutedto
slIghtlyhIgherabsorbenttemperaturedurIngCD
2
extractIon(FIg.17J0).
150
0esIccated
barIumhydroxIdelImealsohasbeenImplIcatedIntheheatandfIresassocIatedwIth
sevoflurane,dIscussedlater.ThIsabsorbenthasbeenremovedfromtheU.S.market.
TherearewelldefInedspecIesdIfferencesInthethresholdforcompoundAInduced
nephrotoxIcIty.ThethresholdIsapproxImatelyJ00ppm
.
hrIn250grats,612ppm
.
hrIn
pIgs,andbetween600and800ppm
.
hrInmonkeys.npatIentsandvolunteersreceIvIng
sevofluraneInclosedcIrcuItorlowflowdelIverysystems,InspIredcompoundA
concentratIonsaveraged8to24and20toJ2ppmwIthsodalImeandbarIumhydroxIde
lIme,respectIvely.
151,152,15J,154
TotalexposuresashIghas
P.4J8
J20to400ppm
.
hrhavehadnocleareffectonclInIcalmarkersofrenalfunctIon.
155,156,157
nrandomIzedandprospectIvevolunteerandpatIentstudIes,noadverserenaleffects
fromlowflow(0.5to1.0L/mIn)orclosedcIrcuItsevofluraneanesthesIaweredetected
usIngbothstandardclInIcalmarkersofrenalfunctIon(serumcreatInIneandbloodurea
nItrogenconcentratIons)andexperImentalmarkersofrenalfunctIonandstructural
IntegrIty(proteInurIa,glucosurIaandenzymurIa).
152,15J,154,158,159,160,161
naprospectIve,
multIcenter,randomIzedstudyInpatIentswIthpreexIstIngrenaldIsease,therewereno
adverserenaleffectsoflongduratIon,lowflowsevoflurane.
162,16J
nfact,transIent
proteInurIa,glucosurIa,andenzymurIahavebeennotedafterdesflurane,Isoflurane,and
propofolanesthesIaIndIcatIngtheseelevatedmarkersofrenalInjurymIghtrepresent
commoneffectsunrelatedtothechoIceofanesthetIc.
151,152
ThemajorItyofcountrIesthat
haveapprovedsevofluraneforclInIcalusehavenoflowrestrIctIonbecauseoftheproven
safetyoftheanesthetIcInscIentIfIcstudIes,wheretherehasnotbeenasInglecasereport
ofrenalInjuryfromsevofluraneafteradecadeofuse,despIteasensItIzedanesthesIa
communIty.
Figure 17-30.CompoundAlevelsproducedfromthreecarbondIoxIdeabsorbents
durIng1mInImumalveolarconcentratIonsevofluraneanesthesIadelIveredto
volunteersat1L/mInfreshgasflow(meanSE).Cassamplesweretakenfromthe
InspIredlImboftheanesthesIacIrcuIt.*0IfferentfrombarIumhydroxIdelImeorsoda
lIme(p0.05).(Adaptedfrom|chaourabA,AraInSF,EbertTJ:LackofdegradatIonof
sevofluranebyanewcarbondIoxIdeabsorbentInhumans.AnesthesIology2001;94:
1007.)
Carbon Monoxide and Heat
CD
2
absorbentsdegradesevoflurane,desflurane,andIsofluranetocarbonmonoxIdewhen
thenormalwatercontentoftheabsorbent(1Jto15)Ismarkedlydecreased5.
164,165,166
ThedegradatIonIstheresultofanexothermIcreactIonoftheanesthetIcswIth
theabsorbent.TheanesthetIcmolecularstructureandthepresenceofastrongbaseInthe
carbondIoxIdeabsorbentareInvolvedIntheformatIonofcarbonmonoxIde(CD).
165
0esfluraneandIsofluranecontaInadIfluoromethoxymoIetythatIsessentIalforthe
formatIonofCD.WhenstudIesareconductedwIthCD
2
absorbentsmaIntaInedatorjust
aboveroomtemperature,desfluranegIvenatjustunder1|ACproducedupto8,000ppm
ofCDversus79ppmwIthnearly2|ACsevoflurane.
166
ndesIccatedbarIumhydroxIde,CD
productIonfromdesfluranewasnearlythreefoldhIgherthanwIthsodalImebutwastrIvIal
wIthsevoflurane.nnormalclInIcaluse,CD
2
canIstertemperaturesare25to45`C,butcan
behIgherwhenemployIngaverylowfreshgasflow.nalaboratorysettIng,whenCD
2
canIstertemperatureIsnotcontrolledandsevofluraneIsadmInIsteredtodesIccated
barIumhydroxIde,theexothermIcreactIoncansubstantIallyIncreasecanIster
temperatures.fthecanIstertemperatureexceeds80`C,sIgnIfIcantCDproductIonIsnoted
wIthsevoflurane.
164
nstancesofCDpoIsonIngofpatIentshavebeenreportedInsItuatIons
wheretheCD
2
absorbenthasbeenpresumablydrIed(desIccated)becauseananesthetIc
machInehasbeenleftonwIthahIghfreshgasflowpassIngthroughtheCD
2
absorbentover
anextendedperIodoftIme.
167,168,169,170
nanexperImentalsettIng,overnIghtdryIngof
barIumhydroxIdefor14hoursat10L/mInfreshgasflowdIdnotresultInsIgnIfIcantCD
productIonfromdesflurane,whereas24to66hoursoffreshgasflowdryIngproduced
sIgnIfIcantCDproductIon.
171
AlthoughdesfluraneproducesthemostCDwIthdesIccatedCD
2
absorbers,thereactIon
wIthsevofluraneproducesthemostheat.
172
ThestrongexothermIcreactIonhascaused
sIgnIfIcantheatproductIon,fIres,andpatIentInjurIes.
17J,174,175
AlthoughsevofluraneIsnot
flammableat11,formaldehyde,methanol,andformatehavebeenIdentIfIed,
176
and
thesealoneorIncombInatIonwIthoxygenmIghtbeflammableathIghcanIster
temperatures.nexperImentalsettIngs,longexposureof1|ACsevofluranetodesIccated
barIumhydroxIderesultedIncanIstertemperaturesInexcessofJ00`C,whIchcanbe
assocIatedwIthsmolderIng,meltIngofplastIccomponents,explosIons,andfIres.
164
8arIum
hydroxIdehasbeenremovedfromtheU.S.market.
TherearenewerCD
2
absorbentsthatdonotdegradeanesthetIcs(toeIthercompoundAor
carbonmonoxIde),andtheyshouldreduceexothermIcreactIons.FromapatIentsafety
perspectIve,wIdespreadadoptIonofanondestructIveCD
2
absorbentshouldbe
axIomatIc.
177
AlthoughthecostofthesenewCD
2
absorbentsAmsorbPlus(Armstrong
|edIcal,ColeraIne,UK)and0ragerSorbFree(0rager,Lubek,Cermany)IshIgherandthe
absorptIvecapacItymaybelowerthaneItherbarIumhydroxIdelImeorsodalIme,theIr
benefItmaybesubstantIal.TheuseofanondestructIveabsorbentelImInatesallofthe
potentIalcomplIcatIonsrelatedtoanesthetIcbreakdownandthereforemInImIzesthe
possIbIlItyofaddItIonalcostsfromthosecomplIcatIons,IncludIngaddItIonallaboratory
tests,hospItaldays,andmedIcal/legalexpenses.AdoptIonofthesenewabsorbentsInto
routIneclInIcalpractIceIsconsIstentwIththepatIentsafetygoalsofouranesthesIa
socIety.
Generic Sevoflurane Formulations
CenerIcformulatIonsofsevofluranewereIntroducedIntotheclInIcalmarketIn2006.The
methodsforsynthesIzIngsevofluranedIfferbetweenmanufacturers.
178
AlthoughtheactIve
IngredIentofsevofluranefromdIfferentmanufacturersIschemIcallyequIvalent,thewater
contentIntheformulatIonsdIffersandthIsaccountsfortheIrdIfferentresIstanceto
degradatIontohydrogenfluorIdewhenexposedtoaLewIsacId(metalhalIdesandmetal
oxIdesthatarepresentInmoderndayvaporIzers).AddIngwatertotheformulatIonInhIbIts
theactIonofLewIsacIdstodegradesevofluranetohydrogenfluorIde.TheformulatIonof
AbbottLabswaschangedtocontaInJ00to400ppmofwater,basedonanearlyadverse
experIencewIthhydrogenfluorIdeformatIonfromalowwaterformulatIonIn1996.The
generIcformulatIonmarketedby8axterLaboratorIesIslowInwater(-65ppm)andhas
beenshownInclInIcalandlaboratorystudIestodegradetotoxIcandcorrosIvehydrogen
fluorIde.
179
FecentreportsIndIcatethatthePenlonSIgma0eltasevofluranevaporIzercan
degradethe8axterlowwaterformulatIonofsevoflurane,resultIngInetchIngofsIteglass
andcorrosIonoftheplastIconthevaporIzeranddIscoloratIonoftheanesthetIc.
180
WhetherthesedIfferencesInformulatIonleadtopatIentsafetyIssuesremaInstobeseen.
Anesthetic Metabolism
Fluoride-Induced Nephrotoxicity
ThemetabolIsmofenfluranemayresultInawelldescrIbedInjurytorenalcollectIng
tubules.
181,182
ThenephrotoxIcItypresentsasahIghoutputrenalInsuffIcIencythatIs
unresponsIvetovasopressInandIscharacterIzedbydIlutepolyurIa,dehydratIon,serum
hypernatremIa,hyperosmolalIty,elevatedbloodureanItrogen,andcreatInIne.An
assocIatIonbetweenIncreasedplasmafluorIdeconcentratIonsandmetabolIsmledtoa
fluorIdehypothesIs.ThIshypothesIshasbeenreexamInedrecentlyInpartbecause
sevofluraneundergoes5metabolIsmthatresultsIntransIentIncreasesInserumfluorIde
concentratIons,butIthasnotbeenassocIatedwItharenalconcentratIngdefect.The
tradItIonalhypothesIsstatedthatboththeduratIonofthehIghsystemIcfluorIde
concentratIons(areaunderthefluorIdetImecurve)andthepeakfluorIdeconcentratIon
(peaksabove50|appeartorepresentthetoxIcthreshold)wererelatedtonephrotoxIcIty
(FIg.17J1).ThesafetyofsevofluranewIthregardtofluorIdeconcentratIonsmaybethe
resultofarapIddeclIneInplasmafluorIdeconcentratIonsbecauseoflessavaIlabIlItyof
theanesthetIcformetabolIsmfromafasterwashoutcomparedwIthenflurane.
18J
n
addItIon,thesIteofmetabolIsmIsanImportant
P.4J9
factorIntoxIcIty,thatIs,IntrarenalmetabolIsmcontrIbutestonephrotoxIcIty.Therefore,
thepotentIalfortoxIcItyfromrelatIvelyhIghplasmalevelsoffluorIdefollowInglong
exposuretosevofluraneIsoffsetbythemInImalamountofrenaldefluorInatIonandthIs
mayexplaInItsrelatIveabsenceofrenalconcentratIngdefects.
184
Figure 17-31.PlasmaInorganIcfluorIdeconcentratIons(meanSE)beforeandafter2
to4hoursofmethoxyflurane,enflurane,sevoflurane,Isoflurane,anddesflurane
anesthesIa.(AdaptedfromKharaschE0,ArmstrongAS,CunnK,etal:ClInIcal
sevofluranemetabolIsmanddIsposItIon..TheroleofcytochromeP4502E1InfluorIde
andhexafluoroIsopropanolformatIon.AnesthesIology1995;82:1J79;|azzeF:
|etabolIsmoftheInhaledanaesthetIcs:mplIcatIonsofenzymeInductIon.8rJ
Anaesth1984;56:27S;andSuttonTS,KoblIn00,CruenkeL0,etal:FluorIde
metabolItesafterprolongedexposureofvolunteersandpatIentstodesflurane.Anesth
Analg1991;7J:180.)
FactorssuchastotaldoseofanesthetIc,lIverenzymeInductIon,andobesItyhavebeen
proventoenhancebIotransformatIon.TheactIvItyofhepatIccytochromeP450enzymesIs
IncreasedbyavarIetyofdrugs,IncludIngphenobarbItal,phenytoIn,andIsonIazId.DbesIty
causesIncreasedmetabolIsm(defluorInatIon)ofIsoflurane.
185
However,theeffectsof
obesItyonthedefluorInatIonofsevofluranearelessclear.
186
Clinical Utility of Volatile Anesthetics
For Induction of Anesthesia
TheappealofmaskInductIonIntheadultpopulatIoncentersonthepotentIalsafetyand
utIlItyofthIstechnIque.
187,188,189,190
SpontaneousventIlatIonIspreservedwIthagas
InductIonsIncepatIentsessentIallyregulatetheIrowndepthofanesthesIa(toomuch
sevofluranewouldsuppressventIlatIon).TheavaIlabIlItyofsevoflurane,whIchIspotent,
poorlysoluble,andnonpungent,andthereforecanbeInhaledeasIly,hasgenerated
renewedInterestInthIstechnIque.
ClInIcalstudIesIndIcatethatstagetwoexcItatIonIsavoIdedwIthhIghconcentratIonsof
sevoflurane.ThetypIcaltImetolossofconscIousnessIs60secondswhendelIverIng8
sevofluranevIathefacemask.SevofluranealsohasbeenadmInIsteredbymaskasan
approachtothedIffIcultadultaIrwaybecauseItpreservesspontaneousventIlatIonand
doesnotcausesalIvatIon.
191
ThetradItIonalawakelookInthesuspecteddIffIcultaIrway
(whereIntravenousdrugsaretItratedtoalevelthatallowsdIrectlaryngoscopyInthe
awakepatIent)hasbeenmodIfIedtoconsIstofspontaneousventIlatIonofhIgh
concentratIonsofsevofluraneuntIllaryngoscopIcevaluatIonIstolerated.Laryngealmask
placementcanbesuccessfullyachIeved2mInutesafteradmInIsterIng7sevofluranevIa
thefacemask.
189
TheaddItIonofnItrousoxIdetotheInspIredgasmIxturedoesnotadd
sIgnIfIcantlytotheInductIonsequence.ThegasInductIontechnIqueIsImprovedby
pretreatmentwIthbenzodIazepInesandworsenedwIthopIoIdpretreatmentbecauseof
apnea.
188
mportantly,patIentacceptanceofthIstechnIquehasbeenrelatIvelyhIgh,
exceedIng90.
187
ThereareanumberoftechnIquestoadmInIstersevofluranevIafacemask.TheseInclude
prImIngthecIrcuIt(emptyIngtherebreathIngbag,openIngthepopoffvalve,dIalIngthe
vaporIzerto8whIleusIngafreshgasflowof8L/mIn,andmaIntaInIngthIsfor60seconds
prIortoapplyIngthefacemasktothepatIent),asInglebreathInductIonfromend
expIratoryvolumetomaxImumInspIredvolume,orsImplybreathIngwhIlethevaporIzerIs
setto8.AllseemtohavethesuccessfulendresultoflossofconscIousness,generally
wIthIn1mInute.
For Maintenance of Anesthesia
ThevolatIleanesthetIcsareclearlythemostpopulardrugusedtomaIntaInanesthesIa.
TheyareeasIlyadmInIsteredvIaInhalatIon,theyarereadIlytItrated,theyhaveahIgh
safetyratIoIntermsofpreventIngrecall,andthedepthofanesthesIacanbequIckly
adjustedInapredIctablewaywhIlemonItorIngtIssuelevelsvIaendtIdalconcentratIons.
TheyareeffectIveregardlessofageorbodyhabItus.TheyhavesomepropertIesthatprove
benefIcIalIntheoperatIngroom,IncludIngrelaxatIonofskeletalmuscle,preservatIonof
cardIacoutputandcerebralbloodflow,relatIvelypredIctablerecoveryprofIles,andorgan
protectIonfromIschemIcInjury.SomeofthedrawbackstotheuseofthecurrentvolatIle
anesthetIcsaretheIrabsenceofanalgesIceffects,theIrassocIatIonwIthpostoperatIve
nauseaandvomItIng,andtheIrpotentIalforcarbonmonoxIdepoIsonIngandhepatItIs.
Pharmacoeconomics and Value-Based Decisions
nthecurrentenvIronmentofcostcontaInment,clInIcIansareconstantlybeIngpressured
touselessexpensIvedrugs,IncludIngantIemetIcs,neuromuscularblockIngdrugs,and
volatIleanesthetIcs.FactorsInvolvedInthevaluebaseddecIsIonIncludetheeffIcacyof
thedrug,thesIdeeffects,ItsdIrectcosts,andItsIndIrecteffects.ntermsofeffIcacy,all
ofthevolatIleanesthetIcsarereasonablysImIlar;thatIs,theycanbeusedtoestablIsha
stateofanesthesIaforsurgIcalInterventIonsandcanbeeasIlyreversed.AcommonsIde
effectofthevolatIleanesthetIcsIsnauseaandvomItIng.TheneedforrescuemedIcatIons
totreatnauseaandvomItIngaftervolatIleanesthesIaneedstobeconsIderedInany
legItImatecostanalysIs.0IrectcostsarenotsImplythecostpermIllIlIteroflIquIdorcost
perbottleofanesthetIc.Father,theyreflectthecombInatIonofthepotencyofthedrugto
establIsha|AClevel,thefreshgasflow,andthecostoftheanesthetIc.Sevofluraneand
IsofluranearegenerIcproducts,whereasdesfluraneIsstIllunderpatentprotectIon.At1
L/mInfreshgasflow,delIverIng1|AC,
P.440
desflurane,sevoflurane,andIsofluranecostaboutUSS11.00perhour,USS5.00perhour,
andUSS2.00perhour,respectIvely,dependIngonthelocalcostofdrugacquIsItIon.The
IndIrectcostsareprobablythemostdIffIculttopInpoInt,butmaybethemostImportant
whenevaluatIngthecostofusIngthenewvolatIleanesthetIcs.ExamplesofIndIrectcosts
IncludecostsassocIatedwIthoperatIngroomtIme,tImeInthepostanesthesIacareunIt
versusbypassIngthepostanesthesIacareunIttoastepdownunIt,laborcosts,and
outcomerelatedcosts,suchaslItIgatIontodefendabadoutcomefromananesthetIcdrug.
Figure 17-32.TherecoverytImestoorIentatIonafteranesthesIaofvaryIngduratIons.
WIththelesssolubleanesthetIcsevoflurane,thetImetoorIentatIonwasIndependent
oftheanesthetIcduratIon.ncontrast,longanesthetIcduratIonswIthIsofluranewere
assocIatedwIthdelayedtImestoorIentatIon.(AdaptedfromEbertTJ,FobInson8J,
UhrIchT0,etal:FecoveryfromsevofluraneanesthesIa:AcomparIsontoIsoflurane
andpropofolanesthesIa.AnesthesIology1998;89:1524.)
DneoftheargumentsforusIngsevofluraneanddesfluranehasbeentheIrrelatIvespeedIn
termsofemergencefromanesthesIa.ThIsargumenthasbeentemperedsomewhatbythe
basIcknowledgethattItratIonofthevolatIleanesthetIcscanspeedemergencetImes.Even
themoresolubledrug,Isoflurane,canbetItrateddownwardbasedonclInIcalexperIence
orwIththeaIdofprocessedEECmonItors,permIttIngfastwakeupsregardlessofthe
choIceofanesthetIcagent.However,thereIsstrongevIdencetosupporttheuseofthe
lesssoluble(butmoreexpensIve)drugsInthelongestsurgIcalcases(FIg.17J2).
192
nthese
casesthehIghdIrectcostoftheanesthetIcIsbalancedbythemuchImprovedrecovery
profIleIncludIngamorerapIdtImetoemergenceandamorerapIddIschargefromthe
recoveryroom.CurIously,thedIschargeadvantagewIththelowsolubleanesthetIcshas
beendIffIculttoshowaftershortersurgIcalprocedures.
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Stock, M. Christine
TableofContentsSectIon7AnesthetIcAgents,Adjuvants,and0rugnteractIonChapter18ntravenous
AnesthetIcs
Chapter18
Paul F. White
Matthew R. Eng
Key Points
1. With the exception of ketamine, intravenous (IV) anesthetics lack
intrinsic analgesic properties.
2. Dexmedetomidine is an
2
-agonist with sedative and opioid-sparing
effects that is used as an anesthetic adjuvant in the operating room
and intensive care unit.
3. Low doses of IV anesthetics produce sedation, and high doses
produce hypnosis (or unconsciousness).
4. All IV anesthetics are sedative-hypnotics and produce dose-
dependent central nervous system (CNS) depression.
5. Compared to thiopental and propofol, methohexital produces less
CNS depression.
6. Propofol possesses unique antiemetic and appetite-stimulating
properties.
7. Etomidate produces less cardiovascular depression than the
barbiturates and propofol.
8. Ketamine possesses analgesic and psychomimetic properties.
9. Midazolam possesses amnestic and anxiolytic properties.
10. IV anesthetics in combination with potent opioid analgesics and/or
local anesthetics can be used to produce total intravenous
anesthesia.
TheconceptofIntravenous(7)anesthesIahasevolvedfromprImarIlyInductIonofgeneral
anesthesIatototal7anesthesIa(T7A).T7AhasassumedIncreasIngImportancefor
therapeutIc,aswellasdIagnostIc,proceduresInbothadultsandchIldren.7anesthetIc
technIquesareusedforproceduresIntheoperatIngroom(DF)andremotefromtheDF.n
manycentersInEuropeandSouthAmerIca,T7Ahasbecomemorepopularforgeneral
anesthesIathanclassIcbalancedanesthesIaorvolatIleanesthetIcbasedtechnIques.ThIs
changehasbeenaresultof(1)thedevelopmentofrapId,shortactIng7hypnotIc,
analgesIc,andmusclerelaxantdrugs;(2)theavaIlabIlItyofpharmacokInetIcanddynamIc
based7delIverysystems;and(J)thedevelopmentoftheelectroencephalogram(EEC)
basedcerebralmonItorIngdevIces,whIchmeasurethehypnotIccomponentofthe
anesthetIcstate.ThIschapterfocusesonthepharmacologIcpropertIesandclInIcalusesof
thecurrentlyavaIlable7anesthetIcs.
FollowIngItsIntroductIonIntoclInIcalpractIce,thIopentalquIcklybecamethegold
standardof7anesthetIcsagaInstwhIchallthenewer7drugswerecompared.|any
dIfferenthypnotIcdrugsarecurrentlyavaIlableforusedurIng7anesthesIa(FIg.181).
However,ItIsclearthattheIdeal7anesthetIcIsyettobedeveloped.ThephysIcaland
pharmacologIcpropertIesthatanIdeal7anesthetIcwouldpossessIncludethefollowIng:
1. 0rugcompatIbIlIty(watersolubIlIty)andstabIlItyInsolutIon.
2. LackofpaInonInjectIon,venoIrrItatIon,andlocaltIssuedamagefollowIng
extravasatIon.
J. LowpotentIaltoreleasehIstamIneorprecIpItatehypersensItIvItyreactIons.
4. FapIdandsmoothonsetofhypnotIcactIonwIthoutexcItatoryactIvIty.
5. FapIdmetabolIsmtopharmacologIcallyInactIvemetabolItes.
6. AsteepdoseresponserelatIonshIptoenhancetItratabIlItyandmInImIzetIssue
accumulatIon.
7. LackofacutecardIovascularandrespIratorydepressIon.
8. 0ecreasesIncerebralmetabolIsmandIntracranIalpressure.
9. FapIdandsmoothreturnofconscIousnessandcognItIveskIllswIthresIdualanalgesIa.
10. AbsenceofpostoperatIvenauseaandvomItIng,amnesIa,psychomImetIcreactIons,
dIzzIness,headache,orprolongedsedatIon(hangovereffects).
0espItethIopental'sprovenclInIcalusefulness,safety,andwIdespreadacceptanceover
manydecadesofuse,IthasbeensupplantedbyavarIetyofagentsfromdIfferentdrug
groups.ThesedatIvehypnotIcdrugsthathavebeenmorerecentlyIntroducedIntoclInIcal
practIce(e.g.,mIdazolam,ketamIne,etomIdate,propofol)haveproventobeextremely
valuableInspecIfIcclInIcalsItuatIons.ThesenewercompoundscombInemanyofthe
characterIstIcsoftheIdeal7anesthetIc,butfaIlInaspectswheretheotherdrugs
succeed.Forsomeofthese7
P.445
sedatIvehypnotIcs,dIsadvantageshaveledtorestrIctedIndIcatIons(e.g.,ketamIne,
etomIdate).8ecausetheoptImalpharmacologIcpropertIesarenotequallyImportantIn
everyclInIcalsItuatIon,theanesthesIologIstmustmakethechoIceofthe7anesthetIc
drugthatbestfItstheneedsoftheIndIvIdualpatIentandtheoperatIve(ordIagnostIc)
procedure.
Figure 18-1.ChemIcalstructuresofcurrentlyavaIlablenonopIoIdIntravenous
anesthetIcs.
General Pharmacology of Intravenous Hypnotics
Mechanism of Action
AwIdelyacceptedtheoryofanesthetIcactIonIsthatboth7andInhalatIonalanesthetIcs
exerttheIrprImarysedatIveandhypnotIceffectsthroughanInteractIonwIththeInhIbItory
amInobutyrIcacId(CA8A)neurotransmIttersystem.
1
CA8AIstheprIncIpalInhIbItory
neurotransmItterwIthIntheCNS.TheCA8AandadrenergIcneurotransmIttersystems
counterbalancetheactIonofexcItatoryneurotransmItters.TheCA8AtypeA(CA8A
A
)
receptorIsareceptorcomplexconsIstIngofuptofIveglycoproteInsubunIts.Whenthe
CA8A
A
receptorIsactIvated,transmembranechlorIdeconductanceIncreases,resultIngIn
hyperpolarIzatIonofthepostsynaptIccellmembraneandfunctIonalInhIbItIonofthe
postsynaptIcneuron.SedatIvehypnotIcdrugsInteractwIthdIfferentcomponentsofthe
CA8Areceptorcomplex(FIg.182).However,theallosterIc(structural)requIrementsfor
actIvatIonofthereceptoraredIfferentfor7andvolatIleanesthetIcs.
8enzodIazepInesbIndtospecIfIcreceptorsItesthatarepartoftheCA8A
A
receptor
complex.ThebIndIngofbenzodIazepInestotheIrreceptorsIteIncreasestheeffIcIencyof
thecouplIngbetweentheCA8AreceptorandthechlorIdeIonchannel.Thedegreeof
modulatIonoftheCA8AreceptorfunctIonIslImIted,whIchexplaInsthemaxImalceIlIng
effectproducedbybenzodIazepIneswIthrespecttoCNSdepressIon.Thedosedependent
CNSdepressanteffectofbenzodIazepInesproducehypnosIs,sedatIon,anxIolysIs,amnesIa,
andantIconvulsanteffects.
2
TheseCNSeffectsarepresumedtobeassocIatedwIth
stImulatIonofdIfferentreceptorsubtypesand/orconcentratIondependentreceptor
occupancy.
1
Forexample,IthasbeensuggestedthatbenzodIazepInereceptoroccupancy
of20provIdesanxIolysIs,whIleJ0to50receptoroccupancyIsassocIatedwIthamnesIa
tosedatIon,and60receptoroccupancyIsrequIredforhypnosIs(orunconscIousness).
2
TheInteractIonofbarbIturatesandpropofolwIthspecIfIcmembranestructuresappearsto
decreasetherateofdIssocIatIonofCA8AfromItsreceptor,therebyIncreasIngthe
duratIonoftheCA8AactIvatedopenIngofthechlorIdeIonchannel(FIg.182).8arbIturates
canalsomImIctheactIonofCA8AbydIrectlyactIvatIngthechlorIdechannels.The
proposedmechanIsmofactIonofthIopentalrelatestoItsabIlItytofunctIonasa
competItIveInhIbItoratthenIcotInIcacetylcholInereceptorsIntheCNS.
J
EtomIdate
augmentsCA8AgatedchlorIdecurrents(I.e.,IndIrectmodulatIon)andat
P.446
hIgherconcentratIonsevokeschlorIdecurrentsIntheabsenceofCA8A(I.e.,dIrect
actIvatIon).AlthoughthemechanIsmofactIonofpropofolIssImIlartothatofthe
barbIturates(I.e.,enhancIngtheactIvItyoftheCA8AactIvatedchlorIdechannel),Italso
possessesIonchannelblockIngeffectsIncerebralcortextIssueandnIcotInIcacetylcholIne
receptors,aswellasanInhIbItoryeffectonlysophosphatIdatesIgnalIngInlIpIdmedIator
receptors.
4
Figure 18-2. A.ThIsmodeldepIctsthepostsynaptIcsIteofamInobutyrIcacId(CA8A)
andglutamatewIthIntheCNS.CA8AdecreasestheexcItabIlItyofneuronsbyItsactIon
attheCA8A
A
receptorcomplex.WhenCA8AoccupIesthebIndIngsIteofthIscomplex,
ItallowsInwardfluxofchlorIdeIon,resultIngInhyperpolarIzIngofthecelland
subsequentresIstanceoftheneurontostImulatIonbyexcItatorytransmItters.
8arbIturates,benzodIazepInes,propofol,andetomIdatedecreaseneuronalexcItabIlIty
byenhancIngtheeffectofCA8AatthIscomplex,facIlItatIngthIsInhIbItoryeffecton
thepostsynaptIccell.ClutamateandItsanalogNmethyl0aspartate(N|0A)are
excItatoryamInoacIds.WhenglutamateoccupIesthebIndIngsIteontheN|0A
subtypeoftheglutamatereceptor,thechannelopensandallowsNa
+
,K
+
,andCa
2+
to
eItherenterorleavethecell.FluxoftheseIonsleadstodepolarIzatIonofthe
postsynaptIcneuronandInItIatIonofanactIonpotentIalandactIvatIonofother
pathways.KetamIneblocksthIsopenchannelandpreventsfurtherIonflux,thus
InhIbItIngtheexcItatoryresponsetoglutamate.(FeprIntedwIthpermIssIonfrom7an
HemelrIjckJ,ConzalesJ|,WhItePF:UseofIntravenoussedatIveagents,PrIncIples
andPractIceofAnesthesIology.EdItedbyFogers|C,TInkerJH,CovIno8C,
Longnecker0E.St.LouIs,|osby,1992,p11J1.)B.SchematIcmodeloftheCA8A
A
receptorcomplexIllustratIngrecognItIonsItesformanyofthesubstancesthatbIndto
thereceptor.C.|odeloftheN|0AreceptorshowIngsItesforantagonIstactIon.
KetamInebIndstothesItelabeledPCP(phencyclIdIne).ThepentamerIcstructureof
thereceptor,composedofacombInatIonofthesubunItsNF1andNF2,IsIllustrated.
(AlteredwIthpermIssIonfromLeesonT0,versenLL:TheglycInesIteontheN|0A
receptor:StructureactIvItyrelatIonshIpsandtherapeutIcpotentIal.J|edChem1994;
J7:405J.)
KetamIneproducesafunctIonaldIssocIatIonbetweenthethalamocortIcalandlImbIc
systems,astatethathasbeentermeddissociativeanesthesIa.KetamInedepresses
neuronalfunctIonInthecerebralcortexandthalamus,whIlesImultaneouslyactIvatIngthe
lImbIcsystem.KetamIne'seffectonthemedIalmedullaryretIcularformatIonmaybe
InvolvedIntheaffectIvecomponentofItsnocIceptIveactIvIty.TheCNSeffectsof
ketamIneappeartobeprImarIlyrelatedtoItsantagonIstIcactIvItyattheNmethyl0
aspartate(N|0A)receptor(FIg.182).UnlIketheother7anesthetIcs,ketamInedoesnot
InteractwIthCA8Areceptors;however,ItbIndstononN|0Aglutamatereceptorsand
nIcotInIc,muscarInIc,monoamInergIc,andopIoIdreceptors.naddItIon,ItalsoInhIbIts
neuronalsodIumchannels(producIngamodestlocalanesthetIcactIon)andcalcIum
channels(causIngcerebralvasodIlatatIon).
ThecentrallyactIve
2
adrenergIcreceptoragonIsts,clonIdIneanddexmedetomIdIne,
havepotentsedatIveandopIoIdanalgesIcsparIngpropertIes.Thesedrugsalsohave
sIgnIfIcanteffectsontheperIpheral
2
receptorsInvolvedInregulatIngthecardIovascular
systembyInhIbItIngnorepInephrInerelease.ThIsclassofanesthetIcadjuvantscanalso
reducebloodpressureandheartratebydecreasIngthetonIclevelsofsympathetIcoutflow
fromtheCNSandaugmentIngcardIacvagalactIvIty,respectIvely.
5,6
However,
dexmedetomIdInefaIledtoblocktheacutehyperdynamIcresponsetoelectroconvulsIve
therapywhenadmInIsteredasanadjuvanttomethohexItalanesthesIa.
7
EarlIerstudIes
wIthclonIdInedemonstratedthatthIs
2
agonIstantagonIstcould
P.447
alsoreducethe7
8
andvolatIle
9
anesthetIcrequIrements,aswellasthepostoperatIve
opIoIdanalgesIcrequIrement.
Pharmacokinetics and Metabolism
AnunderstandIngofbasIcpharmacokInetIcprIncIplesIsIntegraltotheunderstandIngthe
pharmacologIcactIonsandInteractIonsof7anesthetIcandadjunctIvedrugs,andwIll
allowtheanesthesIologIsttodevelopmoreoptImaldosIngstrategIeswhenusIng7
technIques.AlthoughlIpIdsolubIlItyfacIlItatesdIffusIonof7anesthetIcsacrosscellular
membranes,IncludIngthebloodbraInbarrIer,onlythenonIonIzedformIsabletoreadIly
crossneuronalmembranes.TheratIooftheunIonIzedtoIonIzedfractIondependsonthe
pKaofthedrugandthepHofthebodyfluIds.
TherapIdonsetoftheCNSeffectofmost7anesthetIcscanbeexplaInedbytheIrhIgh
lIpIdsolubIlItyandtherelatIvelyhIghproportIonofthecardIacoutput(20)perfusIngthe
braIn.However,avarIabledegreeofhysteresIsexIstsbetweenthebloodconcentratIonof
thehypnotIcdrugandItsonsetofactIonontheCNS.ThehysteresIsIsrelatedInpartto
dIffusIonofthesedrugsIntobraIntIssueandnonspecIfIcCNSreceptorbIndIng.However,
thenumberofCNSbIndIngsItesIsusuallysaturableandonlyasmallfractIonofthe
avaIlablebIndIngsItesneedstobeoccupIedtoproduceclInIcaleffects.Althoughthetotal
amountofdrugInthebloodIsavaIlablefordIffusIon,thedIffusIonratewIllbemore
lImItedfor7anesthetIcswIthahIghdegreeofplasmaproteInbIndIng(90)becauseonly
thefreeunbounddrugcandIffuseacrossmembranesandexertcentraleffects.When
severaldrugscompeteforthesamebIndIngsItes,orwhentheproteInconcentratIonInthe
bloodIsdecreasedbypreexIstIngdIsease(e.g.,hepatIcfaIlure,malnutrItIon),ahIgher
fractIonoftheunbounddrugwIllbeavaIlabletoexertaneffectontheCNS.SInceonly
unbounddrugIsavaIlableforuptakeandmetabolIsmInthelIver,hIghlyproteInbound
drugsmayhavealowerrateofhepatIcmetabolIsmasaresultoftheIrdecreasedhepatIc
extractIonratIo(I.e.,thefractIonofthehepatIcbloodflowthatIsclearedofthedrug).
ThepharmacokInetIcsof7hypnotIcsarecharacterIzedbyrapIddIstrIbutIonand
subsequentredIstrIbutIonIntoseveralhypothetIcalcompartments(determInedbytheIr
effectonbloodflowtovarIoustIssues),followedbyelImInatIon(Table181).TheInItIal
pharmacologIceffectsarerelatedtotheactIvItyofthedrugInthecentralcompartment.
TheprImarymechanIsmfortermInatIngthecentraleffectsof7anesthetIcsadmInIstered
forInductIonofanesthesIaIsredIstrIbutIonfromthecentralhIghlyperfusedcompartment
(braIn)tothelarger,butlesswellperfusedperIpheralcompartments(muscle,fat).Even
fordrugswIthahIghhepatIcextractIonratIo,elImInatIondoesnotusuallyplayamajor
roleIntermInatIngthedrug'sCNSeffectsbecauseelImInatIonofthedrugcanoccuronly
fromthecentralcompartment.TherateofelImInatIonfromthecentralcompartment,the
amountofdrugpresentIntheperIpheralcompartments,andtherateofredIstrIbutIon
fromtheperIpheralcompartmentsbackIntothecentralcompartmentdetermInethe
tImenecessarytoelImInatethedrugfromthebodyanddIrectlyInfluencerecoverytImes.
|ost7anesthetIcagentsareelImInatedvIahepatIcmetabolIsmfollowedbyrenal
excretIonofmorewatersolublemetabolItes.SomemetabolIteshavepharmacologIc
actIvItyandcanproduceprolongeddrugeffects(e.g.,oxazepam,desmethyldIazepam,
norketamIne).|oreover,thereIsconsIderableInterpatIentvarIabIlItyIntheclearance
ratesforcommonlyused7anesthetIcdrugs.TheelImInatIonclearanceIsthedIstrIbutIon
volumeclearedofdrugovertImeandIsameasureoftheeffIcacyoftheelImInatIon
process.TheslowelImInatIonofsomeanesthetIcsIspartlyduetotheIrhIghdegreeof
proteInbIndIngthatreducestheIrhepatIcextractIonratIo.DtherdrugsmayhaveahIgh
hepatIcextractIonratIoandelImInatIonclearancedespIteextensIveplasmaproteIn
bIndIng(e.g.,propofol),IndIcatIngthatproteInbIndIngIsnotalwaysaratelImItIngfactor.
Formostdrugs,thehepatIcenzymesystemsarenotsaturatedatclInIcallyrelevantdrug
concentratIons,andtherateofdrugelImInatIonwIlldecreaseasanexponentIalfunctIon
ofthedrug'splasmaconcentratIon(fIrstorderkInetIcs).However,whenhIghsteadystate
plasmaconcentratIonsareachIevedwIthprolongedInfusIons,hepatIcenzymesystemscan
becomesaturatedandtheelImInatIonratebecomesIndependentofthedrugconcentratIon
(zeroorderkInetIcs).TheelImInatIonhalflIfe(t
1/2
)IsthetImerequIredforthe
anesthetIcconcentratIontodecreaseby50durIngthetermInalphaseoftheplasmadecay
curve.Thet
1/2
dependsonthevolumetobecleared(thedIstrIbutIonvolume)andthe
effIcIencyofthemetabolIcclearancesystem.8ecausetheIrvolumesofdIstrIbutIonare
sImIlar,thewIdevarIatIonInelImInatIonhalflIfevaluesforthe7anesthetIcsIsa
reflectIonofdIfferencesIntheIrclearancevalues.
WhenadrugInfusIonIsadmInIsteredwIthoutaloadIngdose,atleastJtImesthet
1/2
valuemayberequIredtoachIeveatruesteadystateplasmaconcentratIon.Thesteady
stateconcentratIonobtaIneddurIngananesthetIcInfusIondependsontherateofdrug
admInIstratIonandItsclearancerate.WhenanInfusIonIsdIscontInued,therateatwhIch
theplasmaconcentratIon
P.448
decreaseslargelydependsontheclearancerate(asreflectedbythetermInalt
1/2
value).
FordrugswIthshorterelImInatIonhalflIves,plasmaconcentratIonwIlldecreaseatarate
thatallowsforamorerapIdrecovery(e.g.,propofol).0rugswIthlongt
1/2
values(e.g.,
thIopentalanddIazepam)areusuallyonlyadmInIsteredbycontInuous7InfusIonwhenthe
medIcalcondItIonrequIreslongtermtreatment(e.g.,elevatedIntracranIalpressure[CP]
asaresultofbraInInjuryorprolongedsedatIonIntheIntensIvecareunIt[CU]becauseof
respIratoryfaIlure).
Table 18-1 Pharmacokinetic Values for the Currently Available
Intravenous Sedative-Hypnotic Drugs
DRUG NAME
DISTRIBUTION
HALF-LIFE
PROTEIN
BINDING
DISTRIBUTION VOLUME
AT STEADY STATE
CLEARANCE
ELIMINATION
HALF-LIFE
(min) (%) (L/kg) (mL/kg/min) (hr)
ThIopental 24 85 2.5 J.4 11
|ethohexItal 56 85 2.2 11 4
Propofol 24 98 210 20J0 42J
|Idazolam 715 94 1.11.7 6.411 1.72.6
0Iazepam 1015 98 0.71.7 0.20.5 2050
Lorazepam J10 98 0.81.J 0.81.8 1122
EtomIdate 24 75 2.54.5 1825 2.95.J
KetamIne 1116 12 2.5J.5 1217 24
FromWhItePF.TextbookofntravenousAnesthesIa.8altImore,WIllIamsEWIlkIns,
1997,pp.27and77.
CarefultItratIonofananesthetIcdrugtoachIevethedesIredclInIcaleffectIsnecessaryto
avoIddrugaccumulatIonandtheresultantprolongedCNSeffectsaftertheInfusIonhas
beendIscontInued.Althoughthevalueofthet
1/2
IndIcateshowfastadrugIselImInated
fromthebody,amoreusefulIndIcatoroftheacceptabIlItyofahypnotIcInfusIonfor
maIntenanceofanesthesIaorsedatIonIsthecontextsensItIvehalftIme,avaluederIved
fromcomputersImulatIonsofdrugInfusIons.
10
ThecontextsensItIvehalftImeIsdefInedas
thetImenecessaryfortheeffectcompartment(I.e.,effectsIte)concentratIontodecrease
by50InrelatIontotheduratIonoftheInfusIon.ThecontextsensItIvehalftImebecomes
partIcularlyImportantIndetermInIngrecoveryafterprolongedInfusIonsofsedatIve
hypnotIcdrugs.0rugs(e.g.,propofol)mayhavearelatIvelyshortcontextsensItIvehalf
tImedespItethefactthatalargeamountofdrugremaInspresentInthedeep(lesswell
perfused)compartment.TheslowreturnoftheanesthetIcfromthedeepcompartment
contrIbuteslIttletotheconcentratIonofdrugInthecentralcompartmentfromwhIchItIs
rapIdlycleared.Therefore,theconcentratIonInthecentralcompartmentrapIdlydeclInes
belowthehypnotIcthresholdafterdIscontInuatIonoftheInfusIon,contrIbutIngtoshort
emergencetImesdespItethefactthatasubstantIalquantItyofanesthetIcdrugmay
remaInInthebody.
|arkedInterpatIentvarIabIlItyexIstsInthepharmacokInetIcsof7sedatIvehypnotIc
drugs.FactorsthatcanInfluenceanesthetIcdrugdIsposItIonIncludethedegreeofproteIn
bIndIng,theeffIcIencyofhepatIcandrenalelImInatIonprocesses,physIologIcchangeswIth
agIng,preexIstIngdIseasestates,theoperatIvesIte,bodytemperature,anddrug
InteractIons(e.g.,coadmInIstratIonofvolatIleanesthetIcs).Forexample,Increasedage,
leanbody(muscle)mass,andtotalbodywaterdecreaseresultInanIncreaseInthesteady
statevolumeofdIstrIbutIonofmost7anesthetIcs.TheIncreaseddIstrIbutIonvolumeand
decreasedhepatIcclearanceleadstoaprolongatIonoftheIrt
1/2
values.|oreover,a
decreaseofthevolumeofthecentralcompartmentmayresultInhIgherInItIaldrug
concentratIonsandcanatleastpartIallyexplaInthedecreasedInductIonrequIrementIn
theelderly.AddItIonally,theslowerredIstrIbutIonfromthevesselrIchtIssuesto
IntermedIatecompartments(muscles)alsocontrIbutestotheagerelateddecreaseInthe
InductIondoserequIrements.
10
AlthoughprolongatIonoftheelImInatIonhalftImedoesnot
provIdeanexplanatIonforthedecreasedInductIondoserequIrement,ItIsresponsIblefor
producInghIghersteadystateplasmaconcentratIonsatanygIvenInfusIonrate,
contrIbutIngtoaslowerrecoveryfromthesubhypnotes(resIdualeffects).
ThehepatIcclearanceof7anesthetIcswIthahIgh(e.g.,etomIdate,propofol,ketamIne)
orIntermedIate(e.g.,methohexItal,mIdazolam)extractIonratIolargelydependson
hepatIcbloodflow,wIthmostofthedrugbeIngremovedfromthebloodasItflowsthrough
thelIver(socalledperfusIonlImItedclearance).TheelImInatIonrateofdrugswIthlow
hepatIcextractIonratIos(e.g.,thIopental,dIazepam,lorazepam)dependsonthe
enzymatIcactIvItyofthelIverandIslessdependentofhepatIcbloodflow(socalled
capacItylImItedclearance).HepatIcbloodflowdecreasesdurIngupperabdomInaland
laparoscopIcsurgeryand,asaresult,hIgherbloodlevelsofdrugswIthperfusIonlImIted
clearanceareachIevedatanygIvenInfusIonrate.WIthagIng,adecreasedcardIacoutput
andaredIstrIbutIonofbloodflowcanpartlyexplaInthelowerclearanceratefordrugs
wIthperfusIonlImItedclearance.AlthoughconcomItantadmInIstratIonofvolatIle
anesthetIcs(whIchareknowntodecreaselIverbloodflow)haslIttleInfluenceonthe
elImInatIonofthIopental,theycandecreasetheclearanceofetomIdate,ketamIne,
methohexItal,andpropofol.DtherfactorsthatdecreasehepatIcbloodflowInclude
hypocapnIa,congestIveheartfaIlure,IntravascularvolumedepletIon,acutealcohol
IntoxIcatIon,cIrculatorycollapse,IncreaseIntraabdomInalpressure,adrenergIc
blockade,andnorepInephrIneadmInIstratIon.
HepatIcdIseasecanInfluencethepharmacokInetIcsofdrugsby(1)alterIngtheplasma
proteIncontentandchangIngthedegreeofproteInbIndIng,(2)decreasInghepatIcblood
flowandproducIngIntrahepatIcshuntIng,and(J)depressIngthemetabolIcenzymatIc
actIvItyofthelIver.Therefore,theInfluenceofhepatIcdIseaseonpharmacokInetIcsand
dynamIcsof7anesthetIcsIsdIffIculttopredIct.FenaldIseasecanalsoalterthe
concentratIonofplasmaandtIssueproteIns,aswellasthedegreeofproteInbIndIng,
therebyproducIngchangesInfreedrugconcentratIons.8ecause7anesthetIcagentsare
prImarIlymetabolIzedbythelIver,renalInsuffIcIencyhaslIttleInfluenceontheIrrateof
metabolIcInactIvatIonorelImInatIonoftheprImarycompound.
Pharmacodynamic Effects
TheprIncIpalpharmacologIceffectof7anesthetIcsIstoproduceprogressIvelyIncreasIng
sedatIonandultImatelyhypnosIsasaresultofdosedependentCNSdepressIon.However,
allsedatIvehypnotIcsalsodIrectlyorIndIrectlyaffectothermajororgansystems.The
relatIonshIpbetweenthedoseofasedatIvehypnotIcandItsCNSeffectscanbedefInedby
doseresponsecurves.Althoughmost7anesthetIcsarecharacterIzedbysteepdose
responsecurves,theyarenotalwaysparallel(FIg.18J).However,thecharacterIstIcsofa
doseresponse
P.449
curvecanonlybeInterpretedInrelatIontothespecIfIcresponseforwhIchItwas
constructed.
Figure 18-3.0oseresponserelatIonshIpsforsedatIonwIthmIdazolam()and
dIazepam().ThelevelofsedatIon(2=awakeandalertto6=asleepand
unarousable)wasassessed5mInutesafterbolusdosesofmIdazolam(0.05,0.1,or0.15
mg/kg)ordIazepam(0.1,0.2,or0.Jmg/kg).7aluesrepresentmeanvaluesSE|.
(FeprIntedwIthpermIssIonfromWhItePF,7asconesLD,|athesSA,etal:ComparIson
ofmIdazolamanddIazepamforsedatIondurIngplastIcsurgery.JPlastFeconstruct
Surg1988;81:70J.)
Figure 18-4.TheconcentratIonofthIopentalversustImeandspectraledgeInan
elderlypatIent(top)andInayoungerpatIent(bottom).Solid horizontal barsrepresent
thelengthofthIopentalInfusIon.Filled circlesrepresentthemeasuredthIopental
concentratIon(lInearscale),andthesolid linenexttothemrepresentsthefItteddata
fromthepharmacokInetIcmodel.TheaxIsforspectraledgehasbeenInvertedfor
vIsualclarIty.(FeprIntedwIthpermIssIonfromHomerT0,StanskI0F:Theeffectof
IncreasIngageonthIopentaldIsposItIonandanesthetIcrequIrement.AnesthesIology
1985;62:714.)
WhensteadystateplasmaconcentratIonsareachIeved,onecanassumethattheplasma
concentratIonIsInquasIequIlIbrIumwIththeeffectsIteconcentratIon.Underthese
cIrcumstances,ItIspossIbletodescrIbetherelatIonshIpbetweendrugandeffectusInga
concentratIoneffectcurve(FIg.184).8ecauseofthepharmacodynamIcvarIabIlItythat
exIstsamongIndIvIduals,theplasmadrugconcentratIonnecessarytoobtaInapartIcular
effectIsoftendescrIbedIntermsofaneffectIveconcentratIonrange,thesocalled
therapeutIcwIndow.EffIcacyofan7anesthetIcrelatestothemaxImumeffectthatcan
beachIevedwIthrespecttosomemeasureofCNSfunctIon.0ependIngonthedrugeffect
underconsIderatIon,theeffIcacyofsedatIvehypnotIcsmayappeartobe100.For
example,ItIsvIrtuallyImpossIbletoproduceaburstsuppressIveEECpatternwItha
benzodIazepIne.Potency,ontheotherhand,relatestothequantItyofdrugnecessaryto
obtaInthemaxImumCNSeffect.TherelatIvepotencyofsedatIvehypnotIcsalsovarIes
dependIngontheendpoIntchosen.nthepresenceofanantagonIstdrug(e.g.,
flumazenIl),themaxImalresponsethatcanbeobtaInedwIthabenzodIazepIneagonIstIs
furtherreducedbecauseofcompetItIonforthesameCNSreceptorbIndIngsItes.
TheInfluenceofsedatIvehypnotIcsoncerebralmetabolIsm,cerebralhemodynamIcs,and
CPIsofpartIcularImportancedurIngneuroanesthesIa.npatIentswIthreducedcerebral
complIance,asmallIncreaseIncerebralbloodvolumecancausealIfethreatenIng
IncreaseInCP.|ostsedatIvehypnotIcdrugscauseaproportIonalreductIonIncerebral
metabolIsm(C|FD
2
)andcerebralbloodflow(C8F),resultIngInadecreaseInCP.Although
adecreaseInC|FD
2
probablyprovIdesonlyamodestdegreeofprotectIonagaInstCNS
IschemIaorhypoxIa,somehypnotIcsappeartopossesscerebroprotectIvepotentIal(e.g.,
thIopental,propofol).ExplanatIonsfortheallegedneuroprotectIveeffectsofthese
compoundsIncludeabIochemIcalroleasfreeradIcalscavengersandmembranestabIlIzers
(barbIturatesandpropofol)orN|0AreceptorantagonIsts(ketamIne).WIththeexceptIon
ofketamIne,allsedatIvehypnotIcsalsolowerIntraocularpressure.ThechangesIn
Intraocularpressuregenerallyreflecttheeffectsofthe7agentonsystemIcarterIal
pressureandIntracranIalhemodynamIcs.However,noneoftheavaIlablesedatIvehypnotIc
drugsprotectagaInstthetransIentIncreaseInIntraocularpressurethatoccurswIth
laryngoscopyandtrachealIntubatIon.
|ost7hypnotIcshavesImIlarEECeffects.ActIvatIonofhIghfrequencyEECactIvIty(15to
J0Hz)IscharacterIstIcoflowconcentratIons(socalledsedatIvedoses)of7anesthetIcs.
AthIgherconcentratIons,anIncreaseIntherelatIvecontrIbutIonofthelowerfrequency
hIgheramplItudewavesIsobserved.AthIghconcentratIons,aburstsuppressIvepattern
developswIthanIncreaseIntheIsoelectrIcperIods.|ostsedatIvehypnotIcdrugshave
beenreportedtocauseoccasIonalEECseIzurelIkeactIvIty.nterestIngly,thesesamedrugs
alsopossessantIconvulsantpropertIes.
11,12
WhenconsIderIngpossIbleepIleptogenIc
propertIesofCNSdepressantdrugs,ItIsImportanttodIfferentIatebetweentrue
epIleptogenIcactIvIty(e.g.,methohexItal)andmyoclonIclIkephenomena(e.g.,
etomIdate,ketamIne,propofol).|yoclonIcactIvItyIsgenerallyconsIderedtobetheresult
ofanImbalancebetweenexcItatoryandInhIbItorysubcortIcalcenters,producedbyan
unequaldegreeofsuppressIonofthesebraIncentersbylowconcentratIonsofhypnotIc
drugs.EpIleptIcactIvItyreferstoasuddenalteratIonInCNSseIzurelIkeactIvItyresultIng
fromahIghvoltageelectrIcaldIschargeateIthercortIcalorsubcortIcalsItes,wIth
subsequentspreadIngtothethalamIcandbraInstemcenters.AsaresultofIts
vasoconstrIctIveeffectsonthecerebralvasculature,propofolmaybeusefulfortreatment
ofIntractablemIgraIneheadaches.
1J
AlthoughsomeInductIondrugscanIncreaseaIrwaysensItIvIty,coughIngandaIrway
IrrItatIon(e.g.,bronchospasm)areusuallyaresultofmanIpulatIonoftheaIrwaydurIng
lIght(Inadequate)levelsof7anesthesIaratherthantoadIrectdrugeffect.WIththe
exceptIonofketamIne(andtoalesserextent,etomIdate),7anesthetIcsproducedose
dependentrespIratorydepressIon,whIchIsenhancedInpatIentswIthchronIcobstructIve
pulmonarydIsease.TherespIratorydepressIonIscharacterIzedbyadecreaseIntIdal
volumeandmInuteventIlatIon,aswellasatransIentrIghtwardshIftIntheCD
2
response
curve.FollowIngtherapIdInjectIonofalargebolusdoseofan7anesthetIc,transIent
apnealastIngJ0to90secondsIsusuallyproduced.KetamInecausesmInImalrespIratory
depressIonwhenadmInIsteredIntheusualInductIondoses,whIleetomIdateIsassocIated
wIthlessrespIratorydepressanteffectsthanthebarbIturatecompoundsorpropofol.The
2
agonIstdexmedetomIdInehasmInImaldepressanteffectsonrespIratoryfunctIon.
14
The
sympatholytIceffectsofdexmedetomIdInewhenadmInIsteredforpremedIcatIonmay
IncreasetheIncIdenceofIntraoperatIvehypotensIonandbradycardIa.
15
|anydIfferentfactorscontrIbutetothehemodynamIcchangesassocIatedwIth7InductIon
ofanesthesIa,IncludIngthepatIent'spreexIstIngcardIovascularandfluIdstatus,restIng
sympathetIcnervoussystemtone,chronIccardIovasculardrugs,preanesthetIcmedIcatIon,
thespeedofdrugInjectIon,andtheonsetofunconscIousness.naddItIon,cardIovascular
changescanbeattrIbutedtothedIrectpharmacologIcactIonsofanesthetIcandanalgesIc
drugsonthe
P.450
heartandperIpheralvasculature.7anesthetIcscandepresstheCNSandperIpheral
nervoussystemresponses,bluntthecompensatorybaroreceptorreflexmechanIsms,
producedIrectmyocardIaldepressIon,andlowerperIpheralvascularresIstance(and/or
dIlatevenouscapacItancevessels),therebydecreasIngvenousreturn.Profound
hemodynamIceffectsoccuratInductIonofanesthesIaInthepresenceofhypovolemIa
becauseahIgherthanexpecteddrugconcentratIonIsachIevedInthecentral
compartment.NotsurprIsIngly,theacutecardIocIrculatorydepressanteffectsofall7
anesthetIcsareaccentuatedIntheelderly,aswellasInthepresenceofpreexIstIng
cardIovasculardIsease(e.g.,coronaryarterydIsease,hypertensIon).
Theeffectsof7anesthetIcsonneuroendocrInefunctIonarealsoInfluencedbythesurgIcal
stImulI.SurgeryInducedIncreasesInstresshormones(e.g.,vasopressIn,catecholamInes)
canresultInIncreasedperIpheralvascularresIstance,andareductIonofurIneoutput.
SImIlarly,glucosetoleranceappearstobedecreasedbysurgIcalstress,resultIngIn
elevatIonsIntheglucoseconcentratIon.UnlIkeketamIneanddexmedetomIdIne,most7
sedatIvehypnotIcdrugslackIntrInsIcanalgesIcactIvIty.nfact,thIopentalhasbeen
allegedtopossesssocalledantIanalgesIcactIvIty(I.e.,appearIngtolowerthepaIn
threshold).AlthoughpropofolpossessesdosedependenteffectsonthalamocortIcaltransfer
ofnocIceptIveInformatIon,paInevokedcortIcalactIvItyremaInsIntactafterlossof
conscIousness.
16
Hypersensitivity (Allergic) Reactions
AllergIcorhypersensItIvItytypereactIonsto7anesthetIcsarerarebutcanbesevereand
evenlIfethreatenIng.7drugadmInIstratIonbypassesthenormalprotectIvebarrIers
agaInstentranceofforeIgnmoleculesIntothebody.WIththeexceptIonofetomIdate,all
7InductIonagentshavebeenallegedtocausesomehIstamInerelease.However,the
IncIdenceofsevereanaphylactIcreactIonsIsextremelylowwIththecurrentlyavaIlable7
InductIonagents.ThehIghfrequencyofallergIcreactIonstotheCremophorELcontaInIng
formulatIonsledtotheearlywIthdrawalof7anesthetIcscontaInIngthIssolubIlIzIngagent
(e.g.,propofolEL,propanIdId,AlphadIone[AlthesIn]).ThepossIblemechanIsmsfor
ImmunologIcreactIonsInclude(1)dIrectactIononmastcells,(2)classIccomplement
actIvatIonafterprevIousexposureandantIbodyformatIon,(J)complementactIvatIon
throughthealternatIvepathwaywIthoutprevIousantIgenexposure,(4)antIgenantIbody
reactIons,and(5)themIxedtypeofanaphylactoIdreactIons.
SevereanaphylactIcreactIonsto7anesthetIcsareextremelyuncommon;however,
profoundhypotensIonattrIbutedtononImmunologIcallymedIatedhIstamInereleasehas
beenreportedwIththIopentaluse.AlthoughanaphylactIcreactIonstoetomIdatehave
beenreported,ItdoesnotappeartoreleasehIstamIne,andIsconsIderedtobethemost
ImmunologIcallysafe7anesthetIc.PropofoldoesnotnormallytrIggerhIstamInerelease,
butlIfethreatenInganaphylactoIdreactIonshavebeenreportedInpatIentswItha
prevIoushIstoryofmultIpledrugallergIes.8arbIturatescanalsoprecIpItateepIsodesof
acuteIntermIttentporphyrIaandtheIruseIscontraIndIcatedInpatIentswhoare
predIsposedtoacuteIntermIttentporphyrIa.AlthoughbenzodIazepInes,ketamIne,and
etomIdatearereportedtobesafeInhumans,thesedrugshavebeenshowntobe
porphyrogenIcInanImalmodels.ThemostcommoncauseofprofoundhypotensIon
followIng7InductIonofanesthesIaIsthatofdrugInteractIonsand/orunrecognIzed
hypovolemIa.
Comparative Physicochemical and Clinical Pharmacologic
Properties of Intravenous Agents
Barbiturates
ThemostcommonlyusedbarbIturatesarethIopental(5ethyl5[1methylbutyl]2
thIobarbIturIcacId),methohexItal(1methyl5allyl5[1methyl2pentanyl]barbIturIc
acId),andthIamylal(5allyl5[1methylbutyl]2thIobarbIturIcacId).ThIopental(Pentothal)
andthIamylal(SurItal)arethIobarbIturates,whIlemethohexItal(8revItal)Isan
oxybarbIturate.ThIamylalIsslIghtlymorepotentthanthIopentalbuthasasImIlar
pharmacologIcprofIle.AlthoughthelIsomersofthIopentalandthIamylalaretwIceas
potentasthedIsomers,bothhypnotIcsarecommercIallyavaIlableasracemIcmIxtures.
8ecausemethohexItalhastwoasymmetrIccenters,IthasfourstereoIsomers.Thel
IsomerIs4to5tImesmorepotentthanthelIsomer,butItproducesexcessIvemotor
responses.Therefore,methohexItalIsmarketedastheracemIcmIxtureofthetwo
Isomers.
AllthreebarbIturatesareavaIlableassodIumsaltsandmustbedIssolvedInIsotonIc
sodIumchlorIde(0.9)orwatertopreparesolutIonsof2.5thIopental,1to2
methohexItal,and2thIamylal.frefrIgerated,solutIonsofthethIobarbIturatesarestable
forupto2weeks.SolutIonsofmethohexItalarestableforupto6weeks.When
barbIturatesareaddedtoFIngerlactateoranacIdIcsolutIoncontaInIngotherwater
solubledrugs,precIpItatIonwIlloccurandcanoccludethe7catheter.Althoughthe
typIcalsolutIonofthIopental(2.5)IshIghlyalkalIne(pH9)andcanbeIrrItatIngtothe
tIssuesIfInjectedextravenously,ItdoesnotcausepaInonInjectIonandvenoIrrItatIonIs
rare.ncontrast,a1methohexItalsolutIonfrequentlycausesdIscomfortwhenInjected
IntosmallveIns.ntraarterIalInjectIonofthIobarbIturatesIsaserIouscomplIcatIonas
crystalscanformInthearterIolesandcapIllarIes,causIngIntensevasoconstrIctIon,
thrombosIs,andeventIssuenecrosIs.AccIdentalIntraarterIalInjectIonsshouldbetreated
promptlywIthIntraarterIaladmInIstratIonofpapaverIneandlIdocaIne(orprocaIne),as
wellasaregIonalanesthesIaInducedsympathectomy(stellateganglIonblock,brachIal
plexusblock)andheparInIzatIon.
ThIopentalIsmetabolIzedInthelIvertohydroxythIopentalandthecarboxylIcacId
derIvatIve,whIcharemorewatersolubleandhavelIttleCNSactIvIty.WhenhIghdosesof
thIopentalareadmInIstered,adesulfuratIonreactIoncanoccurwIththeproductIonof
pentobarbItal,whIchhaslonglastIngCNSdepressantactIvIty.ThelowelImInatIon
clearanceofthIopental(J.4mL/kg/mIn)contrIbutestoalongelImInatIonhalflIfe(t
1/2
of
11hours).PreexIstInghepatIcandrenaldIseaseresultIndecreasedplasmaproteIn
bIndIng,therebyIncreasIngthefreefractIonofthIopentalandenhancIngItsCNSand
cardIovasculardepressantpropertIes.0urIngprolongedcontInuousadmInIstratIonof
thIopental,theconcentratIonInthetIssuesapproachestheconcentratIonInthecentral
compartment,wIthtermInatIonofItsCNSeffectsbecomIngsolelydependenton
elImInatIonbynonlInearhepatIcmetabolIsm.|ethohexItalIsmetabolIzedInthelIverto
InactIvehydroxyderIvatIves.TheclearanceofmethohexItal(11mL/kg/mIn)IshIgherand
moredependentonhepatIcbloodflowthanthIopental,resultIngInashorterelImInatIon
halflIfe(t
1/2
4hours).
TheusualInductIondoseofthIopentalIsJto5mg/kgInadults,5to6mg/kgInchIldren,
and6to8mg/kgInInfants.8ecausemethohexItalIsapproxImately2.7tImesmorepotent
thanthIopental,adoseof1.5mg/kgIsequIvalentto4mg/kg
P.451
ofthIopentalInadults.ThedoseofbarbIturatesnecessarytoInduceanesthesIaIsreduced
InpremedIcatedpatIents,patIentsInearlypregnancy(7to1Jweeks'gestatIon),andthose
ofmoreadvancedAmerIcanSocIetyofAnesthesIologIstsphysIcalstatus(or7).CerIatrIc
patIentsrequIreaJ0to40reductIonIntheusualadultdosebecauseofadecreaseofthe
volumeofthecentralcompartmentandslowedredIstrIbutIonofthIopentalfromthe
vesselrIchtIssuestoleanmuscle.
17
WhenthecalculatIonoftheInductIondoseIsbasedon
theleanbodymassratherthantotalbodyweIght,dosageadjustmentsforage,sex,or
obesItyarenotnecessary.ThIopentalInfusIonIsseldomusedtomaIntaInanesthesIa
becauseofthelongcontextsensItIvehalftImeandprolongedrecoveryperIod.Plasma
thIopentallevelsnecessarytomaIntaInahypnotIcstaterangebetween10and20mg/mL.
AtypIcalInfusIonratenecessarytotreatIntracranIalhypertensIonorIntractable
convulsIonsIs2to4mg/kg/hr.TheplasmaconcentratIonofmethohexItalneededto
maIntaInhypnosIsdurInganesthesIarangesbetweenJand5mg/mLandcanbeachIeved
wIthanInfusIonrateof50to120mg/kg/mIn.
8arbIturatesproduceaproportIonaldecreaseInC|FD
2
andC8F,therebylowerIngCP.The
maxImaldecreaseInC|FD
2
(55)occurswhentheEECbecomesIsoelectrIc(burst
suppressIvepattern).AnIsoelectrIcEECcanbemaIntaInedwIthathIopentalInfusIonrate
of4to6mg/kg/hr(resultIngInplasmaconcentratIonsofJ0to50g/mL).8ecausethe
decreaseInsystemIcarterIalpressureIsusuallylessthanthereductIonInCP,thIopental
shouldImprovecerebralperfusIonandcomplIance.Therefore,thIopentalIswIdelyusedto
ImprovebraInrelaxatIondurIngneurosurgeryandtoImprovecerebralperfusIonpressure
(CPP)afteracutebraInInjury.AlthoughbarbIturatetherapyIswIdelyusedtocontrolCP
afterbraInInjury,theresultsofoutcomestudIesarenobetterthanwIthotheraggressIve
formsofcerebralantIhypertensIvetherapy.
thasbeensuggestedthatbarbIturatesalsopossessneuroprotectIvepropertIes
secondarytotheIrabIlItytodecreaseoxygendemand.AlternatIveexplanatIonshavebeen
suggested,IncludIngareversesteal(FobInHoodeffect)onC8F,freeradIcalscavengIng,
stabIlIzatIonoflIposomalmembranes,aswellasexcItatoryamInoacIdreceptorblockade.
8asedonevIdencefromexperImentalstudIesandalargerandomIzedprospectIvemultI
InstItutIonalstudy,
18
expertshaveconcludedthatbarbIturateshavenoplaceInthe
therapyfollowIngresuscItatIonofacardIacarrestpatIent.ncontrast,barbIturatesare
frequentlyusedforcerebroprotectIondurIngIncompletebraInIschemIa(e.g.,carotId
endarterectomy,temporaryocclusIonofcerebralarterIes,profoundhypotensIon,and
cardIopulmonarybypass).8yImprovIngthebraIn'stoleranceofIncompleteIschemIaIn
patIentsundergoIngopenheartsurgerywIthcardIopulmonarybypass,barbIturateswere
allegedtodecreasetheIncIdenceofpostbypassneuropsychIatrIcdIsorders.
19
However,
durIngvalvularopenheartcardIacsurgery,aprotectIveeffectofbarbIturateloadIngcould
notbedemonstrated.
20
CIventhelackademonstrableneuroprotectIveeffect,useof
barbIturatesdurIngcardIacsurgeryIsnotrecommended.Useofmoderatedegreesof
hypothermIa(JJtoJ4`C)mIghtprovIdesuperIorneuroprotectIontothebarbIturates
wIthoutprolongIngrecovery.
8arbIturatescausepredIctable,dosedependentEECchangesandpossesspotent
antIconvulsantactIvIty.ContInuousInfusIonsofthIopentalhavebeenusedtotreat
refractorystatusepIleptIcus.However,lowdosesofthIopentalmayInducespIkewave
actIvItyInepIleptIcpatIents.|ethohexItalhaswellestablIshedepIleptogenIceffectsIn
patIentswIthpsychomotorepIlepsy.LowdosemethohexItalInfusIonsarefrequentlyused
toactIvatecortIcalEECseIzuredIschargesInpatIentswIthtemporallobeepIlepsy.tIs
alsothe7anesthetIcofchoIceforelectroconvulsIvetherapy.
21
SIncethefrequencyof
epIleptIformEECactIvItydurIngInductIonofanesthesIawIthmethohexItalIssIgnIfIcantly
lessthanthatwhIchoccursdurIngnormalperIodsofsleepInepIleptIcpatIents,thIs
suggeststhathIgherdosesofmethohexItalproducesantIconvulsantactIvIty.|ethohexItal
alsocausesmyoclonIclIkemuscletremorsandothersIgnsofexcItatoryactIvIty(e.g.,
hIccoughIng).
8arbIturatescausedosedependentrespIratorydepressIon.
22
However,bronchospasmor
laryngospasmfollowIngInductIonwIththIopentalIsusuallytheresultofaIrway
manIpulatIonInlIghtlyanesthetIzedpatIents.Laryngealreflexesappeartobemore
actIveafterInductIonwIththIopentalthanwIthpropofol.ThecardIovasculareffectsof
thIopentalandmethohexItalIncludedecreasesIncardIacoutput,systemIcarterIal
pressure,andperIpheralvascularresIstance.ThedepressanteffectsofthIopentalon
cardIacoutputareprImarIlyaresultofadecreaseInvenousreturncausedbyperIpheral
poolIng,aswellasaresultofadIrectmyocardIaldepressanteffect,whIchassumes
IncreasIngImportanceInthepresenceofhypovolemIaandmyocardIaldIsease.
2J
Useof
approprIatedosescanmInImIzethecardIodepressanteffectsofthIopental,evenInInfants.
8hutadaetal.
24
demonstratedthatthIopentalcouldbeusedforInductIonInInfants
wIthoutImportantchangesInheartrateandbloodpressuredurIngtheIntubatIonperIod.
AnequIpotentdoseofmethohexItalproducesevenlesshypotensIonthanthIopental
becauseofagreatertachycardIcresponsetothebloodpressurelowerIngeffectsofthe
drug.fthebloodpressureremaInsstable,themyocardIaloxygendemand/supplyratIo
remaInsnormaldespItetheIncreaseInheartratebecauseofaconcurrentdecreaseIn
coronaryvascularresIstance.
Propofol
Propofol(2,6dIsopropylphenol),analkylphenolcompound,IsvIrtuallyInsolubleInaqueous
solutIon.TheInItIalCremophorELformulatIonofpropofolwaswIthdrawnfromclInIcal
testIngbecauseofthehIghIncIdenceofanaphylactIcreactIons.Subsequently,propofol(10
mg/mL)wasreIntroducedasanegglecIthInemulsIonformulatIon(0IprIvan),consIstIngof
10soybeanoIl,2.25glycerol,and1.2eggphosphatIde.PaInonInjectIonoccursInJ2to
67ofpatIentswhenInjectedIntosmallhandveInsbutcanbemInImIzedbyInjectIonInto
largerveInsandbyprIoradmInIstratIonofeItherlIdocaIneorapotentopIoIdanalgesIc
(e.g.,fentanylorremIfentanIl).AwIdevarIetyofdrugshavebeenallegedtoreducepaIn
onInjectIonofpropofol(e.g.,metoprolol,
25
granIsetron,
26
dolasetron,
27
andeven
thIopental
28
).0IlutIngtheformulatIonwIthaddItIonalsolvent(ntralIpId)orchangIngthe
lIpIdcarrIer(LIpofundIn)alsoreducedpropofolInducedInjectIonpaIn,probablybecauseof
adecreaseIntheconcentratIonoffreepropofolIntheaqueousphaseoftheemulsIon.A
newpropofolformulatIonwIthsodIummetabIsulphIte(InsteadofdIsodIumedentate)asan
antImIcrobIalhasbeenshowntobeassocIatedwIthlessseverepaInonInjectIon.
29
AlthoughthepresenceofthemetabIsulphItehasraIsedconcernsregardIngItsuseIn
sulphIteallergIcpatIents,thIsdoesnotappeartobeaclInIcallyImportantproblem.Df
Interest,a2formulatIonIsavaIlableforlongtermsedatIontodecreasethefluIdvolume
InfusedaswellasthelIpIdload.
|orerecently,alowerlIpIdformulatIonofpropofol(Ampofol)hasbeenIntroducedInto
clInIcalpractIceforbothgeneralanesthesIa
J0
andsedatIon.
J1
TheIncreasedfree
fractIonofpropofolleadstoIncreasedpaInwhenItIsInjectedIntosmallveIns.Therefore,
ItIsImportanttoaddlIdocaInetotheAmpofolformulatIontomInImIzethepaInon
InjectIon.Anewwatersolubleprodrugofpropofol(Aquavan)IsInclInIcaldevelopment.
ThIsprodrugIsrapIdlyhydrolyzedbyplasma
P.452
alkalInephosphatasesInthecIrculatIontoreleasefreepropofol.
J2
thasasloweronset
thanpropofolbutasImIlarrecoveryprofIle.
JJ
AlthoughAquavandoesnotproduce
InjectIonsItedIscomfort,atransIentburnIngsensatIonhasbeenreportedIntheperIneal
regIonfollowIng7InjectIon.
Propofol'spharmacokInetIcshasbeenstudIedusIngsInglebolusdosIngandcontInuous
InfusIons.
J4
nstudIesusIngatwocompartmentkInetIcmodel,theInItIaldIstrIbutIonhalf
lIfeIs2to4mInutesandtheelImInatIonhalflIfeIs1toJhours.UsIngathree
compartmentmodel,theInItIalandslowdIstrIbutIonhalflIfevaluesare1to8mInutesand
J0to70mInutes,respectIvely.TheelImInatIonhalflIfedependslargelyonthesamplIng
tImeafterdIscontInuIngtheadmInIstratIonofpropofolandrangesfrom2to24hours.ThIs
longelImInatIonhalflIfeIsIndIcatIveoftheexIstenceofapoorlyperfusedcompartment
fromwhIchpropofolslowlydIffusesbackIntothecentralcompartment.PropofolIsrapIdly
clearedfromthecentralcompartmentbyhepatIcmetabolIsmandthecontextsensItIve
halflIfeforpropofolInfusIonsupto8hoursIs40mInutes.PropofolIsrapIdlyand
extensIvelymetabolIzedtoInactIve,watersolublesulphateandglucuronIcacId
metabolItes,whIchareelImInatedbythekIdneys.Propofol'sclearancerate(20J0
mL/kg/mIn)exceedshepatIcbloodflow,suggestIngthatanextrahepatIcrouteof
elImInatIon(lungs)alsocontrIbutestoItsclearance.Nevertheless,changesInlIverblood
flowwouldbeexpectedtoproducemarkedalteratIonsInpropofol'sclearancerate.
SurprIsIngly,fewchangesInpropofol'spharmacokInetIcshavebeenreportedInthe
presenceofhepatIcorrenaldIsease.
TheInductIondoseofpropofolInhealthyadultsIs1.5to2.5mg/kg,wIthbloodlevelsof2
to6g/mLproducIngunconscIousnessdependIngontheconcomItantmedIcatIons(e.g.,
opIoIdanalgesIcs),thepatIent'sageandphysIcalstatus,andtheextentofthesurgIcal
stImulatIon.
J5
noneofthefIrstreportsdescrIbIngtheuseofpropofolforInductIonand
maIntenanceofanesthesIawIthnItrousoxIde,anaverageInfusIonrateof120g/kg/mIn
wasrequIred.
J6
TherecommendedmaIntenanceInfusIonrateofpropofolvarIesbetween
100and200g/kg/mInforhypnosIsand25to75g/kg/mInforsedatIon.AwakenIng
typIcallyoccursatplasmapropofolconcentratIonsof1to1.5g/mL.
J7
8ecausea50
decreaseIntheplasmapropofolconcentratIonIsusuallyrequIredforawakenIng,
emergencefollowInganesthesIaIsusuallyrapIdevenfollowIngprolongedInfusIons.
AnalogoustothebarbIturates,chIldrenrequIrehIgherInductIonandmaIntenancedosesof
propofolonamIllIgramperkIlogrambasIsasaresultoftheIrlargercentraldIstrIbutIon
volumeandhIgherclearancerate.ElderlypatIentsandthoseInpoorhealthrequIrelower
InductIonandmaIntenancedosesofpropofolasaresultoftheIrsmallercentral
dIstrIbutIonvolumeanddecreasedclearancerate.AlthoughsubhypnotIcdosesofpropofol
producesedatIonandamnesIa,
J7
awarenesshasbeenreportedevenathIgherInfusIon
rateswhenpropofolIsusedasthesoleanesthetIc.
J8
PropofoloftenproducesasubjectIve
feelIngofwellbeIng(andeveneuphorIa)onemergence,andhasbeenabusedbyhealth
careprofessIonalsasaresultofthIsCNSactIon.
J9
PropofoldecreasesC|FD
2
andC8F,aswellasCP.
40
However,whenlargerdosesare
admInIstered,themarkeddepressanteffectonsystemIcarterIalpressurecansIgnIfIcantly
decreaseCPP.CerebrovascularautoregulatIonInresponsetochangesInsystemIcarterIal
pressureandreactIvItyofthecerebralbloodflowtochangesIncarbondIoxIdetensIonare
notaffectedbypropofol.EvIdenceforapossIbleneuroprotectIveeffecthasbeenreported
wIthInvItropreparatIons,andtheuseofpropofoltoproduceEECburstsuppressIonhas
beenproposedasamethodforprovIdIngneuroprotectIondurInganeurysmsurgery.ts
neuroprotectIveeffectmayatleastpartIallyberelatedtotheantIoxIdantpotentIalof
propofol'sphenolrIngstructure,whIchmayactasafreeradIcalscavenger,decreasIng
freeradIcalInducedlIpIdperoxIdatIon.ArecentstudyreportedthatthIsantIoxIdant
actIvItymayoffermanyadvantagesInpreventIngthehypoperfusIonreperfusIon
phenomenonthatcanoccurdurIngmajorlaparoscopIcsurgery.
41
AlthoughT7AwIth
propofolandanopIoIdanalgesIcIsasafeandeffectIvealternatIvetostandardInhalatIon
technIques(I.e.,volatIleanesthetIcwIthnItrousoxIde)formaIntenanceofanesthesIa,
concernshavebeenraIsedregardIngthecosteffectIvenessofthIstechnIque.
42
PropofolproducescortIcalEECchangesthataresImIlartothoseofthIopental.However,
sedatIvedosesofpropofolIncreasewaveactIvItyanalogoustothebenzodIazepInes.
nductIonofanesthesIawIthpropofolIsoccasIonallyaccompanIedbyexcItatorymotor
actIvIty(socallednonepIleptIcmyoclonIa).nastudyInvolvIngpatIentswIthoutahIstory
ofseIzuredIsorders,excItatorymovementsfollowIngpropofolwerenotassocIatedwIth
EECseIzureactIvIty.
4J
PropofolappearstopossessprofoundantIconvulsantpropertIes.
44
PropofolhasbeenreportedtodecreasespIkeactIvItyInpatIentswIthcortIcalelectrodes
ImplantedforresectIonofepIleptogenIcfocIandhasbeenusedsuccessfullytotermInate
statusepIleptIcus.TheduratIonofmotorandEECseIzureactIvItyfollowIng
electroconvulsIvetherapyIssIgnIfIcantlyshorterwIthpropofolthanwIthother7
anesthetIcs.PropofolproducesadecreaseIntheearlycomponentsofsomatosensoryand
motorevokedpotentIalsbutdoesnotInfluencetheearlycomponentsoftheaudItory
evokedpotentIals.
PropofolproducesdosedependentrespIratorydepressIon,wIthapneaoccurrIngIn25to
J5ofpatIentsafteratypIcalInductIondose.AmaIntenanceInfusIonofpropofol
decreasestIdalvolumeandIncreasesrespIratoryrate.TheventIlatoryresponsetocarbon
dIoxIdeandhypoxIaIsalsosIgnIfIcantlydecreasedbypropofol.Propofolcanproduce
bronchodIlatIonInpatIentswIthchronIcobstructIvepulmonarydIseaseanddoesnotInhIbIt
hypoxIcpulmonaryvasoconstrIctIon.
Propofol'scardIovasculardepressanteffectsaregenerallyconsIderedtobemoreprofound
thanthoseofthIopental.8othdIrectmyocardIaldepressanteffectsanddecreasedsystemIc
vascularresIstancehavebeenImplementedasImportantfactorsInproducIng
cardIovasculardepressIon.0IrectmyocardIaldepressIonandperIpheralvasodIlatIonare
doseandconcentratIondependent.naddItIontoarterIalvasodIlatIon,propofolproduces
venodIlatIon(causedbothtoareductIonInsympathetIcactIvItyandbyadIrecteffecton
thevascularsmoothmuscle),whIchfurthercontrIbutestoItshypotensIveeffect.The
relaxatIonofthevascularsmoothmusclemaybebecauseofaneffectonIntracellular
calcIummobIlIzatIonorbecauseofanIncreaseIntheproductIonofnItrIcoxIde.
ExperImentsInIsolatedmyocardIumsuggestthatthenegatIveInotropIceffectofpropofol
resultsfromadecreaseInIntracellularcalcIumavaIlabIlItysecondarytoInhIbItIonof
transsarcolemmalcalcIumInflux.
PropofolalsoaltersthebaroreflexmechanIsm,resultIngInasmallerIncreaseInheartrate
foragIvendecreaseInarterIalpressure.
45
ThesmallerIncreaseInheartratewIthpropofol
mayaccountforthelargerdecreaseInarterIalpressurethanwIthanequIpotentdoseof
thIopental.FecentstudIessuggestthatInductIonofanesthesIawIthpropofolattenuates
desfluranemedIatedsympathetIcactIvatIon.
46
AgeenhancesthecardIodepressant
responsetopropofolandareduceddosageIsrequIredIntheelderly.PatIentswIthlImIted
cardIacreserveseemtotoleratethecardIacdepressIonandsystemIcvasodIlatIon
producedbycarefullytItrateddosesofpropofol,andmaIntenanceInfusIonsare
IncreasInglyusedattheendofcardIacsurgerywhenearlyextubatIonIsdesIred.
PropofolappearstopossessantIemetIcpropertIesthatcontrIbutetoalowerIncIdenceof
emetIcsequelaeaftergeneralanesthesIa.
J6
nfact,subanesthetIcdosesofpropofol(10to
P.45J
20mg)havealsobeensuccessfullyusedtotreatnauseaandemesIsIntheearly
postoperatIveperIod.
47
ThepostulatedmechanIsmsIncludeantIdopamInergIcactIvIty,
depressanteffectonthechemoreceptortrIggerzoneandvagalnucleI,decreasedrelease
ofglutamateandaspartateIntheolfactorycortex,andreductIonofserotonIn
concentratIonsIntheareapostrema.However,theabIlItyofpropofoltoproduceasense
ofwellbeIngmayalsocontrIbutetoItsantIemetIcactIon.nterestIngly,propofolalso
decreasestheprurItusproducedbyspInalopIoIds.
PropofoldoesnottrIggermalIgnanthyperthermIaandmaybeconsIderedtheInductIon
agentofchoIceInmalIgnanthyperthermIasusceptIblepatIents.Theuseofpropofol
InfusIonsforsedatIonInthepedIatrIcCUhasbeenlInkedtoseveraldeathsfollowIng
prolongedadmInIstratIonbecauseoflIpIdaccumulatIonandhypotensIon.AlthoughclInIcal
dosesofpropofoldonotaffectcortIsolsynthesIsortheresponsetoadrenocortIcotropIc
hormonestImulatIon,propofolhasbeenreportedtoInhIbItphagocytosIsandkIllIngof
bacterIaInvItroandtoreduceprolIferatIveresponseswhenaddedtolymphocytesfrom
crItIcallyIllpatIents.
48
8ecausefatemulsIonsareknowntosupportthegrowthofmIcro
organIsms,contamInatIoncanoccurasaresultofdIlutIonorfractIonateduse.
49
ncrItIcallyIllchIldrenandadultsreceIvInghIghdoseInfusIonsofpropofol,somepatIents
havebeenreportedtoexperIencepropofolsyndrome,whIchIscharacterIzedby
myocardIalfaIlure,metabolIcacIdosIs,andrhabdomyolysIs.TheetIologyofthIssyndrome
mayberelatedtothelargelIpIdloadassocIatedwIthprolongedInfusIonsofthecurrent
formulatIonsofpropofol.
Benzodiazepines
TheparenteralbenzodIazepInesIncludedIazepam(7alIum),lorazepam(AtIvan),and
mIdazolam(7ersed),aswellastheantagonIstflumazenIl(FomazIcon).0Iazepamand
lorazepamareInsolubleInwaterandtheIrformulatIoncontaInspropyleneglycol,atIssue
IrrItantthatcausespaInonInjectIonandvenousIrrItatIon.0IazepamIsavaIlableInalIpId
emulsIonformulatIon,whIchdoesnotcausepaInorthrombophlebItIsbutIsassocIatedwIth
aslIghtlylowerbIoavaIlabIlIty.|IdazolamIsawatersolublebenzodIazepInethatIs
avaIlableInanacIdIfIed(pHJ.5)aqueousformulatIonthatproducesmInImallocal
IrrItatIonafter7orIntramuscular(|)InjectIon.
50
AtphysIologIcpH,anIntramolecular
rearrangementoccursthatchangesthephysIcochemIcalpropertIesofmIdazolamsuchthat
ItbecomesmorelIpIdsoluble.
8enzodIazepInesundergohepatIcmetabolIsmvIaoxIdatIonandglucuronIdeconjugatIon.
DxIdatIonreactIonsaresusceptIbletohepatIcdysfunctIonandcoadmInIstratIonofother
anesthetIcdrugs.0IazepamIsmetabolIzedtoactIvemetabolItes(desmethyldIazepam,J
hydroxydIazepam),whIchcanprolongdIazepam'sresIdualsedatIveeffectsbecauseoftheIr
longt
1/2
values.ThesemetabolItesundergosecondaryconjugatIontoformInactIve
watersolubleglucuronIdeconjugates.0rugsthatInhIbIttheoxIdatIvemetabolIsmof
dIazepamIncludetheH
2
receptorblockIngdrugcImetIdIne.SeverelIverdIseasereduces
dIazepam'sproteInbIndIngandhepatIcclearancerate,IncreasesItsvolumeof
dIstrIbutIon,andtherebyfurtherprolongsthet
1/2
value.ChronIcrenaldIseasedecreases
proteInbIndIngandIncreasesthefreedrugfractIon,resultIngInenhancedhepatIc
metabolIsmandashortert
1/2
value.nelderlypatIents,theclearancerateofdIazepam
IssIgnIfIcantlydecreased,prolongIngItst
1/2
to75to150hours.
LorazepamIsdIrectlyconjugatedtoglucuronIcacIdtoformpharmacologIcallyInactIve
metabolItes.AgeandrenaldIseasehavelIttleInfluenceonthekInetIcsoflorazepam;
however,severehepatIcdIseasedecreasesItsclearancerate.|Idazolamundergoes
extensIveoxIdatIonbyhepatIcenzymestoformwatersolublehydroxylatedmetabolItes,
whIchareexcretedIntheurIne.However,theprImarymetabolIte,1
hydroxymethylmIdazolam,hasmIldCNSdepressantactIvIty.ThehepatIcclearancerateof
mIdazolamIs5tImesgreaterthanlorazepamand10tImesgreaterthandIazepam.
AlthoughchangesInlIverbloodflowcanaffecttheclearanceofmIdazolam,agehas
relatIvelylIttleInfluenceonmIdazolam'selImInatIonhalflIfe.
ThebenzodIazepInesusedInanesthesIaareclassIfIedaseIthershort(mIdazolam,
flumazenIl),IntermedIate(dIazepam),orlongactIng(lorazepam).8ecausethe
dIstrIbutIonvolumesaresImIlar,thelargedIfferenceIntheelImInatIonhalftImesIs
becauseofdIfferencesIntheIrdIfferIngclearancerates(Table181).ThecontextsensItIve
halftImesfordIazepamandlorazepamareverylong;therefore,onlymIdazolamshouldbe
usedbycontInuousInfusIontoavoIdexcessIveaccumulatIon.
AllbenzodIazepInesproducedosedependentanxIolytIc,anterogradeamnestIc,sedatIve,
hypnotIc,antIconvulsant,andspInallymedIatedmusclerelaxantpropertIes.
8enzodIazepInesdIfferInpotencyandeffIcacywIthregardtotheIrdIstInctIve
pharmacologIcpropertIes.
50
ThedosedependentpharmacologIcactIvItyImplIesthatthe
CNSeffectsofvarIousbenzodIazepInecompoundsdependontheaffInItyforreceptor
subtypesandtheIrdegreeofreceptorbIndIng.AlthoughbenzodIazepInescanbeusedas
hypnotIcs,theyareprImarIlyusedaspremedIcantsandadjuvantdrugsbecauseoftheIr
anxIolytIc,sedatIve,andamnestIcpropertIes.Forexample,mIdazolam(0.04to0.08mg/kg
7/|)IsthemostcommonlyusedpremedIcant.naddItIon,mIdazolam,0.4to0.8mg/kg
admInIsteredorally10to15mInutesbeforeparentalseparatIon,Isanexcellent
premedIcantInchIldren.ncontrasttolorazepam,bothdIazepamandmIdazolamcanbe
usedtoInduceanesthesIabecausetheyhavearelatIvelyshortonsettImeafter7
admInIstratIon.ThehalflIfeofequIlIbratIonbetweentheplasmaconcentratIonof
mIdazolamandItsmaxImalEECeffectIsonly2toJmInutes.ThetherapeutIcwIndowto
maIntaInunconscIousnesswIthmIdazolamIsreportedtobe100to200ng/mL,wIth
awakenIngoccurrIngatplasmaconcentratIonsbelow50ng/mL.However,sIgnIfIcant
hypnotIcsynergIsmoccurswhenmIdazolamandopIoIdanalgesIcsareadmInIsteredIn
combInatIon.
TheusualInductIondoseofmIdazolamInpremedIcatedpatIentsIs0.1to0.2mg/kg7,
wIthInfusIonratesof0.25to1mg/kg/mInrequIredtomaIntaInhypnosIsandamnesIaIn
combInatIonwIthInhalatIonalagentsand/oropIoIdanalgesIcs.HIghermaIntenance
InfusIonratesandprolongedadmInIstratIonwIllresultInaccumulatIonandprolonged
recoverytImes.LowerInfusIonratesaresuffIcIenttoprovIdesedatIonandamnesIadurIng
localandregIonalanesthesIa.
51
PatIentcontrolledadmInIstratIonofmIdazolamdurIng
proceduresunderlocalanesthesIaIswellacceptedbypatIentsandassocIatedwIthfew
perIoperatIvecomplIcatIons.
52
8enzodIazepInesdecreasebothC|FD
2
andC8FanalogoustothebarbIturatesandpropofol.
However,Incontrasttothesecompounds,mIdazolamIsunabletoproduceaburst
suppressIve(IsoelectrIc)patternontheEEC.AccordIngly,thereIsaceIlIngeffectwIth
respecttothedecreaseInC|FD
2
producedbyIncreasIngdosesofmIdazolam.|Idazolam
producesadoserelateddecreaseInregIonalcerebralperfusIonInthepartsofthebraIn
thatsubservearousal,attentIon,andmemory.CerebralvasomotorresponsIvenessto
carbondIoxIdeIspreserveddurIngmIdazolamanesthesIa.npatIentswIthseverehead
Injury,abolusdoseofmIdazolammaydecreaseCPPwIthlIttleeffectonCP.Although
mIdazolammayImproveneurologIcoutcomeafterIncompleteIschemIaInanImal
experIments,benzodIazepIneshavenot
P.454
beenshowntopossessneuroprotectIveactIvItyInhumans.LIketheothersedatIve
hypnotIcdrugs,thebenzodIazepInesarepotentantIconvulsantsthatarecommonlyusedto
treatstatusepIleptIcus.
8enzodIazepInesproducedosedependentrespIratorydepressIon.nhealthypatIents,the
respIratorydepressIonassocIatedwIthbenzodIazepInepremedIcatIonIsInsIgnIfIcant.
However,thedepressanteffectIsenhancedInpatIentswIthchronIcrespIratorydIsease,
andsynergIstIcdepressanteffectsoccurwhenbenzodIazepInesarecoadmInIsteredwIth
opIoIdanalgesIcs.8enzodIazepInesalsodepresstheswallowIngreflexanddecreaseupper
aIrwayreflexactIvIty.
8othmIdazolamanddIazepamproducedecreasesInsystemIcvascularresIstanceandblood
pressurewhenlargedosesareadmInIsteredforInductIonofanesthesIa.However,the
cardIovasculardepressanteffectsofbenzodIazepInesarefrequentlymaskedbythe
stImulusoflaryngoscopyandIntubatIon.ThecardIovasculardepressanteffectsaredIrectly
relatedtotheplasmaconcentratIon;however,aplateauplasmaconcentratIonappearsto
exIstabovewhIchlIttlefurtherchangeInarterIalbloodpressureoccurs.nthepresenceof
heartfaIlure,thedecreaseInpreloadandafterloadproducedbybenzodIazepInesmaybe
benefIcIalInImprovIngcardIacoutput.However,thecardIodepressanteffectof
benzodIazepInesmaybemoremarkedInhypovolemIcpatIents.
AshortactIngIntravenoussedatIve,Fo486791,IsawatersolublebenzodIazepInethathas
fullagonIstIcactIvItyatCNSbenzodIazepInereceptors.ComparedwIthmIdazolam,ItIs2
to2.5foldmorepotent,hasahIgherplasmaclearancerate,andhasasImIlaronsetand
duratIonofactIon.
5J
nastudyInvolvIngoutpatIentsundergoIngendoscopyprocedures,the
tImestoambulatIonandtorecoveryfrompsychomotorImpaIrmentweredecreased
comparedtomIdazolam,althoughthelaterrecoveryendpoInts(e.g.,fItnessfor
dIscharge)weresImIlar.
54
ncontrasttoallothersedatIvehypnotIcdrugs,thereIsaspecIfIcantagonIstfor
benzodIazepInes.FlumazenIl,a1,4ImIdazobenzodIazepInederIvatIve,hasahIghaffInIty
forthebenzodIazepInereceptorbutmInImalIntrInsIcactIvIty.
55
FlumazenIl'smolecular
structureIssImIlartootherbenzodIazepInesexceptfortheabsenceofaphenylgroup,
whIchIsreplacedbyacarbonylgroup.tIswatersolubleandpossessesmoderatelIpId
solubIlItyatphysIologIcpH.FlumazenIlIsrapIdlymetabolIzedInthelIver,andIts
metabolItesareexcretedIntheurIneasglucuronIdeconjugates.FlumazenIlactsasa
competItIveantagonIstInthepresenceofbenzodIazepIneagonIstcompounds.TheresIdual
actIvItyofthebenzodIazepInesInthepresenceofflumazenIldependsontherelatIve
concentratIonsoftheagonIstandantagonIstdrugs.Asaresult,ItIspossIbletoreverse
benzodIazepIneInducedanesthesIa(ordeepsedatIon)eIthercompletelyorpartIally,
dependIngonthedoseofflumazenIl.FlumazenIlIsshortactIng,wIthanelImInatIonhalf
lIfeof-1hour.
FecurrenceofthecentraleffectsofbenzodIazepInes(resedatIon)mayoccurafterasIngle
doseofflumazenIlbecauseofresIdualeffectsofthemoreslowlyelImInatedagonIstdrug.
56
fsustaInedantagonIsmIsdesIred,ItmaybenecessarytoadmInIsterflumazenIlas
repeatedbolusdosesoracontInuousInfusIon.ngeneral,45to90mInutesofantagonIsm
canbeexpectedfollowIngflumazenIl1toJmg7.However,therespIratorydepressIon
producedbybenzodIazepInesIsnotcompletelyreversedbyflumazenIl.
57
Feversalof
benzodIazepInesedatIonwIthflumazenIlIsnotassocIatedwIthadversecardIovascular
effectsorevIdenceofanacutestressresponse.
58
AlthoughflumazenIldoesnotappearto
changeC8ForC|FD
2
followIngmIdazolamanesthesIaforcranIotomy,acuteIncreasesIn
CPhavebeenreportedInheadInjuredpatIentsreceIvIngflumazenIl.
Etomidate
EtomIdateIsacarboxylatedImIdazolecontaInInganesthetIccompound(F1ethyl1[a
methylbenzyl]ImIdazole5carboxylate)thatIsstructurallyunrelatedtoanyother7
anesthetIc.DnlythedIsomerofetomIdatepossessesanesthetIcactIvIty.Analogousto
mIdazolam(whIchalsocontaInsanImIdazolenucleus),etomIdateundergoesan
IntramolecularrearrangementatphysIologIcpH,resultIngInaclosedrIngstructurewIth
enhancedlIpIdsolubIlIty.TheaqueoussolutIonofetomIdate(AmIdate)Isunstableat
physIologIcpHandIsformulatedIna0.2solutIonwIthJ5propyleneglycol(pH6.9),
contrIbutIngtoahIghIncIdenceofpaInonInjectIon,venoIrrItatIon,andhemolysIs.Anew
lIpIdemulsIonformulatIon(EtomIdateLIpuro)hasrecentlybeenIntroducedInEuropeand
appearstobeassocIatedwIthalowerIncIdenceofsIdeeffectscomparedwIththeorIgInal
propyleneglycolformulatIon.
ThestandardInductIondoseofetomIdate(0.20.Jmg/kg7)producesarapIdonsetof
anesthesIa.nvoluntarymyoclonIcmovementsarecommondurIngtheInductIonperIodas
aresultofsubcortIcaldIsInhIbItIonandareunrelatedtocortIcalseIzureactIvIty.The
frequencyofthIsmyoclonIclIkeactIvItycanbeattenuatedbyprIoradmInIstratIonofopIoId
analgesIcs,benzodIazepInes,orsmallsedatIvedoses(0.0Jto0.05mg/kg)prIortoInductIon
ofanesthesIa.
59
Fecently,remIfentanIlreducedetomIdateInducedmyoclonIcactIvIty
wIthoutIncreasIngsIdeeffectslIkeapnea,emesIs,orprurItus.
60
EmergencetImeafter
etomIdateanesthesIaIsdosedependentbutremaInsshortevenafteradmInIstratIonof
repeatedbolusdosesorcontInuousInfusIons.FormaIntenanceofhypnosIs,thetarget
concentratIonIsJ00to500ng/mLandcanberapIdlyachIevedbyadmInIsterIngatwoor
threestageInfusIon(e.g.,100mg/kg/mInfor10mInutesfollowedby10mg/kg/mInor100
mg/kg/mInforJto5mInutes,followedby20mg/kg/mInfor20toJ0mInutes,andthen10
mg/kg/mIn).ThepharmacokInetIcsofetomIdateareoptImallydescrIbedbyathree
compartmentopenmodel.
61
ThehIghclearancerateofetomIdate(18to25mL/kg/mIn)Is
aresultofextensIveesterhydrolysIsInthelIver(formIngInactIvewatersoluble
metabolItes).AsIgnIfIcantdecreaseInplasmaproteInbIndInghasbeenreportedInthe
presenceofuremIaandhepatIccIrrhosIs.SeverehepatIcdIseasecausesaprolongatIonof
theelImInatIonhalflIfesecondarytoanIncreasedvolumeofdIstrIbutIonandadecreased
plasmaclearancerate.
AnalogoustothebarbIturates,etomIdatedecreasesC|FD
2
,C8F,andCP.However,the
hemodynamIcstabIlItyassocIatedwIthetomIdatewIllmaIntaInadequateCPP.EtomIdate
hasbeenusedsuccessfullyforbothInductIonandmaIntenanceofanesthesIafor
neurosurgery.EtomIdate'swellknownInhIbItoryeffectonadrenocortIcalsynthetIc
functIon
62
lImItsItsclInIcalusefulnessforlongtermtreatmentofelevatedCP.Although
clearevIdenceforaneuroprotectIveeffectInhumansIslackIng,etomIdateIsfrequently
useddurIngtemporaryarterIalocclusIonandIntraoperatIveangIography(forthe
treatmentofcerebralaneurysms).EtomIdateproducesanEECpatternthatIssImIlarto
thIopentalexceptfortheabsenceofIncreasedactIvItyatlowerdoses.EtomIdatehas
beenallegedtoproduceconvulsIonlIkeEECpotentIalsInepIleptIcpatIentswIthoutthe
appearanceofmyoclonIcorconvulsantlIkemotoractIvIty,apropertythathasbeen
provenusefulforIntraoperatIvemappIngofseIzurefocI.AnalogoustomethohexItal,
etomIdatepossessesantIconvulsantpropertIesandhasbeenusedtotermInatestatus
epIleptIcus.EtomIdatealsoproducesasIgnIfIcantIncreaseoftheamplItudeof
somatosensoryevokedpotentIalswhIleonlymInImallyIncreasIngtheIrlatency.
Consequently,etomIdatecanbeusedtofacIlItatetheInterpretatIonofsomatosensory
evokedpotentIalswhenthesIgnalqualItyIspoor.
P.455
EtomIdatecausesmInImalcardIorespIratorydepressIonevenInthepresenceof
cardIovascularandpulmonarydIsease.
6J
ThedrugdoesnotInducehIstamInereleaseand
canbesafelyusedInpatIentswIthreactIveaIrwaydIsease.Consequently,etomIdateIs
consIderedtobetheInductIonagentofchoIceforpoorrIskpatIentswIthcardIorespIratory
dIsease,aswellasInthosesItuatIonsInwhIchpreservatIonofanormalbloodpressureIs
crucIal(e.g.,cerebrovasculardIsease).However,etomIdatedoesnoteffectIvelybluntthe
sympathetIcresponsetolaryngoscopyandIntubatIonunlesscombInedwIthapotentopIoId
analgesIc.
EtomIdateIsassocIatedwIthahIghIncIdenceofpostoperatIvenauseaandemesIswhen
usedIncombInatIonwIthopIoIdsforbrIefoutpatIentprocedures.naddItIon,theIncreased
mortalItyIncrItIcallyIllpatIentssedatedwIthanetomIdateInfusIonhasbeenattrIbuted
toItsInhIbItoryeffectoncortIsolsynthesIs.
64
EtomIdateInhIbItstheactIvItyof11
hydroxylase,anenzymenecessaryforthesynthesIsofcortIsol,aldosterone,17
hydroxyprogesterone,andcortIcosterone.EvenafterasIngleInductIondoseof
etomIdate,
64
adrenalsuppressIonpersIstsfor5to8hours.AlthoughtheclInIcalsIgnIfIcance
ofshorttermblockadeofcortIsolsynthesIsIsnotknown,theuseofetomIdatefor
maIntenanceofanesthesIahasbeenquestIoned.Fecently,etomIdatehasbeenreportedto
InhIbItplateletfunctIon,resultIngInprolongatIonofthebleedIngtIme.
65
nspIteofItssIde
effectprofIle,etomIdateremaInsavaluableInductIondrugforspecIfIcIndIcatIons(e.g.,In
patIentswIthseverecardIovascularandcerebrovasculardIsease).
Ketamine
KetamIne(KetalarorKetaject)IsanarylcyclohexylamInethatIsstructurallyrelatedto
phencyclIdIne.
66
KetamIneIsawatersolublecompoundwIthapKaof7.5andIsavaIlable
In1,5,and10aqueoussolutIons.TheketamInemoleculecontaInsachIralcenter
producIngtwooptIcalIsomers.TheS(+)IsomerofketamInepossessesmorepotent
anesthetIcandanalgesIcpropertIesdespItehavIngasImIlarpharmacokInetIcand
pharmacodynamIcprofIleastheracemIcmIxture(ortheF[]Isomer).
67,68
Althoughthe
S(+)ketamIneIsapprovedforclInIcaluseInEurope,thecommonlyusedsolutIonIsa
racemIcmIxtureofthetwoIsomers.KetamIneIsextensIvelymetabolIzedbyhepatIc
mIcrosomalcytochromeP450enzymesandItsprImarymetabolIte,norketamIne,Isone
thIrdtoonefIfthaspotentastheparentcompound.ThemetabolItesofnorketamIneare
excretedbythekIdneyaswatersolublehydroxylatedandglucuronIdatedconjugates.
AnalogoustothebarbIturatesandpropofol,ketamInehasrelatIvelyshortdIstrIbutIonand
redIstrIbutIonhalflIfevalues.KetamInealsohasahIghhepatIcclearancerate(1L/mIn)
andalargedIstrIbutIonvolume(JL/kg),resultIngInanelImInatIonhalflIfeof24hours.
ThehIghhepatIcextractIonratIosuggeststhatalteratIonsInhepatIcbloodflowcan
sIgnIfIcantlyInfluenceketamIne'sclearancerate.
KetamIneproducesdosedependentCNSdepressIonleadIngtoasocalleddIssocIatIve
anesthetIcstatecharacterIzedbyprofoundanalgesIaandamnesIa,eventhoughpatIents
maybeconscIousandmaIntaInprotectIvereflexes.TheproposedmechanIsmforthIs
cataleptIcstateIncludeselectrophysIologIcInhIbItIonofthalamocortIcalpathwaysand
stImulatIonofthelImbIcsystem.AlthoughItIsmostcommonlyadmInIsteredparenterally,
oralandIntranasaladmInIstratIonofketamIne(6mg/kg)hasbeenusedforpremedIcatIon
ofpedIatrIcpatIents.FollowIngbenzodIazepInepremedIcatIon,ketamIne1to2mg/kg7
(or4to8mg/kg|)canbeusedforInductIonofanesthesIa.TheduratIonofketamIne
InducedanesthesIaIsIntherangeof10to20mInutesafterasIngleInductIondose;
however,recoverytofullorIentatIonmayrequIreanaddItIonal60to90mInutes.
EmergencetImesareevenlongerfollowIngrepeatedbolusInjectIonsoracontInuous
InfusIon.S(+)ketamInehasashorterrecoverytImecomparedwIththeracemIcmIxture.
ThetherapeutIcwIndowformaIntenanceofunconscIousnesswIthketamIneIsbetween0.6
and2g/mLInadultsandbetween0.8and4g/mLInchIldren.AnalgesIceffectsare
evIdentatsubanesthetIcdosesof0.1to0.5mg/kg7andplasmaconcentratIonsof
between85and160ng/mL.AlowdoseInfusIonof4g/kg/mIn7wasreportedtoresultIn
equIvalentpostoperatIveanalgesIaasan7morphIneInfusIonat2mg/hr.
AsaresultofItsN|0AreceptorblockIngactIvIty,ketamIneshouldbehIghlyeffectIvefor
preemptIveanalgesIaandopIoIdresIstantchronIcpaInstates.
69
Unfortunately,awell
controlledstudyfaIledtodemonstrateapreemptIveeffectwhenketamInewas
admInIsteredprIortothesurgIcalIncIsIon(vs.IntraoperatIvely).
70
Nevertheless,other
studIes
71,72
descrIbedabenefIcIalopIoIdsparIngeffectofsmalldosesofketamIne(75to
150g/kg7)whenadmInIsteredasanadjuvantdurIngsurgery.
AnImportantconsIderatIonIntheuseofketamIneanesthesIarelatestothehIghIncIdence
ofpsychomImetIcreactIons(namely,hallucInatIons,nIghtmares,alteredshortterm
memory,andcognItIon)durIngtheearlyrecoveryperIod.TheIncIdenceofthesereactIons
IsdosedependentandcanbereducedbycoadmInIstratIonofbenzodIazepInes,
barbIturates,orpropofol.KetamInehasbeentradItIonallycontraIndIcatedforpatIents
wIthIncreasedCPorreducedcerebralcomplIancebecauseItIncreasesC|FD
2
,C8F,and
CP.However,thereIsrecentevIdencethat7InductIondosesofketamIneactually
decreaseCPIntraumatIcbraInInjurypatIentsdurIngcontrolledventIlatIonwIthpropofol
sedatIon.
7J
PrIoradmInIstratIonofthIopentalorbenzodIazepInescanbluntketamIne
InducedIncreasesInC8F.8ecauseketamInehasantagonIstIcactIvItyattheN|0A
receptor,ItmaypossesssomeInherentprotectIveeffectsagaInstbraInIschemIa.However,
ketamInecanadverselyaffectneurologIcoutcomeInthepresenceofbraInIschemIa
despIteItsN|0AreceptorblockIngactIvIty.CortIcalEECrecordIngsfollowIngketamIne
InductIonarecharacterIzedbytheappearanceoffastactIvIty(J0to40Hz)followedby
moderatevoltageactIvIty,mIxedwIthhIghvoltagewavesrecurrIngatJto4second
Intervals.AthIgherdosages,ketamIneproducesaunIqueEECburstsuppressIonpattern
(FIg.185).
AlthoughketamIneInducedmyoclonIcandseIzurelIkeactIvItyhasbeenobservedInnormal
(nonepIleptIc)patIents,ketamIneappearstopossessantIconvulsantactIvIty.
11,12
Two
studIeshavedemonstratedtheopIoIdsparIngeffectsoflowdose
P.456
ketamIne(75to200g/kg)whenadmInIsteredasanadjuvantdurInganesthesIa.
71,72
nterestIngly,smalldosesofketamInehavealsobeenusedInthetreatmentofsevere
depressIonInpatIentswIthchronIcpaInsyndromes.
74,75
However,ketamInecanproduce
adverseeffectswhenadmInIsteredInthepresenceoftrIcyclIcantIdepressantsbecause
bothdrugsInhIbItnorepInephrInereuptakeandcouldproduceseverehypotensIon,heart
faIlure,and/ormyocardIalIschemIa.
75,76
Figure 18-5.ProgressIvechangesIntheelectroencephalogram(EEC)producedby
ketamIne.StagesthroughareachIevedwIthracemIcketamIneandItsS(+)Isomer.
WIthF()ketamIne,StagewasthemaxImalEECdepressIonproduced.(FeprIntedwIth
permIssIonfromShuttlerJ,StanskI0F,WhItePF,etal:PharmacodynamIcmodelIngof
theEECeffectofketamIneandItsenantIomersInman.JPharmacokInet8Iopharm
1987;15:241.)
KetamInehaswellcharacterIzedbronchodIlatoryactIvIty.nthepresenceofactIve
bronchospasm,ketamIneIsconsIderedtobethe7InductIonagentofchoIce.KetamInehas
beenusedInsubanesthetIcdosagestotreatpersIstentbronchospasmIntheDFandCU.t
IsalsousedIncombInatIonwIthmIdazolamtoprovIdesedatIonandanalgesIafor
asthmatIcpatIents.ncontrasttotheother7anesthetIcs,protectIveaIrwayreflexesare
morelIkelytobepreservedwIthketamIne.However,ItmustbeemphasIzedthattheuse
ofketamInedoesnotobvIatetheneedfortrachealIntubatIonInthepatIentwIthafull
stomach(becausetrachealsoIlInghasbeenreportedInthIssItuatIon).KetamInecauses
mInImalrespIratorydepressIonInclInIcallyrelevantdosesandcanfacIlItatethetransItIon
frommechanIcaltospontaneousventIlatIonafteranesthesIa.However,ItsabIlItyto
IncreaseoralsecretIonscanleadtolaryngospasmdurInglIghtanesthesIa.
KetamInehaspromInentcardIovascularstImulatIngeffectssecondarytodIrectstImulatIon
ofthesympathetIcnervoussystem.KetamIneIstheonlyanesthetIcthatactuallyIncreases
perIpheralarterIolarresIstance.AsaresultofItsvasoconstrIctIvepropertIes,ketamInecan
reducethemagnItudeofredIstrIbutIonhypothermIa.
77
nductIonofanesthesIawIth
ketamIneoftenproducessIgnIfIcantIncreasesInarterIalbloodpressureandheartrate.
AlthoughthemechanIsmofthecardIovascularstImulatIonIsnotentIrelyclear,Itappears
tobecentrallymedIated.ThereIsevIdencetosuggestthatketamIneattenuates
baroreceptoractIvItyvIaaneffectonN|0AreceptorsInthenucleustractussolItarIus.
8ecauseoftheIncreasedcardIacworkandmyocardIaloxygenconsumptIon,ketamIne
negatIvelyaffectsthebalancebetweenmyocardIaloxygensupplyanddemand.
Consequently,ItsuseIsnotrecommendedInpatIentswIthseverecoronaryarterydIsease.
ncontrasttothesecondarycardIovascularstImulatIon,ketamInehasIntrInsIcmyocardIal
depressantpropertIesthatonlybecomeapparentIntheserIouslyIllpatIentwIthdepleted
catecholamInereserves.8ecauseketamInecanalsoIncreasepulmonaryarterypressure,Its
useIscontraIndIcatedInadultpatIentswIthpoorrIghtventrIcularreserve.nterestIngly,
theeffectonthepulmonaryvasculatureseemstobeattenuatedInchIldren.
TherenewedInterestInketamIneIsrelatedtotheuseofsmallerdoses(100to250g/kg)
asanadjuvantdurInganesthesIa.
78
TheanesthetIc(sedatIve)andopIoIdanalgesIcsparIng
effectsofketamInecanreduceventIlatorydepressIondurIngmonItoredanesthesIa
care.
79,80,81
TheavaIlabIlItyofthestereoIsomerofketamInehasIncreasedthe
nonanesthetIcadjunctIveuseofketamIne.
82
TheanesthetIcandanalgesIcpotencyofS(+)
ketamIneIsJtImesgreaterthanF()ketamIneandtwIcethatoftheracemIcmIxture(FIg.
186),reflectIngItsfourfoldgreateraffInItyatthephencyclIdInebIndIngsIteontheN|0A
receptorcomparedwIththeF()Isomer.ThetherapeutIcIndexofS(+)ketamIneIs2.5
tImesgreaterthanboththeF()andtheracemIcforms.naddItIon,hepatIc
bIotransformatIonofS(+)ketamIneoccurs20fasterthanthatoftheF()enantIomer,
contrIbutIngtoshorteremergencetImesandfasterreturnofcognItIvefunctIon.8oth
IsomersproducesImIlarcardIovascularstImulatIngeffectsandhormonalresponsesdurIng
surgery.AlthoughtheIncIdenceofdreamIngIssImIlarwIthS(+)ketamIneandtheracemIc
mIxture,subjectIvemoodandpatIentacceptancearehIgherwIththeS(+)Isomer.
67,68
Figure 18-6.ConcentratIonresponserelatIonshIpforracemIcketamIneand
S(+)ketamIneInrelatIontospecIfIcclInIcalendpoInts.TheslowIngofthemedIan
electroencephalogramfrequencywasusedastheeffect(endpoInt)andwasrelatedto
thearterIalbloodconcentratIonsofketamIne.(FeprIntedwIthpermIssIonfrom
SchuttlerJ,KloosS,hmsenH,etal:PharmacokInetIcpharmacodynamIcpropertIesof
S(+)ketamIneversusracemIcketamIne:ArandomIzeddoubleblIndstudyIn
volunteers.AnesthesIology1992;77:AJJ0.)
Dexmedetomidine
0exmedetomIdIneIsahIghlyselectIve
2
adrenoceptoragonIstthathasbeenapprovedby
theFoodand0rugAdmInIstratIonfortheshortterm(24hours)sedatIonofmechanIcally
ventIlatedpatIentsIntheCUsettIng.nthIssettIngItappearstooffersomeclInIcal
advantagesbecauseItproducesaunIquetypeofsedatIonanalgesIawIthlessventIlatory
depressIonthanthecommonlyusedsedatIvehypnotIcandopIoIdanalgesIcdrugs.
14
AlthoughdexmedetomIdIneIsbeIngusedforsedatIngpatIentsundergoIngdIagnostIcand
therapeutIcproceduresoutsIdetheoperatIngandCUenvIronments,theserepresentoff
labelusesofthIsdrug.
WhenusedforpremedIcatIonprIortogeneralanesthesIa,dexmedetomIdIneproduced
preoperatIvesedatIonandanxIolysIscomparabletomIdazolam.
15
However,Itsuseledto
anIncreasedIncIdenceofIntraoperatIvehypotensIonandbradycardIacomparedwIththe
commonlyusedbenzodIazepInecompound.WhenusedforpremedIcatIonprIortoregIonal
anesthesIa,dexmedetomIdInereducedpatIentanxIety,sympathoadrenal(stress)responses,
andperIoperatIveopIoIdanalgesIcrequIrements.
8J
Halletal.
84
alsodemonstratedthe
sedatIve,amnestIc,andanalgesIceffectsoflowdoseInfusIonsofdexmedetomIdIne(0.2to
0.6g/kg/hr).
Asan7adjuvantdurIngInductIonand/ormaIntenanceofgeneralanesthesIa,
dexmedetomIdInewIllblunttheacutehemodynamIcresponsetolaryngoscopyand
IntubatIon.
85
thasalsobeenusedtofacIlItateawakefIberoptIcIntubatIon.
86,87
Whenused
asananesthetIcadjuvantdurInggeneralanesthesIa,dexmedetomIdInehasbeenreported
toImproveperIoperatIvehemodynamIcstabIlItyInneurosurgIcalpatIents,
88
andImprove
postoperatIvepaIncontrolaftermajorsurgery.
89,90
However,arecentstudy
91
faIledto
demonstrateanyclInIcallysIgnIfIcantImprovementsInpatIentoutcomesafterbarIatrIc
surgerydespIteproducIngbothanesthetIcandanalgesIcsparIngeffects.
nsummary,dexmedetomIdIneappearstobeapotentIallyusefuladjuvantdurInglocaland
regIonalanesthesIa.tprovIdescomparablesedatIontomIdazolam
92
buthasaslower
onsetandoffsetofsedatIonthanpropofol.
9J
WhenadmInIsteredasanadjuvantdurIng7
regIonalanesthesIa
94
ItImprovedthequalItyofbothIntraandpostoperatIveanalgesIa.
8ecauseofItshIghcost,dexmedetomIdIne'scostbenefIt
P.457
ratIoasan7adjuvantdurInggeneralanesthesIaclearlyrequIresfurtherInvestIgatIon.
Clinical Uses of Intravenous Anesthetics
Induction Agents
TheInductIoncharacterIstIcsandrecommendeddosagesoftheavaIlable7anesthetIc
agentsaresummarIzedInTable182.AsaresultofdIfferencesInpharmacokInetIc(e.g.,
alteredclearanceanddIstrIbutIonvolumes)andpharmacodynamIc(alteredbraIn
sensItIvIty)varIables,theInductIondosagesofall7anesthetIcsneedtobeadjustedto
meettheneedsofIndIvIdualpatIents.Forexample,advancedage,preexIstIngdIseases
(e.g.,hypothyroIdIsm,hypovolemIa),premedIcatIon(e.g.,benzodIazepInes),and
coadmInIstratIonofadjuvantdrugs(e.g.,opIoIds,
2
agonIsts)decreasetheInductIondose
requIrements.WhenthereIsconcernregardIngapossIbleabnormalresponse,assessIngthe
effectofasmalltestdose(equalto10to20oftheusualInductIondose)wIlloften
IdentIfythosepatIentsforwhomadosageadjustmentIsrequIred.8eforeadmInIsterIng
addItIonalmedIcatIon,adequatetImeshouldbeallowedfortheanesthetIctoexertIts
effect,especIallywhenusIngdrugswIthaslowonsetofactIon(mIdazolam)orInthe
presenceofaslowcIrculatIontImeInelderlypatIentsandthosewIthcongestIveheart
faIlure.
TheclInIcalusesofpropofolhaveexpandedgreatlysInceItsIntroductIonIntoclInIcal
practIceIn1989.
95
7admInIstratIonofpropofolresultsInarapIdlossofconscIousness
(usuallywIthInonearmtobraIncIrculatIon)thatIscomparabletothatofthebarbIturates.
AlthoughanInductIondoseof2.5mg/kgwasInItIallyrecommended,theuseofsmaller
InductIondosesofpropofol(1to2mg/kg)hasmInImIzedItsacutecardIovascularand
respIratorydepressanteffects.Fecoveryfrompropofol'ssedatIvehypnotIceffectsIsrapId
wIthlessresIdualsedatIon,fatIgue(hangover),andcognItIveImpaIrmentthanwIth
otheravaIlablesedatIvehypnotIcdrugsaftershortsurgIcalprocedures.Consequently,
propofolhasbecomethe7drugofchoIceforoutpatIentsundergoIngambulatorysurgery.
WIthbenzodIazepInes,thereIswIdevarIatIonInthedoseresponserelatIonshIpsIn
unpremedIcatedelectIvesurgerypatIents.ComparedwIthmIdazolam,dIazepamand
lorazepamhavesloweronsettImestoachIeveapeakeffectandtheIrdoseeffect
relatIonshIpIslesspredIctable.Asaresult,dIazepamandlorazepamarerarelyusedfor
InductIonofgeneralanesthesIa.naddItIon,theslowhepatIcclearanceofdIazepamand
lorazepammaycontrIbutetoprolongedresIdualeffects(e.g.,sedatIon,amnesIa,fatIgue)
whentheyareusedforpremedIcatIon.|IdazolamhasaslIghtlymorerapIdonsetandmay
beausefulInductIonagentforspecIalIndIcatIons(e.g.,whennItrousoxIdeIs
contraIndIcated,oraspartofatotal7anesthetIctechnIque).However,whenmIdazolam
IsusedforInductIonand/ormaIntenanceofanesthesIa,returnofconscIousnesstakes
substantIallylongerthanwIthothersedatIvehypnotIcdrugs.nspIteofItsextensIve
hepatIcmetabolIsm,recoveryofcognItIvefunctIonIsstIllsloweraftermIdazolam
comparedwIththIopental,methohexItal,etomIdate,orpropofol.
nanefforttooptImIzetheclInIcaluseofmIdazolamdurIngtheInductIonperIod,ItIsused
IncreasInglyasacoInductIonagentwIthothersedatIvehypnotIcdrugs(propofol,
ketamIne).|Idazolam2to5mg7canprovIdeforIncreasedsedatIon,amnesIa,and
anxIolysIsdurIngthepreInductIonperIod.WhenmIdazolamIsusedIncombInatIonwIth
propofol,1.5to2mg/kg7,
112
orketamIne,0.75to1mg/kg7,
96
ItfacIlItatestheonsetof
anesthesIaanddecreasesthepossIbIlItyofIntraoperatIverecallwIthoutdelayIng
emergencetImes.|IdazolamalsoattenuatesthecardIostImulatoryresponsetoketamIne,
aswellasItspsychomImetIcemergencereactIons.UseofmIdazolam,2toJmg7,wIth
propofolreducesrecalldurIngtheInductIonperIod;however,largerdosesofmIdazolam(5
mg7)wIlldelayemergenceafterbrIefsurgIcalprocedures.
AsaresultoftheIrsIdeeffectprofIles,theclInIcaluseofetomIdateandketamInefor
InductIonofanesthesIaIsrestrIctedtospecIfIcsItuatIonsInwhIchtheIrunIque
pharmacologIcprofIlesofferadvantagesoverotheravaIlable7anesthetIcs.Forexample,
etomIdatecanfacIlItatemaIntenanceofastablebloodpressureInhIghrIskpatIentswIth
crItIcalstenosIsofthecerebralvasculatureandInpatIentswIthseverecardIacImpaIrment
orunstableangIna.KetamIneIsausefulInductIonagentforpatIentswIthreactIveaIrway
dIsease,aswellasforthosesItuatIonswherecontInuedspontaneousventIlatIonIs
desIrabledurIngsurgery.
Table 18-2 Induction Characteristics and Dosage Requirements for the
Currently Available Sedative-Hypnotic Drugs
DRUG NAME
INDUCTION
DOSE
(mg/kg)
ONSET
(sec)
DURATION
(min)
EXCITATORY
ACTIVITY
PAIN ON
INJECTION
HEART
RATE
BLOOD
PRESSURE
ThIopental J6 J0 510 + 0+
|ethohexItal 1J J0 510 ++ +
Propofol 1.52.5
15
45
510 + ++ 0
|Idazolam 0.20.4
J0
90
10J0 0 0 0 0/
0Iazepam 0.J0.6
45
90
15J0 0 +/+++ 0 0/
Lorazepam
0.0J
0.06
60
120
60120 0 ++ 0 0/
EtomIdate 0.20.J
15
45
J12 +++ +++ 0 0
KetamIne 12
45
60
1020 + 0
0,none;+,mInImal;++,moderate;+++,severe;,decrease;,Increase.
1997,pp.2746and7792.
P.458
Maintenance of Anesthesia
ThecontInuedpopularItyofvolatIleanesthetIcsformaIntenanceofanesthesIaIsprImarIly
relatedtotheIrrapIdreversIbIlItyandeaseofadmInIstratIonwhenusIngaconventIonal
vaporIzerdelIverysystem.TheavaIlabIlItyof7drugswIthmorerapIdonsetandshorter
recoveryprofIles,aswellasuserfrIendlyInfusIondelIverysystems,hasfacIlItatedthe
maIntenanceofanesthesIawIthcontInuousInfusIonsof7drugs,producIngananesthetIc
state(namely,T7A)thatcomparesfavorablywIththevolatIleanesthetIcs.na
comparIsonoftherequIrementofpostoperatIveanalgesIcsafterInhalatIonandT7A
technIques,notsurprIsIngly,thepostoperatIvepaInwasreducedafterT7A.
97
For
example,InmorbIdlyobesepatIentsundergoIngbarIatrIcsurgery,theuseofT7A
technIquewasassocIatedwIthasuperIorrecoveryprofIlecomparedwIthasevoflurane
basedInhalatIontechnIque.
98
However,T7AtechnIquesaremoreexpensIvethan
InhalatIonorbalancedanesthetIctechnIques.
42
ThetradItIonalIntermIttentbolusadmInIstratIonof7drugsresultsIndepthofanesthesIa
(andanalgesIa)thatoscIllatesaboveandbelowthedesIredlevel.
99
8ecauseofrapId
dIstrIbutIonandredIstrIbutIonofthe7anesthetIcs,thehIghpeakbloodconcentratIon
aftereachbolusIsfollowedbyarapIddecrease,producIngfluctuatIngdruglevelsInthe
bloodandhencethebraIn.ThemagnItudeofthedruglevelfluctuatIondependsonthesIze
ofthebolusdoseandthefrequencyofItsadmInIstratIon.WIdevarIatIonIntheplasma
drugconcentratIonscanresultInhemodynamIcandrespIratoryInstabIlItyasaresultof
changesInthedepthofanesthesIaorsedatIon.8yprovIdIngmorestableblood(andbraIn)
concentratIonswIthacontInuous7InfusIon,ItmIghtbepossIbletoImproveanesthetIc
condItIonsandhemodynamIcstabIlIty,aswellasdecreasIngsIdeeffectsandrecovery
tImeswIth7anesthetIcs.
100
AdmInIstratIonof7anesthetIcsbyavarIablerateInfusIonIs
alogIcalextensIonoftheIncrementalbolusmethodofdrugtItratIon,asacontInuous
InfusIonIsequIvalenttothesequentIaladmInIstratIonofInfInItelysmallbolusdoses.
Althoughan7anesthetIccanbetItratedtoachIeveandmaIntaInthedesIredclInIcal
effect,aknowledgeofbasIcpharmacokInetIcprIncIplesIshelpfulInmoreaccurately
predIctIngtheoptImaldosagerequIrements.TherequIredplasmaconcentratIondepends
onthedesIredpharmacologIceffect(hypnosIs,sedatIon),theconcomItantuseofother
adjunctIvedrugs(opIoIdanalgesIcs,musclerelaxants,cardIovasculardrugs),thetypeof
operatIon(superfIcIal,IntraabdomInal,IntracranIal),andthepatIent'ssensItIvItytothe
drug(age,drughIstory,preexIstIngdIseases).PreexIstIngdIseases(cIrrhosIs,congestIve
heartfaIlure,renalfaIlure)canmarkedlyalterthepharmacokInetIcvarIablesofthehIghly
proteInbound,lIpophIlIc7anesthetIcdrugs.ngeneral,chIldrenhavehIgherclearance
rates,whIletheelderlyhavereducedclearancevalues.7arIousIntraoperatIve
InterventIons(e.g.,laryngoscopy,trachealIntubatIon,skInIncIsIon,entryIntobody
cavItIes)transIentlyIncreasetheanesthetIcand/oranalgesIcrequIrements.Therefore,the
InfusIonschemeshouldbetaIloredtoprovIdepeakdrugconcentratIonsdurIngtheperIods
ofmostIntensestImulatIon.ForspecIfIcsurgIcalInterventIons,thesocalledtherapeutIc
wIndowofan7anesthetIcIsdefInedasthebloodconcentratIonrangerequIredtoproduce
agIveneffect(Table18J).tmustbeemphasIzedthatthetherapeutIcwIndowfor
sedatIvehypnotIcsIsmarkedlyInfluencedbythepresenceofadjunctIvedrugs(e.g.,
opIoIds,
2
agonIsts,nItrousoxIde).
Theuseof7anesthetIctechnIquesrequIrescontInuoustItratIonofthedrugInfusIonrate
tothedesIredpharmacodynamIcendpoInt.
96
|ostanesthesIologIstsrelyonsomatIcand
autonomIcsIgnsforassessIngdepthof7anesthesIa,analogoustothemannerInwhIch
theytItratethevolatIleanesthetIcs.ThemostsensItIveclInIcalsIgnsofdepthof
anesthesIaappeartobechangesInmuscletone(I.e.,electromyography[E|C])and
ventIlatoryrateandpattern.
101
However,IfthepatIenthasbeengIvenmusclerelaxants,
theanesthesIologIstmustrelyonsIgnsofautonomIchyperactIvIty(e.g.,tachycardIa,
hypertensIon,lacrImatIon,dIaphoresIs).Unfortunately,theanesthetIcdrugs(ketamIne),as
wellasadjunctIveagents(
2
agonIsts,betablockers,adenosIne,calcIumchannel
blockers),candIrectlyInfluencethecardIovascularresponsetosurgIcalstImulatIon.
AlthoughthecardIovascularsIgnsofautonomIcnervoussystemhyperactIvItymaybe
masked,otherautonomIcsIgns(e.g.,dIaphoresIs)andpurposefulmovementsmaybemore
relIableIndIcatorsofdepthofanesthesIathanbloodpressurebecausethelatterdepends
ontheabIlItyofthehearttomaIntaInthecardIacoutputInthefaceofacutechangesIn
afterload.TheheartrateresponsetosurgIcalstImulatIonappearstobemoreusefulthan
thebloodpressureresponseIndetermInIngtheneedforaddItIonalanalgesIcmedIcatIon.
|oreover,ItwouldappearthatbloodpressureandheartrateresponsestosurgIcal
stImulatIonarealessusefulguIdewIth7technIquesthanwIthvolatIleanesthetIcs.
nterestIngly,supplementatIonwIthasedatIvehypnotIc(propofol)wasaseffectIveasa
potentopIoIdanalgesIcIncontrollIngacuteautonomIcresponsesdurIngT7A.
102
TheclInIcalassessmentofanesthetIcdepthhasbecomemorechallengIngbecause7
anesthetIctechnIquesInvolveacombInatIonofhypnotIcs,opIoIds,musclerelaxants,and
adjuvantdrugs.TheInteractIonsbetweenthesedrugscanresultInaddItIve,supra
addItIve,InfraaddItIve,orevenantagonIstIceffects.AnIdealdepthofanesthesIa
IndIcatorwouldIntegratethephysIologIcandneurologIcInformatIonfromall
P.459
aspectsoftheanesthetIcstate.ntheabsenceofaglobalcerebralfunctIonmonItor,the
depthofanesthesIadevIceshouldprovIdeanIndIcatIonofoneormoreofthekey
componentsofgeneralanesthesIa(e.g.,hypnosIs,analgesIa,amnesIa,suppressIonofthe
stressresponse,ormusclerelaxatIon).AsImple,nonInvasIvemonItorofthedepthof
anesthesIa,whIchwouldrelIablypredIctapatIent'sresponsetosurgIcalstImulatIon,would
beextremelyvaluablewhenusIng7anesthetIctechnIques.
Table 18-3 Therapeutic Blood Concentrations when Intravenous
Anesthetics are Infused for Hypnosis or Sedation
DRUG NAME
MAJOR SURGERY
PROCEDURES
MINOR SURGERY
PROCEDURES
SEDATIVE
CONCENTRATION
AWAKENING
CONCENTRATION
ThIopental 1020g/mL 1020g/mL 48g/mL 48g/mL
|ethohexItal 615g/mL 510g/mL 1Jg/mL 1Jg/mL
Propofol 46g/mL 24g/mL 12g/mL 11.5g/mL
|Idazolam 100200ng/mL 50200ng/mL
40100
ng/mL
50150ng/mL
EtomIdate
5001000
ng/mL
J00600
ng/mL
100J00
ng/mL
200J50
ng/mL
KetamIne 14g/mL 0.62g/mL 0.11g/mL NA
NA,notavaIlable.
1997,pp.27and77.
TheE|CactIvItyofthefrontalIsmusclesIncreasessIgnIfIcantlyInpatIentswhomoveIn
responsetospecIfIcsurgIcalstImulI.
101
However,E|CchangesoccurlateandtheIr
InterpretatIonIsobscuredbymusclerelaxantdrugs.TheEECchangesdependlargelyon
thetypeofanesthetIcdrugsused.AlthoughacommonEECpatterncanberecognIzedwIth
IncreasIngdepressIonofCNSfunctIonbysedatIvehypnotIcsandopIoIdanalgesIcs,thereIs
nocharacterIstIcEECpatternassocIatedwIthunconscIousandamnestIcstates.
10J
UnIvarIatedescrIptorsofEECactIvItyappeartobeoflImItedclInIcalusefulness,andno
meanIngfulcorrelatIoncouldbefoundbetweenEECspectraledgefrequencyand
hemodynamIcresponsetosurgIcalstImulIdurIngpropofolanesthesIa.
104
AlthoughEEC
varIables(spectraledgefrequency,medIanfrequency)appeartobeusefulIndIcatorsofthe
CNSeffectsofanesthetIcandanalgesIcdrugsIntheexperImentalsettIng,theIrusefulness
InclInIcalpractIceIslImItedbecausethemanyconfoundIngfactorsdurIngtheoperatIon
(changIngdruglevelsandsurgIcalstImulatIon).TheEECbasedbIspectralIndex(8S),
patIentstateIndex,stateentropyandresponseentropy,andcerebralstateIndexrepresent
monItorIngapproachesthatreplyonsophIstIcatedcomputerIzedalgorIthmstoanalyzethe
spontaneousEEC.AllofthesecerebralmonItorIngdevIceshaveprovedtobeauseful
IndIcatorofanesthetIc(hypnotIc)depth.SeveralrecentstudIeshavedemonstratedthat
theuseoftheseIndIcescanImprovetItratIonofboth7andvolatIleanesthetIcsdurIng
surgery,therebyfacIlItatIngtherecoveryprocess.
105
UsIngEECbasedmonItorIngcan
reducethetImerequIredtoachIevefasttrackelIgIbIlItyandfacIlItateearlIerdIscharge
homeafterambulatorysurgery.
106,107
AnalternatIvetothespontaneousEECInvolvestheuseoftheevokedresponseoftheEEC
tosensorystImulI(e.g.,audItoryevokedpotentIalmonItors).TheabIlItytoquantItatIvely
assesstheresponseofthebodytovaryInglevelsofstImulatIon(sensoryoraudItory
evokedresponses)maybeusefulInImprovIngtheassessmentofdepthofanesthesIa.
108
AlthoughallsedatIvehypnotIcdrugsaffectthebraInstemevokedpotentIals,uncertaInty
stIllexIstsregardIngthemostusefulevokedresponse(s)tomeasure.ThecomplexIty
assocIatedwIthrecordIngevokedresponsesIsmuchgreaterthanrecordIngthe
spontaneousEECbecausethevalueIscrItIcallydependentontechnIcalfactors(e.g.,
stImulusIntensIty,stImulusrate,electrodeposItIon),bodytemperature,aswellasthe
anesthetIcdrugs.Althoughmost7anesthetIcsproducedosedependentchangesInthe
somatosensoryevokedpotentIals,thecorrelatIonbetweentheacutehemodynamIc
changestosurgIcalstImulIandtheearlyaudItoryevokedresponsesIspoor.However,the
earlycortIcal(mIdlatency)audItoryevokedresponsemIghtbeusefulIndetectIng
awarenessunderanesthesIa.Furthermore,theaudItoryevokedpotentIalIndexmaybe
moredIscrImInatIngthanthespontaneousEECbaseddevIcesIncharacterIzIngthe
transItIonfromwakefulnesstounresponsIveness.
109
Figure 18-7.SImulateddruglevelcurveswhenaconstantInfusIonIsadmInIstered
followIngafullloadIngdoseequalto[Cp]7d
ss
(Curve A),asmallerloadIngdose
equalto[Cp]7c(Curve B),orIntheabsenceofaloadIng(Curve C).Seetextfor
detaIls.(FeprIntedwIthpermIssIonfromWhItePF:ClInIcalusesofIntravenous
anesthetIcandanalgesIcInfusIons.AnesthAnalg1989;68:161.)
AsaresultoftheavaIlabIlItyofmorerapIdandshorteractIngsedatIvehypnotIcs,
sophIstIcatedcomputertechnology,andnewInsIghtsIntopharmacokInetIcdynamIc
InteractIons,useofT7AtechnIqueshasbeensteadIlyIncreasIngthroughouttheworld
durIngthelastdecade.WhenusIngconstantrate7InfusIons,4to5halflIvesmaybe
requIredtoachIeveasteadystateanesthetIcconcentratIon(FIg.187).TomorerapIdly
achIeveatherapeutIcbloodconcentratIon,ItIsnecessarytoadmInIsteraloadIng(prImIng)
doseandtomaIntaInthedesIreddrugconcentratIonusIngamaIntenanceInfusIon.The
loadIngdose(L0)andInItIalmaIntenanceInfusIonrate(|F)canbecalculatedfrom
prevIouslydetermInedpopulatIonkInetIcvaluesusIngthefollowIngequatIons:
L0=Cp(mg/mL)7d(mL/kg)
|F=Cp(mL/kg)Cl(mL/kg/mIn)
whereCp=plasmadrugconcentratIon,7d=dIstrIbutIonvolume,andCl=drugclearance.
TheuseofthesmallercentralvolumeofdIstrIbutIon(7c)forthe7dcomponentoftheL0
equatIonwIllunderestImatetheL0,whereasuseofthelargersteadystatevolumeof
dIstrIbutIon(7d
ss
)wIllresultIndruglevelsthattransIentlyexceedthosethataredesIred.f
asmallerL0IsadmInIstered,ahIgherInItIal|FwIllberequIredtocompensateforthe
drugthatIsremovedfromthebraInbybothredIstrIbutIonandelImInatIonprocesses.As
theredIstrIbutIonphaseassumeslessImportance,the|FwIlldecreasebecauseIt
becomessolelydependentonthedrug'selImInatIonandthedesIredplasmaconcentratIon.
AnalternatIveapproachIstobegInwItharapIdloadIngInfusIonwIthaboluselImInatIon
transferschemethatcombInesthreefunctIons,asshownInthefollowIngequatIon:
nput=71C
ss
+ClC
ss
+71C
ss
(k
21
e
k21t
)
where71=dIstrIbutIonvolumeofthecentralcompartment,C
ss
=steadystateplasma
concentratIon,Cl=drugclearance;k
21
=redIstrIbutIonconstantfromthecentraltothe
perIpheralcompartment,andk
21
=redIstrIbutIonconstantfromtheperIpheraltothe
centralcompartment.mplementatIonoftheboluselImInatIontransferInfusIonscheme
requIrestheuseofamIcroprocessorcontrolledpump.facontInuousInfusIonIstobeused
InanoptImalmannertosuppressresponsestosurgIcalstImulI,the|FshouldbevarIed
accordIngtotheIndIvIdualpatIentresponses(FIg.188).UsIngan|Flargeenoughto
suppressresponsestothemostIntensesurgIcalstImulIwIllleadtoexcessIvedrug
accumulatIon,postoperatIvesIdeeffects,anddelayedrecovery.|oregradualsIgnsof
InadequateorexcessIveanesthesIacanbetreatedbymakIng50to100changesInthe
|F.AbruptIncreasesInautonomIcactIvItycanbetreatedbygIvIngasmallbolusdose
equalto10to25oftheInItIalloadIngdoseandIncreasIngthe|F.
P.460
Figure 18-8.ThelandscapeofsurgIcalanesthesIa.ThesurgIcalstImulIarenot
constantdurInganoperatIon;therefore,theplasmaconcentratIonofanIntravenous
anesthetIcshouldbetItratedtomatchtheneedsoftheIndIvIdualpatIent.CU,
IntensIvecareunIt.(FeprIntedwIthpermIssIonfromClassPSA,ShaferSL,JacobsJF,
etal:ntravenousdrugdelIverysystems,|Iller'sAnesthesIa,4thed.NewYork,
ChurchIllLIvIngstone,1994,p.J91.)
0espItethemarkedpharmacokInetIcandpharmacodynamIcvarIabIlItythatexIstsamong
surgIcalpatIents,computerprogramshavebeendevelopedthatallowreasonable
predIctIonsofconcentratIontImeprofIlesfor7anesthetIcsandanalgesIcs.ThIsnew
technologyhasledtothedevelopmentoftargetcontrolledInfusIons(TC),wherebythe
anesthesIologIstchoosesatargetbloodorbraIn(effectIvesIte)drugconcentratIonand
themIcropressorcontrolledInfusIonpumpInfusesthedrugattherateneededtorapIdly
achIeveandmaIntaInthedesIredconcentratIonbasedonpopulatIonpharmacokInetIc
dynamIcdata.
109
tIsobvIousthatthetargetconcentratIonmustbealtereddependIngon
theobservedpharmacodynamIceffectandtheantIcIpatedchangesInsurgIcalstImulatIon.
ClosedloopcontrolbasedonplasmadrugconcentratIonsIsnotpossIblebecausethereIsno
avaIlablemethodtoobtaInfrequentmeasurementsofdrugconcentratIonsInrealtIme.A
moreadvancedformofTCusesafeedbacksIgnalgeneratedbysImulatIngamathematIcal
modelofthecontrolprocess.Clearly,theprecIsIonofcontrolachIevablewIthamodel
basedsystemIsonlyasaccurateasthemodel.AnexampleofamodelbaseddrugdelIvery
systemIsthecomputerassIstedcontInuousInfusIonsystem.AnIdealautomatIcanesthesIa
delIverydevIcewouldtItrateanesthetIctomeettheneedsoftheIndIvIdualpatIentusIng
anacquIredfeedbacksIgnalthataccuratelyreflectstheeffectsIteconcentratIonofthe
drug.ThemostsuccessfuleffortsatfeedbackcontrolofanesthesIahaveusedthe8Sand
cortIcalaudItoryevokedresponsestoassessthepharmacodynamIcendpoInt.
108
TherapId,shortactIngsedatIvehypnotIcs(e.g.,methohexItal,propofol)andopIoIds(e.g.,
alfentanIl,remIfentanIl)arebettersuItedforcontInuousadmInIstratIontechnIquesthan
themoretradItIonalanesthetIcandanalgesIcagentsbecausetheycanbemoreprecIsely
tItratedtomeettheunIqueandchangIngneedsoftheIndIvIdualpatIent.TradItIonally,the
elImInatIonhalflIfeofapartIculardrughasbeenusedInattemptIngtopredIctthe
duratIonofdrugactIonandthetImetoawakenIngafterdIscontInuatIonoftheanesthetIc
InfusIon.UsIngconceptualmodelIngtechnIques,Ithasbeenshownthattheconceptof
contextsensItIvehalftImeIsmoreapproprIateInchoosIngdrugsforcontInuous7
admInIstratIon(FIg.189).8ecausenoneofthecurrentlyavaIlable7drugscanprovIdefor
acompleteanesthetIcstatewIthoutproducIngprolongedrecoverytImesandundesIrable
sIdeeffects,ItIsnecessarytoadmInIsteracombInatIonof7drugsthatprovIdefor
hypnosIs,amnesIa,hemodynamIcstabIlIty,analgesIa,andmusclerelaxatIon.SelectInga
combInatIonofdrugswIthsImIlarpharmacokInetIcsandcompatIblepharmacodynamIc
profIlesshouldImprovetheanesthetIcandsurgIcalcondItIons.SedatIvehypnotIcs,opIoIds,
sympatholytIcs,andmusclerelaxantscanbesuccessfullyadmInIsteredusIngcontInuous
InfusIonT7AtechnIquesasalternatIvestothevolatIleanesthetIcsandnItrousoxIde.
Sedation in the Operating Room and Intensive Care Unit
TheuseofsedatIvehypnotIcdrugsaspartofamonItoredanesthesIacaretechnIqueIn
combInatIonwIthlocalanesthetIcsIsbecomIngIncreasInglypopular.
110,111,112
0urInglocal
orregIonalanesthesIa,subhypnotIcdosagesof7anesthetIcscanbeInfusedtoproduce
sedatIon,anxIolysIs,andamnesIaandenhancepatIentcomfort.TheoptImumsedatIon
technIqueachIevesthedesIredclInIcalendpoIntswIthoutproducIngperIoperatIvesIde
effects(e.g.,respIratorydepressIon,nausea,andvomItIng).
11J
naddItIon,Itshould
provIdeforeaseoftItratIontothedesIredlevelofsedatIonwhIleprovIdIngforarapId
returntoaclearheadedstateoncompletIonofthesurgIcalprocedure.
SedatIonalsoconstItutesanessentIalelementInthemanagementofpatIentsIntheCU.
TheIdealsedatIveagentforcrItIcallyIllpatIentswouldhavemInImaldepressanteffects
ontherespIratoryandcardIovascularsystems,wouldnotInfluencebIodegradatIonofother
drugs,andwouldbeIndependentofrenalandhepatIcfunctIonforItselImInatIon.
Fecently,the8SmonItorhasbeenusedtomonItorthedepthofsedatIonIntheCU.For
patIentsundergoIngcardIacsurgery,rapIdreversIbIlItyofthesedatIvestatemayresultIn
earlIerextubatIonandleadtoashorterstayIntheCU.AlthoughIntermIttentbolus
InjectIonsofsedatIvehypnotIcdrugs(e.g.,dIazepam2.5to5mg,lorazepam0.5to1mg,
mIdazolam1.25
P.461
to2.5mg)havebeenadmInIstereddurInglocalanesthesIa,contInuousInfusIontechnIques
wIthpropofolarebecomIngIncreasInglypopularformaIntaInIngastablelevelofsedatIon
IntheDFandCUsettIngs.
Figure 18-9.ContextsensItIvehalftImevaluesasafunctIonofInfusIonduratIonfor
IntravenousanesthetIcs,IncludIngthIopental,mIdazolam,dIazepam,ketamIne,
etomIdate,andpropofol.ThecontextsensItIvehalftImeforthIopentalanddIazepam
IssIgnIfIcantlylongercomparedwIthetomIdate,propofol,andmIdazolam,wIthan
IncreasIngInfusIonduratIonIncrease.(FeprIntedwIthpermIssIonfromHughes|A,
ClassPSA,JacobsJF:ContextsensItIvehalftImeInmultIcompartment
pharmacokInetIcmodelsforIntravenousanesthesIa.AnesthesIology1992;76:JJ4.)
8enzodIazepInes,partIcularlymIdazolam,arestIllthemostwIdelyusedforsedatIonInthe
CUandforrelIefofacutesItuatIonalanxIetydurInglocalandregIonalanesthesIa.
|IdazolamhasasteeperdoseresponsecurvethandIazepam(FIg.18J),
111
andtherefore
carefultItratIonIsnecessarytoavoIdoversedatIonandrespIratorydepressIon.|Idazolam
InfusIon,0.05to5mg/kg/mIn,canbehIghlyeffectIveInprovIdIngsedatIonfor
hemodynamIcallyunstablepatIentsIntheCU.
114
UseofamIdazolamInfusIonhasbeen
showntocontrolagItatIonanddecreaseanalgesIcrequIrementswIthoutproducIng
cardIovascularorrespIratoryInstabIlIty.However,markedvarIabIlItyexIstsformIdazolam
IntheIndIvIdualpatIentdoseeffectrelatIonshIps.naddItIon,markedtolerancemay
developtotheCNSeffectsofmIdazolamwIthprolongedadmInIstratIon.
PropofolsedatIonoffersadvantagesovertheothersedatIvehypnotIcs(IncludIng
mIdazolam)becauseofItsrapIdrecoveryandfavorablesIdeeffectprofIle.naddItIon,the
degreeofsedatIonIsreadIlychangeablefromlIghttodeeplevelsbyvaryIngthe|F.
FollowIngapropofolloadIngdoseof0.25to0.5mg/kg,acarefullytItratedsubhypnotIc
InfusIonof25to75g/kg/mInproducesastablelevelofsedatIonwIthmInImal
cardIorespIratorydepressIonandashortrecoveryperIod.8ecauseevenlowconcentratIons
ofpropofolcandepresstheventIlatoryresponsetohypoxIa,supplementaloxygenshould
alwaysbeprovIded.SedatIveInfusIonsofpropofolproducelessperIoperatIveamnesIathan
mIdazolam,andpropofolInducedamnesIaappearstobedIrectlyrelatedtotheInfusIon
rate.
AsmalldoseofmIdazolam(2mg7)admInIsteredImmedIatelybeforeavarIablerate
InfusIonofpropofolhasalsobeenshowntosIgnIfIcantlydecreaseIntraoperatIveanxIety
andrecallofuncomfortableeventswIthoutcompromIsIngtherapIdrecoveryfrompropofol
sedatIon.
112
PropofolsedatIoncanalsobesupplementedwIthpotentopIoIdandnonopIoId
analgesIcstoprovIdesedatIonanalgesIa.ncomparIngpropofolandmIdazolamforpatIent
controlledsedatIon,
115
mIdazolamwasassocIatedwIthlessIntraoperatIverecallandpaIn
onInjectIonthanpropofol,whIlepropofolwasassocIatedwIthlessresIdualImpaIrmentof
cognItIvefunctIon.ComparedwIthanesthesIologIstcontrolledsedatIon,patIentcontrolled
sedatIonwasassocIatedwIthfewerpropofoldosages,lIghterlevelsofsedatIon,and
reducedpatIentcomfort.
116
ComputertargetcontrolledsedatIonwasalsoassocIated
wIthmorefrequentoversedatIon.
117
FInally,musIccanreducethepropofoldosage
requIrementdurInglocalandregIonalanesthesIa.
118
ComparedwIthmIdazolamIntheCUsettIng,useofpropofolsedatIonallowedformore
rapIdweanIngofcrItIcallyIllpatIentsfromartIfIcIalventIlatIon.
119
thasbeensuggested
thatthemorerapIdweanIngafterpropofolsedatIonmaybecostsavIngcomparedwIth
mIdazolamwhenonlyalImItedperIodofsedatIon(48hours)IsrequIred.
120
Althougha
pharmacokInetIcstudyyIeldednoevIdenceofachangeInreceptorsensItIvItyordrug
accumulatIonovera4daystudyperIod,prelImInarydatasuggestthattolerancetotheCNS
effectsofpropofolmaydevelopwIthmoreprolongedadmInIstratIon(1week).
ncreasIngly,dexmedetomIdIneInfusIonsarebeIngusedIncrItIcallyIllpatIentswhorequIre
bothsedatIonandanalgesIa.
ConcernshavebeenraIsedaboutelevatedlIpIdplasmalevelsInpatIentssedatedwIth
standardformulatIonsofpropofoloveraperIodofseveraldays,especIallywhenhIgh
InfusIonrates(6mg/kg/hr)areused.However,theavaIlabIlItyofapropofolformulatIon
wIthreducedlIpIdcontent(Ampofol)shoulddecreasetherIskofthIsproblemInthefuture.
8ecauseofconflIctIngevIdenceregardIngIncreasedmortalItyasaresultofmyocardIal
faIlurewhenpropofolwasusedforsedatIonIntheneonatalCU,
121,122,12J,124
moresafety
dataareneededtodefInetheIndIcatIonsfortheuseofprolongedpropofolInfusIons,
especIallyInthIspatIentpopulatIon.LowdoseketamIneInfusIons(5to25mg/kg/mIn)can
alsobeusedforsedatIonandanalgesIadurInglocalorregIonalanesthetIcprocedures,as
wellasIntheCUsettIng.
67
|Idazolam,0.07to0.15mg/kgInfusedoverJto5mInutes,
followedbyketamIne,0.25to0.5mg/kg7over1toJmInutes,producedexcellent
sedatIon,amnesIa,andanalgesIawIthoutsIgnIfIcantcardIorespIratorydepressIon.
AnotheralternatIvetopropofolforsedatIonoutsIdetheDFIsdexmedetomIdIne.The
2
agonIstcanbeInfusedatratesof0.25to0.75g/kg/hrtoproducesedatIondurIng
gynecologIcprocedures
90
andIntheCU.AlthoughtheonsetofsedatIonIsslowerthanthat
ofpropofol,ItsopIoIdsparIngeffectsreducetherIskofventIlatorydepressIondurIng
proceduresoutsIdetheDFandmayfacIlItateweanIngfrommechanIcalventIlatIonInthe
CU.ntheambulatorysettIng,recoveryfromdexmedetomIdIne'ssedatIveeffectsIsslower
thanwIthpropofol.
Conclusions
0espItetheIntroductIonofnewanesthetIcagents,ItIsobvIousthatmanyofthegoals
desIrableInanIdeal7anesthetIchavenotbeenachIevedwIthanyofthecurrently
avaIlabledrugs.Nevertheless,eachofthesesedatIvehypnotIcdrugspossesses
characterIstIcsthatmaybeusefulInspecIfIcclInIcalsItuatIonsandwhencombInedwIthan
approprIatemultImodalanalgesIctechnIque(e.g.,opIoIds,nonsteroIdalantIInflammatory
drugs,localanesthetIcs)canprovIdeexcellentanesthetIccondItIons.nsItuatIonsInwhIch
arapIdrecoveryIsnotessentIal(e.g.,InpatIentprocedures),thebarbIturatesthIopental
andmethohexItalmaybethemostcosteffectIve7anesthetIcs.Althoughrecoveryfrom
anesthesIawIthmethohexItalIsmorerapIdthanwIththIopental(andcomparesfavorably
wIthpropofol),excItatorysIdeeffects(e.g.,myoclonus,hIccoughIng)aremorepromInent
thanwIththIopentalorpropofol.|ethohexItalremaInstheanesthetIcofchoIcefor
electroconvulsIvetherapyprocedures.
PropofolIsthe7drugofchoIcewhenarapIdandsmoothrecoveryIsessentIal(e.g.,
outpatIent[ambulatory]anesthesIa);IncreasIngly,propofolhasbeenusedforallInpatIent
proceduresbecauseoftheavaIlabIlItyoflesscostlygenerIcformulatIons.Fecoveryfrom
propofolanesthesIaIscharacterIzedbytheabsenceofahangovereffectandreduced
postoperatIvenauseaandvomItIngsymptoms.ThecardIovasculardepressanteffects
producedbypropofolappeartobemorepronouncedthanthoseofthIopental,butcanbe
mInImIzedbycarefultItratIonandtheuseofavarIablerateInfusIondurIngthe
maIntenanceperIod.TheabIlItytocombInepropofolwIthpotent,rapId,andshortactIng
opIoIdanalgesIcs(e.g.,remIfentanIl)hasfacIlItatedtheuseofT7AtechnIques.
mprovementsIntheTCdelIverysystemsfor7anesthetIcs(propofol)andanalgesIcs
(remIfentanIl)wIllleadtoanevergreateracceptanceofT7AtechnIquesInthefuture.
125
WhenadmInIsteredaloneforInductIonofanesthesIa,benzodIazepInesareassocIatedwIth
asloweronsetandmoreprolongedrecoveryprofIle.ntheusualInductIondoses,
benzodIazepInesareassocIatedwIthmInImalcardIorespIratorydepressIonandtherelIable
amnestIceffectmaybevaluabledurIngT7A(e.g.,foracutesedatIonprIortoInductIonof
anesthesIa,formaIntenanceIntheabsenceofnItrousoxIde).WhenadmInIsteredInsmaller
doses,mIdazolamcanalsobeavaluableadjunctaspartofacoInductIonand/or
maIntenance
P.462
technIque.DthershorteractIngbenzodIazepInesmaybedevelopedInthefuture(e.g.,Fo
486791).
EtomIdatehasmInImalcardIovascularandrespIratorydepressanteffectsandIstherefore
anextremelyusefulInductIonagentInhIghrIskpatIents.tIsalsooccasIonallyusedasan
alternatIvetomethohexItalforelectroconvulsIvetherapyprocedures.Theoccurrenceof
paInonInjectIon,excItatoryphenomena,adrenocortIcalsuppressIon,andahIghIncIdence
ofpostoperatIvenauseaandvomItInghavelImItedtheuseofetomIdatetospecIal
sItuatIonsInwhIchItscardIovascularprofIleofferssIgnIfIcantadvantagesoverother
avaIlable7anesthetIcs.AnewlIpIdformulatIonofetomIdateIsapparentlyassocIated
wIthItsfewersIdeeffectsandmayallowthIs7anesthetIctogaInwIderclInIcal
acceptanceInthefuture.
KetamIneIsaunIque7anesthetIcthatproducesawIdespectrumofpharmacologIceffects
IncludIngsedatIon,hypnosIs,somatIcanalgesIa,bronchodIlatIon,andsympathetIcnervous
systemstImulatIon.nductIonofanesthesIacanberapIdlyachIevedfollowIng|InjectIon,
makIngketamIneavaluablealternatIvetoanInhalatIonInductIonwhen7accessIs
dIffIculttoestablIsh.KetamIneIsalsoIndIcatedforInductIonofanesthesIaInthepresence
ofseverehypovolemIcshock,acutebronchospastIcstates,rIghttoleftIntracardIacshunts,
andcardIactamponade.TheadversehyperdynamIccardIovascular,cerebrodynamIc,and
psychomImetIceffectsofketamInecanbemInImIzedbyprIoradmInIstratIonofa
benzodIazepIne(e.g.,mIdazolam)orasedatIvehypnotIcdrug(e.g.,thIopental,propofol).
KetamIneIsalsousefulaspartofcoInductIonandmaIntenanceanesthetIctechnIqueswhen
avoIdIngopIoIdanalgesIcsIsdesIrable.TheIntroductIonofthemorepotentS(+)ketamIne
mayIncreaseuseofketamIneInsmalldosesorbycontInuousInfusIonasan7adjuvant
durInggeneralanesthesIabecauseofItsanesthetIcandanalgesIcsparIngactIvIty.
nsummary,7anesthesIahasevolvedfrombeIngusedmaInlyforInductIonofanesthesIa
toprovIdIngunconscIousnessandamnesIaforsurgIcalproceduresperformedunderlocal,
regIonal,andgeneralanesthesIa.NewInsIghtsIntothepharmacokInetIcsanddynamIcsof
7anesthetIcs,aswellasthedevelopmentofcomputertechnologytofacIlItate7drug
delIvery(e.g.,TCs),havegreatlyenhancedtheuseofT7AtechnIques.Theshorter
contextsensItIvehalflIfevaluesofthenewersedatIvehypnotIcdrugsmakethese
compoundsmoreusefulascontInuousInfusIonsformaIntenanceofanesthesIaand
sedatIon.WhIlethesearchfortheIdeal7anesthetIccontInues,themajorchallengefor
anesthesIologIstsIstochoosethesedatIvehypnotIcdrugthatmostcloselymatchesthe
patIent'sneedsInspecIfIcclInIcalsItuatIons.
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120.AItkenheadAF,Pepperman|L,WIllattsS|,etal:ComparIsonofpropofoland
mIdazolamforlongtermsedatIonIncrItIcallyIllpatIents.Lancet1989;2:704
121.CarrascoC,|olInaF,CostaJ,etal:Propofolvs.mIdazolamInshort,medIum,
andlongtermsedatIonofcrItIcallyIllpatIents:AcostbenefItanalysIs.Chest199J;10J:
557
122.|cFarlanCS,Anderson8J,ShortTC:TheuseofpropofolInfusIonsInpaedIatrIc
anaesthesIa:ApractIcalguIde.PaedIatrAnaesth1999;9:209
12J.ParkeTJ,StevenJE,FIceASC,etal:|etabolIcacIdosIsandfatalmyocardIal
faIlureafterpropofolInfusIonInchIldren:fIvecasereports.8|J1992;J05:61J
124.|artInPH,|urphy87S,PetrosAJ:|etabolIc,bIochemIcalandhaemodynamIc
effectsofInfusIonofpropofolforlongtermsedatIonofchIldrenundergoIngIntensIve
care.8rJAnaesth1997;79:276
125.EganT0,ShaferSL:TargetcontrolledInfusIonsforIntravenousanesthetIcs.
Stock, M. Christine
TableofContentsSectIon7AnesthetIcAgents,Adjuvants,and0rugnteractIonChapter19DpIoIds
Chapter19
Opioids
Barbara A. Coda
Key Points
1. The term opioid designates all drugs, both natural and synthetic,
including endogenous peptides, which have morphinelike properties.
In its broadest sense, it refers to agonists, partial agonists, and
mixed agonistantagonists at one or more of the opioid receptors.
2. Opioid receptor classification is based on binding activity of specific
ligands: morphine at mu (), ketocyclazocine at kappa (),
enkephalins at delta (), and endorphin at epsilon () receptors, and
specific opioid receptors are responsible for different opioid effects.
Most opioids used in clinical anesthesia today (e.g., fentanyl,
morphine, and their derivatives) are highly selective for -opioid
receptors. Naloxone, the most commonly used opioid antagonist, is
not selective for opioid receptor type. Very few endogenous opioids
exhibit great selectivity for a single receptor type.
3. Opioids are administered primarily for their analgesic effect, which
results from complex interactions at discrete sites in the brain, spinal
cord, and under certain conditions, peripheral tissues, and involves
both
1
and
2
opioid effects. Morphine also appears to exert anti-
inflammatory effects at
3
-opioid receptors. For the mixed agonist
antagonist opioids, analgesic effects are also mediated at receptors.
Opioids act selectively on neurons that transmit and modulate
nociception, leaving other sensory modalities and motor functions
intact.
4. Opioids are used in combination with inhaled anesthetics to produce
balanced anesthesia. Fentanyl and its derivatives reduce the
minimum alveolar concentration (MAC) of volatile agents in a dose-
dependent fashion. An apparent ceiling effect is seen at 70% MAC
reduction, although reduction of up to 90% has been reported for
sufentanil and remifentanil.
5. Fentanyl and its derivatives can be combined with a sedative-
hypnotic agent to provide total intravenous anesthesia (TIVA).
Alfentanil and remifentanil are particularly suited for TIVA because of
their rapid onset and short duration of action.
6. Fentanyl and its derivatives can be given in very high doses for
opioid anesthesia, but even at extremely high doses, that is, those
that produce profound analgesia as well as apnea, unconsciousness is
not assured.
7. Muscle hypertonus occurs with high-dose opioid administration, and
severe chest wall rigidity can interfere with ventilation. It is seen
most often on induction with rapid-acting opioids. Opioid-induced
muscle rigidity is increased in the presence of nitrous oxide and can
be prevented or treated with sedative-hypnotics or low-dose muscle
relaxants.
8. All opioids depress respiratory drive in a dose-dependent manner,
and ventilatory depression is seen even at doses associated with mild
analgesia. Equianalgesic opioid doses produce equivalent magnitudes
of respiratory depression. When given in combination with
benzodiazepines, opioids can blunt hypoxic drive to a greater extent
than the hypercarbic drive and produce profound respiratory
depression.
9. Fentanyl or one of its derivatives is often used as a component of
anesthetic induction. Small opioid doses reduce the dosage
requirements of sedative-hypnotics, and blunt airway reflexes
(sympathetic activity in response to laryngoscopy).
10. In low doses, opioids have minimal cardiovascular effects, but
bradycardia and hypotension are seen with higher doses. A
prominent feature of fentanyl and its derivatives is their remarkable
hemodynamic stability. Morphine and meperidine cause histamine
release, and high doses of these opioids can produce hypotension.
11. All opioids can produce nausea and vomiting through complex
interactions at nausea and vomiting centers in the medulla. In
general, equianalgesic doses of opioids produce similar magnitude of
nausea. Opioid-induced nausea can be exacerbated by vestibular
input, and is particularly problematic in ambulatory patients.
12. Opioids produce smooth muscle spasm throughout the
gastrointestinal tract. They decrease gastric secretions and delay
gastric emptying. Opioids increase the tone of the common bile duct
and sphincter of Oddi, although meperidine and the mixed agonist
antagonists cause less biliary spasm than morphine and fentanyl.
P.466
History
DpIoIdshavebeenusedInthetreatmentofpaInforthousandsofyears.ThedrugopIum,
whIchcontaInsmorethan20alkaloIds,IsobtaInedfromtheexudateofPapaver
somniferumseedpods,andthewordopiumIsderIvedfromopos,theCreekwordforjuIce.
ThefIrstundIsputedreferencetopoppyjuIceIsfoundInthethIrdcentury(8CE)wrItIngsof
Theophrastus.
1
TheCermanpharmacIstSertuenerIsolatedwhathecalledthesoporIfIc
prIncIpleInopIumIn1806,andIn1817namedItmorphIne,aftertheCreekgodofdreams,
|orpheus.
2
solatIonofotheropIumalkaloIdsfollowed,andbythemId1800s,themedIcal
useofpurealkaloIdsratherthancrudeopIumpreparatIonsbegantospread.
1
|orphInewas
usedwIdelytotreatwoundedsoldIersdurIngtheAmerIcanCIvIlWar,andIn1869Itsuseas
apremedIcatIonwasdescrIbedbyClaude8ernard.However,Intheabsenceofmuscle
relaxantsandcontrolledventIlatIon,opIoIdswereassocIatedwIthasIgnIfIcantrIskof
severerespIratorydepressIonanddeath.ThustheIruseInanesthesIawaslImItedatthat
tIme.
WIththeadventofcardIacsurgeryInthelate1950scamethedevelopmentofopIoId
anesthesIa.Adecadelater,LowensteIn
J
reportedtheuseofprogressIvelyhIgherdosesof
morphIne(0.5toJmg/kg),butfoundlImItatIonsIncludIngIncompletesuppressIonofthe
stressresponse,hypotensIon,awarenessdurInganesthesIa,andIncreasedfluIdandblood
requIrements.
Fentanyl,a4anIlInopIperIdInederIvatIveofphenoperIdIne,wassynthesIzedIn1960.The
completelysynthetIcopIoIdsweremorepotentandhadabettersafetymargIn(ratIoof
medIanlethaldosetolowesteffectIvedoseforsurgery)thanmeperIdIne.AdvancesIn
surgIcaltechnIquescreatedtheneedforpotentopIoIdswItharapIdonset,abrIef,
predIctableduratIon,andamaxImalsafetymargInforuseInclInIcalanesthesIa,andledto
developmentofsufentanIl,alfentanIl,andotherfentanylderIvatIvesbetween1974and
1976.ThenewestpotentopIoId,remIfentanIl,hasanultrashortduratIonofactIonbecause
ofrapIdmetabolIsmbyesterhydrolysIsandoffersanadvantageInspecIfIcclInIcalsettIngs.
ThesearchforopIoIdanalgesIcswIthoutpotentIalfordependencewasstImulatedby
concernsaboutopIoIdaddIctIonandledtotheIdentIfIcatIonofmultIpleopIoIdreceptor
types.nthemId1960s,nalorphIne,amorphIneantagonIst,wasalsofoundtohave
analgesIcpropertIes.Twoothercompounds,pentazocIneandcyclazocIne,antagonIzed
someofmorphIne'seffects.PentazocInealsoproducedanalgesIa,andbothproducedsome
psychotropIceffectsthatmorphInedIdnot.TheseandotherobservatIonsled|artIn
4
to
proposethetheoryofreceptordualIsm.ntrInsIctothIstheoryweretwokeyconcepts:(1)
theexIstenceofmultIpleopIoIdreceptors(orIgInallyonlytwowereproposed)and(2)the
IdeaofpharmacologIcredundancy(I.e.,morethanonereceptorcouldmedIatea
physIologIcfunctIon,suchasanalgesIa).Thus,adrugcouldbeastrongagonIst,apartIal
agonIst,oracompetItIveantagonIstatoneormoreofthedIfferentreceptortypes.
SubsequentresearchhasrevealedthreedIstInctfamIlIesofopIoIdpeptIdesandmultIple
categorIesofopIoIdreceptors.
Terminology
ThetermopiatewasorIgInallyusedtorefertodrugsderIvedfromopIum,IncludIng
morphIne,ItssemIsynthetIcderIvatIves,andcodeIne.Themoregeneraltermopioidwas
IntroducedtodesIgnatealldrugs,bothnaturalandsynthetIc,wIthmorphInelIke
propertIes,IncludIngendogenouspeptIdes.ThenonspecIfIctermnarcotichasbeenusedto
refertomorphIneandmorphInelIkeanalgesIcs.However,becauseofItsuseInalegal
context,referrIngtoanydrug(IncludIngnonopIoIdssuchascocaIne)thatcanproduce
dependence,thetermnarcotIcIsnotusefulInapharmacologIcorclInIcalcontext.
Figure 19-1.LogdoseeffectcurvesfortwoagonIsts(Aand8)wIthequaleffIcacybut
dIfferentpotency,andapartIalagonIst(C).NotethatthepotencIesofAandCare
sImIlar,buttheeffIcacyIslessandtheslopeofthedoseresponsecurveIsshallower
forthepartIalagonIst.Notealsothatatlowerdoses,thepartIalagonIstCIsmore
potentthanthefullagonIst8.
nItsbroadestsense,thetermopioidcanrefertoagonIsts,partIalagonIsts,mIxedagonIst
antagonIsts,andcompetItIveantagonIsts.0IfferentIatIonofthesetermsrequIres
understandIngofreceptorlIgandInteractIons.Feceptortheorystatesthatdrugshavetwo
IndependentcharacterIstIcsatreceptorsItes:affinity,theabIlItytobIndareceptorto
produceastablecomplex,andIntrInsIcactIvItyorefficacy,whIchIsdescrIbedbythedose
effectcurveresultIngfromthedrugreceptorcombInatIon.EffIcacycanrangefromzero
(I.e.,noeffect)tothemaxImumpossIbleeffect,depIctedgraphIcallyastheplateauofthe
doseeffectcurve(FIg.191).CIvenahIghenoughdose,anagonistwIllproducethe
maxImumpossIbleeffectofbIndIngwIththereceptor,whereasanantagonistproducesno
dIrecteffectwhenItbIndsthereceptor.Apartial agonisthasadoseeffectceIlIngthatIs
lowerthanthemaxImumpossIbleeffectproducedbyafullagonIst,aswellasadoseeffect
curvethatIslesssteepthanthatofafullagonIst.Amixed agonistantagonistactsasan
agonIst(orpartIalagonIst)atonereceptorandanantagonIstatanother.tIsImportantto
dIfferentIatethetermpotencyfromeffIcacy.WhereaseffIcacydefInestherangeIn
magnItudeofaneffectproducedbyadrugreceptorcombInatIonrelatIvetothemaxImum
possIbleeffect,potencyreferstotherelatIvedoserequIredtoachIeveaneffect,andIs
relatedtoreceptoraffInIty.Thus,atthelowerendoftheeffectrange,apartIalagonIst
maybemorepotentthanafullagonIst(FIg.191).However,evenatverylargedosesthe
effIcacy,ormaxImumeffectachIevedbythepartIalagonIst,wIllbelessthanthe
maxImumpossIbleeffectofafullagonIst.
Endogenous Opioids and Opioid Receptors
AlloftheendogenousopIoIdsarederIvedfromthreeprohormones:proenkephalIn,
prodynorphIn,andproopIomelanocortIn(PD|C).EachoftheseprecursorsIsencodedbya
separategene.ThethreefamIlIesofpeptIdesdIfferIntheIr
P.467
dIstrIbutIon,receptorselectIvIty,andneurochemIcalrole,
5
butsharesomefeatures.For
example,allbegInwIththepentapeptIdesequencesof[Leu]or[|et]enkephalIn.
ProenkephalInIncludesthepentapeptIdesequencesfor[|et]and[Leu]enkephalIn,and
cellsthatsynthesIzeproenkephalInarewIdelydIstrIbutedthroughoutthebraIn,spInal
cord,andperIpheralsItes,partIcularlytheadrenalmedulla.
6
ProopIomelanocortInIsthe
commonprecursorofendorphIn,adrenocortIcotropIchormone(ACTH),andmelanocyte
stImulatInghormone.ThetermendorphinIsreservedforpeptIdesofthePD|CfamIly.The
majorsIteofPD|CsynthesIsIsthepItuItary,butItIsalsofoundInthepancreasand
placenta.ThedynorphInpeptIdesallbegInwIththe[Leu]enkephalInsequenceandare
wIdelydIstrIbutedthroughoutthebraIn,spInalcord,andperIpheralsItes.
EndogenousopIoIdsbIndtoanumberofopIoIdreceptorstoproducetheIreffects.The
InItIalclassIfIcatIonby|artIn
4
ofopIoIdreceptorsIntothethreetypeswasbasedon
bIndIngactIvItyoftheexogenouslIgandsmorphIne,ketocyclazocIne,andSKF10,047atmu
(),kappa(),andsIgma()receptors,respectIvely.DtheropIoIdreceptorsIdentIfIed
sIncethattImearedelta()receptors,boundbyenkephalIns,andepsIlon()receptors,
boundbyendorphIn.
5,6
ThereIsalsoevIdencesupportIngtheexIstenceoftwo,two,
andthreereceptorsubtypes.
7
ncreasIngevIdencesupportsathIrdreceptorsubtype,
presentonhumanvasculartIssuesandleukocytes.
8
WhIleItappearsthatspecIfIcopIoId
receptorsareresponsIblefordIfferentopIoIdeffectsandthatsynthetIcopIoIdsmaybe
hIghlyselectIveforareceptortypeorsubtype,ItIsImportanttonotethatveryfew
endogenousopIoIdsexhIbItgreatselectIvItyforasInglereceptortype.
9
Fememberalso,thatthetheoryofreceptordualIsmIncludestheconceptofpharmacologIc
redundancyofreceptorfunctIon.Thus,observedopIoIdeffectstypIcallyInvolvecomplex
InteractIonsamongthedIfferentreceptorsystemsatsupraspInal,spInal,andperIpheral
sItes.TheexpressIonofendogenousopIoIdsandopIoIdreceptorsIsnotastatIc
phenomenon.Forexample,acuteInflammatIonhasbeenshowntoupregulatethe
expressIonofbothendorphInandmetenkephalInaswellasperIpheralandopIoId
receptors.
10,11
Conversely,chronIcInflammatIonIsassocIatedwIthdownregulatIonof
opIoIdreceptors.
12
opIoIdreceptorexpressIonwasalsodecreasedInthedorsalroot
ganglIaInanerveInjurymodelofneuropathIcpaIn.
1J
Table191summarIzesourcurrent
understandIngofwhIchopIoIdreceptorsareresponsIbleformedIatIngopIoIdanalgesIcand
sIdeeffects.DnecaveatInInterpretIngthIssummaryIsthatspecIesdIfferencesInopIoId
receptorsystemsexIst,sotheresultsofanImalstudIes,fromwhIchmostofthIs
InformatIonIsderIved,maynotalwaysbedIrectlyapplIcabletohumans.|ostopIoIdsused
InclInIcalanesthesIatoday(e.g.,fentanyl,morphIne,andtheIrderIvatIves)arehIghly
selectIveforopIoIdreceptors.Naloxone,themostcommonlyusedopIoIdantagonIst,Is
notselectIveforopIoIdreceptortype.nfact,currentIdentIfIcatIonofanopIoIdreceptor
medIateddrugeffectrequIresdemonstratIonofnaloxonereversIbIlIty.0evelopmentof
selectIve
P.468
opIoIdreceptorsubtypeantagonIsts,suchasnaltrIndole(aopIoIdreceptorantagonIst)
andnorbInaltorphImIne(aopIoIdreceptorantagonIst)arecurrentlyImprovIngour
understandIngofwhIchreceptorsubtypesmedIatespecIfIcopIoIdeffects.
Table 19-1 Tentative Classification of Opioid Receptor Subtypes and Their
Actions
RECEPTOR ANALGESIA RESPIRATORY GASTROINTESTINAL ENDOCRINE OTHER
PerIpheral
CastrIc
secretIon
PrurItus

CtransIt
supraspInal
and
perIpheral
Skeletal
musclerIgIdIty
:UrInary
retentIon
(and/or)
AntIdIarrheal
8IlIaryspasm
(probably1
receptortype)
1
SupraspInal
ProlactIn
release
AcetylcholIne
turnover
Catalepsy
2
SpInaland
supraspInal
(synergIsm
wIth
spInal)
FespIratory
depressIon
CtransIt
spInaland
supraspInal
|ost
cardIovascular
effects
J

AntI
Inflammatory
PerIpheral
A0H
release
SedatIon
1
SpInal AntIprurItIc
2
:
(Pharmacology
unknown)
J
SupraspInal
PerIpheral
:
FespIratory
depressIon
CtransIt
spInal
AntIdIarrheal
spInaland
supraspInal
:Crowth
hormone
release
:UrInary
retentIon
(and/or)
1
SpInal
0opamIne
turnover
2
SupraspInal
Unknown
(receptor
typenot
IdentIfIed)
SupraspInal
PupIllary
constrIctIon
Nauseaand
vomItIng
C,gastroIntestInal;A0H,antIdIuretIchormone.
AdaptedfromPasternakCW:PharmacologIcalmechanIsmsofopIoIdanalgesIcs.ClIn
Neuropharmacol199J;16:1.
Atthecellularlevel,endogenousandexogenousopIoIdsproducetheIreffectsbyalterIng
patternsofInterneuronalcommunIcatIon.FeceptorbIndIngInItIatesaserIesofphysIologIc
functIonsresultIngIncellularhyperpolarIzatIonandInhIbItIonofneurotransmItterrelease,
effectsthataremedIatedbysecondmessengers.AllopIoIdreceptorsappeartobecoupled
toCproteIns,
5
whIchregulatetheactIvItyofadenylatecyclaseamongotherfunctIons.C
proteInInteractIons,Inturn,affectIonchannels;dIfferentIonconductancesmaybe
InvolvedatdIfferentopIoIdreceptortypes.
9
StructureActivity Relationships
ThewIdearrayofdIfferentmoleculesthatproducemorphInelIkeanalgesIaandsIde
effects,IncludIngendogenousopIoIds,allsharesomecommonstructuralcharacterIstIcs.
HornandFodgers
7
suggestedthatthetyrosInemoIetyattheamInotermInalofthe
enkephalInsformedthebasIsofasIgnIfIcantconformatIonalrelatIonshIpbetweenthe
enkephalInsandopIates.ThestructureofthephenanthreneclassofopIumalkaloIdsIs
complexandconsIstsoffIveorsIxfusedrIngs.|orphIne,oneofthreephenanthrenes,hasa
rIgIdfIverIngstructurethatconformstoaTshape(FIg.192).
14
Theother
phenanthrenesarecodeIne,aderIvatIveofmorphIne,andthebaIne,aprecursorof
oxycodoneandnaloxone.ProgressIvelyreducIngthenumberoffusedrIngsfromthe
phenanthrenesyIeldsthemorphInans,wIthfourrIngs;thebenzomorphans,wIththree
rIngs;thephenylpIperIdInes,wIthtworIngs;andfInally,thetyramInemoIetyofthe
endogenousopIoIdpeptIdes,wIthasInglehydroxylatedrIng.AllofthesedIstInctclassesof
drugspossessmorphInelIkeactIvIty.TheopIatereceptormodelofThorpe
14
Isbasedon
thesestructuralsImIlarItIeswIthtwoaromatIcbIndIngsItesandoneanIonIcsIte
responsIbleforbIndIngtheposItIvelychargednItrogen.nthIsmodel,dIfferencesInbIndIng
atthearomatIcoranIonIcsItescouldaccountforreceptorspecIfIcItyorforagonIstversus
antagonIstactIvIty.StructuralmodIfIcatIonsaltersuchImportantpropertIesasopIoId
receptoraffInIty,agonIstversusantagonIstactIvIty,resIstancetometabolIcbreakdown,
lIpIdsolubIlIty,andpharmacokInetIcs.
1
Figure 19-2.TshapeconformatIonofopIoIdmolecules.A.|orphIne,oneofthe
phenanthrenealkaloIds,hasarIgIdfIverIngstructure,wIthaphenylpIperIdInerIng
formIngacrossbarandahydroxylatedaromatIcrIngInthevertIcalaxIs.B.FeducIng
thenumberoffusedrIngstofouryIeldsthemorphInanclassofopIumalkaloIds.C.
8enzomorphanshavethreefusedrIngs.D.PhenylpIperIdInesandthe4
anIlInopIperIdInessuchasfentanylhaveaflexIbletworIngstructure.E.FInally,the
tyramInemoIety,whIchIstheamInotermInalpeptIdeofboth[Leu]and[|et]
enkephalIn,Isshown,wIthasInglearomatIcrIng.AnotherkeyfeatureIstheposItIvely
chargedbasIcnItrogenequIdIstant(4.55)fromthearomatIcrIng.(AdaptedwIth
permIssIonfromThorpe0H:DpIatestructuresandactIvIty:AguIdetounderstandIng
thereceptor.AnesthAnalg1984;6J:14J.)
Pharmacokinetics and Pharmacodynamics
DpIoIdeffectsareInItIatedbythecombInatIonofanopIoIdwIthoneormorereceptorsat
specIfIctIssuesItes.TherelatIonshIpbetweenopIoIddoseandeffectsdependsonboth
pharmacokInetIcandpharmacodynamIcvarIables.PharmacokineticsdetermInesthe
relatIonshIpbetweendrugdoseandItsconcentratIonattheeffectsIte(s).
PharmacodynamicvarIablesrelatetheconcentratIonofadrugatItssIteofactIon,InthIs
caseopIoIdreceptorsInthebraInandothertIssues,andtheIntensItyofItseffects.
PharmacokInetIcsgenerallyreferstothestudyofbloodorplasmadrugconcentratIon
versustImebecausebloodIseasytosample,bearsadefInablerelatIonshIptotIssue
concentratIon,andIsthemedIumbywhIchdrugsaredIstrIbutedthroughoutthebody.
ChangesIndrugconcentratIonovertImeIntheblood,attheeffectsIteandatothersItes,
aredetermInedbyphysIcochemIcalpropertIesofthedrugaswellastheprocessesof
absorptIon,redIstrIbutIon,bIotransformatIon,andelImInatIon.
nclInIcalanesthesIapractIce,opIoIdsaretypIcallyadmInIsteredIntravenously.Afteran
Intravenous(7)bolusdoseorbrIefInfusIon,peakplasmaopIoIdconcentratIonsoccur
wIthInmInutes.PlasmadrugconcentratIonsthenfallrapIdlyasthedrugIsdIstrIbutedto
extravascularsItes,IncludIngsItesofactIon,nonelImInatIngtIssues,andelImInatIng
organs.CompartmentalmodelsdescrIbethetImecourseofchangeInplasma
concentratIon;typIcally,opIoIdsusedInanesthesIaarecharacterIzedbytwoorthree
compartmentmodels(seeChapter7).TheearlyrapIddeclIneInplasmaconcentratIon
afterthepeakIscalledthedistribution phase,andthesubsequentslowerdeclIneIsthe
elimination phase.FromamathematIcalcurvefIttedtomeasuredplasmaconcentratIon
versustImedata,dIstrIbutIonandelImInatIonhalflIves,systemIc
P.469
clearance,compartmentvolumes,andIntercompartmentaltransferrateconstantscanbe
calculated.Table192summarIzestheestImatesofkeypharmacokInetIcparametersand
physIcochemIcalcharacterIstIcsforthemostcommonlyusedopIoIdsInclInIcalanesthesIa.
Table 19-2 Physicochemical Characteristics and Pharmacokinetics of
Commonly Used Opioid Agonists in Adults
PARAMETER MORPHINE MEPERIDINE FENTANYL SUFENTANIL ALFENTANIL REMIFENTANIL
pKa 7.9 8.5 8.4 8.0 6.5 7.26
a
NonIonIzed
(pH7.4)
2J 7 8.5 20 89 58
a
ow
1.4 J9 816 1,757 128 17.9
b
ProteIn
bIndIng()
J5 70 84 9J 92 669J
a
Clearance
(mL/mIn)
1,050 1,020 1,5J0 900 2J8 4,000
7d
ss
(L)
224 J05 JJ5 12J 27 J0
FapId
dIstrIbutIon
halflIfe
(T
1/2
,mIn)
1.21.9 1.4 1.0J.5 0.40.5
Slow
redIstrIbutIon
halflIfe
(T
1/2
,mIn)
1.54.4 416 9.219 17.7 9.517 2.0J.7
ElImInatIon
halflIfe
(T
1/2
,h)
1.7J.J J5 J.16.6 2.24.6 1.41.5 0.170.JJ
ow
,octanol:waterpartItIoncoeffIcIent;7d
ss
,steadystatevolumeofdIstrIbutIon.
a
UnpublIshedInformatIonfromClaxo.J.C.8ovIll,personalcommunIcatIon,1995.
b
ClassPSA,etal:AnesthAnalg1999;89:S7.
Adaptedfrom8ovIllJC:PharmacokInetIcsandpharmacodynamIcsofopIoId
agonIsts.AnaesthPharmacolFev199J;1:122.
tIsImportanttonotethatthereIstremendousvarIabIlItyInthevaluespublIshedfor
opIoIdpharmacokInetIcparameters.ThIsIspartlybecauseofrealpopulatIondIfferences
(e.g.,age,dIseases)andpartlybecauseofdIfferencesInstudydesIgn(e.g.,samplIngsIte,
duratIon,concomItanteventssuchassurgery,orotherdrugsthatmayaffectdIfferentIal
flowtosItesofmetabolIsmorelImInatIon).naddItIon,thedIstrIbutIonalandelImInatIon
halflIvesareoflImIteduseInpredIctIngtheonsetandduratIonofopIoIdactIonInclInIcal
anesthesIa.ContrIbutIonsofdIstrIbutIonprocessesbetweenphysIologIccompartmentsvary
wIthtIme.nanefforttorelatepharmacokInetIcstothetImeofonsetandduratIonof
actIon,conceptssuchaseffect compartmentInpharmacodynamIcmodelIng
15
andcontext-
sensitive half-times
16
havebeendeveloped.TheapplIcatIonoftheseconceptsIs
consIderedlaterInthIschapter.
PhysIcochemIcalpropertIesofopIoIdsInfluencebothpharmacokInetIcsand
pharmacodynamIcs.ToreachItseffectorsItesInthecentralnervoussystem(CNS),an
opIoIdmustcrossbIologIcmembranesfromthebloodtoreceptorsonneuronalcell
membranes.TheabIlItyofopIoIdstocrossthIsbloodbraInbarrIerdependsonsuch
propertIesasmolecularsIze,IonIzatIon,lIpIdsolubIlIty,andproteInbIndIng(Table192).
DfthesecharacterIstIcs,lIpIdsolubIlItyandIonIzatIonassumemajorImportanceIn
determInIngtherateofpenetratIontotheCNS.nthelaboratory,lIpIdsolubIlItyIs
measuredasanoctanol:wateroroctanol:bufferpartItIoncoeffIcIent.0rugIonIzatIonIs
alsoanImportantdetermInantoflIpIdsolubIlIty;nonIonIzeddrugsare1,000to10,000
tImesmorelIpIdsolublethantheIonIzedform.
17
ThedegreeofIonIzatIondependsonthe
pKaoftheopIoIdandthepHoftheenvIronment.AnopIoIdwIthapKamuchlowerthan7.4
wIllhaveamuchgreaternonIonIzedfractIonInplasmathanonewIthapKaclosetoor
greaterthanphysIologIcpH.WhIlegreaterlIpIdsolubIlItycorrelateswIthmembrane
permeabIlIty,therelatIonshIpIsnotsImplyalInearone.Hanschand0unn
18
haveshown
thatthereIsanoptImalhydrophobIcItyforbloodbraInbarrIerpenetratIon,and8ernards
andHIll
19
havedemonstratedasImIlarbIphasIcrelatIonshIpbetweentheoctanol:buffer
dIstrIbutIoncoeffIcIentandspInalmenIngealpermeabIlIty.PlasmaproteInbIndIngalso
affectsopIoIdredIstrIbutIonbecauseonlytheunboundfractIonIsfreetodIffuseacrosscell
membranes.ThemajorplasmaproteInstowhIchopIoIdsbIndarealbumInand
1
acId
glycoproteIn.AlteratIonsIn
1
acIdglycoproteInconcentratIonoccurInavarIetyof
condItIonsanddIseasestatesandresultInacuteorchronIcchangesInopIoIdrequIrements.
TwomaInmechanIsmsareresponsIblefordrugelImInatIon:biotransformationand
excretion.DpIoIdsarebIotransformedInthelIverbytwotypesofmetabolIcprocesses.
PhasereactIonsIncludeoxIdatIveandreductIvereactIons,suchasthosecatalyzedby
cytochromeP450system,andhydrolytIcreactIons.PhasereactIonsInvolveconjugatIon
ofadrugorItsmetabolItetoanendogenoussubstrate,suchas0glucuronIcacId.
17
FemIfentanIlIsmetabolIzedvIaesterhydrolysIs,whIchIsunIqueforanopIoId.WIththe
exceptIonsoftheNdealkylatedmetabolIteofmeperIdIneandthe6andpossIblyJ
glucuronIdesofmorphIne,opIoIdmetabolItesaregenerallyInactIve.DpIoIdmetabolItes
and,toalesserextent,theIrparentcompoundsareexcretedprImarIlybythekIdneys.The
bIlIarysystemandgutareotherroutesofopIoIdexcretIon.
Morphine
|orphIneproducesItsmajoreffectsIntheCNSandthegastroIntestInalsystem,butother
systemsarealsoaffected.CNSeffectsIncludeanalgesIa,sedatIon,changesInaffect,
respIratory
P.470
depressIon,nauseaandvomItIng,prurItus,andchangesInpupIlsIze.|orphInealsoaffects
gastrIcsecretIonsandgutmotIlIty,andhasendocrIne,urInary,andautonomIceffects.t
mImIcstheeffectsofendogenousopIoIdsbyactIngasanagonIstat
1
and
2
opIoId
receptorsthroughoutthebodyandIsconsIderedthestandardagonIsttowhIchother
agonIstsarecompared.
Analgesia
|orphIneanalgesIaresultsfromcomplexInteractIonsatanumberofdIscretesItesInthe
braIn,spInalcord,andundercertaIncondItIons,perIpheraltIssues,andInvolvesboth
1
and
2
opIoIdeffects.|orphIneandrelatedopIoIdsactselectIvelyonneuronsthat
transmItandmodulatenocIceptIon,leavIngothersensorymodalItIesandmotorfunctIons
Intact.AtthespInalcordlevel,morphIneactspresynaptIcallyonprImaryafferent
nocIceptorstodecreasethereleaseofsubstancePandalsohyperpolarIzespostsynaptIc
neuronsInthesubstantIagelatInosaofthedorsalspInalcordtodecreaseafferent
transmIssIonofnocIceptIveImpulses.
20
SpInalmorphIneanalgesIaIsmedIatedby
2
opIoId
receptors.SupraspInalopIoIdanalgesIaorIgInatesIntheperIaqueductalgraymatter,the
locusceruleus,andnucleIwIthInthemedulla,notablythenucleusraphemagnus,and
prImarIlyInvolves
1
opIoIdreceptors.|IcroInjectIonsofmorphIneIntoanyofthese
regIonsactIvatetherespectIvedescendIngmodulatorysystemstoproduceprofound
analgesIa.
6,20
EndogenouspaIntransmIssIonandmodulatIonpathwaysaredIscussedIn
Chapter58.|orphInecanactatanumberofthesedIscreteregIonsIntheCNStoproduce
synergIstIcanalgesIceffects.Forexample,coadmInIstratIonatthelevelofthebraInand
spInalcordIncreasesmorphIne'sanalgesIcpotencynearlytenfold,
21
aneffectmedIatedby
2
opIoIdreceptors.
6
TherearealsosynergIstIcInteractIonsbetweensupraspInalsItesof
opIoIdactIon(e.g.,betweentheperIaqueductalgraymatterandthenucleusraphe
magnus).
6
WhenacuteInflammatIonIspresent,morphInemayalsoproduceanalgesIaby
actIvatIngperIpheralopIoIdreceptors.
11,22
nchronIcpaIncondItIonssuchasneuropathIc
paInorchronIcarthrItIs,spInalandperIpheralreceptorsmaybedownregulated,astate
thatcandecreasemorphIneanalgesIa.
12,1J
AlthoughrapIdlychangIngplasmamorphIneconcentratIons,suchasthosethatfollowbolus
dosIng,donotcorrelatewellwIthanalgesIceffects,constantorveryslowlychangIng(I.e.,
steadystate)plasmaconcentratIonsdocorrelatewItheffectIntensItIes.ThemInImum
effectIveanalgesIcconcentratIon(|EAC)ofmorphIneforpostoperatIvepaInrelIefIs10to
15ng/mL.
2J
FormoreseverepaIn,plasmamorphIneconcentratIonsofJ0to50ng/mLare
neededtoachIeveadequateanalgesIa.
24
Effect on Minimum Alveolar Concentration of Volatile
Anesthetics
agonIstsareusedextensIvelyInconjunctIonwIthInhaledanesthetIcstoprovIde
balancedanesthesIa.nanImals,morphInedecreasesthemInImumalveolar
concentratIon(|AC)ofvolatIleanesthetIcsInadosedependentmanner,
25,26
butthere
appearstobeaceIlIngeffecttotheanesthetIcsparIngabIlItyofmorphIne,wIthaplateau
at65|AC.
25
|orphIne1mg/kgadmInIsteredwIth60nItrousoxIde(N
2
D)blocksthe
adrenergIcresponsetoskInIncIsIonIn50ofpatIents,acharacterIstIccalledMAC-BAR.
27
NeuraxIalmorphInemayalsoreduce|AC.EpIduralmorphIne4mggIven90mInutesprIor
toIncIsIonreduceshalothane|ACbynearlyJ0.
28
TheeffectofIntrathecalmorphIneon
|ACIsunclear.nonestudy,arelatIvelylargedoseofIntrathecalmorphIne(750g)
reducedhalothane|ACapproxImately40,
29
butanequallylargedose(15g/kg)faIledto
reducehalothane|ACInanother.
J0
Other Central Nervous System Effects
|orphInecanproducesedatIon,aswellascognItIveandfInemotorImpaIrment,evenat
plasmaconcentratIonscommonlyachIeveddurIngmanagementofmoderatetosevere
paIn.
J1
DthersubjectIvesIdeeffectsIncludeeuphorIa,dysphorIa,andsleepdIsturbances.
HIghdosesofmorphIneandsImIlaropIoIdsproduceaslowIngofelectroencephalogram
(EEC)actIvItyassocIatedwIthamarkedshIfttowardIncreasedvoltageanddecreased
frequency.
1,J2
nroutIneanalgesIcdoses,morphInecanproducesleepdIsturbances,
IncludIngreductIonInrapIdeyemovementandslowwavesleep,
1
aswellasvIvIddreams.
|orphIneproducesdosedependentpupIllaryconstrIctIon(mIosIs).
JJ
ntheabsenceof
otherdrugs,mIosIsappearstocorrelatewIthopIoIdInducedventIlatorydepressIon.
However,hypoxemIafromsevereopIoIdInducedrespIratorydepressIonwIllcausepupIllary
dIlatIon.
SystemIcandneuraxIaladmInIstratIonofmorphInecanproduceprurItus,althoughthIs
symptomIsmorecommonwIthspInaladmInIstratIon.
1
PrurItusappearstobeareceptor
medIatedeffectproducedatthelevelofthemedullarydorsalhorn,
J4
althoughtheremay
alsobeadIrectantIprurItIceffectmedIatedbyreceptors.
J5
AntIhIstamInesareoften
usedtotreatthIssIdeeffect,butprurItusInducedbymorphInemIcroInjectIonIntothe
medullarydorsalhornIsnothIstamInemedIated.
J4
Thus,theIreffectIvenessIsprobably
relatedtononspecIfIcsedatIveeffects.
|orphInecanalsoaffectthereleaseofseveralpItuItaryhormones,bothdIrectlyand
IndIrectly.nhIbItIonofcortIcotropInreleasIngfactorandgonadotropInreleasInghormone
decreasescIrculatIngconcentratIonsofACTH,endorphIn,follIclestImulatInghormone,
andluteInIzInghormone.ProlactInandgrowthhormoneconcentratIonsmaybeIncreased
byopIoIds,andantIdIuretIchormonereleaseIsInhIbItedbyopIoIds.
1
Respiratory Depression
|orphIneandotheragonIstsproducedosedependentventIlatorydepressIonprImarIlyby
decreasIngtheresponsIvItyofthemedullaryrespIratorycentertoCD
2
.
JJ
Standard
therapeutIcdosesofmorphIneproduceashIfttotherIghtandadecreaseInslopeofthe
ventIlatoryresponsetoCD
2
curve,aswellasabnormalbreathIngpatterns.
J6,J7
The
respIratorydepressanteffectsofmorphInearesImIlarforyoungandelderlypatIents,
J6,J7
butnormalsleepmarkedlypotentIatesmorphIneInducedventIlatorydepressIon.
J8
FrequentperIodsofoxygendesaturatIonassocIatedwIthobstructIveapnea,paradoxIc
breathIng,andslowrespIratoryratehavebeenreportedInpatIentsreceIvIngmorphIne
InfusIonsforpostoperatIveanalgesIa,butoccurredonlywhenthepatIentswereasleep.
J9
SuchreportsemphasIzetheneedtoconsIderboththeexpectedseverItyofpostoperatIve
paInaswellasdIurnalvarIatIonsInpaInandopIoIdsensItIvItywhenIncludInglongactIng
opIoIdssuchasmorphIneInananesthetIc.Sleepapnea,oftenseenInassocIatIonwIth
obesIty,IncreasestherIskofmorphIneInducedrespIratorydepressIon.WIthIncreasIng
morphInedoses,perIodIcbreathIngresemblIngCheyneStokesbreathIng,decreasedhypoxIc
ventIlatorydrIve,andapneacanoccur.
40
However,evenwIthsevereventIlatory
depressIon,patIentsareusuallyarousableandwIllbreatheoncommand.
Cough Reflex
|orphIneandrelatedopIoIdsdepressthecoughreflex,atleastInpartbyadIrecteffecton
themedullarycoughcenter.0osesrequIredtoattenuatethecoughreflexaresmallerthan
theusualanalgesIcdosage,andreceptorsmedIatIngthIseffectappeartobeless
stereospecIfIcandlesssensItIvetonaloxone
P.471
thanthoseresponsIbleforanalgesIa.
1
0extroIsomersofopIoIds,whIchdonotproduce
analgesIa,arealsoeffectIvecoughsuppressants.
1
Muscle Rigidity
Largedosesof7morphIne(2mg/kgInfusedat10mg/mIn)canproduceabdomInalmuscle
rIgIdItyanddecreasethoracIccomplIance;thIseffectplateaus10mInutesaftermorphIne
admInIstratIonIscomplete.
41
SubjectsreceIvIngsmallerdosesof7morphIne(10to15mg)
alsoreportfeelIngsofmuscletensIon,mostfrequentlyIntheneckorlegs,butoccasIonally
Inthechestwall(unpublIshedobservatIons).|usclerIgIdItyIsdrastIcallyIncreasedbythe
addItIonof70N
2
D.
41
DpIoIdInducedmusclerIgIdItyappearstobemedIatedby
receptorsatsupraspInalsItes.
42
|yoclonus,sometImesresemblIngseIzures,butwIthout
EECevIdenceofseIzureactIvIty,hasalsobeenobservedwIthhIghdoseopIoIds.
4J
n
clInIcalpractIce,opIoIdInducedmusclerIgIdItyandmyoclonusaremostoftenobservedon
InductIonofanesthesIa,buthavebeenobservedpostoperatIvely
44
andcanbesevere
enoughtoInterferewIthmanualormechanIcalventIlatIon.Theseeffectsarereducedor
elImInatedbynaloxone,
44
drugsthatfacIlItateamInobutyrIcacIdagonIstactIvIty(such
asthIopental
41
anddIazepam),andmusclerelaxants.
44
Nausea and Vomiting
NauseaandvomItIngareamongthemostdIstressIngsIdeeffectsofmorphIneandIts
derIvatIves.ncreasedpostoperatIvevomItIngIsseenwIthmorphInepremedIcatIonaswell
aswIththeuseofIntraoperatIveopIoIds.
45
TheIncIdenceofopIoIdInducednauseaappears
tobesImIlarIrrespectIveoftherouteofadmInIstratIon,IncludIngoral,7,Intramuscular,
subcutaneous,transmucosal,transdermal,Intrathecal,andepIdural.
45
Furthermore,
laboratoryandclInIcalstudIescomparIngtheIncIdenceorseverItyofnauseaandvomItIng
havefoundnodIfferencesamongopIoIdsInequIanalgesIcdoses,IncludIngmorphIne,
hydromorphone,meperIdIne,fentanyl,sufentanIl,alfentanIl,andremIfentanIl.
45,46,47,48
ThephysIologyandneuropharmacologyofopIoIdInducednauseaandvomItIngarecomplex
(FIg.19J).ThevomItIngcenterreceIvesInputfromthechemotactIctrIggerzone(CTZ)In
theareapostremaofthemedulla,thepharynx,gastroIntestInaltract,medIastInum,and
vIsualcenter.
45,49
TheCTZIsrIchInopIoId,dopamIne,serotonIn,hIstamIne,and
(muscarInIc)acetylcholInereceptors,andalsoreceIvesInputfromthevestIbularportIonof
theeIghthcranIalnerve.|orphIneandrelatedopIoIdsInducenauseabydIrectstImulatIon
oftheCTZandcanalsoproduceIncreasedvestIbularsensItIvIty.
1
Therefore,vestIbular
stImulatIonsuchasambulatIonmarkedlyIncreasesthenauseantandemetIceffectsof
morphIne.ThIscanbeespecIallyproblematIcInoutpatIentsurgery,whenearlyambulatIon
IsaclInIcalprIorIty.HIghdosesofmorphIneandotheropIoIdsalsohavenaloxone
reversIbleantIemetIceffectsatthelevelofthevomItIngcenter.
50
nvolunteerstudIes,
morphIneInducednauseaandvomItIngIncreaseafteramorphIneInfusIonIsstopped,
51
whIchsuggeststhatantIemetIceffectsaremoreshortlIvedthanemetIceffects.Another
possIbleexplanatIonforthIsobservatIonIsthattheactIvemetabolItemorphIne6
glucuronIdeaccumulatesandworsensnausea.ProphylaxIsandtreatmentofopIoIdInduced
nauseaandvomItIngIncludestheuseofdrugsthatactasantagonIstsatthevarIous
receptorsItesIntheCTZaswellagentssuchaspropofolandbenzodIazepInes,whose
antIemetIcmechanIsmsareunknown.
45
Figure 19-3.PharmacologyofnauseaandvomItIng.ThechemotactIctrIggerzone
(CTZ),locatedIntheareapostremaofthebraInstem,contaInsdopamIne,serotonIn,
hIstamIne,andmuscarInIcacetylcholIneaswellasopIoIdreceptors.ThevomItIng
centerreceIvesInputfromtheCTZaswellasperIpheralsItesvIathevagusnerve.As
Illustrated,theroleofopIoIdsIscomplex,andtheyappeartohavebothemetIcand
antIemetIceffects.CN,cranIalnerve;C,gastroIntestInal;n.,nerve.
Gastrointestinal Motility and Secretion
|orphIneandotheropIoIdsaffectgastroIntestInalmotIlItyandpropulsIon,aswellas
gastrIcandpancreatIcsecretIonsvIastImulatIonofopIoIdreceptorsInthebraIn,spInal
cord,enterIcmuscle,andsmoothmuscle,
40,52
andaremedIatedby,,andopIoId
receptorsatdIfferentanatomIcsItes.
52
nrodents,agonIstsInhIbItgastrIcsecretIon,
decreasegastroIntestInalmotIlItyandpropulsIon,andsuppressdIarrheawhenadmInIstered
byIntracerebroventrIcular,Intrathecal,andperIpheralInjectIon.
52
AnImalandhuman
studIesdemonstratethatmethylnaltrexoneandalvImopan,opIoIdantagonIststhatdonot
crossthebloodbraInbarrIer,attenuatemorphIneInducedgastroIntestInaldysfunctIon.
5J,54
SuchstudIesalsosuggestthateffectssuchasdelayedgastrIcemptyIng,Ileus,and
constIpatIonaremedIatedprImarIlybyaperIpheralopIoIdmechanIsm.|orphInedecreases
loweresophagealsphIncter
P.472
toneandproducessymptomsofgastroesophagealreflux,
40
anddIamorphInesIgnIfIcantly
slowsgastrIcemptyIng.Thus,preoperatIveopIoIdadmInIstratIonshouldbeconsIdered
whenevaluatIngtherIskofregurgItatIonandaspIratIonofgastrIccontentsInpatIentswho
wIllbeanesthetIzedorsedated.LIkeotheropIoIdeffects,gastroIntestInaleffectsare
probablydoserelated.ToneInboththesmallandlargebowelIsIncreased,butpropulsIve
actIvItyIsdecreased,leadIngtoconstIpatIon.EpIdurallyadmInIsteredmorphInecanalso
delaygastrIcemptyIng.
55
Biliary Tract
|orphIneandotheropIoIdsIncreasethetoneofthecommonbIleductandsphIncterof
DddI.SymptomsaccompanyIngIncreasesInbIlIarypressurecanvaryfromepIgastrIc
dIstresstotypIcalbIlIarycolIc,andmayevenmImIcangIna.Whenproduced,bIlIaryspasm
canelevateplasmaamylaseandlIpaseforupto24hours.
1
|orphIneandotheragonIsts
suchasfentanylareusedInprovocatIveteststoevaluatesphIncterofDddIdysfunctIon
andbIlIarytypepaIn.nvolunteers,morphInecausedagreaterdelayIngallbladder
emptyIng
56
andanIncreaseIncontractIonsofthesphIncterofDddI
57
thanmeperIdIne.
NItroglycerIne,atropIne,andnaloxonecanreverseopIoIdInducedIncreasesInbIlIary
pressure.
1
thasbeensuggestedthatmorphInecausesbIlIarytractcontractIonvIa
hIstamInerelease,andantagonIsmofmorphIne'sbIlIaryeffectsbydIphenhydramIne
supportsthIshypothesIs.
58
Genitourinary Effects
UrInaryretentIon,seenafterbothsystemIcandspInalmorphIneadmInIstratIon,Iscaused
bycomplexeffectsoncentralandperIpheralneurogenIcmechanIsms.tresultsIn
dyssynergIabetweenthebladderdetrusormuscleandtheurethralsphIncterbecauseofa
faIlureofsphIncterrelaxatIon.
1,59
EstImatesoftheIncIdenceofthIsbothersomesIdeeffect
varywIdelyandareconfoundedbytheeffectsofanesthesIaandsurgeryonurInary
retentIon,butItIsprobablymorecommonafterspInaladmInIstratIon.SpInalmorphIne
appearstocausenaloxonereversIbleurInaryretentIonvIaand/or,butnotopIoId
receptors.
59
nananImalstudy,cholInomImetIcagentsandadrenergIcagonIsts
aggravatedmorphIneInducedhIghIntravesIcalpressures,andthereforemaybeharmful
agentstousefortreatmentofmorphIneInducedurInaryretentIon.
60
Histamine Release
DpIoIdsstImulatethereleaseofhIstamInefromcIrculatIngbasophIlsandfromtIssuemast
cellsInskInandlung.
61,62
|orphInemedIatedhIstamInereleaseIsdosedependent;
IntradermalInjectIonofmorphIneInaconcentratIonof1mg/mLInducesanurtIcarIal
whealandflare.
62
|orphIneInducedhIstamInereleaseIsnotpreventedbypretreatment
wIthnaloxone,
62
suggestIngthathIstamInereleaseIsnotmedIatedbyopIoIdreceptors.
|orphIneInducedhIstamInereleasehasclInIcalrelevance.ThedecreaseInperIpheral
vascularresIstanceseenwIthhIghdosemorphIne(1mg/kg)correlateswellwIthelevated
plasmahIstamIneconcentratIon.
6J
Furthermore,dIfferencesInthereleaseofhIstamIne
couldaccountformostofthehemodynamIcdIfferencesbetweenmorphIneandfentanyl
(FIg.194).
6J
Cardiovascular Effects
ndosestypIcallyusedforpaInmanagementoraspartofbalancedanesthesIa,morphIne
haslIttleeffectonbloodpressureorheartrateandrhythmInthesupIne,normovolemIc
patIent.However,hIgherdosesofmorphInecanproducearterIolarandvenousdIlatIon,
decreasedperIpheralresIstance,andInhIbItIonofbaroreceptorreflexes,
1
whIchcanlead
toposturalhypotensIon.naddItIontohIstamInerelease,morphInemedIatedcentral
sympatholytIcactIvItyanddIrectactIononvascularsmoothmusclemayalsocontrIbuteto
perIpheralvasodIlatIon.
64
Thus,morphIne'seffectonvascularresIstanceIsgreaterunder
condItIonsofhIghsympathetIctone.
57
TheclInIcalImplIcatIonsofthIsfIndIngare
Important.PatIentswhoarecrItIcallyIll(e.g.,patIentswIthseveretraumaorcardIac
dIsease)canbeexpectedtohavehIghsympathetIctone,andthusmayexperIence
hypotensIonInresponsetodosesofmorphInethatwouldnotnormallyproduce
hemodynamIcInstabIlIty.AtclInIcallyrelevantdoses,morphInedoesnotsuppress
myocardIalcontractIlIty.
1
However,opIoIdsdoproducedosedependentbradycardIa,
probablybybothsympatholytIcandparasympathomImetIcmechanIsms.
65
nclInIcal
anesthesIapractIce,opIoIdsareoftenusedtopreventtachycardIaandreducemyocardIal
oxygendemand.PatIentsundergoIngcardIovascularsurgerywhoreceIved1to2mg/kgof
morphIneexperIencedmInImalchangesInheartrate,meanarterIalpressure,cardIac
Index,andsystemIcvascularresIstance.However,outcomewasnodIfferentfromthat
achIevedwIthcarefullyadmInIsteredInhalatIonbasedanesthesIa.
65
|orphIne's
P.47J
specIfIcabIlItytoreducesystemIcInflammatIonbyItsactIonatthe
J
opIoIdreceptormay
benefItpatIentsundergoIngcardIopulmonarybypass.
66
|urphyetal.
67
demonstratedthat
morphInesuppressesseveralcomponentsoftheInflammatoryresponsetocardIopulmonary
bypass.ClInIcalbenefItsofmorphIne40mg,gIvenprIortocardIoplegIa,Includebetter
recoveryofglobalventrIcularfunctIonandpreventIonofpostoperatIvehypothermIa.
68
Figure 19-4.|eanarterIalpressure(8P),systemIcvascularresIstance(S7F),and
plasmahIstamIneconcentratIon(meanSE)beforeandaftermorphIne1mg/kgand
fentanyl50g/kg(bothInfusedover10mInutes).|orphIne,butnotfentanyl,causes
sIgnIfIcantdecrementsIn8PandS7F,whIchparalleltheIncreaseInplasmahIstamIne
concentratIon.(FeprIntedwIthpermIssIonfromFosowCE,|ossJ,PhIlbIn0|,etal:
HIstamInereleasedurIngmorphIneandfentanylanesthesIa.AnesthesIology1982;56:
9J.)
|orphInedoesnotdIrectlyaffectcerebralcIrculatIon,butwIthmorphIneInduced
respIratorydepressIon,CD
2
retentIoncausescerebralvasodIlatIonandanelevatIonIn
cerebrospInalfluIdpressure.ThIseffectIsnotseenwhenmechanIcalventIlatIonIsusedto
preventhypercarbIa.
1
Thus,morphIneandotheragonIstsmustbeusedcautIouslyIn
spontaneouslybreathIngpatIentswIthheadInjuryorothercondItIonsassocIatedwIth
elevatedIntracranIalpressure.
Disposition Kinetics
|orphIneIsrapIdlyabsorbedafterIntramuscular,subcutaneous,andoraladmInIstratIon.
FollowIngIntramuscularadmInIstratIon,peakplasmaconcentratIonIsseenat20mInutes
andabsorptIonhalflIfeIsestImatedat7.7mInutes(range,2to15mInutes).
69
After7
admInIstratIonmorphIneundergoesrapIdredIstrIbutIon,wIthameanredIstrIbutIonhalf
tImebetween1.5and4.4mInutesInawakeandanesthetIzedadults.
69,70,71
|orphInehasa
termInalelImInatIonhalflIfebetween1.7andJ.Jhours.
70,71,72
AgeaffectsmorphIne
pharmacokInetIcs.TheaverageelImInatIonhalflIfeofmorphIneIs7to8hoursInneonates
1weekofageandJto5hoursInolderInfants.
7J
npatIentsbetween61and80yearsold,
morphIne'stermInalelImInatIonhalflIfewas4.5hourscomparedwIth2.9hoursInyounger
patIents.
72
|orphIneIsaboutJ5proteInbound,mostlytoalbumIn.
17
tssteadystatevolumeof
dIstrIbutIonIslarge,wIthestImatesIntherangeofJto4L/kgInnormaladults.
69,70,71
|orphIne'smajormetabolIcpathwayIshepatIcphaseconjugatIon,toformmorphIneJ
glucuronIde(|JC)andmorphIne6glucuronIde(|6C).JClucuronIdatIonIsthe
predomInantpathway,andfollowIngasIngle7dose,40and10ofthedoseareexcreted
IntheurIneas|JCand|6C,respectIvely.
74
UnchangedmorphIneIntheurIneaccountsfor
onlyabout10ofthedose.TherateofhepatIcclearanceofmorphIneIshIgh,wItha
hepatIcextractIonratIoof0.7.
69
Thus,morphIneelImInatIonmaybeslowedbyprocesses
thatdecreasehepatIcbloodflow.
71
ExtrahepatIcsItessuchaskIdney,IntestIne,andlung
havebeensuggestedformorphIneglucuronIdatIon,buttheIrImportanceInhumansIs
unknown.
Active Metabolites
|6CpossessessIgnIfIcantreceptoraffInItyandpotentantInocIceptIveactIvIty.
ApprecIableplasmaconcentratIonsof|6Cand|JChavebeenmeasuredIncancerpatIents
receIvInghIghdosesoforalmorphIne.0urIngchronIcoralmorphInetherapy,plasma|6C
concentratIonscanbehIgherthanthoseoftheparentmorphInecompound.
75
8ecause
morphIneglucuronIdesareelImInatedbythekIdney,ItIsnotsurprIsIngthatveryhIgh|6C
tomorphIneratIoshavebeenreportedInpatIentswIthrenaldysfunctIon.ThIs
accumulatIonoftheactIvemetabolIteIsthoughttoberesponsIblefortheunusual
sensItIvItyofrenalfaIlurepatIentstomorphIne.WhIlecommonwIsdomsuggeststhat
glucuronIdeconjugatesdonotpenetratethebloodbraInbarrIer,|6CconcentratIonIn
cerebrospInalfluIdIs20to80thatofmorphIne.
76
0espIteanImallIteraturedemonstratIng
theanalgesIcpotencyof|6C,thereIslIttleInformatIonInhumansconcernIngthe
magnItudeofanalgesIaandsIdeeffectsof|6CrelatIvetomorphIne.Portenoyetal.
76
demonstratedthatIncancerpatIentsreceIvIngchronIcmorphInetherapy,paInrelIef
correlatedposItIvelywIththe|6CtomorphIneratIo,suggestIngacontrIbutIngroleof|6C
tooverallmorphIneanalgesIa.nastudyofcancerpatIentswhoreceIvedsynthetIc|6C
(upto60g/kg),17of19patIentsexperIencedeffectIveanalgesIaandnoadverse
effects.
77
ncontrast,dIzzIness,nausea,sedatIon,muscleaches,andrespIratorydepressIon
havebeenreportedInvolunteerswhoreceIved|6C.
75
However,theroleof|6CInacute
dosIngIsunclearbecausethereIsalongdelay(6to8hours)betweenthetImecourseof
plasmaconcentratIonandCNSeffects.
78
WhIlethecontrIbutIonof|6CtomorphIne
InducedanalgesIaandsIdeeffectsremaInstobedetermIned,morphIneshouldbe
admInIsteredcautIouslytopatIentswIthrenalfaIlure.
Dosage and Administration of Morphine
ncurrentclInIcalpractIcemorphIneIsusedmaInlyasapremedIcantandforpostoperatIve
analgesIa,andlessoftenasacomponentofbalancedorhIghdoseopIoIdanesthesIa.
ntravenousanalgesIcdosesofmorphIneforadultstypIcallyrangefrom0.01to0.20mg/kg.
WhenusedInabalancedanesthetIctechnIquewIthN
2
D,morphInecanbegIvenIntotal
dosesofuptoJmg/kgwIthremarkablehemodynamIcstabIlIty,butawarenessunder
anesthesIaIsarIsk.WhencombInedwIthotherInhalatIonagents,ItIsunlIkelythatmore
than1to2mg/kgofmorphIneIsnecessary.ThemorphInedoseassocIatedwIthapparent
cardIoprotectIveeffectIsasIngledoseof40mg,gIvenbeforecardIoplegIaand
cardIopulmonarybypass.
68
8ecauseofItshydrophIlIcIty,morphInecrossesthebloodbraIn
barrIerrelatIvelyslowly;andwhIleItsonsetcanbeobservedwIthIn5mInutes,peak
effectsmaybedelayedfor10to40mInutes.ThIsdelaymakesmorphInemoredIffIcultto
tItrateasananesthetIcsupplementthanthemorerapIdlyactIngopIoIds.
Meperidine
|eperIdIne,aphenylpIperIdInederIvatIve(FIg.195),wasthefIrsttotallysynthetIcopIoId.
twasInItIallystudIedasanantIcholInergIcagent,butwasfoundtohavesIgnIfIcant
analgesIcactIvIty.
1
Analgesia and Effect on Minimum Alveolar Concentration of
Volatile Anesthetics
|eperIdIne'sanalgesIcpotencyIsaboutonetenththatofmorphIne'sandIsmostlIkely
medIatedbyopIoIdreceptoractIvatIon.However,meperIdInealsohasmoderateaffInIty
forandopIoIdreceptors.
1,79
UnlIkemorphIne,meperIdIneplasmaconcentratIons
correlatereasonablywellwIthanalgesIceffects.
80
AlthoughthereIsconsIderable
InterpatIentvarIabIlIty,the|EACofmeperIdIneIsapproxImately200ng/mL.ThereIsvery
lIttleInformatIonavaIlableontheeffectofmeperIdIneonthe|ACofInhaledanesthetIcs,
butastudyIndogsdemonstratedadosedependentreductIonInthe|ACofhalothane.
81
|eperIdInealsohaswellrecognIzedweaklocalanesthetIcpropertIes.ComparedwIth
morphIne,fentanyl,andbuprenorphIneInjectedperIneurally,onlymeperIdInealtersnerve
conductIonandproducesanalgesIa.
82
ThIshasledtosomepopularItyforepIduraland
subarachnoIdadmInIstratIon,partIcularlyInobstetrIcanesthesIa.8utbecauseofItslocal
anesthetIceffects,neuraxIalmeperIdInemayalsoproducesensoryandmotorblockadeas
wellassympatholytIceffectsthatarenotseenwIthotheropIoIds.
Side Effects
LIkemorphIne,therapeutIcdosesofmeperIdInecanproducesedatIon,pupIllary
constrIctIon,andeuphorIa,andveryhIgh
P.474
dosesareassocIatedwIthCNSexcItementandseIzures(seelaterdIscussIon).n
equIanalgesIcdoses,meperIdIneproducesrespIratorydepressIonequaltothatof
morphIne,aswellasnausea,vomItIng,anddIzzIness,partIcularlyInambulatorypatIents.
1
Figure 19-5.ChemIcalstructuresofphenylpIperIdIne,meperIdIne,andthe4
anIlInopIperIdInederIvatIvesfentanyl,sufentanIl,alfentanIl,andremIfentanIl.
LIkeotheropIoIds,meperIdInecausessIgnIfIcantdelayIngastrIcemptyIng.WhIle
meperIdInedoesIncreasecommonbIleductpressure,thIsoccurstoalesserextentthan
wIthequIanalgesIcdosesofmorphIneandfentanyl(FIg.196).
56,8J
AnalgesIcdosesofmeperIdIneInawakepatIentsarenotassocIatedwIthhemodynamIc
InstabIlIty,but1mg/kgInpatIentswIthcardIacdIseasedecreasedheartrate,cardIac
Index,andratepressureproduct.
84
nanIsolatedpapIllarymusclepreparatIon,hIgh
concentratIonsofmeperIdInedepressedcontractIlIty.ThIseffectwasnotnaloxone
reversIbleandIsconsIstentwIthanonspecIfIc,localanesthetIceffect.
85
nhIgherdoses,
meperIdInecausessIgnIfIcantlymorehemodynamIcInstabIlItythanmorphIneorfentanyl
andItsderIvatIves,
86
aneffectatleastpartIallyrelatedtohIstamInerelease.na
comparIsonofopIoIdsadmInIsteredaspartofbalancedanesthesIa,Flackeetal.
86
found
that25patIentsInthemeperIdInegroupexperIencedseverehypotensIonandhad
abnormallyelevatedplasmahIstamIneconcentratIons.nterestIngly,onlyonepatIentIn
themorphInegroup(0.6mg/kgmorphInegIven)hadasImIlarhIstamIneplasma
concentratIon.Thus,meperIdIneIsnotrecommendedInhIghdosesforclInIcalanesthesIa.
Shivering
|eperIdIneIseffectIveInreducIngshIverIngfromdIversecauses,IncludInggeneraland
epIduralanesthesIa,fever,hypothermIa,transfusIonreactIons,andadmInIstratIonof
amphoterIcIn8.|eperIdInereducesorelImInatesvIsIbleshIverIngaswellasthe
accompanyIngIncreaseInoxygenconsumptIon
87
followInggeneralandepIduralanesthesIa.
EquIanalgesIcdosesoffentanyl(25g)andmorphIne(2.5mg)dIdnotreducepostoperatIve
shIverIng,suggestIngthattheantIshIverIngeffectofmeperIdIneIsnotmedIatedby
opIoIdreceptors.ThIseffectmaybemedIatedbyopIoIdreceptors.8utorphanol,adrug
wIthsIgnIfIcantagonIstactIvIty,effectIvelyreducespostoperatIveshIverIngInadoseof
1mg.
88
Furthermore,lowdosesofnaloxone,suffIcIenttoblockreceptors,dIdnotreverse
theantIshIverIngeffectofmeperIdIne,buthIghdosenaloxone,desIgnedtoblockboth
andreceptors,dIdreversetheantIshIverIngeffect.
79
TheobservatIonthatothertypesof
drugs,suchas
1
adrenergIcagonIsts(clonIdIne1.5g/kg),serotonInantagonIsts,
89
and
propofol,
90
canreducepostoperatIveshIverIngsuggeststhatanonopIoIdmechanIsmmay
beInvolved.PhysostIgmIne0.04mg/kgcanalsopreventpostoperatIveshIverIng,suggestIng
aroleforthecholInergIcsystem.
91
FollowIng7admInIstratIon,meperIdIneplasmaconcentratIonfallsrapIdly.|eperIdIne's
redIstrIbutIonhalflIfeIs4to16mInutes,andItstermInalelImInatIonhalflIfeIsbetweenJ
and5hours.
92,9J
TheelImInatIonhalflIfeIsnotprolongedInelderlypatIents;however,In
neonatesandInfants,themedIanelImInatIonhalflIfeIs8to10hours,wIthgreater
IndIvIdualvarIabIlIty(threetofIvefold)comparedwIthadults.
|eperIdIneIsmoderatelylIpIdsoluble,andIs40to70proteInbound,mostlytoalbumIn
and
1
acIdglycoproteIn
P.475
(Table192).
94
|eperIdInehasalargesteadystatevolumeofdIstrIbutIon,wIthestImates
IntherangeofJ.5to5L/kgInadults.
92,9J
ThehIghclearancerate(10mL/kg/mIn)reflects
ahIghhepatIcextractIonratIo;ItIsNdemethylatedInthelIvertoformnormeperIdIne,
theprIncIpalmetabolIte,andalsohydrolyzedtomeperIdInIcacId.8othmetabolItesmay
thenbeconjugated
1
andexcretedrenally.NormeperIdIneIspharmacologIcallyactIveand
potentIallytoxIc(seelaterdIscussIon).
Figure 19-6.TheeffectofseveralopIoIdsoncommonbIleductpressuresInpatIents
anesthetIzedwIthenfluraneandN
2
DD
2
.PatIentsreceIvedeItherfentanyl100g/70
kg,morphIne10mg/70kg,meperIdIne75mg/70kg,orbutorphanol2mg/70kg.After
20mInutes,theeffectswerereversedwIthnaloxone.(FeprIntedwIthpermIssIonfrom
FadnayPA,0uncalf0,NovakovIk|,etal:CommonbIleductpressurechangesafter
fentanyl,morphIne,meperIdIne,butorphanol,andnaloxone.AnesthAnalg1984;6J:
441.)
Active Metabolites
NormeperIdInehasapprecIablepharmacologIcactIvItyandcanproducesIgnsofCNS
excItatIon.|oodalteratIonssuchasapprehensIonandrestlessness,aswellasneurotoxIc
effectssuchastremors,myoclonus,andseIzures,havebeenreported.
95
TheelImInatIon
halflIfeofthemetabolItenormeperIdIne(14to21hours)IsconsIderablylongerthanthe
parentcompound,andthereforeIslIkelytoaccumulatewIthrepeatedorprolonged
admInIstratIon,partIcularlyInpatIentswIthrenaldysfunctIon.
95
|yoclonusandseIzures
havebeenreportedInpatIentsreceIvIngmeperIdIneforpostoperatIveorchronIcpaIn.
PatIentswhodevelopedseIzureshadameanplasmanormeperIdIneconcentratIonof0.81
g/mL.
95
tappearsthatatotaldaIlymeperIdInedosageof1,000mgIsassocIatedwIthan
IncreasedrIskofseIzures,evenInpatIentswIthoutrenaldysfunctIon.
Dosage and Administration of Meperidine
AsIngledoseofmeperIdIneIsapproxImatelyonetenthaspotentasmorphInewhengIven
parenterally,buthasashorterduratIonofactIon.ntravenousanalgesIcdosesof
meperIdIneforadultstypIcallyrangefrom0.1to1mg/kg.ntravenousdosesof12.5to50
mgareeffectIveInreducIngpostoperatIveshIverIng.AsdIscussedearlIer,hIghdosesof
meperIdIneforIntraoperatIveusearenotrecommendedbecauseofhemodynamIc
InstabIlIty.naddItIon,largesIngledosesorprolongedadmInIstratIonmayproduceseIzures
becauseofthemetabolItenormeperIdIne;thetotaldaIlydoseshouldnotexceed1,000mg
In24hours.
Methadone
|ethadone,asynthetIcopIoIdIntroducedInthe1940s,IsprImarIlyaagonIstwIth
pharmacologIcpropertIesthataresImIlartomorphIne.AlthoughItschemIcalstructureIs
verydIfferentfromthatofmorphIne,sterIcfactorsforcethemoleculetosImulatethe
pseudopIperIdInerIngconformatIonthatappearstoberequIredforopIoIdactIvIty.
1
8ecauseofItslongelImInatIonhalflIfe,methadoneIsmostoftenusedforlongtermpaIn
managementandfortreatmentofopIoIdabstInencesyndromes.
Analgesia and Use in Anesthesia
FollowIngparenteraladmInIstratIon,theonsetofanalgesIaIsrapId,wIthIn10to20
mInutes.AftersIngledosesofupto10mg,theduratIonofanalgesIaIssImIlarto
morphIne,
1
butwIthlargeorrepeatedparenteraldoses,prolongedanalgesIacanbe
obtaIned.SeveralInvestIgatorshaveadmInIsteredmethadoneIntraandpostoperatIvely
wIththeaImofprovIdIngprolongedpostoperatIveanalgesIa.PatIentswhoreceIved20mg
methadoneIntraoperatIvelyandupto20mgaddItIonalmethadoneIntheImmedIate
postoperatIveperIodhadamedIanduratIonofpostoperatIveanalgesIaofover20
hours.
96,97
Side Effects
SIdeeffectsofmethadonearesImIlarInmagnItudeandfrequencytothoseofmorphIne.
1,96
PatIentswhoreceIved20mgmethadoneatthebegInnIngofsurgeryweresedatedInthe
ImmedIatepostoperatIveperIodbutdIdnotappeartohaveclInIcallysIgnIfIcant
respIratorydepressIon.About50experIencednauseaorvomItIng,whIchwaseasIly
treatedwIthstandardantIemetIctherapy.
96
|ethadoneproducestypIcalopIoIdeffectson
smoothmuscle.LIkemorphIne,ItmarkedlydecreasesIntestInalpropulsIveactIvItyandcan
causeconstIpatIonaswellasbIlIaryspasm.
1
FollowIngan7dose,theplasmaconcentratIontImedataformethadonearedescrIbedby
abIexponentIalequatIon.The
P.476
meanredIstrIbutIonhalftImeIs6mInutes(range,1to24mInutes),andthemeantermInal
elImInatIonhalftImeIsJ4hours(range,9to87hours).
97
|ethadoneIswellabsorbedafter
anoraldose,wIthbIoavaIlabIlItyapproxImately90,andreachespeakplasma
concentratIonat4hoursafteroraladmInIstratIon.
1
tIsnearly90plasmaproteInbound
andundergoesextensIvemetabolIsmInthelIver,mostlyNdemethylatIonandcyclIzatIon
toformpyrrolIdInesandpyrrolIne.
1
Dosage and Administration of Methadone
TheuseofmethadoneInclInIcalanesthesIahasfocusedonattemptstoachIeveprolonged
postoperatIveanalgesIa,provIdIngthatanadequateInItIaldoseIsadmInIstered.8ecause
adverseeffectscanalsobeprolonged,carefultItratIonofthedoseIsnecessary.nopIoId
navepatIents,anInItIalsIngledoseof20mgcanprovIdeanalgesIawIthoutsIgnIfIcant
postoperatIverespIratorydepressIon.
96
WanglerandFosenblatt
98
descrIbedatechnIqueto
avoIdrespIratorydepressIonInwhIch8to12mgmethadoneIsadmInIsteredtotheawake
patIentuntIlthethresholdofrespIratorydepressIon(respIratoryrateof6to8/mIn)Is
reached.mmedIatelyprIortoIncIsIon,anaddItIonaldoseequaltohalftheInItIaldoseIs
gIven.ForadmInIsterIngsupplementalanalgesIcdosesIntheImmedIatepostoperatIve
perIod,ItIsessentIaltoconfIrmthatpatIentswIthongoIngsIgnIfIcantpaInhaveno
depressIonofrespIratIonorlevelofconscIousness,andthataJ0to40mInuteInterval
shouldelapsebetween5mgdosestoallowfullassessmentofadverseeffects.tmaybe
easIerandsafertouseasustaInedreleaseopIoIdpreparatIon(contaInIngoxycodoneor
morphIne)wIthashortertImetopeakeffectIfalongactInganalgesIcIsdesIred.ThIsIs
mosteasIlyaccomplIshedbyadmInIsterIngtheoralmedIcatIonpreoperatIvely,butItIs
alsoImportanttonotethattheselongactIngopIoIdsarenotcurrentlyapprovedfor
prophylaxIsofpostoperatIvepaIn.
Fentanyl
FentanylandItsanalogssufentanIlandalfentanIlarethemostfrequentlyusedopIoIdsIn
clInIcalanesthesIa.Fentanyl,fIrstsynthesIzedIn1960,Isstructurallyrelatedtothe
phenylpIperIdInes(FIg.195)andhasaclInIcalpotencyratIo50to100tImesthatof
morphIne.ClearplasmaconcentratIoneffectrelatIonshIpshavebeendemonstratedfor
fentanyl(Table19J).Scottetal.
99
demonstratedprogressIveEECchangeswIthIncreasIng
serumfentanylconcentratIon(FIg.197).0urIngabrIefInfusIon,thetImelagbetween
IncreasIngserumfentanylconcentratIonandEECslowIngwasJto5mInutes.Afterthe
InfusIonwasstopped,theresolutIonofEECchangeslaggedbehInddecreasIngserum
fentanylconcentratIonby10to20mInutes.
Analgesia
Fentanyl,aopIoIdreceptoragonIst,producesprofounddosedependentanalgesIa,
ventIlatorydepressIon,andsedatIon,andathIghdosesItcanproduceunconscIousness.n
postoperatIvepatIents,themeanfentanyldoserequIrementwas55.8g/hr,andmean
|EACInbloodwas0.6Jng/mL.
100
AlargeInterpatIentvarIabIlItyIn|EAC(0.2Jto1.18
ng/mL)typIcalofopIoIdswasobserved,butoverthe2daystudyperIod,the|EACforany
IndIvIdualpatIentremaInedrelatIvelyconstant.nvolunteers,ameanplasmafentanyl
concentratIonof1.Jng/mLreducedexperImentalpaInIntensItyratIngsby50,
46
consIstentwIthotherestImatesofplasmafentanylconcentratIonsproducIngmoderateto
stronganalgesIa.
101
Table 19-3 Plasma Concentration Ranges (ng/ml) for Various Therapeutic and
Nontherapeutic Opioid Effects
a
EFFECT MORPHINE MEPERIDINE FENTANYL SUFENTANIL ALFENTANIL REMIFENTANIL
|EAC 1015 200 0.6 0.0J 15
|oderateto
stronganalgesIa
2050 400600 1.55
0.05
0.10
4080
50|AC
reductIon
NA 500 0.52 0.145 200 1.J
SurgIcal
analgesIawIth
-70N
2
D
NA NA 1525 NA J00500 47.5
FespIratory
depressIon
threshold
25 200 1
0.02
0.04
50100
50
ventIlatory
responsetoCD
2
50 NA 1.5J 0.04 120J50 0.91.2
Apnea NA NA 722 NA J00600
UnconscIousness
(notrelIably
achIevedwIth
opIoIdsalone)
(SeIzures) 1520 NA
500
1500
a
EffectsweregenerallyachIeveddurIngcontInuousInfusIonsorpatIentcontrolled
analgesIasystems.NotethatplasmaconcentratIonsassocIatedwIthmeasurable
depressIonofventIlatorydrIvearesImIlartothoseassocIatedwIthanalgesIaforall
opIoIds.
|EAC,mInImumeffectIveanalgesIcconcentratIon,defInedInmoststudIesasthe
plasmaopIoIdconcentratIonassocIatedwIthjustperceptIbleanalgesIa;|AC,mInImum
alveolarconcentratIon;NA,InformatIonnotavaIlable.
P.477
Use in Anesthesia
Fentanylreducesthe|ACofvolatIleanesthetIcsInaconcentratIonordosedependent
fashIon.AsIngle7bolusdoseoffentanylJg/kg,gIven25toJ0mInutesprIortoIncIsIon,
reducedbothIsofluraneanddesflurane|ACbyapproxImately50.
102
Fentanyl1.5g/kg
admInIstered5mInutesprIortoskInIncIsIonreducesthemInImumalveolarconcentratIon
thatblocksadrenergIcresponsestostImulI(|AC8AF)ofIsofluraneordesfluraneIn60
N
2
Dby60to70.
10J
NofurtherdropIsseenwIthanIncreaseInfentanyldosetoJg/kg.
0urIngconstantplasmaconcentratIonof0.5to1.7ng/mL,fentanylreducedIsoflurane|AC
by50.
104
FentanylproducesasteepplasmaconcentratIonrelatedreductIonIn
sevoflurane|AC
105
;Jng/mLprovIdesa59reductIon,butaceIlIngeffectIsreached,such
thatathreefoldIncreaseto10ng/mLreduced|ACbyonlyanaddItIonal17.
Figure 19-7.ThetImecourseofelectroencephalogram(EEC)spectraledgeandserum
concentratIonsoffentanyl(A)andalfentanIl(B).nfusIonrateswere150g/mIn
fentanyland1,500g/mInalfentanIl.ncreasIngopIoIdeffectIsseenasadecreaseIn
spectraledge.ChangesInspectraledgefollowserumconcentratIonsmorecloselywIth
alfentanIlthanwIthfentanyl.(FeprIntedwIthpermIssIonfromScottJC,PonganIsK7,
StanskI0F:EECquantItatIonofnarcotIceffect:ThecomparatIvepharmacodynamIcs
offentanylandalfentanIl.AnesthesIology1985;62:2J4.)
EpIduralfentanylalsoreducesInhaledanesthetIcrequIrements.
106
EpIduralfentanyl1,2,
and4g/kgreducedhalothane|ACby45,58,and71,respectIvely,whIlethesamedoses
offentanylgIven7reducedhalothane|ACtoalesserextent,by8,40,and49,
respectIvely.
CombInIngopIoIdswIthpropofolratherthananInhalatIonagentIsatechnIquefor
provIdInggeneralanesthesIa,referredtoastotal intravenous anesthesiaorT7A.Foran7
anesthetIc,thepotencyIndexIsdescrIbedastheplasmaconcentratIonrequIredtoprevent
aresponseIn50(CP
50
)or95(CP
95
)ofpatIentstovarIoussurgIcalstImulI.Plasma
concentratIonsoffentanylandpropofolthatreducehemodynamIcorsomatIcresponsesto
varIoussurgIcalstImulIIn50ofpatIentshavebeendetermInedusIngcomputerassIsted
InfusIon.
107
FentanylplasmaconcentratIonsof1.2,1.8,and2.8ng/mLwererequIredfor
50reductIonsInpropofol'sCP
50
sforskInIncIsIon,perItonealIncIsIon,andabdomInal
retractIon,respectIvely.CreaterfentanylconcentratIonswererequIredtosuppress
hemodynamIcresponsestothesesamestImulI.Thus,fentanylreducesrequIrementsfor
bothvolatIleagentsandpropofolbyasImIlarproportIon.
ComputerassIstedInfusIonoffentanylhasbeenIncludedasacomponentofabalanced
anesthetIctechnIque.
108,109
ncombInatIonwIth50to70N
2
DInoxygen,lossof
conscIousness,andabsenceofresponsetoskInIncIsIonareachIevedatplasmafentanyl
concentratIonsof15to25ng/mLandJ.7ng/mL,respectIvely.ntraoperatIve
concentratIonrequIrementsvarIedbetween1and9ng/mL.SpontaneousventIlatIon
returnedwhenthefentanylconcentratIondroppedto1.5to2ng/mL.
108,109
FentanylhasbeenusedasthesoleagentforanesthesIa,atechnIquethatrequIresalarge
InItIaldoseof50to150g/kgorstableplasmafentanylconcentratIonsIntherangeof20
toJ0ng/mL.
101
ThemajoradvantageofthIstechnIqueIsrelIablehemodynamIcstabIlIty.
HIghdosesoffentanylsIgnIfIcantlybluntthestressresponsethatIs,hemodynamIcand
hormonalresponsestosurgIcalstImulIwhIleproducIngonlymInImalcardIovascular
depressIon.Thus,thetechnIqueIssometImesreferredtoasstress-free anesthesia.There
arealsodIsadvantagestousInghIghdosefentanylasthesoleanesthetIcagent.t
precludesearlyextubatIonandfasttracktechnIquesbecauseofprolongedrespIratory
depressIonaccompanyInghIghdosefentanyl.Furthermore,Itappearsthatnodoseof
fentanylwIllcompletelyblockhemodynamIcorhormonalresponsesInallpatIents.
110
FInally,therehavebeenreportsofIntraoperatIveawarenessandrecallInpatIentswho
receIvedveryhIghdoses(50g/kg)offentanyl.8ecauseopIoIdsdonotproducemuscle
relaxatIon,andhIghdosefentanylcanproducemusclerIgIdIty,amusclerelaxantIs
generallyrequIredtoachIeveadequatesurgIcalcondItIons.ThIscanpotentIallyIncrease
thedIffIcultyIndetectIngsIgnsofIntraoperatIveawareness.
TheeffectsoffentanyloncerebralbloodflowandIntracranIalpressure(CP)havebeen
studIedInpatIentswIthandwIthoutneurologIcdIsease.AnInductIondoseof16g/kg
IncreasedmIddlecerebralarteryflowby25InnormalpatIentshavIngnoncranIal
neurosurgery.
111
Asmallerdose(Jg/kg)resultedInanelevatIonInCPInventIlated
patIentswIthheadtrauma,
112
butInbraIntumorpatIents,adoseof5g/kgoffentanyl
wIthN
2
DD
2
dIdnotresultInelevatedCP.
11J
nallcasesofelevatIonInCPandcerebral
bloodflow,thereweredecreasesInmeanarterIalpressure,whIchmayhavecontrIbutedto
thesechanges.
ThemusclerIgIdItyoftenseenonInductIonwIthhIghdosefentanylandItsderIvatIvesmay
makeItdIffIcultorImpossIbletoventIlatethepatIent.nastudyInnormalvolunteers,
1,500gfentanylInfusedover10mInutesproducedrIgIdItyIn50ofsubjects.
114
AsImIlar
IncIdence,J5,wasseenInpatIentsreceIvIng750to1,000gfentanyldurIngInductIonof
generalanesthesIa,andupto80ofpatIentsreceIvIngJ0g/kgdevelopedmoderateto
severerIgIdIty.
115
|usclerIgIdItyseen
P.478
wIthhIghdosesoffentanylIncreaseswIthage
115
andIsaccompanIedbyunconscIousness
andapnea,
114,115
butlowerdoses,7to8g/kg,haveproducedchestwallrIgIdItywIthout
unconscIousnessorapnea.StreIsandetal.
114
hypothesIzedthathypercarbIafromfentanyl
InducedrespIratorydepressIonmayhaveInfluencedfentanylIonIzatIonandcerebralblood
flowandhencethedelIveryoffentanyltobraIntIssue.twouldfollowthatpatIents
InstructedtodeepbreathedurIngfentanylInductIonmayexperIencelessrIgIdItydurIng
InductIonofanesthesIa.ThIsIsconsIstentwIthobservatIonsbyLunnetal.
116
0urInghIgh
dosefentanylInductIon(75g/kg),PaCD
2
wasmaIntaInedatJ5to40torrbyassIstIngand
thencontrollIngrespIratIons.AlthoughchestwallcomplIancewasreducedIn4of18
patIents,nopatIentdevelopedrIgIdItysuffIcIenttoImpaIrventIlatIon.
FentanylhasbeenassocIatedwIthseIzurelIkemovementsdurInganesthetIcInductIon,
whIcharenotassocIatedwIthseIzureactIvItyontheEEC.
117
SuchactIvItymayrepresent
myoclonus,aresultofopIoIdmedIatedblockadeofInhIbItorymotorpathwaysofcortIcal
orIgIn,ormayrepresentexaggeratIonsofopIoIdInducedmusclerIgIdIty.
117
However,
fentanylcanactIvateepIleptIformEECactIvItyInpatIentshavIngsurgeryforIntractable
temporallobeepIlepsy.
118
FentanylInducedprurItustypIcallypresentsasfacIalItchIng,butcanbegeneralIzed.
EquIanalgesIcplasmaconcentratIonsoffentanyl,morphIne,andalfentanIlproduce
equIvalentIntensItyofprurItus.
46
FentanylhasalsobeenreportedtohaveatussIveeffect.
ThemechanIsmIsunclear,andItIsnotattenuatedbypretreatmentwIthatropIneor
mIdazolam.
119
FentanylproducesapproxImatelythesamedegreeofventIlatorydepressIonas
equIanalgesIcdosesofmorphIne.
46
FespIratorydepressIonexpressedasanelevatIonIn
endtIdalCD
2
,adecreaseIntheslopeoftheCD
2
responsecurve,orthemInuteventIlatIon
atanendtIdalCD
2
of50mmHg(7
E
50)developsrapIdly,reachIngapeakIn-5
mInutes,
99,120,121
andthetImecoursecloselyfollowsplasmafentanylconcentratIon.
120,122
EvenatplasmaconcentratIonsassocIatedwIthmIldanalgesIa,ventIlatorydepressIoncan
bedetected,andthemagnItudeofrespIratorydepressIonIslInearlyrelatedtoIntensItyof
analgesIa(Table19J).
46,12J
npostoperatIvepatIents,plasmafentanylconcentratIonsof
1.5toJ.0ng/mLwereassocIatedwItha50reductIonInCD
2
responsIveness.
124
Fentanyl'srespIratorydepressIonIsgreatlyIncreasedwhenItIsgIvenIncombInatIonwIth
anotherrespIratorydepressantsuchasmIdazolam.8aIleyetal.
121
determInedthat
mIdazolamalone(0.05mg/kg)dIdnotdepressventIlatIonorcausehypoxemIa.Fentanyl
alone(2g/kg)reducedtheslopeoftheCD
2
responsecurveandthe7
E
50by50,and6of
12subjectsbecamehypoxemIc.FentanylandmIdazolamproducednogreaterdepressIonof
theventIlatoryresponsetoCD
2
thanfentanylalone,but11of12subjectsbecame
hypoxemIcand6of12becameapneIcwIthIn5mInutes.TheseobservatIonssuggestthat
thIsfrequentlyusedcombInatIonbluntsthehypoxIcventIlatorydrIvetoagreaterextent
thanthehypercarbIcventIlatorydrIve.PrecautIonssuchassupplementaloxygenandpulse
oxImetrymonItorIngarerecommendedwhensuchdrugcombInatIonsareused.
Airway Reflexes
AlthoughobtundatIonofaIrwayreflexesbygeneralInhalatIonanesthetIcsIswell
descrIbed,lIttleIsknownaboutthedIrecteffectsofopIoIdsontheseprotectIvereflexes.
TagaItoetal.
125
examInedthedoserelatedeffectsoffentanylonaIrwayresponsesto
laryngealIrrItatIondurIngpropofolanesthesIaInhumans.AllpatIentshadlaryngealmask
aIrways;halfbreathedspontaneouslyandhalfhadventIlatIoncontrolledtomaIntaInan
endtIdalCD
2
ofJ8mmHg.nbothgroups,stImulatIonofthelarynx(applIcatIonofwater
tomucosa)elIcItedaforcedexpIratIon,followedbyspasmodIcpantIngmIngledwIthcough
reflexesandbrIeflaryngospasm.WIththreecumulatIvefentanyldoses(50,50,and100g),
expIratIon,pantIng,andcoughIngdecreasedInadosedependentfashIon.ApneawIth
laryngospasmoccurredafterthefIrstdose,butwIthcumulatIvefentanyldosIng,the
duratIonoflaryngospasmshortened.CoughwastheaIrwayreflexmostvulnerableto
depressIonbyfentanyl.AttenuatIonofaIrwayreflexesIsdesIrabledurInggeneral
anesthesIa,butItIsequallydesIrablethattheseprotectIvereflexesreturntobaselIne
rapIdlyafteremergence,andremaInIntactthroughoutconscIoussedatIon.0osesrequIred
tosuppresscoughandotherreflexesInawakeorsedatedIndIvIdualshavenotbeen
characterIzed.
Cardiovascular and Endocrine Effects
solatedheartmusclemodelsdemonstrateconcentratIondependentnegatIveInotropIc
effectsofopIoIds,IncludIngmorphIne,meperIdIne,andfentanyl.
65
AveryhIghfentanyl
concentratIon(10g/mL)reducedcontractIlItyby50,but1g/mLhadnosIgnIfIcant
effectsonpapIllarymusclemechanIcs.nclInIcalpractIce,evenhIghdosefentanyl
admInIstratIon(upto75g/kg)producesmuchlowerplasmaconcentratIons,Intherange
of50ng/mL,
116
andIsassocIatedwIthremarkablehemodynamIcstabIlIty.PatIentswho
receIved7g/kgfentanylatInductIonofanesthesIahadaslIghtdecreaseInheartrate,
butnochangeInmeanarterIalpressurecomparedwIthcontrol.
86
FentanylInduced
bradycardIaIsmoremarkedInanesthetIzedthanconscIoussubjects,andusuallyresolves
wIthatropIne.WIthhIgherfentanyldoses,Intherangeof20to25g/kg,decreasesIn
heartrate,meanarterIalpressure,systemIcandpulmonaryvascularresIstance,and
pulmonarycapIllarywedgepressureofapproxImately15wereseenInpatIentswIth
coronaryarterydIsease.
116,126
7eryhIghfentanyldoses,upto75g/kg,producedno
furtherhemodynamIcchanges.AllofthesepatIentshadbeenpremedIcatedwIth
dIazepam,pentobarbItal,scopolamIne,and/oratropIne.nunpremedIcatedpatIents
undergoIngnoncardIacsurgery,InductIonwIthfentanylJ0g/kgproducednochangesIn
heartrateorsystolIcbloodpressure.
115
HypertensIonInresponsetosternotomyIsthemost
commonhemodynamIcdIsturbancedurInghIghdosefentanylanesthesIaandoccursIn40
and100InpatIentsreceIvIng50to100g/kg.
127
UnlIkemorphIneandmeperIdIne,whIch
InducehypotensIon,atleastInpartbecauseofhIstamInerelease,
64,128
hIghdosefentanyl
(50g/kg)IsnotassocIatedwIthsIgnIfIcanthIstamInerelease(FIg.194).
AlthoughhIghdosesoffentanylareassocIatedwIthmInImalcardIovascularchanges,
combInIngfentanylwIthotherdrugscancompromIsehemodynamIcstabIlIty.The
combInatIonoffentanylanddIazepamproducessIgnIfIcantcardIovascular
depressIon.
115,126
0Iazepam10mggIvenafter20to50g/kgoffentanyldecreasedstroke
volume,cardIacoutput,systemIcvascularresIstance,andmeanarterIalpressure,and
IncreasedcentralvenouspressuresIgnIfIcantly.
126
AddIng60N
2
DtohIghdosefentanyl
producedasIgnIfIcantdecreaseIncardIacoutputandIncreasesInsystemIcandpulmonary
vascularresIstance.
116
HIghdosefentanyl(100g/kg)preventedIncreasesInplasmaepInephrIne,cortIsol,
glucose,freefattyacIds,andgrowthhormone(thestressresponse)durIngsurgery,buta
lowerdoseoffentanyl(5g/kgfollowedbyanInfusIonofJg/kg/h)dIdnot.
129
UnlIke
morphIne,fentanyldoesnotpreventtheInflammatoryeffectsassocIatedwIth
cardIopulmonarybypass,nordoesItproducetheapparentcardIoprotectIveeffectsseen
wIthmorphIne.
67,68
P.479
Smooth Muscle and Gastrointestinal Effects
Fentanyl,lIkemorphIneandmeperIdIne,sIgnIfIcantlyIncreasescommonbIleductpressure
(FIg.196).
8J
LIkeotheropIoIds,fentanylcancausenauseaandvomItIng,partIcularlyIn
ambulatorypatIents,andcandelaygastrIcemptyIngandIntestInaltransIt.
Fentanyl'sextremelIpIdsolubIlIty(Table192)allowsrapIdcrossIngofbIologIcmembranes
anduptakebyhIghlyperfusedtIssuegroups,IncludIngthebraIn,heart,andlung.Thus,
afterasInglebolusdose,theonsetofeffectsIsrapIdandtheduratIonbrIef.Hugand
|urphy
1J0
determInedtherelatIonshIpsbetweenfentanyleffectsandItsconcentratIon
overtImeInplasmaandvarIoustIssuesInratsgIvenfentanyl50g/kg(FIg.198).The
onsetofopIoIdeffectsoccurredwIthIn10secondsandcorrelatedwItharapIdIncreaseIn
braIntIssuefentanylconcentratIon,whIchequIlIbratedwIthplasmaby1.5mInutes.
FecoveryfromfentanyleffectsstartedwIthIn5mInutesandwascompleteby60mInutes.
ElImInatIonfromthecentraltIssues(braIn,heart,andlung)wasalsorapId,asfentanyl
wasredIstrIbutedtoothertIssues,partIcularlymuscleandfat.PeakmuscleconcentratIon
wasseenat5mInutes,whIlefatconcentratIonreachedamaxImumapproxImatelyJ0
mInutesafterthedose.ThedelayInfatuptakedespItefentanyl'shIghlIpIdsolubIlItyIs
becauseofthelImItedbloodsupplytothattIssue.Thus,redIstrIbutIontomuscleandfat
lImItstheduratIonofabolusdoseoffentanyl,andaccumulatIonInperIpheraltIssue
compartmentscanbeextensIvebecauseofthelargemassofmuscleandhIghaffInItyof
fentanylforfat.WIthprolongedadmInIstratIonoffentanyl,fatcanactasareservoIrof
drug.
FentanylpharmacokInetIcshasbeenstudIedInawakeandanesthetIzedIndIvIduals.After
an7dose,plasmafentanylconcentratIonfallsrapIdly,andtheconcentratIontImecurve
hasbeendescrIbedbybothtwoandthreecompartmentmodels.
1J0
|cClaInandHug
120
admInIsteredfentanylJ.2or6.4g/kgtohealthymalevolunteersandfoundthatnearly
99ofthedosewaselImInatedfromplasmaby60mInutes.TheseInvestIgatorsfoundboth
rapIdandslowerdIstrIbutIonphases,wIthhalftImesof1.2to1.9mInutesand9.2to19
mInutes,respectIvely.ThetermInalelImInatIonhalftImerangedfromJ.1to6.6hours,
somewhatlongerthanthatformorphIne.SImIlarvalueswerenotedInsurgIcalpatIents50
yearsold,
11J,1J1
IncludIngmorbIdlyobesepatIents.
11J
Feportsofageeffectsonfentanyl
kInetIcsareconflIctIng.ThefentanylrequIrementdecreaseswIthIncreasIngage(20to89
years),butpharmacokInetIcparametersdonotchange.
1J2
ncontrast,8entleyetal.
1J1
observedamarkeddecreaseInclearanceandanIncreaseIntermInalelImInatIonhalftIme
toapproxImately15hoursInpatIents60yearsoldcomparedwIth4.4hoursInpatIents50
yearsold.
Figure 19-8.FentanyluptakeandelImInatIonInvarIoustIssuesoftheratfollowIng
IntravenousInjectIon.UnchangedfentanyltIssueconcentratIons(meansforsIxrats)
areexpressedaspercentageofdose.CentralrepresentsthecombInedcontentof
braIn,heart,andlungtIssues.Thelargemassofmuscle(50bodyweIghtoftherat)
andhIghaffInItyoffatforfentanyl(despIteslowequIlIbratIon)serveasadraInonthe
centralcompartment.(FeprIntedwIthpermIssIonfromHugCC,|urphy|F:TIssue
redIstrIbutIonoffentanylIntermsofItseffectsInrats.AnesthesIology1981;55:J69.)
UnlIkeItsderIvatIves,fentanylIssIgnIfIcantlyboundtoredbloodcells,approxImately40,
andhasablood:plasmapartItIoncoeffIcIentofapproxImately1.
1JJ
PlasmafentanylIs
hIghlyproteInbound,wIthestImatesIntherangeof79to87.tbIndsavIdlyto
1
acId
glycoproteInbutalsobIndstoalbumIn.
1JJ,1J4
FentanylproteInbIndIngIspHdependent,
suchthatadecreaseInpHwIllIncreasetheproportIonoffentanylthatIsunbound.
1JJ
Thus,apatIentwIthrespIratoryacIdosIswIllhaveahIgherproportIonofunbound(actIve)
fentanyl,whIchcouldexacerbaterespIratorydepressIon.ClearanceoffentanylIsprImarIly
byrapIdandextensIvemetabolIsmInthelIver.ClearanceestImatesof8to21mL/kg/mIn
approachlIverbloodflowandIndIcateahIghhepatIcextractIonratIo.
120,1J2
Thus,hepatIc
metabolIsmoffentanylIsexpectedtobedependentonlIverbloodflow.|etabolIsmIs
prImarIlybyNdealkylatIontonorfentanylandbyhydroxylatIonofboththeparentand
norfentanyl.
1JJ
Dnlyabout6ofthedoseoffentanylIsexcretedunchangedIntheurIne.
120
Dosage and Administration of Fentanyl
FromadmInIstratIonasasInglebolusdose,fentanyldevelopedanearlyreputatIonasa
shortactIngopIoId,butexperIencewIthverylargedosesandmultIpledosesrevealedthat
prolongedrespIratorydepressIonanddelayedrecoverycouldoccur(Table194).These
observatIonsdemonstratethatfentanyl'sclInIcalduratIonIslImItedbyredIstrIbutIon,and
thatwIthprolongedadmInIstratIon,accumulatIoncanoccur,asdIscussedlaterInthIs
chapter.
FentanylcanbeusefulasasedatIve/analgesIcpremedIcatIonwhengIvenashorttIme
prIortoInductIon.ForthIsuse,Incrementaldosesof25to50g7aretItrateduntIlthe
desIredeffectIsachIeved.tIsImportanttonotethatalthoughtheonsetoffentanyl's
effectsIsrapId,peakeffectlagsbehIndpeakplasmaconcentratIonbyupto5mInutes.
99
A
transmucosaldelIverysystemforfentanylIsalsoavaIlableandhasbeenshowntobean
effectIvepremedIcantforpedIatrIcandadultpatIentsaswellasaneffectIvetreatmentfor
breakthroughpaInInchronIcpaInpatIents.0osesof10to20g/kgInchIldrenand400to
800gInadults,admInIsteredJ0mInutesprIortoInductIonorapaInfulprocedure,are
safeandeffectIve,butdosedependentsIdeeffectstypIcalofopIoIdsarereported.
1J5,1J6
8ecauserespIratorydepressIonandhypoxemIacanoccur,transmucosalfentanylusually
shouldbeadmInIsteredInamonItoredenvIronment.
FentanylIsusedfrequentlyasanadjuncttoInductIonagentstobluntthehemodynamIc
responsetolaryngoscopyandtrachealIntubatIon,whIchcanbepartIcularlysevereIn
patIentswIthhypertensIonorcardIovasculardIsease.CommonclInIcalpractIceInvolves
tItratIonoffentanylIndosesof1.5to5g/kgprIortoadmInIstratIonoftheInductIon
agent.8ecauseItspeakeffectlagsbehIndpeakplasmaconcentratIonbyJto5mInutes,
fentanyltItratIonshouldbecompleteapproxImatelyJmInutesprIortolaryngoscopyto
maxImallyblunthemodynamIcresponsestotrachealIntubatIon.Perhapsthemostcommon
clInIcaluseoffentanylandItsderIvatIvesIs
P.480
asananalgesIccomponentofbalancedgeneralanesthesIa.WIththIstechnIque,
Incrementaldosesoffentanyl0.5to2.5g/kgareadmInIsteredIntermIttentlyasdIctated
bytheIntensItyofthesurgIcalstImulusandmayberepeatedapproxImatelyeveryJ0
mInutes.Cenerally,admInIstratIonofuptoJto5g/kg/hrwIllallowrecoveryof
spontaneousventIlatIonattheendofsurgery.AsanalternatIvetoIntermIttentdosIng,a
loadIngdoseof5to10g/kgandcontInuousfentanylInfusIonataratebetween2and10
g/kg/hrarerecommended.
109
tIsImportanttoremember,however,thatanesthetIc
requIrementsvarywIthage,concurrentdIseases,andthesurgIcalprocedure.Forexample,
fentanylrequIrementsdecreaseby50asageIncreasesfrom20to89years.
1J2
Fentanyl
requIrementscanalsobeexpectedtodecreasewIththeduratIonofInfusIon(seeContext
SensItIveHalfTIme).
Table 19-4 Dosage for Fentanyl, Sufentanil, Alfentanil, and Remifentanil
During Elective Surgery in Adults
a
ANESTHETIC PHASE FENTANYL SUFENTANIL ALFENTANIL REMIFENTANIL
Premedication(g) 2550 25 250500
Induction
WIthhypnotIc(g/kg) 1.55 0.11 1050
0.51.0
and/or0.250.5
g/kg/mIn
WIth6070N
2
D(g/kg)
82J 1.J2.8
HIghdoseopIoId(g/kg) 50 10J0 120
25
+/or2g/kg/mIn
Maintenance
8alancedanesthesIa
ntermIttentbolus
(g)
25100 520 250500 2550
nfusIon(g/kg/mIn) 0.0JJ
0.005
0.015
0.51.5 0.250.05
HIghdoseopIoId
(g/kg/mIn)
0.5 2.510 1.0J.0
Transition to PACU
(g/kg/mIn)
0.050.15
Monitored Anesthesia Care
ntermIttentbolus(g)
12.5
50
2.510 125250 12.525
nfusIon(g/kg/mIn) 0.010.2
PACU,postanesthesIacareunIt.
a
0osesareguIdelInesforhemodynamIcallystableadults.Theyshouldbeadjusted
downwardforelderlypatIentsandthosewIthcardIacdysfunctIonand
hemodynamIcInstabIlIty.
FentanylcombInedwIthhIghdosedroperIdolandnItrousoxIde,atechnIquecalled
neuroleptanesthesia,
1J7
IsrarelyusedtodaybecauseofconcernsaboutprolongatIonofthe
QTIntervaloftheelectrocardIogrambyhIghdosedroperIdol.
1J8
HIghdose(e.g.,50to150
g/kg)fentanylanesthesIahasbeenusedextensIvelyforcardIacsurgery.WIththIs
technIque,ameanplasmafentanylconcentratIonof15ng/mL,whIchprevents
hemodynamIcchangesInresponsetonoxIousstImulI,
1J9
canbeachIevedwIthaloadIng
doseof50g/kg,followedbyacontInuousInfusIonofJ0g/kg/hr.WIthhIghdosefentanyl,
musclerelaxantsandmechanIcalventIlatIonarerequIred.
TheuseoffentanylInthemanagementofacuteandchronIcpaInIsdIscussedInChapters
57and58).
Sufentanil
SufentanIl,athIenylderIvatIveoffentanyl(FIg.195)fIrstdescrIbedInthemId1970s,has
aclInIcalpotencyratIo2,000to4,000tImesthatofmorphIneand10to15tImesthatof
fentanyl.
140,141
LIkefentanyl,sufentanIlequIlIbratesrapIdlybetweenbloodandbraIn,and
demonstratesclearplasmaconcentratIoneffectrelatIonshIps.nastudycomparIngeffects
ofsufentanIlandfentanylontheEEC,Scottetal.
141
notedsImIlarpharmacodynamIc
profIles.0urInga4mInutesufentanIlInfusIon,thechangeInspectraledgelaggedbehInd
therIsIngsufentanIlconcentratIonbyapproxImately2toJmInutes,whIleresolutIonofthe
EECchangeslaggedbehIndplasmaconcentratIonchangesby20toJ0mInutes.
Analgesia
SufentanIlIsahIghlyselectIveopIoIdreceptoragonIstandexertspotentanalgesIc
effectsInanImalswhengIvenbyeIthersystemIcorspInalroutes.WhIlethelIterature
descrIbIngclInIcalexperIencewIthsufentanIlasacomponentofgeneralanesthesIaIs
extensIve,avaIlableInformatIonregardIngtheanalgesIcpotencyofsystemIcally
admInIsteredsufentanIlInhumansIslImIted.Celleretal.
142
tItratedan7InfusIonrateto
adequatepostoperatIveanalgesIa,andnotedthatameanrateof8to17g/hrwas
requIreddurIngthefIrst48hours.ThIswasassocIatedwIthafIvefoldrangeInplasma
sufentanIlconcentratIons,between0.02and0.1ng/mL.SImIlarsufentanIlrequIrements
(IncludIngawIdeInterpatIentvarIabIlIty)arenotedInotherstudIesofpostoperatIveand
cancerpatIents.
47,14J
Lehmanetal.
14J
estImatedthatthe|EACofsufentanIlIsnear0.0J
ng/mL,andtheanalgesIcEC
50
ofsufentanIlconcentratIonIsapproxImately0.05ng/mL.
144
Use in Anesthesia
nanImalstudIes,sufentanIldecreasesthe|ACofvolatIleanesthetIcsInadosedependent
manner,wIththemaxImum|ACreductIonbetween70and90.
145
nhumans,aplasma
sufentanIlconcentratIonof0.145ng/mLIsassocIatedwItha50reductIonInIsoflurane
|AC.
146
ncreasIngtheplasmasufentanIlconcentratIonto0.5ng/mLreducedIsoflurane
|ACby78,andaceIlIngeffectwasapproachedwIthgreaterplasmasufentanIl
concentratIons.ThemaxImum|ACreductIonseenInhumanswas89atasufentanIl
concentratIonof1.4ng/mL.
nclInIcalanesthesIapractIce,sufentanIlIsusedasacomponentofbalancedanesthesIa
andhasbeenemployedextensIvelyInhIghdoses(10toJ0g/kg)wIthoxygenandmuscle
relaxantsforcardIacsurgery.nthIsdoserange,sufentanIlIs
P.481
atleastaseffectIveasfentanylInItsabIlItytoproduceandmaIntaInhypnosIs.naddItIon,
hemodynamIcstabIlItyappearstobeasgoodasorbetterthanthatachIevedwIth
fentanyl.
86,140
8aIleyetal.
147
usedacomputerassIstedcontInuousInfusIonsystemto
determInethesufentanIlplasmaconcentratIonresponsetovarIousnoxIousstImulIdurIng
hIghdosesufentanIlanesthesIaforcardIacsurgery.TheyestImatedtheplasma
concentratIonassocIatedwItha50probabIlItyofnoresponse(movement,hemodynamIc,
orsympathetIc)toIntubatIon,IncIsIon,sternotomy,andmedIastInaldIssectIon(CP
50
).The
CP
50
forIntubatIon,IncIsIon,andsternotomy(pooleddata)was7.06ng/mL,andfor
medIastInaldIssectIonCP
50
was12.1ng/mL.AsIstypIcalofopIoIds,awIdeIntersubject
varIabIlIty(threetotenfold)wasnotedInsufentanIlconcentratIonrequIrements.
However,whenusedasthesoleanesthetIcagent,evenhIghdosesmaynotcompletely
blockthehemodynamIcresponsestonoxIousstImulI.
110
EquIanalgesIcdosesofsufentanIlandfentanylproducesImIlarchangesIntheEEC.
140,141
n
patIentswhoreceIvedsufentanIl15g/kg,actIvItybecamepromInentwIthInafew
seconds,andwIthInJmInutes,theEECconsIstedalmostentIrelyofslowactIvIty.
140
FIgIdItyandmyoclonIcactIvItyresemblIngseIzureshavebeenreporteddurIngInductIonof,
andonemergencefrom,anesthesIawIthsufentanIlIndosesofapproxImately1to2
g/kg.
4J,44
npatIentswIthIntracranIaltumors,sufentanIl1g/kgwasassocIatedwIthanelevatIonIn
spInalcerebrospInalpressureandadecreaseIncerebralperfusIonpressure.
148
AsseenwIth
fentanyl,meanarterIalpressurehaddroppedsIgnIfIcantlyInthesepatIents.nnormal
volunteers,asmallerdoseofsufentanIl(0.5g/kg)wasnotassocIatedwIthchangesIn
cerebralbloodflow.
149
7erylargedosesofsufentanIl(20g/kg)Indogsdecreasedcerebral
bloodflowInproportIontocerebralmetabolIsm,andIntracranIalpressuredIdnot
change.
150
LIkeotheropIoIdagonIsts,sufentanIlcausesrespIratorydepressIonIndosesassocIated
wIthclInIcalanalgesIa.
122,12J
FespIratorydepressIoncanbeespecIallymarkedInthe
presenceofInhalatIonanesthetIcs.nspontaneouslybreathIngpatIentsanesthetIzedwIth
1.5halothaneandN
2
D,asmalldoseofsufentanIl(approxImately2.5g)reducedmean
mInuteventIlatIonby50,and4greducedmeanrespIratoryrateby50.
151
PostoperatIverespIratorydepressIonafterapparentrecoveryfromanesthesIahasbeen
reportedforbothfentanylandsufentanIl.
152
ThelackofexogenousstImulatIonIntheearly
postoperatIveperIodmaybeanImportantfactordurIngearlyrecoveryfromanesthesIa.
nnormalvolunteerswhoreceIvedbolusdosesoffentanylandsufentanIl,changesInend
tIdalCD
2
werethesameforfentanylandsufentanIl,buttheslopeoftheventIlatory
responsetoCD
2
wasdepressedtoagreaterextentbyfentanyl.
122
nanothervolunteer
study,afourfoldrangeofequIanalgesIcplasmaconcentratIonsofmorphIneandsufentanIl
producedequIvalentrespIratorydepressIon,measuredasbothIncreasedendtIdalCD
2
and
adecreasedventIlatoryresponsetoCD
2
.
144
Cardiovascular and Endocrine Effects
nanImalstudIes,sufentanIlproducesvasodIlatIonbyasympatholytIcmechanIsmbutmay
alsohaveadIrectsmoothmuscleeffect.
15J
ClInIcally,apromInentfeatureofmanytrIals
InvolvIngsufentanIlIstheremarkablehemodynamIcstabIlItyachIeveddurIngbalancedand
hIghdose(uptoJ0g/kg)opIoIdanesthesIa.DnlyamodestdecreaseInmeanarterIal
pressureIsobservedwhensufentanIl(approxImately15g/kg)IsusedforInductIonof
anesthesIa.
86,154
ngeneral,sufentanIlandfentanylhavebeenfoundtobeequIvalentforuseInbalanced
andhIghdoseopIoIdanesthesIa,
110,155
butoneclInIcalcomparIsonnotedbetteranalgesIa
andrespIratoryfunctIonwIthsufentanIlIntheImmedIatepostoperatIveperIod.
156
The
choIceofpremedIcatIonandmusclerelaxantmaysIgnIfIcantlyaffecthemodynamIcsdurIng
InductIonandmaIntenanceofanesthesIawIthsufentanIl.CombInIngvecuronIumand
sufentanIlcancauseadecreaseInmeanarterIalpressuredurIngInductIon,
157
and
sIgnIfIcantbradycardIaandsInusarrest
158
havebeenreported.8radycardIaIsnotseen
whenpancuronIumIsuseddurInganesthesIawIthsufentanIl.
SufentanIl,lIkefentanyl,reducestheendocrIneandmetabolIcresponsestosurgery.
140
However,evenalargeInductIondose(20g/kg)dIdnotpreventIncreasesIncortIsol,
catecholamInes,glucose,andfreefattyacIdsdurIngandaftercardIopulmonarybypass.
159
SufentanIlIsextremelylIpophIlIcandhaspharmacokInetIcpropertIessImIlartothatof
fentanyl.8ecauseofasmallerdegreeofIonIzatIonatphysIologIcpHandhIgherdegreeof
plasmaproteInbIndIng,ItsvolumeofdIstrIbutIonIssomewhatsmallerandItselImInatIon
halflIfeshorterthanthatoffentanyl(Table192).SufentanIlpharmacokInetIcshasbeen
studIedInanesthetIzedpatIentswhohadreceIvedmethohexItalforanesthetIcInductIon,
followedbythesufentanIldoseof5g/kg,andN
2
DInoxygenJJ.
160
PlasmasufentanIl
concentratIondropsveryrapIdlyafteran7bolusdose,and98ofthedrugIsclearedfrom
plasmawIthInJ0mInutes.PlasmaconcentratIontImedataInthIsstudywerebestfIttedto
athreecompartmentmodel,wIthrapIdandslowerdIstrIbutIonhalftImesof1.4and17.7
mInutes,respectIvely,andanelImInatIonhalflIfeof2.7hours.notherpharmacokInetIc
studIeswIthanesthetIzedpatIents,reportedmeanelImInatIonhalflIveswereIntherange
of2.2to4.6hours.
161,16J
DbesepatIentshavealargertotalvolumeofdIstrIbutIonanda
longerelImInatIonhalflIfe(J.5vs.2.2hours)comparedwIthnonobesepatIents.
161
SufentanIlIslessredcellboundthanfentanyl(22comparedwIth40).
1JJ
PlasmasufentanIl
IsapproxImately92proteInboundatpH7.4,mostlyto
1
acIdglycoproteIn.Clearanceof
sufentanIlIsrapId,andlIkefentanyl,IthasahIghhepatIcextractIonratIo.
1JJ
|etabolIsm
InthelIverIsbyNdealkylatIonandOdemethylatIon,butsufentanIlclearanceand
elImInatIonhalflIfeInpatIentswIthcIrrhosIsaresImIlartocontrols.
162
Dosage and Administration of Sufentanil
SufentanIlIsmostoftenusedasacomponentofbalancedanesthesIa,orasasIngleagent
InhIghdoses,partIcularlyforcardIacsurgery(Table194).SeveralInvestIgatIonshave
foundsImIlarsufentanIldoserequIrementsforInductIonofanesthesIa.
86,147,16J
When
sufentanIlIstItrateddurIngInductIon,lossofconscIousnessIsseenwIthtotaldoses
between1.Jand2.8g/kg.0osesIntherangeof0.Jto1.0g/kggIven1toJmInutesprIor
tolaryngoscopycanbeexpectedtoblunthemodynamIcresponsestoIntubatIon,but
musclerIgIdItycanoccurevenattheselowerdoses,partIcularlyIntheelderly.
8alancedanesthesIaIsmaIntaInedwIthIntermIttentbolusdosesoracontInuousInfusIon.
WIthbolusdosesof0.1to0.5g/kg,meanmaIntenancerequIrementsof0.J5g/kg/hr
havebeenreported.
86
Corketal.
164
admInIsteredanInItIalbolusof0.5g/kgfollowedby
anInfusIonof0.5g/kg/hr,tItratedtopatIentneed.ThIsregImenofsufentanIlIn
combInatIonwIth
P.482
N
2
D70Inoxygen,wIthorwIthoutIsoflurane,provIdedsatIsfactoryanesthesIawIthgood
hemodynamIcstabIlIty.Thus,forbalancedanesthesIa,doserequIrementsforbolus
admInIstratIonandcontInuousInfusIonaresImIlar,Intherangeof0.Jto1g/kg/hr.|uch
hIgherbolusdoses(10g/kg)and/orInfusIonrates(0.15g/kg/mIn)arerequIredto
achIevetheplasmasufentanIlconcentratIonrangeof6to60ng/mLrequIreddurIng
cardIacanesthesIausIngsufentanIlasthesoleagent.
Alfentanil
AlfentanIl,atetrazolederIvatIveoffentanyl(FIg.195),wassynthesIzed2yearsafter
sufentanIlandIntroducedIntoclInIcalpractIceIntheearly1980s.DnamIllIgrambasIs,Its
clInIcalpotencyIsapproxImately10tImesthatofmorphIneandonefourthtoonetenth
thatoffentanylwhengIvenInsIngledoses.AlfentanIldIffersfromfentanylInIts
pharmacokInetIcsaswellasInItsspeedofequIlIbratIonbetweenplasmaandeffectsIteIn
thebraIn.nacomparIsonusIngEECspectraledgeeffectstoquantIfyfentanyland
alfentanIlpharmacodynamIcs,Scottetal.
99
demonstratedthatalfentanIl'seffectfollowed
serumdrugconcentratIonmorecloselythanfentanyl(FIg.198).PeakeffectlaggedbehInd
peakplasmaconcentratIonby1mInute,andresolutIonofeffectfolloweddecreasIng
serumalfentanIlconcentratIonbynomorethan10mInutes.AlfentanIlIsaopIoId
receptoragonIstandproducestypIcalnaloxonereversIbleanalgesIaandsIdeeffectssuch
assedatIon,nausea,andrespIratorydepressIon.
Analgesia
ClearconcentratIonanddoserelatedanalgesIceffectshavebeendemonstratedfor
alfentanIl,but,asIstypIcalforopIoIds,IndIvIdualrequIrementsvarywIdely.For
postoperatIveanalgesIa,the|EACIsapproxImately10ng/mL,wItharangeof2to40
ng/mL.
165
nalaboratoryInvestIgatIon,80ng/mLwasassocIatedwItha50reductIonIn
paInIntensIty.
46
SImIlarresultsareseenInclInIcalstudIes,InwhIchmeanalfentanIl
plasmaconcentratIonsrequIredforrelIefofmoderatetoseverepaInareapproxImately40
to80ng/mL(Table19J).
166
FollowInganadequateloadIngdose,averagealfentanIl
requIrementsforpostoperatIveanalgesIaareapproxImately10to20g/kg/hr.
167,168
Use in Anesthesia
LIkeotheropIoIds,alfentanIldecreasesthe|ACofenfluraneInacurvIlInearfashIonupto
aplateau.
26,169
ndogs,anInfusIonrateof8g/kg/mIn(plasmaconcentratIon,22Jng/mL)
reducedenflurane|ACby69,butIncreasIngtheInfusIonratefourfolddIdnotreduce
enflurane|ACfurther.
158
AlfentanIlplasmaconcentratIonsrequIredtosupplementN
2
DanesthesIahavebeen
determIned.
170
PatIentsreceIvedaloadIngdoseof150g/kg,followedbyanInfusIon
tItratedbetween25and150g/kg/hraccordIngtoresponsestosurgIcalstImulI.Plasma
concentratIonsrequIredalongwIth66N
2
DtoobtundsomatIc,autonomIc,and
hemodynamIcresponsestostImulIIn50ofpatIentswere475,279,and150ng/mLfor
trachealIntubatIon,skInIncIsIon,andskInclosure,respectIvely.TheplasmaalfentanIl
concentratIonassocIatedwIthspontaneousventIlatIonafterdIscontInuatIonofN
2
Dwas22J
ng/mL.NearlyIdentIcalresultswereobtaInedInasImIlarstudyusIngcomputercontrolled
InfusIonstodelIveralfentanIl(FIg.199).
171
PlasmaalfentanIlconcentratIonsrequIredIn
combInatIonwIthpropofoltoobtundresponsestoIntubatIonandsurgIcalstImulIhavealso
beendetermIned.
172
ncontrasttocombInIngalfentanIlandN
2
D,muchloweralfentanIl
plasmaconcentratIons(55to92ng/mL)wererequIredtopreventresponsesIn50of
patIentswhenalfentanIlwascombInedwIthpropofolataplasmaconcentratIonofJg/mL
(FIg.1910).
Figure 19-9.TherelatIonshIpbetweenalfentanIlplasmaconcentratIon(wIth66N
2
D)
andtheprobabIlItyofnoresponseforIntubatIon,skInIncIsIon,andskInclosure;and
therelatIonshIpofplasmaalfentanIlconcentratIon(wIthoutN
2
D)andtherecoveryof
adequatespontaneousventIlatIon.(FeprIntedwIthpermIssIonfromAusems|E,7uyk
J,HugCC,etal:ComparIsonofacomputerassIstedInfusIonvs.IntermIttentbolus
admInIstratIonofalfentanIlasasupplementtonItrousoxIdeforlowerabdomInal
surgery.AnesthesIology1988;68:851.)
HIghdosealfentanIlhasbeenusedasanInductIonagentforpatIentswIthandwIthout
cardIacdIsease
17J
andforInductIonandmaIntenanceofcardIacanesthesIa.
127,174
PatIents
wIthcardIacvalvularorcoronaryarterydIseaserequIredhalfasmuchalfentanIltoInduce
unconscIousness.
17J
WhenusedasthesoleanesthetIcagent,meanplasmaalfentanIl
concentratIonsrequIredtosIgnIfIcantlyblunthemodynamIcresponsestoIntubatIonand
sternotomywere700to8J0ng/mLand1,200to1,800ng/mL,respectIvely.
175
Thesevalues
areapproxImatelytwIcethosereportedforalfentanIlIncombInatIonwIth66nItrous
oxIde.
170,171
However,evendosesthatproducedveryhIghplasmaalfentanIl
concentratIons(1,200to2,000ng/mL)dIdnotelImInateresponsestoIntubatIonand
IntraoperatIvestImulIInallpatIents.
170
ncontrasttofentanylandsufentanIl,theduratIon
ofevenverylargedosesofalfentanIlIsshort,sorepeateddosesoracontInuousInfusIonof
alfentanIlIsrequIred.
AlfentanIlproducesthetypIcalgeneralIzedslowIngoftheEEC.
99,176
LIkefentanyl,
alfentanIlcanIncreaseepIleptIformEECactIvItyInpatIentswIthIntractabletemporallope
epIlepsyhavIngsurgeryundergeneralanesthesIa.
14J
LIkefentanylandsufentanIl,
alfentanIlcanproduceIntensemusclerIgIdItyaccompanIedbylossofconscIousness.n90
to100ofpatIents,InductIondosesof150to175g/kgwereassocIatedwIthmuscle
rIgIdIty,whIchwasnotlImItedtothechestwallortrunk.Father,electromyographyhas
shownIncreasedactIvItyofcomparablemagnItudeInmusclesoftheneck,extremItIes,
chestwall,andabdomen.
148,177
AlfentanIlhasbeenreportedtoIncreasecerebrospInalfluIdpressureInpatIentswIthbraIn
tumors,whereasfentanyldoesnot.
11J
However,whennormocapnIaandbloodpressure
weremaIntaInedatbaselIne,noclInIcallysIgnIfIcantchangesInCPandnoevIdenceof
cerebralvasodIlatIonorvasoconstrIctIonwereseenInneurosurgIcalpatIentswhoreceIved
25and
P.48J
50g/kgofalfentanIlwIthN
2
D.
178
WhentheeffectsofthreedoseregImensofalfentanIl,
10,20,andJ0g/kg,followedby10,20andJ0g/kg/hr,werecomparedwIthplaceboIn
braIntumorpatIentsanesthetIzedwIthpropofolandfentanyl,meanarterIalpressureand
cerebralperfusIonpressuredecreasedInadosedependentfashIon,buttherewereno
changesInsubduralCPorarterIovenousD
2
contentdIfference.
179
Figure 19-10.ThealfentanIlplasmaconcentratIoneffectrelatIonshIpsforIntubatIon,
skInIncIsIon,andtheopenIngoftheperItoneumwhengIvenasasupplementto
propofol.(FeprIntedwIthpermIssIonfrom7uykJ,LImT,EngbersFH|,etal:
PharmacodynamIcsofalfentanIlasasupplementtopropofolornItrousoxIdeforlower
abdomInalsurgeryInfemalepatIents.AnesthesIology199J;78:10J6.)
nanImalandhumanstudIes,antInocIceptIveeffectscouldnotbeseparatedfrom
respIratorydepressIonInvolunteers;mIldventIlatorydepressIon(IncreasedendtIdalCD
2
;
decreasedslopeoftheCD
2
responsecurve)wasseenatplasmaconcentratIonsaslowas20
ng/mL.AtplasmaconcentratIonsassocIatedwIth50reductIonInpaInIntensIty,
respIratorydepressIonwasequIvalentforalfentanIl,fentanyl,andmorphIne.
15
AclInIcal
studyexamInedpostoperatIveanalgesIaandrespIratoryeffectsofalfentanIladmInIstered
byapatIentcontrolledanalgesIasystem.
180
npatIentswhoreceIvedacontInuous
alfentanIlInfusIonat900g/hrplus100to200gdosesasneeded,threeoftenpatIents
developedrespIratorydepressIon(respIratoryrate8/mIn).|eanalfentanIlblood
concentratIonInthIsgroupofpatIentswas80ng/mL.
TwoclInIcalstudIesexamInedtheIntensItyandduratIonofrespIratorydepressanteffects
ofalfentanIlIntheImmedIatepostoperatIveperIod.
181,182
PatIentsreceIvedbalanced
anesthesIa67N
2
DwIthorwIthout0.5halothaneandalfentanIl20to100g/kg/hr.At
theendofsurgerytheInfusIonwasdecreasedto20g/kg/hr,whIchproducedplasma
alfentanIlconcentratIonsbetween106and120ng/mL,andgoodanalgesIa.7entIlatory
responsetoCD
2
wasdecreasedto50ofthebaselInevalue,butPaCD
2
wasonly
moderatelyelevated(42to48torr).8y2hoursafteralfentanIlwasdIscontInued,
respIratoryfunctIonwasnearbaselIne.FecoveryofventIlatoryfunctIonwasfasterwIth
alfentanIlcomparedwIthfentanyl.
182
AnothercomparIsonfoundthatforanesthetIcsof1.5
to2hours'duratIon,recoveryofrespIratoryfunctIonwassImIlarwIthalfentanIland
fentanyl.
18J
LIkeItscongeners,alfentanIlhasbeenassocIatedwIthapneaand
unconscIousnessafterapparentrecoveryfromanesthesIa.
184
ThecardIovasculareffectsofalfentanIlareInfluencedbypreoperatIvemedIcatIon,muscle
relaxantused,methodofadmInIstratIon,andthedegreeofsurgIcalstImulatIon.n
general,heartrateandmeanarterIalpressureareunchangedorslIghtlydecreaseddurIng
InductIonwIthalfentanIl40to120g/kg,
17J
butrapIdInductIonwIth150to175g/kg
alfentanIlcandecreasemeanarterIalpressureby15to20torr.AfterInductIonwIth
etomIdate,alfentanIl120g/kgdecreasedmeanarterIalpressurebyapproxImatelyJ0
torr,
185
andfollowIngthIopental(Jto5mg/kg)InductIon,asmallerdoseofalfentanIl(40
g/kg)decreasedmeanarterIalpressurebyapproxImately40torr.
186
AlfentanIldoesnot
appeartohavenegatIveInotropIceffects,
185
butseverehypotensIonhasbeenobserved
whenalfentanIlIsgIvenafter0.125mg/kgdIazepam.
187
ncombInatIonwIthlorazepam
premedIcatIonorthIopentalInductIon,moderatedoses(10to50g/kg)ofalfentanIlblunt
thecardIovascularandcatecholamIneresponsestolaryngoscopyandIntubatIon,
175,186
but
forpatIents70yearsold,dosesInthIsrangegIvenwIththIopentalcanproducesIgnIfIcant
hypotensIonafterInductIon.
188
AlfentanIlcanalsocausebradycardIa,butthIseffectIs
mInImIzedbypremedIcatIonwIthatropIneandbythevagolytIceffectofpancuronIum.
AlfentanIl50g/kgcombInedwIthpropofol1mg/kgforInductIonofanesthesIacan
producesIgnIfIcantbradycardIaandhypotensIonafterIntubatIon,butpremedIcatIonwIth
glycopyrrolatepreventstheseeffects.
189
P.484
Nausea and Vomiting
ClInIcalcomparIsonsbetweenalfentanIlandsufentanIl
190
orfentanyl
191
andN
2
Drevealed
thesameIncIdenceofnauseaandvomItIng.nnormalvolunteersreceIvIngcomputer
controlledopIoIdInfusIons,theseverItyofnauseaatequIanalgesIcplasmaconcentratIons
wasequIvalentforalfentanIl,fentanyl,andmorphIne,
46
butalfentanIlInducednauseaand
vomItIngresolvedmorequIckly(8.A.Coda,unpublIshedobservatIons,198890).
AlfentanIlpharmacokInetIcsdIffersfromfentanylandsufentanIlInseveralrespects(Table
19J).AunIquecharacterIstIcIsthatalfentanIlIsaweakerbasethanotheropIoIds.
WhereasotheropIoIdshavepKaabove7.4,thepKaofalfentanIlIs6.8;consequently,
nearly90ofunboundplasmaalfentanIlIsnonIonIzedatpH7.4.
1J1
ThIsproperty,together
wIthItsmoderatelIpIdsolubIlIty,enablesalfentanIltocrossthebloodbraInbarrIerrapIdly
andaccountsforItsrapIdonsetofactIon.ComparedwIthfentanylandsufentanIl,whIch
havemeanplasmabraInequIlIbratIonhalftImesof6.4and6.2mInutes,respectIvely,
99,141
alfentanIlhasabloodbraInequIlIbratIonhalftImeof1.1mInutes.
121
AlfentanIlalsohasa
smallervolumeofdIstrIbutIonthanfentanyl,whIchIsaresultoflowerlIpIdsolubIlItyand
hIghproteInbIndIng.
192
ApproxImately92ofalfentanIlIsproteInbound,mostlyto
1
acId
glycoproteIn.
1J1,1J4
After7admInIstratIon,plasmaalfentanIlconcentratIonfallsrapIdly;90ofthe
admInIstereddosehaslefttheplasmabyJ0mInutes,
19J
mostlybecauseofdIstrIbutIonto
hIghlyperfusedtIssues.PlasmaconcentratIondecaycurvesInpatIentsmostoftenfIta
threecompartmentmodel.
24,19J
LIkefentanyl,alfentanIlIsquIcklydIstrIbuted,wIthrapId
andslowdIstrIbutIonhalftImesof1.0toJ.5mInutesand9.5to17mInutes,respectIvely.
However,alfentanIlhasatermInalelImInatIonhalflIfeof84to90mInutes,whIchIs
consIderablyshorterthanthoseoffentanylandsufentanIl.ClearanceofalfentanIl,6.4
mL/kg/mIn,Isjusthalfthatoffentanyl,butbecausealfentanIl'svolumeofdIstrIbutIonIs4
tImessmallerthanfentanyl's,relatIvelymoreofthedoseIsavaIlabletothelIverfor
metabolIsm.
194
ChauvInetal.
195
foundthatalfentanIlhasanIntermedIatehepatIc
extractIoncoeffIcIent(J2to5J)Inhumans,andthatItselImInatIondependsonhepatIc
plasmaflow.
nanImals,alfentanIlundergoesNdealkylatIonandOdemethylatIonInthelIvertoform
InactIvemetabolItes.
1J1
LIverdIseasecansIgnIfIcantlyprolongtheelImInatIonhalflIfeof
alfentanIl.PatIentswIthmoderatehepatIcInsuffIcIencyasaresultofcIrrhosIshave
reducedbIndIngto
1
acIdglycoproteInandaplasmaclearanceonehalfthatofcontrol
patIents.ThesechangesresultInamarkedIncreaseIntheelImInatIonhalflIfe,219
mInutesversus90mInutesIncontrols.
196
FenaldIseasealsodecreasesalfentanIlproteIn
bIndIng,butdoesnotresultIndecreasedplasmaclearanceoraprolongedtermInal
elImInatIonhalflIfe.
197
AlfentanIl'selImInatIonhalflIfeIsprolongedbyaboutJ0Inthe
elderlyandappearstobemuchshorter(about40mInutes)InchIldren5to8yearsold.
198
DbesItyIsalsoassocIatedwItha50decreaseInalfentanIlclearanceandaprolonged(172
mInutes)elImInatIonhalflIfe.
198
ThecombInatIonofmoderatelIpIdsolubIlItyandshortelImInatIonhalflIfesuggeststhat
bothredIstrIbutIonandelImInatIonareImportantInthetermInatIonofalfentanIl's
effects.
182
AfterasInglebolusdose,redIstrIbutIonwIllbethemostImportantmechanIsm,
butafteraverylargedose,repeatedsmalldoses,oracontInuousInfusIon,elImInatIonwIll
beamoreImportantdetermInantoftheduratIonofalfentanIl'seffects.
Dosage and Administration of Alfentanil
8ecauseofItsrapIdonset,alfentanIlhasbeenusedasanInductIonagentaloneorIn
combInatIonwIthotherdrugs(Table194).nhealthypatIents,dosesofabout120g/kg
produceunconscIousnessIn2to2.5mInutes,butmayalsoproducemusclerIgIdIty.
PremedIcatIonwIthabenzodIazepIne(e.g.,lorazepam0.08mg/kg)IsassocIatedwItha
lowerdoserequIrement,40to50g/kg,andafasteronsetofunconscIousness,wIthIn1.5
mInutes,
17J
butmayalsoproducehypotensIon.ForrapIdsequenceInductIon,abolusdose
ofJ6g/kgfollowedbythIopentalandrocuronIumcanyIeldIdealIntubatIngcondItIons
wIthIn40secondsIn95ofpatIents.
199
Alowerdose,15g/kg(range,1JtoJ1g/kg)wIth
sevofluraneandN
2
D,butwIthoutmusclerelaxantsproducedgoodIntubatIngcondItIons
wIthIn90secondsIn95ofpatIents.
200
WIthpropofol2.5mg/kg,analfentanIldoseof10
g/kgappearsoptImalforlaryngealmaskInsertIon,butIsaccompanIedbyapneaforabout
2mInutes.
201
8ecauseofItsbrIefduratIonofactIon,alfentanIlcanbeausefulcomponentofgeneral
anesthesIaInshortsurgIcalprocedures,especIallythoseassocIatedwIthmInImal
postoperatIvepaIn,partIcularlyIntheoutpatIentsurgery.nthIssettIng,loadIngdosesof5
to10g/kgprovIdegoodanalgesIawIthrapIdrecovery.
192
Forlongerprocedures,
alfentanIlcanbeadmInIsteredasneededInrepeatedsmallbolusdoses,butIts
pharmacokInetIcpropertIesmakeItIdealforadmInIstratIonasacontInuousInfusIon.After
InductIonofanesthesIa,aloadIngdoseofalfentanIl10to50g/kgIsfollowedwIth
supplementalbolusdosesofJto5g/kgasneededoracontInuousInfusIonstartIngat0.4
to1.7g/kg/mInwIth60to70N
2
DorapropofolInfusIon.
170,171,192,200,201,202,20J
A
pedIatrIcstudyreporteduseofsImIlardosesofalfentanIlandpropofol,
204
whIleanother
usedhIgheralfentanIldoses(100g/kgloadIngdosefollowedby2.5g/kg/mIn)combIned
wIth70N
2
DwIthoutpropofol.
205
WhenhIghdosealfentanIlIsusedasthesoleanesthetIcagent,acontInuousInfusIonofup
to150to600g/kg/hrIsadjustedaccordIngtothepatIent'sresponsestostImulI,butmuch
lowerdosescanbeeffectIveforcardIacsurgeryIfadequatepremedIcatIonIsgIven.
174
Remifentanil
FemIfentanIl,a4anIlIdopIperIdInewIthamethylestersIdechaIn(FIg.195)thatwasfIrst
descrIbedIn1990andapprovedforclInIcaluseIn1996,wasdevelopedtomeettheneed
foranultrashortactIngopIoId.8ecauseItsestersIdechaInIssusceptIbletometabolIsmby
bloodandtIssueesterases,remIfentanIlIsrapIdlymetabolIzedtoasubstantIallylessactIve
compound.Thus,becauseItsultrashortactIonIsduetometabolIsmratherthanto
redIstrIbutIon,ItdoesnotaccumulatewIthrepeateddosIngorprolongedInfusIon.
FemIfentanIldemonstratespotent,naloxonereversIbleselectIveopIoIdagonIstactIvIty
InanImalassays.
206
Analgesia
nanImalsandhumans,remIfentanIlproducesdosedependentanalgesIceffects.Human
laboratorystudIeshaveexamInedanalgesIceffectsofbolus7doses(0.0625to2.0
g/kg)
207
aswellascomputercontrolledInfusIonswIthtargetedplasmaconcentratIons
(0.75toJ.0ng/mL).
208
8olusdosesproducedapeakanalgesIceffectbetween1andJ
mInutesandaduratIonofapproxImately10mInutes.nvolunteers,|EACIsapproxImately
0.75ng/mLandanalgesIcEC
50
IsapproxImatelyJng/mL.
208
8othstudIesfoundremIfentanIl
tobeabout40tImesaspotentasalfentanIl.
P.485
ClInIcalInvestIgatIonshaveevaluatedearlypostoperatIveanalgesIa.Dnestudyreported
thatafterremIfentanIlpropofolanesthesIa,nearly80ofpatIentsweretItratedto
satIsfactoryanalgesIawIthremIfentanIlInfusIonof0.05to0.15g/kg/mIn.
209
Anotherearly
postoperatIveevaluatIondemonstratedeffectIveanalgesIawIthpatIentcontrolledInfusIon
ofremIfentanIltoameantargetbloodconcentratIonof2ng/mL,butnotedafaIrlyhIgh
IncIdenceofnausea(26)wIththIsregImen.
210
ClInIcalevaluatIonsofremIfentanIlfor
laboranalgesIahaveproducedconflIctIngresults,andsomehavefoundprohIbItIveratesof
unacceptablesIdeeffectssuchasnauseaandrespIratorydepressIon.However,adose
rangIngstudythatusedremIfentanIlvIapatIentcontrolledanalgesIareportedamedIan
effectIvebolusdoseof0.4g/kg(range,0.2to0.8g/kg)andconsumptIonof0.066
g/kg/mIn(range,0.027to0.207g/kg/mIn).
211
AlthoughtheseresultsareprelImInary,
remIfentanIlmayofferanalternatIveforlaborIngpatIentsInwhomregIonalanesthesIaIs
absolutelycontraIndIcated.
Use in Anesthesia
TheeffectofremIfentanIlonthe|ACofvolatIleanesthetIcsIscharacterIzedbysteep
doseeffectorconcentratIoneffectcurvestypIcalofotheropIoIdagonIsts.nanImals,
remIfentanIldecreasesenfluraneandIsoflurane|ACInadosedependentfashIonuptoa
maxImumnear65,sImIlartofentanyl.
212,21J
nhumans,remIfentanIlreducesIsoflurane
|AClogarIthmIcallyInabloodconcentratIondependentfashIon.
214
Awholeblood
remIfentanIlconcentratIonof1.Jng/mLreducedIsoflurane|ACby50,wIthamaxImum
|ACreductIon(91)atJ2ng/mL.FemIfentanIl'seffectsonthe|AC8AF(requIrementfor
bluntIngthesympathetIcresponsetoskInIncIsIon)ofsevoflurane
215
anddesflurane
216
In
60N
2
DaresImIlar.AremIfentanIlplasmaconcentratIonof1ng/mLreduced|AC8AFof
theInhalatIonagentsby60,whIleJng/mLdecreased|AC8AFanotherJ0.
TherapIdonsetandbrIefduratIonofremIfentanIlsuggestthatItIssuItableforInductIon
ofanesthesIa.AlthoughamedIanE0
50
of12g/kgforlossofconscIousnesshasbeen
reported,clInIcalInvestIgatIonshavealsofoundthat,aswIthotheropIoIds,lossof
conscIousnessIsnotrelIablyachIevedwIthremIfentanIlalone,evenIndosesof20g/kgor
more.
217,218
Furthermore,ahIghIncIdenceofmusclerIgIdItyandpurposelessmovement
wasseen.Evenat2g/kgremIfentanIl,moderatemusclerIgIdItywasseenIn40of
patIents,andat20g/kg,60ofpatIentshadseveremusclerIgIdIty.
217
0roverandLemmens
219
usedcomputerassIstedInfusIonstodetermInetheblood
concentratIonsofremIfentanIlrequIredtosupplement66N
2
DInpatIentshavIng
abdomInalsurgery.DtherthanpremedIcatIonwIth1to2mgmIdazolam,nosedatIvesor
hypnotIcsweregIven.0urIngsurgery,theremIfentanIlEC
50
foradequateanesthesIawas
4.1ng/mLformenand7.5ng/mLforwomen.ThereasonforgenderdIfferencesInthese
resultswasnotclear,butcouldhavebeenrelatedtodIfferenttypesofsurgerIes.PedIatrIc
patIentsrequIretwIceasmuchremIfentanIlasadults(0.15g/kg/mInvs.0.08g/kg/mIn)
whenItIsusedwIthpropofolforT7A.
220
nvestIgatIonsofremIfentanIlforbalancedanesthesIa,IncludIngcombInatIonwIth
Isoflurane,
221,222
sevoflurane,
22J
anddesflurane,
224
reportsImIlarfIndIngsofhemodynamIc
stabIlItyandeasytItratabIlIty.AclInIcaltrIalofremIfentanIlanddesfluraneN
2
DIdentIfIed
bloodremIfentanIlconcentratIonsthatprovIdeanoptImalbalancebetweenhemodynamIc
stabIlItyandbluntIngresponsestonoxIousstImulatIonwhIlepermIttIngrapIdrecovery.
224
nthepresenceof2.2to2.7endtIdaldesfluraneandN
2
D,optImalremIfentanIlplasma
concentratIonswere5to7ng/mLforlaryngoscopyandskInclosureand10ng/mLdurIng
abdomInalsurgery.tIsInterestIngtonotethatadjustmentsInremIfentanIlbluntedthe
sympathetIcresponsetonoxIousstImulatIonbutdIdnotalterdesflurane'seffectonthe
bIspectralIndexanalysIsoftheEEC.
FemIfentanIlIsInfusedasacomponentofT7AmorefrequentlythanotheropIoIds.8oth
remIfentanIlandpropofolcanbeadmInIsteredatfIxedInfusIonratesorbycomputer
controlledsystemsthatprovIdetargetplasmaconcentratIons,commonlyreferredtoas
target-controlled infusionsorTC.ThecombInatIonofremIfentanIlandpropofolforT7A
hasbeenusedsuccessfullyforavarIetyofInpatIentprocedures,IncludIngcoronaryartery
bypassgraft;othermajorthoracIc,neurosurgIcal,abdomInal,andorthopaedIcprocedures;
aswellasambulatorysurgeryandotherpaInfulproceduresInadultsandchIldren.Two
studIesdemonstratedthatafaIrlylowplasmaconcentratIonofremIfentanIl,TCatJ.4to4
ng/mL,reducespropofolEC
50
forIntubatIonby66,fromapproxImately6to2
ng/mL,
218,225
butfurtherIncreasesInremIfentanIldosageonlymodestlyreducedpropofol
doserequIrements,anapparentceIlIngeffect.
225
AclInIcaldoserangIngstudyfoundthat
remIfentanIlEC
50
forlaryngoscopywas14.Jand1.4ng/mLwIthpropofolInfusIonsof44and
200g/kg/mIn,respectIvely.
226
FesponsetoIntubatIonwaspreventedIn80ofpatIentsby
approxImatelydoublIngtheremIfentanIl.AsmallbolusdoseofremIfentanIl(20g)gIven
J0secondsbeforeInductIon,canreducethepaInofpropofolInjectIon.
227
AsprevIouslynoted,pedIatrIcpatIentsreceIvIngpropofolInfusIonrequIrehIgher
remIfentanIldosesthanadults.
WhIlehIghdoseremIfentanIl(1to2g/kg/mIn)hasbeenusedasasIngleagentforcardIac
anesthesIa,
228
ItIsmorecommonlyadmInIsteredwIthpropofolorIsofluraneforfasttrack
cardIacanesthesIa.TargetremIfentanIlandpropofolconcentratIonsforcardIac
surgery
228,229
areverysImIlartothoseforotherprocedureswIthlowdosepropofol.na
studycomparIngremIfentanIl,sufentanIl,andfentanylforfasttrackcardIacanesthesIa,
Engorenetal.
2J0
foundthatremIfentanIlpatIentsweremorelIkelytorequIretreatment
forbloodpressurefluctuatIonsdurIngandaftersurgery,butotherwIse,thethreeregImens
producedsImIlaroutcomeswIthrespecttoextubatIon,IntensIvecareunItstay,andcost.
DnedrawbackofremIfentanIluseforgeneralanesthesIaIsthatpatIentsrequIreanalgesIcs
verysoonafteranInfusIonIsstopped.AcontInuatIonofremIfentanIltotransItIonto
postoperatIveanalgesIacanavoIdearlypaInandaccompanyIngdetrImental
sympathoadrenalstImulatIonandIsessentIalforpatIentsundergoIngcardIacorother
majorsurgery.
FemIfentanIladmInIsteredbyInfusIonalsoappearstobeusefuldurIngmonItored
anesthesIacareforconscIoussedatIonInproceduressuchasextracorporealshockwave
lIthotrIpsyandcolonoscopy,
2J1,2J2
orInconjunctIonwIthregIonalanesthesIa.
2JJ,2J4,2J5
WhencomparedwIthpropofol,remIfentanIlprovIdesbetteranalgesIa,butresultsInmore
nauseaandrespIratorydepressIon,whereaspropofolcausesmoreoversedatIon.TImes
requIredforreadInessfordIschargeareclInIcallysImIlar.FormonItoredanesthesIacare,
theIdealadmInIstratIonregImenappearstobesmallbolusdosesofremIfentanIlwItha
contInuousInfusIoncombInedwIthlowdosepropofolormIdazolam.
FemIfentanIlproducesclassIcopIoIdagonIsteffectsontheEEC,thatIs,aconcentratIon
dependentslowIng.TheplasmaconcentratIonassocIatedwIth50maxImalEECchanges
(EC
50
)Is15to20ng/mL.
2J6,2J7
FemIfentanIl'srapIdonsetandveryshortduratIonresultsIn
extremelyclosetrackIngofchangesInEECspectraledgewIthplasmaremIfentanIl
concentratIon.
2J6,2J7
LIkeotheropIoIds,remIfentanIlcanproducemusclerIgIdIty,
especIallywIthbolusdoses.ThIscanbe
P.486
avoIdedwIthusIngsmallerdosesandInjectIngover60secondsormore.
NeItherremIfentanIl(0.5or1.0g/kg)noralfentanIl(10or20g/kg)gIvendurIng
Isoflurane/N
2
DanesthesIawIthcontrolledventIlatIonaffectIntracranIalpressure,andboth
producemodest,dosedependentdecreasesInmeanarterIalpressure.
2J8
AmultIcenter
clInIcaltrIalcomparIngremIfentanIl/N
2
DwIthfentanyl/N
2
DanesthesIafoundthat
IntracranIalpressureandcerebralperfusIonpressureweresImIlarwIththetwo
regImens.
2J9
nastudycomparIngcerebrovascularautoregulatIonIntheawakeand
anesthetIzedstates,remIfentanIl0.5g/kg/mInpluspropofolpreservedcerebral
autoregulatIon,whereasIsoflurane1.8dIdnot.
240
nmanycranIalandspInalneurosurgIcalprocedures,theabIlItytomonItormotorevoked
potentIals(|EPs)IsImportant;opIoIds,sedatIvehypnotIcdrugs,andInhalatIonagentsused
IngeneralanesthesIaareknowntosuppress|EPs.AhumanandanImalstudycomparedthe
effectsofphenylpIperIdIneopIoIdsandhypnotIcsIncludIngthIopental,mIdazolam,and
propofolon|EPs.
241
WhIleallopIoIdsandpropofolsuppressed|EPsInadosedependent
fashIon,remIfentanIlexertedlesssuppressIonthantheotheropIoIdsandpropofol.Atarget
plasmaconcentratIonof9ng/mLreducedamplItudeby50,butthequalItyand
reproducIbIlItyof|EPswaspreservedevenatplasmaconcentratIonof15ng/mL,well
wIthIntheplasmaconcentratIonrangethatprovIdessurgIcalanesthesIa.
AlthoughremIfentanIlhasnotbeenshowntoproduceseIzureactIvIty,Itcanbeusedto
reducemethohexItalrequIrementInpatIentshavIngelectroconvulsIvetherapy.
FemIfentanIl1g/kgalloweda50reductIonInmethohexItaldose,whIchresultsIn
seIzureprolongatIonby50.
242
FemIfentanIlproducesdosedependentrespIratorydepressIonasmeasuredbyIncreasesIn
endtIdalCD
2
anddecreasedoxygensaturatIon.nadoseescalatIonstudyInnormal
volunteers,therespIratorydepressanteffectsofremIfentanIlandalfentanIlwere
compared.
207
PeakrespIratorydepressIonoccurredat5mInutesaftereachdoseof
remIfentanIlandalfentanIl,andthemaxImalrespIratorydepressanteffectseenafter2
g/kgremIfentanIlwassImIlartothatcausedbyJ2g/kgalfentanIl.TheduratIonof
respIratorydepressIon,measuredastImetoreturnofbloodgasestowIthIn10ofbaselIne
values,was10mInutesafter1.5g/kgand20mInutesafter2g/kgremIfentanIlcompared
wIthJ0mInutesafterJ2g/kgalfentanIl.0urIngcontInuousopIoIdInfusIon,theventIlatory
responsetoCD
2
decreasedbyapproxImatelyJ0,45,and60Inresponseto4hour
remIfentanIlInfusIonsof0.025,0.050,and0.075g/kg/mIn,respectIvely.
24J
Fecoveryfrom
remIfentanIlInducedrespIratorydepressIonwasrapId,andmInuteventIlatIonreturnedto
baselIneby8mInutes(range,5to15mInutes)aftertheInfusIonwasstoppedforall
InfusIonrates.ncontrast,a50decreaseInmInuteventIlatIonproducedbya4hour
InfusIonofalfentanIlat0.5g/kg/mInrequIred61mInutes(range,5to90mInutes)to
returntobaselIne.
24J
navolunteerstudy,Classetal.
244
reportedthattheblood
remIfentanIlconcentratIonneededtodepressventIlatoryresponsetoInspIred8CD
2
by
50(EC
50
)was1.17ng/mL.8ouIllonetal.
245
reportedasImIlarEC
50
(0.92ng/mL)andalso
notedthatremIfentanIlconcentratIonsthatarewelltoleratedatsteadystatewIllproduce
clInIcallysIgnIfIcantrespIratorydepressIonwhenachIevedwIthbolusdosIng.ngeneral,
clInIcalcomparIsonsreportthatrespIratoryparameters(respIratoryrate,D
2
saturatIon,
andendtIdalCD
2
)recovermorerapIdlyafterremIfentanIlcomparedwIthotheropIoIds
gIvenInequIpotentdosage.
|aIntenanceofspontaneousrespIratIondurInggeneralanesthesIawIthremIfentanIland
volatIleagentsorpropofolmaynotbefeasIbleunlesslowdosesofremIfentanIlare
used.
246
ClInIcalexperIenceInspontaneouslybreathInghumansreceIvIngremIfentanIl
combInedwItheItherIsofluraneorpropofoldemonstratesrespIratorydepressIonIn10to
J5ofpatIentsreceIvIngremIfentanIlat0.025g/kg/mIn.tIncreasestonearly50In
patIentsreceIvIng0.05g/kg/mInandto90wIthremIfentanIl0.075g/kg/mIn.
247,248
A
sImIlarrateofrespIratorydepressIon(20)wIthneedforassIstedventIlatIonIsseenIn
pedIatrIcpatIentsreceIvIngremIfentanIl/propofolInfusIonsforgeneralanesthesIadurIng
bonemarrowaspIratIon.
249
AsdIscussedearlIer,remIfentanIlaloneorcombInedwIthlow
dosepropofolormIdazolamcanbeusedforconscIoussedatIonandtosupplementregIonal
orlocalanesthesIadurIngmonItoredanesthesIacare.ClInIcalreportsdescrIbIngthese
regImensreportrespIratorydepressIon(respIratoryrate8orSpD
2
90)In2toJ0of
patIents,butInallcases,recoveryfromrespIratorydepressIonwIthremIfentanIlIsmore
rapIdthanotheragents.
2J1,2J2,2JJ,2J4
AswIthotheropIoIds,hIgherratesofrespIratory
depressIonareseenwhenpropofolIscombInedwIthremIfentanIl(15to50ofpatIents),
andcarefulmonItorIngandtItratIonarerequIredtomInImIzethIssIdeeffect.
Hemodynamic Effects
nhealthyvolunteers,remIfentanIlInbolusdoses1.0g/kgproducebrIefIncreasesIn
systolIcbloodpressure(5to20torr)andheartrate(10to25beats/mIn).
207
npatIents
anesthetIzedwIthIsofluraneand66N
2
DInoxygen,remIfentanIl(upto5g/kg)produces
dosedependentdecreasesInsystolIcbloodpressureandheartrate.Theseeffectsare
attenuatedbypremedIcatIonwIthglycopyrrolate0.Jto0.4mgandarereadIlyreversed
wIthephedrIneorphenylephrIne.
248
Sebeletal.
250
evaluatedhemodynamIcresponsesIn
patIentsreceIvIngremIfentanIl2toJ0g/kg(escalatIngdoses)gIvendurInggeneral
anesthesIaandfoundthatsystolIcheartratedecreasedmorethan20fordoses2g/kg.
ThesehemodynamIceffectswerenotmedIatedbyhIstamInerelease.ClInIcalreportsof
experIencewIthpatIentsreceIvIngopIoIdbasedanesthetIcshavecharacterIzed
hemodynamIcchangesdurIngbalancedanesthesIawIthremIfentanIlcombInedwIth
IsofluraneN
2
D/D
2
orpropofol.0urIngacomparIsonofremIfentanIlversusalfentanIl
basedT7A,a20dropInmeanarterIalpressure,wIthmInImalchangeInheartrate,was
notedafterInductIon,wIthJ5to50ofpatIentsexperIencIngatleastoneepIsodeofmean
arterIalpressure70mmHg.
20J
0ecreasesInbloodpressureweretransIentandeasIly
treatedwIthfluIdsanddownwardtItratIonofpropofol.nacomparIsonofremIfentanIl
andfentanylbasedgeneralanesthetIcsIn2,400patIents(80AmerIcanSocIetyof
AnesthesIologygradeand),hypotensIon(systolIcbloodpressure80ortreated
pharmacologIcally)occurredIn12ofpatIentsreceIvIngremIfentanIlcomparedwIth4
wIthfentanyl.
221
8radycardIawaslesscommon,wIth2and1ofpatIentsInthe
remIfentanIlandfentanylgroups,respectIvely.
CreaterhemodynamIcchangescanbeseenInpatIentswIthcoronarydIsease.na
comparIsonofhIghdoseremIfentanIl(2g/kg/mIn)andremIfentanIl0.5g/kg/mInplus
propofoltargetedto2g/mLplasmaconcentratIon,bothtechnIquesproducedsImIlar
changes:J0dropInmeanarterIalpressureand25dropIncardIacIndex.|yocardIal
bloodflowandoxygenconsumptIondecreasedbyaboutJ0and40,respectIvely.|ore
moderatehemodynamIcchangeswerereportedwIthlowerdoses(remIfentanIlTC4to8
ng/mLandpropofol1.2ng/mL).
229
HeartrateandcardIacIndexdropped20and6,
respectIvely,andnohypotensIonwasseen.nanearlyclInIcalreport,0eSouzaetal.
251
reportedaserIesofsevere
P.487
bradycardIa(heartrateJ0beats/mIn)andhypotensIon(systolIcbloodpressure80mm
Hg)InsIxpatIentswhoreceIvedarapIdInjectIonofremIfentanIl1g/kgfollowedbya
contInuousInfusIonat0.1to0.2g/kg/mInonInductIonforcardIacsurgery.HypotensIon
waseffectIvelytreatedbyephedrIneandtemporarydIscontInuatIonofremIfentanIl.These
severeeffectscanoftenbeavoIdedbysloweradmInIstratIon(60secondsorlonger)ofthe
loadIngdose,assmallerbolusdosesofremIfentanIl(0.Jto0.5g/kg)areapparentlynot
assocIatedwIthseverebradycardIaandhypotensIon.
Gastrointestinal Effects
LIkeotheragonIsts,remIfentanIlcancausenauseaandvomItIng,buttheoccurrenceof
theseadverseeffectsIsInfluencedtoalargeextentbysurgery,adjuvantanesthetIc
agents,andantIemetIcprophylaxIs.navolunteerstudy,hIghInfusIonrates(1to8
g/kg/mIn)producednauseaIn70ofsubjects,
2J6
butmuchlowerdosesaretypIcallyused
forgeneralanesthesIa.PhIlIpetal.
202
comparednauseaandvomItIngatmultIpletIme
poIntsInoutpatIentadultsforlaparoscopIcsurgerywhoreceIvedremIfentanIloralfentanIl
combInedwIthN
2
Dandpropofol.Dverall,theIncIdenceofnauseawas44and5Jfor
remIfentanIlandalfentanIl,respectIvely;theIncIdenceofvomItIngwas21and29for
remIfentanIlandalfentanIl,respectIvely.noutpatIentswIthsImIlaropIoIdInfusIons
combInedwIth0.8Isoflurane,nauseaoccurredIn18and20ofpatIentswIthremIfentanIl
andalfentanIl,respectIvely.
252
ncontrast,areportsummarIzIngadverseeventsIn2,400
patIentswhoreceIvedremIfentanIl(range,0.25to2g/kg/mIn)orfentanylwIthIsoflurane
orpropofolforavarIetyofsurgerIes,nauseaandvomItIngwererare.
221
DtherclInIcal
comparIsonsofremIfentanIlpluspropofoltoalfentanIlpluspropofolreportedverylow
IncIdenceofnauseaandvomItIng(6to22).
42,25J
napedIatrIcstudy,theaddItIonof
remIfentanIl0.2g/kg/mIntodesfluraneanesthesIaproducednoIncreaseInnauseaor
vomItIngafterdentalsurgery;nauseaandvomItIngoccurredIn5ofpatIentswho
receIvedremIfentanIl.ForstrabIsmussurgeryInchIldren,vomItIngoccurredwIthequal
frequency(26toJ1)wIthremIfentanIl,alfentanIl,Isoflurane,andpropofol.
254
Thus,
remIfentanIlappearstoproducedosedependentnauseaandvomItIngsImIlartoother
shortactIngagonIstopIoIdsthatcanbeattenuatedbypropofol.Takentogether,
remIfentanIlstudIesconfIrmthewIdevarIabIlItyInoccurrenceofnauseaandvomItIngIn
theclInIcalsettIng.
LIkeotheropIoIds,remIfentanIldelaysgastrIcemptyIng
255
andbIlIarydraInage.
256
As
expected,bIlIaryeffectsresolvemorequIcklythanbIlIarydraInagedelayfrommorphIneof
meperIdIne.
Other Side Effects
PostoperatIveshIverIngoccurredInabout40ofpatIentsundergoIngotorhInolaryngeal
surgerydespIteactIvewarmIngandIndependentoftemperature,
48
whIleanotherstudy
notedshIverIngInonly10ofoutpatIents.
252
nbothofthesestudIes,shIverIngwasless
commonwIthalfentanIl.DnepedIatrIcInvestIgatIonreportedprurItusIn12ofpatIents.
254
nvolunteers,remIfentanIlproducedconcentratIonrelatedsubjectIveandpsychomotor
sIdeeffectstypIcalofopIoIds.
208
SubjectIvesIdeeffectsInducedbyremIfentanIlIncluded
drymouth,ItchIng,flushIng,sweatIng,andturnIngofthestomach.FemIfentanIlalso
ImpaIredperformanceofpsychomotortestsandcausedmIosIsandrespIratorydepressIon.
SomeoftheseeffectslastedanhourormoreafterremIfentanIladmInIstratIonwas
stopped.
ThekeystructuralfeatureofremIfentanIlIsanesterfunctIonalgroupthatIssusceptIbleto
hydrolysIsbybloodandtIssuenonspecIfIcesterasesandresultsInveryrapIdmetabolIsm.
8ecausebutyrocholInesterase(pseudocholInesterase)doesnotappeartometabolIze
remIfentanIl,plasmacholInesterasedefIcIencyandantIcholInergIcadmInIstratIondonot
affectremIfentanIlclearance.
255
UnlIkeotheropIoIds,redIstrIbutIonplaysonlyamInor
roleInremIfentanIlclearance.ThIspropertyreducesItspharmacokInetIcvarIabIlIty
comparedwIthotheropIoIds.FemIfentanIlhasasmallvolumeofdIstrIbutIon,
approxImately0.Jto0.5L/kg,
257,258
orabout25LInanaverageadult.
259
FemIfentanIl's
clearance,Jto5L/mIn,IsapproxImatelyJto4tImesnormalhepatIcbloodflow.
192,240,241
8othtwoandthreecompartmentmodelshavebeenusedtodescrIbetheplasma
concentratIondecaycurveofremIfentanIl.ArapIddIstrIbutIonphaseof0.9mInutesanda
veryshorttermInalelImInatIonhalflIfeof9.5mInutescharacterIzedatwocompartment
modelInadults.
207
npedIatrIcs,elImInatIonhalflIfeIsaboutJ.5to6mInutes.
260
nthe
threecompartmentmodel,rapIdandslowdIstrIbutIonhalftImeswere0.4to0.9and2to6
mInutes,respectIvely,andtheelImInatIonhalftImewasabout10toJ0mInutes.
2J7,258
Asforotherfentanylcongeners,genderdoesnotaffectremIfentanIlpharmacokInetIcs,but
advancedageIsassocIatedwIthadecreaseInclearanceandvolumeofdIstrIbutIon,as
wellasanapparentIncreaseInpotency.
261
FemIfentanIlpharmacokInetIcsaresImIlarIn
lean(wIthIn20IdealbodyweIght)andobese(atleast80overIdealbodyweIght)
patIents,IndIcatIngthatremIfentanIldosIngshouldbebasedonleanbodymass.
262
AlthoughpharmacokInetIcparametersofremIfentanIlareunchangedInpatIentswIth
severelIverdIsease
26J
orrenalfaIlure,
264
patIentswIthhepatIcdIseaseappeartobemore
sensItIvetoremIfentanIlInducedrespIratorydepressIon.
Dosage and Administration of Remifentanil
8ecauseofItsextremelyshortduratIonofactIon,remIfentanIlIsbestadmInIsteredasa
contInuousInfusIon,althoughadmInIstratIonasrepeatedbolusdosescanalsobeeffectIve
(Table194).DutsIdetheUnItedStates,remIfentanIlIsoftenadmInIsteredbyTC,apump
systemdesIgnedtoInfusethedrugbasedonpopulatIonkInetIcstoachIevedesIredtarget
plasmaconcentratIons.TheoretIcally,thIsmakessenseespecIallyforremIfentanIlbecause
ItspharmacodynamIceffectstrackplasmaconcentratIonsveryclosely.However,two
studIeshavefoundthatsImplemanuallycontrolledInfusIonIsaseffectIve
265,266
andIs
moreeconomIcalthancomputercontrolledInfusIons.
NumerousreportshavedescrIbeddosIngregImensforremIfentanIlaloneorIncombInatIon
wIth7andInhaledagentsforInductIonandmaIntenanceofgeneralanesthesIa,andasa
componentofsedatIonandmonItoredanesthesIacare.
Induction Dosage, Intubation, Laryngeal Mask Airway
Placement
AsdescrIbedearlIer,remIfentanIlalonehasnotbeenfoundtobeasatIsfactorysIngle
agentforInductIonofanesthesIabecauseofunrelIabIlItyInlossofconscIousnessand
sIgnIfIcantmusclerIgIdIty.
217
However,InductIonofanesthesIawIthhIghdose
remIfentanIl,4to5g/kg,oranInfusIonof2g/kg/mInhasbeenreported.
228
tIs
Importanttonotethatbolusdosesof2g/kgcandroparterIalpressure20toJ0,whIle
hemodynamIcchangesIncardIacpatIentsreceIvInghIghdoseInfusIonaresImIlarto
remIfentanIlpluspropofol.
267
CombInedwIthapotentInhalatIonagent,aloadIngdoseof1
g/kggIvenslowly(over60seconds)canprovIde
P.488
adequateIntubatIngcondItIonswIthhemodynamIcstabIlIty.8yfarthemostcommonly
reportedremIfentanIlbasedregImenforanesthetIcInductIonandlaryngoscopyconsIstsof
remIfentanIl0.5to1g/kggIvenover60secondspluspropofol1to2mg/kg,followedby
remIfentanIlInfusIonof0.25to0.5g/kg/mIn.
221,222,268,269
ThIsmaybegIvenwIthor
wIthoutamIdazolam1to2mg7premedIcatIon.SImIlarregImensarerecommendedfor
pedIatrIcpatIents,wIthsubstItutIonoforalmIdazolampremedIcatIon0.5mg/kg.nthe
elderly,dosereductIonIsIndIcated,wIthremIfentanIl0.05g/kgover60secondsplus
propofoltItratedtolossofconscIousnessIn10mgIncrements,followedbyremIfentanIl
InfusIonof0.1g/kg/mIn.fTCIsusedforInductIonofanesthesIa,anInItIalremIfentanIl
targetof5to7ng/mLaccompanIedby0.5to1|ACInhaledanesthetIcorpropofolTCof2
ng/mLIsrecommended.
219,259
Maintenance of General Anesthesia
ncombInatIonwIth70N
2
DInD
2
,remIfentanIl0.6g/kg/mInIsgenerallyadequate,but
atleastonestudyreportedawIderangeofInfusIonrates(0.025to2g/kg/mIn).
270
A
sImIlarInfusIonrateforremIfentanIlwIthN
2
DIsrecommendedforpedIatrIcpatIents.A
lowerInfusIonrate(0.2to0.25g/kg/mIn)IsneededwhenremIfentanIlIscombInedwIth
sevoflurane(1to2),
22J
desflurane(JtoJ.6),
224,271
orIsoflurane(0.2to0.8).
221,222,252
ForT7A,maIntenanceInfusIonratesforremIfentanIlandpropofolare0.25to0.5
g/kg/mInand75to100g/kg/mIn,respectIvely.
20J,221,268,272,27J
fN
2
DIsadded,
remIfentanIlInfusIonratesaslowas0.125g/kg/mInandpropofolInfusIonof50to75
g/kg/mIncanbeused.
272
ForelderlypatIentsorthosewIthcardIacdIsease,areductIonIn
propofolbyabout25Isrecommended.AlthoughchIldrenrequIrehIgherremIfentanIldoses
toblockresponsestoskInIncIsIon,effectIveInfusIonratesforanesthetIcmaIntenanceare
sImIlartothoseofadults,wIthremIfentanIlat0.25g/kg/mInandpropofolabout100
g/kg/mIn.ForhIghdoseopIoIdanesthesIaforcardIacsurgery,theremIfentanIlInfusIonIs
maIntaInedat1toJg/kg/mInandshouldbeadjusteddownwardforhypothermIa,as
dIscussedearlIer.
228
AddIngalowdosepropofolInfusIonof50g/kg/mIntothIshIgh
InfusIonrateeffectIvelysuppressedresponsestoskInIncIsIon,sternotomy,andaortIc
cannulatIon.
274
fTCIsused,atargetrangeforremIfentanIlIs4to10ng/mLforbalancedanesthesIaand
T7A,andastartIngrateof25toJ0ng/mLIsrecommendedforhIghdoseopIoId
anesthesIa.
228,259
AdIsadvantageofremIfentanIl,relatedtoItsshortduratIonofactIon,IsthatpatIentsmay
experIencesubstantIalpaInonemergencefromanesthesIa.Thus,Ifmoderatetosevere
postoperatIvepaInIsantIcIpated,contInuIngtheremIfentanIlInfusIonbetween0.05and
0.15g/kg/mInensuresadequateanalgesIaInmostpatIents.
209
Theuseoflocaland
regIonalanesthetIctechnIquesIsalsoeffectIve.WhenonlymIldpostoperatIvepaInIs
antIcIpated,IntraoperatIveadmInIstratIonofanonsteroIdalantIInflammatorydrugJ0to
60mInutesbeforetheendofsurgerymayprovIdeeffectIveanalgesIawIthoutaddItIonal
opIoIds.
FemIfentanIlcanalsobeusedforconscIoussedatIon/analgesIaandasanadjunctfor
sedatIonoranalgesIadurIngregIonalanesthesIa,orforblockplacement,aspartof
monItoredanesthesIacare.WhenlocalorregIonalanesthesIaIsnotusedandthe
procedureIsexpectedtobepaInful,remIfentanIlandpropofolcanbebenefIcIal.0urIng
colonoscopy,acontInuousremIfentanIlInfusIonof0.2to0.25g/kg/mIn,supplemented
wIthsmall(10mg)dosesofpropofolprovIdedgoodanalgesIabutmIldrespIratory
depressIonwascommon.
2J2
nanotherclInIcalevaluatIon,patIentshavIngextracorporeal
shockwavelIthotrIpsyreceIvedlowdosepropofol(50g/kg/mIn)aswellasremIfentanIl.
PatIentswhoreceIvedlowdose(12.5to25g)IntermIttentbolusInjectIonofremIfentanIl
wIthorwIthoutInfusIonat0.05g/kg/mInreportedbetteranalgesIathancontInuous
InfusIonof0.1g/kg/mInalone.
2J1
FemIfentanIl1g/kgwIthorwIthoutasubsequent
InfusIonof0.2g/kg/mInadmInIstered90secondsprIortoplacementofophthalmologIc
blockresultedInexcellentanalgesIa,
275
but14ofpatIentswhoreceIvedanInfusIon
experIencedrespIratorydepressIon.
WhenusedasanadjuncttolocalorregIonalanesthesIa,amuchlowermaIntenance
InfusIonrate,0.05to0.1g/kg/mIn,provIdesadequatesedatIonandanalgesIa.
2J4,2J5
FInally,thedoserequIrementofremIfentanIlforsedatIon/analgesIaIsreduced
approxImately50whencombInedwIthmIdazolamorpropofol.When1to2mgof
mIdazolampremedIcatIonIsgIven,0.01to0.07g/kg/mInremIfentanIlprovIdesgood
sedatIon/analgesIaforproceduresperformedunderlocalorregIonalanesthesIa.
2JJ,2J4
Partial Agonists and Mixed AgonistAntagonists
ThepartIalagonIstandmIxedagonIstantagonIstopIoIdsaresynthetIcorsemIsynthetIc
compoundsthatarestructurallyrelatedtomorphIne.TheyarecharacterIzedbybIndIng
actIvItyatmultIpleopIoIdreceptorsandtheIrdIfferentIaleffects(agonIst,partIalagonIst,
orantagonIst)ateachreceptortype.TheclInIcaleffectofapartIalagonIstattheopIoId
receptorIscomplex(FIg.1911).AdmInIsteredalone,apartIalagonIsthasaflatterdose
responsecurveandalowermaxImaleffectthanafullagonIst(seeFIg.191andthe
lowermostcurveInFIg.1911).CombInedwIthalowconcentratIon(comparethecurve
IndIcatedby[A]=0.25InFIg.1911)ofafullagonIst,
P.489
theeffectsofthepartIalagonIstareaddItIveuptothemaxImumeffectofthepartIal
agonIst.CombInedwIthIncreasIngconcentratIons([A]=0.67to256)offullagonIst,the
partIalagonIstwIllactasanantagonIst.ThesedrugsmedIatetheIrclInIcaleffectsvIa
andopIoIdreceptors,assummarIzedInTable195.TheclassIfIcatIonschemepresented
maychangeasourunderstandIngofthesedrugsandofopIoIdreceptorscontInuestogrow.
8owdle
276
extensIvelyrevIewedthepharmacologyandclInIcalusesoftheseandother
drugsInthIsclass.DnlynalbuphIne,butorphanol,andbuprenorphIneareconsIderedInthIs
chapter.
Table 19-5 Actions of Nalbuphine, Butorphanol, and Buprenorphine at
Opioid Receptors
a
DRUG RECEPTOR RECEPTOR
NalbuphIne PartIalagonIst PartIalagonIst
8utorphanol PartIalagonIst PartIalagonIst
8uprenorphIne PartIalagonIst
a
AlthoughnalbuphIneandbutorphanolhavebeenreportedtobeantagonIstsatthe
opIoIdreceptor,theydocauserespIratorydepressIon,whIchIsnotafunctIonof
agonIsts.Thus,theyappeartohaveatleastpartIalagonIstactIvItyatthe
opIoIdreceptor.
Adaptedfrom8owdleTA:PartIalagonIstandagonIstantagonIstopIoIds:8asIc
pharmacologyandclInIcalapplIcatIons.AnesthPharmacolFev199J;1:1J5.
Figure 19-11.HypothetIcallogdoseeffectcurvesforthecombInatIonofapartIal
agonIst,8(IntrInsIceffIcacyof0.4),wItharangeofconcentratIonsofafullagonIst,A.
TheobservedeffectofthecombInatIonofAand8IsexpressedasafractIonofthe
maxImaleffectofthefullagonIst.AstheconcentratIonofthepartIalagonIst
Increases,theeffectofthecombInatIonconvergesonthemaxImumeffectofthe
partIalagonIst.WhenaddedtoalowconcentratIon(e.g.,[A]=0.25)ofagonIst,the
partIalagonIstIncreasestheresponse;butwhenaddedtoalargeconcentratIonofthe
agonIst,theresponsedecreasesthatIs,8actslIkeanantagonIst.(|odIfIedwIth
permIssIonfrom8owdleTA:PartIalagonIstandagonIstantagonIstopIoIds:8asIc
pharmacologyandclInIcalapplIcatIons.AnaesthPharmacolFev199J;1:1J5.)
ThemajorroleoftheopIoIdagonIstantagonIstandpartIalagonIstdrugscontInuestobeIn
theprovIsIonofpostoperatIveanalgesIa,buttheyhavealsobeenusedforIntraoperatIve
sedatIon,asadjunctsdurInggeneralanesthesIa,andtoantagonIzesomeeffectsoffull
opIoIdagonIsts.
Nalbuphine
NalbuphIneIsaphenanthreneopIoIdderIvatIve.AlthoughoftenclassIfIedasaagonIst
andantagonIst,ItIsmoreaccuratelydescrIbedasapartIalagonIstatbothand
receptors.
276
WhIlestudIeshavenotbeendoneInhumans,|urphyandHug
25
reportedthat
a0.5mg/kgdosereducedenflurane|ACby8Indogs.However,IncreasIngthedose
eIghtfoldproducednofurtherreductIonInenflurane|AC.ThIsmodest|ACreductIon,
comparedwIth65formorphIne,suggestsnalbuphInemaynotbeausefuladjunctfor
generalanesthesIa.However,severalInvestIgatorshaveexamInedItseffectIvenessasa
componentofbalancedanesthesIaforcardIac
277
andlowerabdomInalsurgery.
25,278
CombInedwIthdIazepam0.4mg/kgand50N
2
DInoxygen,aloadIngdoseofJmg/kgwas
followedbyaddItIonaldosesof0.25mg/kgasneededthroughoutsurgery.NosIgnIfIcant
IncreasesInbloodpressure,stresshormones,orhIstamInewereseen,andemergencefrom
anesthesIawasuncomplIcated.
277
NalbuphIne0.2mg/kgwascomparedwIthmeperIdIne0.5
mg/kgasanadjuvanttogeneralanesthesIawIth1halothaneand70N
2
DInoxygenIn
spontaneouslybreathIngpatIentsundergoIngInguInalhernIarepaIr.
279
8othdrugsproduced
asImIlardegreeofrespIratorydepressIon,postoperatIveanalgesIa,andsIdeeffects.The
mostcommonsIdeeffectwasdrowsIness.nadoubleblIndcomparIsonwIthfentanylfor
gynecologIcsurgery,fentanylwasfoundtobetterattenuatehypertensIveresponsesto
IntubatIonandsurgIcalstImulatIon.
278
However,sIgnIfIcantrespIratorydepressIonwas
seenIn8ofJ0patIentswhoreceIvedfentanyl;4requIrednaloxone,comparedwIthno
respIratorydepressIonInthenalbuphInegroup.AnalgesIawassImIlarand,asInother
studIes,postoperatIvesedatIonwascommonInthenalbuphInegroup.
TherespIratorydepressIonproducedbynalbuphIne,mostlIkelymedIatedbyopIoId
receptors,hasaceIlIngeffectequIvalenttothatproducedby-0.4mg/kgmorphIne.
276
AnalgesIaIsmedIatedbybothandreceptors.8ecauseoftheseeffects,nalbuphInehas
beenusedtoantagonIzetherespIratorydepressanteffectsoffullagonIstswhIlestIll
provIdInganalgesIceffects.nadoubleblIndcomparIson,bothnalbuphIneandnaloxone
antagonIzedfentanylInducedpostoperatIverespIratorydepressIon,butpatIentswho
receIvednalbuphInehadlessreversalofanalgesIa.
280
NalbuphInecanalsoantagonIze
respIratorydepressIonfollowInghIghdose(100to120g/kg)fentanylforcardIac
surgery.
281
DnlyJof21patIentsexperIencedpaInafternalbuphIneadmInIstratIon,andthIs
wasadequatelytreatedwIthaddItIonalnalbuphIne.However,Inavolunteerstudy,
nalbuphIne0.21mg/kgdIdnotantagonIzetherespIratorydepressanteffectsof0.21mg/kg
morphIne.
282
WhIlenalbuphIneandotheragonIstantagonIstshaveceIlInganalgesIcand
respIratorydepressanteffects,theycanbeaseffectIveasfullagonIstsInprovIdIng
postoperatIveanalgesIa.NalbuphIne5to10mghasalsobeenusedtoantagonIzeprurItus
InducedbyepIduralandIntrathecalmorphIne.TheusualadultdoseofnalbuphIneIs10mg
asoftenaseveryJhours.tIsImportanttobeawarethatnalbuphInecanprecIpItate
wIthdrawalsymptomsInpatIentswhoarephysIcallydependentonopIoIds.
Butorphanol
8utorphanol,amorphInancongener,haspartIalagonIstactIvItyatandopIoId
receptors,sImIlartothoseofnalbuphIne.ComparedwIthnalbuphIneandsImIlardrugs,
however,butorphanolhasapronouncedsedatIveeffect,whIchIsprobablymedIatedby
receptors.nalaboratorystudyaswellasInclInIcaluseasapremedIcant,butorphanol
produceddosedependentsedatIoncomparabletothatofmIdazolam.
28J
LIkenalbuphIne,
butorphanoldecreasesenflurane|AC,Indogs,byamodestamount,11,at0.1mg/kg.
J0
ncreasIngthebutorphanoldose40folddoesnotproduceafurtherreductIon.However,
lIkenalbuphIne,butorphanolhasalsobeenreportedtobeaneffectIvecomponentof
balancedgeneralanesthesIa.CombInedwIthdIazepamandnItrousoxIde,butorphanoland
morphIneprovIdedequallysatIsfactoryanesthesIa.
276
CIvenalone,butorphanolproducesrespIratorydepressIonwIthaceIlIngeffectbelowthat
offullagonIsts.npostoperatIvepatIentsaparenteraldoseofJmgproducesrespIratory
depressIonapproxImatelyequaltothatof10mgmorphIne.naclInIcalstudyexamInIngIts
effectIvenessInreversIngfentanylInducedrespIratorydepressIon,
284
P.490
patIentsanesthetIzedwIthIsoflurane,nItrousoxIde,andfentanyl5g/kgfollowedbyan
InfusIonofJg/kg/hrreceIvedthreesequentIaldosesofbutorphanol1mgat10to15
mInuteIntervals.AfterthefIrst1mgdose,respIratoryrateandventIlatoryresponseto
CD
2
Increased,whIleendtIdalCD
2
decreasedsIgnIfIcantly.FurtherprogressIvechanges
werenotsIgnIfIcantlydIfferentfromtheInItIalresponsetobutorphanolandanalgesIawas
notsIgnIfIcantlyaffectedIn21of22patIents.
ncontrasttomorphIne,fentanyl,andevenmeperIdIne,butorphanoldoesnotproduce
sIgnIfIcantelevatIonInIntrabIlIarypressure
8J
(FIg.196).8utorphanolhasalsobeen
effectIveInthetreatmentofpostoperatIveshIverIng,
88
butthemechanIsmforthIseffect
Isunknown.8utorphanol'sagonIstactIvItyatthereceptorproducesanantIprurItIceffect
thatIsblockedbyaselectIveantagonIst.
J5
Thus,butorphanolmaybeabletoreduce
morphIneInducedprurItuswIthoutcompletelyblockIngItsanalgesIceffect.Dntheother
hand,ItIsunknownwhetherIncreasedsedatIon,whIchIspossIblewIthsuch
coadmInIstratIon,wouldoutweIghanantIprurItIcbenefIt.
8utorphanolIsIndIcatedforuseasasedatIveandIntreatmentofmoderatepostoperatIve
paIn.PrelImInaryclInIcalexperIencesuggeststhatbutorphanoladmInIsteredaspatIent
controlledanalgesIaIsassocIatedwIthalowerIncIdenceofopIoIdInducedIleuscompared
wIthselectIveopIoIds(P.J.0unbar,personalcommunIcatIon,1996).Adoseaslowas0.5
mgcanprovIdeclInIcallyusefulsedatIon,whIlesIngleanalgesIcdosesrangefrom0.5to2
mg.8utorphanolhasalsobeenadmInIsteredepIdurallyandtransnasally.
Buprenorphine
8uprenorphIneIsahIghlylIpophIlIcthebaInederIvatIve,andIsapartIalopIoIdagonIst.
AtsmalltomoderatedosesItIs25to50tImesmorepotentthanmorphIne.
1
UnlIke
nalbuphIneandbutorphanol,buprenorphInedoesnotappeartohaveagonIstactIvItyatthe
opIoIdreceptor(Table195).
276
AnotherunIquecharacterIstIcofbuprenorphIneIsItsslow
dIssocIatIonfromreceptors,whIchcanleadtoprolongedeffectsnoteasIlyantagonIzed
bynaloxone.8uprenorphInealsoappearstohaveanunusualbellshapeddoseresponse
curvesuchthat,atveryhIghdoses,ItproducesprogressIvelylessanalgesIa.
276
naclInIcal
study,patIentswhoreceIved10or20g/kgbuprenorphInedurIngsurgerywerepaInfree
postoperatIvely,buthalfofthepatIentswhoreceIvedJ0or40g/kghadsIgnIfIcant
postoperatIvepaIn.
285
ThIsobservatIonIsconsIstentwIthbuprenorphIne'sbellshapeddose
effectcurve,andpatIentswhoreceIvedveryhIghbuprenorphInedosesprobablyhad
plasmadrugconcentratIonsIntherangeatwhIchdeclInInganalgesIaIsseen.
8uprenorphInealsoappearstohaveaceIlIngeffecttoItsrespIratorydepressantdose
responsecurve.However,althoughbuprenorphIneInducedrespIratorydepressIoncanbe
preventedbyprIornaloxoneadmInIstratIon,ItIsnoteasIlyreversedbynaloxoneoncethe
effectshavebeenproduced.
1
Adoseof0.JmgbuprenorphInereducesCD
2
responsIveness
toabout50ofcontrolvalues.
286
Largedosesofnaloxone(5to10mg)wererequIredto
antagonIzebuprenorphInerespIratorydepressIonInvolunteers,whIle1mgdoseswerenot
effectIve.naddItIon,themaxImumantagonIsteffectdIdnotoccuruntIlJhoursafter
naloxoneadmInIstratIon,anobservatIonconsIstentwIthbuprenorphIne'sslowdIssocIatIon
fromreceptors.8uprenorphInehasbeencomparedwIthnaloxoneInItsabIlItyto
antagonIzefentanylInducedrespIratorydepressIon,andappearstoIncreaserespIratory
ratewIthoutantagonIzInganalgesIceffectsInslowlyadmInIstereddosesupto0.5mg.
287
8uprenorphInecanbeeffectIveIntreatmentofmoderatetoseverepaIn.tsonsetcanbe
slow,butanalgesIcduratIoncanbe6hours.AsIngledoseof0.Jto0.4mgappearsto
produceanalgesIaequIvalentto10mgmorphIne.
1
Opioid Antagonists (Naloxone and Naltrexone)
UndernormalcondItIons,opIoIdantagonIstsproducefeweffects.TheyarecompetItIve
InhIbItorsoftheopIoIdagonIsts,sotheeffectprofIledependsonthetypeanddoseof
agonIstadmInIsteredaswellasthedegreetowhIchphysIcaldependenceontheopIoId
agonIsthasdeveloped.ThemostwIdelyusedopIoIdantagonIstIsnaloxone,whIchIs
structurallyrelatedtomorphIneandoxymorphone,andIsapureantagonIstat,,and
opIoIdreceptors.
1
NaltrexoneIsalongactIngoralagent,whIchalsohasrelatIvelypure
antagonIstactIvIty.nsomecIrcumstances,naloxonecanantagonIzeeffectsthatappearto
bemedIatedbyendogenousopIoIds.Forexample,naloxonecanreversestressanalgesIa
InanImalsandman,ItcanantagonIzeanalgesIaproducedbylowfrequencystImulatIon
wIthacupunctureneedles,andItcanalsoreverseanalgesIaproducedbyplacebo
medIcatIons.
1
nclInIcalanesthesIapractIce,naloxoneIsadmInIsteredtoantagonIzeopIoIdInduced
respIratorydepressIonandsedatIon.8ecauseopIoIdantagonIstswIllreverseallopIoId
effects,IncludInganalgesIa,naloxoneshouldbecarefullytItratedtoavoIdproducIng
sudden,severepaInInpostoperatIvepatIents.Sudden,completeantagonIsmofopIoId
effectswIthnaloxonehasbeenreportedtocauseseverehypertensIon,tachycardIa,
ventrIculardysrhythmIas,andacute,sometImesfatal,pulmonaryedema.
288
Naloxone
InducedpulmonaryedemacanoccurevenInhealthyyoungpatIentswhohavereceIved
relatIvelysmalldoses(80to500g)ofnaloxone.
289,290
ThemechanIsmforthIs
phenomenonIsthoughttobecentrallymedIatedcatecholamInerelease,whIchcauses
acutepulmonaryhypertensIon.8ecausemostpatIentswIthopIoIdInducedrespIratory
depressIonwIlloftenbreatheoncommand,ItIsImportanttostImulatethemInaddItIonto
admInIsterIngcarefullytItratednaloxonedosesIntheImmedIatepostoperatIveperIod.tIs
alsoessentIaltomonItorvItalsIgnsandoxygenatIoncloselyafternaloxoneIsadmInIstered
todetectoccurrenceofanyofthesepotentIallyserIouscomplIcatIons.
NaloxonewIllprecIpItateopIoIdwIthdrawalsymptomsInopIoIddependentIndIvIduals.
ClInIcIanstendtobeawareofthIsrIskwhentreatIngpatIentswIthknownopIoIdaddIctIon,
butItIsImportanttoconsIderthepotentIalforopIoIdwIthdrawalsyndromewhentreatIng
nonaddIctswhouseopIoIdschronIcally,suchascancerpatIentsandsevereburnand
traumapatIentswIthprotractedrecoverycourses.
NaloxonehasaveryfastonsetofactIon,andthusIseasIlytItrated.Peakeffectsoccur
wIthIn1to2mInutes,andduratIonIsdosedependent,buttotaldosesof0.4to0.8mg
generallylast1to4hours.
1
SuggestedIncrementaldosesfor7tItratIonare20to40g
gIveneveryfewmInutesuntIlthepatIent'sventIlatIonImproves,butanalgesIaIsnot
completelyreversed.8ecausenaloxonehasashortduratIonofactIon,respIratory
depressIonmayrecurIflargedosesand/orlongactIngopIoIdagonIstshavebeen
admInIstered.WhenprolongedventIlatorydepressIonIsantIcIpated,anInItIalloadIngdose
followedbyanaloxoneInfusIoncanbeused.nfusIonratesbetweenJand10g/hrhave
beeneffectIveInantagonIzIngrespIratorydepressIonfromsystemIcaswellasepIdural
opIoIds.
291
P.491
WhIleperIpherallyactIngantagonIstsareundergoIngprelImInarytrIalsInpreventIonof
treatmentofopIoIdmedIatedgastroIntestInaldysfunctIon,
54
theyarenotyetavaIlablefor
clInIcaluse.
Use of Opioids in Clinical Anesthesia
DpIoIdsareusedaloneorIncombInatIonwIthotheragents,suchassedatIvesor
antIcholInergIcagents,aspremedIcatIons.ForthIspurpose,longeractIngopIoIdssuchas
morphIneareadmInIsteredassIngledosesthataregenerallywIthIntheanalgesIcrange.
ThegoalofopIoIdpremedIcatIonIstoprovIdemoderatesedatIon,anxIolysIs,andanalgesIa
whIlemaIntaInInghemodynamIcstabIlIty.PotentIalrIsksofopIoIdpremedIcatIonInclude
oversedatIon,respIratorydepressIon,andnauseaandvomItIng.ForInductIonof
anesthesIa,opIoIdsareoftenusedtobluntorpreventthehemodynamIcresponsesto
trachealIntubatIon.DpIoIdswIthrapIdonsetofactIon,suchasfentanylandIts
derIvatIves,areapproprIateforthIsuse.
ntraoperatIvely,opIoIdsareadmInIsteredascomponentsofbalancedanesthesIa,oralone
InhIghdoseopIoIdanesthesIa.0urIngmaIntenanceofgeneralanesthesIa,opIoIddosageIs
tItratedtothedesIredeffectbasedonthesurgIcalstImulusaswellasIndIvIdualpatIent
characterIstIcs,suchasage,volumestatus,neurologIcstatus,lIverdysfunctIon,orother
systemIcdIseasestates.PlasmaopIoIdconcentratIonsrequIredtoblunthemodynamIc
responsestolaryngoscopy,trachealIntubatIon,andvarIoussurgIcalstImulI,aswellas
plasmaopIoIdconcentratIonassocIatedwIthawakenIngfromanesthesIa,havebeen
determInedforseveralopIoIds.TItratIontoachIevetheseplasmaconcentratIons(Table
19J),whIchreflectbraIn(effectsIte)concentratIons,canbeaccomplIshedby
admInIsterIngrepeatedsmallbolusdosesorbymanualortargetcontrolledInfusIon.
FentanylandItsderIvatIvessufentanIlandalfentanIlaretheopIoIdsmostwIdelyusedas
supplementstogeneralanesthesIa;remIfentanIlIsausefulalternatIvewhenultrashort
duratIonIsdesIrable.AlloftheseopIoIdsaremoreeasIlytItratedthanmorphInebecause
oftheIrrapIdonsetofactIon.However,Shaferand7arvel
15
haveemphasIzedthatmakIng
aratIonalchoIceamongtheseopIoIdsrequIresanunderstandIngoftherelatIonshIps
betweentheIrpharmacokInetIcsandpharmacodynamIcs.Theyhaveusedelegantcomputer
modelstosImulatetherateofdecreaseInplasmaandeffectsIte(braIn)concentratIons
aftervarIousadmInIstratIonmethods,IncludIngbolusdoses,brIefInfusIon,andprolonged
InfusIon.0ecreasesIneffectsIteconcentratIonwIlldetermInetImetorecoveryfrom
varIousopIoIdeffects.ComparablesImulatIonshavealsobeendonefortheneweropIoId
remIfentanIl.
218
mportantpharmacokInetIcdIfferencesamongtheseopIoIdsInclude
volumesofdIstrIbutIonandIntercompartmental(dIstrIbutIonal)andcentral(elImInatIon)
clearances.AsmallerdIstrIbutIonvolumetendstoshortenrecoverytIme,andareductIon
InclearancetendstoIncreaserecoverytIme.
15
ThemajorpharmacodynamIcdIfferences
amongtheseopIoIdsarepotencyandtheequIlIbratIontImesbetweentheplasmaandthe
sIteofdrugeffect.EquIlIbratIonhalftImesbetweenplasmaandeffectsIteare5to6
mInutesforfentanylandsufentanIland1.Jto1.5mInutesforalfentanIland
remIfentanIl.
15,207
ComputersImulatIonsdemonstratethatsImplycomparIngelImInatIon
halflIveswIllnotpredIcttherelatIverateofdeclIneIndrugconcentratIonattheeffect
sIteaftereItherbolusdosesorcontInuousInfusIonoffentanyl,sufentanIl,andalfentanIl.
TherateofrecoveryafteracontInuousInfusIonwIlldependontheduratIonoftheInfusIon
aswellasthemagnItudeofdeclInethatIsrequIred.FIgure1912demonstrateshowthe
tImesrequIredfor20,50,and80decrementsIneffectsIte(I.e.,braIn)concentratIons
varywItheachopIoIddependIngonInfusIonduratIon.fonlya20dropIneffectsIte
concentratIonIsrequIred(upperpanel),recoveryfromallthreeopIoIdswIllberapId,
althoughrecoverytImeIncreasesforfentanylafterJhoursofdrugInfusIon.However,Ifa
50decreaseIsrequIred,recoveryfromsufentanIlwIllbefastestforInfusIons6to8hours
InduratIon,butmorerapIdforalfentanIlIfInfusIonsarecontInuedfor8hours.
Figure 19-12.Fecoverycurvesforfentanyl,sufentanIl,andalfentanIlshowIngthe
tImerequIredfordecreasesof20(A),50(B),and80(C)frommaIntaIned
IntraoperatIveeffectsIte(braIn)concentratIonsaftertermInatIonoftheInfusIon.
(FeprIntedwIthpermIssIonfromShaferSL,7arvelJF:PharmacokInetIcs,
pharmacodynamIcs,andratIonalopIoIdselectIon.AnesthesIology1991;74:5J.)
Context-Sensitive Half-Time
Hughesetal.
16
expandedtheconceptsofShaferand7arvel
15
todefInetherelatIve
contrIbutIonsofdIstrIbutIoncompartmentstocentralcompartment(plasma)drug
dIstrIbutIon.TheserelatIvecontrIbutIonsvaryaccordIngtoInfusIonduratIon.Hughesetal.
devIsedtheconceptofcontextsensItIve
P.492
halftIme,whIchIsdefInedasthetImerequIredforthedrugconcentratIonInthecentral
compartmenttodecreaseby50,anddemonstratedhowthIshalftImechangesasdrug
InfusIonduratIonIncreases.0urInganInfusIon,theperIpheral(fastandslow)
compartmentsbegIntofIllup.AftertheInfusIonIsstopped,drugwIllbeelImInated,but
wIllalsocontInuetoberedIstrIbutedaslongastheconcentratIonInaperIpheral
compartmentIslowerthanthatInthecentralcompartment.ThIsleadstoarapIddropIn
centralcompartmentdrugconcentratIon.Whencentralcompartment(plasma)
concentratIondropsbelowthatoftheperIpheralcompartment(s),thedIrectIonofdrug
redIstrIbutIonwIllreverseandwIllslowthedeclIneInplasmaconcentratIon.Thedegreeto
whIchredIstrIbutIonwIllaffecttherateofdrugelImInatIondependsontheratIoofthe
dIstrIbutIonaltoelImInatIontImeconstants.Thus,adrugthatcanrapIdlyredIstrIbutewIll
haveacorrespondInglylargercontrIbutIonfromtheperIpheralcompartment(s),and
plasmaconcentratIonwIlldropprogressIvelymoreslowlyasInfusIonduratIoncontInues.
FIgure191JIllustratesthecontextsensItIvehalftImesforfentanyl,alfentanIl,sufentanIl,
andremIfentanIl.ThIsmodelpredIctsthetImetoa50concentratIondecreaseInthe
plasma,whIchwIllreflect,butnotbeequalto,effectsIteconcentratIonsdepIctedIn
FIgure1912.
Figure 19-13.ContextsensItIvehalftImesforfentanyl,sufentanIl,alfentanIl,and
remIfentanIl.ThIscomputersImulatIondepIctsthetImenecessarytoachIevea50
reductIonInplasmaopIoIdconcentratIonasafunctIonofInfusIonduratIon.(FeprInted
wIthpermIssIonfromEganT0,LemmensHJ,FIsetP,etal:ThepharmacokInetIcsof
thenewshortactIngopIoIdremIfentanIl(C870848)Inhealthyadultmalevolunteers.
AnesthesIology199J;79:881.)
SometestIngofthesecomputermodelsInhumanshasbeendone.KapIlaetal.
292
comparedmodeledcontextsensItIvehalftImeswIthmeasureddecreasesIndrug
concentratIonanddrugeffect(respIratorydepressIon)InvolunteersreceIvIngremIfentanIl
andalfentanIl.AfterJhouropIoIdInfusIons,measuredwholebloodopIoIdconcentratIons
andrecoveryofventIlatorydrIvecorrespondedcloselytomodeledvaluesforbothdrugs.
AlthoughtheconceptofacontextsensItIvehalftImeappearstobeuseful,Hughesetal.
16
notedthatItIsunknownwhetheradecrementof50provIdesthemostclInIcallyuseful
descrIptIonoftherateofoffsetofopIoIdeffects.fonecloselytItratesInfusIonssothat
mInImumeffectIveconcentratIonsareachIeved,perhapsmuchsmallerdecrementswIllbe
necessary.Forexample,ItcanbeseenIntheupperpanelofFIgure1912thatIfonlya20
declIneIneffectsIteconcentratIonIsneeded,fentanyl,sufentanIl,andalfentanIl
concentratIonsalldroprapIdlyIftheInfusIonduratIonIs2hoursorless.ThIsrapId
resolutIonIsseenforsufentanIlandalfentanIlevenwIthprolonged(5to10hour)
admInIstratIonIfonlya20decrementIsrequIred.npractIce,ItIsrelatIvelyeasyto
admInIsterhIgherthannecessarydosesofopIoIds,partIcularlytomechanIcallyventIlated
patIents,becausehemodynamIcconsequencesaremInImal.TItratIngagaInstaquantIfIable
parameter,suchasmInuteventIlatIonInaspontaneouslybreathIngpatIent,mayallowa
tIghterdosetItratIon,butthIsmaynotbepractIcalformanysurgerIesforexample,those
requIrIngtheuseofmusclerelaxants.tdoesseemclear,however,thatsomecontext
sensItIveIndexIsmoreusefulthantheelImInatIonhalflIfe.UnderstandIngtheseconcepts
canbeusefulwhendecIdIngwhIchopIoIdtouse,aswellasInadaptIngguIdelInesfor
opIoIddosageandInfusIonratesdependIngontheduratIonofanesthesIa.
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279.D'ConnorSA,WIlkInson0J:AdoubleblIndstudyoftherespIratoryeffectsof
nalbuphInehydrochlorIdeInspontaneouslybreathInganesthetIzedpatIents.Anesth
Analg1988;67:J24.
280.8aIleyPL,ClarkNJ,PaceNL,etal:AntagonIsmofpostoperatIveopIoIdInduced
respIratorydepressIon:NalbuphInevs.naloxone.AnesthAnalg1987;66:1109
281.|oldenhauerCC,FoachCW,FInlayson0C,etal:NalbuphIneantagonIsmof
ventIlatorydepressIonfollowInghIghdosefentanylanesthesIa.AnesthesIology1985;62:
647
282.8aIleyPL,ClarkNJ,PaceNL,etal:FaIlureofnalbuphInetoantagonIzemorphIne:
AdoubleblIndcomparIsonwIthnaloxone.AnesthAnalg1986;65:605
P.497
28J.0ershwItz|,FosowCE,0I8IaseP|,etal:ComparIsonofthesedatIveeffectsof
butorphanolandmIdazolam.AnesthesIology1991;74:717
284.8owdleTA,CreIchenSL,8jurstromF,etal:8utorphanolImprovesCD
2
response
andventIlatIonafterfentanylanesthesIa.AnesthAnalg1987;66:517
285.PedersenJE:PerIoperatIvebuprenorphIne:0ohIghdosesshortenanalgesIa
postoperatIvely:ActaAnaesthesIolScand1986;J0:660
286.CalTL:NaloxonereversalofbuprenorphIneInducedrespIratorydepressIon.ClIn
PharmacolTher1989;45:66
287.8oysenK,HertelS,ChraemmerJorgansen8,etal:8uprenorphIneantagonIsmof
ventIlatorydepressIonfollowIngfentanylanaesthesIa.ActaAnesthesIolScand1988;J2:
490
288.PallaschTJ,CIllCJ:NaloxoneassocIatedmorbIdItyandmortalIty.DralSurgDral
|edDralPathol1981;52:602
289.PartrIdge8L,WardCF:PulmonaryedemafollowInglowdosenaloxone
admInIstratIon.AnesthesIology1986;65:709
290.Prough0S,FoyF,8umgarnerJ,etal:AcutepulmonaryedemaInhealthyteenagers
followIngconservatIvedosesofIntravenousnaloxone.AnesthesIology1984;60:485
291.FawalN,SchottU,0ahlstrom8,etal:nfluenceofnaloxoneInfusIononanalgesIa
andrespIratorydepressIonfollowIngepIduralmorphIne.AnesthesIology1986;64:194
292.KapIlaA,ClassPSA,JacobsJF,etal:|easuredcontextsensItIvehalftImesof
remIfentanIlandalfentanIl.AnesthesIology1995;8J:968
Stock, M. Christine
TableofContentsSectIon7AnesthetIcAgents,Adjuvants,and0rugnteractIonChapter20Neuromuscular
8lockIngAgents
Chapter20
Neuromuscular Blocking Agents
Franois Donati
David R. Bevan
Key Points
1. Neuromuscular blocking agents are used to improve conditions for
tracheal intubation, to provide immobility during surgery, and to
facilitate mechanical ventilation.
2. The main site of action of neuromuscular blocking agents (muscle
relaxants) is on the nicotinic cholinergic receptor at the endplate of
muscle. They also have effects at presynaptic receptors located on
the nerve terminal.
3. Succinylcholine is a blocking agent that produces depolarization at
the endplate and binds to extrajunctional receptors. In spite of many
side effects, such as hyperkalemia, its rapid offset makes it the drug
of choice for rapid sequence induction.
4. All other drugs available are nondepolarizing. They compete with
acetylcholine for the same binding sites.
5. Fade in response to high-frequency stimulation (e.g. train-of-four, 2
Hz for 2 seconds) is a characteristic of nondepolarizing blockade.
Train-of-four fade is difficult to evaluate manually or visually during
recovery when ratio is >0.4.
6. The upper airway is particularly sensitive to the effects of
nondepolarizing blockade. Complete recovery does not occur until
train-of-four ratio at the adductor pollicis is >0.9.
7. Residual paralysis is more frequent with long-duration than
intermediate-duration agents.
8. Reversal with anticholinesterases should be attempted when a
certain degree of spontaneous recovery is manifest. Ideally, all four
twitches in response to train-of-four stimulation should be visible
before reversal is given.
9. After injection of the selective binding agent sugammadex,
neuromuscular transmission is restored because of 1:1 binding of
sugammadex to rocuronium.
tappearsparadoxIcalthatdrugshavIngperIpheraleffectsonneuromusculartransmIssIon
mIghthavearoleInanesthesIa.fthepatIentIsanesthetIzed,whyprovIdeagentsto
preventmovement:Yet,theIntroductIonofmusclerelaxants,moreapproprIatelycalled
neuromuscular blocking agents,IntoclInIcalpractIceIn1942wasanImportantmIlestoneIn
thehIstoryofanesthesIa.
1
WhIletheusefulnessofthenewdrugsbecameapparent,there
weredoubtsregardIngpatIentsafety.n1954,8eecherandTodd
2
claImedthatanesthetIc
mortalItyIncreasedsIxfoldwhenmusclerelaxantswereused.ThIssItuatIonwasprobably
becauseofthesuboptImaluseofmechanIcalventIlatIonandreversaldrugs,
P.499
butothercontroversIeshavearIsenInrecentyearsforavarIetyofreasons.
Forexample,theIncIdenceofawarenessappearstobegreaterwhenneuromuscular
blockIngagentsareused,
J
andsomeauthorsrecommendrestrIctIngtheuseofthesedrugs
wheneverpossIble,aspatIentmovementmIghtbeanIndIcatorofconscIousness.However,
anesthetIcsactatthespInalcordleveltoproduceImmobIlIty;thus,movementInresponse
toanoxIousstImulusIndIcatesInadequateanalgesIaanddoesnotnecessarIlymeanthe
patIentIsconscIous.
4
Therefore,awarenessdoesnotoccurbecausetoomuch
neuromuscularblockIngagenthasbeengIven,butbecausetoolIttleanesthetIcIs
admInIstered.ThecontroversyregardIngneuromuscularblockIngagentsandawarenessIs
complIcatedbythefactthatneuromuscularblockadeseemstoaffectthebIspectralIndex
(8S),whIchIsthemostwIdelyusedmeasureofunconscIousness.
5
FeductIonsIn8Shave
beenreportedInawakeIndIvIdualsreceIvIngsuccInylcholIneandInmIldlysedatedpatIents
gIvenmIvacurIum.
CompleteparalysIsIsnotrequIredfortheduratIonofallsurgIcalprocedures.However,
neuromuscularblockIngagentswerefoundtomakeadIfferenceInlowerabdomInal
surgery,wheresurgIcalcondItIonswerebetterInpatIentsreceIvIngvecuronIum(FIg.20
1).
6
naddItIontoprovIdIngImmobIlItyandbettersurgIcalcondItIons,neuromuscular
blockIngagentsImproveIntubatIngcondItIons.ThedosesofopIoIdsrequIredforacceptable
IntubatIngcondItIonsIntheabsenceofmuscleparalysIsproducesIgnIfIcanthypotensIon
(FIg.202).
7
ProvIdIngoptImalIntubatIngcondItIonsIsnotatrIvIalobjectIve.Poor
IntubatIngcondItIonsmayIncreasetheIncIdenceoflaryngealInjury,asmanIfestedby
voIcehoarsenessandvocalcorddamage(FIg.20J),andthebestwaytoImprove
IntubatIngcondItIonsIstoadmInIsterneuromuscularblockIngagents.
8
tIsalsoessentIaltomakesurethattheeffectsofneuromuscularblockIngdrugshaveworn
offorarereversedbeforethepatIentregaInsconscIousness.WIththeIntroductIonof
shorteractIngneuromuscularblockIngagents,manythoughtthatreversalofblockade
couldbeomItted.However,resIdualparalysIsIsstIllaproblem,nearlyJ0yearsafterIfwas
fIrstdescrIbed(Table201),andInspIteoftheavaIlabIlItyofshorteractIngneuromuscular
blockIngdrugsandwIdespreaduseofneuromuscularmonItorIng.
9
PartofthIsmIghtbe
relatedtotherecognItIonthatthethresholdforcompleteneuromuscularrecoveryIsa
traInoffourratIoof0.9,InsteadofthetradItIonal0.7(FIg.204).
1J2
Thus,an
understandIngofthepharmacologyofneuromuscularblockIngagentsandreversaldrugsIs
essentIal.
Figure 20-1.Surgeon'sassessmentofmusclerelaxatIondurInglowerabdomInal
surgery.FatInggoesfrom1(excellent)to4(poor).TheIncIdenceofpoorratIngwas
greaterInpatIentsnotgIvenvecuronIum(29)comparedwIththosewhoreceIvedthe
drug(2).(FedrawnfromKIng|,SujIrattanawImolN,0anIelson0F,etal:
FequIrementsformusclerelaxantsdurIngradIcalretropubIcprostatectomy.
AnesthesIology2000;9J:1J92.)
Figure 20-2.NeuromuscularblockIngagentsprovIdebetterIntubatIngcondItIonsthan
hIghdosesofopIoIds,wIthouthypotensIon.HypnotIcagentwaspropofolorthIopental.
ntubatIngcondItIonsareplottedagaInstdoseofremIfentanIl(InmIcrogramsper
kIlogram).FesultsforsuccInylcholIne(Sux),1mg/kg(wIthlIttleopIoId)aregIvenfor
comparIson.HypotensIonwasseenwIthremIfentanIl,4g/kg.
7
(0ataobtaInedfrom
severaldIfferentstudIes;references7,J7,J8,69,72,159,and160.)
Figure 20-3.NeuromuscularblockIngagentsImproveIntubatIngcondItIonsandreduce
vocalcordsequelae.ThegraphdepIctstheIncIdenceofexcellentandacceptable
(defInedasgoodorexcellent)IntubatIngcondItIonsafteratracurIumorsalIne.The
percentageofpatIentswhoreportedhoarsenessandthosewIthvocalcordlesIons
documentedbystroboscopyIsalsoshown.(0atafrom|enckeetal.
8
)
P.500
P.501
Figure 20-4.UpperesophagealrestIngtoneInvolunteersgIvenvecuronIum.TraInof
fourratIo(TDF)wasmeasuredattheadductorpollIcIsmuscle.StatIstIcallysIgnIfIcant
decreasescomparedwIthcontrolwerefoundatalllevelsofparalysIsuntIlTDF0.9.
(FedrawnfromErIkssonL,SundmanE,DlssonF,etal:FunctIonalassessmentofthe
pharynxatrestanddurIngswallowIngInpartIallyparalyzedhumans:sImultaneous
vIdeomanometryandmechanomyographyofawakehumanvolunteers.AnesthesIology
1997;87:10J5.)
Table 20-1 Selected Reports of Residual Paralysis 19792007
STUDY
LONG-DURATION
DRUGS USED
INTERMEDIATE-DURATION DRUGS USED REVERSAL
TOF
THRESHOLD
7Iby
|ogensen
etal.,
1J8
1979
d
TubocurarIne
PancuronIum
CallamIne
Yes 0.7
8evanet
al.,
16J
1988
PancuronIum Yes 0.7
AtracurIum Yes 0.7
7ecuronIum Yes 0.7
Fawcett
etal.,
90
1995
AtracurIum/vecuronIumbolus Yes 0.7
AtracurIum/vecuronIumInfusIon Yes 0.7
8erget
al.,
1997
140
PancuronIum Yes 0.7
AtracurIum/vecuronIum Yes 0.7
8IssInger
etal.,
164
2000
PancuronIum Yes 0.7
7ecuronIum Yes 0.7
Catkeet
al.,
121
2002
FocuronIumwIthout
A|CmonItorIng
Yes 0.8

FocuronIumwIth
A|CmonItorIng
Yes 0.8
0ebaene
etal.,
120
200J
AtracurIum/vecuronIum/rocuronIum No 0.7
0.9
|urphy
etal.,
66
200J
PancuronIum No 0.8
FocuronIum No 0.8
|urphy
etal.,
67
2004
PancuronIum Yes 0.7
0.9
FocuronIum Yes 0.7
0.9
8aIllard
etal.,
141
2005
AtracurIum/vecuronIum/rocuronIum
No
(94)
0.9
AtracurIum/vecuronIum/rocuronIum
No
(58)
0.9
A|C,acceleromyography;TDF,traInoffourratIo.
Physiology and Pharmacology
Structure
ThecellbodIesofmotorneuronssupplyIngskeletalmusclelIeInthespInalcord.They
receIveandIntegrateInformatIonfromthecentralnervoussystem.ThIsInformatIonIs
carrIedvIaanelongatedstructure,theaxon,todIstantpartsofthebody.Eachnervecell
supplIesmanymusclecells(orfIbers)ashortdIstanceafterbranchIngIntonervetermInals.
ThetermInalportIonoftheaxonIsaspecIalIzedstructure,thesynapse,desIgnedforthe
productIonandreleaseofacetylcholIne.ThesynapseIsseparatedfromtheendplateofthe
musclefIberbyanarrowgap,calledthesynaptic cleft,whIchIsapproxImately50nmIn
wIdth(0.05m)(FIg.205).
11
ThenervetermInalIssurroundedbyaSchwanncell,andthe
synaptIcclefthasabasementmembraneandcontaInsfIlamentsthatanchorthenerve
termInaltothemuscle.
Figure 20-5.SchematIcrepresentatIonoftheneuromuscularjunctIon(notdrawnto
scale).
TheendplateIsaspecIalIzedportIonofthemembraneofthemusclefIberwherenIcotInIc
acetylcholInereceptorsareconcentrated.0urIngdevelopment,multIpleconnectIonsare
madebetweennervetermInalsandasInglemusclefIber.However,asmaturatIon
contInues,mostoftheseconnectIonsatrophyanddIsappear,usuallyleavIngonlyone
connectIonpermusclefIber.ThIsendplatecontInuestodIfferentIatefromtherestofthe
musclefIber.ThenervetermInalenlarges,andfoldsappear.TheacetylcholInereceptors
clusterattheendplate,especIallyatthecrestsofthefolds,andtheIrdensItydecreasesto
almostzeroInextrajunctIonalareas.
12
|ammalIanendplatesusuallyhaveanovalshape
wIththeshortaxIsperpendIculartothefIber.ThewIdthoftheendplateIssometImesas
largeasthedIameterofthefIber,butIsusuallysmaller.However,ItslengthIsonlyasmall
fractIonofthatofthefIber.
Nerve Stimulation
UnderrestIngcondItIons,theelectrIcalpotentIaloftheInsIdeofanervecellIsnegatIve
wIthrespecttotheoutsIde(typIcally90m7).fthIspotentIalIsmadelessnegatIve
(depolarIzatIon),sodIumchannelsopenandallowsodIumIonstoenterthecell.ThIsInflux
ofposItIveIonsmakesthepotentIalInsIdethemembraneposItIvewIthrespecttothe
outsIde.ThIspotentIalchange,Inturn,causesdepolarIzatIonofthenextsegmentof
membrane,causIngmoresodIumchannelstoopen,andanelectrIcalImpulse,oractIon
potentIal,propagates.TheduratIonoftheactIonpotentIalIsbrIef(1msec)becauseof
rapIdInactIvatIonofsodIumchannelsandactIvatIonofpotassIumchannels.AnactIon
potentIalalsotrIggerstheopenIngofcalcIumchannels,allowIngcalcIumIonstopenetrate
thecell.ThIsentryofcalcIumfacIlItatesreleaseoftheneurotransmItteratthenerve
termInal.
ThesodIumchannelsIntheaxonmaybeactIvatedInresponsetoelectrIcaldepolarIzatIon
provIdedbyanervestImulator.AperIpheralnerveIsmadeupofalargenumberofaxons,
eachofwhIchrespondsInanallornonefashIontothestImulusapplIed.Thus,Inthe
absenceofneuromuscularblockIngagents,therelatIonshIpbetweentheamplItudeofthe
musclecontractIonandcurrentapplIedIssIgmoId.Atlowcurrents,thedepolarIzatIonIs
InsuffIcIentInallaxons.AscurrentIncreases,moreandmoreaxonsaredepolarIzedto
thresholdandthestrengthofthemusclecontractIonIncreases.WhenthestImulatIng
currentreachesacertaInlevel,allaxonsaredepolarIzedtothresholdand
P.502
propagateanactIonpotentIal.ncreasIngcurrentbeyondthIspoIntdoesnotIncreasethe
amplItudeofmusclecontractIon:thestImulatIonIssupramaxImal(FIg.206).|ost
commercIallyavaIlablestImulatorsdelIverImpulseslastIng0.1to0.2msec.
Figure 20-6.ExampleofIncreasIngstImulatIngcurrentInonepatIent.Currentpulses,
0.2msecduratIon,weredelIveredtotheulnarnerveatthewrIstevery10seconds.
TheforceofcontractIonoftheadductorpollIcIsmusclewasmeasuredandappearsas
spIkes.NotwItchwasseenIfthecurrentwas28mA.Atcurrentstrengthsof40mA,
thecurrentbecamesupramaxImal;IncreasIngthecurrentproducedlIttlechangeIn
force.
Release of Acetylcholine
AcetylcholIneIssynthesIzedfromcholIneandacetateandpackagedInto45nmvesIcles.
EachvesIclecontaIns5,000to10,000acetylcholInemolecules.SomeofthesevesIcles
clusternearthecellmembraneopposItethecrestsofthejunctIonalfoldsoftheendplate,
Inareascalledactive zones(FIg.205).
12
tIsnowwIdelyacceptedthatacetylcholIneIsreleasedInpackets,orquanta,andthata
quantumrepresentsthecontentsofonevesIcle.ntheabsenceofnervestImulatIon,
quantaarereleasedspontaneously,atrandom,andthIsIsseenassmalldepolarIzatIonsof
theendplate(mInIatureendplatepotentIal).WhenanactIonpotentIalInvadesthenerve
termInal,approxImately200to400quantaarereleasedsImultaneously,unloadIng
approxImately1to4mIllIonacetylcholInemoleculesIntothesynaptIccleft.
11
CalcIum,
whIchentersthenervetermInalthroughchannelsthatopenInresponsetodepolarIzatIon,
IsrequIredforvesIclefusIonandrelease.CalcIumchannelsarelocatedneardockIng
proteIns,andthIsspecIalgeometrIcarrangementprovIdeshIghIntracellularconcentratIons
ofcalcIumtoallowbIndIngofspecIalIzedproteInsonthevesIclemembranewIthdockIng
proteIns.
12
8IndIngproducesfusIonofthemembranesandreleaseofacetylcholIneensues.
WhenthecalcIumconcentratIonIsdecreased,orIftheactIonofcalcIumIsantagonIzedby
magnesIum,thereleaseprocessIsInhIbItedandtransmIssIonfaIluremayoccur.Dther
proteInsregulatestorageandmobIlIzatIonofacetylcholInevesIcles.tappearsthatasmall
proportIonofvesIclesIsImmedIatelyreleasable,whIleamuchlargerreservepoolcanbe
mobIlIzedmoreslowly.EachImpulsereleases0.2to0.5ofthe75,000to100,000vesIcles
InthenervetermInal.WIthrepetItIvestImulatIon,theamountofacetylcholInereleased
decreasesrapIdlybecauseonlyasmallfractIonofthevesIclesIsInaposItIontobe
releasedImmedIately.TosustaInreleasedurInghIghfrequencystImulatIon,vesIclesmust
bemobIlIzedfromthereservepool.
Postsynaptic Events
The1to10mIllIonreceptorslocatedattheendplatebIndtoacetylcholIneasthe
physIologIcallIgand,andbelongtotheclassofnIcotInIcreceptors.CholInergIcnIcotInIc
receptorsrespondtoacetylcholIneandotheragonIstsbyallowIngpassageofIons.NIcotInIc
receptorsaremadeupoffIveglycoproteInsubunItsarrangedIntheformofarosetteand
lyIngacrossthewholecellmembrane(FIg.207).ThenIcotInIcsubtypepresentatthe
neuromuscularjunctIonIsmadeupoftwoIdentIcalsubunIts,desIgnated,andthree
others,called,,andor.TherearetwoacetylcholInebIndIngsItes,eachlocatedon
theoutsIdepartofthesubunIt.WhentwoacetylcholInemoleculesbIndsImultaneouslyto
eachbIndIngsIte,anopenIngIscreatedInthecenteroftherosette,allowIngsodIumIons
toenterthecellandpotassIumIonstoexIt.
11,12
TheInwardmovementofsodIumIs
predomInantbecauseItIsattractedbythenegatIvevoltageoftheInsIdeofthecell.ThIs
movementofsodIumdepolarIzestheendplate;thatIs,ItsInsIdebecomeslessnegatIve.
ThereIsahIghdensItyofsodIumchannelsInthefoldsofsynaptIccleftsandInthe
perIjunctIonalarea.
12,1J
ThesechannelsopenwhenthemembraneIsdepolarIzedbeyonda
crItIcalpoInt,allowIngmoresodIumtoenterthecellandproducIngfurtherdepolarIzatIon.
ThIsdepolarIzatIongeneratesanactIonpotentIal,whIchpropagatesbyactIvatIonof
sodIumchannelsalongthewholelengthofthemusclefIber.ThemuscleactIonpotentIal
hasaduratIonof5to15msecandcanberecordedasanelectromyogram(E|C).t
precedestheonsetofcontractIon,ortwItch,whIchlasts100to200msec.WIthhIgh
frequency(10Hz)stImulatIon,themusclefIberdoesnothavetImetorelaxbeforethe
nextImpulse,socontractIonsfuseandaddup,andatetanusIsobtaIned.
TherearetwotypesofnIcotInIcacetylcholInereceptors.EarlyIndevelopment,receptors
areevenlydIstrIbutedalongthewholelengthofthemusclefIber.Thesereceptors,called
fetalreceptors,haveasubunIt(FIg.207).Whentheendplatedevelops,receptorstend
toclusterattheneuromuscularjunctIonandleaveonlyfewreceptorsInthe
extrajunctIonalareas.AsmaturatIoncontInues,thesubunItIssubstItutedbyan
subunIt,whIchIscharacterIstIcoftheadulttype,junctIonalreceptor.
12
nhumans,the
swItchoccursInthethIrdtrImesterofpregnancy.|aIntenanceofadultreceptorsatthe
endplatedependsontheIntegrItyofnervesupply.Afewtype,extrajunctIonalreceptors
stIllpersIstInadultsandcanprolIferateIncasesofdenervatIon.8othtypesofreceptor
have
P.50J
twobIndIngsItesforacetylcholIne,locatedoneachofthesubunIts,buttheyhave
slIghtlydIfferentsensItIvItIestoagonIstandantagonIstdrugs.
12
Figure 20-7.TherearetwotypesofnIcotInIcreceptorsInmuscle.8othhavethesame
fIvesubunIts,exceptforasubstItutIonoftheforthesubunIts.TheacetylcholIne
bIndIngsItesarerepresentedbyashadedovalarea.TheyareonthesubunIt,atthe
andorInterface,respectIvely.AccordIngtosomeauthors,theorderoftheand
IsInverted.
ThemaInactIonofnondepolarIzIngneuromuscularblockIngdrugsIstobIndtoatleastone
ofthetwosubunItsofthepostsynaptIcreceptor.ThIspreventsaccesstothereceptorby
acetylcholIneanddoesnotproduceopenIngofthereceptor.UndernormalcIrcumstances,
onlyasmallfractIonofavaIlablereceptorsmustbIndtoacetylcholInetoproducesuffIcIent
depolarIzatIontotrIggeramusclecontractIon.notherwords,thereIsawIdemargInof
safety.
1J
ThIsredundancyImplIesthatneuromuscularblockIngdrugsmustbeboundtoa
largenumberofreceptorsbeforeanyblockadeIsdetectable.AnImalstudIessuggestthat
75ofreceptorsmustbeoccupIedbeforetwItchheIghtdecreasesInthepresenceofd
tubocurarIne,andblockadeIscompletewhen92ofreceptorsareoccupIed.
14
Theactual
numberdependsonspecIesandtypeofmuscle,andhumansmIghthaveareducedmargIn
ofsafetycomparedwIthotherspecIes.
1J
SoItIsfutIletocorrelatereceptoroccupancy
dataobtaInedIncatswIthcertaInclInIcaltestsInhumans,suchashandgrIpandheadlIft,
whIchInvolvedIfferentmusclegroups.However,thegeneralconceptthatalarge
proportIonofreceptorsmustbeoccupIedbeforeblockadebecomesdetectable,andthat
measurableblockadeoccursoveranarrowrangeofreceptoroccupancy,remaIns
applIcabletoclInIcalpractIce.8ecauseItmustovercomethemargInofsafety,theInItIal
doseofneuromuscularblockIngagentIsgreaterthanmaIntenancedoses.
AcetylcholIneIshydrolyzedrapIdlybytheenzymeacetylcholInesterase,whIchIspresent
InthefoldsoftheendplateaswellasembeddedInthebasementmembraneofthe
synaptIccleft.ThepresenceoftheenzymeInthesynaptIccleftsuggeststhatnotallthe
acetylcholInereleasedreachestheendplate;someIshydrolyzedenroute.
12,15
Presynaptic Events
ThereleaseofacetylcholInenormallydecreasesdurInghIghfrequencystImulatIonbecause
thepoolofreadIlyreleasableacetylcholInebecomesdepletedfasterthanItcanbe
replenIshed.UndernormalcIrcumstances,thereducedamountreleasedIswellabovewhat
IsrequIredtoproducemusclecontractIonbecauseofthehIghmargInofsafetyatthe
neuromuscularjunctIon.naddItIon,aposItIvefeedbacksystemInvolvIngactIvatIonof
presynaptIcreceptorshelpsInthemobIlIzatIonofacetylcholInevesIcles.AlthoughstudIes
aImedatIdentIfyIngthesereceptorsareextremelydIffIculttoperform,thereIssome
evIdencethattherethepresynaptIcandpostsynaptIcreceptorsareofdIfferentsubtypes.
PresynaptIcreceptorsaremostlIkelyofthe
J
2
subtype,thatIstheyaremadeupofonly
andsubunIts.
16,17
8oththesubunItsareslIghtlydIfferentfromthosefoundIn
postsynaptIcreceptors(thusthedesIgnatIonas
J
,Insteadofthe
1
gIventopostsynaptIc
receptors).TheotherthreesubunItsareallIdentIcal(
2
),andslIghtlydIfferentfromthe
1
subunItfoundInpostsynaptIcreceptors.
ThephysIologIcalroleofthepresynaptIcreceptorsIstomaIntaInthenumberofvesIcles
readytobereleased.NondepolarIzIngneuromuscularblockIngdrugsproducecharacterIstIc
TDFandtetanIcfade,probablybyblockIngpresynaptIcnIcotInIcreceptors,
16
thus
preventIngmobIlIzatIonofacetylcholInevesIclesandleadIngtoreducedacetylcholIne
releasedurInghIghfrequencystImulatIon.SuccInylcholInehasvIrtuallynoeffectonthese
presynaptIcreceptors,whIchwouldexplaInthelackoffadeobservedwIththIsdrug.
17
Fade
constItutesakeypropertyofnondepolarIzIngneuromuscularblockIngdrugsandIsuseful
formonItorIngpurposes.
NeuromuscularblockIngdrugsInteractwIththeacetylcholInereceptoreItherby
depolarIzIngtheendplate(depolarIzIngagents)orbycompetIngwIthacetylcholInefor
bIndIngsItes(nondepolarIzIngagents).TheonlydepolarIzIngagentstIllInuseIs
succInylcholIne.AllothersareofthenondepolarIzIngtype.
Pharmacologic Characteristics of Neuromuscular Blocking
Agents
TheeffectofneuromuscularblockIngdrugsIsmeasuredasthedepressIonofadductor
musclecontractIon(twItch)followIngelectrIcalstImulatIonoftheulnarnerve.Thevalue
IscomparedwIthacontrolvalue,obtaInedbeforeInjectIonofthedrug.Eachdrughas
characterIstIconset,potency,duratIonofactIon,andrecoveryIndex.
PotencyofeachdrugIsdetermInedbyconstructIngdoseresponsecurves,whIchdescrIbe
therelatIonshIpbetweentwItchdepressIonanddose(FIg.208).
18
Then,theeffectIvedose
50,orE0
50
,whIchIsthemedIandosecorrespondIngto50twItchdepressIon,IsobtaIned.
8ecauseclInIcallyusefulrelaxatIonIsattaInedwhentwItchIsabolIshedalmostcompletely,
theE0
95
,correspondIngto95block,Ismorecommonlyused.Forexample,theE0
95
for
vecuronIumIs0.05mg/kg,whIchmeansthathalfthepatIentswIllachIeveatleast95
blockofsIngletwItch(comparedwIththeprevecuronIumvalue)wIththatdose,andhalf
thesubjectswIllreach95block.FocuronIumhasanE0
95
of0.Jmg/kg.Therefore,Ithas
onesIxththepotencyofvecuronIum.notherwords,comparedwIthvecuronIum,6tImes
asmuchrocuronIumhastobegIventoproducethesameeffect.TheE0
95
ofknown
neuromuscularblockIngagentsvaryovertwoordersofmagnItude(Table202).
Onset time,ortImetomaxImumblockade,canbeshortenedIfthedoseIsIncreased.When
twoormoredrugsare
P.504
compared,ItIsmeanIngfultocompareonlyequIpotentdosesandusuallyclInIcally
relevantdoses(2E0
95
)areconsIdered.
18
Figure 20-8.ExampleofadoseresponserelatIonshIp.Theactualnumbersare
approxImatelythoseforrocuronIum.TheE0
50
IsthedosecorrespondIngto50
blockadeandE0
95
IsthedosecorrespondIngto95blockade.
Duration of actionIsthetImefromInjectIonoftheneuromuscularblockIngagenttoreturn
of25twItchheIght(comparedwIthcontrol).0uratIonIncreaseswIthdose,socomparIsons
arenormallymadewIth2E0
95
doses.The25twItchheIghtfIgurewaschosenbecause
rapIdreversalcannormallybeachIevedatthatlevel.CategorIeswereproposedfor
neuromuscularblockIngdrugsaccordIngtotheIrduratIonofactIon(Table202).
18
Same
duratIonagentsmayhavemarkedlydIfferentonsets.
Table 20-2 Potency, Onset Time, Duration, and Recovery Index of
a
AGENT
ED
95
(mg/kg)
ONSET
TIME (min)
DURATION TO 25%
RECOVERY (min)
RECOVERY INDEX (2575%
RECOVERY) (min)
ULTRASHORT-DURATION AGENTS
SuccInylcholIne 0.J 11.5 68 24
CantacurIum
b
0.19 1.7 68 2.5
SHORT-DURATION AGENTS
|IvacurIum
c
0.08 J4 1520 710
FapacuronIum
c
0.75 11.5 1525 57
INTERMEDIATE-DURATION AGENTS
AtracurIum
0.2
0.25
J4 J545 1015
CIsatracurIum 0.05 57 J545 1215
FocuronIum 0.J 1.5J J040 812
7ecuronIum 0.05 J4 J545 1015
LONG-DURATION AGENTS
AlcuronIum
c
0.25 J5 6090 J040
0oxacurIum 0.025 510 40120 J040
d-TubocurarIne
c
0.5 24 60120 J045
CallamIne
c
2 1.5J 60120 J060
|etocurIne
c
0.J J5 60150 4060
PancuronIum 0.07 24 60120 J040
PIpecuronIum
c
0.05 J5 901J0 J545
a
TypIcalvaluesfortheaverageyoungadultpatIent.DnsetandduratIondata
dependondose.ThevaluespresentedarethebestestImatesavaIlablefortwIce
theE0
95
andaremeasuredattheadductorpollIcIsmusclewIthnItrousoxIdeand
novolatIleagent.ActualvaluesmayvarymarkedlyfromoneIndIvIdualtothe
next,andmaybeaffectedbyage,othermedIcatIons,and/ordIseasestates.The
categorIesunderwhIchthedrugsareclassIfIedaresomewhatarbItrary.
b
8eIngInvestIgatedatthetImeofwrItIng.
c
NolongerusedorverylImIteduseInNorthAmerIca.
Recovery indexIsthetImeIntervalbetween25and75twItchheIght.tprovIdes
InformatIonaboutthespeedofrecoveryoncereturnoftwItchIsmanIfest.Contraryto
duratIonofactIon,ItdoesnotdependheavIlyonthedosegIven.ThevaluesforE0
95
,onset
tIme,duratIonofactIon,andrecoveryIndexdependonwhIchmuscleIsusedtomake
measurements.ForconsIstency,theadductorpollIcIsmusclehasbeenretaInedasthegold
standard,notbecauseofItsphysIologIcalsIgnIfIcancebutbecauseItIsmostcommonly
monItoredanddataonItaremostabundant.
ThepharmacologIccharacterIstIcsofneuromuscularblockIngagentsarecompletedbyan
assessmentofintubating conditions,whIchdonotalwaysparalleltwItchheIghtatthe
adductorpollIcIsmuscle.ntubatIngcondItIonsdependonparalysIsofcentrallylocated
muscles,butalsoonthetypeandquantItyofopIoIdandhypnotIcdrugsgIvenforInductIon
ofanesthesIa.TodecreasevarIabIlItybetweenstudIes,crIterIatogradeIntubatIng
condItIonsasexcellent,good,poor,orImpossIbleInascorIngsystemwereadoptedbya
groupofexpertswhometInCopenhagenIn1994.
19
Depolarizing Drugs: Succinylcholine
AmongdrugsthatdepolarIzetheendplate,onlysuccInylcholIneIsstIllusedclInIcally.n
spIteofalonglIstofundesIredeffects,succInylcholIneremaInspopularbecauseItIsthe
onlyultrarapIdonset/ultrashortduratIonneuromuscularblockIngdrugcurrentlyavaIlable.
Neuromuscular Effects
TheeffectsofsuccInylcholIneattheneuromuscularjunctIonarenotcompletely
understood.ThedrugdepolarIzespostsynaptIcandextrajunctIonalreceptors.However,
whenthereceptorIsIncontactwIthanyagonIst,IncludIngacetylcholIne,foraprolonged
tImeItceasestorespondtotheagonIst.Normally,thIsdesensItIzatIonprocessdoesnot
occurwIthacetylcholInebecauseofItsrapIdbreakdown(1msec).However,
succInylcholIneremaInsattheendplateformuchlonger,sodesensItIzatIondevelopsafter
abrIefperIodofactIvatIon.
17
AnotherpossIblemechanIsmIstheInactIvatIonofsodIum
channelsInthejunctIonalandperIjunctIonalareas,whIchoccurswhenthemembrane
remaInsdepolarIzed.
17
ThIsInactIvatIonpreventsthepropagatIonoftheactIonpotentIal.
8othdesensItIzatIonofthereceptorandInactIvatIonofsodIumchannelsmIghtbepresent
together.
WIthIn1mInuteaftersuccInylcholIneInjectIonandbeforeparalysIsIsmanIfest,some
dIsorganIzedmuscularactIvItyIsfrequentlyobserved.ThIsphenomenonIscalled
fasciculation.
P.505
ThIsactIvItyprobablyreflectstheagonIsteffectofsuccInylcholIne,beforedesensItIzatIon
takesplace.SmalldosesofnondepolarIzIngdrugsareeffectIveInreducIngtheIncIdenceof
fascIculatIons.
20
SuccInylcholInehasyetanotherneuromusculareffect.nsomemuscles,lIkethemasseter
andtoalesserextenttheadductorpollIcIs,asustaInedIncreaseIntensIonthatmaylast
forseveralmInutescanbeobserved.ThemechanIsmofactIonofthIstensIonchangeIs
uncertaInbutIsmostlIkelymedIatedbyacetylcholInereceptorsbecauseItIsblockedby
largeamountsofnondepolarIzIngdrugs.
21
TheIncreaseInmasseterIctone,whIchIs
probablyalwayspresenttosomedegreebutgreaterInsomesusceptIbleIndIvIduals,may
leadtoImperfectIntubatIngcondItIonsInasmallproportIonofpatIents.|assetermuscle
spasmmaybeanexaggeratedformofthIsresponse.
Characteristics of Depolarizing Blockade
AfterInjectIonofsuccInylcholIne,sIngletwItchheIghtIsdecreased.However,theresponse
tohIghfrequencystImulatIonIssustaIned:mInImaltraInoffourandtetanIcfadeIs
observed.TheblockIsantagonIzedbynondepolarIzIngagentssothattheE0
95
IsIncreased
byafactortwoIfasmalldoseofnondepolarIzIngdrugIsgIvenbefore.
22
SuccInylcholIne
blockadeIspotentIatedbyInhIbItorsofacetylcholInesterase,suchasneostIgmIneand
edrophonIum.
2J
Phase II Block
AfteradmInIstratIonof7to10mg/kg,orJ0to60mInutesofexposuretosuccInylcholIne,
traInoffourandtetanIcfadebecomeapparent.NeostIgmIneoredrophonIumcan
antagonIzethIsblock,whIchhasbeentermednondepolarizing,dual,orphase IIblock.The
onsetofphaseblockcoIncIdeswIthtachyphylaxIs,asmoresuccInylcholIneIsrequIredfor
thesameeffect.
Pharmacology of Succinylcholine
SuccInylcholIneIsrapIdlyhydrolyzedbyplasmacholInesterase(alsocalled
pseudocholinesterase),wIthanelImInatIonhalflIfeof1mInuteInpatIents.
24
8ecauseof
therapIddIsappearanceofsuccInylcholInefromplasma,themaxImumeffectIsreached
quIckly.SubparalyzIngdoses(upto0.Jto0.5mg/kg)reachtheIrmaxImaleffectwIthIn
approxImately1.5to2mInutesattheadductorpollIcIsmuscle,
22
andwIthIn1mInuteat
morecentralmuscles,suchasthemasseter,thedIaphragm,andthelaryngealmuscles.
WIthlargerdoses(1to2mg/kg),abolItIonoftwItchresponsecanbereachedevenmore
rapIdly.
ThemeandoseproducIng95blockade(E0
95
)attheadductorpollIcIsmuscleIs0.J0to0.J5
mg/kgwIthopIoIdnItrousoxIdeanesthesIa.
22
ntheabsenceofnItrousoxIde,theE0
95
Is
Increasedto0.5mg/kg.
25
ThesevaluesaredoubledIfdtubocurarIne,0.05mg/kg,IsgIven
asadefascIculatIngagent.
22
ThetImeuntIlfullrecoveryIsdosedependentandreaches10
to12mInutesafteradoseof1mg/kg.
Side Effects
Cardiovascular
SInusbradycardIawIthnodalorventrIcularescapebeats(orboth)mayoccur,especIallyIn
chIldren,andasystolehasbeendescrIbedafteraseconddoseofsuccInylcholIneInboth
pedIatrIcandadultpatIents.TheseeffectscanbeattenuatedwIthatropIneor
glycopyrrolate.
26
ThemechanIsmsforthecardIovascularsIdeeffectsofsuccInylcholIneare
notknownbecausesuccInylcholIneappearstohavelIttleeffectofautonomIccholInergIc
receptors.
17
SuccInylcholIneIncreasescatecholamInerelease,andtachycardIaIsseen
frequently.
Anaphylaxis
SuccInylcholInehasbeenIncrImInatedasthetrIggerofallergIcreactIonsmoreoftenthan
anyotherdrugusedInanesthesIa.SuccessIvestudIesconductedInFranceIndIcatethatthe
numberofreportedeventsIsdecreasIng,correspondIngtothegradualreplacementof
succInylcholInebynondepolarIzIngdrugs.
27
TheIncIdenceofanaphylactIcreactIonsto
succInylcholIneIsdIffIculttoestablIsh,butIsprobablyoftheorderof1:5,000to1:10,000.
Fasciculations
TheprevalenceoffascIculatIonsIshIgh(60to90)aftertherapIdInjectIonof
succInylcholIne,especIallyInmuscularadults.FascIculatIonsareabenIgnsIdeeffectofthe
drug,butmanyclInIcIansprefertopreventfascIculatIons.nthIsrespect,asmalldoseofa
nondepolarIzIngneuromuscularblockIngdrugIsgIvenJto5mInutesbeforesuccInylcholIne
IseffectIve.
20
WhenthedrugwasavaIlable,dtubocurarIne0.05mg/kgwasusedforthIs
purpose.FocuronIumIsanacceptablealternatIve,aslongasapproprIatedoses(0.0Jto
0.04mg/kg,or10oftheE0
95
)aregIven.
28
nonestudy,rocuronIum,0.0Jmg/kg,
decreasedtheIncIdenceoffascIculatIonsfrom90to10.
29
Adoseof0.06mg/kgleadsto
anunacceptablyhIghIncIdenceofsymptomsofneuromuscularweakness,suchasblurred
vIsIon,heavyeyelIds,voIcechanges,dIffIcultyswallowIng,orevendyspnea,Intheawake
patIent.
J0
ArecentmetaanalysIsshowsthatthesesIdeeffectshavebeenobserved
frequentlyInstudIesofdefascIculatIngdosesofneuromuscularblockIngagents,
20
butthese
sIdeeffectsaremostlIkelyrelatedtothehIghdosegIven.
28
AtracurIum,0.02mg/kg,Is
alsoeffectIve.PancuronIum,vecuronIum,cIsatracurIum,andmIvacurIumarenotas
effectIveasdefascIculants.AfterthesenondepolarIzIngdrugs,thedoseofsuccInylcholIne
mustbeIncreasedfrom1mg/kgto1.5oreven2mg/kgbecauseoftheantagonIsm
betweendepolarIzIngandnondepolarIzIngdrugs.
22
Dtherdrugs,suchasdIazepam,
lIdocaIne,fentanyl,calcIum,vItamInC,magnesIum,anddantrolene,haveallbeenusedto
preventfascIculatIons.TheresultsarenobetterthanwIthnondepolarIzIngrelaxantsand
theymayhaveundesIrableeffectsoftheIrown.TheadmInIstratIonofsmall(10mg)doses
ofsuccInylcholIne1mInutebeforetheIntubatIngdose,doesnotappeartobeeffectIve
29
andhaslargelybeenabandoned.
Muscle Pains
CeneralIzedachesandpaIns,sImIlartothemyalgIathatfollowsvIolentexercIse,are
common24to48hoursaftersuccInylcholIneadmInIstratIon.TheIrIncIdenceIsvarIable
(1.5to89ofpatIentsreceIvIngsuccInylcholIne)andaremorecommonInyoung,
ambulatorypatIents.
J1
TheIntensItyofmusclepaInsIsnotalwayscorrelatedwIththe
IntensItyoffascIculatIons,butthemethodsthathavebeenshowneffectIvetoprevent
fascIculatIonsusuallypreventmusclepaIns.Forexample,aprecurarIzatIondoseofa
nondepolarIzIngneuromuscularblockIngagentIseffectIve.LIdocaIne(1to1.5mg/kg),
especIallyInconjunctIonwIthprecurarIzatIon,hasalsobeenshowntobeofvalue.
J1
CalcIum,vItamInC,benzodIazepInes,magnesIum,anddantrolenehavebeentrIedwIth
InconclusIveresults.
J1
Intragastric Pressure
SuccInylcholIneIncreasesIntragastrIcpressure,andthIseffectIsblockedby
precurarIzatIon.However,succInylcholIne
P.506
causesevengreaterIncreasesInloweresophagealsphIncterpressure.Thus,
succInylcholInedoesnotappeartoIncreasetherIskofaspIratIonofgastrIccontentsunless
theloweresophagealsphIncterIsIncompetent.
Intraocular Pressure
ntraocularpressureIncreasesby5to15mmHgafterInjectIonofsuccInylcholIne.The
mechanIsmIsunknownbutoccursafterdetachmentofextraocularmuscle,suggestIngan
IntraocularetIology.PrecurarIzatIonwIthanondepolarIzIngblockerhaslIttleornoeffect
onthIsIncrease.ThIsInformatIonhasledtothewIdespreadrecommendatIontoavoId
succInylcholIneInopeneyeInjurIes.However,ItmustbeapprecIatedthatInadequate
anesthesIa,elevatedsystemIcbloodpressure,andInsuffIcIentneuromuscularblockade
durInglaryngoscopyandtrachealIntubatIonmIghtIncreaseIntraocularpressuremorethan
succInylcholIne.naddItIon,thereIslIttleevIdencethattheuseofsuccInylcholInehasled
toblIndnessorextrusIonofeyecontent.
J2
Intracranial Pressure
SuccInylcholInemayIncreaseIntracranIalpressure,andthIsresponseIsprobably
dImInIshedbyprecurarIzatIon.
JJ
AgaIn,laryngoscopyandtrachealIntubatIonwIth
InadequateanesthesIaormusclerelaxatIonarelIkelytoIncreaseIntracranIalpressure
evenmorethansuccInylcholIne.
Hyperkalemia
SerumpotassIumIncreasesbyapproxImately0.5mEq/LafterInjectIonofsuccInylcholIne.
ThIsIncreaseIsnotpreventedcompletelybyprecurarIzatIon.nfact,onlylargedosesof
nondepolarIzIngblockersrelIablyabolIshthIseffect.
J4
SubjectswIthpreexIstIng
hyperkalemIa,suchaspatIentsInrenalfaIlure,donothaveagreaterIncreaseInpotassIum
levels,buttheabsolutelevelmIghtreachthetoxIcrange.SuccInylcholIneIssafeIn
normokalemIcrenalfaIlurepatIents.
J5
SeverehyperkalemIa,occasIonallyleadIngto
cardIacarrest,hasbeendescrIbedInpatIentsaftermajordenervatIonInjurIes,spInalcord
transectIon,perIpheraldenervatIon,stroke,trauma,extensIveburns,andprolonged
ImmobIlItywIthdIsease,andmayberelatedtopotassIumlossvIaaprolIferatIonof
extrajunctIonalreceptors.
J4
HyperkalemIahasbeenreportedwIthmyotonIaandmuscle
dystrophIes,andcardIacarrestshavebeenreportedInchIldrenbeforethedIagnosIsofthe
dIseasewasmade.
J4
SeverehyperkalemIaaftersuccInylcholIneresultIngIncardIacarrest
hasalsobeenobservedInacIdotIchypovolemIcpatIents.
Abnormal Plasma Cholinesterase
PlasmacholInesteraseactIvItycanbereducedbyanumberofendogenousandexogenous
causes,suchaspregnancy,lIverdIsease,uremIa,malnutrItIon,burns,plasmapheresIs,and
oralcontraceptIves.ThesecondItIonsusuallyleadtoaslIght,clInIcallyunImportant
IncreaseIntheduratIonofactIonofsuccInylcholIne.
J6
PlasmacholInesteraseactIvItyIs
reducedbysomeantIcholInesterases(e.g.,neostIgmIne)sothattheduratIonof
succInylcholInegIvenafterneostIgmIne,butnotafteredrophonIum,IsIncreased.
2J
AsmallproportIonofpatIentshaveagenetIcallydetermInedInabIlItytometabolIze
succInylcholIne.EItherplasmacholInesteraseIsabsentoranabnormalformoftheenzyme
Ispresent.DnlypatIentshomozygousforthecondItIon(approxImately1:2,000IndIvIduals)
haveprolongedparalysIs(Jto6hours)afterusualdosesofsuccInylcholIne(1to1.5mg/kg).
nheterozygouspatIents(1:J0cases),theduratIonofactIonIsonlyslIghtlyprolonged
comparedwIthnormalIndIvIduals.TradItIonalmethodsforIdentIfyIngplasma
cholInesterasephenotypeInvolvemeasurementofenzymeactIvItywIthasubstrateand
InhIbItIonwIthdIbucaIne,fluorIde,andchlorIde.ThesetestsareonlycapableofIdentIfyIng
someenzymevarIants.ThecompleteamInoacIdsequenceofplasmacholInesterasehas
nowbeendetermInedusIngmoleculargenetIcstechnIques.ThecholInesterasegeneIs
locatedonchromosomeJatq26,
J6
andover20mutatIonsInthecodIngregIonofthe
plasmacholInergIcgenehavebeenIdentIfIed.Wholebloodorfreshfrozenplasmacan
acceleratesuccInylcholInemetabolIsmInpatIentswIthloworabsentplasma
cholInesterase,butthebestcourseofactIonIsprobablymechanIcalventIlatIonofthe
lungsuntIlfullrecoveryofneuromuscularfunctIoncanbedemonstrated.NeostIgmIneand
edrophonIumareunpredIctableInthereversalofabnormallyprolongedsuccInylcholIne
blockadeandarebestavoIded.
Clinical Uses
ThemaInIndIcatIonforsuccInylcholIneIstofacIlItatetrachealIntubatIon.nadults,a
doseof1.0mg/kgyIelds75to80excellentIntubatIoncondItIonswIthIn1to1.5mInutes
afteranInductIonsequencethatIncludesahypnotIc(propofolorthIopental)anda
moderateopIoIddose.
J7,J8
ThedosemustbeIncreasedto1.5to2.0mg/kgIfa
precurarIzIngdoseofnondepolarIzIngblockerhasbeenused.
22
ntubatIngcondItIons
wIthoutprecurarIzatIonareonlymargInallyImprovedbyIncreasIngthedoseto2mg/kg.
J8
SuccInylcholIneIsespecIallyIndIcatedforrapIdsequenceInductIon,whenapatIent
presentswIthafullstomachandthepossIbIlItyofaspIratIonofgastrIccontents.nthIs
sItuatIon,manualventIlatIonofthelungsIsavoIded,IfpossIble,toreducetheprobabIlIty
ofaspIratIonbecauseofexcessIveIntragastrIcpressurecausedbygasforcedvIafacemask.
Thus,theIdealneuromuscularblockIngagenthasbothafastonset,toreducethetIme
betweenInductIonandIntubatIonoftheaIrway,andarapIdrecovery,toallowreturnof
normalbreathIngbeforethepatIentbecomeshypoxIc.TheduratIonofactIonof
succInylcholIne,gIvenatadoseof1mg/kg,IsshortenoughsothatInthemajorItyof
properlypreoxygenatedpatIentsresumerespIratoryefforts(5to6mInutes)beforehypoxIa
canbedetected.
J9
thasbeenarguedthatthIsIsvalIdonlyInrelatIvelyhealthysubjects
andnotInallcases.Asaresult,alowerdosehasbeensuggested.However,adoseof0.5
to0.6mg/kgresultsInsubstantIallyfewerpatIentswIthexcellentIntubatIngcondItIons,
andthedecreaseInduratIonIsmodest.
J7,J8
FormaIntenanceofrelaxatIon,typIcalInfusIon
ratesareapproxImately50to100g/kg/mIn.However,theavaIlabIlItyofshortand
IntermedIatenondepolarIzIngdrugsmakessuccInylcholIneInfusIonsobsolete.
ChIldrenareslIghtlymoreresIstanttosuccInylcholInethanadults,
40
anddosesof1to2
mg/kgarerequIredtofacIlItateIntubatIon.nInfants,2toJmg/kgmayberequIred.
PrecurarIzatIonIsnotnecessaryInpatIentsyoungerthan10yearsbecausefascIculatIons
areuncommonInthIsagegroup.8radycardIaIscommonInchIldrenunlessatropIneor
glycopyrrolateIsgIven.
26
SuccInylcholIne,atadoseof4mg/kg,IstheonlyeffectIve
IntramuscularneuromuscularblockIngagentInchIldrenwIthdIffIcultIntravenousaccess
andprovIdesadequateIntubatIngcondItIonsInabout4mInutes.However,thIsrouteof
admInIstratIonshouldnotbethemethodofchoIce.
41
nobeseIndIvIduals,thedoseofsuccInylcholIne,InmIllIgramsperkIlogramofactualbody
weIght,IsthesameasInleanerpatIents.CalculatIngthedoseperkIlogramIdealbody
weIghtmIghtleadtounderdosIngandInadequateIntubatIngcondItIons.
42
Thevolumeof
dIstrIbutIon,expressedperkIlogramofactualbodyweIght,ofsuccInylcholIneIsprobably
P.507
decreasedInobeseIndIvIduals,butthIsIscompensatedbyanIncreaseInplasma
cholInesteraseactIvIty.
Nondepolarizing Drugs
NondepolarIzIngneuromuscularblockIngdrugsbIndtothepostsynaptIcreceptorIna
competItIvefashIon,bybIndIngtooneofthesubunItsofthereceptor(FIg.207).
12
Characteristics of Nondepolarizing Blockade
ThefadeobservedInresponsetohIghfrequencystImulatIon(0.1Hz)IscharacterIstIcof
nondepolarIzIngblockade.
16
WIthE|CrecordIngs,fadeIsrelatIvelyconstantIntherange2
to50Hz.
4J
|echanIcalfadeIsgreaterwIth100HzthanwIth50Hz.
44
TetanIcstImulatIonIs
followedbyposttetanIcfacIlItatIon,whIchIsanIncreasedresponsetoanystImulatIon
applIedsoonafterthetetanus.TheIntensItyandduratIonofthIseffectdependonthe
frequencyandduratIonofthetetanIcstImulatIon.WItha50Hztetanusof5second
duratIon,twItchresponseshavebeenfoundtofallwIthIn10oftheIrpretetanIcvaluesIn
1to2mInutes
45
(FIg.209).
FInally,nondepolarIzIngblockadecanbeantagonIzedwIthantIcholInesteraseagentssuch
asedrophonIum,neostIgmIne,orpyrIdostIgmIne.tIsalsoantagonIzedbydepolarIzIng
agentssuchassuccInylcholIneprovIdedthatthenondepolarIzIngblockadeIsIntenseand
thatthesuccInylcholInedoseIstoosmalltoproduceablockofItsown.
Pharmacokinetics
AsIsthecaseforotherdrugsusedInanesthesIa,theelimination half-lifeofneuromuscular
blockIngagentsdoesnotalwayscorrelatewIthduratIonofactIonbecausetermInatIonof
actIonsometImesdependsonredIstrIbutIonInsteadofelImInatIon.However,knowledgeof
thekInetIcsofthedrughelpsusunderstandthebehavIorofthedrugInspecIalsItuatIons
(prolongedadmInIstratIon,dIseaseoftheorgansofelImInatIon,andsoon).
SeveralmechanIsmscanexplaInthevarIouscategorIesofduratIonsofactIonlIstedIn
Table20J:
1. Alllong-durationdrugsallhavealong(1to2hours)elImInatIonhalflIfeanddependon
lIverand/orkIdneyfunctIonfortermInatIonofactIon.
Figure 20-9.CharacterIstIcsofnondepolarIzIngblockade.TraInoffourresponses
areequalbeforeadmInIstratIonofvecuronIum(arrow).ForagIventwItch
depressIon,fadeIslessdurIngonset(top trace)thanrecovery(bottom trace).A50
HztetanuswasapplIeddurIngrecovery.TetanIcfadeIsseenwIthposttetanIc
facIlItatIon,thatIsagreatertraInoffourresponseafterthanbeforethetraIn.
2. Intermediate-durationdrugseItherhaveanIntermedIateelImInatIonhalflIfe
(atracurIumandcIsatracurIum)ortheyhavelongelImInatIonhalflIves(1to2hours)but
dependonredIstrIbutIonratherthanelImInatIonfortermInatIonofeffect(vecuronIum
androcuronIum;FIg.2010).
J. Short-durationdrugshaveeIthershortelImInatIonhalflIves(theactIveIsomersof
mIvacurIum)orlongelImInatIonhalflIfebutextensIveredIstrIbutIon(rapacuronIum).
4. Ultrashort-durationdrugshaveaveryshortelImInatIonhalflIfe(succInylcholIne).
Thevolume of distributionofalltheseagentsIsapproxImatelyequaltoextracellularfluId
(ECF)volume(0.2to0.4L/kg;Table20J).nInfants,InwhomtheECFvolumeasa
proportIonofbodyweIght,IsIncreased,thevolumeofdIstrIbutIonofneuromuscular
blockIngdrugsparallelsECFvolumeclosely.
Onset and Duration of Action
Onset timeofneuromuscularblockIngdrugsIsdetermInedbythetImerequIredfordrug
concentratIonsatthesIteofactIontoreachacrItIcallevel,usuallythatcorrespondIngto
100block.DnsettIme(2to7mInutes)IslongerthantImetopeakplasmaconcentratIons
(1mInute).ThIsdelayreflectsthetImerequIredfordrugtransferbetweenplasmaand
neuromuscularjunctIonandIsrepresentedquantItatIvelybyarateconstant(k
eo
).ThIsrate
constantcorrespondstohalftImesof5to10mInutesformostnondepolarIzIngdrugsandIs
determInedbyallthefactorsthatmodIfyaccessofthedrugto,andItsremovalfrom,the
neuromuscularjunctIon.TheseIncludecardIacoutput,dIstanceofthemusclefromthe
heart,andmusclebloodflow.Thus,onsettImesarenotthesameInallmusclesbecauseof
dIfferentbloodflows.Also,IfmetabolIsmorredIstrIbutIonIsveryrapId,forexample,In
thecaseofsuccInylcholIne,theonsettImeIsaccelerated.FInally,potentdrugshavea
sloweronsetofactIonthanlesspotentagents(FIg.2011).
46
ThIsIsbecausealarge
proportIonofreceptorsmustbeoccupIedbeforeblockadecanbeobserved.8lockadeof
thesereceptorswIlloccurfaster,andonsetwIllbemorerapId,Ifmoredrugmoleculesare
avaIlable,thatIs,IfpotencyIslow.Table202showsthatonsettendstobeslowerIfa
drugIspotent,thatIs,IfE0
95
Issmall.
Duration of actionIsdetermInedbythetImerequIredfordrugconcentratIonsatthesIteof
actIontodecreasebelowacertaInlevel,usuallycorrespondIngto25fIrsttwItch
blockade.0uratIonIsdetermInedchIeflybyplasmaconcentratIons,atleastfor
IntermedIateandlongduratIondrugs.
P.508
Figure 20-10.ConcentratIonsattheneuromuscularjunctIonforsIxrepresentatIve
drugs,afterbolusdosesof2E0
95
.ConcentratIonsattheneuromuscularjunctIonlag
somewhatbehIndplasmaconcentratIons.ThelevelcorrespondIngto25recoveryIs
IndIcated.Thecurvesweremovedupordownsothatthe25levelmatched.
SuccInylcholIneandtheactIvemIvacurIumIsomershavearapIdelImInatIon.
PancuronIumhasalonghalflIfeandrecoveryoccursdurIngtheelImInatIonphase.
CIsatracurIumhasanIntermedIatetermInalhalflIfe,andrecoveryalsooccursdurIng
theelImInatIonphase.FocuronIumandvecuronIumhaveanelImInatIonhalflIfe
comparablewIththatofpancuronIum.However,anImportantredIstrIbutIonoccurs
before,and25recoveryoccursdurIngthatredIstrIbutIonprocess.Asaresult,both
rocuronIumandvecuronIumhaveaduratIonofactIoncomparablewIththatof
cIsatracurIum.
Figure 20-11.NeuromuscularblockadeasafunctIonoftImeforfourneuromuscular
blockIngagents.DnsetIsfasterforthelesspotentsuccInylcholIneandrocuronIumthan
forthemorepotentvecuronIumandcIsatracurIum.(FromKopmanAF,KlewIcka||,
Kopman0J,etal:|olarpotencyIspredIctIveofthespeedofonsetofneuromuscular
blockforagentsofIntermedIate,short,andultrashortduratIon.AnesthesIology1999;
90:425,wIthpermIssIon.)
Table 20-3 Typical Pharmacokinetic Data for Neuromuscular Blocking
Agents in Adults, Except where Stated
DRUG
VOLUME OF DISTRIBUTION
(L/kg)
CLEARANCE
(mL/kg/min)
ELIMINATION HALF-LIFE
(min)
ULTRASHORT-DURATION AGENTS
SuccInylcholIne 0.04 J7 0.65
SHORT-DURATION AGENTS
|IvacurIum
Transtrans 0.05 29 2.4
CIstrans 0.05 46 2.0
CIscIs 0.18 7 J0
FapacuronIum 0.2 7 100
INTERMEDIATE-DURATION AGENTS
AtracurIum
CIsatracurIum
0.14 5.5 20
Adults 0.12 5 2J
ntensIvecare 0.26 6.5 25
FocuronIum
Adults 0.J J 90
ntensIvecare 0.7 J JJ0
7ecuronIum 0.4 5 70
LONG-DURATION AGENTS
0oxacurIum 0.2 2.5 95
dTubocurarIne
Adults 0.J 1J 90
Elderly 0.J 0.8 270
Neonates 0.7 1.1 J00
nfants 0.5 1.0 J00
ChIldren 0.J 1.5 90
PancuronIum 0.J 1.8 140
P.509
Individual Nondepolarizing Agents
SInce1942,nearly50nondepolarIzIngneuromuscularblockIngagentshavebeenIntroduced
IntoclInIcalanesthesIa.ThIssectIoncoversonlythosedrugscurrentlyavaIlableInNorth
AmerIcaandEurope,plusafewothersofhIstorIcalInterest.ThefIrstagenttoundergo
clInIcalInvestIgatIonwasntocostrIn,ordtubocurarIne,thepurIfIedandstandardIzed
productofcurareobtaInedfromtheplantChondodendrom tomentosum.
1
dTubocurarIne
hasbeencompletelyreplacedbymoremodernsynthetIcanalogues.
d-Tubocurarine
ThedoseofdtubocurarInerequIredtoproduce95twItchblockofattheadductorpollIcIs
muscle,orE0
95
,Is0.5mg/kg.Atthatdose,theduratIonofactIonIstypIcalofalong
duratIonagent(Table202).
47
Pharmacology
ThemoleculeundergoesmInImalmetabolIsmsothat24hoursafterItsadmInIstratIon
about10ofthecompoundIsfoundIntheurIneand45InthebIle.LIkemostother
neuromuscularblockIngdrugs,ItIsnotextensIvely(J0to50)proteInbound.ExcretIonIs
ImpaIredInrenalfaIlure.
HypotensIonfrequentlyaccompanIestheadmInIstratIonofdtubocurarIneevenatdoses
E0
95
.ThemechanIsmInvolvedIsmaInlyhIstamInerelease,andskInflushIngIsfrequently
observed.AutonomIcganglIonIcblockademayalsoplayamInorrole.
Age
PharmacokInetIcstudIeshavebeenperformedInallagegroups,andtheresultsarehelpful
InunderstandIngthebehavIorofallnondepolarIzIngagentsInpatIentsattheextremesof
age.ThepotencyofdtubocurarIneonamIllIgramperkIlogrambasIsdoesnotvarygreatly
wIthage.nfantsdemonstrategreaterblockadethanolderchIldrenoradultsIfthesame
concentratIonofdtubocurarIneIsapplIed.However,InfantshaveanIncreasedvolumeof
dIstrIbutIon,whenexpressedInmIllIlItersperkIlogramofbodyweIght,sothatthesame
mIllIgramperkIlogramdoseproducesareducedconcentratIon.TheneteffetIssImIlar
blockadeafteragIvenmIllIgramperkIlogramdoseInInfants,olderchIldren,andadults
(Table20J).
48
ThIsphenomenonhasalsobeenobservedwIthotherneuromuscularblockIng
agents.However,thedecreasedglomerularfIltratIonrateIntheveryyoungandthevery
oldresultsInanIncreasedelImInatIonhalflIfeandprolongedduratIonofactIon.
48
The
onsetofactIonIsmorerapIdIntheyoungasaresultofamorerapIdcIrculatIontIme.
Burns
PatIentswIthmassIveburnsdemonstrateresIstancetodtubocurarIneandother
nondepolarIzIngdrugsthatdependsonthesIzeoftheburnandthetImesInceInjury.
49
HIgherconcentratIonsofthefreedrugarerequIredtoproduceagIvendegreeoftwItch
depressIoncomparedwIthnonthermallyInjuredpatIents.ComparedwIthnormalsubjects,
thenumberofacetylcholInereceptorsIsIncreasedInmusclesclosetothesIteofburn
Injury,butalso,toalesserextent,InmoredIstantmuscles.
50
Clinical Use
ThelongduratIonandcardIovasculareffectsofdtubocurarInehaverestrIctedItsuseand
constItutedastImulusfortheproductIonofalternatIveagents.nItIally,thIsledtothe
IntroductIonofpancuronIum,whIchreplacedthehypotensIonofdtubocurarInewIth
hypertensIonandtachycardIa.|orerecently,drugsofIntermedIateduratIon(atracurIum,
cIsatracurIum,vecuronIum,androcuronIum)wIthvIrtuallynocardIovasculareffectshave
almostelImInatedtheuseofdtubocurarIne.WhenavaIlable,dtubocurarInehasbeen
maInlyconfInedtobeusedasaprecurarIzatIon(Jmg/70kg)beforesuccInylcholIneto
reducefascIculatIonsandmusclepaIns.FocuronIumhaslargelyreplacedd-tubocurarInefor
thIsIndIcatIon.
Alcuronium
AlthoughIthasneverbeenavaIlableInNorthAmerIca,alcuronIumstIllenjoyslImIteduse
InsomecountrIes.TheE0
95
IsapproxImately0.2to0.25mg/kg.ntubatIngdosesare
usuallylImItedto0.Jmg/kgbecauseofthelongduratIonofactIon.AlthoughItwas
IntroducedasanIntermedIateduratIondrug,ItsrecoveryIndex(J7mInutes)makesIta
longactIngneuromuscularblockIngagent.
51
Atracurium
AtracurIumIsabIsquaternaryammonIumbenzylIsoquInolInecompoundofIntermedIate
duratIonofactIon.tIsdegradedvIatwometabolIcpathways.DneofthesepathwaysIs
theHofmannreactIon,anonenzymatIcdegradatIonwItharatethatIncreasesas
temperatureand/orpHIncreases.ThesecondpathwayIsnonspecIfIcesterhydrolysIs.The
enzymesInvolvedInthIsmetabolIcpathwayareagroupoftIssueesterases,whIchare
dIstInctfromplasmaoracetylcholInesterases.
52
ThesamegroupofenzymesIsInvolvedIn
thedegradatIonofesmololandremIfentanIl.thasbeenestImatedthattwothIrdsof
atracurIumIsdegradedbyesterhydrolysIsandonethIrdbyHofmannreactIon.Subjects
wIthabnormalplasmacholInesterasehaveanormalresponsetoatracurIum.
TheendproductsofthedegradatIonofatracurIumarelaudanosIneandacrylate
fragments.LaudanosInehasbeenreportedascausIngseIzuresInanImals,butatdoses
largelyexceedIngtheclInIcalrange.NodeleterIouseffectoflaudanosInehasbeen
demonstratedconclusIvelyInhumans.
52
LaudanosIneIsexcretedbythekIdney.Acrylates
havebeenshowntoInhIbIthumancellprolIferatIonInvItro.
5J
However,the
concentratIonsandexposuretImesrequIredtoobtaInthIseffectaremuchgreaterthan
whatIsobtaInednormallyInclInIcalpractIce.
Pharmacology
AtracurIumIsanIntermedIateduratIondrug,wIthatermInalhalflIfeofapproxImately20
mInutes.TermInatIonofeffectoccursdurIngtheelImInatIonphaseofthedrug.0uratIonof
actIondoesnotdependonage,renalfunctIon,orhepatIcfunctIon.
TheE0
95
ofatracurIumIs0.2to0.25mg/kg.TheonsetofactIon(Jto5mInutesat2E0
95
)
ofequIpotentdosesIssImIlarforatracurIum,pancuronIum,dtubocurarIne,and
vecuronIum.tIsslowerthansuccInylcholIne.AswIthanyneuromuscularblockIngagent,
onsetofatracurIumcanbeshortenedIfthedoseIsIncreased,butItIsnotrecommendedto
exceed0.5mg/kgbecauseofhypotensIonandhIstamInerelease.TheduratIonofactIonIs
alsodoserelated.ThetImeto25fIrsttwItchrecoveryafter0.5mg/kgIsapproxImately
J0to40mInutes.
LIkedtubocurarIne,atracurIumreleaseshIstamIneInadoserelatedmanner.flargedoses
(0.5mg/kg)areadmInIstered,hypotensIon,tachycardIa,andskInflushIngarefrequent
manIfestatIons.8ronchospasmmayalsooccur.TheseresponsescanbeavoIdedbyslow
InjectIonofatracurIumover1toJmInutesorbypretreatmentwIthH
1
andH
2
receptor
blockade.ThIshIstamInerelease,whIchoccursInvIrtuallyeverysubjectgIvenalarge
enoughdose,shouldnotbeconfusedwIthananaphylactIcreactIon,whIchIsobserved
IrrespectIveofdoseInasmallnumberofIndIvIduals.AnaphylactIcreactIonstoatracurIum
havebeendescrIbed,buttheydonotappeartobemorefrequentthanafterother
neuromuscularblockIngdrugs.
27
P.510
Special Situations
0osagerequIrementsaresImIlarIntheelderly,youngeradults,andchIldren,presumably
reflectIngtheorganIndependenceofatracurIum'selImInatIon.SImIlarly,nodosage
adjustmentIsrequIredInIndIvIdualswIthrenalorhepatIcfaIlure.AswIthother
nondepolarIzIngagents,thedosemustbeIncreasedInburnpatIents,partlybecauseof
IncreasedproteInbIndIngandpartlybecauseofupregulatIonofreceptors,causIng
resIstanceattheendplate.ntheobesepatIent,thedoseofatracurIum,asforall
neuromuscularblockIngagents,shouldbecalculatedbasedonleanbodymass.
Clinical Uses
ToobtaInadequateIntubatIngcondItIons,relatIvelylargedosesmustbeused(0.5mg/kg),
andlaryngoscopyshouldbeattemptedonlyafter2toJmInutes.CardIovascular
manIfestatIonsofhIstamInereleaseareoftenseenatthatdose,andperfectIntubatIng
condItIonsareseenInonlyhalfthepatIents(FIg.20J).
8
ncreasIngthedosemayImprove
IntubatIngcondItIons,butattheexpenseofgreatercardIovasculareffects.ForIntubatIon,
therehasbeenatendencytoreplaceatracurIumbyagentswIthashorteronsettImeand
morecardIovascularstabIlIty,suchasrocuronIum.However,atracurIumIsconvenIentand
versatIleformaIntenanceofrelaxatIon,eItherasacontInuousInfusIon(5to10g/kg/mIn)
orasIntermIttentInjectIons(0.05to0.1mg/kgevery10to15mInutes).
Cisatracurium
nanattempttoIncreasethemargInofsafetybetweentheneuromuscularblockIngdose
andthehIstamInereleasIngdose,apotentIsomerofatracurIum,cIsatracurIum,was
IdentIfIed.LIkeatracurIum,ItscardIovasculareffectsaremanIfestonlyatdosesexceedIng
0.4mg/kg,butItsE0
95
(0.05mg/kg)Ismuchlower.Asaresult,manIfestatIonsofhIstamIne
releasearenotseenInpractIce.ThemetabolIsmofcIsatracurIumIssImIlartothatof
atracurIum,wIthHofmannandesterhydrolysIsbothplayIngarole.
52
Pharmacology
8ecausecIsatracurIumIsapotentdrug,ItsonsettImeIslongerthanthatofatracurIumand
longerstIllthanthatofrocuronIum.Forexample,equIpotentdosesofcIsatracurIum(0.092
mg/kg)androcuronIum(0.72mg/kg)hadonsettImesof4mInutesand1.7mInutes,
respectIvely.
54
TheelImInatIonhalflIfe(22to25mInutes)IssImIlartothatof
atracurIum,
55
sotheduratIonofactIonfor2E0
95
doses(0.1mg/kg)IsJ0to45mInutes.
However,Inanattempttoaccelerateonset,therecommendedIntubatIngdoseIs
Increasedto0.15mg/kg.ThIsdoseIswellbelowthethresholdforhIstamInerelease,but
theduratIonofactIonIsprolongedto45to60mInutes.
8ecausethedosesrequIredtoobtaInparalysIsareconsIderablylessforcIsatracurIumthan
foratracurIum,lesslaudanosIneandlessacrylatebyproductsareproduced.
52,5J
Thus,the
concernsraIsedbythepotentIaltoxIceffectsofthesemetabolItesarevIrtuallyelImInated.
Special Situations
LIkeatracurIum,thereIsnoneedtoadjustdosageIntheelderly,chIldren,orInfants,when
comparedwIthyoungadults.TheexperIenceInburnpatIentsIslImIted,butthesame
prIncIplesthatarevalIdforatracurIumareexpectedtoapply.nobeseIndIvIduals,the
doseofcIsatracurIumshouldbecalculatedonthebasIsofIdealbodyweIght.
56
Side Effects
ncontrasttoatracurIum,cIsatracurIumIsdevoIdofhIstamInereleasIngpropertIeseven
athIghdoses(8E0
95
).tIsalsodevoIdofcardIovasculareffects.However,anaphylactIc
reactIonshavebeendescrIbed.
27
Clinical Use
CIsatracurIummaybeusedtofacIlItatetrachealIntubatIonatdosesequIvalenttoJto4
tImestheE0
95
(0.15to0.2mg/kg)whenmanualventIlatIonIspossIbleafterInductIonof
anesthesIaandwhentheduratIonoftheprocedureIsexpectedtoexceed1hour.0uratIon
IsshorterwIthlowerdoses,butonsettImeIsprolongedandIntubatIngcondItIonsareless
Ideal.NeuromuscularblockadeIseasIlymaIntaInedatastablelevelbycontInuous
IntravenousInfusIonofcIsatracurIum(1to2g/kg/mIn)ataconstantrateanddoesnot
changewIthtIme,suggestIngthelackofasIgnIfIcantcumulatIvedrugeffectandlackof
dependenceonrenaland/orhepatIcclearancemechanIsms.
57
TherateofrecoveryIs
IndependentofthedoseofcIsatracurIumandtheduratIonoftheadmInIstratIon.
8ecausecIsatracurIumdoesnotdependonendorganfunctIonforItselImInatIon,thedrug
appearssuItableforadmInIstratIonIntheIntensIvecareunIt(CU).TheInfusIonratesto
keeppatIentsparalyzedaregreaterthanIntheoperatIngroom(typIcally5g/kg/mIn),
wIthwIdeInterIndIvIdualvarIabIlIty.
58
tIslIkelythatprolongedexposureofthereceptors
toaneuromuscularblockIngagentcausessomeupregulatIon,wIthacorrespondIng
requIrementforahIgherdose.
49
Doxacurium
0oxacurIumIsapotent,longactIngbenzylIsoquInolInecompoundthatIsnotdegradedby
HofmannelImInatIonoresterhydrolysIs.thasaprolongedelImInatIonhalflIfe(1to2
hours)anddependsonthekIdneyandthelIverforItsdIsposItIon.Thus,duratIonofactIon
IsprolongedIntheelderlyandInsubjectswIthImpaIredrenalorhepatIcfunctIon.The
E0
95
fordoxacurIumIs25g/kg(Table202).
59
0oxacurIumhasalImItedplaceInclInIcal
practIcebecauseofItsveryslowonsetandlongduratIonofactIon.Nevertheless,Its
cardIovascularstabIlItymaybeusefulInpatIentswIthIschemIcheartdIseasewhoare
undergoIngprolongedanesthesIaorlongtermmechanIcalventIlatIonofthelungs.tIs
unsuItableforfacIlItatIngtrachealIntubatIonorforprovIdIngskeletalmusclerelaxatIon
durIngbrIefsurgIcalprocedures.WhenInfusedforseveraldaystopatIentsIntheCU,
recoveryafterstoppIngtheInfusIonexceeded10hours.
Gallamine
CallamInewasIntroducedIn1948andhasonlyhIstorIcalInterest.tIsalowpotency
nondepolarIzIngdrug(E0
95
=2mg/kg)wIthalongduratIonofactIon.CallamIneproduces
sIgnIfIcanttachycardIabecauseofavagolytIceffect,evenatdosesassocIatedwIth
IncompleteblockadeattheadductorpollIcIsmuscle.tIseffectIvewhenusedtoprevent
succInylcholIneInducedfascIculatIons.
20
Gantacurium
CantacurIumIsanewcompound,stIllunderInvestIgatIon.tIsanondepolarIzIngdrugand
belongstotheclassofasymmetrIcmIxedonIumchlorofumarates.tsmaIndegradatIon
pathwayInvolvescysteIneIntheplasmaandIsIndependentofplasmacholInesterase.The
E0
95
InhumansIsapproxImately0.19mg/kg.
60
CardIovasculareffectsareobservedatdoses
exceedIngJE0
95
,andaremostprobablyrelatedtohIstamInerelease.Atdoses
antIcIpatedtoberequIredfortrachealIntubatIon(0.4to0.6mg/kg),onsetattheadductor
pollIcIsmuscleIs1.5mInutesandduratIonto25T
1
recoveryIs8to10mInutes,
comparablewIththatofsuccInylcholIne.
Metocurine
|etocurIne,producedbymethylatIonoftwohydroxygroupsofdtubocurarIne,IstwIceas
potentastheparentcompound
P.511
andproduceslesshIstamInerelease.tsE0
95
IsapproxImately0.Jmg/kg.
47
tsduratIonof
actIonIscomparablewIththatofdtubocurarIne,makIngItalongactIngagent.
|etocurIneenjoyedabrIefperIodofpopularItybeforetheIntroductIonofatracurIumand
vecuronIum.|etocurIneandpancuronIumcombInedwerefoundtobesynergIstIcwIth
opposIngcardIovasculareffects,andthemIxturewasrecommendedforuseInpatIents
wIthseverecardIovasculardIsease.However,theIntroductIonofshorterduratIon
alternatIveswIthoutcardIovasculareffectshasmademetocurIneobsolete.
Mivacurium
|IvacurIumIsabenzylIsoquInolInederIvatIvewIthashortduratIonofactIonthatIs
hydrolyzedbyplasmacholInesterase,lIkesuccInylcholIne.
61
ContrarytosuccInylcholIne,
however,mIvacurIumproducesnondepolarIzIngblockade.ThedrugIspresentedasa
mIxtureofthreeIsomers.Two,thecIstransandtranstrans,haveshorthalflIves,butthe
cIscIsIsomerhasamuchlongerhalflIfe(Table20J).ThepharmacologyofmIvacurIumIs
governedlargelybythebehavIorofthetranstransandcIstransIsomers,becausethecIs
cIsIsomeraccountsforonly6ofthemIxtureandhaslesspotentthattheothertwo
Isomers.
Pharmacology
TheE0
95
ofmIvacurIumhasbeenestImatedIntherange0.08to0.15mg/kg(Table202).
ntubatIngdosesare0.2or0.25mg/kgbutIntubatIngcondItIonsarenotasgoodaswIth
succInylcholIne.
62
DnsettImeIssurprIsInglylongforadrugwhoseactIveIsomershavea
termInalhalflIfeof2mInutes.At2toJE0
95
,twItchdIsappearsIn2.5to4mInutes.
61
ThIslongonsettImeIsprobablytheresultofthehIghpotencyofmIvacurIum.
46
Fecovery
to25doesnotdependheavIlyondose,beIngIntherangeof15to25mInutesfordosesof
0.15to0.25mg/kg.TheInfusIonratetomaIntaInblockadeconstantdoesnotvarywIth
tIme,andrecoveryIsasrapIdaftermanyhoursofInfusIonthanafterabolusdose.
61
Side Effects
LIkeatracurIum,mIvacurIumreleaseshIstamIneInadoserelatedfashIon.HypotensIon,
tachycardIa,andcutaneoussIgns,suchaserythemaandflushIng,areseenfrequentlywhen
dosesareIncreasedto0.2mg/kgormore.ThesehIstamInerelatedeffectsareshortlIved
(2toJmInutes)andshouldnotnormallybeconsIderedamanIfestatIonofanaphylaxIs,
whIchIsarareevent.8ronchospasmIsrare.|anIfestatIonsofhIstamInereleasemaybe
decreasedIfthedrugIseIthergIvenslowly(InJ0seconds)orIndIvIdeddoses(0.15mg/kg
followedJ0secondslaterby0.1mg/kg).
Special Situations
nInfantsandchIldrentheE0
95
IsapproxImatelythesameasInadults,butonsetofblock
andrecoveryaremorerapId.
6J
CardIovasculareffectsarenotasImportantasInadults,so
dosesupto0.Jmg/kghavebeenused.TheInfusIonraterequIredtomaIntaInblockadeIs
greaterInchIldrenthanInadults,andlessIntheelderlythanInyoungeradults.
Burns
nburnpatIents,upregulatIonofthereceptors,andtoalesserextentIncreasedproteIn
bIndIng,causesaresIstancetoallnondepolarIzIngneuromuscularblockIngagents.
However,formIvacurIum,thesItuatIonIsdIfferentbecauseplasmacholInesteraseactIvIty
IsdecreasedInburnpatIents.TheneteffectIseItheranormalorevenanenhancedeffect
ofusualdoses.
64
Reversal
AdmInIstratIonofantIcholInesteraseagentsaftermIvacurIumhasbeencontroversIal.
NeostIgmInehastwoopposIngeffectsonmIvacurIum:ItInhIbItsplasmacholInesterase,
thusInterferIngwIththebreakdownofmIvacurIum,butItalsoreversesnondepolarIzIng
blockade.nfact,neostIgmInehasbeenshowntodelayrecoveryIfgIvendurIngIntense
mIvacurIumneuromuscularblock,
65
buttoacceleraterecoveryIfsIgnsofspontaneous
recoveryarepresent(twotwItchesormorepresent).EdrophonIumdoesnotInterferewIth
plasmacholInesteraseactIvItyandwasfoundtoacceleraterecovery,evenwhengIven
whenblockadeIsprofound(onetwItchInthetraInoffour).
65
|IvacurIumreversalhas
beensuggestedtobeunnecessarybecausespontaneousrecoveryIsrapId.However,
resIdualblockmaybeseen,partIcularlyIflargedosesofmIvacurIumareuseduptothe
endofanesthesIa.
Plasma Cholinesterase
|IvacurIumIsmetabolIzedbyplasmacholInesterasesomewhatmoreslowlythan
succInylcholIne.ThecondItIonsassocIatedwIthadecreaseplasmacholInesteraseactIvIty
knowntoaffectsuccInylcholInemetabolIsmalsoaltermIvacurIumduratIonofactIon.
Clinical Use
|IvacurIumIsnolongeravaIlableInNorthAmerIca,butItIsusedInotherpartsofthe
world.tIswellsuItedtosurgIcalproceduresrequIrIngbrIefmusclerelaxatIon,partIcularly
thoseInwhIchrapIdrecoveryIsrequIred,suchasambulatoryandlaparoscopIcsurgery.
However,ItIsnotrecommendedforrapIdsequenceInductIon.CardIovasculareffectsmay
beavoIdedbyadmInIsterIngthedrugslowlyorbysplIttIngthedoseIntotwoInjectIonsJ0
secondsapart.SmalldosesofmIvacurIum(0.04to0.08mg/kg)havebeensuggestedto
facIlItateInsertIonofalaryngealmaskaIrway.CondItIonsandsuccessrateareusually
betterthanIntheabsenceofneuromuscularblockIngagent.|aIntenanceofrelaxatIonIs
accomplIshedmoreeasIlybyconstantInfusIon(5to7g/kg/mInInyoungandmIddleaged
adults)thanbyIntermIttentbolusInjectIon.ThIsInfusIonratehastobeIncreasedIn
chIldrenandreducedIntheelderly.nchIldren,mIvacurIumhasafasteronsetofactIon
andmorerapIdrecoverythanInadults,sothedrugcanbeusedforIntubatIonand
maIntenanceofrelaxatIonforshortprocedures.
6J
Pancuronium
PancuronIumbelongstoaserIesofbIsquaternaryamInosteroIdcompounds.tIs
metabolIzedtoaJDHcompound,whIchhasonehalftheneuromuscularblockIngactIvIty
oftheparentcompound.TheE0
95
ofpancuronIumIs0.07mg/kg.TheduratIonofactIonIs
long,beIng1.5to2hoursaftera0.15mg/kgdose.ClearanceIsdecreasedInrenaland
hepatIcfaIlure,demonstratIngthatexcretIondependsonbothorgans.TheonsetofactIon
IsmorerapIdInInfantsandchIldrenthanInadults,andrecoveryIsslowerIntheelderly.
PancuronIumIsassocIatedwIthIncreasesInheartrate,bloodpressure,andcardIacoutput,
partIcularlyafterlargedoses(2E0
95
).ThecauseIsuncertaInbutIncludesavagolytIc
effectatthepostganglIonIcnervetermInal,asympathomImetIceffectasaresultof
blockIngofmuscarInIcreceptorsthatnormallyexertsomebrakIngonganglIonIc
transmIssIon,andanIncreaseIncatecholamInerelease.PancuronIumdoesnotrelease
hIstamIne.
Clinical Use
TheslowonsetofactIonofpancuronIumlImItsItsusefulnessInfacIlItatIngtracheal
IntubatIon.AdmInIstratIonIndIvIdeddoses,wIthasmalldosegIvenJmInutesbefore
InductIonofanesthesIa(prImIngprIncIple),producesasmallbutmeasurableacceleratIon.
However,theIntermedIateactIngcompoundsaremoresuItablewhensuccInylcholIneIs
contraIndIcated.ncardIacanesthesIa,pancuronIumhasenjoyedpopularItybecauseIt
counteractsthebradycardIceffectofhIghdosesofopIoIds.WIththeIncreasedtendency
toward
P.512
earlyextubatIonIncardIacsurgery,theapproprIatenessofpancuronIumInthIssettIng
mustbereevaluated.TheuseofpancuronIumInsteadofrocuronIumIsassocIatedwItha
greaterIncIdenceofmuscularweaknessaftercardIacsurgery,
66
andreversalInthIssettIng
shouldbeconsIderedserIously.ThecontInuedpopularItyofpancuronIumrelatestocost:
generIcpancuronIumIscheaperthanothernondepolarIzIngrelaxants.nnoncardIac
patIents,ItsuseIsassocIatedwIthahIghIncIdenceofresIdualblockInthepostanesthesIa
careunIt,evenwhenreversalIsgIven(Table201).
9,67
PancuronIumneuromuscularblock
IsmoredIffIculttoreversethanthatoftheIntermedIateduratIonagents.
68
Pipecuronium
PIpecuronIumwasdevelopedInanefforttoobtaInapancuronIumwIthoutcardIovascular
sIdeeffects.tsE0
95
IsslIghtlyless(0.05mg/kg)thanthatofpancuronIum,andItIs
vIrtuallywIthoutanycardIovasculareffects.However,pIpecuronIumsoonbecameobsolete
becauseIthadthedrawbacksoflongactIngagents(dIffIcultytoreverse,resIdualparalysIs,
lackofversatIlIty),andtheabsenceofcardIovasculareffectswasalsoseenwIththe
shorteractIngvecuronIumandrocuronIum.
Rapacuronium
FapacuronIumIsalsoanamInosteroIdcompoundthatwasIntroducedforclInIcaluseIn
1999.twaswIthdrawnIn2001becauseofrare,butsevere,casesofbronchospasmafter
IntubatIon.8eInglesspotentthanrocuronIum,IthadamorerapIdonsetofactIon.
FollowIng1.5mg/kg,goodtoexcellentIntubatIoncondItIonswereproducedat60seconds,
meanclInIcalduratIonwas17mInutes,andspontaneousrecoverytotraInoffourratIoof
0.7occurredInJ5mInutes.
69
TheIntubatIngcondItIonswerenotasgoodaswIth
succInylcholIneandtheduratIonofactIonwaslonger.FapacuronIumIsmetabolIzedtoan
actIve17DHderIvatIve(DFC9488)thathastwIcetheneuromuscularblockIngactIvItyof
theparentcompoundandIsexcretedslowlyvIathekIdneys.
FapacuronIumproducedmIlddoserelatedtachycardIaandhypotensIon.ncreasesIn
aIrwaypressureandbronchospasmwereobservedInmorepatIentsgIvenrapacuronIum
thansuccInylcholIne.
69
ThemechanIsmforthIseffectIsnotanallergIcorhIstamIne
relatedreactIon,butIsmostlIkelyrelatedtotheeffectofrapacuronIumon|2and|J
muscarInIcreceptorsInthelung.ActIvatIonofthepostsynaptIc|Jreceptorsby
acetylcholIneproducesbronchosconstrIctIonInthelungs,andtheeffectIstermInatedby
presynaptIc|2receptorsthatcounteractthIseffect.FapacuronIumhasthepotentIalto
blockbothreceptors,butIthasagreateraffInItyforthe|2receptor.TheconcentratIons
requIredfor|2blockadearewellwIthIntheclInIcalrange,whIlemuchmoreIsrequIred
for|JInhIbItIon.TheneteffectIsthatIf|2receptorsareblockedselectIvely,for
example,InsusceptIbleIndIvIduals,bronchoconstrIctIonbyactIvatIonofthe|Jreceptors
Isunopposed.
70
DtherneuromuscularblockIngagents,suchasvecuronIumand
cIsatracurIum,havesImIlardIfferentIaleffectsonthe|2and|Jreceptors,butat
concentratIonshIgherthanencounteredclInIcally.
70
Rocuronium
FocuronIumIsanamInosteroIdcompoundwIthstructuralsImIlarItywIthvecuronIumand
pancuronIum.tsduratIonofactIonIscomparablewIththatofvecuronIum,butItsonsetIs
shorter.
Pharmacology
PlasmaconcentratIonsofrocuronIumdecreaserapIdlyafterbolusInjectIonbecauseof
hepatIcuptake.
71
Thus,theduratIonofactIonofthedrugIsdetermInedchIeflyby
redIstrIbutIon,ratherthanbyItsratherlongtermInalelImInatIonhalflIfe(1to2hours;
FIg.2010).|etabolIsmto17deacetylrocuronIumIsaverymInorelImInatIonpathway.
|ostofthedrugIsexcretedunchangedIntheurIne,bIle,orfeces.
71
WIthanE0
95
of0.Jmg/kg,rocuronIumhasonesIxththepotencyofvecuronIum,amore
rapIdonset,butasImIlarduratIonofactIonandsImIlarpharmacokInetIcbehavIor.WIth
equIpotentdoses,rocuronIumonsetattheadductorpollIcIsmuscleIsmuchfasterthan
thatofcIsatracurIum,atracurIum,andvecuronIum(FIg.2011).
46
Afterdosesof0.6mg/kg
(2E0
95
)maxImalblockoccursIn1.5to2mInutes.namultIcenterstudyofJ49patIents,
IntubatIngcondItIonsat60secondsafter0.6mg/kgrocuronIumweregoodtoexcellentIn
77ofcases.ToobtaInresultssImIlartothoseafter1mg/kgsuccInylcholIne,thedoseof
rocuronIumhadtobeIncreasedto1.0mg/kg,whIchprovIded92goodorexcellent
condItIons.
72
However,theduratIonofactIonIslongerthanforsuccInylcholIne,rangIng
betweenJ0and40mInutesfora0.6mg/kgdosetoapproxImately60mInutesafter1mg/kg
Inadults.Thus,rocuronIumIsanIntermedIateduratIondrug.
AsforothernondepolarIzIngagents,theonsetofactIonofrocuronIumIsmorerapIdatthe
dIaphragmandadductorlaryngealmusclesthanattheadductorpollIcIsmuscle,
7J
probably
aresultofagreaterbloodflowtocentrallylocatedmuscles.Laryngealadductormuscles
areImportantInanesthesIabecausetheyclosethevocalcordsandInsuffIcIentrelaxatIon
preventseasypassageofthetrachealtube.LaryngealadductormusclesareresIstantto
theeffectofrocuronIum,andtheplasmaconcentratIonrequIredforequIvalentblockadeIs
greateratthelarynxthanattheadductorpollIcIsmuscle.
74
ThesameIstrueofthe
dIaphragm,whIchIsresIstanttotheeffectofrocuronIumandotherneuromuscular
blockIngagents.FecoveryIsfasteratthedIaphragmandlarynxthanattheadductor
pollIcIsmuscle.
75
NohemodynamIcchanges(bloodpressure,heartrate,orECC)wereseenInhumans,and
therewerenoIncreasesInplasmahIstamIneconcentratIonsafterdosesofupto4E0
95
(1.2mg/kg).
76
DnlyslIghthemodynamIcchangesareobserveddurIngcoronaryartery
bypasssurgery.AnaphylactIcreactIonshavebeendescrIbed,andaFrenchstudyIndIcated
thattheseeventsoccurredmorefrequentlywIthrocuronIumthanwIthother
neuromuscularblockIngagents,
27
contrarytothefIndIngsofanAustralIanstudy.
77
However,ItnowappearsthatmanyofthesereportsmIghtnotbeatrueanaphylactIc
reactIontorocuronIumbecauseupto50ofthegeneralpopulatIonshowaposItIve
IntradermalorpIcktesttothedrug.
78
Clearly,manypatIentswhowereInvestIgatedfora
possIbleanaphylactIcreactIonwerefalselylabeledallergIctothedrugbecauseofthehIgh
rateoffalseposItIvetests.tIspossIblethatoverdIagnosIshasplayedaroleInthe
relatIvelyhIghIncIdenceofrocuronIumanaphylaxIsreportedInNorway(29casesIn150,000
admInIstratIons,or1:5,000)
79
orInFrance,
27
whIlereportsfromotherNordIccountrIes
suggestamuchlowerIncIdence(7casesIn800,000admInIstratIons,or1:100,000).
79
AnotherhypothesIsthatwasputforwardrecentlyIssensItIzatIonofpatIentsbyoverthe
countercoughmedIcatIoncontaInIngpholcodIne.nastudycomparIngsubjectsfrom
Norway,wherethenumberofreportedanaphylactIccasesIshIgh,andSweden,where
thosereportsarevIrtuallynonexIstent,ItwasfoundthatalargeproportIonofNorwegIans
wassensItIzedtopholcodIne,butthIssensItIzatIondIdnotoccurInSwedes.
80
PholcodIneIs
avaIlableasanantItussIveIncoughsyrupsIncertaIncountrIeslIkeNorway,France,
reland,theUnItedKIngdom,andAustralIa.tIsnotavaIlableInSweden,0enmark,
Cermany,theUnItedStates,andCanada.ntheUnItedStates,theIncIdenceof
anaphylactIcreactIonsto
P.51J
rocuronIumandvecuronIummaybeaslowas1:1,000,000.
81
tIshypothesIzedthatcross
sensItIzatIonmayoccurbetweenpholcodIneandneuromuscularblockIngagentssuchas
rocuronIumandsuccInylcholIne.However,Itsshouldberememberedthattheroleof
pholcodIneInthecontextremaInsahypothesIs,andtheIncIdenceofanaphylactIc
reactIonstorocuronIumremaInsverylow,evenIncountrIeswherepholcodIneIsavaIlable.
Thus,currentevIdencesuggeststhatwIthholdIngrocuronIumbecauseofthefearof
anaphylactIcreactIonsIsunjustIfIed.
Special Situations
ThepotencyofrocuronIumhasbeenreportedtobeslIghtlygreaterInwomenthanInmen,
theE0
95
beIng0.27and0.J9mg/kg,respectIvely,wIthanIncreasedduratIonInwomen.
82
SomeethnIcgroupsaremoresensItIvetothedrug.ChInesesubjectslIvIngIn7ancouver
werefoundtobemoresensItIvethanwhItes.
8J
AswIthothernondepolarIzIngdrugs,
potencyhasbeenreportedtovaryaccordIngtogeographIcaldIstrIbutIon.|oststudIes
reportedagreaterpotencyInNorthAmerIcacomparedwIthEurope,
84
wIthonereport
showIngapotencyofrocuronIumInmaInlandChInaasIntermedIatebetweenEuropeanand
AmerIcanvalues.
84
ChIldren(2to12yearsold)requIremorerocuronIumandduratIonof
actIonIsless.DnsetofactIonIsshorterInthepedIatrIcthanIntheadultpopulatIon.For
example,adoseof1.2mg/kgprovIdesanonsettIme(J9seconds)comparablewIththatof
succInylcholIne,2mg/kg,andmeanduratIonofactIonIs41mInutes.
85
Thus,the
recommendeddosesare0.9to1.2mg/kgInthIsagegroup.FocuronIumIsmorepotentIn
InfantsthanInolderchIldren.0osesof0.6mg/kghavealongerduratIonInneonates(1
month)thanInInfants(5to12months),soareduceddosage(0.45mg/kg)Is
recommended.
86
FocuronIummaybeusedforrapIdsequenceInductIonassuccInylcholIne
IsrelatIvelycontraIndIcatedbecauseofthepossIblepresenceofundIagnosedmuscle
dystrophyInpedIatrIcpatIents,especIallyInboys.
J4
TheuseofrocuronIumInlargedoses
(1.2mg/kg)mIghtbecomewIdespreadInallagegroupsforrapIdsequenceInductIonIfand
whentheselectIvebIndIngagentsugammadexbecomesavaIlable(seeSugammadex).
nelderlypatIents,theE0
95
IssImIlartothatfoundInyoungeradults,buttheduratIonof
actIonIsprolongedslIghtly.
87
FocuronIumhasanIncreasedtermInalhalflIfeInrenal
faIlurepatIents,probablybecauseofItspartIalrenalelImInatIon,butthIstranslatesInto
verymInor,Ifany,prolongatIonofblock.
88
nhepatIcdIsease,thesloweruptakeand
elImInatIonofrocuronIumbythelIvertendstoprolongtheduratIonofactIonofthedrug,
butthIsIscompensatedtosomeextentbythelargervolumeofdIstrIbutIon.
89
Clinical Use
TherapIdonsetandIntermedIateduratIonofactIonmakesthIsagentapotentIal
replacementforsuccInylcholIneIncondItIonswhererapIdtrachealIntubatIonIsIndIcated.
However,largedoses(1mg/kg)arerequIred,wIththedrawbackbeIngaprolonged
duratIonofactIon.ContrarytosuccInylcholIne,theoptIontowaItforspontaneous
breathIngtoresumebeforehypoxIaIsmanIfestdoesnotexIstwIthrocuronIum.Toshorten
theonsettIme,theprImIngprIncIple,whIchInvolvestheadmInIstratIonofasmalldose
ofrocuronIumusuallyJmInutesbeforeInductIon,hasbeenadvocated.Unfortunately,the
optImalprImIngdose,thatIsthelargestdosethatwIllnotproducesymptomsofweakness
IntheawakepatIent,Israthersmall.AswIthdefascIculatIngdosesbeforesuccInylcholIne,
ItIsnotrecommendedtoadmInIstermorethan0.1E0
95,
28
whIch,Inthecaseof
rocuronIum,amountsto0.0Jmg/kg.SuchasmalldosehasmInImaleffectsononsettImes
provIdedbymuchlargerdoses(0.6to1.0mg/kg).However,prImIngmIghthaveaneffectIf
theIntubatIngdoseIssmall(0.45mg/kg).AtImIngprIncIplehasbeendescrIbedInwhIch
0.6mg/kgrocuronIumIsgIvenbeforetheInductIonagent,whIchIsadmInIsteredatthe
onsetofptosIs.ConsIderIngthatlossofconscIousnessdoesnotoccurImmedIatelyafter
InjectIonoftheInductIonagent,thIstechnIqueIsnotrecommended.FocuronIumand
thIopentaldonotmIx.TheyformaprecIpItatewhentheyareInthesameIntravenouslIne.
fthIopentalIsusedforInductIonofanesthesIa,thelInemustbeflushedcarefullybefore
rocuronIumIsgIven.
FocuronIumhasgraduallyreplacedvecuronIumasanIntermedIateduratIonrelaxant
becauseofItsmorerapIdonset.nItIaldosesof0.6mg/kgIntravenouslywIllusually
producegoodIntubatIngcondItIonswIthIn90seconds.0uratIonofactIonIsJ0to40
mInutes.Smallerdoses(typIcally,0.45mg/kg)haveashorterduratIonofactIon,buttIme
toIntubatIonmustbeIncreased.Subsequentdosesof0.1to0.2mg/kgwIllprovIdeclInIcal
relaxatIonfor10to20mInutes.AlternatIvely,rocuronIummIghtbegIvenbycontInued
InfusIon,tItratedwIththehelpofanervestImulator.nfusIonratesareIntherange5to10
g/kg/mIn.
57
FecoveryafterInfusIonsIsslowerthanafterbolusdoses.
Vecuronium
7ecuronIumIsanIntermedIateduratIonamInosteroIdneuromuscularrelaxantwIthout
cardIovasculareffects.tsE0
95
Is0.04to0.05mg/kg.tsduratIonandrecovery
characterIstIcsarecomparablewIththoseofrocuronIum.However,ItsonsetofactIonIs
slower.
Pharmacology
7ecuronIumIsamonoquaternaryammonIumcompoundproducedbydemethylatIonofthe
pancuronIummolecule.7ecuronIumundergoesspontaneousdeacetylatIontoproduceJDH,
17DH,andJ,17(DH)
2
metabolItes.ThemostpotentofthesemetabolItes,JDH
vecuronIum,about60oftheactIvItyofvecuronIum,IsexcretedbythekIdneyandmaybe
responsIble,Inpart,forprolongedparalysIsInpatIentsIntheCU.LIkerocuronIum,
vecuronIumhasbeenfoundlesspotentandwIthashorterduratIonofactIonInmenthanIn
women,probablybecauseofagreatervolumeofdIstrIbutIonInmen.
0uratIonofactIonofvecuronIum,lIkethatofrocuronIum,IsgovernedbyredIstrIbutIon,
notbyelImInatIon(FIg.2010).AttemptshavebeenmadetospeedtheonsetofactIonby
usIngtheprImIngprIncIple,thatIs,byadmInIsterIngasmall,subparalyzIngdoseseveral
mInutesbeforetheprIncIpaldoseIsgIven.WIththeavaIlabIlItyofrocuronIum,whIchhasa
morerapIdonsetofactIonthanthatofvecuronIum,prImIngbecomesanobsolete
practIce.
7ecuronIumusuallyproducesnocardIovasculareffectswIthclInIcaldoses.tdoesnot
InducehIstamInerelease.8radycardIahasbeendescrIbedwIthhIghdoseopIoIdanesthesIa,
andthIsmIghtbethereflectIonoftheopIoIdeffect.AllergIcreactIonshavebeen
descrIbed,butnomorefrequentlythanaftertheuseofotherneuromuscularblockIng
drugs.
27,81
Clinical Use
ThecardIovascularneutralItyandIntermedIateduratIonofactIonmakevecuronIuma
suItableagentforuseInpatIentswIthIschemIcheartdIseaseorthoseundergoIngshort,
ambulatorysurgery.AswIthrocuronIum,careshouldbetakenwhenvecuronIumIs
admInIsteredImmedIatelyafterthIopentalbecauseaprecIpItateofbarbIturIcacIdmaybe
formedthatmayobstructtheIntravenouscannula.
Largedoses(0.1to0.2mg/kg)canbeusedtofacIlItatetrachealIntubatIonInsteadof
succInylcholIne.FormaIntenanceofrelaxatIon,vecuronIummaybegIvenusIng
IntermIttentboluses,0.01to0.02mg/kg,orbycontInuousInfusIonatarateof1to2
g/kg/mIn.However,therateofspontaneousrecoveryofneuromuscularfunctIonIs
slowerafteradmInIstratIon
P.514
byInfusIonthanbyIntermIttentboluses.
90
7ecuronIumhasnowlargelybeenreplacedby
themorerapIdrocuronIum.
Drug Interactions
nteractIonsbetweenneuromuscularblockIngdrugsandseveralanesthetIcand
nonanesthetIcdrugshavebeensuggested.AlthoughsomeInteractIonshavebeen
confIrmed,manyremaInasIsolatedcasereportsortheoretIcalpossIbIlItIes.Dnlysomeof
themostclInIcallyrelevantInteractIonswIllbedIscussedhere.
Anesthetic Agents
Inhalational Agents
TheanesthetIcvaporspotentIateneuromuscularblockadeInadoserelatedfashIon.
StudIesattemptIngtoquantIfythemagnItudeofthIseffecthaveledtoconflIctIngresults
becausethetImefactorIsalsoImportant.Theolderhalogenatedagentshalothane,
enflurane,andIsofluranemaytake2hoursormoretoequIlIbratewIthmuscle,soIn
practIcethepotentIatIngeffectofthesevaporsmIghtnotbeImmedIatelyapparent.At
sImIlarmInImumalveolarconcentratIon(|AC),enfluraneappearstopotentIate
nondepolarIzIngblockademorethandoesIsoflurane,whIchInturnpotentIatestoagreater
extentthanhalothane.TheneweragentssevofluraneanddesfluraneequIlIbratemore
rapIdlywIthmuscle,buttheeffectmaybemeasurableonlyafterJ0mInutesormore.For
example,theduratIonofactIonofabolusdoseofmIvacurIumgIvenatInductIonof
anesthesIaIsnotalteredbythepresenceofsevoflurane(1|AC).However,theInfusIon
raterequIredtomaIntaInblockdecreasesby75overthenext1.5hours,comparedwIth
nochangeunderpropofolanesthesIa.
91
ThedegreeofpotentIatIonIncreaseswIththe
concentratIonofsevoflurane.FecoveryrateIslongerInthepresenceofsevoflurane,even
IftheInfusIonrateofmIvacurIumwasless.ThereIsevIdencethatdesfluranemIghthavea
greaterpotentIatIngeffectontheneuromuscularjunctIonthansevoflurane.
92
NItrousoxIde(70InspIred)hasbeenconsIderedashavIngnoeffectonneuromuscular
blockade.FecentevIdencesuggeststhatthepresenceofnItrousoxIdehasaslIght
potentIatIngeffectonneuromuscularblock,decreasIngtheE0
50
ofrocuronIumby
approxImately20.
9J
ThemechanIsmofactIonofpotentIatIonbyhalogenatedagentsIsuncertaIn,butItappears
thattheyproducetheIreffectsattheneuromuscularjunctIon.sofluraneandsevoflurane
InhIbItcurrentthroughthenIcotInIcreceptorattheneuromuscularjunctIon,andthIs
InhIbItIonIsdosedependent.
94
AlthoughsomeslIghtpotentIatIonofneuromuscularblockadehasbeendemonstratedwIth
hIghdosesofmostIntravenousInductIonagentsInanImals,clInIcaldosesofdrugssuchas
mIdazolam,thIopental,propofol,fentanyl,andketamInehavelIttleornoneuromuscular
effectInhumans.
Local Anesthetics
LIdocaIne,procaIne,andotherlocalanesthetIcagentsproduceneuromuscularblockadeIn
theIrownrIghtaswellaspotentIatIngtheeffectsofdepolarIzIngandnondepolarIzIng
neuromuscularblockIngdrugs.ContrarytothefIndIngsofotherstudIes,alongerduratIon
ofactIonofvecuronIumwasfoundInpatIentsundergeneralanesthesIawIthanepIdural
catheterInjectedwIthmepIvacaIne.
95
TheexactmechanIsmsforthIsInteractIonare
uncertaIn,butItIsunlIkelythatthesystemIclevelsoflocalanesthetIcaresuffIcIentto
producethIseffectattheneuromuscularjunctIon.
Interactions Between Nondepolarizing Blocking Drugs
CombInatIonsoftwonondepolarIzIngneuromuscularblockIngdrugsareeItheraddItIveor
synergIstIc,dependIngonwhIchtwodrugsareInvolved.AddItIonoccurswhenthetotal
effectequalsthatofequIpotentdosesofeachdrug.ForInstance,pancuronIumand
vecuronIumhaveanaddItIveInteractIon.
96
AnE0
95
ofeItherpancuronIum(0.07mg/kg)or
vecuronIum(0.05mg/kg)yIelds95blockade.HalftheE0
95
ofpancuronIum(0.0J5mg/kg)
admInIsteredwIthhalftheE0
95
ofvecuronIum(0.025mg/kg)wIllalsoproduce95block.
However,somecombInatIonsaresynergIstIc;thatIs,theIrcombInedeffectIsgreaterthan
IfanequIpotentdoseofeItheroneoftheconstItuentsIsgIvenalone.Forexample,
cIsatracurIum(E0
95
=0.05mg/kg)androcuronIum(E0
95
=0.Jmg/kg)wIllproduceagreater
blockadethanequIpotentamountsofeachdruggIvenalone.fhalftheE0
95
of
cIsatracurIum(0.025mg/kg)IsadmInIsteredwIthhalftheE0
95
ofrocuronIum(0.15mg/kg),
theeffectwIllbe95twItchdepressIon.Toget95block,onlyapproxImatelyonefourth
theE0
95
ofeachdrugneedstobegIventogether;thatIs,cIsatracurIum,0.0125mg/kgwIth
rocuronIum,0.075mg/kg.
97
Cenerally,combInatIonsofchemIcallysImIlardrugsfor
example,pancuronIumvecuronIum,dtubocurarInemetocurIne,andatracurIum
mIvacurIumhaveaddItIveeffects.CombInatIonsofdIssImIlaragentstendtoshow
potentIatIon,buttheruleIsnotalwaysfollowed.ThefIrstsuchsynergIsmwas
demonstratedforpancuronIummetocurInecombInatIons,andthemIxturewasadvocated
forItslackofcardIovasculareffects.TheuseofcombInatIonsmayberecommendedto
reducecostortotakeadvantageofthepropertIesoftwodrugs.Forexample,synergIsm
occursbetweenmIvacurIumandrocuronIum,andthemIxtureretaInsthefastonsetof
rocuronIum,whIlehavIngtheshortduratIonofactIonofmIvacurIum.
ThemechanIsmbywhIchtwodrugsproduceagreatereffectthaneItheronealoneIs
uncertaIn.SynergIsmIsexpectedbetweenmIvacurIumandpancuronIumbecauseofthe
InhIbItIonofplasmacholInesterasethatpancuronIumproduces,thusaccentuatIngthe
effectofmIvacurIum.However,suchasImplemechanIsmIsabsentInmostcases.
SurprIsIngly,whendrugmIxturesareapplIedtoreceptorsInvItro,nopotentIatIonIs
observed.
98
nteractIonsofadIfferentnatureoccurwhenadmInIstratIonofanondepolarIzIngagentIs
followedbyInjectIonofanothernondepolarIzIngagent.Usually,theduratIonofactIonof
thesecondagentIsthatofthefIrstdruggIven.Forexample,IfvecuronIum,an
IntermedIateactIngagent,IsgIvenafterthelongactIngpancuronIum,Ithasalong
duratIonofactIon.
99
Dnthecontrary,IfvecuronIumIsthefIrstdrug,pancuronIumgIvenas
atopupdosehasanIntermedIateduratIonofactIon.Thus,swItchIngfromalongduratIon
agenttoanIntermedIateduratIondrugtoobtaInparalysIsofIntermedIateduratIonatthe
endofacasewIllnotprovIdeparalysIsofIntermedIateduratIon.Thereasonwhythe
characterIstIcsofthefIrstagentgIvenaredetermInantIsthatthesIzeoftheloadIngdose
IsgreaterthanthatofthemaIntenancedose,sothatevenwhentheseconddoseIsgIven,
themajorItyofreceptorsIsstIlloccupIedbythefIrstdrug.
NondepolarizingDepolarizing Interactions
0epolarIzIngandnondepolarIzIngrelaxantsaremutuallyantagonIstIc.WhendtubocurarIne
orothernondepolarIzIngagentsaregIvenbeforesuccInylcholInetopreventfascIculatIons
andmusclepaIn,thesuccInylcholIneIslesspotentandhasashorterduratIonofactIon.
22
TheexceptIonIswIthpancuronIumbecauseItInhIbItsplasmacholInesterase.However,
nondepolarIzIngdrugsaresomewhatmoreeffectIvewhenadmInIsteredaftertheeffectof
succInylcholInehaswornoff,comparedwIthnoprIorsuccInylcholIne.
17
FInally,the
responsetoasmalldoseofsuccInylcholIneattheendofananesthetIcInwhIcha
nondepolarIzIngagenthasbeenusedIs
P.515
dIffIculttopredIct.tmayeItherantagonIzeorpotentIatetheblockade,dependIngonthe
degreeofnondepolarIzIngblock.AntagonIsmIsmorelIkelyIfblockadeIsdeepand
potentIatIonIfblockadeIsshallow.fanantIcholInesteraseagenthasbeengIven,thenthe
effectofthesuccInylcholIneIspotentIatedbecauseofInhIbItIonofplasmacholInesterase.
Antibiotics
NeomycInandstreptomycInarethemostpotentoftheamInoglycosIdesIndepressIng
neuromuscularfunctIon.
100
ThepolymyxInsalsodepressneuromusculartransmIssIon.
100
TheseantIbIotIcsarenolongerusedfrequently.DtheramInoglycosIdes(e.g.,gentamIcIn,
netIlmIcIn,tobramycIn)alsopotentIatenondepolarIzIngneuromuscularblockade.They
prolongtheactIonofsteroIdalneuromuscularagents,buttheIreffecton
benzylIsoquInolInecompoundsIslessapparent.
101
ThelIncosamIdesclIndamycInand
lIncomycInhaveprejunctIonalandpostjunctIonaleffects,butprolongatIonofblockadeby
clIndamycInIsunlIkelytooccurclInIcallyunlesslargedosesareused.ThepenIcIllIns,
cephalosporIns,tetracyclInes,anderythromycInaredevoIdofneuromusculareffectsat
clInIcallyrelevantdoses.|etronIdazoledoesnotappeartohaveclInIcallysIgnIfIcant
effectsattheneuromuscularjunctIon.
Anticonvulsants
AcuteadmInIstratIonofphenytoInproducesaugmentatIonofneuromuscularblock.
102
FesIstancetopancuronIum,metocurIne,vecuronIum,androcuronIumhasbeen
demonstratedInpatIentsreceIvIngchronIcantIconvulsanttherapywIthcarbamazepIneor
phenytoIn.
10J,104
TherequIrementsforatracurIum,mIvacurIum,andcIsatracurIumarethe
sameorIncreasedslIghtlybychronIcadmInIstratIonofantIconvulsantdrugs.
105
Aleastpart
ofthephenomenonhasapharmacokInetIcorIgIn.npatIentswIthchronIccarbamazepIne
therapy,theclearanceofvecuronIumwasfoundtobeIncreasedandItstermInalhalflIfe
decreased.
10J
Cardiovascular Drugs
8etablockIngdrugsandcalcIumchannelantagonIstshavebeenfoundtohave
neuromusculareffectsInvItro,butInpractIce,theduratIonofactIonofneuromuscular
blockIngagentsIsnotalteredInpatIentstakIngthesedrugschronIcally.
104
EphedrInegIven
atInductIonofanesthesIahasbeenfoundtoaccelerateonsetofactIonofrocuronIum
whIleesmololprolongsonsettIme.
106
ThemechanIsmforthIseffectIsprobablyby
alteratIonofdrugdelIverytothesIteofactIonbychangesIncardIacoutput.tIspossIble
totakeadvantageofthIsphenomenontoImproveIntubatIngcondItIons.UseofephedrIne,
5to10mgIntheaverageadult,atInductIonhasbeenshowntoImproveIntubatIng
condItIonsprovIdedbyrocuronIum.
107
Magnesium
CalcIumIsrequIredforthereleaseofacetylcholIne,
12
andmagnesIumantagonIzesthIs
effect.ndosesofJ0mg/kgatInductIonfollowedby10mg/kg/hr,magnesIumwasfoundto
reducemaIntenancerocuronIumrequIrementsby50andtoIncreaserecoverytImes.
108
SImIlareffectshavebeenreportedwIthothernondepolarIzIngagents.PrevIous
admInIstratIonofmagnesIumabolIshessuccInylcholIneInducedfascIculatIons,butItdoes
notprolongtheduratIonofneuromuscularblockade.
109
Miscellaneous
|etoclopramIdeInhIbItsplasmacholInesteraseandthusprolongstheactIonof
succInylcholIneandmIvacurIum.nconsIstentInteractIonshavebeendescrIbedfor
dIuretIcs,dIgoxIn,andcortIcosteroIds,probablybecausethesedrugsInducechronIcfluId
andelectrolyteshIfts,themagnItudeofwhIchdependsonthecondItIonbeIngtreated.
Altered Responses to Neuromuscular Blocking Agents
Intensive Care Unit
NeuromuscularblockIngagentsareusefulIntheCUtofacIlItatemechanIcalventIlatIon,
andtheIruseIsfrequentInpatIentsrequIrIngventIlatIonIntheproneposItIon,permIssIve
hypercapnIa,hIghposItIveendexpIratorypressure,andelevatedaIrwayspressure.
110
tIs
essentIaltoprovIdesedatIontopatIentswhoreceIveparalyzIngagents,toprevent
dIscomfortassocIatedwIththeInabIlItytomove.EnthusIasmforthelIberaluseof
neuromuscularblockIngagentsIntheCUhaswanedconsIderablyoverthepast10to20
yearsbecauseofseveralreportsofcrItIcallyIllpatIentswhodemonstratedresIdual
weaknessforunexpectedlylongperIodsafterdIscontInuatIonofaneuromuscularblockIng
agent.nsome,recoverytookseveralmonths.
111
PancuronIumandvecuronIumhavebeen
usedmostfrequently,butrecentdescrIptIonsofsImIlarsyndromesafteratracurIumand
cIsatracurIumsuggestthatthefrequencyofreportsofweaknessreflectsthepopularItyof
thedrugsratherthanapartIcularassocIatIonwIthsteroIdbasedcompounds.
ElectromyographIcstudIeshaveshownvarIablelesIonsfrommyopathytoaxonal
degeneratIonofmotorandsensoryfIbers.ThepIctureIscomplIcatedbythesyndromeof
crItIcalIllnessneuropathy,whIchoccursInpatIentswIthsepsIsandmultIorganfaIlure,
evenInIndIvIdualsnotgIvenneuromuscularblockIngagents.AdmInIstratIonof
cortIcosteroIdsIsalsoconsIderedarIskfactor.
110
SymptomsIncludefaIluretoweanfrom
mechanIcalventIlatIon,lImbweakness,andImpaIreddeeptendonreflexes,butsensory
functIonIsusuallynotaffected.TherearenocontrolledclInIcalstudIestoallowthe
severalInItIatIngfactorstobeIdentIfIedandmatchedwIthpartIcularsyndromes.nthe
absenceofmoredefInItIvestudIes,ItIsrecommendedtoadmInIsterneuromuscular
blockIngagentsonlytopatIentswhocannotbemanagedotherwIse,tolImIttheduratIonof
admInIstratIontoafewdaysorless,touseonlythedosethatIsnecessary,andtoInterrupt
temporarIlytheadmInIstratIonoftheneuromuscularblockIngagenteverydayorso.
110
StudIesInCUpatIentsInwhomtheadmInIstratIonofrelaxantwasadjustedaccordIngto
strIctneuromuscularmonItorIngcrIterIahaveshownconsIderablevarIatIonInthe
requIrementforneuromuscularblockIngagenttomaIntaInthesameeffectamongpatIents
andawIdewIthInpatIentpharmacokInetIcvarIabIlIty.
58
7ecuronIumandrocuronIumhave
beenassocIatedwIthprolongedrecoverytImes.Forexample,ameanofJhourswasfound
betweentheendofrocuronIumInfusIonandatraInoffourratIoof0.7.
112
WIth
cIsatracurIum,thIsIntervalwasshorter(approxImately1hour)andlessvarIable.
58
0rug
requIrementIsvarIablefrompatIenttopatIent,IsusuallygreaterthanIntheoperatIng
room,andtendstoIncreasewIthtIme.Thesereportssuggesttheneedformorecareful
monItorIngofneuromuscularblockInCUpatIents,althoughtheoptImalmethodandlevel
ofblocktobeachIevedareuncertaIn.tIssuggestedtotItrateneuromuscularblockIng
agentstothemInImumInfusIonratethatwIlloptImIzeoxygenatIon.
Myasthenia Gravis
|yasthenIagravIsIsanautoImmunedIseaseInwhIchcIrculatIngantIbodIesproducea
functIonalreductIonInthenumberofpostsynaptIcacetylcholInereceptors.
11J
P.516
Diagnosis and Management
ThehallmarkofmyasthenIagravIsIsfatIgue.PresentatIonIsextremelyvarIedbut
typIcally,ocularsymptoms,suchasdIplopIaandptosIs,occurfIrst.8ulbarInvolvementIs
usuallyseennext.PatIentsmayproceedtohaveextremItyweaknessandrespIratory
dIffIcultIes.
11J
ThecharacterIstIcE|CfIndIngInmyasthenIagravIsIsavoltagedecrement
torepeatedstImulatIonat2to5Hz.ThIsfIndIngIsalsocharacterIstIcofnondepolarIzIng
blockadeInnonmyasthenIcIndIvIduals.EdrophonIum,2to8mg,producesbrIefrecovery
frommyasthenIagravIsandcanbeusedasadIagnostIctest.FInally,upto80ofpatIents
haveanIncreasedtIteroftheacetylcholInereceptorantIbody.
TreatmentIslargelysymptomatIc.AntIcholInesteraseagentssuchaspyrIdostIgmIneare
usedtoIncreaseneurotransmIssIonattheneuromuscularjunctIon.CortIcosteroIdsand
ImmunotherapywIthazathIoprInemIghtproducelongtermImprovement.PlasmapheresIs
mIghtbeeffectIvebyelImInatIngthecIrculatIngantIbody.FInally,manymyasthenIc
patIentshaveanassocIatedthymoma,andsurgIcalremovalofthethymusmaybe
IndIcated.
11J
Response to Neuromuscular Blocking Agents
PatIentswIthmyasthenIagravIsareusuallyresIstanttosuccInylcholIne,wIthlargerthan
usualdosesrequIredtoproducecompleteblockade.ThIseffectmIghtbeoffsetbythe
InhIbItIonofplasmacholInesteraseactIvItyprovIdedbypyrIdostIgmIne.SensItIvItyto
nondepolarIzIngneuromuscularblockIngdrugsIsIncreasedtoavarIableextent,dependIng
ontheseverItyofthedIsease.TheE0
95
ofvecuronIumwasfoundtobedecreasedbymore
thanhalfInmyasthenIcpatIents,andtheresponseoftheorbIcularIsoculImuscleIs
depressedevenmorethanthatoftheadductorpollIcIsmuscle,reflectIngsomedegreeof
ocularInvolvement.
114
Management of Anesthesia
TradItIonally,neuromuscularblockIngdrugshavebeenavoIdedInthepatIentwIth
myasthenIagravIsbytheuseofInhalatIonalvaporswIthorwIthoutlocalanesthesIa.|ore
recently,therehavebeenseveralreportsofthesuccessfuluseofsmall,tItrateddosesof
atracurIum,mIvacurIum,vecuronIum,orrocuronIum,admInIsteredundercareful
neuromuscularmonItorIng.
11J
TheeffectofreversaldrugsmIghtbelessthanexpected
becausemyasthenIcpatIentsalreadyreceIvedrugsthatproducecholInesteraseInhIbItIon.
Thus,ItIspreferabletocontInuemechanIcalventIlatIonuntIlspontaneousrecoveryIs
manIfest.
Afterthymectomy,theneedformechanIcalsupportofventIlatIoncanusuallybepredIcted
frompreoperatIvelungfunctIontests.ThedoseofantIcholInesterasesshouldbeadjusted
andIsusuallyIsreducedfor1to2daysaftersurgery.
Myotonia
|yotonIaIscharacterIzedbyanabnormaldelayInmusclerelaxatIonaftercontractIon.
SeveralformshavebeendescrIbed:myotonIcdystrophy(dystrophIamyotonIca,myotonIa
atrophIca,SteInertdIsease),myotonIacongenIta(ThomsendIsease),hyperkalemIcperIodIc
paralysIs,andparamyotonIacongenIta.
Diagnosis
FepeatednervestImulatIonleadstoagradualbutpersIstentIncreaseInmuscletensIon.
TheE|CIspathognomonIc;myotonIcafterdIschargesareseenInperIpheralmuscle,
consIstIngofrapIdburstsofpotentIalproducedbytappIngthemuscleormovIngthe
needle.TheyproducetypIcaldIvebombersoundsontheloudspeaker.
ThecharacterIstIcresponsetosuccInylcholIneIsasustaIned,doserelatedcontracturethat
maymakeventIlatIondIffIcultforseveralmInutes.|usclemembranefragIlItymaybe
responsIblefortheexaggeratedhyperkalemIathatIsproducedaftersuccInylcholIne.
J4
|ostcasereportssuggestthattheresponsetonondepolarIzIngdrugsIsnormal.However,
myotonIcresponseshavebeenobservedafterreversalwIthneostIgmIne.
Anesthesia
SuccInylcholIneIsbestavoIded.ShortorIntermedIateduratIonnondepolarIzIngagents
maybeusedInusualdoseswIthcarefulneuromuscularmonItorIng.Feversalagentsare
bestavoIded.Thus,mechanIcalventIlatIonshouldbemaIntaIneduntIltheeffectsof
nondepolarIzIngagentshavewornoffcompletely.
Muscular Dystrophy
ThemusculardystrophIesareagroupofmanydIseases,wIthvarIabIlItyInpresentatIonand
typIcalageatonsetofsymptoms.ThemostcommonoftheseIsthe0uchennetype
musculardystrophy(0|0),anXlInkedheredItarydIseasethatusuallybecomesapparentIn
chIldhood.DthertypesofmusculardystrophyInclude8ecker,lImbgIrdle,fascIohumeral,
Emery0reIfuss,nemalInerod,andoculopharyngealdystrophy.Therehavebeenseveral
reportsofcardIacarrestafteradmInIstratIonofsuccInylcholIneInchIldren,often
assocIatedwIthhyperkalemIa.FesuscItatIonwasfoundtobedIffIcult,andseveralofthese
caseswerefatal.
J4
ThemostlIkelyexplanatIonfortheseadverseeventsIsprevIously
undIagnosed,latent,musculardystrophy.
nmostcasereports,theresponsetonondepolarIzIngagents,suchasvecuronIum,
atracurIum,andmIvacurIum,hasbeendescrIbedasnormal,althoughtherehavebeen
sporadIcInstancesofIncreasedsensItIvIty.TherearelIttledataontheresponseto
antIcholInesterases.ThereIsconsIderablecontroversyoverwhether0|0patIentsare
susceptIbletomalIgnanthyperthermIa.
Anesthesia
SuccInylcholIneshouldbeavoIdedInpatIentswIthmusculardystrophy,especIallyIfonset
ofsymptomsoccurredInchIldhoodoradolescence.ThepossIbIlItyoflatentor
unrecognIzed0|0Inyoungmales(10yearsold)maybeareasontoavoIdsuccInylcholIne
InthIspatIentpopulatIon.CarefultItratIonofshortorIntermedIateduratIon
nondepolarIzIngagentsshouldbedone.Feversalagentsdonotappeartobe
contraIndIcated.
Upper Motor Neuron Lesions
PatIentswIthhemIplegIaorquadrIplegIaasaresultofcentralnervoussystemlesIonsshow
anabnormalresponsetobothdepolarIzIngandnondepolarIzIngagents.HyperkalemIaand
cardIacarresthavebeendescrIbedaftersuccInylcholIne,probablyasaresultof
extrajunctIonalreceptorprolIferatIon.HyperkalemIaIstypIcallyseenIfthedrugIsgIven
betweenfrom1weekto6monthsafterthelesIon,butmaybeseenbeforeandafterthat
perIod.
J4
ThereIsresIstancetonondepolarIzIngneuromuscularblockIngdrugsbelowthe
levelofthelesIon.nhemIplegIcpatIents,monItorIngoftheaffectedsIdeshowsthatthe
blockIslessIntenseandrecoveryIsmorerapIdthanontheunaffectedsIde.However,the
apparentlynormal
P.517
sIdealsodemonstratessomeresIstancetonondepolarIzIngdrugs.SImIlarfIndIngshave
beenreportedafterastroke,wIthagreaterresIstanceontheaffectedsIde.
Burns
AsaresultoftheprolIferatIonofextrajunctIonalreceptors,succInylcholIneproduces
severehyperkalemIaInpatIentswIthburns,andthIsmayleadtocardIacarrest.The
magnItudeoftheproblemdependsontheextentoftheInjury.tmayappearasearlyas24
to48hoursaftertheburnInjuryandusuallyendswIthhealIng.
J4
FesIstancetotheeffects
ofnondepolarIzIngneuromuscularblockIngagentsIsmanIfest,evenInmusclesthatare
apparentlynotaffectedbytheburn.
49,50
Miscellaneous
0enervatedmuscledemonstratespotassIumreleaseaftersuccInylcholIneandresIstanceto
nondepolarIzIngrelaxants.ContracturesInresponsetosuccInylcholInehavealsobeen
observedInamyotrophIclateralsclerosIsandmultIplesclerosIs.TherehavebeenIsolated
reportsofhyperkalemIaaftersuccInylcholIneInseveralneurologIcdIseases,IncludIng
FrIedrIch'sataxIa,polyneurItIs,andParkInsondIsease.
Monitoring Neuromuscular Blockade
Why Monitor?
0eeplevelsofparalysIsareusuallydesIreddurInganesthesIatofacIlItatetracheal
IntubatIonandtoobtaInanImmobIlesurgIcalfIeld.However,completereturnof
respIratoryfunctIonmustbeattaInedbeforethetracheaIsextubated.AdmInIstratIonof
neuromuscularblockIngdrugmustbeIndIvIdualIzedbecauseblockadeoccursovera
narrowrangeofreceptoroccupancy,andbecausethereIsconsIderableInterIndIvIdual
varIabIlItyInresponse.Thus,ItIsImportantfortheclInIcIantoassesstheeffectof
neuromuscularblockIngdrugswIthouttheconfoundIngInfluenceofvolatIleagents,
IntravenousanesthetIcs,andopIoIds.Dneshouldremember,however,thatmonItorIngIsa
tool,notacure.NeuromuscularblockIngagentshavethesameeffects,whetherornot
monItorIngIsused.|oststudIesfoundthatmonItorIngIsnotassocIatedwIthadecreaseIn
theIncIdenceofresIdualparalysIs.
9
TotestthefunctIonoftheneuromuscularjunctIon,a
perIpheralnerveIsstImulatedelectrIcally,andtheresponseofthemuscleIsassessed.
Figure 20-12.ElectrodeplacementtoobtaIncontractIonoftheadductorpollIcIs
muscle.ThetradItIonalmethodIstoapplytheelectrodesoverthecourseoftheulnar
nerveatthewrIst,wIththenegatIveelectrodedIstal(right).AnalternatemethodIs
toposItIontheelectrodesovertheadductorpollIcIsmuscle(left),thenegatIve
electrodeonthepalmofthehand,theposItIveInthesamelocatIon,butonthe
dorsumofthehand.ThedevIcefIxedtothethumbIsanaccelerometer.
Stimulator Characteristics
TheresponseofthenervetoelectrIcalstImulatIondependsonthreefactors:thecurrent
applIed,theduratIonofthecurrent,andtheposItIonoftheelectrodes.StImulatorsshould
delIveramaxImumcurrentIntherangeof60to80mA.|oststImulatorsaredesIgnedto
provIdeconstantcurrent,IrrespectIveofImpedancechangesbecauseofdryIngofthe
electrodegel,coolIng,decreasedsweatglandfunctIon,andsoforth.However,thIs
constantcurrentfeaturedoesnotholdforhIghImpedances(5k).Thus,electrodes
shouldbefIrmlyapplIedtotheskIn.AcurrentdIsplaymonItoronthestImulatorIsanasset
becauseaccIdentaldIsconnectIoncanbeIdentIfIedeasIlybyacurrentapproachIng0mA.
TheduratIonofthecurrentpulseshouldbelongenoughforallaxonsInthenerveto
depolarIzebutshortenoughtoavoIdthepossIbIlItyofexceedIngtherefractoryperIodof
thenerve.npractIce,pulseduratIonsof0.1to0.2msecareacceptable.Atleastone
electrodeshouldbeontheskInoverlyIngthenervetobestImulated.fthenegatIve
electrodeIsusedforthIspurpose,thethresholdtosupramaxImalstImulatIonIslessthan
fortheposItIveelectrode.However,thedIfferenceIsnotlargeInpractIce.TheposItIonof
theotherelectrodeIsnotcrItIcal,butItshouldnotbeplacedInthevIcInItyofother
nerves.ThereIsnoneedtouseneedleelectrodes.SIlversIlverchlorIdesurfaceelectrodes,
usedtomonItortheelectrocardIogram,areadequateforperIpheralnervestImulatIon,
wIthouttherIskofbleedIng,InfectIon,andburns.npractIce,applyIngtheseelectrodes
alongthecourseofanervegIvesthebestresults(FIg.2012).
P.518
Monitoring Modalities
0IfferentstImulatIonmodalItIeswereIntroducedIntoclInIcalpractIcetotakeadvantage
ofthecharacterIstIcfeaturesofnondepolarIzIngneuromuscularblockade:fadeand
posttetanIcfacIlItatIonwIthhIghfrequencystImulatIon.Thus,thefollowIngdIscussIon
refersmostlytonondepolarIzIngblock.
Single Twitch
ThesImplestwaytostImulateanerveIstoapplyasInglestImulus,atIntervalsof10
seconds(frequency,0.1Hz).ThIsIntervalIsneededtoallowtheneuromuscularjunctIon
torecoverIfnondepolarIzIngagentsareused.WIthshorterIntervals,fademIghtbe
present.WIthdepolarIzIngagentslIkesuccInylcholIne,lIttlefadeoccursandahIgher
frequency,suchas1Hz,maybeusedwIthoutconcernforfade.TheamplItudeofresponse
IscomparedwIthacontrol,preblockadetwItchheIght.ThesIngletwItchmodalItyIsuseful
toconstructdoseresponsecurvesandtoevaluateonsettIme.However,becauseacontrol
valueIsrequIred,theclInIcalusefulnessofthIsmodeofstImulatIonIslImIted.
Tetanus
WhenstImulatIonIsapplIedatafrequencyofJ0Hz,themechanIcalresponseofthe
muscleIsfusIonofIndIvIdualtwItchresponses.ntheabsenceofneuromuscularblockIng
drugs,nofadeIspresentandtheresponseIssustaIned.0urIngnondepolarIzIngblockade,
themechanIcalresponseappearsasapeak,followedbyafade(FIg.209).ThesensItIvIty
oftetanIcstImulatIonInthedetectIonofresIdualneuromuscularblockadeIsgreaterthan
thatofsIngletwItch;thatIs,tetanIcfademIghtbepresentwhIletwItchheIghtIsnormal.
|ostnervestImulatorsprovIdea5secondtraInatafrequencyof50Hz.ThIsfrequency
wasadoptedbecauseat100Hz,somefademaybeseenevenIntheabsenceof
neuromuscularblockIngdrugs.However,morefadeIsseenwIth100Hzthan50Hz
frequencIes,and100Hz,5secondtraInsaremostusefulInthedetectIonofresIdual
block.
44,115
WIthtetanIcstImulatIon,nocontrolprerelaxantresponseIsrequIred,asthe
degreeofmuscleparalysIscanbeassessedbythedegreeoffadefollowIngtetanIc
stImulatIon.However,themaIndIsadvantageofthIsmodeofstImulatIonIsposttetanIc
facIlItatIon(FIg.209),theextentofwhIchdependsonthefrequencyandduratIonofthe
tetanIcstImulatIon.Fora50HztetanusapplIedfor5seconds,theduratIonofthIsInterval
appearstobeatleast1to2mInutes.
45
fsIngletwItchstImulatIonIsperformeddurIngthat
tIme,theresponseIsspurIouslyexaggerated.
Train-of-Four
WIth2HzstImulatIon,themechanIcalorelectrIcalresponsedecreaseslIttleafterthe
fourthstImulus,andthedegreeoffadeIssImIlartothatfoundat50Hz.
4J
Thus,applyIng
traInoffourstImulatIonat2HzprovIdesmoresensItIvItythansIngletwItchand
approxImatelythesamesensItIvItyastetanIcstImulatIonat50Hz.naddItIon,thIs
relatIvelylowfrequencyallowstheresponsetobeevaluatedmanuallyorvIsually.
|oreover,thepresenceofasmallnumberofImpulses(four)elImInatestheproblemof
posttetanIcfacIlItatIon.TraInoffourstImulatIoncanberepeatedevery12to15seconds.
ThereIsafaIrlycloserelatIonshIpbetweensIngletwItchdepressIonandtraInoffour
response,
116
andnocontrolIsrequIredforthelatter.0urIngrecovery,thesecondtwItch
reappearsat80to90sIngletwItchblock,thethIrdat70to80,andwhenblockadeIs65
to75,allfourtwItchesbecomevIsIble.
117
Then,thetraInoffourratIo,theheIghtofthe
fourthtwItchtothatofthefIrsttwItch,IslInearlyrelatedtofIrsttwItchheIghtwhen
blockadeIs70.WhensIngletwItchheIghthasrecoveredto100,thetraInoffourratIo
IsapproxImately70.
Figure 20-13.PosttetanIccount(PTC).0urIngprofoundblockade,noresponseIsseen
totraInoffour(TDF)ortetanus.However,becausethereIsposttetanIcfacIlItatIon,
sometwItchescanbeseenaftertetanIcstImulatIon.nthIsexample,thePTCIs9.
Posttetanic Count
0urIngprofoundneuromuscularblockade,thereIsnoresponsetosIngletwItch,tetanIc,or
traInoffourstImulatIon.ToestImatethetImerequIredbeforethereturnofaresponse,
onemayuseatechnIquethatdependsontheprIncIpleofposttetanIcfacIlItatIon.A50Hz
tetanusIsapplIedfor5seconds,followedbyaJsecondpauseandbystImulatIonat1Hz.
ThetraInoffourandtetanIcresponsesareundetectable,butfacIlItatIonproducesa
certaInnumberofvIsIbleposttetanIctwItches(FIg.201J).ThenumberofvIsIbletwItches
correlatesInverselywIththetImerequIredforareturnofsIngletwItchortraInoffour
responses.
118
ForIntermedIateduratIondrugs,thetImefromaposttetanIccount(PTC)of1
toreappearanceoftwItchIs15to20mInutes.
Double-Burst Stimulation
TraInoffourfademaybedIffIculttoevaluatebyvIsualortactIlemeansdurIngrecovery
fromneuromuscularblockade.rrespectIveofexperIence,ItIsdIffIcultfor
anesthesIologIststodetecttraInoffourfadewhenactualtraInoffourratIoIs0.4or
greater,meanIngthatresIdualparalysIscangoundetected.
115
ThIsshortcomIngcanbe
overcome,toacertaInextent,byapplyIngtwoshorttetanIcstImulatIons(threeImpulses
at50Hz,separatedby750msec),andbyevaluatIngtheratIoofthesecondtothefIrst
response.ThedoubleburststImulatIonratIocorrelatescloselywIththetraInoffourratIo,
butIseasIertodetectmanually.
115
Atleast12to15secondsmustelapsebetweentwo
consecutIvedoubleburststImulatIons.
Recording the Response
Visual and Tactile Evaluation
WhenelectrIcalstImulatIonIsapplIedtoanerve,theeasIestandleastexpensIvewayto
assesstheresponseIstoobserveorfeeltheresponseofthemuscle.ThIsmethodIseasIly
adaptabletoanysuperfIcIalmuscle.However,serIouserrorsInassessmentcanbemade.n
thecaseofevaluatIngtheresponseoftheadductorpollIcIsmuscletoulnarnerve
stImulatIon,thetraInoffourcountcanbemaderelIablydurIngasurgIcalprocedure,
117
butthequantItatIveassessmentoftraInoffourratIoIsdIffIculttomakedurIngrecovery.
SeveralInvestIgatIonssuggestthattraInoffourratIosaslowas0.J
115
canremaIn
undetected.
P.519
ThedetectIonratefortetanIcfade(50Hz)Isnobetter.
115
WIthdoubleburststImulatIon,
fadecanbedetectedrelIablyuptotraInoffourratIosIntherangeof0.6to0.7.
115
WIth
100HztetanIcstImulatIon,fademIghtbedetectedattraInoffourratIosof0.8to1.0
44,115
andmaybeseenInIndIvIdualswIthnoneuromuscularblock.
Measurement of Force
AforcetransducercanovercometheshortcomIngsofone'ssenses.fapplIedcorrectly,the
devIceprovIdesaccurateandrelIableresponses,dIsplayedaseItheradIgItalorananalog
sIgnalonamonItor.ForcemeasurementcanbemeasuredaftersIngletwItch,tetanus,
traInoffour,doubleburst,orposttetanIcstImulatIon.However,theavaIlabIlItyoftetanus
anddoubleburststImulatIonIssuperfluousIfaccuratemeasurementofthetraInoffour
responsecanbemade.Unfortunately,transducersareexpensIve,bulky,cumbersome,and
canbeapplIedtoonlyonemuscle,usuallytheadductorpollIcIs.
Electromyography
tIspossIbletomeasuretheelectrIcalInsteadofthemechanIcalresponseofthemuscle.
DneelectrodeshouldbeposItIonedovertheneuromuscularjunctIon,whIchIsusuallyclose
tothemIdportIonofthemuscle,andtheotherneartheInsertIonofthemuscle.AthIrd,
neutralelectrodecanbelocatedanywhereelse.TheoretIcally,anysuperfIcIalmusclecan
beusedforE|CrecordIngs.npractIce,suchrecordIngsarelImItedtothehypothenar
emInence,thefIrstdorsalInterosseous,andtheadductorpollIcIsmuscles,whIchare
supplIedbytheulnarnerve.|ostE|CrecordIngdevIcescomputetheareaundertheE|C
curvedurIngaspecIfIedtImewIndowafterthestImulusIsapplIed.ThereIsusuallygood
correlatIonbetweenE|CandforceoftheadductorpollIcIsmuscleIftheE|CsIgnalIs
takenfromthethenaremInence.ThesIgnalobtaInedfromthehypothenaremInenceIs
largerandlesssubjecttomovementartIfacts,butItcanunderestImatethedegreeof
paralysIswhencomparedwIththeadductorpollIcIsmuscle.
119
Accelerometry
AccordIngtoNewton'slaw,acceleratIonIsproportIonaltoforceIfmassremaIns
unchanged.ThedevIceIsusuallyattachedtothetIpofthethumb(FIg.2012)andadIgItal
readoutIsobtaIned.ThesetupIssensItIvetoInadvertentdIsplacementofthethumband,
IntheabsenceofneuromuscularblockIngdrugs,traInoffourratIos100canbe
obtaIned.
116
nspIteoftheseshortcomIngs,accelerometershavebecomeIncreasIngly
popularbecausetheyareeasytouse,arelesscumbersome,canbeusedonmusclesother
thantheadductorpollIcIs,andarerelatIvelyInexpensIve.TheuseofaccelerometryIs
helpfulInthedIagnosIsofresIdualparalysIs
120
and,IncertaIncIrcumstances,
121
butnot
all,
9
ItcanreducetheIncIdenceofthecondItIon.
Displacement
AvarIetyofdevIceshavebeenproposedthatrespondtomotIonordIsplacement.Theyare
desIgnedfortheadductorpollIcIsmuscle.AthoroughevaluatIonofthesedevIceshasnot
beenmade,butdataIndIcatethatthereareslIghtbutclInIcallyInsIgnIfIcantdIfferences
betweentheresultssuchdIsplacementtransducersandmechanomyographyprovIde.
122
Phonomyography
AcontractIngmuscleemItslowfrequencysounds.TraInoffourresponseandfadecanbe
heardwIthastethoscopeplacedovertheadductorpollIcIsmuscle.AquantItatIveresponse
canbeobtaInedwIthspecIalmIcrophonessensItIvetofrequencIes(2Hz)belowthe
thresholdofthehumanear.AnexcellentcorrelatIonbetweenphonomyographyandforce
measurementhasbeenfoundatseveralmuscles,IncludIngtheadductorpollIcIsandthe
corrugatorsupercIlII.
12J
AtthetImeofwrItIng,nocommercIaldevIcesusIng
phonomyographywereavaIlable.
Choice of Muscle
|usclesdonotrespondInaunIformfashIontoneuromuscularblockIngdrugs.After
admInIstratIonofaneuromuscularblockIngagent,dIfferencescanbemeasuredwIth
respecttoonsettIme,maxImumblockade,andduratIonofactIon.tIsnotpractIcalto
monItorthemusclesofphysIologIcalImportance,forexample,theabdomInalmuscles
durIngsurgery,ortherespIratoryandupperaIrwaymusclespostoperatIvely.Abetter
approachIstochooseamonItorIngsItethathasaresponsesImIlartothemuscleof
Interest.Forexample,monItorIngtheresponseofthefacIalnervearoundtheeyeIsagood
IndIcatorofIntubatIngcondItIons,andtheuseoftheadductorpollIcIsmuscledurIng
recoveryreflectsupperaIrwaymusclefunctIon.AnotherstrategyIstostIcktoone
monItorIngsIte,suchastheadductorpollIcIsmuscle,andInterprettheInformatIon
provIdedfromknowledgeofthedIfferentresponsesbetweenmuscles(FIg.2014).
Adductor Pollicis Muscle
TheadductorpollIcIsmuscleIsaccessIbledurIngmostsurgIcalprocedures.tIssupplIedby
theulnarnerve,whIchbecomessuperfIcIalatthewrIstwhereanegatIveelectrodecanbe
posItIoned.TheposItIveelectrodeIsapplIedafewcentImetersproxImally(FIg.2012).The
forceofcontractIonoftheadductorpollIcIsmusclecanbemeasuredeasIly,andIthas
becomeastandardInresearch.AfterInjectIonofadosethatproduceslessthan100
blockade,thetImetomaxImalblockadeIslongerthanIncentrallylocatedmuscles.
124,125
TheadductorpollIcIsmuscleIsrelatIvelysensItIvetonondepolarIzIngneuromuscular
blockIngdrugs,anddurIngrecoveryItIsblockedmorethansomerespIratorymusclessuch
asthedIaphragm,
124
laryngealadductors,
125
andabdomInalmuscles(FIg.2014).
126
There
IsevIdencethatrecoveryoftheadductorpollIcIsandofupperaIrwaymusclesoccursmore
orlesssImultaneously(FIg.2014).
127
Figure 20-14.ApproxImatetImecourseoftwItchheIghtafterrocuronIum,0.6mg/kg,
atdIfferentmuscles.0Iaphragm,dIaphragm;larynx,laryngealadductors(vocalcords);
CS,corrugatorsupercIlIImuscle(eyebrow);Abd,abdomInalmuscles;DD,orbIcularIs
oculImuscle(eyelId);CH,genIohyoIdmuscle(upperaIrway);AP,adductorpollIcIs
muscle(thumb).(0ataaretakenorInferredfromreferences75,126,127,and129.)
P.520
TheadductorpollIcIsmusclecanalsobestImulatedbyapplyIngelectrodesdIrectlyoverIt.
ThIscanbeaccomplIshedbyplacIngthetwoelectrodesInthespacelyIngbetweenthe
baseofthefIrstandsecondmetacarpals,onthepalmaranddorsalaspectsonthehand,
respectIvely(FIg.2012).SuchastImulatIonavoIdstheconfoundIngmovementof
hypothenarmuscles.0IrectmusclestImulatIonwIththIselectrodeposItIondoesnot
normallyoccurbecauseneuromuscularblockIngagentsabolIshtheresponsecompletely.
128
TheabIlItytodetectfadebyvIsualortactIlemeansIsthesame,whetherthestImulatIng
electrodesareapplIedatthewrIstorthehand.
115
Other Muscles of the Hand
UlnarnervestImulatIonalsoproducesflexIonandabductIonofthefIfthfInger,whIch
usuallyrecoversbeforetheadductorpollIcIsmuscle,thedIscrepancyInfIrsttwItchor
traInoffourratIobeIngoftheorderof15to20.
119
FelyIngontheresponseofthefIfth
fIngermIghtoverestImaterecoveryfromblockade.AbductIonoftheIndexfIngeralso
resultsfromstImulatIonoftheulnarnervebecauseofcontractIonofthefIrstdorsal
Interosseous,thesensItIvItyofwhIchIscomparablewIththatoftheadductorpollIcIs
muscle.ThehypothenaremInence(nearthefIfthfInger)andthefIrstdorsalInterosseous
arepartIcularlywellsuItedforE|CrecordIngs.
119
StImulatIonInthehand(FIg.2012)
elImInatescontractIonofthehypothenarmuscles,butmayevokemovementofthefIrst
dorsalInterosseous.
Muscles Surrounding the Eye
ThereseemtobemajordIfferencesIntheresponseofmusclesInnervatedbythefacIal
nerveandlocatedaroundtheeye,andthesedIfferenceshaveIntroducedsomeconfusIon
InthelIterature.TheorbIcularIsoculImuscleessentIallycoverstheeyelId,andIts
responsetoneuromuscularblockIngagentsIssImIlartothatoftheadductorpollIcIs
muscle.
129
However,ItIscustomarytoobservethemovementoftheeyebrow,and
recordIngsatthatsItearesImIlartothatofthelaryngealadductors(FIg.2014).
129
Dnset
ofblockadeIsmorerapIdandrecoveryoccurssoonerthanattheadductorpollIcIs.Thus,
facIalnervestImulatIonwIthInspectIonoftheresponseoftheeyebrow(whIchmostlIkely
representstheeffectofthecorrugatorsupercIlII,nottheorbIcularIsoculImuscle)Is
IndIcatedtopredIctIntubatIngcondItIonsandtomonItorprofoundblockade.ThefacIal
nervecanbestImulated2toJcmposterIortothelateralborderoftheorbIt.ThereIsno
needtousestImulatIngcurrents20toJ0mA.
Muscles of the Foot
TheposterIortIbIalnervecanbestImulatedbehIndtheInternalmalleolustoproduce
flexIonofthebIgtoebycontractIonoftheflexorhallucIsmuscle.TheresponseofthIs
muscleIscomparablewIththatoftheadductorpollIcIsmuscle.StImulatIonoftheexternal
peronealnerveproducesdorsIflexIon,butthesensItIvItyofthemusclesInvolvedhasnot
beenmeasured.
Clinical Applications
Monitoring Onset
ThequalItyofIntubatIngcondItIonsdependschIeflyonthestateofrelaxatIonofmusclesof
thejaw,pharynx,larynx,andrespIratorysystem.DnsetofactIonIsfasterInallthese
musclesthanInthehandorfootbecausetheyareclosertothecentralcIrculatIonand
theyreceIveagreaterbloodflow.Amongthesecentralmuscles,thedIaphragmand
especIallythelaryngealadductorsarethemostresIstanttonondepolarIzIngagents.The
dIaphragmIsanImportantmusclebecauseItsblockadepreventscoughIng,andIflaryngeal
musclesareparalyzed,vocalcordsarerelaxed,allowIngeasypassageofatrachealtube.
TherelatIonshIpbetweenonsettImeInlaryngealandhandmusclesdependsondose.At
relatIvelylowdoses(e.g.,rocuronIum,0.Jto0.4mg/kg),onsettImeIssloweratthe
adductorpollIcIsthanatthelaryngealmuscles.fthedoseIsIncreased(e.g.,rocuronIum,
0.6to1.0mg/kg),onsetIsfasterattheadductorpollIcIsmusclebecausethesedoses
produce100blockadeattheadductorpollIcIswIthoutblockInglaryngealmuscles
completely(FIg.2014).
7J
DnsettImedecreasesconsIderablyInanymuscleIfthedose
gIvenIssuffIcIenttoreach100.FInally,IfthedoseIslargeenoughtoblockthelaryngeal
musclescompletely,onsettImeagaInbecomesshorteratthelarynx.tIsnotsurprIsIng
thatmonItorIngtheadductorpollIcIsmusclepredIctsIntubatIngcondItIonspoorly.FacIal
nervestImulatIonwIthvIsualobservatIonoftheresponseovertheeyebrowgIvesbetter
resultsbecausetheresponseofthecorrugatorsupercIlIIIsclosetothatofthevocalcords.
TraInoffourfadetakeslongertodevelopthansIngletwItchdepressIon(FIg.209),and
durIngonset,traInoffourstImulatIondoesnothaveanyadvantagesoversIngletwItch
stImulatIonat0.1Hz.
Monitoring Surgical Relaxation
AdequatesurgIcalrelaxatIonIsusuallyobtaInedwhenfewerthantwoorthreevIsIble
twItchesareobservedattheadductorpollIcIsmuscle.However,thIscrIterIonmIghtprove
InadequateIncertaIncIrcumstanceswhenprofoundrelaxatIonIsrequIredowIngtothe
dIscrepancybetweentheadductorpollIcIsandothermuscles.nthIscase,thePTCcanbe
usedattheadductorpollIcIsmuscle,
118
provIdedthatthIstypeofstImulatIonIsnot
repeatedmoreoftenthanevery2toJmInutes.AsuItablealternatIveIsstImulatIonofthe
facIalnervewIthobservatIonoftheresponseovertheeyebrow,whIchrecoversatthe
samerateassuchresIstantmusclesasthedIaphragm.
124,129
Monitoring Recovery
CompletereturnofneuromuscularfunctIonshouldbeachIevedattheconclusIonofsurgery
unlessmechanIcalventIlatIonIsplanned.Thus,monItorIngIsusefulIndetermInIngwhether
spontaneousrecoveryhasprogressedtoadegreethatallowsreversalagentstobegIven
andtoassesstheeffectoftheseagents.
TheeffectIvenessofantIcholInesteraseagentsdependsdIrectlyonthedegreeofrecovery
presentwhentheyareadmInIstered.Preferably,reversalagentsshouldbegIvenonlywhen
fourtwItchesarevIsIbleattheadductorpollIcIsmuscle,
1J0
whIchcorrespondstoafIrst
twItchrecoveryof25.ThepresenceofspontaneousbreathIngIsnotasIgnofadequate
neuromuscularrecovery.ThedIaphragmrecoversearlIerthanthemuchmoresensItIve
upperaIrwaymuscles,suchasthegenIohyoId,whIchrecovers,onaverage,atthesame
tImeastheadductorpollIcIsmuscle.
127
TopreventupperaIrwayobstructIonafter
extubatIon,ItIspreferabletousetheadductorpollIcIsmuscletomonItorrecovery,
InsteadofthemoreresIstantmusclesofthehypothenaremInenceorthosearoundtheeye.
FInally,theadequacyofrecoveryshouldbeassessed.TradItIonally,atraInoffourratIoof
0.7wasconsIderedtobethethresholdbelowwhIchresIdualweaknessoftherespIratory
musclescouldbepresent.ThereIsabundantevIdencethatsIgnIfIcantweaknessmayoccur
uptotraInoffourratIovaluesof0.9.
10,12J
AwakevolunteersgIvenmIvacurIumfaIledto
performtheheadlIfttestwhenthetraInoffourratIoattheadductorpollIcIsmuscle
decreasedbelow0.62,butneededatraInoffourratIoofatleast0.86toholdatongue
depressor
P.521
betweentheIrteeth(FIg.2015).
1J1
ThIssuggeststhattheheadlIfttestdoesnotguarantee
fullrecovery,andthattheupperaIrwaymusclesusedtoretaInatonguedepressorare
verysensItIvetotheresIdualeffectsofneuromuscularblockIngdrugs.Furthermore,
ImpaIrmentInswallowIngandlaryngealaspIratIonofapharyngealfluIdwasobservedat
traInoffourratIosashIghas0.9InvolunteersgIvenvecuronIum(FIg.204).
1J2
Figure 20-15.CorrelatIonbetweentraInoffour(TDF)responsesattheadductor
pollIcIsmuscleandcertaInclInIcaltestsofneuromuscularrecovery.7olunteerswere
gIvenmIvacurIumandwereaskedtolIfttheIrheadsfor5seconds(headlIft),lIfttheIr
legsfor5seconds(leglIft),orholdatonguedepressorbetweentheIrteethagaInst
force(tonguedepressor).ThemInImumTDFratIo(andS0)wheneachofthesetests
waspassedIsIndIcated.(0atafromKopmanetal.
1J1
)
AnesthetIzedpatIentsappearconsIderablymoresensItIvetotheventIlatoryeffectsof
neuromuscularblockIngdrugsthanareawakepatIents.WhereastIdalvolumeandendtIdal
CD
2
arepreservedInawakepatIentsreceIvIngrelatIvelyhIghdosesofneuromuscular
blockIngdrugs,
1JJ
anesthetIzedadultshaveadecreasedtIdalvolumeandIncreasedPCD
2
wIthdosesofpancuronIumaslowas0.5mg.
1J4
nconscIousvolunteers,admInIstratIonof
smalldosesofvecuronIumtomaIntaIntraInoffourat0.9leadstosevereImpaIrmentof
theventIlatoryresponsetohypoxIa(FIg.2016).
1J5
TheresponsetohypercapnIaIs
maIntaIned,andthIsIndIcatesthattheresponsetohypoxIaIsnotaresultofrespIratory
muscleweakness.
1J5
Takentogether,theresultsoftheseInvestIgatIonsIndIcatethatnormalrespIratoryand
upperaIrwayfunctIondoesnotreturntonormalunlessthetraInoffourratIoatthe
adductorpollIcIsmuscleIs0.9ormore.However,Ithasbecomeapparentthathuman
sensesfaIltodetecteItheratraInoffouror50HztetanIcfadewhenthetraInoffour
ratIoIsaslowas0.J.
115
WIthdoubleburststImulatIon,detectIonfaIluresmayoccurat
traInoffourratIosof0.6to0.7.
115
ComparedwIththetraInoffour,theabIlItytodetect
fadeIsnotImprovedbyusIngtetanIcstImulatIonat50Hzfor5seconds.However,fadecan
bedetectedvIsuallyattraInoffourratIosof0.8to0.9byusIng100HztetanIc
stImulatIon,
46,115
althoughthIsthresholdmayvaryfrompatIenttopatIent.
115
8ecauseof
thepresenceofposttetanIcfacIlItatIon,50or100HzstImulIshouldnotbeapplIedmore
oftenthanevery2mInutes.8ecauseofthelImItatIonsofone'ssenses,Ithasbeen
advocatedthatquantItatIveassessmentofthetraInoffourratIobemaderoutInely.
10
|echanographIcandE|CequIpmentgIverelIablevaluesoftraInoffourratIo,buttheuse
ofthIsequIpmentIslImItedbysIze,cost,andconvenIence.Accelerometersarelessbulky
andcheaper,buttheycanoverestImatethevalueoftraInoffourratIodurIngrecovery.
116
thasbeensuggestedthatatraInoffourratIoof1.0obtaInedbyaccelerometrymustbe
obtaInedbeforeneuromuscularfunctIoncanbeconsIderedcomplete.
115
|onItorIngdevIces
basedonthemeasurementofdIsplacementorsoundmayprovetohavemorerelIable
traInoffourratIosthanaccelerometry.nonestudy,atransmIssIonmodulesensItIveto
bendInganddeformatIonwasfoundtoyIeldtraInoffourratIovaluescomparableto
mechanomyographydurIngtherecoveryperIod.
122
Figure 20-16.FesponsetohypoxIaIsImpaIreddurIngrecoveryfromvecuronIum
blockade.NormalresponseIsanIncreaseInmInutevolume(|7)ortIdalvolume(T7;
control).TheseIncreasesaredecreasedsIgnIfIcantlywhenvecuronIumproducesa
traInoffourratIo(TDF)of0.7attheadductorpollIcIsmuscle.Theyreturntonear
normalvaluesataTDF0.9.(0atafromErIkssonetal.
1J5
)
nresponsetotheshortcomIngsofvIsualortactIleevaluatIons,anotherapproachto
recoveryIstowaItuntIlsuffIcIentspontaneousrecoveryIspresentandgIvereversalagents
systematIcally.fgIvenatatraInoffourcountof2durIngcIsatracurIumorrocuronIum
blockade,completerecoveryIsnotachIeveduntIl15mInutesorsolater,wIthsome
patIentsstIllhavIngtraInoffourratIos0.9afterJ0mInutes.
1J6
Thus,the
recommendatIonIstowaItuntIlallfourtwItcheshavereappeared.nanyevent,clInIcIans
mustbeawareofthelImItatIonsoftheteststheyareusIngandcompletetheIrevaluatIons
wIthclInIcaltests.
Factors Affecting the Monitoring of Neuromuscular Blockade
|anydrugsInterferewIthneuromuscularfunctIonandthesearedealtwIthelsewhere(see
0rugnteractIons).However,certaInsItuatIonsmaketheInterpretatIonofdataon
neuromuscularfunctIondIffIcult.CentralhypothermIamayslowthemetabolIsmof
neuromuscularblockIngagentsandprolongblockadeInallmusclesofthebody.
1J7
fthe
extremItywheremonItorIngIsperformedIscold,thedegreeofblockwIllbeaccentuated.
Thus,IfonlythemonItoredhandIscold,wIthoutcentralhypothermIa,thedegreeof
paralysIswIllappeartobeIncreased.
1J7
FesIstancetonondepolarIzIngneuromuscular
blockIngdrugsoccurswIthnervedamage,IncludIngperIpheralnervetrauma,cord
transectIon,andstroke.nthIscase,monItorIngoftheInvolvedlImbwouldtendto
underestImatethedegreeofmuscleparalysIs.ThelevelofparalysIsshouldalsobe
adjustedforthetypeofpatIent,aswellasthetypeofsurgery.Forexample,ItIsnot
necessarytoparalyzefraIlIndIvIdualsorpatIentsattheextremesofagetothesame
extentasyoungmuscularadults.ThesameapplIestopatIentswIthdebIlItatIngmuscular
dIseases.
NeuromuscularmonItorIngbyItselfdoesnotguaranteeadequaterelaxatIondurIngsurgery
andcompleterecoverypostoperatIvely.ThesurgIcalfIeldmaybepoorInspIteoffull
paralysIsofthehandbecauseofdIfferenceInresponsebetweenmuscles.Forexample,
evIdenceofbreathIngeffortscanbemanIfestontheexpIredCD
2
curvewhennotwItchIs
presentattheadductorpollIcIsmusclefollowIngulnar
P.522
nervestImulatIon,reflectIngtheearlIerrecoveryofthedIaphragm.
124,126
FesIdual
paralysIsmIghtoccurbecauseofexcessneuromuscularblockIngagentsgIven,early
admInIstratIonofreversal,oranabnormalresponseofthepatIent.Theeffectofthe
neuromuscularblockIngdrugIsthesamewhetherornotmonItorIngIsused.Neuromuscular
monItorIngcanhelpInthedIagnosIsofInadequateskeletalmusclerelaxatIondurIng
surgeryorInsuffIcIentrecoveryaftersurgery,butdoesnot,InItself,treatthese
condItIons.
9
Antagonism of Neuromuscular Block
nmostcIrcumstances,alleffortsshouldbemadetoensurethatthepatIentleavesthe
operatIngroomwIthunImpaIredmusclestrength.SpecIfIcally,respIratoryandupper
aIrwaymusclesmustfunctIonnormallysothepatIentcanbreathe,cough,swallow
secretIons,andkeephIsorheraIrwaypatent.TwostrategIescanbeadoptedtoachIeve
thIsgoal.ThefIrstIstotItrateneuromuscularblockIngagentscarefullysothatnoresIdual
effectIsmanIfestattheendofsurgery.ThesecondIstoacceleraterecoverybygIvInga
reversaldrug.ThIssecondoptIonIsprobablysafer,butbothstrategIesrequIrecareful
assessmentofblockade.AthIrdpossIbIlItythatmIghtbeavaIlableInthenearfutureIs
selectIvebIndIngofneuromuscularblockIngagentswIthacyclodextrInmoleculetorestore
neuromuscularfunctIon.
Assessment of Neuromuscular Blockade
SpontaneousbreathIngcanresumeevenIfrelatIvelydeepdegreesofparalysIsarestIll
presentbecauseoftherelatIvedIaphragmsparIngeffectofneuromuscularblockIngagents.
SpontaneousventIlatIon,adequatetopreventhypercapnIa,canbemaIntaIneddespIte
consIderablemeasurableskeletalmuscleweaknessIfapatentaIrwayIsensured.The
abIlItytoperformmaneuverssuchasvItalcapacIty,maxImumvoluntaryventIlatIon,and
forcedexpIratoryflowraterecoversatlessIntenselevelsofparalysIsbecauseItrequIresa
greaterstrength.
1JJ
However,suchtestsaredIffIculttoperformIneverydaypractIce,
partIcularlywhenthepatIentIsrecoverIngfromgeneralanesthesIa.|oreover,the
weakestpoIntIntherespIratorysystemIstheupperaIrway.WhengIvenvecuronIum,
swallowIngwasImpaIredandlaryngealaspIratIonoccurredwhenthetraInoffourratIo
was0.9.
1J2
TheseproblemsaredIffIculttodIagnosewhenatrachealtubeIsInplace.
Consequently,severalIndIrectIndIces,whIchareeasIertomeasure,havebeencorrelated
wIththemorespecIfIctestsoflungandupperaIrwayfunctIon.
Clinical Evaluation
Severalcrudetestshavebeensuggested,IncludIngheadlIftfor5seconds,tongue
protrusIon,andtheabIlItytolIftthelegsoffthebedtodetermInerecoveryof
neuromuscularfunctIon.PavlInetal.
1JJ
correlatedthemaxImumInspIratorypressurewIth
testsofskeletalmusclestrengthandofaIrwaymusculatureInconscIousvolunteers
receIvIngdtubocurarIne.AsthedosewasIncreased,headlIftandlegraIsIngwereaffected
fIrst.Then,theabIlItytoswallow,touchteeth,andmaIntaInapatentaIrwaywas
ImpaIred.AtthattIme,handgrIpstrengthwasdecreasedmarkedly.Nevertheless,aslong
asthemandIblewaselevatedbyanobserver,endtIdalCD
2
wasnormalevenwhenthe
subjectfaIledallothertests.Fromthesedata,ErIkssonetal.
1J2
concludedthatabIlItyto
maIntaInheadlIftfor5secondsusuallyIndIcatessuffIcIentstrengthtoprotecttheaIrway
andsupportventIlatIon.However,Kopmanetal.
1J1
haveshown,Involunteers,thatthe
mostsensItIvetestIstheabIlItytoclampthejawsshutandpreventremovalofatongue
depressor.ThIsmaneuvercorrelatedwIthatraInoffourratIomeasuredattheadductor
pollIcIsmuscleof0.86,whereasheadlIftandleglIftcouldbeperformedatmoreIntense
levelsofparalysIs(traInoffourapproxImately0.6;FIg.2015).AllsubjectscomplaInedof
vIsualsymptomsuntIltraInoffourwas0.9.PressuremeasurementsIntheupper
esophagushavebeenshowntobedecreased(FIg.204)andlaryngealaspIratIondetected
atatraInoffourratIo0.9.
1J2
Thus,ItappearsthatanormalheadlIftorleglIftIs
InsuffIcIenttoguaranteenormalupperaIrwayfunctIon.TheabIlItytoresIstremovalofan
object(suchasatonguedepressororatrachealtube)fromthemouthbyclosIngtheteeth
probablycorrelatesbetterwIthadequateupperaIrwayfunctIon.
Evoked Responses to Nerve Stimulation
TheclInIcaltestsprevIouslydescrIbedareusuallyunobtaInableInthepatIentrecoverIng
fromanesthesIa.Furthermore,ItIspreferabletoassessthedegreeofrecoverybefore
emergence.EvokedresponsestonervestImulatIonarethenapproprIate.ThetargetIsa
traInoffour0.9,consIderIngthatupperaIrwayfunctIondoesnotrecovercompletelyuntIl
thetraInoffourratIoattheadductorpollIcIsmuscleIsatleast0.9.
WIththeIntroductIonofshortandIntermedIateduratIonnondepolarIzIngagentsInto
clInIcalpractIce,theuseofreversalagentshasbeenconsIderedbysomeasoptIonal.The
decIsIontoomItpharmacologIcreversalofneuromuscularblockademustbemade
carefullybecausethepresenceofresIdualparalysIsmaybemIssed.AsmentIonedearlIer,
manualandtactIleevaluatIonofneuromuscularblockadebytraInoffouror50HztetanIc
stImulatIonmayfaIltodetectfade.
115
0oubleburststImulatIonIsmoresensItIve,but
becomesunrelIableattraInoffourratIosIntherangeof0.6to0.9.
115
ThemostsensItIve
testIstheabIlItytomaIntaInsustaInedcontractIonto100Hztetanusfor5seconds.Fade
maybedetectedwhentraInoffourratIoIsashIghas0.8to0.9.
46,115
TetanIcstImulatIon
at100HzIspaInfulandmustbeperformedonlyInadequatelyanesthetIzedpatIents.
8ecauseofthelImItatIonsofthevIsualandtactIleestImateofthetraInoffourresponse
durIngrecovery,objectIvemeasurementhasbeenadvocated.
10
AcceleromyographIc
recordIngsmIghtbethemostpractIcalbecauseaccelerometersarecheapandeasytouse.
However,ItmustbeapprecIatedthatthetraInoffourratIoobtaInedwIthaccelerometry
IsgreaterthanthatmeasuredwIthmechanomyographyandmayexceed1.0.An
accelerographIctraInoffourratIoof1.0hasbeenproposedastheequIvalentofa
mechanomyographIctraInoffourof0.9.
115
Residual Paralysis
SeveralstudIeshavedemonstratedthatresIdualneuromuscularblockadeIsfrequentIn
patIentsIntherecoveryroomaftersurgery.7Iby|ogensenetal.
1J8
foundIn72adult
patIentsgIvenlongactIngagentsthatthetraInoffourratIowas0.7InJ0(42)patIents,
andthat16ofthe68patIents(24)whowereawakewereunabletosustaInheadlIftfor5
seconds.nthatstudy,thepatIentsreceIvedapproprIatedosesofneostIgmIne.SImIlar
resultshavebeenobtaInedInotherpartsoftheworld(Table201).
9,1J9
TheIncIdenceof
traInoffourratIo0.7IsreducedfromaboutJ0to10IftheIntermedIateagents
atracurIumorvecuronIumaresubstItutedforthelongactIngdrugsandIfreversalIs
gIven.
9,1J9,140
However,theactualIncIdenceofresIdualparalysIswascertaInly
underestImatedIntheearlIerstudIesbecauseofthecrIterIonused(traInoffourratIoof
0.7).
P.52J
Fecently,therehasbeenatrendforagreaterIncIdenceofresIdualparalysIs,evenwIth
IntermedIateduratIondrugs.ThIscanbeexplaInedbytwofactors.Thethresholdfor
resIdualparalysIshasbeenraIsedfromatraInoffourratIoof0.7to0.8andthento0.9.
9
However,themostImportantreasonforhIghIncIdenceofresIdualparalysIsseemstobe
omIssIonofreversal.nonestudy,moresystematIcInstItutIonofpharmacologIcreversal
wasassocIatedwIthadecreaseIntheIncIdenceofresIdualparalysIs(traInoffour0.9)
from62toJ.
141
Clinical Importance
FesIdualparalysIsIntherecoveryroomhasbeenshowntobeassocIatedwIthsIgnIfIcant
morbIdIty.n1997,8ergetal.
140
studIednearly700generalsurgIcalpatIentswhorandomly
receIvedpancuronIum,vecuronIum,oratracurIumtoproducesurgIcalrelaxatIon.n
patIentswhohadreceIvedpancuronIum,theIncIdenceofpostoperatIvepartIalparalysIs,
defInedbythethenacceptedcrIterIonofatraInoffourratIo0.7,was5tImesthatIn
patIentsreceIvIngeItherofthetwoIntermedIateactIngdrugs(26vs.5).naddItIon,the
IncIdenceofatelectasIsdemonstratedonchestradIographstaken2dayslaterwasgreater
InpatIentswhohadreceIvedpancuronIumandwhohadnotattaInedatraInoffourratIo
of0.7(16)thanInthosewhoexceededthIsthreshold(4.8).
140
ntenseresIdualblockhas
beendemonstratedInpatIentsaftercardIacsurgery,especIallyIfpancuronIumwaschosen
overrocuronIum.
66
Reversal Agents
Sofar,theonlycompoundsthathavebeenwIdelyusedtoreversetheeffectof
neuromuscularblockIngagentsaretheantIcholInesterasedrugs.ThepharmacologIc
prIncIpleInvolvedIsInhIbItIonofacetylcholInebreakdowntoIncreaseItsconcentratIonof
acetylcholIneattheneuromuscularjunctIon,thustIltIngthecompetItIonforreceptorsIn
favoroftheneurotransmItter.
1J9
DtherdrugssuchassuramInandJ4amInopyrIdIneare
notaseffectIve,ormoretoxIc,orboth.ThemonopolyoccupIedbyantIcholInesterase
agentsmIghtbechallengedsoonwIththeIntroductIonofaselectIvebIndIngagent,
sugammadex,whIchIsnowundergoIngclInIcaltrIalsInNorthAmerIcaandEurope.
Anticholinesterases: Mechanism of Action
NeostIgmIne,edrophonIum,andpyrIdostIgmIneInhIbItacetylcholInesterase,butthIsmay
notbetheonlymechanIsmbywhIchblockadeIsantagonIzed.ThIsInhIbItIonIspresentat
allcholInergIcsynapsesIntheperIpheralnervoussystem.Thus,theantIcholInesterases
havepotentparasympathomImetIcactIvIty,whIchIsattenuatedorabolIshedbythe
admInIstratIonofanantImuscarInIcagent,atropIneorglycopyrrolate.NeostIgmIne,
edrophonIum,andpyrIdostIgmInearequaternaryammonIumcompounds,whIchdonot
penetratethebloodbraInbarrIerwell.Thus,althoughtheseagentshavetheabIlItyto
affectcholInergIcfunctIonInthecentralnervoussystem,theconcentratIonsInthebraIn
areusuallytoosmallforsuchaneffect.PhysostIgmIneIsanantIcholInesterasethatcan
crossthebloodbraInbarrIereasIly.ForthIsreason,ItIsnotusedtoreverseneuromuscular
blockade.
NeostIgmIneandpyrIdostIgmIneareattachedtotheanIonIcandesteratIcsItesofthe
acetylcholInesterasemoleculeandproducelongerlastIngInhIbItIonthanedrophonIum.
NeostIgmIneandpyrIdostIgmIneareInactIvatedbytheInteractIonwIththeenzyme,
whereasedrophonIumIsunaffected.
1J9
nhIbItIonofacetylcholInesteraseresultsInanIncreasedamountofacetylcholInereachIng
thereceptorandInalongertImeforacetylcholInetoremaInInthesynaptIccleft.ThIs
causesanIncreaseInthesIzeandduratIonoftheendplatepotentIals.
142
ThereIs
evIdencethatsomeoftheeffectsofneostIgmInearenottheresultofcholInesterase
InhIbItIon.
142
AntIcholInesterasesalsohavepresynaptIceffects.ntheabsenceofneuromuscular
blockIngdrugs,theypotentIatethenormaltwItchresponseInawaysImIlarto
succInylcholIne,probablyasaresultofthegeneratIonofactIonpotentIalsthatspread
antIdromIcally.AceIlIngeffect,thatIs,theInabIlItyforlargedosestoproducean
IncreasIngeffect,hasbeendemonstratedInvItro
14J
andcanbeobservedInpatIents.
144
Neostigmine Block
LargedosesofantIcholInesterases,especIallyIfgIvenwhenneuromuscularblockIsabsent,
mayproduceevIdenceofneuromusculardysfunctIon.Forexample,dosedependent
decreasesIntheE|CactIvItyofthegenIoglossusandthedIaphragmhavebeenmeasured
followIngneostIgmIneadmInIstratIonInrats.
145
TheproblemmIghtbelesswhensome
degreeofneuromuscularblockadeIspresentbeforeneostIgmIneIsgIven.ThemechanIsm
InvolvedIsuncertaIn.TherearenoclInIcalreportsofpostoperatIveweaknessattrIbutedto
reversalagents.StIll,ItappearsprudenttoreducethedoseofantIcholInesteraseagentIf
recoveryfromneuromuscularblockIsalmostcomplete.
Potency
0oseresponsecurveshavebeenconstructedforedrophonIum,neostIgmIne,and
pyrIdostIgmIne.0urIngaconstantInfusIonofneuromuscularblockIngdrugs,thecurvesare
obtaInedbyplottIngthepeakeffectversusthedoseofreversalagent.nthIssItuatIon,
neostIgmInewasfoundtobeapproxImately12tImesaspotentasedrophonIum.
146
However,thecurvesarenotparallel,thatofedrophonIumbeIngflatter.ThIsIndIcates
thatedrophonIumIseffectIveoveranarrowerrangeofblockadeandlesseffectIveagaInst
deepblockade.ThIswasverIfIedwhenneostIgmIneandedrophonIumwereusedtoreverse
atracurIumblockade.|oreneostIgmIneandedrophonIumwererequIredtoreversedeep
(99)thanmoderate(90)block,butthedIfferencewasgreaterforedrophonIum.
147
There
IsnodIfferenceInthedoseresponserelatIonshIpofantIcholInesterasesIfvecuronIumIs
InfusedInsteadofpancuronIum,butthereIsamarkedshIfttotheleftforthecurves
obtaIneddurIngvecuronIumblockIfthereversalagentIsgIvendurIngspontaneous
recovery.
148
ThIsIndIcatesthatantIcholInesteraseassIstedrecoveryIsthesumoftwo
components:(1)spontaneousrecoveryfromtheneuromuscularblockIngagentItself,whIch
dependsonthepharmacokInetIccharacterIstIcsofthedrug,and(2)assIstedrecovery,
whIchIsafunctIonofthedoseandtypeofantIcholInesteraseagentgIven.
Pharmacokinetics
FollowIngbolusIntravenousInjectIon,theplasmaconcentratIonoftheantIcholInesterases
decreasesrapIdlydurIngthefIrst5to10mInutesandthenmoreslowly.
1J9
7olumesof
dIstrIbutIonareIntherangeof0.7to1.4L/kgandtheelImInatIonhalflIfeIs60to120
mInutes.Thedrugsarewatersoluble,IonIzedcompoundssothattheIrprIncIpalrouteof
excretIonIsthekIdney.TheIrclearancesareIntherangeof8to16mL/kg/mIn,whIchIs
muchgreaterthantheglomerularfIltratIonratebecausetheyareactIvelysecretedInto
thetubularlumen.TheIrclearanceIsreducedmarkedlyInpatIentsInrenalfaIlure.
P.524
Figure 20-17.FeversalofpancuronIumblockadeat10twItchrecovery.FeversalIs
gIvenattImezero.EdrophonIumIsfasterthenneostIgmIne,whIchIsfasterthan
pyrIdostIgmIne.(FedrawnfromFergusonA,EgerszegIP,8evan0F:NeostIgmIne,
pyrIdostIgmIne,andedrophonIumasantagonIstsofpancuronIum.AnesthesIology1980;
5J:J90.)
Pharmacodynamics
TheonsetofactIonofedrophonIum(1to2mInutes)topeakeffectIsmuchmorerapIdthan
thatofneostIgmIne(7to11mInutes)orpyrIdostIgmIne(15to20mInutes;FIg.2017).
162
ThereasonforthedIfferencesIsuncertaIn,butmayberelatedtothedIfferentratesof
bIndIngtotheenzyme.TheduratIonofactIon(1to2hours)IssImIlartotheIrelImInatIon
halflIfe.EvenwhenusedtoreverseblockadeproducedbylongactIngagents,duratIonof
actIonofantIcholInesteraseagentsIscomparablewIthormostoftenexceedsthatofthe
neuromuscularblockIngdrug.WelldocumentedrecurarIzatIonhasnotbeenreported.n
practIce,casesofapparentreparalysIsIntherecoveryroomareIncompletereversalthat
wasInItIallythoughttobecomplete.EIthermanualorvIsualassessmentIsperformedusIng
thetraInoffourortetanusmode,whIchcanyIeldtogrossunderevaluatIonofresIdual
paralysIs,orrespIratoryfunctIonappearedadequatewhenthetrachealtubeIsInplace,
butonceextubated,thepatIentcannotmaIntaInapatentaIrway.
Factors Affecting Reversal
SeveralfactorsmodIfytherateofrecoveryofneuromuscularactIvItyafterreversal.
Intensity of Block
ThemoreIntensetheblockatthetImeofreversal,thelongertherecoveryof
neuromuscularactIvIty(FIg.2018).
144
naddItIon,neostIgmIneIsmoreeffectIvethan
edrophonIumorpyrIdostIgmIneInantagonIzIngIntense(90)blockade.WhenreversalIs
admInIsteredafterspontaneousrecoveryto25T
1
hasoccurred,recoveryIsrapIdandthe
tImefromreversaltotraInoffour0.9IsusuallyonlyafewmInutes,althoughrecovery
afterpancuronIummaynotbecomplete.
68
Thus,Kopmanetal.
1J6
recommendedthat
reversalshouldnotbeattempteduntIlT
1
25whenfourtwItchestotraInoffour
stImulatIonarevIsIble.AttemptedreversalatonlytwotwItchesmaytakeJ0mInutesor
moretoreachtraInoffourof0.9.
Figure 20-18.NeostIgmIneIsmoreeffectIveatgreaterdegreeofrecoveryfrom
rocuronIumblockade.TImetoreachatraInoffourratIoof0.8aftervarIousdosesof
neostIgmIne.ThIstImeIslessIfneostIgmIneIsgIvenat25thanat10fIrsttwItch
recovery.NotIceaceIlIngeffectforneostIgmIneatdoses0.0J5mg/kg.Adoseof0
IndIcatesnoreversalgIven.(0atafrom|cCourtetal.
144
)
DnemIghtarguethatreversalcanbeattemptedearlIer,forInstancewhenthereIsonly
oneornotwItchvIsIblefollowIngtraInoffourstImulatIon,becauseonewouldotherwIse
spendtImewaItIngforallfourtwItchestoreappear.SeveralstudIesdealtwIththe
problemoftotaltImebetweenInjectIonoftheneuromuscularblockIngagentuntIl
completerecovery,wIththereversalagentgIvenatdIfferentlevelsofspontaneous
recovery.8evanetal.
148
admInIsteredlargedosesofneostIgmIne(0.07mg/kg)after
rocuronIumandvecuronIumandmeasuredtImeuntIltraInoffourratIowas0.9.
NeostIgmInedecreasedthetImetorecovery,nomatterwhenItwasgIven.However,tIme
fromInjectIontofullreversalwasnotlesswhenneostIgmInewasgIven5mInutesafter
rocuronIum(42.1mInutes)thanat25recovery(28.2mInutes;FIg.2019).
148
naddItIon,
gIvIngthereversalagenttooearlyleadstoaperIodofblIndparalysIsbecause
neostIgmIneassIstedrecoveryIscharacterIzedbyanearly,rapIdphase,followedbyslower
recovery.Asaresult,theIntervalbetweenatraInoffourratIoof0.4to0.9,thatIs,the
tImewhenfadeIsdIffIculttodetect,IslIkelytobemuchlongerwIthearlyneostIgmIne
admInIstratIon.Thus,thereIslIttleadvantageInattemptIngearlyreversal.
Dose
DveracertaIndoserange,thedegreeandrateofreversaldependsdIrectlyondose.
144,147
However,allantIcholInesteraseagentsdemonstrateaceIlIngeffect(FIg.2018).Usually,
thereIsnoaddedbenefItIngIvIngdosesexceedIng0.07mg/kgneostIgmIne,or1.0mg/kg
edrophonIum.
Choice of Neuromuscular Blocking Agent
FecoveryofneuromuscularactIvItyafterreversaldependsontherateofspontaneous
recoveryaswellastheacceleratIonInducedbythereversalagent.Consequently,the
overallrecoveryofIntermedIateactIngagents(atracurIum,vecuronIum,mIvacurIum,
rocuronIum)followIngthesamedoseofantIcholInesteraseIsmorerapIdandmore
completethanafterpancuronIum,
P.525
dtubocurarIne,orgallamIne.
68
ThIsdIfferenceIsprobablywhyresIdualparalysIsIsmore
frequentwIthlongeractIngneuromuscularblockIngagents.AfterprolongedInfusIons,
recoveryIsslowerthanafterIntermIttentbolusadmInIstratIon.
Figure 20-19.TImefromInjectIonofrocuronIumuntIlrecoverytotraInoffourratIo
(TDF)of0.9Inadults.FeversalwIthneostIgmInewaseIthernotgIven(Spont)orgIven
at25,10,or1twItchrecovery,orgIven5mInutesafterrocuronIum,whenthere
wasnotwItch.TImesfromrocuronIumInjectIonto1fIrsttwItch,25fIrsttwItch,
andTDFof0.9areIndIcated.NeostIgmInewasoptImalwhengIvenat10to25.CIvIng
Itearlyhadnoadvantage.(0atafrom8evanetal.
148
)
Age
FecoveryofneuromuscularactIvItyoccursmorerapIdlywIthsmallerdosesof
antIcholInesterasesInInfantsandchIldrenthanInadults(FIg.2020).
148
FesIdualweakness
IntherecoveryroomIsfoundlessfrequentlyInchIldrenthanInadults.TheeffectIveness
ofreversalhasnotbeenstudIedextensIvelyIntheelderly.AlthoughtheelImInatIonof
antIcholInesterasesIsreducedInthIsagegroup,thIsreductIonIscounterbalancedbythe
tendencyforneuromuscularblockadetowearoffmoreslowly.ThIsIsespecIallytrueof
steroIdalneuromuscularblockIngagents,suchasvecuronIumandrocuronIum,whIchhave
aslowerrecoveryIndexIntheelderly.
Figure 20-20.SamegraphasInFIgure2019,butInchIldren2to12yearsold.
SpontaneousrecoveryfromrocuronIumblockade(Spont)IsmorerapId,aswellas
neostIgmIneassIstedrecovery.(0atafrom8evanetal.
148
)
Drug Interactions
0rugsthatpotentIateneuromuscularblockadecanslowreversalorproducerecurarIzatIon
IfgIvenafterantIcholInesteraseadmInIstratIon.Halogenatedagents,whencontInuedafter
neostIgmIneadmInIstratIon,prolongtImetofullreversal.EvenwhentheyaredIscontInued
atthetImeofantIcholInesterasedrugadmInIstratIon,reversaltImeIsnotreduced
sIgnIfIcantly,probablybecausewashoutofthevaporfrommuscletIssuetakestIme.Care
mustbetakenIfamInoglycosIdeantIbIotIcsormagnesIummustbegIvenshortlyafter
reversalagents.
Renal Failure
AntIcholInesterasesareactIvelysecretedIntothetubularlumensothattheIrclearanceIs
reducedInrenalfaIlure.
1J9
Thus,duratIonofactIonofneostIgmIneandedrophonIumIs
IncreasedInrenalfaIlure,atleasttoacomparableextentasduratIonofactIonofthe
neuromuscularblockIngagent.NocasesofrecurarIzatIonhavebeenreported.
Anticholinesterases: Other Effects
Cardiovascular
AntIcholInesterasesprovokeprofoundvagalstImulatIon.ThetImecourseofthevagal
effectsparallelsthereversalofblock,whIchIsrapIdforedrophonIumandslowerfor
neostIgmIne.However,thebradycardIaandbradyarrhythmIascanbepreventedwIth
antIcholInergIcagents.AtropInehasarapIdonsetofactIon(1mInute),duratIonofJ0to60
mInutes,andcrossesthebloodbraInbarrIer.tstImecoursemakesItapproprIateforuse
IncombInatIonwIthedrophonIum,
146
whereasglycopyrrolate(onset2toJmInutes)Ismore
suItablewIthneostIgmIneorpyrIdostIgmIne.8ecauseglycopyrrolatedoesnotcrossthe
bloodbraInbarrIer,ItIsbelIevedthattheIncIdenceofmemorydefIcItsafteranesthesIaIs
lessthanthatafteratropIne.fatropIneIsgIvenwIthneostIgmIne,thedoseIs
approxImatelyhalfthatofneostIgmIne(atropIne20g/kgforneostIgmIne40g/kg).Such
acombInatIonleadstoanInItIaltachycardIafollowedbyaslIghtbradycardIa.WIth
glycopyrrolate,thedoseIsonefourthtoonefIfththatofneostIgmIne.AtropIne
requIrementsarelesswIthedrophonIumthanwIthneostIgmIne(atropIne7to10g/kgwIth
edrophonIum0.5mg/kg).
Other Cholinergic Effects
AntIcholInesterasesproduceIncreasedsalIvatIonandbowelmotIlIty.AlthoughatropIne
blockstheformer,ItappearstohavelIttleeffectonperIstalsIs.SomereportsclaIman
IncreaseInbowelanastomotIcleakageafterthereversalofneuromuscularblockade.
TherehasbeenconcernoverthepossIbleImpactofantIcholInesteraseagentson
postoperatIvenauseaandvomItIng(PDN7).AmetaanalysIs,publIshedIn1999,concluded
thatneostIgmInehadnoeffectontheoverallIncIdenceofPDN7,butlargedoses(2.5mgor
moreInadults)wasassocIatedwIthahIgherIncIdenceofPDN7thannoreversal,whIle
lowerdosesledtolessPDN7.
149
AmorerecentmetaanalysIsreanalyzedthedataand
IncorporatedaddItIonalstudIes.tconcludedthattherewasnorelatIonbetween
admInIstratIon
P.526
ofneostIgmIneandPDN7.
150
Atanyrate,possIblenauseaandvomItIngIspreferableto
sIgnsandsymptomsofrespIratoryparalysIs.
Respiratory Effects
AntIcholInesterasesmaycauseanIncreaseInaIrwayresIstance,butantIcholInergIcsreduce
thIseffect.Severalotherfactors,suchaspaIn,thepresenceofanendotrachealtube,or
lIghtanesthesIa,maypredIsposetobronchoconstrIctIonattheendofsurgerysothatItIs
dIffIculttoIncrImInatethereversalagents.
Clinical Use
SeveralstrategIeshavebeenproposedtorestoreneuromuscularfunctIonattheendof
surgeryandanesthesIa.DneofthemInvolvesrestrIctIngthedoseofnondepolarIzIng
blockIngagentatInductIonofanesthesIatowhatIsnecessaryfortheduratIonofthe
procedure,mInImaladdItIonaldosesandrelIanceofcompletespontaneousrecoveryInan
attempttoavoIdreversalwIthantIcholInesteraseagents.ThIsapproachIsnotwIthout
dangers.EvenrelatIvelymodestdoses(2E0
95
)ofatracurIum,vecuronIum,orrocuronIum
areassocIatedwIthresIdualparalysIs(traInoffourratIo0.9)afteraslongas4hoursafter
InjectIon.
120
7IsualortactIlemonItorIngwIthtraInoffour,50Hztetanus,ordoubleburst
stImulatIonstImulatIoncannotruleoutsomedegreeofresIdualparalysIs.
115
Dnlya
sustaInedresponsetoa100HztetanusmayruleoutthepresenceofresIdualparalysIsby
tactIleorvIsualmeans.
44,115
TheuseofobjectIvemonItorIng,suchasacceleromyography,
Isevenbetter.
115
StIll,pharmacologIcallyassIstedrecoveryIsexpectedInmostcases,asIt
IsIllusorytoaImforcompleterecoveryonlybycarefultItratIonofneuromuscularblockIng
agents.nastudyexamInInganesthetIcoutcomesInTheNetherlands,theuseofreversal
agentswasfoundtobeassocIatedwIthatenfoldreductIonInmortalIty.
151
NotsurprIsIngly,
themoresystematIcuseofreversalagentsInoneInstItutIonledtoasubstantIaldecrease
InresIdualparalysIs.
141
AdmInIstratIonofantIcholInesteraseagentswIllacceleraterecovery,nomatterwhenthey
aregIvenInthecourseofrecovery(FIg.2019).However,thereareadvantagesIngIvIng
reversalagentswhenspontaneousrecoveryIswellunderway,preferablywhenfour
twItchesarepresentaftertraInoffourstImulatIon.fneostIgmIneIsgIvenwhendeep
blockadeIspresent(notwItchoronlyonetwItchpresent;FIgs.2018and2019),reversal
takeslongerthanIffourtwItchesarepresent.Asaresult,tImefromInjectIonof
rocuronIumuntIlfullrecovery(traInoffour0.9)Isnotreduced,andmyInfactbe
Increased,IfneostIgmIneIsgIventooearly(FIg.2019).Furthermore,thepatIentmIghtbe
moredIffIculttomanagewIthearlyreversal:duratIonofblIndparalysIs(fromtraInoffour
of0.4,whentraInoffourfadebecomesundetectable,untIltraInoffourIs0.9)Islonger
wIthearlyreversal.ThIsmeansthatmIssIngresIdualparalysIsIsmorelIkelywIthhasty
admInIstratIonofantIcholInesteraseagents.Therefore,IffourtwItchesarenotvIsIble
aftertraInoffourstImulatIon,ItIsrecommendedtokeepthepatIentanesthetIzedand
mechanIcallyventIlateduntIlfourtwItchesreappearandthenadmInIster
antIcholInesterases.
ntenseblockadeIsnotexpectedtobereversedeffectIvelybyIncreasIngthedoseof
antIcholInesterase(FIg.2018).ngeneral,neostIgmInedosesof0.04to0.05mg/kgshould
besuffIcIent,andthereIsnoadvantageInexceedIng0.07mg/kgbecauseoftheceIlIng
effectofthedrug.EdrophonIumIsnotrecommendedforIntenseblock.PyrIdostIgmInehas
aslowonsetofactIonanddoesnotappeartoacceleratereversalofshortand
IntermedIateduratIondrugstoagreatextent.
WhenrecoveryappearsalmostcompletethatIs,whenfourseemInglyequaltwItchesare
seenaftertraInoffourstImulatIonareduceddoseofneostIgmIne(0.015to0.02mg)Is
probablyadequate.nthIssItuatIon,edrophonIum(0.2to0.5mg/kg)mayalsobegIven,
wIththeaddedadvantageofrapIdrecovery(2mInutes).EItherdrugIspreferabletono
reversalatallbecausetheyreducetheduratIonofblIndparalysIs.
Sugammadex
AnewmethodofreversIngneuromuscularblockademIghtbeavaIlableInthenearfuture.
Sugammadex,prevIouslycalledORG 25969,leadstorestoratIonofnormalneuromuscular
functIonnotbyInterferIngwIthacetylcholIne,thenIcotInIcreceptoror
acetylcholInesterase,butbyselectIvelybIndIngtorocuronIum,andtoalesserextentto
vecuronIumandpancuronIum.
152
ThecompoundIsacyclodextrIn,madeupofeIghtsugars
arrangedInarIngtomakeacentertoaccommodatetherocuronIummolecule.Dnce
bound,rocuronIumIsheldInplacebypolarsIdechaInsattachedtotherIng.8ecause
sugammadexdoesnotbIndtoanyknownreceptor,ItIsdevoIdofmajorcardIovascularor
othersIdeeffects.tdoesnotbIndneuromuscularblockIngdrugsthatdonothaveasteroId
nucleus.ThebenzylIsoquInolInes,suchasatracurIum,cIsatracurIumandmIvacurIum,and
succInylcholIneareunaffectedbysugammadex.
Mechanism of Action
SugammadexhasamolecularweIghtof2,1780altons
152
andbIndswIthrocuronIumIna1:1
molarratIo.TherocuronIummoleculeIslessbulky(6100altons),soJ.6mg(ormg/kg)of
sugammadexIsrequIredtobInd1.0mg(ormg/kg)ofrocuronIum.8IndIngIstIght,butnot
IrreversIble.ThIsmeansthatrocuronIumsugammadexcomplexesformwhIlesomeothers
breakupIntotheIrtwoconstItuents.ThedIssocIatIonconstanthasbeenestImatedtobe
0.1|,
152
andItIsnotknownwhetherItIsaffectedbypH,temperature,typeoffluIdor
tIssue,orotherfactors.AfterInjectIonofsugammadex,evIdencesuggeststhatbIndIngof
rocuronIumtosugammadexInplasmaleadstoamarkeddecreaseInfree(unbound)
rocuronIumconcentratIon,
15J
leadIngtotheestablIshmentofaconcentratIongradIentof
rocuronIumbetweentheneuromuscularjunctIonandplasma.ThIsfavorsmovementof
rocuronIumfromneuromuscularjunctIontoplasma,producInglessneuromuscularblock.
7ecuronIumhaslessaffInItyforsugammadexthanrocuronIumdoes,andpancuronIumhas
lessstIll.
Pharmacology
npatIentsreceIvIngrocuronIum,returnoftraInoffourratIoto0.9Isacceleratedby
sugammadexInadosedependentmanner.fsugammadexIsgIvenonreturnofthesecond
twItchInthetraInoffour,dosesof2to4mg/kgresultInthereturnoftraInoffourratIo
to0.9wIthInapproxImately2mInutes.
154
ThIsIntervalIsshorterthanaftereIther
neostIgmIneoredrophonIumreversal,whengIvenatapproxImatelythesamelevelof
recovery.WIthlowerdoses(0.5to1mg/kg)recoverytImeIslonger
154
andreparalysIsmay
beobserved.
155
ExperIencewIthvecuronIumIslImIted,butstudIessuggestthat
approxImatelythesame,orperhapshIgher,dosesofsugammadexarerequIredforthe
sameeffect.
154
SugammadexIsalsoeffectIvewhenblockadeIsdeep,butlargerdosesarerequIred(FIg.
2021).WhenaPTCof2Ispresent,whIchforrocuronIumoccurs15to20mInutesbefore
returnoftwItch,therequIreddoseIsprobably4to8mg/kg.
156
P.527
SugammadexcouldalsobeusedInthecaseofafaIledIntubatIon.frocuronIum0.6mg/kg
wasgIven,sugammadex8mg/kgmIghtbeeffectIveasearlyasJmInutesafterrocuronIum
InjectIon,andIfthedoseofrocuronIumIsdoubledto1.2mg/kg,onemIghtneed16mg/kg
ofsugammadex.
157
TheavaIlabIlItyofsugammadexmIghtmakesuccInylcholIneobsolete
forIntubatIon.
152
Figure 20-21.FelatIonshIpbetweentImetoachIeveatraInoffourratIoof0.9and
doseofsugammadexatmoderate(spontaneousrecoverytoT
2
ortwovIsIbletwItches)
orprofound(posttetanIccount[PTC]of2).0oseofsugammadexrequIredIsgreater
wIthprofoundblockade.*NodataavaIlableformoderateblockade.(0atafrom
references15J,154,and156.)
Pharmacokinetics
SugammadexhasavolumeofdIstrIbutIonthatIssImIlartoECF(1JL).tstermInalhalflIfe
IsapproxImately2hours.
158
8othsugammadexandsugammadexrocuronIumcomplexesare
excretedunchangedvIathekIdney.NodataareavaIlableInrenalfaIlurepatIents.n
patIentsreceIvIngrocuronIum,InjectIonofsugammadexIncreasesthetotal(freeplus
bound)plasmaconcentratIonsofrocuronIum,whIchsuggeststhatItcausessequestratIonof
rocuronIumIntheplasmabydrawIngItfromperIpheraltIssues.
Clinical Use
AtthetImeofwrItIng(endof2007),sugammadexhadnotbeenapprovedforclInIcaluse
anywhereIntheworld.NotallclInIcaldatahadbeenpublIshed,sothefollowIngcomments
shouldbetakenwIthcautIon.AlthoughadmInIstratIonofdosesashIghas40mg/kghave
beenreportedassafe,ItappearsprudenttousethelowesteffectIvedose,tokeepcosts
downandbecausesafetyofhIghdoseswIllbeestablIshedonlyafteruseIswIdespread.
8ecausetheeffectIvedosedependsonthedepthofblockade,monItorIngIsrecommended,
IfnotessentIal.ForreversalofrocuronIumblockadewhenspontaneousrecoveryhas
alreadystarted(twotofourtwItchespresent),sugammadex2to4mg/kgwIllproduce
fasterrecoverythanneostIgmInewould,wIthoutcardIovascularsIdeeffects.
154
When
recoveryIsevengreater(fourapparentlyequaltwItches),0.5to1mg/kgmIghtbe
suffIcIent,butmoredataareneededonthIs.
TheusefulnessofsugammadexmIghtbeevengreaterIncasesofdeepblockade,whenno
twItchIsseenaftertraInoffourstImulatIon.TheuseofthePTCmodeofstImulatIonwIll
probablybeusefulInestablIshIngthedose,butIfanyPTCcountIspresent,ItIsexpected
that4to8mg/kgwIllberequIred.
156
ThedosewIllbedoubledIncasesofdeeperblockade
(noPTCcount)orrescueafterfaIledIntubatIon.tIsexpectedthatasconfIdenceInthe
effIcacyofsugammadexInthecontextofprofoundblockadebuIldsup,clInIcIansmIght
haveatendencytogIvelargerdosesofrocuronIum.ThIschangeInpractIcecouldyIeld
somebenefIts.|oreprofoundrelaxatIonprovIdesbetterandfasterIntubatIngcondItIons,
bettersurgIcalcondItIons,andlessdamagetothelaryngealstructures.Fasterandmore
predIctablerecoverycoulddImInIshtheIncIdenceofresIdualparalysIsandreduceturn
aroundtIme.8utthesebenefItswIllcomeatacost.Dfcourse,ItwIllbemoreexpensIveto
establIshmusclerelaxatIonIfthedoseofrocuronIumIsIncreased,andthecostofreversal
wIllundoubtedlybesubstantIal,especIallyIflargedosesaregIvenconsIstently.naddItIon,
however,allmovementwIllbeabolIsheddurIngsurgery,soanImportantsIgnof
InadequateanalgesIaandanesthesIawIllbelost.tIsunclearwhetherawarenesscanbe
totallyavoIdedbytheuseof8SmonItorIng,aslargedosesofneuromuscularblockIng
agentscandepress8SIncertaIncIrcumstances.
5
FInally,manyforeseeableproblems
regardIngsugammadexhavenotbeenaddressed,suchasItsuseInrenalfaIlurepatIents,
themanagementofapatIentwhohasrecentlyreceIvedsugammadexwhoneedssurgery
(forreexploratIonforInstance),theInteractIonwIthsteroIdtypedrugsornaturally
occurrIngmolecules,andthepotentIalforbypassIngthepostanesthesIacareunIt.Future
experIencewIththIsnewagentwIllbecrItIcal.
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neostIgmIneasantagonIstsofmoderateandprofoundatracurIumblockade.Anesth
Analg1989;68:1J
148.8evanJC,CollInsL,FowlerC,etal:EarlyandlatereversalofrocuronIumand
vecuronIumwIthneostIgmIneInadultsandchIldren.AnesthAnalg1999;89:JJJ
149.Tramer|F,Fuchs8uderT:DmIttIngantagonIsmofneuromuscularblock:effecton
postoperatIvenauseaandvomItIngandrIskofresIdualparalysIs.AsystematIcrevIew.
8rJAnaesth1999;82:J79
150.ChengCF,Sessler0,ApfelCC:0oesneostIgmIneadmInIstratIonproducea
clInIcallyImportantIncreaseInpostoperatIvenauseaandvomItIng:AnesthAnalg2005;
101:1J49
151.Arbous|S,|eursIngAE,vanKleefJW,etal:mpactofanesthesIamanagement
characterIstIcsonseveremorbIdItyandmortalIty.AnesthesIology2005;102:257
152.NaguIb|:Sugammadex:anothermIlestoneInclInIcalneuromuscular
pharmacology.AnesthAnalg2007;104:575
15J.CIjsenberghF,FamaelS,HouwIngN,etal:FIrsthumanexposureofDrg25969,a
novelagenttoreversetheactIonofrocuronIumbromIde.AnesthesIology2005;10J:695
154.SuyK,|orIasK,CammuC,etal:EffectIvereversalofmoderaterocuronIumor
vecuronIumInducedneuromuscularblockwIthsugammadex,aselectIverelaxant
bIndIngagent.AnesthesIology2007;106:28J
155.Eleveld0J,KuIzengaK,ProostJH,etal:AtemporarydecreaseIntwItchresponse
durIngreversalofrocuronIumInducedmusclerelaxatIonwIthasmalldoseof
sugammadex.AnesthAnalg2007;104:582
156.CroudIneS8,SotoF,LIenC,etal:ArandomIzed,dosefIndIng,phasestudyofthe
selectIverelaxantbIndIngdrug,Sugammadex,capableofsafelyreversIngprofound
rocuronIumInducedneuromuscularblock.AnesthAnalg2007;104:555
157.de8oerH0,0rIessenJJ,|arcus|A,etal:FeversalofrocuronIumInduced(1.2
mg/kg)profoundneuromuscularblockbysugammadex:amultIcenter,dosefIndIngand
safetystudy.AnesthesIology2007;107:2J9
158.SparrHJ,7ermeyenK|,8eaufortA|,etal:EarlyreversalofprofoundrocuronIum
InducedneuromuscularblockadebysugammadexInarandomIzedmultIcenterstudy:
effIcacy,safety,andpharmacokInetIcs.AnesthesIology2007;106:9J5
159.0urmus|,EnderC,KadIr8A,etal:FemIfentanIlwIththIopentalfortracheal
IntubatIonwIthoutmusclerelaxants.AnesthAnalg200J;96:1JJ6
160.KlemolaU|,|ennanderS,SaarnIvaaraL:TrachealIntubatIonwIthouttheuseof
musclerelaxants:remIfentanIloralfentanIlIncombInatIonwIthpropofol.Acta
161.ErIkssonL,LennmarkenC,WyonN,etal:AttenuatedventIlatoryresponseto
hypoxaemIaatvecuronIumInducedpartIalneuromuscularblock.ActaAnaesthesIol
Scand1992;J6:710
162.FergusonA,EgerszegIP,8evan0F:NeostIgmIne,pyrIdostIgmIne,andedrophonIum
asantagonIstsofpancuronIum.AnesthesIology1980;5J:J90
16J.8evan0F,SmIthCE,0onatIF:PostoperatIveneuromuscularblockade:a
comparIsonbetweenatracurIum,vecuronIum,andpancuronIum.AnesthesIology1988;
69:272
164.8IssIngerU,SchImekF,LenzC:PostoperatIveresIdualparalysIsandrespIratory
status:acomparatIvestudyofpancuronIumandvecuronIum.PhysIolFes.2000;49:455
Stock, M. Christine
TableofContentsSectIon7AnesthetIcAgents,Adjuvants,and0rugnteractIonChapter21LocalAnesthetIcs
Chapter21
Local Anesthetics
Spencer S. Liu
Yi Lin
Key Points
1. Local anesthetics provide anesthesia and analgesia by blocking the
transmission of pain sensation along nerve fibers
2. The key target of local anesthetics is the voltage-gated sodium
channel. The binding is intracellular and is mediated by hydrophobic
interactions.
3. The degree of nerve blockade depends on both drug concentration
and volume.
4. Most clinically relevant agents contain a lipid-soluble benzene ring
connected to an amide group and are categorized as either
aminoesters or aminoamides, based on their chemical linkage.
5. Potency is related to hydrophobicity and physiochemical properties of
the agent. In general, more potent agents are more lipid soluble.
6. Efficacy for clinical use of local anesthetics may be increased by
addition of epinephrine, opioids, and
2
-adrenergic agonists. The
value of alkalinization of local anesthetics appears to be debatable as
a clinically useful tool to improve anesthesia.
7. Systemic toxicity from the clinical use of local anesthetics is an
uncommon occurrence. Patients with cardiovascular collapse from
bupivacaine, ropivacaine, and levo-bupivacaine may be especially
difficult to resuscitate; however intravenous lipid infusion is a
promising new therapy.
LocalanesthetIcsblocktheconductIonofImpulsesInelectrIcallyexcItabletIssues.Dneof
theImportantusesIstoprovIdeanesthesIaandanalgesIabyblockIngthetransmIssIonof
paInsensatIonalongnervefIbers.ThemoleculartargetoftheseagentsIsspecIfIcandthe
InteractIonhasbeenextensIvelystudIed.ExIstIngclInIcalapplIcatIonsarenumerousand
contInuetoexpand.AcomprehensIveunderstandIngofthemechanIsmsandthe
physIochemIcalpropertIesoftheseagentswouldenableoptImIzatIonofthetherapeutIc
potentIalandavoIdcomplIcatIonsassocIatedwIthInadvertentsystemIctoxIcIty.
Mechanisms of Action of Local Anesthetics
Anatomy of Nerves
LocalanesthetIcsareusedtoblocknervesIntheperIpheralnervoussystem(PNS)and
centralnervoussystem(CNS).ntheperIpheralnervoussystem,nervescontaInboth
afferentandefferentfIbers,whIcharebundledIntooneormorefascIclesandorganIzed
wIthInthreetIssuelayers.
1
ndIvIdualnervefIberswIthIneachfascIclearesurroundedby
theendoneurIum,alooseconnectIvetIssuecontaInIngglIalcells,fIbroblasts,andblood
capIllarIes.AdenselayerofcollagenousconnectIvetIssuecalledtheperineuriumsurrounds
eachfascIcle.AfInallayerofdenseconnectIvetIssue,theepIneurIum,encasesgroupsof
fascIclesIntoacylIndrIcalsheath(FIg.211).TheselayersoftIssueofferprotectIontothe
surroundednervefIbersandactasbarrIerstopassIvedIffusIonoflocalanesthetIcs.
2
NervesInboththecentralandperIpheralnervoussystemaredIfferentIatedbythe
presenceortheabsenceofmyelInsheath.|yelInatednervefIbersaresurroundedby
SchwanncellsInthePNSandbyolIgodendrocytesIntheCNS.Thecellsforma
concentrIcallywrappedlIpIdbIlayersheatharoundtheaxonsthatcoverthelengthofthe
nerve.
J
ThemyelInsheathIsInterruptedatshort,regularIntervalsbyspecIalIzedregIons
callednodes of Ranvier,whIchcontaIndenselyclusteredproteInelementsessentIalfor
transmIssIonofneuronalsIgnals
4
(FIg.212).AselectrIcalsIgnalsarerenewedateach
node,nerveImpulsesmoveInmyelInatedfIbersbysaltatoryconductIon.ncontrast,there
arenonodesofFanvIerInnonmyelInatednervefIbers.AlthoughthesenervefIbersare
sImIlarlyencasedInSchwanncells,theplasmamembranedoesnotwraparoundtheaxons
concentrIcally.SeveralnervefIbersmaybesImultaneouslyembeddedwIthInasIngle
Schwanncell
1
(FIg.21J).
P.5J2
Figure 21-1.SchematIccrosssectIonoftypIcalperIpheralnerve.TheepIneurIum,
consIstIngofcollagenfIbers,IsorIentedalongthelongaxIsofthenerve.The
perIneurIumIsadIscretecelllayer,whereastheendoneurIumIsamatrIxof
connectIvetIssue.8othafferentandefferentaxonsareshown.SympathetIcaxons(not
shown)arealsopresentInmIxedperIpheralnerves.(AdaptedfromStrIchartzCF:
NeuralphysIologyandlocalanesthetIcactIon,Neural8lockadeInClInIcalAnesthesIa
and|anagementofPaIn.EdItedbyCousIns|J,8rIdenbaughPD.PhIladelphIa,
LIppIncottFaven,1998,pJ5,wIthpermIssIon.)
NervefIbersarecommonlyclassIfIedaccordIngtotheIrsIze,conductIonvelocIty,and
functIon(Table211).ngeneral,nervefIberswIthcrosssectIonaldIametergreaterthan1
mIcronaremyelInated.8othalargernervesIzeandthepresenceofmyelInsheathare
assocIatedwIthfasterconductIonvelocIty.
5
NervefIberswIthlargedIametershavebetter
IntrInsIcelectrIcconductance.|yelInImprovestheelectrIcalInsulatIonofnervefIbersand
permItsmorerapIdImpulsetransmIssIonvIasaltatoryconductIon.LargedIameter,
myelInatedfIbers,manyofwhIchareclassIfIedasAfIbers,aretypIcallyInvolvedInmotor
andsensoryfunctIonsInwhIchspeedofnervetransmIssIonIscrItIcal.ncontrast,the
smalldIameter,nonmyelInatedCfIbershaveslowerconductIonvelocItyandrelaysensory
InformatIonsuchaspaIn,temperature,andautonomIcfunctIons.
Figure 21-2.0IagramofnodeofFanvIerdIsplayIngmItochondrIa(|),tIghtjunctIons
Inparanodalarea(P),andSchwanncell(S)surroundIngnode.(AdaptedfromStrIchartz
CF:|echanIsmsofactIonoflocalanesthetIcagents,PrIncIplesandPractIceof
AnesthesIology.EdItedbyFogers|C,TInkerJH,CovIno8C,etal.St.LouIs,|osby
Year8ook,199J,p1197,wIthpermIssIon.)
Figure 21-3.SchwanncellsformmyelInaroundonemyelInatedaxonorencompass
severalunmyelInatedaxons.(AdaptedfromCarpenterFL,|ackey0C:Local
anesthetIcs,ClInIcalAnesthesIaJe.EdItedby8arashPC,Cullen8F,StoeltIngFF.
PhIladelphIa,LIppIncottFaven,1996,p41J,wIthpermIssIon.)
Electrophysiology of Neural Conduction and Voltage-Gated
Sodium Channels
TransmIssIonofelectrIcalImpulsesalongthecellmembraneformsthebasIsofsIgnal
transductIonalongnervefIbers.EnergynecessaryforthepropagatIonandmaIntenanceof
theelectrIcpotentIalIsmaIntaInedonthecellsurfacebyIonIcdIsequIlIbrIaacrossthe
semIpermeablecellmembrane.
6
TherestIngmembranepotentIal,approxImately60to70
m7Inneurons(theextracellularelectrIcpotentIalIsbyconventIondefInedaszero,and
theIntracellularpotentIalIsthusnegatIvetoIt),IsderIvedpredomInantlyfroma
dIfferenceIntheIntracellularandextracellularconcentratIonsofpotassIumandsodIum
Ions.NeuronsatrestaremorepermeabletopotassIumIonsthansodIumIonsbecauseof
potassIumleakchannels;thereforemembranepotentIalIsclosertotheequIlIbrIum
potentIalofpotassIum(E
K
80m7)thanthatofsodIum(E
Na
+60m7).TheIongradIentIs
contInuouslyregeneratedbyproteInpumps,cotransporters,andchannelsvIaadenosIne
trIphosphatedependentprocess.
ElectrIcalImpulsesareconductedalongnervefIbersasactIonpotentIals.TheyarebrIef,
localIzedspIkesofposItIvecharge,ordepolarIzatIons,onthecellmembranecausedby
rapIdInfluxofsodIumIonsdownItselectrochemIcalgradIent.
7
AnactIonpotentIalIs
InItIatedbylocalmembranedepolarIzatIon,suchasatthecellbodyornervetermInalby
lIgandreceptorcomplex.WhenacertaInchargethresholdIsreached,anactIonpotentIal
IstrIggeredandfurtherdepolarIzatIonoccursInanallornonefashIon.
8
ThespIkeIn
membranepotentIalpeaksaround+50m7,atwhIchpoInttheInfluxofsodIumIsreplaced
wIthaneffluxofpotassIum,causIngareversalofmembranepotentIal,orrepolarIzatIon.
ThepassIvedIffusIonofmembranedepolarIzatIontrIggersotheractIonpotentIalsIneIther
adjacentcellmembraneInnonmyelinatednervefIbersoradjacentnodesofFanvIerIn
myelinatednervefIbers,resultIngInawaveofactIonpotentIalbeIngpropagatedalongthe
nerve.AshortrefractoryperIodthatensuesaftereachactIonpotentIalpreventsthe
retrogradespreadofactIonpotentIalonprevIouslyactIvatedmembranes.
7
TheflowofIonsresponsIbleforactIonpotentIalsIsmedIatedbyavarIetyofchannelsand
pumps,themostImportant
P.5JJ
ofwhIcharethevoltagegatedsodIumchannels.TheyareessentIalfortheInfluxofsodIum
IonsdurIngtherapIddepolarIzatIonphaseofactIonpotentIalandbelongtoafamIlyof
channelproteInsthatalsoIncludesvoltagegatedpotassIumandvoltagegatedcalcIum
channels.EachvoltagegatedsodIumchannelIsacomplexmadeupofoneprIncIpalalpha
subunItandoneormoreauxIlIarybetasubunIts.
9
ThealphasubunItIsasInglepolypeptIde
transmembraneproteInthatcontaInsmostofthekeycomponentsofthechannelfunctIon.
TheyIncludefourhomologousalphahelIcaldomaIns(01to04)thatformthechannelpore
andcontrolIonselectIvIty,voltagesensIngregIonsthatregulategatIngfunctIonand
InactIvatIon,andphosphorylatIonsItesformodulatIonbyproteInkInases.8etasubunItsare
shortpolypeptIdeproteInswIthasIngletransmembranedomaIn.TheyarelInkedtoalpha
subunItsbyeIthernoncovalentordIsulfIdebonds;althoughtheyaredIspensablefor
channelactIvIty,evIdencesuggeststhattheyperhapsplayaroleInmodulatIonofchannel
expressIon,localIzatIonandfunctIon.
Table 21-1 Classification of Nerve Fibers
CLASSIFICATION
DIAMETER
()
MYELIN
CONDUCTION
(m/sec)
LOCATION FUNCTION
Aalpha,A
beta
622 + J0120
Afferents/efferents
formusclesand
joInts
|otorand
proprIoceptIon
Agamma J6 + 15J5
Efferenttomuscle
spIndle
|uscletone
Adelta 14 + 525
Afferentsensory
nerve
PaIn
Touch
Temperature
8 J + J15
PreganglIonIc
sympathetIc
AutonomIc
functIon
C
0.J
1.J
0.71.J
PostganglIonIc
sympathetIc
Afferentsensory
nerve
AutonomIc
functIon
PaIn
Temperature
ntheabsenceofastImulus,voltagegatedsodIumchannelsexIstpredomInantlyInthe
restIngorclosedstate(FIg.214).DnmembranedepolarIzatIon,posItIvechargesonthe
membraneInteractwIthchargedamInoacIdresIduesInthevoltagesensIngregIons(S4).
10
ThIsInducesaconformatIonalchangeInthechannel,convertIngIttotheopenstate.
SodIumIonsrushthroughtheopenedpore,whIchIslInedwIthnegatIvelychargedresIdues.
onselectIvItyIsdetermInedbytheseamInoacIdresIdues;changesIntheIrcomposItIon
canleadtoIncreasedpermeabIlItyforothercatIons,suchaspotassIumandcalcIum.
11
WIthInmIllIsecondsafteropenIng,channelsundergoatransItIontotheInactIvatedstate.
0ependIngonthefrequencyandthevoltageoftheInItIaldepolarIzIngstImulus,the
channelmayundergoeItherafastorslowInactIvatIon.SloworfastInactIvatIonrefersto
theduratIonInwhIchthechannelremaInsrefractorytorepeatdepolarIzatIonbefore
resettIngtotheclosedstate.FastInactIvatIoncompleteswIthInamIllIsecondandIs
sensItIvetotheactIonoflocalanesthetIcs.tIsmedIatedbyashortmobIleIntracellular
polypeptIdeloopconnectIngdomaIns0Jand04thatclosesthechannelfromInsIdethecell
vIaahIngelIdmechanIsm.
12
AtrIadofhIghlyhydrophobIcamInoacIds(IsoleucIne,
phenylalanIne,andmethIonIne,orF|)appearstobeanImportantstructuraldetermInant
offastactIvatIon;dIsruptIngthelooporchangIngthehydrophobIcItyoftheamInoacIds
abrogatesfastInactIvatIon.
1J,14
SlowactIvatIon,lastIngsecondstomInutes,IsdIstInct
fromfastactIvatIon.tIsresIstanttotheactIonoflocalanesthetIcsandItsmechanIsmIs
lesswellunderstood.toftenoccursafterprolongeddepolarIzatIonandIsbelIevedtobe
ImportantInregulatIngmembraneexcItabIlIty.
NIneIsoformsofvoltagegatedsodIumchannels(Na
7
1.1toNa
7
1.9)havebeenIdentIfIed,
eachrelatestoaunIquealphasubunItsubtype(Table212).EachIsoformvarIesslIghtlyIn
ItschannelkInetIcs,suchasthresholdofactIvatIonandmodeofInactIvatIon,andIts
sensItIvItytoblockIngagentslIketetrodotoxInsandlocalanesthetIcs.CellandtIssue
expressIonofIndIvIdualIsoformsmaybequItespecIfIc;forInstance,Na
7
1.2Isfound
almostexclusIvelyIntheCNS,whereasNa
7
1.6IsrestrIctedtonodesofFanvIerInbothCNS
andPNS.
15
LIkewIse,severalIsoformscouldbepresentonasInglecelltype;bothNa
7
1.8
andNa
7
1.9havebeenfoundInsmalltomedIumsIzedneuronsIndorsalrootganglIonsthat
areconnectedtoAdeltaandCfIbers.WhetherIndIvIdualIsoformseachhasaseparateand
defInedroleremaInstobeseen;
P.5J4
however,cluesoftheIrfunctIonmaybeInferredfromstudIesofseveralInherIteddIseases
thathavebeenassocIatedwIthsodIumchannelopathIes.HyperexcItabIlItyofNa
7
1.7has
beenImplIcatedInseveralpaInfuldIseasestates,suchasprImaryerythromelalgIaand
paroxysmalextremepaIndIsorder.
16,17
Conversely,nullmutatIonofNa
7
1.7IslInkedtoa
raregenetIccondItIonInwhIchotherwIsenormalIndIvIdualshaveseverelyImpaIred
perceptIontopaIn.
18,19
Table 21-2 Voltage-Gated Sodium Channels
NAME TISSUE EXPRESSION TETRODOTOXIN ASSOCIATED CHANNELOPATHIES
Na
7
1.1
CNS,heart SensItIve nherItedfebrIleepIlepsy
Na
7
1.2
CNS
nonmyelInated
axons
SensItIve nherItedfebrIleepIlepsy
Na
7
1.J
Fetal0FC SensItIve Noneknown
Na
7
1.4
Skeletalmuscle SensItIve
HyperkalemIcperIodIcparalysIs,
paramyotonIacongenIta
Na
7
1.5
Heart,
embryonIc
neurons
nsensItIve 8rugadasyndrome,longQTsyndrome
Na
7
1.6
Nodesof
FanvIer
SensItIve Noneknown
Na
7
1.7
CNS,0FC,
sympathetIc
neurons
SensItIve
ErythromelalgIa,paroxysmalextreme
paIndIsorder,congenItalInsensItIvItyto
paIn
Na
7
1.8
Small0FC
neurons
nsensItIve Noneknown
Na
7
1.9
Small0FC
neurons
nsensItIve Noneknown
0ataadaptedfrom8enarrochEE:SodIumchannelsandpaIn.Neurology2007:68:
2JJ,andKoopmannTT,8ezzInaCF,WIldeAA:7oltagegatedsodIumchannels:
ActIonplayerswIthmanyfaces.Ann|ed2006:J8:472.
Figure 21-4.llustratIonofdomInantformofsodIumchanneldurInggeneratIonofan
actIonpotentIal.F,restIngform;D,openform;,InactIveform.A.Theconcurrent
generatIonofanactIonpotentIalasthemembranedepolarIzesfromrestIngpotentIal.
B.TheconcurrentchangesInIonflux,asInwardsodIumcurrent(
NA+
)andoutward
potassIumcurrent(
K+
)togetheryIeldthenetIonIccurrentacrossthemembrane(
I
).
(AdaptedfromStrIchartzCF:NeuralphysIologyandlocalanesthetIcactIon,Neural
8lockadeInClInIcalAnesthesIaand|anagementofPaIn.EdItedbyCousIns|J,
8rIdenbaughPD.PhIladelphIa,LIppIncottFaven,1998,pJ5,wIthpermIssIon.)
Molecular Mechanisms of Local Anesthetics
LocalanesthetIcsblockthetransmIssIonofnerveImpulsesbytargetIngthefunctIonof
voltagegatedsodIumchannels.AlthoughseverallocalanesthetIcscanbIndtoother
receptorslIkevoltagegatedpotassIumchannelsandnIcotInIcacetylcholInereceptors,and
theIramphIpathIcnaturemayenablethemtoInteractwIthplasmamembranes,ItIswIdely
acceptedthattheyInduceanesthesIaandanalgesIathroughdIrectInteractIonswIththe
sodIumchannels.DthermoleculeswIthlocalanesthetIcpropertIessuchastrIcyclIc
antIdepressantsandantIconvulsantsmaylIkewIseInteractwIthvoltagegatedsodIum
channels;however,ItIsunclearIftheyactthroughsImIlarmechanIsms.Therefore,the
followIngdIscussIonIslImItedtothetradItIonalsetoflocalanesthetIcmolecules.
LocalanesthetIcsreversIblybIndtheIntracellularportIonofvoltagegatedsodIumchannels
(FIg.215).EarlyexperImentswIthgIantsquIdaxonsdemonstratedthataderIvatIveof
lIdocaInewIthapermanentposItIvecharge,QXJ14,whIchcannotcrosstheplasma
membrane,blocksIoncurrentthroughvoltagegatedsodIumchannelsonlywIthIntra
axoplasmIcInjectIons,butnotwIthexternalapplIcatIon.
20
SubsequentmutatIonalanalyses
havesupportedtheobservatIonandIdentIfIedspecIfIcsItesonthechannelInvolvedIn
drugrecognItIon.
21
SeveralhydrophobIcaromatIcresIdues(aphenylalanIneatposItIon
1764andatyrosIneatposItIon1771InNa
7
1.2)locatedwIthInanalphahelIx(S6)of
domaIns1,J,and4areessentIalfordrugbIndIng(FIg.216).TheylIneanInnercavIty
wIthIntheIntracellularportIonofthechannelporeandspanaregIonabout11apart,
roughlythesIzeofalocalanesthetIcmolecule.ChangesIneItherresIdueseverelyreduce
thebIndIngaffInIty.AnotherhydrophobIcamInoacId(anIsoleucIneatposItIon1760),
locatedneartheouterporeopenIng,hassImIlarlybeenfoundtoInfluencethedIssocIatIon
oflocalanesthetIcsfromthechannelbyantagonIzIngthereleaseofdrugsthroughthe
channelpore.
ApplIcatIonoflocalanesthetIcstypIcallyproducesaconcentratIondependentdecreaseIn
thepeaksodIumcurrent.
22,2J
KnownastonIcblockade,ItreflectsthereductIonofthe
numberofsodIumchannelsforagIvendrugconcentratIonpresentIntheopenstateat
equIlIbrIum.ncontrast,repetItIvestImulatIonofthesodIumchannelsoftenleadstoa
shIftInthesteadystateequIlIbrIum,resultIngInagreaternumberofchannelsbeIng
blockedatthesamedrugconcentratIon.Termeduse-dependent blockade,theexact
mechanIsmIsIncompletelyunderstoodandhasbeenthesubjectofmanycompetIng
hypotheses.Dnepopulartheory,themodulated-receptor
P.535
theory,proposesthatlocalanesthetIcsbIndtotheopenortheInactIvatedchannelsmore
avIdlythantherestIngchannels,suggestIngthatdrugaffInItyIsafunctIonofachannel's
conformatIonalstate.Analternatetheory,theguarded-receptor theory,assumesthatthe
IntrInsIcbIndIngaffInItyremaInsessentIallyconstantregardlessofachannel's
conformatIon;rather,theapparentaffInItyIsassocIatedwIthIncreasedaccesstothe
recognItIonsIteresultIngfromchannelgatIng.ExperImentalevIdencesofarhasbeen
InconclusIve.
Figure 21-5.0IagramofbIlayerlIpIdmembraneofconductIvetIssuewIthsodIum
channelspannIngthemembrane.TertIaryamInelocalanesthetIcsexIstasneutralbase
(N)andprotonated,chargedform(NH+)InequIlIbrIum.Theneutralbase(N)Ismore
lIpIdsoluble,preferentIallypartItIonsIntothelIpophIlIcmembraneInterIor,andeasIly
passesthroughthemembrane.Thechargedform(NH+)IsmorewatersolubleandbInds
tothesodIumchannelatthenegatIvelychargedmembranesurface.8othformscan
affectfunctIonofthesodIumchannel.TheNformcancausemembraneexpansIonand
closureofthesodIumchannel.TheNH+formwIlldIrectlyInhIbItthesodIumchannel
bybIndIngwIthalocalanesthetIcreceptor.ThenaturallocalanesthetIc
tetrodotoxIn(TTX)bIndsattheexternalsurfaceofthesodIumchannelandhasno
InteractIonwIthclInIcallyusedlocalanesthetIcs.(AdaptedfromStrIchartzCF:Neural
physIologyandlocalanesthetIcactIon,Neural8lockadeInClInIcalAnesthesIaand
|anagementofPaIn.EdItedbyCousIns|J,8rIdenbaughPD.PhIladelphIa,LIppIncott
Faven,1998,pJ5,wIthpermIssIon.)
Figure 21-6.0IagramoflocalanesthetIcbIndIngsIte,depIctIngahydrophobIcpocket
wIthInthechannelpore.(AdaptedfromFagsdale0S,|cPheeJC,ScheuerT,etal:
|oleculardetermInantsofstatedependentblockofNa+channelsbylocalanesthetIcs.
ScIence1994;265:1724,wIthpermIssIon.)
Mechanism of Nerve Blockade
LocalanesthetIcsblockperIpheralnervesbydIsruptIngthetransmIssIonofactIon
potentIalsalongnervefIbers.TogettoItssIteofactIon,prIncIpallythevoltagegated
sodIumchannels,localanesthetIcshavetoreachthetargetednervemembrane.ThIs
entaIlsthedIffusIonofdrugsthroughtIssuesandthegeneratIonofaconcentratIon
gradIent.EvenwIthcloseproxImItyofdeposItIon,onlyabout1to2oftheInjectedlocal
anesthetIcsultImatelypenetrateIntothenerve.
24
AsdIscussedearlIer,theperIneural
sheathencasIngnervefIbersappearstobeanImportantdetermInant;nervesthathave
beendesheathedInvItrorequIreaboutahundredfoldlowerlocalanesthetIc
concentratIon(Inthe0.7to0.9m|rangeforlIdocaIne)thannervesInvIvo(thetypIcal2
lIdocaIneusedclInIcallyIsequIvalentto75m|concentratIon).AlthoughItmayvarywIth
anatomIclocatIonandnervephysIology,functIonalblocktypIcallyoccurswIthIn5mInutes
ofInjectIonInratscIatIcnerves,andthIstImecoursecorrespondstothepeakInthe
IntraneuraldrugabsorptIon.
ThedegreeofnerveblockadedependsonthelocalanesthetIcconcentratIonandvolume.
ForagIvendrug,amInImalconcentratIonIsnecessarytoeffectcompletenerveblockade.
treflectsthepotencyofthelocalanesthetIcsandtheIntrInsIcconductIonpropertIesof
nervefIbers,whIchInturnlIkelydependonthedrug'sbIndIngaffInItytotheIonchannels
andthedegreeofdrugsaturatIonnecessarytohaltthetransmIssIonofactIonpotentIals.
AccordIngly,IndIvIdualtypesofnervefIbersdIfferIntheIrmInImalblockIngconcentratIon,
suchthatsomeAfIbersareblockedbylowerdrugconcentratIonsthanCfIbers.
25
LIkewIse,
thepatternofstImulatIon(tonIcvs.usedependentblockade)Influencesthedegreeof
conductIonfaIlure;repetItIvestImulatIons,whIchcanleadtoashIftInsteadystate
equIlIbrIumofblockedsodIumchannels,areassocIatedwIthhIgherconductIonfaIlurethan
tonIcstImulatIonatagIvendrugconcentratIon.
26
DfequalImportanceasdrugconcentratIonIsthelocalanesthetIcsvolume.AsuffIcIent
volumeIsneededtosuppresstheregeneratIonofnerveImpulseoveracrItIcallengthof
nervefIber.AccordIngtothemodelofdecrementalconductIon(FIg.217),asmembrane
depolarIzatIonfromanactIonpotentIalpassIvelydecayswIthdIstancealongnervefIbers,
thepresenceoflocalanesthetIcsdecreasestheabIlItyofadjacentmembraneorsuccessIve
nodesofFanvIertoregeneratetheImpulse.
27
TransmIssIonstopsoncethemembrane
depolarIzatIonfallsbelowthethresholdforactIonpotentIalactIvatIon.Tooshortan
exposurelengthallowsImpulsestoskIpovermembranesornodesthatareblockedby
eventhehIghestdrugconcentratIon,whereasexposureofalongnervesegmenttoa
relatIvelylowdrugconcentratIoncanstIllresultIngradualextInctIonofImpulsesby
decrementaldecay.
NotallsensoryandmotormodalItIesareblockedbylocalanesthetIcsequally.thasbeen
longobservedthatapplIcatIonoflocalanesthetIcsproducedanorderedprogressIonof
sensoryandmotordefIcIts,startIngcommonlywIththedIsappearanceoftemperature
sensatIon,followedbyproprIoceptIon,motorfunctIon,sharppaIn,andthenlIghttouch.
Termeddifferential blockade,hIstorIcallythIshadbeenthoughttoberelatedsImplytothe
dIameterofthenervefIbers,wIththesmallerfIbersInherentlymoresusceptIbletodrug
blockadethanlargerfIbers.
28
However,whIlethesIzeprIncIpleofdIfferentIalblockade
IsconsIstentwIthmanyexperImentalfIndIngs,ItdoesnotappeartobeunIversallytrue.
Larger,myelInatedAdeltafIbers(belIevedtomedIatesharppaIn)havebeenfoundtobe
blockedpreferentIallyoversmall,nonmyelInated
P.5J6
CfIbers(dullpaIn).Furthermore,wIthIntheCfIbersarefastandslowcomponentsof
ImpulsetransmIssIon,eachwIthdIstInctsusceptIbIlItytodrugblockade.
29
These
observatIonsargueagaInstapurelypharmacokInetIcmechanIsmasthesolebasIsfor
explaInIngdIfferentIalblockade.nstead,ItmayalsolIkelydependontheIntrInsIc
excItatorypropertIesofthenervefIbers,namely,thepatternedexpressIonofvoltage
gatedsodIumchannels.ndeed,twochannelIsoforms,Na
7
1.7andNa
7
1.8,bothpresenton
dorsalrootganglIons,havebeenshowntopossessdIfferentsensItIvItIestolIdocaIne
blockade.
J0
tremaInstobeseenhowdIfferentIalblockadeofcertaInchannelsmIght
translateIntoselectIveInhIbItIonofpaInandothersensorymodalItIes.
Figure 21-7.0IagramIllustratIngtheprIncIpleofdecrementalconductIonblockby
localanesthetIcatamyelInatedaxon.ThefIrstnodeofFanvIeratleftcontaInsno
localanesthetIcandgIvesrIsetoanormalactIonpotentIal(solid curve).fthenodes
succeedIngthefIrstareoccupIedbyaconcentratIonoflocalanesthetIchIghenoughto
block74to84ofthesodIumconductance,thentheactIonpotentIalamplItudes
decreaseatsuccessIvenodes(amplItudesareIndIcatedbyInterruptedbars
representIngthreeIncreasIngconcentratIonoflocalanesthetIc).Eventually,the
ImpulsedecaystobelowthresholdamplItudeIftheserIesoflocalanesthetIc
contaInIngnodesIslongenough.PropagatIonoftheImpulseIsthenblockedby
decrementalconductIon,eventhoughnoneofthenodesarecompletelyblocked.
ConcentratIonsoflocalanesthetIcthatblockmorethan84ofthesodIum
conductanceatthreesuccessIvenodespreventanyImpulsepropagatIonatall.
(AdaptedfromFInk8F:|echanIsmsofdIfferentIalaxIalblockadeInepIduraland
spInalanesthesIa.AnesthesIology1989;70:851,wIthpermIssIon.)
Pharmacology and Pharmacodynamics
Chemical Properties and Relationship to Activity and Potency
|ostclInIcallyrelevantlocalanesthetIcsaremadeupofalIpIdsoluble,aromatIcbenzene
rIngconnectedtoanamIdegroupvIaeItheranamIdeorestermoIety.ThetypeoflInkage
dIvIdesthembroadlyIntotwocategorIes,theaminoestersandtheaminoamides.AsIde
fromadIfferenceIntheIrmetabolIcpathways(amInoestersarehydrolyzedbyplasma
cholInesterasesandamInoamIdesaredegradedbyhepatIccarboxylesterase)andthe
IncIdenceofallergIcreactIonsattrIbuted,theIrmembershIpIneIthercategoryofferslIttle
IndIstInctIonoftheIrbIophysIcalpropertIes.Father,thedIstInguIshIngphysIochemIcal
characterIstIcsareassocIatedwIththealkalInItyoftheamIdegroup,thelIpophIlIcIty
conferredbythealkylsubstItutIonontheamIdegroupandthebenzenerIng,andthe
stereochemIstryofrelatedIsomers.
ThetertIaryamIdefoundInlocalanesthetIcsIscapableofacceptIngaproton,albeItwIth
lowaffInIty;thus,thesecompoundsareclassIfIedasweakbases.AtphysIologIcalpH,local
anesthetIcsInsolutIonareInequIlIbrIumbetweentheprotonated,catIonIcformandthe
lIpIdsoluble,neutralforms.TheratIoofthetwoformsdependsonthepK
a
orthe
dIssocIatIonconstant,ofthelocalanesthetIcsandthesurroundIngpH(Table21J).AratIo
wIthhIghconcentratIonofthelIpIdsolubleformfavorsentryIntothecellasthemaIn
pathwayforentryIsbypassIveadsorptIonoflIpIdsolubleformthroughthecell
membrane.
2
ClInIcally,alkalIzatIonoftheanesthetIcsolutIonIncreasestheratIoofthe
lIpIdsolubleformtocatIonIcform,therebyfacIlItatIngcellentry.DnceInsIdethecell,
equIlIbrIumIsreestablIshedbetweenthecatIonIcandtheneutralforms,andItappears
thatthecatIonIcformIsthemorepotentofthetwoInItsactIvItyonsodIumchannels.
J1
LIpIdsolubIlItyoflocalanesthetIcsIsdetermInedbythedegreeofalkylgroupsubstItutIon
ontheamIdegroupandthebenzenerIng.nthelaboratory,ItIsmeasuredbythepartItIon
coeffIcIentInoctanol,ahydrophobIcsolvent,andcompoundswIthhIghoctanol:buffer
partItIoncoeffIcIentsaremorelIpIdsoluble.
J2
AposItIvecorrelatIonexIstsbetweenthe
potencyofthelocalanesthetIcsandItsoctanol:bufferpartItIoncoeffIcIent;hIghlylIpId
solubleagentsaremorepotentandtendtohavealongerduratIonofactIonthanonesthat
arelesslIpIdsoluble.
JJ
ThIsIsconsIstentwIthexperImentalfIndIngsthatshowlocal
anesthetIcsbIndtoahydrophobIcpocketwIthInthesodIumchannels,suggestIngthat
lIgandbIndIngmaybemedIatedprImarIlybyhydrophobIcandvanderWaalsInteractIons
21
(FIg.216).
WhereasthecorrelatIonbetweenlocalanesthetIcpotencyandhydrophobIcItygenerally
holdstrueInvItro,ItmaynotbeasexactInvIvo.AsopposedtosetupswIthIsolated
nerves,otherfactorsmayInfluencethepotencyoflocalanesthetIcsonnervesInsItu.
J4
Forexample,hIghlylIpIdsolubleagentsmaybesequesteredIntosurroundIngadIposecells.
7asodIlatorypropertIesoflocalanesthetIcsmaylIkewIsealterdrugredIstrIbutIonIntothe
neIghborIngtIssues.
J5,J6
FelatIvepotencyoflocalanesthetIcshasbeendetermInedfor
dIfferentclInIcalapplIcatIonsandthesevaluesarelIstedInTable214.
FInally,anesthetIcactIvItyandpotencyareaffectedbythestereochemIstryoflocal
anesthetIcs.|anyolderdrugsexIstasracemIcmIxtures;thatIs,enantIomerIc
stereoIsomersdIfferIngInthearrangementattheasymmetrIcorchIralcarbonatomareIn
equalproportIon.Neweragents,namelyropIvacaIneandlevobupIvacaIne,areavaIlableas
purelysIngleenantIomers.TheywereInItIallydevelopedaslesscardIotoxIcalternatIvesto
bupIvacaIne.WhIlethedesIredImprovementInthesafetyIndexhasbeengenerally
supportedbyclInIcalstudIes,Itappearsthatoverall,thIsIsattheexpenseofaslIght
decreaseInpotencyandshorterduratIonofactIoncomparedwIththeracemIc
P.5J7
mIxtures.
J7,J8
AtheoretIcalbasIsforthedIfferencebetweentheenantIomerIc
stereoIsomerscanbereadIlyhypothesIzed;however,lIttleIsknownoftheexact
mechanIsmsInvolved.LIkely,ItmayIncludesubtlestereoselectIvepreferenceInlocal
anesthetIcbIndIngamongtheIndIvIdualsodIumchannelIsoforms.
Table 21-3 Physicochemical Properties of Clinically Used Local
Anesthetics
pK
a
% IONIZED (at pH PARTITION COEFFICIENT (LIPID % PROTEIN
LOCAL ANESTHETIC 7.4) SOLUBILITY) BINDING
A|0ES
8upIvacaIne
a
8.1 8J J,420 95
EtIdocaIne 7.7 66 7,J17 94
LIdocaIne 7.9 76 J66 64
|epIvacaIne 7.6 61 1J0 77
PrIlocaIne 7.9 76 129 55
FopIvacaIne 8.1 8J 775 94
ESTEFS
ChloroprocaIne 8.7 95 810 N/A
ProcaIne 8.9 97 100 6
TetracaIne 8.5 9J 5,822 94
N/A,notavaIlable.
a
LevobupIvacaInehassamephysIcochemIcalpropertIesasracemate.
0atafromLIuSS:LocalanesthetIcsandanalgesIa,The|anagementofPaIn.EdIted
byAshburn|A,FIceLJ.NewYork,ChurchIllLIvIngstone,1997,pp141.
Table 21-4 Relative Potency of Local Anesthetics for Different Clinical
Applications
BUPIVACAINE
CHLORO-
PROCAINE
LIDOCAINE MEPIVACAINE PRILOCAINE ROPIVACAINE
PerIpheral
nerve
J.6 N/A 1 2.6 0.8 J.6
SpInal 9.6 1 1 1 1 N/A
EpIdural 4 0.5 1 1 1 4
N/A,notavaIlable.
0atafromCamorcIa|:|InImumlocalanalgesIcdosesofropIvacaIne,
levobupIvacaIne,andbupIvacaIneforIntrathecallaboranalgesIa.AnesthesIology
2005;102:646.FaccendaKA:AcomparIsonoflevobupIvacaIne0.5andracemIc
bupIvacaIne0.5forextraduralanesthesIaforcaesareansectIon.FegAnesthPaIn
|ed200J;28:J94.|c0onaldS8.HyperbarIcspInalropIvacaIne:AcomparIsonto
bupIvacaIneInvolunteers.AnesthesIology1999;90:971.|arsanA:PrIlocaIneor
mepIvacaIneforcombInedscIatIcfemoralnerveblockInpatIentsreceIvIng
electIvekneearthroscopy.|InervaAnestesIol2004;70:76J.CasatIA:LIdocaIne
versusropIvacaIneforcontInuousInterscalenebrachIalplexusblockafteropen
shouldersurgery.ActaAnaesthesIolScand200J;47:J5.CasatIA:AdoubleblInd
studyofaxIllarybrachIalplexusblockby0.75ropIvacaIneor2mepIvacaIne.Eur
JAnaesthesIol1998;15:549.FanellIC:AdoubleblIndcomparIsonofropIvacaIne,
bupIvacaIne,andmepIvacaInedurIngscIatIcandfemoralnerveblockade.Anesth
Analg,1998;87:597.YoosJF:SpInal2chloroprocaIne:acomparIsonwIthsmall
dosebupIvacaIneInvolunteers.AnesthAnalg2005;100:566.KourI|E:SpInal2
chloroprocaIne:AcomparIsonwIthlIdocaIneInvolunteers.AnesthAnalg2004;98:
75.
Additives to Increase Local Anesthetic Activity
Epinephrine
FeportedbenefItsofepInephrIneIncludeprolongatIonoflocalanesthetIcblock,Increased
IntensItyofblock,anddecreasedsystemIcabsorptIonoflocalanesthetIc.
J9
EpInephrIne's
vasoconstrIctIveeffectsaugmentlocalanesthetIcsbyantagonIzIngInherentvasodIlatIng
effectsoflocalanesthetIcs,decreasIngsystemIcabsorptIonandIntraneuralclearance,and
perhapsbyredIstrIbutIngIntraneurallocalanesthetIc.
J9,40
0IrectanalgesIceffectsfromepInephrInemayalsooccurvIaInteractIonwIth
2
adrenergIc
receptorsInthebraInandspInalcord,
41
especIallybecauselocalanesthetIcsIncreasethe
vascularuptakeofepInephrIne.
42
ClInIcaluseofepInephrIneIslIstedInTable215.The
smallestdoseIssuggestedbecauseepInephrInecombInedwIthlocalanesthetIcsmayhave
toxIceffectsontIssue,
4J
thecardIovascularsystem,
44
perIpheralnerves,andthespInal
cord.
J9
Alkalinization of Local Anesthetic Solution
LocalanesthetIcsolutIonsarealkalInIzedInordertohastenonsetofneuralblock.
45
ThepH
ofcommercIalpreparatIonsof
P.5J8
localanesthetIcsrangesfromJ.9to6.47andIsespecIallyacIdIcIfprepackagedwIth
epInephrIne.
46
AsthepK
a
ofcommonlyusedlocalanesthetIcsrangesfrom7.6to8.9(Table
21J),JofthecommercIallypreparedlocalanesthetIcexIstsasthelIpIdsolubleneutral
form.TheneutralformIsbelIevedtobethemostImportantforpenetratIonIntothe
neuralcytoplasm,whereasthechargedformprImarIlyInteractswIththelocalanesthetIc
receptorwIthInthesodIumchannel.Therefore,theratIonaleforalkalInIzatIonwasto
IncreasethepercentageoflocalanesthetIcexIstIngasthelIpIdsolubleneutralform.
However,clInIcallyusedlocalanesthetIcscannotbealkalInIzedbeyondapHof6.05to8
beforeprecIpItatIonoccurs,
46
andsuchpHswIllonlyIncreasetheneutralformtoabout
10.
Table 21-5 Effects of Addition of Epinephrine to Local Anesthetics

INCREASE
DURATION
DECREASE BLOOD
LEVELS (%)
DOSE/CONCENTRATION OF
EPINEPHRINE
NEF7E8LDCK
8upIvacaIne +/ 1020 1:200,000
LIdocaIne ++ 20J0 1:200,000
|epIvacaIne ++ 20J0 1:200,000
FopIvacaIne 0 1:200,000
EP0UFAL
8upIvacaIne +/ 1020 1:J00,0001:200,000
LevobupIvacaIne +/ 10 1:200,0001:400,000
ChloroprocaIne ++ 1:200,000
LIdocaIne ++ 20J0 1:600,0001:200,000
|epIvacaIne ++ 20J0 1:200,000
FopIvacaIne 0 1:200,000
SPNAL
8upIvacaIne +/ 0.2mg
LIdocaIne ++ 0.2mg
TetracaIne ++ 0.2mg
++,overallsupported;,overallnotsupported;+/,InconsIstent.
byAshburn|A,FIceLJ.NewYork,ChurchIllLIvIngstone,1997,pp141;andKopacz
0J:AcomparIsonofepIdurallevobupIvacaIne0.5wIthorwIthoutepInephrInefor
lumbarspInesurgery.AnesthAnalg2001;9J:755.
ClInIcalstudIesthathaveshownanassocIatIonbetweenalkalInIzatIonoflocalanesthetIcs
andhastenIngofblockonsethaveshownadecreaseof5mInuteswhencomparedwIth
commercIalpreparatIons.
45,47
naddItIon,astudyInratssuggeststhatalkalInIzatIonof
lIdocaInedecreasestheduratIonofperIpheralnerveblocksIfthesolutIondoesnotalso
contaInepInephrIne.
48
Dverall,thevalueofalkalInIzatIonoflocalanesthetIcsappears
debatableasaclInIcallyusefultooltoImproveanesthesIa.
Opioids
DpIoIdshavemultIplecentralneuraxIalandperIpheralmechanIsmsofanalgesIcactIon.
SpInaladmInIstratIonofopIoIdsprovIdesanalgesIaprImarIlybyattenuatIngCfIber
nocIceptIon
49
andIsIndependentofsupraspInalmechanIsms.
50
CoadmInIstratIonofopIoIds
wIthcentralneuraxIallocalanesthetIcsresultsInsynergIstIcanalgesIa.
51
AnexceptIonto
thIsanalgesIcsynergyIs2chloroprocaIne,whIchappearstodecreasetheeffectIvenessof
epIduralopIoIdswhenusedforepIduralanesthesIa.
52
ThemechanIsmforthIsactIonIs
unclearbutdoesnotappeartoInvolvedIrectantagonIsmofopIoIdreceptors.
5J
Dverall,
clInIcalstudIessupportthepractIceofcentralneuraxIalcoadmInIstratIonoflocal
anesthetIcsandopIoIdsInhumansforprolongatIonandIntensIfIcatIonofanalgesIaand
anesthesIa.
51
ThedIscoveryofperIpheralopIoIdreceptorsInItIallyofferedanothercIrcumstanceIn
whIchthecoadmInIstratIonoflocalanesthetIcsandopIoIdsmaybeuseful.
54
However,
cumulatIveevIdencenowsuggeststhatneItherIntraartIcularadmInIstratIonoflocal
anesthetIcandopIoIdforpostoperatIveanalgesIa
55
norcombInInglocalanesthetIcsand
opIoIdsfornerveblocksIncreaseseffIcacy.
56
2
-Adrenergic Agonists
2
AdrenergIcagonIstscanbeausefuladjuvanttolocalanesthetIcs.
2
AgonIsts,suchas
clonIdIne,produceanalgesIavIasupraspInalandspInaladrenergIcreceptors.
57
ClonIdIne
alsohasdIrectInhIbItoryeffectsonperIpheralnerveconductIon(AandCnervefIbers).
58
Thus,addItIonofclonIdInemayhavemultIpleroutesofactIondependIngontypeof
applIcatIon.PrelImInaryevIdencesuggeststhatcoadmInIstratIonofan
2
agonIstandlocal
anesthetIcresultsIncentralneuraxIalandperIpheralnerveanalgesIcsynergy,
59
whereas
systemIc(supraspInal)effectsareaddItIve.
60
Dverall,clInIcaltrIalsIndIcatethatclonIdIne
enhancesIntrathecalandepIduralanesthesIa,perIpheralnerveblocks,
61
andIntravenous
regIonalanesthesIa.
62
Pharmacokinetics of Local Anesthetics
PlasmaconcentratIonoflocalanesthetIcsIsafunctIonofthedoseadmInIsteredandthe
ratesofsystemIcabsorptIon,tIssuedIstrIbutIon,anddrugelImInatIon.Elevatedlevelsmay
produceunIntendedeffectsInotherelectrIcsensItIvesystems,mostImportantly,the
cardIovascularandthecentralnervoussystems.HavIngathoroughunderstandIngofthe
factorsInvolvedwouldenableonetomaxImIzethelocalanesthetIcpotentIalwhIle
avoIdIngpossIblecomplIcatIonsarIsIngfromsystemIclocalanesthetIctoxIcIty.
Systemic Absorption
0ecreasIngsystemIcabsorptIonoflocalanesthetIcsIncreasestheIrsafetymargInInclInIcal
uses.TherateandextentofsystemIcabsorptIondependsonthesIteofInjectIon,thedose,
thedrug'sIntrInsIcpharmacokInetIcpropertIes,andtheaddItIonofavasoactIveagent.The
vascularItyofthetIssuemarkedlyInfluencestherateofdrugabsorptIon,suchthat
deposItIonoflocalanesthetIcsInvesselrIchtIssuesresultsInhIgherpeakplasmalevelsIn
ashorterperIodoftIme.AccordIngly,therateofsystemIcabsorptIonIsgreatestwIth
Intercostalnerveblocks,andfollowedIndecreasIngorder,bycaudalandepIdural
InjectIons,brachIalplexusblock,andfemoralandscIatIcnerveblocks(Table216).Thus,
thesameamountoflocalanesthetIcsInjectedwouldresultInunequalpeakplasmalevels,
dependIngonthesIteofdrugdelIvery.
ForagIvensIteofInjectIon,therateofsystemIcabsorptIonandthepeakplasmalevelare
dIrectlyproportIonaltothedoseoflocalanesthetIcdeposIted.ThIsrelatIonshIpIsnearly
lInear(FIg.218)andIndependentofthedrugconcentratIonandthespeedofInjectIon.
6J
TherateofsystemIcabsorptIondIfferswIthIndIvIduallocalanesthetIcs.ngeneral,more
potent,lIpIdsolubleagentsareassocIatedwIthaslowerrateofabsorptIonthanlesslIpId
solublecompounds(FIg.219).SequestratIonIntolIpIdrIchcompartmentsmaynotbethe
onlyexplanatIon.LocalanesthetIcsexertdIrecteffectsonvascularsmoothmusclesIna
concentratIondependentmanner.AtlowconcentratIons,morepotentagentsappearto
causemorevasoconstrIctIonthanlesspotentagents,therebydecreasIngtherateof
vascularabsorptIon.
J6
AthIghconcentratIons,vasodIlatoryeffectsseemtopredomInate
formostlocalanesthetIcs.
Distribution
SystemIcabsorptIonoflocalanesthetIcsleadstorapIddIstrIbutIonthroughoutthebody.
WhIletheapparentvolumeofdIstrIbutIon(70
ss
)adequatelydescrIbesthesteadystate
concentratIonoflocalanesthetIcsInplasma(Table217),ItofferslIttleInformatIon
regardIngthepatternofdIstrIbutIon.FegIonaldIfferences
P.5J9
InlocalanesthetIcconcentratIonsareseenamongIndIvIdualorgansystemsandthepattern
ofdIstrIbutIonlargelydependsonorganperfusIon,thepartItIoncoeffIcIentbetween
compartments,andplasmaproteInbIndIng.
64
Drgansthatarewellperfused,suchasthe
heartandthebraIn,havehIgherdrugconcentratIons.Unfortunately,theyarealsothe
organsmostserIouslyaffectedbylocalanesthetIctoxIcIty.
Table 21-6 Typical C
max
After Regional Anesthetics with Commonly Used
Local Anesthetics
LOCAL ANESTHETIC TECHNIQUE
DOSE
(mg)
C
max
(g/mL)
T
max
(min)
TOXIC PLASMA
CONCENTRATION (g/mL)
8upIvacaIne
8rachIalplexus 150 1.0 20 J
CelIacplexus 100 1.50 17
EpIdural 150 1.26 20
ntercostal 140 0.90 J0
Lumbar
sympathetIc
52.5 0.49 24
ScIatIcfemoral 400 1.89 15
LevobupIvacaIne
EpIdural 75 0.J6 50 4
8rachIalplexus 250 1.2 55
LIdocaIne
8rachIalplexus 400 4.00 25 5
ntercostal 400 6.8 15
|epIvacaIne
8rachIalplexus 500 J.68 24 5
ScIatIc/femoral 500 J.59 J1
FopIvacaIne
8rachIalplexus 190 1.J 5J 4
C
max
,peakplasmalevels;T
max
,tImeuntIlC
max
.
byAshburn|A,FIceLJ.NewYork,ChurchIllLIvIngstone,1997,pp141.8errIsford
FC:PlasmaconcentratIonsofbupIvacaIneandItsenantIomersdurIngcontInuous
extrapleuralIntercostalnerveblock.8rJAnaesth199J;70:201.Kopacz0J:A
comparIsonofepIdurallevobupIvacaIne0.5wIthorwIthoutepInephrInefor
lumbarspInesurgery.AnesthAnalg2001;9J:755.CrewsJC:LevobupIvacaInefor
axIllarybrachIalplexusblock:ApharmacokInetIcandclInIcalcomparIsonIn
patIentswIthnormalrenalfunctIonorrenaldIsease.AnesthAnalg2002;95:219.
Figure 21-8.ncreasIngdosesofropIvacaIneusedforwoundInfIltratIonresultIn
lInearlyIncreasIngmaxImalplasmaconcentratIons(C
max
).(0atafrom|ulroy|F,
8urgessFW,Emanuelsson8|:FopIvacaIne0.25and0.5,butnot0.125,provIde
effectIvewoundInfIltratIonanalgesIaafteroutpatIenthernIarepaIr,butwIth
sustaInedplasmadruglevels.FegAnesthPaIn|ed1999;24:1J6.)
Figure 21-9.FractIonofdoseabsorbedIntothesystemIccIrculatIonovertImefrom
epIduralInjectIonoflIdocaIneorbupIvacaIne.8upIvacaIneIsamorelIpIdsoluble,
morepotentagentwIthlesssystemIcabsorptIonovertIme.(AdaptedfromTuckerCT,
|atherLE:PropertIes,absorptIon,anddIsposItIonoflocalanesthetIcagents,Neural
8lockadeInClInIcalAnesthesIaand|anagementofPaIn.EdItedbyCousIns|J,
8rIdenbaughPD.PhIladelphIa,LIppIncottFaven,1998,p55,wIthpermIssIon.)
Elimination
ThemetabolIcpathwayforclearanceoflocalanesthetIcsIsprImarIlydetermInedbytheIr
chemIcallInkage.AmInoestersarehydrolyzedbyplasmacholInesterasesandamInoamIdes
aretransformedbyhepatIccarboxylesterasesandcytochromeP450enzymes.SeverelIver
dIseasemayslowtheclearanceofamInoamIdelocalanesthetIcsandsIgnIfIcantdruglevels
maythereforeaccumulate.
65
Clinical Pharmacokinetics
TheprImarybenefItofknowledgeofthesystemIcpharmacokInetIcsoflocalanesthetIcsIs
theabIlItytopredIctthepeakplasmalevel(C
max
)aftertheagentsareadmInIstered,
therebyavoIdIngtheadmInIstratIonoftoxIcdoses(Tables216,218,and219).However,
pharmacokInetIcsaredIffIculttopredIctInanygIvencIrcumstanceasbothphysIcaland
pathophysIologIccharacterIstIcswIllaffecttheIndIvIdualpharmacokInetIcs.ThereIssome
evIdenceforIncreasedsystemIclevelsoflocalanesthetIcsIntheveryyoungandInthe
elderlyowIngtodecreasedclearanceandIncreasedabsorptIon,
66
whereascorrelatIonof
resultantsystemIcbloodlevelsbetweendoseoflocalanesthetIcandpatIentweIghtIs
oftenInconsIstent(FIg.2110).
67
EffectsofgenderonclInIcalpharmacokInetIcsoflocal
anesthetIcshavenotbeenwelldefIned,
68
althoughpregnancymaydecreaseclearance.
69
PathophysIologIcstatessuchascardIacandhepatIcdIseasewIllalterexpected
pharmacokInetIcparameters(Table2110),andlowerdosesoflocalanesthetIcsshouldbe
usedforthesepatIents.Asexpected,renal
P.540
dIseasehaslIttleeffectonpharmacokInetIcparametersoflocalanesthetIcs(Table2110).
AllofthesefactorsshouldbeconsIderedwhenusInglocalanesthetIcsandmInImIzIng
systemIctoxIcIty,thecommonlyacceptedmaxImaldosages(Table219)notwIthstandIng.
Table 21-7 Pharmacokinetic Parameters of Clinically Used Local
Anesthetics
LOCAL ANESTHETIC VDss (L/kg) CL (L/kg/hr) T
1/2
(hr)
8upIvacaIne 1.02 0.41 J.5
LevobupIvacaIne 0.78 0.J2 2.6
ChloroprocaIne 0.50 2.96 0.11
EtIdocaIne 1.9 1.05 2.6
LIdocaIne 1.J 0.85 1.6
|epIvacaIne 1.2 0.67 1.9
PrIlocaIne 2.7J 2.0J 1.6
ProcaIne 0.9J 5.62 0.14
FopIvacaIne 0.84 0.6J 1.9
70ss,volumeofdIstrIbutIonatsteadystate;CL,totalbodyclearance;T
1/2
,
termInalelImInatIonhalflIfe.
0atafrom0enson00:PhysIologyandpharmacologyoflocalanesthetIcs,Acute
PaIn.|echanIsmsand|anagement.EdItedbySInatraFS,HordAH,CInsberg8,et
al.St.LouIs,|osbyYear8ook,1992.p124;and8urmAC,vander|eerA0,van
KleefJWetal:PharmacokInetIcsoftheenantIomersofbupIvacaInefollowIng
IntravenousadmInIstratIonoftheracemate.8rJClInPharmacol1994;J8:125.
Clinical Use of Local Anesthetics
LocalanesthetIcsareusedInavarIetyofwaysInclInIcalanesthesIapractIce.Probablythe
mostcommonclInIcaluseoflocalanesthetIcsforanesthesIologIstsIsforregIonal
anesthesIaandanalgesIa.CentralneuraxIalanesthesIaandanalgesIacanbeaccomplIshed
byepIduralorspInalInjectIonsoflocalanesthetIcs.PlacementofepIduralandspInal
catheterscanallowcontInuousInfusIonoflocalanesthetIcsandotheranalgesIcsfor
extendedduratIons.ntravenousregIonalanesthesIaandperIpheralnerveblocksallowfor
anesthesIaoftheheadandneck,IncludIngtheaIrway,upperextremItIes,trunk,andlower
extremItIes.CathetersforcontInuousperIpheralnerveblocksandcontInuoussurgIcal
woundInfusIonscanalsobeplacedtoallowcontInuousInfusIonsoflocalanesthetIcsfor
prolongedanalgesIa.
70
TopIcalapplIcatIonoflocalanesthetIcstotheaIrway,eye,andskInprovIdessuffIcIent
anesthesIaforpaInlessperformanceofmInoranesthetIcandsurgIcalproceduressuchas
trachealIntubatIon,Intravenouscatheterplacement,orduralpuncture.
71
TypIcal
applIcatIonsforeachlocalanesthetIcarelIstedInTable219.
72
DthercommonclInIcalusesforlocalanesthetIcsIncludeadmInIstratIonoflIdocaIneto
bluntresponsestotrachealInstrumentatIonandtosuppresscardIacdysrhythmIas.
ntravenousortopIcaladmInIstratIonsoflIdocaInehavebeenusedwIthvarIablesuccessto
blunthemodynamIcresponsetotrachealIntubatIonandextubatIon.
7J
naddItIonto
hemodynamIcresponses,InstrumentatIonoftheaIrwaycanresultIncoughIng,
bronchoconstrIctIon,andotheraIrwayresponses.ntravenouslIdocaInecanbeeffectIve
fordecreasIngaIrwaysensItIvItytoInstrumentatIonbydepressIngaIrwayreflexesand
decreasIngcalcIumfluxInaIrwaysmoothmuscle.
74
0osesofIntravenouslIdocaInefrom2
to2.5mg/kgareneededtoconsIstentlyblunthemodynamIcandaIrwayresponsesto
tracheal
P.541
InstrumentatIon.
74,75
ntravenouslIdocaIneIsalsoeffectIveforattenuatIngIncreasesIn
Intraocularpressure,IntracranIalpressure,andIntraabdomInalpressuredurIngaIrway
InstrumentatIon.
76
AttenuatIonofalltheseresponsesmaybebenefIcIalInselectedclInIcal
sItuatIons(e.g.,corneallaceratIonorIncreasedIntracranIalpressure).ntravenous
lIdocaInehaswellrecognIzedcardIacantIdysrhythmIceffects.
77
Table 21-8 Relative Potency for Systemic Central Nervous System Toxicity
by Local Anesthetics and Ratio of Dosage Needed for Cardiovascular
System: Central Nervous System (CVS:CNS) Toxicity
AGENT RELATIVE POTENCY FOR CNS TOXICITY CVS:CNS
8upIvacaIne 4.0 2.0
LevobupIvacaIne 2.9 2.0
ChloroprocaIne 0.J J.7
EtIdocaIne 2.0 4.4
LIdocaIne 1.0 7.1
|epIvacaIne 1.4 7.1
PrIlocaIne 1.2 J.1
ProcaIne 0.J J.7
FopIvacaIne 2.9 2.0
TetracaIne 2.0
0atafromLIuSS:LocalAnesthetIcsandAnalgesIa,The|anagementofPaIn.
EdItedbyAshburn|A,FIceLJ.NewYork,ChurchIllLIvIngstone,1997,pp141;and
CrobanL:CentralnervoussystemandcardIaceffectsfromlongactIngamIdelocal
anesthetIctoxIcItyIntheIntactanImalmodel.FegAnesthPaIn|ed200J;28:J.
Table 21-9 Clinical Profile of Local Anesthetics
LOCAL ANESTHETIC
CONCENTRATION
(%)
CLINICAL USE ONSET
DURATION
(hr)
RECOMMENDED
MAXIMUM
SINGLE DOSE
(mg)
A|0ES
8upIvacaIne 0.25 nfIltratIon Fast 28
175/225+
epInephrIne
LevobupIvacaIne
0.250.5
PerIpheral
nerve
block
Slow 412 150
0.50.75
EpIdural
anesthesIa
|oderate 25 150
0.0J0.25
EpIdural
analgesIa
NA NA NA
0.50.75
SpInal
anesthesIa
Fast 14 20
EtIdocaIne
0.5 nfIltratIon Fast 28
J00/400+
epInephrIne
0.51
PerIpheral
nerve
block
Fast J12
J00/400+
epInephrIne
11.5
EpIdural
anesthesIa
Fast 24
J00/400+
epInephrIne
LIdocaIne
J00/500+
epInephrIne
0.250.5
7regIonal
anesthesIa
Fast 0.51 J00
11.5
PerIpheral
nerve
block
Fast 1J
J00/500+
epInephrIne
1.52
EpIdural
anesthesIa
Fast 12
J00/500+
epInephrIne
1.55
SpInal
anesthesIa
Fast 0.51 100
4 TopIcal Fast 0.51 J00
|epIvacaIne
400/500+
epInephrIne
11.5
PerIpheral
nerve
block
Fast 24
400/500+
epInephrIne
1.52
EpIdural
anesthesIa
Fast 1J
400/500+
epInephrIne
24
SpInal
anesthesIa
Fast 12 100
PrIlocaIne
0.51 nfIltratIon Fast 12 600
0.250.5
7regIonal
anesthesIa
Fast 0.51 600
1.52
PerIpheral
nerve
block
Fast 1.5J 600
2J EpIdural Fast 1J 600
FopIvacaIne
0.20.5 nfIltratIon Fast 26 200
0.51
PerIpheral
nerve
block
Slow 58 250
0.51
EpIdural
anesthesIa
|oderate 26 200
0.050.2
EpIdural
analgesIa
NA NA NA
|XTUFE
LIdocaIne+
prIlocaIne
2.5/2.5
SkIn
topIcal
Slow J5 20gm
ESTEFS
8enzocaIne Upto20 TopIcal Fast 0.51 200
ChloroprocaIne
1 nfIltratIon Fast 0.51
800/1000+
epInephrIne
2
PerIpheral
nerve
block
Fast 0.51
800/1000+
epInephrIne
2J
EpIdural
anesthesIa
Fast 0.51
800/1000+
epInephrIne
CocaIne 410 TopIcal Fast 0.51 150
ProcaIne 10
SpInal
anesthesIa
Fast 0.51 1,000
TetracaIne 2 TopIcal Fast 0.51 20
0.5
SpInal
anesthesIa
Fast 26 20
7,Intravenous.
AdaptedfromCovIno8C,WIldsmIthJAW:ClInIcalpharmacologyoflocalanesthetIc
agents.
Neural8lockadeInClInIcalAnesthesIaand|anagementofPaIn.EdItedbyCousIns
|J,8rIdenbaughPD.PhIladelphIa,LIppIncottFaven,1998,pp97,wIthpermIssIon.
Table 21-10 Effects of Cardiac, Hepatic, and Renal Disease on Lidocaine
Pharmacokinetics
VD
ss
(L/Kg) CL (mL/kg/min) T
1/2
(hr)
Normal 1.J2 10.0 1.8
CardIacfaIlure 0.88 6.J 1.9
HepatIcdIsease 2.J1 6.0 4.9
FenaldIsease 1.2 1J.7 1.J
70ss,volumeofdIstrIbutIonatsteadystate;CL,totalbodyclearance;T
1/2
,
termInalelImInatIonhalflIfe.
0atafromThomsonP0:LIdocaInepharmacokInetIcsInadvancedheartfaIlure,
lIverdIsease,andrenalfaIlureInhumans.Annntern|ed197J;78:499.
Figure 21-10.LackofcorrelatIonbetweenpatIentweIghtandpeakplasma
concentratIonafterepIduraladmInIstratIonof150mgofbupIvacaIne.(0atafrom
SharrockNE,|atherLE,CoC,etal:ArterIalandpulmonaryconcentratIonsofthe
enantIomersofbupIvacaIneafterepIduralInjectIonInelderlypatIents.AnesthAnalg
1998;86:812.)
FInally,IntravenouslIdocaIne(1to5mg/kg)IsaneffectIveanalgesIcandhasbeenusedto
treatpostoperatIve
78
andchronIcneuropathIcpaIn.
79
PerIpheralandcentralInhIbItIonof
generatIonandpropagatIonofspontaneouselectrIcalactIvItyInInjuredCnervefIbersand
AnervefIbersarethoughttobeprImarymechanIsmsasopposedtotypIcalconductIon
block.
80
PosItronemIssIontomographyInpatIentswIthneuropathIcpaInsuggeststhat
alteredactIvItyIncerebralbloodflowtothethalamus
81
mayalsocontrIbutetosystemIc
analgesIceffectsoflocalanesthetIcs.TheabIlItyoflocalanesthetIcstoprovIdesystemIc
analgesIceffectsatcentralandperIpheralsItesmaypartlyexplaIntheabIlItyofasIngle
neuralblocktoprovIdelonglastInganalgesIafromneuropathIcpaIn.
Toxicity of Local Anesthetics
Systemic Toxicity of Local Anesthetics
Central Nervous System Toxicity
LocalanesthetIcsreadIlycrossthebloodbraInbarrIer,andgeneralIzedCNStoxIcItymay
occurfromsystemIcabsorptIonordIrectvascularInjectIon.SIgnsofgeneralIzedCNS
toxIcItybecauseoflocalanesthetIcsaredosedependent(Table2111).Lowdosesproduce
CNSdepressIon,andhIgherdosesresultInCNSexcItatIonandseIzures.
82
Therateof
IntravenousadmInIstratIonoflocalanesthetIcwIllalsoaffectsIgnsofCNStoxIcIty,as
hIgherratesofInfusIonofthesamedosewIlllessentheappearanceofCNSdepressIon
whIleleavIngexcItatIonIntact.
8J
ThIsdIchotomousreactIontolocalanesthetIcsmaybea
resultofagreatersensItIvItyofcortIcalInhIbItoryneuronstotheImpulseblockIngeffects
oflocalanesthetIcs.
82,84,85
Table 21-11 Dose-Dependent Systemic Effects of Lidocaine
PLASMA CONCENTRATION (g/mL) EFFECT
15 AnalgesIa
510
LIghtheadedness
TInnItus
Numbnessoftongue
1015
SeIzures
UnconscIousness
1525
Coma
FespIratoryarrest
25 CardIovasculardepressIon
LocalanesthetIcpotencyforgeneralIzedCNStoxIcItyapproxImatelyparallelsactIon
potentIalblockIngpotency(Tables214and218).
82
ngeneral,decreasedlocalanesthetIc
proteInbIndIngandclearancewIllIncreasepotentIalCNStoxIcIty.Externalfactorscan
IncreasepotencyforCNStoxIcIty,suchasacIdosIsandIncreasedPCD
2
,perhapsvIa
IncreasedcerebralperfusIonordecreasedproteInbIndIngoflocalanesthetIc.
82
Thereare
alsoexternalfactorsthatcandecreaselocalanesthetIcpotencyforgeneralIzedCNS
toxIcIty.Forexample,seIzurethresholdsoflocalanesthetIcsareIncreasedby
admInIstratIonofbarbIturatesandbenzodIazepInes.
86
AddItIonofvasoconstrIctorssuchasepInephrInemayreduceorpromotethepotentIalfor
generalIzedlocalanesthetIcCNStoxIcIty.AddItIonofepInephrInetolocalanesthetIcswIll
decreasesystemIcabsorptIonandpeakbloodlevelsandIncreasethesafetymargIn.Dnthe
otherhand,theconvulsIvethresholdforIntravenousadmInIstratIonoflIdocaIneIntherat
Isdecreasedbyabout42whenepInephrIne(1:100,000),norepInephrIne,orphenylephrIne
IsaddedtotheplaInsolutIon.
87
ThemechanIsmsofIncreasedtoxIcItywIthaddItIonof
epInephrIneareunclearbutappeartodependonthedevelopmentofhypertensIonfrom
vasoconstrIctIon.AhyperdynamIccIrculatorysystemmayenhancethetoxIceffectsoflocal
anesthetIcsbycausIngIncreasedcerebralbloodflowanddelIveryoflIdocaInetothe
braIn
88
orthroughdIsruptIonofthebloodbraInbarrIer.
89
naddItIontoenhancIng
dIstrIbutIonoflocalanesthetIctothebraIn,hyperdynamIccIrculatorychangescanalso
decreaseclearanceoflocalanesthetIcfromthebodybecauseofchangesIndIstrIbutIonof
bloodflowawayfromthelIver.ChangesIntotalbodyclearancefromhyperdynamIc
cIrculatorychangesInducedbylocalanesthetIcseIzureshavebeenstudIedIndogs.
90
SeIzuressIgnIfIcantlyIncreasedheartrate,bloodpressure,andcardIacoutputwhIle
sIgnIfIcantlydecreasIngtotalbodyclearance(29to68)oflIdocaIne,mepIvacaIne,
bupIvacaIne,andetIdocaIne.
ClInIcalreportssuggesttoxIcItyfromlocalanesthetIcsusedforregIonalanesthesIaIs
uncommon.SurveysfromFranceandtheUnItedStatesofover280,000casesofregIonal
anesthesIareportanIncIdenceofseIzureswIthepIduralInjectIonapproxImatIng1/10,000
andanIncIdenceof7/10,000wIthperIpheralnerveblocks.
84,85
Thereappearstobea
hIgherIncIdenceoflocalanesthetIctoxIcItydurIngperIpheralnerveblocks,perhaps
P.542
becauseofdIfferencesInpractIceorlessclInIcalawareness.Nonetheless,InananalysIsof
closedmalpractIceclaImsIntheUnItedStatesfrom1980to1999,epIduralanesthesIa
(prImarIlyobstetrIcal)constItutedallofthecasesofdeathorbraIndamageresultIngfrom
unIntentIonalIntravenousInjectIonoflocalanesthetIc.
91
Cardiovascular Toxicity of Local Anesthetics
ngeneral,muchgreaterdosesoflocalanesthetIcsarerequIredtoproducecardIovascular
toxIcItythanCNStoxIcIty.SImIlartoCNStoxIcIty,potencyforcardIovasculartoxIcIty
reflectstheanesthetIcpotencyoftheagent(Tables214and218).AttentIonhasfocused
ontheIncreasedcardIotoxIcItyofthemorepotent,morelIpIdsolubleagents(bupIvacaIne,
levobupIvacaIne,ropIvacaIne).TheseagentsappeartohaveadIfferentsequenceof
cardIovasculartoxIcItythanlesspotentagents,wIthbupIvacaInebeIngthemost
cardIotoxIc.Forexample,IncreasInglytoxIcdosesoflIdocaIneleadstohypotensIon,
bradycardIa,andhypoxIa,whereastoxIcdosesofbupIvacaIne,levobupIvacaIne,and
ropIvacaIneoftenresultInsuddencardIovascularcollapseasaresultofventrIcular
dysrhythmIasthatareresIstanttoresuscItatIon(FIg.2111).
82,86,92
UseofthesIngleoptIcalIsomerpreparatIonsofropIvacaIneandlevobupIvacaInemay
ImprovethesafetyprofIleforlonglastIngregIonalanesthesIa.8othropIvacaIneand
levobupIvacaIneappeartobeapproxImatelyequIpotenttoracemIcbupIvacaInefor
epIduralandplexusanesthesIa(Table214).
9J,94
8othropIvacaIneandlevobupIvacaIne
haveapproxImatelyJ0to40lesssystemIctoxIcItythanbupIvacaIneonamIllIgramto
mIllIgrambasIsInanImalstudIes
82,92,95
(FIg.2112),althoughhumanstudIesareless
dramatIc(FIg.211J).
96,97
FeducedpotentIalforcardIotoxIcItyIslIkelybecauseofreduced
affInItyforbraInandmyocardIaltIssuefromtheIrsIngleIsomerpreparatIon.
18,82,98
n
addItIontostereoselectIvIty,thelargerbutylsIdechaInInbupIvacaInemayalsohave
moreofacardIodepressanteffectasopposedtothepropylsIdechaInofropIvacaIne.
99
Cardiovascular Toxicity Mediated at the CNS
thasbeendemonstratedthatthecentralandperIpheralnervoussystemsmaybeInvolved
IntheIncreasedcardIotoxIcItywIthbupIvacaIne.ThenucleustractussolItarIIInthe
medullaIsanImportantregIonforautonomIccontrolofthecardIovascularsystem.Neural
actIvItyInthenucleustractussolItarIIofratsIsmarkedlydImInIshedbyIntravenousdoses
ofbupIvacaIneImmedIatelyprIortodevelopmentofhypotensIon.Furthermore,dIrect
IntracerebralInjectIonofbupIvacaInecanelIcItsuddendysrhythmIasandcardIovascular
collapse.
100
Figure 21-11.SuccessofresuscItatIonofdogsaftercardIovascularcollapsefrom
IntravenousInfusIonsoflIdocaIne,bupIvacaIne,levobupIvacaIne(LbupIv),and
ropIvacaIne.SuccessratesweregreaterforlIdocaIne(100),thanropIvacaIne(90),
thanlevobupIvacaIne(70),andthanbupIvacaIne(50).FequIreddosestoInduce
cardIovascularcollapseweregreaterforlIdocaIne(127mg/kg),thanropIvacaIne(42
mg/kg),thanlevobupIvacaIne(27mg/kg),andthanbupIvacaIne(22mg/kg).(0ata
fromCrobanL,0eal00,7ernonJC,etal:CardIacresuscItatIonafterIncremental
overdosagewIthlIdocaIne,bupIvacaIne,levobupIvacaIne,andropIvacaIneIn
anesthetIzeddogs.AnesthAnalg2001;92:J7.)
Figure 21-12.SerumconcentratIonsInsheepateachtoxIcmanIfestatIonfor
bupIvacaIne,levo(L)bupIvacaIne,andropIvacaIneInsheep.8othlevobupIvacaIne
andropIvacaInerequIredsIgnIfIcantlygreaterserumconcentratIonsthanbupIvacaIne.
(0atafromSantosAC,0eArmasP:SystemIctoxIcItyoflevobupIvacaIne,bupIvacaIne,
andropIvacaInedurIngcontInuousIntravenousInfusIontononpregnantandpregnant
ewes.AnesthesIology2001;95:1256.)
PerIpheraleffectsofbupIvacaIneontheautonomIcandvasomotorsystemsmayalso
augmentItscardIovasculartoxIcIty.
P.54J
8upIvacaInepossessesapotentperIpheralInhIbItoryeffectonsympathetIcreflexes
100
that
hasbeenobservedevenatbloodconcentratIonssImIlartothosemeasuredafter
uncomplIcatedregIonalanesthesIa.
101
FInally,bupIvacaInealsohaspotentdIrect
vasodIlatIngpropertIes,whIchmayexacerbatecardIovascularcollapse.
102
Figure 21-13.|IldprolongatIonInQFSIntervalandchangeIncardIacoutputafter
IntravenousInfusIonsofbupIvacaIne(10Jmg),levobupIvacaIne(LbupIv;J7mg),and
ropIvacaIne(115mg)Inhealthyvolunteers.(0atafromKnudsenK,8eckmanSuurkula
|,etal:CentralnervousandcardIovasculareffectsofI.v.InfusIonsofropIvacaIne,
bupIvacaIneandplaceboInvolunteers.8rAnaesth1997;78:507;andStewartJ,
KellettN,Castro0:ThecentralnervoussystemandcardIovasculareffectsof
levobupIvacaIneandropIvacaIneInhealthyvolunteers.AnesthAnalg200J;97:412.)
Cardiovascular Toxicity Mediated at the Heart
ThemorepotentlocalanesthetIcsappeartopossessgreaterpotentIalfordIrectcardIac
electrophysIologIctoxIcIty.
82,92,98
AlthoughalllocalanesthetIcsblockthecardIac
conductIonsystemvIaadosedependentblockofsodIumchannels,twofeaturesof
bupIvacaIne'ssodIumchannelblockIngabIlItIesmayenhanceItscardIotoxIcIty.FIrst,
bupIvacaIneexhIbItsamuchstrongerbIndIngaffInItytorestIngandInactIvatedsodIum
channelsthanlIdocaIne.
10J
Second,localanesthetIcsbIndtosodIumchannelsdurIng
systoleanddIssocIatedurIngdIastole(FIg.2114).8upIvacaInedIssocIatesfromsodIum
channelsdurIngcardIacdIastolemuchmoreslowlythanlIdocaIne.ndeed,bupIvacaIne
dIssocIatessoslowlythattheduratIonofdIastoleatphysIologIcheartrates(60to180
beats/mIn)doesnotallowenoughtImeforcompleterecoveryofsodIumchannelsand
bupIvacaIneconductIonblockaccumulates.ncontrast,lIdocaInefullydIssocIatesfrom
sodIumchannelsdurIngdIastoleandlIttleaccumulatIonofconductIonblockoccurs(FIg.
2115).
10J,104
Thus,enhancedelectrophysIologIceffectsofmorepotentlocalanesthetIcson
thecardIacconductIonsystemmayexplaIntheIrIncreasedpotentIaltoproducesudden
cardIovascularcollapsevIacardIacdysrhythmIas.
ncreasedpotencyfordIrectmyocardIaldepressIonfromthemorepotentlocalanesthetIcs
IsanothercontrIbutIngfactortoIncreasedcardIotoxIcIty(FIg.2116).
82,99
AgaIn,multIple
mechanIsmsmayaccountfortheIncreasedpotencyformyocardIaldepressIonfrommore
potentlocalanesthetIcs.8upIvacaIne,themostcompletelystudIedpotentlocal
anesthetIc,possessesahIghaffInItyforsodIumchannelsInthecardIacmyocyte.
82,98
Furthermore,bupIvacaIneInhIbItsmyocytereleaseandutIlIzatIonofcalcIum
105
and
reducesmItochondrIalenergymetabolIsm,especIallydurInghypoxIa.
106
Thus,multIple
dIrecteffectsofbupIvacaIneonactIvItyofthecardIacmyocytemayexplaInthe
cardIotoxIcItyofbupIvacaIneandotherpotentlocalanesthetIcs.
Figure 21-14.0IagramIllustratIngrelatIonshIpbetweencardIacactIonpotentIal(top),
sodIumchannelstate(middle),andblockofsodIumchannelsbybupIvacaIne(bottom).
F,restIngform;D,openform;,InactIveform.SodIumchannelsarepredomInantlyIn
therestIngformdurIngdIastole,opentransIentlydurIngtheactIonpotentIalupstroke,
andareIntheInactIveformdurIngtheactIonpotentIalplateau.8lockofsodIum
channelsbybupIvacaIneaccumulatesdurIngtheactIonpotentIal(systole)wIth
recoveryoccurrIngdurIngdIastole.FecoveryofsodIumchannelsIsfromdIssocIatIonof
bupIvacaIneandIstImedependent.FecoverydurIngeachdIastolIcIntervalIs
IncompleteandresultsInaccumulatIonofsodIumchannelblockwIthsuccessIve
heartbeats.(AdaptedfromClarksonCW,HondeghamL|:|echanIsmsforbupIvacaIne
depressIonofcardIacconductIon:FastblockofsodIumchannelsdurIngtheactIon
potentIalwIthslowrecoveryfromblockdurIngdIastole.AnesthesIology1985;62:J96,
wIthpermIssIon.)
Figure 21-15.HeartratedependenteffectsoflIdocaIneandbupIvacaIneonvelocIty
ofthecardIacactIonpotentIal([7wIthdotabove]
max
).8upIvacaIneprogressIvely
decreases[7wIthdotabove]
max
atheartratesabove10beats/mInbecauseof
accumulatIonofsodIumchannelblock,whereaslIdocaInedoesnotdecrease[7wIth
dotabove]
max
untIlheartrateexceeds150beats/mIn.(AdaptedfromClarksonCW,
HondeghamL|:|echanIsmsforbupIvacaInedepressIonofcardIacconductIon:Fast
blockofsodIumchannelsdurIngtheactIonpotentIalwIthslowrecoveryfromblock
durIngdIastole.AnesthesIology1985;62:J96wIthpermIssIon.)
Treatment of Systemic Toxicity from Local Anesthetics
ThebestmethodforavoIdIngsystemIctoxIcItyfromlocalanesthetIcsIsthrough
preventIon.ToxIcsystemIclevelscanoccurbyunIntentIonalIntravenousorIntraarterIal
InjectIon
P.544
orbysystemIcabsorptIonofexcessIvedosesplacedInthecorrectarea.UnIntentIonal
IntravascularandIntraarterIalInjectIonscanbemInImIzedbyfrequentsyrIngeaspIratIon
forblood,useofasmalltestdoseoflocalanesthetIc(approxImatelyJmL)totestfor
subjectIvesystemIceffectsfromthepatIent(e.g.,tInnItus,cIrcumoralnumbness),and
eItherslowInjectIonorfractIonatIonoftherestofthedoseoflocalanesthetIc.
86
0etaIled
knowledgeoflocalanesthetIcpharmacokInetIcswIllalsoaIdInreducIngtheadmInIstratIon
ofexcessIvedosesoflocalanesthetIcs.deally,heartrate,bloodpressure,andthe
electrocardIogramshouldbemonItoreddurIngadmInIstratIonoflargedosesoflocal
anesthetIcs.PretreatmentwIthabenzodIazepIne,suchasmIdazolam,mayalsolowerthe
probabIlItyofseIzurebyraIsIngtheseIzurethreshold.
Figure 21-16.PlasmaconcentratIonsrequIredtoInducemyocardIaldepressIonIndogs
admInIsteredbupIvacaIne,levo(L)bupIvacaIne,ropIvacaIne,andlIdocaIne.
dP/dtmax,J5reductIonofInotropyfrombaselInemeasure;EF,J5reductIonIn
ejectIonfractIonfrombaselInemeasure;CD,25reductIonIncardIacoutputfrom
baselInemeasure.(0atafromCrobanL,0eal00,7ernonJC,etal:0oeslocal
anesthetIcstereoselectIvItyorstructurepredIctmyocardIaldepressIonInanesthetIzed
canInes:FegAnesthPaIn|ed2002;27:460.)
TreatmentofsystemIctoxIcItyIsprImarIlysupportIve.njectIonoflocalanesthetIcshould
bestopped.DxygenatIonandventIlatIonshouldbemaIntaIned,assystemIctoxIcItyoflocal
anesthetIcsIsenhancedbyhypoxemIa,hypercarbIa,andacIdosIs.
86
fneeded,thepatIent's
tracheashouldbeIntubatedandposItIvepressureventIlatIonInstItuted.AsprevIously
dIscussed,sIgnsofCNStoxIcItywIlltypIcallyoccurprIortocardIovascularevents.SeIzures
canIncreasebodymetabolIsmandcausehypoxemIa,hypercarbIa,andacIdosIs.
PharmacologIctreatmenttotermInateseIzuresmaybeneededIfoxygenatIonand
ventIlatIoncannotbemaIntaIned.ntravenousadmInIstratIonofthIopental(50to100mg),
mIdazolam(2to5mg),andpropofol(1mg/kg)cantermInateseIzuresfromsystemIclocal
anesthetIctoxIcIty.SuccInylcholIne(50mg)cantermInatemuscularactIvItyfromseIzures
andfacIlItateventIlatIonandoxygenatIon.However,succInylcholInewIllnottermInate
seIzureactIvItyIntheCNS,andIncreasedcerebralmetabolIcdemandswIllcontInue
unabated.
CardIovasculardepressIonfromlesspotentlocalanesthetIcs(e.g.,lIdocaIne)IsusuallymIld
andcausedbymIldmyocardIaldepressIonandvasodIlatIon.HypotensIonandbradycardIa
canusuallybetreatedwIthephedrIne(10toJ0mg)andatropIne(0.4mg).AsprevIously
dIscussed,potentlocalanesthetIcs(e.g.,bupIvacaIne)canproduceprofound
cardIovasculardepressIonandmalIgnantdysrhythmIasthatshouldbepromptlytreated.
DxygenatIonandventIlatIonmustbeImmedIatelyInstItuted,wIthcardIopulmonary
resuscItatIonIfneeded.7entrIculardysrhythmIasmaybedIffIculttotreatandmayneed
largeandmultIpledosesofelectrIcalcardIoversIon,epInephrIne,vasopressIn,and
amIodarone.TheuseofcalcIumchannelblockersInthIssettIngIsnotrecommended,asIts
cardIodepressanteffectIsexaggerated.
86
AnovelandpromIsIngtreatmentforcardIactoxIcItyIstheadmInIstratIonofIntravenous
lIpIdtotheoretIcallyremovebupIvacaInefromsItesofactIon.AdmInIstratIonof100mLof
20lIpIdsolutIonhasbeenreportedtoallowsuccessfulresuscItatIonofapatIentfrom
bupIvacaIneInduceddysrhythmIasrefractorytoconventIonaltherapy.
107
ThesefIndIngs
raIsethequestIonofwhetherstandardpropofolIna10lIpIdsolutIonwouldbeapreferred
treatmentforcardIactoxIcIty.However,thedoseoflIpIdInastandardInductIondoseof
propofolwouldbetoosmallandthedoseofpropofolwouldleadtounacceptablecardIac
depressIon.
107
Neural Toxicity of Local Anesthetics
naddItIontosystemIctoxIcIty,localanesthetIcscancauseInjurytothecentraland
perIpheralnervoussystemsfromdIrectexposure.|echanIsmsforlocalanesthetIc
neurotoxIcItyremaInspeculatIve,butprevIousstudIeshavedemonstratedlocalanesthetIc
InducedInjurytoSchwanncells,InhIbItIonoffastaxonaltransport,dIsruptIonoftheblood
nervebarrIer,decreasedneuralbloodflowwIthassocIatedIschemIa,anddIsruptIonofcell
membraneIntegrItyvIaadetergentpropertyoflocalanesthetIcs.
108,109
Althoughall
clInIcallyusedlocalanesthetIcscancauseconcentratIondependentnervefIberdamageIn
perIpheralnerveswhenusedInhIghenoughconcentratIons,prevIousstudIeshave
demonstratedthatlocalanesthetIcsInclInIcallyusedconcentratIonsaregenerallysafefor
perIpheralnerves.
110
ThespInalcordandthenerveroots,ontheotherhand,aremore
pronetoInjury.
ConcentratIondependentspInalcordtoxIcItyoflocalanesthetIcshasbeenassessedby
admInIstratIonoflocalanesthetIcstorabbItsvIaIntrathecalcatheters.ThesestudIes
suggestthatbupIvacaIne(2),lIdocaIne(8),andtetracaIne(1)causehIstopathologIc
changesandneurologIcdefIcIts.Dntheotherhand,clInIcallyrelevantconcentratIonsof
ropIvacaIne(2)dIdnotdIsruptspInalcordhIstologyorcauseneurologIcdefIcIts.
111
0esheathedperIpheralnervemodels,desIgnedtomImIcunprotectednerverootsInthe
caudaequIna,havebeenusedtofurtherassesselectrophysIologIcneurotoxIcItyoflocal
anesthetIcs.
112,11J
LIdocaIne5andtetracaIne0.5causedIrreversIbleconductIonblockIn
thesemodels,whereaslIdocaIne1.5,bupIvacaIne0.75,andtetracaIne0.06dIdnot.
AlthoughsuchstudIesdonotreflectInvIvocondItIons,theysuggestthatlIdocaIneand
tetracaInemaybeespecIallyneurotoxIcInaconcentratIondependentfashIonandthat
neurotoxIcItycouldtheoretIcallyoccurwIthclInIcallyusedsolutIons.
Nonetheless,clInIcalInjuryIsrare.AsystematIcrevIewofapproxImately2.7mIllIon
centralneuraxIalblocksdetermInedratesofoccurrenceofradIculopathytobe
approxImately0.0JandofparaplegIatobeapproxImately0.0008.
114
Transient Neurologic Symptoms After Spinal Anesthesia
ProspectIve,randomIzedstudIesreveala4to40IncIdenceoftransIentneurologIc
symptoms(TNS),IncludIngpaInorsensoryabnormalItIesInthelowerback,buttocks,or
lowerextremItIes,afterlIdocaInespInalanesthesIa
115,116
(seealsoChapterJ4).These
symptomshavebeenreportedwIthotherlocalanesthetIcsaswell(Table2112)buthave
notresultedInpermanentneurologIcInjury.
116
ncreasedrIskofTNSIsassocIatedwIth
lIdocaIne,thelIthotomyposItIon,andambulatoryanesthesIa,butnotwIthbarIcItyof
solutIonordoseoflocalanesthetIc.
115,116
ThepotentIalneurologIcetIologyofthIs
syndromecoupledwIthknownconcentratIondependenttoxIcItyoflIdocaIneledto
concernsoveraneurotoxIcetIologyforTNSfromspInallIdocaIne.
AsprevIouslydIscussed,laboratoryworkInbothIntrathecalanddesheathedperIpheral
nervemodelshasprovedthattheconcentratIonoflIdocaIneIsacrItIcalfactorIn
neurotoxIcIty.However,TNSdoesnotdIsplayadosedependentresponse,as0.5lIdocaIne
resultsInsImIlarIncIdencesofTNSas5spInallIdocaIne.
117
Furthermore,avolunteer
studycomparIngIndIvIdualswIthandwIthoutTNSsymptomsafterlIdocaInespInal
anesthesIashowednodIfferencedetectedbyelectromyography,nerveconductIonstudIes,
orsomatosensoryevokedpotentIals.FInally,effectIvetreatmentforTNSIncludes
nonsteroIdalantIInflammatoryagentsandtrIggerpoIntInjectIons.ThesearetypIcally
effectIvetreatmentsformyofascIalpaInandnotforneuropathIcpaIn.
115
Dverall,thereIs
lIttleevIdencetosupportaneurotoxIcetIologyforTNS.
115
DtherpotentIaletIologIesfor
TNSIncludepatIentposItIonIng,scIatIcnervestretch,musclespasm,andmyofascIal
straIn.
115
Myotoxicity of Local Anesthetics
ToxIcItytoskeletalmuscleIsanuncommonsIdeeffectoflocalanesthetIcInjectIon.
ExperImentaldatasuggest,however,thatlocalanesthetIcshavethepotentIalfor
myotoxIcItyInclInIcally
P.545
applIcableconcentratIons(FIg.2117).HIstopathologIcevIdenceshowsthattheInjectIonof
theseagentscausesdIffusemyonecrosIs,whIchIstypIcallybothreversIbleandclInIcally
ImperceptIble.
118
ThereversIblenatureofthIsInjuryIspossIblybecauseoftherelatIve
resIlIenceofmyoblasts,whIchregeneratedamagedtIssue.TheoretIcalmechanIsmsof
InjuryarenumerousbutdysregulatIonofIntracellularcalcIumconcentratIonsIsthemost
lIkelyculprIt.LaboratorystudIesdemonstratethatropIvacaIneIslessmyotoxIcthan
bupIvacaIne,prImarIlybecauseofthelattercausIngapoptosIs(programmedcelldeath).
118
FurtherInvestIgatIonIsneededtodetermInetheclInIcalrelevanceoflocalorsystemIc
myotoxIcItyfollowIngsIngleInjectIonorcontInuousInfusIonoflocalanesthetIcs.
Table 21-12 The Incidence of Transient Neurologic Symptoms (TNS) Vary
with Type of Spinal Local Anesthetic and Surgery
LOCAL ANESTHETIC
CONCENTRATION
(%)
TYPE OF SURGERY
APPROXIMATE INCIDENCE OF
TNS (%)
LIdocaIne
25
LIthotomy
posItIon
J0J6
25 Kneearthroscopy 1822
0.5 Kneearthroscopy 17
25
|IxedsupIne
posItIon
48
|epIvacaIne 1.54 |Ixed 2J
ProcaIne 10 Kneearthroscopy 6
8upIvacaIne 0.50.75 |Ixed 1
LevobupIvacaIne 0.5 |Ixed 1
PrIlocaIne 25 |Ixed 1
FopIvacaIne 0.50.75 |Ixed 1
0atafromPollockJE:TransIentneurologIcsymptoms:EtIology,rIskfactors,and
management.FegAnesthPaIn|ed2002;27:581;and8reebaart|8:UrInary
bladderscannIngafterdaycasearthroscopyunderspInalanaesthesIa:ComparIson
betweenlIdocaIne,ropIvacaIne,andlevobupIvacaIne.8rJAnaesth200J;90:J09.
Figure 21-17.SkeletalmusclecrosssectIonwIthcharacterIstIchIstologIcchanges
aftercontInuousexposuretobupIvacaInefor6hours.AwholespectrumofnecrobIotIc
changescanbeencountered,rangIngfromslIghtlydamagedvacuolatedfIbersand
fIberswIthcondensedmyofIbrIlstoentIrelydIsIntegratedandnecrotIccells.The
majorItyofthemyocytesaremorphologIcallyaffected.AddItIonally,amarked
InterstItIalandmyoseptaledemaappearswIthInthesectIons.However,scattered
fIbersremaInIntact.(FeprIntedfromZInkW,Craf8:LocalanesthetIcmyotoxIcIty.
FegAnesthPaIn|ed2004;29:JJJJ40,wIthpermIssIon.)
Allergic Reactions to Local Anesthetics (see also Chapter 12)
TrueallergIcreactIonstolocalanesthetIcsarerareandusuallyInvolvetype
(ImmunoglobulInE)ortype7(cellularImmunIty)reactIons.
119,120
TypereactIonsare
worrIsome,asanaphylaxIsmayoccur,andaremorecommonwIthesterthanamIdelocal
anesthetIcs.TruetypeallergytoamInoamIdeagentsIsextremelyrare.
120
ncreased
allergenIcpotentIalwIthestersmaybearesultofhydrolytIcmetabolIsmtopara
amInobenzoIcacId,whIchIsadocumentedallergen.AddedpreservatIvessuchas
methylparabenandmetabIsulfItecanalsoprovokeanallergIcresponse.SkIntestIngwIth
IntradermalInjectIonsofpreservatIvefreelocalanesthetIcshasbeenadvocatedasa
meanstodetermInetolerancetolocalanesthetIc.ThesetestsshouldbeundertakenwIth
cautIonbecausepotentIallysevereandevenfatalreactIonscanoccurIntrulyallergIc
patIents.
120
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Stock, M. Christine
TableofContentsSectIon7AnesthetIcAgents,Adjuvants,and0rugnteractIonChapter220rugnteractIons
Chapter22
Drug Interactions
Carl E. Rosow
Wilton C. Levine
Key Points
1. Drug combinations are a useful and necessary part of anesthesia
practice, but they are occasionally a source of morbidity. The
qualitative nature of most anesthetic interactions is predictable even
though the magnitude of the response might not be known with
certainty. Drugs that interact to produce a totally unexpected or
dangerous effect stand out because of their rarity.
2. A pharmaceutical interaction is a chemical or physical interaction that
occurs before a drug is administered or absorbed systemically.
3. A pharmacokinetic interaction occurs when one drug alters the
absorption, distribution, metabolism, or elimination of another.
4. A pharmacodynamic interaction occurs when one drug alters the
sensitivity of a target receptor or tissue to the effects of a second
drug. We commonly classify these interactions by their direction and
intensity, that is, additive, antagonistic, or supra-additive
(synergistic).
5. Additive interactions are most likely to occur when drugs with
identical mechanisms are combined.
6. The most common antagonistic interactions are those involving
deliberate reversal with competitive antagonists. Antagonism that is
unintended is a much less common event.
7. Synergistic interaction is most likely to occur when drugs with
different mechanisms are combined.
8. Most cardiovascular drugdrug interactions are simply extensions of
the known pharmacology of the agents. With few exceptions, there is
little reason to withhold most vasoactive medications before surgery.
9. Combinations of central nervous system (CNS) depressants almost
always produce additive or synergistic increases in CNS effect. These
interactions are usually useful and predictable.
10. Among the thousands of herbal preparations available, only a few
have been documented to cause problems either through intrinsic
toxicity or pharmacokinetic and pharmacodynamic interactions. There
are no studies demonstrating specific adverse interactions between
herbals and anesthetic drugs.
|oderndrugregImensformedIcalaIlmentssuchashypertensIon,angIna,bronchospasm,or
malIgnancynearlyalwaysInvolvetheuseofmultIpleagents.ThIsstrategyIsfrequently
successfulbecausemanymedIcalcondItIonsareresponsIvetogroupsofdrugsthatactby
dIfferentmechanIsmsandhavedIfferentdoselImItIngtoxIcItIes.ThegoalIneachcaseIs
toproduceanIncreasedtherapeutIceffectwIthdecreasedtoxIcItycomparedwIth
treatmentwIthIndIvIdualagents.Unfortunately,themIxIngofdrugsIsnotwIthoutrIsk,
andhundredsofresearchartIclesonthebenefItsanddrawbacksofdrugInteractIons
appeareveryyear.AsIzableIndustryhasnowevolvedtoprovIdeclInIcIanswIthreference
booksandcomputerdatabasesonthesubject.
AnesthesIologIstsfacethesamedIlemmaasallotherphysIcIans:drugcombInatIonsarea
usefulandnecessarypartofpractIce,buttheyareoccasIonallyasourceofmorbIdIty.ThIs
chapterrevIewsthereasonsthatdrugsarecombInedandthewaysInwhIchthe
combInatIonscanaltereItherpharmacokInetIcsorpharmacodynamIcs.ThIsIsnota
comprehensIvelIstofanesthetIcdrugInteractIonsentIrebookshavebeendevotedtothe
subject.
1
TheexamplesIncludedhavebeenchosenlargelyonthebasIsofprovenorlIkely
clInIcalrelevanceandthestrengthoftheIrdocumentatIon.WhenpossIble,prototypIcal
InteractIonsareIllustratedwIthexamplesthathavedIrectrelevancetoanesthesIa,
althoughInsomecasesnosuchexamplesareavaIlable.TheemphasIsthroughoutIson
mechanIsm,butItwIllquIcklybeapparentthatourunderstandIngofmechanIsmIs
IncompleteformanypharmacodynamIcInteractIons.FInally,ItIsImportanttoknowhow
toreadtherelevantlIterature,andashortsectIonIsdevotedtosomeofthecommonways
InteractIonscanbestudIed.
P.550
Historical Perspective
HIstorIcally,anesthesIologIstsweretraInedtoregarddrugInteractIonsasadangerand
somethIngtobeavoIded.ThegeneratIonsofclInIcIanswhoadmInIsteredopendropdIethyl
etherprobablyhadgoodreasontolImItthenumberofanesthetIcdrugsadmInIstered:
etherbyItselfcouldproducehypnosIs,reasonablelevelsofanalgesIa,andmuscle
relaxatIon.7entIlatIonandbloodpressurewereusuallywellmaIntaInedbecauseetherhas
respIratorystImulantandsympathomImetIcpropertIes.ClInIcIanscouldadjustthedoseof
thIssIngleagentfaIrlyaccuratelyusIngCuedel'scrIterIaforpupIlsIze,respIratorypattern,
muscletone,andsoforth.ThIsmeantthatapatIentrequIrIngevenmajorabdomInal
surgerycouldbeanesthetIzedusIngnothIngmorethanacanofetherandasImplemask.
8eforeWorldWar,endotrachealIntubatIonandcontrolledventIlatIonwereusuallynot
optIons,andmusclerelaxantshadnotbeenIntroduced.ClInIcIansInthIserawerewell
servedtokeepthIngssImple:IfananesthesIologIstchosetoaddmorphInetoanether
anesthetIc,thepupIlandrespIratorysIgnswouldnolongerberelIable,musclerelaxatIon
wouldprobablydecrease,andventIlatorydepressIon(IfItoccurred)couldnotbetreated
easIly.
TheIntroductIonofmusclerelaxants,opIoIdbasedanesthesIa,andmodernIntravenous
(7)andInhaledanesthetIcscompletelychangedtheseconsIderatIons.ThesIgnsandstages
ofetheranesthesIaarenolongerapplIcable,andcontrolledorassIstedventIlatIonIsoften
necessarybecausemostofthesedrugshaveprofoundeffectsonrespIratIon.|ost
Importantly,clInIcIansnowrealIzethatanesthetIcsarehIghlyspecIfIcdrugs,andnosIngle
agentcanproduceallthedesIrablecomponentsofanesthesIa.ThereIsgoodevIdence
thateventhepotentvolatIleanesthetIcsarenotsuffIcIenttoproduceoptImalanesthetIc
condItIonswhengIvenalone.ZbInden,etal.
2
showedthatevenmoderatelyhIgh
concentratIonsofIsofluraneInoxygencannotsuppressmanycardIovascularresponsesto
surgIcalstImulI.ThIsfIndIngIsreflectedIncommonclInIcalpractIcebecauseIsofluraneIs
routInelysupplementedwIthopIoIdsandotherdrugstocontrolbloodpressureandheart
rate.
DurvIewsofwhatIsdesIrableInanesthesIahavealsochangedmarkedly.Forexample,
mostpatIentsnowexpectandpreferan7hypnotIc,ratherthanamask,foranesthetIc
InductIon.SImIlarly,thelongemergenceafteretherIsnolongerexpectedoracceptable.A
smoothrecovery,freeofpaInordelIrIum,IsnowcommonwIthInmInutesaftermajor
surgIcalInterventIons.ThesegoalsaredIffIculttoaccomplIshwIthoutusIngmultIpledrugs.
Problems Created by DrugDrug Interactions
TherearealmostnodataonthetrueIncIdenceofperIoperatIvedrugInteractIon,although
therearedataongeneralInpatIentpopulatIons.tIslogIcalthattheprobabIlItyofdrug
drugInteractIonIncreaseswIththenumberofdrugsadmInIstered.
J
|anypatIentsare
routInelytakIngthreeorfourantIhypertensIves,antIdepressants,orgastroIntestInaldrugs
InthepreoperatIveperIod.|ostalsoreceIvefIvetotendrugsdurInggeneralanesthesIa,
butwedonotnormallyhearaboutsIgnIfIcantcomplIcatIonsattrIbutabletodrug
InteractIon.ThereareanumberofpossIbleexplanatIonsforthIs:
1. nteractIonsmayoccur,buttheyusuallydonotpresentaproblem.ToxIcItyfromadrug
InteractIonIslIkelytobecomeasourceofmorbIdItyprImarIlywhenItoccursInasettIng
whereItIsnotrapIdlyrecognIzedandtreated.Forexample,thIscanhappenwhen
opIoIdandmIdazolamcombInatIonsareusedbyuntraInedpersonnelforendoscopIc,
radIologIc,andoutpatIentproceduresperformedunderconscIoussedatIon.The
unexpectedlylargesedatIveandventIlatoryeffectscanleadtodeath.
4
2. |anyoftheeffectsIntroducedbymIxIngdrugsarehardtodIstInguIshfromclInIcal
noIse.7arIabIlItyInresponsetoanesthetIcdrugsIstherule:thedataon7opIoIds
5
andhypnotIcs,
6
forexample,showthatdIfferentpatIentsmayhaveathreetofIvefold
dIfferenceInthetherapeutIcandtoxIceffectsofagIvendoseevenwhenthedrugIs
gIvenalone.
J. ThequalItatIvenatureofmostanesthetIcInteractIonsIspredIctableeventhoughthe
magnItudeoftheresponsesmIghtnotbeknownwIthcertaInty.CombInIngtwo
cardIovasculardepressantswIllproducemorehypotensIon;twoCNSdepressantswIll
producemoresedatIon,andsoforth.0rugsthatInteracttoproduceatotallyunexpected
ordangerouseffectstandoutbecauseoftheIrrarIty.AnotorIousexampleofsuchan
IdIosyncratIcInteractIonIstheCNSexcItatIonthatmayoccurwhenmeperIdIneIs
admInIsteredtopatIentstakIngmonoamIneoxIdaseInhIbItors(|ADs).
4. |any7anesthetIcdrugs(dIazepam,fentanyl)havelargesafetymargInsespecIally
whenrespIratIonIssupportedsochangesIndrugeffecthavefewconsequences.The
merefactthatameasurableInteractIonexIstsdoesnotmeanItwIllcauseadIfference
InoutcomeortheneedforInterventIon.0angerousInteractIonsmostoftenInvolvedrugs
suchaswarfarIn,dIgoxIn,andtheophyllIne,agentswIthonlysmalldIfferencesbetween
therapeutIcandtoxIcconcentratIons.
5. FInally,ItIslIkelythatmanyInstancesofanesthetIcdrugInteractIongounrecognIzed.
ExcessIvedrugeffectsareoftenattrIbutedtosomeIlldefInedpatIentsensItIvIty.
Whenadrugfailstoproduceaneffect,ItIsbecausethepatIentIstolerantor
resIstant.tIsalmostneverconsIderedadrugreactIonorInteractIon.
Why Combine Drugs?
ThegoalofcombInIngdrugsIstodecreasetoxIcItywhIlemaIntaInIngorIncreasIng
effIcacy.tIsInstructIvetoseehowthIsprIncIplehasbeenapplIedInotherareasof
medIcIne:
1. CombInatIontherapycanreducetoxIcIty.Forexample,aadrenergIcantagonIstanda
vasodIlatorhaveatleastaddItIveeffectsonbloodpressure,buttheIrsIdeeffectsare
dIfferentand(presumably)nonaddItIve.LowerdosesofeachdrugmaybeusedIn
combInatIonsodoserelatedsIdeeffectsaredecreased.
2. CombInatIonchemotherapyformalIgnancycanIncreaseeffIcacy.Toproducethe
maxImumdecreaseIntumorburden,eachchemotherapeutIcdrugIsgIvenatIts
maxImallytolerateddose,anendpoIntdetermInedbyItstoxIceffectsonsomenormal
cellpopulatIon.0rugssuchasalkylatIngagentsandvIncaalkaloIdsarecombIned
becausetheyhavedIfferentdoselImItIngorgantoxIcItIes(bonemarrowandnerve,
respectIvely),soeachdrugcanbegIvenatafulltumorsuppressIngdose.
J. SIngledrugtherapyIssometImespreferable.ThemaInstaydrugsforprophylaxIsof
seIzures(phenytoIn,carbamazepIne)havesImIlardoselImItIngsIdeeffectssuchas
ataxIaanddrowsIness,sothereIslIttletobegaInedbycombInIngthem.
Pharmaceutical Interactions
ApharmaceuticalInteractIonIsachemIcalorphysIcalInteractIonthatoccursbeforea
drugIsadmInIsteredorabsorbed
P.551
systemIcally.ThemostobvIouspharmaceutIcalInteractIonsaretheIncompatIbIlItIesthat
canoccurbetweendrugsInsolutIon:
PrecIpItatIonofthIopentalmayoccurwhenItIsInjectedtogetherwIthsuccInylcholIne
Intothe7catheterlIne.
8IcarbonatecandecreasethesolubIlItyofbupIvacaIneandcauseIttoprecIpItate.
CatecholamInesolutIons(norepInephrIne,epInephrIne)canbeInactIvatedIftheyare
alkalInIzedbytheaddItIonofsodIumbIcarbonate,acIrcumstancethatcouldoccur
durIngcardIopulmonaryresuscItatIon.
ThenumberoftheseIncompatIbIlItIesIslarge,andtheanesthesIologIstshouldavoId
mIxIngdrugsunlesstheyareknowntobecompatIble.nformatIononspecIfIc7drug
IncompatIbIlItIesIsreadIlyavaIlablefrommosthospItalpharmacIsts.
DccasIonally,twodrugsmayInteractchemIcallytoformatoxIccompound:
ThehalogenatedanesthetIcsdesflurane,enflurane,andIsofluranehavebeenshownto
InteractwIthdrysodalImeor8aralymetoproducecarbonmonoxIde
7
andheat.
8
0esIccatIonofsodalImeIsmostlIkelytooccurwhenoxygenhasbeenleftflowIng
throughthecanIsterovernIght.DlderanesthesIologIstsrecallthattrIchloroethylene
InteractedwIthsodalImetoproducetheneurotoxIn,dIchloroacetylene.
NItrIcoxIde(ND)IsaselectIvepulmonaryvasodIlatorthathasbeenapprovedInthe
UnItedStatesfortreatmentofprImarypulmonaryhypertensIonInthenewborn.fNDIs
allowedmorethanfleetIngcontactwIthoxygen,ItformsnItrogendIoxIde(ND
2
).The
lattercompoundcanbequItetoxIc,andconcentratIons10ppmcanproducepulmonary
edemaandalveolarhemorrhage.TheproblemIscIrcumventedbyallowIngoxygenand
NDtomIxInthebreathIngcIrcuItjustbeforeadmInIstratIon.
Pharmacokinetic Interactions
ApharmacokineticInteractIonoccurswhenonedrugalterstheabsorptIon,dIstrIbutIon,
metabolIsm,orelImInatIonofanother.|anyofthebasIcpharmacokInetIcprIncIples
underlyIngtheseInteractIonsarerevIewedInChapter7.
Absorption
AlteratIonofabsorptIonmayoccurbecauseofdIrectchemIcalorphysIcalInteractIon
betweendrugsInthebodyorbecauseonedrugaltersthephysIologIcmechanIsms
governIngabsorptIonofthesecond:
DrallyadmInIsteredtetracyclInecanbeInactIvatedbychelatIonIfItIsgIventogether
wIthantacIdscontaInIngpolyvalentcatIonssuchas|g
2+
,Ca
2+
,orAl
J+
.
DralantIdIarrhealdrugssuchaskaolInandpectIncanphysIcallyadsorbdIgoxInand
preventItfrombeIngabsorbed.
ThebIleacIdbIndIngresIn,cholestyramIne,canbIndtowarfarInandpreventIts
absorptIon.tcanalsoreducetheabsorptIonofvItamInKandotherfatsoluble
compounds.
AnotherInteractIonofsIgnIfIcancetoanesthesIologIstsIsthedelayofgastrIcemptyIng
producedbymedIcatIonssuchasopIoIdsandantIcholInergIcs.DpIoIdsproducehypertonus
ofsmoothmuscle,reductIonofperIstalsIs,andcontractIonofsphInctersthroughoutthe
gastroIntestInaltract,andItappearsthatbothcentralandperIpheralmechanIsmsplaya
roleInthIseffect.|urphy,etal.
9
gavevolunteers500mLofdIstIlledwatertodrInkand
showedthat0.09mg/kgofmorphIneIncreasedthehalftImeforgastrIcemptyIngfrom5.5
to21mInutes.|orphInecanalsoreducetheabsorptIonoforallyadmInIstereddrugs
becausetheprImarysIteforabsorptIonIsthesmallIntestIne,andgastrIcemptyIngIsrate
lImItIng.AsaI,etal.
10
demonstratedthatmorphInesIgnIfIcantlyreducestheabsorptIonof
oralacetamInophenInpatIents.
ChangesInregIonalbloodflow(vasodIlators,vasoconstrIctors)canaffecttheabsorptIonof
parenterallyadmInIstereddrugs.ShockorcongestIveheartfaIluredecreasesperfusIonof
perIpheraltIssuessuchasskInandmuscle,sotheonsetandIntensItyofeffectmaybecome
unpredIctablefordrugsgIvenbyIntramuscularorsubcutaneousInjectIon:
LocaladmInIstratIonofepInephrIneandothervasoconstrIctorsretardabsorptIonof
InfIltratedlocalanesthetIcsandthereforeprolongtheIreffects.
0rugsthatdecreaseeffectIvepulmonaryventIlatIonhavethepotentIaltoreducethe
uptakeofvolatIleanesthetIcs.0rugsthatIncreasemInuteventIlatIon,reduce
IntrapulmonaryshuntIng,orrelIevebronchospasmcanIncreasetheuptakeofvolatIle
anesthetIcseventhoughtheInspIredconcentratIonremaInsconstant.
TherapIduptakeofnItrousoxIdecanIncreasethealveolarconcentratIonof
concomItantlyadmInIsteredvolatIleanesthetIcs(thesecondgaseffect).
Distribution
|anydrugdrugInteractIonsoccurwhenonedrugaltersthedIstrIbutIonofasecond.ThIs
mayoccurbecauseofalteratIonsInhemodynamIcs,drugIonIzatIon,orbIndIngtoplasma
andtIssueproteIns.|uchhasbeenwrIttenabouttheInvolvementofthesemechanIsmsIn
drugInteractIons(partIcularlythelasttwo),buttherearefewexamplesofproven
relevancetoanesthesIa.
0rugssuchasvolatIleanesthetIcs,betablockers,calcIumchannelblockers,and
vasodIlatorscandecreasecardIacoutputandproducesIgnIfIcantchangesIndrug
dIstrIbutIon.AdecreaseIncardIacoutputIncreasesthearterIalconcentratIonsofother
drugsInhIghlyperfusedtIssuessuchasthebraInandmyocardIum
11
:
napatIentwIthdepressedcardIacfunctIon,normaldosesof7agentssuchaspropofol,
thIopental,andremIfentanIlcanproducesubstantIallygreatercardIovascularandCNS
effects.ThIscanbeduetoanIncreaseIntIssuedrugconcentratIonsoranIncreaseIn
tIssuesensItIvItytotheeffectsofthedrug.
12,1J,14
ThesameeffectIsseenwIthvolatIleanesthetIcs.LowcardIacoutputIncreasesendtIdal
concentratIonsandIntensIfIescardIovascularandCNSeffects.
0rugInducedchangesInpHInapartIcularbodyregIonorfluIdcompartmentcanalterthe
dIstrIbutIonofotherdrugsbysocalledIontrappIng.|ostofourtherapeutIcagentsare
weakacIdsorbasesthatarepartIallyIonIzedatnormalbodypH.tIsonlythenonIonIzed
fractIonthatcancrosslIpIdmembranesandcometoequIlIbrIum.TheamountIonIzedcan
bedetermInedforacIdsorbasesfromthegeneralformoftheHendersonHasselbalch
equatIon:
FecallthatanunprotonatedacIdIsIonIzed,whereasanunprotonatedbaseIsnonIonIzed.
tIsapparentfromthIsrelatIonshIpthataweakbase(fentanyl,lIdocaIne)wIllbe
progressIvelyIonIzedasthepHdecreases,whereasaweakacId(aspIrIn,phenobarbItal)
wIllbemorenonIonIzed.
P.552
ForcertaInmembranebarrIers,suchasthoseInthestomach,placenta,orrenaltubules,
thepHoneIthersIdeIsverydIfferent,andthIscreatesthenecessarycondItIonsforIon
trappIng.ConsIderthecaseofaweakacId(IonIzatIonconstant[pK
a
]=J.4)thatIs
dIstrIbutIngbetweenstomachandblood.nstomachacId(pH2.4),theratIoofuncharged
tochargedrugIs:
nblood(pH7.4),
AtequIlIbrIum,theconcentratIonsofnonIonIzed(uncharged)drugmustbethesameon
eIthersIdeofthegastrIcmembranebarrIer.ThIsmeansthata10,000foldconcentratIon
gradIentIsestablIshedfortotaldrug(nonIonIzed+IonIzed):
STOMACH (pH 2.4) BLOOD (pH 7.4)
NonIonIzeddrug 1 1
onIzeddrug 0.1 10,000
Totaldrug 1.1 10,001
tIseasytoseewhyweakacIdssuchasaspIrInarewellabsorbedfromthestomach.The
potentIalfordrugInteractIonIsgreat.EvenmoderatechangesInpHcanhavelargeeffects
onthIsequIlIbrIumraIsIngIntragastrIcpHto5.4decreasestheconcentratIongradIentby
100fold:
AdmInIstratIonofantacIds,hIstamInetype2receptorantagonIsts,orprotonpump
InhIbItorssuchasomeprazolecanreducethegastrIcabsorptIonofsomeacIdIcdrugs.
AlteratIonofpHhasbeenshowntochangetheoralbIoavaIlabIlItyofketoconazole
15
and
mIdazolam.
16
LIpIdsolublebasIcdrugssuchasfentanylandmeperIdInecandIffuseintothestomach
fromthebloodstream.TheybecomeIonIzedandtrappedIngastrIcacIdonlytobe
reabsorbedwhentheyenterthemorealkalIneenvIronmentoftheproxImaljejunum.
ThIsgastrIcrecyclIngIsbelIevedtobethebasIsforsecondaryIncreasesInplasma
concentratIonsoftheseopIoIds.
17
AlteratIonofurInepHcanmarkedlyaffecttherenalclearanceofcertaIndrugs
(descrIbedIn0rugElImInatIon).
|uchhasbeenwrIttenabouttheroleofplasmaproteInbIndIngIndrugdrugInteractIon.
ThefractIonofadosethatremaInsIntravascularIseItherfreeorboundtocIrculatIng
proteIns.AcIdIcdrugsusuallybIndtoalbumInandvarIousglobulInfractIons.|anybasIc
drugssuchasmeperIdIne,lIdocaIne,bupIvacaIne,andpropranololbIndto
1
acId
glycoproteIn,anacutephasereactant.0rugbIndIngby
1
acIdglycoproteIncanIncrease
aftersurgeryandIncertaInothercondItIonssuchasburns,myocardIalInfarctIon,trauma,
andmalIgnancIes.Conversely,hepatIccIrrhosIsandthenephrotIcsyndromeareoften
accompanIedbyhypoproteInemIaanddecreasesInbothalbumInandglobulInbIndIng.
TheextenttowhIchdrugIsboundversusfreeIsImportantbecauseItIsonlytheunbound
fractIonthatIsavaIlableforcrossIngmembranes,enterIngtIssues,andbIndIngto
receptorstoproducethepharmacologIceffect.ProteInbounddrugIsnotfIlteredbya
normalglomerulusand(forsomedrugs)IsnotactedonbydrugmetabolIzIngenzymes.A
drugthatIshIghlyboundtoplasmaproteIneffectIvelyexIstsInadepot,notunlIkea
druggIvenbydeepIntramuscularInjectIon.ThepotentIalthereforeexIststhatonedrug
couldalterthedIsposItIon,clearance,orbIologIcaleffectofanotherbyaffectIngIts
bIndIng:
TheclassIcexampleofsuchanInteractIonIsdrugdIsplacementofbIlIrubInInInfants.
PrematureInfantshaveImmatureglucuronyltransferaseandareunabletoconjugate
bIlIrubInformedbydestructIonoferythrocytes.|uchoftheloadofunconjugated
bIlIrubInIsboundtoalbumInandthuspreventedfromenterIngtIssues.SulfonamIdesand
otherdrugscancompeteforalbumInbIndIngsItes,andthebIlIrubIntheydIsplacecan
entertIssues.ExcessIvelevelsofbIlIrubInInthebraIncanleadtokernIcterus,a
potentIallyfatalproblem.ThIseffectwasdIscoveredaccIdentallyIn1956durInga
clInIcaldrugtrIal.WhenprematureInfantsweregIvenapenIcIllInsulfonamIdemIxture,
themortalItyrateIncreased,andmanywerefoundtohavekernIcterusatautopsy.
18
ThesamemechanIsmhasbeenpostulatedfornumerousdrugdrugInteractIons.HIghly
bound,potentIallytoxIcdrugssuchaswarfarInandphenytoInmaybedIsplacedbyother
hIghlybounddrugs.WarfarInIs98boundtoalbumIn,meanIngthatonly1to2ofthe
cIrculatIngdrugaccountsfortheentIrebIologIcaleffect.PhenylbutazoneIsa
nonsteroIdalantIInflammatorydrug(NSA0)thatcompeteseffectIvelyforthesame
bIndIngsItes.fphenylbutazonedIsplacesonly2ofwarfarIn,thIstheoretIcallydoubles
thefree(actIve)fractIonandgreatlyIncreasesthewarfarIneffect.
ThIstypeofdrugdrugInteractIonhasbeendogmaforyears,butItIsnearlyImpossIbleto
fInddocumentedevIdencethatItcausesharm
19
:
1. |ostdrugsarewIdelydIstrIbutedInthebody,somostoftheadmInIstereddoseIs
extravasculartwothIrdsofthetotaldoseInthecaseofwarfarIn.Evenalargechange
InplasmaunboundfractIon(e.g.,10)wIllthereforereleaseonlyJto4oftotal
warfarInInthebody.
2. ThebodyactsasasInkorbufferagaInstlargechangesInunboundfractIon(anyunbound
drugInplasmaIsrapIdlydIstrIbutedIntoperIpheraltIssues).
SomecautIonIsstIllwarrantedforanesthesIologIstsandotherclInIcIanswhouse7drug
regImenswIthdosesoftenInthetoxIcrange(e.g.,hIghdosesofopIoIds,hypnotIcs,and
musclerelaxants).nthesecIrcumstances,ItIspossIblethatevenatemporarychangeIn
freedrugconcentratIoncanhaveclInIcalconsequences.
Metabolism
TherearenumerousexamplesInanesthesIaofdrugsthatIncreaseordecreasethe
metabolIsmofothers.nteractIonsmayoccurInextrahepatIcorhepatIcsItesof
metabolIsm.
|anydrugsespecIallythosewIthesterlInkagesundergohydrolysIsbyspecIfIcor
nonspecIfIcesterasesfoundInbloodandperIpheraltIssues:
0rugsgIventoInhIbItacetylcholInesteraseatthemotorendplateusuallyInhIbIt
butyrylcholInesterase(pseudocholInesterase)Inplasma.Thus,admInIstratIonof
neostIgmIneorpyrIdostIgmIneIntensIfIesandprolongstheeffectsofsuccInylcholIneand
canalsotheoretIcallyaffectesterlocalanesthetIcs(procaIne,chloroprocaIne,
tetracaIne,cocaIne).EnzymeInhIbItIonneedstobesubstantIal(20ofnormalactIvIty
remaInIng)beforetheclInIcaleffectsoftheselocalanesthetIcsbecomeprolonged.
20,21
TheprolongatIonofeffectdependsonthespecIfIcInhIbItor.NeostIgmIne,forexample,
canprolongtheeffectofsuccInylcholInebyseveralhours.Theorganophosphate,
echothIophate,IsapowerfulmIotIcusedtopIcallyforrefractoryglaucoma.ThIs
compoundIrreversIblyInhIbItspseudocholInesterase,
20,22
andthe
P.55J
effectpersIstsforweeks,sotherIskforInteractIonIsprolonged.
0rugssuchasesmololandremIfentanIlarehydrolyzedbysocallednonspecIfIcesterases
InbloodandperIpheraltIssues.ThesedrugsarenotgoodsubstratesforcholInesterases,
sotheyarenotsubjecttothIsInteractIon.
2J
ThenonspecIfIcesterasesconstItutealarge
groupofIsozymeswIthextremelyhIghcapacItyandlowsubstratespecIfIcIty.ThIs
enzymesystemIsnotlIkelytobeInvolvedIndrugdrugInteractIonsbecauseInhIbItIonof
anyoneIsozymeusuallydoesnotaffectoveralldrugclearance.
Monamide Oxidase Interactions
Theenzyme,monamIdeoxIdase(|AD),IsdIstrIbutedthroughoutthebody,wIththelargest
amountsfoundInthelIver,kIdney,andbraIn.|ADIslocatedontheoutersurfaceof
mItochondrIaInthepresynaptIctermInalsofnoradrenergIc,dopamInergIc,and
serotonergIcneuronsIntheCNSandperIphery.tactstoregulatethepresynaptIcpoolof
norepInephrIne,dopamIne,epInephrIne,andserotonInavaIlableforsynaptIctransmIssIon
(seeChapter15).|ADexIstsIntwoIsoforms:|ADApredomInatesInthegutwall,whereas
|AD8IsthemajorIsoformIntheCNS.
The|ADsareusedmaInlyforthetreatmentofrefractoryendogenousdepressIonand
certaInothermooddIsorders.TheyhavegaInedsomenotorIetyInmedIcInebecausethey
arethecauseofmoreclInIcallyImportantdrugdrugInteractIonsthanalmostanyother
classofdrugs.|anyofthepurportedInteractIonsarepoorlydocumented,althoughthey
cannotbedIscountedcompletely.
Therearecurrentlyonlythree|ADsmarketedIntheUnItedStates.PhenelzIne(NardIl)Is
anolder,nonselectIve|ADderIvedfromhydrazIne.tIrreversIblyInhIbItstheenzyme,
andsynthesIsofnewenzymecantake10to14days.TranylcypromIne(Parnate)IsaslIghtly
shorteractIng|ADderIvedfromamphetamIne.ThenewestmemberofthIsclassIs
selegIlIne(deprenyl,Eldepryl),whIchIsusedasanadjunctInthetreatmentofParkInson
dIsease.nlowerdoses,selegIlIneIsrelatIvelyselectIvefor|AD8.TheantIbIotIcs,
furazolIdoneandlInezolId,andthechemotherapeutIcdrug,procarbazIne,alsocause
substantIalInhIbItIonof|ADandcanpotentIallycausemanyofthesameInteractIons.
Feported|ADInteractIonsarebroadlyoftwotypes:thefIrstgroupInvolvesdrugsthat
affectsympathetIcneurotransmIssIon:
ThewellknownInteractIonwIthIndIrectactIngsympathomImetIcdrugs(ephedrIne,
amphetamIne)occursbecause|ADtreatmentIncreasestheamountofpresynaptIc
transmItterthatcanbereleasedbythesedrugs.NormaldosesofephedrInehave
producedseverehypertensIvecrIses,occasIonallyleadIngtocerebralhemorrhageand
death.
ThewIneandcheesereactIonIsessentIallythesameInteractIon.|anyfoodssuchas
agedcheesecontaIntyramIne,aphenylethylamInethathasephedrInelIkeactIonsat
sympathetIcnerveendIngs.Normally,exogenoustyramIneIsdegradedby|ADAInthe
gutwallandlIver,butpatIentstakIngan|ADmayachIevehIghsystemIcconcentratIons
andconsequentlyhavehypertensIvecrIses.SelegIlIneIsnowbeIngmarketedIna
transdermalpatchformulatIon(Emsam)thatmayreducetheexposureofgutandlIver
|ADtotheInhIbItor.ThIswouldnotbeexpectedtoreducetheInteractIonswIth7
agents,however.
ParadoxIcally,apatIentwhohasbeentakIngan|ADforsometImemayactuallyhave
decreasedadrenergIcresponsIveness(someoftheolder|ADsweremarketedas
treatmentsforhypertensIon).EvenwIthgooddIetarycomplIance,thesepatIentsabsorb
sometyramIne.ChronIcexposuretolowlevelsoftyramIneallowsthIscompoundtobe
takenupbyadrenergIctermInals(InplaceoftyrosIne),whereItIsmetabolIzedto
octopamIne(ratherthannorepInephrIne).DctopamIneIsafalsetransmItterwIthlIttle
actIvIty,sosympathetIcnervefunctIonmayeventuallybeImpaIred.
8ecause|ADplaysonlyasmallroleInthemetabolIsmofcompoundsInthesynaptIc
cleft,theresponsetosympathomImetIcsthatactdIrectlyonpostsynaptIcreceptorsItes
(phenylephrIne,norepInephrIne,epInephrIne)shouldbeaffectedlessbysuch
InteractIons.nasmallstudyoffourhealthyvolunteers(tworeceIvIngtranylcypromIne
andtworeceIvIngphenelzIne),therewasamoderate(twofold)IncreaseIntheresponse
tophenylephrIne,buttheresponsestonorepInephrIneandepInephrInewerenot
exaggerated.
24
ThIsIsreassurIng,butanysympathomImetIcdrugshouldstIllbe
admInIsteredwIthcautIontopatIentstakIngan|AD.
AdverseInteractIonshavebeendescrIbedwItholder|ADsandlevodopa,possIbly
becausebothdrugsIncreasedopamIneconcentratIons.Nevertheless,thereIssome
experIencethatlevodopaandselegIlInemaybecombInedsafelyInpatIentswIth
ParkInsondIsease.The|ADIsgIvenInthIscasetodecreasetheclearanceoflevodopa
frombraIntIssueandtopreventfreeradIcalformatIonbelIevedtobeInvolvedIn
neuronaldegeneratIon.
25
nhIbItIonofnorepInephrInereuptakebytrIcyclIcantIdepressants(TCAs)Increasesthe
amountofneurotransmItterInthesynaptIccleft.ThIswouldseemtobearecIpefor
adverseInteractIonwIth|ADs,butwIthcarefulmonItorIng,thIscombInatIonhasbeen
usedsuccessfullyfortherapy.
Thesecondgroupof|ADInteractIonsInvolvesCNSdepressants.AsstatedprevIously,
someofthesearepoorlydocumented,andthemechanIsmsareunknown:
ThemostImportantInteractIonIsunquestIonablywIthmeperIdIneandotherdrugsthat
InhIbItserotonInreuptake.WhenmeperIdIneIsgIventoapatIenttakIngan|AD,alIfe
threatenIngserotonInsyndromemayoccur,accompanIedbyexcItatIon,hyperpyrexIa,
hypertensIon,profusesweatIng,andrIgIdIty.
26
ThIsmayprogresstoseIzures,coma,and
death.ThereactIondoesnotoccurIneveryInstance.thasalsobeendescrIbedwIth
selegIlIne,
27
andcasereportssuggestthattoxIcInteractIonsmayoccurwIththe
antItussIve,dextromethorphan,
28
andtheanalgesIcs,propoxyphene,
29
andtramadol.
26
Dtherthansomepoorlydocumentedcasereports,theevIdencesuggeststhatmorphIne
andfentanyldonotproducethIsInteractIon.
J0
AnecdotalreportshaveappearedregardIngadverse|ADInteractIonswIthother
psychotropIcdrugs,IncludIngalcohol,phenothIazIne,benzodIazepInes,and
barbIturates,
J1
buttheevIdenceIsweak.SomewInes,suchasChIantI,couldbe
dangerousbecausetheycontaIntyramIne.tIspossIble(butprobablynotadvIsable)to
useketamIneforInductIonofanesthesIaInpatIentstakIngan|AD.
J2
Should|ADsbedIscontInuedbeforeelectIvesurgery:TheIssueIsstIllamatterof
debate,
JJ,J4
althoughdrugpackageInsertsusuallyadvIseanextremelyconservatIve
posItIon(I.e.,waItIng2weeksfortheenzymetoregenerate).CurrentclInIcalopInIon
probablyfavorscontInuIng|ADtherapyuptothetImeofsurgery,andourownexperIence
supportsthIsvIew.|ostpatIentsarereceIvIngthesedrugsformoderatetosevere
psychIatrIcdIsordersthathavenotrespondedtoothertreatments.tIsunpleasantand
possIblyrIskyforapatIent
P.554
wIthrefractorydepressIontoendure2toJweekswIthouteffectIvetherapy.fageneral
anesthetIcIsplanned,ItseemsprudenttousethefewestpossIbledrugs.AvoIdIngdrugs
wIthsubstantIalsympathetIceffects(e.g.,pancuronIum,cocaIne,ketamIne)probably
makessense.
Figure 22-1.TheeffectsofIncreasIngordecreasInghepatIcbloodflowwIth
Isoproterenol(A)andnorepInephrIne(NE)(B)onsteadystatearterIallIdocaIne
concentratIonsIntherhesusmonkey.ThepressorswereadmInIstereddurIngthe
perIodIndIcatedbytheshaded bar.Thedashed linesshowthesteadystate
concentratIonexpectedIntheabsenceofpressors.(FeprIntedfrom8enowItzNL,
ForsythFP,|elmonKL,etal:LIdocaInedIsposItIonkInetIcsInmonkeyandman:.
EffectsofhemorrhageandsympathomImetIcdrugadmInIstratIon.ClInPharmacol
Ther1974;16:99,wIthpermIssIon.)
ThereIslIttledoubtthatpatIentstakIng|ADshavethepotentIalforperIoperatIve
hemodynamIcInstabIlIty,yetbetablockers,dIrectvasodIlators,anddIrectactIngpressors
appeartobesafeandeffectIvetreatmentsInmostcIrcumstances.FoIzen
J5
concluded,
ThemajorproblemwIthcontInuIng|ADInhIbItorspreoperatIvelyIsnotthehemodynamIc
fluctuatIonsthatmIghtoccurbutrathertherareInstanceofhyperpyrexIccoma
followIngnarcotIcadmInIstratIon.8ecauseopIoIdssuchasfentanylappearsafeand
therearenomajorInteractIonswIthlocalanesthetIcsorNSA0s,provIdInganalgesIa
wIthoutmeperIdIneshouldnotbeahardshIp.
Hepatic Biotransformation
|anyanesthetIcdrugsundergooxIdatIvemetabolIsmbyoneoftheIsoformsofcytochrome
P450foundInlIvermIcrosomes.TheP450IsoformshavelowsubstratespecIfIcIty,whIch
meansthatdrugsofdIversestructures,suchasgeneralInhalatIonanesthetIcs,meperIdIne,
barbIturates,andbenzodIazepInes,canbebIotransformedbyasInglegroupofenzymes.t
IsnotsurprIsIngthatInhIbItorsorInducersoftheseenzymescanalsoaffecttheclearance
ofbroadgroupsofdrugs.
TheremovalofdrugfromthebloodbyhepatIcbIotransformatIon(hepatIcclearance)Isa
functIonoftwoIndependentvarIables,thehepatIcbloodflowandtheIntrInsIcclearance
(themaxImalabIlItyofthelIvertometabolIzethatdrug).TheIntrInsIcclearanceIsoften
expressedastheextraction ratio(EF)thefractIonofdrugthatcanbemetabolIzedIna
sInglepassthroughthelIver(seeChapter7).
whereC
a
IsthedrugconcentratIoncomIngtothelIver(mIxedportalveIn+hepatIcartery)
andC
v
IsthedrugconcentratIonleavIng(hepatIcveIn).So,
HepatIcclearance=EFhepatIcbloodflow
0rugsmaybeclassedbroadlyashIghextractIonandlowextractIon,adIstInctIonwIth
ImportantImplIcatIonsfordrugInteractIon:
AhIghextractIondrug(e.g.,lIdocaIne,propranolol)mayhaveanEFof0.7to0.8ormore
(70to80IsclearedInonepassthroughthelIver).Forthesedrugs,hepatIcbloodflowIs
theratelImItIngfactorInoverallhepatIcclearance,thatIs,thedelIveryofdrugtothe
lIverdetermInestheamountcleared.ClearanceIsdecreasedbydrugsormaneuversthat
lowerhepatIcbloodflow,suchasbetablockade,cImetIdIne,halothane,hypotensIon,and
upperabdomInalsurgery.TheclearanceoftheserapIdlymetabolIzeddrugsIsmuchless
sensItIvetochangesInenzymeactIvIty.NordoesplasmaproteInbIndInghavealarge
effect;theenzymesaresoactIvethatadrugsuchaslIdocaIneIssImplystrIppedoffIts
bIndIngproteInsasIttraversesthelIver:
0ecreasesInhepatIcbloodflowsecondarytodecreasedcardIacoutputelevatelIdocaIne
concentratIonsInhumans.
J6
PressoradmInIstratIoncanalsoaccomplIshthesamethIng.ThIseffectwaselegantly
demonstratedby8enowItz,etal.
J7
Inrhesusmonkeys(FIg.221).SteadystateInfusIons
oflIdocaInewereestablIshed,thenhepatIcbloodflowwasIncreasedordecreasedby
InfusIonsofIsoproterenolornorepInephrIne,respectIvely.0urIngIsoproterenolInfusIon,
theconcentratIonoflIdocaInedecreased,IndIcatIngIncreasedclearance.0urIng
norepInephrIneInfusIon,lIdocaIneconcentratIonsIncreased.
LIdocaIneclearanceIsdecreasedandtoxIcItyIsIncreasedwhenpatIentsaretreated
chronIcallywIthcImetIdIne.
J8
tIsnotclearwhethersIngledosepremedIcatIonwIth
cImetIdIneproducesthesameeffect.
P.555
DtherhIghextractIondrugs,suchasmorphIneandsufentanIl,areaffectedthesame
way.TheclearanceofmorphInemaybeveryslowInapatIentwIthdecreasedhepatIc
bloodflow.
LowextractIondrugssuchasdIazepam,alfentanIl,ormepIvacaInehaveEFsof0.Jorless.
ThesedrugsbehavequItedIfferentlybecausehepatIcenzymeactIvItyIsratelImItIng
(hepatIcclearanceIslImItedbyIntrInsIcclearance).StImulatIonorInhIbItIonofenzyme
actIvItycanhavealargeeffectonoverallpharmacokInetIcs.ProteInbIndIngIsalsomore
lIkelytoaffectclearancebecausetheboundformsofthesedrugsareprotectedfrom
hepatIcmetabolIsm.ThemostcommonreasonforIncreasedIntrInsIcclearanceIsenzyme
InductIon.|anydrugsofImportanceInanesthesIologyaremetabolIzedbythecytochrome
P450enzymes(socalledmIcrosomalorCYPenzymes).SeveralfamIlIesandnumerous
subfamIlIesoftheseenzymeshavebeenIdentIfIedbasedonthehomologyoftheIramIno
acIdsequences.ThemostImportantsubfamIlyappearstobeCYPJA,whIchIsfoundIn
greatestabundanceInhumanlIverandIsresponsIbleforthemetabolIsmofahugenumber
ofdrugs.DthersubfamIlIesplayImportantrolesIndrugmetabolIsm,suchasCYP2C19
(dIazepam)orCYP2E1(defluorInatIonofvolatIleanesthetIcs).Therearehundredsofdrugs
andenvIronmentaltoxInsthatcanstImulateorInducemIcrosomalenzymes.TypIcally,a
sIngleInducercanaffecttheproductsofseveralgenefamIlIes.Forexample,phenobarbItal
canIncreasetheamountoftheP450enzymesCYP28,2C,2E,JA,and48.
J9
AnIncreaseIn
thequantItyofenzymeproteIncanthereforeIncreasetheclearanceofmanydrugs
sImultaneously.However,notallInducersaffectthesameenzymes.
TreatmentwIthanenzymeInducer(Table221)canmakeanotherwIsestabledrug
regImenIneffectIveorInconsIstentlyeffectIve:
AclassIcexampleIstheInteractIonbetweenphenobarbItalandcoumarIntype
antIcoagulants(FIg.222).ncreasedmetabolIsmmayalsoresultIntheproductIonofan
actIveortoxIcmetabolIte.
nratmIcrosomalpreparatIons,thelIberatIonofInorganIcfluorIdebyIsoflurane,
methoxyflurane,andenfluranecanbeIncreasedbypretreatmentwIthbarbIturates,
40
butthIsInteractIonappearstobeclInIcallyImportantonlyformethoxyflurane.
41
n
humans,phenobarbItaldoesnotInducedefluorInatIonofenflurane.
FeductIvepathwaysalsoInvolveP450enzymes,andtheproductIonoftoxIcreduced
IntermedIateshasbeenpostulatedasamechanIsmforhalothanehepatItIs.nanImal
models,admInIstratIonofhalothaneafterenzymeInducerscanleadtocentrIlobular
necrosIs.
42
TheclInIcalrelevanceofthIsfIndIngIsunknown.
TherearemanyexamplesofdrugsthatInhIbItthehepatIcbIotransformatIonofotherdrugs
(Table221):
Table 22-1 Drugs That Induce or Inhibit Hepatic Drug Metabolism in
Humans
INDUCERS INHIBITORS
PhenobarbItal CImetIdIne
PhenytoIn Ketoconazole
FIfampIcIn ErythromycIn
CarbamazepIne 0IsulfIram
Ethanol FItonavIr
Figure 22-2.EffectofphenobarbItalonplasmalevelsofbIshydroxycoumarIn.The
antIcoagulantwasgIvenatadoseof75mg/day.PhenobarbItal,65mg/day,wasgIven
durIngtheperIodsIndIcatedonthexaxIs.nductIonofhepatIcenzymesdecreased
antIcoagulantconcentratIonsandreducedtheeffect.(FeprIntedfromCucInellSA,
ConneyAH,Sansur|,etal:0rugInteractIonsInman:.LowerIngeffectof
phenobarbItalonplasmalevelsofbIshydroxycoumarIn[dIcumarol]and
dIphenylhydantoIn[0IlantIn].ClInPharmacolTher1965;6:420,wIthpermIssIon.)
WhentwodrugsaresubstratesforthesameP450enzymes,theycanInteract
competItIvelyandreducetheclearanceofboth.Forexample,Ithasbeendemonstrated
thatmIdazolamandfentanylarecompetItIveInhIbItorsin vitroofmetabolIsmby
CYPJA4.
4J
ThIspharmacokInetIcInteractIonIsprobablyfarlessImportantthanthe
pharmacodynamIcInteractIonbetweenthesedrugs(descrIbedlater).
AnotherstudyconcludedthatpropofolcompetItIvelyInhIbItsCYPJA4,andItcanreduce
theclearanceofmIdazolambyJ7.
44
PropofolItselfappearstobemetabolIzedbya
dIfferentIsoform,CYP286.
45
AlfentanIlanderythromycInarebothmetabolIzedbyCYPJA4,andtheantIbIotIcgreatly
prolongstheeffectoftheopIoId.
46
SufentanIlandfentanylarealsometabolIzedby
CYPJA4,
47
buttheclearanceofsufentanIlIsnotchangedbyerythromycIn.
48
PerhapsthIs
IsbecauseItIsahIghclearanceopIoId.
CImetIdInehasanImIdazolegroupthatbIndstothehemeIronofcytochromeP450and
formsanInactIvecomplex.CImetIdIneInhIbItsthemetabolIsmofmanydrugs,IncludIng
warfarIn,dIazepam,phenytoIn,andmorphIne.SeveralstudIeshavedemonstratedthat
coadmInIstratIonofcImetIdIneanddIazepamcausesclInIcallysIgnIfIcantelevatIonsIn
theconcentratIonofbothdIazepamandItsactIvemetabolIte.
49
AsstatedprevIously,
cImetIdInecandecreasehepatIcbloodflow,soItcanalsodecreasetheclearanceof
hIghextractIondrugs.
J8
ProteaseInhIbItorssuchassaquInavIr
50
andrItonavIr
51
canInhIbItthemetabolIsmof
mIdazolamandfentanyl,respectIvely,byInhIbItIngCYPJA4.
DtherImIdazoledrugssuchastheantIfungals,ketoconazoleandItraconazole,canInhIbIt
awIdevarIetyofmIcrosomalenzymes.Theyhavebeenshowntodecreasetheclearance
(andIncreasethetoxIcIty)ofglyburIde,terfenadIne,dIgoxIn,mIdazolam,theophyllIne,
andwarfarIn.
TherelatedbenzImIdazole,etomIdate,blocksthesynthesIsofcortIsolandaldosterone
byInhIbItIngtheP450dependentmItochondrIalenzymes,17hydroxylaseand11
hydroxylase.
52
EtomIdatecanInhIbItthemetabolIsmofotherdrugs,buttheeffectsdo
notappeartobeclInIcallyImportant.
P.556
Drug Elimination
ThefInalcategoryofpharmacokInetIcInteractIonIsthroughalteratIonIndrugelImInatIon.
TheseInteractIonsusuallyInvolvealteredrenalclearance,buttheymayalsoInvolve
changesInpulmonaryexcretIon.
ThemechanIsmforIontrappIngwasdIscussedearlIer.ontrappIngcanbethebasIsfor
largechangesInrenaldrugexcretIonwhenthepK
a
ofthedrugIsclosetothenormalrange
ofurInepH:
AweakacIdsuchasphenobarbItal(pK
a
=7.4)IslargelynonIonIzedwhentheurInepHIs
6.0.ThIsmeansthatmuchofthefIltereddrugIsInarelatIvelylIpIdsolubleformand
avaIlablefortubularreabsorptIon.ftheurInepHIsraIsedto8or9(e.g.,wIthsodIum
bIcarbonate),mostofthephenobarbItalbecomesIonIzed,reabsorptIondecreases,and
clearanceIncreases.Foraweakbase,thereversesItuatIonIstrueexcretIoncanbe
promotedwhentheurIneIsacIdIfIed.ThIstypeofInteractIonhasbeenused
therapeutIcallyIncertaIncasesofdrugoverdose.
DrganIcanIonsandcatIonsareactIvelysecretedbyseparatetransportersIntherenal
tubule.ThecatIonsystemhandlestheelImInatIonofatropIne,Isoproterenol,neostIgmIne,
andmeperIdIne.TheanIonsystemIsInvolvedIntheexcretIonofsalIcylate,penIcIllIns,
cephalosporIns,andmostofthepotentdIuretIcs.ThevarIousanIonsandcatIonscan
competefortheIrrespectIvetransportsItes:
ProbenecIdInhIbItsthesecretIonofpenIcIllIn,IncreasIngplasmaconcentratIonsand
prolongIngtheduratIonofactIon.
QuInIdInehasbeenshowntodecreaseboththevolumeofdIstrIbutIonandtherenal
clearanceofdIgoxIn,andplasmadIgoxInconcentratIonsmayIncreasebytwoto
fIvefold.
5J
TherenaleffectIsbelIevedtobeduetoareductIonIntubularsecretIonof
dIgoxIn.
Pharmacodynamic Interactions
UptothIspoInt,wehavebeendIscussIngpharmacokInetIcInteractIonsthatchangethe
amountofactIvedrugreachIngreceptorsItes.ApharmacodynamicInteractIonoccurs
whenonedrugaltersthesensItIvItyofatargetreceptorortIssuetotheeffectsofasecond
drug.ThIsmeansthatthedoseresponseorconcentratIonresponsecurveforonedrugIs
shIftedbyanother(FIg.22J).tIsoftendIffIculttoassIgnaspecIfIcmechanIsmtothese
InteractIons.WecommonlyclassIfythembytheIrdIrectIonandIntensIty,thatIs,addItIve,
antagonIstIc,orsupraaddItIve(synergIstIc).
Additive interactionsaremostlIkelytooccurwhendrugswIthIdentIcalmechanIsmsare
combIned.TheclInIcIannormallyexpectsaddItIvItywhencombInIngtwobenzodIazepInes,
twofentanylanalogs,ortwovolatIleanesthetIcs.|ostaddItIveInteractIonstendnottobe
partIcularlysurprIsIng,althoughsomeareclInIcallyuseful:
TheadmInIstratIonoftwoamInosteroIdnondepolarIzIngmusclerelaxants,suchas
rocuronIumandvecuronIum,gIvesanaddItIveeffect
54
(FIg.224).Notably,the
InteractIonsbetweennondepolarIzIngrelaxantsofdIfferentchemIcalclassesareoften
synergIstIc(seelaterdIscussIon).
TheInteractIonoftwovolatIleanesthetIcsornItrousoxIdewIthvolatIleanesthetIcsIs
addItIve.
55,56,57
nanImals,mIxturesoflIdocaInetetracaIneorlIdocaIneetIdocaIneproduce
approxImatelyaddItIveCNStoxIcItywhengIvenIntravenously.
58
Figure 22-3.0oseresponsecurvesforlossofconscIousnessafteranIntravenousbolus
doseofpropofol(Prop)alone,propofolplusmIdazolam(|Idaz),propofolplus
alfentanIl(Alfent),orallthreedrugs.0rugcombInatIonsweregIvenasconstantratIos,
basedonthemeasuredE0
50
softheIndIvIdualdrugs.8oththebenzodIazepIneandthe
opIoIdshIftedthedoseresponsecurveforpropofolsIgnIfIcantlytotheleft.(Fedrawn
fromdataInShortTC,PlummerJL,ChuIPT:HypnotIcandanaesthetIcInteractIons
betweenmIdazolam,propofolandalfentanIl.8rJAnaesth1992;69:162,wIth
permIssIon.)
Themostcommonantagonistic drug interactionsInanesthesIaarethoseInvolvIng
delIberatereversalofeffectwIthcompetItIveantagonIstssuchasneostIgmIne,naloxone,
orflumazenIl.PharmacodynamIcantagonIsmthatIsunintendedIsamuchlesscommon
event:
AnantagonIstIcInteractIonoccursbetweensuccInylcholIneandthenondepolarIzIng
relaxants.
59
WhenepIduralmorphIneorfentanylIsadmInIsteredafterestablIshIngablockwIth2
chloroprocaIne,boththeduratIonandtheIntensItyofopIoIdanalgesIaaredecreased.
60
ThemechanIsmforthIsInteractIonIsunclear.
WhenbutorphanolIscombInedwIthmIdazolam,themIxtureIncreasessedatIonbuthas
lessanterogradeamnestIceffectthanmIdazolamalone(FIg.225).ThIsIllustratesthe
ImportantconceptthatadrugcombInatIon
P.557
maysImultaneouslybesynergIstIcandantagonIstIcfordIfferenteffects.nthecaseof
theamnestIceffect,butorphanolmaysImplybedIlutIngtheeffectsofmIdazolam.
61
Figure 22-4.TheInteractIonofrocuronIumandvecuronIumIsaddItIveInman.Log
doseprobItgraphplotstwItchheIght(TH)aspercentageofcontrolvalue.0oseIsgIven
IntermsofE0
50
multIples.0Iamonds(blue),squares(green),andcIrcles(red)
representrocuronIum,vecuronIum,andthecombInatIon,respectIvely.Thedose
responsecurveforthecombInatIoncannotbedIstInguIshedfromthoseofthe
IndIvIdualdrugs.(FeprIntedfromNaguIb|,SamarkandIAH,8akhameesHS,etal:
ComparatIvepotencyofsteroIdalneuromuscularblockIngdrugsandIsobolographIc
analysIsoftheInteractIon.8rJAnaesth1995;75:J7,wIthpermIssIon.)
Figure 22-5.|emoryscoresofpatIents5mInutesafterreceIvIngbutorphanol,
mIdazolam,orthecombInatIon.L,|,andHsIgnIfylow,medIum,andhIghdoses(7.1,
22.5,and71.4g/kgbutorphanol;4.J,1J.6,and42.9g/kgmIdazolam;orJ.6+2.2,
11.J+6.8,andJ5.7+21.5g/kgbutorphanolandmIdazolamIncombInatIon).The
dashed lineIndIcatesmeanpretreatmentvalue.|Idazolam,butnotbutorphanol,
producedaprofoundanterogradeamnestIceffect.CIvIngonehalfthedoseofeach
drugIncombInatIonproducedaneffectthatwaslessthanthataftermIdazolamalone.
(FeprIntedfrom0ershwItz|,FosowCE,0I8IaseP|,etal:AcomparIsonofthe
sedatIveeffectsofbutorphanolandmIdazolam.AnesthesIology1991;74:717,wIth
permIssIon.)
ThemostInterestIngandclInIcallyImportantInteractIonstendtobethesynergistic
interactions,InwhIchsmalldosesoftwoormoredrugscansometImesproducelarge
effects.SynergyIsmostlIkelytooccurwhendrugsofdIfferentclasses,oreventhosewIth
slIghtlydIfferentmechanIsms,areusedtoproducethesameeffects:
ThepotentIatIonofopIoIdsbyNSA0sIsaclassIcandusefulInteractIonbetween
analgesIcdrugswIthcompletelydIfferentmechanIsms.
62
ThepotentIatIonofnondepolarIzIngrelaxantsbythevarIousvolatIleanesthetIcsIsa
usefulInteractIononadaIlybasIs.TheexactmechanIsmIsunknown,butseveral
theorIeshavebeenproposed,IncludIngIncreasedbloodflowtomuscle,depressIonof
centrallymedIatedmuscletone,decreasedneurotransmItterrelease,anddecreased
sensItIvItyofpostjunctIonalormusclemembranes.
AmuchmoresubtlesupraaddItIveInteractIonoccursbetweenamInosteroIdand
benzylIsoquInolInes.PancuronIumanddtubocurarInewereshowntoproducea
synergIstIcrelaxanteffectIncombInatIon,
6J
andthIsIsalsoseenwIthsImIlar
combInatIonsacrossthesetwochemIcalclasses(atracurIumandvecuronIum,d
tubocurarIneandvecuronIum,mIvacurIumandrocuronIum).7arIousmechanIsmshave
beenproposed,IncludIngmultIplebIndIngsItes
64
(presynaptIcforamInosteroIdversus
postsynaptIcforbenzylIsoquInolInes)andallosterIcInteractIonsbetweenseparate
agonIstandantagonIstbIndIngsItes.
65
SedatIvesandhypnotIcswIthrelated(butnotIdentIcal)mechanIsmsofactIonusually
InteractsynergIstIcallytoproducegreaterCNSdepressIon.ThIsIsdIscussedInmore
detaIllaterInthIschapter.
Studying Drug Interactions
AsalreadydIscussed,astudythatdemonstratesthatadrugdrugInteractIonexIstsdoesnot
necessarIlyestablIshItsmechanIsm,ItsmagnItude,orItsclInIcalrelevance.What
InformatIonIsneededtoconcludethatanInteractIonIspharmacodynamIcratherthan
pharmacokInetIc:HowdoweknowItIsreallysynergIstIc:LetusconsIderfourclInIcal
experImentstostudytheInteractIonofmIdazolamandthIopental.CIventhedIfferent
mechanIsmsforthesetwodrugs,wemIghtpredIctasynergIstIcInteractIon:
benzodIazepInesIncreaseneuronalchlorIdeconductancebyfacIlItatIngamInobutyrIc
acId(CA8A)bIndIng,whereasbarbIturatesbIndtoaseparatesIteandIncreaseCA8A
effIcacy:
1. nthesImpleststudydesIgn,twogroupsofpatIentsarerandomlyassIgnedtoreceIve
mIdazolamthIopentalorplacebothIopental.ThepercentagethatbecomesunresponsIve
IneachgroupIsassessedatastandardtImeafterthIopentaladmInIstratIon.Thedata
showthatmIdazolamIncreasesthepercentageunresponsIve.
Such a study is severely limited: it tells us that an interaction has occurred, but the
results cannot be generalized beyond the conditions examined (a single dose of
midazolam, a single dose of thiopental). Nothing may be inferred about mechanism.
2. Amorecomplex(butmoreuseful)experImentwouldbetostudyathIopentaldose
responsecurveInthepresenceandabsenceofmIdazolam.ThIswouldshowthatthe
doseofthIopentalrequIredtoproducehypnosIsInhalfthepatIents(E0
50
)Isdecreased
bymIdazolam.
These results allow us to conclude that the interaction occurs over a range of thiopental
doses relevant to clinical practice. The data still apply only to a single dose of
midazolam, and they tell us nothing about the mechanism of the interaction.
J. AusefulmodIfIcatIonofthIsexperImentIstoadmInIsterthethIopentalbyaconstant
rateInfusIon(wIthorwIthoutmIdazolam)andmeasureItsconcentratIonovertIme.The
datashowthatconcentratIonsofthIopentalrIseatthesamerateInbothgroups,but
mIdazolamdecreasestheconcentratIonneededtoproducehypnosIsIn50ofthe
patIents(theEC
50
).
This tells us that midazolam has not changed the pharmacokinetics of thiopental, so the
interaction must have a pharmacodynamic mechanism.
4. FInally,thereareanumberofexperImentaldesIgnsfordemonstratIngsynergy,and
thesehavebeenrevIewedIntheclInIcallIterature.
66
Twoofthemostcommon
technIquesusedbyexperImentalpharmacologIstsarealgebraIc(fractIonal)
67
and
IsobolographIc
68,69
analysIs,andclInIcalanesthesIastudIesusIngthesemethodshave
beenappearIngfrequently.TheInteractIonofthIopentalandmIdazolamwasstudIed
wIthanIsobolographIctechnIque,andtheresultsareshownInFIgure226.
70
ngeneral,
thIsanalysIs
P.558
requIresamInImumofthreedoseresponseexperIments,onewItheachdrugaloneand
onewIththedrugsIncombInatIon.ThedrugcombInatIoncanbestudIedasafIxedratIo,
oroneofthedrugscanbegIvenatafIxeddoseandthedoseoftheseconddrugvarIed.
FromtheseexperIments,threeestImatesofE0
50
aremade,andanIsobologramIs
constructedasshownInFIgure226.TheE0
50
sforthIopentalandmIdazolamaloneare
graphedonthetwoaxes,andthesepoIntsareconnectedbythetheoretIclIneof
addItIvIty.fthetwodrugsaresImplyaddItIvewhencombIned,wewouldexpectthe
E0
50
ofthemIxturetofallsomewherealongthIslIne.8ecausetheactualE0
50
ofthe
mIxtureIssIgnIfIcantlylessthanpredIctedbythIslIne,theInteractIonIssynergIstIc(an
E0
50
greaterthanpredIctedwouldsIgnIfyantagonIsm).
Figure 22-6.sobolographIcanalysIsoftheInteractIonbetweenmIdazolamand
thIopentalInhumans(seetextfordetaIls).TheE0
50
ofthecombInatIonwas
sIgnIfIcantlylessthanpredIctedbytheredlIneofaddItIvIty.(Fedrawnfromdataof
Tverskoy|,FleyshmanC,8radleyELJretal:|IdazolamthIopentalanesthetIc
InteractIonInpatIents.AnesthAnalg1988;67:J42,wIthpermIssIon.)
Pharmacodynamic Interactions Affecting Hemodynamics
ThetreatmentofhypertensIon,angIna,dysrhythmIas,andcongestIveheartfaIlureInvolves
theuseofdrugswIthpowerfuleffectsonautonomIcfunctIonandcardIovascular
homeostasIs.UntIlthe1970s,theteachIngwasgenerallythatcardIovasculardepressantor
stImulantmedIcatIonsshouldbedIscontInuedbeforesurgerybecausetheyInterferedwIth
protectIveresponsestothetraumaofanesthesIaandsurgery.Someolder
antIhypertensIveslIkereserpIneandmethyldopaalteredthedepthofanesthesIa,and
thIswasbelIevedtobeundesIrable.ThereIsnowasubstantIalbodyofevIdenceshowIng
thatmostcardIovascularmedIcatIonsneednotandshouldnotbestoppedbeforesurgery.
HypertensIvepatIentswhoremaInwellcontrolledarelesslIkelytohavewIdeswIngsIn
pressuredurIngsurgery.EvensmalldosesofbetablockersgIvenbeforesurgerycanreduce
theIncIdenceofmyocardIalIschemIaandImproveoutcome.
71,72
Dneweekof
perIoperatIvetreatmentwIthatenololcanproducelongtermbenefIts.
7J,74
Conversely,the
abruptdIscontInuatIonofvasoactIvemedIcatIonscanactuallyIncreasecardIovascular
InstabIlIty,andInthecaseofbetablockersandclonIdIne,thereboundhypertensIonand
dysrhythmIasmaybedangerous.
CIventheforegoIngobservatIons,ItIsfortunatethatmostcardIovasculardrugdrug
InteractIonsaresImplyextensIonsoftheknownpharmacologyoftheagents(Table222).n
short,thehypotensIveeffectsofgeneralorregIonalanesthesIamaybeIncreasedbyall
antIhypertensIvemedIcatIons.UsIngsImIlarlogIc,antIdysrhythmIcdrugssuchas
amIodaroneorprocaInamIdeIncreasethepossIbIlItyofbradycardIa,hypotensIon,and
decreasedcardIacoutput.
WIththepossIbleexceptIonofangIotensInconvertIngenzymeInhIbItors(ACEs)and
angIotensInreceptorblockers(AF8s),thereIslIttlereasontowIthholdmostvasoactIve
medIcatIonsbeforesurgery.tmaybeprudenttostopdIuretIctreatmentbefore
procedureswIthlargeantIcIpatedfluIdrequIrementsorsIgnIfIcantuseofnephrotoxIc
antIbIotIcs.SeveralstudIessuggestthatcontInuatIonoftheACEsandAF8sleadstoahIgh
IncIdenceofsevere,sometImesrefractory,hypotensIondurIngInductIonofgeneral
anesthesIa.
75,76
Thesedrugsdecreaseafterload,andtheyalsopotentIateanesthetIc
InducedreductIonInpreload.TheeffectonpreloadmaybequIteImportantIn
hypertensIvepatIentswhohavepreexIstIngdIastolIcdysfunctIon.
LIkethebaroreceptorreflexes,therenInangIotensInsystemIsanImportantwaythebody
canrespondtohypovolemIaorhypotensIon.WIthInmInutesafterapressuredecreaseIs
P.559
sensedbythejuxtaglomerularapparatus,angIotensIncausesvasoconstrIctIonbyboth
centralandperIpheralactIons.ChronIcblockadeofthIssystemnotonlyInhIbItsthe
angIotensInresponse,butItalsoreducesthevasoconstrIctorresponsetonorepInephrIne.
77
ThIsmayexplaInwhyACEInducedandAF8InducedhypotensIoncanbesoresIstantto
sympathetIcdrugssuchasphenylephrIne,ephedrIne,andnorepInephrIne.
78
7asopressIn
andvarIousvasopressInanalogscanrestoresympathetIcresponse
79,80
andmaybeuseful
pressorsIncasesofrefractoryhypotensIon.
Table 22-2 Effects of Antihypertensive Drugs During Anesthesia
CLASS DRUGS CLASS EFFECTS
Alphablockers
PhenoxybenzamIne HypotensIon/vasodIlatIon
PhentolamIne FeflextachycardIa
PrazosIn
8etablockers
Propranolol HypotensIon
|etoprolol 0ecreasedcontractIlIty
Atenolol
8radycardIa
A7block
|Ixedalpha/betablocker Labetalol
HypotensIon/vasodIlatIon
8radycardIa
A7block
CalcIumchannelblockers
7erapamIl HypotensIon/vasodIlatIon
0IltIazem 0ecreasedcontractIlIty
NIfedIpIne 8radycardIa
NIcardIpIne A7block
0IrectvasodIlators
NItroglycerIn HypotensIon/vasodIlatIon
sosorbIde FeflextachycardIa
HydralazIne
AngIotensInconvertIngenzyme
InhIbItors
CaptoprIl
EnalaprIl
LIsInoprIl
HypotensIon/vasodIlatIon
HyperkalemIa
AngIotensInblocker Losartan HypotensIon/vasodIlatIon
7alsartan HyperkalemIa
0IuretIcs
ThIazIdes HypovolemIa
FurosemIde HypokalemIa
8umetanIde PossIblevasodIlatIon
A7,atrIoventrIcular.
ThereIscurrentlynoconsensusonthepreoperatIvemanagementofpatIentstakIngACEs
orAF8s.WIthholdIngthemfor24hoursmaydecreasehypotensIonbutalsomakeblood
pressureextremelylabIledurIngsurgery.SomehavefoundthemtobebenefIcIaldurIng
surgery.
81,82
naddItIon,ACEsdonotappeartosIgnIfIcantlyImpactthehemodynamIc
managementofneuraxIalanesthesIa.
8J
TheconsIderatIonsareprobablydIfferentfor
patIentsreceIvIngACEsforchronIccongestIveheartfaIlure.ACEsaregIventothese
patIentsforafterloadreductIon;theyImprovebaroreceptorsensItIvIty,reduceventrIcular
remodelIng,anddecreasethemortalItyrate.PerIoperatIveuseofACEsInthIspopulatIon
maynotIncreasethealreadyhIghIncIdenceofhypotensIondurIngInductIon.
84
|ostperIoperatIvehemodynamIcInteractIonsInvolvetheuseofcardIovascular
depressants.tIsalsousefultoconsIderseveralgroupsofpatIentswhoaretreated(orwho
selftreat)beforesurgerywIthcardIovascularstimulants:
1. PatIentswIthbronchospasmmayrequIretreatmentwIthrapIdactIng
2
agonIsts
(albuterol,terbutalIne),antIcholInergIcs(IpratropIum),orphosphodIesteraseInhIbItors
(theophyllIne).ThesepatIentsareatIncreasedrIskfortachydysrhythmIasandectopIc
rhythms.SImIlarconsIderatIonsapplytothepatIentreceIvIngthe7
2
agonIst,
rItodrIne,forprematurelabor.
2. PatIentswhoreceIveTCAssuchasImIpramIne,desIpramIne,amItrIptylIne,and
nortrIptylInepresentseveralpossIblescenarIosforadversedrugInteractIon.Thesedrugs
workbyblockIngpresynaptIcreuptakeofnorepInephrIneorserotonIn,sotheycan
theoretIcallyIncreasetheeffectsofdIrectactIngorIndIrectactIngagonIstsatthese
synapses.|ostTCAsalsohavepromInentantIcholInergIceffects.noverdosesItuatIons,
TCAscancreatetheentIrerangeofcardIovasculartoxIcIty,IncludIngmyocardIal
InfarctIonandsuddendeath.nspIteofthIs,hypotensIonandtachydysrhythmIasarenot
commonIntraoperatIveproblemsforpatIentstakIngtheseolderantIdepressants.tIs
stIllreasonabletomInImIzetheuseofpancuronIum,halothane,ketamIne,andother
agentswIththepotentIaltoIncreasetheIncIdenceofdysrhythmIas.fTCAInduced
hypotensIonoccurs,thereIsdIsagreementaboutthebestwaytotreatIt.
85
Dnecase
reportdescrIbesapatIentonchronIcnIfedIpIneandnortrIptylInetherapywhohad
hypotensIonthatwasresIstanttoephedrIne,phenylephrIne,anddopamIne
(norepInephrInewaseventuallysuccessful).
86
J. FInally,wemustallbepreparedtotreatpatIentswhoareacutelyorchronIcally
IntoxIcatedwIthcocaIne.naddItIontoItslocalanesthetIcpropertIes,cocaIne
decreasesnorepInephrInereuptake,lIkeTCAs.AcuteIntoxIcatIonpresentsapartIcular
challenge.Young,otherwIsehealthypeoplemaypresentwIthfulmInanthypertensIon,
tachycardIa,andmyocardIalIschemIa(thelattermaybeseverebecausecocaInecan
alsoInduceathrombotIcdIathesIs).|anagementoftheacutecardIovasculareffectsIs
sImIlartothatforpheochromocytoma:thesepatIentsneedbothvasodIlatorsandbeta
blockers.AbetablockershouldnotbegIvenalonebecauseunopposedadrenergIc
stImulatIoncancauseafurtherIncreaseInsystemIcvascularresIstance.PatIentswIth
chronIccocaIneIntoxIcatIonarelessofaproblem,buttheyarestIllatrIskfor
dysrhythmIas(avoIdInghalothane,pancuronIum,atropIne,andsympathomImetIcsstIll
seemslIkeagoodIdea).ChronIccocaIneexposureIncreaseshalothanemInImumalveolar
concentratIon(|AC)Indogs
87
andIsoflurane|ACInsheep,
88
andacuteIngestIonmay
antagonIzethesedatIveeffectsofbenzodIazepInesInhumans.
89
ThIsIsanInterestIng
contrasttochronIctreatmentwIthamphetamIne,whIchappearstodecrease|ACIn
dogs.
90
tmIghtbebelIevedthattheadrenergIcoveractIvItyInducedbycocaInewould
producereceptordownregulatIonovertIme,butseveralanImalstudIessuggestthat
chronIccocaInetreatmentdoesnotdecreasebraIncatecholamInecontentor
sympathetIcresponsIveness.
91,92
TherelevanceofthesedatatohumancardIovascular
responsesremaInstobeproven.
Pharmacodynamic Interactions Affecting Analgesia or Hypnosis
CombInatIonsofCNSdepressantsalmostalwaysproduceaddItIveorsynergIstIcIncreasesIn
CNSeffect.TheseInteractIonsareusuallyusefulandpredIctable.Allthecommon7and
InhaledanesthetIcagentshavebeentestedIncombInatIonInhumans.ThefollowIng
sectIonshIghlIghtsomeofthemostImportantInteractIons.
OpioidHypnotic Interactions
ThIsIsarguablythemostcommonlyusedsynergIstIccombInatIonIn7anesthesIa:
FentanylandalfentanIlhavebeenshowntoreducetherequIrementforbarbIturates,
andthereIssomeevIdencethattheInteractIonIsbenefIcIal.FeducIngthetotaldoseof
thIopental
9J
orthIamylal
94
durIngshortproceduresdecreasesthetImetoawakenIngand
orIentatIon.
DpIoIdsalsopotentIatepropofol,butIthasbeenmuchmoredIffIculttoshowthatthe
combInatIonImprovesrecoverycomparedwIthpropofolalone.Short,etal.
95
foundthat
asmalldoseofalfentanIlcanreducetheInductIondoseofpropofolby50(FIg.22J).
0urIngtotal7anesthesIa,InfusIonsofremIfentanIloralfentanIltremendouslyreduce
theInfusIonrateofpropofolneededtosuppressresponsetovoIceandmovement
responsestosurgIcalstImulI.
96,97
TargeteffectsIteconcentratIonsofonly1to2g/mL
ofpropofolproduceadequateanesthesIaInmanycases.TheseareroutInelyachIeved
wIthpropofoldosesusedforconscIoussedatIon(25to50g/kgpermInute).
OpioidBenzodiazepine Interactions
ThIsImportantInteractIonwasalludedtoearlIer,andItIllustrateswhyopIoIdsareso
commonlyusedIncombInatIonwIthdIazepamormIdazolam.DpIoIdsarehIghlyselectIve
CNSdepressants;theycanproducesedatIon,buttheyarerelatIvelyweakhypnotIcs.Even
hugedosesoffentanylandItscongenersdonotdependablyproducesleepbythemselves.
98
Forexample,alfentanIldosesashIghas100to200g/kgcannotalwaysInduce
unconscIousnessInunpremedIcatedpatIents.
99
SuchopIoIddosesunIformlyproduceapnea,
rIgIdIty,andprofoundanalgesIa.
KIssInetal.
100
found,however,thatatInydoseofalfentanIl(Jg/kg)IssuffIcIentto
reducethehypnotIcE0
50
ofmIdazolamby50.ThIsdoseIssubanalgesIcandsubhypnotIc
whengIvenalone.ThIsmeansthatasmalldoseofopIoId
P.560
(50gfentanyl,500galfentanIl)mayhavealmostnohypnotIceffectbyItself,butcan
stIllbeanextremelyeffectIvepotentIatorofotherhypnotIcs.talsomeansthatwhen
fentanylandmIdazolamarecombInedforconscIoussedatIon,theopIoIdIsproducIngsleep
aswellasanalgesIa.
BenzodiazepineHypnotic Interactions
ThetheoretIcalbasIsfortheInteractIonbetweenbarbIturatesandbenzodIazepIneswas
dIscussedearlIer,andthethIopentalmIdazolamInteractIonIsshownInFIgure226.
ThIopentalmIdazolamInteractIonhasbeenstudIedInhumans,andthecombInatIonwas
foundtohave1.8tImestheexpectedpotencyoftheIndIvIdualagents.
70,101
SImIlar
resultshavebeendescrIbedwIththecombInatIonofmIdazolamandmethohexItal.
102
PropofolalsoactsbymodulatIonofCA8AneurotransmIssIon,andItshypnotIceffectsare
potentIatedwhenItIscombInedwIthmIdazolam.
95
TheclInIcalbenefItsofbenzodIazepInepremedIcatIonaremostobvIousdurIngthe
preoperatIveperIod.ntraoperatIvebenefIts(I.e.,IncreasedeffIcacyorreducedtoxIcIty)
ofbenzodIazepInehypnotIccombInatIonshavenotbeendemonstrated.ThepatIent
premedIcatedwIthmIdazolamneedslessthIopentalorpropofolforInductIon(or
maIntenance),butIthasnotbeenestablIshedthatthIsresultsInasmootheranesthetIcor
morerapIdawakenIng.
Volatile AnestheticOpioid Interactions
DpIoIdsproducedosedependentandconcentratIondependentdecreasesIn|ACforallthe
InhalatIonanesthetIcs:
AsteadystateplasmafentanylconcentratIonof1.67ng/mLdecreaseshumanIsoflurane
|ACby50
10J
(FIg.227).
Figure 22-7.TheInteractIonbetweenfentanylandIsoflurane.Thegreen line
representstheconcentratIonofthetwodrugsthatpreventsmovementIn50of
patIents.|AC,mInImumalveolarconcentratIon;C,confIdenceInterval.(FeprInted
from|cEwanA,SmIthC,0yarD,etal:sofluranemInImumalveolarconcentratIon
reductIonbyfentanyl.AnesthesIology199J;78:864,wIthpermIssIon.)
DpIoIdpartIalagonIstssuchasnalbuphIneandbutorphanolproducesmallerreductIonsIn
|AC.
104
AnImaldataconsIstentlyshowthatanapproxImately70reductIonIn|ACIsthe
maxImumeffectobtaInablewIthafullagonIstlIkefentanyl.
105
ThemechanIsmforthIs
InteractIonIsunknown,butLIcIna,etal.
106
showedthatadmInIstratIonoflumbar
IntrathecalmorphIne(15g/kg)doesnotalterhalothane|ACInhumans.ThIssuggests
thattheeffectmaybeduetosupraspInalopIoIdactIons.FampIl,etal.
107
showedthat
|ACIntheratIsnotalteredwhenthecerebralcortexandallotherprecollIcularbraIn
structuresareremoved.|ACthereforeappearstoreflectanactIonofthevolatIle
anesthetIcsonthespInalcord,whereas|ACreductIonbyopIoIdsIsmostlIkelytobe
medIatedbystructuresInthebraInstemorhIgher.DnepossIblesIteforInteractIonIsthe
locuscoeruleus(LC).
DpIoIdsandvolatIleagentsareoftencombInedtosmooththeIntraoperatIveand
postoperatIvecourse.nsomepatIents,thecombInatIonofopIoIdandvolatIleagentIs
hemodynamIcallybettertoleratedthanthevolatIleagentalone.AddItIonofanopIoIdmay
alsoreducetheIncIdenceofemergencedelIrIum.
sthereanyevIdencethatdecreasIngthedoseoftheInhaledagentInthIsmannerspeeds
awakenIng:TwostudIesIndIcatethat|ACawake(theconcentratIonatwhIch50of
subjectsrespondtovoIce)IsmuchlessaffectedbyopIoIdsthan|AC.
108,109
ThIssuggests
thatthecombInatIonmIghtspeedemergence,buttherehavebeennostudIesspecIfIcally
desIgnedtotestthIshypothesIs.
Dther7agentssuchaslIdocaIne,
110
mIdazolam,
111
and
2
agonIstshavebeenshownto
decrease|ACInexperImentalanImals.ForlIdocaIneandmIdazolam,theplasma
concentratIonsrequIredtoproduceameanIngfuldecreaseIn|ACaresohIghthatthe
InteractIonIsunlIkelytohaveclInIcalutIlIty.ThereIssomeevIdencethatthe
sImultaneoususeofvolatIleanesthetIcsandbenzodIazepInescausesIncreasedcortIcal
bIndIngofthelatter.
112
2
-Agonist Interactions
thaslongbeenknownthatdrugsthatdepressCNSsympathetIcfunctIoncanproduce
sedatIonandpotentIateanesthesIa.DlderantIhypertensIvessuchasreserpIneand
methyldopacanproducedrowsInessandreducehalothane|AC.
11J
ThenewerautonomIc
modulators
2
agonIstssuchasclonIdIneordexmedetomIdInearepowerfulsedatIvesand
analgesIcsInhumans.
nanImals,dexmedetomIdIneproducesmarkedpotentIatIonofopIoIdanalgesIaand
benzodIazepIneInducedhypnosIs.
114
0exmedetomIdInealsolowershalothane|ACbynearly100throughaspecIfIc
postsynaptIc
2
mechanIsm.
115
0exmedetomIdIneInteractswIthbothpresynaptIcandpostsynaptIc
2
adrenergIcreceptors
todecreasecentralsympathetIctone.tshypnotIceffectIslargelytheresultofdepressIon
offunctIonIntheLCInthepons.
116
ThIsIsthemaInadrenergIcnucleusInthebraInandan
ImportantInputforendogenoussleeppathwaysthroughtheventrolateralpreoptIcnucleus.
ThereIsevIdencetosuggestthattheLCIsanImportantsIteforcontrolofsleep,attentIon,
memory,analgesIa,andautonomIcfunctIon.
117
TheLCcontaInsreceptorsforglutamate,
CA8A,acetylcholIne,opIoIds,andbenzodIazepInes,andexperImentalevIdencesuggests
thatItmaybethesIteforsomeImportantanesthetIcdrugeffectsandInteractIons:
1. TheLCIstherostralportIonofanImportantdescendIngInhIbItorypathway,whIchplays
apartIntheproductIonofopIoIdanalgesIa.
118
P.561
J. ntherat,destroyIngtheLCproducesastateofnarcolepsyanddecreaseshalothane|AC
byJ0to40.
119
4. AgonIstsatCA8A,opIoId,and
2
receptorsareallInhIbItorywhenmIcroInjectedIntothe
LC.ThesedrugsallhavesedatIvehypnotIcpropertIes,andallofthemlowerthe
requIrementforvolatIleanesthetIcs.
5. AcetylcholIneandglutamatereceptoragonIstsareexcItatoryIntheLC,andantagonIsts
atthesereceptors(e.g.,scopolamIne,ketamIne)arehypnotIcs.Someglutamateeffects
aremedIatedbyND,andInhIbItorsofneuronalNDsynthasecandecreasethe
requIrementforhalothane
120
andIsoflurane.
121
Three-Way Interactions
nclInIcalpractIce,ItIscommontocombInemorethantwodrugswIthsedatIvehypnotIc
effects.WehaverelatIvelylIttleInformatIononwhathappenswhenathIrddrugIsadded
totwothatalreadyhavesynergIstIceffects:
Short,etal.
95
performedaclInIcalstudyofhypnotIcInteractIonsamongpropofol,
mIdazolam,andalfentanIl(FIg.22J).PropofolrequIrementwasreducedby82wIththe
threewaycombInatIon,butItproducedlesspotentIatIonthanwouldhavebeen
predIctedbyaddIngtheeffectsofthetwowaycombInatIons.
7InIk,etal.
122
studIedthesamecombInatIonandalsofoundprofoundhypnotIc
synergIsm:thedoseofpropofolcouldbedecreasedby86InthepresenceofalfentanIl
andmIdazolam.ThedataalsosuggestedthattheInteractIonbetweenmIdazolamand
alfentanIlwasamarkedpotentIatIon,buttheaddItIonofpropofoldIdnotproduce
sIgnIfIcantaddItIonalchange.FIgure228showsthedatafromthIsexperImentanalyzed
wIthathreewayIsobologram.
AthreewayInteractIonInvolvIngenflurane,dexmedetomIdIne,andfentanylwas
InvestIgatedIndogs.Salmenpera,etal.
12J
foundthateachofthetwo7agentslowered
enflurane|AC,andcombInIngthethreedrugsproduceda|ACreductIonthatwas
probablygreaterthanpredIctedbysImpleaddItIvIty.nthIscase,thethreeway
combInatIonproducedmorebradycardIathanenfluranealone.
Figure 22-8.E0
50
IsobologramsforthethreewayhypnotIcInteractIonsamong
mIdazolam,alfentanIl,andpropofol.ThereadercanImagIneatrIangularplaneof
addItIvItywIthItscornersattheIndIvIdualE0
50
values.TheE0
50
forthetrIple
combInatIonwassIgnIfIcantlylowerthanpredIctedbyaddItIvIty.(FeprIntedfrom7InIk
HF,8radleyELJr,KIssIn:TrIpleanesthetIccombInatIon:PropofolmIdazolam
alfentanIl.AnesthAnalg1994;78:J54,wIthpermIssIon.)
Herbal Preparations and Drug Interactions
AmerIcanhaveIncreasInglyusedherbal,vItamIn,andoverthecounterpreparatIonsInan
attempttotreatvarIousaIlments.WhIletheuseofthesepreparatIonsIncreased
sIgnIfIcantlydurIngthe1990s,overrecentyearstheuseseemstohaveslowed.
1
n200J,
overthecountersalesofherbalsandvItamInswereapproxImatelyS62.9bIllIon,an8
growthfrom2002.
124
AsurveyofJ,842patIentsdurIngpreoperatIveevaluatIonsfoundthat
22usedherbalmedIcatIonsand51usedvItamIns.ThemostlIkelypatIentstousethese
productswerewomenages40to60years.
125
Anothersurveyof1,017patIentsfoundJ2
usedoneormoreherbrelatedcompounds,and70dIdnotreportthIsInformatIonwhen
askeddurIngroutInepreanesthetIcassessment.
126
HerbalpreparatIonsareclassIfIedasdIetarysupplementsInthe0IetarySupplementHeath
andEducatIonActof1994.
127
8ythIsact,herbalpreparatIonsareexemptfromthesafety
andeffIcacyrequIrementsandregulatIonsthatprescrIptIonandoverthecounterdrugs
mustfulfIll.nstead,theU.S.Foodand0rugAdmInIstratIonmustprovelackofsafety.
128
ThereIsnoregulatoryoversIghtofthespecIfIccontentsoftheherbalpreparatIons,and
dIfferentbatchesorbrandsofthesameherbaloftendonotcontaInequalamountsofthe
actIvecompound.
ThePhysicians' Desk Reference for Herbal MedicinesIsnowInItsfourthedItIon,
129
but
thereIsstIllrelatIvelylIttlepeerrevIewedlIteratureaddressIngherbalsanddIetary
supplementswIthspecIfIcreferencetoperIoperatIvecare.Amongthethousandsofherbal
preparatIonsavaIlable,onlyafewhavebeendocumentedtocauseproblemseIther
throughIntrInsIctoxIcItyorthroughpharmacokInetIcandpharmacodynamIc
InteractIons.
1J0,1J1,1J2
TheherbalsmostcommonlycItedareechInacea,ephedra(ma
huang),garlIc,gIngko,gInseng,kava,andSt.John'swort.AsFugh8erman
1JJ
noted,many
oftheartIclesonherbalscontaInsIgnIfIcanterrorsandunsubstantIatedconclusIons.Some
commonlymentIonedherbalbasedInteractIonsarelIstedInTable22J,alongwIthan
assessmentofthestrengthoftheevIdence.WewereunabletofIndclInIcaltrIalsprovIng
thattherearespecIfIcadverseInteractIonsbetweenherbalsandanesthetIcdrugs.
Models for the Future: Drug Interaction During Total
Intravenous Anesthesia
AnesthesIamustalwaysbetItratedtoeffect,buttheclInIcIanusuallybegInsdosIngeach
drugwIthsomenotIonofanormaldoserangeandareasonableIncrementaldose.As
addItIonaldrugsareaddedtotheanesthetIc,thesedosesneedtobemodIfIed.Arethere
anyrelIabledatatoguIdetheadmInIstratIonofanesthetIcdrugsIncombInatIon:The
answerformostroutInebalancedanesthetIcsIsprobablyno.Aswehaveseen,almostall
anesthetIcdrugsInteractInanonlInear,synergIstIcfashIon,andthemagnItudeofthe
InteractIondependsonthespecIfIcdosesofeachagent.fthedrugsaregIvenbybolus
InjectIonorvarIablerateInfusIon,theInteractIonchangesconstantlywIthtIme.PredIctIng
anesthetIcInteractIon,then,IslIkeaImIngatamovIngtarget.EvenarelatIvelysImple
anesthetIcseemstorequIretheanalysIsofanImpossIblylargenumberofpotentIal
varIables.
nspIteoftheobstacles,therehavebeensomeattemptstoapplyquantItatIvemodelsto
totalIntravenousanesthesIa(T7A).TheT7AtechnIqueoffersseveraladvantagesInthIs
regard:
1. AnesthesIaIsoftenInducedandmaIntaInedwIthonlytwodrugs,arapIdactInghypnotIc
(e.g.,propofol)andarapIdactIngopIoId(e.g.,alfentanIl,remIfentanIl).The
P.562
P.56J
pharmacokInetIcsandpharmacodynamIcsofthesedrugsareexceptIonallywellstudIed.
Figure 22-9.ComputersImulatIonofthedecayInbloodpropofolandplasma
alfentanIlconcentratIonsdurIngthefIrst40mInutesafterthetermInatIonofa
computercontrolledInfusIon(seetextfordetaIls).(FeprIntedfrom7uykJ,LImT,
EngbersFH|,etal:ThepharmacodynamIcInteractIonofpropofolandalfentanIl
durInglowerabdomInalsurgeryInwomen.AnesthesIology1995;8J:8,wIth
permIssIon.)
2. ThedrugshavepharmacokInetIcswellsuItedtoadmInIstratIonbycontInuousInfusIon
wIthmIcroprocessordrIvenpumps.0urInganesthesIa,plasmaconcentratIonsofthe
drugsmaybeheldrelatIvelyconstant,sobloodandbraInattaInpseudoequIlIbrIum.The
researchermayvarytheInfusIonofeachdrugIndependentlyandrelatestableplasma
concentratIonstoclInIcaleffects.
Table 22-3 Published Evidence for Herbal Toxicity
NAME(S) COMMON USE
CLAIMED
TOXICITY
130
,
132
,
133
,
135
PUBLISHED EVIDENCE
a
Ephedra
|ahuang
EphedrIne
ChInese
joIntfIr
WeIghtloss
AntItussIve
8acterIostatIc
Halothane:
arrhythmIas
|AD:enhanced
sympathetIc
effects
DxytocIn:
hypertensIon
Stroke,
hypertensIon,
cardIacarrest
7ephedrInewell
characterIzed
nadequatedataon
specIfIcInteractIonswIth
oralephedra
Dralephedraknownto
causeadverseCNSand
cardIacevents
1J6
Echinacea
Commoncold
preventIon
HepatotoxIcIty
NoevIdenceof
hepatotoxIcIty
1JJ
nhIbItorofCYP1A2and
IntestInalCYPJA
actIvIty
1J7
nducerofhepatIc
CYPJA
1J7
Purple
cone
flower
Woundsand
burns
UrInarytract
InfectIons
Coughsand
bronchItIs
0ecrease
cortIcosteroId
effect
LaboratoryevIdenceof
macrophageactIvatIon
andenhancednatural
kIllercellactIvatIon
1J8
,
1J9
LIpIdlowerIng
NocontrolledtrIals
demonstratIngInteractIon
Garlic
Ajo
HypertensIon
AntIplatelet,
antIoxIdant
PotentIate
warfarIn
wIthwarfarIn
140
0ecreasedplatelet
aggregatIonIn
vItro
141
,
142
,
14J
,
144
,
145
,
146
Ginger
Nausea
AntIspasmodIc
nhIbIt
thromboxane
synthetase
nvItroevIdenceof
thromboxanesynthetase
InhIbItIon
147
,
148
,
149
,
150
Noeffectonplatelet
functIonwIth2g,but
InhIbItIonwIth5g
151
,
152
Ginkgo
|aIdenhaIr
tree
FossIltree
CIrculatory
stImulant
nhIbItPAF
CasereportsofIncreased
bleedIngInhumans
15J
nvItroevIdenceofPAF
InhIbItIon
154
,
155
Goldenseal 0IuretIc DxytocIc NoevIdence
Drange
root
AntI
Inflammatory
ParalysIsIn
overdose
Yellowroot LaxatIve Edema

Cround
raspberry
HemostatIc HypertensIon
TumerIcroot
Eyeroot
Kava AnxIolytIc HepatotoxIcIty
Casereportsof
hepatotoxIcIty
156
,
157
Ava/ava
pepper
Kawa
PotentIate
barbIturates,
benzodIazepInes
|ayInteracttoIncrease
sedatIonvIaCA8A
receptoractIvatIon
158
ClInIcalandanImal
studIesdemonstratIng
sedatIonand
anxIolysIs
159
,
160
Licorice
CastrIc/duodenal
ulcer
HypertensIon
LIcorIceabusecancause
hypokalemIa
Sweetroot CastrItIs HypokalemIa
Uncontrolled,studIes
showreductIonsIn
Coughand
bronchItIs
Edema
A0H,aldosterone,and
plasmarenIn
actIvIty
161
,
162
St. John's
wort
0epressIon
0ecreased
effIcacyof
dIgoxIn
ClInIcaldatashow
decreaseddIgoxIn
Hardhay
0ecreased
effIcacyof
warfarIn
level
16J
Amber
0ecreased
effIcacyof
antIconvulsants
nductIonofCYPJA4
164
Coatweed
0ecreasedserum
levelof
cyclosporIn
Enzyme
InductIon
Prolonged
anesthesIa
ClInIcalevIdenceforP
glycoproteInandCYP
InductIon
16J
Casereportsofprolonged
emergence,
cardIovascular
toxIcIty
165
,
166
Valerian
Allheal
Setwall
7andal
root
SedatIve
AnxIolytIc
PotentIate
barbIturates
SmallcontrolledclInIcal
trIalshoweddecreased
sleeplatency
167
,
168
AntIagIng
Preventstroke,
pulmonary ncreased
0ecreasedplatelet
aggregatIonIn
vItro
169
,
170
,
171
Vitamin E
embolI
Prevent
atherosclerosIs
Promotewound
healIng
bleedIng
ncreased
hypertensIon
SmallclInIcaltrIalshows
reductIonInplatelet
aggregatIon
80
NoevIdencefor
hypertensIon
7,Intravenous;|AD,monamIdeoxIdaseInhIbItor;CNS,centralnervoussystem;
PAF,plateletactIvatIngfactor;CA8A,amInobutyrIcacId;A0H,antIdIuretIc
hormone.
a
8asedonsearchof|edlIneandCochranedatabases,January1,1966,to
November1,2007.
noneofthefIrstquantItatIvestudIesofdrugInteractIondurIngT7A,7uykand
colleagues
96
gavecomputercontrolledInfusIonsofpropofolandalfentanIltowomen
undergoInglowerabdomInalsurgery.FIrst,thetargetconcentratIonofalfentanIlwasheld
constantandpropofolwasvarIed;then,thereverseexperImentwasdone.Theonsetof
sleepandthetImetoawakenIngweremeasured,aswaspresenceorabsenceofsomatIc
andhemodynamIcresponsestolaryngoscopy,IntubatIon,IncIsIon,andopenIngof
perItoneum.ArterIalbloodsampleswerecollected,andtheEC
50
ofalfentanIlforeach
clInIcalendpoIntwasrelatedtobloodpropofolconcentratIon.Asexpected,thedata
showedthatpropofolpotentIatedtheanalgesIceffectsofalfentanIl,andalfentanIl
potentIatedthehypnotIceffectsofpropofol.|oreImportantly,theauthorswereableto
relatevarIousconcentratIonsofeachagenttoagIvenendpoInt.
TheInterestInthesedatalIeInthewaytheycanbeusedtomodeldrugInteractIons.
1J4
n
FIgure229,7uyk,etal.
96
sImulatedthetImetoregaInconscIousnessatdIfferentratIosof
propofolandalfentanIl.ThegraphIssomewhatcomplex,butItIsworthconsIderIngfora
fewmoments.7uykandcolleaguesassumethata180mInuteanesthetIchasbeengIven
wIthpropofolandalfentanIltargetedatvarIousconcentratIons.FegardlessoftheratIoof
thetwodrugs,theresultInganesthetIcIssuffIcIenttopreventtheresponsetoIntra
abdomInalsurgeryIn50ofpatIents.ThethreeaxIsgraphrelatestheconcentratIonsof
eachdrugtothetImeafterdIscontInuatIonoftheInfusIons.AttIme0(thefloorofthe
graph),weseethesteadystateconcentratIonsjustwhentheInfusIonsarestopped.The
dIsappearanceofbothdrugsIsshown,andthefamIlyofplasmadecaycurves(allpossIble
combInatIonsofpropofolandalfentanIl)IsdepIctedonthegraphsurface.ThecurvedlIne
thatcrossesthetImeversusconcentratIonsurfaceIdentIfIesthetImeatwhIchapatIent
hasa50probabIlItyofawakenIng.Thefastestemergence(10mInutes)occurswhen
propofolandalfentanIlaretargetedatconcentratIonsofJ.5g/mLand85ng/mL,
respectIvely.EmergenceIssIgnIfIcantlylongerIftheanesthetIcIsmostlypropofolor
mostlyalfentanIl.
HowwIllthesedatahelpanyonegIveananesthetIc:WhatIftheInfusIonIsmuchshorteror
longerthan180mInutes:WhatIfthepatIentsareoldandsIck:WhatIftheanesthesIologIst
doesnothaveacomputeroranInfusIonpump:Theanswercouldbeanothersetof
questIons:WhatIsthevalueofknowIngthatthe|ACofhalothaneIs0.74vol,the
InductIondoseofpropofolIs2.5mg/kg,ortheanalgesIcdoseofmorphIneIs0.1mg/kg:
WeallunderstandthatthevalueofsuchnumbersIstogIveusaframeofreferencefor
tItratIngtheagents.Thevalueofthemodelcreatedby7uykandcolleagues
96
Isnotasa
recIpeforagood7anesthetIc,ItIsawaytothInkaboutdosIngguIdelInesfortwoor
moredrugssImultaneously.tIsnotfarfetchedtoImagInethattheFoodand0rug
AdmInIstratIonwIllsomedayrequIreInformatIononoptImalcombInatIonsforeachnew
pharmacologIcagent.
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Stock, M. Christine
TableofContentsSectIon7PreanesthetIcEvaluatIonandPreparatIonChapter2JPreoperatIvePatIent
Assessmentand|anagement
Chapter2J
Preoperative Patient Assessment and Management
Tara M. Hata
John R. Moyers
Key Points
1. The Joint Commission requires that all patients receive a preoperative
anesthetic evaluation, and the American Society of Anesthesiologists
(ASA) published a Practice Advisory for Preanesthesia Evaluation in
2002 and Approved Basic Standards for Preoperative Care.
2. The goals of a preoperative evaluation are to reduce patient risk and
morbidity associated with surgery and coexisting diseases, promote
efficiency and reduce costs, as well as to prepare the patient
medically and psychologically for surgery and anesthesia.
3. It is important for the evaluation to be complete, accurate, and clear,
not only to allow the information to be relayed to others who may
care for the patient perioperatively, but also for medicolegal
purposes.
4. The preoperative evaluation serves as a screening tool to anticipate
and avoid airway difficulties or problems with anesthetic drugs. In
addition to the history and physical, previous anesthesia records
should be re-viewed. Contraindications to specific drugs, such as
succinylcholine, nitrous oxide, or volatile agents, should be sought.
5. Review of the patient's allergies and medication list, including over-
the-counter and herbal medications, should specifically screen for
latex allergy and potential drug interactions. It should also alert the
anesthesiologist to the need for steroid coverage.
6. When evaluating the patient with hypertension, diabetes, or obesity
it is important to determine the presence of end-organ damage such
as heart, lung, renal, and cerebrovascular dysfunction.
7. Exercise tolerance is the most important determinant of cardiac risk.
The algorithm for preoperative evaluation of cardiac patients
undergoing noncardiac surgery is a useful guide to determine the
need for further testing and evaluation.
8. Preoperative laboratory tests should be ordered on the basis of
positive findings from the history and physical examination, or
anticipated physiological disturbances during surgery such as blood
loss.
9. Optimization of the patient's health status prior to surgery includes
clear instruction regarding nothing by mouth times as well as which
medications to administer immediately before surgery. In general,
most medications for hypertension or cardiac disease should be
considered, and consideration should be given to initiating a beta-
blocker in patients at risk. The need for subacute bacterial
endocarditis prophylaxis should be anticipated. Likewise, drugs for
asthma or chronic obstructive pulmonary disease should be
continued or administered prophylactically. Medications taken for the
treatment of reflux should be continued, or initiated for those
patients with untreated symptoms. For diabetic patients, oral
hypoglycemic agents should often be held, but patients requiring
insulin will need to continue to take adjusted doses.
10. Although preoperative sedation is generally limited to drugs given
immediately prior to anesthesia, the timing of administration must be
planned when oral sedation is needed in children to allow optimal
effect and avoid operating room delays.
P.570
ThegoalsofpreoperatIveevaluatIonaretoreducepatIentrIskandthemorbIdItyof
surgery,aswellastopromoteeffIcIencyandreducecosts.TheJoIntCommIssIonrequIres
thatallpatIentsreceIveapreoperatIveanesthetIcevaluatIon.TheAmerIcanSocIetyof
AnesthesIologIsts(ASA)approved8asIcStandardsforPreanesthetIcCare,whIchoutlInes
themInImumrequIrementsforapreoperatIveevaluatIon.ConductIngapreoperatIve
evaluatIonIsbasedonthepremIsethatItwIllmodIfypatIentcareandImproveoutcome.
ThereIsevIdence,althoughnotentIrelyconvIncIngInallInstances,thatthepreoperatIve
evaluatIonwIllIncreasepatIentsafety.ThatIs,armedwIthknowledgepreoperatIvely,the
anesthesIologIstcanformulateandconductananesthetIcplanthatavoIdsdangers
InherentInpatIentdIseasestates.Furthermore,preoperatIveevaluatIonsmayreduce
costsandcancellatIonrates,IncreasIngresourceutIlIzatIonIntheoperatIngroom.ThIs
notIonassumesthatevaluatIonsaredonebyanesthesIologIstsandothersfamIlIarwIth
anesthetIcs,surgery,andperIoperatIveevents.
ThepreoperatIveevaluatIonhasseveralcomponentsandgoals.DneshouldobtaInahIstory
andperformaphysIcalexamInatIonpertInenttothepatIentandcontemplatedsurgery.
8asedonthehIstoryandphysIcalexamInatIon,theapproprIatelaboratorytestsand
preoperatIveconsultatIonsshouldbeobtaIned.Throughthese,oneneedstodetermIne
whetherthepatIent'spreoperatIvecondItIonmaybeImprovedprIortosurgery.CuIdedby
thesefactors,theanesthesIologIstshouldchoosetheapproprIateanesthetIcandcareplan.
FInally,theprocessshouldbeusedtoeducatethepatIentaboutanesthesIaandthe
perIoperatIveperIod,answerallquestIons,andobtaInInformedconsent.
ThefIrstpartofthIschapteroutlInesclInIcalrIskfactorspertInenttopatIentsscheduled
foranesthesIaandsurgeryandtheuseofteststoconfIrmdIagnoses.Thesecondpart
dIscussespreoperatIvemedIcatIon.ThechapterprovIdesonlyanovervIewofthe
preoperatIvemanagementprocess;formoredetaIls,thereaderIsreferredtochapters
focusIngonspecIfIcorgansystems.
Changing Concepts in Preoperative Evaluation
nthepast,patIentswereadmIttedtothehospItalatleastadayprIortosurgery.
Currently,moreandmorepatIentsareadmIttedtothehospItalfromthepostanesthesIa
careunIt.DlderpatIentsarescheduledformorecomplexprocedures,andthereIsmore
pressureontheanesthesIologIsttoreducethetImebetweencases.ThefIrsttImethe
anesthesIologIstperformIngtheanesthetIcseesthepatIentmaybejustprIortoanesthesIa
andsurgery.DthersmayhaveseenthepatIentprevIouslyInapreoperatIveevaluatIon
clInIc.DnlyashorttImeexIststoengendertrustandanswerlastmInutequestIons.tIs
oftenImpossIbletoaltermedIcaltherapyatthIsjunctureImmedIatelypreoperatIvely.
However,preoperatIvescreenIngclInIcsarebecomIngmoreeffectIveandclInIcalpractIce
guIdelInesarebecomIngmoreprevalent.nformatIontechnologyhashelpedthe
anesthesIologIstInprevIewIngtheupcomIngpatIentswhowIllbeanesthetIzed.
PreoperatIvequestIonnaIresandcomputerdrIvenprogramshavebecomealternatIvesto
tradItIonalInformatIongatherIng.FInally,whenanesthesIologIstsareresponsIblefor
orderIngpreoperatIvelaboratorytests,costsavIngoccursandcancellatIonsofplanned
surgIcalproceduresbecomelesslIkely.nthIssettIngItIsImportantthatthereIs
communIcatIonbetweenthepreoperatIveevaluatIonclInIcandtheanesthesIologIst
performIngtheanesthetIc.
Approach to the Healthy Patient
ThepreoperatIveevaluatIonformIsthebasIsforformulatIngthebestanesthetIcplan
taIloredtothepatIent.tshouldaIdtheanesthesIologIstInIdentIfyIngpotentIal
complIcatIons,aswellasserveasamedIcolegaldocument.TheImportanceofthedesIgn
hasIncreasedbecauseItIsmorecommontodayfortheevaluatIontobecompletedIna
preoperatIonclInIcbyanotherphysIcIanorhealthprofessIonalwhowIllnotpersonallybe
performIngtheanesthetIc,butalsobecauseregulatoryagencIessuchasJCAHDdemand
betterdocumentatIon.Therefore,theInformatIonobtaInedneedstobecomplete,concIse,
andlegIble.nthosehospItalsthathaveelectronIcmedIcalrecords,legIbIlItyIsnolonger
anIssue.AgroupfromUnIversItyofCalIfornIa,San0IegostudIedthequalItyof
preoperatIveevaluatIonformsacrosstheUnItedStatesandratedthemInthreecategorIes:
InformatIonalcontent,easeofuse,andeaseofreadIng.
1
TheIrresultsrevealedthata
surprIsInglyhIghpercentageofformsaremIssIngImportantInformatIon.FIgure2J1Isan
exampleofthepreoperatIveevaluatIonformInuseattheUnIversItyofowaHospItals,
whIchattemptstodocumentallpertInentInformatIon.
TheapproachtothepatIentshouldalwaysbegInwIthathoroughhIstoryandphysIcal
examInatIon.ThesetwoevaluatIonsalonemaybesuffIcIent(wIthoutaddItIonalroutIne
laboratorytests).
TheIndIcatIonforthesurgIcalprocedureIspartofthepreoperatIvehIstorybecauseItwIll
helpdetermInetheurgencyofthesurgery.Trueemergencyprocedures,whIchare
assocIatedwItharecognIzedhIgheranesthetIcmorbIdItyandmortalIty,requIreamore
abbrevIatedevaluatIon.AlessdefInedareaIstheapproachtourgentprocedures.For
example,IschemIclImbsrequIresurgerysoonafterpresentatIon,butcanusuallybe
delayedfor24hoursforfurtherevaluatIon.TheIndIcatIonforthesurgIcalproceduremay
alsohaveImplIcatIonsonotheraspectsofperIoperatIvemanagement.Forexample,the
presenceofasmallbowelobstructIonhasImplIcatIonsregardIngtherIskofaspIratIonand
theneedforarapIdsequenceInductIon.TheextentofalungresectIonwIlldIctatethe
needforfurtherpulmonarytestIngandperIoperatIvemonItorIng.PatIentsundergoIng
carotIdendarterectomymayrequIreamoreextensIveneurologIcexamInatIon,aswellas
testIngtoruleoutcoronaryarterydIsease(CA0).Frequently,furtherInformatIonwIllbe
requIredthatnecessItatescontactIngthesurgeon.PerIoperatIvecareofthepatIent,as
wellaseffIcIencyIntheoperatIngroom,IsalwaysenhancedbyclosecommunIcatIonwIth
thesurgeons.
TheabIlItytorevIewprevIousanesthetIcrecordsIshelpfulIndetectIngthepresenceofa
dIffIcultaIrway,ahIstoryofmalIgnanthyperthermIa,andtheIndIvIdual'sresponseto
surgIcalstressandspecIfIcanesthetIcs.ThepatIentshouldbequestIonedregardIngany
prevIousdIffIcultywIthanesthesIaorotherfamIlymembershavIngdIffIcultywIth
anesthesIa.ApatIenthIstoryrelatInganallergytoanesthesIashouldmakeonesuspIcIous
formalIgnanthyperthermIa.
ThehIstoryshouldIncludeacompletelIstofmedIcatIons,IncludIngoverthecounterand
herbalproducts,todefIneapreoperatIvemedIcatIonregImen,antIcIpatepotentIaldrug
InteractIons,andprovIdecluestounderlyIngdIsease.AcompletelIstofdrugallergIes,
IncludIngprevIousreactIons,shouldbeobtaIned,aswellasanInquIryconcernIngreactIon
tolatex.
TheanesthesIologIstshoulddetermInewhenthepatIentlastate,aswellasnotethesItes
ofpreexIstIngIntravenouscannulaeandInvasIvemonItors.DncethegeneralIssuesare
completed,thepreoperatIvehIstoryandphysIcalexamInatIoncanfocusonspecIfIc
systems.
Figure 23-1.ExampleofpreanesthetIcevaluatIonform.
P.571
Systems Approach
Airway
AbasIcconcernoftheanesthesIologIstIsalwaysthepatIent'saIrway.TheabIlItytorevIew
prevIousanesthetIcrecordsIsespecIallyusefulInuncoverIngunsuspecteddIffIcult
aIrwaysortoconfIrmprevIousuneventfulIntubatIons,assumIngthepatIent'sbodyhabItus
hasnotchangedIntheInterIm.EvaluatIonoftheaIrwayInvolvesdetermInatIonofthe
thyromentaldIstance,theabIlItytoflexthebaseoftheneckandextendthehead,and
examInatIonoftheoralcavIty,IncludIngdentItIon.The|allampatIclassIfIcatIonhas
becomethestandardforassessIngtherelatIonshIpofthetonguesIzerelatIvetotheoral
cavIty(Table2J1),
2
althoughbyItselfthe|allampatIclassIfIcatIonhasalowposItIve
predIctIvevalueInIdentIfyIngpatIentswhoaredIffIculttoIntubate.
J,4
|ost
anesthesIologIstsfIndamultIfactorIalapproachveryhelpful(Table2J2).ntrauma
patIents,aswellasthosewIthsevererheumatoIdarthrItIsor0ownsyndrome,assessment
ofthecervIcalspIneIscrItIcal.napproprIatepatIents,thepresenceofpaInorsymptoms
ofcervIcalcordcompressIononmovementshouldbeassessed.notherInstances,
radIographIcexamInatIonmayberequIred.
Pulmonary
AscreenIngevaluatIonshouldIncludequestIonsregardIngthehIstoryoftobaccouse,
shortnessofbreath,cough,wheezIng,strIdor,andsnorIngorsleepapnea.ThepatIent
shouldalsobequestIonedregardIngthepresenceorrecenthIstoryofanupperrespIratory
tractInfectIon.PhysIcalexamInatIonshouldassesstherespIratoryrateaswellasthechest
excursIon,useofaccessorymuscles,naIlcolor,andthepatIent'sabIlItytocarryona
conversatIonortowalkwIthoutdyspnea.AuscultatIonshouldbeusedtodetectdecreased
breathsounds,wheezIng,
P.572
strIdor,orrales.ForthepatIentwIthposItIvefIndIngs,seethesectIononthepreoperatIve
evaluatIonofthepatIentwIthPulmonary0Isease.
Table 23-1 Airway Classification System
CLASS DIRECT VISUALIZATION, PATIENT SEATED LARYNGOSCOPIC VIEW
Softpalate,fauces,uvula,pIllars EntIreglottIc
Softpalate,fauces,uvula PosterIorcommIssure
Softpalate,uvularbase TIpofepIglottIs
7 Hardpalateonly Noglottalstructures
|odIfIedfrom|allampatIFS,CattSP,CugInoL0,etal:AclInIcalsIgntopredIct
dIffIculttrachealIntubatIon:AprospectIvestudy.CanAnaesthSocJ1985;J2:429,
wIthpermIssIon.
Table 23-2 Components of the Airway Physical Examination
a
AIRWAY EXAMINATION COMPONENT SUGGESTIVE OF DIFFICULTY WITH INTUBATION
1.LengthofupperIncIsors
Longcomparedtotherestof
dentItIon
2.FelatIonofmaxIllaryandmandIbular
IncIsorsdurIngnormaljawclosure
PromInentoverbIte
J.FelatIonofmaxIllaryandmandIbular
IncIsorsdurIngvoluntaryprotrusIonof
mandIble
PatIentcannotbrIngmandIbular
IncIsorsanterIortomaxIllary
IncIsors
4.nterIncIsordIstance LessthanJcm
5.7IsIbIlItyofuvula
NotvIsIblewhentongueIs
protrudedwIthpatIentInsIttIng
posItIon
6.Shapeofpalate HIghlyarchedorverynarrow
7.ComplIanceofmandIbularspace
StIff,Indurated,occupIedbymass,
ornonresIlIent
8.ThyromentaldIstance LessthanthreefIngerbreadths
9.Lengthofneck Shortneck
10.ThIcknessofneck ThIckneck
11.FangeofmotIonofheadandneck
PatIentcannottouchtIpofchInto
chestorIsunabletoextendneck
a
ThIstabledIsplayssomefIndIngsoftheaIrwayphysIcalexamInatIonthatmay
suggestdIffIcultywIthIntubatIon.ClInIcalcontextandjudgmentdetermInewhIch
ofthecomponentsapplytoapartIcularpatIent.TheorderofpresentatIonInthIs
tablefollowsthelIneofsIghtthatoccursdurIngconventIonalorallaryngoscopy.
|odIfIedfromtheTaskForceon0IffIcultAIrway|anagement:PractIceguIdelInes
formanagementofthedIffIcultaIrway:AnupdatedreportbytheAmerIcan
SocIetyofAnesthesIologIstTaskForceon|anagementofthe0IffIcultAIrway.
Anesthesiology200J;98:1269.
Cardiovascular System
WhenscreenIngapatIentforcardIovasculardIseaseprIortosurgery,theanesthesIologIstIs
mostInterestedInrecognIzIngsIgnsandsymptomsofuncontrolledhypertensIonand
unstablecardIacdIseasesuchasmyocardIalIschemIa,congestIveheartfaIlure,valvular
heartdIsease,andsIgnIfIcantcardIacdysrhythmIas.SymptomsofcardIovasculardIsease
shouldbecarefullydetermIned,especIallythecharacterIstIcsofchestpaIn,Ifpresent.
CertaInpopulatIonsofpatIents,suchastheelderly,women,ordIabetIcs,maypresentwIth
moreatypIcalfeatures.ThepresenceofunstableangInahasbeenassocIatedwIthahIgh
perIoperatIverIskofmyocardIalInfarctIon(|).
5
TheperIoperatIveperIodIsassocIated
wIthahypercoagulablestateandsurgesInendogenouscatecholamInes,bothofwhIchmay
exacerbatetheunderlyIngprocessInunstableangIna,IncreasIngtherIskofacute
InfarctIon.
6
ThepreoperatIveevaluatIoncanaffectbothapatIent'sshortandlongterm
healthbyInstItutIngtreatmentofunstableangIna.SymptomsofclInIcallyImportant
valvulardIseaseshouldbesought,suchasangIna,syncope,orcongestIveheartfaIlure
fromaortIcstenosIsthatwouldrequIrefurtherevaluatIon.AhIstoryofothervalvular
dIseasesuchasmItralvalveprolapsemaysImplydIctatetheneedforsubacutebacterIal
endocardItIsprophylaxIs.
TheexamInatIonofthecardIovascularsystemshouldIncludebloodpressure,measurIng
botharmswhenapproprIate.TheanesthesIologIstshouldtakeIntoaccounttheeffectsof
preoperatIveanxIetyandmaywantarecordofrestIngbloodpressuremeasurements.
However,8edfordandFeInsteIn
7
reportedthattheadmIssIonbloodpressurewasthebest
predIctorofHFand8Presponsetolaryngoscopy.AuscultatIonoftheheartIsperformed,
specIfIcallylIstenIngforamurmurradIatIngtothecarotIdssuggestIveofaortIcstenosIs,
abnormalrhythms,oragallopsuggestIveofheartfaIlure.ThepresenceofbruItsoverthe
carotIdarterIeswouldwarrantfurtherworkuptodetermInetherIskofstroke.The
extremItIesshouldalsobeexamInedforthepresenceofperIpheralpulsestoexclude
perIpheralvasculardIseaseorcongenItalcardIovasculardIsease.
Neurologic System
AscreenIngoftheneurologIcsystemIntheapparentlyhealthypatIentmostlycanbe
accomplIshedthroughsImpleobservatIon.ThepatIent'sabIlItytoanswerhealthhIstory
questIonspractIcallyensuresanormalmentalstatus.QuestIonscanbedIrectedtoexclude
thepresenceofIncreasedIntracranIalpressure,cerebrovasculardIsease,seIzurehIstory,
preexIstIngneuromusculardIsease,ornerveInjurIes.TheneurologIcexamInatIonmaybe
cursoryInhealthypatIents,orextensIveInpatIentswIthcoexIstIngdIsease.TestIngof
strength,reflexes,andsensatIonmaybeImportantInpatIentsIftheanesthetIcplanor
surgIcalproceduremayresultInachangeInthecondItIon.
Endocrine System
EachpatIentshouldbescreenedforendocrInedIseasesthatmayaffecttheperIoperatIve
course:dIabetes,thyroIddIsease,parathyroIddIsease,endocrInesecretIngtumors,and
adrenalcortIcalsuppressIon.
Evaluation of the Patient with Known Systemic Disease
Cardiovascular Disease
ThepreoperatIveevaluatIonofthepatIentwIthsuspectedcardIovasculardIseasehasbeen
approachedIntwoways:clInIcal
P.57J
rIskIndIcesandpreoperatIvecardIactestIng.ThegoalsaretodefInerIsk,determInewhIch
patIentswIllbenefItfromfurthertestIng,formanapproprIateanesthetIcplan,andIdentIfy
patIentswhowIllbenefItfromperIoperatIvebetablockade,InterventIontherapy,oreven
surgery.ClInIcalrIskIndIcesrangefromthephysIcalstatusIndexoftheAmerIcanSocIety
ofAnesthesIologIsts(Table2JJ)totheColdmanCardIacFIskndex,whIchhasrecently
beenupdated.
Table 23-3 American Society of Anesthesiologists (ASA) Physical Status
Classification
DISEASE STATE
ASAClass1 NoorganIc,physIologIc,bIochemIcal,orpsychIatrIcdIsturbance
ASAClass2
|IldtomoderatesystemIcdIsturbancethatmaynotberelatedto
thereasonforsurgery
ASAClassJ
SeveresystemIcdIsturbancethatmayormaynotberelatedto
thereasonforsurgery
ASAClass4
SeveresystemIcdIsturbancethatIslIfethreatenIngwIthor
wIthoutsurgery
ASAClass5
|orIbundpatIentwhohaslIttlechanceofsurvIvalbutIs
submIttedtosurgeryasalastresort(resuscItatIveeffort)
Emergency
operatIon(E)
AnypatIentInwhomanemergencyoperatIonIsrequIred
FromInformatIonderIvedfromAmerIcanSocIetyofAnesthesIologIsts:New
classIfIcatIonofphysIcalstatus.AnesthesIology196J;24:111.
nanupdateoftheColdmanCardIacFIskndex,theInvestIgatorsstudIed4,J15patIents
aged50yearsandolderwhowereundergoIngelectIve,majornoncardIacprocedures.
8
SIx
IndependentpredIctorsofcomplIcatIonswereIdentIfIedandIncludedInarevIsedrIsk
Index:hIghrIsktypeofsurgery,hIstoryofIschemIcheartdIsease,hIstoryofcongestIve
heartfaIlure,hIstoryofcerebrovasculardIsease,preoperatIvetreatmentwIthInsulIn,and
preoperatIveserumcreatInIne2.0mg/dL.CardIaccomplIcatIonsrosewIthanIncreaseIn
thenumberofrIskfactorspresent.FatesofmajorcardIaccomplIcatIonswIth0,1,2,orJ
ofthesefactorswere0.5,1.J,4,and9,respectIvely,InthederIvatIoncohortand0.4,
0.9,7,and11,respectIvely,among1,422patIentsInthevalIdatIoncohort(FIg.2J2).
Figure 23-2.CardIacrIskIndex(CF).8arsrepresentrateofmajorcardIac
complIcatIonsInentIrepatIentpopulatIon(bothderIvatIonandvalIdatIoncohorts
combIned)forpatIentsInrevIsedCFclassesaccordIngtotypeofprocedure
performed.Notethat,bydefInItIon,patIentsundergoIngabdomInalaortIcaneurysm
(AAA),thoracIc,andabdomInalprocedureswereexcludedfromClass.nallsubsets
exceptpatIentsundergoIngAAA,therewasastatIstIcallysIgnIfIcanttrendtoward
greaterrIskwIthhIgherrIskclass.SeetextfordetaIls.(FeproducedfromLeeTH,
|arcantonIoEF,|angIoneC|,etal:0erIvatIonandprospectIvevalIdatIonofasImple
IndexforpredIctIonofcardIacrIskofmajornoncardIacsurgery.CIrculatIon1999;100:
104J,wIthpermIssIon.)
WhIlealloftheseIndIcesprovIdeInformatIontoassesstheprobabIlItyofcomplIcatIons
andprovIdeanestImateofrIsk,theydonotprescrIbeperIoperatIvemanagement.n
contrast,theanesthesIologIstIsmostconcernedwIthformIngananesthetIcplanafter
defInIngthecardIovascularrIskfactors.
npatIentswIthsymptomatIccoronarydIsease,thepreoperatIveevaluatIonmayleadto
therecognItIonofachangeInthefrequencyorpatternofangInalsymptoms.CertaIn
populatIonsofpatIentsforexample,theelderly,women,ordIabetIcsmaypresentwIth
moreatypIcalfeatures.ThepresenceofunstableangInahasbeenassocIatedwIthahIgh
perIoperatIverIskof|.
5
nvIrtuallyallstudIes,thepresenceofactIvecongestIveheartfaIlurepreoperatIvelyhas
beenassocIatedwIthanIncreasedIncIdenceofperIoperatIvecardIacmorbIdIty.
9,10
StabIlIzatIonofventrIcularfunctIonandtreatmentforpulmonarycongestIonareImportant
prIortoelectIvesurgery.8ecausethetypeofperIoperatIvemonItorIngandtreatments
wouldbedIfferent,clarIfyIngthecauseofheartfaIlureIsImportant.CongestIvesymptoms
maybearesultofnonIschemIccardIomyopathyorcardIacvalvularInsuffIcIencyand/or
stenosIs.
AdultswIthaprIor|almostalwayshavecoronaryarterydIsease,(CA0).TradItIonally,
rIskassessmentfornoncardIacsurgerywasbasedonthetImeIntervalbetweenthe|and
surgery.|ultIpleolderstudIeshavedemonstratedanIncreasedIncIdenceofreInfarctIonIf
the|waswIthIn6monthsofsurgery.
11,12,1J
WIthImprovementsInperIoperatIvecare,
thIsdIfferencehasdecreased.Therefore,theImportanceoftheIntervenIngtImeInterval
maynolongerbevalIdInthecurrenteraofInterventIonaltherapyandrIskstratIfIcatIon
afteranacute|.AlthoughmanypatIentswIthan|maycontInuetohavemyocardIumat
rIskforsubsequentIschemIaandInfarctIon,otherpatIentsmayhavetheIrcrItIcalcoronary
stenoseseIthertotallyoccludedorwIdelypatent.Forexample,theuseofpercutaneous
translumInalcoronaryangIoplasty,thrombolysIs,andearlycoronaryarterybypassgraftIng
(CA8C)haschangedthenaturalhIstoryofthedIsease.
14,15
Therefore,patIentsshouldbe
evaluatedfromtheperspectIveoftheIrrIskforongoIngIschemIa.TheAmerIcanHeart
AssocIatIon/AmerIcanCollegeofCardIologyTaskForceonPerIoperatIveEvaluatIonofthe
CardIacPatIentUndergoIngNoncardIacSurgeryhasdefInedthreerIskgroupsmajor,
IntermedIate,andmInor(Table2J4).TheyIndIcatethatrecent|(J0days)places
patIentsInthegroupathIghestrIsk;afterthatperIod,aprIor|placesthepatIentat
IntermedIaterIsk.
16
Patients with Coronary Artery Disease
ForthosepatIentswIthoutovertsymptomsorhIstory,theprobabIlItyofCA0varIeswIth
thetypeandnumberof
P.574
atherosclerotIcrIskfactorspresent.PerIpheralarterIaldIseasehasbeenshowntobe
assocIatedwIthCA0InmultIplestudIes.
17
.0IabetesmellItusIsacommondIseaseInthe
elderlyandrepresentsaprocessthataffectsmultIpleorgansystems.ComplIcatIonsof
dIabetesmellItusarefrequentlythecauseofurgentoremergentsurgery,especIallyInthe
elderly.0IabetesacceleratestheprogressIonofatherosclerosIs,soItIsnotsurprIsIngthat
dIabetIcshaveahIgherIncIdenceofCA0thannondIabetIcs.ThereIsahIghIncIdenceof
bothsIlent|andmyocardIalIschemIa.
18
Eagle,etal.
19
demonstratedthatdIabetesIsan
IndependentrIskfactorforperIoperatIvecardIacmorbIdIty.nattemptIngtodetermIne
thedegreeofthIsIncreasedprobabIlIty,thelengthofthedIseaseandotherassocIated
endorgandysfunctIonshouldbetakenIntoaccount.AutonomIcneuropathyhasbeenfound
tobethebestpredIctorofsIlentCA0.
20
8ecausethesepatIentsareatveryhIghrIskfora
sIlent|,anelectrocardIogram(ECC)shouldbeobtaInedtoexamIneforthepresenceofQ
waves.
Table 23-4 Clinical Predictors of Increased Perioperative Cardiovascular
Risk (Myocardial Infarction, Congestive Heart Failure, Death)
MAJOR
Unstablecoronarysyndromes
FecentmyocardIalInfarctIon
a
wIthevIdenceofImportantIschemIcrIskby
clInIcalsymptomsornonInvasIvestudy
Unstableorsevere
b
angIna(CanadIanClassor7)
c
0ecompensatedcongestIveheartfaIlure
SIgnIfIcantdysrhythmIas
HIghgradeatrIoventrIcularblock
SymptomatIcventrIculararrhythmIasInthepresenceofunderlyIngheartdIsease
SupraventrIculararrhythmIaswIthuncontrolledventrIcularrate
SeverevalvulardIsease
INTERMEDIATE
|IldangInapectorIs(CanadIanClassor)
PrIormyocardIalInfarctIonbyhIstoryorpathologIcQwaves
CompensatedorprIorcongestIveheartfaIlure
0IabetesmellItus
MINOR
Advancedage
AbnormalECC(leftventrIcularhypertrophy,leftbundlebranchblock,STT
abnormalItIes)
FhythmotherthansInus(e.g.,atrIalfIbrIllatIon)
LowfunctIonalcapacIty(e.g.,InabIlItytoclImboneflIghtofstaIrswIthabagof
grocerIes)
HIstoryofstroke
UncontrolledsystemIchypertensIon
ECC,electrocardIogram.
a
TheAmerIcanCollegeofCardIologyNatIonal0atabaseLIbrarydefInesrecent
myocardIalInfarctIonas7daysbut1month(J0days).
b
|ayIncludestableangInaInpatIentswhoareunusuallysedentary.
c
CampeauL:CradIngofangInapectorIs.CIrculatIon1976;54:522.
FeproducedfromEagleK,8rundage8,ChaItman8,etal:CuIdelInesfor
perIoperatIvecardIovascularevaluatIonofthenoncardIacsurgery.Areportofthe
AmerIcanHeartAssocIatIon/AmerIcanCollegeofCardIologyTaskForceon
Assessmentof0IagnostIcandTherapeutIcCardIovascularProcedures.CIrculatIon
1996;9J:1278,wIthpermIssIon.
HypertensIonhasalsobeenassocIatedwIthanIncreasedIncIdenceofsIlentmyocardIal
IschemIaandInfarctIon.
18
HypertensIvepatIentswhohaveleftventrIcularhypertrophyand
areundergoIngnoncardIacsurgeryareatahIgherperIoperatIverIskthannonhypertensIve
patIents.
21
nvestIgatorshavesuggestedthatthepresenceofastraInpatternonECCsuggestsa
chronIcIschemIcstate.
22
Therefore,thesepatIentsshouldalsobeconsIderedtohavean
IncreasedprobabIlItyofCA0andforperIoperatIvemorbIdIty.
ThereIscontroversyregardIngatrIggertodelayorcancelasurgIcalprocedureInapatIent
wIthuntreatedorInadequatelytreatedhypertensIon.HypertensIonhasbeendIvIdedInto
threestages,wIthstageJdenotIngthatwhIchmIghtbeusedasacutoff(Table2J5).
2J
AggressIvetreatmentofbloodpressureIsassocIatedwIthIncreasedreductIonInlongterm
rIsk,althoughtheeffectdImInIshesInallbutdIabetIcpatIentsasdIastolIcbloodpressureIs
reducedbelow90mmHg.AlthoughtherehasbeenasuggestIonInthelIteraturethata
caseshouldbedelayedIfthedIastolIcpressureIs110mmHg,thestudyoftenquotedas
thebasIsforthIsdetermInatIondemonstratednomajormorbIdItyInthatsmallgroupof
patIents.
24
DtherauthorsstatethatthereIslIttleassocIatIonbetweenbloodpressuresof
180mmHgsystolIcor110mmHgdIastolIcandpostoperatIveoutcomes.However,such
patIentsarepronetoperIoperatIvemyocardIalIschemIa,ventrIculardysrhythmIas,and
labIlItyInbloodpressure.tIslessclearInpatIentswIthbloodpressuresabove180/100mm
Hg,althoughnoabsoluteevIdenceexIststhatpostponIngsurgerywIllreducerIsk.
25,26
n
theabsenceofendorganchanges,suchasrenalInsuffIcIencyorleftventrIcular
hypertrophywIthstraIn,thebenefItsofoptImIzIngbloodpressuremustbeweIghedagaInst
therIsksofdelayIngsurgery.
SeveralotherrIskfactorshavebeenusedtosuggestanIncreasedprobabIlItyofCA0.These
IncludetheatherosclerotIcprocessesassocIatedwIthtobaccouseand
hypercholesterolemIa.AlthoughtheserIskfactorsIncreasetheprobabIlItyofdevelopIng
CA0,theyhavenotbeenshowntoIncreaseperIoperatIverIsk.WhenattemptIngto
determInetheoverallprobabIlItyofdIsease,thenumberofrIskfactorsandseverItyof
eachareImportant.
Importance of Surgical Procedure
ThesurgIcalprocedureInfluencesthescopeofpreoperatIveevaluatIonrequIredby
determInIngthepotentIalrangeofphysIologIcfluxdurIngtheperIoperatIveperIod.Few
harddataexIstdefInIngthesurgeryspecIfIcIncIdenceofcomplIcatIons.tIsknownthat
perIpheralprocedures,suchasthoseIncludedInastudyofambulatorysurgerycompleted
atthe|ayoClInIc,areassocIatedwIthanextremelylowIncIdenceofmorbIdItyand
mortalIty,
27
whIlemajorvascularprocedures
P.575
areassocIatedwIththehIghestIncIdenceofcomplIcatIons.Eagle,etal.
28
publIsheddata
ontheIncIdenceofperIoperatIve|andmortalItybyprocedureforpatIentsenrolledIn
theCoronaryArterySurgeryStudy.TheydetermInedtheoverallrIskofperIoperatIve
morbIdItyInpatIentswIthknownCA0treatedeIthermedIcallyorwIthprIorCA8C.They
foundthathIghrIskproceduresIncludemajorvascular,abdomInal,thoracIc,and
orthopaedIcsurgery.TheAmerIcanHeartAssocIatIon/AmerIcanCollegeofCardIology
CuIdelInesdescrIbedrIskstratIfIcatIonfornoncardIacsurgerythatIsshownInTable2J6.
16
Table 23-5 Blood Pressure
CATEGORY SYSTOLIC (mm Hg) DIASTOLIC (mm Hg)
DptImal 120 and 80
Normal 1J0 and 85
HIghnormal 1J01J9 or 8589
HypertensIon
Stage1 140159 or 9099
Stage2 160179 or 100109
StageJ 180 or 110
FeproducedfromSIxthreportoftheJoIntNatIonalCommItteeonPreventIon,
0etectIon,EvaluatIon,andTreatmentofHIgh8loodPressure.Archntern|ed
1997;157:241J,wIthpermIssIon.
Table 23-6 Cardiac Risk
a
Stratification for Noncardiac Surgical Procedures
in Patients with Known Coronary Artery Disease
HIGH
(FeportedcardIacrIskoften5)
EmergentmajoroperatIons,partIcularlyIntheelderly
AortIcandothermajorvascular
PerIpheralvascular
AntIcIpatedprolongedsurgIcalproceduresassocIatedwIth
largefluIdshIftsand/orbloodloss
(FeportedcardIacrIskgenerally5)
INTERMEDIATE
CarotIdendarterectomy
Headandneck
ntraperItonealandIntrathoracIc
DrthopaedIc
Prostate
LOW
b
(FeportedcardIacrIskgenerally1)
EndoscopIcprocedures
SuperfIcIalprocedures
Cataract
8reast
a
CombInedIncIdenceofcardIacdeathandnonfatalmyocardIalInfarctIon.
b
0onotgenerallyrequIrefurtherpreoperatIvecardIactestIng.
Importance of Exercise Tolerance
ExercIsetoleranceIsoneofthemostImportantdetermInantsofperIoperatIverIskandthe
needforfurthertestIngandInvasIvemonItorIng.AnexcellentexercIsetolerance,evenIn
patIentswIthstableangIna,suggeststhatthemyocardIumcanbestressedwIthoutfaIlIng.
fapatIentcanwalkamIlewIthoutbecomIngshortofbreath,theprobabIlItyofextensIve
CA0Issmall.AlternatIvely,IfpatIentsexperIencedyspneaassocIatedwIthchestpaIn
durIngmInImalexertIon,theprobabIlItyofextensIveCA0IshIgh,whIchhasbeen
assocIatedwIthgreaterperIoperatIverIsk.AddItIonally,thesepatIentsareatrIskfor
developInghypotensIonwIthIschemIa,andthereforemaybenefItfrommoreextensIve
monItorIng,coronaryInterventIontherapy,orrevascularIzatIon.ExercIsetolerancecanbe
assessedwIthformaltreadmIlltestIngorwIthaquestIonnaIrethatassessesactIvItIesof
daIlylIvIng(Table2J7).
16
FeIlly,etal.
29
haveevaluatedthepredIctIvevalueofselfreportedexercIsetolerancefor
serIousperIoperatIvecomplIcatIonsanddemonstratedthatapoorexercIsetolerance
(couldnotwalkfourblocksandclImbtwoflIghtsofstaIrs)IndependentlypredIcteda
complIcatIonwIthanoddsratIoof1.94.ThelIkelIhoodofaserIousadverseeventwas
Inverselyrelatedtothenumberofblocksthatcouldbewalked.Therefore,thereIsgood
evIdencetosuggestthatmInImaladdItIonaltestIngIsnecessaryIfthepatIentIsableto
descrIbeagoodexercIsetolerance.
Indications for Further Cardiac Testing
|ultIplealgorIthmshavebeenproposedtodetermInewhIchpatIentsrequIrefurther
testIng.AsdescrIbedprevIously,therIskassocIatedwIththeproposedsurgIcalprocedure
InfluencesthedecIsIontoperformfurtherdIagnostIctestIngandInterventIons.CuIdelInes
mustbetemperedbyrecentstudIesInwhIchperIoperatIvecardIacmorbIdItywasgreatly
reducedbyperIoperatIveadrenergIcblockadeadmInIstratIon.
J0
P.576
WIththereductIonInperIoperatIvemorbIdIty,IthasbeensuggestedthatextensIve
cardIovasculartestIngIsnotnecessary.However,untIlthesefIndIngscanbeconfIrmed,
furthertestIngmaybewarranted.
Table 23-7 Estimated Energy Requirement for Various Activities
a
1
|ET
Canyoutakecareof
yourself:
Eat,dress,orusethe
toIlet:
WalkIndoorsaround
thehouse:
Walkablockortwo
onlevelgroundat2
JmphorJ.24.8
km/hr:
0olIghtworkaround
thehouse,lIke
dustIngorwashIng
dIshes:
4
|ETs
Walkonlevelgroundat4mphor6.4
km/hr:
FunashortdIstance:
0oheavyworkaroundthehouse,lIke
scrubbIngfloorsorlIftIngormovIng
heavyfurnIture:
PartIcIpateInmoderaterecreatIonal
actIvItIeslIkegolf,bowlIng,dancIng,
doublestennIs,orthrowIngabaseball
orfootball:
4
|ETs
ClImbaflIghtof
staIrsorwalkupa
hIll:
10
|ETs
PartIcIpateInstrenuoussportslIke
swImmIng,sInglestennIs,football,
basketball,orskIIng
|ET,metabolIcequIvalent.
a
Adaptedfromthe0ukeActIvItyStatusndexandAmerIcanHeartAssocIatIon
ExercIseStandards.
ThealgorIthmtodetermInetheneedfortestIngproposedbytheAmerIcanCollegeof
CardIology/AmerIcanHeartAssocIatIonTaskForceupdatedIn2002,
J1
andagaInIn2007
J2
Is
basedontheavaIlableevIdenceandexpertopInIonthatIntegratesclInIcalhIstory,
surgeryspecIfIcrIsk,andexercIsetolerance(FIg.2JJ).
16
nstepone,theclInIcIan
evaluatestheurgencyofthesurgeryandtheapproprIatenessofaformalpreoperatIve
assessment.Next,oneshoulddetermIneIfthepatIenthasundergonearecent
revascularIzatIonprocedureorcoronaryevaluatIon.ThosepatIentswIthunstablecoronary
syndromesshouldbeIdentIfIed,andapproprIatetreatmentInstItuted.FInally,thedecIsIon
toundergofurthertestIngdependsontheInteractIonoftheclInIcalrIskfactors,surgery
specIfIcrIsk,andfunctIonalcapacIty.ForpatIentsatIntermedIateclInIcalrIsk,both
exercIsetoleranceandtheextentofthesurgeryaretakenIntoaccounttodetermInethe
needforfurthertestIng.mportantly,nopreoperatIvecardIovasculartestIngshouldbe
performedIftheresultswIllnotchangeperIoperatIvemanagement.
Cardiovascular Tests
Electrocardiogram
PreoperatIve12leadelectrocardIogramcanprovIdeImportantInformatIononthestateof
thepatIent'smyocardIumandcoronarycIrculatIon.AbnormalQwavesInhIghrIskpatIents
arehIghlysuggestIveofapast|.ConfIrmatIonofactIveIschemIausuallyrequIreschanges
Inatleasttwoleads.thasbeenestImatedthatapproxImatelyJ0of|soccurwIthout
symptoms(sIlentInfarctIons)andcanonlybedetectedonroutIneECCs,wIththehIghest
IncIdenceoccurrIngInpatIentswItheItherdIabetesorhypertensIon.TheFramIngham
studyshowedthatlongtermprognosIsIsnotImprovedbylackofsymptoms.
18
Theabsence
ofQwavesontheECCdoesnotexcludetheoccurrenceofaQwave|Inthepast.
8etween5and27ofQwavesdIsappearoverthe10yearperIodfollowInganInfarctIon
durIngthe1970s.
JJ
ThosepatIentsInwhomtheECCrevertstonormalhaveImproved
survIvalcomparedwIththosewIthconsIstentabnormalItIes,wIthorwIthoutQwaves.The
presenceofQwavesonapreoperatIveECCInahIghrIskpatIent,regardlessofsymptoms,
shouldalerttheanesthesIologIsttotheIncreasedperIoperatIverIskandthepossIbIlItyof
actIveIschemIa.
thasnotbeenestablIshedthatInformatIonobtaInedfromthepreoperatIveECCaffects
clInIcalcare.ArevIewofclInIcalstudIesonthematterIsInconclusIve.none
retrospectIverevIewofadultpatIentsundergoIngambulatorysurgery,thepreoperatIve
ECCwasnotpredIctIveofperIoperatIverIsk.
J4
AlthoughcontroversyexIsts,thereare
currentrecommendatIonsfortheneedforapreoperatIveECC.ApreoperatIverestIng12
leadECCIsrecommendedforpatIentswIthbI thbI th bI bI , e e awabI th *! s *! s *! s *! controv nonrs *!ebI mat m
nooooe at controvers datereare
curre ( ]]]]]] r a nonr em e houldonrs gambul com 0 tha p
m rhype!Ide th th t th t
n t
nh th a edthatI
that
nh e*! ncrep InIc p * t] ol pol pol po]]* goents, ol po]]* ! ts ECC.A a o
studIesdemonstratedthesuperIorvalueofdobutamInestressechocardIography;however,
therewassIgnIfIcantoverlapoftheconfIdenceIntervalswIthothertests.Themost
ImportantdetermInantwIthrespecttothechoIceofpreoperatIvetestIngIstheexpertIse
ofthelocalInstItutIon.
CurrentrecommendatIonsarethatpatIentswIthactIvecardIaccondItIonssuchasunstable
angIna,congestIveheartfaIlure,sIgnIfIcantdysrhythmIasandseverevalvulardIsease
shouldundergononInvasIvestresstestIngbeforenoncardIacsurgery.NonInvasIvestress
testIngforpatIentswIthmultIpleclInIcalrIskfactorsandpoorfunctIonalcapacIty(less
thanfourmetabolIcequIvalents)whorequIrevascularsurgeryIsreasonableIfItwIll
changemanagement.NonInvasIvetestIngInotherpatIentsabouttogounder
IntermedIaterIsknoncardIacsurgeryorvascularsurgeryIslessclear.
J2
Assessment of Ventricular and Valvular Function
8othechoandradIonuclIdeangIographycanassesscardIacejectIonfractIonatrestand
understress,butechoIslessInvasIveandIsalsoabletoassessregIonalwallmotIon
abnormalItIes,wallthIckness,valvularfunctIon,andvalvearea.Pulsewave0opplercan
beusedtodetermInethevelocItytImeIntegral.EjectIonfractIoncanthenbecalculated
bydetermInIngthe
P.577
P.578
crosssectIonalareaoftheventrIcle.ConflIctIngresultsexIstwIthregardtothepredIctIve
valueofejectIonfractIonusIngeItherechocardIographIcorradIonuclIdemeasurements.t
IsreasonableforthosewIthdyspneaofunknownorIgInandforthosewIthcurrentorprIor
heartfaIlurewIthworsenIngdyspneaorotherchangeInclInIcalstatustohave
preoperatIveevaluatIonsofleftventrIcularfunctIon.ThewIsdomofreassessmentofleft
ventrIcularfunctIonInclInIcallystablepatIentswIthprevIouscardIomyopathyIs
unknown.
J2
EchocardIographycanprovIdeImportantInformatIonregardIngvalvular
functIon,whIchmayhaveImportantImplIcatIonsforeIthercardIacornoncardIacsurgery,
andIsdIscussedmorefullylaterInthIstext.AortIcstenosIshasbeenassocIatedwItha
poorprognosIsInnoncardIacsurgIcalpatIents,andknowledgeofvalvularlesIonsmay
modIfyperIoperatIvehemodynamIctherapy.
9
Figure 23-3.TheAmerIcanHeartAssocIatIon/AmerIcanCollegeofCardIologyTask
ForceonPerIoperatIveEvaluatIonofCardIacPatIentsUndergoIngNoncardIacSurgery
hasproposedanalgorIthmfordecIsIonsregardIngtheneedforfurtherevaluatIon.ThIs
representsoneofmultIplealgorIthmsproposedInthelIterature.tIsbasedonexpert
opInIonandIncorporatessIxsteps.FIrst,theclInIcIanmustevaluatetheurgencyof
thesurgeryandtheapproprIatenessofaformalpreoperatIveassessment.Next,heor
shemustdetermInewhetherthepatIenthashadaprevIousrevascularIzatIon
procedureorcoronaryevaluatIon.ThosepatIentswIthunstablecoronarysyndromes
shouldbeIdentIfIed,andapproprIatetreatmentshouldbeInstItuted.ThedecIsIonto
havefurthertestIngdependsontheInteractIonoftheclInIcalrIskfactors,surgery
specIfIcrIsk,andfunctIonalcapacIty.(AdaptedfromEagleK,8rundage8,ChaItman8,
etal:CuIdelInesforperIoperatIvecardIovascularevaluatIonofnoncardIacsurgery.A
reportoftheAmerIcanHeartAssocIatIon/AmerIcanCollegeofCardIologyTaskForce
onAssessmentof0IagnostIcandTherapeutIcCardIovascularProcedures.CIrculatIon
1996;9J:1278,wIthpermIssIon.)
Coronary Angiography
CoronaryangIographyIscurrentlythebestmethodfordefInIngcoronaryanatomy.n
addItIon,InformatIonregardIngventrIcularandvalvularfunctIoncanalsobeassessed.
HemodynamIcIndIcescanbedetermInedsuchasventrIcularpressuresandpressure
gradIentsacrossvalves.ThIsInformatIonIsroutInelyavaIlableInpatIentsscheduledfor
CA8C.NarrowIngoftheleftmaIncoronaryarteryandcertaInotherlesIonsmaybe
assocIatedwIthagreaterperIoperatIverIsk.0IffuseatherosclerosIsInsmallvessels,as
seenIndIabetIcs,mayleadtoIncompleterevascularIzatIonandarIskofdevelopIng
IschemIadespIteCA8C.CoronaryangIographyIsusedbycardIologIststodetermIne
whethercoronaryvascularIzatIonIsanoptIon.
UnlIketheexercIseorpharmacologIcstresstestsdIscussedearlIer,coronaryangIography
provIdesanatomIc,notfunctIonal,InformatIon.AlthoughacrItIcalcoronarystenosIs
delIneatesanareaofrIskfordevelopIngmyocardIalIschemIa,thefunctIonalresponseof
thatIschemIacannotbeassessedbyangIographyalone.AcrItIcalstenosIsmayormaynot
betheunderlyIngcauseforaperIoperatIve|thatoccurs.ntheambulatorypopulatIon,
manyInfarctIonsaretheresultofacutethrombosIsofanoncrItIcalstenosIs.Therefore,the
valueofroutIneangIographyprIortononcardIacsurgerydependsontheIdentIfIcatIonof
lesIonsthatwIllcausemorbIdItyandmortalIty.
PatIentswIthrestrIctedphysIcalactIvItyInwhomfunctIonalcapacItyIsdIffIcultto
determInemaybenefItfromsophIstIcatedImagIngtechnIquessuchascardIaccomputed
tomography.
J8
Perioperative Coronary Interventions
ThestrategIestoreducetheperIoperatIverIskofnoncardIacsurgeryhaverecentlybeen
studIed.ThereareseverallargestudIesthatsuggestthatInpatIentswhosurvIveCA8C,
therIskofsubsequentnoncardIacsurgeryIslow.
5,8
AlthoughtherearelIttledatato
supportthenotIonofcoronaryrevascularIzatIonsolelyforthepurposeofImprovIng
perIoperatIveoutcome,ItIstruethatforsomepatIentsscheduledforhIghrIsksurgery,
longtermsurvIvalmaybeenhancedbyrevascularIzatIon.TwostudIesusedtheCoronary
ArterySurgeryStudydatabaseandfoundthatCA8CsIgnIfIcantlyImprovedsurvIvalInthose
patIentswIthbothperIpheralvasculardIseaseandtrIplevesselcoronarydIsease,
especIallythegroupwIthdepressedventrIcularfunctIon.
6
AfterrevIewIngallavaIlable
data,mostclInIcIansbelIevetheIndIcatIonforCA8CprIortononcardIacsurgeryremaIns
thesameasInothersettIngsandIsIndependentoftheproposednoncardIacsurgery.
ThevalueofpercutaneoustranslumInalcoronaryangIoplastyIslesswellestablIshed.The
currentevIdencedoesnotsupporttheuseofpercutaneoustranslumInalcoronary
angIoplastybeyondestablIshedIndIcatIonsfornonoperatIvepatIents.
EarlysurgeryaftercoronarystentplacementhasbeenassocIatedwIthadversecardIac
events.AsIgnIfIcantIncIdenceofperIoperatIvedeathandofhemorrhageInpatIentsafter
stentplacementhasbeenreported.ThewaItIngperIodforsurgeryafterbaremetalstent
placementIsgenerallyrecognIzedtobeJto4weeks,whIlethewaItIngperIodfordrug
elutIngstentsIsfrom6to12months.ThIsdIfferenceIsbecausetheIncIdenceofstent
thrombosIsforthedrugelutIngstentshasbeenfoundtobesImIlartothebaremetalstents
Intheearlyphaseafterplacement,butlesswelldefInedoveralongerperIodoftIme.
Currently,patIentsareInvarIablytakIngaspIrInandclopIdogrelasantIplatelettherapy
afterstentplacement.PerIoperatIvemanagementweIghstherIskofbleedIngversusa
stentthrombosIs.ThedecIsIonmustInvolveanesthesIologIst,surgeons,cardIologIsts,and
IntensIvIsts.nthosepatIentswhohaveahIghrIskforstentthrombosIsmanyadvocate
thatatleastaspIrInbecontInuedIntheperIoperatIveperIod.Also,theanesthesIologIst
mustweIghtherIskofregIonalversusgeneralanesthesIawhenthesepatIentsaretakIng
antIplatelettherapy.SurgeryInpatIentswIthrecentstentplacementshouldprobablyonly
beconsIderedIncenterswhere24hourInterventIonalcardIologIstsareavaIlable.
J9,40,41
Pulmonary Disease
PulmonarycomplIcatIonsremaInamajorcauseofmorbIdItyandmortalItyforpatIents
undergoIngsurgeryandanesthesIa.TheyoccurmorefrequentlythancardIac
complIcatIons,wIthanIncIdenceof5to10InthosehavIngmajornoncardIacprocedures.
PerIoperatIvepulmonarycomplIcatIonsIncludeatelectasIs,pneumonIa,bronchItIs,
bronchospasm,hypoxemIa,exacerbatIonofchronIcobstructIvepulmonarydIsease,and
respIratoryfaIlurerequIrIngmechanIcalventIlatIon.
42
ThesIteandtypeofsurgeryarethestrongestpredIctorsofcomplIcatIons.WIthregardto
thesurgIcalsite,thoracIc,aortIc,orupperabdomInalsurgeryIsassocIatedwIththe
hIghestrIskforpostoperatIvepulmonaryproblems.FIskIncreasesastheIncIsIon
approachesthedIaphragm.
42,4J,44,45
0ecreasesInpostoperatIvevItalcapacItyand
functIonalresIdualcapacIty,aswellasdIaphragmatIcdysfunctIon,contrIbuteto
hypoxemIaandatelectasIs.
46
FunctIonalresIdualcapacItymaytakeupto2weekstoreturn
tobaselIne.0IaphragmatIcdysfunctIonoccursdespIteadequateanalgesIaandIstheorIzed
tobebecauseofphrenIcnerveInhIbItIon.
47
ThetypesofsurgerycarryIngthehIghestrIsks
wereabdomInalaortIcaneurysmrepaIr,thoracIc,andupperabdomInalsurgery,followed
byneck,perIpheralvascular,andneurosurgery.Neurosurgeryandnecksurgerymaybe
assocIatedwIthperIoperatIveaspIratIonpneumonIa.
TheneedforemergencysurgeryandtheneedforgeneralanesthesIaarealsoassocIated
wIthaslIghtlyIncreasedrIsk.NotonlycanthesurgeryaffectpulmonaryfunctIon,but
generalanesthesIaalsoresultsInmechanIcalchangessuchasadecreaseInthefunctIonal
resIdualcapacItyandaltereddIaphragmatIcmotIonleadIngto[7wIthbarabove]/[QwIth
dotabove]mIsmatchwIthshuntInganddeadspaceventIlatIon.CeneralanesthesIaalso
aggravatesthesechangesbyItseffectsatthemIcroscopIclevel:InhIbItIonofmucocIlIary
clearance,IncreasedalveolarcapIllarypermeabIlIty,InhIbItIonofsurfactantrelease,
IncreasednItrIcoxIdesynthetase,andIncreasedsensItIvItyofthepulmonaryvasculature
toneurohumoralmedIators.SubanesthetIclevelsofIntravenousorvolatIleagentshave
theabIlItytoblunttheventIlatoryresponsetohypoxemIaandhypercarbIa.0uratIonof
anesthesIaIsawellestablIshedrIskfactorforpostoperatIvepulmonarycomplIcatIons,wIth
morbIdItyratesIncreasIngafter2toJhours.
48
However,althoughlaparoscopIcsurgeryIs
oftenlongerInduratIon,thedecreasedpulmonarycomplIcatIonspostoperatIvelycompared
wIthan
P.579
openprocedureusuallyoutweIghtherIsksofIncreasedanesthesIatIme.
49
Table 23-8 Potential Patient-Related Risk Factors for Postoperative
Pulmonary Complications
POTENTIAL RISK
FACTOR
TYPE OF SURGERY
UNADJUSTED RELATIVE RISK ASSOCIATED WITH
FACTOR
SmokIng Coronarybypass J.4
AbdomInal 1.44.J
ASAClass Unselected 1.7
ThoracIcor
abdomInal
1.5J.2
Age70yr Unselected 1.92.4
ThoracIcor
abdomInal
0.91.9
DbesIty Unselected 1.J
ThoracIcor
abdomInal
0.81.7
CDP0 Unselected 2.7J.6
ThoracIcor
abdomInal
4.7
ASA,AmerIcanSocIetyofAnesthesIologIsts;CDP0,chronIcobstructIvepulmonary
dIsease.
AdaptedfromSmetanaCW:PreoperatIvepulmonaryevaluatIon.NEnglJ|ed
1999;J40:942.
Patient-Related Factors
PreoperatIveevaluatIonofpatIentswIthpreexIstIngpulmonarydIseaseshouldInclude
assessmentofthetypeandseverItyofdIsease,aswellasItsreversIbIlIty(Table2J8).
8ecauseclInIcalobservatIonsareoftenthebestpredIctorsforthedevelopmentof
postoperatIvepulmonarycomplIcatIons,acarefulhIstoryandphysIcalexamInatIonIs
ImperatIve.TheanesthesIologIstshouldInquIreaboutexercIseIntolerance,chronIccough,
orunexplaIneddyspnea.DnphysIcalexamInatIon,fIndIngsofwheezIng,rhonchI,decreased
breathsounds,dullnesstopercussIon,andaprolongedexpIratoryphaseareImportant.
PreoperatIvepulmonaryfunctIontestIngIsusuallyreservedforthosescheduledforlung
resectIon,orforthosescheduledformajorsurgerywhohaveunexplaInedpulmonarysIgns
andsymptomsafteracarefulhIstoryandphysIcalexamInatIon.EarlyInterventIonhelpsto
ensurethatthepatIent'smedIcalstatusIsoptImalprIortosurgery.
Tobacco
TheuseoftobaccoIsanImportantrIskfactor,butonethatusuallycannotbeInfluenced.
EvenamongsmokerswhohavenotdevelopedchronIclungdIsease,smokIngIsknownto
IncreasecarboxyhemoglobInlevels,decreasecIlIaryfunctIon,andIncreasesputum
productIon,aswellascausestImulatIonofthecardIovascularsystemsecondarytothe
nIcotIne.WhIlecessatIonofsmokIngfor2dayscandecreasecarboxyhemoglobInlevels,
abolIshthenIcotIneeffects,andImprovemucousclearance,prospectIvestudIesshowthat
smokIngcessatIonforatleast4to8weekswasnecessarytoreducetherateof
postoperatIvepulmonarycomplIcatIons.
50,51
8ecausesmokersoftenshowIncreasedaIrway
reactIvItyundergeneralanesthesIa,ItIsusefultoadmInIsterabronchodIlatorsuchas
albuterolpreoperatIvely.
Asthma
AsthmaIsoneofthemostcommoncoexIstIngdIseasesthatconfrontstheanesthesIologIst.
ngeneral,thepreoperatIvemanagementofasthmaIsthesameasforpatIentswIth
asthmanotundergoIngsurgery.0urIngthepatIentIntervIewItIsImportanttoelIcIt
InformatIonregardIngIncItIngfactors,severIty,reversIbIlIty,andcurrentstatus.Frequent
useofbronchodIlators,hospItalIzatIonsforasthma,andtherequIrementforsystemIc
steroIdsareallIndIcatorsoftheseverItyofthedIsease.AfteranepIsodeofasthma,aIrway
hyperreactIvItymaypersIstforseveralweeks.
52
naddItIontobronchodIlators,
perIoperatIvesteroIdsareworthconsIderIngasprophylaxIsforthesevereasthmatIc;for
example,hydrocortIsone100mgIntravenouslyevery8hoursonthedayofsurgery.The
possIbIlItyofadrenalInsuffIcIencyIsalsoaconcernInthosepatIentswhohavereceIved
morethanaburstandtaperofsteroIdsIntheprevIous6months.ThIsgroupofpatIents
shouldbeadmInIsteredstressdosesofsteroIdsperIoperatIvely.KabalIn,etal.
5J
found
therewasalowcomplIcatIonrateforasthmatIcstreatedwIthshorttermsteroIds
undergoIngsurgery.SIgnIfIcantly,theyfoundnoassocIatIonwIthImpaIredwoundhealIng
orInfectIons.ForpatIentsusIngInhaledsteroIds,theyshouldbeadmInIsteredregularly,
startIngatleast48hoursprIortosurgeryforoptImaleffectIveness.
Obstructive Sleep Apnea
DbstructIvesleepapnea(DSA)IsasyndromedefInedbyperIodIcobstructIonoftheupper
aIrwaydurIngsleep,leadIngtoepIsodIcoxygendesaturatIonandhypercarbIa.ThIsepIsodIc
desaturatIonInturncausesepIsodIcarousal,leadIngtochronIcsleepdeprIvatIonwIth
daytImehypersomnolenceandevenbehavIoralchangesInchIldren.0ependIngonthe
frequencyandseverItyofevents,ItmayleadtootherchangessuchaschronIcpulmonary
hypertensIonandrIghtheartfaIlure.tIsestImatedtobepresentIn9ofwomenand24
ofmen,wIththegreatmajorItyofthesebeIngundIagnosed.FactorscommonlyassocIated
wIthanIncreasedrIskofsleepapneaIncludeobesIty(bodymassIndexJ5kg/m
2
or95th
percentIleforage),IncreasedneckcIrcumference,severetonsIllarhypertrophy,and
anatomIcabnormalItIesoftheupperaIrway.
8ecauseoftheIrpropensItyforaIrwaycollapseandsleepdeprIvatIon,patIentswIthDSA
areespecIallysusceptIbletotherespIratorydepressantandaIrwayeffectsofsedatIves,
narcotIcs,andInhaledanesthetIcsbothIntraoperatIvelyandpostoperatIvely.PreoperatIve
IdentIfIcatIonofthosepatIents
P.580
atrIskallowsthemtoundergoaformalsleepstudytodetermInethepresenceandseverIty
ofsymptoms,andalsoallowspreoperatIveInItIatIonofcontInuousposItIveaIrwaypressure
(CPAP).TheASAIn2006publIshedpractIceguIdelInesfortheperIoperatIvemanagementof
patIentswIthDSA,andthefollowIngwIllattempttosummarIzethoseguIdelInes.
54
0urIng
thepreoperatIveevaluatIon,specIfIcquestIonsshouldbedIrectedtowardthepatIentand
famIlyregardIngthepresenceofsymptomsandsIgnsofDSA:
0oesthepatIentsnoreloudlyenoughtobeheardthroughadoor,orsnorefrequently:
ArethereobservedpausesInbreathIngdurIngsleep:
AretherefrequentarousalsdurIngsleep,orawakenIngswIthachokIngsensatIon:
sfrequentdaytImesomnolence,fatIgue,orfallIngasleepeasIlyInanonstImulatIng
envIronmentnoted:
0othechIld'sparentsnotIcerestlesssleepordIffIcultywIthbreathIng:
sthechIldoverlyaggressIveorhavetroubleconcentratIng:
fapatIenthaspredIsposInganatomyand/orsIgnsorsymptomsIntwoormoreareas,heor
sheshouldbereferredforasleepstudy.fthIsIsnotpossIble,thepatIentshouldbe
managedashavIngDSA.TherIskofperIoperatIvecomplIcatIonsInpatIentswIthDSA
IncreaseswIththeseverItyofsleepapnea,theInvasIvenessofsurgeryandanesthesIa,and
theamountofpostoperatIveopIoIdsrequIred.ThereIsageneralconsensusthat
preoperatIveInItIatIonofaIrwaysupportsuchasCPAPreducesperIoperatIverIsk,perhaps
bydecreasIngthesleepdeprIvatIonandsecondaryhypersomnolence.
54
mportantly,DSAIs
alsoassocIatedwIthdIffIcultaIrwaymanagement,makIngItprudenttoexamIneprevIous
anesthesIarecordsaswellastoperformathoroughaIrwayexamInatIon.ThedIffIcult
aIrwayalgorIthm
54
shouldbefollowedandemergencyaIrwayequIpmentshouldbereadIly
avaIlableatthesurgIcalcenter.
TherearemultIplemanagementdecIsIonstomakeIncoordInatIonwIththesurgeonwIth
respecttotheDSApatIent:
0etermInewhethertherearenonInvasIvewaysofperformIngthesurgerythatwould
decreasetheneedfornarcotIcspostoperatIvely.
0IscusswhetherItIsfeasIbletoperformsurgeryunderneuraxIal,regIonal,orlocal
anesthesIa,decreasIngthetotalamountofanesthesIaoropIoIdsneeded.
0etermInewhethernonsteroIdalantIInflammatoryagentsareacceptablefor
postoperatIveanalgesIa.
0IscusswhetheroutpatIentsurgeryasafeoptIon.
0etermInewhetherthepatIentwIllbeabletouseCPAPpostoperatIvely.
0etermInewhetherpostoperatIveadmIssIontoanIntensIvecareunItIsrequIredforthe
patIentwhoIsafIrsttImeuserofCPAP.
TheASApractIceguIdelInesrecommendhospItalIzatIonafteruvulopalatoplastysurgeryand
aftertonsIllectomyforDSAInchIldrenyoungerthanJyears.PostoperatIvehospItalIzatIon
IsalsorecommendedforthoseDSApatIentswIthothercoexIstIngdIseases.When
proceduresareperformedonanoutpatIentbasIs,prolongedpostoperatIvemonItorIng
shouldbecontInuedtoensurethatthepatIentIsabletomaIntaInroomaIrsaturatIon
wIthoutobstructIonwhenleftundIsturbedInrecovery.FecoveryInthenonsupIneposItIon
(elevatIonoftheheadandthorax)IsalsorecommendedtooptImIzeaIrwaypatency.The
taskforcerecommendscontInuouspulseoxImetrydurInghospItalIzatIon,aswellas
supplementaloxygenuntIlthepatIentcanmaIntaIntheIrbaselInesaturatIononroomaIr.
Endocrine Disease
Diabetes Mellitus
0IabetesmellItusIsthemostcommonendocrInopathy,wIththeIncIdenceoftype1
dIabetesat0.4ofthepopulatIon,andtype2dIabetesaffectIngapproxImately8to10of
AmerIcans,butprojectedtodevelopInJ0ofAmerIcansbornafter2000,largelybecause
oftherIseInobesIty.
55
CrItIcalIllnessInducedhyperglycemIa,defInedasabloodglucose
200mg/dLIntheabsenceofknowndIabetes,occursfrequently,partIcularlyInthe
elderly.
56
0IabeteshasacuteandchronIcdIseasemanIfestatIons,makIngItmorelIkelyfor
dIabetIcstorequIresurgery.ThemajorItyofdIabetIcsdevelopsecondarydIseaseInoneor
moreorgansystems,whIchmustbeIdentIfIedpreoperatIvelysothatanapproprIateplan
canbedevelopedforperIoperatIvemanagement.WhIlelongterm,closecontrolofglucose
maylImItsomeofthemIcrovasculareffectsofdIabetes(retInopathy,neuropathy,and
nephropathy),macrovasculareventssuchas|sorstrokemaynotbedecreased.0IabetIcs
haveanIncreasedrIskofCA0,hypertensIon,congestIveheartfaIlure,andperIoperatIve
|.The2002AmerIcanCollegeofCardIology/AmerIcanHeartAssocIatIonguIdelIneson
perIoperatIvecardIacassessmentofpatIentsundergoIngnoncardIacsurgeryplace
dIabetIcs,especIallythosereceIvIngInsulIn,atamInImumofIntermedIaterIsk.
57
They
alsostatethatmostdIabetIcpatIents65yearsofagehavesIgnIfIcantCA0,wIththe
IncIdenceofsIlentIschemIaIncreasedbyassocIateddIabetIcautonomIcneuropathy.
0IabetIcsarealsomorelIkelythanthegeneralpopulatIontohavecerebralvascular,
perIpheralvascular,andrenalvasculardIsease.0IabetesIstheleadIngcauseofrenal
faIlurerequIrIngdIalysIs.PerIpheralneuropathIesandvasculardIseasemakethesepatIents
moresusceptIbletoposItIonIngInjurIesdurIngsurgeryaswellaspostoperatIvely.
AutonomIcneuropathyIsalsocommonIndIabetIcs,andmaypredIsposethepatIentto
hemodynamIcInstabIlItydurInganesthesIa,andtheoretIcallyIncreasetherIskof
pulmonaryaspIratIonbecauseoftheassocIatedgastroparesIs.ThesedefIcItsshouldbe
documentedprIortoanesthesIaandtheanesthetIcplanadjustedaccordIngly.StIffjoInt
syndromeduetoglycosylatIonofproteInsandabnormalcollagencrosslInkIng,may
sIgnIfIcantlyaffectthetemporomandIbular,atlantooccIpItal,andcervIcalspInejoIntsIn
patIentswIthlongstandIngtype1dIabetes,resultIngIndIffIcultywIthIntubatIon.A
thoroughaIrwayexamInatIonshouldbeperformedprIortoanesthesIaandahIghIndexof
suspIcIonmaIntaInedforapotentIallydIffIcultaIrway.SomesuggestusIngtheprayer
sIgnasanevaluatIontool:patIentswhoareunabletocompletelyopposetheIrhands
(wIthnospacebetween)shouldbesuspectedofalsohavIngchangesInotherjoInts
potentIallyImpactIngaIrwaymanIpulatIon.
FegImensforperIoperatIveglycemIccontrolvaryenormously,notonlybetweentype1and
type2dIabetIcs,butalsowIthIneachgroup.PatIentswIthtype1dIabeteshavean
absoluteInsulIndefIcIencyusuallyduetodestructIonofpancreatIcbetacells.These
patIentsmustreceIveInsulIntopreventdIabetIcketoacIdosIs.Homeglucosemanagement
mostoftenrelIesonacombInatIonofshortandIntermedIateorlongactIngInsulIn
regImens.nsulInpumpsareIncreasInglycommonandareusedtoadmInIsteracontInuous
subcutaneousInfusIonofashortactIngInsulIn,supplementedbybolusesdIctatedby
glucoselevels,dIet,andexercIse.Type2dIabetesaccountsforthegreatmajorItyof
dIabetIcsandIsdefInedbyvarIabledegreesofInsulIndefIcIencyandresIstance.Although
mostcommonlyassocIatedwIthobesIty,ItmayalsobeInducedbycortIcosteroIdsor
pregnancy.KetoacIdosIsIsuncommonIntype2dIabetes,andthestressofsevereInfectIon
orIllnessIsmorelIkelytoprovokeanonketotIc
P.581
hyperosmolarstate,whIchIscharacterIzedbyseveredehydratIon,hyperglycemIa,and
hyperosmolarIty.ntype2dIabetIcs,glucosecontrolIsmostcommonlyachIevedwIthdIet,
exercIse,and/ororalhypoglycemIcdrugs.TheseagentsprImarIlyworkbyIncreasIng
endogenousInsulInrelease,IncreasIngInsulInsensItIvIty,and/ordecreasInghepatIc
gluconeogenesIs.ThesedrugsfallunderthemaIncategorIesofsulfonylureas,bIguanIdes,
thIazolIdInedIones,andmeglItInIdes.fglycemIccontrolIsunsuccessful,thenInsulInIs
generallyaddedtotheregImen.
deally,bothtype1and2dIabetIcpatIentsshouldbeevaluatedbythepreoperatIveclInIc
aswellasthepatIent'sendocrInologIst1to2weeksbeforeelectIvesurgery.naddItIonto
athoroughhIstoryandphysIcal,ajudIcIouslaboratoryInvestIgatIonshouldIncludeablood
glucose,hemoglobInA1c,serumelectrolytes,creatInIne,andanECC.fthepatIent's
glycemIccontrolIsInadequatebasedonahemoglobInA1coutofthetargetrange(7to9
for5yearsold;6to8for5yearsold),abnormalelectrolytes,orketonurIa,then
electIvesurgeryshouldbedelayedtoallowoptImIzatIonofpreoperatIveglycemIccontrol.
AdmInIstratIonofperIoperatIvebetablockersshouldbeconsIderedIndIabetIcpatIents
wIthCA0InanattempttolImItperIoperatIvemyocardIalIschemIa,asthereIsnoevIdence
ofworsenedglucoseIntoleranceormaskIngofhypoglycemIcsymptoms.However,the
physIcIanshouldbeattentIvetothepossIbIlItyofprecIpItatIngheartfaIlure.
Preoperative Glucose Management
AnesthesIaandsurgeryInterrupttheregularmealscheduleandInsulInadmInIstratIonof
dIabetIcs.PerIoperatIvestressmayIncreaseserumglucoseconcentratIonssecondarytothe
releaseofcortIsolandcatecholamInes.ThemajorItyofavaIlablelIteraturesuggeststhat
betterglycemIccontrolmaylImItmorbIdIty(lengthofhospItal/IntensIvecareunItstay,
InfectIonrate,woundhealIng,outcomesafterstrokes/|s)andmortalItypartIcularlyIn
cardIacsurgerypatIents,carotIdendarterectomypatIents,andthecrItIcallyIll,
56,58,59,60
althougharecentrandomIzedtrIalfoundanIncreaseIntheIncIdenceofdeathand
perIoperatIvestrokeIncardIacsurgerypatIentswhereanattemptwasmadetomaIntaIn
theglucosebetween80and100mg/dL.
61
|orestudIesareneededtodetermInewhether
strIctglycemIccontrolwIllImproveoutcomeInalldIabetIcsundergoIngsurgery.
8ecausegoodevIdenceIslackIngtobeabletosetstandardsfortheperIoperatIveglucose
managementofdIabetIcpatIents,atamInImum,anattemptshouldbemadetocontrol
theglucosewIthInarangeof100to200mg/dL,althoughsomewIllarguethattIghter
controlwIthatoplImItof150mg/dLIswarranted.ThefollowIngrecommendatIonscan
serveasageneralguIde:
PlanwIththesurgeontoschedulethesurgeryasthefIrstcaseofthedaytoprevent
prolongedfastIng.
Asageneralrule,oralhypoglycemIcagentsareheldonthedayofsurgerytoavoId
reactIvehypoglycemIa.TheexceptIonIsmetformIn,whIchshouldbeheldforatleast24
hourspreoperatIvelytoavoIdtherIskdrugInducedlactIcacIdosIs.
nsulInshouldbecontInuedthroughtheevenIngbeforesurgery,IncludIngtheusualdose
ofInsulInglargIne(Lantus).
PatIentsshouldbecounseledtotakeaglucosetabletorclearjuIceIfhypoglycemIa
occursprIortoarrIvalatthehospItal,Inordertopreventdelayofthesurgery.
SchedulethepatIenttoarrIvewIthouthavIngIngestedanythIngbymouthInearly
mornIngandcheckbloodglucose,electrolytes,andketones.
Type1dIabetIcsshouldbecontInuedonbasalInsulInreplacementevenwhIlenothIngby
mouthstatustopreventketoacIdosIs.AdmInIsterhalftheusualmornIngdoseof
IntermedIateorlongactIngInsulInafterarrIvaltothesurgerycenter,butholdtheusual
doseofrapIdorshortactIngInsulIn.
PatIentsonInsulInpumpsmaybemanagedbycontInuIngthepumpforshortsurgerIes,or
changIngovertoanIntravenousInsulInInfusIonformoderateormajorsurgerIes.
UsethepatIent'sownslIdIngscaletoadmInIsterashortactIngInsulInsubcutaneouslyto
maIntaIntheglucosebetween100and200mg/dLprIortothescheduledsurgery.
ThIsstrategy,alongwIthbloodglucosedetermInatIonsevery1to2hours,maybeallthat
IsnecessaryforwellcontrolleddIabetIcsundergoIngshort,nonInvasIveoutpatIent
surgerIes.AddItIonally,ItIsImportanttopreventpostoperatIvenauseaandvomItIngand
toencouragetheearlyresumptIonofdIet,allowIngreturntotheIrprevIousInsulIn
regImen.Fortype1or2dIabetIcsundergoIngmoderateormajorsurgery,InsulInIs
generallyadmInIsteredIntheformofanInfusIonofregularInsulIn.0IscontInuIngthe
patIent'sownInsulInpumptoavoIdproblemswIthInsulInpreparatIonsandpump
technologyIsoftenadvIsed.
ThereareseveralmethodsofadmInIsterInganInsulInInfusIon,noneofwhIchhasproved
superIortotheothers.SomerecommendacombInedInfusIonofglucose,InsulIn,and
potassIumbecauseoftheInherentsafetyofavoIdIngthepossIbIlItyofhavIngaglucose
InfusIonInadvertentlystoppedwhIleanInsulInInfusIoncontInues.However,concurrent
separateInfusIonsofInsulInandglucosearemoreeasIlyadjustedandmayprovIdebetter
glycemIccontrol.ToIncreasethesafety,theInsulInInfusIon(whIchIsonaseparatepump)
IsaddedvIaasIdeporttothesamelInedelIverIngtheglucoseInfusIon.Aseparate
nonglucoseIsotonIcsolutIonshouldbeusedtoreplacedefIcItsandIntraoperatIvefluId
losses.AllprotocolsrelyonthefrequentdetermInatIonofaplasmaglucoselevelatleast
every1to2hourstoallowtItratIonofInsulIn.
62,6J,64
Thyroid and Parathyroid Disease
ThyroIdandparathyroIddIseasehaveclInIcalmanIfestatIonsthatareImportanttothe
preoperatIveevaluatIon(Table2J9).ThyroIddIseaseIsusuallyadequatelyevaluatedby
clInIcalhIstory,althoughofcoursethethyroIdfunctIontestsaremoresensItIve.The
preoperatIveevaluatIonshouldfocusonevaluatIngthesIgnsandsymptomsof
hyperthyroIdIsmandhypothyroIdIsm.HypothyroIdIsmcanleadtothedevelopmentof
hypothermIa,hypoglycemIa,hypoventIlatIonandhyponatremIa,aswellasasusceptIbIlIty
todepressantdrugs.AnesthesIologIstsshouldbealertedtothepossIbIlItyofthe
hypermetabolIcstateofthyroIdstormInpatIentswIthhyperthyroIdIsm.AlargethyroId
massmaydIstorttheupperaIrway,producIngInspIratorystrIdororwheezIng,especIally
evIdentInthesupIneposItIon.nthesecases,achestxrayshouldbeobtaInedlookIngfor
evIdenceoftrachealdevIatIonornarrowIng.Acomputedtomographyscanoftheupper
aIrwayandtracheawIllprovIdebetterdetaIlofanyaIrwaycompromIse.PatIentswIth
hyperparathyroIdIsmoftenhavehypercalcemIa,IndIcatIngtheneedforpreoperatIve
determInatIonofaserumcalcIumlevel.
Adrenal Disorders
TheclassIcfIndIngsforpheochromocytomaIncludeIntermIttenthypertensIon,headache,
dIaphoresIs,andtachycardIa.npatIentswIthotherendocrInetumors,a
pheochromocytomashouldberuledoutasthecauseofunexplaInedhypertensIonaspartof
amultIpleendocrIneneoplasIasyndrome.DvertImethemortalItyforsurgIcalresectIonof
apheochromocytomahasdecreasedbecauseofImprovements
P.582
InperIoperatIvetherapyforpatIentswIththesyndrome.TheImportantIssueIstoIdentIfy
patIentswIthapheochromocytomapreoperatIvelybeforetheyarescheduledforother
typesofsurgery.
Table 23-9 Clinical Manifestations of Thyroid and Parathyroid Diseases
HYPERTHYROIDISM HYPOTHYROIDISM HYPERPARATHYROIDISM
Ceneral
WeIghtloss;heat
Intolerance;
warm,moIstskIn
ColdIntolerance
WeIghtloss,
polydIpsIa
CardIovascular
TachycardIa,
atrIalfIbrIllatIon,
congestIveheart
faIlure
8radycardIa,
congestIveheart
faIlure,
cardIomegaly,
perIcardIalor
pleuraleffusIon
HypertensIon,
heartblock
NeurologIc
Nervousness,
tremor,
hyperactIve
reflexes
Slowmental
functIon,mInImal
reflexes
Weakness,
lethargy,
headache,
InsomnIa,
apathy,
depressIon
|usculoskeletal
|uscleweakness, Largetongue,
8onepaIns,
arthrItIs,
boneresorptIon amyloIdosIs pathologIc
fractures
CastroIntestInal 0Iarrhea
0elayedgastrIc
emptyIng
AnorexIa,
nausea,
vomItIng,
constIpatIon,
epIgastrIcpaIn
HematologIc
AnemIa,
thrombocytopenIa

Fenal
mpaIredfreewater
clearance
PolyurIa,
hematurIa
AdaptedfromFoIzen|F:AnesthesIaforthepatIentwIthendocrInedIsease,Part
1.CurrFevClInAnesth1987;6:4J.
npatIentstakInglongtermcortIcosteroIds,oneshouldhaveahIghIndexofsuspIcIonfor
adrenalcortIcalsuppressIonandCushIngsyndrome.ThehallmarksymptomsfoundIn
CushIngsyndromeIncludemoonfacIes,strIatIonsoftheskIn,trunkobesIty,hypertensIon,
easybruIsabIlIty,andhypovolemIa.ThepreoperatIvepreparatIonIncludescorrectIonof
thefluIdandelectrolyteabnormalItIes.ThereIsconsensusthatforpatIentstakIng
cortIcosteroIdsforlongperIods,perIoperatIvesteroIdsupplementatIonIsIndIcatedto
coverthestressesofanesthesIaandsurgery.However,InpatIentswhohavehadonlya
shortcourseofsteroIdswIthInthe12monthsprIortosurgery,theuseofsteroId
supplementatIonIscontroversIal,althoughmostclInIcIanswouldfavortheIruse
preoperatIvely(Table2J10).
Other Organ Systems
FenaldIseasehasImportantImplIcatIonsforfluIdandelectrolytemanagement,aswellas
metabolIsmofdrugs.LIverdIseaseIsassocIatedwIthalteredproteInbIndIngandvolumeof
dIstrIbutIonofdrugs,aswellascoagulatIonabnormalItIes.CoagulatIondIsordersmay
InfluencethechoIceofregIonalanesthesIa.TheanesthesIologIstshouldInquIreabout
bruIsIng,bleedIng,andtheuseofmedIcatIonsthatInfluenceplateletfunctIonsuchas
aspIrIn,othernonsteroIdalantIInflammatorydrugs,andantIcoagulants.|usculoskeletal
dIsordershavebeenassocIatedwIthanIncreasedrIskofmalIgnanthyperthermIa.
DsteoarthrItIsmayresultIndIffIcultyexposIngtheglottIcopenIngfortrachealIntubatIon
ordIffIcultyInposItIonIngforregIonalanesthetIc.8ecauserheumatoIdarthrItIsIsa
multIsystemdIsease,ItIsImportantInsuchpatIentstoperformathoroughrevIewof
systems.ThesepatIentsmayhaverestrIctIvelungdIsease,pleuraleffusIons,perIcardItIs,
anemIa,andatlantooccIpItalInstabIlIty.FInally,theanesthesIologIstshouldInquIreabout
InfectIousdIseasessuchashumanImmunodefIcIencyvIrusorantIbIotIcresIstantInfectIons.
Table 23-10 Perioperative Corticosteroid Coverage
For
mInor
surgery
ThepatIentshouldtake1.52tImeshIsorherusualprednIsone
dosageonthemornIngofsurgery.ThefollowIngdaythepatIent
shouldtakehIsorhernormalprednIsonedose(orparenteral
equIvalentIfgutcannotbeused).ThesurgeonandanesthesIologIst
shouldbeawarethatthepatIentIsglucocortIcoIddependentand
shouldbepreparedtoadmInIstermoresteroIdsIfthesurgery
becomesprolongedormoreextensIve.
For
moderate
surgery
ThepatIentshouldbegIven2tImeshIsorherusualglucocortIcoId
dosageorally(IfpossIble)onthemornIngofsurgeryand/or25mg
hydrocortIsone7beforetheoperatIon,then75mghydrocortIsone7
durIngtheoperatIon,and50mghydrocortIsone7afterthe
operatIon;thenthedoseshouldberapIdlytaperedover48hrtothe
usualdoseIfthepostoperatIvecourseIsuncomplIcated.
For
major
surgery
ThepatIentshouldbegIven2tImeshIsorherusualglucocortIcoId
dosageorally(IfpossIble)onthemornIngofsurgeryand/or50mg
hydrocortIsone7beforetheoperatIon,then100mghydrocortIsone
7durIngtheoperatIon.AftertheoperatIon,100mg7q8hr24hr
shouldbeadmInIsteredandthenrapIdlytapered(over4872hr)to
thepatIent'susualglucocortIcoIddosageIfthepostoperatIvecourse
IsuncomplIcated.
7,Intravenously.
Adaptedfrom8russelT,Chernow8:PerIoperatIvemanagementofendocrIne
problems:ThyroId,adrenalcortex,pItuItary.AmSocAnesthesIol1990;J:48.
P.58J
Preoperative Laboratory Testing
The Value of Preoperative Testing: Normal Values
nattemptIngtodetermInetheoptImalchoIceofpreoperatIvetests,ItIsImportantto
understandtheInterpretatIonoftheresults.deally,testswouldeItherconfIrmorexclude
thepresenceofadIsease;however,mosttestsonlyIncreaseordecreasetheprobabIlItyof
dIsease.ndetermInIngreferencerangesfordIagnostIctests,valuesthatfalloutsIdethe
95confIdenceIntervalsfornormalIndIvIdualsareconsIderedabnormal.Therefore,upto
5ofnormalIndIvIdualscanhaveabnormaltestresults.TodetermIneItsclInIcal
relevance,atestmustbeInterpretedwIthInthecontextoftheclInIcalsItuatIon.
PerformIngtestsInpatIentswIthnorIskforhavIngthepathophysIologIcprocessofInterest
canyIeldahIghnumberoffalseposItIveresults.Forexample,alowpotassIumvalue(J.0
mg/dL)InanotherwIsehealthyIndIvIdualIsmostlIkelyanormalresult.nterpretIngthIs
testasabnormal,andInItIatIngtreatment,couldleadtoharmwIthoutanybenefIt.
Risks and Costs Versus Benefits
TheuseofmedIcaltestIngIsassocIatedwIthsIgnIfIcantcost,bothInrealdollarsandIn
potentIalharm.FoutInepreoperatIvetestInghasbeenestImatedtocostSJbIllIon
annually.AnabnormaltestthatIslaterdetermInedtobeafalseresultcanleadto
sIgnIfIcantcostandrealharm.Forexample,aposItIveexercIseelectrocardIographIcstress
testInahealthy40yearoldwomanmayleadtocoronaryangIography.Coronary
angIographyIsnotabenIgnprocedure,andcanleadtovascularInjurIes.8asedon8ayesIan
analysIs,aposItIvetestresultInthIspatIentIsmostlIkelyafalseposItIve,andthetest
wasInapproprIatelyused.Therefore,thewomanandherphysIcIanwouldgaInno
addItIonalInformatIon,thousandsofdollarsInmedIcalcostswouldaccrue,andshewould
sustaInmorbIdIty.
Figure 23-4.AdecIsIonalgorIthmevaluatIngthedecIsIonbetweenvascularsurgery
aloneorcoronaryarteryrevascularIzatIonbeforevascularsurgery.Thereare
currentlynorandomIzedtrIalstoaddresstheoptImalstrategy.8youtlInIngthe
multIpledecIsIonpoIntsatwhIchapatIentcansustaInmortalItybychoosIngto
undergocoronaryrevascularIzatIonfIrst,theoptImalstrategyforpreoperatIve
evaluatIoncanbedemonstrated.SpecIfIcally,varIatIonInmortalItIesateachdecIsIon
poIntcanchangetheoptImalstrategy.(FeproducedfromFleIsherLA,SkolnIckE0,
HolroydKJ,etal:CoronaryarteryrevascularIzatIonbeforeabdomInalaortIcaneurysm
surgery:AdecIsIonanalytIcapproach.AnesthAnalg1994;79:661,wIthpermIssIon.)
SeveralstudIeshaveevaluatedtheImplIcatIonsofreducedtestIng.Colub,etal.
65
retrospectIvelyrevIewedtherecordsofJ25patIentswhohadundergonepreadmIssIon
testIngprIortoambulatorysurgery.Dfthese,272(84)hadatleastoneabnormal
screenIngtestresult,whIleonly28surgerIesweredelayedorcanceled.Theauthors
estImatedthatonlythreepatIentspotentIallybenefItedfrompreadmIssIontestIng,
IncludInganewdIagnosIsofdIabetesInoneandnonspecIfIcECCchangesIntwo,oneof
whIchhadknownIschemIcheartdIsease.
nastudypublIshedIn1991,Narretal.
66
atthe|ayoClInIcdemonstratedmInImalbenefIts
fromroutInetestIngandproposedthatroutInelaboratoryscreenIngtestswerenot
requIredInhealthypatIents.nafollowupstudypublIshedIn1997,acohortofpatIents
whohadnopreoperatIvetestIngdurIng1994wasrevIewedandfoundtoIncludenodeaths
ormajorperIoperatIvemorbIdIty.
67
TheauthorsconcludedthatcurrentanesthetIcand
medIcalpractIcesrapIdlyIdentIfyIndIcatIonsforlaboratoryevaluatIonwhennecessary,
andthereforeroutInetestIngwasnotIndIcatedInthIshealthycohort.
EvenIftestIngbetterdefInesadIseasestate,therIsksofanyInterventIonbasedonthe
resultsmayoutweIghthebenefIt.CardIovasculartestIngIsaclassIcexample(FIg.2J4).f
anonInvasIvetestIsposItIve,coronaryangIographymaybeperformed.AposItIve
angIogrammaythenresultInCA8CprIortotheplannednoncardIacsurgery.Although
cardIovascularmorbIdItyandmortalItymaybereducedInpatIentswIthsIgnIfIcantCA0
whohaveundergonecoronaryrevascularIzatIon,themorbIdItyassocIatedwIthboththe
testIngandrevascularIzatIonproceduremaybegreaterthananypotentIalbenefIt.FoIzen
andCohn
68
havesuggestedaprotocolforscreenIngtestsbasedonthepreoperatIve
evaluatIonusIngarIskbenefItanalysIs.ThefollowIngIsmodIfIedfromthose
recommendatIonsandthePractIceAdvIsoryforPreanesthetIcEvaluatIonfromtheASA
(Class C proceduresarehIghlyInvasIveandcommonlynecessItatebloodadmInIstratIon,
InvasIvemonItorIngandpostoperatIvecareInacrItIcalcareunIt).
P.584
Recommended Laboratory Testing
Blood Count
Neonates
PhysIologIcage75years
ClassCprocedure
|alIgnancy
FenaldIsease
Tobaccouse
AntIcoagulantuse
8leedIngdIsorder
Coagulation Studies
Chemotherapy
HepatIcdIsease
8leedIngdIsorder
AntIcoagulants
Electrolytes
FenaldIsease
0Iabetes
0IuretIc,dIgoxIn,orsteroIduse
CNSdIsease
EndocrInedIsorders
Blood Urea Nitrogen/Creatinine
ClassCprocedure
CardIovasculardIsease
FenaldIsease
0Iabetes
0IuretIcordIgoxInuse
CNSdIsease
Blood Glucose
ClassCprocedure
0Iabetes
SteroIduse
CNSdIsease
Liver Function Tests
HepatIcdIsease
HepatItIsexposure
|alnutrItIon
Chest X-Ray
FecentupperrespIratoryInfectIon
PulmonarydIsease
|alIgnancy
FadIatIonTherapy
Tobacco20packyears
ECG
ClassCprocedure
PulmonarydIsease
FadIatIontherapy
0Iabetes
0IgoxInuse
CNSdIsease
Pregnancy Test
PossIblepregnancy
Albumin
ClassCprocedure
|alnutrItIon
Type and Screen
ClassCprocedure
Complete Blood Count and Hemoglobin Concentration
TheuseofapreoperatIvehemoglobInhasbeensuggestedastheonlytestnecessaryIn
manypatIentsprIortoelectIvesurgery;however,eventhIsmInImalstandardhasbeen
questIoned.8aron,etal.
69
revIewedtherecordsof1,86JpedIatrIcpatIentsscheduledfor
electIveoutpatIentprocedures.nonly1.1ofpatIentswasthehematocrItabnormal,and
InnoneofthesepatIentswastheprocedurecanceledortheanesthetIcplanmodIfIed.
However,abaselInehematocrItIsstIllIndIcatedInanyprocedurewItharIskofbloodloss.
ThestandardregardIngthelowestacceptableperIoperatIvehematocrItandIndIcatIonfor
apreoperatIvetransfusIonhaschangeddurIngthepastdecade.Thecurrent
recommendatIonsoftheNatIonal8loodFesourceEducatIonCommItteearethata
hemoglobInlevelof7g/dLIsacceptableInpatIentswIthoutsystemIcdIsease.npatIents
wIthsystemIcdIsease,sIgnsofInadequatesystemIcoxygendelIvery(tachycardIa,
tachypnea)areanIndIcatIonfortransfusIon.
Electrolytes
nthepast,patIentsroutInelyreceIvedachemIstrypanelprIortosurgery.8ecauseof
technologyIssues,ItmaybecheapertoobtaInastandardbatterythantodetermIneone
partIculartest.However,testIngrarelyleadstoanychangeInperIoperatIvemanagement.
TherearenumerousguIdelInesregardIngtheneedforpreoperatIveelectrolytes.Theonly
consensusIsthelackofroutInetestIngInasymptomatIcadults,althoughacreatInIneand
glucosehasbeenrecommendedInolderpatIents.npatIentswIthsystemIcdIseasesoron
medIcatIonsthataffectthekIdneys,abloodureanItrogenandcreatInIneevaluatIonare
IndIcated.
Coagulation Studies
CoagulatIondIsorderscanhavesIgnIfIcantImpactonthesurgIcalprocedureand
perIoperatIvemanagement.However,abnormallaboratorystudIesIntheabsenceof
clInIcalabnormalItIeswIthhemophIlIaorvonWIllebranddIsease,requIrepreoperatIve
preparatIonofthepatIent.tIsImportanttoIdentIfysuchdIsordersfromahIstoryof
bleedIngproblems.AprothrombInandpartIalthromboplastIntImeanalysIsareIndIcated
wIthapasthIstoryofbleedIngdIsordersfollowIngInjurIes,toothextractIon,orsurgIcal
procedures;andInpatIentswIthknownorsuspectedlIverdIsease,malabsorptIon,or
malnutrItIon,andoncertaInmedIcatIonssuchasantIbIotIcsandchemotherapeutIcagents.
8leedIngtImeprevIouslywasadvocatedasameansofdetermInIngthepresenceofa
qualItatIveplateletdefect.However,recentlyclInIcIanshavequestIonedthevalueofthIs
testInclInIcalpractIce.ThetestIsextremelyoperatordependent,andsomeauthorshave
suggestedthatthetestshouldbeabandonedInfavorofclInIcalhIstory.ntheabsenceofa
clInIcalbleedIngdIathesIs,complIcatIonsareextremelyrare.fsuchahIstoryexIsts,It
maybeprudenttoavoIdregIonalanesthesIa.
Pregnancy Testing
FoutInepregnancytestIngInwomenofchIldbearIngpotentIalIsasubjectofconsIderable
debate.TheratIonaleIsthatspecIfIcagentsmaybeavoIded,orsurgerymaybedelayed.
nformatIonregardIngthelastmenstrualperIodcanhelpdefInethepotentIal,butdoesnot
elImInatethepossIbIlIty.FoIzenandCohn
68
suggestthatpregnancytestIngshouldbe
lImItedtofemale
P.585
patIentswhobelIevetheyarepregnantorcannottellIftheyarepregnant.However,a
numberofstudIeshaveevaluatedthevalIdItyofhIstoryasameansofassessIngpregnancy
statusInadolescentswIthconflIctIngresults.CurrentpractIcevarIesdramatIcallyamong
centers,andanesthesIologIstsandmaybeafunctIonofthepopulatIonservedwIthregard
totheneedtoroutInelytestthosewomenwIthanegatIvepregnancyhIstory.
Chest X-Rays
ApreoperatIvechestxraycanIdentIfyabnormalItIesthatmayleadtoeItherdelayor
cancellatIonoftheplannedsurgIcalprocedureormodIfIcatIonofperIoperatIvecare.For
example,IdentIfIcatIonofpneumonIa,pulmonaryedema,pulmonarynodules,ora
medIastInalmasscouldallleadtomodIfIcatIonofcare.However,routInetestIngInthe
populatIonwIthoutrIskfactorscanleadtomoreharmthanbenefIt.FoIzenandCohn
68
havedemonstratedsubstantIalharmfromaddItIonalproceduresbasedonshadows
performedsolelyasaroutInepreoperatIvechestxray.
TheAmerIcanCollegeofPhysIcIanssuggeststhatachestxrayIsIndIcatedInthepresence
ofactIvechestdIseaseoranIntrathoracIcprocedure,butnotonthebasIsofadvancedage
alone.
70
DtherguIdelInessuggestthatapreoperatIvechestxrayIsreasonableInpatIents
overtheageof60years.nametaanalysIs,Archer,etal.
71
revIewedthepublIshed
reportsfrom1966to1992IntheEnglIsh,French,andSpanIshlIterature.Twentyone
reportswereIdentIfIedwIthsuffIcIentdatatoevaluatetheuseoftestIng.Dnaverage,
abnormalItIeswerereportedIn10ofroutInepreoperatIvechestxrays,ofwhIchonly1.J
wereunexpected.ThesefIndIngsresultInmodIfIcatIonInmanagementInonly0.1of
patIents,wIthunknownInfluenceonoutcome.TheauthorsestImatedthateachfIndIng
thatInfluencedmanagementwouldcostS2J,000,concludIngthatroutInechestxrays
wIthoutaclInIcalIndIcatIonwerenotjustIfIed.Therefore,apreoperatIvechestxrayIs
IndIcatedInpatIentswIthahIstoryorclInIcalevIdenceofactIvepulmonarydIsease,and
maybeIndIcatedroutInelyonlyInpatIentswIthadvancedage.
Pulmonary Function Tests
PulmonaryfunctIontestscanbegenerallydIvIdedIntotwocategorIes,spIrometryandan
arterIalbloodgas.SpIrometrycanprovIdeInformatIononforcedvItalcapacIty(F7C),
forcedexpIratoryvolumeIn1second(FE7
1
),ratIoofFE7
1
/F7C,andaverageforced
expIratoryflowfrom25to75(FEF2575).Althougheachofthesemeasureshasasound
physIologIcbasIs,theIrpractIcalassessmentcanvarygreatlyamonghealthypersons.
DbjectIvemeasuresdefInInghIghrIskforpulmonaryresectIonhavebeenproposed.For
nonpulmonarysurgery,theyrarelyprovIdeaddItIonalInformatIonbeyondthatobtaIned
fromhIstory.PossIbleIndIcatIonsaretheuseofpulmonaryfunctIontestIngwIth
bronchodIlatortherapytoassessresponsIvenessInapatIentwhoIswheezIngandwhenthe
hIstoryandphysIcalleavethedegreeofperIoperatIverIskuncertaIn.
WIththeadventofthepulseoxImeter,theuseofpreoperatIvearterIalbloodgassamplIng
hasbecomelessImportant.tmaystIllbeIndIcated,sIncedetermInIngthebaselIneCD
2
Is
usefulInmanagIngpostoperatIveventIlatIonsettIngsandrestInghypercapnIaIsassocIated
wIthIncreasedperIoperatIverIsk.However,thephysIcalactofobtaInInganarterIalblood
gascanleadtohyperventIlatIonandchangethePaco
2
.DnemethodofassessIngthe
probabIlItyofCD
2
retentIonIsevaluatIonoftheserumbIcarbonate.Anormalserum
bIcarbonatewIllvIrtuallyexcludethedIagnosIsofCD
2
retentIon.ftheserumbIcarbonate
Iselevated,thenanarterIalbloodgastesteItherpreoperatIvelyorImmedIatelyprIorto
InductIonmaybeIndIcated.
AnotherIndIcatIonforanarterIalbloodgashasbeendetermInatIonofoxygen
concentratIon.WIththeadventandavaIlabIlItyofpulseoxImetryInthepreoperatIve
screenIngclInIc,thIsIsrarelyanIndIcatIon.
Summary of the Preoperative Evaluation
ThepreoperatIveevaluatIonofthesurgIcalpatIentcontInuestobeanImportant
componentoftheanesthesIologIst'srole.AthoroughhIstoryandphysIcalexamInatIoncan
beusedtoIdentIfythosemedIcalcondItIonsthatmIghtaffectperIoperatIvemanagement
anddIrectfurtherlaboratorytestIng.nthecurrenteraofcapItatedcareandthedesIreto
reduceInapproprIateutIlIzatIonofmedIcaltechnology,theanesthesIologIstcanhavea
sIgnIfIcantImpactonhealthresourceutIlIzatIonbyperformIngapproprIatelaboratory
tests.8ycombInIngdatafromthehIstory,physIcalexamInatIon,exercIsetolerance,and
thestressofthesurgIcalprocedure,InapproprIatetestIngcanbereduced;butmore
Importantly,approprIatescreenIngtestswIllbeperformed.
Preoperative Medication
AnesthetIcmanagementforpatIentsbegInswIthpreoperatIvepsychologIcalpreparatIon
and,Ifnecessary,preoperatIvemedIcatIon.SpecIfIcpharmacologIcactIonsshouldbekept
InmIndwhenthesedrugsareadmInIsteredbeforeoperatIon,andtheyshouldbetaIlored
totheneedsofeachpatIent.TheanesthesIologIstshouldassessthepatIent'smentaland
physIcalcondItIondurIngthepreoperatIvevIsIt.8ecauseItIsactuallythebegInnIngofthe
anesthetIc,choIceofpreoperatIvemedIcatIonshouldbebasedonthesameconsIderatIons
asthechoIceofanesthesIa,IncludIngconsIderatIonsofthepatIent'smedIcalproblems,
requIrementsofthesurgery,andtheanesthesIologIst'sskIlls.SatIsfactorypreoperatIve
preparatIonandmedIcatIonfacIlItateanuneventfulperIoperatIvecourse.Poor
preparatIonmaybegInaserIesofproblemsandmIsadventures.
NoconsensusexIstsonthechoIceofpreoperatIvemedIcatIons.TheIrusehasbeen
domInatedbytradItIon,whIchhasbeenmodIfIedsomewhatbythechangeInanesthetIc
agentsandtechnIquesovertheyears.8eecher
72
statedthatempIrIcalproceduresfIrmly
establIshedInthehabItsofgooddoctorshavealIfe,nottosay,ImmortalItyoftheIrown.
SImIlarly,theemotIonalattachmentofananesthesIologIsttohIsownregImenIsoften
moreobvIousthanhIsobjectIveassessmentofItseffects.
7J
Anotherreasonforlackof
consensusmaybethatseveraldIfferentdrugsorcombInatIonsofdrugscanaccomplIshthe
samegoals.However,thereIsgeneralagreementthatmostpatIentsshouldenterthe
operatIngroomafteranxIetyhasbeenrelIevedandotherspecIfIcgoalshavebeenmet
throughpreoperatIvepreparatIonandmedIcatIon.AnxIolysIsshouldbeaccomplIshed
wIthoutunduesedatIon,whIchcanInterferewIthpatIentsafetyor,gIventhedramatIc
IncreaseInthenumberofoutpatIentsurgIcalprocedures,prolonglengthofstayInthe
operatIngroom.
Psychological Preparation
PsychologIcalpreparatIonofthepatIentInvolvesthepreoperatIvevIsItandIntervIewwIth
thepatIentandfamIlymembers.TheanesthesIologIstshouldexplaInantIcIpatedevents
andtheproposedanesthetIcmanagementInanefforttoreduceanxIetyandallay
apprehensIon.PatIentsmayperceIvethedayofsurgeryasthebIggest,mostthreatenIng
dayIntheIrlIves;theydonotwIshtobetreatedImpersonallyIntheoperatIngroom.The
anesthesIologIst'sfIrstdIrectencounterwIththepatIentmaybeIntheImmedIate
preoperatIveperIod.AgrowIng
P.586
numberofpatIentsreceIvetheIrpreanesthetIcevaluatIonsbyothersInpreoperatIve
evaluatIonclInIcsorjustprIortosurgery.PreoperatIvevIsItsmustbeconducted
effIcIently,buttheymustalsobeInformatIveandreassurIng,answerIngallquestIons.|ost
oftheanesthesIologIst'stImeIsspentwIthanunconscIousorsedatedpatIent;therefore,he
orshemusttaketImebeforetheoperatIontoearnthetrustandconfIdenceofthat
patIent.
Table 23-11 Comparison of Preoperative Visit (Percentage Of Patients) and
Pentobarbital (2 mg/kg IM)

FELT
DROWSY
FELT
NERVOUS
ADEQUATE
PREPARATION
Controlgroup 18 58 J5
PentobarbItalgroup J0 61 48
PreoperatIvevIsIt 26 40 65
PreoperatIvevIsItand
pentobarbItal
J8 J8 71
|,Intramuscularly.
0atafromEgbertL0,8attItCE,TurndorfH,etal:ThevalueofthepreoperatIve
vIsItbytheanesthetIst.JA|A196J;185:55J.
|ostpatIentsareanxIousbeforesurgery.StudIesshowthat,dependIngontheIntensItyof
InquIry,40to85ofpatIentsareapprehensIvebeforesurgery.PreoperatIveanxIetystates
areatahIghlevel,andmostpatIentsexpectapprehensIontoberelIevedbeforethey
arrIveIntheoperatIngroom.TheclassIcstudybyEgbert,etal.
74
showedthatanaverage
of57ofpatIentsfeltanxIousbeforeoperatIon.AnInformatIveandcomfortIng
preoperatIvevIsItmayreplacemanymIllIgramsofdepressantmedIcatIon.Forexample,
thestudybyEgbertetal.showedthatmorepatIentswereadequatelypreparedforsurgery
afterapreoperatIveIntervIewthanafter2mg/kgofpentobarbItalgIvenIntramuscularly1
hourbeforesurgery(Table2J11).
74
However,psychologIcalpreparatIoncannotaccomplIsh
everythIngandwIllnotrelIeveallanxIety.
8esIdespsychologIcalpreparatIon,thereareothergoalsofpreoperatIvemedIcatIon.
ControlofpaInandsatIsfactorylevelsofamnesIaorsedatIoncannotbeachIevedwIth
consIstentsuccessatthepreoperatIvevIsItalone.naddItIon,emergencysItuatIonsmay
provIdelIttleornotImeforapreoperatIveIntervIew.|oreserIouslyIllorelderlypatIents,
conversely,maynottoleratethephysIologIceffectsofsedatIvemedIcatIons.Always
rememberthatthesubstItutIonofpreoperatIvedepressantdrugsforacomfortIngand
tactfulpreoperatIvevIsItmaycompromIsepatIentsafety.
Pharmacologic Preparation
TheIdealdrugorcombInatIonofdrugsforpreoperatIvepharmacologIcpreparatIonIsas
elusIveasIstheIdealanesthetIctechnIqueandIsnotbasedonalargebodyofdatathatIs
eItherdefInItIveorpersuasIve.FoutIneadmInIstratIonofthesamedrugstoallpatIentshas
fallenIntodIsfavorasaselectIveapproachhasemerged.nselectIngtheapproprIatedrugs
forpreoperatIvemedIcatIon,thepatIent'spsychologIcalcondItIon,physIcalstatus,andage
mustbeconsIdered.ThesurgIcalprocedureandItsduratIonareImportantfactors,aswell.
sthIsanoutpatIentprocedure:sItelectIvesurgeryoremergencysurgery:The
anesthesIologIstmustknowthepatIent'sweIght,prIorresponsetodepressantdrugs,
IncludIngunwantedsIdeeffects,andallergIes.FInally,theanesthesIologIst'sexperIence
andfamIlIarItywIthcertaInpreoperatIvemedIcatIonsmorethanothersaredetermInants.
Table 23-12 Various Goals for Preoperative Medicine
1. FelIefofanxIety
2. SedatIon
J. AmnesIa
4. AnalgesIa
5. 0ryIngofaIrwaysecretIons
6. PreventIonofautonomIcreflexresponses
7. FeductIonofgastrIcfluIdvolumeandIncreasedpH
8. AntIemetIceffects
9. FeductIonofanesthetIcrequIrements
10. FacIlItatIonofsmoothInductIonofanesthesIa
11. ProphylaxIsagaInstallergIcreactIons
|odIfIedfromStoeltIngFK:PsychologIcalpreparatIonandpreoperatIve
medIcatIon.AnesthesIa.EdItedby|IllerF0.NewYork,ChurchIllLIvIngstone,1981.
ThegoalstobeachIevedforeachpatIentwIthpreoperatIvemedIcatIonareIntImately
InvolvedIntheselectIonprocess(Table2J12).ThedesIredgoalsmaybemultIpleand
shouldbetaIloredtotheneedsofeachpatIent.Someofthegoals,suchasrelIefofanxIety
andproductIonofsedatIon,applytoalmosteverypatIent,whereasothersareImportant
onlyoccasIonally.ProphylaxIsagaInstallergIcreactIonsapplIesInonlyafewInstances.
PreventIonofautonomIcreflexesmedIatedthroughthevagusnerveoranantIemetIc
effectmaybebetterattemptedImmedIatelybeforetheantIcIpatedneedratherthan
achIevedatthetImeofpreoperatIvemedIcatIon.PreoperatIvemedIcatIonregImens
shouldnotproducesuffIcIentobtundatIontobeclInIcallysIgnIfIcantInreducInganesthetIc
requIrement.
SomepatIentsshouldnotreceIvedepressantdrugsbeforesurgery.PatIentswIthlIttle
physIologIcreserve,attheextremesofage,wIthaheadInjury,orwIthhypovolemIamay
beharmedmorethanhelpedbymanyofthemedIcatIonsnormallyusedbeforeoperatIon.
ncontrast,thecondItIonsofothersdemandthatattemptsbemadepharmacologIcallyto
reduceanxIety,provIdeanalgesIa,ordrysecretIonsIntheaIrwaytoproduceasafer
perIoperatIvecourse.ForelectIvesurgery,theanesthesIologIstwIll,InmostInstances,
wantthepatIenttoentertheoperatIngroomfreeofanxIetyandsedated,yeteasIly
arousedandcooperatIve.ThepatIentshouldnotbeoverlyobtundedordIsplayother
unwantedsIdeeffectsofthepreoperatIvedrugs.ThepatIentwhoaskstobeasleep
beforeleavIngthehospItalroomshouldbetoldthatapprehensIonandsedatIonmaybe
reducedbutItwouldbeunsafetoproduceacomatosestate.ThetImeandrouteof
admInIstratIonofthepreoperatIvemedIcatIonsareImportant.Asageneralrule,oral
medIcatIonsshouldbegIventothepatIent60to90mInutesbeforearrIvalIntheoperatIng
room.tIsacceptabletoadmInIsteroraldrugswIthupto150mLofwater.
75
ntravenous
agentsproduceeffectsafterafewcIrculatIontImes,whIleforfulleffect,Intramuscular
medIcatIonsshouldbegIvenatleast20mInutesandpreferablyJ0to60mInutesbeforethe
patIent'sarrIvalIntheoperatIngroom.Everyattemptshouldbemadetohavethe
preoperatIvemedIcatIonsachIevetheIrfulleffectbeforethepatIent'sarrIvalInthe
operatIngroomratherthanafterInductIonofanesthesIa.Thedrug(s),doses,routeof
admInIstratIon,andeffectsshouldberecordedontheanesthetIcrecord.AlIstofcommon
preoperatIvemedIcatIonsIspresentedInTable2J1J.
P.587
Table 23-13 Common Preoperative Medications, Doses, and Administration
Routes
MEDICATION ADMINISTRATION ROUTE DOSE (mg)
Lorazepam Dral,7 0.54
|Idazolam 7 TItratIonof1.02.5mgdoses
Fentanyl 7 TItratIonof25100gdoses
|orphIne 7 TItratIonof1.02.5mgdoses
|eperIdIne 7 TItratIonof1025mgdoses
CImetIdIne Dral,7 150J00
FanItIdIne Dral 50200
|etoclopramIde 7 510
AtropIne 7 0.J0.4
Clycopyrrolate 7 0.10.2
ScopolamIne 7 0.10.4
7,Intravenous.
|odIfIedfromStoeltIngFK,|IllerF0,eds:8asIcsofAnesthesIa.NewYork,
ChurchIllLIvIngstone,1984.
SedativeHypnotics and Tranquilizers
Benzodiazepines
8enzodIazepInesareamongthemostpopulardrugsusedforpreoperatIvemedIcatIon
(Table2J14).TheyareusedtoproduceanxIolysIs,amnesIa,andsedatIon.8ecausethesIte
ofactIonofbenzodIazepInesIsonspecIfIcreceptorsInthecentralnervoussystem(FIg.2J
5)thereIsrelatIvelylIttledepressIonofventIlatIonorofthecardIovascularsystemwIth
premedIcantdoses.8enzodIazepIneshaveawIdetherapeutIcIndexandalowIncIdenceof
toxIcIty.DtherthancentralnervoussystemdepressIon,therearefewsIdeeffectsofthIs
groupofdrugs.SpecIfIcally,nauseaandvomItIngarenotusuallyassocIatedwIth
admInIstratIonofbenzodIazepInesforpreoperatIvemedIcatIon.
TherearesomehazardsandunwantedsIdeeffectsofbenzodIazepInes.Thecentral
nervoussystemdepressIonthesedrugscauseIssometImeslongandexcessIve,especIally
wIthuseoflorazepam.ThesedrugsarenotanalgesIcagents.8enzodIazepInesmaynot
alwaysproduceacalmIngeffectbutmaycauseagItatIon,asevIdencedbyrestlessnessand
delIrIum.
Lorazepam
LorazepamresemblesoxazepamstructurallyandIs5to10tImesaspotentasdIazepam.
LorazepamcanproduceprofoundamnesIa,relIefofanxIety,andsedatIon(FIg.2J6).
76
WhenlorazepamIscomparedwIthdIazepam,theIreffectsareverysImIlar.AlthoughItIs
InsolubleInwaterandrequIresasolventsuchaspolyethyleneglycolorpropyleneglycol,
admInIstratIonoflorazepam,unlIkedIazepam,IsnotassocIatedwIthpaInonInjectIonor
phlebItIs.ProlongedsedatIonIsmorelIkelyafterlorazepamadmInIstratIon.Eventhough
theelImInatIonhalflIfeofdIazepamIslongerthanthatoflorazepam(20to40hoursvs.10
to20hours),theeffectofdIazepammaybeshorterbecauseItmorerapIdlydIssocIates
fromthebenzodIazepInereceptor.
77
naddItIontotheIntravenousroute,lorazepamIsrelIablyabsorbedorally.8radshaw,et
al.
78
demonstratedclInIcaleffectsJ0to60mInutesafteroraladmInIstratIonoflorazepam.
PeakplasmaconcentratIonsmaynotoccuruntIl2to4hoursafteroraladmInIstratIon.
Therefore,lorazepammustbeorderedwellbeforesurgerysothatthedrughastImetobe
effectIvebeforethepatIentarrIvesIntheoperatIngroom.LorazepamalsomaybegIven
sublIngually.AsstatedprevIously,theelImInatIonhalflIfeIs10to20hours.Theusualdose
Isabout25to50g/kg.Thedoseforanadultshouldusuallynotexceed4.0mg.
76,77
WIth
recommendeddoses,anterogradeamnesIamaybeproducedforaslongas4to6hours
wIthoutexcessIvesedatIon.HIgherdosesleadtoprolongedandexcessIvesedatIonwIthout
moreamnesIa.8ecauseofItsslowonsetandlengthofactIon,lorazepamIsnotusefulIn
InstancesInwhIchrapIdawakenIngIsnecessary,suchaswIthoutpatIentanesthesIa.There
arenoactIvemetabolItesoflorazepam;becauseItsmetabolIsmIsnotdependenton
mIcrosomalenzymes,thereIslessInfluenceonItseffectfromageorlIverdIsease.AswIth
dIazepam,lIttlecardIorespIratorydepressIonoccurswIthlorazepam.However,thereIsthe
dangerofunwantedrespIratorydepressIonInthosewIthlungdIsease.
Table 23-14 Comparison of Pharmacologic Variables of Benzodiazepines
DIAZEPAM LORAZEPAM MIDAZOLAM
0oseequIvalent(mg) 10 12 J5
TImetopeakeffectafteroraldose(hr) 11.5 24 0.51
ElImInatIonhalftIme(hr) 2040 1020 14
Clearance(mL/kg/mIn) 0.20.5 0.71.0 6.411.1
7olumeofdIstrIbutIon(L/kg) 0.71.7 0.81.J 1.11.7
AdaptedfromFevesJC,FragenFJ,7InIckHF,etal:|Idazolam:Pharmacologyand
uses.AnesthesIology1985;62:J10;andStoeltIngFK:PharmacologyandPhysIology
InAnesthetIcPractIce.PhIladelphIa,J8LIppIncott,1987.
P.588
Figure 23-5.SchematIcdIagramofthebenzodIazepInesIteontheCA8A(
amInobutyrIcacId)receptor.[FeproducedwIthpermIssIonfromCarlsonN:FoundatIons
ofPhysIologIcalPsychology(7thedItIon).8oston,PearsonEducatIon,nc,2007,p115)]
Midazolam
|IdazolamhaspredomInantlyreplacedtheuseofdIazepamforpreoperatIvemedIcatIon
andconscIoussedatIon.tIscommontoadmInIstersedatIvedosesIntravenouslyjustprIor
tothetrIptotheoperatIngroom.ThephysIcochemIcalpropertIesofthedrugallowforIts
watersolubIlItyandrapIdmetabolIsm.AswIthotherbenzodIazepInes,mIdazolamproduces
anxIolysIs,sedatIon,andamnesIa.tIs2toJtImesaspotentasdIazepambecauseofIts
IncreasedaffInItyforthebenzodIazepInereceptor.TheusualIntramusculardoseIs0.05to
0.1mg/kgandtItratIonof1.0to2.5mgatatImeIntravenously.ThereIsnoIrrItatIonor
phlebItIswIthInjectIonofmIdazolam.TheIncIdenceofsIdeeffectsafteradmInIstratIonIs
low,althoughdepressIonofventIlatIonandsedatIonmaybegreaterthanexpected,
especIallyInelderlypatIentsorwhenthedrugIscombInedwIthothercentralnervous
systemdepressants.ThereIsmorerapIdonsetofactIonandpredIctableabsorptIonafter
IntramuscularInjectIonofmIdazolamthanafterdIazepam.ThetImeofonsetafter
IntramuscularInjectIonIs5to10mInutes,wIthpeakeffectoccurrIngafterJ0to60
mInutes.TheonsetafterIntravenousadmInIstratIonof5mgwouldbeexpectedtooccur
after1to2mInutes.naddItIontoquIckeronset,morerapIdrecoveryoccursafter
mIdazolamadmInIstratIoncomparedwIthdIazepam.ThIsIsprobablytheresultofthelIpId
solubIlItyofmIdazolamandItsrapIddIstrIbutIonIntheperIpheraltIssuesandmetabolIc
bIotransformatIon.Forthesereasons,mIdazolamusuallyshouldbegIvenwIthInanhourof
InductIon.
6J
|IdazolamIsmetabolIzedbyhepatIcmIcrosomalenzymestoessentIally
InactIvehydroxylatedmetabolItes.H
2
receptorantagonIstsdonotInterferewIthIts
metabolIsm.TheelImInatIonhalflIfeofmIdazolamIsapproxImately1to4hoursandmay
beextendedIntheelderly.TestsshowthatmentalfunctIonusuallyreturnstonormal
wIthIn4hoursofadmInIstratIon.
79
AfteradmInIstratIonof5mg,amnesIalastsfrom20to
J0mInutes.ntramuscularadmInIstratIonmayproducelongerperIodsofamnesIa.Thelack
ofrecallmaybeaugmentedbyconcomItantadmInIstratIonofscopolamIne.ThepropertIes
ofmIdazolammakeItIdealforshorterprocedures.
Figure 23-6.PercentageofpatIentsIneachgroupfaIlIngtorecallspecIfIceventsof
theoperatIveday.|edIcatIonswereadmInIsteredIntramuscularly.D.F.,operatIng
room;.7.,Intravenous.(FeprIntedfromFragenFJ,CaldwellN:Lorazepam
premedIcatIon:LackofrecallandrelIefofanxIety.AnesthAnalg1976;55:792,wIth
permIssIon.)
Other Benzodiazepines
Dxazepam,anotherbenzodIazepInethathasbeenusedforpreoperatIvemedIcatIon,Isone
ofthepharmacologIcallyactIvemetabolItesofdIazepam.tIsabsorbedslowlyafteroral
admInIstratIonandhasanelImInatIonhalflIfeof5to15hours.TemazepamhasbeengIven
Inoraldosesof20toJ0mgbeforesurgery.tmustbegIvenwellbeforesurgerybecause
peakplasmalevelsdonotoccuruntIlapproxImately2to2.5hoursafteradmInIstratIon.
TrIazolamIsashortactIngbenzodIazepIne.TheadultoraldoseofthedrugIs0.25to0.5
mg.PeakplasmaconcentratIonsoccurInabout1hourandItselImInatIonhalflIfeIs1.7to
5.2hours.ThedrugmaybecomelongactIngIntheelderly.SImIlarly,astudybyPInnock,
etal.dIdnotshowtrIazolamtobeofshortduratIonwhencomparedwIthdIazepamfor
premedIcatIonformInorgynecologIcsurgery.
80
Alprazolam(1mg)gIventoadultshasbeen
showntoproduceamodestreductIonInanxIetybeforesurgery.
Other Sedative Drugs
Diphenhydramine
0IphenhydramIneIsahIstamInereceptorantagonIstwIthsedatIveandantIcholInergIc
actIvIty.tIsalsoanantIemetIc.Adoseof50mgwIlllastJto6hoursInanadult.
0IphenhydramInehasbeenusedrecentlyIncombInatIonwIthcImetIdIne,steroIds,and
otherdrugsforprophylaxIsInpatIentswIthchronIcatopy,latexallergy,andfor
prophylaxIsbeforechemonucleolysIsanddyestudIes.0IphenhydramIneblocksthe
hIstamIne1receptortopreventeffectsofhIstamIneperIpherally.
P.589
Opioids
|orphIneandmeperIdInewerehIstorIcallythemostfrequentlyusedopIoIdsfor
IntramuscularpreoperatIvemedIcatIon.Fecently,theuseofIntravenousfentanyljust
beforesurgeryhasbecomemuchmorepopular.DpIoIdsareusedwhenanalgesIaIsneeded
beforeoperatIon.Cohenand8eecher
81
opInedthatunlessthereIspaIn,thereIsnoneed
fornarcotIcInpreanesthetIcmedIcatIon.ForthepatIentexperIencIngpaInbefore
operatIon,theopIoIdscanproducegoodanalgesIaandeveneuphorIa.DpIoIdshavebeen
orderedforpatIentsbeforeoperatIontoamelIoratethedIscomfortthatmayoccurdurIng
regIonalanesthesIaortheInsertIonofInvasIvemonItorIngcathetersorlargeIntravenous
lInes.ThedoseofopIoIdmayneedtobereducedInthedebIlItatedorelderlypatIent.The
elderlypatIentoftenexhIbItsareducedsensItIvItytopaIn.Furthermore,elderlypatIents
canhaveanIncreasedanalgesIcresponsetoopIoIds.DpIoIdsalsohavebeenusedbefore
operatIonIntheopIoIddependentpatIent.
PreoperatIveadmInIstratIonofopIoIdsInothersettIngshasbeencontroversIal.
PreoperatIveopIoIdsprIortoanItrousoxIdeopIoIdanesthetIcmayhelptoestablIsha
basalstateofanesthesIawhenthepatIentarrIvesIntheoperatIngroomandtogeta
prevIewofthepatIent'sresponsetoopIoIds.DpIoIdshavebeengIventopatIentsbefore
operatIontoprovIdeanalgesIaontheIrawakenIngIntherecoveryroom.Theother
approachIstotItratetheopIoIdIntravenouslydurIngemergenceoronthepatIent'sarrIval
Intherecoveryroom.PreoperatIveadmInIstratIonofopIoIdscanloweranesthetIc
requIrements.SomeanesthesIologIstsuseopIoIdsIncombInatIonwIthotherdrugsbefore
operatIontofacIlItateanesthetIcInductIonbymask,althoughopIoIdsdodecrease
ventIlatoryresponseandthereforedecreaseuptakeofInhalatIondrugs.fnecessary,the
anesthesIologIstmaywanttouseassIstedorcontrolledventIlatIonofthelungsto
overcometherespIratorydepressanteffectsoftheopIoIds.FInally,opIoIdsdonotrelIeve
apprehensIon,producesedatIon,orpreventrecall.
DpIoIdsadmInIstratIonhasthepotentIaltocauseseveralsIdeeffects.PreoperatIvely,
opIoIdsusuallyexhIbItnodIrectmyocardIaleffects.However,someopIoIdsdoInterfere
wIththecompensatoryconstrIctIonofsmoothmusclesoftheperIpheralvasculature.ThIs
venodIlatIonmayleadtoorthostatIchypotensIon.HIstamInereleaseafterInjectIonof
morphInemaycompoundthesecIrculatoryeffects.AswIthmostpreoperatIvemedIcatIons,
ItIsprobablysafesttohavethepatIentremaInatbedrestafteropIoIdpremedIcatIon.The
analgesIcpropertIesandrespIratorydepressanteffectsofopIoIdsusuallygohandInhand.
ThedecreaseInthecarbondIoxIdedrIveatthemedullaryrespIratorycentermaybe
prolonged.Furthermore,thereIsadecreaseIntheresponsIvenesstohypoxIaatthecarotId
bodyafterInjectIonofonlylowdosesofopIoIds.
82
TheanesthesIologIstmaywIshto
consIdersupplementaloxygenforthepatIentreceIvIngopIoIdpremedIcatIon.
ngeneral,theopIoIdagonIstantagonIstsproducelessrespIratorydepressIon,buttheyalso
producelessanalgesIa.FatherthaneuphorIa,theopIoIdsmayproducedysphorIa.When
thIssIdeeffectdoesoccur,ItIsmostcommonlyseenInapatIentwhodoesnothavepaIn
beforeoperatIonandhasreceIvedtheopIoIdpremedIcatIon.NauseaandvomItIngmay
resultfromopIoIdadmInIstratIon.TheeffectofopIoIdsonthevestIbularapparatusleadIng
tomotIonsIcknessorstImulatIonofthemedullarychemoreceptortrIggerzoneIsa
postulatedreasonfornauseaandvomItIng.CholedochoduodenalsphIncter(sphIncterof
DddI)spasmhasoccasIonallybeennotedsubsequenttoInjectIonofopIoIds.TheopIoId
producessmoothmuscleconstrIctIon,whIchleadstorIghtupperquadrantpaIn.PaInrelIef
maybeachIevedwIthnaloxoneorpossIblyglucagon.DccasIonally,thepaInfrombIlIary
tractspasmIsdIffIculttodIfferentIatefromthepaInofangInapectorIs.TheadmInIstratIon
ofnItroglycerInshouldrelIeveangInapectorIsandpaInresultIngfrombIlIarytractspasm;
anopIoIdantagonIstshouldrelIeveonlypaInresultIngfrombIlIarytractspasm.Some
questIontheuseofopIoIdpremedIcatIonInpatIentswIthbIlIarytractdIsease.AllopIoIds
havethepotentIaltoInducecholedochoduodenalsphIncterspasm.Fentanyland
meperIdInearelesslIkelythanmorphInetoproducethIssIdeeffect.DpIoIdsmayproduce
prurItus.|orphIne,possIblythroughhIstamInerelease,oftenproducesItchIng,especIally
aroundthenose.DpIoIdsalsomaycauseflushIng,dIzzIness,andmIosIs.
DtherdrugsareoftencombInedwIthopIoIdsfortheIraddItIveeffectsortoovercomethe
dIsadvantagesofopIoIdsIdeeffects.AsedatIvehypnotIcIsoftenusedwIthopIoIdsto
producesedatIon,anxIolysIs,andamnesIaInaddItIontoanalgesIa.
Morphine
|orphIneIswellabsorbedafterIntramuscularInjectIon.Theonsetofeffectshouldoccur
wIthIn15toJ0mInutes.ThepeakeffectoccursIn45to90mInutesandlastsaslongas4
hours.AfterIntravenousadmInIstratIon,thepeakeffectusuallyoccurswIthIn20mInutes.
|orphIneIsnotrelIablyabsorbedafteroraladmInIstratIon.AswIththeotheropIoIds,
depressIonofventIlatIonandorthostatIchypotensIonmayoccurafterInjectIonof
morphIne.TheeffectofmorphIneonthechemoreceptIvetrIggerzonemayproducenausea
andvomItIng.NauseaandvomItIngmayalsooccurowIngtoavestIbularcomponent.
Meperidine
|eperIdIneIsaboutonetenthaspotentasmorphIne.tmaybegIvenorallyor
parenterally.AsIngledoseofmeperIdIneusuallylasts2to4hours.Theonsetafter
IntramuscularInjectIonIsunpredIctable,andagreatdealofvarIabIlItyIntImetopeak
effectexIsts.
Fentanyl
FentanylIsasynthetIcopIoIdagonIststructurallysImIlartomeperIdIne.tIs75to125
tImesmorepotentthanmorphIneInItsanalgesIccharacterIstIcs.ThelIpIdsolubIlItyof
fentanylIsgreaterthanthatofmorphIne,whIchcontrIbutestoItsrapIdonsetofactIon.
PeakplasmaconcentratIonsoccurwIthIn6to7mInutesfollowIngIntravenous
admInIstratIonandItselImInatIonhalftImeIsJto6hours.Thedrug'sshortduratIonof
actIonIsattrIbutedtoredIstrIbutIontoInactIvetIssues,suchasthelungs,fat,andskeletal
muscle.|etabolIsmoccursprImarIlybyNdemethylatIontonorfentanyl,whIchIsaless
potentanalgesIc.AdecreasedclearancerateIntheelderlymayprolongelImInatIon.
ndosesof1to2g/kgIntravenously,fentanylmaybeusedtoprovIdepreoperatIve
analgesIa.DraltransmucosalfentanylpreparatIonsoffentanylareavaIlable,delIverIng5
to20g/kgofthedrug.ThIsformhasbeenexamInedasapremedIcantInbothadultsand
chIldrentorelIeveanxIetyandpaIn.FentanylcausesneIthermyocardIaldepressIonnor
hIstamInerelease,butmaybeassocIatedwIthventIlatorydepressIonandprofound
bradycardIa.SynergIstIceffectswIthbenzodIazepIneswarrantcloseobservatIonwhenthIs
combInatIonIsgIvenInthepreoperatIveperIod.
Gastric Fluid pH and Volume
|anypatIentswhocometotheoperatIngroomareatrIskforaspIratIonpneumonItIs.The
classIcexampleIsthepatIentwIthacutepaInandafullstomachwhomusthave
emergencysurgery.ThepregnantpatIent,theobesepatIent,thedIabetIc,thepatIentwIth
hIatalhernIaorgastroesophagealreflux,allmaybeatrIskforaspIratIonofgastrIc
contentsandsubsequentchemIcalpneumonItIs.AlthoughuncertaInItIsbelIeved,Ifadults
aspIratemorethan25mLofgastrIcfluIdwIthapHlowerthan2.5,pulmonarysequelaewIll
result.ThIsfacthasnotbeen,andprobablyneverwIllbe,provedInhumans.
P.590
However,usIngtheseguIdelInes,somehaveestImatedthat40to80ofpatIentsscheduled
forelectIvesurgerymaybeatrIsk.
8J,84
However,clInIcallysIgnIfIcantpulmonary
aspIratIonofgastrIccontentsIsveryrareInhealthypatIentshavIngelectIvesurgIcal
procedures,andfewanesthesIologIstsadvocateroutIneprophylaxIs.
85
Table 23-15 Summary of Fasting Recommendations to Reduce The Risk of
Pulmonary Aspiration
a
NCESTE0|ATEFAL
|N|U|FASTNCPEFD0,APPLE0TDALL
ACES(hr)
ClearlIquIds
b
2
8reastmIlk 4
nfantformula 6
NonhumanmIlk 6
LIghtmeal(toastandclear
lIquIds)
6
a
ApplIesonlytohealthypatIentswhoareundergoIngelectIveproceduresandare
notIntendedforwomenInlabor.FollowIngtheguIdelInesdoesnotguarantee
completegastrIcemptyIng.
b
ExamplesofclearlIquIdsIncludewater,fruItjuIceswIthoutpulp,carbonated
beverages,cleartea,andblackcoffee.
AdaptedfromPractIceCuIdelInesforPreoperatIveFastIngandtheUseof
PharmacologIcAgentstoFeducetheFIskofPulmonaryAspIratIon:ApplIcatIonto
HealthyPatIentsUndergoIngElectIveProcedures.AFeportbytheAmerIcan
SocIetyofAnesthesIologIstsTaskForceonPreoperatIveFastIng.AnesthesIology
1999;90:896.
|anyanesthesIologIstsfollowtheAmerIcanSocIetyofAnesthesIologIstspractIce
recommendatIons,
85
howeverthenecessItyofprolongedfastIng(nothIngbymouthafter
mIdnIght)beforeInductIonofanesthesIaforelectIvesurgeryhasbeenchallenged.
86
Some
InstItutIonsallowIngestIonofclearlIquIdsuntIlJoreven2hoursbeforesurgeryIn
selectedpatIents.ndeed,gastrIcfluIdvolumemaynotbeIncreasedbyIngestIonof150mL
ofwater,coffee,ororangejuIce2toJhoursprIortotheInductIonofanesthesIa.For
example,astudybyShevdeandTrIvedIdescrIbedtheadmInIstratIonof240mLofwater,
coffee,orpulpfreeorangejuIcetohealthyvolunteers.AllhadgastrIcvolumesoflessthan
25mLwIthaslIghtdecreaseInpHwIthIn2hoursoftakIngoneofthethreelIquIds.
87
There
Isconcernaboutcomfort,hypovolemIa,andhypoglycemIaInthepedIatrIcagegroup
perIoperatIvelyafterprolongedfastIng.StudIesInInfants,chIldren,andhealthyadults
scheduledforelectIvesurgeryhavefoundthatdrInkIngclearfluIduptoJhoursbefore
scheduledsurgerydoesnothaveameasurableeffectongastrIcvolumeandpH.tmustbe
apprecIated,however,thatthesedataarefromhealthypatIentsnotatrIskfor
aspIratIonandapplyonlytoIngestIonofclearlIquIds.Asstatedbefore,mostclInIcIans
adheretoTheAmerIcanSocIetyofAnesthesIologIsts'preoperatIvefastIngguIdelInes,whIch
wereadaptedIn1998(Table2J15).
85
|anydIfferentkIndsofdrugshavebeenusedtoaltergastrIcfluIdvolumeandIncreasethe
pHofgastrIcfluId.AntIcholInergIcs,H
2
receptorantagonIsts,antacIds,andgastrokInetIc
agentshaveallbeenusedtoreducethepossIbIlItyofaspIratIonpneumonItIs.
Anticholinergics
NeItheratropInenorglycopyrrolatehasbeenshowntobeveryeffectIveInIncreasIng
gastrIcfluIdpHorreducInggastrIcfluIdvolume.
8J,84
Furthermore,Intravenousdosesof
antIcholInergIcsmaycauserelaxatIonofthegastroesophagealjunctIon(FIg.2J7).
Therefore,therIskofaspIratIonpneumonItIsmaybeIncreased,butthIsspecIfIceffectof
IntramuscularadmInIstratIonofantIcholInergIcsforpreoperatIveusehasnotbeenproved.
Figure 23-7.8arrIerpressure(esophagealsphIncterpressuremInusgastrIcpressure)
beforeandafterIntravenousadmInIstratIonofglycopyrrolate,0.Jmg,toadult
patIents.|eanSE.(FeprIntedfrom8rockUtneJC,WelmanFS,|oshal|C,etal:
Theeffectofglycopyrrolate[FobInul]ontheloweresophagealsphIncter.CanAnaesth
SocJ1978;25:144,wIthpermIssIon.)
Histamine Receptor Antagonists
TheH
2
receptorantagonIstscImetIdIne,ranItIdIne,famotIdIne,andnIzatIdInereduce
gastrIcacIdsecretIon.TheyblocktheabIlItyofhIstamInetoInducesecretIonofgastrIc
fluIdwIthahIghhydrogenIonconcentratIon.Therefore,theH
2
receptorantagonIsts
IncreasegastrIcfluIdpH.TheIrantagonIsmofthehIstamInereceptoroccursInaselectIve
andcompetItIvemanner.tIsImportanttorememberthatthesedrugscannotbeexpected
relIablytoaffectgastrIcfluIdvolumeorgastrIcemptyIngtIme.ComparedwIthother
premedIcants,theyhaverelatIvelyfewsIdeeffects.8ecausetherearefewsIdeeffects,
manyanesthesIologIstshaveadvocatedthelIberalpreoperatIveuseofH
2
receptor
antagonIsts.|ultIpledoseregImensmaybemoreeffectIveInIncreasInggastrIcpHthana
sIngledosebeforeoperatIononthedayofsurgery.AnH
2
antagonIstalsomaybeusedfor
theallergIcpatIentorInpreparIngapatIentforexposuretoatrIggeroftheallergIc
response,suchasradIologIcdye.
Cimetidine
CImetIdIneusuallyIsadmInIsteredIn150toJ00mgdosesorallyorparenterally.
AdmInIstratIonofJ00mgofcImetIdIneorally1to1.5hoursbeforesurgeryhasbeenshown
toIncreasethegastrIcfluIdpHabove2.5In80ofpatIents.
88,89
CImetIdInecanbegIven
IntravenouslyforthoseunabletotakeoralmedIcatIons.CImetIdInecancrosstheplacenta,
butadversefetaleffectsareunproved.ThegastrIceffectsofcImetIdInelastaslongasJor
4hours,andthereforethIsdrugIssuItableforoperatIonsofthatduratIon.
CImetIdInehasfewsIdeeffects,buttherearesomeofnote.tInhIbItsthehepatIcmIxed
functIonoxIdaseenzymesystem;therefore,ItcanprolongthehalflIfeofmanydrugs,
IncludIngdIazepam,chlordIazepoxIde,theophyllIne,propranolol,andlIdocaIne.The
clInIcalsIgnIfIcanceofthIsafteroneortwopreoperatIvedosesofcImetIdIneIsuncertaIn.
LIfethreatenIngcardIacdysrhythmIas,hypotensIon,cardIacarrest,andcentralnervous
systemdepressIonhavebeenreportedaftercImetIdIneadmInIstratIon.ThesesIdeeffects
maybeespecIallylIkelytooccurIncrItIcallyIllpatIentsafterrapIdIntravenous
P.591
admInIstratIon.AsdIscussedprevIously,cImetIdInedoesnotaffectgastrIcfluIdalready
present.
Ranitidine
FanItIdIneIsmorepotent,specIfIc,andlongeractIngthancImetIdIne.Theusualoraldose
Is50to200mg.FanItIdIne,50to100mg,gIvenparenterallywIlldecreasegastrIcfluIdpH
wIthIn1hour.tIsaseffectIveInreducIngthenumberofpatIentsatrIskforgastrIc
aspIratIonascImetIdIneandproducesfewercardIovascularorcentralnervoussystemsIde
effects.TheeffectsofranItIdInelastupto9hours.Thus,ItmaybesuperIortocImetIdIne
attheconclusIonoflengthyproceduresInreducIngtherIskofaspIratIonpneumonItIs
durIngemergencefromanesthesIaandextubatIonofthetrachea.
Other Histamine Receptor Antagonists
FamotIdIneIsathIrdH
2
receptorblockerthathasbeengIvenpreoperatIvelytoraIse
gastrIcfluIdpH.tspharmacokInetIcsaresImIlartothoseofcImetIdIneandranItIdIne,
wIththeexceptIonofhavIngalongerserumelImInatIonhalflIfethantheothertwodrugs.
FamotIdIneInadoseof40mgorally1.5toJhourspreoperatIvelyhasbeenshowntobe
effectIveInIncreasInggastrIcpH.NIzatIdIne150toJ00mgorally2hoursbeforesurgery
wIllsImIlarlydecreasepreoperatIvegastrIcacIdIty.
90,91,92
Antacids
AntacIdsareusedtoneutralIzetheacIdIngastrIccontents.AsIngledoseofantacIdgIven
15toJ0mInutesbeforeInductIonofanesthesIaIsalmost100effectIveInIncreasIng
gastrIcfluIdpHabove2.5.ThenonpartIculateantacId,0.J|sodIumcItrate,Iscommonly
gIvenbeforeoperatIonwhenanIncreaseIngastrIcfluIdpHIsdesIred.ThenonpartIculate
antacIdsdonotproducepulmonarydamagethemselvesIfaspIratIonofgastrIcfluId
contaInIngtheseantacIdsshouldoccur.ColloIdantacIdsuspensIonmaybemoreeffectIve
thanthenonpartIculateantacIdsInIncreasInggastrIcfluIdpH.However,aspIratIonof
gastrIcfluIdcontaInIngpartIculateantacIdsmaycausesIgnIfIcantandpersIstentpulmonary
damage,despItetheIncreaseIngastrIcfluIdpH.TheserIouspulmonarysequelaehave
beenmanIfestedIntheformofpulmonaryedemaandarterIalhypoxemIa.
AntacIdsworkatthetImegIven.ThereIsnolagtIme,aswIththeH
2
receptorblockers.
AntacIdsareeffectIveonthefluIdalreadypresentInthestomach.ThIsmakesthem
especIallyattractIveInemergencysItuatIonsforthosepatIentswhoareabletotake
medIcatIonsorally.
However,antacIdsdoIncreasegastrIcfluIdvolume,unlIkeH
2
receptorblockers.
88
TherIsk
ofaspIratIondependsonboththepHandthevolumeofgastrIccontent.TheIncreaseIn
gastrIcfluIdvolumefromantacIdadmInIstratIonmaybecomereadIlyapparentafter
repeateddoses,suchasdurInglabor,durIngwhIchopIoIdadmInIstratIonmayalso
contrIbutetodelayedgastrIcemptyIng.WIthholdIngantacIdsbecauseofconcernabout
IncreasInggastrIcvolumeIsnotwarranted,consIderInganImalevIdencedocumentIng
IncreasedmortalItyafteraspIratIonoflowvolumesofacIdIcgastrIcfluId(0.JmL/kg,pH1)
comparedwIthaspIratIonoflargevolumesofbufferedgastrIcfluId(1to2mL/kg,pH
1.8).
9J
AntacIdsmayslowgastrIcemptyIng,andcompletemIxIngwIthallgastrIccontents
maybequestIonableIntheImmobIlepatIent.TheeffectofantacIdsonfoodpartIcles
wIthInthestomachIsunknown.
Omeprazole
DmeprazolesuppressesgastrIcacIdsecretIonInadosedependentmannerbybIndIngtothe
protonpumpoftheparIetalcell.ForanadultpatIent,Intravenousdosesof40mgJ0
mInutesbeforeInductIonhavebeenused.Draldosesof40to80mgmustbegIven2to4
hoursbeforesurgerytobeeffectIve.EffectongastrIcpHmaylastaslongas24hours.
|uchlIketheotherH
2
receptorantagonIsts,InvestIgatorshavefoundIncreasesIngastrIc
pHandInconsIstenteffectsongastrIcvolumewIthadmInIstratIonofomeprazole.
94,95,96
Gastrokinetic Agents
CastrokInetIcagentsareusefulbecauseoftheIreffectIvenessInreducInggastrIcfluId
volume.
Metoclopramide
|etoclopramIdeIsadopamIneantagonIstthatstImulatesuppergastroIntestInalmotIlIty,
IncreasesgastroesophagealsphInctertone,andrelaxesthepylorusandduodenum.talso
hasantIemetIcpropertIes.|etoclopramIdespeedsgastrIcemptyIngbuthasnoknown
effectonacIdsecretIonandgastrIcfluIdpH.tmaybeadmInIsteredorallyorparenterally.
Aparenteraldoseof5to10mgIsusuallygIven15toJ0mInutesbeforeInductIon.When
thedrugIsadmInIsteredIntravenouslyoverJto5mInutes,Itusuallypreventsthe
abdomInalcrampIngthatcanoccurfrommorerapIdadmInIstratIon.Anoraldoseof10mg
achIevesonsetwIthInJ0to60mInutes.TheelImInatIonhalflIfeofmetoclopramIdeIs
approxImately2to4hours.
TheclInIcalusefulnessofthegastrokInetIcagentsIsfoundInthosepatIentswhoarelIkely
tohavelargegastrIcfluIdvolumes,suchasparturIents,patIentsscheduledforemergency
surgerywhohavejusteaten,obesepatIents,patIentswIthtrauma,outpatIents,andthose
wIthgastroparesIssecondarytodIabetesmellItus.However,ItIsnotrecommendedIn
thosepatIentswIthbowelobstructIon.
However,theadmInIstratIonofmetoclopramIdedoesnotguaranteegastrIcemptyIng.
SIgnIfIcantgastrIcfluIdvolumemaystIllbepresentdespIteItsadmInIstratIon.Theeffect
ofmetoclopramIdeontheuppergastroIntestInaltractmaybeoffsetbyconcomItant
atropIneadmInIstratIonorprIorInjectIonofopIoIds.twIllnotfurtherreducegastrIc
volumeInpatIentsundergoIngelectIvesurgerywIthalreadysmallgastrIcvolumes.tmay
notbeeffectIveafteradmInIstratIonofsodIumcItrate.ncontrast,metoclopramIdemay
beespecIallyeffectIveInreducIngtherIskofaspIratIonpneumonItIswhencombInedwIth
anH
2
receptorantagonIst(e.g.,ranItIdIne)beforeelectIvesurgery.
AsmentIonedprevIously,thedrugsusedtoaltergastrIcfluIdpHandvolumearerelatIvely
freeofsIdeeffects.TherIskbenefItratIoforthesedrugsInreducIngtherIskofpulmonary
sequelaefromaspIratIonIsoftenveryfavorable.ndeed,thedrugsdodecreasethenumber
ofpatIentsatrIsk.However,noneofthedrugsorcombInatIonsofdrugsIsabsolutely
relIableInpreventIngtherIskofaspIratIonpneumonItIsInallpatIentsallofthetIme.
Therefore,theIrusedoesnotelImInatetheneedforcarefulanesthetIctechnIquesto
protecttheaIrwaydurIngInductIon,maIntenance,andemergencefromanesthesIa.
Antiemetics
ThereareseveralgroupsofpatIentsInwhomtheantIemetIceffectsofdrugsmaybe
helpfulInreducIngnauseaandvomItIng.ThesearepatIentsscheduledforophthalmologIc
surgery,patIentswIthaprIorhIstoryofnauseaandvomItIngormotIonsIckness,patIents
scheduledforlaparoscopIcsurgeryorgynecologIcprocedures,andpatIentswhoareobese.
ArIskscoreforpredIctIngpostoperatIvenauseaandvomItIngafterInhalatIonanesthesIa
IdentIfIedfourrIskfactors:femalegender,prIorhIstoryofmotIonsIcknessorpostoperatIve
nausea,nonsmokIng,andtheuseofpostoperatIveopIoIds.TheInvestIgatorssuggested
prophylactIcantIemetIctherapywhentwoormoreoftherIskfactorswerepresentwhen
usIngvolatIleanesthetIcs.0roperIdol,metoclopramIde,ondansetron,anddexamethasone,
sInglyorIncombInatIon,areagentsIncommonusage.
97,98
|anyanesthesIologIstsprefer
nottoadmInIsterantIemetIcsaspartofapreoperatIveregImen,butbelIevethat
antIemetIcsshouldbeadmInIsteredIntravenouslyjustbeforetheyareneededatthe
conclusIonofsurgery.
Anticholinergics
PrevIously,antIcholInergIcdrugswerewIdelyusedwhenInhalatIonanesthetIcsproduced
copIousrespIratorytract
P.592
secretIons,andIntraoperatIvebradycardIawasafrequentdanger.Theadventofnewer
InhalatIonagentshasalmostcompletelydIspelledtheroutIneuseofantIcholInergIcdrugs
forpreoperatIvemedIcatIon.TheIrroutIneusehasbeenquestIonedbyseveralauthorswho
belIevethatthesamecareInselectIonofantIcholInergIcsshouldbeexhIbItedasInthe
choIceofotherdrugs.SpecIfIcIndIcatIonsforanantIcholInergIcbeforesurgeryare(1)
antIsIalagogueeffectand(2)sedatIonandamnesIa(Table2J16).UsesthatarelessfIrmly
establIshedandnotunIversallyagreedonIncludethepreoperatIveprescrIptIonof
antIcholInergIcsfortheIrvagolytIcactIonorInanattempttodecreasegastrIcacId
secretIon.
Table 23-16 Comparison of Some of the Effects of Anticholinergic Drugs
ATROPINE GLYCOPYRROLATE SCOPOLAMINE
ncreasedheartrate +++ ++ +
AntIsIalagogue + ++ +
SedatIon + 0 +++
0,noeffect;+,smalleffect;++,moderateeffect;+++,largeeffect.
AdaptedfromStoeltIngFK:PharmacologyandPhysIologyInAnesthetIcPractIce.
PhIladelphIa,J8LIppIncott,1991.
Antisialagogue Effect
AntIcholInergIcshavebeenprescrIbedInaselectIvefashIonwhendryIngoftheupper
aIrwayIsdesIrable.Forexample,whenendotrachealIntubatIonIscontemplated,an
anesthesIologIstmaywanttoreducesecretIons.nthestudybyFalIckandSmIler,
99
condItIonsweremoreoftenratedassatIsfactoryafterendotrachealIntubatIonwhenan
antIcholInergIcdrughadbeenadmInIstered.
TheantIsIalagogueeffectmaybeImportantforIntraoraloperatIonsandInstrumentatIons
oftheaIrwaysuchasbronchoscopIcexamInatIon.AdmInIstratIonofantIcholInergIcsmay
bedesIrablebeforetheuseoftopIcalanesthesIafortheaIrwaytopreventadIlutIonal
effectofsecretIonsandtoallowcontactofthelocalanesthetIcwIththemucosa.
ScopolamIneIsamorepotentdryIngagentthanatropIne.tIslesslIkelytoIncreaseheart
rateandmorelIkelytoproducesedatIonandamnesIa.ClycopyrrolateIsamorepotentand
longeractIngantIsIalagoguethanatropIne,wIthlesslIkelIhoodofIncreasIngheartrate.
8ecauseglycopyrrolateIsaquaternaryamIne,ItdoesnoteasIlycrossthebloodbraIn
barrIeranddoesnotproducesedatIon.AntIcholInergIcsarenottheonlydrugsthatcandry
secretIons.AsdemonstratedbythestudyofForrest,etal.,
100
severalotherdrugsand
placebo(presumablyareflectIonofapprehensIon)cancauseapatIenttohaveadrymouth
beforeoperatIon.
Sedation and Amnesia
WhensedatIonandamnesIaaredesIredbeforeoperatIon,scopolamIneIsfrequentlythe
antIcholInergIcchosen,especIallyIncombInatIonwIthmorphIne.ScopolamIneand
atropInebothcrossthebloodbraInbarrIer.ScopolamIneIsamuchmorepotentsedatIve
andamnestIcdrugthanatropIne.nastudyofpatIentacceptanceofpreoperatIve
medIcatIon,thecombInatIonofmorphIneandscopolamInewassuperIortothatof
morphIneandatropIne.
101
ScopolamInedoesnotproduceamnesIaInallpatIents.tmay
notbeaseffectIveaslorazepamordIazepamInpreventIngrecall.ScopolamInehasan
addItIveamnestIceffectwhencombInedwIthbenzodIazepInes.ThestudybyFrumIn,et
al.
102
showedthatthecombInatIonofdIazepamandscopolamIneproducedamnesIamore
oftenthandIddIazepamalone.
Vagolytic Action
7agolytIcactIonoftheantIcholInergIcdrugsIsproducedthroughtheblockadeofeffectsof
acetylcholIneonthesInoatrIalnode.AtropInegIvenIntravenouslyIsmorepotentthan
glycopyrrolateandscopolamIneInIncreasIngheartrate.ThevagolytIcactIonofthe
antIcholInergIcdrugsIsusefulInthepreventIonofreflexbradycardIadurIngsurgery.
8radycardIamayresultfromtractIononextraocularmusclesorabdomInalvIscera,from
carotIdsInusstImulatIon,oraftertheadmInIstratIonofrepeateddosesofIntravenous
succInylcholIne.ThepreventIonofreflexbradycardIawIthIntramusculardosesofthe
antIcholInergIcsIsunrelIable,gIventhedrugdosagesandtImIngusuallyInvolvedwIth
preoperatIvemedIcatIonadmInIsteredontheward.|anyanesthesIologIstsprefertogIve
atropIneorglycopyrrolateIntravenouslyjustbeforesurgeryandtheantIcIpated
bradycardIcstImulus.AtropIneandglycopyrrolategIvenIntravenouslyImmedIatelybefore
surgeryhavebeenequallyeffectIveInpreventIngbradycardIaresultIngfromrepeated
dosesofsuccInylcholIne.
Side Effects of Anticholinergic Drugs
ScopolamIneandatropInemaycausecentralnervoussystemtoxIcIty,thesocalledcentral
antIcholInergIcsyndrome.ThIssyndromeIsmostlIkelytooccuraftertheadmInIstratIonof
scopolamIne,butcanbeseenafterhIghdosesofatropIne.Thesymptomsofcentral
nervoussystemtoxIcItyresultIngfromantIcholInergIcdrugsIncludedelIrIum,restlessness,
confusIon,andobtundatIon.ElderlypatIentsandpatIentswIthpaInappeartobe
partIcularlysusceptIble.ThecentralnervoussystemtoxIceffectofantIcholInergIcshas
beennotedtobepotentIatedbyInhalatIonanesthetIcs.TheadmInIstratIonof1to2mgof
physostIgmIneIntravenouslycansuccessfullytreatthesyndrome.
|ydrIasIsandcycloplegIafromantIcholInergIcdrugsIsunwantedInpatIentswIthglaucoma
becauseofresultIngIncreasedIntraocularpressure,whIchseemsunlIkelywIththesmall
dosesusedforpreoperatIvemedIcatIon.AtropIneandglycopyrrolatemaybelesslIkelyto
IncreaseIntraocularpressurethanscopolamIne.npatIentswIthglaucoma,most
anesthesIologIstsfeelsafeIncontInuIngmedIcatIonsforglaucomaupuntIlthetImeof
surgeryandusIngatropIneorglycopyrrolatewhennecessary.
8ecauseantIcholInergIcdrugsblockvagalactIvIty,relaxatIonofbronchIalsmoothmuscle
occursandrespIratorydeadspaceIncreases.ThemagnItudeoftheIncreaseIndeadspace
dependsonprIorbronchomotortone,butIncreasesaslargeas25toJJhavebeen
reported.AntIcholInergIcdrugscausesecretIonstodryandthIcken.ntheory,adoseof
antIcholInergIcdruggIvenbeforeoperatIoncouldleadtoInspIssatIonofsecretIonsandan
IncreaseInaIrwayresIstance.ThethreatofInspIssatedsecretIonsmaydevelopIntomore
thanatheoretIcalIssueforpatIentswIthdIseasessuchascystIcfIbrosIs.
SweatglandsofthebodyareInnervatedbythesympathetIcnervoussystemanduse
cholInergIctransmIssIon.Therefore,admInIstratIonofantIcholInergIcagentsInterferes
wIththe
P.59J
sweatIngmechanIsm,whIchmaycausebodytemperaturetoIncrease.ThIssIdeeffectof
antIcholInergIcmedIcatIonmustbeconsIderedcarefullyInachIldwIthafever.
AtropIneIsmorelIkelythanglycopyrrolateorscopolamInetocauseanIncreaseInheart
rate.UnwantedIncreasesInheartratearemuchmorelIkelyafterIntravenous
admInIstratIonthanafterIntramuscularadmInIstratIon.nfact,heartratemaytransIently
decreaseafterIntramuscularadmInIstratIonasaresultofaperIpheralagonIsteffectofthe
antIcholInergIcagent.
Adrenergic Agonists
2
AdrenergIcagonIstshavebeenusedaspremedIcants.
10J,104
ClonIdIneIndosesof2.5to5
g/kghasbeenadmInIsteredpreoperatIvelytoproducesedatIon,reducemaxImum
allowableconcentratIon,andpreventhypertensIonandtachycardIafromendotracheal
IntubatIonandsurgIcalstImulatIon.thasevenbeenusedaspartofanesthetIctechnIque
toproduceInducedhypotensIon.0exmedetomIdIneIsanother
2
adrenergIcagonIststudIed
forpreoperatIveusetoattenuateIntraoperatIvesympathoadrenalresponses.
10J
Afterthe
admInIstratIonofclonIdInepreoperatIvely,oneIsmorelIkelytoseeepIsodesof
hypotensIonandbradycardIadurInganesthesIawhenthereareperIodsoflIttlesurgIcal
stImulatIon.Furthermore,someanesthesIologIstsaskIfpreoperatIve
2
adrenergIc
agonIstsareasubstItuteforaproperlyconductedanesthetIcIfapproprIateattentIonIs
gIventodepthofanesthesIa.
Other Drugs Given with Preoperative Medications
AlthoughtheyarenotpreoperatIvemedIcatIonsInthestrIctsense,otherdrugsareoften
gIvenatthetImeofpreoperatIvemedIcatIon.ExamplesofsuchdrugsareInsulIn,steroIds,
antIbIotIcs,andmethadoneforpatIentswhoareaddIctedtoopIoIds.Theymaybe
prescrIbedbyeIthertheanesthesIologIstorthesurgeontobegIvenonthewardorInthe
operatIngroomImmedIatelyprIortosurgery.Fegardlessofthesefactors,theIractIonsmay
affecttheanesthetIc,andtheanesthesIologIstmustbeknowledgeableabouttheIr
admInIstratIonandactIons.
Beta-Blockers
ForpatIentswIthknownorsuspectedCA0,preoperatIvebetablockersmayaddtosafetyIn
theperIoperatIveperIod.ClInIcalstudIeshaveshownthatbetablockersInthIssettIng
havereducedmortalItyandtheIncIdenceofnonfatal|aftersurgery.
104
8ecausebenefIt
hasbeenshownwIthseveraldIfferentbetablockers,ItIsprobablyadrugclasseffector
hemodynamIceffectratherthantheresultofemployIngaspecIfIcbetablocker.
ContraIndIcatIonstopreoperatIvebetablockertherapyIncludeknownallergytobeta
blockers,secondorthIrddegreeheartblock,congestIveheartfaIlure,acute
bronchospasm,lowsystolIcbloodpressure(100mmHg),slowheartrate(60beatsper
mInute),andotherhemodynamIcInstabIlIty.|anyclInIcIansuseeItheratenolol(50to100
mgorallydaIly)ormetoprolol(25to50mgorallytwIcedaIly).Theyarechosenbecauseof
theIrlongactIonandrelatIve
1
selectIvIty.
AlthoughshowntobeeffectIveInpatIentswIthIschemIcheartdIseaseperIoperatIvely,the
bestbetablockertoadmInIster,thedose,andtargetheartrateareunknown.AttentIonto
perIoperatIveheartratemaybethemostImportantfactor.CurrentguIdelInesrecommend
thatbetablockersbecontInuedInthosereceIvIngbetablockerstotreatsuchmaladIesas
angIna,symptomatIcarrhythmIas,hypertensIonorforotherIndIcatIons.PerIoperatIve
betablockertherapyshouldbeInItIatedforpatIentsabouttoundergovascularsurgeryat
hIghcardIacrIskduetosIgnsofIschemIaonpreoperatIvetestIng.8etablockersshould
probablybestartedInpatIentsabouttoundergovascularsurgerywhohaveevIdenceof
CA0.
105
ntheambulatorysurgerypopulatIon,currentevIdencedoesnotsupportbetablockadefor
thosenotcurrentlytakIngbetablockersandforwhomlongtermtherapyIs
unwarranted.
106
Althoughunproven,manystrIveforheartratenear60to70beatspermInute,whIle
maIntaInIngasystolIcbloodpressure110mmHg.ThebetablockadeIsusuallymaIntaIned
throughouttheperIoperatIveperIodtoachIevemaxImumeffect.ntravenousmetoprolol
maybegIvenjustprIortosurgeryIfInadequateblockadehasbeenachIevedwIththeoral
medIcatIons.TheoralbetablockersmaybestartedseveraldaysprIortosurgery.
Statins
LIkebetablockers,statIndrugshavebeenrecommendedpreoperatIvelyInpatIentswIth
cardIovasculardIsease.StudIeshaveshownthatstatInscanreducecardIovascular
morbIdItyandmortalIty,havealIpIdlowerIngeffect,enhancenItrIcoxIdemedIated
pathways,reducevascularInflammatIon,andhavedIrectcardIoprotectIveeffects.There
IsasmallrIskofrhabdomyolysIswIthstatIntherapy.
SomehaverecommendedthesemedIcatIonsbegIvenIntheperIoperatIveperIodforthose
wIthCA0.CurrentguIdelInesrecommendcontInuIngstatIntherapyIntheperIoperatIve
perIodforthosealreadytakIngthemedIcatIon.|orestudIesareneededInregardto
InItIatIngstatIntherapypreoperatIvelyInothers.ThereIssomeevIdencethatthIsclassof
drugsmayhavebenefItInthoseundergoIngvascularsurgeryandInthosewIthoneclInIcal
rIskfactorformyocardIalIschemIaabouttoundergoanIntermedIaterIsksurgIcal
procedure.fIndeedstatIntherapyIseffectIvepreoperatIvely,thedose,tImIngof
InItIatIonoftherapy,andthelengthoftherapyareyettobedetermIned.
107,108
Antibiotics
AntIbIotIcsareoftenadmInIstered1hour,15mInutesbeforeoperatIonforcontamInated,
potentIallycontamInated,ordIrtysurgIcalwounds.ProphylactIcantIbIotIcsmaybe
warrantedforcleansurgIcalprocedureswhenInfectIonwouldbecatastrophIc.Dther
InstancesfortheuseofprophylactIcantIbIotIcsIncludeIntheImmunosuppressedpatIent,
Intheaged,orInpatIentstakIngsteroIds.AntIbIotIcsgIvenImmedIatelybeforesurgeryare
alsousedforthepreventIonofendocardItIs.
109
thasbeenestImatedthat60to70of
surgIcalpatIentsreceIveantIbIotIcsjustbeforesurgeryorIntraoperatIvely.AntIbIotIc
admInIstratIoncomesundertheanesthesIologIst'spurvIewbecauseofthedesIretohave
suchagentsgIvenImmedIatelybeforeexposuretopathogens,whIchIsjustbeforethe
begInnIngofsurgery.
CephalosporInsarethemostpopularantIbIotIcsbecausetheycoverthemIcrobesonthe
skIn.ForIntestInalsurgeryanaerobIcandCramnegatIvecoverageIsneeded.TheNatIonal
SurgIcalnfectIonProjectrecommendsthatantIbIotIcsbeadmInIstered1hourprIorto
IncIsIon.
110,111
TherearetwoexceptIonstothIspolIcy:(1)vancomycInshouldbegIven2
hoursprIortoIncIsIon,and(2)whenatournIquetIsused,theantIbIotIcsshouldbe
admInIsteredprIortoItsInflatIon.
ThoseallergIctopenIcIllIn,cephalosporIns,andrelatedcompounds(betalactamallergy)
mayreceIveeIthervancomycInorclIndamycIn.TheoptImaldoseofantIbIotIcsInobese
patIentsIsunderrevIew.ThereIssomequestIonastothedoseneededtoachIeve
adequatetIssuelevelsInmorbIdlyobesepatIents.Furthermore,obesepatIentsmayhave
otherfactorsthatpredIsposethemtoInfectIons,suchasdIabetesmellItus.
Steroids
SteroIdadmInIstratIonmaybenecessaryImmedIatelybeforesurgeryInthepatIenttreated
forhypoadrenocortIcIsmorInthepatIentwIthsuppressIonofthepItuItaryadrenalaxIs
owIngtopresentorprevIousadmInIstratIonofcortIcosteroIds.tIsImpossIbletoIdentIfy
thespecIfIcduratIonoftherapyor
P.594
doseofsteroIdsthatproducespItuItaryandadrenalsuppressIon.|arkedvarIabIlItyamong
patIentsexIsts.CertaInly,moresuppressIonmaybeexpectedwIthahIgherdoseanda
longerduratIonoftherapy.AconservatIveestImateIstoconsIdertreatmentInanypatIent
whohasreceIvedcortIcosteroIdtherapyforatleast1monthInthepast6to12months.
8ecauseofdIseasestatesofthepItuItaryadrenalaxIsorItssuppressIonfromsteroId
therapy,patIentsmaynotbeabletorespondtothestressofsurgery.Thedoseand
duratIonofsupplementalsteroIdadmInIstratIondependonanestImateofthestressofthe
surgIcalprocedureIntheperIoperatIveperIod.DneregImenIstoadmInIster25mgof
cortIsolpreoperatIvelyandthengIveanIntravenousInfusIonof100mgofcortIsoloverthe
next12to24hoursforadultpatIents.AnothermethodIstoadmInIster100mgof
hydrocortIsoneIntravenouslybefore,durIng,andaftersurgery.ThIsdoseIsmeanttoequal
theestImatedmaxImumamountofsteroIdthatstresscouldproduceInpatIents
perIoperatIvely.WhenconsIderIngwhethertoadmInIstersteroIdsorahIgherdoseof
steroIds,theanesthesIologIstshouldkeepInmIndthattherIskbenefItratIoIsusuallyvery
small.
Insulin
See0Iabetes|ellItus.
Opioid Dependency
WIthdrawalproducedbydrugcessatIonIsapreoperatIveIssueInthepatIentwhoIstakIng
methadoneorIsdependentonotheropIoIds.ThereshouldbeanattempttomaIntaIn
opIoIduseattheusuallevelbycontInuIngmethadoneorsubstItutIngotherapproprIate
agentsformethadone.TheanesthesIologIstshouldbecautIonedaboutusIngagonIst
antagonIstdrugsInthesepatIentsInthepreoperatIveperIodforfearofproducIng
wIthdrawal.
Differences in Preoperative Medication Between Pediatric and
Adult Patients
ComparedwIthadults,preoperatIvemedIcatIonsforchIldrenIncludeaspectsof
psychologIcalpreparatIon,theemphasIsonoralmedIcatIonswhenpharmacologIc
preparatIonIsdesIred,andmorefrequentuseofantIcholInergIcsfortheIrvagolytIc
actIvIty.WhatremaInsthesameIstheneedtoassesstheneedsofeachchIldIndIvIdually
andtotaIlorthepsychologIcalpreparatIonandpreoperatIvemedIcatIonaccordIngly.
Psychological Factors in Pediatric Patients
HospItaladmIssIonandmajorsurgerycanproducelonglastIngpsychologIcaleffectsIn
somechIldren.ThehospItalstayIsstressfulandfullofapprehensIonovertheshortterm
foralmostallchIldren.ThedemeanorandcommunIcatIveeffortsoftheanesthesIologIst
canmakeadIfferencetothechIldandfamIlywhoaregettIngreadyforatrIptothe
operatIngroom,anesthesIa,andsurgery.
AgeIsprobablythemostImportantaspectwhenpsychologIcalpreparatIonofthepedIatrIc
patIentIsconsIdered.Ababyyoungerthan6to8monthsofageIsnotemotIonallyupset
whenseparatedfromhIsorhermother.DthersInthehealthcareteamcansubstItutevery
easIly.PreoperatIvepreparatIonInthIsagegroupIsoftendIrectedtowardothergoals,for
example,obtundatIonofvagalreflexresponses.However,preschoolchIldrenareatanage
whenhospItalIzatIonmaybethemostupsettIngandwIllbecomeupsetwhenseparated
fromtheIrparentsandtheyfeartheoperatIngroom.tIsdIffIculttoexplaInthe
forthcomIngeventstochIldrenInthIsagegroup.tIseasIertocommunIcatewIthpatIents
fromage5yearstoadolescence.TheanesthesIologIstcanexplaInandofferreassurance
aboutsuchIssuesasseparatIonfromparentsandthehome,operatIngroomevents,and
anyofthepatIent'sperceIvedfearsofsurgeryandanesthesIa.AdolescentpatIentsmay
alreadybeanxIousandapprehensIve.TheymayalsobeworrIedaboutlossof
conscIousness,haveafearofdeath,orbeapprehensIveaboutwhattheywIlldoorsay
afterpreoperatIvesedatIonordurInganesthesIa.ThemorefearfulchIldmaybedIffIcultto
IdentIfy,butIsusuallythechIldwhoIsquIetdurIngthepreoperatIveIntervIewandappears
nonchalantorevendetached.fthesepatIentscanbeIdentIfIedbeforeoperatIon,theyare
oftencandIdatesforheavypharmacologIcpreparatIon.
Psychological Preparation
FortheprevIouslymentIonedreasons,agoodpreoperatIvevIsItandproperpsychologIcal
preparatIonmaybeevenmoreImportantInchIldrenthanadults.TheartofpsychologIcal
preparatIonthatIsacquIredbytheanesthesIologIstmakesthepreoperatIvevIsItatImeof
reassuranceandexplanatIon.tIsanopportunItytogaInthechIld'strust.|ost
anesthesIologIstswIllwanttoInvolvetheparentswhenpossIble.SomehospItalshave
foundbrochures,motIonpIctures,andslIdeshowstobehelpfulInpreparIngpedIatrIc
patIentsfortheoperatIngroombutarenotunIformlysatIsfactory.ThechIldmaywantto
brIngapersonalbelongIng,suchasastuffedanImalorblanket,totheoperatIngroomfor
securIty.SomechIldrenwIshtotakeanactIverolebydoIngsuchthIngsasholdIngtheface
maskdurIngInhalatIonInductIonofanesthesIa.tmaybehelpfulInacasewIthsupportIve
parentstohavethemaccompanythechIldtotheoperatIngroomsuIteafteran
explanatIonofeventsthatmayoccurdurIngInductIon.TheemphasIsIsonsupportfrom
theparentratherthansImplytheIrpresence.
112
tIscommonInmanyhospItalsfora
parenttogoIntotheoperatIngroomandstayuntIlInductIonIscomplete.
Differences in Pharmacologic Preparation
ThedIscussIonofpharmacologIcpreparatIonforthepedIatrIcpatIentpresumesproper
psychologIcalpreparatIon,asatIsfactoryoperatIngroomenvIronment,andpreparatIonfor
aneffIcIentandtImelyInductIonofanesthesIa.
SedativeHypnotics
AsInadults,thesedatIvehypnotIcmedIcatIonsareusedtoreduceapprehensIon,produce
sedatIonandamnesIa,andtofacIlItatesmoothInductIonofanesthesIawhenanInhalatIon
methodIstobeused.TheuseofpreoperatIvemedIcatIonIscontroversIalInpedIatrIc
patIentsandmaynotbecompletelysuccessfulInasmanyas20ofInstances.
11J
thasnot
beenprovedtoreduceunwantedpsychologIcaloutcomeaftersurgeryandanesthesIa.
NeItherhasItbeenshownthattheuneventfulInductIonofanesthesIaIslesslIkelyto
producelonglastIngpsychologIcalproblemsInchIldren.After6monthsto1yearofage,
thechIldscheduledforasurgIcalproceduremaybenefItfromasedatIvehypnotIcdrug
beforesurgery.ThereIsemphasIsonavoIdIngIntramuscularInjectIonsInchIldren.Theoral
routeIsoftenpreferredforpreoperatIvemedIcatIonIntheolderchIld,whereasIn
preschoolchIldrendrugsmayalsobegIvenrectally.|anydIfferentsedatIvehypnotIcdrugs
vIadIfferentroutes(oral,Intranasal,andrectal)havebeenprescrIbedforchIldrenbefore
operatIon.|Idazolam
P.595
canbegIvenIntramuscularly(0.05to0.2mg/kg).However,themostcommon,effectIve
andacceptablerouteformIdazolamIstheoralrouteatadoseof0.5to0.75mg/kg(FIg.
2J8).
114,115
ThecherryflavoredoralpreparatIonIsacceptabletomostchIldren.tIs
effectIveInproducIngsedatIonandcomplIance,butnotusuallysleep,Inabout15mInutes
andlastsforJ0to60mInutes.DralketamIne(5to10mg)hasbeenprescrIbed20toJ0
mInutesbeforeInductIon.AlthoughoftenallowIngsmoothseparatIonfromparents,oral
secretIonsandpreoperatIveorpostoperatIvedelIrIumcanbeproblems.ntramuscular
ketamIne(5to10mg/kg)canbepartIcularlyhelpfulIntheextremelyrecalcItrantor
combatIvechIld.8othketamIne(Jto8mg/kg)andmIdazolam(0.2mg/kg)canbegIven
usInganasalatomIzer,wIththecaveatthatIrrItatIonofthenasalcavItyandbItter
aftertastearedIsadvantageous.KetamIne(5mg/kg)andmIdazolam(0.Jto1.0mg/kg)
havealsobeengIvenrectallybeforeInductIonofanesthesIa.AfurtheroptIonInthe
pharmacologIcpreparatIonofchIldrenIstherectaladmInIstratIonofmethohexItal(FIg.2J
9).|ethohexItal(20toJ0mg/kg)maybegIvenImmedIatelybeforeoperatIon,usIngpulse
oxImetryandwhIlethechIldIsstIllIntheparent'sarms.TheIntramuscularrouteIsalso
possIble.
Figure 23-8.PercentageofpatIentsexhIbItInganxIetyfrombaselInetotImeafteroral
mIdazolam.TherewasaposItIveassocIatIonbetweendoseandonsetofanxIolysIs(p=
0.01);alargerproportIonofchIldrenachIevedsatIsfactoryanxIolysIswIthIn10mInutes
atthehIgherdoses.(FeprIntedfromCotCJ,CohenT,SureshS,etal:AcomparIson
ofthreedosesofacommercIallypreparedoralmIdazolamsyrupInchIldren.Anesth
Analg2002;94:J7,wIthpermIssIon.)
Opioids
ThereIstheoccasIonalneedforopIoIdpremedIcatIonInchIldren.|ethadonehasthe
advantageoforaladmInIstratIon,usuallyprescrIbedInthe0.1to0.2mg/kgdoserange.
TransmucosaladmInIstratIonoffentanyl(5to20g/kg)appearstobeeffectIveIn
producIngsedatIonpreoperatIvely.However,transmucosalfentanylmayIncreasegastrIc
fluIdvolumeandalsoIncreasetheIncIdenceofrIgIdIty,respIratorydepressIon,prurItus,
nausea,andvomItIng.
68
Fentanyl(2g/kg)andsufentanIl(J.0g/kg)gIvenbythe
IntranasalroutehavebeenshowntocalmpedIatrIcpatIentspreoperatIvely.AgaIn,
postoperatIvenauseaandvomItIng,InaddItIontorespIratorycomplIcatIons,haveresulted
InlackofenthusIasmforthIstechnIque.
ForInformatIononanesthesIaforambulatorysurgery,seeChapterJ2.
Figure 23-9.FrequencydIstrIbutIonofsleepInductIontImesafterrectalInstIllatIonof
methohexItal.PatIentsaveragedJ.JyearsInageand15kgInbodyweIght.(FeprInted
fromLIuL|P,CoudsouzIanNC,LIuPL:FectalmethohexItalpremedIcatIonInchIldren,
adosecomparIsonstudy.AnesthesIology1980;5J:J4J,wIthpermIssIon.)
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1992;69:404
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Stock, M. Christine
TableofContentsSectIon7PreanesthetIcEvaluatIonandPreparatIonChapter24|alIgnantHyperthermIaAnd
DthernherIted0Isorders
Chapter24
Malignant Hyperthermia And Other Inherited
Disorders
Henry Rosenberg
Barbara W. Brandom
Nyamkhishig Sambuughin
Key Points
1. Malignant hyperthermia syndrome (MH) is an uncommon
pharmacogenetic disorder of skeletal muscle. MH susceptibility is
inherited. MH is induced by pharmacologic agents in almost all cases.
A few well-documented cases have resulted from exercise and heat
exposure. The increase in metabolism that is pathognomonic of MH is
due to the biochemical effect of uncontrolled, increased calcium in
muscle sarcoplasm.
2. Unexpected elevation of end-tidal carbon dioxide in the absence of
equipment malfunction is the most sensitive and specific sign of MH.
Other signs include tachycardia, tachypnea, acidosis, muscle rigidity,
and sometimes rhabdomyolysis. MH may occur at any time in the
course of an anesthetic from induction to emergence.
3. Masseter muscle rigidity after succinylcholine is more common in
children than adults. It is predictive of MH susceptibility in up to 25%
of cases and is associated with myoglobinuria. Trigger agents should
be discontinued after masseter muscle rigidity. With generalized
rigidity the likelihood of MH is very high.
4. Sudden cardiac arrest in a young male during general anesthesia,
with or without succinylcholine, is likely a result of hyperkalemia in a
patient with an occult myopathy, most often Duchenne muscular
dystrophy.
5. Disorders that predispose patients to MH include central core disease,
multiminicore disease, and rarer forms of myotonia.
6. Trigger agents for MH include all potent inhalation agents and
succinylcholine.
7. The gold standard test for diagnosis of MH susceptibility is the
caffeine-halothane contracture test (of freshly biopsied muscle)
wherein muscle is exposed to incremental doses of caffeine or to
halothane. See www.mhaus.org for the addresses of MH diagnostic
centers.
8. The essential points in treatment of MH are the immediate
discontinuation of trigger agents, hyperventilation, administration of
dantrolene in doses of 2.5 mg/kg, repeated as needed to control
signs of MH, and cooling by all routes available (especially nasogastric
lavage), treatment of hyperkalemia in a standard fashion. Following
an MH episode the patient should be observed in a hospital and
treated with dantrolene for at least 36 hours.
9. To minimize injury from MH it is necessary to monitor core body
temperature and end-tidal CO
2
along with minute ventilation during
general anesthesia, have dantrolene immediately available, obtain a
thorough personal and family history related to anesthetic
complications, and avoid MH trigger agents in susceptible patients
and their relatives.
10. MH susceptibility is inherited in an autosomal dominant pattern in
humans. MH has been associated with mutations in three genes,
most frequently the ryanodine receptor gene (RYR1), rarely the
dihydropyridine receptor gene, and the gene that elaborates the
sodium channel of muscle. In humans, over 28 mutations in RYR1
have been found to be causal for MH. These RYR1 mutations increase
the sensitivity of the ryanodine receptor calcium channel to agonists,
leading to increased calcium release from the sarcoplasmic reticulum.
There are over 150 DNA variants in RYR1 whose significance in
regard to MH susceptibility is yet to be determined.
11. Molecular genetic testing for MH susceptibility, using examination of
part of RYR1, is available in the United
P.599
States, Europe, and several other countries. Genetic testing may be
recommended for those with positive caffeine halothane contracture
test results and a confirmed MH episode in a family member. Despite
low sensitivity, approximately 25%, many patients were able to be
diagnosed as being MH-susceptible without resorting to the muscle
contracture test.
|anyInherIteddIsordershavesIgnIfIcantImplIcatIonsforanesthetIcmanagement.nthIs
chapterwedIscussthosedIsordersthatareprecIpItatedbydrugsoftenadmInIsteredby
anesthesIologIsts.nsomecases,suchastheporphyrIas,theIllnessmaybeInducedby
agentsotherthananesthetIcs.notherenzymatIcdIsorders,suchaspseudocholInesterase
abnormalItIes,ItwouldbeunlIkelyforapatIenttohaveanyproblemuntIlexposedtothe
depolarIzIngneuromuscularblockIngagentsuccInylcholIne.|alIgnanthyperthermIa(|H)
ormalIgnanthyperpyrexIaIsperhapsthemostsIgnIfIcantInherIteddIsordertrIggeredby
exposuretoanesthetIcdrugs.
Malignant Hyperthermia
Historical Aspects
|HwasfIrstformallydescrIbedIn1960InLancetby0enboroughandLovell.
1
ThatfIrstcase
descrIbedwelltheclInIcalpresentatIonof|H.TheyoungpatIentclaImedthatseveralof
hIsrelatIvesdIedwIthoutapparentcausedurInganesthesIa.HewasanesthetIzedwIth
halothaneanddevelopedtachycardIa,hotsweatyskIn,perIpheralmottlIng,andcyanosIs.
EarlyrecognItIonandsymptomatIctreatmentsavedhIm.ThIsnewsyndromewasunIque:
patIentswerehealthyunlessexposedtoanesthesIa,temperatureelevatIonwasahallmark,
aherItablecomponentwaspresent,anddeathwascommon.twassoonrealIzedthatIt
waspossIbletoabortthemalIgnanteffectsofthesyndromewIthearlyrecognItIonand
treatment.
TheassocIatIonbetweenporcInestresssyndrome(PSS)orpalesoftexudatIvepork
syndromeand|HwasdescrIbedIntheearly1970s,thusprovIdIngananImalmodelfor
|H.
2
.PorcInebreedssuchastheLandrace,PolandChIna,andPIetraInshowtheclassIc
presentatIonsof|HwhenpotentInhalatIonagentsand/orsuccInylcholIneare
admInIstered.ThedevelopmentofanInvItrodIagnostIcbIoassayofmusclewassuggested
byKalowetal.
J
n1975,HarrIson
4
reportedthatdantrolenecouldbeeffectIveIntreatIng
andpreventIng|HInpIgs.n1979IntravenousdantrolenewasapprovedbytheU.S.Food
and0rugAdmInIstratIonfortreatmentofthehumanformof|H.nthe1980s,lay
organIzatIonsIntheUnItedStates,Canada,andCreat8rItaInwereformedtodIssemInate
InformatIontopatIentsaffectedby|HaswellastoIncreaseawarenessofthesyndrome
amongphysIcIans.ThemusclebIoassay,thedIagnostIchalothanecaffeInecontracturetest,
wasstandardIzedbyworkfromtheNorthAmerIca|HFegIstry,createdIntheUnIted
StatesInthelate1980s.AvarIetyofothertestsfordIagnosIng|HsusceptIbIlItywere
Introduced,whIchsubsequentlywerefoundtohavelIttlevalIdIty.
AmajorstepforwardIntheunderstandIngofthepathophysIologyof|HoccurredIn1985,
whenLopezandcolleagues
5
demonstratedIncreasedIntracellularconcentratIonofcalcIum
IonInmusclefrom|HsusceptIblepIgsandhumans.TheIntracellularcalcIum
concentratIondramatIcallyIncreaseddurIngan|HcrIsIsandwasreversedbythe
admInIstratIonofdantrolene.
nthe1990smolecularbIologIctechnIquesIdentIfIedgenesassocIatedwIth|H
susceptIbIlIty.ThIsallowed,In200J,theIntroductIonofaclInIcallyusefulgenetIctestfor
|H,althoughwIthlImItedsensItIvIty.Later,|HcausatIvemutatIonswereIntroducedIn
mIcewhothendIsplayedclInIcalsIgnsof|HonexposuretotrIggeragentsandheat.
6,7
AnalysIsofepIdemIologIcdatagatheredbythe|alIgnantHyperthermIaAssocIatIonofthe
UnItedStates(|HAUS)IntheNorthAmerIcan|HFegIstryledtodIfferentIatIonbetween
|HandsomeotherlIfethreatenInganesthetIccomplIcatIons.npartIcular,somedeathsIn
chIldrenformerlyattrIbutedto|HwerereallytheresultofdestructIonofmusclecellsthat
occurreddurInganesthesIawIthvolatIleagentsandsuccInylcholIneInpatIentswIth
unrecognIzedmyopathIes,specIfIcallythedystrophInopathIesand0uchenneand8ecker
musculardystrophy.
8
Clinical Presentations
AsunderstandIngof|Hgrew,thedefInItIonof|Hchanged.AtfIrst,|HwasthoughtInall
casestobeaherItablesyndromeconsIstIngofanextremelyelevatedbodytemperature,
skeletalmusclerIgIdIty,andacIdosIsassocIatedwIthahIghmortalItyrate.However,ItIs
moreusefultothInkof|HIntermsofItsunderlyIngpathophysIologIccharacterIstIcs
becauserecognItIonof|HprIortohyperthermIawIllfacIlItatetreatment.|HIsa
hypermetabolIcdIsorderofskeletalmusclewIthvarIedpresentatIons,dependIngon
specIes,breed,exposuretotrIggerIngagents,andgenetIcmakeupoftheIndIvIdual.The
pathophysIologIcprocessInthIsdIsorderIsIntracellularhypercalcemIaInskeletalmuscle,
whIchactIvatesmetabolIcpathwaysresultIngInadenosInetrIphosphate(ATP)depletIon,
acIdosIs,membranedestructIon,andcelldeath.TheherItablecomponentIsnotalways
apparentfromfamIlyhIstoryunlessthereIsahIstoryofanesthetIcproblemssuggestIveof
thesyndrome.0IsordersthatmayhavesymptomsandsIgnssImIlartothoseof|H,suchas
neuroleptIcmalIgnantsyndrome(N|S),andheatstrokedonotappeartohaveanInherIted
basIs.
Classic Malignant Hyperthermia
ntheclassIccase,theInItIalsIgnsoftachycardIaandtachypnearesultfromsympathetIc
nervoussystemstImulatIonsecondarytounderlyInghypermetabolIsmderIvedprImarIly
fromtheskeletalmuscle.8ecausemanypatIentsreceIveneuromuscularblockersand
controlledventIlatIondurInggeneralanesthesIa,tachypneausuallyIsnotrecognIzed.
ShortlyaftertheIncreaseInheartrate,anIncreaseInbloodpressureoccurs,often
assocIatedwIthventrIculardysrhythmIasInducedbysympathetIcnervoussystem
stImulatIonresultIngfromhypercarbIa,hyperkalemIa,andorcatecholamInerelease.An
IncreaseInmuscletonemay(ormaynot)becomeapparent.ncreaseInbodytemperature,
atarateof1to2`Cevery5mInutes,follows.CD
2
absorbentbecomeswarmtothetouch
(becausethereactIonwIthCD
2
IsexothermIc).ThepatIentmaydIsplayperIpheral
mottlIng,sweatIng,andcyanosIs.8loodgasanalysIsrevealsrespIratoryand/ormetabolIc
acIdosIswIthoutmarkedoxygendesaturatIon.
ElevatIonofendtIdalCD
2
IsoneoftheearlIest,mostsensItIveandspecIfIcsIgnsof|H.
However,vIgoroushyperventIlatIonmaymasksuchhypercarbIaanddelaythedIagnosIs.
9
A
mIxedvenousbloodsamplewIllshowevenmoredramatIcevIdenceofCD
2
retentIonand
metabolIcacIdosIs.
10
HyperkalemIa,hypercalcemIa,lactacIdemIa,andmyoglobInurIaare
characterIstIc.AnIncreaseIncreatInekInase(CK)levelsIsdramatIc,oftenexceedIng
20,000unItsInthefIrst12to24hours.8utIncreasedCKIsnotaconstantfeature,
partIcularlyIfthesyndromeIsdetectedpromptlyandtreatmentbegunrapIdly.
11
0eath
resultsunlessthesyndromeIsrecognIzedandtreated
P.600
promptly.EvenwIthtreatment,thepatIentIsatrIskformyoglobInurIcrenalfaIlureand
dIssemInatedIntravascularcoagulatIon.AnothersIgnIfIcantclInIcalproblemIsa25
recrudescencerateofthesyndromewIthInthefIrst24toJ6hours.
12,1J
fsuccInylcholIneIs
useddurIngInductIonofanesthesIa,anacceleratIonofthemanIfestatIonsof|Hmayoccur
wIthtachycardIa,hypertensIon,markedtemperatureelevatIon,anddysrhythmIasoverthe
courseof5to10mInutes.However,acompletelynormalresponsetosuccInylcholInedoes
notruleoutthesubsequentdevelopmentof|HwhenpotentvolatIleagentsareused.
Masseter Muscle Rigidity
FIgIdItyofthejawmusclesafteradmInIstratIonofsuccInylcholIneIsreferredtoas
masseter muscle rigidity(||F)ormasseter spasm.ThIsphenomenonwasassocIatedwIth
|Hfromcasereportsof||FprecedIng|H.Although||FprobablyoccursInpatIentsof
allages,ItIsmorecommonInchIldrenandyoungadults.AretrospectIvestudyfromthe
0anIsh|alIgnantHyperthermIaFegIstryfoundthattheIncIdenceof||Fwas1In12,000
(IncludIngadultsandchIldren).
14
AprospectIvestudyfound||FIn1of500apparently
normalchIldrenwhoreceIvedhalothaneandthenIntravenoussuccInylcholIne.
15
nmost
casesof||F,anesthesIawasInducedbyInhalatIonofhalothaneorsevoflurane,after
whIchsuccInylcholInewasadmInIstered.Althoughlesscommon,||Fmayfollow
succInylcholIneadmInIstratIonafterIntravenousInductIon.
16
||Fmayevenoccurafter
InductIonwIthanyanesthetIcagent,IntravenousorInhalatIon,beforesuccInylcholIne
admInIstratIon.
17
FepeatdosesofsuccInylcholInedonotrelIeve||Fnordo
nondepolarIzIngrelaxants.AperIpheralnervestImulatorusuallyrevealsflaccIdparalysIs.
fgeneralIzedrIgIdItyIsnoted,thelIkelIhoodof|HsusceptIbIlItyIsveryhIgh.TachycardIa
anddysrhythmIasarenotInfrequent.DnlyInaboutJ0ofcasesdoesfrank|Hsupervene
ImmedIatelyafter||F.|orecommonly(IftheanesthetIcIscontInuedwIthatrIggerIng
agent),theInItIalsIgnsof|HappearIn20mInutesormore.However,astudybyLIttleford
etal.
18
hasshownthatalthoughacIdosIsandrhabdomyolysIsmaybepresentwhen
anesthesIaIscontInuedwIthavolatIleInhalatIonagentInchIldrenafter||F,fulmInant
|Hmaynotoccur.ftheanesthetIcIsdIscontInued,thepatIentusuallyappearstorecover
uneventfully.However,wIthIn12hours,myoglobInurIaoftenoccursandCKelevatIonIs
detectable.Therefore,If||Foccurs,urIneshouldbeexamInedformyoglobIn.PatIents
experIencIng||FshouldbehospItalIzedforatleast24hours.
|usclebIopsywIthcaffeInehalothanecontracturetestInghasshownthatmanypatIents
whoexperIence||FarealsosusceptIbleto|H.
19,20
8utreportshavealsoshownthat
succInylcholIneIncreasesjawmuscletoneInpatIentswIthnormalmuscle.
21,22,2J
ThIs
normalagonIstIceffectofsuccInylcholIne,furtherIncreasedbytemperature
24
and
epInephrIneInthepresenceofhalothane,accountsforsomecasesof||F.When||FIs
accompanIedbyrIgIdItyofchestorlImbmuscles,|HIsmorelIkelytofollowthanafter
IsolatedjawrIgIdIty.
25,26
ThedIfferentIaldIagnosIsof||FconsIstsofthefollowIng:(1)myotonIcsyndrome,(2)
temporomandIbularjoIntdysfunctIon,(J)underdosIngwIthsuccInylcholIne,(4)notallowIng
suffIcIenttImeforsuccInylcholInetoactbeforeIntubatIon,(5)IncreasedrestIngtensIon
aftersuccInylcholIneInthepresenceoffeverorelevatedplasmaepInephrIne,and(6)|H.
SIgnsoftemporomandIbulardysfunctIonaswellasmyotonIashouldbesoughtfollowIngthe
||FepIsode.frIgIdItyprecludInglaryngoscopyoccurredwIthouttemporomandIbularjoInt
dysfunctIon,thepatIentshouldbeevaluatedbyaneurologIstforthepresenceofoccult
myopathyandcounseledregardIngtheneedforamusclebIopsywIthdIagnostIc
contracturetesttoevaluate|HsusceptIbIlIty.tIsIncumbentontheanesthesIologIstto
alertthepatIenttothepossIbIlItythat|HmayfollowInsubsequentprocedures.
DuradvIceregardIng||FIsasfollows:
1. WhenItoccurs,theanesthesIologIstshould,IfatallpossIble,dIscontInuetheanesthetIc
andpostponesurgery.fendtIdalCD
2
monItorInganddantroleneareavaIlableandthe
anesthesIologIstIsexperIencedInmanagIng|H,heorshemayelecttocontInuewItha
nontrIggerInganesthetIc.
2. 0antroleneadmInIstratIonIsadvIsedonlyIfthereIsgeneralIzedrIgIdItyand/orsIgnsof
hypermetabolIsm.
J. After||F,thepatIentshouldbeadmIttedtothehospItalforaperIodof12to24hours
wIthmonItorIngformyoglobInurIaandsIgnsof|H.AdmInIstratIonof1to2mg/kgof
dantroleneshouldbeconsIdered.
4. ThefamIlyshouldbeInformedoftheepIsodeof||FandItsImplIcatIons.
5. CKlevelsshouldbechecked6,12,and24hoursaftertheepIsode.ftheCKlevelIsstIll
grosslyelevatedat12hours,addItIonalsamplesshouldbedrawnuntIlCKreturnsto
normal.
6. ftheCKlevelIs20,000UIntheperIoperatIveperIodandaconcomItantmyopathyIs
notpresent,thedIagnosIsof|HIsverylIkely.
25,27
fcontracturetestresultsarewIthIn
normallImItsafteranepIsodeof||F,wecurrentlydonotrecommendthatotherfamIly
membersundergotestIng,butadvIsethatsuccInylcholInebeavoIdedInfuture
anesthetIcsforthatpatIent.
Variations in Presentation of Malignant Hyperthermia
TherearealargenumberofvarIatIonsInthepresentatIonof|H.SomepatIentsmay
undergomultIpleanesthetIcsbeforeexperIencIng|H.SImIlarly,|Hmaypresentafter
severalhoursofanesthesIaorrarelyIntheearlypostoperatIveperIod,wIthIn1hourof
dIscontInuInganesthesIa.nsomecasesrIgIdItyIsnotfoundatall,andInothers
temperatureelevatIonIsunImpressIve.nterestIngly,postoperatIvemyoglobInurIamaybe
theonlysIgnof|HandmayoccurwIthoutanobvIousIncreaseInmetabolIsm.
28
However
thedIfferentIaldIagnosIsofpostoperatIvemyoglobInurIaIslarge.SuccInylcholInemay
causerhabdomyolysIsInpatIentswhohaveothermuscledIsordersthatmaynotbe
clInIcallyobvIousoncursoryexamInatIon.
8,29
|yoglobInurIamayfollowsuccInylcholIneIn
patIentswhoaretakIngInhIbItorsofcholesterolformatIonInpatIentswIthapparently
normalmuscle.
J0
CrossmyoglobInurIa(darkorcolacoloredurIne)IsserIous,asrenalfaIlureIslIkely.The
patIentshouldbeevaluatedandtreatmentbegunwIthIntravenousfluIdsandpossIbly
mannItolandbIcarbonatetoavoIdrenalInjury.UrInedIpstIckcanbeusedtoscreenfor
myoglobInurIa.fthedIpstIckIsnegatIveforblood,thenthereIsnomyoglobInpresent.f
thereIsastrongposItIvereactIonforbloodandnoredbloodcellsareseen
mIcroscopIcally,thenmyoglobInurIaIslIkelyandconfIrmatorytestsIndIcated.
Myodystrophies Exacerbated by Anesthesia
Duchenne muscular dystrophy(0|0)occursIn1InJ,000males.8oysareusually
asymptomatIcuntIltheageof4or5years,butelevatedCKIsaconstantfIndIngfrom
bIrth.0ystrophInIsamajorelementInthedystroglycancomplexthatprovIdesstabIlItyto
themusclecellmembrane.Becker dystrophy,anorderofmagnItudelesscommonthan
0uchennemusculardystrophyIsduetolowerthannormallevelsofdystrophInandoften
doesnotproducesymptomsuntIladolescence.AnypatIentwIthdystrophinopathymay
experIencehyperkalemIccardIacarrestafteradmInIstratIonofsuccInylcholIne.
P.601
ThesamemayoccurfollowIngadmInIstratIonofvolatIleanesthetIcagentsonly.
J1
These
adverseeventswerefIrstbelIevedtorepresentaformof|H.
J2,JJ
tnowappearsthatthe
pathophysIologyofthehyperkalemIcepIsodesand|HIsdIfferent.Casereportscollected
bythe|HAUSandtheNorthAmerIcan|HFegIstryIndIcatethatwhenanapparently
healthychIldexperIencesasuddenunexpectedcardIacarrestonInductIonofanesthesIa,
oncehypoxemIaandventIlatoryproblemsareruledout,hyperkalemIashouldbe
consIdered.Df29patIentswIthsuchapresentatIon,60dIed.n50therewasevIdenceof
undIagnosedmyopathy(usuallymusculardystrophy).
8
ThetreatmentofthehyperkalemIc
arrestIncludesadmInIstratIonofcalcIumchlorIde,glucose,InsulIn,bIcarbonate,and
hyperventIlatIon,butnotdantrolene.
8ecauseofthepotentIallyfatalhyperkalemIceventInpatIentswIthundIagnosed
myopathy,succInylcholIneshouldnotbeusedroutInelyInchIldrenandyoungadolescents.
Dfcourse,InspecIalcIrcumstances,suchasaIrwayemergencIesandthepresenceofafull
stomach,succInylcholInemaystIllbeapproprIateInchIldrenwIthoutsIgnsofamyopathy.
However,admInIstratIonofrapIdactIngnondepolarIzIngneuromuscularblockersInthese
sItuatIonsmaybeanapproprIatealternatIvetouseofsuccInylcholIne.
ncontrasttodystrophInopathIes,congenItalmyopathIesareaheterogeneousgroupof
dIseasesdefInedhIstopathologIcally,wIthIncIdenceofapproxImately1In16,500bIrths.
J4
ThereIsmarkedphenotypIcvarIabIlItyaswellasgenetIcandhIstologIcoverlapbetween
thesecondItIons;central core disease(CC0),nemaline myopathy,multiminicore disease,
J5
andcentronuclear myopathy.CC0,themostcommoncongenItalmyopathy,IsdefInedby
muscleweaknessthathasavarIableonsetandprogressIon.ThesyndromederIvesItsname
fromthehIstologIcappearanceofreducedoxIdatIveactIvItyInareasalongthe
longItudInalaxIsofthefIber.ThesearethehIstologIccentralcores,whIchmaynotbe
presentatayoungage.AmongCC0patIentsthereIssIgnIfIcantvarIabIlItyInmuscle
weakness,evenwIthInaffectedfamIlIes,butweaknessusuallyInvolvesthespIneand
pelvIs.FootdeformItIesandpatellarInstabIlItyarecommon.CC0IsgenerallyInherItedIn
anautosomaldomInantmannerlInkedwIthRYR1mutatIons.|anycasesof|Hhavebeen
reportedInpatIentswIthCC0.Therefore,precautIonsregardIng|Hmustbetakenforall
patIentswIthCC0.
J4
FecessIveInherItanceofRYR1mutatIonshasbeenreportedInafew
patIentswIthcongenItalmyopathy
J6
andmulItmInIcores
J5
orcentralnucleI.|HepIsodes
werereportedInonly4of28suchpatIents,butexposuretoanesthetIc|HtrIggerswasnot
descrIbed.
J7
Myotoniasandperiodic paralysesareavarIedsetofInherIteddIsordersduetopoInt
mutatIonsInanIonchannel.|utatIonsInthehumanskeletalmusclesodIumchannel
producehyperkalemIcperIodIcparalysIs,potassIumaggravatedmyotonIa,paramyotonIa
congenItal,andhypokalemIcperIodIcparalysIstype2.HypokalemIcperIodIcparalysIsIs
duetopoIntmutatIonsInthecalcIumchannel.|yotonIacongenItaIscausedbymutatIons
InthechlorIdechannel.
J8
ThecommonpathophysIologIcprocessIsprolonged
depolarIzatIonofthemusclemembranefollowIngactIvatIon.PatIentswIthanyformof
myotonIawIlldIsplaymusclecontracturesaftersuccInylcholIne.HypokalemIcperIodIc
paralysIsandarareformofmyotonIa,myotonIafluctuans,havebeenlInkedto|H
susceptIbIlItybythehalothanecaffeInecontracturetest.
J9,40
PerIodIcparalysesare
characterIzedbymarkedmuscleweaknessresultIngfromsmalldevIatIonsInpotassIum
concentratIons.KingorKing-DenboroughsyndromeIsararemyopathycharacterIzedby
cryptorchIdIsm,markedlyslantedeyes,lowsetears,pectusdeformIty,scolIosIs,small
stature,andhypotonIa.ThIssyndromewasassocIatedwIth|HsoonaftertheorIgInal
descrIptIonof|H.SeveralpatIentswIththIsdIsorderhavebeendIagnosedas|H
susceptIblebothclInIcallyandbymusclebIopsy.
41,42
SkeletalabnormalItIessuchasosteogenesIsImperfecta
4J
andtheSchwartzJampel
44
syndromehavebeenassocIatedwIthsIgnsof|H.|etabolIsmIsIncreasedInosteogenesIs
ImperfectabecauseofthebonedIseasewIthoutexposuretodrugs.FeverdurInganesthesIa
IscommonInthesepatIents.
45
TheSchwartzJampelsyndromeIsanautosomalrecessIve
myotonIclIkecondItIonwIthosteoartIculardeformItIes.nsomepatIentsthereIsan
abnormalItyofmuscle;Inothers,aneurologIcabnormalItyIspresentandthesymptoms
canbeblockedbynondepolarIzIngneuromuscularblockers.FeverIscommonInthese
patIentsbecauseofcontInuousmuscleactIvIty.nboththesecondItIons,assocIatIonwIth
|HIsunlIkely.0espIteafewwelldocumentedcasesof|HInpatIentswIthosteogenesIs
Imperfecta,we(andothers
46
)havenotconfIrmed|HsusceptIbIlItyInthreecasesof
osteogenesIsImperfectatestedwIththehalothanecaffeInecontracturetest.nhalatIon
anesthetIcshavebeenadmInIsteredwIthoutcomplIcatIontomanypatIentswIth
osteogenesIsImperfecta.
Syndromes with a Clinical Resemblance to Malignant
Hyperthermia
PheochromocytomamaybemIstakenfor|HbecauseItpresentswIthtachycardIa,
hypertensIon,andfeverdurInganesthesIa.However,pheochromocytomadoesnot
predIsposeto|H.
47
ThyrotoxicosiscouldalsobemIstakenfor|H.CarbondIoxIde
productIonIslowerIntheseendocrInedIsordersthanIn|H.HypertensIonIsusuallygreater
InpheochromocytomathanInthyrotoxIcosIs,andevenlessIn|H.NeItherendocrInecrIsIs
IsassocIatedwIthmusclerIgIdIty,asIs|H.|etabolIcacIdosIsIsgenerallynotpresent
durIngthyrotoxIcosIsandnotasgreatdurIngpheochromocytomaasdurIng|H.ThyroId
crIsIsdIdnottrIgger|H,wIthoutexposuretoanesthetIctrIggers,evenInsusceptIble
pIgs.
48
SepsisIsoftenconfusedwIth|H.PatIentsmostatrIskarethoseundergoIngurInarytract
surgery,oralsurgery,orappendectomy.TheyareafebrIleIntraoperatIvelybutdevelop
fever,rIgors(whIchmaybemIstakenfor|HrelatedrIgIdIty),andsometImesacIdosIsIn
thepostanesthesIacareunIt.HyperkalemIamayalsoappeardurIngepIsodesofsepsIs.
UnlIke|H,however,persIstentmusclerIgIdItyIsrare.naddItIon,sIgnsofsepsIsmaybe
treatedeffectIvelywIthnonsteroIdalantIInflammatoryagents,antIbIotIcs,and
cardIovascularsupport.|HwIllnotrespondtosuchnonspecIfIctherapy.0antrolene
admInIstratIonInthepresenceofsepsIsmaybefollowedbyacutereductIonoffever
becausedantrolenereducesthemetabolIsmofnormalmuscle.
Hypoxic encephalopathyIscharacterIzedbyfaIluretoawakenfromanesthesIa,posturIng,
opIsthotonus,andhyperthermIa.thasbeenmIstakenfor|H.AmarkedhypoxIcepIsode
wIthorwIthoutoutrIghtcardIacarrestprecedessuchclInIcalsIgns.
Mitochondrial myopathiesresemble|HInthatweaknessandacIdosIsmaybeobservedIn
bothsyndromes.0efectswIthInthemItochondrIalgenomeaffectoxIdatIvephosphorylatIon
andresultInImpaIredproductIonofATP.|ItochondrIaldIseasehasmanymanIfestatIons,
usuallypresentIngatanearlyagewIthcentralnervoussystem,gastroIntestInal,and
musclepathology.FaIluretothrIve,developmentaldelays,muscleweakness,
cardIomyopathy,andIntolerancetoheatmaybepresent.Elevatedserumlactateand
pyruvatearefoundonlaboratoryexamInatIon.CKmaybeelevated.AnesthesIafor
patIentswIthmItochondrIaldIseaseshouldbedesIgnedtobestressfree.SuccInylcholIne
IsbestavoIdedInthesepatIentsbecauseofthepotentIalforhyperkalemIa.Thegeneral
consensusIsthatmItochondrIalmyopathIesdonotpredIsposeto|H.
P.602
Malignant Hyperthermia Outside the Operating Room
TheoftenrepeatedobservatIonthatan|HlIkesyndromecanoccurIncertaInpIgbreeds
InresponsetostressfulsItuatIonssupportsthesuggestIonthat|HmayoccuroutsIdethe
operatIngroomInhumans.However,sucheventsareexceedInglyrare.Cronertetal.
49
havedescrIbedapatIentwhohadepIsodIcfeversandwhosemuscleproduceda
contractureconsIstentwIth|HsusceptIbIlIty.Thefeverswerecontrolledbydantrolene.A
mutatIonInRYR1,knowntobecausatIveof|H,wasfoundInapatIentwhosurvIved
anesthesIaInduced|HandthendIedaftersoccerpractIce.DtherfamIlymembersalsohad
thesamemutatIon.
50
AfewpatIentswIthexercIseInducedrhabdomyolysIshavebeen
foundtoharboroneofthe|HrelatedmutatIons.
51
ExercIseInducedrhabdomyolysIsmay
occurInpatIentswIthothermyopathIeswIthorwIthoutexposuretomyotoxIcdrugssuch
asthosethatlowerserumcholesterol.
52
8utmostcasesofheatstroke,evenwIthmarked
rhabdomyolysIs,arenotassocIatedwIth|HsusceptIbIlIty.
5J
Neuroleptic Malignant Syndrome and Other Drug-Induced
Hyperthermic Reactions
ThesymptomsandsIgnsoftheN|SIncludefever,rhabdomyolysIs,tachycardIa,
hypertensIon,agItatIon,musclerIgIdIty,andacIdosIs.
54
N|SresultsfromtreatmentwItha
varIetyofantIpsychotIcagents,IncludIngtheatypIcalantIpsychotIcsandhaloperIdol.N|S
complIcatessuchtreatmentIn0.1ofpatIentstakIngsuchmedIcatIons.0eathIs
uncommonIfdIagnosedrapIdlyandtreatedpromptly.NeverthelesshundredsofpeopledIe
fromN|Seachyear.AvarIetyofdrugshavebeenfoundusefulInthetreatmentofN|S
IncludIngbenzodIazepInes,bromocrIptIne,anddantrolene.8ecauseoftheclInIcal
resemblanceto|H,ItIsnotunusualforananesthesIologIsttobeconsultedInthe
managementofpatIentswIththIsdIsorder.A24/7HelplInestaffedbypsychIatrIsts
experIencedInthetreatmentofN|SandserotonInsyndromeIsavaIlableat1888667
8J67.TheNeurolept|alIgnantSyndromenformatIonServIceIsavaIlableat
www.nmsIs.org.
AlthoughtheresemblanceofN|Sto|HIsstrIkIng,therearesIgnIfIcantdIfferences
betweenthetwo.|HIsacute,whereasN|Softenoccursafterlongertermdrugexposure.
PhenothIazInes,haloperIdol,oranyofthenewerpotentantIpsychotIcsareusually
trIggerIngagentsforN|S.SuddenwIthdrawalofdrugsusedtotreatParkInsondIseasemay
alsotrIggerN|S.ElectroconvulsIvetherapywIthsuccInylcholInedoesnotappeartotrIgger
thesyndrome.
55
Also,N|SdoesnotseemtobeInherIted,andtherearenocasereportsof
ItInfamIlymemberswhohavehadanepIsodeof|H.
N|SIsrelatedtodopamInedepletIonInthecentralnervoussystembypsychoactIve
agents.nsupportofthIstheory,therapywIthbromocrIptIne,adopamIneagonIst,Isoften
usefulIntreatmentofN|S.AlthoughthereappeartobesImIlarItIesbetween|Hand
N|S,
54
acommonpathophysIologyIsnotreadIlyapparent.FromananesthesIologIst's
vIewpoInt,ItIsbesttomonItorpatIentswIthN|SasthoughtheyweresusceptIbleto|H.
However,drugssuchassuccInylcholInehavebeenusedforelectroconvulsIvetherapy
wIthoutproblemsIn|HpatIents.
AsImIlarsetofsIgnsmaybeobservedInsomepatIentstakIngserotonInuptakeInhIbItors
(socalledserotonInsyndrome).
56
DtherdrugsknowntoInduceahypermetabolIcsyndromeandrhabdomyolysIs,probablyby
stImulatIonofthesympathetIcnervoussystemanduncouplIngproteIns,mechanIsmsnot
relatedtothoseof|H,arecocaIne,amphetamInes,and|0|A(I.e.,thestreetdrug
Ecstasy).0antrolenehasbeenusedsporadIcallyasanadjuncttotreatmentofmarked
hyperthermIaInthesecasesandInN|S.
57
ExperImentalevIdenceInanImalssupports
treatmentwIth
J
blockersuchascarvedIlol.
58
Table 24-1 Safe Versus Unsafe Drugs in Malignant Hyperthermia
SAFE DRUGS UNSAFE DRUGS
AntIbIotIcs
AntIhIstamInes
8arbIturates
8enzodIazepInes
0roperIdol
KetamIne
LocalanesthetIcs
NItrousoxIde
NondepolarIzIngneuromuscular
blockers
DpIoIds
Propofol
Propranolol
7asoactIvedrugs
AllInhalatIonagents(exceptnItrous
oxIde)
SuccInylcholIne
Drugs That Trigger Malignant Hyperthermia
tIsclearlyestablIshedthatthepotentInhalatIonagents,IncludIngsevoflurane,
desflurane,Isoflurane,halothane,methoxyflurane,andcyclopropane,maytrIgger|H.
SuccInylcholIneIsalsoatrIgger.DtheranesthetIcdrugsandadjuvantsarenot|HtrIggers
(Table241).AlllocalanesthetIcsaresafefor|HsusceptIblepatIents.
59
AmIdelocal
anesthetIcsgIvendurIngan|HcrIsIs(e.g.,fordysrhythmIacontrol)donotworsenthe
epIsode.
AlthoughplasmacatecholamInesIncreasedurIngan|HcrIsIs,suchanelevatIonIsusually
secondarytometabolIcandcardIovascularchanges.7asopressorsandother
catecholamInesarenotInvolvedIntrIggerIng|H.
60
Therefore,thesedrugsshouldbegIven
asnecessary,butonlywIthsImultaneoustreatmentofthe|HcrIsIs.
7ecuronIum,rocuronIum,cIsatracurIum,pancuronIum,andallothernondepolarIzIngdrugs
areconsIderedsafetouseInpatIentswIth|H.ClInIcalstudIeshaveshownthat
antIcholInesteraseantIcholInergIccombInatIonsaresafeforreversalofnondepolarIzIng
relaxantsIn|HsusceptIblepatIents.
61
0IgoxIn,quInIdIne,andcalcIumsaltsdonotInduce|HInswIne.
62
Therefore,ItIs
reasonabletoassumethattheyaresafetouseInclInIcalsItuatIons.NeItherketamInenor
propofolare|HtrIggers.AlthoughawIdevarIetyofdrugsmayprecIpItateN|S,thesedo
notproduce|HcrIses.ThetwosyndromesarenotrelatedInthIsmanner.
Incidence and Epidemiology
TheIncIdenceof|HvarIesfromcountrytocountry,basedondIfferencesIngenepools,
exposuretotrIggers,andreportIngmechanIsms.ntheuppermIdwestoftheUnItedStates
therearemanylargefamIlIesof|HsusceptIblepeople.ncontrast,otherareasofthIs
countryandtheworldhaverarelyreported|H.8achandandcolleagues
6J
examInedthe
IncIdenceof|HInaprovInceofQuebec,Canada,wheremanyfamIlIeshadundergone
bIopsy.TheytracedthepedIgreesofpatIentstothe
P.60J
orIgInalImmIgrantsfromFranceandfoundanIncIdenceof|HsusceptIbIlItyof0.2InthIs
provInce.However,thatrepresentedonlyfIveextendedfamIlIes.ThebestepIdemIologIc
studyof|HwasdoneInthemId1980sbyDrdIng
14
basedonthe0anIsh|alIgnant
HyperthermIaFegIstry.ShefoundthatfulmInant|HoccurredonceIn250,000admInIstered
anesthetIcs.However,IfthedefInItIonof|HwasexpandedtoIncludeabortIvecasesof
|H,theIncIdenceIncreasedto1In4,000exposurestoInhalatIonanesthetIcsand
succInylcholIne!
AbetterunderstandIngoftheprevalenceof|HsusceptIbIlItymayemergefromtheuseof
moleculargenetIcs.Forexample,|onnIerandcolleagues
64
estImatethatoneIn2,000to
J,000personsInFranceharboroneoftheknown|HcausatIvemutatIons.AsImIlar
prevalencehasbeenreportedIntheJapanesepopulatIon,althoughassocIatedwIth
dIfferentmutatIonsthanfoundInEurope.
65
Currently,theconsensusIsthatmortalItyfrom
|HIsunder5InWesterncountrIes.However,theepIdemIologIccharacterIstIcsof|Hare
verydIffIculttodefIneforthefollowIngreasons:
1. WIdespreaddIagnostIctestIngfor|HIsdIffIculttoapply.
2. TheclInIcaldIagnosIsof|HIsoftenquestIonable.
J. TrIggerIngof|HmaynotoccuroneachanesthetIcexposure.SusceptIblepatIentshave
receIvedtrIggerIngagentsformorethantenanesthetIcswIthoutanyproblems,onlyto
have|HtrIggeredonthesubsequentanesthetIc.nvestIgatIonofthe0anIsh|alIgnant
HyperthermIaFegIstryfoundthe|HgenotypetobeexpressedInonlyJ4to54of
anesthetIcexposures.
66
4. FegIstrIesof|Hcasesdonotcaptureallrelevantdata.ThereIsapaucItyofdata
concernIngthefrequencyofuseofanesthesIaInthegeneralpopulatIon.
Diagnostic Tests for Malignant Hyperthermia
ThegoldstandardmusclebIoassayfor|HsusceptIbIlItyderIvesfromtheobservatIonthat
vIablemusclebIopsIedfrom|HpatIentsrespondswIthmarkedrIgIdItytohalothane,
caffeIne,chlorocresol,andavarIetyofotheragentsknowntoreleasecalcIumfromthe
sarcoplasmIcretIculum.AlthoughthetestIsconductedsomewhatdIfferentlyInEurope
67,68
thanInNorthAmerIca,
69,70,71
theprIncIplesofthetestaresImIlar.
Halothane-Caffeine Contracture Test
AlthoughsomeproceduresandInterpretatIonsdIfferbetweentheEuropean|alIgnant
HyperthermIaCroup(E|HC)andNorthAmerIcan|alIgnantHyperthermIaCroup(NA|HC)
protocols,thefollowIngstepsaresImIlar.Skeletalmuscle(1toJg)IsusuallybIopsIedfrom
athIghmuscle,usuallythevastuslateralIsmuscle.StrIpsofmuscleweIghIng100to200mg
andmeasurIng15toJ0mm(25mmpreferred)Inlengthby2toJmmInwIdthby2toJ
mmInthIcknessarecarefullyIsolatedandmountedInastandardmusclebathapparatus
(FIg.241).ThetIssuebathcontaInsamodIfIedKrebssolutIonatJ7`CbubbledwIthD
2
and
CD
2
(95/5),andtherestIngtensIonIsadjustedtotheoptImumlengthformaxImaltwItch
tensIon(usuallyabout2g).ThebundlesarestImulatedsupramaxImallywIthpulsesof
frequency0.1to0.2HzwIth2msecpulsestoverIfyvIabIlIty.Aftera15to60mInute
equIlIbratIonwIthD
2
/CD
2
(95/5),halothaneIsaddedtothegasphase,eItherasabolus
doseorInIncrementallyIncreasIngconcentratIons(FIg.242).TheconcentratIonof
halothaneIsverIfIedbygaschromatography.AsecondsetofmusclestrIpsIsequIlIbrated
andsubsequentlyexposedtoIncrementallyIncreasIngconcentratIonsofcaffeInefreebase
(FIg.242).tIsrecommendedthatthecaffeInestrIpsbetestedearlyIntheprocedure
becausetheytendtobemoresensItIvetoInstabIlItyovertIme.TestIngIsusually
completedwIthInabout5hoursofbIopsytoensureadequatevIabIlItyofthemuscle
preparatIons.Therefore,ItIsessentIalthatthebIopsybeperformed1hourawayfromthe
testInglaboratory.Usually,hIstologIcandbIochemIcalevaluatIonaccompanIesthe
contracturetesttocharacterIzepotentIalmuscledIsorders.
Figure 24-1.0IagramofthemusclebathapparatususedforcontracturetestIngfor
dIagnosIng|HsusceptIbIlIty.
Sensitivity and Specificity of the Halothane-Caffeine
Contracture Test
ThesensItIvItyoftheNA|HCprotocolcaffeInehalothanecontracturetestIs100wIth
specIfIcIty78(falsenegatIvesaretobeavoIded).
70,71
TheE|HCtestInvItrocontracture
testhassensItIvItyof98wIthspecIfIcItyof9J.tIsdIffIculttobecertaInofthe
sensItIvItyandspecIfIcItyofthecontracturetestbecausealthoughonecanbefaIrly
certaInoftheclInIcalphenotypeof|HSbasedonanesthetIcexposures,ItIsalmost
ImpossIbletobeassuredthatcontrolsubjectsdonotharboracausatIvemutatIon.
0etermInatIonofthesensItIvItyandspecIfIcItyIsbasedoncontracturestudIesofpatIents
wIthnoknown|HhIstoryundergoIngroutInesurgery(controls)comparedwIthcontracture
studIesfrompatIentswhoexperIencedanunequIvocalclInIcalepIsodeof|H.
Other Agents used in the Contracture Tests
nattemptstofurtherImprovethespecIfIcItyandsensItIvItyofthecontracturetest,other
agentshavebeentestedfortheIreffectonskeletalmuscle.
Ryanodine
AnaddItIonalcontracturetestusIngtheplantalkaloIdryanodInewasproposedforInclusIon
IntheE|HCprotocol.FyanodInebIndstoandactIvatesthecalcIumreleasechannelofthe
sarcoplasmIcretIculum.twasreasonedthatthIstestwouldaffordmaxImumspecIfIcIty
for|H,andearlystudIessupportedthIsconcept.
72,7J,74,75
ThebasIctestIngcondItIonsforryanodInearesImIlartothosedescrIbedforhalothaneand
caffeInetestIng.HIghpurItyryanodIneIsemployed.AbolusofryanodInetoproduceone
|/LIsaddedtothebathandthetImetoonsetofcontracture,tImeto
P.604
P.605
0.2gcontracture,tImeto1gcontracture,andthetImeandamplItudeofmaxImum
contracturearerecorded.0IscrImInatIonwasImprovedbyusIngthetImetoInItIal
contractureandtImetodevelopmentofa10mN(1g)contracture.
76
Figure 24-2.|usclestrIpsweIghIngapproxImately150mgandstImulated
supramaxImallyareexposedtoJhalothaneorIncrementaldosesofcaffeIne.A.AJg
contractureIsrecordedfromthIsstrIpfromapatIentwIthmalIgnanthyperthermIa
syndrome(|HS)afterexposureofthemuscletoJhalothane(top);anormalresponse
toJhalothane(bottom).B.Contracturesnotedafterexposureto0.5,1,and2mM
caffeIne(Caff)In|HSmuscle(top);nocontractureresponsetothesamecaffeIne
concentratIons.TwItchheIghtaugmentatIonIsnormalfollowIngcaffeIneaddItIon
(bottom).
4-Chloro-m-Cresol
4Chloromcresol(4CmC)IsapotentactIvatorofryanodInereceptormedIatedCa
2+
release.CumulatIveadmInIstratIonof25,50,75,100,150,and200mol/Lof4CmC
producedconcentratIondependentcontractures.ContracturesdevelopedearlIerandtoa
greatermagnItudeInmusclefrompatIentsIdentIfIedas|HSbytheE|HCprotocolthanIn
normalmuscle.
77
TheE|HCapprovedbIoassayIncludesadmInIstratIonofasInglebolusof
4CmCsothatthebathedmuscleIsexposedtoaconcentratIonof75mol/L.
Pitfalls in the Contracture Test
deally,eachlaboratoryshouldderIvespecImensfrompatIentswhoareclearlyand
unequIvocallynormalandthosewhoareclearlyandunequIvocally|HsusceptIbletoverIfy
thatcutpoIntsfor|HsusceptIbIlItyaredIagnostIcwIthInthelaboratory.Unfortunately,
becauseofthevarIatIonInpresentatIonof|H,ItIsnotalwayspossIbletohavecomplete
agreementonthe|HstatusofapatIentbasedonaclInIcalhIstory,evenamongexpertsIn
thefIeld.
TherehavebeenafewreportsdescrIbIngpatIentswhoweredIagnosedasnonsusceptIble
bycontracturetestIngsubsequentlyexperIencIngclInIcalepIsodeshIghlysuggestIveof|H;
andInonecase,theestImatedfalsenegatIveratewas4of171subjects(2).
78,79
|H
expertsarenotconvIncedthatthesewerevalIdcasesof|H.AmImIcof|HsuchassepsIs
mayexplaIntheclInIcalproblem.
79
ncontrast,studIeshavereportedpatIentswIth
negatIveresultsfor|HreceIvIngtrIggerIngagentsonmultIpleoccasIons,
80,81
allwIthout
complIcatIons.Unfortunately,studIeslIkethesearedIffIculttoconductbecausethey
requIrelargepatIentpopulatIonsandtrackIngofsubjectsdIagnosedseveralyearsbefore
theactualstudy.
Tests with More Limited Usefulness in Malignant Hyperthermia
Diagnosis
AlternatIveteststhathavenotgaInedacceptancewIthIntheE|HCorNA|HChavebeen
revIewedelsewhere.
82,8J
ElevatedrestIngCKvaluesareassocIatedwIth|HsusceptIbIlItyInafewfamIlIes.
However,manysubjectssusceptIbleto|HdonothaveelevatedCKvalues,makIngthIs
methodofdIagnosIsrelatIvelyInsensItIve.
8J
Also,severalmuscledIsordersareassocIated
wIthelevatedrestIngCKvalues,makIngthIstestnonspecIfIc.
8J
ElevatedCKvaluesmaybe
usefulInprelImInarIlyIdentIfyIngkeyfamIlymemberstobereferredforcontracture
testIngandInIdentIfyIngmuscledIseaseInchIldrentooyoungtoundergocontracture
testIng.
AlthoughtheuseofrestIngCKvaluesforgeneralscreenIngof|HsusceptIbIlItyIsneIther
sensItIvenorspecIfIc,thereIsarelatIonshIpbetweenhIghpostoperatIveCKvalues
assocIatedwIth||FandtheprobabIlItyofdIagnosIsas|HsusceptIblebythecontracture
test.
20,27
AlthoughItIsnotaperfectIndIcatorof|HsusceptIbIlIty,
84
thechancesareabout
80thataCKvalue20,000after||FwIllyIeldaposItIvedIagnosIsbycontracture
testIng.
20,27
ArelatIvelynormalCKlevelpostoperatIvelydoesnotruleoutthepossIbIlItyof
anacute|HreactIondurIngthatanesthetIc.
11,85
AvarIetyofmInImallyInvasIvedIagnostIctestshavebeenpresented.Dneusesnuclear
magnetIcresonancespectroscopytoevaluateATPdepletIondurInggradedexercIseInvIvo.
|HpatIentshaveagreaterbreakdownofATPandcreatInephosphateaswellasan
IncreaseInacIdcontentcomparedwIthnormalpatIents.
86
UsIngculturedmusclecells
87
or
8lymphocytes,
88
IthasbeenshownthatagentssuchascaffeIneandchlorocresolwIllraIse
IntracellularcalcIumIonconcentratIonstoagreaterextentIntIssuederIvedfrom|HS
IndIvIdualsthannormalpatIents.
8yfInedIssectIonofmuscletoseparatesInglemusclefIbersIthasbeenshownthat
specIallypreparedfIberswIlldemonstrateaccentuatedcontractures,aswIththemuscle
bundles.DneadvantageIsthatthemusclemaybepreservedforrepeatedstudIes.Dnthe
otherhand,evenIn|Hmuscle,somefIbersmaybehavenormally.ThIstestIsused
routInelyInJapan.
ArathernovelapproachentaIlsInjectIonofasmallamountofcaffeIneorInhalatIon
anesthetIcthroughamIcrodIalysIscatheterInsertedIntothethIghmuscleandsamplIng
localCD
2
and/orlactatelevels.
89
ThIsmethodIsbeIngstudIedfurther.
90,91,92
Clinical Diagnosis of Malignant Hyperthermia: The Grading Scale
AclInIcalgradIngscalehasbeendevelopedtoaddressconcernsforobjectIvelyevaluatIng
theclInIcalepIsode.
9J
ThIsscalelackssensItIvItybecauseIncompleterecordIngof
necessarydataorearlytermInatIonofthecrIsIswouldnotyIeldscoresIndIcatIveof|H,
evenInthepresenceofatrue|HepIsode.ThevalueofthegradIngscaleIsmaInlyIn
IdentIfyIngthosesubjectswIththemostconvIncIngepIsodesof|Hforsubsequent
evaluatIonofthesensItIvItyofthedIagnostIctests.TheclInIcalgradIngscale(Table242)
IsusefulfordocumentatIonofclInIcalepIsodesInthosecasesInwhIchthesubjectIsrated
a06(0IagnostIcrank6,almostcertaInly|H),butlowerscoresshouldnotbeusedfor
dIagnosIs.WeencouragethepractIceofsendIngpatIentsrated06fordIagnostIcmuscle
contracturetestIngbecausetheseIndIvIdualsarerareandessentIalforthecontInuIng
P.606
evaluatIonofthesensItIvItyandspecIfIcItyofthecontracturetestandforstudyofthe
genetIcsof|H.
Table 24-2 Criteria Used in the Malignant Hyperthermia Clinical Grading
Scale
Process:|usclerIgIdIty
CeneralIzedrIgIdIty 15
|asseterrIgIdIty 15
Process:|yonecrosIs
ElevatedCK20,000(aftersuccInylcholIneadmInIstratIon) 15
ElevatedCK10,000(wIthoutexposuretosuccInylcholIne) 15
ColacoloredurIne 10
|yoglobInInurIne60g/L 5
8lood/plasma/serumK
+
6mEg/L J
Process:FespIratoryacIdosIs
PetCD
2
55wIthcontrolledventIlatIon
15
PaCD
2
60wIthcontrolledventIlatIon
15
PetCD
2
60wIthspontaneousventIlatIon
15
napproprIatehypercarbIa 15
napproprIatetachypnea 10
Process7:TemperatureIncrease
FapIdIncreaseIntemperature 15
napproprIatetemperatureJ8.8`CInperIoperatIveperIod 10
Process7:CardIacInvolvement
napproprIatetachycardIa J
7entrIculartachycardIaorfIbrIllatIon J
CK,creatInekInase.
SeeLarach,etal.
9J
forfulldetaIlsofthIsscorIngsystem.8rIefly,acasemay
receIve15poIntsfortheworstpresentatIonInfIveofthefIrstsIxcategorIes.A
sumofmorethan50poIntsIstermedD6,almostcertaInlyacaseofmalIgnant
hyperthermIa(|H).AsumofJ5to49poIntsIsD5,verylIkelytobeacaseof|H.
Molecular Genetic Testing for Malignant Hyperthermia
Susceptibility
ThedIscoveryofmultIple|HcausIngmutatIonsIntheRYR1
94
hasledtotheIntroductIonof
genetIctestIngof|HsusceptIbIlItyonalImItedbasIsInEuropeandtheUnItedStates.The
guIdelInespublIshedbytheEuropean|alIgnantHyperthermIaCroup(www.emhg.org)
suggestthatforclInIcaldIagnosIs,apanelof28RYR1mutatIonsshouldbeexamIned.A
lImItatIonofgenetIctestIngIntheUnItedStateshasbeensensItIvItyofabout2Jwhen
testIngfor21mutatIons.
95
ScreenIngoftheentIrecodIngregIonoftheRYR1IdentIfIes
sequencevarIantsIn70
65,96
to86
97
ofpatIents.Therefore,sensItIvItyofgenetIctests
wIllImproveasmoremutatIonsareIdentIfIedascausatIveof|H.
PatIentsshouldconsIdergenetIctestIngIf:
1. TheyhavehadaposItIvecontracturetest.
2. AfamIlymemberhashadaposItIvecontracturetest.
J. TheyhavesufferedaverylIkely|HepIsode,buthavenothadacontracturetest.
4. AfamIlymemberhasbeenfoundtohaveacausalmutatIon.
WhenamutatIonknowntobecausatIvefor|HIsIdentIfIedInafamIlymemberwhohas
hadanabnormalcontractureresponsetohalothaneorcaffeIne,ItIspossIbletodetermIne
|HsusceptIbIlItyInothermembersofthatfamIlybyexamInatIonoftheIrRYR10NAfor
thatmutatIon.ThosewIththemutatIonare|HsusceptIble(wIthhIghspecIfIcIty)butthose
wIthoutthemutatIoncannotbeconsIdered|HnegatIveastheymayharboranother
mutatIon.ThepatIentcannotbepresumedtobe|HnegatIvewIthoutnegatIveresultson
musclecontracturetestIng.
98
ThedecIsIontoundergogenetIctestIngIscomplex.Thepros
andconsoftestIngshouldbedIscussedwItheItheran|HexpertoragenetIccounselor.At
thecurrenttIme,therearetwoclInIcallaboratorIesofferIngmoleculargenetIctestIngfor
|H:
LABORATORY CONTACT
PreventionGenetics, LLC
ErIcW.Johnson,Ph0
J7000ownwInd0rIve
|arshfIeld,W54449
www.preventIongenetIcs.com
ACollegeofAmerIcanPathologydIagnostIclaboratory
715J870484
clInIcaltestIng@preventIongenetIcs.com
Center for Medical Genetics
University of Pittsburgh Medical Center
J.Kant,|0,Ph0
S701ScaIfeHall
J550TerraceStreet
PIttsburgh,PA1521J
http://path.upmc.edu/dIvIsIons/mdx/dIagnostIcs.html
0eannaSteele,CCC
8004548155
or
4126488519
(laboratory)
SeethesectIononpathogenesIsandetIologyof|HformoredetaIls.
Treatment of Malignant Hyperthermia
|HIsatreatabledIsorder.AllInstItutIonsInwhIchanesthetIcagentsknowntotrIgger|H
areadmInIsteredshouldhavedantroleneavaIlable(J6ampules[720mg]Isrecommended)
andamanagementplan.
The Acute Episode
ThefollowIngstepsshouldbetakenImmedIatelywhen|HIsdIagnosed:
1. AdmInIstratIonofallInhalatIonagentsandsuccInylcholIneshouldbedIscontInuedand
assIstanceshouldbesecured.(tIshelpfultohaveadedIcatedcartavaIlablecontaInIng
theagentsfortreatmentof|H.)
2. HyperventIlatIonwIth100oxygenshouldbeInstItutedat10L/mIn.Dxygenflowshould
be10L/mIntohastenpurgIngofresIdualanesthetIcgases.TImeshouldnotbewastedIn
securInganotheranesthetIcmachIne,butanAmbubagandEcylInderofoxygenmaybe
used.
J. AssIstanceshouldbeobtaInedInmIxIngdantrolene.ThepresentpreparatIonof
dantroleneIspoorlysoluble.EachvIalcontaInIng20mgshouldbemIxedwIth50mLof
bacterIostatIcsterIledIstIlledwater(notsalInesolutIon).tIsImportanttostoresterIle
waterInclearlylabeledcontaInersofadIfferentsIzefromthatusedforroutIne
IntravenoussolutIons.tmaybehelpfultokeepamIxIngsystemadjacent.0antrolene
wIlldIssolvefasterastemperatureofthedIluentIncreasesfrom20to40`C
99
or41`C.
100
ntravenoustherapyshouldbestartedwIth2.5mg/kgwIthrepeatdosesasneeded.|ore
than10mg/kgofdantrolenemaybegIvenasdIctatedbyclInIcalcIrcumstances;
however,manyacuteepIsodesarecontrolledwIth2toJmg/kg.ThereareJgof
mannItolwItheach20mgofdantrolene.Therefore,abladdercathetershouldbe
InsertedtofacIlItatemonItorIngurIneoutput.
4. TItratIonofdantrolenetoheartrate,bodytemperature,andPaCD
2
IsthebestclInIcal
guIdelIneoftherapy.
5. nfulmInantcasesInwhIchsIgnIfIcantmetabolIcacIdosIsIspresent,2to4mEq/kg
bIcarbonateshouldbegIven.LargevolumesoffluIdmaybeneededtoreplacelossInto
edematoustIssuesandIntotheurIne.
6. fItIsnotalreadyavaIlable,acapnometershouldbeobtaInedsothatCD
2
excretIoncan
bedocumented.
7. 0ysrhythmIacontrolusuallyfollowshyperventIlatIon,dantrolenetherapy,andcorrectIon
ofacIdosIs.CalcIumchannelblockersshouldnotbeusedIntheacutetreatmentof|H.
7erapamIlcanInteractwIthdantrolenetoproducehyperkalemIaandmyocardIal
depressIon.
101,102
LIdocaInecanbegIvensafelydurIngan|HcrIsIs.
8. 8odytemperatureelevatIonshouldbemanagedbygIvIngcoolfluIdIntravenously,
placIngIcepacksonthegroInandIntheaxIllae,andbyuseofgastrIc,wound,andrectal
lavage.SomehaverecommendedperItonealdIalysIsandothersrecommend
cardIopulmonarybypass.CoolIngshouldbestoppedwhencoretemperaturereachesJ8`C
toavoIdhypothermIa.
9. AlthougharterIalbloodIsusefulforassessIngacIdosIs,centralmIxedvenousbloodgas
determInatIons(or,IfnotavaIlable,femoralvenousbloodgasreadIngs)serveasabetter
guIdelInefortherapy.SerumpotassIumshouldbemeasuredearly.
10. HyperkalemIashouldbemanagedIntheusualfashIonwIthglucose,InsulIn,bIcarbonate,
andhyperventIlatIon(seeChapter14).fhyperkalemIaIsassocIatedwIthsIgnIfIcant
cardIaceffects,calcIumchlorIde,1gramor10mg/kg,shouldbegIven.HypokalemIa
frequentlyresultsdurIngtherapyof|H.However,potassIumreplacementshouldbe
undertakenverycautIously,Ifatall,becausepotassIummayretrIggeran|HepIsode.
11. 8aselInelaboratorytestsshouldIncludecreatInIne,coagulatIonprofIle,CKaswellas
lIverfunctIontests.CKelevatIonsmaynotoccurfor6to12hoursafteran|HepIsode
P.607
andshouldbefollowedasaroughguIdetotherapy.|yoglobInlevelsInbloodandurIne
shouldbeobtaInedearlyIntheepIsode.
Management After the Acute Episode
AftertheacuteepIsode,theclInIcIanshouldbeconcernedaboutthreecomplIcatIonsof
|H:
1. Fecrudescenceof|H.Asmanyas25ofpatIentsmayexperIenceacuterecrudescence,a
relapse,wIthInhoursofthefIrstepIsode.
1J
2. 0IssemInatedIntravascularcoagulatIon(0C)
10J
(seeChapter16).0Chasoftenbeen
descrIbedIncasesof|H,probablyresultIngfromreleaseofthromboplastInssecondary
toshockandcoretemperature41`C
104
and/orreleaseofcellularcontentson
membranedestructIon.TheusualregImenfortreatmentof0Cshouldbefollowed.
J. |yoglobInurIcrenalfaIlure(seeChapter52).|yoglobInurIamayoccurwIthInhoursafter
theepIsodebegIns.ftheurIneIsacId,bIcarbonateshouldbegIventodecreasethe
chancethatmyoglobInwIllInjurerenaltubules.|annItolshouldbegIventoproduce1
ml/kg/hrurIneoutput.
TheguIdelInesforthedoseandduratIonofdantrolenetherapyafterresolutIonofacute|H
areempIrIcal.twouldseemprudenttocontInuedantrolene,1mg/kgevery6hours
Intravenously,foratleast24toJ6hours,butmoremaybegIvenIfsIgnsof|Hreappear.
SomerecommendconversIonofdantrolenetherapyfromIntravenoustooralform(4mg/kg
perdayormore)wIthcontInuatIonforseveraldays.
SIgnIfIcantmuscleweaknessandpaInmayfollow|H,resultIngfrommuscledestructIon
alongwIthdantroleneadmInIstratIon;thIsshouldbemanagedsymptomatIcally.Fecovery
ofstrengthmayrequIreweekstomonths.
AvarIetyofotherelectrolytechangesmayoccur,suchashypocalcemIaand
hyperphosphatemIa.SodIumandchlorIdechangesmayoccursecondarytofluIdshIfts
durIngtheacuteepIsode.AllthesechangesusuallyrespondtocontroloftheacuteepIsode.
Dantrolene
0antrolenesodIumIsahydantoInderIvatIve(1[[[5(4nItrophenyl)2
furanyl]methylene]amIno]2,4ImIdazolIdInedIone).n1979,Intravenousdantrolenewas
approvedfortreatmentof|H.UntIlthattIme,theprImaryuseofdantrolenewasInthe
managementofspastIcIty.0antroleneIsaunIquemusclerelaxant.UnlIkeneuromuscular
blockIngagents(whosesIteofactIonIsatthenIcotInIcreceptoroftheneuromuscular
junctIon)orthenonspecIfIcrelaxants(whIchmodulatespInalcordsynaptIcreflexes),
dantroleneactswIthInthemusclecellItselfbyreducIngcalcIumreleasebythe
sarcoplasmIcretIculum.[
J
H]AzIdodantrolene,apharmacologIcallyactIve,photoaffInIty
analogofdantrolene,specIfIcallybIndstoasIteontheryanodInereceptor.
105,106
0urIngan
|HepIsode,dantrolenereducesIntracellularcalcIumlevels.Therefore,dantroleneIsa
specIfIcandeffectIveagentInthetreatmentof|H.ntheusualclInIcaldoses,dantrolene
haslIttleeffectonmyocardIalcontractIlIty.
107
StudIeshavealsoIndIcatedthatdosesofneuromuscularblockIngagentsneednotbe
changedsIgnIfIcantlyafterdantroleneadmInIstratIon.However,thedrugshouldbeused
cautIouslyInpatIentswIthneuromusculardIsease.
108
TheserumlevelofdantrolenerequIredforprophylaxIsagaInst|HIsabout2.5g/mL.The
halflIfeofIntravenousdantrolene,theonlyformrecommended,IsapproxImately12
hours.However,thetherapeutIclevelofdantroleneusuallypersIstsfor4to6hoursaftera
usualIntravenousdoseof2.5mg/kg.
109,110
Therefore,dantroleneshouldbesupplemented
atleastevery6hoursafteraclInIcalepIsode.|uscleweaknessmaypersIstfor24hours
afterdantrolenetherapyIsdIscontInued.NauseaandphlebItIsareothercomplIcatIonsof
acutedantroleneadmInIstratIon.HepatotoxIcItyhasbeendemonstratedonlywIthlong
termuseoforaldantrolene.ProphylaxIsfor|HshouldbecarrIedoutwIthIntravenousor
oraldantrolene
111
(5mg/kgper24hours)InthoseraresItuatIonsInwhIchprophylaxIsIs
desIred.
Management of the Patient Susceptible to Malignant
Hyperthermia
8ecauseofanIncreasIngawarenessof|HandmorewIdespreaduseofdIagnostIctests,ItIs
notunusualforananesthesIologIsttobeconfrontedwItha|HsusceptIblepatIentora
patIentwhohasafamIlyhIstoryof|H.ThemanagementofsuchpatIentsshouldbe
carefullyplanned.
nthepreoperatIveIntervIew,theanesthesIologIstshouldtrytoobtaInsuffIcIent
InformatIonregardIngprevIousepIsodesof|HandtheIrdocumentatIon.fthefamIlyhas
partIcIpatedIntheNorthAmerIcan|alIgnantHyperthermIaFegIstry,theFegIstrymaybe
abletogIvedetaIlstotheanesthesIaprovIder.TheanesthesIologIstshouldallowadequate
tImetoreassurepatIentsandtheIrfamIlIesthatheorsheIsfamIlIarwIth|HandIts
ImplIcatIonsandthatapproprIatemonItorIngandtherapywIllbeInstItutedasnecessary.t
maybeworthmentIonIngthattherehavebeennodeathsfrom|HInprevIouslydIagnosed
|HsusceptIblepatIentswhentheanesthesIateamwasawareoftheproblem.AnesthesIa
andpremedIcatIonshouldbedesIgnedtoproducealownormalheartrate.Standard
premedIcantdrugssuchasopIoIds,benzodIazepInes,ataractIcs,barbIturates,
antIhIstamInes,andantIcholInergIcsdonotcauseproblemsIn|HsusceptIblepatIents
whenadmInIsteredInapproprIatedoses;however,phenothIazInesarenotrecommended.
0antroleneneednotbegIvenpreoperatIvelybecausenontrIggerIngagentsareusedand
endtIdalCD
2
andcoretemperaturearemonItored.0antrolenemustbeImmedIately
avaIlableIntheoperatIngroom,andequIpmentforrapIdmeasurementofbloodgasesand
electrolytesshouldbeavaIlable.
TheanesthesIamachIneIspreparedbydraInIng,removIng,ordIsablInganesthetIc
vaporIzers,andchangIngtubIngandCD
2
absorbentandflowIngoxygenat10L/mInfor10
mInutesorlonger.ThemodernanesthesIaworkstatIonIslargerthanolderanesthesIa
machInesandcanrequIre10mInutestopurgeofInhalatIonagentsunlessmany
componentshavebeenreplaced.
112,11J
DbvIously,IcedsolutIonsandadequatesupplIesof
dantrolenemustbeavaIlableInthevIcInItyoftheoperatIngroomwhen|HsusceptIble
patIentsareanesthetIzed.
ExhaledCD
2
shouldbemonItoredbecausetheearlIestsIgnof|HIsanIncreaseInCD
2
productIonandexcretIon.ArterIalandcentralvenousmonItorIngIsrecommendedfor|H
susceptIblepatIents,onlyasdIctatedbythesurgIcalprocedure.8odycoretemperature
shouldbemonItoredbynasopharyngeal,rectal,oresophagealroutesInallpatIentsforall
surgIcalprocedures.SkIntemperature,althoughacceptable,IsnotasdesIrablebecauseIt
maynotreflectcoretemperature.
114
fpossIble,aregIonal,local,ormajorconductIonanesthetIcshouldbeused.fnot
possIble,IntravenousInductIonofanesthesIafollowedbynItrousoxIde,oxygen,anda
nondepolarIzIngrelaxantwIthopIoIdsupplementatIonIsrecommended.Agentsthathave
notbeenImplIcatedIn|HaremIdazolam,dexmedetomIdIne,dIazepam,droperIdol,and
propofol.
NeuromuscularblockIngagentssuchaspancuronIum,vecuronIum,atracurIum,
cIsatracurIum,androcuronIumaresafe.FoutInereversalofnondepolarIzIngrelaxantswIth
antIcholInesteraseandantIcholInergIcagentsIsrecommended.
|anythousandsofsafeanesthetIcshavebeenadmInIsteredwIthnItrousoxIdeIn|H
susceptIblepatIents.Twocaseshave
P.608
beenreportedInwhIchearlysIgnsof|HhavebeendocumenteddespItetheuseofasafe
anesthetIctechnIque.
115
Therefore,evenunderthemostcontrolledcIrcumstances,the
anesthesIologIstshouldbealerttotheearlysIgnsof|H.
AdmInIstratIonofdantroleneaftersurgeryIsnotrecommendedIftherearenosIgnsof|H.
fthereIsnosIgnof|HInthefIrsthourpostoperatIvelyaftersafeanesthetIctechnIques
wereused,ItIsveryunlIkelythat|HwIlloccurlater.ThepatIentmaybedIschargedon
thesamedayassurgery.
116,117
CompleterehydratIonwIthIntravenousfluIdandadequate
oralIntakedecreasesthechancethatfeverwIlloccurpostdIschargeasaresultof
dehydratIon.
ThesameprecautIonsshouldbetakenfortheobstetrIcpatIentasfortheroutInesurgIcal
patIent.EvIdencethatthestressoflabormayprecIpItate|HIsnotconvIncIng,andwell
conductedepIduralanesthesIaforlaboranddelIverywIthoutdantrolenepretreatmentbut
wIthcarefulmonItorIngofvItalsIgnsIsrecommended.fanemergencycesareansectIon
wIthgeneralanesthesIaIsnecessary,alternatIvestosuccInylcholIneshouldbeused.The
maternal:fetalpartItIonratIofordantroleneIsprobably0.4.
118
0antrolenehasnotbeen
reportedtoproducesIgnIfIcantproblemsforthefetusornewborn,butexIstIngdataare
veryscanty.
Malignant Hyperthermia in Species Other Than Pigs and
People
|HhasbeenreportedsporadIcallyInmanyspecIes.ClInIcalepIsodeshavebeen
documentedIncats,dogs,andhorses.
119
Capture myopathyIsasyndromecharacterIzedby
temperatureelevatIon,rhabdomyolysIs,acIdosIs,anddeathInwIldanImals(e.g.,zebra,
elk).ThIsalsohasbeensuggestedtobean|HvarIant.
Medicolegal Aspects
tIsnotsurprIsIngthat|HcaseshavebeenthesubjectofmalpractIcesuIts.8ecause|H
maybeconsIderedanInborngenetIcproblemwItharelatIvelyfIxedassocIatedmortalIty
thatmaygounrecognIzedbeforeapatIent'sexposuretotrIggerIngagents,Itmaybeused
asacoverforotherproblems.
Fever,opIsthotonIcposturIng,andneurologIcabnormalItIesmayaccompanyhypoxIcbraIn
Injury,andbecauseoftheIrsImIlarItyto|H,|HmaybeIncorrectlyImplIcatedInthe
dIfferentIaldIagnosIs.Furthermore,aftercardIacarrestfromanycause,CKandpotassIum
levelsmaybesIgnIfIcantlyelevated.
Somehavestatedthat,wIththeadventofdantrolene,thereshouldbenodeathsfrom|H.
ThIsIsunrealIstIcbecausethesyndromemaybetrulyexplosIveInsomecasesand
ImpossIbletocontrolwIthcurrenttherapy.WhenmuscleIsrIgId,perfusIonwIlldecrease;
delIveryofdantrolenetomusclemaybeImpaIred,andIncreasIngmuscleacIdosIsand
temperaturewIllproduceresIstancetotheeffectsofdantrolene.Thedoseofdantrolene
neededtopreventrecrudescencecannotbedetermInedwIthcertaInty.Nevertheless,
certaIncommonthemesunderlIethebasIsforlItIgatIonIn|H:
1. FaIluretoobtaInathoroughpersonalhIstoryInregardtoanesthetIcproblemsanda
famIlyhIstoryofanyunexplaInedperIoperatIveproblems.
2. FaIluretomonItorcoretemperaturecontInuouslywIthanelectronIctemperature
monItorIngdevIce.ntraoperatIvetemperaturemonItorIngIsnowconsIderedastandard
ofcareIntheUnItedStates.
J. FaIluretohaveadequatesupplIesofdantroleneonhandwIthaplanofmanagementof
|H.
4. FaIluretoInvestIgateunexplaInedIncreasesInbodytemperatureandIncreasedskeletal
muscletone(especIallyaftersuccInylcholIneadmInIstratIon)whenassocIatedwIth
IncreasedheartrateanddysrhythmIas.
SeveralexamplesofmedIcolegalcasesInvolvIngtheseprIncIplesaredescrIbed:
1. AyoungfemalepatIenthadshouldersurgerywIthIsofluranenItrousoxIdeoxygen.
TemperaturewasnotmonItoredcontInuously.Attheendoftheprocedure,premature
ventrIcularbeatsandIncreasIngendtIdalCD
2
werenoted.ThepatIenthadacardIac
arrestasthedysrhythmIawasbeIngtreated.AsthedrapeswerebeIngremoved,the
patIentfeltwarm.AtemperatureproberevealedareadIngofnearly42`C.ThepatIent
wasdIagnosedashavInganacuteepIsodeof|H.0antrolenewasadmInIsteredanhour
later.ThepatIentdeveloped0CoverthenextdayanddIed.Thecasewassettledoutof
court.
2. A26yearoldwomanwasundergoIngabreastaugmentatIonInaplastIcsurgeon'soffIce
usInggeneralanesthesIawIthIsoflurane.Towardtheendoftheprocedure,herheart
rateIncreasedasdIdendtIdalCD
2
andskIntemperature.0antrolenewasnotavaIlable
andthepatIentwassenttoanearbyemergencydepartment.8ythetImedantrolenewas
gIven,hertemperaturewasabout4J`C.Shedeveloped0CanddIed.Thecasewas
settledwIthoutjurytrIal.ThecompanyprovIdIngInsuranceforthephysIcIannow
mandatesthatdantrolenebeImmedIatelyavaIlablewherevergeneralanesthesIaIs
admInIstered.
J. SymptomsofbowelobstructIondevelopedInamIddleagedman.Hewastakentoalocal
hospItal,andanesthesIawasadmInIsteredwIthnItrousoxIdeoxygenhalothaneand
succInylcholIne.HIstemperaturewasnotmonItored,butanunexplaInedtachycardIa
(140to160beats/mIn)waspresentthroughoutthe2hourprocedure.DnarrIvalInthe
IntensIvecareunItaftertheoperatIon,thepatIentwasslIghtlyhypotensIve.nvasIve
monItorIngwasstarted.0espItemarkedmetabolIcandrespIratoryacIdosIs,aPaco
2
of
100mmHg,andarecordedtemperatureofnearly42`C,|HwasnotdIagnosed.AcoolIng
blanketandantIbIotIcsfaIledtoarrestthedecreaseInthepatIent'sbloodpressure,
whIcheventuallyledtocardIacarrest.AjudgmentagaInstthephysIcIansandhospItalof
S4.5mIllIonwasreached.
TherehavebeenseveralmalpractIcecasesfIledagaInstanesthesIologIstsInwhIchcardIac
arrestanddeathoccurredaftersuccInylcholInewasusedInpatIentswIthanundIagnosed
myopathy.TheusualoutcomeIsanoutofcourtsettlement.
ThemessageIsclear.AllfacIlItIeswheregeneralanesthesIaIsadmInIstered(IncludIng
hospItals,outpatIentsurgerycenters,physIcIanoffIces,anddentaloffIces)shouldhavea
fullsupplyofdantroleneavaIlable.AllpatIentsundergoInggeneralanesthesIashouldhave
standardmonItorIng,IncludIngendtIdalCD
2
and,exceptforbrIefcases,body
temperature.
Patient Support Services
ToanswertheneedsofpatIentsandfamIlIeswhowIshedtolearnmoreabout|Handof
thosefamIlIeswhoserelatIveshavedIedfrom|H,supportgroupswerefoundedInseveral
countrIes.The|HAUSprovIdesavarIetyofservIces,suchasaquarterlynewsletter,The
Communicator,wIthexcerptsfromthemedIcallIterature,explanatoryartIcles,questIons
andanswers,andrelatedInformatIon,muchofwhIchIsavaIlableontheWebsIte
(www.mhaus.org).naddItIon|HAUSorganIzedtwohotlInessothatahealthcareprovIder
wIthanurgentquestIonabout|HorN|ScanbeplacedIncontact
P.609
wIthaknowledgeablevolunteerspecIalIst.ApproxImatelyJ0to40callsamonthare
handledbythe|HHotlIne,180064497J7,andasmallernumberbytheNeurolept
|alIgnantSyndromenformatIonServIce,18886678J67.
Theaddressofthe|alIgnantHyperthermIaAssocIatIonoftheUnItedStatesIs11EState
Street,8ox1069,Sherburne,NY1J4601069;FAX,6076747910;phone,16076747901.The
hotlInenumberIs1800|HHyper,(64497J7).
n1989,theNorthAmerIcan|HFegIstrywasformed.NowbasedInPIttsburgh,
PennsylvanIa(ChIldren'sHospItalofPIttsburgh,4126925464),theFegIstryIsthereposItory
forpatIentandfamIlyspecIfIcInformatIonfor|HsusceptIblepatIents.|HsusceptIble
patIentsareInvItedtocontacttheFegIstry.fan|HSIndIvIdualwIshestojoInthe
FegIstry,heorshemustcompleteaquestIonnaIreandsIgnaconsentform.AdescrIptIonof
theFegIstryIsavaIlableatwww.anesth.upmc.edu.TheformsusedIntheFegIstrycanbe
revIewedatwww.mhaus.org.
Pathogenesis and Etiology
WIthIn10yearsofthefIrstdescrIptIonof|HItbecameclearthattherootcausewasan
abnormalIty(orabnormalItIes)InskeletalmusclebIochemIstry.ThIswasfIrst
demonstratedbytheobservatIonthatIsolatedskeletalmuscleInvItrodIsplayedenhanced
contractureresponsestohalothaneandtocalcIumreleasIngcompoundsIn|HsusceptIble
peopleandswIne.SeveralothermajordevelopmentscontrIbutedtothepresent
understandIngofthecomplexpathophysIologyof|H.DnewastherecognItIonthatthe
syndromeIsgenetIcallytransmItted.ThIsfIndIngIssIgnIfIcantbecauseItsuggeststhata
rIgorousapplIcatIonofmodernmoleculargenetIcswIllleadtotheIdentIfIcatIonof
mutatIonsInspecIfIcproteInscausIngthedIsorder(seeChapter6).Anotherwasthe
recognItIonofsImIlarItIesbetweenhuman|HandporcInestresssyndrome.ThIsanImal
modelwasusedtoevaluatedrugsthatcausedthesyndromeandelucIdatetheroleof
alteredCa
2+
regulatIonIn|H.ThIsledtothefIndIngthatamutatIonIntheryanodIne
receptorgenewasassocIatedwIth|HInswIne
120
andInmanyhumans.Yetanotherwas
that|HIsaheterogenetIc(morethanonegene)dIsorder.HeterogeneItymayaccountfor
somevarIabIlItyInpresentatIonandforcesInvestIgatorstoconsIdertheroleofafInal
commonpathwayresultIngfromamutatIonInanyoneofseveraldIfferentproteIns.
FInally,theobservatIonthatpIgsorhumansubjectswIth|HsusceptIbIlItydonotalways
experIence|HwhenexposedtoadequatetrIggerIngagentshassuggestedthatmodulators
InfluencetheexpressIonofthesyndrome.
121,122
thasbeenobservedthatmutatIons(0NAvarIants)IntheryanodInereceptorgeneare
assocIatedwIth80ofallcasesof|H.
97
8utothergenetIclocImayalsolessoftenbe
assocIatedwIth|HS(Table24J).RYR1varIantshavealsobeenassocIatedwIthCC0,
J4,12J
adIsorderknowntopredIsposeto|H.
Altered Calcium Regulation: The Common Final Pathway
UltImately,themaInproblemInskeletalmuscleleadIngtothesIgnsof|HIsalackof
controlofmyoplasmIcCa
2+
concentratIondurInganesthesIa.
5,124
Ca
2+
levelsarecontrolled
byacomplexInteractIonofCa
2+
releasefromthetermInalcIsternae,theATPdrIvenCa
2+
pumpsatthesarcoplasmIcretIculumandsarcolemma,whIchresequesterreleasedcalcIum,
Na
+
/Ca
2+
exchange,severalCa
2+
bufferIngproteIns(calsequestrIn,parvalbumIn),and
mItochondrIalCa
2+
regulatIon(FIg.24J).Althoughseveralofthesesystemsmaybecome
Involvedasthe|HSprogresses,thedIffIcultyInCa
2+
regulatIonappearstoorIgInateInthe
Ca
2+
releasemechanIsmInthetermInalcIsternae,thatIs,thecalcIumchannelknownas
theryanodInereceptor.TheCa
2+
releasemechanIsmcouldbemadesensItIveto
anesthetIcsbyanyofseveralpossIbIlItIes,IncludIngamutatIonIntheskeletalmuscle
calcIumreleasechannel(theryanodInereceptor,RYR1),aproteIndIrectlycoupledtoRYR1
(e.g.,dIhydropyrIdInereceptor),oranalteredmodulatorofRYR1functIon(e.g.,fatty
acIds).SuccInylcholIneopenstheacetylcholInereceptoranddepolarIzesthemuscle
membranebyopenIngthevoltagedependentsodIumchannels,whIchmayhavealtered
functIonIn|H.0epolarIzatIonleadstoCa
2+
releasefromthesarcoplasmIcretIculum.
0antroleneantagonIzesCa
2+
releasefromthesarcoplasmIcretIculum,lowerselevated
IntracellularCa
2+
levels,andreversesanepIsodeof|H.
5
Understanding the Malignant Hyperthermia Defect: Necessary
Concepts
AhypothesIsexplaInIng|HmustaccountforthepuzzlIngclInIcalobservatIonssurroundIng
thIsdIsorder.|ostImportantly,thelargemajorItyofthesepatIentsfunctIonnormallyIn
theabsenceofanesthetIcs.Therefore,thedefectshouldnotsIgnIfIcantlyInterferewIth
normalmusclephysIology.Thedefect,atleastInhumans,appearstobeexpressed
sIgnIfIcantlyonlyInskeletalmuscle.TheexpressIonofthesyndromeshowsalarge
varIabIlItyamongIndIvIduals.Forexample,J0ofpatIentshavehaduptothree
uneventfulanesthetIcsbeforeexperIencIng|H.
66,125
AspectrumofpresentatIonscan
occur,rangIngfromrelatIvelymInorIntraoperatIvecomplIcatIonstorapIdtemperature
rIse,musclerIgIdIty,acIdosIs,dysrhythmIas,anddeath.Somecaseshaveagreaterlatency
toonsetandarenotmademanIfestuntIlseveralhourspostoperatIvely.|Hdoesnot
alwaysoccurInresponsetotrIggerIngagents.ThelargevarIabIlItyamongIndIvIdualsmay
beexplaInedbydIfferentgenescausIng|HIndIfferentfamIlIesorbyotherpredIsposIng
factorsbeIngexpresseddIfferentlyIndIfferentpatIentsorfamIlIes.
126
ThefunctIonof
manydIfferentproteInshasbeenreportedtobealteredIn|Hskeletalmuscle.Thus,ItIs
reasonabletoassumethatsystemsotherthanthosedIrectlyInvolvedInCa
2+
regulatIonare
secondarIlyalteredIn|HandthesemayplayacrucIalroleInmodIfyIng
P.610
theresponsetotrIggerIngagents.TheInvolvementofsecondarysystemswouldexplaInthe
hIghvarIabIlItyInthephenotype.SuchmodIfyIngproteIns,genes,orotherchemIcal
compoundsareyettobeclearlydefIned.
Table 24-3 Molecular Genetics of Malignant Hyperthermia
LOCUS
NAME
GENE
SYMBOL
CHROMOSOMAL
LOCUS
PROTEIN NAME
|HS1 RYR1 19q1J.1 FyanodInereceptortype1
|HS5 CACNA1S 1qJ2
7oltagedependentLtypecalcIumchannel
subunItalpha1S
Figure 24-3.ExcItatIoncontractIoncouplIngandmalIgnanthyperthermIa.TheactIon
potentIalgeneratedattheendplateregIonoftheneuromuscularjunctIonIs
propagateddownthesarcolemma(muscleplasmamembrane)bytheopenIngof
voltagedependentNa
+
channels(1).TheactIonpotentIalcontInuesdownIntothet
tubules(2)tothedIhydropyrIdInereceptors(3).ThedIhydropyrIdInereceptorsIn
skeletalmusclefunctIonasvoltagesensorsandarecoupledtotheCa
2+
release
channels(4).ThroughthIscoupledsIgnalIngprocess,theCa
2+
releasechannelsare
opened,someoftheavaIlabletermInalcIsternaeCa
2+
stores(5)arereleased,andthe
levelsofmyoplasmIcCa
2+
areelevated.TheCa
2+
thendIffusestothemyofIbrIls(6)
andInteractswIththetroponIn/tropomyosIncomplexassocIatedwIthactIn(thin lines)
andallowsInteractIonofactInwIthmyosIn(thick lines)formechanIcalmovement.
TheCa
2+
dIffusesawayfromthemyofIbrIlsandthIsCa
2+
sIgnalIstermInatedbyan
adenosInetrIphosphate(ATP)drIvenCa
2+
pump(7),whIchpumpsCa
2+
Intothe
longItudInalsarcoplasmIcretIculum(8).TheCa
2+
dIffusesfromthelongItudInal
sarcoplasmIcretIculumtothetermInalcIsternae,whereItIsconcentratedforrelease
byCa
2+
bIndIngproteIns.Na
+
enterIngdurIngtheactIonpotentIalIssubsequently
extrudedfromthecellbytheNa
+
/K
+
ATPase(9)andpossIblythroughNa
+
/Ca
2+
exchange(10).ThIslatterprocesswouldelevateIntracellularCa
2+
andcouldresult
fromdelayedInactIvatIonofNa
+
currents.AmajorformofenergyforsupplyIng
cellularATPfortheIonpumpsandnumerousotherenergyconsumIngprocessesIsfatty
acIds(FA)derIvedfromtheserum(dIetaryFA),orfromIntramusculartrIglycerIde(TC)
stores.Therefore,adefectIntheIntracellularCa
2+
regulatIngprocesses(Increased
Ca
2+
releaseordecreasedCa
2+
uptake),oradefectInthesarcolemmacouldaccount
foranIncreaseInmyoplasmIcCa
2+
.
The Sarcolemma and MH
Thesarcolemma(FIg.24J)maIntaInsthemembranepotentIalofthemusclecellandacts
asapermeabIlItybarrIertoIons,IncludIngNa
+
,K
+
,Cl
,andCa
2+
.Skeletalmuscle,Inmost
cases,doesnotrequIreextracellularCa
2+
fornerveorelectrIcallyevokedcontractIlIty.n
contrast,halothaneInducedcontractures
124,127
and,toalesserextent(dependIngonthe
specIes),caffeIneInducedcontractures
124
requIreextracellularCa
2+
.However,the
sarcolemmapersehasnotbeenImplIcateddIrectlyInthepathophysIologyof|H.
Terminal Cisternae: Ca
2+
Release
ThetermInalcIsternaeofthesarcoplasmIcretIculumarethesItesofCa
2+
sequestratIon.
TheyarecoupledtothettubulesthroughtheryanodInereceptorandthedIhydropyrIdIne
receptor(FIg.244;alsoseeFIg.24J).SeveralInvestIgatorshavereportedahypersensItIve
Ca
2+
InducedCa
2+
releaseIntermInalcIsternaepreparatIonsfromporcIne|H
muscle.
128,129,1J0
nmusclepreparatIonscontaInIngtrIadsandsarcoplasmIcretIculum,halothaneat
clInIcallyrelevantconcentratIonscannotInduceasustaInednetCa
2+
releaseIfphysIologIc
levelsofATPand|g
2+
areIncluded.ThIsabIlItytoovercometheeffectsofhalothane
underapproxImatephysIologIccondItIonsIsbecauseoftheenormouscapacItyoftheCa
2+
pumpIngsystem.TheaddItIonoffattyacIds,eventovesIclesIsolatedfromnormalmuscle,
markedly(approxImately20toJ0fold)decreasestheconcentratIonofhalothanerequIred
forthesustaInedopenIngoftheCa
2+
releasechannelInthepresenceofATPand|g
2+
.
UnderthesecondItIons,fattyacIdscancauseasustaInedCa
2+
releaseatclInIcal
concentratIonsofhalothane.UnlIkestudIesofCa
2+
releaseIntheabsenceoffattyacIds,
thereIsanabsolutetemperaturedependence(occursatJ7`C,notat25`C)ofthefatty
acIdenhancementofhalothaneInducedCa
2+
release,whIchIsconsIstentwIththe
temperaturedependenceofhalothaneInducedcontracturesof|Hmuscle.
1J1
Hence,the
typeandconcentratIonoffattyacIdsmaymodulatetheexpressIonof|H.
Mitochondria
|ItochondrIaoxIdIzeavarIetyofsubstratestogeneratetheformofenergy(ATP)most
usefulfordrIvIngcellularreactIons.0efectsInmItochondrIalfunctIondonotappearto
InItIatethe|HS,althoughtheymayproduceIncreasedtemperature,acIdosIs,and
cardIovascularfaIlure.
P.611
Figure 24-4.SchematIcIllustratIonofthehomotetramerIcryanodInereceptor,the
calcIumreleasechannelsItuatedInthemembraneofthesarcoplasmIcretIculum.The
cytosolIcpartoftheproteIncomplex,thesocalledfoot,brIdgesthegapbetweenthe
transversetubularsystemandthesarcoplasmIcretIculum.|utatIonshavebeen
descrIbedfortheskeletalmuscleryanodInereceptor(RYR1),whIchcausesusceptIbIlIty
tomalIgnanthyperthermIa(|H)andcentralcoredIsease(CC0).(FeprIntedfrom
TrevesS,AndersonAA,0ucreuxS,etal:FyanodInereceptor1mutatIons,
dysregulatIonofcalcIumhomeostasIsandneuromusculardIsorders.Neuromusc0Isord
1:2005;5:577,wIthpermIssIon.)
Longitudinal Sarcoplasmic Reticulum: Ca
2+
Uptake
ThelongItudInalsarcoplasmIcretIculum(FIg.24J)IsprImarIlyInvolvedInremovIngCa
2+
fromthemyoplasmthroughtheATPdrIvenCa
2+
pump.WhIleearlIerstudIeshadsuggested
adefectInCa
2+
uptakemIghtcausethelossofCa
2+
regulatIonassocIatedwIth|H,
subsequentstudIeshaveruledoutarolefortheCa
2+
pumpIncausIng|H.
Myofibrils
NodefectIntheCa
2+
sensItIvItyofthefastorslowfIbersofthecontractIlesystemfrom|H
skeletalmusclehasbeenobserved.
Calcium Release Channel of Skeletal Muscle and its role in MH
ThehumanskeletalmusclecalcIumreleasechannelIsencodedbyaryanodInereceptor
type1(RYR1)genelocatedonchromosome19q1J.1.
1J2
(FIg.244).Thereareothertypesof
FYFthatexIstIncardIacmuscle(type2)andbraIn(typeJ)tIssues,respectIvely.However,
thoseorgansdonotappeartobeInvolvedprImarIlyInthepathophysIologyof|H.RYR1Is
theprImaryconduItthroughwhIchthesarcoplasmIcretIculumstoresofCa
2+
arereleased
tothesarcoplasm.RYR1Isanextremelylargehomotetramer,havIngsubunItsofabout
560,000|Weach.RYR1hasbIndIngsItesforthecontractureInducIngplantalkaloId
ryanodIne
1JJ
andthepreservatIve4CmC.
1J4
SusceptIbIlItyto|HIsassocIatedwIthmutatIonsInRYR1.
94,1J5,1J6
ThehypothesIsthat
mutatIonInRYR1causes|HsusceptIbIlItyIssupportedbyphysIologIcstudIesshowIng
subtleeffectsofhalothaneonIsolatedRYR1currentsInhuman|Hmuscle.
1J7
Halothane
canopenahypersensItIveRYR1,leadIngtoanuncontrolledreleaseofCa
2+
Intothe
myoplasmandthe|HS.However,thebufferIngcapacItyoftheCa
2+
pumpInthepresence
ofATPIsabletosustaInnormalCa
2+
regulatIonInthepresenceofhalothaneIntermInal
cIsternaepreparatIonsIsolatedfrom|Hmuscle.TheseobservatIonsareconsIstentwIth
theobservedInterIndIvIdualvarIabIlItyInhuman|HandtheoccurrenceofnonrIgId|H.
WhenATPIslow,thesyndromeoccurs,andthelowertheenergystores,theworsethe|H
syndromeIs.
ConsIstentwIththealteredfunctIonofRYR1,therehasbeenaspecIfIcmutatIonIdentIfIed
(Arg
615
toCys
615
)InRYR1InsusceptIbleswIne.
1J8
ThemutatIonIsonthecytoplasmIc
surfaceofRYR1.
1J9
taccountsforthealteredfunctIonalstatesofRYR1andryanodIne
bIndIngIntheseanImals.ThehumanequIvalent(Arg
614
toCys
614
)totheswIneRYR1
mutatIonhasbeenIdentIfIedIn2to11of|HfamIlIes,dependIngonpopulatIonstudIed.
However,InsomecasesthereIsadIscordancebetweenthepresenceofthIsmutatIonand
theoutcomeofthedIagnostIccontracturetest.
140,141,142
Amajorreasonforthe
attenuatedeffectsoftheRYR1mutatIonInhumanmuscleIslIkelythedomInantmodeof
InherItancewIthreducedpenetranceandgenetIcheterogeneItyof|HversusrecessIve
mutatIonInthepIg.Thus,normalcopIesofRYR1areexpressedInhuman|Hmuscle,but
notsusceptIbleanImalmuscle.ThenumberofsequencevarIantsInRYR1assocIatedwIth
|HtodateIs150,IncludIngArg614Cys,andthIsnumberIsconstantlyrIsIng.|anyofthese
arefoundInonlyafewfamIlIes.
nsummary,therearephysIologIc,bIochemIcal,pharmacologIc,andmoleculargenetIc
datasupportIngamutatIonInRYR1asanImportantfactor,andperhapsanInItIatIng
factor,In70ofthefamIlIeswIth|H.TheeffectsofthealteredRYR1functIononCa
2+
regulatIondetermInedInvItroarenotaspronouncedInhumansasInswIne,possIblyowIng
tothedomInantmodeofInherItanceandgenetIcheterogeneItyof|HInhumans.tIs
hIghlyprobablethatothersystemscomeIntoplayasmodulatorsofthe|Hresponse.ThIs
maybetterexplaIntheextremeIntraandInterIndIvIdualvarIabIlItyInthehuman|H
syndrome,whIchIsIncontrasttothemoreconsIstentresponseIn|HswIne.
Molecular Biology of Malignant Hyperthermia
TheIdentIfIcatIonoftheporcInemutatIoncausIngporcInestresssyndrome,andthe
locatIonofthehumanRYR1geneonchromosome19q1J.1,hashelpedtoestablIshadIrect
lInkofthIsgeneto|H.
1J2,14J
About70of|HfamIlIeshaveaRYR1varIant.
RYR1Isoneofthelargesthumangenes.tcontaIns106exonsthataretranscrIbedIntoa
15,J64nucleotIdemFNA.TranscrIptIonoccursmaInlyInskeletalmuscle.|orethan200
dIfferentsequencevarIantshavebeenIdentIfIedInRYR1.ThemajorItyareclusteredIn
threeregIons:theNtermInalregIonbetweencodonsJ4and614,thecentralregIon
betweencodons216Jand2458,andtheCtermInalregIonbetweencodons41J6and
497J.
94,96,12J,1J5,144
ThIspreferentIallocalIzatIonraIsedspeculatIonsconcernIngthe
specIfIcroleoftheseregIons.ThecentralregIonIsclosetotheregIonwheretheproteIn
P.612
wouldInteractwIththeregulatoryproteIn,FK8P12,andthedIhydropyrIdInereceptor,a
voltagesensorofRYR1.TheCtermInalregIoncorrespondstothetransmembranedomaIn
oftheproteIn.
12J
ThepathogenIccharacterofmanyRYR1mutatIonshasbeenstudIedby
measuresofIntracellularcalcIumreleaseInresponsetocaffeIneorhalothanewIthuseof
dIfferentcelllInes.
145,146
SeIandcolleagues
147
andCIrardandcolleagues
148
have
demonstratedthepresenceofcalcIumchannelssImIlartothosefoundInskeletalmuscleIn
the8lymphocytealongwIthenhancedIntracellularcalcIumlevelsarefoundIn
lymphocytesfromcelllIneswIthmutatedryanodInegenesonexposuretocaffeIneor
chlorocresol.
ThephenotypeandgenotypecorrelatIonstudIesareverylImItedIn|HbecauseItIs
dIffIculttoestablIshcorrelatIonbetweenthemutatIonandcontractIledatabecauseof
varIablesamongdIagnostIclaboratorIesandbecauseofadearthofdefInItIveclInIcal
epIsodesof|HSasaresultofsuccessfulInterventIondurIngonsetofanepIsode.
Nevertheless,themostseverephenotypeassocIatedwIthRYR1mutatIon(s)IsCC0,
characterIzedbymarkedhypotonIaandmuscleweakness.nterestIngly,themajorItyof
RYR1mutatIonscausIngCC0arelocatedInthetransmembraneregIonoftheproteIn,
suggestIngacrItIcalroleofthIsregIonInCa
2+
regulatIon.naddItIon,themutatIons
causIngboth|HandCC0(F16JC,F216JH,andF24J5H)exhIbItmoreseverecaffeIneand
halothaneresponsesthanthoseassocIatedwIth|Halone.
149
CenetIcstudIeshaveIdentIfIedlInkageoffourotherchromosomalregIonsto|H,
suggestInggenetIcheterogeneItyofthedIsorder,IncludIng|HS2at17q11.2q24,|HSJat
7q21q22,and|HS6at5p.However,onlyonegeneotherthanRYR1hasbeenIdentIfIed
(Table24J).TheArg1086HIsmutatIonwasIdentIfIedIntheCACNL1A3,alsoreferredtoas
theCACNA1Sgene,ofalargeFrench|HfamIly.CACNL1A3codesforthe
1
subunItofthe
dIhydropyrIdInereceptor(DHPR)thevoltagesensorforRYR1.
150
|utatIonalscreenIng
studIes,however,IndIcatethatonly1of|HSfamIlIesexhIbItmutatIonsIntheDHPR.No
mutatIonhasbeenfoundInthe|HSJlocusIna|HSfamIly.
AsmentIonedalready,dIscordancebetweensegregatIonofmutatIonsIdentIfIedInRYR1
andtheoutcomeoftheInvItrocontracturetestfor|H
140,141,151,152
hasbeenreported.
ThIsdIscordanceIsuncommonandthereasonsforItrangefromspecImenmIxuporfalse
posItIvecontracturetesttosIlencIngoftheexpressIonoftheabnormalgene.ncontrast,a
studyInswInehasdemonstratedthatthereIsanexcellentcorrelatIonbetweenthe
contracturetestoutcomeandthegenetIcsusceptIbIlItyfor|H.nhumanfamIlIes,specIfIc
ryanodInemutatIonsusuallycorrelateextremelywellwIththeInvItrocontracturetest
result.Hence,InapartIcularfamIlythepresenceofthefamIlIal|HmutatIonpredIcts|H
susceptIbIlItywIthanextremelyhIghspecIfIcIty.
15J
Do Fatty Acids Contribute to the Pathophysiology of Malignant
Hyperthermia?
DnetheoryaccountIngfortheobservedclInIcalvarIabIlItyofthe|HSpostulatesarolefor
freefattyacIdsInthepathophysIologyofthesyndrome.
LIpIdsareanImportantcomponentofacell,astheyprovIdeenergyandstructure(e.g.,
membranes)andpartIcIpateInfunctIon.SeverallIpIdmetabolItes,IncludIngfattyacIds,
servesecondmessengerfunctIons.
154
FattyacIdsarethemajorsourceofenergyInthe
restIngstateofskeletalmuscleandcanalsocontrIbuteupto65oftheenergydurIng
exercIse.
155
FattyacIdsprovIdeabout70oftheenergyInrestIngmuscle.Therefore,fatty
acIdutIlIzatIonIslIkelyupregulatedIn|Hmuscletocompensatefortheenergyconsumed
bytheadenosInetrIphosphatasestomaIntaInNa
+
andCa
2+
homeostasIs.
naddItIontoexIstIngInafreeform,fattyacIdsareesterIfIedtophospholIpIds,
trIacylglycerIdes,dIacylglycerIdes,monoacylglycerIdes,cholesterolesters,andmany
proteIns.FreefattyacIdsaremaIntaInedatverylowlevelsInacell(sIncetheyarenot
onlyessentIal,butverytoxIc)andmostofthefreefattyacIdsactuallyareboundtofatty
acIdbIndIngproteIns.
156
FattyacIdproductIonIselevatedInmItochondrIalfractIonsandwholemuscle
homogenatesfromswIneand|HsusceptIblepatIents.ThereIsanagerelatedIncreaseIn
fattyacIdproductIonInskeletalmusclethatparallelsanagerelatedIncreaseIn
susceptIbIlItytothePSS.
157
WhenonlystatIclevelsoffreefattyacIdsareexamIned,they
areatnormallevelsInhuman|HandPSSmuscle.However,thefluxoffattyacIdsthrough
oxIdatIoncanstIllbeIncreasedtoalargeextentIn|HmusclewIthoutIncreasIngthe
levelsoffreefattyacIds.ThefattyacIdfluxIsderIvedfromtrIacylglycerIdes,andthIs
lIkelyaccountsforthelowlevelsoftrIacylglycerIdes(ortotalneutrallIpId)InbIopsIed|H
orPSSskeletalmuscle.TheeffectsoffattyacIdsonCa
2+
releasefromskeletalmuscle
sarcoplasmIcretIculumaresIgnIfIcant,butnotdramatIc,Intheabsenceof
anesthetIcs,
158,159
andtheyarenotmedIatedthroughRYR1.
160
However,thefattyacIds
actInsynergywIthhalothaneanddecreasetheamountofhalothanerequIredforsustaIned
Ca
2+
releaseby20toJ0fold!
122,129
ThIsfattyacIdenhancementofhalothaneInducedCa
2+
release,IncontrastwIthallotherstudIesofCa
2+
release,exhIbItsthesametemperature
dependence(I.e.,ItoccursonlyatJ7`C,notat25`C)ashalothaneInducedcontracturesof
skeletalmuscleandIsmedIatedthroughRYR1.
122
WhIletheconcentratIonoffattyacId
requIredforthIseffectexceedsthatofthenormalunboundform,halothanecandIsplace
fattyacIdsfromfattyacIdbIndIngproteIns.
161
Therefore,ItIshIghlylIkelythatsuffIcIent
concentratIonsoffattyacIdscouldbeachIevedatthesIteofhalothaneactIon.fthe
productIonoffreefattyacIdsIssustaInedbyacceleratedtrIacylglycerIdebreakdownand
thefattyacIdsareshuntedtowardacylatIonofRYR1andthesodIumchannel,thenthIs
couldleadtogreatlyelevatedmyoplasmIcCa
2+
levels.nthecaseofRYR1,thIswouldlead
toagreatersensItIvItytohalothane.
The Future of Research in Malignant Hyperthermia
WhIlemoleculargenetIcshasdomInatedtheresearchIn|HInrecentyears,adeeper
understandIngofthephysIologyandbIochemIstryoftheInterplayamongRYR1,theNa
+
channel,andfattyacIdmetabolIsmstIllIsneeded.0NAbasedlInkageanalysesareno
longerpursuedtothesameextentasIntheearly1990s.nstead,thefocusofrecent
moleculargenetIcstudIeshasbeenonIdentIfyIngnewmutatIonsInRYR1andthe
phenotypIceffectsassocIatedwIthsuchmutatIons.
162
FurtherlInkagestudIesarenecessary
toIdentIfyothergeneslInkedto|H.
tseemsclearthattheaccuracyofmoleculargenetIctestIngfor|HsusceptIbIlItywIll
ImproveasaddItIonalmutatIonsarefoundtobecausalfor|H.Assuch,genetIctestIngwIll
IncreasInglyreplacethecontracturetestdespItethenumerous0NAchangesthatarelIkely
tobecausal.WIthadvancesInmoleculargenetIcstechnology,ItIslIkelythatItwIllbe
possIbletoscreenforallmutatIonsInacosteffectIvemanner.
DneofthemajorclInIcalconcernsof|HsusceptIblepatIentsIstheIrpossIblerIskforheat
stroke,exercIseInducedrhabdomyolysIs,andotherenvIronmentalstressorsthatmIght
affectmusclefunctIon.0NAtestIngfacIlItatesevaluatIonofthosewhohaveexperIenced
oneofthesenonanesthetIcassocIatedproblems.8uttoruleoutthedIagnosIsof|HS,ItIs
stIllnecessarytoundergomusclebIopsyandcontracturetestIng.CenesotherthanRYR1
InfluencetheresponseofmuscletoexercIse.
16J
CreatIonoftheknockInmousemodel
for|H,wherebyoneofthecausalmutatIonsIsIncorporatedIntothemousegenome,has
shownthatIndeedhIghenvIronmental
P.61J
temperature
6,7
IsfatalIntheseanImals.SuchartIfIcIalconstructswIlllIkelyrevealmore
InformatIonconcernInggenotypeandphenotype.
Summary
|utatIonsassocIatedwIthskeletalmusclecontrolofIntracellularcalcIumbytheRYR1
channelarecausalformostcasesofclassIc|H.AnyoneofthreedIfferentgenesmay
cause|H,althoughtheexactproteInsthatareabnormalIn|HremaIntobeIdentIfIedIn
somecases.|utatIonshavebeenIdentIfIedInRYR1andInthedIhydropyrIdInereceptor
gene.AvarIetyofpoorlyunderstoodbIochemIcaland/orgeneexpressIonfactorsInfluence
theclInIcalmanIfestatIonsof|H.Forexample,mutatIonsInasodIumchannelsubunItmay
beassocIatedwIthsomesIgnsof|H,butthIsclInIcal|HrequIrestheexpressIonofother
factorsalso.AdIsturbanceInfattyacIdmetabolIsm,asasecondaryeffect,altersthe
functIonofseveralorganellesandcanleadtoahypersensItIveRYR1responsetohalothane
andalteredNa
+
channelsubunItexpressIonInskeletalmuscle.The|HSIstheresultofa
complexandpoorlyunderstoodInteractIonamongseveralsystemsInskeletalmuscle.
Other Inherited Disorders
nherIteddIseasesaffecteverybodIlyorganandeveryphysIologIcandbIochemIcalprocess.
SomearemIldandallowarelatIvelynormallIfespan,whereasothersareIncompatIble
wIthextrauterIneexIstenceevenforafewdays.AddIngtothecomplexItyIsanatural
varIabIlItyofgenetIcpenetranceandexpressIvItyevenInasInglefamIly.Allofthese
dIsordershaveasacommonfeatureanabnormalItyInoneormoregenesthataffectsthe
functIonofoneormoreenzymes.ThemetabolIcbasIsofInherIteddIseasesIsthesubject
ofseveralwellknownbooks,whIchmaybeconsultedforanIndepthapprecIatIonofour
stateofknowledgeofmanyofthesedIsorders.
Disorders of Plasma Cholinesterase
Plasma cholinesterase, pseudocholinesterase,orbutyrylcholInesterase(8ChE)Isanenzyme
wIthamolecularweIghtofJ20,000andatetrahedralstructure.Thefourexonsthatcode
forthIsproteInarelocatedonchromosomeJq26.8ChEIsfoundInplasmaandmosttIssue
butnotInredbloodcells.8ChEdegradesacetylcholInereleasedattheneuromuscular
junctIon,aswellasothercholIneandalIphatIcesters.
164
ThehalflIfeof8ChEhasbeen
estImatedtobe8to16hours.tIsverystableInserumsamplesandcanbestoredforlong
perIodsoftImeat20`CwIthlIttleornoactIvItyloss.8ChEIssynthesIzedInthelIver.
Therefore,8ChEactIvItyIsdecreasedInadvancedcasesofhepatocellulardysfunctIonfrom
anycause.
nherItedvarIantsof8ChEareofInteresttotheanesthesIologIstbecausetheduratIonof
actIonofsuccInylcholIneand(Insomecases)esterlInkedlocalanesthetIcs,aswellasthe
toxIcItyofcocaIne,
165
IsafunctIonoftheactIvItyofthIsenzyme(seeChapter20).
ProlongedapneaaftersuccInylcholIneadmInIstratIonoccursInpatIentswhohavelow
absoluteactIvItyof8ChEorenzymevarIants.
166,167
Low8ChEactIvItypredIsposespatIents
totoxIcItyfromstandarddosesofantIAlzheImerdrugs.
168
DtherwIse,8ChEdefIcIent
patIentshavenosymptoms.
|anyphysIologIc,pharmacologIc,andpathologIcfactorscaneItherIncreaseordecrease
theactIvItyofthIsenzymetoasIgnIfIcantextent(Table244).DnlywhenthereIsa75
decreaseInthelevelsofthenormal8ChEIsthereclInIcallyevIdentprolongatIonof
succInylcholIneactIvIty.
Table 24-4 Some Causes of Changes in Cholinesterase Activity
a
INHERITED
CholInesterasevarIantsthatmayleadtodecreasedorIncreasedactIvIty(e.g.,
sIlentgeneorC5varIant)
PHYSIOLOGIC
0ecreasesInlasttrImesterofpregnancy
FeducedactIvItyofthenewborn
ACQUIRED DECREASES
LIverdIseases
CarcInoma
0ebIlItatIngdIseases
CollagendIseases
UremIa
|alnutrItIon
|yxedema
ACQUIRED INCREASES
DbesIty
AlcoholIsm
ThyrotoxIcosIs
NephrosIs
PsorIasIs
Electroshocktherapy
DRUGS RELATED TO DISEASES
NeostIgmIne
PyrIdostIgmIne
ChlorpromazIne
EchothIophateIodIde
CyclophosphamIde
|onoamIneoxIdaseInhIbItors
PancuronIum
ContraceptIves
DrganophosphorusInsectIcIdes
HexafluorenIum
OTHER CAUSES OF DECREASED ACTIVITY
PlasmapheresIs
ExtracorporealcIrculatIon
Tetanus
FadIatIontherapy
8urns
a
ThesIgnIfIcanceofthesefactorsdependsontheseverItyofdIsease,drugdosage,
andIndIvIdualvarIatIon.
AdaptedfromWhIttaker|:PlasmacholInesterasevarIantsandtheanesthetIst.
AnaesthesIa1980;J5:174.
Succinylcholine-Related Apnea
SuccInylcholIneIshydrolyzedbyatwostepprocess,fIrsttosuccInylmonocholIneandthen
tosuccInIcacId.thasbeenestImatedthatonlyabout5oftheInjecteddrugreachesthe
endplateregIonbecauseofacombInatIonofbothhydrolysIsanddIffusIonfromtheplasma.
UrInaryexcretIonandproteInbIndIngplayunImportantrolesInthedIsposItIonofthedrug
when8ChEactIvItyIsnormal.TherateofmetabolIsmdetermInestheduratIonofactIonof
succInylcholIne.
AvarIetyofassayproceduresareavaIlablefor8ChE.However,mostInvolvethereactIon
ofathIocholIne(e.g.,butyrylthIocholIne)
P.614
wIthserumorplasmacontaInIngcholInesterase.ThereactIonproductIscoupledwIth5,5
dIthIobIs(2nItrobenzoIcacId)andformsacoloredproductthatcanbefollowed
spectrophotometrIcally.TheuseofbenzoylcholIne,aspecIfIcsubstratefor8ChE,avoIds
contamInatIonoftheassayfor8ChEbytheesteraseInredbloodcellsthatIsreleased
whenhemolysIsoccurs.
Table 24-5 Biochemical Characteristics of Some Cholinesterase Variants
GENOTYPE ACTIVITY
DIBUCAINE
NUMBER
FLUORIDE
NUMBER
CHLORIDE
NUMBER
SUCCINYLCHO-
LINENUMBER
EuEu
677
1,860
7886 5565 112 8998
EaEa 140525 1826 16J2 4658 419
EuEa
285
1008
5170 J855 15J4 5178
EuEf 579900 7480 4748 14J0 8791
EfEa 475661 4959 25JJ J1J6 5659
EfEs J51 6J 26 25 81
Eu,normalenzymegene;Ea,atypIcalenzymegene;Ef,fluorIderesIstantgene;Es,
sIlentgene.
Feproducedfrom7Iby|ogensenJ:SuccInylcholIneneuromuscularblockadeIn
subjectshomozygousforatypIcalplasmacholInesterase.AnesthesIology1981;55:
429,wIthpermIssIon.
KalowandCenest
169
werethefIrsttoshowthatqualItatIveaswellasquantItatIve
dIfferencesIn8ChEdetermInetheduratIonofsuccInylcholIneapnea.TheyfoundthatIn
certaInpersonsdIsplayIngsuccInylcholInesensItIvIty,thelocalanesthetIcdIbucaIne
(NupercaIne)InhIbItedthehydrolysIsofabenzoylcholInesubstratelessthanItInhIbIted
thereactIonInthosedIsplayInganormalresponsetosuccInylcholIne.Thus,thIsatypIcal
phenotypemaybereferredtoasdibucaine-resistant.ThepercentageInhIbItIonofthe
reactIonwastermedthedibucaine number.twasfoundtobeconstantforapersonand
dIdnotdependontheconcentratIonoftheenzyme.
AdIscontInuousdIstrIbutIonofdIbucaInenumberssuggestedanInherItancepatternbased
onalteratIonatasInglegenelocus(Table245).ThosewIthdIbucaInenumbersInthe
rangeof80wouldbehomozygousnormalwIthanormalresponsetosuccInylcholIne;those
wIthdIbucaInenumbersof20wouldbehomozygousatypIcalwIthamarkedprolongatIonof
succInylcholIneactIvIty;andthosewIthdIbucaInenumbersInthe60rangewouldbe
heterozygousand,Ingeneral,haveanormalresponsetosuccInylcholIne.
|anypoIntmutatIonshavebeendIscovered.Nevertheless,theeffectsofthesemutatIons
arestIlldescrIbedbyafewcategorIesoffunctIonalchange.nonecase,thesIlenttype,
enzymeIsnotproduced.ntheother,thereIsadIfferentIalInhIbItIonof8ChEby
fluorIde.
170
nthosewIthprolongedduratIonofsuccInylcholIneactIvItywIththIsgenotype,
fluorIdeIonInhIbItstheInvItrohydrolysIsofsubstratebytheenzymelessthanItdoesIn
normalpatIents.Thus,thephenotypemaybereferredtoasfluoride-resistant.Afluoride
number,sImIlartoadIbucaInenumber,Istherebycreated.DthervarIantsexIst,IncludIng
theKvarIant,whIchcanbeIdentIfIedonlybygenetIcanalysIs,notbythecurrenttestsof
substratedegradatIon.
WhenthereIsaquestIonofsuccInylcholInesensItIvIty,theabsoluteactIvItyof8ChEshould
bedetermInedaswellasthedIbucaIneandfluorIdenumbers.nsomecases,becauseof
bIologIcvarIabIlItyorunusualcombInatIonsofgenotype(e.g.,combInatIonofatypIcaland
fluorIdegenes),ItIshelpfultouseotherInhIbItorsofthecholInesterasereactIonIn
genotypIngthepatIent.8romIde,urea,sodIumchlorIde,andsuccInylcholInehavebeen
usedtodIstInguIshthevarIousgenotypes(Table245).
|oleculargenetIctechnIqueshavebeensuccessfullyapplIedto8ChEvarIants.PrImo
Parmaetal.
171
and|cCuIreetal.
172
IdentIfIedapoIntmutatIonInthegeneforhuman
8ChEInwhIchanucleotIdechangeleadstoanalteratIonofasIngleamInoacId(adenIneto
guanIne)IntheproteIn.ThIschangeapparentlyalterstheaffInItyofatypIcal8ChEfor
cholIneesters.DtherbasepaIralteratIonsaccountforotheratypIcalvarIants,IncludIng
theKandJsIlentgenevarIants,whIch,althoughcommon,producelIttletonoclInIcal
prolongatIonofsuccInylcholIneactIon(Table246).
nEuropeanstudIes,theapproxImatepercentagesInthepopulatIonofthegenotypesare
asfollows:EuEu(96),EuEa(2.5),EuEforEuEs(0.J),EaEf(0.005),EaEa(0.05),and
EfEforEfEs(0.006).
17J
PatIentshomozygousforatypIcal,fluorIde,orsIlentgenesaswell
asthosewIththecombInatIonofatypIcalwIthfluorIde,atypIcalwIthsIlentgenes,or
fluorIdewIthsIlentgenesshouldwearsafetyIdentIfIcatIonbraceletsIndIcatIngthat
succInylcholIneadmInIstratIonwIllleadtoprolongedapnea.FelatIvesshouldbetestedas
well.
Clinical Implications of Pseudocholinesterase Abnormalities
mportantquestIonsfortheanesthesIologIstare:WhIchpatIentsareatrIskfor
developmentofanabnormalresponsetosuccInylcholIne:WhataretheclInIcal
characterIstIcsofthIsresponse:WhatarethetreatmentoptIons:
SIgnIfIcantprolongatIonofsuccInylcholIne'seffectsoccursInthefollowInggenotypes:
EaEa,EfEf,EaEs,EfEa,andEsEs.ThemorecommonsItuatIonsInwhIchhomozygotenormal
patIentsandheterozygotesareatrIskareasfollows:patIentswhohavebeenreceIvIng
echothIophateeyedrops(upto2weeksaftertherapyIsdIscontInued),patIentswhoare
undergoIngplasmapheresIs,patIentswIthseverelIverdIsease,andpatIents(partIcularly
heterozygotes)whohavereceIvedsuccInylcholIneafterreversalofnondepolarIzIng
blockadewIthneostIgmIne.
Table 24-6 Structural Changes of Bche Variants
FluorIde2 117CLYFrameshIft
AtypIcal 70ASPCLY
SIlent 117CLYFrameshIft
FluorIde1 24JTHF|ET
FluorIde2 J90CLY7AL
K7arIant 5J9ALATHF
H7arIant 1427AL|ET
J7arIant 497CLU7AL
P.615
7Iby|ogensen
166,167
hasstudIedthequestIonof8ChEapneaIndetaIl.HIscholInesterase
unItfoundthat6.2ofpatIentswhodIsplayedapneafor50to250mInutesafterausual
doseofsuccInylcholInehadanacquIreddefIcIencyof8ChE.HethenstudIed70patIents
whoweregenotypIcallynormalfor8ChEandadmInIstered1.0mg/kgofsuccInylcholIne
durInga50nItrousoxIdeoxygen1halothaneanesthetIcandfollowedthedepressIonand
returnofthumbtwItch.HefoundthattherewasIndeedarelatIonshIpbetweenthe
duratIonofapnea,thereturnofafulltwItchresponse,and8ChEactIvIty.However,only
moderateprolongatIonofapneawasfoundwhen8ChEwasdepressedbyasmuchas70.
ApneaIssIgnIfIcantlyprolongedonlywIthextremedepressIonof8ChEactIvIty.
nasecondstudywIthasImIlarprotocol,hefoundthatheterozygoteshavIngonenormal
gene(e.g.,EuEa,EuEf)hadanormalresponsetosuccInylcholIne,IncludIngtypIcal
fascIculatIonsandadepolarIzIngtypeofblockwIthtraInoffourstImulatIons.
167
However,
heterozygoteswIthouttheusualgene(e.g.,EaEf)hadaprolongedresponseto
succInylcholIne,wIthapnealastIngaslongas24mInutes.Apnealastsfrom120mInutesto
J00mInutesInhomozygousatypIcalpatIents(EaEa)whentheyaregIven
succInylcholIne.
167
TheotherclassofpatIentswhoregularlydIsplayprolongedapneaafter
succInylcholIneadmInIstratIoncomprIsespatIentswhoarehomozygousforthesIlentgene.
Treatment of Succinylcholine Apnea
ThesafestcourseoftreatmentwhenthepatIentfaIlstobreathe10to15mInutesafter
succInylcholIneadmInIstratIonIstocontInuemechanIcalventIlatIonuntIladequatemuscle
tonehasreturned.TwounItsoffreshfrozenplasmamaycontaInadequateamountsof
8ChEtohydrolyzethesuccInylcholIne,
174
althoughbloodtransfusIonIsnotrecommended
forroutInetreatmentofsuccInylcholIneInducedapnea.
TheuseofcholInesteraseInhIbItorsIntreatIngsuccInylcholIneapneaIscontroversIal.f
theyareadmInIsteredbeforethereIsevIdenceoffadewIthtraInoffourstImulatIon,there
maybeatransIentImprovementfollowedbyIntensIfIcatIonoftheneuromuscularblock.
FememberthatneostIgmIneInhIbItsthedegradatIonofsuccInylcholIneby8ChE.Thebest
chanceforreversalofsuccInylcholInerelatedapneaInthesesItuatIonsoccurswhenno
morethan0.0Jmg/kgofneostIgmIneIsgIven90to120mInutesaftersuccInylcholInewhen
anondepolarIzIngtypeofblockadeIspresent.
C5 Variant
AnIsoenzymeof8ChEhasbeendemonstratedwherebythehydrolysIsofsuccInylcholIneIs
Increased,andthereforetheduratIonofapneaIsdecreasedaftersuccInylcholIne
admInIstratIon.ThegenedoesnotappeartobeanalleleoftheEuandEageneandIs
foundInfrequentlyInthepopulatIon.
175
Figure 24-5.8IosynthesIsofhemeandsItesofdefectsIncertaInporphyrIas.n
IntermIttentacuteporphyrIa,thereIsapartIaldefIcIencyoftheenzymeatsIte1.n
heredItarycoproporphyrIa,thereIsanenzymedefIcIencyatsIte2.nvarIegate
porphyrIa,theenzymeproblemIsatsIteJ.nporphyrIacutaneatarda,thereIsa
defIcIencyatsIte4.ALA,amInolevulInIcacId;P8C,porphobIlInogen;UFD,
uroporphyrInogen;CDPFD,coproporphyrInogen;PFDTD,protoporphyrInogen;PFD,
protoporphyrIn.(FeprIntedfrom|ees0L,FrederIcksonEL:AnesthesIaandthe
porphyrIas.South|edJ1975;68:29,wIthpermIssIon.)
Plasma Cholinesterase Abnormalities and the Metabolism of
Local Anesthetics
AlthoughtheesterlInkedlocalanesthetIcs(e.g.,procaIne,tetracaIne,2chloroprocaIne)
aremetabolIzedby8ChE,prolongatIonofblockand/orclInIcaltoxIcItyoftheselocal
anesthetIcsInhomozygousatypIcalpatIentshasrarelybeendocumented.
176,177
Jatlowet
al.
178
haveshowndelayedhydrolysIsofcocaIneInvItrowIthplasmafromhomozygote
atypIcalpatIents.TheytheorIzedthatsuchpersonsmaybeatrIskfortoxIcreactIonfrom
normaldosesofcocaIne.
The Porphyrias
AlltheporphyrIasresultfromadefectInhemesynthesIs.ThehemepIgmentsare
tetrapyrrolesthataretheessentIalelementsInhemoglobIn,myoglobIn,andthe
cytochromes.ThatIs,compoundsthatareInvolvedInthetransportofoxygen,actIvatIon
ofoxygen,andtheelectrontransportchaIn.CytochromeP450IsahemoproteInIntImately
InvolvedIntheconversIonoflIpIdsolublenonpolardrugstosolublepolarcompoundsthat
maybeexcretedIntheurIne.
AcompletedefIcIencyofenzymesthatareInvolvedInhemesynthesIsIsIncompatIblewIth
lIfe.However,apartIaldefIcIencymayleadtotheaccumulatIonofoneormoreofthe
molecularIntermedIatesInhemeproductIon.SuchanaccumulatIonofprecursorsIs
responsIblefortheclInIcalmanIfestatIonsoftheporphyrIasInanasyetunexplaIned
manner.
TheratelImItIngstepInhemesynthesIsIstheconjugatIonofsuccInylCoAwIthglycIneto
form0amInolevulInIcacId(theenzymeIsamInolevulInIcacIdsynthetase).nthe
porphyrIas,thereIsapartIaldefIcIencyofenzymessubsequenttothIsInItIalstep,whIch
resultsInastImulatIonofthIsreactIontoformamInolevulInIcacId.TheresultIs
overproductIonofIntermedIateproductsbeforethedefIcIentstep(FIg.245).
TheporphyrIasgenerallymanIfestafterpuberty.nherItanceIsautosomaldomInant,
exceptfortheautosomalrecessIvecongenItalerythropoIetIcporphyrIa.
AfunctIonalclassIfIcatIonfortheanesthesIologIstIsbasedonadIvIsIonoftheporphyrIas
IntoInducIbleandnonInducIble.TheInducIbleporphyrIasarethoseInwhIchtheacute
symptomsareprecIpItatedondrugexposure(Table246).
179
AcuteIntermIttentporphyrIa,
varIegateporphyrIa,andheredItarycoproporphyrIaareInducIble.TheseporphyrIascause
anacuteneurologIcsyndromewIthavarIetyofpresentatIons.CutaneousmanIfestatIons,
wIthpartIcularsensItIvIty
P.616
toultravIoletlIghtexhIbItedbyskInfragIlItyandbleedIng,areotherchIeffeaturesofthe
porphyrIas.About80ofpatIentswIthvarIegateporphyrIaarephotosensItIve.Some
patIentswIthheredItarycoproporphyrIaalsomayhaveskInlesIons.TheporphyrIasare
verydIffIculttodIagnoseInthelatentphaseofthedIsorder.0Irectassayofthe
IntermedIatesthemselvesmaybeusedIntheacutestatetomeasuretheelevatedlevelsof
thehemeIntermedIates.
Figure 24-6.Theglycogenglucoselactatepathway.CLU6,glucose6phosphatase.
Thecentral,perIpheral,andautonomIcnervoussystemsmaybeInvolvedIntheporphyrIas.
AfrequentmanIfestatIonIscolIckyabdomInalpaIn,oftenwIthnauseaandvomItIng,whIch
maysuggestthedIagnosIsofacuteabdomen,leadIngtoexploratorylaparotomy.Dther
symptomsarepsychIatrIcdIsturbance,quadrIplegIa,hemIplegIa,alteratIonsof
conscIousness,andpaIn.HyponatremIaandhypokalemIamayresultfromvomItIngdurIng
theacuteattackormayberelatedtohypothalamIcdIsturbance.0eathmayresultfrom
paralysIsoftherespIratorymuscles.ThecauseofthesechangesIsunknown;theymaybe
relatedtometabolItesoftheIntermedIatesorresultfromdefIcIencyofthehemepIgment
InthenervecellItself.
8ecausetheporphyrIasareunusualdIsorders,thereIslImItedexperIencewIththeclInIcal
useofmanyanesthetIcdrugs.nvItrostudIessuggestthatcertaInanesthetIcsoranesthetIc
adjuvantsmaybecontraIndIcated,butsuffIcIentclInIcalexperIenceIslackIng.
180
Management of Patients with Porphyria
tIsImportanttorecognIzeporphyrIaInpatIentswhoarescheduledforsurgery.tmay
becomeapparentthroughacarefulfamIlyhIstoryandpersonalhIstoryrelatedto
anesthesIa.AcarefulhIstoryInthepatIentwIthporphyrIashouldconcentrateon
neurologIcbackground.LaboratoryworkshouldIncludeelectrolyteandbloodureanItrogen
levels.PhysIcalexamInatIonIncludesInspectIonofcutaneouslesIonsoverthebody.
ntheanesthetIcmanagementofpatIentswIthporphyrIa,thechIefconcernIstoavoIdthe
admInIstratIonofdrugsthatcanInduceacrIsIs;thedrugsthatInducecytochromeenzyme
productIoncantrIggerthesyndrome.ChIefamongthosearethebarbIturates;therefore,
allbarbIturatesarecontraIndIcatedInporphyrIa.Ethylalcohol,nonbarbIturatesedatIves,
hydantoInantIconvulsants,andavarIetyofotherdrugsalsocanInduceacrIsIs(Table24
7).Dtherfactors,suchasfastIng,InfectIon,andestrogens,mayalsoprecIpItateporphyrIa.
0IagnosIscanbeespecIallydIffIcultbecauseattacksmayoccuratavarIabletImeafter
drugadmInIstratIonortheymaynotoccuratalldespIteadmInIstratIonofInducIngdrugs.
Table 24-7 Drugs Known to Precipitate Porphyria
SEDATIVES
8arbIturates
HypnotIcssuchaschlordIazepoxIde,glutethImIde,dIazepam
ANALGESICS
PentazocIne,antIpyrIne,amInopyrIdIne
LIdocaIne
ANTICONVULSANTS
PhenytoIn,methsuxImIde
ANTIBIOTICS
SulfonamIdes,chloramphenIcol
STEROIDS
Estrogens,progesterones
HYPOGLYCEMIC SULFONYLUREAS
TolbutamIde,chlorpropamIde
TOXINS
Lead,ethanol
MISCELLANEOUS
ErgotpreparatIons
AmphetamInes
|ethyldopa
PropofolappearstobeasafeInductIonagent.
181
NItrousoxIde,musclerelaxants,and
opIoIdsareunequIvocallysafedrugs.ExperIencewIthotherInhalatIonagents
182
and
reversalagentshasbeenfavorable,butInvItrostudIessuggestthattheymIghtexacerbate
acrIsIs.
|ostexpertshaveadvIsedthatregIonaltechnIquesbeavoIdedtopreventconfusIonshould
neurologIcsIgnsdevelopafteroperatIon.However,reportsofuneventfulepIdural
anesthesIaIntheparturIentwIthacuteIntermIttentporphyrIamayIndIcatethatthIs
technIquecanbesafelyperformedInthesepatIents.
18J
8lIsteredorfragIleskInareas
shouldbepaddedandgIvenspecIalattentIon.ClucoseInfusIonshouldbestartedbecause
starvatIonmayInduceanattack.
TheacuteattackshouldbetreatedwIthglucoseInfusIonandcorrectIonofhyponatremIa,
hypokalemIa,andhypomagnesemIa.PyrIdoxIneandhematInalsohavebeenvaluableIn
somecases.SupportIvetherapyforrespIratoryInsuffIcIencyandtreatmentofpaInIsalso
suggested.
Glycogen Storage Diseases
ThemetabolIcpathwaysInvolvIngglucosedegradatIontolactate,glucoseconversIonto
glycogen,andthebreakdownofglycogentoglucoseareImportanttothewholebody
bIochemIstryaswellastocellularphysIology.ClucosemetabolIsmhas
P.617
beenstudIedIntensIvelysIncetheearlIestdaysofmodernbIochemIstry.TheInherIted
glycogenstoragedIseasesarecharacterIzedbydysfunctIonofoneofthemanyenzymes
InvolvedInglucosemetabolIsm.SomeoftheglycogenstoragedIseasesareIncompatIble
wIthlIfepastInfancy,whereasothersarenot.AnesthetIcexperIencewIththesedIseasesIs
lImIted,butseveralsIgnIfIcantproblemshavebeenIdentIfIed.
184,185
Hypoglycemia.HypoglycemIaIsaconstantrIskInthesepatIents.tresultsfromfaIlureto
metabolIzestoredglycogentoglucose.
Acidosis.ThIsIsrelatedtofatandproteInmetabolIsmbecauseglycogenstoresarenot
metabolIcallyavaIlable.
Cardiac and Hepatic Dysfunction.ThIsIssecondarytodestructIonanddIsplacementof
normaltIssuebytheaccumulatedglycogen.
0etaIleddescrIptIonsofglucosemetabolIsmaregIvenelsewhere.FIgure246outlInesthe
glycogenglucoselactatepathway.Thereare,ofcourse,multIpleenzymatIcstepstoreach
eachoftheendpoInts.
Defects in Glucose Metabolism
Type I (Von Gierke Disease; Glucose-6-Phosphate Deficiency)
nherItanceIsautosomalrecessIve.TheprognosIsIsmoderatelygood,wIthmanypatIents
survIvIngIntoadulthood.ShortstatureandlIverenlargementarecharacterIstIc.These
patIentstoleratefastIngverypoorly.HypoglycemIa,acIdosIs,andconvulsIonsmaybea
problem.ProlongedbleedInghasbeendescrIbed.Dften,preoperatIvehyperalImentatIonIs
usedtoreducelIverglycogenstores.PortacavalshunthasbeenperformedwIthlImIted
successInthesepatIents.
Type II (Pompe Disease)
nherItanceIsconsIderedautosomalrecessIve.ThIsIsadevastatIngdIseasewIthavery
poorprognosIs.ThereIsadefIcIencyoflysosomalacIdmaltasewIthanaccumulatIonof
glycogenInthelysosomes,especIallyIntheheart,lIver,muscle,andcentralnervous
system.CardIaccompromIseresultIngfromoutflowobstructIonofhypertrophIedmuscle
occurs,asdoescongestIveheartfaIluresecondarytomyocardIaldIsruptIonbyglycogen
stores.AlateonsetformwIthabetterprognosIshasalsobeendescrIbed.Enzyme
replacementtherapymayImproveclInIcaloutcome.
186
Type III (Forbes Disease; Debranching Enzyme Deficiency)
nherItanceofthIsdIseaseIsautosomalrecessIve.
Type IV (Andersen Disease; Branching Enzyme Deficiency)
ThIsIsaveryraredIsorder,characterIzedbyadefectInthesynthesIsofnormalglycogen.
CIrrhosIsofthelIveranddeatharecharacterIstIcbefore2yearsofage.
Type V (McArdle Disease; Muscle Phosphorylase Deficiency)
AnautosomalrecessIveInherItancepatternandcrampIngwIthexercIsearecharacterIstIc
ofthIsdIsorder.SkeletalmuscleIsnotabletomobIlIzeglycogenstores,theusualfuelIn
muscle,forsustaInedexercIse.|yoglobInurIaoccurswIthoverexertIonInthesepatIents
andmayoccuraftersuccInylcholIneadmInIstratIonaswell.|uscleatrophyoccursIn
adulthood.TournIquetsshouldnotbeusedInthesepatIents,andfrequentautomatedblood
pressurereadIngsshouldbedonewIthcautIon.SevererhabdomyolysIshasbeenobserved
afterbypassforcardIacsurgery.
187
Type VI (Hers Disease; Reduced Hepatic Phosphorylase)
AdecreasedabIlItytomobIlIzehepatIcglycogenoccursInthIsdIsorder,wIthnormal
muscleandcardIacphysIology.
Type VII (Muscle Phosphofructokinase Deficiency)
ThIsdIsorderIssImIlarto|cArdledIseaseandIscharacterIzedbymusclecrampIng.The
sameenzymatIcdefectInerythrocytesleadstochronIchemolysIs.
Type VIII (Deficient Hepatic Phosphorylase Kinase)
Type7resultsfromadefIcIencyIntheregulatoryenzymecontrollIngthephosphorylase
enzyme.AcasereporthasdescrIbedfeverandacIdosIsdurIngsuccInylcholIne,halothane,
andketamIneanesthesIa.
188
LIvertransplantatIonhasbeenusedwIthsuccessInthemore
severeformsoftheglycogenstoragedIseases.
The Mucopolysaccharidoses
ThemucopolysaccharIdesarepolysaccharIdesthatyIeldmIxturesofmonosaccharIdesand
derIvedproductsafterhydrolysIs.ThemucopolysaccharIdescontaInNacetylated
hexosamIneInacharacterIstIcrepeatIngunIt.Forexample,chondroItInsulfateAIsa
monosaccharIdeofdglucuronIcacIdandNacetyldgalactosamIne4sulfate.
|ucopolysaccharIdesarefoundInallcells.
ThemucopolysaccharIdosesaregenetIcallydetermIneddIseasesInwhIch
mucopolysaccharIdesarestoredIntIssuesInabnormalquantItIesandexcretedInlarge
amountsIntheurIne.ThedIsordersresultfromadefIcIencyofaspecIfIclysosomalenzyme
thatIsrequIredtobreakdownthesecompounds.Asaresult,mucopolysaccharIdes
accumulateIntIssues,producIngspecIfIcclInIcalmanIfestatIons.TherearesevenbasIc
formsofmucopolysaccharIdosesandseveralsubgroups.|ostofthemucopolysaccharIdoses
areInherItedasautosomalrecessIvetraIts.AllthemucopolysaccharIdosesareprogressIve,
andpatIentscharacterIstIcallyaremarkedbycoarsefacIalfeatures(gargoylIsm);
assocIatedskeletalabnormalItIessuchaslumbarlordosIs,stIffjoInts,chestdeformIty,
dwarfIng,andhypoplasIaoftheodontoIdprocess(|orquIosyndrome);cornealopacItIes;
lImItatIonofjoIntmotIon;andheart,lIver,andspleenenlargementresultIngfrom
mucopolysaccharIdeaccumulatIon.|entaldeterIoratIonalsooccursfrequently.Some
caseshavebeensuccessfullytreatedbybonemarrowtransplantatIonatayoungage.
TheHunterandHurlersyndromesarethebestknownvarIantsofthe
mucopolysaccharIdoses.TheHuntersyndromeIsanXlInkedrecessIvedIsease.
189
FespIratoryInfectIonandheartdIsease,bothvalvularandIschemIc,oftenleadtodeathat
ayoungage.ThethIck,softtIssuesandthecopIous,thIcksecretIonsmakeperIoperatIve
andIntraoperatIveaIrwaymanagementapartIcularproblem.ntheserIesofLeroyand
Crocker,
189
mInordIffIcultIesoccurredwIthanesthesIaInpatIentsInmorethanonethIrdof
60operatIons.TheuseofalaryngealmaskaIrwaymaynotbesuccessful.
190
PostoperatIve
respIratoryobstructIonwasnotedInseveralcases.
191
8ecauseoftheunderlyIngheart
dIsease,thesepatIentsshouldhaveelectrocardIogramsandechocardIographIctests
performedbeforesurgery.ThesameconsIderatIonsapplyInotherevenlessfrequent
lysosomalstoragedIseases.
192
|ucopolysaccharIdosIs7(|orquIosyndrome)IsassocIatedwIthperhapsthemost
sIgnIfIcantskeletaldeformItIes.naddItIon
P.618
tocardIovasculardIsordersandrespIratoryInsuffIcIencyfrommarkedchestwalldeformIty,
acute,subacute,orchronIcmyelopathyIsextremelycommon.ThIsIssecondarytosevere
hypoplasIaorabsenceoftheodontoIdprocessofthesecondcervIcalvertebra.n
anesthesIacare,theheadshouldbeposItIonedcarefully,andprecautIonssuchas
avoIdanceofsuccInylcholIneshouldbetakenwIthpatIentswIthspInalcordcompromIse.
Osteogenesis Imperfecta
DsteogenesIsImperfectaIsseenInapproxImately1of50,000bIrths.|ostcasesare
autosomaldomInant;someareautosomalrecessIve.ThepathophysIologIccharacterIstIcs
IncludedecreasedcollagensynthesIs,whIchleadstoosteoporosIs,joIntlaxIty,andtendon
weakness.ThemanIfestatIonsofosteogenesIsImperfectaaresmallbowedlImbs,large
head,shortneck,bluesclerae,otosclerosIs,joIntlaxIty,brIttleteeth,andatendencyto
fractures.AbnormalplateletfunctIonproducesIncreasedsurgIcalbloodloss,anddIlatIon
ofthevalverIngsmaycauseaortIcandmItralvalvedysfunctIon.KyphoscolIosIsmay
producepulmonarycompromIse.TemperatureelevatIonIscommon,possIblybecauseof
elevatedbasalmetabolIcrate.
ThepatIentshouldbehandledcarefullybecausemInortraumamayleadtofractures.
AIrwaymanagementmayalsobedIffIcultbecauseofcervIcalspIneInvolvement.PatIents
haveshortnecks,andmandIbularfracturesfrequentlyoccur.PartIcularcareshouldbe
takentopadtheareasthatwIllreceIvepressure.PlatelettransfusIonmaybeneeded.Core
temperatureshouldbemonItoredbecausehyperthermIahasbeenreported.
19J
SIgns
consIstentwIth|Hhavebeenobserved,butcontracturetestsfor|HsusceptIbIlItyhave
notconfIrmedaconstantassocIatIonbetweenosteogenesIsImperfectaand|H.
46
LactIc
acIdosIshasalsobeenobservedwIthnoIncreaseIntemperature.
194
Summary Note
|anyotherInherIteddIsordersImpactdrugdIsposItIon,metabolIsm,andotheraspectsof
anesthesIacarerangIngfromalteredaIrwayanatomyInTreacherCollInssyndrometo
abnormalphysIologIcresponsestoanesthetIcagentsInfamIlIaldysautonomIa.Thereaders
shouldconsultthelIteraturewhenconfrontedwIthoneofthenumerousdIsordersaffectIng
drugmetabolIsmanddIsposItIon.Atpresent,assessmentofprevIousanesthetIcexperIence
ofthepatIentandfamIlyIsstIllthemosteffIcIentwaytoantIcIpatevarIableresponseto
analgesIcsandanesthetIcdrugs.
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Stock, M. Christine
TableofContentsSectIon7PreanesthetIcEvaluatIonandPreparatIonChapter25FareandCoexIstIng0Iseases
Chapter25
Rare and Coexisting Diseases
Stephen F. Dierdorf
J. Scott Walton
Key Points
1. The cytoskeleton of the muscle membrane in patients with muscular
dystrophy is abnormal and is susceptible to damage from
succinylcholine. Massive release of intracellular contents, including
potassium, may occur.
2. Myotonic dystrophy produces cardiac conduction delay that can
manifest as high-grade atrioventricular block.
3. Patients with myasthenia gravis are exquisitely sensitive to
nondepolarizing muscle relaxants. Short-acting muscle relaxants and
objective monitoring of neuromuscular function are indicated.
4. Many types of cancer, in addition to small cell lung carcinoma, can
produce myasthenic syndrome.
5. Patients with multiple sclerosis should be advised that an
exacerbation of their neurologic symptoms may occur during the
perioperative period.
6. Repeated episodes of sickling in patients with sickle cell disease cause
pulmonary hypertension. Pulmonary hypertension in sickle cell
patients is associated with increased mortality.
7. Rheumatoid arthritis is a multisystem disease that causes subclinical
cardiac and pulmonary dysfunction.
8. Many patients with rheumatoid arthritis have significant degeneration
of the cervical spine with few neurologic symptoms. Cervical
manipulation during laryngoscopy and intubation requires special
precautions.
9. Esophageal dysfunction in patients with scleroderma or
dermatomyositis increases the risk of aspiration pneumonitis.
10. Patients with epidermolysis bullosa can have undiagnosed dilated
cardiomyopathy.
AvarIetyofraredIsordersmayInfluencetheselectIonandconductofanesthesIa.Fecent
advancesInmoleculargenetIcsandbIologyhaveclarIfIedthedIseasemechanIsmsand
InherItanceofmanyuncommondIseases.ThesedIscoverIeshaveradIcallyalteredthe
treatmentofsomedIsorders.AnesthesIologIstsmustperIodIcallyupdatetheIrdIagnostIc
skIllsandclInIcalknowledgetorecognIzewhenaddItIonalevaluatIonortreatmentmaybe
requIredandhowthesedIseasesInfluencethemanagementofanesthesIa.
Musculoskeletal Diseases
ThecytoskeletonofthemusclecellIscomposedofproteInssuchasdystrophIn,merosIn,
utrophIn,syntrophIn,dystrobrevIn,andsarcoglycans(FIg.251).AbnormalproteInsor
InsuffIcIentquantItIesofnormalproteInsmaydImInIshtheIntegrItyofthemuscle
membrane,makIngItmoresusceptIbletodamage.ThemusculardystrophIesaredIseases
assocIatedwIthabnormalItIesofthemusclemembrane(Table251).
1
|usculardystrophIesarecharacterIzedbyaprogressIvelossofskeletalmusclefunctIon
(FIg.252).AlthoughlessevIdent,cardIacandsmoothmusclearealsoaffected.
Muscular Dystrophy
Duchenne Muscular Dystrophy
0uchennemusculardystrophyIscausedbyalackofproductIonofdystrophIn,amajor
componentoftheskeletonofthemusclemembrane.0uchennedystrophyIscharacterIzed
bypaInlessdegeneratIonandatrophyofskeletalmuscle.ThIsdIsorderIsasexlInked
recessIvetraItclInIcallyevIdentInboys.
P.62J
ProgressIvemuscleweaknessproducessymptomsbetweentheagesof2and5yearsand
sIgnIfIcantlImItatIonbyage12years.AxIalmuscleImbalanceproduceskyphoscolIosIsthat
mayrequIreoperatIveInstrumentatIonforstabIlIzatIon.0eathIsusuallysecondaryto
congestIveheartfaIlureorpneumonIa.AggressIvetreatmentofcardIopulmonary
dysfunctIonhasImprovedsurvIvalformanypatIentsuntIltheageofJ0years.Serum
creatInekInaselevelsreflecttheprogressIonofthedIsease.EarlyInthepatIent'slIfethe
creatIvekInaselevelIsIncreased.Later,assIgnIfIcantamountsofmusclehave
degenerated,thecreatInekInaseleveldecreases.
Figure 25-1.|usclecellcytoskeleton.(FeprIntedfrom0uggan0J,CorospeJF,FanIn
|,etal:|utatIonsInthesarcoglycangenesInpatIentswIthmyopathy.NEnglJ|ed
1997;JJ6:618624,wIthpermIssIon.)
AsthepatIentages,lossofcardIacmuscleIsreflectedbyaprogressIvedecreaseInFwave
amplItudeInthelateralprecordIalleadsoftheelectrocardIogram(ECC).SerIal
echocardIographycanprovIdeImportantInformatIonaboutcardIacfunctIon.ProgressIve
lossofmyocardIaltIssueresultsIncardIomyopathy,ventrIculardysrhythmIas,andmItral
regurgItatIon.TreatmentofcardIacdysfunctIonIncludesangIotensInconvertIngenzyme
(ACE)InhIbItors,adrenergIcblockers,anddysrhythmIasurveIllance.
2
0ImInIshedmusclestrengthproducesanIneffectIvecough,resultIngInretentIonof
pulmonarysecretIons,pneumonIa,anddeath.SmoothmuscleInvolvementcauses
IntestInalhypomotIlIty,delayedgastrIcemptyIng,andgastroparesIs.
AlthoughthegenetIcdefectthatcauses0uchennedystrophyIsknown,specIfIcgenetIc
therapyremaInselusIve.CurrenttreatmentIssupportIveanddIrectedatbetternutrItIon
andImprovementofcardIorespIratoryfunctIon.ProlongedtherapywIthcortIcosteroIds
mayImproveskeletalmusclefunctIon.
Emery-Dreifuss Muscular Dystrophy
Emery0reIfussmusculardystrophyIscharacterIzedbycontracturesoftheelbows,ankles,
spIne,andhumeropectoral
P.624
weakness.TheskeletalmusclemanIfestatIonsareusuallymIld,whereascardIacconductIon
defectscanbefatal.
J
mplantabledefIbrIllatIngpacemakersareoftenIndIcatedfor
patIentswIthEmery0reIfussmusculardystrophy.
Table 25-1 Types of Muscular Dystrophy
0uchenne
8ecker
Emery0reIfuss
LImbgIrdle
Dculopharyngeal
FascIoscapulohumeral
CongenItalmusculardystrophy
Figure 25-2.0IstrIbutIonofpredomInantmuscleweaknessIndIfferenttypesof
musculardystrophy.A.0uchennetypeand8eckertype.B.Emery0reIfuss.C.LImb
gIrdle.D.FascIoscapulohumeral.E.0Istal.F.Dculopharyngeal.(Feproducedfrom8|J
PublIshIngCroup.EmeryAEH:ThemusculardystrophIes.8|J1998;J17:991995,wIth
permIssIon.)
Limb-Girdle Muscular Dystrophy
PatIentswIthlImbgIrdlemusculardystrophyexhIbItweaknessoftheshoulderandpelvIc
gIrdles.CardIomyopathyandatrIoventrIcularconductIondefectscanoccur.FIfteen
dIfferentgenetIcdefectshavebeendIscovered,andmostcauseanabnormalItyInthe
sarcoglycanproteIns.
Facioscapulohumeral Muscular Dystrophy
PatIentswIththIsdIseasehavedIverseclInIcalmanIfestatIonssuchasweaknessofthe
facIal,scapulohumeral,anterIortIbIal,andpelvIcgIrdlemuscles.DtherabnormalItIes
IncluderetInalvasculardIsease,deafness,andneurologIcdysfunctIon.CardIacconductIon
defectsanddysrhythmIasmayoccur.
Oculopharyngeal Muscular Dystrophy
DculopharyngealmusculardystrophytypIcallypresentsInlateadulthoodwIthptosIsand
dysphagIa.0ysphagIaIssecondarytopharyngealskeletalmuscleweaknessandesophageal
smoothmuscledysfunctIon.Weaknessofthehead,neck,andarmsmayalsodevelop.
Congenital Muscular Dystrophy
CongenItalmusculardystrophyIscharacterIzedbyearlyonsetofmuscleweakness,mental
retardatIon,feedIngdIffIcultIes,andrespIratorydysfunctIon.ncludedInthIsgroupof
musculardystrophIesaremerosIndefIcIentmusculardystrophy,Fukuyamamuscular
dystrophy,WalkerWarburgsyndrome,UlrIchdIsease,muscleeyebraIndIsease,rIgIdspIne
musculardystrophy,centralcoredIsease,myotubularmyopathy,andnemalInemyopathy.
4
|ostofthesIgnIfIcantcomplIcatIonsfromanesthesIaInpatIentswIthmusculardystrophy
aresecondarytotheeffectsofanesthetIcdrugsonmyocardIalandskeletalmuscle.
5
There
arenumerouscasereportsofcardIacarrestoccurrIngdurIngtheadmInIstratIonofgeneral
anesthesIaInchIldrenwIth0uchennemusculardystrophy.ThesecasesareassocIatedwIth
rhabdomyolysIsandhyperkalemIaandhaveoccurredwIthvolatIleanesthetIcsaloneorIn
combInatIonwIthsuccInylcholIne.nvIewoftheweakenedmusclestructureofpatIents
wIthmusculardystrophy,succInylcholInemaydamagethemusclemembraneandrelease
Intracellularcontents.TheeffectofvolatIleanesthetIcsonabnormalskeletalmuscleIsnot
known.7olatIleanesthetIcscoulddamagethemusclemembraneandcauserhabdomyolysIs
byreleasIngcalcIumfromthesarcoplasmIcretIculum.SomepatIentswIthmuscular
dystrophymaybesusceptIbletomalIgnanthyperthermIa.tmaybeprudenttouse
IntravenousanesthetIcsandavoIdvolatIleanesthetIcsandsuccInylcholIneforpatIents
wIthmusculardystrophy.
6
PatIentswIth0uchennemusculardystrophymayhaveprolonged
recoveryfromnondepolarIzIngmusclerelaxants.
0egeneratIonofgastroIntestInalsmoothmusclewIthhypomotIlItyoftheIntestInaltract
anddelayedgastrIcemptyIngInconjunctIonwIthImpaIredswallowIngIncreasestherIskof
perIoperatIveaspIratIonofgastrIccontents.7IgorousrespIratorytherapyandmechanIcal
ventIlatIonmayberequIreddurIngtheearlypostoperatIveperIod.
Table 25-2 Classification of Myotonic Dystrophy
Myotonic dystrophy type 1
CongenItal
ChIldhoodonset
Adultonset
Lateonset
Myotonic dystrophy type 2
ProxImalmyotonIcdystrophy
ProxImalmyotonIcmyopathy
ProxImalmyotonIcmyopathy
syndrome
The Myotonias
|yotonIaIsthedelayedrelaxatIonofskeletalmuscleaftervoluntarycontractIon.
ElectromyographydemonstratesrepetItIvemusclefIberdIschargesthatfluctuate.These
abnormalItIesaresecondarytodysfunctIonofIonchannelsInthemusclemembrane.There
aretwotypesofmyotonIcdystrophycausedbyabnormalItIesIntwodIstInctgenelocI:
myotonIcdystrophytype1andmyotonIcdystrophytype2(Table252).ThegenetIc
alteratIonIntype1IsanunstabletrInucleotIdeexpansIononchromosome19q;type2Is
causedbyaquadnucleotIdeexpansIononchromosomeJq.|yotonIcdystrophytype1Isthe
morecommonformandIsfurthersubdIvIdedbyageofonsetIntocongenItal,chIldhood
onset,adultonset(mostprevalent),andlateonset.
7
AdultonsetmyotonIcdystrophyIsanautosomallydomInantInherIteddIsorderwIth
symptomsoccurrIngdurIngthesecondandthIrddecadesoflIfe.DtherclInIcalfeatures
IncludemuscledegeneratIon,cataracts,prematurebaldIng,dIabetesmellItus,thyroId
dysfunctIon,adrenalInsuffIcIency,gonadalatrophy,andcardIacabnormalItIes.CardIac
manIfestatIonsIncludeatrIoventrIcularconductIondelay,atrIaltachydysrhythmIas,
dIastolIcdysfunctIon,cardIomyopathy,andmItralvalveprolapse.FIrstdegree
atrIoventrIcularblockmayprecedetheonsetofskeletalmusclesymptoms.Suddendeath
maybesecondarytothIrddegreeatrIoventrIcularblockorventrIculardysrhythmIas.
EchocardIographymayrevealsubclInIcalevIdenceofleftventrIcularsystolIcanddIastolIc
dysfunctIon.
8
AlthoughcardIacabnormalItIesarelesscommonlyreportedInpatIentswIth
myotonIcdystrophytype2,fataldysrhythmIascanoccur.
PulmonaryfunctIonstudIesdemonstratearestrIctIvelungdIseasepattern,mIldarterIal
hypoxemIa,anddImInIshedventIlatoryresponsestohypoxIaandhypercapnIa.8raInstem
respIratorycontrolmechanIsmsmayalsobedefectIve.WeaknessoftherespIratorymuscles
dImInIshestheeffectIvenessofcoughandmayleadtopneumonIa.|yotonIaofthe
respIratorymusclescanproduceIntensedyspnearequIrIngtreatmentwIthprocaInamIde.
AlteratIonofsmoothmusclefunctIonproducesgastrIcatonyandIntestInalhypomotIlIty.
PharyngealmuscleweaknessInconjunctIonwIthdelayedgastrIcemptyIngIncreasesthe
rIskofaspIratIonofgastrIccontents.
PregnancymayproduceanexacerbatIonofmyotonIcdystrophy,andcongestIveheart
faIlureIsmorelIkelytooccurdurIngpregnancy.CesareansectIonIsoftenrequIredbecause
ofuterInesmoothmuscledysfunctIon.SomeInfantsofmotherswIthmyotonIcdystrophy
maydevelopcongenItalmyotonIcdystrophy.CongenItalmyotonIcdystrophyIs
characterIzedbyhypotonIa,respIratoryInsuffIcIency,anddIffIcultywIthfeedIng.
TherapyformyotonIcdystrophyIsdIrectedattreatmentofcardIacdysrhythmIas
(pacemakerImplantatIon)andsurgIcaltherapyforcataractsandgallbladderdIsease.
SodIumchannelblockers,IncludIngmexIletIne,phenytoIn,procaInamIde,
P.625
taurIne,clomIpramIne,andImIpramInehavebeenusedforthetreatmentofmyotonIawIth
lessthanconclusIveresults.
Figure 25-3.AdmInIstratIonoflowdosesofsuccInylcholInetoapatIentwIthmyotonIc
dystrophyproducesanexaggeratedcontractIonofskeletalmuscle.(FeprIntedfrom
|Itchell||,AlIHH,SavareseJJ:|yotonIaandneuromuscularblockIngdrugs.
ConsIderatIonsforanesthesIaforpatIentswIthmyotonIcdystrophyIncludethepresenceof
cardIacandrespIratorymuscledIseaseandtheabnormalresponsestodrugsuseddurIng
anesthesIa.SuccInylcholIneproducesanexaggeratedcontractureandItsuseshouldbe
avoIded(FIg.25J).ThemyotonIcresponsetosuccInylcholInecanbesoseverethat
ventIlatIonandtrachealIntubatIonaredIffIcultorImpossIble.|ostpatIentswIthmyotonIc
dystrophydevelopachronIcmyopathyandtheresponsetonondepolarIzIngmuscle
relaxantsmaybeenhanced.FeversalwIthneostIgmInemayprovokemyotonIa.The
responsetotheperIpheralnervestImulatormustbecarefullyInterpretedbecausemuscle
stImulatIonmayproducemyotonIa.ThemyotonIcresponsemaybemIsInterpretedas
sustaInedtetanuswhensIgnIfIcantneuromuscularblockadestIllexIsts.
PatIentswIthmyotonIcdystrophyaresensItIvetotherespIratorydepressanteffectsof
opIoIds,barbIturates,benzodIazepInes,andInhaledanesthetIcs.FespIratorycomplIcatIons
aremorelIkelytooccurIntheearlypostoperatIveperIodafterupperabdomInalsurgeryor
InthosepatIentsInwhompreoperatIveupperextremItyweaknesswasevIdent.
9
NospecIfIcanesthetIctechnIquehasbeenshowntobesuperIorforpatIentswIthmyotonIc
dystrophy.CarefullycontrolledpropofolInfusIonshavebeenusedsuccessfully.nhaled
anesthetIcsmaybeusedbutclosemonItorIngofcardIacrhythmandcardIovascular
functIonIsIndIcated.PostoperatIvemechanIcalventIlatIonshouldbeemployeduntIl
musclestrengthandfunctIonreturn.
10
FegIonalanesthesIahasbeendescrIbedforboth
chIldrenandadultswIthmyotonIcdystrophy.
11
SkeletalmuscleweaknessandmyotonIaareexacerbateddurIngpregnancy.LaborIs
typIcallyprolongedandthereIsanIncreasedIncIdenceofpostpartumhemorrhage
(placentaaccreta).SpInalandepIduralanesthesIahavebeensuccessfullyusedforpregnant
patIents.
Familial Periodic Paralysis
ThefamIlIalperIodIcparalysesareasubgroupofdIseasesreferredtoastheskeletal muscle
channelopathies.ThIsgroupofdIseasesIncludehyperkalemIcandhypokalemIcperIodIc
paralysIs,paramyotonIacongenIta,potassIumaggravatedmyotonIa,normokalemIc
perIodIcparalysIs,andAndersensyndrome.ThecommonmechanIsmforthesedIseases
appearstobeapersIstentsodIumInwardcurrentdepolarIzatIoncausIngmusclemembrane
InexcItabIlItyandsubsequentmuscleweakness.
12
Table 25-3 Clinical Features of Familial Periodic Paralysis
Hypokalemic
CalcIumchanneldefect
PotassIumlevelJmEq/LdurIngsymptoms
PrecIpItatIngfactors
HIghglucosemeals
StrenuousexercIse
ClucoseInsulInInfusIons
Stress
HypothermIa
ChronIcmyopathywIthagIng
Hyperkalemic
SodIumchanneldefect
PotassIumlevel5.5mEq/LdurIngsymptoms
PrecIpItatIngfactors
FestafterexercIse
PotassIumInfusIons
|etabolIcacIdosIs
HypothermIa
SkeletalmuscleweaknessmaybelocalIzedtotongueandeyelIds
Hyperkalemic Periodic Paralysis
HyperkalemIcperIodIcparalysIsIscharacterIzedbyepIsodesofmyotonIaandmuscle
weaknessthatmaylastforseveralhoursafterexposuretoatrIgger.Weaknesscanoccur
durIngrestafterstrenuousexercIse,InfusIonofpotassIum,metabolIcacIdosIs,or
hypothermIa(Table25J).TheweaknessmaybesoseverethatventIlatorysupportIs
requIred.ThehyperkalemIaIsoftentransIentandoccursonlyatthetImeofweakness,and
potassIumlevelsmeasureddurIngtheattackmaybenormalordecreased.Treatment
consIstsofalowpotassIumdIetandtheadmInIstratIonofthIazIdedIuretIcs.
Hypokalemic Periodic Paralysis
HypokalemIcperIodIcparalysIsIscausedbyadefectInthecalcIumIonchannel.ParalysIs
maybeproducedbyadecreaseInserumpotassIumlevels,IngestIonofcarbohydrates,
strenuousexercIse,andInfusIonofglucoseandInsulIn(Table25J).ParalysIsIsusually
Incomplete,affectIngthelImbsandtrunk,butsparIngthedIaphragm.LowpotassIumlevels
durIngacuteepIsodescancausecardIacdysrhythmIas.ChronIcmuscleweaknessoccursIn
mostpatIentswIthhypokalemIcperIodIcparalysIsastheyage.
1J
TreatmentconsIstsofpotassIumInfusIonandtheadmInIstratIonofacetazolamIdeand
dIchlorphenamIde.PotassIumsparIngdIuretIcssuchastrIamtereneandspIronolactonemay
bebenefIcIal.
TheprImarygoalwIthbothformsofperIodIcparalysIsIsmaIntenanceofnormalpotassIum
levelsandavoIdanceofeventsthatprecIpItateweakness.AnyelectrolyteabnormalIty
shouldbecorrectedprIortosurgery.ThesepatIentsmaybesensItIvetonondepolarIzIng
musclerelaxants,andshortactIngmusclerelaxantsarepreferred.SuccInylcholIneIsbest
avoIdedasItsadmInIstratIonmayalterpotassIumlevels.|etabolIcchanges(acIdosIsand
alkalosIs)ormedIcatIons(glucoseandInsulIn,dIuretIcs)thatreducepotassIumlevelsmay
InItIateanepIsodeofparalysIs.8ecausechangesIn
P.626
potassIumlevelsmayprecedetheonsetofweakness,serIalmeasurementofpotassIum
levelsdurIngprolongedsurgIcalproceduresandtheearlypostoperatIveperIodshouldbe
consIdered.TheECCshouldbemonItoredforevIdenceofpotassIumrelateddysrhythmIas.
DtherrecommendatIonsIncludetheavoIdanceofcarbohydrateloads,hypothermIa,and
excessIvehyperventIlatIon.AnycauseofpotassIumdepletIoncanproducemuscle
weakness.HalogenatedInhaledanesthetIcshavebeenadmInIsteredwIthoutcomplIcatIon
andregIonalanesthesIahasbeenused.
14
|alIgnanthyperthermIahasbeenassocIatedwIth
bothformsofperIodIcparalysIs.
Table 25-4 Different Presentations of Myasthenia Gravis
TYPE ETIOLOGY ONSET SEX THYMUS COURSE
Neonatal
myasthenIa
Passageof
antIbodIes
from
myasthenIc
mothers
acrossthe
placenta
Neonatal
8oth
sexes
Normal TransIent
CongenItal
myasthenIa
CongenItal
endplate
pathology,
genetIc
autosomal
recessIve
patternof
InherItance
02yr
|ale
female
Normal
NonfluctuatIng
compatIble
wIthlong
survIval
JuvenIle
myasthenIa
AutoImmune
dIsorder
220yr
Female
male
(4:1)
HyperplasIa
Slowly
progressIve,
tendencyto
relapseand
remIssIon
Adult
myasthenIa
AutoImmune
dIsorder
2040yr
Female
male
thymoma
HyperplasIa
wIthInJ5
yr
|axImum
severIty
Elderly
myasthenIa
AutoImmune
dIsorder
40yr
|ale
female
Thymoma
(benIgnor
locally
InvasIve)
FapId
progress,
hIgher
mortalIty
Feproducedfrom8arakaA:AnesthesIaandmyasthenIagravIs.CanJAnaesth1992;J9:
476,wIthpermIssIon.
Myasthenia Gravis
|yasthenIagravIsIsanautoImmunedIseasewIthantIbodIesdIrectedagaInstthenIcotInIc
acetylcholInereceptororothermusclemembraneproteIns.EIghtyfIvepercentofpatIents
wIthmyasthenIagravIshaveIdentIfIableantIacetylcholInereceptorantIbodIesandare
consIderedseroposItIve.ThemajorItyofseronegatIvepatIentshaveantIbodIestoother
musclemembraneproteInssuchasmusclespecIfIcreceptortyrosInekInase,rapsyn,or
agrIn.TheseautoantIbodIesdamagemusclemembranesbyactIvatIonofcomplement,
degradatIonofacetylcholInereceptormolecules,orblockadeoftheacetylcholIne
receptor.ThedIfferentpathophysIologIcmechanIsmsexplaIntheheterogeneItyofthe
clInIcalmanIfestatIonsofmyasthenIagravIs.
15
ThethymusmayplayacentralroleInthe
pathogenesIsofmyasthenIagravIsas90ofpatIentshavehIstologIcabnormalItIessuchas
thymoma,thymIchyperplasIa,orthymIcatrophy.
TheclInIcalhallmarkofmyasthenIagravIsIsskeletalmuscleweakness.TheweaknessIs
aggravatedbyrepetItIvemuscleuseandthereareperIodsofexacerbatIonalternatIngwIth
remIssIon.Anyskeletalmusclemaybeaffected,althoughthereIsapredIlectIonfor
musclesInnervatedbycranIalnerves.nItIalsymptomsIncludedIplopIa,dysarthrIa,
dysphagIa,orlImbmuscleweakness.|yasthenIccrIsesoccurIn15to50ofpatIentsand
areoftenprecIpItatedbypulmonaryInfectIonsandresultInrespIratoryfaIlurerequIrIng
mechanIcalventIlatIon.CardIacmanIfestatIonsofmyasthenIagravIsIncludefocal
myocardItIs,atrIalfIbrIllatIon,atrIoventrIcularconductIondelay,andleftventrIcular
dIastolIcdysfunctIon.
7IralInfectIon,pregnancy,extremeheat,stress,andsurgerymayInItIateorexacerbate
thesymptomsofmyasthenIa,buttheresponsetostressorsIsunpredIctable.Somepregnant
patIentshavearemIssIondurIngpregnancywhIleothers(20to40)haveIncreased
symptomsdurInggestatIon.PostpartumrespIratoryfaIlurecanoccur.FIfteento20of
neonatesborntomyasthenIcmothershavetransIentmyasthenIafrompassIvetransferof
acetylcholInereceptorantIbodIes.SIgnsandsymptomsofneonatalmyasthenIabegIn12to
48hoursafterbIrthandmaypersIstforseveralweeks.
16
0IseaseclassIfIcatIonIsbasedonskeletalmusclegroupsaffectedaswellasageofonset
(Table254).TheDssermanstagIngsystemIsbasedontheseverItyofthedIsease:type,
ocularsIgnsandsymptomsonly;typeA,generalIzedmuscleweakness;type8,
generalIzedmoderateweaknessand/orbulbardysfunctIon;type,acutefulmInant
presentatIonand/orrespIratorydysfunctIon;andtype7,severegeneralIzedmyasthenIa.
ThedIagnosIsofmyasthenIaIsbasedontheclInIcalhIstory,theedrophonIumtest,
electromyography,andthedetectIonofcIrculatIngacetylcholInereceptorantIbodIes.No
sIngletestIsdefInItIve.
TreatmentIncludestheadmInIstratIonofcholInesteraseInhIbItors,cortIcosteroIds,
Immunosuppressants,plasmapheresIs,andIntravenousImmunoglobulIn.CholInesterase
InhIbItorsfunctIonbyIncreasIngtheconcentratIonofacetylcholIneatthepostsynaptIc
membrane.ConsIstentcontrolofmyasthenIawIthcholInesteraseInhIbItorscanbequIte
challengIng.UnderdosIngwIllresultInIncreasedmuscleweakness,whereasoverdosIngwIll
produceacholInergIccrIsIscharacterIzedbyabdomInalpaIn,salIvatIon,bradycardIa,
andskeletalmuscleweakness.
CortIcosteroIdsproduceanImprovementInmusclestrengthInmyasthenIcpatIents,
althoughtheprecIsemechanIsmIsunknown.mmunosuppressantsusedforthetreatment
ofmyasthenIcIncludeazathIoprIne,cyclosporIne,cyclophosphamIde,tacrolImus,
rItuxImab,andmycophenolatemofetIl.PlasmapheresIsremovesacetylcholInereceptor
antIbodIesfromthecIrculatIonandIseffectIvedurIngamyasthenIccrIsIs.ntravenous
ImmunoglobulInmayalsobeeffectIve.
P.627
Figure 25-4.0oseresponseforvecuronIumInnormalpatIentsandpatIentswIth
myasthenIagravIs.(FeprIntedfromEIsenkraftJ8,8ookWJ,PapatestasAE:SensItIvIty
tovecuronIumInmyasthenIagravIs:Adoseresponsestudy.CanJAnaesth1990:J7:
J01J06,wIthpermIssIon.)
TheroleofthymectomyforthetreatmentofmyasthenIaIsnotclearlyestablIshed.
AlthoughathymomaIsaclearIndIcatIonforthymectomy,theoperatIonforother
myasthenIcpatIentsIscontroversIal.0IfferentsurgIcaltechnIquesIncludesternalsplIttIng
wIthextendedthymectomy,transcervIcal,vIdeoassIstedthoracoscopy,androbotIc
surgery.
17
LessInvasIveapproachesofferfewerpostoperatIvecomplIcatIons,butmay
resultInIncompleteresectIonofthethymus.
TheprImaryconcernforanesthesIaIsthepotentIalInteractIonbetweenthedIsease,
treatmentofthedIsease,andneuromuscularblockIngdrugs.Theuncontrolledorpoorly
controlledmyasthenIcpatIentIsexquIsItelysensItIvetonondepolarIzIngmusclerelaxants
(FIg.254).SmalldefascIculatIngdosesofnondepolarIzIngdrugscanproducesIgnIfIcant
respIratorymuscleweaknessandrespIratorydIstress.AnanesthetIctechnIquethatavoIds
theuseofamusclerelaxantmaybepreferred.
18
soflurane,sevoflurane,anddesflurane
depressneuromusculartransmIssIonandmayprovIdeadequatemusclerelaxatIonfor
trachealIntubatIon.
CholInesteraseInhIbItordrugsusedtotreatmyasthenIawIllInfluencetheresponsetoboth
depolarIzIngandnondepolarIzIngmusclerelaxants.fmusclerelaxatIonIsrequIred,small
dosesofshortactIngnondepolarIzIngmusclerelaxantsshouldbeadmInIstered.Close,
objectIvemonItorIngofneuromusculartransmIssIonandclInIcaleffectIsnecessary.
AlthoughpatIentswIthmyasthenIahavearesIstancetosuccInylcholIne,adoseof1.5to2
mg/kgwIllbeadequateforrapIdtrachealIntubatIon.PreoperatIveadmInIstratIonof
pyrIdostIgmIne,however,mayprolongtheduratIonofactIonofsuccInylcholIne.
19
AdjuvantdrugsthatmayexacerbatemuscleweaknessInmyasthenIcpatIentsInclude
amInoglycosIdeantIbIotIcs,polymyxIns,adrenergIcblockers,procaInamIde,
cortIcosteroIds,andphenytoIn.PatIentswIthmyasthenIahavecentralrespIratory
depressIon,andtherespIratorydepressanteffectsofbarbIturates,benzodIazepInes,
opIoIds,andpropofolmaybeaccentuated.
|ostanesthetIctechnIquespermItweanIngformmechanIcalventIlatIonandtracheal
extubatIonofmyasthenIcpatIentssoonaftersurgery;however,thesepatIentscanbequIte
challengIngtoweanfromventIlatorysupport.
20
EpIduralanalgesIacanbeuseddurInglaboranddelIvery.|usclerelaxatIonInducedby
regIonalanesthesIamaycompoundtheweaknesscausedbymyasthenIa.AmIdelocal
anesthetIcsmaybebetterthanesterlocalanesthetIcsasthemetabolIsmofamIdesIsnot
affectedbycholInesteraseactIvIty.ExacerbatIonsofmyasthenIamustbeantIcIpated
durIngpregnancy.
Myasthenic Syndrome (Lambert-Eaton)
TheLambertEatonmyasthenIcsyndromeIsadIsorderofneuromusculartransmIssIon
assocIatedwIthcarcInomas,partIcularlysmallcellcarcInomaofthelungand
lymphoprolIferatIvedIseases(Table255).LambertEatonmyasthenIcsyndromeIsan
autoImmunedIseaseInwhIchantIbodIesagaInstvoltagegatedcalcIumIonchannels
(presynaptIc)areproduced.TheresultIsadecreasedreleaseofacetylcholIneInresponse
tonervestImulatIon.ThetypIcalpatIentIsamanolderthan40yearsofagewIthproxImal
extremItyweakness(hIp,shoulder)thataffectsgaItandtheabIlItytostandandclImb
staIrs.AutonomIcdysfunctIon,suchasxerostomIa,Impotence,orthostatIchypotensIon,
constIpatIon,andalteredsweatIngresponsesmaydevelop.
21
TreatmentoftheunderlyIngneoplasmmayImprovetheneurologIccondItIon.Themost
effectIvedrugfortreatmentof
P.628
myasthenIcsyndromeIsJ,4dIamInopyrIdIne,whIchprolongstheactIonpotentIaland
IncreasesreleaseofacetylcholIne.mmunosuppressIonwIthcortIcosteroIds,azathIoprIne
andcyclosporInemaybeeffectIve.PlasmapheresIsandIntravenousImmunoglobulInmay
produceshorttermImprovement.
22
Table 25-5 Comparison of Myasthenic Syndrome and Myasthenia Gravis
MYASTHENIC SYNDROME MYASTHENIA GRAVIS
|anIfestatIons
ProxImallImbweakness(arms
legs)
Extraocular,bulbar,and
facIalmuscleweakness
StrengthImproveswIthexercIse FatIguewIthexercIse
|usclepaIncommon |usclepaInuncommon
Feflexesabsentordecreased Feflexesnormal
Cender |alefemale Femalemale
CoexIstIng
pathology
SmallcellcarcInomaoflung Thymoma
Fesponseto
muscle
relaxants
SensItIvetosuccInylcholIneand
nondepolarIzIngmusclerelaxants
FesIstantto
succInylcholIne
SensItIveto
nondepolarIzIngmuscle
relaxants
Poorresponseto
antIcholInesterases
Poorresponseto
antIcholInesterases
FeprIntedfromStoeltIngFK,0IerdorfSF,eds:AnesthesIaandCoExIstIng0Isease,
Jrded.NewYork,ChurchIllLIvIngstone,199J,wIthpermIssIon.
PatIentswIthmyasthenIcsyndromearesensItIvetotheeffectsofbothdepolarIzIngand
nondepolarIzIngmusclerelaxants.TheadmInIstratIonofJ,4dIamInopyrIdIneshouldbe
contInuedtothetImeofsurgery.
Guillain-Barr Syndrome (Polyradiculoneuritis)
CuIllaIn8arrsyndromeIstheacuteformofagroupofdIsordersclassIfIedasInflammatory
neuropathIes.DtherInflammatoryneuropathIesIncludeacuteInflammatory
polyneuropathy,acutemotoraxonalneuropathy,acutemotorsensoryaxonalneuropathy,
|IllerFIshersyndrome,andchronIcInflammatorydemyelInatIngneuropathy.CuIllaIn
8arrsyndromeIsanautoImmunedIseasecausedbyabacterIalorvIralInfectIonthat
trIggersanImmuneresponsethatproducesantIbodIesthatdamagethemyelInsheathand
causeaxonaldegeneratIon.
2J
|ostpatIentshaveahIstoryofarespIratoryorgastroIntestInalInfectIonwIthIn4weeksof
theonsetofneurologIcsymptoms.CuIllaIn8arrsyndromeIscharacterIzedbytheacuteor
subacuteonsetofskeletalmuscleweaknessorparalysIsofthelegs.ParesthesIasmay
precedetheonsetofparalysIs.TheparalysIsprogressescephaladtoIncludethemusclesof
thetrunkandarms.0IffIcultyswallowIngandImpaIredventIlatIonsecondarytoIntercostal
muscleparalysIscanoccur.ProgressIonoccursover10to12days,followedbygradual
recovery.ThemostserIousImmedIateproblemIsventIlatoryInsuffIcIency.fthevItal
capacItydecreasesto15to20mL/kg,mechanIcalventIlatIonofthelungsIsIndIcated.
ThemorerapIdtheonsetofquadrIplegIa,themorelIkelyIstheneedformechanIcal
ventIlatIon.Although85ofpatIentswIththIssyndromeachIeveagoodrecovery,chronIc
recurrentneuropathydevelopsInJto5ofpatIents.
ntensIverespIratorycareandmanagementofautonomIcdysfunctIonhavereduced
mortalItyto5.PlasmapheresIsandtheadmInIstratIonofIntravenousImmunoglobulIn
maymodulatethedIsorderedImmuneresponse.
AutonomIcnervoussystemdysfunctIoncanproducewIdefluctuatIonsIncardIovascular
parameters.namannersImIlartoautonomIchyperreflexIa,physIcalstImulatIoncan
precIpItatehypertensIon,tachycardIa,andcardIacdysrhythmIas.
AutonomIcnervoussystemdysfunctIonmaycausehypotensIonsecondarytopostural
changes,bloodloss,orposItIveaIrwaypressure.NoxIousstImulIsuchaslaryngoscopyand
trachealIntubatIonmayproduceexaggeratedIncreasesInheartrateandbloodpressure.
TheadmInIstratIonofsuccInylcholIneshouldbeavoIdedbecauseofthedangerof
potassIumreleaseandhyperkalemIa.ThIsrIskmaypersIstafterclInIcalrecoveryfromthe
dIsease.
24
AshortactIng,nondepolarIzIngmusclerelaxantwIthmInImalcardIovascular
effectssuchascIsatracurIumorrocuronIumwouldbeausefulchoIce.ThesensItIvItyto
nondepolarIzIngmusclerelaxantsmayvaryfromextremesensItIvItytoresIstance,
dependIngonthephaseofthedIsease.
25
tIslIkelythatmechanIcalventIlatIonwIllbe
requIreddurIngtheImmedIatepostoperatIveperIod.PatIentswIthCuIllaIn8arrsyndrome
whohavepronouncedsensorydIsturbancesmaybenefItformtheadmInIstratIonof
neuraxIalopIoIds.
Central Nervous Sytem Diseases
Multiple Sclerosis
|ultIplesclerosIsIscharacterIzedbyInflammatIonandmultIplesItesofdemyelInatIonIn
thebraInandspInalcord.ThecauseofmultIplesclerosIsInvolvesacomplexserIesof
ImmunologIceventsoccurrIngIngenetIcallysusceptIbleIndIvIduals.AvIrusorothertrIgger
agentInItIatesanInflammatoryreactIonthatcausesaTcellmedIatedautoImmune
responsetomyelIn.0emyelInatIonexposestheaxontoharmfulfactorsandInterfereswIth
neuraltransmIssIon.LymphocytesthatmIgrateIntothecentralnervoussystem(CNS)
medIatemuchoftheInflammatoryreactIon.TheabIlItyofneuraltIssuetorepaIrItself
durIngtheearlyphasesoftheprocessexplaInstherelapsIngnatureofthedIsease.
26
ThesymptomsofmultIplesclerosIsdependonthesItesofInjuryInthebraInandspInal
cord.0emyelInatIonoftheoptIctractsproducesvIsualdIsturbances,whereas
demyelInatIonoftheoculomotorpathwaysresultsInnystagmus.LesIonsofthespInalcord
producelImbweaknessandparesthesIas.Thelegsareaffectedmorethanthearms.8owel
retentIonandurInaryIncontInencearefrequentcomplaInts.8raInstemInvolvementcan
producedIplopIa,trIgemInalneuralgIa,cardIacdysrhythmIas,andautonomIcdysfunctIon,
whIlealteratIonsInventIlatIoncanleadtohypoxemIa,apnea,andrespIratoryfaIlure.The
courseofmultIplesclerosIsIscharacterIzedbyexacerbatIonofsymptomsatunpredIctable
IntervalsoveraperIodofyears.0urIngtheearlyphaseofthedIseasepatIentsare
classIfIedaseItherrelapsIngremIttIngmultIplesclerosIs(85)orprImaryprogressIve
multIplesclerosIs.DvertIme,manypatIentswIthrelapsIngremIttIngmultIplesclerosIs
developneurodegeneratIonandarecategorIzedassecondaryprogressIvemultIple
sclerosIs.PatIentswIthprImaryprogressIvemultIplesclerosIsaregenerallydevoIdofacute
epIsodes,butdevelopprogressIvedegeneratIon.PregnancyIsassocIatedwIthan
ImprovementInsymptoms,butrelapsefrequentlyoccursInthefIrstJpostpartummonths.
ClInIcalcrIterIafordIagnosIsIncludeageofonsetbetween10and50years,neurologIc
sIgnsandsymptomsofCNSwhItematterdIsease,twoormoreattacksseparatedbya
monthormore,andInvolvementoftwoormorenoncontIguousanatomIcareas.Elevated
levelsofImmunoglobulIn(g)CandalbumInInthecerebrospInalfluIdarecharacterIstIcof
multIplesclerosIs.|agnetIcresonanceImagIng(|F)IsasensItIvedIagnostIctoolfor
multIplesclerosIsandprovIdesdIrectevIdenceofthelocatIonofdemyelInatedplaquesIn
theCNS.
TherapyformultIplesclerosIsIsdIrectedatmodulatIngtheImmunologIcandInflammatory
responsesthatdamagetheCNS.CortIcosteroIdsaretheprImaryagentsfortreatmentof
acuteexacerbatIonsofmultIplesclerosIs.CortIcosteroIdshavedIverseeffectsthat
suppresscellularImmuneresponsesandInflammatoryedema.nterferonaltersthe
InflammatoryresponseandaugmentsnaturaldIseasesuppressIonandhasbeenshownto
reducetherelapserate.ClatIramerIsamIxtureofpolypeptIdesthatmImIcthestructure
ofmyelInandservesasadecoyforautoantIbodIes.PatIentresponseto
ImmunosuppressantshasbeenvarIable.|Itoxantrone,whIchcanbecardIotoxIc,canbe
usedtotreataggressIvemultIplesclerosIs.
27
SymptomatIctherapyIncludesdIazepam,
dantrolene,andbaclofenforspastIcIty.PaInfuldysesthesIa,tonIcseIzures,dysarthrIa,and
ataxIacanbetreatedwIthcarbamazepIne.NonspecIfIcmeasuresIncludetheavoIdanceof
excessIvefatIgue,emotIonalstress,andhyperthermIa.0emyelInatednervefIbersare
extremelysensItIvetoIncreasesIntemperature.AtemperatureIncreaseof0.5`Ccanblock
ImpulseconductIonIndemyelInatedfIbers.
P.629
TheeffectofsurgeryandanesthesIaonthecourseofmultIplesclerosIsIscontroversIal.
FegIonalanesthesIaandgeneralanesthesIahavebeenreportedtoexacerbatemultIple
sclerosIs,whIleotherreportshavefoundnocorrelatIonbetweenanesthesIaandthecourse
ofthedIsease.FactorsotherthananesthesIasuchasInfectIon,emotIonalstress,and
hyperpyrexIamaycontrIbutetoanIncreasedrIskofaperIoperatIveexacerbatIon.
PreoperatIvely,thepatIentshouldbeadvIsedthatsurgeryandanesthesIacouldproducea
relapsedespIteawellmanagedanesthetIc.
AlthoughthemechanIsmIsnotknown,spInalanesthesIahasbeenassocIatedwIthan
exacerbatIonofthedIsease.tcouldbespeculatedthatdemyelInatedareasofthespInal
cordaremoresensItIvetotheeffectsofthelocalanesthetIc,causIngarelatIve
neurotoxIcIty.EvIdenceforthIstheoryIsfoundbytheobservatIonthathIgher
concentratIonsofbupIvacaIne(0.25)usedforlaborepIduralanalgesIaweremorelIkelyto
causerelapsethanlowerconcentratIons.
28
WIthsuchaprecautIon,epIduralanalgesIacan
besafelyprovIdedforwomendurInglabor.
PatIentsbeIngtreatedwIthcortIcosteroIdsmayrequIreIntravenouscortIcosteroId
supplementatIondurIngtheperIoperatIveperIod.mmunosuppressantscanproduce
cardIotoxIcItyandsubclInIcalcardIacdysfunctIon.8aclofencanproduceanIncreased
sensItIvItytonondepolarIzIngmusclerelaxants,whIleantIconvulsantsproduceresIstance
tonondepolarIzIngmusclerelaxants.ntheory,succInylcholInecouldproducean
exaggeratedreleaseofpotassIum,althoughthIshasnotbeenreported.AutonomIc
dysfunctIonmayexaggeratethehypotensIveeffectsofvolatIleanesthetIcs.FespIratory
muscleweaknessandrespIratorycontroldysfunctIonIncreasethelIkelIhoodoftheneedfor
supplementaloxygenand/ormechanIcalventIlatIondurIngtheImmedIatepostoperatIve
perIod.
29
Epilepsy
AseIzureIsacommonmanIfestatIonofmanytypesofCNSdIseasesandIstheexternal
manIfestatIonofepIlepsy.AseIzureresultsfromanexcessIvedIschargeoflargenumbersof
neuronsthatbecomedepolarIzedInasynchronousfashIon.dIopathIcseIzuresusually
begIndurIngchIldhood.ThesuddenonsetofseIzuresInayoungormIddleagedadultmay
IndIcatefocalbraIndIsease,partIcularlyatumor.TheonsetofseIzuresafter60yearsof
agecanbearesultofcerebrovasculardIsease,headInjury,tumor,InfectIon,ormetabolIc
dIsturbances.SomerareformsofepIlepsyarecausedbymutatIonsInIonchannels.The
avaIlabIlItyofnewantIseIzuredrugshasIncreasedthetherapeutIcoptIonsforpatIents
wIthepIlepsy(Table256).
J0
Table 25-6 Anticonvulsant Drugs
DRUG SEIZURE TYPE
THERAPEUTIC BLOOD
LEVELS (g/mL)
SIDE EFFECTS*
PhenobarbItal CeneralIzed 15J5
SedatIon,Increaseddrug
metabolIsm
7alproate
CeneralIzed
Absence
50100
PancreatItIs,hepatIc
dysfunctIon
Felbamate
CeneralIzed
PartIal
20140 nsomnIa,ataxIa,nausea
PhenytoIn
CeneralIzed
PartIal
1020
CIngIvalhyperplasIa
0ermatItIs
FesIstancetoN|
blockers
FosphenytoIn
CeneralIzed
PartIal
ParesthesIas
HypotensIon
CarbamazepIne
CeneralIzed
PartIal
612
CardIotoxIc,hepatItIs
FesIstancetoN|
blockers
LamotrIgIne
CeneralIzed
PartIal
216
Fash
StevensJohnson
syndrome
TopIramate
CeneralIzed
PartIal
410
SeveremetabolIc
acIdosIs
HyperthermIa
CabapentIn
CeneralIzed
PartIal
416 FatIgue,somnolence
PrImIdone
CeneralIzed
PartIal
612 Nausea,ataxIa
Clonazepam Absence 0.010.07 AtaxIa
EthosuxImIde Absence 40100
LeukopenIa,
ErythemamultIforme
LevetIracetam
CeneralIzed
PartIal
545
0IzzIness,headache
Somnolence
DxcarbazepIne PartIal 10J5
HyponatremIa,dIplopIa
Somnolence
TIagabIne PartIal Tremor,depressIon
ZonIsamIde CeneralIzed 1040
AnorexIa
0ecreasedcognItIon
PartIallIstIngN|,neuromuscular.
P.6J0
ThemostfrequentlyencounteredtypesofseIzuresare:
1. Grand mal seizure:AgrandmalseIzureIscharacterIzedbygeneralIzedtonIcclonIc
actIvIty.AllrespIratoryactIvItyIsarrestedandaperIodofarterIalhypoxemIaensues.
ThetonIcphaselastsfor20to40secondsandIsfollowedbytheclonIcphase.nthe
postIctalperIod,thepatIentIslethargIcandconfused.0IazepamandthIopentalare
effectIvefortreatmentofacute,generalIzedseIzures.EpIleptIcpatIentsresIstantto
drugtherapymaybenefItfromsurgIcalresectIonofaseIzurefocusorvagalnerve
stImulatorImplantatIon.
2. Focal cortical seizure:FocalcortIcalseIzuresmaybesensoryormotor,dependIngonthe
sIteofneuronaldIscharge.ThereIsusuallynolossofconscIousness,althoughtheseIzure
actIvItymayspreadtoproduceagrandmalseIzure.
J. Absence seizure (petit mal):AbsenceseIzuresarecharacterIzedbyabrIeflossof
awarenesslastIngJ0seconds.AddItIonalmanIfestatIonsIncludestarIng,blInkIng,and
rollIngoftheeyes.AbsenceseIzurestypIcallyoccurInchIldrenandyoungadults.
4. Akinetic seizure:AkInetIcseIzuresarecharacterIzedbyasudden,brIeflossof
conscIousnessandposturaltone.ThesetypesofseIzuresusuallyoccurInchIldrenand
canresultInsevereheadInjuryfromafall.
5. Status epilepticus:StatusepIleptIcusIsdefInedastwoconsecutIvetonIcclonIcseIzures
wIthoutregaInIngconscIousness,orseIzureactIvItythatIsunabatedforJ0mInutesor
more.CrandmalstatusepIleptIcustypIcallylastsfor48hourswIthaseIzurefrequency
offourtofIveperhour;mortalItycanbeashIghas20.AstheseIzureprogresses,
skeletalmuscleactIvItydImInIshesandseIzureactIvItymaybeevIdentonlyonthe
electroencephalogram(EEC).FespIratoryeffectsofstatusepIleptIcusIncludeInhIbItIon
oftherespIratorycenters,uncoordInatedskeletalmuscleactIvItythatImpaIrs
ventIlatIon,andabnormalautonomIcactIvItythatproducesbronchoconstrIctIon.There
IsahIghlIkelIhoodofpermanentneuronaldamagefromcontInuedseIzures.0Iazepam
andlorazepamareconsIderedthedrugsofchoIceforthetreatmentofstatus
epIleptIcus.8ecausetheeffectsofbenzodIazepInesaretransIent,alongeractIng
antIconvulsantsuchasphenytoInorphenobarbItalmustalsobeadmInIstered.ThIopental
IsquIteeffectIvefortheInItIaltreatmentofstatusepIleptIcus,buttheeffectIsbrIef.Dn
rareoccasIons,generalanesthesIawIthIsofluraneorbarbIturatesmayberequIred.
PatIentsreceIvIngantIseIzuremedIcatIonsshouldbemaIntaInedontheIrnormal
medIcatIonregImenuntIlthetImeofsurgeryandadmInIstratIonresumedassoonas
possIbleaftersurgery.AdeclIneInbloodlevelsofantIconvulsantdrugsIncreasesthe
lIkelIhoodofpostoperatIveseIzures.AnanesthesIatechnIqueshouldbeusedthat
mInImIzestherIskofseIzureactIvIty.StImulatIonofthehepatIcmIcrosomalenzymesby
antIconvulsantsmayIncreasetherateofbIotransformatIonofvolatIlehalogenated
anesthetIcsandIncreasetherIskoforgantoxIcIty.SIdeeffectsofantIconvulsantsInclude
leukopenIa,anemIa,hepatItIs,pancreatItIs,hepatIcfaIlure,coagulopathy,aplastIc
anemIa,cardIotoxIcIty,hypothyroIdIsm,rash,andhypersensItIvIty.
J1
AlthoughmostInhaledanesthetIcs,IncludIngnItrousoxIde,havebeenreportedtoproduce
seIzureactIvIty,suchactIvItydurIngtheadmInIstratIonofIsofluraneanddesfluraneIs
extremelyrare.ThesedrugsgenerallyproduceadosedependentdepressIonofEEC
actIvIty.However,sevofluranemaybeepIleptogenIc,althoughtheclInIcalsIgnIfIcanceof
thIsfIndIngIsuncertaIn.
J2
KetamIneandmethohexItalmayproduceseIzureactIvItyIn
patIentswIthknownseIzuredIsorders.twouldseemtobereasonabletoavoIdtheuseof
ketamIneandmethohexItalInpatIentswIthseIzuredIsorderswhenalternatIvedrugssuch
asthIopental,propofol,andbenzodIazepInesareavaIlable.PotentopIoIdssuchas
fentanyl,sufentanIl,alfentanIl,andremIfentanIlmayproducemyoclonIcactIvItyorchest
wallrIgIdItythatcanbeconfusedwIthseIzureactIvIty.PatIentsreceIvIngphenytoInor
carbamazepIneexhIbItresIstancetonondepolarIzIngmusclerelaxants.
Parkinson Disease
ParkInsondIseaseIsadegeneratIvedIseaseoftheCNScausedbylossofdopamInergIc
fIbersInthebasalganglIaofthebraIn.ThecharacterIstIcpathologIcfeatureIsdestructIon
ofdopamInecontaInIngnervecellsInthesubstantIanIgraofthebasalganglIa.Lewy
bodIes,ahallmarkofthepathologyofParkInsondIsease,arecytoplasmIcaggregatesof
synucleIn.SynucleInInclusIonsoccurInotherareasofthebraInandperIpheralnerves.
ThecauseofParkInsondIseaseIsmultIfactorIal,wIthgenetIcandenvIronmentalfactors.
DtherthanthewellknownpostencephalItIcParkInsondIsease,however,thereIslIttle
evIdencethatParkInsondIseaseIscausedbyavIrus.
JJ
TheclInIcaleffectsofParkInsondIseasearecausedbydopamInedefIcIency.0opamIne
defIcIencyIncreasesactIvItyofamInobutyrIcacId,whIchInhIbItsthalamIcandbraInstem
nucleI,whIchsuppressescortIcalmotoractIvIty,therebycausIngtremor,akInesIa,andgaIt
andpostureabnormalItIes.ThemostcharacterIstIcclInIcalfeaturesofParkInsondIsease
arerestIngtremor,cogwheelrIgIdItyoftheextremItIes,bradykInesIa,shufflInggaIt,
stoopedposture,andfacIalImmobIlIty.ThesefeaturesaresecondarytodImInIshed
InhIbItIonoftheextrapyramIdalmotorsystemasaresultofdopamInedepletIonInthe
basalganglIa.DtherclInIcalfeaturesareseborrhea,sIalorrhea,orthostatIchypotensIon,
bladderdysfunctIon,papIllaryabnormalItIes,dIaphragmatIcspasm,oculogyrIccrIses,
dementIa,andmentaldepressIon.
TreatmentIsdIrectedtowardIncreasIngdopamInelevelsInthebraIn,butpreventIngthe
adverseperIpheraleffectsofdopamIne.LevodopaIsthesInglemosteffectIvetherapyfor
patIentswIthParkInsondIsease.WhenadmInIsteredorally,levodopaIsconvertedto
dopamIneandcausessIdeeffectssuchasnausea,vomItIng,andhypotensIon.ToavoIdsuch
sIdeeffects,levodopaIsadmInIsteredwIthaperIpheraldecarboxylaseInhIbItor
(carbIdopa).CardIovasculareffectsoflevodopaIncludedepletIonofmyocardIal
norepInephrInestores,perIpheralvasoconstrIctIon,hypovolemIa,andhypotensIon.|ore
recently,entacapone,acatecholDmethyltransferaseInhIbItorhasbeenaddedtothe
combInatIonoflevodopaandcarbIdopa.EntacaponeblockstheperIpheralmetabolIsmof
levodopaandIncreasesthebIoavaIlabIlItyoflevodopa.DtherdrugsthatImprovefunctIon
InpatIentswIthParkInsondIseaseIncludethemonoamIneoxIdase8InhIbItorsselegIlIne
andrasagIlIne.0opamInereceptoragonIsts,suchasbromocrIptIne,pergolIde,cabergolIne,
pramIpexole,ropInIrole,exerttheIreffectondopamInereceptorsInthebraIn.Theergot
relateddopamIneagonIsts(pergolIdeandcabergolIne)havebeenassocIatedwIththe
developmentofcardIacvalvularfIbrosIs.PallIdotomyandImplantatIonofdeepbraIn
stImulatorsmaybeagoodoptIonforselectedpatIents.ThetherapeutIcregImenfor
patIentswIthParkInsondIseaseIscomplexandrequIresaskIlledneurologIstto
IndIvIdualIzetherapy.
J4
ThepatIent'smedIcatIonsshouldbeadmInIsteredonthemornIngofsurgery.ThehalflIfe
oflevodopaIsshort,andInterruptIonoftherapyformorethan6to12hourscanresultIn
severeskeletalmusclerIgIdItythatInterfereswIthventIlatIon.ApomorphIneIsadopamIne
agonIstthatcanbeadmInIstered
P.6J1
subcutaneouslyorIntravenouslyIforallevodopacannotbeadmInIstered.0opamIne
antagonIstssuchasphenothIazInes,droperIdol,andmetoclopramIdeshouldbeavoIded.
AlfentanIlandfentanylmayproduceacutedystonIcreactIonsInpatIentswIthParkInson
dIsease.AlthoughketamInecouldproduceanexaggeratedsympathetIcnervoussystem
responsewIthresultanttachycardIaandhypertensIon,IthasbeenusedwIthoutdIffIcultyIn
patIentswIthParkInsondIsease.TherearenoreportsofadverseresponsestoIsoflurane,
sevoflurane,ordesflurane.ThelIkelIhoodofcoexIstIngheartdIseaseInelderlypatIents
wIthParkInsondIseasemayInfluencetheselectIonofanesthetIcsandmonItorIng
technIques.AlthoughdefInItIvestudIesofanesthesIaforpatIentsreceIvIngmonoamIne
oxIdase8InhIbItors(selegIlIne,rasagIlIne)havenotbeenperformed,clInIcalexperIence
IndIcatesthatanesthesIaIsusuallyuneventful.TherehavebeenreportsofagItatIon,
musclerIgIdIty,andhyperthermIaInpatIentsreceIvIngmeperIdIneandselegIlIne.PatIents
beIngtreatedwIthdopamIneagonIstsmaybeatrIskforneuroleptIcmalIgnantsyndrome.
AutonomIcdysfunctIonIscommon.ThemostconsIstentcardIovascularabnormalItyIs
orthostatIchypotensIonthatmaybecompoundedbythevasodIlatoryeffectsofantI
ParkInsondrugs.PatIentswIthParkInsondIseasewouldbemorelIkelytodevelop
exaggeratedresponsesInbloodpressureInresponsetoInhaledhalogenatedanesthetIcs.
CastroIntestInaldysfunctIonIsmanIfestedbeexcessIvesalIvatIonandesophageal
dysfunctIon.ThepatIentwIthParkInsondIseaseshouldbeconsIderedtobeatrIskfor
aspIratIonpneumonItIs.
PerIoperatIverespIratorycomplIcatIonsarecommon.
J5
UpperaIrwayobstructIonmay
occurasaresultofpoorcoordInatIonofupperaIrwaymusclessecondaryto
neurotransmItterImbalancecausedthedIseaseprocessorInducedbytheadmInIstratIonof
antIdopamInergIcdrugs.SomepatIentswIthupperaIrwayobstructIonmayrespondtoantI
ParkInsondrugs.
nthepostoperatIveperIod,patIentswIthParkInsondIseasearesusceptIbletomental
confusIonandhallucInatIons.SuchalteratIonsInmentalfunctIonmaynotappearuntIlthe
dayaftersurgery.
Huntington Disease
HuntIngtondIseaseIsanautosomaldomInantInherIteddIseasecharacterIzedby
progressIveneurodegeneratIon.HuntIngtondIseaseIsoneofthetrInucleotIderepeat
dIsorders.AnIncreaseIncytosIne,adenIne,andguanIne(CAC)repeatsequenceson
chromosome4IsthegenetIcdefectthatproducesamutanthuntIngtInproteInthatcauses
HuntIngtondIsease.HuntIngtInIsfoundInallhumancells,butmostnotablybraIncells.
TheprecIsefunctIonofthIsproteInIsunknown.NeuronsfrompatIentswIthHuntIngton
dIseaseshowabnormalInclusIonscontaInIngmutanthuntIngtInandpolyglutamIne.thas
beenspeculatedthatdegradatIonofthemutanthuntIngtInbycaspase6producesa
cytotoxIcmetabolIte.8raInspecImensshowmarkedatrophyandcelllossInthecaudate
andputamen.dentIfIcatIonoftheHuntIngtongeneprovIdesarelIablepredIctIvetest;
however,thedelayednatureoftheclInIcalmanIfestatIonsofthedIseasepresentslegal
andethIcalconcernsaboutpredIctIvetestIng.
J6
ClInIcalfeaturesarechoreIformmovementsanddementIa.DnsetIstypIcallybetweenthe
agesofJ5and40years,butonsethasbeenreportedasearlyasage2andaslateasage80.
ThedIseaseprogressesforseveralyearsanddepressIonmakessuIcIdeafrequent
occurrence.0eathusuallyresultsfrommalnutrItIonandaspIratIonpneumonItIs.
HypothalamIcatrophycancauseendocrInechangessuchaselevatedcortIsollevels,
reducedtestosteronelevels,anddIabetes.TheduratIonofHuntIngtondIseaseaverages17
yearsfromthetImeofdIagnosIstodeath.
ThereIsnospecIfIctherapyforHuntIngtondIsease.0rugsusedforthetreatmentofchorea
IncludehaloperIdol,fluphenazIne,olanzapIne,amantadIne,rIluzole,andtetrabenazIne.
AntIdepressantsarecommonlyusedtoallevIatedepressIon.CoenzymeQ10and
mInocyclIneareunderInvestIgatIonasneuroprotectants.
ThemedIcallIteratureIssparsewIthregardtotheanesthetIcmanagementofpatIentswIth
HuntIngtondIsease.
J7
|anyofthemanIfestatIonsofHuntIngtondIseasearetypIcalof
patIentswIthneurodegeneratIvedIsorders.AsthedIseaseprogresses,thepharyngeal
musclesbecomedysfunctIonalandtherIskofaspIratIonpneumonItIsIncreases.Although
therearenospecIfIccontraIndIcatIonstotheuseofInhaledorIntravenousanesthetIcs,
recoveryfrompropofolmaybefasterthanfromotherIntravenoushypnotIcs.ShortactIng
musclerelaxantswouldbepreferabletolongeractIngrelaxants.0ecreasedplasma
cholInesterasemayprolongtheeffectofsuccInylcholIne.SpInalanesthesIahasbeen
successfullyused.
AsforanypatIentwIthaprogressIveneurologIcdIsease,delayedemergenceandan
IncreasedlIkelIhoodofrespIratorycomplIcatIonsmustbeantIcIpatedIntheImmedIate
postoperatIveperIod.
Alzheimer Disease
AlzheImerdIseaseIsthemajorcauseofdementIaIntheUnItedStates.TheIncIdenceof
AlzheImerdIseaseIs1In60yearoldpatIentsandJ0In85yearoldpatIents.Although
dementIaIscausedby60dIsorders,AlzheImerdIseaseIsresponsIblefor50to60ofthe
cases.|emoryImpaIrmentandlanguagedeterIoratIonoccurearlyInthedIseaseprocess.
|otorandsensoryabnormalItIes,gaItdIsturbances,seIzures,agItatIon,andpsychosIsare
laterfeaturesofthedIsease.Computedtomography(CT),|F,andposItronemIssIon
tomographyarehelpfulIndIfferentIatIngAlzheImerdIseasefromothercausesofdementIa.
EvIdenceofhIppocampalatrophymayprecedetheonsetofclInIcalsymptoms.
ThedeposItIonofamyloIdbetapeptIdeolIgomersappearstobecentraltotheprocessof
degeneratIonanddeathofneurons.0eposItIonofthIspeptIdeproducesneurItIcplaques
andneurofIbrIllarytanglesandactIvatestheapoptotIccelldeathcascadethatcauses
neurotransmItterdysfunctIon.TherapyIscurrentlylImItedbutongoIngresearchIsdIrected
atthreeareas:(1)antIamyloIddeposItIon:statIns,metalchelatIon(copper,zInc),
antIfIbrIllatIon,betaandgammasecretaseInhIbItIon;(2)neuroprotectIon:antIoxIdants,
nervegrowthfactor,antIInflammatIon,caspaseInhIbItIon,monoamIneoxIdaseInhIbItIon,
cholInesteraseInhIbItIon;and(J)neurorestoratIon:nervegrowthfactor,cell
transplantatIon,andstemcelltherapy.
J8
TheadmInIstratIonofcholInesteraseInhIbItorsIs
consIderedstandardofcareforpatIentswIthearlyAlzheImerdIsease.Thethreemost
commonlyusedcholInesteraseInhIbItorsaredonepezIl,rIvastIgmIne,andgalantamIne.
CholInesteraseInhIbItorsImprovethepatIent'sabIlItytoperformdaIlylIvIngactIvItIesand
mayImprovecognItIon.SIdeeffectsofcholInesteraseInhIbItorsIncludenausea,vomItIng,
bradycardIa,syncope,andfatIgue.
SelectIonofanesthetIcdrugsandtechnIquesforpatIentswIthAlzheImerdIseaseIsguIded
bythepatIent'sgeneralphysIologIccondItIon,thedegreeofneurologIcImpaIrment,and
thepotentIalforInteractIonbetweenanesthetIcsandmedIcatIonsthepatIentIsreceIvIng.
ThepatIent'spreoperatIvedruglIstshould
P.6J2
berevIewedforthepossIbIlItyofInteractIonswIthanesthetIcs.PatIentsarelIkelytobe
dIsorIentedanduncooperatIvebecauseofdementIa.SedatIvepremedIcatIonsarerarely
IndIcatedasfurthermentalconfusIoncouldresult.AnesthetIcsknowntoresultInrapId
recovery,suchaspropofol,desflurane,andsevoflurane,areadvantageous.Although
IsofluranemayIncreaseamyloIdbetaproteIngeneratIonandaggregatIonInIsolated
humanneurons,theclInIcalsIgnIfIcanceIsunknown.
J9
fanantIcholInergIcIsrequIred,
glycopyrrolate,whIchdoesnotcrossthebloodbraInbarrIer,IspreferabletoatropIneor
scopolamIne.AnantIcholInergIcthatcrossesthebloodbraInbarrIercouldexacerbate
dementIa.PatIentsreceIvIngcholInesteraseInhIbItorsmayhaveaprolongedresponseto
succInylcholIne.
Amyotrophic Lateral Sclerosis
AmyotrophIclateralsclerosIs(ALS,LouCehrIgdIsease,motorneurondIsease)Isa
degeneratIvedIseaseofmotorcellsthroughouttheCNS.Upperandlowermotorneurons
areInvolved.ProgressIonofthedIseaseIsrelentlessanddeathusuallyfollowswIthInJto5
yearsofdIagnosIs,although10ofALSpatIentssurvIvefor10years.ThecauseofALSIs
unknownandmanyhypotheseshavebeenproposed,IncludIngheavymetalexposureand
envIronmentalcauses.CurrentresearchhascenteredonglutamateexcItotoxIcItyand
oxIdantstress.FIveto10ofALScasesareheredItaryandpatIentsexhIbItamutatIonof
superoxIdedIsmutase.
40
ThesIgnsandsymptomsofALSreflecttheupperandlowermotorneurondysfunctIon.
Dnsetpatternssuchasbulbar,cervIcal,andlumbararedetermInedbytheareaoftheCNS
fIrstaffected.nItIalsymptomsareweakness,atrophy,andskeletalmusclefascIculatIon.
AsthedIseaseprogresses,theatrophyandweaknessInvolvemostskeletalmuscles,
IncludIngthoseofthetongue,pharynx,larynx,andchest.0ysarthrIaanddysphagIaarea
resultofbulbarInvolvement.PulmonaryfunctIontestsdemonstrateadecreaseInvItal
capacIty,maxImalvoluntaryventIlatIon,anddImInIshedexpIratorymusclereserve.
FespIratoryfaIlureeventuallydevelopsandventIlatorysupportIsrequIred.PatIentswIth
ALShaveautonomIcdysfunctIonasevIdencedbyanIncreasedrestIngheartrate,
orthostatIchypotensIon,andelevatedlevelsofepInephrIneandnorepInephrIne.There
maybedecreasedFFIntervalvarIatIonontheECCandadecreasedheartrateresponse
toatropIne.ThecauseofdeathforpatIentswIthALSIsusuallyrespIratoryfaIlure.Sudden
deathfromcIrculatorycollapsemayoccurInventIlatordependentpatIentswIthALS.
FIluzole,aglutamatereleaseInhIbItor,Istheonlydrugcurrentlyapprovedforthe
treatmentofALS.AlthoughnotcuratIve,rIluzolemaymodestlyprolongsurvIval(4to18
months)anddelaytheneedfortracheostomy.TherapeutIcagentsunderInvestIgatIon
IncludeantIoxIdants,mItochondrIalenhancers,antIapoptotIcs,Immunomodulators,antI
InflammatorIes,andproteasomeInhIbItors.
NeuromusculartransmIssIonIsmarkedlyabnormalInpatIentswIthALS,andthesepatIents
canbeverysensItIvetonondepolarIzIngmusclerelaxants.AswIthotherpatIentswIth
motorneurondIsease,ALSpatIentsshouldbeconsIderedtobevulnerabletohyperkalemIa
InresponsetosuccInylcholIne.0ysfunctIonofpharyngealandlaryngealmusclespredIsposes
patIentswIthALStopulmonaryaspIratIon.TheneedforpostoperatIveventIlatorysupport
IslIkelyforthesepatIents.ThereIsnoevIdencethataspecIfIcanesthetIcdrugor
combInatIonofdrugsIsbestforpatIentswIthALS.SubclInIcalautonomIcdysfunctIoncan
produceexaggerateddecreasesIncardIovascularfunctIonInresponsetoanesthesIa.
41
Creutzfeldt-Jakob Disease
CreutzfeldtJakobdIsease(CJ0)IsoneofagroupofdIseasestermedthetransmissible
spongiform encephalopathies.PathologIcally,thesedIseasesarecharacterIzedby
vacuolatIonofbraIntIssueandneuronaldeath.TherearefourtypesofCJ0:famIlIal(fCJ0,
sporadIc(sCJ0),IatrogenIc(iCJ0),andvarIant(vCJ0).CJ0IsmostlIkelyanInfectIon
causedbyaprIon(PrP),asmallproteInaceoussubstancedevoIdofnucleIcacIds.
Presumably,thepathologIcprIon(PrP
Sc
)convertsnaturallyoccurrIngprIonmaterIal(PcP
C
)
toPrP
Sc
.PrP
Sc
InItIallyInvadesperIpheralnervesandthenspreadscentrally.Hematogenous
andlymphoIdretIcularsystem(tonsIls,spleen)spreadmayalsooccur.sCJ0Isararecause
ofdementIa,butthedIscoveryoftransmIssIonofaprIondIsease(bovInespongIform
encephalopathy,madcowdIsease)fromcowstohumansInthemId1990scatapultedCJ0
topromInence.ThIsdIseaseIsvCJ0.
42
TheclInIcalcharacterIstIcsofsCJ0aresubacutedementIa,myoclonus,andEECchanges.
TheEECpatternIsrelatIvelycharacterIstIc,wIthdIffuseslowactIvItyandperIodIc
complexes.ProgressIvelossofcognItIveandneurologIcfunctIonoccurs.PatIentswIthvCJ0
presentatanearlIeragewIthpsychIatrIcfeaturessuchasdysphorIa,wIthdrawal,anxIety,
andInsomnIa.NeurologIcfeaturesdevelop1to2monthsafterthepsychIatrIcchanges
commence.TransmIssIonofvCJ0IsbyIngestIonofcontamInatedanImalproducts.
atrogenIctransmIssIonofiCJ0hasbeenlInkedtocontamInatedduralgraftmaterIal,
cornealtransplants,contamInatedsurgIcalInstruments,pooledhumangrowthhormone,
andblood.
4J
ThereIsnotreatmentforCJ0.nvestIgatIonaltherapIesareaImedat
preventIngprIontransportfromtheperIpherytotheCNSandatneuronregeneratIon.
CJ0IsatransmIssIbledIseaseandapproprIateprecautIonsmustbeobservedwhen
admInIsterInganesthesIa.HIghrIskpatIenttIssuesIncludebraIn,spInalcord,cerebrospInal
fluId,lymphoIdtIssue,andblood.SIngleuseanesthesIasupplIes,IncludIngfacemasks,
breathIngcIrcuIts,laryngoscopes,andtrachealtubes,shouldbeemployed.
44
PatIentswIthdegeneratIveneurologIcdIseasesarepronetoaspIrategastrIccontents
becausetheyhaveImpaIredswallowIngfunctIonanddecreasedlaryngealreflexes.8ecause
lowermotorneurondysfunctIonoccursInCJ0patIents,succInylcholIneshouldbeavoIded.
TheautonomIcandperIpheralnervoussystemsmaybeadverselyaffectedandabnormal
cardIovascularresponsestoanesthesIaandvasoactIvedrugsmayoccur.
Anemias
AnemIaIsanabsoluteorrelatIvedefIcIencyIntheconcentratIonofcIrculatIngredblood
cells.AnemIascanbeclassIfIedasnutrItIonal,hemolytIc,andgenetIc
(hemoglobInopathIes,thalassemIas;Table257).CompensatorymechanIsmsdevelopto
offsetthedecreasedoxygencarryIngcapacItyoftheblood(Table258).nahealthy
person,symptomsdonotdevelopuntIlthehemoglobInleveldecreasesbelow7g/dL.
SymptomsarevarIableanddependonconcurrentdIseaseprocesses.ThereIsnounIversally
acceptedhematocrItlevelthatdemandstransfusIon.ThepatIent'sphysIologIccondItIon
andcoexIstIngdIseasesmustbefactoredIntoasubjectIvedecIsIon.
Nutritional Deficiency Anemias
ThethreeprImarycausesofnutrItIonaldefIcIencyanemIaareIrondefIcIency,vItamIn8
12
defIcIency,andfolIcacIddefIcIency.
P.6JJ
ChronIcIllness,cancer,andpoordIetaryIntakecanresultInnutrItIonaldefIcIencyanemIa.
Table 25-7 Types of Anemias
Nutritional
rondefIcIency
7ItamIn8
12
defIcIency
FolIcacIddefIcIency
ChronIcIllness
Hemolytic
SpherocytosIs
Clucose6phosphatedehydrogenasedefIcIency
mmunemedIated
0rugInducedA8DIncompatIbIlIty
Genetic
HemoglobInS(sIcklecell)
ThalassemIamajor(Cooley'sanemIa)
ThalassemIaIntermedIa
ThalassemIamInor
rondefIcIencyanemIaproducesamIcrocytIc,hypochromIcredbloodcell.rondefIcIency
anemIamaybeanabsolutedefIcIencysecondarytodecreasedoralIntakeorarelatIve
defIcIencycausedbyarapIdturnoverofredbloodcells(e.g.,chronIcbloodloss,
hemolysIs).
|egaloblastIcanemIacanbecausedbyvItamIn8
12
(cobalamIn)defIcIency,folate
defIcIency,orrefractorybonemarrowdIsease.AbsorptIonofvItamIn8
12
bythe
gastroIntestInaltractdependsonreleaseofIntrInsIcfactor,aglycoproteInproducedby
gastrIcparIetalcells.AtrophyofthegastrIcmucosacausesvItamIn8
12
defIcIencyand
megaloblastIcanemIa.ChronIcgastrItIsandgastrIcatrophymaybecausedby
autoantIbodIestogastrIcparIetalcells.naddItIontoanemIa,vItamIn8
12
defIcIencycan
InterferewIthmyelInatIonandcausenervoussystemdysfunctIon.ThIsIsmanIfestedbya
perIpheralneuropathysecondarytodegeneratIonofthelateralandposterIorspInalcord
columns.SymmetrIclossofproprIoceptIonandvIbratorysensatIonInthelowerextremItIes
occur.AdmInIstratIonofparenteralvItamIn8
12
reversesboththehematologIcand
neurologIcchangesInadults.ThecoexIstIngneuropathyofvItamIn8
12
defIcIencymustbe
consIderedwhenregIonalorperIpheralnerveblocksmIghtbeused.TheclInIcal
sIgnIfIcanceoftheeffectsofnItrousoxIdeonvItamIn8
12
metabolIsmIscontroversIal.
NItrousoxIdeInactIvatesthevItamIn8
12
componentofmethIonInesynthetaseand
prolongedexposuretonItrousoxIdeproducesmegaloblastIcanemIaandneurologIcchanges
sImIlartothosethatoccurwIthpernIcIousanemIa.nsusceptIblepatIents(thosewIth
chronIcIllness,theelderly)thereIsalsoevIdencethatshorttermexposuretonItrousoxIde
cancausemegaloblastIcredbloodcellchanges.
45
TheIssueofnItrousoxIdecausIng
postoperatIveneurologIcdysfunctIonIsalsocontroversIalandcasereportsofneuropathy
lInkedtoIntraoperatIvenItrousoxIdeexposurehaveIncreased.
Table 25-8 Compensatory Mechanisms to Increase Oxygen Delivery with
Chronic Anemia
ncreasedcardIacoutput
ncreasedredbloodcell2,JdIphosphoglycerate
ncreasedP50
ncreasedplasmavolume
0ecreasedbloodvIscosIty
FolIcacIddefIcIencyalsoproducesmegaloblastIcanemIa.AlthoughperIpheralneuropathy
mayoccur,ItIsnotascommonaswIthvItamIn8
12
defIcIency.CausesoffolIcacId
defIcIencyIncludealcoholIsm,pregnancy,andmalabsorptIonsyndromes.|ethotrexate,
phenytoIn,andethanolareamongthedrugsknowntoInterferewIthfolIcacIdabsorptIon.
Hemolytic Anemias
ThenormallIfespanofanerythrocyteIs120days.AbnormalItIesIntheerythrocytemay
resultInprematuredestructIonofthecell(hemolysIs).CausesofhemolytIcanemIaInclude
structuralerythrocyteabnormalItIes,enzymedefIcIencIes,andImmunehemolytIc
anemIas.
Hereditary Spherocytosis
SpherocytosIs,ellIptocytosIs,pyropoIkIlocytosIs,andstomatocytosIsarethefourtypesof
heredItarymembranedefectsresultIngInabnormallyshapedredbloodcells.
SpherocytosisIsthemostcommonoftheredcellmembranedefectsproducInghemolysIs.
ThIsdefectIscausedbyanabnormalItyIntheproteInsthatcomprIsetheskeletonofthe
redbloodcellmembrane.TheredbloodcellIsrounded,fragIle,andmoresusceptIbleto
hemolysIsthanthenormalbIconcaveredbloodcell.Thespleendestroystheabnormalred
bloodcellsandchronIcanemIaensues.CholelIthIasIsfromchronIchemolysIsandelevatIon
oftheserumbIlIrubInoccurInpatIentswIthheredItaryspherocytosIs.PatIentswIth
heredItaryspherocytosIsmayhavehemolytIccrIsesaccompanIedbyanemIa,vomItIng,and
abdomInalpaIn.ThesecrIsesmaybetrIggeredbyInfectIonorfolIcacIddefIcIency.
HeredItaryspherocytosIsIstreatedbysplenectomythatIsusuallydelayeduntIlthepatIent
Isage6yearsorolder.SplenectomybeforethatageIsassocIatedwIthahIghIncIdenceof
bacterIalInfectIons,especIallypneumococcaltype.TransfusIonIsrarelynecessarybecause
adequatecompensatorymechanIsmsforchronIcanemIahavedeveloped.
Glucose-6-Phosphate Dehydrogenase Deficiency
Clucose6phosphatedehydrogenase(C6P0)defIcIencyIsthemostcommonenzymopathyIn
humansandafflIcts400mIllIonpeopleworldwIde.C6P0defIcIencymayconfermalarIal
resIstanceandthedIstrIbutIonofthIsvarIantparallelsthegeographIcdIstrIbutIonof
malarIa.AfrIcanAmerIcans,AfrIcans,AsIans,ndIans,and|edIterraneanpopulatIonsare
susceptIbletotheabnormalIty.C6P0InItIatesthehexosemonophosphateshuntthatbegIns
themetabolIsmofglucoseIntheredbloodcell.ThIspathwayproducesnIcotInamIde
adenInedInucleotIdephosphate(NA0PH).WIthoutNA0PH,theredbloodcellIsvulnerable
todamagebyoxIdatIon.AdefIcIencyofC6P0resultsIndecreasedlevelsofglutathIone
whentheerythrocyteIsexposedtooxIdants.ThIsIncreasestherIgIdItyoftheredblood
cellmembraneandacceleratesclearanceofthecellfromthecIrculatIon.nsevereforms
ofC6P0defIcIency,oxIdatIonproducesdenaturatIonofglobInchaInsandcauses
IntravascularhemolysIs.NA0PHcontrIbutestothesynthesIsofendogenousnItrIcoxIdeand
adefIcIencyofNA0PHcausedbyC6P0defIcIencymayadverselyaffectneutrophIlfunctIon,
therebyIncreasIngtherIskofsepsIsIncrItIcallyIllpatIents.
ThereareanumberofdrugsthatenhancethedestructIonoferythrocytesInpatIentswIth
C6P0defIcIency(Table259).ThereIsconsIderablevarIabIlItyInthehemolytIcresponseto
drugs;manydrugs(e.g.,aspIrIn)causehemolysIsonlyInveryhIghdoses.PatIentswIth
C6P0defIcIencyareunabletoreducemethemoglobInproducedbysodIumnItrate;
therefore,sodIumnItroprussIdeandprIlocaIneshouldnotbeadmInIstered.
P.6J4
CharacterIstIcally,thecrIsIsbegIns2to5daysafterdrugadmInIstratIon.ThehemolytIc
epIsodeIsusuallyselflImItedasonlytheolderredbloodcellsareaffected.8acterIal
InfectIonscantrIggerhemolytIcepIsodesandoxIdantsproducedbyactIvewhItebloodcells
mayhemolyzesusceptIbleredbloodcells.AnesthetIcdrugshavenotbeenImplIcatedas
hemolytIcagents;however,earlypostoperatIveevIdenceofhemolysIsmIghtsuggesta
C6P0defIcIency.
Table 25-9 Drugs that Produce Hemolysis in Patients with Glucose-6-
Phosphate Dehydrogenase Deficiency
PhenacetIn NalIdIxIcacId
AspIrIn(hIghdoses) sonIazId
PenIcIllIn PrImaquIne
StreptomycIn QuInIne
ChloramphenIcol QuInIdIne
SulfacetamIde 0oxorubIcIn
SulfanIlamIde |ethyleneblue
SulfapyrIdIne NItrofurantoIn
Pyruvate Kinase Deficiency
PyruvatekInaseIsaglycolytIcenzymeoftheEmbden|eyerhofpathway.ThIspathway
convertsglucosetolactateandIstheprImarypathwayforadenosInetrIphosphate
synthesIsIntheredbloodcell.AdefIcIencyofpyruvatekInaseresultsInapotassIumleak
fromtheredbloodcell,IncreasIngtheIrrIgIdItyandacceleratIngdestructIonInthespleen.
ClInIcally,thesepatIentsexhIbItanemIa,prematurecholelIthIasIs,andsplenomegaly.The
degreeofanemIavarIesfromverymIldtoasevere,transfusIondependentanemIa.The
clInIcalfeaturesresemblethoseforpatIentswIthspherocytosIs.TherearenospecIal
consIderatIonsforanesthesIaotherthanthoseforanypatIentwIthchronIcanemIa.
Immune Hemolytic Anemia
TheImmunehemolytIcanemIasarecharacterIzedbyImmunologIcalteratIonsInthered
bloodcellmembraneandarecausedbydrugs,dIsease,orerythrocytesensItIzatIon.There
arethreetypesofImmunehemolytIcanemIa:autoImmunehemolysIs,drugInduced
ImmunehemolysIs,andalloImmunehemolysIs(erythrocytesensItIzatIon).
46
AutoImmune
hemolytIcanemIaIncludesbothwarmandcoldantIbodyhemolytIcanemIa.Cold
autoImmunehemolytIcanemIaIsofspecIalconcerntotheanesthesIologIstbecauseofthe
lIkelIhoodthatthecoldoperatIngroomenvIronmentandhypothermIadurIng
cardIopulmonarybypassmayInItIateahemolytIccrIsIs.ColdhemagglutInIndIseaseIs
causedbyg|autoantIbodIesthatreactwIthantIgensofredbloodcells.|aIntaInInga
warmenvIronmentIsessentIalforpreventIonofhemolysIs.PlasmapheresIstoreducethe
tIterofcoldantIbodyIsrecommendedbeforehypothermIcproceduressuchas
cardIopulmonarybypass.CollagenvasculardIseases,solIdorgantransplant,blood
transfusIon,neoplasIa,andInfectIonscanproduceImmunehemolytIcanemIabyavarIety
ofmechanIsmsIncludIngwarmandcoldantIbodymedIatedhemolysIs.
TherearethreetypesofdrugInducedImmunehemolysIs:autoantIbodytype,hapten
Inducedtype,andImmunecomplextype.HemolysIsInducedbymethyldopaIsofthe
autoImmunetypemedIatedbyangCantIbodythatdoesnotfIxcomplement.Thehapten
InducedtypeIscharacterIstIcoftheresponsetopenIcIllIn.TheImmunetypeofreactIon
canoccuraftertheadmInIstratIonofquInIdIne,quInIne,sulfonamIdes,IsonIazId,
phenacetIn,acetamInophen,cephalosporIns,tetracyclInes,hydralazIne,and
hydrochlorothIazIde.
TheclassIcexampleofalloImmunehemolysIs(erythrocytesensItIzatIon)IshemolytIc
dIseaseofthenewbornproducedbyFhsensItIzatIon.AnFhnegatIvemotherwIthFh
antIbodIesproduceshemolysIsInanFhposItIvefetus.0IfferencesInfetalandmaternal
A8DgroupsmayalsocausehemolysIs.However,thIsIsunusualbecauseAand8antIbodIes
areoftheg|classanddonotreadIlycrosstheplacenta.
TreatmentofImmunehemolytIcanemIasIswIthcortIcosteroIdsandImmunosuppressants.
SplenectomymaybebenefIcIalInsomepatIents.
Hemoglobinopathies
HemoglobInopathIesaredIseasescausedbygenetIcerrorsInhemoglobInsynthesIsand
productIon.llnessIscausedbyanemIa,accumulatIonofInapproprIatehemoglobIn
precursors,ImmunocompromIse,tIssueInfarctIon,InflammatIonandotherfactors.
ThehemoglobInopathIesconveysurvIvalprotectIonInmalarIalendemIcareasby
decreasIngerythrocytelIfespanandpromotIngerythrocyteturnover.nthecaseofsIckle
celldIsease,survIvaladvantageIsconveyedonlytoheterozygouscarrIersofthedIsease.
ThehemoglobInopathIesmostlIkelytobeencounteredaresIcklecelldIsease,hemoglobIn
C,andthethalassemIas.
Sickle Cell Disease
SIcklecelldIsease(SC0)wasoneofthefIrstdIseasesdetermInedtobecausedbyasIngle
molecularabnormalIty.SC0resultsfrommutatIonofchromosome11thatcauses
substItutIonofvalIneforglutamIcacIdatthesIxthposItIonoftheglobInproteIn.Persons
heterozygousforthesIcklecellgene(HbSA)areusuallyasymptomatIcandlIveanormal
lIfewhIlehomozygousIndIvIdualssufferSC0(HbSS).
47
NormalhemoglobInmoleculesarecomposedoffourglobInproteInsboundtoasIngleIron
contaInInghemestructure.ThenormaladultglobInarrangementIstwoglobInsandtwo
globIns.ThIsstructureIshemoglobInA(HbA)andcomprIses95to98ofhemoglobInIn
thenormaladult.nSC0theglobInsareabnormal,causIngInstabIlItyanddecreased
solubIlItyofthe
SIckle
(
S
)globIn.ThehemoglobInofSC0Istermedhemoglobin S(HbS).
WhensIcklecellhemoglobIn(HbS)IsexposedtolowoxygenconcentratIons,a
conformatIonalchangeof
S
causespolymerIzatIonandprecIpItatIonofHbSwIth
deformatIonoftheerythrocyte,hemolysIs,andprematureredbloodcelldestructIon.Fed
bloodcelllIfespanInSC0Isonly12to17daysversusanormallIfespanof120days.
HemoglobInelectrophoresIscanbeperformedtodIagnoseSC0anddetermInetherelatIve
concentratIonsofHbA,HbF,andHbS.SIcklecelltraItmayalsobecombInedwIth
hemoglobInC(HbC)orthalassemIa.HemoglobInCIsproducedbyamutatIonaffectIngthe
sameamInoacIdontheglobInasHbS.Thenumber6glutamIcacIdIsreplacedbylysIne
InHbC.HbCIsmIldlyunstableandeventhosehomozygousforH8Chavefewsymptoms.
ndIvIdualswIthHbSCsuffersymptomsapproachIngtheseverItyofSC0.
LInkIngthemolecularbasIsofSC0toItsmanyvarIedclInIcalmanIfestatIonshasproven
dIffIcult.ThetradItIonalexplanatIonhasbeenthevIcIouscycletheory.ErythrocytesIna
deoxygenatedcapIllarydeformtothesIckleshapeandcreateamechanIcalobstructIonto
bloodflow.TheslowIngofbloodflowcreatesstasIsandfurtherreductIonsInoxygenatIon.
ThesIcklIngofaddItIonalerythrocytescausesavIcIouscyclethatmanIfestsaspaIn,tIssue
IschemIa,andInfarctIon.Atbest,thIstheoryIsIncompleteandmanyothermechanIsms
areoperable(Table2510).
48
P.6J5
Table 25-10 Mechanisms of Cellular and Tissue Injury in Sickle Cell Disease
ErythrocyteandplateletadhesIontoendothelIum
ActIvatIonofcoagulatIonsystemwIththrombosIsandIschemIa
FeperfusIonInjury
LeukocytosIsandImmunesystemactIvatIon
FreeradIcalInjuryduetoleukocytesuperoxIderelease
0ecreasednItrIcoxIdeduetoleukocytesuperoxIderelease
ActIvatIonofcytokIneandInflammatorymedIators
HemolysIsandreleaseoffreehemoglobIn
FreeradIcalInjurysecondarytofreehemoglobIn
0ecreasednItrIcoxIdeduetouptakebyfreehemoglobIn
EndothelIaldysfunctIonsecondarytoInflammatIonand
depletIonofnItrIcoxIde
ExcessIveIronstoressecondarytorepeatederythrocytetransfusIon
TheclInIcalmanIfestatIonsofSC0aredIverseandInvolveallorgansystems(Table2511).
ThemostcommonproblemIspaInthatmaybepoorlylocalIzed,bIlateral,anddescrIbedas
achIng.WhenthepaInbecomessevere,thepatIentmaybeexperIencIngapaInfulcrIsIs.
ThepaIncanbetreatedwIthnonsteroIdalantIInflammatorydrugs(NSA0s)andnarcotIcs.
HydratIonandsupplementaloxygenareoftenadmInIsteredtoImprovetIssueoxygen
delIvery.8loodtransfusIonIsrequIredwhenroutInemeasuresfaIltorelIevethesymptoms.
SplenIcautoInfarctIonIsaunIversalfeatureofSC0,andlIfelongpenIcIllIntherapyandan
aggressIveImmunIzatIonprogramarerequIredtocompensateforfunctIonalasplenIa.
SepsIs,aplastIccrIsIs,splenIcsequestratIoncrIsIs,andacutechestsyndrome(ACS)arefour
lIfethreatenIngeventsthatmustberecognIzedandpromptlytreated.AplastIccrIsIs
occurswhenbonemarrowsuppressIonpreventsthetImelyreplacementoferythrocytes.
TransfusIonofredbloodcellsmustbeperformeduntIlnormalmarrowfunctIonIsre
establIshed.AvIralInfectIonIsafrequentprecIpItantofaplastIccrIsIs.SplenIc
sequestratIoncrIsIsoccurswhenlargenumbersoferythrocytesaretrappedbyanenlarged
spleen.TheensuInganemIaandhypovolemIarequIrevolumeresuscItatIonandredblood
celltransfusIons.SplenectomyIsperformedafterresolutIonofthecrIsIs.
Table 25-11 Clinical Manifestations of Sickle Cell Disease
Hematologic
HemolytIcanemIa
AplastIcanemIa
LeukocytosIs
Spleen
nfarctIon
HyposplenIsm
SplenIcsequestratIon
Stroke
Hemorrhage
Aneurysm
|enIngItIs
Musculoskeletal
PaInfulcrIses
8onemarrowhyperplasIa
AvascularnecrosIs
DsteomyelItIs
8oneInfarcts
SkeletaldeformIty
CrowthretardatIon
CutaneousulceratIon
Cardiac
CardIomegaly
PulmonaryhypertensIon
Corpulmonale
0IastolIcdysfunctIon
CardIomyopathy
Renal
PapIllarynecrosIs
ClomerularsclerosIs
FenalfaIlure
Pulmonary
Acutechestsyndrome
HypoxemIa
PulmonaryInfarctIon
FIbrosIs
Asthma
Sleepapnea
ThromboembolIsm
PneumonIa
Genitourinary
PrIapIsm
nfectIon
Hepatobiliary
JaundIce
HepatItIs
CIrrhosIs
CholelIthIasIs
CholestasIs
Eye
FetInopathy
Hemorrhage
7Isualloss
Immune System
mmunosuppressIon
LeukocytosIs
Psychosocial
0epressIon
AnxIety
Substanceabuse
NarcotIcdependence
ACSrepresentsthesInglegreatestthreattothepatIentwIthSC0.ThemortalItyofACSIs1
to20.SIgnsandsymptomsofACSIncludedyspnea,wheezIng,chestpaIn,hypoxemIa,and
pulmonaryInfIltrates.ACSmayprogresstoadultrespIratorydIstresssyndrome,respIratory
faIlure,andpneumonIa.TreatmentIncludessupplementaloxygen,erythrocytetransfusIon,
InhaledbronchodIlators,antIbIotIcs,andInsomecasessteroIds.|echanIcalventIlatIon
maybenecessary.PrecIpItantsofACSIncludepulmonaryInfectIon,fatembolIsmfrom
bonyInfarcts,worsenIngofasthma,andperIoperatIverespIratorydysfunctIon.
49
|osttreatmentofSC0IssupportIveanddIrectedatearlytreatmentofcomplIcatIons.
|anySC0patIentsaretreatedwIthhydroxyureatoIncreasecIrculatInglevelsoffetal
hemoglobIn.AllSC0patIentsshouldbeenrolledInamultIdIscIplInaryclInIcalcare
program.AdvancesInpreventIveandacutecarehaveImprovedthemeanageofsurvIval
forSC0patIentsto50years.CuratIvetreatmentforsomepatIentsIspossIblewIthbone
marrowtransplantatIonfromamatchedsIblIng.8onemarrowtransplantatIonIstypIcally
reservedforSC0patIentswIthseveresymptomsatanearlyage.
PreparatIonoftheSC0patIentforsurgeryshouldbedoneInclosecollaboratIonwIththe
sIcklecellspecIaltyservIcethatprovIdesthepatIent'sroutInecare.TheunderlyIng
condItIonofthepatIentandtheextentofthesurgerywIlldetermInetheneedfor
preoperatIvetestInganderythrocytetransfusIon.AgeJ0years,hIstoryofACS,asthma,
restInghypoxemIa,pulmonaryhypertensIon,prevIousstroke,andfrequentpaInfulcrIses
IncreasetherIskofperIoperatIvecomplIcatIons.|InorproceduressuchasmyrIngotomy,
tonsIllectomyandadenoIdectomy,andvascularaccessprocedureshavemIldperIoperatIve
rIskandgenerallydonotrequIretransfusIon.However,patIentswIthseveredIseasemay
requIretransfusIonforevenmInorprocedures.ntraabdomInalandorthopaedIc
proceduresposemoderaterIskandtransfusIonIsusuallyIndIcated.ThoracIc,cardIac,and
IntracranIaloperatIonsshouldbeconsIderedhIghrIskwIthtransfusIonrequIred.
TransfusIonoferythrocytestoraIsethehematocrIttoJ0toJ5IsdesIred.FoutIne
preoperatIvetestIngshouldIncludeahematocrItbeforeandaftertransfusIon,creatInIne,
bloodureanItrogen,electrolytes,roomaIroxImetry,andprothrombIntIme/partIal
thromboplastIntImewIthInternatIonalnormalIzedratIo.ECC,echocardIography,chest
radIography,andarterIalbloodgasanalysIsshouldbeconsIderedforpatIentswIth
symptomssuggestIveofcardIacdIsease,pulmonaryhypertensIon,ahIstoryofACS,
exertIonaldyspnea,orchronIchypoxemIa.PulmonaryhypertensIonanddIastolIc
dysfunctIonarerelatIvelycommonandareassocIatedwIthIncreasedmorbIdItyand
mortalIty.
50
PreventIonofcondItIonsthatfavorsIcklIngIsthebasIsofperIoperatIvemanagement.
AdequateoxygenatIon,avoIdanceofIncreasedoxygenconsumptIon,andpreventIonof
vascularstasIsareImperatIve.NormothermIashouldbeachIevedtoavoIdproblems
assocIatedwIthhyperthermIaandhypothermIa.HyperthermIaIncreasesoxygen
consumptIonandhypothermIa
P.6J6
causesvascularconstrIctIonthatpromotesbloodstasIs.PerIoperatIveshIverIngIncreases
oxygenconsumptIonandIsundesIrable.TheuseoftournIquetsmaybeconsIderedIf
essentIaltothesuccessoftheoperatIon.
0rugsusedforanesthesIaarenotknowntohavedIrecteffectsonthesIcklIngprocess.
CeneralanesthesIaIsusuallyemployed,butregIonalanesthesIacanbeusedIfIndIcated
(e.g.,laboranddelIvery,cesareansectIon).ThepresenceofpulmonaryhypertensIonor
cardIacdysfunctIonmayrequIremoreaggressIveperIoperatIvemonItorIngand
postoperatIvemanagementtoavoIddecompensatIon.TenpercentofSC0patIentsmay
experIenceACSIntheperIoperatIveperIod.Supplementaloxygen,chestphysIotherapy,
goodpaIncontrol,andmaIntenanceofthehematocrItbetweenJ0andJ5mayreducethe
rIskofpostoperatIveACS.Anecdotally,maInstembronchIalIntubatIonmayprecIpItateACS
andInadvertentonelungventIlatIonIstobeavoIded.
47,48,50
Thalassemia
ThalassemIaIsahemoglobInopathyInwhIchthereIsInadequatesynthesIsofeItherthe
orglobInproteIns.ThalassemIaIsmorecommonInthe|edIterranean,|IddleEastern,
andSoutheastAsIanregIons.fglobInsynthesIsIsInadequate,theexcessglobInIs
reactIveandcausesprematuredestructIonoferythrocytes.fglobInsynthesIsIs
Inadequate,theexcessglobInformsnonfunctIonaltetramerscalledhemoglobin H.
ErythrocytelIfeIsshortenedwIthresultanthemolytIcanemIa,splenomegaly,
hepatomegaly,cholelIthIasIs,andjaundIce.8onemarrowhyperplasIacausesskeletal
abnormalItIessuchasgrowthretardatIon,facIaldysmorphIsm,andpathologIcfractures.
ExtramedullarybonemarrowthatIssusceptIbletospontaneoushemorrhagemayformIn
thepleura,paranasalsInuses,andepIduralspace.
TheexpressIonofthalassemIaIsvarIable,rangIngfromasymptomatIcmIldanemIato
deathatanearlyage.Thetermsthalassemia major, intermedia,andmInorrefertothe
clInIcalseverIty.PatIentswIththalassemIamajorrequIrelIfelongtransfusIons.
HypertransfusIonIsusedtomaIntaInthepatIent'shemoglobInat9to10g/dLInorderto
suppressthalassemIcerythropoIesIs.ThIssuppressesextramedullarybonemarrow
formatIonandreducesthelIkelIhoodofskeletaldeformIty,causeslesshemolysIs,and
decreasedproductIonoftoxIchemoglobInprecursors.ChelatIontherapymustbeInstItuted
earlytopreventthecomplIcatIonsofIronoverload.ThepathophysIologyofthalassemIaIs
verysImIlartothatofSC0.ChronIchemolysIs,globInexcess,andIronoverloadresultIn
chronIcInflammatIon,depletIonofnItrIcoxIde,endothelIaldysfunctIon,andactIvatIonof
thecoagulatIonsystem.TheseresultInpulmonaryhypertensIon,cardIomyopathy,
cIrrhosIs,andsplenomegaly.
51
AnesthetIcconsIderatIonsarerelatedtothedegreeofanemIa,skeletaldeformIty,and
secondaryorgandamage.ThecranIofacIaldeformItIescommonInpatIentswIth
thalassemIamaymakedIrectlaryngoscopyandtrachealIntubatIondIffIcult.NeuraxIal
anesthesIamaybecomplIcatedbyskeletalabnormalItIesandextramedullarybonemarrow
deposIts.SpInalanesthesIa,however,hasbeenusedforcesareansectIon.ngeneral,many
oftheassessmentandmanagementrecommendatIonsforSC0arealsoapplIcablefor
patIentswIththalassemIa.
52
Figure 25-5.|agnetIcresonanceImagIngofacervIcalspIneInapatIentwIth
rheumatoIdarthrItIs.AlthoughthepatIenthadnoneurologIcsymptoms,thereIs
severespInalstenosIsIntheuppercervIcalspIne.
Collagen Vascular Diseases
ThefourmostcommoncollagenvasculardIseasesarerheumatoIdarthrItIs,systemIclupus
erythematosus,scleroderma,anddermatomyosItIs/polymyosItIs.AlthoughmanypatIents
canbecategorIzedashavIngdIscretedIseasesyndromes,manyotherswIthcollagen
vasculardIseasesareconsIderedtohaveoverlapsyndromes(mIxedconnectIvetIssue
dIseases)wIthfeaturesofdIfferentcollagenvasculardIseasesandcannotbeconvenIently
classIfIed.TheetIologyofthecollagenvasculardIseasesIsunknown,althoughtheImmune
systemIsclearlyInvolvedInthecascadeofpathologIceventsthatcauseclInIcal
manIfestatIonsofthedIseases.AlthoughallofthesedIseaseshaveeffectsonjoInts,each
hasdIffusesystemIceffectsaswell.ThealteratIonsInjoIntfunctIonandsystemIceffects
wIllbothhavesIgnIfIcantImpactonthemanagementofanesthesIa.
Rheumatoid Arthritis
FheumatoIdarthrItIsIsachronIcInflammatorydIseasecharacterIzedbysymmetrIc
polyarthropathyandavarIetyofsystemIceffects.AlthoughtheetIologyofrheumatoId
arthrItIsIsunknown,extensIveresearchhasrevealedthepathogenesIs.ActIvated
endothelIalcellsattractadhesIonmoleculesthatbIndtoproteInsandInItIateasequence
ofeventsthatstImulateTcellsand8lymphocytes.CytokInes(tumornecrosIsfactor,
InterleukIn1,InterleukIn6)arereleasedthatacceleratetheInflammatorycascade.8
lymphocytesproduceautoantIbodIes(rheumatoIdfactor)thatenhancecytokIneproductIon
andcanbefoundIn75ofpatIentswIthrheumatoIdarthrItIs.ThepathologIcchangesof
rheumatoIdarthrItIsbegInwIthcellularhyperplasIaofthesynovIumfollowedbyInvasIon
ofthesynovIumbylymphocytes,plasmacells,andfIbroblasts.CartIlageandartIcular
surfacesareultImatelydestroyed.
5J
ThehandsandwrIstsareInvolvedfIrst,partIcularlythemetacarpophalangealand
InterphalangealjoInts.ThekneeIsInvolvedmostfrequentlyInthelowerextremIty.The
uppercervIcalspIneIsaffectedInnearly80ofpatIentswIthrheumatoIdarthrItIs.
nstabIlItyoftheuppercervIcalspInecanmanIfestasatlantoaxIalInstabIlIty,cranIal
settlIng,andsubaxIalInstabIlIty.PlaInradIographyandCTofthecervIcalspInewIll
demonstratethebonychangescausedbyrheumatoIdarthrItIs.|FIsbettersuItedtostudy
theeffectsofthebonyandsofttIssueschangesonthespInalcord.However,thedegreeof
cordcompressIonmaynotcorrelatewIththepatIent'ssymptoms.Althoughaveryrare
event,spInalcorddamageafterlaryngoscopyandtrachealIntubatIonhasbeenreported.
54
ntraduralcordcompressIonsecondarytorheumatoIdnodulesorpannusformatIoncanalso
occur.FheumatoIdarthrItIscommonlyaffectsthejoIntsofthelarynx,resultIngIn
lImItatIonofvocalcordmovementandgeneralIzederythemaandedemaofthelaryngeal
mucosathatmayprogresstoaIrwayobstructIon.ArthrItIcchangesInthe
temporomandIbularjoIntsalsooccur.AlloftheseabnormalItIescancomplIcate
laryngoscopyandtrachealIntubatIon.
ExtraartIcularandsystemIcmanIfestatIonsofrheumatoIdarthrItIsaredIverse(Table25
12).CardIovasculardIseaseIsacommoncauseofmortalItyInpatIentswIthrheumatoId
arthrItIsandthereIsahIghIncIdenceofsubclInIcalcardIacdysfunctIon.
55
PerIcardItIs
occursInonethIrdofpatIentswIthrheumatoIdarthrItIsandcanproduceconstrIctIve
perIcardItIsorcardIactamponade.DthercardIovascularmanIfestatIonsIncludecoronary
arterydIsease,myocardItIs,pulmonaryhypertensIon,dIastolIcdysfunctIon,dysrhythmIas,
andaortItIs(aortIcrootdIlatIon,aortIcvalveregurgItatIon).PulmonarychangesInclude
pleuraleffusIons,pulmonarynodules,InterstItIallungdIsease,reduceddIffusIoncapacIty,
obstructIvelungdIsease,andrestrIctIvelungdIsease.SeveraloftheantIrheumatIcdrugs
cancauseoraccentuatepulmonarydysfunctIon.FenalfaIlureIsacommoncauseofdeath
InpatIentswIthrheumatoIdarthrItIsandmaybesecondarytovasculItIs,amyloIdosIs,and
antIrheumatIcdrugs.
|IldanemIaIspresentInalmostallpatIentswIthrheumatoIdarthrItIs.TheanemIamaybe
secondarytoadecreaseInerythropoIesIsormaybeasIdeeffectofdrugtherapy.
P.6J7
Table 25-12 Extra-Articular Manifestations of Rheumatoid Arthritis
Skin
Faynaudphenomenon
0IgItalnecrosIs
Eyes
SclerItIs
CornealulceratIon
Lung
PleuraleffusIon
PulmonaryfIbrosIs
Heart
PerIcardItIs
CardIactamponade
CoronaryarterItIs
AortIcInsuffIcIency
Kidney
nterstItIalfIbrosIs
ClomerulonephrItIs
AmyloIddeposItIon
Peripheral Nervous System
CompressIonsyndromes
|ononeurItIs
0uralnodules
NecrotIzIngvasculItIs
Liver
HepatItIs
Blood
AnemIa
LeukopenIa
NeurologIccomplIcatIonsofrheumatoIdarthrItIsIncludeperIpheralnervecompressIon
(carpaltunnelsyndrome)andcervIcalnerverootcompressIon.|ononeurItIsmultIplexIs
presumedtobecausedbydeposItIonofImmunecomplexesInbloodvesselssupplyIngthe
affectednerves.FheumatoIdvasculItIsmayaffectcerebralbloodvessels,producInga
cerebralnecrotIzIngvasculItIs.
ThereIsnocureforrheumatoIdarthrItIs.ThedIseaseprocessofImmunoInflammatIonthat
causesrheumatoIdarthrItIsIsextremelycomplexandmonotherapyIsunlIkelytobe
completelysuccessful.ThegoalsoftherapyareInductIonofaremIssIon,Improved
functIon,andmaIntenanceofaremIssIon.Therearethreegroupsofdrugsusedfor
treatment:NSA0s,cortIcosteroIds,anddIseasemodIfyIngantIrheumatIcdrugs(0|AF0s).
8ecauseNSA0sdonotaffectthecourseofthedIsease,theyareusedInconjunctIonwIth
0|AF0s.CortIcosteroIdsareeffectIvebutthesIdeeffectsassocIatedwIthlongterm
treatmentlImIttheIrusefulness.0|AF0sarenowthefIrstlIneoftherapyfortheearly
treatmentofrheumatoIdarthrItIs.|ethotrexatehasproventobeveryeffectIveandIs
oftentheInItIaldrugofchoIce.DtherlesscommonlyusedsynthetIc0|AF0sInclude
leflunomIde,cyclosporIne,azathIoprIne,gold,sulfasalazIne,mInocyclIne,and
hydroxychloroquIne.8IologIc0|AF0sthatInhIbIttumornecrosIsfactorInclude
InflIxImab,etanercept,andadalImumab.AnakInraInhIbItsInterleukIn1andtocIlIzumab
InhIbItsInterleukIn6.AbataceptIsacytotoxIcTlymphocyteImmunoglobulInandrItuxImab
IsamonoclonalantIbodydIrectedatantIgenson8lymphocytes.TheprImarysIdeeffectof
bIologIc0|AF0sIsanIncreasedsusceptIbIlItytoInfectIon.
56
|ostofthedrugsusedforthe
treatmentofrheumatoIdarthrItIshavesIgnIfIcantsIdeeffectsthatmaylImIttheIr
usefulness(Table251J).SurgIcalproceduressuchassynovectomy,tenolysIs,andjoInt
replacementareperformedtorelIevepaInandrestorejoIntfunctIon.
8ecauserheumatoIdarthrItIsIsamultIsystemdIseaseandtheclInIcalmanIfestatIonsare
sodIverse,IndIvIdualIzedpreoperatIveevaluatIonIsImportantIntheIdentIfIcatIonof
systemIceffects.
ThejoInteffectsIncludIngarthrItIcchangesInthetemporomandIbularjoInts,
crIcoarytenoIdjoInts,andcervIcalspInecanrenderrIgId,dIrectlaryngoscopyandtracheal
IntubatIondIffIcult.ThemobIlItyofthesejoIntsshouldbeevaluatedbeforesurgerysothat
aplanforaIrwaymanagementcanbeformulated.fatlantoaxIalInstabIlItyexIsts,flexIon
oftheneckmaycompressthespInalcord.NeckpaInradIatIngtotheoccIputmaybethe
fIrstsIgnofcervIcalspIneInvolvement.PatIentswIthsymptomsorevIdenceofcervIcal
cordcompressIoncanbefIttedwIthacervIcalcollarpreoperatIvelytomInImIzetherIskof
overmanIpulatIonoftheneckdurIngsurgery.|anypatIentswIthrheumatoIdarthrItIs,
however,areasymptomatIcwIthrespecttocervIcalspInedIsease(FIg.255).PreoperatIve
ImagIng(radIography,CT,|F)maybeIndIcatedIfthedegreeofcervIcalInvolvementIs
unknown.AlthoughtherehavebeennodocumentedreportsofspInalcorddamageIn
patIentswIthrheumatoIdarthrItIsundergoIngtrachealIntubatIonforelectIvesurgery,
allegedneurologIcdamageafterlaryngoscopyhasbeenthesourceoflItIgatIonagaInst
anesthesIologIsts.ftrachealIntubatIonIsrequIred,awake,fIberoptIcassIstedtracheal
IntubatIonmaybethebestwaytomInImIzetherIskofneurologIcdamageInpatIentswIth
sIgnIfIcantcervIcalspIneInvolvement.CrIcoarytenoIdarthrItIsproduceserythemaand
edemaofthevocalcordsandmayreducethesIzeoftheglottIcInlet,necessItatIngtheuse
ofasmallerthanpredIctedtrachealtube.
ThedegreeofcardIopulmonaryInvolvementbytherheumatoIdprocessInfluencesthe
selectIonofthetypeofanesthesIa.PreoperatIveevaluatIonoftheheartandlungsIs
necessaryIftheclInIcalhIstorysuggestsdysfunctIon.TheneedforpostoperatIve
ventIlatorysupportshouldbeantIcIpatedIfseverepulmonarydIseaseIspresent.
|edIcatIonsthatthepatIentIsreceIvIngcanInfluencethemanagementofanesthesIa.
CortIcosteroIdsupplementatIonmaybenecessarydurIngtheperIoperatIveperIod.AspIrIn
andotherantIInflammatorydrugsInterferewIthplateletfunctIonandclottIngmaybe
abnormal.|anyrheumatoIdmedIcatIonssuppressredbloodcellformatIon,andanemIaIs
common.0rugInducedhepatIcandrenaldysfunctIonmaybepresent.
P.6J8
Table 25-13 Adverse Effects of Drugs Used to Treat Collagen Vascular
Diseases
CLASS OF DRUGS EFFECTS
Immunosuppressants
|ethotrexate HepatotoxIcIty,anemIa,leucopenIa
AzathIoprIne 8IlIarystasIs,leucopenIa
CyclosporIne FenaldysfunctIon,hypertensIonhypomagnesemIa
CyclophosphamIde
LeukopenIa,hemorrhagIccystItIs,InhIbItIonof
pseudocholInesterase
LeflunomIde HepatotoxIcIty,weIghtloss,hypertensIon
|ycophenolate
mofetIl
Nausea,vomItIng,dIarrhea
TNF Antagonists
Etanercept nfectIons,tuberculosIs
nflIxImab Lymphoma,heartfaIlure
AdalImumab
Interleukin-1 Antagonists
AnakInra nfectIon,skInIrrItatIon
T-Cell Inhibitors
Abatacept nfectIon
Interleukin-6 Antagonists
TocIlIzumab nfectIon,headache,stomatItIs,fever
CD20 Monoclonal Antibody
FItuxImab nfectIon,InfusIonreactIon
Corticosteroids
HypertensIon,fluIdretentIon,osteoporosIs,InfectIon,
glucoseIntolerance
Aspirin PlateletdysfunctIon,peptIculcer,hypersensItIvIty
NSAIDs PeptIculcer,leukopenIa,coronaryarterydIsease
COX-2 Inhibitors FenaldysfunctIon
Adverse cardiovascular events
Gold AplastIcanemIa,dermatItIs,nephrItIs
Antimalarials |yopathy,retInopathy
Penicillamine ClomerulonephrItIs,myasthenIa,aplastIcanemIa
TNF,tumornecrosIsfactor;NSA0s,nonsteroIdalantIInflammatorydrugs;CDX2,
cyclooxygenase2.
FestrIctIonofjoIntmobIlItynecessItatescarefulposItIonIngofthepatIentdurIngthe
operatIon.TheextremItIesshouldbeposItIonedtomInImIzetherIskofneurovascular
compressIonandfurtherjoIntInjury.PreoperatIveexamInatIonofjoIntmotIonwIllhelp
determInehowtheextremItIesshouldbeposItIoned.
FheumatoIdarthrItIsIsamultIsystemdIsease.JoIntdIsabIlItIeshavebeenwell
documentedInthemedIcallIteratureandareoftenobvIous.|oresIgnIfIcantandless
evIdentaretheeffectsofthespInalcord,heart,lungs,kIdneys,andlIver.Thetypeand
severItyofsystemIcdysfunctIonmustbeconsIderedwhenplannIngananesthetIcfor
patIentswIthrheumatoIdarthrItIs.
57,58
Systemic Lupus Erythematosus
SystemIclupuserythematosus(SLE)IsanautoImmunedIsorderwIthdIverseclInIcaland
ImmunologIcmanIfestatIons.TheetIologyofSLEIsunknown,butappearstobeacomplex
InteractIonbetweengenetIcsusceptIbIlItyandhormonalandenvIronmentalfactors.
PatIentswIthSLEarepredomInantlyfemaleofchIldbearIngageandofAfrIcanandAsIan
ethnIcIty.PatIentswIthSLEproduceautoantIbodIesprImarIlyto0NA,butalsoFNA
polymerase,cardIolIpIn,andrIbosomalphosphoproteIns.thasbeenspeculatedthatcell
apoptosIsreleasesIntracellularproteInsthatgenerateanantIbodyresponseInsusceptIble
patIents.SomeoftheclInIcalmanIfestatIonsofSLEmaybetheresultoftheproductIonof
anautoantIbodyhIghlyspecIfIcforasIngleproteInwIthInanorgan.|anypatIentswIthSLE
havedetectableantI0NAantIbodIes2to9yearsbeforedIagnosIs.
59
TheclInIcalmanIfestatIonsofSLEaredIverse.ThemostcommonpresentIngfeaturesare
polyarthrItIsanddermatItIs.ThearthrItIsIsmIgratoryandanyjoIntcanbeInvolved,
IncludIngthecervIcalspIne.TheclassIcmalarrashIspresentInonlyonethIrdofSLE
patIents.FenaldIseaseIspresentIn50to60ofthepatIentsandIsacommoncauseof
morbIdItyandmortalIty.0IalysIsorrenaltransplantatIonIsrequIredIn10to20ofSLE
patIents.ProteInurIa,hypertensIon,anddecreasedcreatInIneclearancearetheusual
manIfestatIonsoflupusnephrItIs.CNSInvolvementoccursIn50ofthepatIentsandIs
secondarytovasculItIs.CNSmanIfestatIonsIncludeseIzures,stroke,dementIa,psychosIs,
myelItIs,andperIpheralneuropathy.
SLEproducesadIffuseserosItIsthatmanIfestsaspleurItIsandperIcardItIs.Although60of
SLEpatIentshaveperIcardIaleffusIons,cardIactamponadeIsuncommon.nrarecases,
however,tamponademaybethepresentIngsIgnofSLE.AcceleratedarterIosclerosIs,
cardIacconductIonabnormalItIes,andventrIculardysfunctIonareothercardIacfeaturesof
SLE.AnonInfectIousendocardItIs(LIbmanSachsendocardItIs)maycausemItral
regurgItatIon.PulmonarymanIfestatIonsofSLEIncludepleuraleffusIon,pneumonItIs,
pulmonaryhypertensIon,andalveolarhemorrhage.PulmonaryfunctIonstudIestypIcally
demonstratearestrIctIvedIseasepatternanda
P.6J9
decreaseddIffusIngcapacIty.ThereIsahIghIncIdenceofpulmonaryhypertensIonInSLE
patIentswhohaveFaynaudsyndrome.PatIentswIthSLEaresusceptIbletoInfectIonthat
maypresentaspneumonIaoradultrespIratorydIstresssyndrome.CrIcoarytenoIdarthrItIs
canmanIfestashoarseness,strIdor,oraIrwayobstructIon.
NearlyonethIrdofSLEpatIentshasdetectableantIphospholIpIdantIbodIesandmayhave
thromboembolIccomplIcatIons.CastroIntestInalmanIfestatIonsoflupusIncludeperItonItIs,
pancreatItIs,andbowelIschemIa.LupoIdhepatItIsIsanautoImmunehepatItIsthatoccurs
In10ofpatIentswIthSLE.
0espItethedIverseeffectsofSLEandthelackofspecIfIctherapy,currenttreatment
regImenshaveImprovedsurvIval.NSA0sareusedformIldarthrItIs.AntImalarIals
(hydroxychloroquIne)controlarthrItIsanddermatItIsandexertantIthrombotIceffects.
CortIcosteroIdsareeffectIveformoderateandsevereSLE.mmunosuppressantssuchas
cyclophosphamIde,azathIoprIne,methotrexate,cyclosporIne,andmycophenolatemofetIl
areeffectIveandpermItlowerdosagesofcortIcosteroIds.ThepotentIalforsIdeeffects
fromanyofthedrugsIssIgnIfIcantandcancausemorbIdIty.
60
|orethan80drugshavebeenreportedtocausedrugInducedlupus,wIththemost
commonagentsbeIngprocaInamIde,quInIdIne,hydralazIne,methyldopa,enalaprIl,
captoprIl,clonIdIne,IsonIazId,andmInocyclIne.0rugInducedlupusmaybecausedbydrug
metabolItesthatstImulateTcells.TheclInIcalmanIfestatIonsofdrugInducedlupusare
generallymIldandIncludearthralgIa,fever,anemIa,andleukopenIa.Theseeffects
typIcallyresolvewIthInweekstomonthsafterdIscontInuatIonofthedrug.
CarefulpreoperatIveevaluatIonofthepatIentwIthSLEIsnecessarybecauseofthedIverse
systemIceffectsofthedIsease.PreoperatIvechestradIography,echocardIography,or
pulmonaryfunctIontestIngmaybenecessaryIftheclInIcalhIstorysuggests
cardIopulmonarydysfunctIon.AlthoughtherearenospecIfIccontraIndIcatIonstoa
partIculartypeofanesthetIc,myocardIaldysfunctIonwIllcertaInlyInfluencethechoIceof
anesthetIcandthetypeofIntraoperatIvemonItors.8ecauserenaldysfunctIonIsso
common,renalfunctIonshouldbequantIfIedIfthereIsasuggestIonofarecentchangeIn
renalfunctIon.AlthoughmInorabnormalItIesInhepatIcfunctIonareoftenpresent,these
changesareusuallynotsIgnIfIcant.PatIentswIthSLEareatIncreasedrIskfor
postoperatIveInfectIons.
ArthrItIcInvolvementofthecervIcalspIneIsunusualInpatIentswIthSLEandtracheal
IntubatIonIsgenerallynotdIffIcult.However,thepotentIalforlaryngealInvolvementand
upperaIrwayobstructIondoesrequIreclInIcalevaluatIonoflaryngealfunctIon.Should
postextubatIonlaryngealedemaorstrIdoroccur,IntravenousadmInIstratIonof
cortIcosteroIdsIseffectIveforallevIatIonofsymptoms.
0rugsusedforthetreatmentofSLEmayInfluencethechoIceofdrugs.PatIentsreceIvIng
cortIcosteroIdswIllusuallyrequIrecortIcosteroIdreplacementdurIngtheperIoperatIve
perIod.CyclophosphamIdeInhIbItsplasmacholInesteraseandmayprolongtheresponseto
succInylcholIne.
Scleroderma
SclerodermaresultsInexcessIvefIbrosIsIntheskInandInternalorgans.EndothelIalcell
actIvatIongIvesrIsetoInflammatIonandIncreasedImmunecellactIvItywIthactIvatIonof
Tcellsand8lymphocytes.TheendothelIalcellsappeartobedefIcIentInIntrInsIc
vasodIlatorswhIlehavIngIncreasedlevelsofthepotentvasoconstrIctorendothelIn1.ThIs
processcausesInflammatIonandoblIteratIonofsmallarterIesandarterIolesand
ultImatelyfIbrosIsandatrophyoforgans.AutoantIbodIesarefrequentlypresentandmay
correlatewIthdIseaseactIvIty.
61
ThemanIfestatIonsofsclerodermaaremostevIdentIntheskIn,whIchbecomesthIckened
andswollen.EventuallytheskInbecomesatrophIcandsmallarterIesareoblIterated.The
skInbecomesfIbrotIcandtautandproducessevererestrIctIonofjoIntmobIlIty.Faynaud
phenomenonIspresentIn85ofpatIentswIthsclerodermaandIsoftenthepresentIng
symptom.
ThesamepathologIcprocessthataffectsthevascularsystemoftheskInaffectssmall
bloodvesselsInotherorgans.LungInvolvementoccursIn80to90ofpatIentswIth
sclerodermaandIscharacterIzedbyInterstItIalfIbrosIs,pulmonaryhypertensIon,andan
ImpaIreddIffusIngcapacIty.ThesechangesInconjunctIonwIththeeffectsofchronIc
aspIratIonpneumonItIsproducearestrIctIvelungdIsease.|yocardIalfIbrosIsoccursIn70
to80ofpatIentswIthscleroderma,althoughonly25haveclInIcalsymptoms.
EchocardIographymayrevealadecreasedejectIonfractIonandImpaIredleftventrIcular
fIllIng.0egeneratIonofthecardIacconductIontIssuemaycauseconductIondefectsand
cardIacdysrhythmIas.PerIcardItIswItheffusIonIsverycommon.
FenaldysfunctIonIsrelatIvelycommonandIssecondarytopathologIcchangesIntherenal
vasculaturesImIlartothechangesInthedIgItalarterIesthatproduceFaynaud
phenomenon.FenaldysfunctIoncanbesoseverethatasclerodermarenalcrIsIsdevelops
wIthhypertensIon,retInopathy,andarapIddeterIoratIonInrenalfunctIon.
CastroIntestInalmotIlItyIsdecreasedandIsverypronouncedIntheesophagus.The
frequentepIsodesofgastroesophagealrefluxandaspIratIonpneumonItIsexacerbate
pulmonarydysfunctIon.nvolvementofthecolonandsmallIntestInemayresultInpseudo
obstructIon.
TherapyhasbeendIrectedatanumberofpathways.CortIcosteroIdsarebenefIcIal,butthe
lIkelIhoodofsIdeeffectsIsgreat.CyclophosphamIdeIstheImmunosuppressantwIththe
greatesteffect.7asodIlatorssuchascalcIumchannelblockers,ACEInhIbItors,and
prostacyclInsareoftenusedforthetreatmentofcardIacdysfunctIon,pulmonary
hypertensIon,andFaynaudphenomenon.StatInsmaybeeffectIvebyvIrtueoftheIr
endothelIalprotectIveeffectsandantIInflammatoryeffects.TheendothelInAreceptor
antagonIstsambrIsentanandsItaxsentanarecurrentlyunderInvestIgatIon.
Scleroderma,lIkeothercollagenvasculardIseases,IsamultIsystemdIseasewIthmany
systemIcmanIfestatIons.TherearenospecIfIccontraIndIcatIonstotheuseofanytypeof
anesthesIa,althoughtheselectIonmustbeguIdedbyIdentIfIcatIonoforgandysfunctIon.
TrachealIntubatIoncanbequItedIffIcult.FIbrotIcandtautfacIalskIncanmarkedlyhInder
actIveandpassIvemotIonofthetemporomandIbularjoInt.Awake,fIberoptIcassIsted
laryngoscopymayberequIred;tracheostomymaybenecessaryInseverelyaffected
patIents.DrotrachealIntubatIonIspreferredasthefragIlItyofthenasalmucosaIncreases
therIskofseverenasalhemorrhageformnasotrachealIntubatIon.
ThepatIentwIthsclerodermaIsatrIskforaspIratIonpneumonItIsdurIngtheInductIonof
anesthesIabecauseofthehIghIncIdenceofesophagealdysmotIlItyandgastroesophageal
reflux.
ChronIcarterIalhypoxemIaIsoftenpresentbecauseofrestrIctIonoflungexpansIonand
ImpaIredoxygendIffusIon.CompromIsedmyocardIalfunctIonanddecreasedcoronary
vascularreserveoftennecessItatetheuseofInvasIvecardIovascularmonItorsbecausethe
responsetoInhaledanesthetIcsmaybeexaggerated.TransesophagealechocardIography
canprovIdevaluableInformatIonaboutcardIacfunctIon,althoughpassageoftheprobe
maybedIffIcultbecauseofesophagealstrIcture.7enousaccesscanbedIffIcultanda
P.640
venouscutdownorcentralvenouscatheterIzatIonmayberequIred.|yopathywIth
subsequentmuscleweaknessIspresentInmostpatIentswIthsclerodermaandIncreased
sensItIvItytomusclerelaxantsshouldbeantIcIpated.
FegIonalanesthesIamaybeadmInIsteredtopatIentswIthscleroderma,althoughthe
responsetolocalanesthetIcsmaybeprolonged.TheanesthesIologIstIsoftenconsultedas
totheeffIcacyofsympathetIcblockadeforthetreatmentofvasospasmsecondaryto
Faynaudphenomenon.
Polymyositis/Dermatomyositis (Inflammatory Myopathies)
ThreedIseasescomprIsetheInflammatorymyopathIes:polymyosItIs,dermatomyosItIs,and
InclusIonbodymyosItIs.AlthoughtheclInIcalfeaturesofthethreedIseasesaredIverse,
severemuscleweaknessandnonInfectIousmuscleInflammatIonarepresentInallthree.
0ermatomyosItIsIstheresultofanantIbodyInducedcomplementactIvatIonthatlyses
musclecapIllarIesandcausesmusclenecrosIs.|usclefIbernecrosIsInpolymyosItIsand
InclusIonbodymyosItIsIscausedbycytotoxIcTcells.
62
CommonpresentIngsymptomsofpolymyosItIsaremusclepaIn,tenderness,andproxImal
muscleweakness.PatIentswIthdermatomyosItIshaveacharacterIstIcskInrashthatoften
precedestheonsetofweakness.TheskInrashIscharacterIzedbyapurplIshdIscoloratIon
oftheeyelIds(helIotroperash),perIorbItaledema,erythematouslesIonsontheknuckles,
andaphotosensItIverashontheface,neck,andchest.nclusIonbodymyosItIspresents
wIthweaknessofthequadrIcepsandankledorsIflexorsInmen50yearsofage.FIfty
percentofpatIentswIthpolymyosItIsanddermatomyosItIshaveevIdenceofpulmonary
dIsease.PulmonarymanIfestatIonsIncludeInterstItIalpneumonItIs,alveolItIs,and
bronchopneumonIa.AspIratIonpneumonItIsIsverycommonInpatIentswIthpolymyosItIs.
ntrInsIclungdIseaseandthoracIcmuscleweaknessproducearestrIctIvepulmonary
patternandadecreaseddIffusIoncapacIty.|yocardIalfIbrosIscanresultIncongestIve
heartfaIlureandcardIacdysrhythmIas.PatIentswIthpolymyosItIsanddermatomyosItIsare
atIncreasedrIsktodevelopcancerandcarefulscreenIngIsIndIcated.
ThemosteffectIvetreatmentfortheInflammatorymyopathIesIscortIcosteroIds
(prednIsone).mmunosuppressantssuchasmethotrexate,azathIoprIne,cyclophosphamIde,
cyclosporIne,andmycophenolatemofetIlarealsoeffectIve.ntravenousImmunoglobulIn
hasbeenshowntobeeffectIveInpatIentsresIstanttocortIcosteroIds.|onoclonal
antIbodIessuchasInflIxImab,etanercept,andrItuxImabarecurrentlyunder
InvestIgatIon.
6J
|obIlItyofthetemporomandIbularjoIntsandcervIcalspIneIsusuallyadequateInpatIents
wIthpolymyosItIs.SomepatIents,however,haverestrIctedmobIlItythatcanmakedIrect
laryngoscopydIffIcult.Awake,fIberoptIcassIstedtrachealIntubatIonmayberequIredfor
thosepatIentswIthrestrIctedneckmobIlItyandInadequatemouthopenIng.
0ysphagIaandgastroesophagealrefluxareverycommonandthereIsanIncreased
lIkelIhoodofaspIratIonpneumonItIs.CastroIntestInalperforatIonsthatnecessItatesurgIcal
InterventIonarerelatIvelycommonInpatIentswIthpolymyosItIs.
AlthoughtheelectromyographIcchangesofpolymyosItIssuggestthepotentIalfor
hyperkalemIaaftersuccInylcholIne,IthasbeenadmInIsteredtopatIentswIthpolymyosItIs
wIthoutcomplIcatIon.
64
Prolongedneuromuscularblockademayoccurafterthe
admInIstratIonofnondepolarIzIngmusclerelaxants.ThIsprolongedresponsemaybe
secondarytothemyopathyoranInteractIonbetweenthemusclerelaxantand
Immunosuppressants.ThereportedexperIencewIthanesthesIaforpatIentswIth
InflammatorymyopathIesIsverylImItedandgeneralIzatIonsfromafewcasereportsmust
beInterpretedwIthcautIon.tshouldbeantIcIpatedthatconsIderablevarIatIonIn
responsetomusclerelaxantswIlloccur.tmaybeprudenttoavoIdtheadmInIstratIonof
succInylcholIneandtouseshortactIngmusclerelaxants.8ecauseofthepreoperatIve
muscleweakness,postoperatIvemechanIcalventIlatIonmaybenecessary.
ThedegreeofcardIopulmonarydysfunctIonInfluencesthechoIceofanesthetIcsand
IntraoperatIvemonItors.ThecardIacdysfunctIonmaybesubclInIcalandpreoperatIve
echocardIographymaybenecessarytoquantIfycardIacfunctIon.
Skin Disorders
|ostprImarydIseasesoftheskInarelocalIzedandcausefewsystemIceffectsor
complIcatIonsdurIngtheadmInIstratIonofanesthesIa.TwoblIsterIngskIndIsorderscan
resultIncomplIcatIonsdurIngtheperIoperatIveperIod:epIdermolysIsbullosaand
pemphIgus.
Epidermolysis Bullosa
EpIdermolysIsbullosaIsarareskIndIseasethatcanbeInherItedoracquIred.PatIentswIth
herItableformshaveabnormalItIesIntheanchorIngsystemsofskInlayers.TheacquIred
formsareautoImmunedIsordersInwhIchautoantIbodIesareproducedthatdestroythe
basementmembraneoftheskInandmucosa.TheendresultIsthelossorabsenceof
normalIntercellularbrIdgesandseparatIonofskInlayers,IntradermalfluIdaccumulatIon,
andbullaeformatIon(FIg.256).LateralshearIngforcesapplIedtotheskInareespecIally
damagIng.PressureapplIedperpendIculartotheskInIsnotashazardous.Althoughdefects
In10dIfferentgeneshavebeendIscoveredandthereareoverJ0subtypesofepIdermolysIs
bullosa,thesedIsorderscanbecategorIzedIntoJgroupsdependIngonwheretheactual
skInseparatIonoccurs:epIdermolysIssImplex,junctIonalepIdermolysIs,andepIdermolysIs
bullosadystrophIca.AlthoughserIouscomplIcatIonsfromskInandmucosallosscanoccur
wIthanyformofepIdermolysIs,thesImplexformIsgenerallybenIgn.Therearetwoforms
ofjunctIonalepIdermolysIs(JE8):HerlItztype(HJE8)andnonHerlItz(NHJE8).HJE8Is
lethalby1yearofageandoftenhaslaryngealInvolvement.
65
EpIdermolysIsbullosadystrophIca(0E8)IscausedbyadefectIntype7collagen.0E8
producesseverescarrIngofthefIngersandtoeswIthpseudosyndactylyformatIonand
ankylosIsoftheInterphalangealjoIntsandresorptIonofthemetacarpalsandmetatarsals
(FIg.257).SecondaryInfectIonofbullaeandmalIgnantdegeneratIonoftheskInare
common.nvolvementoftheesophagusIspresentInmostpatIents,resultIngIndysphagIa
andesophagealstrIcturesthatcontrIbutetopoornutrItIon.0IlatedcardIomyopathywItha
markedlydecreasedejectIonfractIonandformatIonofIntracardIacthrombIcandevelopIn
patIentswIth0E8andserIalechocardIographymaybeIndIcated.
66
ClomerulonephrItIsmay
besecondarytostreptococcalInfectIon.HypoalbumInemIa,secondarytonephrItIs,proteIn
lossIntobullae,andpoornutrItIonIsusual.AnemIaIsusuallypresentasaresultofpoor
nutrItIonandrepeatedInfectIons.HypoplasIaoftoothenamelresultsIncarIous
degeneratIonoftheteethandtheneedforextensIvedentalrestoratIons.PatIentswIth
0E8rarelysurvIvebeyondthethIrddecade.
|edIcaltherapyfor0E8hasnotbeenverysuccessful.CortIcosteroIdsarenoteffectIve.
PhenytoIn,acollagenaseInhIbItor,mayproduceshorttermImprovement.SkIn
transplantatIonwIthgenetIcallymodIfIedsheetsofepIdermalcells
P.641
IsunderInvestIgatIonandmaybeeffectIveforsomeformsofepIdermolysIs.SurgIcal
therapyIsdIrectedatpreservatIonandImprovementofhandfunctIon.
Figure 25-6.TheultrastructureofthezonesoftheskIn.ThedIagramdemonstrates
whereskInseparatIonoccursIndIfferenttypesofepIdermolysIsbullosa(E8).
(FeproducedfromUIttoJ,ChrIstIanoA|:|oleculargenetIcsofthecutaneous
basementmembranezone.JClInnvest1992;90:687692,wIthpermIssIon.)
tIscrItIcalthattraumatotheskInandmucousmembranesbeavoIdedormInImIzed
durIngtheIntraoperatIveperIod.CelpadscanbeusedforECCelectrodes.Theblood
pressurecuffshouldbewellpaddedwIthloosecottondressIng,andIntravascularcatheters
shouldbeanchoredwIthsuturesoragauzedressIngratherthantape.Traumafromaface
maskcanbemInImIzedbylubrIcatIonofthemaskandthepatIent'sface.Theuseofupper
aIrwayInstruments,IncludIngoropharyngealandnasopharyngealaIrways,shouldbekeptto
amInImumbecausethesquamouscellepIthelIallInIngoftheoropharynxandesophagusIs
susceptIbletobullousformatIon.FrIctIonaltraumatotheoropharynxcanresultInthe
formatIonoflargeIntraoralbullae,aIrwayobstructIon,andextensIvehemorrhagefrom
denudedmucosa.ForsImIlarreasons,InsertIonofanesophagealstethoscopeshouldbe
avoIded.LaryngealInvolvementIsrareInpatIentswIth0E8.ftrachealIntubatIonIs
requIred,thelaryngoscopeandtrachealtubeshouldbewelllubrIcatedtoreducefrIctIon
agaInsttheoropharyngealmucosa.ScarrIngoftheoralcavItycancausemIcrostomIaand
ImmobIlItyofthetonguethatIncreasesthedIffIcultyoftrachealIntubatIon.FIberoptIc
assIstedtrachealIntubatIonmayberequIred.AlthoughtrachealIntubatIonIsgenerallysafe
forpatIentswIth0E8,sImIlarsafetyhasnotbeenestablIshedforpatIentswIthJE8.JE8
affectsallmucosa,IncludIngtherespIratoryepIthelIum.ThetypesofsurgIcalprocedures
P.642
(IntraabdomInal)requIredInInfantswIthJE8,however,usuallymandatetracheal
IntubatIon.
Figure 25-7.EpIdermolysIsbullosa.A.8ullouslesIonofthefIngerInaneonatewIth
epIdermolysIs.B.HandsofanolderchIldwIthepIdermolysIsprogressIontoproduce
severescarrIngandpseudosyndactyly.(CourtesyofJamesE.8ennett,|0,0IvIsIonof
PlastIcSurgery,ndIanaUnIversItySchoolof|edIcIne,ndIanapolIs,N.)
SurgIcalproceduresforpatIentswIth0E8areusuallyperIpheralandInvolvethehands.
KetamIneIsveryusefulforsuchproceduresbecauseItprovIdesgoodanalgesIaanddoes
notgenerallyrequIresupplementalInhaledanesthesIa.However,thereareno
contraIndIcatIonstoInhaledanesthetIcs.FegIonalanesthesIa,IncludIngspInal,epIdural,
andbrachIalplexusanesthesIa,hasbeenusedsuccessfullyforpatIentswIth0E8.
0espIteallthepotentIalcomplIcatIonswIthanesthesIaforpatIentswIthepIdermolysIs,
IntraoperatIvemanagementIsassocIatedwIthsurprIsInglyfewadverseeffects.ThIsIs
especIallytruewhencareIsprovIdedatacenterexperIencedwIththemanagementof
patIentswIthepIdermolysIsbullosa.
67,68
Pemphigus
PemphIgusIsavesIculobullousdIseasethatInvolvesextensIveareasoftheskInandmucous
membranes.PemphIgusIsanautoImmunedIseaseInwhIchgCantIbodIesattackthe
desmosomalproteInsdesmogleInJanddesmogleIn1,leadIngtolossofcelladhesIonand
separatIonofepIthelIallayers.AnumberofdrugshavebeenImplIcatedasthecauseof
pemphIgus,IncludIngpenIcIllamIne,cephalosporIns,ACEInhIbItors,phenobarbItal,
propranolol,levodopa,nIfedIpIne,andNSA0s.
69
AlthoughthereareseveraltypesofpemphIgus,pemphIgusvulgarIsIsthemostcommon
typeandthemostsIgnIfIcantfortheanesthesIologIstbecauseoftheoccurrenceoforal
lesIons.DrallesIonsdevelopIn50to70ofpatIentswIthpemphIgusvulgarIsandmay
precedethecutaneouslesIons.
70
LesIonsofthepharynx,larynx,esophagus,conjunctIva,
urethra,cervIx,andanuscandevelop.ExtensIveoropharyngeallesIonsmaymakeeatIng
paInfultotheextentthatmalnutrItIonoccurs.SkIndenudatIonandbullaeformatIoncan
causesIgnIfIcantfluIdandproteInlossesandtherIskofsecondarybacterIalInfectIonIs
great.AswIthepIdermolysIsbullosa,lateralshearIngforceIsmorelIkelytoproducebullae
thanpressureexertedperpendIculartotheskInsurface.SystemIccortIcosteroIdsarethe
mosteffectIvetherapyforpemphIgusvulgarIs.mprovementmaybeseenwIthIndaysof
cortIcosteroIdtherapy,wIthfullhealIngIn6to8weeks.0apsone,anantIInflammatory
agent,canbeusedInconjunctIonwIthcortIcosteroIdsorasmonotherapy.
mmunosuppressantssuchasmethotrexate,cyclophosphamIde,andmycophenolatemofetIl
canbeusedtoreducecortIcosteroIddosesandsIdeeffects.FItuxImab,anantIC020
monoclonalantIbody,hasalsobeenshowntobeeffectIve.SevereprogressIvepemphIgus
hasalsobeentreatedwIthIntravenousImmuneglobulIn.
71
ParaneoplastIcpemphIgusIsanautoImmunedIseaseassocIatedwIthanumberofmalIgnant
tumors,especIallylymphomasandleukemIas.gCantIbodIesareproducedthatreactto
desmogleInJand1.DralandcutaneouslesIonsoccurInmostpatIents.DbstructIve
respIratoryfaIluremayresultformInflammatIonandsloughIngofthetracheobronchIal
tree.
PreoperatIvedrugtherapyandtheextremefragIlItyofthemucousmembranesarethe
prImaryconcernsformanagementofanesthesIaforpatIentswIthpemphIgus.
CortIcosteroIdsupplementatIonwIllbenecessarydurIngtheperIoperatIveperIodIfthe
patIent'stherapyIncludessteroIds.|anagementoftheaIrwayandtrachealIntubatIon
shouldbeperformedasdescrIbedforpatIentswIthepIdermolysIsbullosa.KetamIneand
regIonalanesthesIahavebeenusedsuccessfullyforpatIentswIthpemphIgus.
72
TherearenospecIfIccontraIndIcatIonstotheuseofanyInhaledorIntravenousanesthetIc.
|ethotrexateproduceshepatorenaldysfunctIonandbonemarrowsuppressIon,and
cyclophosphamIdemayprolongtheactIonofsuccInylcholInebyInhIbItIngcholInesterase
actIvIty.
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Stock, M. Christine
TableofContentsSectIon7PreanesthetIcEvaluatIonandPreparatIonChapter26TheAnesthesIaWorkstatIon
and0elIverySystems
Chapter26
The Anesthesia Workstation and Delivery Systems
Kevin T. Riutort
Russell C. Brockwell
Sorin J. Brull
J. Jeffrey Andrews
Key Points
1. The low-pressure circuit (LPC) is the vulnerable area of the
anesthesia workstation because it is most subject to breakage and
leaks. The LPC is located downstream from all anesthesia machine
safety features except the oxygen analyzer (or, in some cases, the
ratio controller), and it is the portion of the machine where a leak is
most likely to go unrecognized if an inappropriate LPC leak test is
performed. Leaks in the LPC can cause delivery of a hypoxic or
subanesthetic mixture, leading to patient hypoxic injury or
awareness during anesthesia. Hypoxic delivery is typically caused by
a cracked oxygen flow tube that is located downstream to the
nitrous/air/helium tubes. Hypoxic mixtures would not likely occur in
the workstations that have electronically metered fresh gas. Even
with these workstations, however, hypoxic mixtures could be
delivered as the oxygen is consumed from the rest of the breathing
circuit.
2. Because most General Electric (GE) Healthcare/Datex-Ohmeda
anesthesia machines have a one-way check valve in the LPC, a
negative leak test is required to detect leaks in the LPC. A positive
pressure leak test will not detect leaks in the LPC of most GE
Healthcare/Datex-Ohmeda products.
3. Internal vaporizer leaks can be detected only with the vaporizer
turned to the on position.
4. Prior to an anesthetic, the circle system must be checked for leaks
and for flow. To test for leaks, the circle system is pressurized to 30-
cm water pressure and the circle system airway pressure gauge is
observed (static test). To check for appropriate flow to rule out
obstructions and faulty valves, the ventilator and a test lung
(breathing bag) are used (dynamic test). Additionally, the manual
circuit must be actuated by compressing the reservoir bag in order to
rule out obstructions to flow in the manual mode.
P.645
6. Many new anesthesia workstation self-tests do not detect internal
vaporizer leaks unless each vaporizer is individually turned on during
repeated self-tests.
7. In the event of a pipeline crossover, two actions must be taken. The
backup oxygen cylinder must be turned on (because the yoke valve
should always be turned off during normal operation) and the wall
supply sources must be disconnected.
8. The oxygen failure cutoff valves (also known previously as fail-safe
valves, hypoxic guards, or proportioning systems) help minimize
delivery of a hypoxic mixture, but they are not foolproof. Delivery of
a hypoxic mixture may still result from: (1) the wrong supply gas,
either in the cylinder or in the main pipeline; (2) a defective or
broken safety device; (3) leaks downstream from the safety devices;
(4) inert gas administration (for instance, helium may not be subject
to the oxygen failure cutoff valve); and (5) dilution of the inspired
oxygen concentration by high concentrations of inhaled anesthetics.
9. Because of its low boiling point and high vapor pressure, controlled
vaporization of desflurane requires specially designed vaporizers,
such as the GE Healthcare/Datex-Ohmeda Tec 6 and the Aladin
Cassette vaporizer.
10. Misfilling an empty variable bypass vaporizer with desflurane could
theoretically be catastrophic, resulting in delivery of a hypoxic
mixture and a massive overdose of inhaled desflurane anesthetic.
11. Inhaled anesthetics can interact with CO
2
absorbents and produce
toxic compounds. During sevoflurane (only) anesthesia, compound A
can be formed, particularly at low fresh gas flow rates, and during
desflurane, and to a lesser extent sevoflurane anesthesia, carbon
monoxide can be produced, particularly with desiccated absorbents.
12. Desiccated strong base absorbents (particularly barium hydroxide
lime, Baralyme) can react with sevoflurane, producing extremely high
absorber temperatures and combustible decomposition products.
These in combination with the oxygen or nitrous oxide-enriched
environment of the circle system can produce high temperatures and
fires within the breathing system.
13. Anesthesia ventilators with ascending bellows (bellows that ascend
during the expiratory phase) were initially thought to be safer than
descending bellows because disconnections would readily manifest
with ascending bellows. The descending bellows machines, however,
have been carefully redesigned to address these initial limitations.
Current ventilators have featherlight bellows, they have an electric
eye at the bottom to detect bellows movement, and the canister is
subjected to positive end-expiratory pressure (PEEP), such that in
case of disconnection, the bellows would actually rise and stay up.
14. With older-design machines, use of the oxygen flush valve during the
inspiratory phase of mechanical ventilation could cause barotrauma,
particularly in pediatric patients. The newer workstations have fresh
gas decouplers or peak-inspiratory pressure limiters that were
designed to prevent these complications. Ventilators that use fresh
gas decoupling technology virtually eliminate the possibility of
barotrauma by oxygen flushing during the inspiratory phase because
fresh gas flow and oxygen flush flow are diverted to the reservoir
breathing bag. However, if the breathing bag has a large leak or is
absent altogether, patient awareness under anesthesia and delivery
of a lower than expected oxygen concentration could occur because
of entrainment of room air.
15. Modern ventilators compensate for the fresh gas flow as the tidal
volume is delivered. Thus, the delivered tidal volume does not
change as a function of the fresh gas flow. This compensation is
achieved either by fresh gas decoupling (in Drger Narkomed 6000
series, Apollo and Fabius machines) or by fresh gas compensation
in GE Healthcare/Datex-Ohmeda machines.
16. With newer GE Healthcare/Datex-Ohmeda anesthetic ventilators such
as the 7100 and 7900 SmartVent, both the patient gas and the drive
gas are scavenged, resulting in substantially increased volumes of
scavenged gas. Thus, the scavenging systems must be set
appropriately high to accommodate the increased volume; otherwise,
undesired PEEP and pollution of the operating room environment
could result.
ThefunctIonoftheanesthesIamachIneIsto(1)extractgasesfromthecentralsupplyand
cylInders,(2)meterthemandloadthemwIthanesthetIcvapors,and(J)delIverthemto
thepatIentforbreathIng.
1
TheanesthesIamachIneIs,conceptually,apumpfordelIverIng
medIcalgasesandInhalatIonagentstothepatIent'slungs.ThIsmachInehasevolvedover
thepast160yearsfromarathersImpleetherInhalertoacomplexdevIceofvalves,
pIstons,vaporIzers,monItors,andelectronIccIrcuItry.
ThepumpInthemodernanesthesIamachIneIseItheramechanIcalventIlatororthe
lungsofthespontaneouslybreathIngpatIent,orperhaps,acombInatIonofthetwo.The
anesthesIapumphasasupplysystem:medIcalgasesfromeItherapIpelInesupplyoragas
canIster,alongsIdevaporIzesdelIverIngInhalatIonagentsthataremIxedwIththemedIcal
gases.TheanesthesIapumpalsohasanexhaustsystem,thewastegasscavengIngsystem,
whIchremovesexcessgasesfromthemachIne'scIrcuIt.ThebreathIngcIrcuItIsaserIesof
hoses,valves,fIlters,swItches,andregulatorsthatInterconnectthesupplysystem,the
patIent,andtheexhaustsystem.
|odernanesthesIamachInes(FIgs.261and262)arenowmoreproperlyreferredtoas
anesthesia workstations.TheanesthesIaworkstatIon,asdefInedbyAST|nternatIonal
(orIgInallyknownastheAmerIcanSocIetyforTestIngand|aterIals),Isasystemfor
admInIsterInganesthetIcstopatIentsconsIstIngoftheanesthesia gas supply device,the
anesthesia ventilator,monitoring devices,andprotection devices.
2
TheprotectIondevIceIs
desIgnedtopreventthepatIentfromhazardousoutputduetoIncorrectdelIveryofenergy
orsubstances,forexample,theadjustablepressurelImItIngvalvepreventsbarotrauma.
nthIschapter,theanesthesIaworkstatIonIsexamInedpIecebypIece.Thenormal
operatIon,functIon,andIntegratIonofmajoranesthesIaworkstatIonsubsystemsare
descrIbed.|oreImportantly,thepotentIalproblemsandhazardsassocIatedwIththe
varIouscomponentsoftheanesthesIadelIverysystem,andtheapproprIatepreoperatIve
checksthatmayhelptodetectandpreventsuchproblems,areIllustrated.
Anesthesia Workstation Standards and Pre-Use Procedures
Afewyearsago,afundamentalknowledgeofthebasIcanesthesIamachInepneumatIcs
wouldhavesuffIcedformostanesthesIaprovIders.Today,adetaIledunderstandIngof
pneumatIcs,electronIcs,andevencomputerscIenceIsnecessarytofully
P.646
understandthecapabIlItIesandcomplexItIesoftheanesthesIaworkstatIon.AlongwIththe
changesInthecomposItIonoftheanesthesIaworkstatIontoIncludemorecomplex
ventIlatIonsystemsandIntegratedmonItorIng,recentlytherehasalsobeenIncreasIng
dIvergencebetweenanesthesIaworkstatIondesIgnsfromdIfferentmanufacturers.n199J,
ajoInteffortbetweentheAmerIcanSocIetyofAnesthesIologIsts(ASA)andtheU.S.Food
and0rugAdmInIstratIon(F0A)producedthe199JF0AAnesthesIaApparatusPreUse
CheckoutFecommendatIons(AppendIxA).ThIspreusechecklIstwasversatIleandcouldbe
applIedtomostcommonlyavaIlableanesthesIamachInesequallywellanddIdnotrequIre
userstovarythepreuseproceduresIgnIfIcantlyfrommachInetomachIne.
Figure 26-1.0rager|edIcalFabIusCSanesthesIaworkstatIon.(Courtesyof0rager
|edIcalAC.)
Figure 26-2.CeneralElectrIcHealthcareAIsysanesthesIaworkstatIon.(CourtesyofCE
Healthcare.)
Today,becauseofIncreasIngfundamentalanesthesIaworkstatIondesIgnvarIatIons,the
199JF0ApreusechecklIstmaynolongerbeapplIcabletomanyanesthesIaworkstatIons.
AnesthesIaprovIdersmustbeawareofthIslImItatIon,andtheorIgInalequIpment
manufacturer'srecommendedpreusechecklIstshouldbefollowed.Someofthenewer
workstatIonsevenhavecomputerassIstedselfteststhatautomatIcallyperformallora
partofthepreusemachInecheckoutprocedure.TheavaIlabIlItyofsuchautomated
checkoutfeaturesfurtheraddstothecomplexItyofconstructIngastandardIzedpreuse
anesthesIamachInechecklIstsuchastheoneusedIntherecentpast.UltImately,the
responsIbIlItyofperformIngadequatepreusetestIngoftheanesthesIaworkstatIonfallsto
theIndIvIdualuser:regardlessoftheleveloftraInIngandthequalItyoftechnIcalsupport,
theanesthesIacareprovIderhastheultImateresponsIbIlItyforproperfunctIonofall
anesthesIaequIpment.TheanesthesIaprovIderofrecordmustbeawareofwhIch
anesthesIaworkstatIoncomponentsaretestedbytheautomatedselftestsandwhIchones
arenot.8ecauseofthenumberofmachInesavaIlableandthevarIabIlItyamongtheIrself
testIngprocedures,thefollowIngdIscussIonwIllbelImItedtogeneraltopIcsrelatedto
thesesystems.
Standards for Anesthesia Machines and Workstations
StandardsforanesthesIamachInesandworkstatIonsprovIdeguIdelInestomanufacturers
regardIngtheIrmInImumperformance,desIgncharacterIstIcs,andsafetyrequIrements.
0urIngthepast2decades,theprogressIonofanesthesIamachInestandardshasbeenas
follows:
1979:AmerIcanNatIonalStandardsnstItute,Z79.81979
J
1988:AmerIcanSocIetyforTestIngand|aterIals,F116188
4
1994:AST|F116194(reapprovedIn1994anddIscontInuedIn2000)
5
2005:nternatIonalElectrIcalCommIssIon(EC),606011
6
2005:AST|F185000(reapproved)
2
P.647
TheAST|F185000specIfIcatIonapplIestoworkstatIondesIgnInconjunctIonwIththeEC
publIcatIon606011.ECpublIcatIon606011IsanumbrellaspecIfIcatIonthatdescrIbes
generalrequIrementsforbasIcsafetyandessentIalperformanceofmedIcalelectrIcal
equIpment.TocomplywIththe2005AST|F185000standard,newlymanufactured
workstatIonsmusthavemonItorsthatmeasurethefollowIngparameters:contInuous
breathIngsystempressure,exhaledtIdalvolume,ventIlatoryCD
2
concentratIon,anesthetIc
vaporconcentratIon,InspIredoxygenconcentratIon,oxygensupplypressure,arterIal
hemoglobInoxygensaturatIon,arterIalbloodpressure,andcontInuouselectrocardIogram.
TheanesthesIaworkstatIonmusthaveaprIorItIzedalarmsystemthatgroupsthealarms
IntothreecategorIes:hIgh,medIum,andlow.ThesemonItorsandalarmsmaybeenabled
automatIcallyandmadetofunctIonbyturnIngontheanesthesIaworkstatIon,orthe
monItorsandalarmscanbeenabledmanuallyandmadefunctIonalbyfollowIngapreuse
checklIst.
2
PerhapsjustasImportantasthespecIfIcatIonsfornewanesthesIamachInesand
workstatIonsthatareIntroducedIntoclInIcalcarearethecharacterIstIcsthatrenderolder
machInesobsolete.ThIsIsnotanInconsequentIalIssuebecauseontheonehand,the
fInancIalInvestmentforreplacIngoldermachInesIssIgnIfIcant,whIleontheotherhand,
theImplIcatIonsforpatIentsafetyarehuge.TheCuIdelInesfor0etermInIngAnesthesIa
|achIneDbsolescencedocumentaddressessomeoftheabsoluteaswellasrelatIve
crIterIathatcanhelpInstItutIonsmakeadecIsIononwhenevenotherwIsefunctIonIng
equIpmentshouldbereplaced.
7
Failure of Anesthesia Equipment
An11yearstudyof1,000anesthesIaIncIdentsIntheUnItedKIngdomrevealedthatthe
mostcommonfaIlurewasduetoanequIpmentleak(61/1,000).
8
Theauthorsstatedthe
mostlIkelyunderlyIngcauseofsystemleakswasduetodesIgnweakness;forexample,
pushontapersInbreathIngcIrcuItsthatcaneasIlybecomedIsconnected.PoorequIpment
maIntenanceandsetupwerethesecondmostcommonunderlyIngcausesofequIpment
faIlure.EquIpmentfaIlurefromentrappedcablesmayresultIntheInabIlItytoventIlate
thepatIent(thuswarrantIngcarefulattentIontoorganIzatIonandtIdInessofthe
anesthesIaworkstatIonenvIronmentbytheanesthesIaprovIder).
9
Theauthorsfoundthat
pulseoxImetryalarmwasthemostcommonprIncIpalmonItoralertIngtheanesthesIologIst
toanequIpmentproblem.
narevIewoftheASAClosedClaImsdatabase,Caplanetal.
10
foundthatalthough
claImsrelatedtothemedIcalgasdelIverysystemwererare,whentheyoccurred,they
wereusuallysevere,oftenresultIngIndeathorpermanentbraInInjury.Themostcommon
malfunctIon,Intheauthors'revIew,wasthebreathIngcIrcuIt(J9),followedbyvaporIzers
(21),ventIlators(17),gastanksorgaslInes(11),andtheanesthesIamachIneItself(7).
Safety Features of Newer Anesthesia Workstations
DlderorconventIonalanesthesIamachIneshavedesIgnlImItatIonsthatlImIttheIrsafety.
Forexample,machInessuchasthe0ragerNarkomedserIesandtheNarkomedC(0rager
|edIcal,nc.,Telford,PA)maylackfeaturestopreventbarotraumasdurIngoxygenflush,
lackautomatedcheckout,oftenhavemultIpleexternalconnectIons,mayhavegasdrIven
ventIlatorbellowsthatdonotfullyempty,andallowbreathstackIngaswellasInaccurate
tIdalvolumedelIvery.
11
NewerworkstatIonsIncludIngtheCeneralElectrIc(CE)Healthcare/0atexDhmeda
AestIva/5wIth7900ventIlator(CEHealthcare,|adIson,W),theAnesthesIa0elIveryUnIt
(A0U),andthe0rager|edIcalFabIusCSv1.J,JulIan,andNarkomed6400havedesIgns
thatIncorporateaddItIonalsafetyfeaturessuchasfreshgasflowdecouplIngtoprevent
barotraumadurIngoxygenflush;Integrated,softwaredrIvenselfcheckoutroutInes;
lImItedexternalconnectIons;andelectronIc,pIstondrIvenventIlatorsthatdelIver
accuratetIdalvolumes.
11
Table261summarIzesrelevantsafetyfeaturesofnewer
anesthesIaworkstatIons.
Checkout of the Anesthesia Workstation
AcompleteanesthesIaapparatuscheckoutproceduremustbeperformedeachdayprIorto
thefIrstuseoftheanesthesIaworkstatIon.AnabbrevIatedcheckoutprocedureshouldbe
performedbeforeeachsubsequentcase.The199JF0AAnesthesIaApparatusCheckout
FecommendatIonsreproducedInAppendIxAremaInapplIcabletothemajorItyofolder
anesthesIamachInesInuseworldwIde.
12,1J,14,15,16
n2007theASApublIshedrecommendatIonsforpreanesthesIacheckoutmachInes,takIng
IntoconsIderatIonnewerworkstatIonsthatperformautomatedcheckout.
17
8ecausethe
desIgnofnewerworkstatIonsvarIesconsIderably,nosInglepreuseprocedureIsapplIcable.
Hence,theSubcommItteeofASACommItteeonEquIpmentandFacIlItIesdevelopedIn2007
theFecommendatIonsforPreanesthesIaCheckoutProcedures.TheseguIdelInespresenta
templateforIndIvIdualdepartmentsandpractItIonerstodesIgnpreanesthesIacheckout
proceduresspecIfIctotheIrneedsandequIpment(AppendIx8).Samplecheckout
proceduresarepublIshedontheASAWebsIte
a
andtheyencompassadultaswellas
pedIatrIcequIpmentfrombothmajorequIpmentmanufacturersIntheUnItedStates.
ThethreemostImportantpreoperatIvechecksare:(1)oxygenanalyzercalIbratIon,(2)the
lowpressurecIrcuItleaktest,and(J)thecIrclesystemtest.EachIsdIscussedInthe
followIngsectIons.AddItIonaldetaIlsregardIngthesesystemswIllbepresentedbrIeflyIn
subsequentsectIonsdescrIbIngtheanatomyoftheanesthesIaworkstatIon;foramore
comprehensIverevIew,thereaderIsencouragedtoconsulthIsorherownequIpment
manufacturer'susermanual.ForasImplIfIeddIagramofatwogasanesthesIamachIneand
thecomponentsdescrIbedInthefollowIngdIscussIon,pleaserefertoFIgure26J.A
comprehensIvedIscussIonofFIgure26JcanalsobefoundInAnesthesIaWorkstatIon
PneumatIcs.
Oxygen Analyzer Calibration
TheoxygenanalyzerIsoneofthemostImportantmonItorsontheanesthesIaworkstatIon.
tIstheonlymachInesafetydevIcethatevaluatestheIntegrItyofthelowpressurecIrcuIt
InanongoIngfashIon.DthermachInesafetydevIces,suchastheoxygenfaIlurecutoff
(faIlsafe)valve,theoxygensupplyfaIlurealarm,andtheproportIonIngsystem,areall
upstreamfromtheflowcontrolvalves.TheonlymachInemonItorthatdetectsproblems
downstreamfromtheflowcontrolvalvesIstheoxygenanalyzer.CalIbratIonofthIs
monItorIsdescrIbedInAppendIxA(AnesthesIaApparatusCheckoutFecommendatIons,
199J,Step9).TheactualprocedureforcalIbratIngtheoxygenanalyzerhasremaIned
reasonablysImIlarovertherecentgeneratIonsoftheanesthesIaworkstatIons(CuIdelIne
for0esIgnIngPreanesthesIaCheckoutProcedures,2007,tem10InAppendIx8).Cenerally,
theoxygenconcentratIonsensIng
P.648
P.649
P.650
elementmustbeexposedtoroomaIrforcalIbratIonto21.ThIsmayrequIremanually
settIngadIalonoldermachInes,butonnewerones,ItusuallyInvolvesonlytemporary
removalofthesensor,selectIngandthenconfIrmIngthattheoxygencalIbratIonIstobe
performedfromasetofmenusontheworkstatIon'sdIsplayscreen,andfInallyreInstallIng
thesensor.ThefunctIonofthelowoxygenalarmshouldbeverIfIedbysettIngthealarmto
trIggerabovethecurrentoxygenreadIng.NewerworkstatIonshaveautomatIcoxygen
sensorcalIbratIon.
Table 26-1 Comparison of Anesthesia Workstation Functions
Anesthesia Workstation
Function
Drger
Narkomed AV2+
Ohmeda 7800z
Drger- Narkomed
6400
Drger Julian
Drger Fabius GS
1.3
ncreaseInFCF
Increases7T
Yes Yes No No
Preusesystem
leakageIs
measured
No No Yes Yes
ProxImalleak
compensatIon
No No No No
Leakage
measurement
durIngoperatIon
No No Yes Yes
HosecomplIance
compensatIon
No No Yes Yes
System
complIance
compensatIon
No No Yes Yes
Thereported
exhaled7TIs
adjustedforhose
complIance
No No Yes No
Thefreshgas
InflowIsdIstalto:
Absorber Absorber Absorber |Idabsorber
Thefreshgas
InflowIsproxImal
to:
nspIratory
valve
nspIratory
valve
0ecouplIng
valve
|Idabsorber
AtlowFCF,what
gasfIllsthe
reservoIrbag:
Exhaled Exhaled Scrubbed Exhaled
|echanIsmof7C7
lImIt
|echanIcal |etered 0Isplacement |etered
LImItIngof
pressurecontrol
ventIlatIon
Pressure
lImIted
None
Flow/pressure
lImIted
Flow/pressure
lImIted
FD
2
compensated
forvolatIleagent
No No No No
SynchronIzed
IntermIttent
mechanIcal
ventIlatIon
No No Yes No
Themanufacturer
specIfIedmInImum
7T(mL)
N/A 18 10 50
FCFcontrol
Needle
valve
Needle
valve
Needlevalve
0IgItal
control
FCFmeasurement Flowtubes Flowtubes Flowtubes ElectronIc
8ackupflowtube N/A N/A N/A No
ntegrated
capnography
No No Yes Yes
ntegrated
anesthetIcgas
monItorIng
No No Yes Yes
Effectoflost
oxygenpressureon
FCF
NoFCF NoFCF NoFCF AutoaIron
Sampledgas
returnedtocIrcuIt
No No No No
|echanIcalaIrway
pressuregauge
Yes Yes No No
Absorber
removabledurIng
7C7
No No No No
FoomaIr
entraIneddurInga
cIrcuItleak
No No Yes Yes
FoomaIr
entraInedwIth
InadequateFCF
No No No No
EffectofD
2
flush
durIng7C7
InspIratIon
7T,held
atpressure
lImIt
7T,end
at
pressure
lImIt
None
7T,heldat
pressurelImIt
FaIlsafeIntegrated
wIththeratIo
controller
No No No
Yes,
electronIc
|ethodtofInda
low
pressure/vaporIzer
leak
PosItIve
pressure
NegatIve
pressure
AutomatIc,
vaporIzer
open
AutomatIc,
vaporIzer
open
7entIlatordrIve
gasscavengIng
No No N/A Yes
FCF,freshgasflow;7T,tIdalvolume;7C7,volumecontrolventIlatIon;N/A,notavaIlable.
AdaptedfromDlympIo|A:|odernanesthesIamachInesoffernewsafetyfeatures.APSFNewsletter200J;18:17.
Figure 26-3.0IagramofagenerIctwogasanesthesIamachIne.(|odIfIedfromCheck
Dut,ACuIdeforPreoperatIvenspectIonofanAnesthesIa|achIne.ParkFIdge,L,
AmerIcanSocIetyofAnesthesIologIsts,1987,wIthpermIssIon.)
Low-Pressure Circuit Leak Test
ThelowpressureleaktestcheckstheIntegrItyoftheanesthesIamachInefromtheflow
controlvalvestothecommonoutlet.tevaluatestheportIonofthemachInethatIs
downstreamfromallsafetydevIcesexcepttheoxygenanalyzer.Thecomponentslocated
wIthInthIsareaarepreciselytheonesmostsubjecttobreakageandleaks.LeaksInthe
lowpressure
P.651
cIrcuItcancausehypoxIaorpatIentawareness.
18,19
Flowtubes,themostdelIcate
pneumatIccomponentofthemachIne,cancrackorbreak.AtypIcalthreegasanesthesIa
machInehas16DrIngsInthelowpressurecIrcuIt.LeakscanoccurattheInterface
betweentheglassflowtubesandthemanIfold,andattheDrIngjunctIonsbetweenthe
vaporIzerandItsmanIfold.LoosefIllercapsonvaporIzersareacommonsourceofleaks,
andtheseleakscanleadtodelIveryofsubanesthetIcdosesofInhaledagents,causIng
patIentawarenessdurInggeneralanesthesIa.
18,20
SeveraldIfferentmethodshavebeenusedtocheckthelowpressurecIrcuItforleaks.They
Includetheoxygenflushtest,thecommongasoutletocclusIontest,thetradItIonal
posItIvepressureleaktest,theNorthAmerIcan0ragerposItIvepressureleaktest,the
Dhmeda8000InternalposItIvepressureleaktest,theDhmedanegatIvepressureleaktest,
the199JF0AunIversalnegatIvepressureleaktest,andothers.Dnereasonforthelarge
numberofmethodsIsthattheInternaldesIgnofvarIousmachInesdIffersconsIderably.The
mostnotableexampleIsthatmostCEHealthcare/0atexDhmeda(hereafterreferredtoas
0atexDhmeda)workstatIonshaveacheckvalvenearthecommongasoutlet,whereas
0rager|edIcalworkstatIonsdonot.Thepresenceorabsenceofthecheckvalveprofoundly
InfluenceswhIchpreoperatIvecheckIsIndIcated.
SeveralmIshapshaveresultedfromapplIcatIonofthewrongleaktesttothewrong
machIne.
21,22,2J,24
Therefore,ItIsmandatorytoperformtheapproprIatelowpressureleak
testeachday.TodothIs,ItIsessentIaltounderstandtheexactlocatIonandoperatIng
prIncIplesofthe0atexDhmedacheckvalve.|any0atexDhmedaanesthesIaworkstatIons
haveamachIneoutletcheckvalvelocatedInthelowpressurecIrcuIt(Table261).The
checkvalveIslocateddownstreamfromthevaporIzersandupstreamfromtheoxygen
flushvalve(FIg.26J).tIsopen(FIg.264,left)Intheabsenceofbackpressure.Casflow
fromthemanIfoldmovestherubberflappervalveoffItsseatandallowsgastoproceed
freelytothecommonoutlet.Thevalvecloses(FIg.264,right)whenbackpressureIs
exertedonIt.
1J
8ackpressuresuffIcIenttoclosethecheckvalvemayoccurwIththe
followIngcondItIons:oxygenflushIng,peakbreathIngcIrcuItpressuresgenerateddurIng
posItIvepressureventIlatIon,oruseofaposItIvepressureleaktest.
Figure 26-4.|achIneoutletcheckvalve.SeetextfordetaIls.(Feproducedfrom8owIe
E,HuffmanL|:TheAnesthesIa|achIne:EssentIalsforUnderstandIng.|adIson,
Dhmeda,nc.,a0IvIsIonof8DCHealthCare,1985,wIthpermIssIon.)
CenerallyspeakIng,thelowpressurecIrcuItofanesthesIaworkstatIonswIthoutanoutlet
checkvalvecanbetestedusIngaposItIvepressureleaktest,andmachIneswIthcheck
valvesmustbetestedusInganegatIvepressureleaktest.WhenperformIngaposItIve
pressureleaktest,theoperatorgeneratesposItIvepressureInthelowpressurecIrcuIt
usIngflowfromtheanesthesIamachIneorfromaposItIvepressurebulbtodetectaleak.
WhenperformInganegatIvepressureleaktest,theoperatorcreatesnegatIvepressureIn
thelowpressurecIrcuItusIngasuctIonbulbtodetectleaks.TwodIfferentlowpressure
cIrcuItleaktestsaredescrIbedhere.
Oxygen Flush Positive-Pressure Leak Test
HIstorIcally,olderanesthesIamachInesdIdnothavecheckvalvesInthelowpressure
cIrcuIt.Therefore,ItwascommonpractIcetopressurIzethebreathIngcIrcuItandthelow
pressurecIrcuItwIththeoxygenflushvalvetotestforInternalanesthesIamachIneleaks.
8ecausemanymodern0atexDhmedamachInesnowhavecheckvalvesInthelowpressure
cIrcuIt,applIcatIonofaposItIvepressureleaktesttothesemachInescanbemIsleadIngor
evendangerous(FIg.265).napproprIateuseoftheoxygenflushvalveorthepresenceofa
leakIngflushvalvemayleadtoInadequateevaluatIonofthelowpressurecIrcuItforleaks.
nturn,thIscanleadtheworkstatIonuserIntoafalsesenseofsecurItydespItethe
presenceoflargeleaks.
21,22,2J,25,26
PosItIvepressurefromthebreathIngcIrcuItresultsIn
closureoftheoutletcheckvalve,andthevalueontheaIrwaypressuregaugewIllfaIlto
declIne.ThesystemappearstobetIght,butInactualIty,onlythecIrcuItrydownstream
fromthecheckvalveIsleakfree.
27
Thus,avulnerableareaexIstsfromthecheckvalve
backtotheflowcontrolvalvesbecausethIsareaIsnottestedbyaposItIvepressureleak
test.
Figure 26-5.napproprIateuseoftheoxygenflushvalvetocheckthelowpressure
cIrcuItofanDhmedamachIneequIppedwIthacheckvalve.TheareawIthInthe
rectangleIsnotcheckedbytheInapproprIateuseoftheoxygenflushvalve.The
componentslocatedwIthInthIsareaarepreciselytheonesmostsubjecttobreakage
andleaks.PosItIvepressurewIthInthepatIentcIrcuItclosesthecheckvalve,andthe
valueontheaIrwaypressuregaugedoesnotdeclIne,despIteleaksInthelowpressure
cIrcuIt.
Verifying the Integrity of the Gas Supply Lines Between the
Flowmeters and the Common Gas Outlet
The199JF0AunIversalnegatIvepressureleaktest(AppendIxA,Step5)wasnamed
unIversalbecauseatthattImeItcouldbeusedtocheckallcontemporaryanesthesIa
machInesregardlessofthepresenceorabsenceofcheckvalvesInthelowpressure
cIrcuIt.
14
tremaInseffectIveformanyolderanesthesIaworkstatIons,butmanynewer
machInesarenolongercompatIblewIththIsunIversaltest.Table261descrIbeshow
newerworkstatIonstestforlowpressurecIrcuItandvaporIzerleaks.LeaksInthegas
supplylInesbetweentheflowmetersandthecommongasoutletshouldbecheckeddaIlyor
wheneveravaporIzerIschanged(AppendIx8,tem8).ThemostthoroughtechnIqueIsto
checkeachvaporIzerIndIvIduallybyturnIngItonandthenevaluatIngforleaks.tIs
ImportanttonotethatautomatedcheckoutproceduresmaynotnecessarIlyevaluateleaks
atthevaporIzer,IfthevaporIzerIsnotturnedondurIngtestIng.AddItIonally,vaporIzers
shouldbeadequatelyfIlledandfIllerportsshouldbetIghtlyclosed(AppendIx8,tem7).As
mentIonedprevIously,theASAnowrecommendsthatIndIvIdualInstItutIonsdevelop
InternalguIdelInesspecIfIctotheIrownequIpmentandneeds.
The199JF0AcheckIsbasedonthe0atexDhmedanegatIvepressureleaktest(FIg.266).
tIsperformedusInganegatIvepressureleaktestIngdevIce,whIchIsasImplesuctIon
bulb.ThemachInemasterswItch,theflowcontrolvalves,andvaporIzersareturnedoff.
ThesuctIonbulbIsattachedtothecommonfreshgasoutletandsqueezedrepeatedlyuntIl
ItIsfullycollapsed.ThIsactIoncreatesavacuumInthelowpressurecIrcuItry.The
machIneIsleakfreeIfthehandbulbremaInscollapsedforatleast10seconds.AleakIs
presentIfthebulbreInflatesdurIngthIsperIod.ThetestIsrepeatedwItheachvaporIzer
IndIvIduallyturnedtotheonposItIonbecauseInternalvaporIzerleakscanbedetected
onlywIththevaporIzerturnedon.fthebulbreInflatesIn10seconds,aleakIspresent
somewhereInthelowpressurecIrcuIt.
Evaluation of the Circle System
ThecIrclesystemtests(AppendIx8,tems12and1J)evaluatetheIntegrItyofthecIrcle
breathIngsystem,whIchspansfromthecommongasoutlettotheYpIece(FIg.267).thas
twocomponents:(1)breathing system pressure and leak testingand(2)verification that
gas flows properly through the breathing circuit during both inspiration and exhalation.To
thoroughlycheckthecIrclesystemforleaks,valveIntegrIty,andobstructIon,bothtests
mustbeperformedpreoperatIvely.The2008recommendatIonscallforperformIngthe
breathIngsystemtestandleaktestprIortoeachcase,suchthatpressurecanbedeveloped
InthesystemdurIngmanualandmechanIcalventIlatIon.AutomatedleaktestIngroutInes
areImplementedInmodernworkstatIons;systemcomplIanceIsalsocalculatedandusedto
adjustvolumedelIverydurIngmechanIcalventIlatIon(AppendIx8,tem12).8ecause
pressureandleaktestIngcannotIdentIfyallobstructIonsInthebreathIngcIrcuItorconfIrm
thefunctIonoftheInspIratoryandexpIratoryunIdIrectIonalvalves,atestlungorsecond
reservoIrbagcanbeusedtoconfIrmcIrcuIt
P.652
IntegrIty.However,vIsualInspectIonoftheunIdIrectIonalvalvesshouldbeperformeddaIly
becausesubtledamagetothesevalvesIsverydIffIculttodetermIne.Dlder199JF0A
checkoutprocedurestoIdentIfyvalveIncompetencethatmaynotbevIsuallyobvIouscan
beImplemented,butaretypIcallytoocomplexfordaIlytestIng(AppendIx8,tem1J).
Figure 26-6.Foodand0rugAdmInIstratIonnegatIvepressureleaktest.Left.A
negatIvepressureleaktestIngdevIceIsattacheddIrectlytothemachIneoutlet.
SqueezIngthebulbcreatesavacuumInthelowpressurecIrcuItandopensthecheck
valve.Right.WhenaleakIspresentInthelowpressurecIrcuIt,roomaIrIsentraIned
throughtheleakandthesuctIonbulbInflates.(FeprIntedfromAndrewsJJ:
UnderstandInganesthesIamachInes,1988FevIewCourseLectures.Cleveland,
nternatIonalAnesthesIaFesearchSocIety,1988,p.78,wIthpermIssIon.)
nthe199JF0AAnesthesIaApparatusCheckoutFecommendatIons,aleak testIsperformed
byclosIngthepopoffvalve,occludIngtheYpIece,andpressurIzIngthecIrcuIttoJ0cm
waterpressureusIngtheoxygenflushvalve.ThevalueonthepressuregaugewIllnot
declIneIfthecIrclesystemIsleakfree,butthIsdoesnotassurevalveIntegrIty.Thevalue
onthegaugewIllreadapressureofJ0cmH
2
DevenIftheunIdIrectIonalvalvesarestuck
shutorIfthevalvesareIncompetent.AddItIonally,aflow testcheckstheIntegrItyofthe
unIdIrectIonalvalves,andItdetectsobstructIonInthecIrclesystem.tcanbeperformed
byremovIngtheYpIecefromthecIrclesystemandbreathIngthroughthetwocorrugated
hosesIndIvIdually.Thevalvesshouldbepresent,andtheyshouldmoveapproprIately.The
operatorshouldbeabletoInhalebutnotbeabletoexhalethroughtheInspIratorylImb.
TheoperatorshouldbeabletoexhalebutnotInhalethroughtheexpIratorylImb.Theflow
testcanalsobeperformedbyusIngtheventIlatorandabreathIngbagattachedtotheY
pIeceasdescrIbedInthe199JF0AAnesthesIaApparatusCheckoutFecommendatIons
(AppendIxA,Steps11and12).
14
Figure 26-7.ComponentsofthecIrclesystem.APL,adjustablepressurelImItIng;8,
reservoIrbag;7,ventIlator.(Feproducedfrom8rockwellFC:nhaledanesthetIc
delIverysystems,AnesthesIa,6thedItIIon.EdItedby|Iller:PhIladelphIa,ChurchIll
LIvIngstone,2004,p.295,wIthpermIssIon.)
Workstation Self-Tests
AsmentIonedprevIously,manynewanesthesIaworkstatIonsnowIncorporatetechnology
thatallowsthemachInetoeItherautomatIcallyormanuallywalktheuserthroughaserIes
ofselfteststocheckforfunctIonalItyofelectronIc,mechanIcal,andpneumatIc
components.TestedcomponentscommonlyIncludethegassupplysystem,flowcontrol
valves,thecIrclesystem,ventIlator,andIntegratedvaporIzers.ThecomprehensIvenessof
theseselfdIagnostIctestsvarIesfromonemodelandmanufacturertoanother.fthese
testsaretobeemployed,usersmustbesuretoreadandstrIctlyfollowallmanufacturer
recommendatIons.AlthoughathoroughunderstandIngofwhatthepartIcularworkstatIon's
selftestsIncludeIsveryhelpful,thIsInformatIonIsoftendIffIculttoobtaInandmayvary
greatlybetweendevIces.
DnepartIcularlyImportantpoIntofcautIonwIthselftestsshouldbenotedonsystemswIth
manIfoldmountedvaporIzerssuchasthe0ragerApollo,0ragerFabIusCS,andNarkomed
6000serIes.AmanIfoldmountedvaporIzerdoesnotbecomeapartofananesthesIa
workstatIon'sgasflowstreamuntIlItsconcentratIoncontroldIalIsturnedtotheon
posItIon.Therefore,todetectInternalvaporIzerleaksonthIstypeofasystem,theleak
testportIonoftheselfdIagnostIcmustberepeatedseparatelywItheachIndIvIdual
vaporIzerturnedtotheonposItIon.fthIsprecautIonIsnottaken,largeleaksthatcould
potentIallyresultInpatIentawareness,suchthosefromaloosefIllercaporcrackedfIll
IndIcator,couldgoundetected.
P.65J
Anesthesia Workstation Pneumatics
Anatomy of an Anesthesia Workstation
AsImplIfIeddIagramofagenerIctwogasanesthesIamachIneIsshownInFIgure26J.The
pressureswIthIntheanesthesIaworkstatIoncanbedIvIdedIntothreecIrcuIts:ahIgh
pressure,anIntermedIatepressure,andalowpressurecIrcuIt.Thehigh-pressure circuitIs
confInedtothecylIndersandthecylInderprImarypressureregulators.Foroxygen,the
pressurerangeofthehIghpressurecIrcuItextendsfromahIghof2,200poundspersquare
Inchgauge(psIg)to45psIg,whIchIstheregulatedcylInderpressure.FornItrousoxIdeIn
thehIghpressurecIrcuIt,pressuresrangefromahIghof750psIgInthecylIndertoalowof
45psIg.Theintermediate-pressure circuitbegInsattheregulatedcylIndersupplysourcesat
apressureof45psIgandItIncludesthepIpelInesourcesat50to55psIgandextendstothe
flowcontrolvalves.0ependIngonthemanufacturerandspecIfIcmachInedesIgn,second
stagepressureregulatorsmaybeusedtodecreasethepIpelInesupplypressurestotheflow
controlvalvestoevenlowerpressuressuchas14psIgor26psIgwIthIntheIntermedIate
pressurecIrcuIt.
28,29
FInally,thelow-pressure circuitextendsfromtheflowcontrolvalves
tothecommongasoutlet.Therefore,thelowpressurecIrcuItIncludestheflowtubes,
vaporIzermanIfold,vaporIzers,andtheonewaycheckvalveonmostCE
Healthcare/0atexDhmedamachInes.
29
8othoxygenandnItrousoxIdehavetwosupplysources.TheseconsIstofapIpelInesupply
sourceandacylIndersupplysource.ThepIpelInesupplysourceIstheprImarygassource
fortheanesthesIamachIne.ThehospItalpIpelInesupplysystemprovIdesgasestothe
machIneatapproxImately50psIg,whIchIsthenormalworkIngpressureofmostmachInes.
ThecylIndersupplysourceservesasabackupIfthepIpelInesupplyfaIls,oractsasthe
prImarysupplyIftheanesthesIaworkstatIonIsbeIngusedInalocatIonwIthoutthe
avaIlabIlItyofpIpelInesupplIedgases.AsprevIouslydescrIbed,theoxygencylIndersource
Isregulatedfrom2,200toapproxImately45psIg,andthenItrousoxIdecylIndersourceIs
regulatedfrom745toapproxImately45psIg.
28,29,J0
AsafetydevIcetradItIonallyreferredtoasthefailsafevalve(andcurrentlymore
approprIatelytermedtheoxygen failure cutoff valve)Islocateddownstreamfromthe
nItrousoxIdesupplysource.tservesasanInterfacebetweentheoxygenandnItrousoxIde
supplysources.ThIsvalveshutsoff,orproportIonallydecreases,thesupplyofnItrousoxIde
(andothergases)Iftheoxygensupplypressuredecreases.TomeetAST|standards,
contemporarymachIneshaveanalarmdevIcetomonItortheoxygensupplypressure.A
hIghprIorItyalarmIsactuatedasdeclInIngoxygensupplypressurereachesa
predetermInedthreshold,suchasJ0psIg.
28,29,J0
|anyCEHealthcare/0atexDhmedamachIneshaveasecondstageoxygenregulator
locateddownstreamfromtheoxygensupplysourceIntheIntermedIatepressurecIrcuIt.t
IsadjustedtoaprecIsepressurelevel,suchas14psIg.
28
ThIsregulatorsupplIesaconstant
pressuretotheoxygenflowcontrolvalveregardlessoffluctuatIngoxygenpIpelIne
pressures.Forexample,theflowfromtheoxygenflowcontrolvalvewIllbeconstantIfthe
oxygensupplypressureIs14psIg.
TheflowcontrolvalvesrepresentanImportantanatomIclandmarkwIthIntheanesthesIa
workstatIonbecausetheyseparatetheIntermedIatepressurecIrcuItfromthelowpressure
cIrcuIt.ThelowpressurecIrcuItIsthatpartofthemachInethatlIesdownstreamfromthe
flowcontrolvalves.TheoperatorregulatesflowenterIngthelowpressurecIrcuItby
adjustIngtheflowcontrolvalves.TheoxygenandnItrousoxIdeflowcontrolvalvesare
lInkedmechanIcallyorpneumatIcallybyaproportIonIngsystemtohelpprevent
InadvertentdelIveryofahypoxIcmIxture.AfterleavIngtheflowtubes,themIxtureof
gasestravelsthroughacommonmanIfoldandmaybedIrectedtoacalIbratedvaporIzer.
PrecIseamountsofInhaledanesthetIccanbeadded,dependIngonvaporIzercontroldIal
settIng.ThetotalfreshgasflowplustheanesthetIcvaporthentraveltowardthecommon
gasoutlet.
28,29
|any0atexDhmedaanesthesIamachIneshaveaonewaycheckvalvelocatedbetweenthe
vaporIzersandthecommongasoutletInthemIxedgaspIpelIne.tspurposeIstoprevent
backflowIntothevaporIzerdurIngposItIvepressureventIlatIon,thereforemInImIzIngthe
effectsofdownstreamIntermIttentpressurefluctuatIonsonInhaledanesthetIc
concentratIon(see7aporIzers:ntermIttent8ackPressure).Thepresenceorabsenceof
thIscheckvalveprofoundlyInfluenceswhIchpreoperatIveleaktestIsIndIcated(see
CheckoutoftheAnesthesIaWorkstatIon).TheoxygenflushconnectIonjoInsthemIxed
gaspIpelInebetweentheonewaycheckvalve(whenpresent)andthemachIneoutlet.
Thus,whenoxygenflushvalveIsactIvatedthepIpelIneoxygenpressurehasastraIght
shottothecommongasoutletInmachInesthatdonotusefreshgasdecouplIng
technology.
28,29
Pipeline Supply Source
UndernormalcondItIons,thepIpelInesupplyservesastheprImarygassourceforthe
anesthesIamachIne.|osthospItalstodayhaveacentralpIpIngsystemtodelIvermedIcal
gasessuchasoxygen,nItrousoxIde,andaIrtotheoperatIngroom.ThecentralpIpIng
systemmustsupplythecorrectgasesattheapproprIatepressurefortheanesthesIa
workstatIontofunctIonproperly.Unfortunately,thIsdoesnotalwaysoccur.Evenas
recentlyas2002,largemedIcalcenterswIthhugecryogenIcbulkoxygenstoragesystems
arenotImmunetocomponentfaIluresthatmaycontrIbutetocrItIcaloxygenpIpelIne
supplyfaIlures.
J1
nthe2002case,afaultyjoIntrupturedatthebottomoftheprImary
cryogenIcoxygenstoragetank,releasIng8,000gallonsoflIquIdoxygentofloodthestreets
InthesurroundIngarea.ThIsmIshapsuddenlycompromIsedtheoxygendelIverytoamajor
medIcalcenter.
nasurveyofapproxImately200hospItalsIn1976,J1reporteddIffIcultIeswIthpIpelIne
systems.
J2
ThemostcommonproblemwasInadequateoxygenpressure,followedby
excessIvepIpelInepressures.ThemostdevastatIngreportedhazard,however,was
accIdentalcrossIngofoxygenandnItrousoxIdepIpelInes,whIchhasledtomanydeaths.
ThIsproblemcaused2JdeathsInanewlyconstructedwIngofageneralhospItalIn
Sudbury,DntarIo,durInga5monthperIod.
J2,JJ
|orerecently,In2002,twoaddItIonal
hypoxIcdeathswerereportedInNewHaven,ConnectIcut.TheseresultedfromamedIcal
gassystemfaIlureInwhIchanalteredoxygenflowmeterwasInadvertentlyconnectedtoa
wallsupplysourcefornItrousoxIde.
J4
ntheeventthatapIpelInecrossoverIssuspected,theworkstatIonusermustImmedIately
maketwocorrectIveactIons.FIrst,thebackupoxygencylIndershouldbeturnedon.Then
thepIpelInesupplymustbedIsconnected.ThIssecondstepIsmandatorybecausethe
machInewIllpreferentIallyusethe(potentIally)InapproprIate50psIgpIpelInesupply
sourceInsteadofthelowerpressure(45psIg)oxygencylIndersourceIfthewallsupplyIs
notdIsconnected.
CasenterstheanesthesIamachInethroughthepIpelIneInletconnectIons(FIg.26J,
arrows).ThepIpelIneInletfIttIngsaregasspecIfIc0IameterndexSafetySystemthreaded
bodyfIttIngs.The0IameterndexSafetySystemprovIdesthreaded,nonInterchangeable
connectIonsformedIcalgaslInes,whIchmInImIzetherIskofmIsconnectIon.Acheckvalve
IslocateddownstreamfromtheInlet.tpreventsreverseflowofgasesfromthemachIne
tothepIpelIneortheatmosphere.
P.654
Cylinder Supply Source
AnesthesIaworkstatIonshaveEcylIndersforusewhenapIpelInesupplysourceIsnot
avaIlableorIfthepIpelInesystemfaIls.AnesthesIaprovIderscaneasIlybecome
complacentandfalselyassumethatbackupgascylIndersareInfactpresentonthebackof
theanesthesIaworkstatIon,andfurther,Iftheyarepresent,thattheycontaInanadequate
supplyofcompressedgas.ThepreusechecklIstshouldcontaInstepsthatconfIrmboth.
|edIcalgasessupplIedInEcylIndersareattachedtotheanesthesIamachInevIathe
hangeryokeassembly.ThehangeryokeassemblyorIentsandsupportsthecylInder,
provIdesagastIghtseal,andensuresaunIdIrectIonalflowofgasesIntothemachIne.
29
EachhangeryokeIsequIppedwIththePInndexSafetySystem.ThIssystemIsasafeguard
IntroducedtoelImInatecylInderInterchangIngandthepossIbIlItyofaccIdentallyplacIng
theIncorrectgasonayokedesIgnedtoaccommodateanothergas.TwometalpInsonthe
yokeassemblyarearrangedsothatthattheyprojectIntocorrespondIngholesonthe
cylIndervalve.EachgasorcombInatIonofgaseshasaspecIfIcandunIquepIn
arrangement.
J5
DncethecylIndersareturnedon,compressedgasesmaypassfromtheIrrespectIvehIgh
pressurecylIndersourcesIntotheanesthesIamachIne(FIg.26J).AcheckvalveIslocated
downstreamfromeachcylInderIfadoubleyokeassemblyIsused.ThIscheckvalveserves
severalfunctIons.FIrst,ItmInImIzesgastransferfromacylInderathIghpressuretoone
wIthlowerpressure.Second,ItallowsanemptycylIndertobeexchangedforafullone
whIlegasflowcontInuesfromtheothercylInderIntothemachInewIthmInImallossofgas
orsupplypressure.ThIrd,ItmInImIzesleakagefromanopencylIndertotheatmosphereIf
onecylInderIsabsent.
28,29
AcylIndersupplypressuregaugeIslocateddownstreamfrom
thecheckvalves.ThegaugewIllIndIcatethepressureInthecylInderhavIngthehIgher
pressurewhentworeservecylIndersofthesamegasareopenedatthesametIme.
EachcylIndersupplysourcehasapressurereducIngvalveknownasthecylinder pressure
regulator.treducesthehIghandvarIablestoragepressurepresentInacylIndertoa
lower,moreconstantpressuresuItableforuseIntheanesthesIamachIne.Theoxygen
cylInderpressureregulatorreducestheoxygencylInderpressurefromahIghof2,200psIg
toapproxImately45psIg.ThenItrousoxIdecylInderpressureregulatorreceIvespressureof
upto745psIgandreducesIttoapproxImately45psIg.
28,29
ThegassupplycylIndervalvesshouldbeturnedoffwhennotInuse,exceptdurIngthe
preoperatIvemachInecheckIngperIod.fthecylIndersupplyvalvesarelefton,the
reservecylIndersupplycanbesIlentlydepletedwheneverthepressureInsIdethemachIne
decreasestoavaluelowerthantheregulatedcylInderpressure.Forexample,oxygen
pressurewIthInthemachInecandecreasebelow45psIgwIthoxygenflushIngorpossIbly
evendurIngtheuseofapneumatIcallydrIvenventIlator,partIcularlyathIghInspIratory
flowrates.AddItIonally,thepIpelInesupplypressuresofallgasescanfallto45psIgIf
problemsexIstInthecentralpIpIngsystem.fthecylIndersareleftonwhenthIsoccurs,
theywIlleventuallybecomedepletedandnoreservesupplymaybeavaIlableIfa
completecentralpIpelInefaIlureoccurred.
27,28
TheamountoftImethatananesthesIamachInecanoperatefromtheEcylIndersupplyIs
Importantknowledge,andIspartIcularlyImportantnowthatanesthesIaIsbeIngprovIded
morefrequentlyInoffIcebasedandInremote(outsIdetheoperatIngroom)hospItal
settIngs.Foroxygen,thevolumeofgasremaInIngInthecylInderIsproportIonaltothe
cylInderpressure.DneauthorhasproposedthefollowIngequatIontohelpestImatethe
remaInIngtIme.
J6
tshouldbenotedthatthIscalculatIonwIllprovIdeonlyagrossestImateofremaInIngtIme
andmaynotbeexact.Furthermore,usersshouldbecautIonedthatuseofapneumatIcally
drIvenmechanIcalventIlatorwIlldramatIcallyIncreaseoxygenutIlIzatIonratesand
decreasetheremaInIngtImeuntIlcylInderdepletIon.HandventIlatIngwIthlowfreshgas
flowratesmayconsume5theamountofoxygen,ascomparedwIthIntermedIate
flowmetersettIngscoupledwIththeuseofpneumatIcallypoweredmechanIcal
ventIlatIon.
J1
8ecausepIstontypeanesthesIaventIlatorssuchasfoundInthe0rager
|edIcalFabIusCSandNarkomed6000serIesdonotaffectoxygenconsumptIonrates,they
maybepreferabletoconventIonalgasdrIvenventIlatorsInpractIcesettIngsthatdepend
ontheuseofcompressedgascylIndersastheprImarygassources.
Oxygen Supply Pressure Failure Safety Devices
DxygenandnItrousoxIdesupplysourcesexIstedasIndependententItIesInoldermodelsof
anesthesIamachInes,andtheywerenotpneumatIcallyormechanIcallyInterfaced.
Therefore,abruptorInsIdIousoxygenpressurefaIlurehadthepotentIaltoleadtothe
delIveryofahypoxIcmIxture.The2000AST|F185000standardstatesthat,The
anesthesIagassupplydevIceshallbedesIgnedsothatwheneveroxygensupplypressureIs
reducedtobelowthemanufacturerspecIfIedmInImum,thedelIveredoxygen
concentratIonshallnotdecreasebelow19atthecommongasoutlet.
J7
Contemporary
anesthesIamachIneshaveanumberofsafetydevIcesthatacttogetherInacascade
mannertomInImIzetherIskofdelIveryofahypoxIcgasmIxtureasoxygenpressure
decreases.SeveralofthesedevIcesaredescrIbedInthefollowIngsectIons.
Pneumatic and Electronic Alarm Devices
|anyolderanesthesIamachIneshaveapneumatIcalarmdevIcethatsoundsawarnIng
whentheoxygensupplypressuredecreasestoapredetermInedthresholdvaluesuchasJ0
psIg.The2000AST|F185000standardmandatedthatamedIumprIorItyalarmbe
actIvatedwIthIn5secondswhentheoxygenpressuredecreasesbelowamanufacturer
specIfIcpressurethreshold.
J7
ElectronIcalarmdevIcesarenowusedtomeetthIsguIdelIne.
Oxygen Failure Cut Off (Failsafe) Valves
AnoxygenfaIlurecutoffvalveIspresentInthegaslInesupplyIngeachoftheflowmeters
exceptoxygen.Controlledbyoxygensupplypressure,thevalveshutsoff(orproportIonally
decreases)thesupplypressureofallothergases(e.g.,nItrousoxIde,aIr,CD
2
,helIum,
nItrogen)astheoxygensupplypressuredecreases.Unfortunately,themIsnomerfaIlsafe
hasledtothemIsconceptIonthatthevalvepreventsadmInIstratIonofahypoxIcmIxture.
|achInesthatareeIthernotequIppedwIthaflowproportIonIngsystem(see
ProportIonIngSystems)oroneswhosesystemmaybedIsabledbytheusercandelIvera
hypoxIcmIxtureundernormalworkIngcondItIons.Dnsuchasystem,theoxygenflow
controlvalvecanbeclosedIntentIonallyoraccIdentally.NormaloxygenpressurewIllkeep
othergaslInesopensothatahypoxIcmIxturecanresult.
28,29
|any0atexDhmedamachInesareequIppedwIthafaIlsafevalveknownasthepressure-
sensor shutoff valve(FIg.268).ThIsvalveoperatesInathresholdmannerandIseIther
openor
P.655
closed.Dxygensupplypressureopensthevalve,andthevalvereturnsprIngclosesthe
valve.FIgure268showsanItrousoxIdepressuresensorshutoffvalvewIthathreshold
pressureof20psIg.nFIgure268A,anoxygensupplypressure20psIgIsexertedonthe
mobIledIaphragm.ThIspressuremovesthepIstonandpInupwardandthevalveopens.
NItrousoxIdeflowsfreelytothenItrousoxIdeflowcontrolvalve.nFIgure2688,the
oxygensupplypressureIs20psIg,andtheforceofthevalvereturnsprIngcompletely
closesthevalve.
28
NItrousoxIdeflowstopsattheclosedfaIlsafevalveandItdoesnot
advancetothenItrousoxIdeflowcontrolvalve.
Figure 26-8.Pressuresensorshutoffvalve.ThevalveIsopenInAbecausetheoxygen
supplypressureIsgreaterthanthethresholdvalueof20psIg.ThevalveIsclosedInB
becauseofInadequateoxygenpressure.(Fedrawnfrom8owIeE,HuffmanL|:The
AnesthesIa|achIne:EssentIalsforUnderstandIng.|adIson,W,Dhmeda,a0IvIsIonof
8DCHealthCare,nc,1985,wIthpermIssIon.)
0ragerusesadIfferentfaIlsafevalveknownastheOxygen Failure Protection Device(DFP0)
toInterfacetheoxygenpressurewIththatofothergases,suchasnItrousoxIdeorother
Inertgases.ThIsIsIncontrastto0atexDhmeda'soxygenpressuresensorshutoffvalve
becausetheDFP0IsbasedonaproportIonIngprIncIpleratherthanathresholdprIncIple.
ThepressureofallgasescontrolledbytheDFP0wIlldecreaseproportIonallywIththe
oxygenpressure.TheDFP0consIstsofaseatnozzleassemblyconnectedtoasprIngloaded
pIston(FIg.269).TheoxygensupplypressureIntheleftpanelofFIgure269Is50psIg.ThIs
pressurepushesthepIstonupward,forcIngthenozzleawayfromthevalveseat.NItrous
oxIdeand/orothergasesadvancetowardtheflowcontrolvalveat50psIg.Theoxygen
pressureIntherIghtpanelIszeropsIg.ThesprIngIsexpandedandforcesthenozzle
agaInsttheseat,preventIngflowthroughthedevIce.FInally,thecenterpanelshowsan
IntermedIateoxygenpressureof25psIg.TheforceofthesprIngpartIallyclosesthevalve.
ThenItrousoxIdepressuredelIveredtotheflowcontrolvalveIs25psIg.ThereIsa
contInuumofIntermedIateconfIguratIonsbetweentheextremes(0to50psIg)ofoxygen
supplypressure.TheseIntermedIatevalveconfIguratIonsareresponsIbleforthe
proportIonalnatureoftheDFP0.AnImportantconcepttobeunderstoodwIththese
partIcularfaIlsafedevIcesIsthatthe0atexDhmedaPressureSensorShutoff7alveIs
thresholdInnature(allornothIng),whereasthe0ragerDFP0IsavarIable,flowtype
proportIonIngsystem.
Figure 26-9.DxygenfaIlureprotectIondevIce/sensItIveoxygenratIocontroller
(DFP0/SDFC),whIchrespondsproportIonallytochangesInoxygensupplypressure.
(FedrawnfromNarkomed2AAnesthesIaSystem:TechnIcalServIce|anual,6thed.
Telford,PA,NorthAmerIcan0rager,June1985,wIthpermIssIon.)
Second-Stage Oxygen Pressure Regulator
|ostcontemporary0atexDhmedaworkstatIonshaveasecondstageoxygenpressure
regulatorsetataspecIfIcvalue,rangIngfrom12to19psIg.Dutputfromtheoxygen
flowmeterIsconstantwhentheoxygensupplypressureexceedsthethreshold(mInImal)
value.Thepressuresensorshutoffvalveof0atexDhmedaIssetatahIgherthresholdvalue
(20toJ0psIg)toensurethatoxygenIsthelastgasflowIngIfoxygenpressurefaIlure
occurs.
Flowmeter Assemblies
Theflowmeterassembly(FIg.2610)precIselycontrolsandmeasuresgasflowtothe
commongasoutlet.WIthtradItIonalglassflowmeterassemblIes,theflowcontrolvalve
regulatestheamountofflowthatentersatapered,transparentflowtubeknownasa
Thorpe tube.AmobIleIndIcatorfloatInsIdetheflowtubeIndIcatestheamountofflow
passIngthroughtheassocIatedflowcontrolvalve.ThequantItyofflowIsIndIcatedona
scaleassocIatedwIththeflowtube.
28,29
SomeneweranesthesIa
P.656
workstatIonshavenowreplacedtheconventIonalglassflowtubeswIthelectronIcflow
sensorsthatmeasuretheflowsoftheIndIvIdualgases.Theseflowratedataarethen
presentedIneIthernumerIcalformat,graphIcalformat,oracombInatIonofthetwo.The
IntegratIonoftheseelectronIcflowmetersIsanessentIalstepIntheevolutIonofthe
anesthesIaworkstatIonIfItIstobecomefullyIntegratedwIthanesthesIadatacapturIng
systemssuchascomputerIzedanesthesIarecordkeepers.
Figure 26-10.Dxygenflowmeterassembly.TheoxygenflowmeterassemblyIs
composedoftheflowcontrolvalveassemblyplustheflowmetersubassembly.
(Feproducedfrom8owIeE,HuffmanL|:TheAnesthesIa|achIne:EssentIalsfor
UnderstandIng.|adIson,W,Dhmeda,a0IvIsIonof8DCHealthCare,nc,1985,wIth
permIssIon.)
Operating Principles of Conventional Flowmeters
DpenIngtheflowcontrolvalveallowsgastotravelthroughthespacebetweenthefloat
andtheflowtube.ThIsspaceIsknownastheannular space(FIg.2611).TheIndIcatorfloat
hoversfreelyInanequIlIbrIumposItIonwheretheupwardforceresultIngfromgasflow
equalsthedownwardforceonthefloatresultIngfromgravItyatagIvenflowrate.The
floatmovestoanewequIlIbrIumposItIonInthetubewhenflowIschanged.These
flowmetersarecommonlyreferredtoasconstant pressureflowmetersbecausethe
pressuredecreaseacrossthefloatremaInsconstantforallposItIonsInthetube.
29,J8,J9
Flowtubesaretapered,wIththesmallestdIameteratthebottomofthetubeandthe
largestdIameteratthetop.Thetermvariable orificedesIgnatesthIstypeofunItbecause
theannularspacebetweenthefloatandtheInnerwalloftheflowtubevarIeswIththe
posItIonofthefloat.FlowthroughtheconstrIctIoncreatedbythefloatcanbelamInaror
turbulent,dependIngontheflowrate(FIg.2612).ThecharacterIstIcsofagasthat
InfluenceItsflowratethroughagIvenconstrIctIonarevIscosIty(lamInarflow)anddensIty
(turbulentflow).8ecausetheannularspaceIstubular,atlowflowrateslamInarflowIs
presentandviscositydetermInesthegasflowrate.TheannularspacesImulatesanorIfIce
athIghflowrates,andturbulentgasflowthendependspredomInantlyonthedensityof
thegas.
28,29
Figure 26-11.Theannularspace.Theclearancebetweentheheadofthefloatand
theflowtubeIsknownastheannularspace.tcanbeconsIderedanequIvalenttoa
cIrcularchannelofthesamecrosssectIonalarea.(Fedrawnfrom|acIntoshF,|ushIn
WW,EpsteInHC:PhysIcsfortheAnaesthetIst,JrdedItIon.Dxford,England,8lackwell
ScIentIfIcPublIcatIons,196J,wIthpermIssIon.)
Components of the Flowmeter Assembly
Flow Control Valve Assembly
TheflowcontrolvalveassemblyIscomposedofaflowcontrolknob,aneedlevalve,a
valveseat,andapaIrofvalvestops(FIg.2610).
28
TheassemblycanreceIveItspneumatIc
InputeItherdIrectlyfromthepIpelInesource(50psIg)orfromasecondstagepressure
regulator.ThelocatIonoftheneedlevalveInthevalveseatchangestoestablIshdIfferent
orIfIceswhentheflowcontrolvalveIsadjusted.
P.657
CasflowIncreaseswhentheflowcontrolvalveIsturnedcounterclockwIse,andIt
decreaseswhenthevalveIsturnedclockwIse.ExtremeclockwIserotatIonmayresultIn
damagetotheneedlevalveandvalveseat.Therefore,flowcontrolvalvesareequIpped
wIthvalvestopstopreventthIsoccurrence.
29
Figure 26-12.FlowtubeconstrIctIon.ThelowerpaIrofIllustratIonsrepresentsthe
lowerportIonofaflowtube.Theclearancebetweentheheadofthefloatandthe
flowtubeIsnarrow.TheequIvalentchannelIstubularbecauseItsdIameterIsless
thanItslength.7IscosItyIsdomInantIndetermInInggasflowratethroughthIstubular
constrIctIon.TheupperpaIrofIllustratIonsrepresentstheupperportIonofaflow
tube.TheequIvalentchannelIsorIfIcIal(orIfIcelIke)becauseItslengthIslessthanIts
wIdth.0ensItyIsdomInantIndetermInInggasflowratethroughthIsorIfIcIal
constrIctIon.(Fedrawnfrom|acIntoshF,|ushInWW,EpsteInHC:PhysIcsforthe
AnaesthetIst,JrdedItIon.Dxford,England,8lackwellScIentIfIcPublIcatIons,196J,wIth
permIssIon.)
Safety Features
ContemporaryflowcontrolvalveassemblIeshavenumeroussafetyfeatures.Theoxygen
flowcontrolknobIsphysIcallydIstInguIshablefromothergasknobs.tIsdIstInctIvely
fluted,projectsbeyondthecontrolknobsoftheothergases,andIslargerIndIameterthan
theflowcontrolknobsofothergases.AllknobsarecolorcodedfortheapproprIategas,
andthechemIcalformulaornameofthegasIspermanentlymarkedoneach.Flowcontrol
knobsarerecessedorprotectedwIthashIeldorbarrIertomInImIzeInadvertentchange
fromapresetposItIon.fasInglegashastwoflowtubes,thetubesarearrangedInserIes
andarecontrolledbyasIngleflowcontrolvalve.
J7
nmanyofthenewanesthesIaworkstatIons,theflowmetershavebeenreplacedby
electronIccontrolpanelsthatcontaInsoftkeys.nordertoadjustanygasflow,the
operatormustperformfollowIngsteps:(1)selectandpressthesoftkeytoIdentIfythe
anesthetIcagentselected,(2)turntheselectorknobtoadjustthedesIredflowlevel,and
(J)presstheselectorknobagaIntoconfIrmtheselectedflowlevelandanesthetIcagent
(seeElectronIcFlowmeters).
Flowmeter Subassembly
TheflowmetersubassemblyconsIstsoftheflowtube,theIndIcatorfloatwIthfloatstops,
andtheIndIcatorscale(FIg.2610).
29
Flow Tubes
Contemporaryflowtubesaremadeofglass.|osthaveasIngletaperInwhIchtheInner
dIameteroftheflowtubeIncreasesunIformlyfrombottomtotop.|anufacturersprovIde
doubleflowtubesforoxygenandnItrousoxIdetoprovIdebettervIsualdIscrImInatIonat
lowflowrates.AfIneflowtubeIndIcatesflowfromapproxImately200mL/mInto1L/mIn,
andacoarseflowtubeIndIcatesflowfromapproxImately1L/mInto10to12L/mIn.The
twotubesareconnectedInserIesandsupplIedbyasIngleflowcontrolvalve.Thetotalgas
flowIsthatshownonthehIgherflowmeter.
Indicator Floats and Float Stops
ContemporaryanesthesIamachInesuseseveraldIfferenttypesofbobbInsorfloats,
IncludIngplumbbobfloats,rotatIngskIrtedfloats,andballfloats.FlowIsreadatthetop
ofplumbbobandskIrtedfloatsandatthecenteroftheballontheballtypefloats.
29
Flow
tubesareequIppedwIthfloatstopsatthetopandbottomofthetube.Theupperstop
preventsthefloatfromascendIngtothetopofthetubeandpluggIngtheoutlet.talso
ensuresthatthefloatwIllbevIsIbleatmaxImumflowsInsteadofbeInghIddenInthe
manIfold.ThebottomfloatstopprovIdesacentralfoundatIonfortheIndIcatorwhenthe
flowcontrolvalveIsturnedoff.
28,29
Scale
TheflowmeterscalecanbemarkeddIrectlyontheflowtubeorlocatedtotherIghtofthe
tube.
J7
CradatIonscorrespondIngtoequalIncrementsInflowrateareclosertogetherat
thetopofthescalebecausetheannularspaceIncreasesmorerapIdlythandoesthe
InternaldIameterfrombottomtotopofthetube.FIbguIdesareusedInsomeflowtubes
wIthballtypeIndIcatorstomInImIzethIscompressIoneffect.TheyaretaperedglassrIdges
thatrunthelengthofthetube.ThereareusuallythreerIbguIdesthatareequallyspaced
aroundtheInnercIrcumferenceofthetube.nthepresenceofrIbguIdes,theannular
spacefromthebottomtothetopofthetubeIncreasesalmostproportIonallywIththe
InternaldIameter.ThIsresultsInanearlylInearscale
29
FIbguIdesareemployedonmany
0rager|edIcalflowtubes.
Figure 26-13.FlowmetersequenceapotentIalcauseofhypoxIa.ntheeventofa
flowmeterleak,apotentIallydangerousarrangementexIstswhennItrousoxIdeIs
locatedInthedownstreamposItIon(AandB).ThesafestconfIguratIonexIstswhen
oxygenIslocatedInthedownstreamposItIon(CandD).SeetextfordetaIls.(|odIfIed
fromEgerE,HyltonFF,rwInFH,etal:AnesthetIcflowmetersequenceacausefor
hypoxIa.AnesthesIology196J;24:J96,wIthpermIssIon.)
Safety Features
TheflowmetersubassemblIesforeachgasonthe0atexDhmeda|odulus,|odulus,
|odulusPlus,C0,andAestIvaarehousedInIndependent,colorcoded,pInspecIfIc
modules.TheflowtubesareadjacenttoagasspecIfIc,colorcodedbackIng.Theflowscale
andthechemIcalformula(ornameofthegas)arepermanentlyetchedonthebackIngto
therIghtoftheflowtube.FlowmeterscalesareIndIvIduallyhandcalIbratedusIngthe
specIfIcfloattoprovIdeahIghdegreeofaccuracy.Thetube,float,andscalemakean
InseparableunIt.TheentIresetmustbereplacedIfanycomponentIsdamaged.
0rager|edIcaldoesnotuseamodularsystemfortheflowmetersubassembly.Theflow
scale,thechemIcalsymbol,andthegasspecIfIccolorcodesareetcheddIrectlyontothe
flowtube.ThescaleInuseIsobvIouswhentwoflowtubesforthesamegasareused.
Problems with Flowmeters
Leaks
FlowmeterleaksareasubstantIalhazardbecausetheflowmetersarelocateddownstream
fromallmachInesafetydevIcesexcepttheoxygenanalyzer.
40
LeakscanoccurattheD
rIngjunctIonsbetweentheglassflowtubesandthemetalmanIfoldorIncrackedorbroken
glassflowtubes,themostfragIlepneumatIccomponentoftheanesthesIamachIne.Even
thoughgrossdamagetoconventIonalglassflowtubesIsusuallyapparent,subtlecracksand
chIpsmaybeoverlooked,resultIngInerrorsofdelIveredflows.
41
TheuseofelectronIc
flowmetersandtheremovalofconventIonalglassflowtubesfromsomeneweranesthesIa
workstatIons(0atexDhmedaS/5A0Uandthe0rager|edIcalFabIus)mayhelptoelImInate
thesepotentIalsourcesofleaks(seeElectronIcFlowmeters).
Egeretal.
42
In196Jdemonstratedthat,Inthepresenceofaflowmeterleak,ahypoxIc
mIxtureIslesslIkelytooccurIftheoxygenflowmeterIslocateddownstreamfromallother
flowmeters.FIgure261JIsamorecontemporaryversIonofthefIgureIntheorIgInal
publIcatIonofEgeretal.TheunusedaIrflowtubehasalargeleak.NItrousoxIdeand
oxygenflowratesaresetataratIoofJ:1.ApotentIallydangerousarrangementIsshownIn
FIgure261JAand261J8becausethenItrousoxIdeflowmeterIslocatedInthedownstream
posItIon.AhypoxIcmIxturecanresultbecauseasubstantIalportIonofoxygenflowpasses
throughtheleak,andallnItrousoxIdeIsdIrectedtothecommongasoutlet.Asafer
confIguratIonIsshownInFIgure261JCand261J0.TheoxygenflowmeterIslocatedInthe
downstreamposItIon.AportIonofthenItrousoxIdeflowescapesthroughtheleak,andthe
remaIndergoestowardthecommongasoutlet.AhypoxIcmIxtureIslesslIkelybecauseall
the
P.658
oxygenflowIsadvancedbythenItrousoxIde.
42
NorthAmerIcan0ragerflowmetersare
arrangedasInFIgure261JC,and0atexDhmedaflowmetersarearrangedasInFIgure26
1J0.
Figure 26-14.Dxygenflowtubeleak.AnoxygenflowtubeleakcanproduceahypoxIc
mIxtureregardlessofflowtubearrangement.(Feproducedfrom8rockwellFC:nhaled
anesthetIcdelIverysystems,AnesthesIa,6thedItIon.EdItedby|IllerF0.PhIladelphIa,
ChurchIllLIvIngstone,2004,p.281,wIthpermIssIon.)
AleakIntheoxygenflowtubemayresultIncreatIonofahypoxIcmIxtureevenwhen
oxygenIslocatedInthedownstreamposItIon(FIg.2614).
40,41
Dxygenescapesthroughthe
leakandnItrousoxIdecontInuestoflowtowardthecommonoutlet,partIcularlyathIgh
ratIosofnItrousoxIdetooxygenflow.
Inaccuracy
FlowmeasurementerrorcanoccurevenwhenflowmetersareassembledproperlywIth
approprIatecomponents.0IrtorstatIcelectrIcItycancauseafloattostIck,andtheactual
flowmaybehIgherorlowerthanthatIndIcated.StIckIngofIndIcatorfloatIsmore
commonInthelowflowrangesbecausetheannularspaceIssmaller.Adamagedfloatcan
causeInaccuratereadIngsbecausetheprecIserelatIonshIpbetweenthefloatandtheflow
tubeIsaltered.8ackpressurefromthebreathIngcIrcuItcancauseafloattodropsothatIt
readslessthantheactualflow.FInally,IfflowmetersarenotalIgnedproperlyInthe
vertIcalposItIon(plumb),readIngscanbeInaccuratebecausetIltIngdIstortstheannular
space.
2J,29,41
Ambiguous Scale
8eforethestandardIzatIonofflowmeterscalesandthewIdespreaduseofoxygen
analyzers,atleasttwodeathsresultedfromconfusIoncreatedbyambIguousscales.
2J,41,4J
TheoperatorreadthefloatposItIonbesIdeanadjacentbuterroneousscaleInbothcases.
TodaythIserrorIslesslIkelytooccurbecausecontemporaryflowmeterscalesaremarked
eItherdIrectlyontotheflowtubeorImmedIatelytotherIghtofIt.
J7
ThepossIbIlItyof
confusIonIsmInImIzedwhenthescaleIsetcheddIrectlyontothetube.
Electronic Flowmeters
AsmentIonedprevIously,someneweranesthesIaworkstatIonssuchasthe0atexDhmeda
S/5A0UandtheNorthAmerIcan0ragerFabIusCSamongothershaveconventIonalcontrol
knobsandflowcontrolvalves,buthaveelectronIcflowsensorsanddIgItaldIsplaysrather
thanglassflowtubes.TheoutputfromtheflowcontrolvalveIsrepresentedgraphIcally
and/ornumerIcallyInlIterspermInuteontheworkstatIon'sIntegrateduserInterface.
ThesesystemsdependonelectrIcalpowertoprovIdeaprecIsedIsplayofgasflow.
However,evenwhenelectrIcalpowerIstotallyInterrupted,becausetheflowcontrol
valvesthemselvesarenotelectronIc,oxygenshouldcontInuetoflow.8ecausethese
machInesdonothaveIndIvIdualflowtubesthatphysIcallyquantIfytheflowofeachgas,
electronIcflowsensorsandoftenasmallconventIonalpneumatIcfreshgasortotal
flowIndIcatorsareprovIdedthatgIvetheuseranestImateofthetotalquantItyoffresh
gasflowIngfromallflowcontrolvalves.ThIsmInIatureflowtubeIndIcatorservesto
InformtheuseroftheapproxImatequantItyofgasthatIsleavIngtheanesthesIa
workstatIon'scommongasoutlet,andIsfunctIonalevenIntheeventofatotalpower
faIlure.
Figure 26-15.DhmedaLInk25proportIonlImItIngcontrolsystem.SeetextfordetaIls.
Proportioning Systems
|anufacturersequIpanesthesIaworkstatIonswIthproportIonIngsystemsInanattemptto
preventcreatIonanddelIveryofahypoxIcmIxture.NItrousoxIdeandoxygenare
InterfacedmechanIcallyand/orpneumatIcallysothatthemInImumoxygenconcentratIon
atthecommongasoutletIsbetween2Jand25dependIngonmanufacturer.
Datex-Ohmeda Link-25 Proportion Limiting Control System
ConventIonal0atexDhmedamachInesusetheLInk25System.TheheartofthesystemIs
themechanIcalIntegratIonofthenItrousoxIdeandoxygenflowcontrolvalves.tallows
IndependentadjustmentofeIthervalve,yetautomatIcallyIntercedestomaIntaIna
mInImum25oxygenconcentratIonwIthamaxImumnItrousoxIdeoxygenflowratIoofJ:1.
TheLInk25automatIcallyIncreasesoxygenflowtopreventdelIveryofahypoxIcmIxture.
FIgure2615Illustratesthe0atexDhmedaLInk25System.ThenItrousoxIdeandoxygen
flowcontrolvalvesareIdentIcal.A14toothsprocketIsattachedtothenItrousoxIdeflow
controlvalveanda28toothsprocketIsattachedtotheoxygenflowcontrolvalve.AchaIn
physIcallylInksthesprockets.WhenthenItrousoxIdeflowcontrolvalveIsturnedthrough
tworevolutIons,or28teeth,theoxygenflowcontrolvalvewIllrevolveoncebecauseof
the2:1gearratIo.ThefInalJ:1flowratIoresultsbecausethenItrousoxIdeflowcontrol
valveIssupplIedbyapproxImately26psIg,whereastheoxygenflowcontrolvalveIs
supplIedby14psIg.Thus,thecombInatIonofthemechanIcalandpneumatIcaspectsofthe
systemyIeldsthefInaloxygenconcentratIon.The0atexDhmedaLInk25proportIonIng
systemcanbethoughtofasasystemthatincreases oxygen flowwhennecessarytoprevent
delIveryofafreshgasmIxturewIthoxygenconcentratIonoflessthan25.
AfewreportshavedescrIbedfaIluresofthe0atexDhmedaLInk25system.
4J,44,45,46
The
authorsofthesereportsdescrIbefaIluresthatresultedIneItherInabIlItytoadmInIster
oxygenwIthoutnItrousoxIdeorthatallowedcreatIonofahypoxIcmIxture.
North American Drger Oxygen Ratio Monitor
Controller/Sensitive Oxygen Ratio Controller System
NorthAmerIcan0rager'sproportIonIngsystem,theDxygenFatIo|onItorController
(DF|C),IsusedontheNorthAmerIcan0ragerNarkomed2A,28,J,and4.AnequIvalent
systemIsknownastheSensItIveDxygenFatIoController(SDFC)onsomenewer0rager
anesthesIaworkstatIonssuchasthe0rager
P.659
FabIusCSandNarkomed6000serIes.TheDF|CandtheSDFCarepneumatIcoxygen
nItrousoxIdeInterlocksystemsdesIgnedtomaIntaInafreshgasoxygenconcentratIonofat
least25J.TheycontrolthefreshgasoxygenconcentratIontolevelssubstantIallyhIgher
than25atoxygenflowrates1L/mIn.TheDF|CandSDFClImItnItrousoxIdeflowto
preventdelIveryofahypoxIcmIxture.ThIsIsunlIkethe0atexDhmedaLInk25,whIch
actIvelyIncreasesoxygenflow.
Figure 26-16.NorthAmerIcan0ragerDxygenFatIo|onItorController.Seetextfor
detaIls.(FedrawnfromSchreIberP:SafetyCuIdelInesforAnesthesIaSystems.Telford,
PA,NorthAmerIcan0rager,1984,wIthpermIssIon.)
AschematIcoftheDF|CIsshownInFIgure2616.tIscomposedofanoxygenchamber,a
nItrousoxIdechamber,andanItrousoxIdeslavecontrolvalve.AllareInterconnectedbya
mobIlehorIzontalshaft.ThepneumatIcInputIntothedevIceIsfromtheoxygenandthe
nItrousoxIdeflowmeters.TheseflowmetersareunIquebecausetheyhavespecIfIcresIstors
locateddownstreamfromtheflowcontrolvalves.TheseresIstorscreatebackpressures
dIrectedtotheoxygenandnItrousoxIdechambers.Thevalueoftheoxygenflowtube
resIstorIsJto4tImesthatofthenItrousoxIdeflowtuberesIstor,andtherelatIvevalueof
theseresIstorsdetermInesthevalueofthecontrolledfreshgasoxygenconcentratIon.The
backpressureIntheoxygenandnItrousoxIdechamberspushesagaInstrubberdIaphragms
attachedtothemobIlehorIzontalshaft.|ovementoftheshaftregulatesthenItrousoxIde
slavecontrolvalve,whIchfeedsthenItrousoxIdeflowcontrolvalve.
ftheoxygenpressureIsproportIonallyhIgherthanthenItrousoxIdepressure,thenItrous
oxIdeslavecontrolvalveopensmorewIdely,allowIngmorenItrousoxIdetoflow.Asthe
nItrousoxIdeflowIsIncreasedmanually,thenItrousoxIdepressureforcestheshafttoward
theoxygenchamber.ThevalveopenIngbecomesmorerestrIctIveandlImItsthenItrous
oxIdeflowtotheflowmeter.
FIgure2616IllustratestheactIonofasIngleDF|C/SDFCunderdIfferentsetsof
cIrcumstances.ThebackpressureexertedontheoxygendIaphragm,Intheupper
confIguratIon,IsgreaterthanthatexertedonthenItrousoxIdedIaphragm.ThIscausesthe
horIzontalshafttomovetotheleft,openIngthenItrousoxIdeslavecontrolvalve.NItrous
oxIdeIsthenabletoproceedtoItsflowcontrolvalveandoutthroughtheflowmeter.n
thebottomconfIguratIon,thenItrousoxIdeslavecontrolvalveIsclosedbecauseof
Inadequateoxygenbackpressure.
J0
TosummarIze,Incontrasttothe0atexDhmedaLInk
25systemthatactIvelyIncreasesoxygenflowtomaIntaInafreshgasoxygenconcentratIon
25,the0ragerDF|CandSDFCaresystemsthatlImItnItrousoxIdeflowtoprevent
delIveryofafreshgasmIxturewIthanoxygenconcentratIonof25.
Limitations
ProportIonIngsystemsarenotfoolproof.WorkstatIonsequIppedwIthproportIonIngsystems
canstIlldelIverahypoxIcmIxtureundercertaIncondItIons.FollowIngIsadescrIptIonof
someofthesItuatIonsInwhIchthIsmayoccur.
Wrong Supply Gas
8oththe0atexDhmedaLInk25andthe0ragerDF|C/SDFCwIllbefooledIfagasother
thanoxygenIspresentIntheoxygenpIpelIneandwIllallowdelIveryofhypoxIcgas
mIxtures.ntheLInk25System,thenItrousoxIdeandoxygenflowcontrolvalveswIll
contInuetobemechanIcallylInked.Nevertheless,ahypoxIcmIxturecanproceedtothe
commongasoutlet.nthecaseofthe0ragerDF|CorSDFC,therubberdIaphragmfor
oxygenwIllreflectadequatesupplypressureontheoxygensIdeeventhoughtheIncorrect
gasIspresent,andflowofboththewronggasplusnItrousoxIdewIllresult.Theoxygen
analyzerIstheonlyworkstatIonmonItorbesIdesanIntegratedmultIgasanalyzerthat
woulddetectthIscondItIonIneIthersystem.
Defective Pneumatics or Mechanics
NormaloperatIonofthe0atexDhmedaLInk25andtheNorthAmerIcan0ragerDF|C/S
DFCIscontIngentonpneumatIcandmechanIcalIntegrIty.
47
PneumatIcIntegrItyInthe
0atexDhmedaSystemrequIresproperlyfunctIonIngsecondstageregulators.AnItrous
oxIdeoxygenratIootherthanJ:1wIllresultIftheregulatorsarenotprecIse.ThechaIn
connectIngthetwosprocketsmustbeIntact;IfthechaInIscutorbroken,a97nItrous
oxIdeconcentratIoncanoccur.
48
ntheNorthAmerIcan0ragerSystem,afunctIonalDFP0
IsnecessarytosupplyapproprIatepressuretotheDF|C.ThemechanIcalaspectsofthe
DF|C/SDFC,suchastherubberdIaphragms,theflowtuberesIstors,andthenItrousoxIde
slavecontrolvalve,mustlIkewIsebeIntact.
Downstream Leaks
TheDF|C/SDFCandtheLInk25functIonattheleveloftheflowcontrolvalves.Aleak
downstreamfromthesedevIces,suchasabrokenoxygenflowtube(FIg.2614),canresult
IndelIveryofahypoxIcmIxturetothecommongasoutlet.nthIssItuatIon,oxygen
escapesthroughtheleakandthepredomInantgasdelIveredIsnItrousoxIde.Theoxygen
monItorand/orIntegratedmultIgasanalyzeraretheonlymachInesafetydevIcesthatcan
detectthIsproblem.
40
ForthemajorItyofItsproducts,0rager|edIcalrecommendsa
preoperatIveposItIvepressureleaktesttodetectsuchaleak.However,InaddItIontothIs
test,formanyNorthAmerIcan0ragerproducts,applIcatIonofthenegatIvepressureleak
testaswellmayprovIdeamoresensItIvewaytodetectsuchaleak.0atexDhmedaalmost
unIversallyrecommendsapreoperatIvenegatIvepressureleaktestforItsworkstatIons
becauseofthefrequentlypresentcheckvalvelocatedatthecommongasoutlet(see
CheckoutoftheAnesthesIaWorkstatIon).
Inert Gas Administration
AdmInIstratIonofathIrdInertgas,suchashelIum,nItrogen,orCD
2
,cancauseahypoxIc
mIxturebecausecontemporaryproportIonIngsystemslInkonlynItrousoxIdeandoxygen.
49
UseofanoxygenanalyzerIsmandatory(orpreferentIallyamultIgasanalyzer,when
avaIlable)IftheoperatorusesathIrdgas.
Dilution of Inspired Oxygen Concentration by Volatile Inhaled
Anesthetics
7olatIleInhaledanesthetIcs,lIkeInertgases,areaddedtothemIxedgasesdownstream
fromboththeflowmeters
P.660
andtheproportIonIngsystem.ConcentratIonsoflesspotentInhaledanesthetIcssuchas
desfluranemayaccountforalargerpercentageofthetotalfreshgascomposItIonthan
morepotentagents.8yexamInIngthemaxImumvaporIzerdIalsettIngsofthevarIous
volatIleagents,onecanassesstherIskofthIsphenomenon(e.g.,desfluranemaxImumdIal
settIng18vs.IsofluranemaxImumdIalsettIngof5).8ecausesIgnIfIcantpercentagesof
theseInhaledanesthetIcsmaybeaddeddownstreamoftheproportIonIngsystem,the
resultInggas/vapormIxturemaycontaInanInspIredoxygenconcentratIonthatIs21
oxygendespIteafunctIonalproportIonIngsystem.TheanesthesIaprovIdermustbeaware
ofthIspossIbIlIty,partIcularlywhenhIghconcentratIonsoflesspotentvolatIleInhaled
anesthetIcsareused.
Oxygen Flush Valve
TheoxygenflushvalveallowsdIrectcommunIcatIonbetweentheoxygenhIghpressure
cIrcuItandthelowpressurecIrcuIt(FIg.26J).Flowfromtheoxygenflushvalveentersthe
lowpressurecIrcuItdownstreamfromthevaporIzersand,mostImportantly,downstream
fromthe0atexDhmedamachIneoutletcheckvalve.ThesprIngloadedoxygenflushvalve
stayscloseduntIltheoperatoropensItbydepressIngtheoxygenflushbutton.ActuatIonof
thevalvedelIvers100oxygenatJ5to75L/mIntothebreathIngcIrcuIt.
28
TheoxygenflushvalvecanprovIdeahIghpressureoxygensourcesuItableforjet
ventIlatIonunderthefollowIngcIrcumstances:(1)theanesthesIamachIneIsequIppedwIth
aonewaycheckvalveposItIonedbetweenthevaporIzersandtheoxygenflushvalve,and
(2)whenaposItIvepressurerelIefvalveexIstsdownstreamofthevaporIzers,thIspressure
relIefvalvemustbeupstreamoftheoutletcheckvalve.8ecausetheDhmeda|odulus
hassuchaonewaycheckvalveandItsposItIvepressurerelIefvalveIsupstreamfromthe
checkvalve,theentIreoxygenflowofJ5to75L/mInIsdelIveredtothecommongas
outletatahIghpressureof50psIg.Dntheotherhand,theDhmeda|odulusPlusand
someDhmedaExcelmachInesarenotcapableoffunctIonIngasanapproprIateoxygen
sourceforjetventIlatIon.TheDhmeda|odulusplus,whIchdoesnothavethecheck
valve,provIdesonly7psIgatthecommongasoutletbecausesomeoxygenflowtravels
retrogradethroughanInternalrelIefvalvelocatedupstreamfromtheoxygenflushvalve.
TheDhmedaExcel210,whIchdoeshaveaonewaycheckvalve,alsohasaposItIve
pressurerelIefvalvedownstreamfromthecheckvalveandthereforeIsunsuItableforjet
ventIlatIon.DlderNorthAmerIcan0ragermachInessuchastheNarkomed2A(whIchalso
doesnothavetheoutletcheckvalve)provIdeanIntermedIatepressureof18psIgtothe
commongasoutletbecausesomepressureIsventedretrogradethroughapressurerelIef
valvelocatedInthevaporIzers.
50
SeveralhazardshavebeenreportedwIththeoxygenflushvalve.AdefectIveordamaged
valvecanstIckInthefullyopenposItIon,resultIngInbarotrauma.
51
AvalvestIckIngIna
partIallyopenposItIoncanresultInpatIentawarenessdurInggeneralanesthesIabecause
theoxygenflowfromtheIncompetentvalvedIlutestheInhaledanesthetIc.
26
mproperuse
ofnormallyfunctIonIngoxygenflushvalvesalsocanresultInproblems.Dverzealous
IntraoperatIveoxygenflushIngcandIluteInhaledanesthetIcs.DxygenflushIngdurIngthe
InspIratoryphaseofposItIvepressureventIlatIoncanproducebarotraumaInpatIentsIfthe
anesthesIamachInedoesnotIncorporatefreshgasdecouplIngoranapproprIatelyadjusted
InspIratorypressurelImIter.AnesthesIasystems(0ragerNarkomed6000serIes,JulIan,
FabIusCSand0atascopeAnestar)wIthfreshgasdecouplIngareInherentlysaferfromthe
standpoIntofmInImIzIngthechanceofproducIngbarotraumafromInapproprIateoxygen
flushvalveuse.ThesesystemsphysIcallyseparatethefreshgasInflowfromeItherthe
flowmetersortheoxygenflushvalvefromthedelIveredtIdalvolumepresentedtothe
patIent'slungs.WIthtradItIonalanesthesIabreathIngcIrcuIts,excessvolumecannotbe
venteddurIngtheInspIratoryphaseofmechanIcalventIlatIonbecausetheventIlatorrelIef
valveIsclosedandtheadjustablepressurelImItIng(APL)valveIseItheroutofcIrcuItor
closed.
52
AnalternatIvewaytomanagethIsproblemcanbeseenonthe0atexDhmedaS/5
A0UandAestIva.ThesecIrclesystemsuseanIntegratedadjustablepressurelImIter.fthIs
devIceIsproperlyadjusted,ItfunctIonslIketheAPLvalvetolImItthemaxImumaIrway
pressuretoasafelevel,therebyreducIngthepossIbIlItyofbarotrauma.
SomeveryoldanesthesIasystemsmadeuseofafreestandIngvaporIzerdownstreamfrom
thecommongasoutlet;onthesesystems,oxygenflushIngcouldrapIdlydelIverlarge
quantItIesofInhaledanesthetIctothepatIent.FInally,InapproprIatepreoperatIveuseof
theoxygenflushtoevaluatethelowpressurecIrcuItforleakscanbemIsleadIng,
partIcularlyon0atexDhmedamachIneswIthaonewaycheckvalveatthecommon
outlet.
25
8ecausebackpressurefromthebreathIngcIrcuItclosestheonewaycheckvalve
InanaIrtIghtmanner,majorlowpressurecIrcuItleakscangoundetectedwIththIsleak
test(seeCheckoutoftheAnesthesIaWorkstatIon).
Web-Based Anesthesia Software Simulation, the Virtual
Anesthesia Machine
ThegrowthofnternetWebbasedapplIcatIontechnologyaswellastrendstoIncorporate
sImulatIonIntoanesthesIatraInIngandeducatIonhasgenerateddevelopmentofonlIne
sImulatIonanesthesIasImulatIonresources.The7IrtualAnesthesIa|achIne(7A|)Isa
WebbasedanesthesIasImulatIonenvIronmentthatprovIdesInformatIononthefunctIonof
anesthesIamachInesalongwIthtutorIalsandoperatIonalscenarIos,IncludIngfaIluremodes
ofnewandtradItIonalanesthesIaworkstatIons(FIg.2617).
5J
tIsavaIlableforusefreeof
charge.The7A|allowstheusertomodIfymostofthecontrolsfoundonamodern
anesthesIaworkstatIon,suchasgasflowsandventIlatorsettIngs.Theauthorsofthe7A|,
IncollaboratIonwIththeAnesthesIaPatIentSafetyFoundatIon(APSF),havecreatedThe
AnesthesIaPatIentSafetyFoundatIonAnesthesIa|achIneWorkbook.Theworkbook
provIdesaddItIonalInformatIonandtutorIalscoverIngsIxanesthesIamachInesubsystems:
thehIghpressuresystem,thelowpressuresystem,thebreathIngcIrcuIt,manual
ventIlatIon,mechanIcalventIlatIon,andthescavengIngsystem.
54
Vaporizers
AsdramatIcallyastheevolutIonoftheanesthesIaworkstatIonhasbeenInrecentyears,
vaporIzershavealsochangedfromrudImentaryetherInhalersandcopperkettlestothe
presenttemperaturecompensated,computercontrolled,andflowsensIngdevIcesweuse
today.n199J,wIththeIntroductIonofdesfluranetotheclInIcalsettIng,anevenmore
sophIstIcatedvaporIzerwasIntroducedtohandletheunIquephysIcalpropertIesofthIs
agent.Now,anewgeneratIonofanesthesIavaporIzersblendIngbotholdcopper
kettlelIketechnologyandnewcomputerIzedcontroltechnologyhasemergedInthe
0atexDhmedaAladInCassettevaporIzersystem.8eforethedIscussIonofvarIablebypass
vaporIzers,the0atexDhmedaTec6desfluranevaporIzer,andthe0atexDhmedaAladIn
CassettevaporIzer,certaInphysIcalprIncIpleswIllberevIewedbrIeflytofacIlItate
understandIngoftheoperatIngprIncIples,constructIon,anddesIgnofcontemporary
volatIleanesthetIcvaporIzers.
P.661
Figure 26-17.The7IrtualAnesthesIa|achIne(7A|)sImulator,anInteractIvemodel
ofananesthesIamachIne.(FeproducedwIthpermIssIonfromLampotangSandLIzdas
0E,7IrtualAnesthesIa|achIneWebsIte:http://vam.anest.ufl.edu/wIp.html.)
Physics
Vapor Pressure
ContemporaryInhaledvolatIleanesthetIcsexIstInthelIquIdstateattemperaturesbelow
20`C.WhenavolatIlelIquIdIsInaclosedcontaIner,moleculesescapefromthelIquId
phasetothevaporphaseuntIlthenumberofmoleculesInthevaporphaseIsconstant.
ThesemoleculesInthevaporphasebombardthewallofthecontaInerandcreatea
pressureknownasthesaturated vapor pressure.AsthetemperatureIncreases,more
moleculesenterthevaporphase,andthevaporpressureIncreases(FIg.2618).7apor
pressureIsIndependentofatmospherIcpressureandIscontIngentonlyonthetemperature
andphysIcalcharacterIstIcsofthelIquId.Theboiling pointofalIquIdIsdefInedasthat
temperatureatwhIchthevaporpressureequalsatmospherIcpressure.
J8,55,56
At760mm
Hg,theboIlIngpoIntsfordesflurane,Isoflurane,halothane,enflurane,andsevofluraneare
approxImately22.8,48.5,50.2,56.5,and58.5`C,respectIvely.UnlIkeothercontemporary
InhaledanesthetIcs,desfluraneboIlsattemperaturesthatmaybeencounteredInclInIcal
settIngssuchaspedIatrIcandburnoperatIngrooms.ThIsunIquephysIcalcharacterIstIc
alonemandatesaspecIalvaporIzerdesIgntocontrolthedelIveryofdesflurane.fagent
specIfIcvaporIzersareInadvertentlymIsfIlledwIthIncorrectlIquIdanesthetIcagents,the
resultIngmIxturesofvolatIleagentsmaydemonstrateunIquepropertIesfromthoseofthe
IndIvIdualcomponentagents.ThealteredvaporpressureandotherphysIcalpropertIesof
theresultIngazeotropIcmIxturesthatresultfromthemIxIngofvarIousagentsmayalter
theoutputoftheanesthetIcvaporIzer(see7arIable8ypass7aporIzers:Hazardsand
|IsfIllIng).
57
Figure 26-18.7aporpressureversustemperaturecurvesfordesflurane,Isoflurane,
halothane,enflurane,andsevoflurane.ThevaporpressurecurvefordesfluraneIsboth
steeperandshIftedtohIghervaporpressureswhencomparedwIththecurvesforother
contemporaryInhaledanesthetIcs.(FromInhaledanesthetIcpackageInsertequatIons
andfromSusaySF,SmIth|A,LockwoodCC:Thesaturatedvaporpressureof
desfluraneatvarIoustemperatures.AnesthAnalg1996;8J:864).
Latent Heat of Vaporization
WhenamoleculeIsconvertedfromalIquIdtothegaseousphase,energyIsconsumed
becausethemoleculesofalIquIdtendtocohere.TheamountofenergythatIsconsumed
foragIvenlIquIdasItIsconvertedtoavaporIsreferredtoasthelatent heat of
vaporization.tIsmoreprecIselydefInedasthenumberofcalorIesrequIredtochange1g
oflIquIdIntovaporwIthoutatemperaturechange.TheenergyforvaporIzatIonmustcome
eItherfromthelIquIdItselforfromanoutsIdesource.ThetemperatureofthelIquIdItself
wIlldecreasedurIngvaporIzatIonIntheabsenceofanoutsIdeenergysource.ThIsenergy
losscanleadtosIgnIfIcantdecreasesIntemperatureoftheremaInInglIquId,andcan
greatlydecreasesubsequentvaporIzatIon.
J8,55,58
Specific Heat
Thespecific heatofasubstanceIsthenumberofcalorIesrequIredtoIncreasethe
temperatureof1gofasubstanceby1`C.
19,J8,55
ThesubstancecanbeasolId,lIquId,or
gas.TheconceptofspecIfIcheatIsImportanttothedesIgn,operatIon,andconstructIonof
vaporIzersbecauseItIsapplIcableIntwoways.FIrst,thespecIfIcheatvalueforanInhaled
anesthetIcIsImportantbecauseItIndIcateshowmuchheatmustbesupplIedtothelIquId
tomaIntaInaconstanttemperaturewhenheatIsbeInglostdurIngvaporIzatIon.Second,
manufacturersselectvaporIzercomponentmaterIalsthathaveahIghspecIfIcheatto
mInImIzetemperaturechangesassocIatedwIthvaporIzatIon.
P.662
Thermal Conductivity
Thermal conductivityIsameasureofthespeedwIthwhIchheatflowsthroughasubstance.
ThehIgherthethermalconductIvIty,thebetterthesubstanceconductsheat.
55
7aporIzers
areconstructedofmetalsthathaverelatIvelyhIghthermalconductIvIty,thusmaIntaInIng
aunIformInternaltemperature.
Ambient Pressure Effects
See0atexDhmedaTec67aporIzerfor0esflurane:Factorsthatnfluence7aporIzer
Dutput:7arIedAltItudes.
Variable Bypass Vaporizers
The0atexDhmedaTec4,Tec5,andTec7,aswellastheNorthAmerIcan0rager7apor
19.nand20.nvaporIzers,areclassIfIedasvarIablebypass,flowover,temperature
compensated,agentspecIfIc,outofbreathIngcIrcuItvaporIzers.
55
Variable bypassrefers
tothemethodforregulatIngtheanesthetIcagentconcentratIonoutputfromthe
vaporIzer.TheconcentratIoncontroldIalsettIngdetermInestheratIoofflowthatgoes
throughthebypasschamberandthroughthevaporIzIngchamberasfreshgasfromthe
flowmetersentersthevaporIzerInlet.ThegaschanneledthroughthevaporIzIngchamber
flowsoverawIcksystemsaturatedwIththelIquIdanesthetIcandsubsequentlyalso
becomessaturatedwIthvapor.Thus,flow-overreferstothemethodofvaporIzatIonandIs
Incontrasttoabubble-throughsystemthatmaybeseenInsomecopperkettletype
vaporIzersofold.TheTec4,Tec5,andTec7,andthe0rager7apor19.nand20.nare
furtherclassIfIedastemperature compensated.EachoftheseIsequIppedwIthan
automatIctemperaturecompensatIngdevIcethathelpsmaIntaInaconstantvaporIzer
outputoverawIderangeofoperatIngtemperatures.ThesevaporIzersareagent-specific
andout-of-circuitbecauseeachIsdesIgnedtoaccommodateasIngleanesthetIcagentand
tobephysIcallylocatedoutsIdethebreathIngcIrcuIt.7arIablebypassvaporIzersareused
todelIverhalothane,enflurane,Isoflurane,andsevoflurane,butnotdesflurane.
Basic Operating Principles
AdIagramofagenerIc,varIablebypassvaporIzerIsshownInFIgure2619.7aporIzer
componentsIncludetheconcentratIoncontroldIal,thebypasschamber,thevaporIzIng
chamber,thefIllerport,andthefIllercap.UsIngthefIllerport,theoperatorfIllsthe
vaporIzIngchamberwIthlIquIdanesthetIc.ThemaxImumsafefIlllevelIspredetermIned
bytheposItIonofthefIllerport,whIchIsposItIonedtomInImIzethechanceofoverfIllIng.
favaporIzerIsoverfIlledortIlted,lIquIdanesthetIccanspIllIntothebypasschamber.f
anesthetIclIquIdentersthebypasschamber,boththevaporIzIngchamberflowandthe
bypasschamberflowcouldpotentIallybecarryIngsaturatedanesthetIcvapor,andan
overdosewouldresult.TheconcentratIoncontroldIalIsavarIablerestrIctor;Itcanbe
locatedeItherInthebypasschamberorIntheoutletofthevaporIzIngchamber.The
functIonoftheconcentratIoncontroldIalIstoregulatetherelatIveflowratesthroughthe
bypassandvaporIzIngchambers.
Figure 26-19.CenerIcvarIablebypassvaporIzer.SeetextfordetaIls.
FlowfromtheflowmetersenterstheInletofthevaporIzer.|orethan80oftheflow
passesstraIghtthroughthebypasschambertothevaporIzeroutlet,andthIsaccountsfor
thenamebypass chamber.Lessthan20oftheflowfromtheflowmetersIsdIverted
throughthevaporIzIngchamber.0ependIngonthetemperatureandvaporpressureofthe
partIcularInhaledanesthetIc,thefreshgasesenterIngthevaporIzIngchamberentraIna
specIfIcflowoftheInhaledanesthetIcagent.ThemIxturethatexItsthevaporIzerIsthe
combInatIonofflowthroughthebypasschamber,flowthroughthevaporIzIngchamber,
andflowofentraInedanesthetIcvapor.ThefInalconcentratIonofInhaledanesthetIcIsthe
ratIooftheflowoftheInhaledanesthetIctothetotalgasflow.
55,59
TheamountoflIquId
volatIleanesthetIc(InmIllIlIters)thatatypIcalvaporIzerusesIsproportIonaltotheflow
rateandcanbeapproxImatedfromthefollowIngformula:Jfreshgasflow(L/mIn)
volume=mLlIquIdofvolatIleanesthetIcperhour.
60
ThevaporpressureofanInhaledanesthetIcdependsontheambIenttemperature(FIg.26
18).Forexample,at20`CthevaporpressureofIsofluraneIs2J8mmHg,whereasatJ5`C
thevaporpressurealmostdoubles(450mmHg).7arIablebypassvaporIzershavean
InternalmechanIsmtocompensateforvarIatIonsInambIenttemperature.The
temperaturecompensatIngvalveofthe0atexDhmedaTec4IsshownInFIgure2620.At
relatIvelyhIghambIenttemperatures,suchasthosecommonlyseenInoperatIngrooms
desIgnatedforthecareofpedIatrIcorburnpatIents,thevaporpressureInsIdethe
vaporIzIngchamberIs
P.66J
hIgh.TocompensateforthIsIncreasedvaporpressure,thebImetallIcstrIpofthe
temperaturecompensatIngvalveleanstotherIght,decreasIngtheresIstancetoflow
throughthebypasschamber.ThIsdecreasedresIstanceallowsmoreflowtopassthrough
thebypasschamberandlessflowtopassthroughthevaporIzIngchamber.ncontrast,Ina
coldoperatIngroomenvIronment,thevaporpressureInsIdethevaporIzIngchamberIs
reduced.TocompensateforthIsdecreaseInvaporpressure,thebImetallIcstrIpleansto
theleft.ThIschangeIncreasestheresIstancetoflowthroughthebypasschamber,causIng
moreflowtopassthroughthevaporIzIngchamberandlesstopassthroughthebypass
chamber.TheneteffectInbothsItuatIonsIsmaIntenanceofrelatIvelyconstantvaporIzer
output.
Figure 26-20.SImplIfIedschematIcoftheDhmedaTecType7aporIzer.Seetextfor
detaIls.
Factors That Influence Vaporizer Output
fanIdealvaporIzerexIsted,wIthafIxeddIalsettIng,Itsoutputwouldbeconstant
regardlessofvarIedflowrates,temperatures,backpressures,andcarrIergases.0esIgnIng
suchavaporIzerIsdIffIcultbecauseasambIentcondItIonschange,thephysIcalpropertIes
ofgasesandofvaporIzersthemselvescanchange.
59
ContemporaryvaporIzersapproach
IdealbutstIllhavesomelImItatIons.EventhoughsomeofthemostsophIstIcatedvaporIzer
systemsnowavaIlableusecomputercontrolledcomponentsandmultIplesensors,they
haveyettobecomesIgnIfIcantlymoreaccuratethanconventIonalvaporIzers.Several
factorsthataffectvaporIzerperformanceIngeneralaredescrIbedhere.
Flow Rate
WIthafIxeddIalsettIng,vaporIzeroutputcanvarywIththerateofgasflowIngthrough
thevaporIzer.ThIsvarIatIonIspartIcularlynotableatextremesofflowrates.Theoutput
ofallvarIablebypassvaporIzersIslessthanthedIalsettIngatlowflowrates(250
mL/mIn).ThIsresultsfromtherelatIvelyhIghdensItyofvolatIleInhaledanesthetIcs.At
lowflowrates,InsuffIcIentturbulenceIsgeneratedInthevaporIzIngchambertoadvance
thevapormoleculesupwardly.AtextremelyhIghflowrates,suchas15L/mIn,theoutput
ofmostvarIablebypassvaporIzersIslessthanthedIalsettIng.ThIsdIscrepancyIs
attrIbutedtoIncompletemIxIngandfaIluretosaturatethecarrIergasInthevaporIzIng
chamber.Also,theresIstancecharacterIstIcsofthebypasschamberandthevaporIzIng
chambercanvaryasflowIncreases.ThesevarIatIonscanresultIndecreasedoutput
concentratIon.
59
Temperature
8ecauseofImprovementsIndesIgn,theoutputofcontemporarytemperaturecompensated
vaporIzersIsalmostlInearoverawIderangeoftemperatures.AutomatIctemperature
compensatIngmechanIsmsInthebypasschambermaIntaInaconstantvaporIzeroutput
wIthvaryIngtemperatures.
28
AsprevIouslydescrIbed,abImetallIcstrIp(ofthe
temperaturecompensatIngvalve;FIg.2620)oranexpansIonelement(FIg.2621)dIrectsa
greaterproportIonofgasflowthroughthebypasschamberastemperaturesIncrease.
59
AddItIonally,thewIcksystemsareplacedIndIrectcontactwIththemetalwallofthe
vaporIzertohelpreplaceenergy(heat)consumeddurIngvaporIzatIon.ThematerIalsfrom
whIchvaporIzersareconstructedarechosenbecausetheyhavearelatIvelyhIghspecIfIc
heatandhIghthermalconductIvIty.ThesefactorshelpmInImIzetheeffectofcoolIngof
thelIquIdanesthetIcdurIngvaporIzatIon.
Figure 26-21.SImplIfIedschematIcoftheNorthAmerIcan0rager7apor19.1
vaporIzer.SeetextfordetaIls.
Intermittent Back Pressure
ntermIttentbackpressurethatresultsfromeItherposItIvepressureventIlatIonoruseof
theoxygenflushvalvemayresultInhIgherthanexpectedvaporIzeroutput.ThIs
phenomenon,knownasthepumping effect,Ismorepronouncedatlowflowrates,lowdIal
settIngs,andlowlevelsoflIquIdanesthetIcInthevaporIzIngchamber.
55,59,61,62
AddItIonally,thepumpIngeffectIsIncreasedbyrapIdrespIratoryrates,hIghpeakInspIred
pressures,andrapIddropsInpressuredurIngexhalatIon.
J8,52,55,56,6J
NewervarIablebypass
vaporIzerssuchasthe0atexDhmedaTec4,Tec5,andTec7,andNorthAmerIcan0rager
7apor19.nand20.n(7apor2000)arerelatIvelyImmunefromthepumpIngeffect.Dne
proposedmechanIsmforthepumpIngeffectdependsonretrogradepressuretransmIssIon
fromthepatIentcIrcuIttothevaporIzerdurIngtheInspIratoryphaseofposItIvepressure
ventIlatIon.CasmoleculesarecompressedInboththebypassandvaporIzIngchambers.
WhenthebackpressureIssuddenlyreleaseddurIngtheexpIratoryphaseofposItIve
pressureventIlatIon,vaporexItsthevaporIzIngchambervIaboththevaporIzIngchamber
outletandretrogradethroughthevaporIzIngchamberInlet.ThIsoccursbecausethe
outputresIstanceofthebypasschamberIslowerthanthatofthevaporIzIngchamber,
partIcularlyatlowdIalsettIngs.TheenhancedoutputconcentratIonresultsfromthe
IncrementofvaporthattravelsIntheretrogradedIrectIontothebypasschamber.
59,61,62
TodecreasethepumpIngeffect,thevaporIzIngchambersofnewersystemsaresmaller
thanthoseofearlyvarIablebypassvaporIzerssuchastheFluotec|ark(750mL).
61
Therefore,nosubstantIalvolumesofvaporcanbedIschargedfromthevaporIzIngchamber
IntothebypasschamberdurIngtheexpIratoryphase.TheNorthAmerIcan0rager7apor
19.1and20.n(FIg.2621)havealongspIraltubethatservesastheInlettothevaporIzIng
chamber.
61
WhenthepressureInthevaporIzIngchamberIsreleased,someofthevapor
entersthIstubebutdoesnotenterthebypasschamberbecauseoftubelength.
56
TheTec4
(FIg.2620)hasanextensIvebafflesystemInthevaporIzIngchamber,andaonewaycheck
valvehasbeenInsertedatthecommongasoutlettomInImIzethepumpIngeffect.ThIs
checkvalveattenuatesbutdoesnotelImInatethepressureIncreasebecausegasstIllflows
fromtheflowmeterstothevaporIzerdurIngtheInspIratoryphaseofposItIvepressure
ventIlatIon.
55,64
Carrier Gas Composition
7aporIzeroutputIsInfluencedbythecomposItIonofthecarrIergasthatflowsthroughthe
vaporIzer.
65,66,67,68,69,70,71,72
0urIngexperImentalcondItIons,whenthecarrIergasIs
rapIdlychangedfrom100oxygento100nItrousoxIde,asuddentransIentdecreaseIn
vaporIzeroutputoccurs,followedbyaslowIncreasetoanewsteadystatevalue(FIg.26
228).
66,69
8ecausenItrousoxIdeIsmoresolublethanoxygenInthehalogenatedlIquId
wIthInthevaporIzersump,whenthIsswItchoccurstheoutputfromthevaporIzIng
chamberIstransIentlyreduced.
66
DncetheanesthetIclIquIdIstotallysaturatedwIth
nItrousoxIde,vaporIzIngchamberoutputIncreasessomewhat,andanewsteadystateIs
establIshed(FIg.2622C).
TheexplanatIonforthenewsteadystateoutputvalueIslesswellunderstood.
71
WIth
contemporaryvaporIzerssuchastheNorthAmerIcan0rager7apor19.nand20.nandthe
DhmedaTectypeconventIonalvaporIzers,thesteadystateoutputvalueIslesswhen
nItrousoxIderatherthanoxygenIsthecarrIergas(FIg.26228).Conversely,theoutputof
someoldervaporIzersIsenhancedwhennItrousoxIdeIsthecarrIergasInsteadof
oxygen.
68,72
ThesteadystateplateauIsachIevedmorerapIdlywIthIncreasedflowrates,
regardlessoftheultImateoutputvalue.
69
FactorsthatcontrIbutetothecharacterIstIc
steadystateresponseresultIngwhenvarIouscarrIergases
P.664
areusedIncludethevIscosItyanddensItyofthecarrIergas(dependIngonwhetherthe
flowIslamInarorturbulent),therelatIvesolubIlItIesofthecarrIergasIntheanesthetIc
lIquId,theflowsplIttIngcharacterIstIcsofthespecIfIcvaporIzer,andtheconcentratIon
controldIalsettIng.
66,68,69,71
Figure 26-22.HalothaneoutputofaNorthAmerIcan0rager7apor19.1vaporIzerwIth
dIfferentcarrIergases.TheInItIaloutputconcentratIonIsapproxImately4halothane
whenoxygenIsthecarrIergasatflowsof6L/mIn(A).WhenthecarrIergasIsquIckly
swItchedto100nItrousoxIde(B),thehalothaneconcentratIondecreasestoJwIthIn
8to10seconds.Then,anewsteadystateconcentratIonofapproxImatelyJ.5Is
attaInedwIthIn1mInute.SeetextfordetaIls.(|odIfIedfromCould08,Lampert8A,
|acKrellTN:EffectofnItrousoxIdesolubIlItyonvaporIzeraberrance.AnesthAnalg
1982;61:9J9,wIthpermIssIon.)
Safety Features
NewergeneratIonsofanesthesIavaporIzersIncludIngtheNorthAmerIcan0rager19.nand
20.n,andthe0atexDhmedaTec4,Tec5,andTec7nowhavebuIltInsafetyfeaturesthat
havemInImIzedorelImInatedmanyhazardsonceassocIatedwIthvarIablebypass
vaporIzers.AgentspecIfIc,keyedfIllIngdevIceshelppreventfIllIngavaporIzerwIththe
wrongagent.DverfIllIngofthesevaporIzersIsmInImIzedbecausethefIllerportIslocated
atthemaxImumsafelIquIdlevel.FInally,today'svaporIzersarefIrmlysecuredtoa
vaporIzermanIfoldontheanesthesIaworkstatIon.Thus,problemsassocIatedwIth
vaporIzertIppInghavebecomemuchlessfrequent.ContemporaryInterlocksystems
preventadmInIstratIonofmorethanoneInhaledanesthetIc.
Hazards
0espItemanysafetyfeatures,somehazardsarestIllassocIatedwIthcontemporary
varIablebypassvaporIzers.
Misfilling
7aporIzersnotequIppedwIthkeyedfIllershavebeenoccasIonallymIsfIlledwIththewrong
anesthetIclIquId.
7J
ApotentIalformIsfIllIngexIstsevenoncontemporaryvaporIzers
equIppedwIthkeyedfIllers.
74,75,76
WhenavaporIzermIsfIllIngoccurs,patIents
InadvertentlycanberenderedInadequately,orexcessIvely,anesthetIzed,dependIngon
whIchdrugIsplacedInthevaporIzer.TheuseofamultIgasanalyzermayalerttheuserto
suchaproblem.
Contamination
ContamInatIonofanesthetIcvaporIzercontentshasoccurredbyfIllInganIsoflurane
vaporIzerwIthacontamInatedbottleofIsoflurane.ApotentIallyserIousIncIdentwas
avoIdedbecausetheoperatordetectedanabnormalacrIdodor.
77
Tipping
TIppIngofavaporIzercanoccurwhentheyareIncorrectlyswItchedoutormoved.
However,tIppIngIsunlIkelywhenavaporIzerIsattachedtotheanesthesIaworkstatIon
manIfoldshortoftheentIremachInebeIngturnedover.ExcessIvetIppIngcancausethe
lIquIdagenttoenterthebypasschamberandcancauseoutputwIthextremelyhIghagent
concentratIon.
78
TheTec4IsslIghtlymoreresIstanttotIppIngthantheNorthAmerIcan
0rager7apor19.nbecauseofItsextensIvebafflesystem.However,IfeIthervaporIzerIs
tIpped,ItshouldnotbeuseduntIlIthasbeenflushedfor20toJ0mInutesathIghfreshgas
flowrates.0urIngthIsprocedure,havIngthevaporIzerconcentratIoncontroldIalsetata
lowconcentratIonmaxImIzesbypasschamberflowandwIllaIdInremovalofanyresIdual
lIquIdanesthetIcInthatarea.
55
AfterfollowIngthIsprocedure,theuseofamultIgas
analyzerIsstronglyrecommended.The0rager7apor20.nserIesvaporIzersnowhavea
transport(T)dIalsettIngthathelpspreventtIppIngrelatedproblems.WhenthedIalIs
placedInthIsposItIon,thevaporIzersumpIsIsolatedfromthebypasschamber,thereby
reducIngthelIkelIhoodoftIppIngandaresultIngaccIdentaloverdose.Therefore,anytIme
oneofthesevaporIzersIsmovedseparatefromtheanesthesIaworkstatIon,thecontrol
dIalshouldbeplacedIntheTposItIon.
ThedesIgnoftheTec6andtheAladInCassettevaporIzersystems,bothfrom0atex
Dhmeda,haspractIcallyelImInatedthepossIbIlItyoftIppIngfromtheseproducts.8ecause
theAladInCassettevaporIzer'sbypasschamberIsphysIcallyseparatedfromthecassette,
andpermanentlyresIdesIntheanesthesIaworkstatIon,thepossIbIlItyoftIppIngIsvIrtually
elImInated.TIppIngoftheAladInCassettesthemselveswhentheyarenotInstalledInthe
vaporIzerIsnotproblematIc.SImIlarly,0rager's07aporvaporIzerIshermetIcallytIghtand
canbetransportedInanyposItIonwIthoutprIordraInIng.
Overfilling
mproperfIllIngprocedurescombInedwIthfaIlureofthevaporIzersIghtglasscancause
overfIllIngandpatIentoverdose.LIquIdanesthetIcentersthebypasschamberandupto10
tImestheIntendedvaporconcentratIoncanbedelIveredtothecommongasoutlet.
79
|ost
modernvaporIzersarenowrelatIvelyImmunetooverfIllIngbecauseofsIdefIllratherthan
topfIlldesIgns.SIdefIllsystemslargelypreventoverfIllIng.
Underfilling
JustaswIthoverfIllIng,underfIllIngofanesthetIcvaporIzersmayalsobeproblematIc.
WhenaTec5sevofluranevaporIzerIsInalowfIllstateandusedundercondItIonsofhIgh
freshgasflowrates(7.5L/mIn)andhIghdIalsettIng(suchasseendurIngInhalatIonal
InductIons),thevaporIzeroutputmayabruptlydecreaseto2.ThecausesofthIsproblem
aremostlIkelymultIfactorIal.However,thecombInatIonoflowvaporIzerfIllstate(25
full)IncombInatIonwIththehIghvaporIzIngchamberflowcanresultInaclInIcally
sIgnIfIcantandreproducIblefallInvaporIzeroutput.
80
Simultaneous Inhaled Anesthetic Administration
DnsomeolderanesthesIamachInesfrom0atexDhmedathatareequIppedwIththeSelect
aTecthreevaporIzermanIfoldthatdoesnotuseavaporInterlocksystem,twoInhaled
anesthetIcscanbeadmInIsteredsImultaneouslywhenthecentervaporIzerIsremoved.Dn
suchmachInes,eIthertheleftortherIghtvaporIzershouldbemovedtothecentral
posItIonIfthecentralvaporIzerIsremoved(asIndIcatedbythemanIfoldwarnInglabel).
DncethIsIsdone,thevaporIzer'sInterlocksystemwIllallowonlyoneagenttobe
admInIsteredatatIme.|orecontemporarySelectaTecvaporIzermanIfoldshaveabuIlt
InvaporInterlockorvaporexclusIondevIcethatpreventsthIsproblem.Dnthesenewer
threevaporIzersystems,aUshapedplastIcdevIcelInksthevaporIzerextensIonrodseven
whenthevaporIzersarenotadjacenttooneanotheronthemanIfold.Dnsuchasystem,
themanIfoldplusthevaporIzersthemselvescomprIsethevaporInterlockorvapor
exclusIonsystem.
P.665
Leaks
7aporIzerleaksoccurfrequently,andcanpotentIallyresultInpatIentawarenessdurIng
anesthesIa.
18,22,62,81
orInpollutIonoftheoperatIngroomenvIronment.AloosefIllercapIs
themostcommonsourceofvaporIzerleaks.WIthsomekeyfIlledPenlonand0rager
vaporIzers,aloosefIllerscrewclampallowsescapeofsaturatedanesthetIcvapor.
18
Leaks
canoccurattheDrIngjunctIonsbetweenthevaporIzerandItsmanIfold.Todetectaleak
wIthInavaporIzer,theconcentratIoncontroldIalmustbeIntheonposItIon.Eventhough
vaporIzerleaksIn0ragersystemspotentIallycanbedetectedwIthaconventIonalposItIve
pressureleaktest(becauseoftheabsenceofanoutletcheckvalve),anegatIvepressure
leaktestIsmoresensItIveandallowstheusertodetectevensmallleaks.0atexDhmeda
recommendsanegatIvepressureleaktestIngdevIce(suctIonbulb)todetectvaporIzer
leaksInthe|odulus,|odulus,Excel,andtheAestIvaworkstatIonsbecauseofthecheck
valvelocatedjustupstreamofeachmachIne'sfreshgasoutlet(seeCheckoutofthe
AnesthesIaWorkstatIon).
|anyneweranesthesIaworkstatIonsarecapableofperformIngselftestIngprocedures
that,Insomecases,mayelImInatetheneedfortheconventIonalnegatIvepressureleak
testIng.However,ItIsofvItalImportancethatanesthesIaprovIdersunderstandthatthese
selftestsmaynotdetectInternalvaporIzerleaksonsystemswIthaddonvaporIzers.For
theselfteststodetermIneIfanInternalvaporIzerleakIspresent,theleaktestmustbe
repeatedforeachvaporIzersequentIally,whIleItsconcentratIoncontroldIalIsturnedto
theonposItIon.FecallthatwhenavaporIzer'sconcentratIoncontroldIalIssetIntheoff
posItIon,ItmaynotbepossIbletodetectevenmajorInternalleakssuchasanabsentor
loosefIllercap.
Anesthesia Vaporizers and Environmental Considerations
Todaymorethanever,anesthetIcsarebeIngadmInIsteredtopatIentsoutsIdethe
operatIngroom.DnesuchlocatIonthathasprovedsometImesdIffIculttoworkInIsthe
magnetIcresonanceImagIng(|F)suIte.ThepresenceofapowerfulmagnetfIeld,the
sIgnIfIcantnoIsepollutIon,andlImItedaccesstothepatIentdurIngtheprocedureall
complIcatecareInthIssettIng.tIsImperatIvethatonlynonferrous(|FcompatIble)
equIpmentbeusedInthesesettIngs.SomeanesthesIavaporIzers,althoughtheymay
appearnonferrousbytestIngwIthahorseshoemagnet,mayIndeedcontaInsubstantIal
Internalferrouscomponents.napproprIateuseofsuchadevIceInan|FsuItemay
potentIallyturnthemIntoadangerousmIssIleIfleftunsecured.
82
The Datex-Ohmeda Tec 6 Vaporizer for Desflurane
8ecauseofItsunIquephysIcalcharacterIstIcs,thecontrolledvaporIzatIonofdesflurane
requIredanovelapproachtovaporIzerdesIgn.0atexDhmedadevelopedtheTec6
vaporIzer,thefIrstsuchsystem,andreleasedItIntoclInIcaluseIntheearly1990s.The
Tec6vaporIzerIsanelectrIcallyheated,pressurIzeddevIcespecIfIcallydesIgnedto
delIverdesflurane.
8J,84
ThevaporpressureofdesfluraneIsJto4tImesthatofother
contemporaryInhaledanesthetIcs,andItboIlsat22.8`C,
85
whIchIsnearroomtemperature
(FIg.2618).0esfluranehasamInImumalveolaranesthetIcconcentratIon(|AC)valueof6
to7.
85
0esfluraneIsvaluablebecauseIthasalowbloodgassolubIlItycoeffIcIentof0.45
atJ7`C,andrecoveryfromanesthesIaIsmorerapIdthanwIthmanyotherpotentInhaled
anesthetIcs.
85
n2004,0rager|edIcalreceIvedF0AapprovalforItsownversIonoftheTec
6desfluranevaporIzer,the07apor.TheoperatIngprIncIplesdescrIbedInthefollowIng
dIscussIonareapplIcabletoeIthersystem,eventhoughwerefertotheTec6specIfIcally.
Unsuitability of Contemporary Variable Bypass Vaporizers for
Controlled Vaporization of Desflurane
0esflurane'shIghvolatIlItyandmoderatepotencyprecludeItsusewIthcontemporary
varIablebypassvaporIzerssuchas0atexDhmedaTec4,Tec5,andTec7,ortheNorth
AmerIcan0rager7apor19.nor20.nfortwoprImaryreasons
8J
:
1. At20`CthevaporpressureofdesfluraneIsnear1atmosphere(atm).
Thevaporpressuresofenflurane,Isoflurane,halothane,anddesfluraneat20`Care172,
240,244,and669mmHg,respectIvely(FIg.2618).
85
Equalamountsofflowthrougha
tradItIonalvaporIzerwouldvaporIzemanymorevolumesofdesfluranethananyotherof
theotheragents.Forexample,at1atmand20`C,100mL/mInpassIngthroughthe
vaporIzIngchamberwouldentraIn7J5mL/mIndesfluraneversus29,46,and47mL/mIn
ofenflurane,Isoflurane,andhalothane,respectIvely.
8J
UnderthesesamecondItIons,to
produce1desfluraneoutputtheamountofbypassflownecessarytoachIevesuffIcIent
dIlutIonofthelargevolumeofdesfluranesaturatedanesthetIcvaporwouldbe
approxImately7JL/mIn,comparedwIth5L/mInfortheotherthreeanesthetIcs.
AddItIonally,above22.8`Cat1atm,desfluranewIllboIl.Theamountofvaporproduced
wouldbelImItedonlybytheheatenergyavaIlablefromthevaporIzerowIngtoIts
specIfIcheat.
8J
2. ContemporaryvaporIzerslackanexternalheatsource.
ThelatentheatofvaporIzatIonfordesfluraneIsapproxImatelyequaltothatof
enflurane,Isoflurane,andhalothane;however,Its|ACIs4to9tImeshIgherthanthose
oftheotherthreeInhaledanesthetIcs.Thus,theabsoluteamountofdesflurane
vaporIzedoveragIventImeperIodIsconsIderablygreaterthantheotheranesthetIc
drugs.SupplyIngdesfluranevIaaconventIonalvaporIzerInhIgher(equIvalent|AC)
concentratIonswouldleadtoexcessIvecoolIngofthevaporIzerandwouldsIgnIfIcantly
reduceItsoutput.ntheabsenceofanexternalheatsource,temperaturecompensatIon
usIngtradItIonalmechanIcaldevIceswouldbealmostImpossIble.8ecauseofthebroad
rangeoftemperaturesseenIntheclInIcalsettIng,andbecauseofdesflurane'ssteep
vaporpressureversustemperaturecurve(FIg.2618),thedelIveryofdesfluraneIna
conventIonalanesthetIcvaporIzeratbestwouldbeunpredIctable.
8J
Operating Principles of the Tec 6 and Tec 6 Plus
ToachIevecontrolledvaporIzatIonofdesflurane,0atexDhmedaIntroducedtheTec6
vaporIzertowIdespreadclInIcalpractIceIn199J.ThIswasthefIrstclInIcallyavaIlable
vaporIzertobeelectrIcallyheatedandpressurIzed.ThephysIcalappearanceand
operatIonoftheTec6aresImIlartocontemporaryvaporIzers,butsomeaspectsofthe
InternaldesIgnandoperatIngprIncIplesareradIcallydIfferent.TheTec6Plusrepresentsa
laterversIonoftheorIgInalTec6.TheTec6PlushasthesamebasIcTec6desIgn,butalso
IncorporatesanenhancedaudIblealarmsystemnotprevIouslyavaIlableontheTec6.
FunctIonally,theoperatIonoftheTec6IsmoreaccuratelydescrIbedasadualgasblender
thanasavaporIzer.AsImplIfIedschematIcoftheTec6IsshownInFIgure262J.The
vaporIzerhastwoIndependentgascIrcuItsarrangedInparallel.ThefreshgascIrcuItIs
shownIngray,andthevaporcIrcuItIsshownInwhIte.Thefreshgasfromtheflowmeters
entersatthefreshgasInlet,passesthroughafIxedrestrIctor(F1),andexItsatthe
vaporIzergasoutlet.ThevaporcIrcuItorIgInatesatthedesfluranesump,whIchIs
electrIcallyheatedandthermostatIcallycontrolledtoJ9`C,atemperaturewellabovethe
boIlIngpoIntofdesflurane.TheheatedsumpassemblyservesasareservoIrofdesflurane
vapor.AtJ9`C,thevaporpressureInthesumpIsapproxImately1,J00mmHgabsolute,
86
or
P.666
approxImately2atmabsolute(FIg.2618).JustdownstreamfromthesumpIstheshutoff
valve.AfterthevaporIzerwarmsup,theshutoffvalvefullyopenswhentheconcentratIon
controlvalveIsturnedtotheonposItIon.ApressureregulatIngvalvelocateddownstream
fromtheshutoffvalveregulatesthepressuredownwardtoapproxImately1.1atmabsolute
(74mmHggauge)atafreshgasflowrateof10L/mIn.Theoperatorcontrolsdesflurane
outputbyadjustIngtheconcentratIoncontrolvalve(F2),whIchIsavarIablerestrIctor.
8J
Figure 26-23.SImplIfIedschematIcoftheTec6desfluranevaporIzer.F1,fIxed
restrIctor;F2,varIablerestrIctor.SeetextfordetaIls.(FromAndrewsJJ:DperatIng
PrIncIplesoftheDhmedaTec60esflurane7aporIzer:ACollectIonofTwelveColor
llustratIons.WashIngton,0C,LIbraryofCongress,1996,wIthpermIssIon.)
ThevaporflowthroughF2joInsthefreshgasflowthroughF1atapoIntdownstreamfrom
therestrIctors.UntIlthIspoInt,thetwocIrcuItsarephysIcallydIvorced.Theyare
InterfacedpneumatIcallyandelectronIcally,however,throughdIfferentIalpressure
transducers,acontrolelectronIcssystem,andapressureregulatIngvalve.Whena
constantfreshgasflowrateencountersthefIxedrestrIctor,F1,aspecIfIcbackpressure,
proportIonaltothefreshgasflowrate,pushesagaInstthedIaphragmofthecontrol
dIfferentIalpressuretransducer.ThedIfferentIalpressuretransducerconveysthepressure
dIfferencebetweenthefreshgascIrcuItandthevaporcIrcuIttothecontrolelectronIcs
system.ThecontrolelectronIcssystemregulatesthepressureregulatIngvalvesothatthe
pressureInthevaporcIrcuItequalsthepressureInthefreshgascIrcuIt.ThIsequalIzed
pressuresupplyIngF1andF2IstheworkIngpressure,andtheworkIngpressureIsconstant
atafIxedfreshgasflowrate.ftheoperatorIncreasesthefreshgasflowrate,moreback
pressureIsexertedonthedIaphragmofthecontrolpressuretransducer,andtheworkIng
pressureofthevaporIzerIncreases.
8J
Table262showstheapproxImatecorrelatIonbetweenfreshgasflowrateandworkIng
pressureforatypIcalvaporIzer.Atafreshgasflowrateof1L/mIn,theworkIngpressureIs
10mIllIbars,or7.4mmHggauge.Atafreshgasflowrateof10L/mIn,theworkIngpressure
Is100mIllIbars,or74mmHggauge.Therefore,thereIsalInearrelatIonshIpbetweenfresh
gasflowrateandworkIngpressure.WhenthefreshgasflowrateIsIncreasedtenfold,the
workIngpressureIncreasestenfold.
8J
LIstedInthefollowIngsectIonaretwospecIfIcexamplestodemonstratetheoperatIng
prIncIplesoftheTec6.
8J
ExampleA:Constantfreshgasflowrateof1L/mIn,wIthanIncreaseInthedIalsettIng.
WIthafreshgasflowrateof1L/mIn,theworkIngpressureofthevaporIzerIs7.4mm
Hg.ThatIs,thepressuresupplyIngF1andF2Is7.4mmHg.AstheoperatorIncreasesthe
dIalsettIng,theopenIngatF2becomeslarger,allowIngmorevaportopassthroughF2.
SpecIfIcvaporflowratesatdIfferentdIalsettIngsareshownInTable26J.
Example8:ConstantdIalsettIngwIthanIncreaseInfreshgasflowfrom1to10L/mIn.
Atafreshgasflowrateof1L/mIn,theworkIngpressureIs7.4mmHg,andatadIal
settIngof6thevaporflowrate
P.667
throughF2Is64mL/mIn(Tables262and26J).WIthatenfoldIncreaseInthefreshgas
flowrate,thereIsaconcomItanttenfoldIncreaseIntheworkIngpressureto74mmHg.
TheratIoofresIstancesofF2toF1IsconstantatafIxeddIalsettIngof6.8ecauseF2Is
supplIedby10tImesmorepressure,thevaporflowratethroughF2Increasestenfoldto
640mL/mIn.7aporIzeroutputIsconstantbecauseboththefreshgasflowandthevapor
flowIncreaseproportIonally.
Table 26-2 Fresh gas Flow Rate Versus Working Pressure
FRESH GAS FLOW RATE (L/min)
WORKING PRESSURE AT R1 AND R2 GAS INLET PRESSURE, PSIG
mbar cm water mm Hg
1 10 10.2 7.4
5 50 51.0 J7.0
10 100 102.0 74.0
F1,fIxedrestrIctor;F2,varIablerestrIctor.
FeprIntedfromAndrewsJJ,JohnstonF7Jr:ThenewTec6desfluranevaporIzer.
AnesthAnalg199J;76:1JJ8,wIthpermIssIon.
Table 26-3 Dial Setting Versus Flow Through Restrictor R2
DIAL SETTING
(VOL%)
a
FRESH GAS FLOW RATE
(L/min)
APPROXIMATE VAPOR FLOW RATE THROUGH R2
(mL/min)
1 1 10
6 1 64
12 1 1J6
18 1 220
a
7olumepercent=[(vaporflowrate)/(freshgasflowrate)+(vaporflowrate)]
100.
FeprIntedfromAndrewsJJ,JohnstonF7Jr:ThenewTec6desfluranevaporIzer.
AnesthAnalg199J;76:1JJ8,wIthpermIssIon.
Factors that Influence Vaporizer Output
7arIedaltItudeandcarrIergascomposItIonInfluenceTec6output.EachIsdIscussedInthe
followIngsectIons.
Varied Altitudes
AlthoughambIentpressurechangesaffectconventIonalvaporIzeroutputsIgnIfIcantlyIn
termsofvolumespercent(v/v;I.e.,concentratIon),theIreffectonanesthetIcpotency
(I.e.,partIalpressure)IsmInImal.ThIseffectIsIllustratedusIngtheexampleofIsoflurane
shownInTable264.WIthaconstantdIalsettIngof0.89,at1atm(760mmHg),If
perfectlycalIbrated,thevolumespercentdelIveredwouldbe0.89andthepartIal
pressureofIsofluranewouldbe6.8mmHg.|aIntaInIngthesamedIalsettIngandlowerIng
ambIentpressureto0.66atmor502mmHg(roughlyequIvalentto10,000ftelevatIon)
wouldresultInanIncreaseIntheconcentratIonoutputto1.75(almostdouble),butthe
partIalpressureonlyIncreasesto8.77mmHg(onlya29Increase)becauseofthe
proportIonatedeclIneInambIentpressure(FIg.2624).
tIsgenerallyconsIderedthatthepartIalpressureoftheanesthetIcagentInthecentral
nervoussystem,notItsconcentratIon,IsresponsIblefortheanesthetIceffect.ToobtaIna
consIstentdepthofanesthesIawhengrosschangesInbarometrIcpressureoccur,the
volumespercentmustbechangedInInverseproportIontothebarometrIcpressure.Forthe
mostpart,tradItIonalvarIablebypassvaporIzersautomatIcallycompensateforthIs
change,andforpractIcalpurposestheeffectofbarometrIcpressurecangenerallybe
Ignored.
ThIscompensatIonshouldbeconsIderedInstarkcontrasttotheresponseoftheTec6
desfluranevaporIzeratvarIedaltItudes(FIg.2624andTable264).Dnemustremember
thIsdevIceIsmoreaccuratelydescrIbedasadualgasblenderthanavaporIzer.
FegardlessoftheambIentpressure,theTec6
P.668
wIllmaIntaInaconstantconcentratIonofvaporoutput(volumespercent),notaconstant
partIalpressure.ThIsmeansthatathIghaltItudes,thepartIalpressureofdesfluranefor
anygIvendIalsettIngwIllbedecreasedInproportIontotheatmospherIcpressuredIvIded
bythecalIbratIonpressure(normally760mmHg)perthefollowIngformula:
Figure 26-24.PerformanceofTECtypevaporIzerversustheTec6desflurane
vaporIzeratvaryIngambIentatmospheres(1atmosphere=760mmHg).
Table 26-4 Performance of TEC Type Vaporizers Versus the Tec 6
Desflurane Vaporizer at Varying Ambient Pressures
a
ATMOSPHERES
AMBIENT
PRESSURE
ISOFLURANE VAPORIZER WITH A DIAL SETTING OF
0.89%
TEC 6
DESFLURANE
VAPORIZER WITH
A DIAL SETTING
OF 6%
(mm Hg)
MILLILITERS OF
ISOFLURANE VAPOR
ENTRAINED BY 100 mL
O
2
OUTPUT
CONCENTRATION
(%)
PARTIAL
PRESSURE
OUTPUT
(mm Hg)
PARTIAL
PRESSURE
OUTPUT OF
DESFLURANE
(mm Hg)
0.66(2/J)
500
(10,000
feet)
91 1.75J 8.77 J0
0.74 560 74 1.429 8.0 JJ.6
0.80
608
(6,564
feet)
64.J2 1.25 7.6 J6.5
1.0 760 46 0.89 6.8 45.6
1.5 1,140 26.4 0.515 5.87 68.4
2 1,520 19 0.J6 5.5 91.2
J 2,280 11.65 0.228 5.198 1J6
a
ThefollowIngwereassumed:5,000mLbypasschamberflow,100mLvaporIzIng
chamberflow,equIvalenttoanIsofluranedIalsettIngof0.89.
Forexample,atanaltItudeof2000m(6564ft)wheretheambIentpressureIs608mmHg,
theTec6dIalsettIngmustbeadvancedfrom10v/vto12.5v/vtoavoIdunderdosIngthat
couldpotentIallyresultInpatIentawareness.Conversely,theTec6'smaIntenanceofa
constantvolumespercentInhyperbarIccondItIonscouldproducesIgnIfIcantIncreasesIn
partIalpressureoutput,andIfnotaccountedfor,thepotentIalforanesthetIcoverdose.
Therefore,InhyperbarIcsettIngstheTec6dIalsettIngwouldneedtobereducedto
maIntaInthedesIredpartIalpressureoutputofdesflurane.
Carrier Gas Composition
7aporIzeroutputapproxImatesthedIalsettIngwhenoxygenIsthecarrIergasbecausethe
Tec6vaporIzerIscalIbratedusIng100oxygen.AtlowflowrateswhenacarrIergasother
than100oxygenIsused,however,acleartrendtowardreductIonInvaporIzeroutput
emerges.ThIsreductIonparallelstheproportIonaldecreaseInvIscosItyofthecarrIergas.
NItrousoxIdehasalowervIscosItythanoxygen,sothebackpressuregeneratedbyresIstor
F1(FIg.262J)IslesswhennItrousoxIdeIsthecarrIergas,andtheworkIngpressureIs
reduced.AtlowflowratesusIngnItrousoxIdeasthecarrIergas,vaporIzeroutputIs
approxImately20lessthanthedIalsettIng.ThIssuggeststhat,atclInIcallyusefulfresh
gasflowrates,thegasflowacrossresIstorF1IslamInar,andtheworkIngpressureIs
proportIonaltoboththefreshgasflowrateandthevIscosItyofthecarrIergas.
87
Safety Features
8ecausethevaporpressureofdesfluraneIsnear1atm,mIsfIllIngcontemporaryvaporIzers
wIthdesfluranecouldtheoretIcallyresultInbothdesfluraneoverdoseandcreatIonofa
hypoxIcgasmIxture.
88
0atexDhmedahasIntroducedaunIque,anesthetIcspecIfIcfIllIng
systemtomInImIzeoccurrenceofthIspotentIalhazard.TheagentspecIfIcfIllerofthe
desfluranebottleknownastheSaf-T-FilladapterIsIntendedtopreventItsusewIth
tradItIonalvaporIzers.ThefIllIngsystemalsomInImIzesspIllageoflIquIdorvapor
anesthetIcbymaIntaInIngaclosedsystemdurIngthefIllIngprocess.Eachdesflurane
bottlehasasprIngloadedfIllercapwIthanDrIngonthetIp.ThesprIngsealsthebottle
untIlItIsengagedInthefIllerportofthevaporIzer.Thus,thIsanesthetIcspecIfIcfIllIng
systemInterlocksthevaporIzerandthedIspensIngbottle,preventInglossofanesthetIcto
theatmosphere.0espItethesesafetyfeaturesdesIgnedtomInImIzefIllIngerrors,acase
reportdescrIbedthemIsfIllIngofaTec6desfluranevaporIzerwIthsevoflurane.ThIserror
waspossIblebecauseofsImIlarItIesbetweenanewtypeofkeyedfIllerforsevofluraneand
thedesfluraneSafTFIlladapter.nthIscase,however,thedesfluranevaporIzerdetected
thIserrorandautomatIcallyshutItselfoff.
74
|ajorvaporIzerfaultscausetheshutoffvalvelocatedjustdownstreamfromthe
desfluranesump(FIg.262J)toclose,producInganooutputsItuatIon.ThevalveIsclosed
andanooutputalarmIsactIvatedImmedIatelyIfanyofthefollowIngcondItIonsoccur:
(1)theanesthetIcleveldecreasestobelow20mL,(2)thevaporIzerIstIlted,(J)apower
faIlureoccurs,or(4)thereIsadIsparItybetweenthepressureInthevaporcIrcuItversus
thepressureInthefreshgascIrcuItexceedIngaspecIfIedtolerance.
Summary
TheTec6vaporIzerIsanelectrIcallyheated,thermostatIcallycontrolled,constant
temperature,pressurIzed,electromechanIcallycoupleddualcIrcuIt,gasvaporblender.
ThepressureInthevaporcIrcuItIselectronIcallyregulatedtoequalthepressureInthe
freshgascIrcuIt.Ataconstantfreshgasflowrate,theoperatorregulatesvaporflowusIng
aconventIonalconcentratIoncontroldIal.WhenthefreshgasflowrateIncreases,the
workIngpressureIncreasesproportIonally.ForagIvenconcentratIonsettIngevenwhen
varyIngthefreshgasflowrate,thevaporIzeroutputIsconstantbecausetheamountof
flowthrougheachcIrcuItremaInsproportIonal.
8J
The Datex-Ohmeda Aladin Cassette Vaporizer
ThevaporIzersystemusedInthe0atexDhmedaS5/AnesthesIa0elIveryUnIt(A0U)Is
unIqueInthatthesIngleelectronIcallycontrolledvaporIzerIsdesIgnedtodelIverfIve
dIfferentInhaledanesthetIcsIncludInghalothane,Isoflurane,enflurane,sevoflurane,and
desflurane.ThevaporIzerconsIstsofapermanentInternalcontrolunIthousedwIthInthe
A0UandanInterchangeableAladInagentcassettethatcontaInsanesthetIclIquId.The
AladInagentcassettesarecolorcodedforeachanesthetIcagent,andtheyarealso
magnetIcallycodedsothatthe0atexDhmedaA0UcanIdentIfywhIchanesthetIccassette
hasbeenInserted.ThecassettesarefIlledusIngagentspecIfIcfIllers.
55
AlthoughverydIfferentInexternalappearance,thefunctIonalanatomyoftheS/5A0U
cassettevaporIzer(AladIn,FIg.2625)IsverysImIlartothatofthe0ragervapor19.1and
20.nandthe0atexDhmedaTec4,Tec5,andTec7vaporIzers.TheAladInsystemIs
functIonallysImIlartotheseconventIonalvaporIzersbecauseItIsalsomadeupofabypass
chamberandvaporIzIngchamber.AfIxedrestrIctorIslocatedInthebypasschamber,and
flowmeasurementsensorsarelocatedbothInthebypasschamberandIntheoutletofthe
vaporIzIngchamber.TheheartoftheS/5A0UcassettevaporIzerIstheelectronIcally
regulatedflowcontrolvalvelocatedInthevaporIzIngchamberoutlet.ThIsvalveIs
controlledbyacentralprocessIngunIt(CPU).TheCPUreceIvesInputfrommultIplesources
IncludIngtheconcentratIoncontroldIal,apressuresensorlocatedInsIdethevaporIzIng
chamber,atemperaturesensorlocatedInsIdethevaporIzIngchamber,aflow
P.669
measurementunItlocatedInthebypasschamber,andaflowmeasurementunItlocatedIn
theoutletofthevaporIzIngchamber.TheCPUalsoreceIvesInputfromtheflowmeters
regardIngthecomposItIonofthecarrIergas.UsIngdatafromthesemultIplesources,the
CPUIsabletoprecIselyregulatetheflowcontrolvalvetoattaInthedesIredvapor
concentratIonoutput.ApproprIateelectronIccontroloftheflowcontrolvalveIsessentIal
totheproperfunctIonofthIsvaporIzer.
55,89
Figure 26-25.SImplIfIedschematIcof0atexDhmedaAladInCassette7aporIzer.The
black arrowsrepresentflowfromtheflowmeters,andthewhite circlesrepresent
anesthetIcvapor.TheheartofthevaporIzerIstheelectronIcallycontrolledflow
controlvalvelocatedIntheoutletofthevaporIzIngchamber.CPU,centralprocessIng
unIt;F
8C
,flowmeasurementunIt,whIchmeasuresflowthroughthebypasschamber;
F
7C
,flowmeasurementunIt,whIchmeasuresflowthroughthevaporIzIngchamber;P,
pressuresensor;T,temperaturesensor.(|odIfIedfromAndrews,JJ:DperatIng
PrIncIplesofthe0atexDhmedaAladInCassette7aporIzer:ACollectIonofColor
llustratIons.WashIngton,0C,LIbraryofCongress,2000.)
AfIxedrestrIctorIslocatedInthebypasschamber,andItcausesflowfromthevaporIzer
InlettosplItIntotwoflowstreams(FIg.2625).Dnestreampassesthroughthebypass
chamber,andtheotherportIonenterstheInletofthevaporIzIngchamberandpasses
throughaonewaycheckvalve.ThepresenceofthIscheckvalveIsunIquetotheAladIn
system.ThIsonewayvalvepreventsretrogradeflowoftheanesthetIcvaporbackIntothe
bypasschamber,andItspresenceIscrucIalwhendelIverIngdesfluraneIftheroom
temperatureIsgreaterthantheboIlIngpoIntfordesflurane(22.8`C).
55
AprecIseamountof
vaporsaturatedcarrIergaspassesthroughtheflowcontrolvalve,whIchIsregulatedby
theCPU.ThIsflowthenjoInsthebypassflowandIsdIrectedtotheoutletofthe
vaporIzer.
55
AsmentIonedInthedIscussIonoftheTec6,thecontrolledvaporIzatIonofdesflurane
presentsaunIquechallenge,partIcularlywhentheroomtemperatureIsgreaterthanthe
boIlIngpoIntofdesflurane(22.8`C).AthIghertemperatures,thepressureInsIdethe
vaporIzersumpIncreases,andthesumpbecomespressurIzed.Whenthesumppressure
exceedsthepressureInthebypasschamber,theonewaycheckvalvelocatedInthe
vaporIzIngchamberInletcloses,preventIngcarrIergasfromenterIngthevaporIzIng
chamber.AtthIspoInt,thecarrIergaspassesstraIghtthroughthebypasschamberandIts
flowsensor.UnderthesecondItIons,theelectronIcallyregulatedflowcontrolvalvesImply
metersIntheapproprIateflowofpuredesfluranevaporneededtoachIevethedesIred
fInalconcentratIonselectedbytheuser.AtleastonecasereporthasdescrIbedafaIlureof
thevaporIzIngchamberInletcheckvalvetofunctIonasdesIgned.nthIscase,an
anesthetIcoverdoseoccurredasaresultofspIlloverofdesfluranefromthevaporIzIng
chamberInaretrogradefashIonIntothebypasschamber.ThIsreportremIndsA0Uusersto
becautIousofthIspotentIalproblemwhendesfluraneIsused.
89
0urIngoperatIngcondItIonsInwhIchhIghfreshgasflowratesand/orhIghdIalsettIngsare
used,largequantItIesofanesthetIclIquIdarerapIdlyvaporIzed.Asaresult,the
temperatureoftheremaInInglIquIdanesthetIcandthevaporIzerItselfdecreaseasa
resultofenergyconsumptIonofthelatentheatofvaporIzatIon.TooffsetthIscoolIng
effect,theS/5A0UIsequIppedwIthafanthatforceswarmedaIrfromanagentheatIng
resIstoracrossthecassette(vaporIzersump)toraIseItstemperaturewhennecessary.The
fanIsactIvateddurIngtwocommonclInIcalscenarIos:(1)desfluraneInductIonand
maIntenance,and(2)sevofluraneInductIon.AsummaryofthecharacterIstIcsofvarIous
vaporIzermodelscurrentlyInuseIsfoundInTable265.
The MAQUET 950 Series Injection Vaporizer
|AQUET,nc.(8rIdgwater,NJ)manufacturesInjectIontypevaporIzersforusewIth
halothane,enflurane,andIsoflurane.ThesevaporIzersshouldbeusedwIththe|AQUET
Servo7entIlator.
90
TheInjectIonvaporIzerIssImIlarInappearancetotradItIonalvarIable
bypassvaporIzersandhasagraduatedconcentratIonknob,keyedfIllportwIthplugand
lockIngscrew,andafIlllevelInspectIonwIndow.naddItIon,thereIsanon/offswItchwIth
asafetylock.
FIgure2626descrIbestheoperatIonoftheInjectIonvaporIzer.|Ixedgas(1)flowsIntothe
vaporIzerthrougharegulatorvalve(2)thatpreventsflowIntothegascIrcuItwhenthe
ventIlatorbellowsIffull.WhenthebellowsIsempty,gasIsallowedtoflowIntothe
vaporIzerIftheon/offswItch(J)Issettoon.nthevaporIzer,anadjustablethrottlevalve
(4)restrIctsgasflow,thuscontrollIngpressurebydIrectIngexcessgasIntothelIquId
reservoIr(5).CaspressurewIthInthereservoIrforcesanesthetIcagentthrougha
vaporIzatIonnozzle(6)andbackIntothegasstream.ThepressuredIfferencebetweenthe
gasstreamandthereservoIrIsproportIonaltothedegreeofthrottlIng,whIchIscontrolled
bythedIalonthevaporIzer.
P.670
ThedelIveredconcentratIonIsmostlyIndependentoftheventIlatorsettIngs.ThereIs
normallynoneedfortemperaturecompensatIon,asthereIsnovaporIzatIonofagentper
se.TheaccuracyofthedelIveredagentIs10or0.1volume(whIcheverIshIgher),and
theconcentratIonofthedelIveredanesthetIcagentwIlldevIateslIghtlydependIngonthe
mIxtureofthecarrIergas.
90
ThevaporIzershouldnotbeturnedupsIdedownortIlted
sIdewaysIfthereIslIquIdInthereservoIr.AccumulatIonofthestabIlIzatIonagentIn
halothanemayInterferewIthnormaloperatIon,andvaporIzerscontaInInghalothane
shouldbeemptIedonceeverymonth.ThevaporIzershouldbecheckedforleakage
annually,accordIngto|AQUET,nc.,andsoshouldtheconcentratIonofthedelIvered
anesthetIcagent.
90
Table 26-5 Vaporizer Models and Characteristics
TYPE OF
VAPORIZER
TEC 4, TEC 5, SEVOTEC,
VAPOR 19.N, VAPOR 2000,
ALADIN
TEC 6 (DESFLURANE),
D-VAPOR
(DESFLURANE)
MAQUET 950 SERIES
INJECTION VAPORIZER
CarrIergas
flow
7arIablebypass 0ualcIrcuIt
ConcentratIon
calIbratedInjector
7aporIzatIon
method
Flowover
Cas/vapor
blender
None;Injected
Temperature
compensatIon
AutomatIc
ThermostatIcally
controlledat
J9`C
Noneneeded
a
CalIbratIon AgentspecIfIc AgentspecIfIc AgentspecIfIc
PosItIon DutofcIrcuIt DutofcIrcuIt DutofcIrcuIt
FIllcapacIty
Tec4:125mL
Tec5:J00mL
7apor19.n:200mL
7apor2000:J60mL
(drywIck)
AladIn:250mL
Tec6:425mL
d7apor:J00mL
125mL(105mL
betweenmIn.and
max.fIlllevels)
a
A10`CIncreaseIntemperaturewIllresultIna10IncreaseInoutput
concentratIon.
Figure 26-26.TheoryofoperatIonofthe|AQUET950serIesInjectIonvaporIzer.See
textfordetaIls.
P.671
Figure 26-27.|aplesonbreathIngsystemsAF.FCF,freshgasflow.(Fedrawnfrom
WIllIs8A,PenderJW,|aplesonWW:FebreathIngInaTpIece:7olunteerand
TheoretIcalStudIesoftheJacksonFees|odIfIcatIonofAyre'sTpIecedurIng
spontaneousrespIratIon.8rJAnaesth1975;47:12J9,wIthpermIssIon.)
Anesthetic Breathing Circuits
AstheprescrIbedmIxtureofgasesfromtheflowmetersandvaporIzerexItstheanesthesIa
workstatIonatthecommongasoutlet,ItthenentersananesthetIcbreathIngcIrcuIt.The
functIonoftheanesthesIabreathIngcIrcuItIsnotonlytodelIveroxygenandanesthetIc
gasestothepatIent,butalsotoelImInateCD
2
.CD
2
canberemovedeItherbywashoutwIth
adequatefreshgasInfloworbytheuseofCD
2
absorbentmedIa(e.g.,sodalIme
absorptIon).ThefollowIngdIscussIonfocusesonthesemIclosedrebreathIngcIrcuItsandthe
cIrclesystem.
Mapleson Systems
n1954|apleson
91
descrIbedandanalyzedfIvedIfferentsemIclosedanesthetIcsystems;
thesearenowclassIcallyreferredtoastheMapleson systemsandaredesIgnatedwIth
lettersAthroughE(FIg.2627).SubsequentlyIn1975,WIllIsetal.
92
descrIbedtheFsystem
thatwasaddedtotheorIgInalfIve.The|aplesonsystemsconsIstofseveralcommon
components.ThesescomponentscommonlyIncludeafacemask,asprIngloadedpopoff
valve,reservoIrtubIng,freshgasInflowtubIng,andareservoIrbag.WIthInthe|apleson
systems,threedIstInctfunctIonalgroupscanbeseen:theseIncludetheA,the8/C,and
0/E/Fgroups.The|aplesonA,alsoknownastheMagill Circuit,hasasprIngloadedpopoff
valvelocatednearthefacemask,andthefreshgasflowenterstheopposIteendofthe
cIrcuItnearthereservoIrbag.nthe8andCsystems,thesprIngloadedpopoffvalveIs
locatednearthefacemask,butthefreshgasInlettubIngIslocatednearthepatIent.The
reservoIrtubIngandbreathIngbagserveasablIndlImbwherefreshgas,deadspacegas,
andalveolargascancollect.FInally,Inthe|apleson0/E/FgrouporTpIecegroup,the
freshgasentersnearthepatIent,andexcessgasIspoppedoffattheopposIteendofthe
cIrcuIt.
EventhoughthecomponentsandcomponentarrangementaresImple,functIonalanalysIs
ofthe|aplesonsystemscanbecomplex.
9J,94
TheamountofCD
2
rebreathIngassocIated
wItheachsystemIsmultIfactorIal,andvarIablesthatdIctatetheultImateCD
2
concentratIonInclude:(1)thefreshgasInflowrate,(2)themInuteventIlatIon,(J)the
modeofventIlatIon(spontaneousorcontrolled),(4)thetIdalvolume,(5)therespIratory
rate,(6)theInspIratorytoexpIratorytImeratIo,(7)theduratIonoftheexpIratorypause,
(8)thepeakInspIratoryflowrate,(9)thevolumeofthereservoIrtube,(10)thevolumeof
thebreathIngbag,(11)ventIlatIonbymask,(12)ventIlatIonthroughanendotrachealtube,
and(1J)theCD
2
samplIngsIte.
Theperformanceofthe|aplesonsystemsIsbestunderstoodbystudyIngtheexpIratory
phaseoftherespIratorycycle.
95
llustratIonsofthevarIous|aplesonsystemcomponent
arrangementsmaybefoundInFIgure2627.0urIngspontaneousventIlatIon,the|apleson
AhasthebesteffIcIencyofthesIxsystems,requIrIngafreshgasInflowrateofonlyone
tImesthemInuteventIlatIontopreventrebreathIngofCD
2
.8utIthastheworsteffIcIency
durIngcontrolledventIlatIon,requIrIngamInuteventIlatIonashIghas20L/mIntoprevent
rebreathIng.Systems0EFareslIghtlymoreeffIcIentthansystems8C.Toprevent
rebreathIngCD
2
,the0EFsystemsrequIreafreshgasInflowrateofapproxImately2.5tImes
themInuteventIlatIon,whereasthefreshgasInflowratesrequIredfor8Csystemsare
somewhathIgher.
9J
ThefollowIngsummarIzestherelatIveeffIcIencyofdIfferent|aplesonsystemswIth
respecttopreventIonofrebreathIng,durIngspontaneousventIlatIon:A0/F/EC/8.
0urIngcontrolledventIlatIon,0/F/E8/CA.
91,9J
The|aplesonA,8,andCsystemsare
rarelyusedtoday,butthe0,E,Fsystemsarecommonlyemployed.ntheUnItedStates,
themostpopularrepresentatIvefromthe0,E,andFgroupIsthe8aIncIrcuIt,andItwIll
bedIscussedInthenextsectIon.
Bain Circuit
The8aIncIrcuItIsacoaxIalcIrcuItandamodIfIcatIonofthe|apleson0system.Thefresh
gasflowsthroughanarrowInnertubewIthIntheoutercorrugatedtubIng.
96
Thecentral
freshgastubIngenterstheoutercorrugatedhosenearthereservoIrbag,butthefreshgas
actuallyemptIesIntothecIrcuItatthepatIentend(FIg.2628).Exhaledgasesenterthe
corrugatedtubIngandareventedthroughtheexpIratoryvalvenearthereservoIrbag.The
8aIncIrcuItmaybeusedforbothspontaneousandcontrolledventIlatIon.Thefreshgas
InflowratenecessarytopreventrebreathIngIs2.5tImesthemInuteventIlatIon.
The8aIncIrcuIthasmanyadvantagesoverothersystems.tIslIghtweIght,convenIent,
easIlysterIlIzed,andmaybereusable.ScavengIngofthegasesfromtheexpIratoryvalveIs
facIlItatedbecausethevalveIslocatedawayfromthepatIent.ExhaledgasesIntheouter
reservoIrtubIngaddwarmthbycountercurrentheatexchangetoInspIredfreshgases.The
P.672
maInhazardsrelatedtotheuseofthe8aIncIrcuItareeItheranunrecognIzed
dIsconnectIonorkInkIngoftheInnerfreshgashose.TheseproblemscancausehypercarbIa
fromInadequategasfloworIncreasedrespIratoryresIstance.AswIthothercIrcuIts,an
obstructedantImIcrobIalfIlterposItIonedbetweenthe8aIncIrcuItandtheendotracheal
tubecanresultInIncreasedresIstanceInthecIrcuIt,whIchInturnmayproduce
hypoventIlatIonandhypoxemIa,andmayevenmImIcthesIgnsandsymptomsofsevere
bronchospasm.
97
Figure 26-28.The8aIncIrcuIt.(Fedrawnfrom8aInJA,SpoerelWE:AstreamlIned
anaesthetIcsystem.CanAnaesthSocJ1972;19:426,wIthpermIssIon.)
TheoutercorrugatedtubeshouldbetransparenttoallowongoIngInspectIonoftheInner
tube.TheIntegrItyoftheInnertubecanbeassessedasdescrIbedbyPethIck.
98
WIthhIs
technIque,hIghflowoxygenIsfedIntothecIrcuItwhIlethepatIentendIsoccludeduntIl
thereservoIrbagIsfIlled.ThepatIentendIsopened,andoxygenIsflushedIntothecIrcuIt.
ftheInnertubeIsIntact,theventurIeffectoccursatthepatIentend.TheventurI
InduceddecreaseInpressurewIthInthecIrcuItresultsInthereservoIrbagdeflatIng.
Conversely,aleakIntheInnertubeallowsthefreshgastoescapeIntotheexpIratorylImb,
andthereservoIrbagwIllremaInInflated.ThIstestIsrecommendedasapartofthe
preanesthesIacheckIfa8aIncIrcuItIsused.
Circle Breathing Systems
Formanyyears,theoveralldesIgnofthecIrclebreathIngsystemhaschangedverylIttle
fromoneanesthesIaworkstatIonmanufacturertothenext.8oththeIndIvIdualcomponents
andtheorderInwhIchtheyappearedInthecIrclesystemwereconsIstentacrossmajor
platforms.|orerecently,however,wIththeIncreasIngtechnologIcalcomplexItyofthe
anesthesIaworkstatIon,thecIrclesystemhasgonethroughsomemajorchangesaswell.
ThesechangeshaveresultedInpartfromanefforttoImprovepatIentsafety(asInthe
IntegratIonoffreshgasdecouplIngandInspIratorypressurelImIters),buthavealsoallowed
thedeploymentofnewtechnologIcaladvances.ExamplesofmajornewtechnologIes
Include:(1)areturntotheapplIcatIonofsInglecIrcuItpIstontypeventIlators,and(2)use
ofnewspIrometrydevIcesthatarelocatedattheYconnectorInsteadofatthetradItIonal
locatIonontheexpIratorycIrcuItlImb.ThefollowIngdIscussIonfocusesfIrstonthe
tradItIonalcIrclebreathIngsystem,andthenfollowsabrIefdIscussIonofsomevarIatIons
InthedesIgnsofnewercIrclesystems.
The Traditional Circle Breathing System
ThecIrclesystemremaInsthemostpopularbreathIngsystemIntheUnItedStates.tIsso
namedbecauseItscomponentsarearrangedInacIrcularmanner(FIg.267).DneversIon
ofthetradItIonalcIrclesystem,referredtoaseItheraUniversal Forsingle-limb circuit,
hasIncreasedInpopularItyoverrecentyears.AlthoughthesesystemsappearverydIfferent
externally,theyhavethesameoverallfunctIonallayoutasthetradItIonalcIrclesystem
andthefollowIngdIscussIonIsapplIcabletoboththetradItIonalcIrclesystemandthe
UnIversalFsystem.
ThecIrclesystempreventsrebreathIngofCD
2
byuseofCD
2
absorbentsbutallowspartIal
rebreathIngofotherexhaledgases.TheextentofrebreathIngoftheotherexhaledgases
dependsonbreathIngcIrcuItcomponentarrangementandthefreshgasflowrate.AcIrcle
systemcanbesemIopen,semIclosed,orclosed,dependIngontheamountoffreshgas
Inflow.
99
AsemIopensystemhasnorebreathIngandrequIresaveryhIghflowoffreshgas.
AsemIclosedsystemIsassocIatedwIthsomerebreathIngofexhaledgasesandIsthemost
commonlyusedsystemIntheUnItedStates.AclosedsystemIsoneInwhIchtheInflowgas
exactlymatchesthatbeIngtakenup,orconsumed,bythepatIent.naclosedsystem,
thereIscompleterebreathIngofexhaledgasesafterabsorptIonofCD
2
,andtheoverflow
(popofforAPL)valveorventIlatorrelIefvalveremaInsclosed.
ThecIrclesystem(FIg.267)consIstsofsevenprImarycomponents,IncludIng:(1)afresh
gasInflowsource;(2)InspIratoryandexpIratoryunIdIrectIonalvalves;(J)InspIratoryand
expIratorycorrugatedtubes;(4)aYpIececonnector;(5)anoverfloworpopoffvalve,
referredtoastheadjustable pressure-limiting(APL)valve;(6)areservoIrbag;and(7)a
canIstercontaInIngCD
2
absorbent.TheInspIratoryandexpIratoryvalvesareplacedInthe
systemtoensuregasflowthroughthecorrugatedhosesremaInsunIdIrectIonal.Thefresh
gasInflowentersthecIrclebyaconnectIonfromthecommongasoutletoftheanesthesIa
machIne.
NumerousvarIatIonsofthecIrclearrangementarepossIble,dependIngontherelatIve
posItIonsoftheunIdIrectIonalvalves,thepopoffvalve,thereservoIrbag,theCD
2
absorber,andthesIteoffreshgasentry.However,topreventrebreathIngofCD
2
in a
traditional circle system,threerulesmustbefollowed:(1)aunIdIrectIonalvalvemustbe
locatedbetweenthepatIentandthereservoIrbagonboththeInspIratoryandexpIratory
lImbsofthecIrcuIt,(2)thefreshgasInflowcannotenterthecIrcuItbetweenthe
expIratoryvalveandthepatIent,and(J)theoverflow(popoff)valvecannotbelocated
betweenthepatIentandtheInspIratoryvalve.ftheserulesarefollowed,any
arrangementoftheothercomponentswIllpreventrebreathIngofCD
2
.
100
Somenewer
anesthesIaworkstatIonsnowemploylesstradItIonalcIrclebreathIngsystems.Twoofthese
systems(the0atexDhmedaS/5A0UbreathIngsystemandthe0ragerNarkomed6000serIes
andFabIusCSworkstatIonsbreathIngsystem)aredIscussedlaterIngreaterdetaIl(see
AnesthesIaWorkstatIon7arIatIons).
ThemosteffIcIentcIrclesystemarrangementwIththehIghestconservatIonoffreshgases
IsoneInwhIchtheunIdIrectIonalvalvesarenearthepatIentandthepopoffvalveIs
locatedjustdownstreamfromtheexpIratoryvalve.ThIsarrangementmInImIzesdead
spacegasandpreferentIallyelImInatesexhaledalveolargases.AmorepractIcal
arrangement,theoneusedonmostconventIonalanesthesIamachInes(FIg.267),Is
somewhatlesseffIcIentbecauseItallowsalveolaranddeadspacegasestomIxbeforethey
arevented.
101,102
ThemaInadvantagesofthecIrclesystemoverotherbreathIngsystemsIncludeIts(1)
maIntenanceofrelatIvelystableInspIredgasconcentratIons,(2)conservatIonof
respIratorymoIstureandheat,and(J)preventIonofoperatIngroompollutIon.
AddItIonally,thecIrclesystemcanbeusedasasemIclosedsystemorasaclosedsystem
wIthverylowfreshgasflows.ThemajordIsadvantageofthecIrclesystemstemsfromIts
complexdesIgn.Commonly,thecIrclesystemmayhavetenormoredIfferentconnectIons.
ThesemultIpleconnectIonsItessetthestageformIsconnectIons,dIsconnectIons,
obstructIons,andleaks.nanASAClosedClaImsanalysIsofadverseanesthetIcoutcomes
arIsIngfromgasdelIveryequIpment,overonethIrd(25/72)ofmalpractIceclaImsresulted
frombreathIng
P.67J
cIrcuItmIsconnectIonsordIsconnectIons.
10
|alfunctIonofthecIrclesystem'sunIdIrectIonal
valvescanresultInlIfethreatenIngproblems.FebreathIngcanoccurIfthevalvesstIckIn
theopenposItIon,andtotalocclusIonofthecIrcuItcanoccurIftheyarestuckshut.fthe
expIratoryvalveIsstuckIntheclosedposItIon,breathstackIngandbarotraumaor
volutraumacanresult.DbstructedfIlterslocatedIntheexpIratorylImbofthecIrcle
breathIngsystemhavecausedIncreasedaIrwaypressures,hemodynamIccollapse,and
bIlateraltensIonpneumothorax.CausesofcIrclesystemobstructIonandfaIlureInclude
manufacturIngdefects,debrIs,patIentsecretIons,andpartIculateobstructIonfromother
oddsourcessuchasalbuterolnebulIzatIon.
10J,104,105,106
Somesystems,suchasthe0atex
Dhmeda7900Smart7ent,useflowtransducerslocatedonboththeInspIratoryand
expIratorylImbsofthecIrclesystem.nonereport,cracksIntheflowtransducertubIng
usedbythIssystemproducedaleakInthecIrclesystemthatwasdIffIculttodetect.
107
CO
2
Absorbents
ntheearly2000s,therewereseveralreportsofadversechemIcalreactIonsbetweenCD
2
absorbentmaterIalsandanesthetIcagents.SomeoftheseundesIrableInteractIonsare
quItedramatIc,suchassevofluraneInteractIngwIthdesIccated8aralyme,resultIngInfIres
wIthInthebreathIngsystemandseverepatIentInjury.
108,109
Althoughothersourcesof
IgnItIonandfIreInthebreathIngsystemcontInuetobedescrIbed,
110
the8aralyme
sevofluraneproblemIssomewhatunIqueInthatnothIngunusualIsaddedtoorremoved
fromthebreathIngsystemforthIstooccur.DtherreactIonsbetweenagentssuchas
desfluraneorsevofluraneanddesIccatedstrongbaseabsorbentscanproducemore
InsIdIouspatIentmorbIdItyandevendeathfromthereleaseofbyproductssuchascarbon
monoxIdeorcompoundA.
111
AlthoughabsorbentmaterIalsmaybeproblematIc,theystIll
representanImportantcomponentofthecIrclebreathIngsystem.0IfferentanesthesIa
breathIngsystemselImInateCD
2
wIthvaryIngdegreesofeffIcIency.Theclosedand
semIclosedcIrclesystembothrequirethatCD
2
beabsorbedfromtheexhaledgasesto
avoIdhypercapnIa.fonecoulddesIgnanIdealCD
2
absorbent,ItscharacterIstIcswould
IncludelackofreactIvItywIthcommonanesthetIcs,lackoftoxIcIty,lowresIstancetoaIr
flow,lowcost,easeofhandlIng,andeffIcIentInCD
2
absorptIon.
The Absorber Canister
DnmodernanesthesIamachInes,theabsorbercanIsterIscomposedoftwoclearplastIc
canIstersarrangedInserIes(FIg.267).ThecanIsterscanbefIlledwItheItherloosebulk
absorbentorwIthabsorbentsupplIedbythefactoryInprefIlledplastIcdIsposable
cartrIdgescalledprepacks.FreegranulesfrombulkabsorbentcancreateaclInIcally
sIgnIfIcantleakIftheylodgebetweentheclearplastIccanIsterandtheDrInggasketofthe
absorber.LeakshavealsobeencausedbydefectIveprepacks,whIchwerelargerthan
factoryspecIfIcatIons.
112
PrepackscanalsocausetotalobstructIonofthecIrclesystemIf
theclearplastIcshIppIngwrapperIsnotremovedprIortouse.
11J
ThenewestworkstatIons
fromCEHealthcare/0atexDhmedaIncorporateproprIetaryCD
2
absorbentcanIstersthat
allowexchangeofthecanIsterswhIlemaIntaInIngthebreathIngcIrcuItIntegrIty.
Chemistry of Absorbents
ThreeformulatIonsofCD
2
absorbentsarecommonlyavaIlabletoday:sodalIme,8aralyme
(amIxtureofcalcIumhydroxIdeandbarIumhydroxIde),andcalcIumhydroxIdelIme
(Amsorb).Dftheseagents,themostcommonlyusedIssodalIme.AllservetoelImInateCD
2
fromthebreathIngcIrcuItwIthvaryIngdegreesofeffIcIency.
8yweIght,theapproxImatecomposItIonofhIghmoIsturesodalImeIs80calcIum
hydroxIde,15water,4sodIumhydroxIde,and1potassIumhydroxIde(anactIvator).
SmallamountsofsIlIcaareaddedtoproducecalcIumandsodIumsIlIcate.ThIsaddItIon
producesaharderandmorestablepelletandtherebyreducesdustformatIon.The
effIcIencyofthesodalImeabsorptIonvarIesInverselywIththehardness;therefore,lIttle
sIlIcateIsusedIncontemporarysodalIme.SodIumhydroxIdeIsthecatalystfortheCD
2
absorptIvepropertIesofsodalIme.
114,115
8aralymeIsamIxtureofapproxImately20
barIumhydroxIdeand80calcIumhydroxIde.tmayalsocontaInsomepotassIum
hydroxIde.8aralymeIstheprImaryCD
2
absorbentImplIcatedasanagentthatmayproduce
fIresInthebreathIngsystemwhenusedwIthsevoflurane.CalcIumhydroxIdelImeIsoneof
thenewestclInIcallyavaIlableCD
2
absorbents.tconsIstsprImarIlyofcalcIumhydroxIde
andcalcIumchlorIdeandcontaInstwosettIngagents:calcIumsulfateand
polyvInylpyrrolIdone.ThelattertwoagentsservetoenhancethehardnessandporosItyof
theagent.
116
ThemostsIgnIfIcantadvantageofcalcIumhydroxIdelImeoverotheragents
IsItslackofthestrongbases,sodIumandpotassIumhydroxIde.Theabsenceofthese
chemIcalselImInatestheundesIrableproductIonofcarbonmonoxIde,thenephrotoxIc
substanceknownascompound A,andmayreduceorelImInatethepossIbIlItyofafIreIn
thebreathIngcIrcuIt.
117
ThemostsIgnIfIcantdIsadvantagesofcalcIumhydroxIdelImeare
(1)lessabsorptIvecapacItyabout50lessthanstrongbasecontaInIngabsorbents,and(2)
generallyhIghercostperunItthanotherabsorbents.
118,119
ThesIzeoftheactualabsorptIvegranuleshasbeendetermInedovertImebytrIaland
error.ThecurrentsIzepartIclesrepresentacompromIsebetweenresIstancetoaIrflow
andabsorptIveeffIcIency.
120
ThesmallerthegranulesIze,thegreaterthesurfacearea
thatIsavaIlableforabsorptIon.However,aspartIclesIzedecreases,aIrflowresIstance
Increases.ThegranularsIzeofsodalImeand8aralymeusedInclInIcalpractIceIsbetween
4and8mesh,asIzeatwhIchabsorptIvesurfaceareaandresIstancetoflowareoptImIzed.
|eshsIzereferstothenumberofopenIngsperlInearInchInasIevethroughwhIchthe
granularpartIclescanpass.A4meshscreenmeansthattherearefourquarterInch
openIngsperlInearInch.LIkewIse,an8meshscreenhaseIghtperlInearInch.
114
TheabsorptIonofCD
2
byabsorbentssuchassodalImeoccursbyaserIesofchemIcal
reactIons;ItIsnotaphysIcalprocesslIkesoakIngwaterIntoasponge.CD
2
combIneswIth
watertoformcarbonIcacId.CarbonIcacIdreactswIththehydroxIdestoformsodIum(or
potassIum)carbonateandwater.CalcIumhydroxIdeacceptsthecarbonatetoformcalcIum
carbonateandsodIum(orpotassIum)hydroxIde.TheequatIonsareasfollows:
1. CD
2
+H
2
DH
2
CD
J
2. H
2
CD
J
+2NaDH(KDH)Na
2
CD
J
(K
2
CD
J
)+2H
2
D+Heat
J. Na
2
CD
J
(K
2
CD
J
)+Ca(DH)
2
CaCD
J
+2NaDH(KDH)
SomeCD
2
mayreactdIrectlywIthCa(DH)
2
,butthIsreactIonIsmuchslower.
ThereactIonwIth8aralymedIffersfromthatofsodalImebecausemorewaterIslIberated
byadIrectreactIonofbarIumhydroxIdeandCD
2
.
1. 8a(DH)
2
+8H
2
D+CD
2
8aCD
J
+9H
2
D+Heat
2. 9H
2
D+9CD
2
9H
2
CD
J
ThenbydIrectreactIonsandbyKDHandNaDH,
J. 9H
2
CD
J
+9Ca(DH)
2
CaCD
J
+18H
2
D+Heat
P.674
Figure 26-29. AandB.EthylvIolet.SeetextfordetaIls.(FeprIntedfromAndrewsJJ,
JohnstonF7Jr,8ee0Eetal:PhotodeactIvatIonofethylvIolet:ApotentIalhazardof
Sodasorb.AnesthesIology1990;72:59,wIthpermIssIon.)
Absorptive Capacity
ThemaxImumamountofCD
2
thatcanbeabsorbedbysodalImeIs26LofCD
2
per100gof
absorbent.TheabsorptIvecapacItyofcalcIumhydroxIdelImeIssIgnIfIcantlyless,andhas
beenreportedat10.2Lper100gofabsorbent.
116,118
However,asprevIouslymentIoned,
absorptIvecapacItyIstheproductofbothavaIlablechemIcalreactIvItyandphysIcal
(granule)avaIlabIlIty.AstheabsorbentgranulesstackupIntheabsorbercanIsters,small
passagewaysInevItablyform.ThesesmallpassageschannelgasespreferentIallythrough
lowresIstanceareas.8ecauseofthIsphenomenon,functIonalabsorptIvecapacItyofeIther
sodalImeorcalcIumhydroxIdelImemaybesubstantIallydecreased.npractIce,because
ofchannelIng,theeffIcIencyofsodalImemaybereducedtoallowonly10to20Lorlessof
CD
2
toactuallybeabsorbedper100gofabsorbent.
121
Indicators
EthylvIoletIsthepHIndIcatoraddedtobothsodalImeand8aralymetohelpassessthe
functIonalIntegrItyoftheabsorbent.ThIscompoundIsasubstItutedtrIphenylmethanedye
wIthacrItIcalpHof10.J.
115
EthylvIoletchangesfromcolorlesstovIoletIncolorwhenthe
pHoftheabsorbentdecreasesasaresultofCD
2
absorptIon.WhentheabsorbentIsfresh,
thepHexceedsthecrItIcalpHoftheIndIcatordye,andItexIstsInItscolorlessform(FIg.
2629A).However,asabsorbentbecomesexhausted,thepHdecreasesbelow10.J,and
ethylvIoletchangestoItsvIoletform(FIg.26298)becauseofalcoholdehydratIon.ThIs
changeIncolorIndIcatestheabsorptIvecapacItyofthematerIalhasbeenconsumed.
Unfortunately,InsomecIrcumstancesethylvIoletmaynotalwaysbearelIableIndIcatorof
thefunctIonalstatusofabsorbent.Forexample,prolongedexposureofethylvIoletto
fluorescentlIghtscanproducephotodeactIvatIonofthIsdye.WhenthIsoccurs,the
absorbentappearswhIteeventhoughItmayhaveareducedpHandItsabsorptIvecapacIty
hasbeenexhausted.
122
EvenIntheabsenceofcolorchanges,clInIcalsIgnsthattheCD
2
absorbentIsexhaustedInclude:
1. ncreasedspontaneousrespIratoryrate(onlyrelIablewhennomusclerelaxantIsused)
2. nItIalIncreaseInhemodynamIcs(bloodpressureandheartrate),followedlaterbya
decreaseInboth
J. ncreasedsympathetIcdrIve:skInflushIng,sweatIng,tachyarrhythmIa,hypermetabolIc
state(IncreasedCD
2
productIon;mustruleoutmalIgnanthyperthermIa)
4. FespIratoryacIdosIsonarterIalbloodgasanalysIs
5. ncreasedsurgIcalbleedIngduetobothhypertensIonandcoagulopathy.
Interactions of Inhaled Anesthetics With Absorbents
tIsImportantanddesIrabletohaveCD
2
absorbentsthatneItherreleasetoxIcpartIclesor
fumesnorproducetoxIccompoundswhenexposedtocommonanesthetIcs.SodalImeand
8aralymegenerallyfItthIsdescrIptIon,butInhaledanesthetIcsdoInteractwIthabsorbents
tosomeextent.HIstorIcallyspeakIng,anuncommonanesthetIc,trIchloroethylene,reacts
wIthsodalImetoproducetoxIccompounds.nthepresenceofalkalIandheat,
trIchloroethylenedegradesIntothecerebralneurotoxIndIchloroacetylene,whIchcan
causecranIalnervelesIonsandencephalItIs.Phosgene,apotentpulmonaryIrrItant,Isalso
producedandphosgenecancauseadultrespIratorydIstresssyndrome.
12J
SevofluranehasbeenshowntoproducedegradatIonproductsonInteractIonwIthCD
2
absorbents.
111,124,125
ThemajordegradatIonproductproducedIsanolefIncompound
knownasfluoromethyl2,2dIfluoro1(trIfluoromethyl)vInylether,orcompoundA.0urIng
sevofluraneanesthesIa,factorsapparentlyleadIngtoanIncreaseIntheconcentratIonof
compoundAInclude(1)lowfloworclosedcIrcuItanesthetIctechnIques,(2)theuseof
8aralymeratherthansodalIme,(J)hIgherconcentratIonsofsevofluraneIntheanesthetIc
cIrcuIt,(4)hIgherabsorbenttemperatures,and(5)freshabsorbent.
124,125,126,127
nterestIngly,thedehydratIonof8aralymeIncreasestheconcentratIonofcompoundA,but
thedehydratIonofsodalImedecreasestheconcentratIonofcompoundA.
128,129
Apparently,thedegradatIonproductsreleaseddurIngclInIcalcondItIonsdonotcommonly
resultInadverseeffectsInhumansevendurInglowflowanesthesIa,
127
butfurtherstudIes
areneededtoverIfythIs.
1J0,1J1,1J2
0esIccatedstrongbaseabsorbentscanalsodegradecontemporaryInhaledanesthetIcsto
clInIcallysIgnIfIcantconcentratIonsofcarbonmonoxIde(CD)aswellastrIfluoromethane,
whIchcanInterferewIthanesthetIcgasmonItorIng.
111
UndercertaIncondItIons,thIs
processcanproduceveryhIghcarboxyhemoglobInconcentratIons,reachIngJ5ormore.
1JJ
HIgherlevelsofcarbonmonoxIdearemorelIkelyafterprolongedcontactbetween
absorbentandanesthetIcs,andafterdIsuseofanabsorberforatleast2days,especIally
overaweekend.Thus,casereportsdescrIbIngcarbonmonoxIdepoIsonInghavebeenmost
commonInpatIentsanesthetIzedon|ondaymornIng,presumablybecausecontInuousflow
fromtheanesthesIamachInedehydratedtheabsorbentsovertheweekend.
1J4,1J5
Freshgas
flowratesof5L/mInthroughthebreathIngsystemandabsorbent(wIthoutapatIent
connected)aresuffIcIenttocausecrItIcaldryIngoftheabsorbentmaterIal.0essIcatIonIs
evenworsewhenthebreathIngbagIsleftoffthebreathIngcIrcuIt.Absenceofthe
reservoIrbagfacIlItatesretrogradeflowthroughthecIrclesystem(FIg.26J0).
1JJ
8ecause
theInspIratory
P.675
valveleafletproducessomeresIstancetoflow,thefreshgasflowtakestheretrograde
pathofleastresIstancethroughtheabsorbentandoutthe22mmbreathIngbagmount.
Figure 26-30.The0rager|edIcalNarkomed6000wIthItssInglecIrcuItventIlator.
Thehorizontal arrowIndIcatesthepIstoncylInderunItofthe0Ivan7entIlator.The
vertical arrowIndIcatestherectangularvalvemanIfoldforfreshgasdecouplIng.
SeveralfactorsappeartoIncreasetheproductIonofcarbonmonoxIdeandresultIng
elevatedcarboxyhemoglobInlevels.ThosefactorsInclude(1)theInhaledanesthetIcused
(foragIven|ACmultIple,themagnItudeofCDproductIonfromgreatesttoleastIs
desfluraneenfluraneIsofluranehalothane=sevoflurane);(2)theabsorbentdryness
(completelydryabsorbentproducesmoreCDthanhydratedabsorbent);(J)thetypeof
absorbent(atagIvenwatercontent,8aralymeproducesmoreCDthandoessodalIme);(4)
thetemperature(IncreasedtemperatureIncreasesCDproductIon);(5)theanesthetIc
concentratIon(moreCDIsproducedfromhIgheranesthetIcconcentratIons)
1J6
;(6)low
freshgasflowrates;and(7)reducedexperImentalanImal(patIent)sIze
111,1J7
per100gof
absorbent.
SeveralInterventIonshavebeensuggestedtoreducetheIncIdenceofcarbonmonoxIde
exposureInhumansundergoInggeneralanesthesIa.
1J5
TheseInterventIonsInclude(1)
educatInganesthesIapersonnelregardIngtheetIologyofCDproductIon,(2)turnIngoffthe
anesthesIamachIneattheconclusIonofthelastcaseofthedaytoelImInatefreshgasflow
thatdrIestheabsorbent,(J)changIngCD
2
absorbentIffreshgaswasfoundflowIngdurIng
themornIngmachInecheck,(4)rehydratIngdesIccatedabsorbentbyaddIngwatertothe
absorbent,
118
(5)changIngthechemIcalcomposItIonofsodalImetoreduceorelImInate
potassIumhydroxIde(suchproductsnowavaIlableInclude0ragersorb800plus,SofnolIme,
andSpherasorb),and(6)usIngabsorbentmaterIalssuchascalcIumhydroxIdelImethatare
freeofbothsodIumandpotassIumhydroxIdes.TheelImInatIonofsodIumandpotassIum
hydroxIdesfromdesIccatedsodalImedImInIshesorelImInatesdegradatIonofdesfluraneto
carbonmonoxIdeandsevofluranetocompoundA,butdoesnotcompromIseCD
2
absorptIon.
117,1J8
8ecauseoftheIncreasIngevIdencethatexposureofvolatIleanesthetIcs
todesIccatedCD
2
absorbents,theAPSFconvenedIn2005aconferenceentItled,Carbon
0IoxIdeAbsorbent0esIccatIon:APSFConferenceonSafetyConsIderatIons.Theconsensus
statementfollowIngthIsconferenceIncludedtwobroadrecommendatIons:1)theuseof
CD
2
absorbentsthat,whenexposedtovolatIleanesthetIcs,donotresultInsIgnIfIcant
degradatIon;and(2)thatInstItutIonshaveInplacepolIcIesthataddresspreventIonofCD
2
desIccatIonIfconventIonalCD
2
absorbentsareused.ncIrcumstanceswhereabsorbents
thatdegradevolatIleanesthetIcsareused(suchasthestrongbaseabsorbents),theAPSF
conferenceexpertsagreedwIththefollowIngrecommendatIons:1)turnoffallgasflow
whenthemachIneIsnotInuse,2)changeabsorbentsregularly(on|ondaymornIngs,as
theabsorbentmayhavebecomedesIccatedovertheweekend),J)changeabsorbent
wheneverthecolorchangeIndIcatesexhaustIon,4)change8DTHcanIstersInatwo
canIstersystem,5)changeabsorbentwheneverthefreshgasflowhasbeenleftonforan
extensIveorIndetermInateperIodoftIme,and6)IfcompactcanIstersareused,consIder
changIngthemmorefrequently.
1J9
Dneextremelyrare,butpotentIallylIfethreatenIng,complIcatIonrelatedtoCD
2
absorbentuseIsthedevelopmentoffIreswIthInthebreathIngsystem.SpecIfIcally,thIs
canoccurastheresultofInteractIonsbetweenthestrongbaseabsorbents(partIcularly
8aralyme)andtheInhaledanesthetIc,sevoflurane.nAugust200J,AbbottLaboratorIes
changedthepackageInsertforsevofluranetodescrIbethIsrarephenomenonandthe
condItIonsunderwhIchItcouldoccur.Almost1yearlater,Inthefallof2004,severalcase
reportsdescrIbIngpatIentInjurIesrelatedtothIsproblemwerepublIshed(allInvolvIng
8aralyme).tseemsthatwhendesIccatedstrongbaseabsorbentsareexposedto
sevoflurane,absorbertemperaturesofseveralhundreddegreesmayresultfromtheIr
InteractIon.
109
ThebuIldupofveryhIghtemperatures,theformatIonofcombustIble
degradatIonbyproducts(formaldehyde,methanol,andformIcacId),plustheoxygenor
nItrousoxIdeenrIchedenvIronmentprovIdeallthesubstratesnecessaryforafIreto
occur.
111
AvoIdanceoftheuseofthecombInatIonofsevofluranewIthstrongbase
absorbents,partIcularly8aralyme,especIallyIfIthasbecomedesIccated,Isthebestway
topreventthIsunusualandpotentIallylIfethreatenIngcomplIcatIon.
Anesthesia Ventilators
TheventIlatoronthemodernanesthesIaworkstatIonservesasamechanIzedsubstItutefor
themanualsqueezIngofthereservoIrbagofthecIrclesystem,the8aIncIrcuIt,oranother
breathIngsystem.Asrecentlyasthelate1980s,anesthesIaventIlatorsweremereadjuncts
totheanesthesIamachIne.Today,InneweranesthesIaworkstatIons,theyhaveattaIneda
promInentcentralrole.naddItIontothenearubIquItousroleoftheanesthesIaventIlator
Intoday'sanesthesIaworkstatIon,manyadvancedIntensIvecareunItstyleventIlatIon
featureshavealsobeenIntegratedIntoanesthesIaventIlators(FIg.26J0).Althoughmany
sImIlarItIesexIstbetweentoday'sanesthesIaventIlatorandIntensIvecareunItventIlator,
somefundamentaldIfferencesInventIlatIonparametersandcontrolsystemsstIllremaIn.
ThIsdIscussIonfocusesontheclassIfIcatIon,operatIngprIncIples,andhazardsassocIated
wIthcontemporaryanesthesIaventIlators.
Classification
7entIlatorscanbeclassIfIedaccordIngtotheIrpowersource,drIvemechanIsm,cyclIng
mechanIsm,andbellowstype.
140,141
Power Source
ThepowersourcerequIredtooperateamechanIcalventIlatorIsprovIdedbycompressed
gas,electrIcIty,orboth.DlderpneumatIcventIlatorsrequIredonlyapneumatIcpower
sourcetofunctIonproperly.ContemporaryelectronIcventIlatorsfrom0rager|edIcal,
0atexDhmeda,andothercompanIesrequIreeItheranelectrIcalonlyorbothanelectrIcal
andapneumatIcpowersource.
Drive Mechanism and Circuit Designation
0oublecIrcuItventIlators(InwhIchonecIrcuItcontaInspatIentgasandtheothercIrcuIt
contaInsdrIvegas)areused
P.676
mostcommonlyonmodernanesthesIaworkstatIons.Cenerally,theseconventIonal
ventIlatorsarepneumatIcallydrIven.nadoublecIrcuItventIlator,adrIvIngforcesuchas
pressurIzedgascompressesacomponentanalogoustothereservoIrbagknownasthe
ventilator bellows.ThebellowsthenInturndelIverventIlatIontothepatIent.ThedrIvIng
gasInthe0atexDhmeda7000,7810,7100,and7900Is100oxygen.ntheNorthAmerIcan
0ragerA7EandA72+,aventurIdevIcemIxesoxygenandaIr.SomenewerpneumatIc
anesthesIaworkstatIonshavetheabIlItyfortheusertoselectwhethercompressedaIror
oxygenIsusedasthedrIvInggas.
nrecentyears,wIththeIntroductIonofcIrclebreathIngsystemsthatIntegratefreshgas
decouplIng,resurgencehasbeenseenIntheutIlIzatIonofmechanIcallydrIvenanesthesIa
ventIlators.ThesepIstontypeventIlatorsuseacomputercontrolledsteppermotor
InsteadofcompresseddrIvegastoactuategasmovementInthebreathIngsystem.nthese
systems,ratherthanhavIngdualcIrcuIts,asInglepatIentgascIrcuItIspresent.Thus,they
areclassIfIedaspIstondrIven,sInglecIrcuItventIlators.ThepIstonoperatesmuchlIkethe
plungerofasyrIngetodelIverthedesIredtIdalvolumeoraIrwaypressuretothepatIent.
SophIstIcatedcomputerIzedcontrolsareabletoprovIdeadvancedtypesofventIlatory
supportsuchassynchronIzedIntermIttentmandatoryventIlatIon,pressurecontrolled
ventIlatIon,andpressuresupportassIstedventIlatIon,InaddItIontotheconventIonal
controlmodeventIlatIon.8ecausethepatIent'smechanIcalbreathIsdelIveredwIthoutthe
useofcompressedgastoactuateabellows,thesesystemsconsumedramatIcallyless
compressedgasdurIngventIlatoroperatIonthantradItIonalpneumatIcventIlators.ThIs
ImprovementIneffIcIencymayhaveclInIcalsIgnIfIcancewhentheanesthesIaworkstatIon
IsusedInasettIngwherenopIpelInegassupplyIsavaIlable(e.g.,remotelocatIonsor
offIcebasedanesthesIapractIces).
Cycling Mechanism
|ostanesthesIamachIneventIlatorsaretImecycledandprovIdeventIlatorsupportInthe
controlmode.nspIratoryphaseIsInItIatedbyatImIngdevIce.DlderpneumatIc
ventIlatorsuseafluIdIctImIngdevIce.ContemporaryelectronIcventIlatorsuseasolId
stateelectronIctImIngdevIceandarethusclassIfIedastImecycledandelectronIcally
controlled.|oreadvancedventIlatIonmodessuchassynchronIzedIntermIttentmandatory
ventIlatIon,pressurecontrolledventIlatIon,andmodesthatuseapressuresupportoptIon
mayhaveanadjustablethresholdpressuretrIggeraswell.nthesemodes,pressuresensors
provIdefeedbacktotheventIlatorcontrolsystemtoallowIttodetermInewhentoInItIate
and/ortermInatetherespIratorycycle.
Bellows Classification
ThedIrectIonofbellowsmovementdurIngtheexpIratoryphasedetermInesthebellows
classIfIcatIon.Ascending (standing) bellowsascenddurIngtheexpIratoryphase(FIg.26
J18),whereasdescending (hanging) bellowsdescenddurIngtheexpIratoryphase.Dlder
pneumatIcventIlatorsandsomenewanesthesIaworkstatIonsuseweIghteddescendIng
bellows,whIlemostcontemporaryelectronIcventIlatorshaveanascendIngbellowsdesIgn.
DfthetwoconfIguratIons,theascendIngbellowsIsgenerallythoughttobesafer.An
ascendIngbellowswIllnotfIllIfatotaldIsconnectIonoccurs.However,thebellowsofa
descendIngbellowsventIlatorwIllcontInueItsupwardanddownwardmovementdespItea
patIentdIsconnectIon.ThedrIvInggaspushesthebellowsupwarddurIngtheInspIratory
phase.0urIngtheexpIratoryphase,roomaIrIsentraInedIntothebreathIngsystematthe
sIteofthedIsconnectIonbecausegravItyactsontheweIghtedbellows.ThedIsconnectIon
pressuremonItorandthevolumemonItormaybefooledevenIfadIsconnectIonIs
complete.
40
SomecontemporaryanesthesIaworkstatIondesIgnshavereturnedtothe
descendIngbellowstoIntegratefreshgasdecouplIng(0rager|edIcalJulIanand0atascope
Anestar).AnessentIalsafetyfeatureonanyanesthesIaworkstatIonthatusesadescendIng
bellowsIsanIntegratedCD
2
apneaalarmthatcannotbedIsabledwhIletheventIlatorIsIn
use.
Operating Principles of Ascending Bellows Ventilators
ContemporaryexamplesofascendIngbellows,doublecIrcuIt,electronIcventIlatorsInclude
the0rager|edIcalA7E,A72+,the0atexDhmeda7000,7800,and7900serIes.AgenerIc
ascendIngbellowsventIlatorIsIllustratedInFIgure26J1.tmaybevIewedasabreathIng
bag(bellows)locatedwIthInaclearplastIcbox.ThebellowsphysIcallyseparatesthe
drIvInggascIrcuItfromthepatIentgascIrcuIt.ThedrIvInggascIrcuItIslocatedoutsIde
thebellows,andthepatIentgascIrcuItIsInsIdethebellows.0urIngtheInspIratoryphase
(FIg.26J1A,left)thedrIvInggasentersthebellowschamber,causIngthepressurewIthIn
IttoIncrease.ThIsIncreaseInpressureIsresponsIblefortwoevents.FIrst,theventIlator
relIefvalvecloses,preventInganesthetIcgasfromescapIngIntothescavengIngsystem.
Second,thebellowsIscompressed,andtheanesthetIcgaswIthInthebellowsIsdelIvered
tothepatIent'slungs.ThIscompressIonactIonIsanalogoustothehandofthe
anesthesIologIstsqueezIngthebreathIngbag.
52
0urIngtheexpIratoryphase(FIg.26J18),thedrIvInggasexItsthebellowshousIng.ThIs
producesadroptoatmospherIcpressurewIthInboththebellowshousIngandthepIlotlIne
totheventIlatorrelIefvalve.ThedecreaseInpressuretotheventIlatorrelIefvalvecauses
themushroomvalveportIonoftheassemblytoopen.ExhaledpatIentgasesrefIllthe
bellowsbeforeanyscavengIngcanbegIn.ThebellowsrefIllfIrstbecauseaweIghtedball
(lIkethoseusedInballtypeposItIveendexpIratorypressure[PEEP]valves)orsImIlar
devIceIsIncorporatedIntothebaseoftheventIlatorrelIefvalve.ThIsballproduces2toJ
cmwaterofbackpressure;therefore,scavengIngoccursonlyafterthebellowsfIlls
completelyandthepressureInsIdethebellowsexceedsthepressurethresholdoftheball
valve.ThIsdesIgncausesallascendIngbellowsventIlatorstoproduce2toJcmwater
pressureofPEEPwIthInthebreathIngcIrcuItwhentheventIlatorIsInuse.ScavengIng
occursonlydurIngtheexpIratoryphase,astheventIlatorrelIefvalveIsopenonlydurIng
expIratIon.
52
tIsImportanttounderstandthatonmostanesthesIaworkstatIons,gasflowfromthe
anesthesIamachIneIntothebreathIngcIrcuItIscontInuousandIndependentofventIlator
actIvIty.0urIngtheInspIratoryphaseofmechanIcalventIlatIon,theventIlatorrelIefvalve
Isclosed(FIg.26J1A),andthebreathIngsystem'sAPLorpopoffvalveIsmostcommonly
outofcIrcuIt.Therefore,thepatIent'slungsreceIvethevolumefromthebellowsplusthat
fromtheflowmetersdurIngtheInspIratoryphase.FactorsthatInfluencethecorrelatIon
betweensettIdalvolumeandexhaledtIdalvolumeIncludetheflowmetersettIngs,the
InspIratorytIme,thecomplIanceofthebreathIngcIrcuIt,externalleakage,andthe
locatIonofthetIdalvolumesensor.Usually,thevolumegaInedfromtheflowmetersdurIng
InspIratIonIscounteractedbythevolumelosttocomplIanceofthebreathIngcIrcuIt,and
settIdalvolumegenerallyapproxImatestheexhaledtIdalvolume.However,certaIn
condItIonssuchasInapproprIateactIvatIonoftheoxygenflushvalvedurIngtheInspIratory
phasecanresultInbarotraumaand/orvolutraumabecauseexcesspressureandvolume
maynotbeabletobeventedfromthecIrclesystem.
52
Problems and Hazards
NumeroushazardsareassocIatedwIthanesthesIaventIlators.TheseIncludeproblemswIth
thebreathIngcIrcuIt,thebellowsassembly,andthecontrolassembly.
P.677
Figure 26-31.nspIratory(A)andexpIratory(B)phasesofgasflowInatradItIonal
cIrclesystemwIthanascendIngbellowsventIlator.ThebellowsphysIcallyseparates
thedrIvInggascIrcuItfromthepatIentgascIrcuIt.ThedrIvInggascIrcuItIslocated
outsIdethebellowsandthepatIentgascIrcuItIsInsIdethebellows.0urIngInspIratory
phase(A),thedrIvInggasentersthebellowschamber,causIngthepressurewIthInItto
Increase.ThIscausestheventIlatorrelIefvalvetoclose,preventInganesthetIcgas
fromescapIngIntothescavengIngsystemandthebellowstocompress,delIverIng
anesthetIcgaswIthInthebellowstothepatIent'slungs.0urIngexpIratoryphase(B),
pressurewIthInthebellowschamberandthepIlotlInedecreasestozero,causIngthe
mushroomportIonoftheventIlatorrelIefvalvetoopen.CasexhaledbythepatIent
refIllsthebellowsbeforeanyscavengIngoccursbecauseaweIghtedballIs
IncorporatedIntothebaseoftheventIlatorrelIefvalve.ScavengIngoccursonlydurIng
theexpIratoryphasebecausetheventIlatorrelIefvalveIsopenonlydurIngexpIratIon.
(FeprIntedfromAndrewsJJ:TheCIrcleSystem.ACollectIonofJ0ColorllustratIons.
WashIngton,0C,LIbraryofCongress,1998,wIthpermIssIon.)
Traditional Circle System Problems
8reathIngcIrcuItmIsconnectIonsanddIsconnectIonarealeadIngcauseofcrItIcalIncIdents
InanesthesIa.
10,142
ThemostcommondIsconnectIonsIteIsattheYpIece.0IsconnectIons
canbecompleteorpartIal(leaks).nthepast,acommonsourceofleakswItholder
absorberswasfaIluretoclosetheAPLorpopoffvalveonInItIatIonofmechanIcal
ventIlatIon.Dntoday'sanesthesIaworkstatIons,thebag/ventIlatorselectorswItchhas
vIrtuallyelImInatedthIsproblem,astheAPLvalveIsusuallyoutofcIrcuItwhenthe
ventIlatormodeIsselected.PreexIstIngundetectedleakscanexIstIncompressed,
corrugated,dIsposableanesthetIccIrcuIts.TodetectsuchaleakpreoperatIvely,thecIrcuIt
mustbefullyexpandedbeforethecIrcuItIscheckedforleaks.
14J
AsprevIouslymentIoned,
dIsconnectIonsandleaksmanIfestmorereadIlywIththeascendIngbellowsventIlator
systemsbecausetheyresultInasItuatIonInwhIchthebellowswIllnotrefIll.
40
SeveraldIsconnectIonmonItorsexIst,althoughnoneshouldreplacevIgIlance.|onItorIngof
breathsoundsandobservatIonofchestwallexcursIonshouldcontInuedespIteuseofboth
mechanIcal(spIrometersandpressuresensors)andphysIologIcmonItors.
PneumatIcandelectronIcpressuremonItorsarehelpfulIndIagnosIngdIsconnectIons.
FactorsthatInfluencemonItoreffectIvenessIncludethedIsconnectIonsIte,thepressure
sensorlocatIon,thethresholdpressurealarmlImIt,theInspIratoryflowrate,andthe
resIstanceofthedIsconnectedbreathIngcIrcuIt.
144,145
7arIousanesthesIaworkstatIonsand
ventIlatorshavedIfferentlocatIonsfortheaIrwaypressuresensoranddIfferentvaluesfor
thethresholdpressurealarmlImIt.ThethresholdpressurealarmlImItmaybepresetatthe
factoryoradjustable.AnaudIbleorvIsualalarmIsactuatedIfthepeakInspIratory
pressureofthebreathIngcIrcuItdoesnotexceedthethresholdpressurealarmlImIt.When
anadjustablethresholdpressurealarmlImItIsavaIlable,suchasonmanyworkstatIons
from0rager|edIcal,theoperatorshouldsetthepressurealarmlImIttowIthIn5cmwater
ofthepeakInspIratorypressure.Dnsystemsthathaveanautosetfeature,when
actIvated,thethresholdlImItIsautomatIcallysetatJto5cmwaterpressurebelowthe
currentpeakInspIratorypressure.Dnsuchsystems,faIluretoresetthethresholdpressure
alarmlImItmayresultIneItheranApneaPressureorThresholdLowalert.FIgure26J2
IllustrateshowapartIaldIsconnectIon(leak)maybeunrecognIzedbythelowpressure
P.678
monItorIfthethresholdpressurealarmlImItIssettooloworIfthefactorypresetvalueIs
relatIvelylow.
Figure 26-32.ThresholdpressurealarmlImIt.Top.ThethresholdpressurealarmlImIt
(dotted line)hasbeensetapproprIately.AnalarmIsactuatedwhenapartIal
dIsconnectIonoccurs(arrow)becausethethresholdpressurealarmlImItIsnot
exceededbythebreathIngcIrcuItpressure.Bottom.ApartIaldIsconnectIonIs
unrecognIzedbythepressuremonItorbecausethethresholdpressurealarmlImIthas
beensettoolow.(Fedrawnfrom8aromed8reathIngPressure|onItor:Dperator's
nstructIon|anual.Telford,PA,NorthAmerIcan0rager,August1986,wIthpermIssIon.)
FespIratoryvolumemonItorsareusefulIndetectIngdIsconnectIons.7olumemonItorsmay
senseexhaledtIdalvolume,InhaledtIdalvolume,mInutevolume,orallthree.Theuser
shouldbracketthehIghandlowthresholdvolumesslIghtlyaboveandbelowtheexhaled
volumes.Forexample,IftheexhaledmInutevolumeofapatIentIs10L/mIn,reasonable
alarmlImItswouldbe8to12L/mIn.|anyoftheolder0atexDhmedaventIlatorsare
equIppedwIthvolumemonItorsensorsthatuseInfraredlIght/turbInetechnology.These
volumesensorsareusuallylocatedIntheexpIratorylImbofthebreathIngcIrcuItandthus
measureexhaledtIdalvolume.nthecaseofthe0atexDhmedaS/5A0U,aspecIal
attachmentknownasthe0lItespIrometryconnectorIsplacedInthebreathIngcIrcuIt.
ThIsdevIceIsactuallyplacedatornearthelevelofthepatIentconnectIonandpermIts
measurementofbothInhaledandexhaledvolumesandpressures(seeAnesthesIa
WorkstatIon7arIatIons).WIththeolderInfraredtypesensors,exposuretoadIrectbeam
oflIghtfromtheoverheadsurgIcallIghtIngcouldcauseerroneousvolumereadIngsasthe
surgIcalbeamInterferedwIththeInfraredsensor.
146
DthertypesofexpIratoryvolume
sensorscanbeseenInsystemssuchasthe0atexDhmedaAestIva,AespIre,andother
workstatIonsthatIncorporatethe7100ventIlatoror7900Smart7ent.Thesesystems
generallyusedIfferentIalpressuretransductIontechnologytodetermIneInhaledand
exhaledvolumesandtomeasureaIrwaypressures.The0rager|edIcalNarkomed6000
serIes,28,andFabIusCSworkstatIonscommonlyuseanultrasonIcflowsensorlocatedon
theexpIratorylImb.StIllothersystemsfrom0ragermeasureexhaledvolumeusInghot
wIresensortechnology.WIththIstypeofsensor,atInyarrayoftwoplatInumwIresIs
electrIcallyheatedtoahIghtemperature.AsgasflowspasttheheatedwIres,theytendto
becooled.TheamountofenergyrequIredtomaIntaInthetemperatureofthewIreIs
proportIonaltothevolumeofgasflowIngpastIt.ThIssystem,however,hasbeen
assocIatedInatleastonereportofaccIdentalfIreInthebreathIngcIrcuIt.
110
CD
2
monItorsareprobablythebestdevIcesforrevealIngpatIentdIsconnectIons.CD
2
concentratIonIsmeasuredneartheYpIeceeItherdIrectly(maInstream)orbyaspIratIonof
agassampletotheInstrument(sIdestream).EItherasuddenchangeInthedIfferences
betweentheInspIratoryandendtIdalCD
2
concentratIonsortheacuteabsenceof
measuredCD
2
IndIcatesadIsconnectIon,anonventIlatedpatIent,orotherproblems.
40
mportantly,anabsenceofexhaledCD
2
canbeanIndIcatIonofabsentcardIacoutput
ratherthanamechanIcalequIpmentproblem.
|IsconnectIonsofthebreathIngsystemareunfortunatelyrelatIvelycommon.0espItethe
effortsofstandardscommItteestoelImInatethIsproblembyassIgnIngdIfferentdIameters
tovarIoushosesandhosetermInals,theycontInuetooccur.AnesthesIaworkstatIons,
breathIngsystems,ventIlators,andscavengIngsystemsIncorporatemanyofthese
dIameterspecIfIcconnectIons.TheabIlItyofanesthesIaprovIderstooutwItthese
foolproofsystemshasledtovarIoushosesbeIngcleverlyadaptedorforcefullyfIttedto
InapproprIatetermInalsandeventovarIousothersolIdcylIndrIcallyshapedprotrusIonsof
theanesthesIamachIne.
40
DcclusIon(obstructIon)ofthebreathIngcIrcuItmayoccur.Trachealtubescanbecome
kInked.HosesthroughoutthebreathIngcIrcuItaresubjecttoocclusIonbyInternal
obstructIonorexternalmechanIcalforces,whIchcanImpIngeonflowandhavesevere
consequences.Forexample,blockageofabacterIalfIlterIntheexpIratorylImbofthe
cIrclesystemhasresultedInbIlateraltensIonpneumothorax.
104
ncorrectInsertIonofflow
dIrectIonsensItIvecomponentscanresultInanoflowstate.
40
Examplesofthese
componentsIncludesomePEEPvalvesandcascadehumIdIfIers.0ependIngonthelocatIon
oftheocclusIonrelatIvetothepressuresensor,ahIghpressurealarmmay(ormaynot)
alertpractItIonerstotheproblem.
ExcessInflowtothebreathIngcIrcuItfromtheanesthesIamachInedurIngtheInspIratory
phasecancausebarotrauma.ThebestexampleofthIsphenomenonIsoxygenflushIng.
ExcessvolumecannotbeventedfromthesystemdurIngInspIratIonbecausetheventIlator
relIefvalveIsclosedandtheAPLvalveIsoutofcIrcuIt.
52
AhIghpressurealarm,If
present,maybeactIvatedwhenthepressurebecomesexcessIve.WIthmany0rager
|edIcalsystems,bothaudIbleandvIsualalarmsareactuatedwhenthehIghpressure
thresholdIsexceeded.nthe|odulusPlusSystem,the0atexDhmeda7810ventIlator
automatIcallyswItchesfromtheInspIratorytotheexpIratoryphasewhentheadjustable
peakpressurethresholdIsexceeded.
DnworkstatIonsequIppedwIthadjustableInspIratorypressurelImIterssuchasthe0atex
DhmedaS/5A0U,AestIva,andAIsys,and0rager|edIcal'sNarkomed6000serIes,28,2C,
CS,FabIusCS,andApollo,maxImalInspIratorypressuremaybesetbytheusertoa
desIredpeakaIrwaypressure.AnadjustablepressurerelIefvalvewIllopenwhenthe
predetermIneduserselectedpressureIsreached.ThIstheoretIcallypreventsgeneratIonof
excessIveaIrwaypressure.Unfortunately,thIsfeaturedependsontheuserhavIngpreset
theapproprIatepopoffpressure.fthesettIngIstoolow,InsuffIcIentpressurefor
ventIlatIonmaybegenerated,resultIngInInadequatemInuteventIlatIon;IfsettoohIgh,
theexcessIveaIrwaypressuremaystIlloccur,resultIngInbarotrauma.ThepIstondrIven
FabIusCS,aswellasothers,mayalsoIncludeafactorypresetInspIratorypressuresafety
valvethatopensatapresetaIrwaypressuresuchas75cmofwaterpressuretomInImIze
therIskofbarotrauma.ThesestrategIesmayreducetherIskofbarotraumaand
volutrauma;however,theyarenosubstItuteforvIgIlance.
Bellows Assembly Problems
LeakscanoccurInthebellowsassembly.mproperseatIngoftheplastIcbellowshousIng
canresultInInadequateventIlatIon
P.679
becauseaportIonofthedrIvInggasIsventedtotheatmosphere.AholeInthebellowscan
leadtoalveolarhyperInflatIonandpossIblybarotraumaInsomeventIlatorsbecausehIgh
pressuredrIvInggascanenterthepatIentcIrcuIt.TheoxygenconcentratIonofthepatIent
gasmayIncreasewhenthedrIvInggasIs100oxygen,orItmaydecreaseIfthedrIvInggas
IscomposedofanaIroxygenmIxture.
147
TheventIlatorrelIefvalvecancauseproblems.HypoventIlatIonoccursIfthevalveIs
IncompetentbecausetheanesthetIcgasesaredelIveredtothescavengIngsystemdurIng
theInspIratoryphaseInsteadoftothepatIent.CasmoleculespreferentIallyexItIntothe
scavengIngsystembecauseItrepresentsthepathofleastresIstance,andthepressure
wIthInthescavengIngsystemcanbesubatmospherIc.7entIlatorrelIefvalveIncompetency
canresultfromadIsconnectedpIlotlIne,arupturedvalve,orfromadamagedflapper
valve.
148,149
AventIlatorrelIefvalvestuckIntheclosedorpartIallyclosedposItIoncan
produceeItherbarotraumaorundesIredPEEP.
150
ExcessIvesuctIonfromthescavengIng
systemcandrawtheventIlatorrelIefvalvetoItsseatandclosethevalvedurIngboththe
InspIratoryandexpIratoryphases.
40
nthIscase,breathIngcIrcuItpressureescalates
becauseexcessanesthetIcgascannotbevented.tIsworthwhIletonotethatdurIng
expIratoryphase,somenewermachInesfrom0atexDhmeda(S/5A0U,7100and7900
Smart7ent)scavengebothexcesspatIentgasesandtheexhaustedventIlatordrIvegas.
ThatIs,whentheventIlatorrelIefvalveopens,andwasteanesthetIcgasesarevented
fromthebreathIngcIrcuIt,thedrIvegasfromthebellowshousIngjoInswIthIttoenterthe
scavengIngsystem.UndercertaIncondItIons,thelargevolumeofexhaustedgasescould
overwhelmthescavengIngsystem,resultIngInpollutIonoftheoperatIngroomwIthwaste
anesthetIcgases(seeScavengIngSystems).DthermechanIcalproblemsthatcanoccur
IncludeleakswIthInthesystem,faultypressureregulators,andfaultyvalves.UnlIkely
problemssuchasanoccludedmuffleronthe0ragerA7EventIlatorcanresultIn
barotrauma.nthIscase,obstructIonofdrIvInggasoutflowclosestheventIlatorrelIef
valve,andexcesspatIentgascannotbevented.
151
Control Assembly and Power Supply Problems
ThecontrolassemblycanbethesourceofbothelectrIcalandmechanIcalproblems.
ElectrIcalfaIlurecanbetotalorpartIal;theformerIsthemoreobvIous.AsanesthesIa
workstatIonsarebecomIngmoredependentonIntegratedcomputercontrolledsystems,
powerInterruptIonsbecomemoresIgnIfIcant.8atterybackupsystemsaredesIgnedto
contInueoperatIonofessentIalelectronIcsdurIngbrIef(uptoseveralhours)outages.
However,evenwIththesesystems,IntheeventofafaIlure,sometImemayberequIredto
rebootafteranelectrIcaloutagehasoccurred.0urIngthIstImetheavaIlabIlItyofcertaIn
workstatIonfeaturessuchasmanualormechanIcalventIlatIoncanbevarIable.Dnecluster
ofelectrIcalfaIluresthatcouldhavepotentIallyresultedInoperatIngroomfIreswas
reportedearlyonafterthereleaseofthe0rager|edIcalNarkomed6000.ProblemswIth
theworkstatIon'spowersupplyprIntedcIrcuItboardspromptedacorrectIverecallactIon
InNovember2002.
152
Anesthesia Workstation Variations
TheneedforadaptatIonofcurrenttechnologytosuccessfullyallowItsIntegratIonInto
exIstIngsystemsoftencomeswIththeIntroductIonofnewtechnology.DtherwIse,amore
comprehensIveredesIgnofanentIreanesthesIasystemfromthegroundupcouldbe
necessary.DnesuchexampleofadaptatIonIntheanesthesIaworkstatIoncanbeseenwIth
twonewdesIgnvarIatIonsofthecIrclebreathIngsystem.ThefIrstoftheseIsfoundonthe
0atexDhmedaS/5A0U,andthesecondIsIncorporatedIntothe0ragerNarkomed6000
serIesandFabIusCSworkstatIons.8ecauseuseofthecIrclesystemIsfundamentaltothe
daytodaypractIceformostanesthesIologIsts,acomprehensIveunderstandIngofthese
newsystemsIscrucIalfortheIrsafeuse.
The Datex-Ohmeda S/5 Anesthesia Delivery Unit and Aisys
The0atexDhmedaS/5A0UdebutedastheAS/JA0UIn1998.AlongwIthItsmore
comprehensIvesafetyfeaturesandIntegrateddesIgnthatelImInatedglassflowtubesand
conventIonalanesthesIavaporIzersInexchangeforacomputerscreenwIthdIgItalfresh
gasflowscalesandthebuIltInAladInCassettevaporIzersystem,themachInehada
radIcallydIfferentappearanceIngeneral.tIsnotuntIlcloserInspectIonthattheother
unIquepropertIesoftheA0UbegIntostandout.TheprIncIpaldIfferenceInthecIrcle
systemoftheA0UlIesIntheIncorporatIonofthespecIalIzed0lIteflowandpressure
transducerfIttIngIntothecIrcleattheleveloftheYconnector.The0lItespIrometry
modulewasredesIgnedtoaccommodatelowflowanesthesIaandIscurrentlyadesIgn
featureoftheCEHealthcare/0atexDhmedaAIsysworkstatIon.DnmosttradItIonalcIrcle
systems,exhaledtIdalvolumeIsmeasuredbyaspIrometrysensorlocatedInproxImItyto
theexpIratoryvalve.Theplacementofthe0lItefIttIngattheYconnectorprovIdesa
betterlocatIontoperformexhaledvolumemeasurement,allowsaIrwaygascomposItIon
andpressuremonItorIngtobedonewIthasIngleadapterInsteadofwIthmultIplefIttIngs
addedtothebreathIngcIrcuIt,andItprovIdestheabIlItytoassessbothInspIratoryand
expIratorygasflowandthereforegeneratIonofcompleteflowvolumespIrometry.The
relocatIonofthespIrometersensortotheYconnectoralsomakesItpossIbletomovethe
locatIonofthefreshgasInlettothepatIentsIdeoftheInspIratoryvalvewIthout
adverselyaffectIngaccuracyofexhaledtIdalvolumemeasurement.Dntheotherhand,
placementofthe0lItesensornearthepatIentaddsbulkandweIghttothebreathIng
cIrcuItandmayInterferewIthmaskventIlatIon.
ThIsatypIcalcIrclesystemarrangementwIththefreshgasenterIngonthepatIentsIdeof
theInspIratoryvalveIsadvantageousforseveralreasons.tIslIkelytobemoreeffIcIentIn
delIverIngfreshgastothepatIent,whIlepreferentIallyelImInatIngexhaledgases.
mportantly,ItIsalsolesslIkelytocausedesIccatIonoftheCD
2
absorbent(see
nteractIonsofnhaledAnesthetIcswIthAbsorbents).DthernotablechangesontheS/5
A0UcIrclesystemIncludeacompactproprIetaryCD
2
absorbentcanIsterdesIgnthatcanbe
changeddurIngventIlatIonwIthoutlossofcIrclesystemIntegrItyandtherelocatIonofthe
InspIratoryandexpIratoryunIdIrectIonalvalvesfromahorIzontalposItIontoavertIcal
posItIononthecompactblockassemblyjustbelowtheabsorbentcanIster.The
reorIentatIonoftheunIdIrectIonalvalvesreducesthebreathIngcIrcuItresIstance
encounteredbyaspontaneouslyventIlatedpatIent.ThevertIcallyorIentedunIdIrectIonal
valvesonlyhavetobetIppedawayfromthevertIcalposItIontobeopened,unlIke
conventIonalhorIzontalvalvedIscs,whIchhavetobephysIcallylIftedoffthevalveseat
agaInstgravItytobeopened.nthelatestworkstatIon,theAIsys,theInspIratoryand
expIratorycheckvalvesareposItIonedhorIzontally,butthecIrclesystemarrangementIn
whIchfreshgasentersthecIrcuItdownstreamfromtheInspIratoryvalveIsretaIned.
The Drger Medical Narkomed 6000 Series, Fabius GS and
Apollo Workstations
SeveralImportantdIfferencesexIstbetweenthetradItIonalcIrclebreathIngsystemsofthe
newest0ragerproducts.AtfIrst
P.680
glance,themostnotabledIfferencelIesIntheappearanceanddesIgnoftheventIlators
usedwIththesesystems.FromtheInconspIcuoushorIzontallymounted0IvanpIston
ventIlatoroftheNarkomed6000tothevertIcallymountedandvIsIblepIstonventIlatorof
theFabIusCSwIthItsabsentflowtubesandglowIngelectronIcfreshgasflowIndIcators,
thesesystemsappeardrastIcallydIfferentfromtradItIonalanesthesIasystems.ThepIston
ventIlatorsofthe0ragerNarkomed6000(0IvanventIlator)andFabIusSerIes(E7ent
ventIlator)anesthesIasystemsareclassIfIedaselectrIcallypowered,pIstondrIven,sIngle
cIrcuIt,electronIcallycontrolledwIthfreshgasdecouplIng.TheventIlatorfoundonthe
ApolloworkstatIon,theE7entplus,IsanelectrIcallydrIvenandelectronIcallycontrolled,
freshgasdecoupled,hIghspeedpIstonventIlatorthatrequIresnodrIvegas(unlIkethe
tradItIonalbellowsventIlators).TheE7entplusventIlatoroffersmodesofventIlatIon
prevIouslyfoundonlyInIntensIvecareunIts:synchronIzedvolumemodewIthadjustable
flowtrIggerandpressuresupport.
Figure 26-33.nspIratory(A)andexpIratory(B)phaseofgasflowsofa0rager
Narkomed6000typecIrclesystemwIthpIstonventIlatorandfreshgasdecouplIng.NPF
valve,negatIvepressurerelIefvalve.SeetextfordetaIls.(FeprIntedfrom8rockwell
FC:NewCIrcleSystem0esIgns.AcollectIonoffIguresprIvatelypublIshedIn
8IrmIngham,AL,200J,wIthpermIssIon.)
ThecIrclebreathIngsystemsusedbythese0ragerworkstatIonsIncorporateafeature
knownasfresh gas decoupling(FC0).TheIncorporatIonofthIspatIentsafetyenhancIng
technologyhasrequIredasIgnIfIcantredesIgnofthetradItIonalcIrclesystem.AfunctIonal
schematIcofacIrclesystemsImIlartotheoneusedbythe0ragerNarkomed6000serIes
durIngbothInspIratoryandexpIratoryphaseofmechanIcalventIlatIoncanbeseenIn
FIgure26JJ,Aand8.TounderstandtheoperatIngprIncIplesofFC0,ItIsImportantto
haveagoodunderstandIngofgasflowsInatradItIonalcIrclesystembothdurIng
InspIratoryandexpIratoryphasesofmechanIcalventIlatIon.AcompletedIscussIonofthIs
waspresentedearlIerInthesectIonDperatIngPrIncIplesofAscendIng8ellows
7entIlators.
ThekeyconceptofthefreshgasdecoupledbreathIngsystemcanbeIllustrateddurIngthe
InspIratoryphaseofmechanIcalventIlatIon.WIththetradItIonalcIrclesystem,several
eventsareoccurrIng(FIg.26JJA):(1)contInuousfreshgasflowfromtheflowmeters
and/ortheoxygenflushvalveIsenterIngthecIrclesystematthefreshgasInlet,(2)the
ventIlatorIsdelIverIngtheprescrIbedtIdalvolumetothepatIent'slungs,and(J)the
ventIlatorrelIefvalve(ventIlatorexhaustvalve)Isclosed,sonogasIsescapIngthecIrcle
systemexceptIntothepatIent'slungs.
15J
natradItIonalcIrclesystem,whentheseevents
coIncIdeandfreshgasInflowIscoupleddIrectlyIntothecIrclesystem,thetotalvolume
delIveredtothepatIent'slungsIsthesumofthevolumedelIveredbytheventIlator,plus
thevolumeofgasthatentersthecIrclevIathefreshgasInlet.ncontrast,whenFC0Is
used,durIngtheInspIratoryphase(FIg.26JJA)thefreshgascomIngfromtheanesthesIa
workstatIonvIathefreshgasInletIsdIvertedIntothereservoIrbagbyadecouplIngvalve
thatIslocatedbetweenthefreshgassourceandtheventIlatorcIrcuIt.ThereservoIr
(breathIng)bagservesasanaccumulatorforfreshgasuntIltheexpIratoryphasebegIns.
0urIngexpIratoryphase(FIg.26JJ8),thedecouplIngvalveopens,allowIngthe
accumulatedfreshgasInthereservoIrbagtobedrawnIntothecIrclesystemtorefIllthe
pIstonventIlatorchamberordescendIng
P.681
bellows.8ecausetheventIlatorexhaustvalvealsoopensdurIngexpIratoryphase,excess
freshgasandexhaledpatIentgasesareallowedtoescapetothescavengIngsystem.
CurrentfreshgasdecoupledsystemsaredesIgnedwItheItherpIstontypeordescendIng
bellowstypeventIlators.8ecausethebellowsIneItherofthesetypeofsystemsrefIlls
underslIghtnegatIvepressure,ItallowstheaccumulatedfreshgasfromthereservoIrbag
tobedrawnIntotheventIlatorfordelIverytothepatIentdurIngthenextventIlatorcycle.
8ecauseofthIsdesIgnrequIrement,ItIsunlIkelythatfreshgasdecouplIng,asdescrIbed
here,canbeusedwIthconventIonalascendIngbellowsventIlators,whIchrefIllunderslIght
posItIvepressure.
ThemostsIgnIfIcantadvantageofcIrclesystemsusIngFC0IsdecreasedrIskofbarotrauma
andvolutrauma.WIthatradItIonalcIrclesystem,IncreasesInfreshgasflowfromthe
flowmetersorfromInapproprIateuseoftheoxygenflushvalvemaycontrIbutedIrectlyto
tIdalvolume,whIchIfexcessIve,mayresultInpneumothoraxorotherInjury.8ecause
systemswIthFC0IsolatefreshgascomIngIntothesystemfromthepatIentwhIlethe
ventIlatorexhaustvalveIsclosed,therIskofbarotraumaIsgreatlyreduced.
|odernventIlatorscompensateforthefreshgasflowastIdalvolumeIsdelIvered.Thus,
delIveredtIdalvolumedoesnotchangeasafunctIonoffreshgasflow.ThIscompensatIon
IsachIevedeItherbyfreshgasdecouplIng(Inthe0rager6000serIes,ApolloandFabIus
machInes)orbyfreshgascompensatIonIntheCEHealthcare/0atexDmedamachInes.
PossIblythegreatestdIsadvantagetothenewanesthesIacIrclesystemsthatuseFC0Isthe
possIbIlItyofentraInIngroomaIrIntothepatIentgascIrcuIt.AsprevIouslydIscussed,Ina
freshgasdecoupledsystemthebellowsorpIstonrefIllsunderslIghtnegatIvepressure.f
thevolumeofgascontaInedInthereservoIrbagvolumeplusthereturnIngvolumeofgas
exhaledfromthepatIent'slungsIsInadequatetorefIllthebellowsorpIston,negatIve
patIentaIrwaypressurescoulddevelop.TopreventthIs,anegatIvepressurerelIefvalveIs
placedInthebreathIngsystem(FIg.26JJ,Aand8).fbreathIngsystempressurefalls
belowapresetvaluesuchas2cmH
2
Dpressure,thentherelIefvalveopensandambIent
aIrIsentraInedIntothepatIentgascIrcuIt.fthIsgoesundetected,theentraIned
atmospherIcgasescouldleadtodIlutIonofeItherorboththeInhaledanesthetIcagentsor
theenrIchedoxygenmIxture(resultIngInalowerIngoftheenrIchedoxygenconcentratIon
toward21).funnotIced,thIsdIlutIonofpatIentgasescouldleadtoeItherIntraoperatIve
awarenessorhypoxIa.HIghprIorItyalarmswIthbothaudIbleandvIsualalertsshouldnotIfy
theuserthatfreshgasflowIsInadequateandroomaIrIsbeIngentraIned.
AnotherpotentIalproblemwIthanFC0systemsuchasseenontheNarkomed6000serIes
lIesInItsrelIanceonthereservoIrbagtoaccumulatetheIncomIngfreshgas.fthe
reservoIrbagIsremoveddurIngmechanIcalventIlatIon,orIfIthasasIgnIfIcantleakfrom
poorfItonthebagmountoraperforatIon,roomaIrmayenterthebreathIngcIrcuItasthe
ventIlatorpIstonunItrefIllsdurIngexpIratoryphase.ThIsmayalsoresultIndIlutIonof
eItherorboththeInhaledanesthetIcagentsoranenrIchedoxygenmIxture,potentIally
resultIngInawarenessdurInganesthesIaorhypoxIa.Furthermore,thIstypeofadIsruptIon
couldleadtosIgnIfIcantpollutIonoftheoperatIngroomwIthanesthetIcgasesasfresh
gaseswouldbeallowedtoescapeIntotheatmosphere.DtherFC0desIgns,suchasthose
seenInthe0rager|edIcalFabIusCSandtherecentlyreleasedApolloanesthesIasystems
donotusethebreathIngbagasthefreshgasreservoIr,butInsteadhaveanalternate
locatIonforfreshgasaccumulatIondurIngtheInspIratoryphase.
Scavenging Systems
ScavengIngIsthecollectIonandthesubsequentremovalofwasteanesthetIcgasesfrom
theoperatIngroom.
154
nmostcases,theamountofgasusedtoanesthetIzeapatIentfora
gIvenanesthetIcfarexceedsthemInImalamountneeded.Therefore,scavengIngmInImIzes
operatIngroompollutIonbyremovIngthIsexcessofgases.n1977,theNatIonalnstItute
forDccupatIonalSafetyandHealth(NDSH)preparedadocumententItledCrIterIafora
FecommendedStandard:DccupatIonalExposuretoWasteAnesthetIcCasesand7apors.
155
AlthoughItwasmaIntaInedthatamInImalsafelevelofexposurecouldnotbedefIned,the
NDSHproceededtoIssuetherecommendatIonsshownInTable266.
155
tshouldbe
rememberedthatthe2partspermIllIonceIlIngforvolatIleanesthetIcswasestablIshedIn
1977,beforedesfluraneandsevofluranewereIntroducedIntoclInIcalpractIce.However,
thIslImItIslIkelytobeapplIcableforthenewervolatIleanesthetIcs.
156
n1991theAST|
releasedtheAST|F1J4J91standardentItledStandardSpecIfIcatIonforAnesthetIc
EquIpmentScavengIngSystemsforAnesthetIcCases.
157
ThedocumentprovIded
guIdelInesfordevIcesthatsafelyandeffectIvelyscavengewasteanesthetIcgasesto
reduce
P.682
contamInatIonInanesthetIzIngareas.
157
8ecauseoflackofsafetydataonexposuretothe
newhalogenatedanesthetIcagents(Isoflurane,desfluraneandsevoflurane),NDSHhas
requestedcommentsandInformatIonrelevanttotheevaluatIonofhealthrIsksassocIated
wIthoccupatIonalexposuretotheseagents,InordertoestablIshrecommendedexposure
levels.
158
n1999,theASATaskForceonTraceAnesthetIcCasesdevelopedabooklet
entItledWaste Anesthetic Gases: Information for Management in Anesthetizing Areas and
the Postanesthesia Care Unit.ThIspublIcatIonaddressesanalysIsofthelIterature,therole
ofregulatoryagencIes,scavengIngandmonItorIngequIpment,andrecommendatIons.
159
Table 26-6 Niosh Recommendations for Trace GAS Level
a
ANESTHETCCAS |AX|U|TWA
b
CDNCENTFATDN(ppm)
Halogenatedagentalone 2
NItrousoxIde 25
CombInatIonofhalogenatedagent
plusnItrousoxIde:
Halogenatedagent 0.5
NItrousoxIde 25
0entalfacIlItIes(nItrousoxIdealone) 50
NDSH,NatIonalnstItuteforDccupatIonalSafetyandHealth.
a
Note:0espItebeIngInclInIcaluseforover15years,Isoflurane,desflurane,and
sevofluranehavenotbeentestedformaxImumrecommendedtracegaslevels(see
text).
b
TWA,tImeweIghtedaverage.TImeweIghtedaveragesamplIng,alsoknownas
tImeIntegratedsamplIng,IsasamplIngmethodthatevaluatestheaverage
concentratIonofanesthetIcgasoveraprolongedperIodoftIme,suchas1to8
hours.
FeprIntedfromU.S.0epartmentofHealth,EducatIon,andWelfare:CrIterIafora
recommendedstandard:DccupatIonalexposuretowasteanesthetIcgasesand
vapors.WashIngton0C,US0epartmentofHealthEducatIonEWelfare,|arch
1977,wIthpermIssIon.
Figure 26-34.ComponentsofascavengIngsystem.APL,adjustablepressurelImItIng
valve.
ThetwomajorcausesofwastegascontamInatIonIntheoperatIngroomaretheanesthetIc
technIqueemployedandequIpmentIssues.
159,160
FegardIngtheanesthetIctechnIque,the
followIngfactorscauseoperatIngroomcontamInatIon:(1)faIluretoturnoffgasflow
controlvalvesattheendofananesthetIc;(2)poorlyfIttIngmasks,flushIngthecIrcuIt;(J)
fIllInganesthetIcvaporIzers;(4)useofuncuffedendotrachealtubes;and(5)useof
breathIngcIrcuItssuchastheJacksonFees,whIcharedIffIculttoscavenge.EquIpment
faIlureorlackofunderstandIngofproperequIpmentusecanalsocontrIbutetooperatIng
roomcontamInatIon.LeakscanoccurInthehIghpressurehoses,thenItrousoxIdetank
mountIng,thehIghpressurecIrcuItandlowpressurecIrcuItoftheanesthesIamachIne,or
InthecIrclesystem,partIcularlyattheCD
2
absorberassembly.TheanesthesIaprovIder
mustbecertaInthatthescavengIngsystemIsoperatIonalandadjustedproperlytoensure
adequatescavengIng.fsIdestreamCD
2
ormultIgasanalyzersareused,theanalyzedgas
(wIthdrawnfromthecIrcuItatarateof50to250mL/mIn)mustbedIrectedtothe
scavengIngsystemorreturnedtothebreathIngsystemtopreventpollutIonofthe
operatIngroom.
159,160
Components
ScavengIngsystemsgenerallyhavefIvecomponents(FIg.26J4):(1)thegascollectIng
assembly,(2)thetransfermeans,(J)thescavengIngInterface,(4)thegasdIsposal
assemblytubIng,and(5)anactIveorpassIvegasdIsposalassembly.
155
AnactIvesystem
usesacentralevacuatIonsystemtoelImInatewastegases.TheweIghtorpressureofthe
wastegasItselfproducesflowthroughapassIvesystem.
Gas-Collecting Assembly
ThegascollectIngassemblycapturesexcessanesthetIcgasanddelIversIttothetransfer
tubIng.
140
WasteanesthetIcgasesareventedfromtheanesthesIasystemeItherthrough
theAPLvalveorthroughtheventIlatorrelIefvalve.AllexcesspatIentgasIseIthervented
Intotheroom(e.g.,fromapoorfacemaskfItorendotrachealtubeleak)orexItsthe
breathIngsystemthroughoneofthesevalves.CaspassIngthroughthesevalves
accumulatesInthegascollectIngassemblyandIsdIrectedtothetransfermeans.nsome
newer0atexDhmedasystemssuchastheS5/A0UandothersthatIncorporateeItherthe
7100or7900ventIlators,theventIlatordrIvegasIsalsoexhaustedIntothescavengIng
system.Thus,ItIsImportanttorecognIzethatundercondItIonsofhIghfreshgasflowsand
hIghmInuteventIlatIon,thegasesflowIngIntothescavengIngInterfacemayoverwhelm
theevacuatIonsystem.fthIsoccurs,wasteanesthetIcgasesmayoverflowthesystemvIa
theposItIvepressurerelIefvalve(closedsystems)orthroughtheatmospherIcvents(open
systems),pollutIngtheoperatIngroom.ncontrast,mostotherpneumatIcventIlatorsfrom
both0atexDhmedaand0ragerexhausttheIrdrIvegas(100oxygenoroxygen/aIrmIxture)
IntotheoperatIngroomthroughasmallventonthebackoftheventIlatorcontrolhousIng.
Transfer Means
ThetransfermeanscarrIesexcessgasfromthegascollectIngassemblytothescavengIng
Interface.ThetubIngmustbeeIther19orJ0mm,asspecIfIedbytheAST|F1J4J91
standard.
157
ThetubIngshouldbesuffIcIentlyrIgIdtopreventkInkIng,andasshortas
possIbletomInImIzethechanceofocclusIon.Somemanufacturerscolorcodethetransfer
tubIngwIthyellowbandstodIstInguIshItfrom22mmbreathIngsystemtubIng.|any
machIneshaveseparatetransfertubesfortheAPLvalveandfortheventIlatorrelIef
valve.ThetwotubesfrequentlymergeIntoasInglehosebeforetheyenterthescavengIng
Interface.DcclusIonofthetransfermeanscanbepartIcularlyproblematIcbecauseItIs
upstreamfromthepressurebufferIngfeaturesofthescavengIngInterface.fthetransfer
meansIsoccluded,baselInebreathIngcIrcuItpressurewIllIncrease,andbarotraumacan
occur.
P.68J
Scavenging Interface
ThescavengIngInterfaceIsthemostImportantcomponentofthesystembecauseIt
protectsthebreathIngcIrcuItorventIlatorfromexcessIveposItIveornegatIvepressure.
154
TheInterfaceshouldlImItthepressuresImmedIatelydownstreamfromthegascollectIng
assemblytobetween0.5and+10cmwaterwIthnormalworkIngcondItIons.
157
PosItIve
pressurerelIefIsmandatory,IrrespectIveofthetypeofdIsposalsystemused,tovent
excessgasIncaseofocclusIondownstreamfromtheInterface.fthedIsposalsystemIsan
actIvesystem,negatIvepressurerelIefIsnecessarytoprotectthebreathIngcIrcuItor
ventIlatorfromexcessIvesubatmospherIcpressure.AreservoIrIshIghlydesIrablewIth
actIvesystemsasItstoreswastegasesuntIltheevacuatIonsystemcanremovethem.
nterfacescanbeopenorclosed,dependIngonthemethodusedtoprovIdeposItIveand
negatIvepressurerelIef.
154
Open Interfaces
AnopenInterfacecontaInsnovalvesandIsopentotheatmosphere,allowIngbothposItIve
andnegatIvepressurerelIef.DpenInterfacesshouldbeusedonlywIthactIvedIsposal
systemsthatuseacentralevacuatIonsystem.DpenInterfacesrequIreareservoIrbecause
wastegasesareIntermIttentlydIschargedInsurges,whereasflowfromtheevacuatIon
systemIscontInuous.
154
|anycontemporaryanesthesIamachInesareequIppedwIthopenInterfaceslIkethose
shownInFIgure26J5,Aand8.
161
AnopencanIsterprovIdesreservoIrcapacIty.The
canIstervolumeshouldbelargeenoughtoaccommodateavarIetyofwastegasflowrates.
CasentersthesystematthetopofthecanIsterandtravelsthroughanarrowInnertubeto
thecanIsterbase.CasesarestoredInthereservoIrbetweenbreaths.PosItIveandnegatIve
pressurerelIefIsprovIdedbyholesInthetopofthecanIster.TheopenInterfaceshownIn
FIgure26J5AdIfferssomewhatfromtheoneshownInFIgure26J58.Theoperatorcan
regulatethevacuumbyadjustIngthevacuumcontrolvalveshownInFIgure26J58.
161
TheeffIcIencyofanopenInterfacedependsonseveralfactors.Thevacuumflowrateper
mInutemustequalorexceedthemInutevolumeofexcessgasestopreventspIllage.The
volumeofthereservoIrandtheflowcharacterIstIcswIthIntheInterfaceareImportant.
SpIllagewIlloccurIfthevolumeofasIngleexhaledbreathexceedsthecapacItyofthe
reservoIr.TheflowcharacterIstIcsofthesystemareImportantbecausegasleakagecan
occurlongbeforethevolumeofwastegasequalsthereservoIrvolumeIfsIgnIfIcant
turbulenceoccurswIthIntheInterface.
162
Figure 26-35. AandB.TwoopenscavengIngInterfaces.EachrequIresanactIve
dIsposalsystem.APL,adjustablepressurelImItIngvalve.SeetextfordetaIls.(|odIfIed
from0orschJA,0orschSE:ControllIngtracegaslevels,UnderstandIngAnesthesIa
EquIpment,4thedItIon.EdItedby0orschJA,0orschSE.8altImore,WIllIamsEWIlkIns,
1999,p.J55,wIthpermIssIon.)
Closed Interfaces
AclosedInterfacecommunIcateswIththeatmospherethroughvalves.AllclosedInterfaces
musthaveaposItIvepressurerelIefvalvetoventexcesssystempressureIfobstructIon
occursdownstreamfromtheInterface.AnegatIvepressurerelIefvalveIsmandatoryto
protectthebreathIngsystemfromsubatmospherIcpressureIfanactIvedIsposalsystemIs
used.
154
TwotypesofclosedInterfacesarecommercIallyavaIlable.DnehasposItIve
pressurerelIefonly;theotherhasbothposItIveandnegatIvepressurerelIef.EachtypeIs
dIscussedInthefollowIngsectIons.
Positive Pressure Relief Only
ThIsInterfacehasasIngleposItIvepressurerelIefvalveandIsdesIgnedtobeusedonly
wIthpassIvedIsposalsystems(FIg.26J6,left).WastegasenterstheInterfaceatthewaste
gasInlets.TransferofthewastegasfromtheInterfacetothedIsposalsystemrelIesonthe
weIghtorpressureofthewastegasItselfasanegatIvepressureevacuatIonsystemIsnot
used.TheposItIvepressurerelIefvalveopensatapresetvaluesuchas5cmofwaterIfan
obstructIonbetweentheInterfaceandthedIsposalsystemoccurs.
16J
DnthIstypeof
system,areservoIrbagIsnotrequIred.
Positive and Negative Pressure Relief
ThIsInterfacehasaposItIvepressurerelIefvalve,andatleastonenegatIvepressurerelIef
valve,InaddItIontoareservoIrbag.tIsusedwIthactIvedIsposalsystems.FIgure26J6
(right)IsaschematIcofthe0rager|edIcalclosedInterfaceforsuctIonsystems.AvarIable
volumeofwastegasIntermIttentlyenterstheInterfacethroughthewastegasInlets.The
reservoIrIntermIttentlyaccumulatesexcessgasuntIltheevacuatIonsystemelImInatesIt.
TheoperatorshouldadjustthevacuumcontrolvalvesothatthereservoIrbagIsproperly
Inflated(AInFIg.26J6),notoverdIstended(8InFIg.26J6),orcompletelydeflated(CIn
FIg.26J6).CasIsventedtotheatmospherethroughtheposItIvepressurerelIefvalveIf
thesystempressureexceeds+5cmofwater.FoomaIrIsentraInedthroughthenegatIve
pressurerelIefvalveIfthesystempressureIsmorenegatIvethan0.5cmH
2
D.Dnsome
systems,abackupnegatIvepressurerelIefvalveopensat1.8cmH
2
DIftheprImary
negatIvepressurerelIefvalvebecomesoccluded.
TheeffectIvenessofaclosedsystemInpreventIngspIllagedependsontherateofwaste
gasInflow,theevacuatIonflowrate,andthesIzeofthereservoIr.Leakageofwastegases
IntotheatmosphereoccursonlywhenthereservoIrbagbecomesfullyInflatedandthe
pressureIncreasessuffIcIentlytoopentheposItIvepressurerelIefvalve.ncontrast,the
effectIvenessofanopensystemtopreventspIllagedependsnotonlyonthevolumeofthe
reservoIrbutalsoontheflowcharacterIstIcswIthIntheInterface.
162
Gas-Disposal Assembly Conduit
ThegasdIsposalassemblyconduIt(FIg.26J4)conductswastegasfromthescavengIng
InterfacetothegasdIsposalassembly.tshouldbecollapseproofandshouldrun
overhead,IfpossIble,tomInImIzethechancesofaccIdentalocclusIon.
157
Gas-Disposal Assembly
ThegasdIsposalassemblyultImatelyelImInatesexcesswastegas(FIg.26J5).Thereare
twotypesofdIsposalsystems:actIveandpassIve.
ThemostcommonmethodofgasdIsposalIstheactIveassembly,whIchusesacentral
evacuatIonsystem.AvacuumpumpservesasthemechanIcalflowInducIngdevIcethat
removesthewastegasesusuallytotheoutsIdeofthebuIldIng.
P.684
AnInterfacewIthanegatIvepressurerelIefvalveIsmandatorybecausethepressure
wIthInthesystemIsnegatIve.AreservoIrIsverydesIrable,andthelargerthereservoIr,
thelowerthesuctIonflowrateneeded.
154,162
Figure 26-36.ClosedscavengIngInterfaces.Left.nterfaceusedwIthapassIve
dIsposalsystem.Right.nterfaceusedwIthanactIvesystem.SeetextfordetaIls.
(|odIfIedwIthpermIssIon(left)fromScavengernterfaceforAIrCondItIonIng:
nstructIon|anual.Telford,PA,NorthAmerIcan0rager,Dctober1984;(right)from
Narkomed2AAnesthesIaSystem:TechnIcalServIce|anual.Telford,PA.North
AmerIcan0rager,1985.)
ApassIvedIsposalsystemdoesnotuseamechanIcalflowInducIngdevIce.nstead,the
weIghtorpressurefromtheheavIerthanaIranesthetIcgasesproducesflowthroughthe
system.PosItIvepressurerelIefIsmandatory,butnegatIvepressurerelIefandareservoIr
areunnecessary.ExcesswastegasescanbeelImInatedfromthesurgIcalsuIteInanumber
ofways.SomeIncludeventIngthroughthewall,ceIlIng,floor,ortotheroomexhaustgrIll
ofanonrecIrculatIngaIrcondItIonIngsystem.
154,162
Hazards
ScavengIngsystemsmInImIzeoperatIngroompollutIon,yettheyaddcomplexItytothe
anesthesIasystem.AscavengIngsystemfunctIonallyextendstheanesthesIacIrcuItallthe
wayfromtheanesthesIamachInetotheultImatedIsposalsIte.ThIsextensIonIncreases
thepotentIalforproblems.DbstructIonofscavengIngpathwayscancauseexcessIve
posItIvepressureInthebreathIngcIrcuIt,andbarotraumacanoccur.ExcessIvevacuum
applIedtoascavengIngsystemcanresultInundesIrablenegatIvepressureswIthInthe
breathIngsystem.FInally,In2004,anotherunusualproblemthatresultedfromwastegas
scavengIngwasreportedbyAllenandLees.
164
TheyreportedcasesoffIresInengIneerIng
equIpmentroomsthathousethevacuumpumpsusedforwasteanesthetIcgasevacuatIon.
tseemsthatInsomehospItals,wastegasesarenotdIrectlyventedoutsIde,butmaybe
ventedIntomachIneroomsthathaveventsthatopentotheoutsIde.8ecausesomenew
anesthesIamachInessuchasthe0atexDhmedaS5/A0UandAestIva,amongothers,now
alsoscavengeventIlatordrIvegas(whIchIs100oxygenInmostcases)InaddItIontogas
fromthebreathIngsystem,theenvIronmentsInthesemachIneroomsmaybecomehIghly
enrIchedwIthoxygengas.TheresultofthIshasbeentheproductIonoffIresInthesespaces
outsIdetheoperatIngroom.ThesesItesmaycontaInequIpmentormaterIalssuchas
petroleumdIstIllates(pumps/oIl/grease)thatInthepresenceofanoxygenenrIched
atmospherecouldbeexcessIvelycombustIbleandaseverefIrehazard.
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57.Korman8,FIchIe|:ChemIstryofhalothaneenfluranemIxturesapplIedto
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2
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128.EgerE,,onescuP,Laster|J,WeIskopfF8:8aralymedehydratIonIncreasesand
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129.SteffeyEP,Laster|J,onescuPetal:0ehydratIonofbaralymeIncreases
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anesthesIa.AnesthesIology1997;86:12J1
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141.SpearmanC8,SandersHC:|echanIcal7entIlatIon.NewYork,ChurchIll
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faIluresInanesthesIamanagement:consIderatIonsforpreventIonanddetectIon.
14J.FeInhart0J,FrIzF:UndetectedleakIncorrugatedcIrcuIttubIngIncompressed
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145.SleeTA,PavlInEC:FaIlureoflowpressurealarmassocIatedwIthuseofa
humIdIfIer.AnesthesIology1988;69:791
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147.FeeleyTW,8ancroft|L:ProblemswIthmechanIcalventIlators.ntAnesthesIolClIn
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WIlkIns,2007
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ASANewsletter2004;68(10):22
Appendix A
1993 FDA Anesthesia Apparatus Checkout Recommendations
ThIscheckout,orareasonableequIvalent,shouldbeconductedbeforeadmInIstratIonof
anesthesIa.TheserecommendatIonsarevalIdonlyforananesthesIasystemthatconforms
tocurrentandrelevantstandardsandIncludesanascendIngbellowsventIlatorandatleast
thefollowIngmonItors:capnograph,pulseoxImeter,oxygenanalyzer,respIratoryvolume
monItor(spIrometer),andbreathIngsystempressuremonItorwIthhIghandlowpressure
alarms.ThIsIsaguIdelInethatusersareencouragedtomodIfytoaccommodate
dIfferencesInequIpmentdesIgnandvarIatIonsInlocalclInIcalpractIce.Suchlocal
modIfIcatIonsshouldhaveapproprIatepeerrevIew.Usersshouldrefertotheoperator's
manualforthemanufacturer'sspecIfIcproceduresandprecautIons,especIallythe
manufacturer'slowpressureleaktest(step5).
Emergency Ventilation Equipment
*1. Verify Backup Ventilation Equipment is Available and Functioning
High-Pressure System
*2. Check Oxygen Cylinder Supply
a. DpenD
2
cylInderandverIfyatleasthalffull(about1,000psI).
b. ClosecylInder.
*3. Check Central Pipeline Supplies
a. CheckthathosesareconnectedandpIpelInegaugesreadabout50psI.
Low-Pressure System
*4. Check Initial Status of Low-Pressure System
a. CloseflowcontrolvalvesandturnvaporIzersoff.
b. CheckfIlllevelandtIghtenvaporIzers'fIllercaps.
*5. Perform Leak Check of Machine Low-Pressure System
a. 7erIfythatthemachInemasterswItchandflowcontrolvalvesareDFF.
b. AttachsuctIonbulbtocommon(fresh)gasoutlet.
c. SqueezebulbrepeatedlyuntIlfullycollapsed.
d. 7erIfythatbulbstaysfullycollapsedforatleast10seconds.
e. DpenonevaporIzeratatImeandrepeatcanddasabove.
f. FemovesuctIonbulb,andreconnectfreshgashose.
*6. Turn on Machine Master Switch and all other necessary electrical equipment.
*7. Test Flowmeters
a. AdjustflowofallgasesthroughtheIrfullrange,checkIngforsmoothoperatIonof
floatsandundamagedflowtubes.
b. AttempttocreateahypoxIcD
2
/N
2
DmIxtureandverIfycorrectchangesInflowand/or
alarm.
Scavenging System
*8. Adjust and Check Scavenging System
a. EnsureproperconnectIonsbetweenthescavengIngsystemandbothadjustable
pressurelImItIng(APL;popoff)valveandventIlatorrelIefvalve.
b. Adjustwastegasvacuum(IfpossIble).
c. FullyopenAPLvalveandoccludeYpIece.
d. WIthmInImumD
2
flow,allowscavengerreservoIrbagtocollapsecompletelyand
verIfythatabsorberpressuregaugereadsaboutzero.
e. WIththeD
2
flushactIvated,allowthescavengerreservoIrbagtodIstendfully,and
thenverIfythatabsorberpressuregaugereads10cmofH
2
D.
Breathing System
*9. Calibrate O
2
Monitor
a. EnsuremonItorreads21InroomaIr.
b. 7erIfylowD
2
alarmIsenabledandfunctIonIng.
P.688
d. FeInstallsensorIncIrcuItandflushbreathIngsystemwIthD
2
.
e. 7erIfythatmonItornowreads90.
10. Check Initial Status of Breathing System
a. SetselectorswItchto8agmode.
b. CheckthatbreathIngcIrcuItIscomplete,undamaged,andunobstructed.
c. 7erIfythatCD
2
absorbentIsadequate.
d. nstallbreathIngcIrcuItaccessoryequIpment(e.g.,humIdIfIer,posItIveendexpIratory
pressurevalve)tobeuseddurIngthecase.
11. Perform Leak Check of the Breathing System
a. Setallgasflowstozero(ormInImum).
b. CloseAPL(popoff)valveandoccludeYpIece.
c. PressurIzebreathIngsystemtoaboutJ0cmofH
2
DwIthD
2
flush.
d. EnsurethatpressureremaInsfIxedforatleast10seconds.
e. DpenAPL(popoff)valveandensurethatpressuredecreases.
Manual and Automatic Ventilation Systems
12. Test Ventilation Systems and Unidirectional Valves
a. PlaceasecondbreathIngbagonYpIece.
b. SetapproprIateventIlatorparametersfornextpatIent.
c. SwItchtoautomatIcventIlatIon(7entIlator)mode.
d. TurnventIlatorDNandfIllbellowsandbreathIngbagwIthD
2
flush.
e. SetD
2
flowtomInImum,othergasflowstozero.
f. 7erIfythatdurIngInspIratIonbellowsdelIversapproprIatetIdalvolumeandthatdurIng
expIratIonbellowsfIllscompletely.
g. Setfreshgasflowtoabout5L/mIn.
h. 7erIfythattheventIlatorbellowsandsImulatedlungsfIllandemptyapproprIately
wIthoutsustaInedpressureatendexpIratIon.
I. CheckforproperactIonofunIdIrectIonalvalves.
j. ExercIsebreathIngcIrcuItaccessorIestoensureproperfunctIon.
k. TurnventIlatorDFFandswItchtomanualventIlatIon(bag/APL)mode.
l. 7entIlatemanuallyandassureInflatIonanddeflatIonofartIfIcIallungsand
approprIatefeelofsystemresIstanceandcomplIance.
m. FemovesecondbreathIngbagfromYpIece.
Monitors
13. Check, Calibrate, and/or Set Alarm Limits of all Monitors
a. Capnometer
b. Dxygenanalyzer
c. PressuremonItorwIthhIghandlowaIrwaypressurealarms
d. PulseoxImeter
e. FespIratoryvolumemonItor(spIrometer)
Final Position
14. Check Final Status of Machine
a. 7aporIzersoff.
b. APLvalveopen.
c. SelectorswItchto8ag.
d. Allflowmeterstozero(ormInImum).
e. PatIentsuctIonleveladequate.
f. 8reathIngsystemreadytouse.
*fananesthesIaprovIderusesthesamemachIneInsuccessIvecases,thesestepsneednot
berepeatedormaybeabbrevIatedaftertheInItIalcheckout.
Appendix B
Recommendations for Preanesthesia Checkout Procedures
(2008)
SubCommItteeofASACommItteeonEquIpmentandFacIlItIes
TaskForce|embers*
FussellC.8rockwell,|0
Jerry0orsch,|0
Susan0orsch,|0
JamesEIsenkraft,|0
JeffreyFeldman,|0(TaskForceChaIr)
JulIanColdman,|0
P.689
CarolynC.Holland,CFNA,|SN(AANA)
TomC.KrejcIe,|0
SamsunLampotang,Ph0
0onald|artIn,|0(ChaIr,ASACommItteeonEquIpmentEFacIlItIes)
JulIe|Ills(CEHealthcare)
|IchaelA.DlympIo,|0
CerardoTrejo(AmerIcanSocIetyofAnesthesIaTechnIcIansandTechnologIsts,ASATT)
ContrIbutors(ndIvIdualswhohavecontrIbutedInsomefashIonIntheprocessof
developIngthenewcheckoutguIdelInes)
AbeAbramovItch(0atascope)
Charles8Iddle,CFNA,Ph0
FobertClark(0rager|edIcal)
AnnCulp,CFNA,|SN
Chad0rIscoll,CFNA,|HS
AnnCraham(F0A)
|arcJans(0rager|edIcal)
|IchaelWIlkenIng(0rager|edIcal)
WIllIamNorfleet,|0(F0A)
*TaskForce|embersareASAmembersunlessotherwIseIndIcated.
Guidelines for Preanesthesia Checkout Procedures
Background
mproperlycheckInganesthesIaequIpmentprIortousecanleadtopatIentInjuryandhas
alsobeenassocIatedwIthanIncreasedrIskofseverepostoperatIvemorbIdItyand
mortalIty.
1,2
n199JapreanesthesIacheckout(PAC)wasdevelopedandwIdelyacceptedas
anImportantstepIntheprocessofpreparIngtodelIveranesthesIacare.
J
0espItethe
acceptedImportanceofthePAC,avaIlableevIdencesuggeststhatthecurrentversIonIs
neItherwellunderstoodnorrelIablyusedbyanesthesIaprovIders.
4,5,6
Furthermore,
anesthesIadelIverysystemshaveevolvedtothepoIntthatonecheckoutprocedureIsnot
applIcabletoallanesthesIadelIverysystemscurrentlyonthemarket.Forthesereasons,a
newapproachtothePAChasbeendeveloped.ThegoalwastoprovIdeguIdelInes
applIcabletoallanesthesIadelIverysystemssothatIndIvIdualdepartmentscandevelopa
PACthatcanbeperformedconsIstentlyandexpedItIously.
General Considerations
ThefollowIngdocumentIsIntendedtoservenotasaPACItself,butratherasatemplate
fordevelopIngcheckoutproceduresthatareapproprIateforeachIndIvIdualanesthesIa
machInedesIgn.WhenusIngthIstemplatetodevelopacheckoutprocedureforsystems
thatIncorporateautomatedcheckoutfeatures,Itemsthatarenotevaluatedbythe
automatedcheckoutneedtobeIdentIfIed,andsupplementalmanualcheckoutprocedures
Includedasneeded.
SImplybecauseanautomatedcheckoutprocedureexIstsdoesnotmeanItcancompletely
replaceamanualcheckoutprocedureorthatItcanbeperformedsafelywIthoutadequate
traInIngandathoroughunderstandIngofwhattheautomatedcheckoutaccomplIshes.An
automatedcheckoutprocedurecanbeIncompleteand/ormIsleadIng.Forexample,the
leaktestperformedbysomecurrentautomatedcheckoutsdoesnottestforleaksatthe
vaporIzers.Asaresult,aloosevaporIzerfIllercap,oraleakatthevaporIzermount,could
easIlybemIssed.
AnIdeallyautomatedcheckoutprocedureshouldclearlyrevealtotheuserthefunctIons
thatarebeIngchecked,anydefIcIentfunctIonthatIsfound,andrecommendatIonsto
correcttheproblem.0ocumentatIonoftheautomatedcheckoutprocesspreferablyshould
beInamannerthatcanberecordedontheanesthesIarecord.
Dperator'smanuals,whIchaccompanyanesthesIadelIverysystems,IncludeextensIve
recommendatIonsforequIpmentcheckout.AlthoughtheserecommendatIonsarequIte
extensIveandtypIcallynotusedbyanesthesIaprovIders,theyareneverthelessImportant
referencesfordevelopIngmachInespecIfIcandInstItutIonspecIfIccheckoutprocedures.
Personnel Performing the PreAnesthesia Checkout
TheprevIouslyacceptedAnesthesIaApparatusCheckoutFecommendatIonplacedallofthe
responsIbIlItyforpreusecheckoutontheanesthesIaprovIder.SolerelIanceonone
IndIvIdualtocompletethecheckoutprocessmayIncreasethelIkelIhoodthatoneormore
stepswIllbeomIttedorperformedImproperly.ThIsguIdelIneIdentIfIesthoseaspectsof
thePACthatcouldbecompletedbyaqualIfIedanesthesIaand/orbIomedIcaltechnIcIan.
UsIngtechnIcIanstoperformsomeaspectsofthePACmayImprovecomplIancewIththe
PAC.StepscompletedbyatechnIcIanmaybepartofthemornIngpreusecheckorpartof
aprocedureperformedattheendofeachday.CrItIcalcheckoutsteps(e.g.,avaIlabIlItyof
backupventIlatIonequIpment)wIllbenefItfromIntentIonalredundancy(I.e.,havIngmore
thanoneIndIvIdualresponsIbleforcheckIngtheequIpment).Regardless of the level of
training and support by technicians, the anesthesia care provider is ultimately
responsible for proper function of all equipment used to provide anesthesia care.
AdaptatIonofthePACtolocalneeds,assIgnmentofresponsIbIlItyforthecheckout
procedures,andtraInIngaretheresponsIbIlItIesoftheIndIvIdualanesthesIadepartment.
TraInIngproceduresshouldbedocumented.ProperdocumentatIonshouldIncluderecords
ofcompletedcoursework(e.g.amanufacturercourse)orforInhousetraInIng,alIstIngof
thecompetencyItemstaught,andrecordsofsuccessfulcompletIonbytraInees.
P.690
Objectives for a new PAC
DutlInetheessentIalItemsthatneedtobeavaIlableandfunctIonIngproperlyprIorto
delIverIngeveryanesthetIc.
dentIfythefrequencywIthwhIcheachoftheItemsneedstobechecked.
SuggestwhIchItemsmaybecheckedbyaqualIfIedanesthesIatechnIcIan,bIomedIcal
technIcIanoramanufacturercertIfIedservIcetechnIcIan.
Basic Principles
TheanesthesIacareprovIderIsultImatelyresponsIbleforensurIngthattheanesthesIa
equIpmentIssafeandreadyforuse.ThIsresponsIbIlItyIncludesadequatefamIlIarIty
wIththeequIpment,followIngrelevantlocalpolIcIesforperformInganddocumentIng
thePACandbeIngknowledgeableaboutthoseprocedures.
0ependIngonthestaffIngresourcesInapartIcularInstItutIon,anesthesIatechnIcIans
and/orbIomedIcaltechnIcIanscanpartIcIpateInthePAC.8IomedIcaltechnIcIansare
oftentraInedandcertIfIedbymanufacturerstoperformonsItemaIntenanceof
anesthesIadelIverysystemsandthereforecanbeausefulresourceforcompletIng
regularcheckoutprocedures.AnesthesIatechnIcIansarenotcommonlytraInedto
performcheckoutprocedures.nvolvIngtheanesthesIatechnIcIansIsIntendedto
enhancecomplIancewIththePAC.EachdepartmentshoulddecIdewhetherornotthe
avaIlabletechnIcIanscanorshouldbetraInedtoassIstwIthcheckoutprocedures.
FormalcertIfIcatIonbytheAmerIcanSocIetyofAnesthesIaTechnIcIansand
TechnologIstsIsencouragedbutdoesnotnecessarIlyguaranteefamIlIarItywIthcheckout
procedures.
CrItIcalItemswIllbenefItfromredundantcheckstoavoIderrorsandomIssIons.
WhenmorethanonepersonIsresponsIbleforcheckInganItem,allpartIesshould
performthecheckIfIntentIonalredundancyIsdeemedImportant,oreItherpartymay
beacceptable,dependIngontheavaIlableresources.
WhoeverconductsthePACshouldprovIdedocumentatIonofsuccessfulperformance.The
anesthesIaprovIdershouldIncludethIsdocumentatIononthepatIentchart.
WheneverananesthesIamachIneIsmovedtoanewlocatIon,acompletebegInnIngof
thedaycheckoutshouldbeperformed.
AutomatedchecksshouldclearlydIstInguIshthecomponentsofthedelIverysystemthat
arecheckedautomatIcallyfromthosethatrequIremanualcheckout.
deally,thedate,tIme,andoutcomeofthemostrecentcheck(s)shouldberecordedand
theInformatIonmadeaccessIbletotheuser.
SpecIfIcproceduresforpreusecheckoutcannotbeprescrIbedInthIsdocumentasthey
varywIththedelIverysystems.ClInIcIansmustlearnhowtoeffectIvelyperformthe
necessarypreusecheckforeachpIeceofequIpmenttheyuse.
EachdepartmentorhealthcarefacIlItyshouldworkwIththemanufacturer(s)oftheIr
equIpmenttodeveloppreusecheckoutproceduresthatsatIsfyboththefollowIng
guIdelInesandtheneedsofthelocaldepartment.
0efaultsettIngsforventIlators,monItors,andalarmsshouldbecheckedtodetermIneIf
theyareapproprIate.
ThesecheckoutrecommendatIonsareIntendedtoreplacethepreexIstIngF0Aapproved
AnesthesIaApparatusCheckoutFecommendatIons.TheyarenotIntendedtobea
replacementforrequIredpreventIvemaIntenance.
ThePACIsessentIaltosafecarebutshouldnotdelayInItIatIngcareIfthepatIentneeds
aresourgentthattImetakentocompletethePACcouldworsenthepatIent'soutcome.
Guidelines for Developing Institution-Specific Checkout
Procedures Prior to Anesthesia Delivery
TheseguIdelInesdescrIbeabasIcapproachtocheckoutproceduresandratIonalethatwIll
ensurethattheseprIorItIesaresatIsfIed.TheyshouldbeusedtodevelopInstItutIon
specIfIccheckoutproceduresdesIgnedfortheequIpmentandresourcesavaIlable.
(ExamplesofInstItutIonspecIfIcproceduresforcurrentanesthesIadelIverysystemsare
publIshedonthesameWebsIteasthIsdocument.)
Requirements for Safe Delivery of Anesthesia Care
FelIabledelIveryofoxygenatanyapproprIateconcentratIonupto100.
FelIablemeansofposItIvepressureventIlatIon.
8ackupventIlatIonequIpmentavaIlableandfunctIonIng.
ControlledreleaseofposItIvepressurefromthebreathIngcIrcuIt.
AnesthesIavapordelIvery(IfIntendedaspartoftheanesthetIcplan).
AdequatesuctIon.
|eanstoconformtostandardsforpatIentmonItorIng.
7,8
Specific Items
ThefollowIngItemsneedtobecheckedaspartofacompletePAC.TheIntentIstoIdentIfy
whattocheck,therecommendedfrequencyofcheckIng,andtheIndIvIdual(s)whocould
beresponsIblefortheItem.FortheseguIdelInes,theresponsIblepartywouldfallIntoone
offourcategorIes:provIder,technIcIan,technIcIanorprovIder,ortechnIcIanand
provIder.ThedesIgnatIontechnIcIanandprovIdermeansthattheprovIdermustperform
thecheckwhetherornotIthasbeencompletedbyatechnIcIan.tIsnotIntendedtomake
theuseoftechnIcIanchecksmandatory.TheIntentIsnottospecIfyhowanItemneedsto
bechecked,asthespecIfIccheckoutprocedurewIlldependontheequIpmentbeIngused.
Item 1: Verify that auxiliary oxygen cylinder and self-inflating manual ventilation
device are available and functioning.
Frequency:0aIly.
Responsible Parties:ProvIderandtechnIcIan.
P.691
Rationale:FaIluretobeabletoventIlateIsamajorcauseofmorbIdItyandmortalIty
relatedtoanesthesIacare.8ecauseequIpmentfaIlurewIthresultIngInabIlItyto
ventIlatethepatIentcanoccuratanytIme,aselfInflatIngmanualventIlatIondevIce
(e.g.,Ambubag)shouldbepresentateveryanesthetIzInglocatIonforeverycaseand
shouldbecheckedforproperfunctIon.naddItIon,asourceofoxygenseparatefrom
theanesthesIamachIneandpIpelInesupply,specIfIcallyanoxygencylInderwIth
regulatorandameanstoopenthecylIndervalve,shouldbeImmedIatelyavaIlable
andchecked.AftercheckIngthecylInderpressure,ItIsrecommendedthatthemaIn
cylIndervalvebeclosedtoavoIdInadvertentemptyIngofthecylInderthroughaleaky
oropenregulator.
Item 2: Verify patient suction is adequate to clear the airway.
Frequency:PrIortoeachuse.
Rationale:SafeanesthetIccarerequIrestheImmedIateavaIlabIlItyofsuctIontoclear
theaIrwayIfneeded.
Item 3: Turn on anesthesia delivery system and confirm that AC power is available.
Frequency:0aIly
Responsible Parties:ProvIderortechnIcIan
Rationale:AnesthesIadelIverysystemstypIcallyfunctIonwIthbackupbatterypowerIf
ACpowerfaIls.UnlessthepresenceofACpowerIsconfIrmed,thefIrstobvIoussIgnof
powerfaIlurecanbeacompletesystemshutdownwhenthebatterIescannolonger
powerthesystem.|anyanesthesIadelIverysystemshavevIsualIndIcatorsofthe
powersourceshowIngthepresenceofbothACandbatterypower.TheseIndIcators
shouldbecheckedandconnectIonofthepowercordtoafunctIonalACpowersource
shouldbeconfIrmed.0esfluranevaporIzersrequIreelectrIcalpower,and
recommendatIonsforcheckIngpowertothesevaporIzersshouldalsobefollowed.
Item 4: Verify availability of required monitors and check alarms.
Responsible Parties:ProvIderortechnIcIan.
Rationale:StandardsforpatIentmonItorIngdurInganesthesIaareclearlydefIned.
7,8
TheabIlItytoconformtothesestandardsshouldbeconfIrmedforeveryanesthetIc.
ThefIrststepIstovIsuallyverIfythattheapproprIatemonItorIngsupplIes(e.g.,blood
pressurecuffs,oxImetryprobes)areavaIlable.AllmonItorsshouldbeturnedonand
propercompletIonofpowerupselftestsconfIrmed.CIventheImportanceofpulse
oxImetryandcapnographytopatIentsafety,verIfyIngproperfunctIonofthesedevIces
beforeanesthetIzIngthepatIentIsessentIal.CapnometerfunctIoncanbeverIfIedby
exhalIngthroughthebreathIngcIrcuItorgassensortogenerateacapnogram,or
verIfyIngthatthepatIent'sbreathIngeffortsgenerateacapnogrambeforethepatIent
IsanesthetIzed.7IsualandaudIblealarmsIgnalsshouldbegeneratedwhenthIsIs
dIscontInued.PulseoxImeterfunctIon,IncludInganaudIblealarm,canbeverIfIedby
placIngthesensoronafIngerandobservIngforaproperrecordIng.ThepulseoxImeter
alarmcanbetestedbyIntroducIngmotIonartIfactorremovIngthesensor.
AudIblealarmshavealsobeenreconfIrmedasessentIaltopatIentsafetybyAmerIcan
SocIetyofAnesthesIologIsts,AmerIcanAssocIatIonofNurseAnesthetIsts,AnesthesIa
PatIentSafetyFoundatIon,andJoIntCommIssIonontheAccredItatIonofHealthcare
DrganIzatIons(currentlynamedTheJoIntCommIssIon).
PropermonItorfunctIonIngIncludesvIsualandaudIblealarmsIgnalsthatfunctIonas
desIgned.
Item 5: Verify that pressure is adequate on the spare oxygen cylinder mounted on
the anesthesia machine.
Frequency:0aIly
Responsible Parties:ProvIderandtechnIcIan
Rationale:AnesthesIadelIverysystemsrelyonasupplyofoxygenforvarIousmachIne
functIons.AtamInImum,theoxygensupplyIsusedtoprovIdeoxygentothepatIent.
PneumatIcallypoweredventIlatorsalsorelyonagassupply.DxygencylInder(s)should
bemountedontheanesthesIadelIverysystemanddetermInedtohaveanacceptable
mInImumpressure.TheacceptablepressuredependsontheIntendeduse,thedesIgn
oftheanesthesIadelIverysystem,andtheavaIlabIlItyofpIpedoxygen.
TypIcally,anoxygencylInderwIllbeusedIfthecentraloxygensupplyfaIls.
fthecylInderIsIntendedtobetheprImarysourceofoxygen(e.g.,remotesIte
anesthesIa),thenacylIndersupplysuffIcIenttolastfortheentIreanesthetIcIs
requIred.fapneumatIcallypoweredventIlatorthatusesoxygenasItsdrIvInggas
wIllbeused,afullEoxygencylIndermayprovIdeonlyJ0mInutesofoxygen.nthat
case,themaxImumduratIonofoxygensupplycanbeobtaInedfromanoxygen
cylInderIfItIsusedonlytoprovIdefreshgastothepatIentInconjunctIonwIth
manualorspontaneousventIlatIon.|echanIcalventIlatorswIllconsumetheoxygen
supplyIfpneumatIcallypoweredventIlatorsthatrequIreoxygentopowerthe
ventIlatorareused.ElectrIcallypoweredventIlatorsdonotconsumeoxygen,sothe
duratIonofacylIndersupplywIlldependonlyontotalfreshgasflow.
TheoxygencylIndervalveshouldbeclosedafterIthasbeenverIfIedthatadequate
pressureIspresent,unlessthecylInderIstobetheprImarysourceofoxygen(I.e.,If
pIpedoxygenIsnotavaIlable).fthevalveremaInsopenandthepIpelInesupply
shouldfaIl,theoxygencylIndercanbecomedepletedwhIletheanesthesIaprovIder
Isunawareoftheoxygensupplyproblem.DthergassupplycylInders(e.g.,HelIox,
CD
2
,aIr,N
2
D)needtobecheckedonlyIfthatgasIsrequIredtoprovIdeanesthetIc
care.
Item 6: Verify that piped gas pressures are 50 psig.
Frequency:0aIly
Responsible Parties:ProvIderandtechnIcIan
Rationale:AmInImumgassupplypressureIsrequIredforproperfunctIonofthe
anesthesIadelIverysystem.CassupplIedfromacentralsourcecanfaIlforavarIetyof
reasons.Therefore,thepressureInthepIpedgassupplyshouldbecheckedatleast
oncedaIly.
Item 7: Verify that vaporizers are adequately filled and, if applicable, that the filler
ports are tightly closed.
P.692
Responsible Parties:ProvIder.TechnIcIanIfredundancydesIred.
Rationale:fanesthetIcvapordelIveryIsplanned,anadequatesupplyIsessentIalto
reducetherIskoflIghtanesthesIaorrecall.ThIsIsespecIallytrueIfananesthetIc
agentmonItorwIthalowagentalarmIsnotbeIngused.PartIallyopenfIllerportsare
acommoncauseofleaksthatmaynotbedetectedIfthevaporIzercontroldIalIsnot
openwhenaleaktestIsperformed.ThIsleaksourcecanbemInImIzedbytIghtly
closIngfIllerports.NewervaporIzerdesIgnshavefIllIngsystemsthatautomatIcally
closethefIllerportwhenfIllIngIscompleted.
HIghandlowanesthetIcagentalarmsareusefultohelppreventoverorunderdosage
ofanesthetIcvapor.UseofthesealarmsIsencouragedandtheyshouldbesettothe
approprIatelImItsandenabled.
Item 8: Verify that there are no leaks in the gas supply lines between the flowmeters
and the common gas outlet.
Frequency:0aIlyandwheneveravaporIzerIschanged.
Rationale:ThegassupplyInthIspartoftheanesthesIadelIverysystempassesthrough
theanesthetIcvaporIzer(s)onmostanesthesIadelIverysystems.nordertoperforma
thoroughleaktest,eachvaporIzermustbeturnedonIndIvIduallytocheckforleaksat
thevaporIzermount(s)orInsIdethevaporIzer.Furthermore,somemachIneshavea
checkvalvebetweentheflowmetersandthecommongasoutlet,requIrInganegatIve
pressuretesttoadequatelycheckforleaks.AutomatedcheckoutprocedurestypIcally
IncludealeaktestbutmaynotevaluateleaksatthevaporIzer,especIallyIfthe
vaporIzerIsnotturnedondurIngtheleaktest.WhenrelyIngonautomatedtestIngto
evaluatethesystemforleaks,theautomatedleaktestwouldneedtoberepeatedfor
eachvaporIzerInplace.ThIstestshouldalsobecompletedwheneveravaporIzerIs
changed.TherIskofaleakatthevaporIzerdependsonthevaporIzerdesIgn.
7aporIzerdesIgnsInwhIchthefIllerportclosesautomatIcallyafterfIllIngcanreduce
therIskofleaks.
TechnIcIanscanprovIdeusefulassIstancewIththIsaspectofthemachInecheckoutas
ItcanbetImeconsumIng.
Item 9: Test scavenging system function.
Frequency:0aIly
Rationale:AproperlyfunctIonIngscavengIngsystempreventsroomcontamInatIonby
anesthetIcgases.ProperfunctIondependsoncorrectconnectIonsbetweenthe
scavengIngsystemandtheanesthesIadelIverysystem.TheseconnectIonsshouldbe
checkeddaIlybyaprovIderortechnIcIan.0ependIngonthescavengIngsystemdesIgn,
properfunctIonmayalsorequIrethatthevacuumlevelIsadequate,whIchshouldalso
beconfIrmeddaIly.SomescavengIngsystemshavemechanIcalposItIveandnegatIve
pressurerelIefvalves.PosItIveandnegatIvepressurerelIefIsImportanttoprotectthe
patIentcIrcuItfrompressurefluctuatIonsrelatedtothescavengIngsystem.Proper
checkoutofthescavengIngsystemshouldensurethatposItIveandnegatIvepressure
relIefIsfunctIonIngproperly.8ecauseofthecomplexItyofcheckIngforeffectIve
posItIveandnegatIvepressurerelIef,andthevarIatIonsInscavengIngsystemdesIgn,a
properlytraInedtechnIcIancanfacIlItatethIsaspectofthecheckoutprocess.
Item 10: Calibrate, or verify calibration of, the oxygen monitor and check the low
oxygen alarm.
Frequency:0aIly
Rationale:ContInuousmonItorIngoftheInspIredoxygenconcentratIonIsthelastlIne
ofdefenseagaInstdelIverInghypoxIcgasconcentratIonstothepatIent.Theoxygen
monItorIsessentIalfordetectIngadulteratIonoftheoxygensupply.|ostoxygen
monItorsrequIrecalIbratIononcedaIly,althoughsomeareselfcalIbratIng.Self
calIbratIngoxygenmonItorsshouldbeverIfIedtoread21whensamplIngroomaIr.
ThIsIsastepthatIseasIlycompletedbyatraInedtechnIcIan.Whenmorethanone
oxygenmonItorIspresent,theprImarysensorthatwIllberelIedonforoxygen
monItorIngshouldbechecked.
The low oxygen concentration alarm should also be checked at this time by setting
the alarm above the measured oxygen concentration and confirming that an
audible alarm signal is generated.
Item 11: Verify that carbon dioxide absorbent is not exhausted.
Frequency:PrIortoeachuse
Rationale:ProperfunctIonofacIrcleanesthesIasystemrelIesontheabsorbentto
removecarbondIoxIdefromrebreathedgas.ExhaustedabsorbentasIndIcatedbythe
characterIstIccolorchangeshouldbereplaced.tIspossIbleforabsorbentmaterIalto
losetheabIlItytoabsorbCD
2
yetthecharacterIstIccolorchangemaybeabsentor
dIffIculttosee.SomenewerabsorbentsdochangecolorwhendesIccated.
CapnographyshouldbeusedforeveryanesthetIcand,whenusIngacIrcleanesthesIa
system,rebreathIngcarbondIoxIdeasIndIcatedbyanInspIredCD
2
concentratIon0
canalsoIndIcateexhaustedabsorbent.(SeeNote2toAppendIx8.)
Item 12: Breathing system pressure and leak testing.
Rationale:ThebreathIngsystempressureandleaktestshouldbeperformedwIththe
cIrcuItconfIguratIontobeuseddurInganesthetIcdelIvery.fanycomponentsofthe
cIrcuItarechangedafterthIstestIscompleted,thetestshouldbeperformedagaIn.
AlthoughtheanesthesIaprovIdershouldperformthIstestbeforeeachuse,anesthesIa
technIcIanswhoreplaceandassemblecIrcuItscanalsoperformthIscheckandadd
redundancytothIsImportantcheckoutprocedure.PropertestIngwIlldemonstrate
thatpressurecanbedevelopedInthebreathIngsystemdurIngbothmanualand
mechanIcalventIlatIonandthatpressurecanberelIeveddurIngmanualventIlatIonby
openIngtheadjustablepressurelImItIngvalve.
AutomatedtestIngIsoftenImplementedIntheneweranesthesIadelIverysystemsto
evaluatethesystemforleaksandalsotodetermInethecomplIanceofthebreathIng
system.ThecomplIancevaluedetermIneddurIngthIstestIngwIllbeusedto
automatIcallyadjustthevolumedelIveredbytheventIlatortomaIntaInaconstant
volumedelIverytothepatIent.tIsImportantthatthecIrcuItconfIguratIonthatIsto
beusedIsInplacedurIngthetest.
P.69J
Item 13: Verify that gas flows properly through the breathing circuit during both
inspiration and exhalation.
Rationale:PressureandleaktestIngdoesnotIdentIfyallobstructIonsInthebreathIng
cIrcuItorconfIrmproperfunctIonoftheInspIratoryandexpIratoryunIdIrectIonal
valves.AtestlungorsecondreservoIrbagcanbeusedtoconfIrmthatflowthrough
thecIrcuItIsunImpeded.CompletetestIngIncludesbothmanualandmechanIcal
ventIlatIon.ThepresenceoftheunIdIrectIonalvalvescanbeassessedvIsuallydurIng
thePAC.ProperfunctIonofthesevalvescannotbevIsuallyassessedbecausesubtle
valveIncompetencemaynotbedetected.CheckoutprocedurestoIdentIfyvalve
IncompetencethatmaynotbevIsuallyobvIouscanbeImplementedbutaretypIcally
toocomplexfordaIlytestIng.AtraInedtechnIcIancanperformregularvalve
competencetests.(SeeNote4toAppendIx8)CapnographyshouldbeuseddurIng
everyanesthetIcandthepresenceofcarbondIoxIdeIntheInspIredgasescanhelpto
detectanIncompetentvalve.
Item 14: Document completion of checkout procedures.
Rationale:EachIndIvIdualresponsIbleforcheckoutproceduresshoulddocument
completIonoftheseprocedures.0ocumentatIongIvescredItforcompletIngthejob
andcanbehelpfulIfanadverseeventshouldoccur.Someautomatedcheckout
systemsmaIntaInanaudIttraIlofcompletedcheckoutproceduresthataredatedand
tImed.
Item 15: Confirm ventilator settings and evaluate readiness to deliver anesthesia
care. (ANESTHESIA TIME OUT)
Frequency:mmedIatelyprIortoInItIatIngtheanesthetIc.
Responsible Parties:ProvIder
Rationale:ThIsstepIsIntendedtoavoIderrorsduetoproductIonpressureorother
sourcesofhaste.ThegoalIstoconfIrmthatapproprIatecheckshavebeencompleted
andthatessentIalequIpmentIsIndeedavaIlable.TheconceptIsanalogoustothe
tImeoutusedtoconfIrmpatIentIdentItyandsurgIcalsIteprIortoIncIsIon.mproper
ventIlatorsettIngscanbeharmful,especIallyIfasmallpatIentIsfollowIngamuch
largerpatIentorvIceversa.PressurelImItsettIngs(whenavaIlable)shouldbeusedto
preventexcessIvevolumedelIveryfromImproperventIlatorsettIngs.
temstocheck:
|onItorsfunctIonal:
Capnogrampresent:
DxygensaturatIonbypulseoxImetrymeasured:
FlowmeterandventIlatorsettIngsproper:
|anual/ventIlatorswItchsettomanual:
7aporIzer(s)adequatelyfIlled:
Summary of Checkout Recommendations by Frequency and
Responsible Party
ITEM TO BE COMPLETED RESPONSIBLE PARTY
TO BE COMPLETED DAILY
1:
7erIfythatauxIlIaryoxygencylInderandselfInflatIngmanualventIlatIondevIce
areavaIlableandfunctIonIng
ProvIderandtechnIcIan
2: 7erIfypatIentsuctIonIsadequatetocleartheaIrway ProvIderandtechnIcIan
J: TurnonanesthesIadelIverysystemandconfIrmthatACpowerIsavaIlable ProvIderortechnIcIan
4: 7erIfyavaIlabIlItyofrequIredmonItors,IncludIngalarms ProvIderortechnIcIan
5: 7erIfythatpressureIsadequateonthespareoxygencylIndermountedonthe
anesthesIamachIne
6: 7erIfythatthepIpedgaspressuresare50psIg ProvIderandtechnIcIan
7:
7erIfythatvaporIzersareadequatelyfIlledand,IfapplIcable,thatthefIller
portsaretIghtlyclosed
ProvIderortechnIcIan
8: 7erIfythattherearenoleaksInthegassupplylInesbetweentheflowmeters
andthecommongasoutlet
9: TestscavengIngsystemfunctIon ProvIderortechnIcIan
10:
CalIbrate,orverIfycalIbratIonof,theoxygenmonItorandcheckthelow
oxygenalarm
11: 7erIfycarbondIoxIdeabsorbentIsnotexhausted ProvIderortechnIcIan
12: 8reathIngsystempressureandleaktestIng ProvIderandtechnIcIan
1J:
7erIfythatgasflowsproperlythroughthebreathIngcIrcuItdurIngboth
InspIratIonandexhalatIon
14: 0ocumentcompletIonofcheckoutprocedures ProvIderandtechnIcIan
15:
ConfIrmventIlatorsettIngsandevaluatereadInesstodelIveranesthesIacare
(ANESTHESAT|EDUT)
ProvIder
TO BE COMPLETED PRIOR TO EACH PROCEDURE
2: 7erIfypatIentsuctIonIsadequatetocleartheaIrway ProvIderandtechnIcIan
4: 7erIfyavaIlabIlItyofrequIredmonItors,IncludIngalarms ProvIderortechnIcIan
7:
7erIfythatvaporIzersareadequatelyfIlledand,IfapplIcable,thatthefIller
portsaretIghtlyclosed
ProvIder
11: 7erIfythatcarbondIoxIdeabsorbentIsnotexhausted ProvIderortechnIcIan
12: 8reathIngsystempressureandleaktestIng ProvIderandtechnIcIan
1J:
7erIfythatgasflowsproperlythroughthebreathIngcIrcuItdurIngboth
InspIratIonandexhalatIon
14: 0ocumentcompletIonofcheckoutprocedures ProvIderandtechnIcIan
15:
Confirm ventilator settings and evaluate readiness to deliver anesthesia
care (ANESTHESIA TIME OUT)
ProvIder
P.694
Appendix B References
1.CooperJ8,NewbowerFS,KItzFJ:AnanalysIsofmajorerrorsandequIpmentfaIlures
InanesthesIamanagement:ConsIderatIonsforpreventIonanddetectIon.AnesthesIology
1984;60:J4
2.Arbous|S,|eursIngAE,vanKleefJWetal:mpactofanesthesIamanagement
characterIstIcsonseveremorbIdItyandmortalIty.AnesthesIology2005;102:257
J.AnesthesIaApparatusCheckoutFecommendatIons,199J.http:
//www.fda.gov/cdrh/humfac/anesckot.html
4.|arch|C,CrowleyJJ:AnevaluatIonofanesthesIologIsts'presentcheckoutmethods
andthevalIdItyoftheF0AchecklIst.AnesthesIology1991;75:724
5.LampotangS,|oonS,LIzdas0Eetal:AnesthesIamachInepreusechecksurvey:
PrelImInaryresults[abstract].AnesthesIology2005;A1195
6.LarsonEF,NuttallCA,Dgren80etal:AprospectIvestudyonanesthesIamachIne
faultIdentIfIcatIon.AnesthAnalg2007;104:154
7.AmerIcanSocIetyofAnesthesIologIsts:Standardsfor8asIcAnesthetIc|onItorIng.
Dctober25,2005.http://www.asahq.org/publIcatIonsAndServIces/standards/02.pdf
8.ScopeandStandardsforNurseAnesthesIaPractIce,IntheProfessIonalPractIce
|anualfortheCertIfIedFegIsteredNurseAnesthetIst.ParkFIdge,L:AmerIcan
AssocIatIonofNurseAnesthetIsts,2006.
Appendix (To Appendix B) Additional Notes on Preanesthesia
Checkout
Notes
1. Testing the flowmeters:ThIsstepIspresentInthe199JCheckoutFecommendatIonand
IsIntendedtopromptcheckIngoftheoxygen/nItrousoxIdeproportIonIngsystem.thas
beenelImInatedfromthePreanesthesIaCheckoutIntheseguIdelInesbecauseproper
functIonIsverIfIeddurIngthepreventIvemaIntenanceandfaIluresofthIssystemIna
properlymaIntaIneddelIverysystemarerare.
2. Desiccated carbon dioxide absorbent:thasbeenwellestablIshedthatcarbondIoxIde
absorbentsthatcontaInsodIum,potassIum,orbarIumhydroxIdemaybecomedangerous
whendesIccated,producIngcarbonmonoxIdeand/orexcessIveheatleadIngtofIres.
Unfortunately,ItIsnotpossIbletorelIablyIdentIfywhentheabsorbentmaterIalhas
beendesIccated.SomedepartmentselecttochangeallabsorbentmaterIalon|onday
mornIngtoelImInatethepossIbIlItyofusIngabsorbentexposedtocontInuousfreshgas
flowthroughouttheweekend.DtherdepartmentselecttouseabsorbentmaterIalsthat
donotposearIskwhendesIccated.tIsImportanttohaveastrategytopreventthe
hazardsrelatedtousIngabsorbentscontaInIngtheproblematIchydroxIdesthathave
desIccated.TherearenostepsthatcouldbeIncludedInthecheckoutrecommendatIon
thatcanrelIablyIdentIfydesIccatedabsorbent.fadepartmentusesabsorbentthatmay
behazardouswhendesIccated,ItmaybeprudenttochangetheabsorbentmaterIal
whenevertheduratIonoftImeexposuretohIghfreshgasflowcannotbedetermInedand
IslIkelytohavebeenprolonged.
AprotocolforpreventIngabsorbenthazardsshouldbepartofeverydepartment'srIsk
managementstrategy.
J. Anesthesia information systems and automated record keepers:ThesesystemsarebeIng
adoptedbyanIncreasIngnumberofanesthesIadepartmentsandarethemaInstayofthe
recordkeepIngprocessInthosedepartments.FelIablyfunctIonIngsystemsaretherefore
ImportanttotheconductofananesthetIc,althoughnotessentIaltopatIentsafetyInthe
samefashIonastheanesthesIadelIverysystemandpatIentmonItors.Fordepartments
thatrelyonthesesystems,ItwouldbeprudenttohaveaprotocolforcheckIng
connectIonsandtheproperfunctIonIngoftheassocIatedcomputers,dIsplays,and
networkfunctIon.
4. Testing circle system valve competence:AspartofthetestItem1J(7erIfythatgasflows
properlythroughthebreathIngcIrcuItdurIngbothInspIratIonandexhalatIon),the
InspIratoryandexpIratoryvalvesarevIsuallyobservedforpropercyclIng(openIngand
closIngfully).7IsualInspectIonwIllalsodetectamIssIngvalveleaflet.AscertaInIngfull
closureofthevalveIssubjectIve.ncompetenceofthevalvemayalsobedetected
durIngItem1JthroughspIrometryattheexpIratorylImb.ForexpIratoryvalve
malfunctIon,aspIrometerwIthreverseflowdetectIonwIllalarmwhengasflows
retrogradeIntheexpIratorylImb.ForInspIratoryvalvemalfunctIon,themeasured
exhaledtIdalvolumewIllbelessthantheexpectedvalue.Capnographymayalsohelpto
detectIncompetenceoftheunIdIrectIonalvalves.ntraoperatIvely,anInspIratoryvalve
malfunctIonmaynotbeIndIcatedbyanelevatIonoftheInspIredCD
2
baselIne.fthe
delIveredtIdalvolumeexceedsthevolumeofgasIntheInspIratorylImbcontaInIngCD
2
,
rebreathIngwIllappearonthecapnogramasagradual,Insteadofsharp,downstroke.An
expIratoryvalvemalfunctIonIsIndIcatedbyanelevatedCD
2
baselIneasthereIs
typIcallyalargevolumeofexhaledgascontaInIngCD
2
thatcanreturntothepatIent.
Acknowledgment
PortIonsofthIschapterhaveappearedwIthpermIssIonInAndrewsJJ,8rockwellFC:
nhaledanesthesIadelIverysystems,AnesthesIa,6thedItIon.EdItedby|IllerF0.
PhIladelphIa,ChurchIllLIvIngstone,2004,p27J.
Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapter27Standard|onItorIngTechnIques
Chapter27
Standard Monitoring Techniques
Steven B. Greenberg
Glenn S. Murphy
Jeffery S. Vender
Key Points
1. Although the authors believe that electronic monitors augment
clinical judgments when used properly, there is little high-grade
evidence that electronic monitors, by themselves, reduce mortality or
morbidity.
2. Alterations in ventilation, cardiac output, distribution of pulmonary
blood flow, and metabolic activity can all influence the capnograph
display during carbon dioxide gas analysis.
3. During direct invasive arterial pressure monitoring, systemic fidelity
is optimized when the catheter and tubing are stiff, the mass of the
fluid is small, and the length of the connecting tubing is not
excessive. On the basis of available evidence, it is difficult to draw
meaningful conclusions regarding the effectiveness of pulmonary
artery catheter (PAC) monitoring in reducing morbidity and mortality
in critically ill patients. Expert opinion suggests that perioperative
complications may be reduced if PACs are used in the appropriate
patients and settings, and if clinicians interpret and apply the data
provided by the PAC correctly.
4. New, noninvasive devices have been developed to generate similar
parameters as the PAC as well as potentially to be able to predict
fluid responsiveness.
|onItorIngrepresentstheprocessbywhIchanesthesIologIstsrecognIzeandevaluate
potentIalphysIologIcproblemsInatImelymanner.ThetermIsderIvedfrommonere,
whIchInLatInmeanstowarn,remInd,oradmonIsh.nperIoperatIvecare,monItorIng
IncludesthefollowIngfouressentIalfeatures:observatIonandvIgIlance,InstrumentatIon,
InterpretatIonofdata,andInItIatIonofcorrectIvetherapywhenIndIcated.
|onItorIngIsanessentIalaspectofanesthesIacare.twouldseemthateffectIve
monItorIngreducesthepotentIalforpooroutcomesthatmayfollowanesthesIaby
IdentIfyIngderangementsbeforetheyresultInserIousorIrreversIbleInjury.ElectronIc
monItorsImproveaphysIcIan'sabIlItytorespondbecauseheorsheIsabletomake
repetItIvemeasurementsathIgherfrequencIesthanhumansanddonotfatIgueorbecome
dIstracted.|onItorIngdevIcespotentIallyIncreasethespecIfIcItyandprecIsIonofclInIcal
judgments.DurunderstandIngofthephysIologIceffectsofanesthesIaandItsInherentrIsks
canbeenhancedbytheapproprIateuseofIntraoperatIvephysIologIcmonItorIng.
ThIschapterdIscussesthemethodsbywhIchanesthesIologIstsmonItororganfunctIon
durInganesthesIacare.ThedescrIptIonsofthetechnologIcandscIentIfIcprIncIplesusedIn
monItorIngdevIceshavebeensImplIfIedforclarIty.
CostcontaInmenthasbeenraIsedasareasontodIscouragetheuseofexpensIve,
technologIcallyadvancedmonItorIngsystems.ThevalueofagIvenmonItordependsonthe
clInIcalexpertIseoftheanesthesIologIst,theclInIcalsettIng,theanesthetIctechnIque,and
theperformancecharacterIstIcsofthespecIfIcequIpmentInquestIon.|onItorIngdevIces
shouldnotbedenIedsolelyonthebasIsofexpense.
1
AlthoughItIsapproprIateforsocIety
todemandcostcontaInment,anesthesIologIstshavearesponsIbIlItytoassesshow
monItorIngshouldbeapproprIatelyemployed.ProfessIonalsocIetIes,regulatoryagencIes,
andthelegalprofessIonhaveplayedImportantrolesInestablIshIngcurrentmonItorIng
practIces.
StandardsforbasIcanesthetIcmonItorInghavebeenestablIshedbytheAmerIcanSocIety
ofAnesthesIologIsts(ASA).SInce1986,thesestandardshaveemphasIzedtheevolutIonof
technologyandpractIce.Today'sstandards(lastaffIrmedonDctober25,2005)emphasIze
theImportanceofregularandfrequentmeasurements,IntegratIonofclInIcaljudgment
andexperIence,andthepotentIalforextenuatIngcIrcumstancesthatcanInfluencethe
applIcabIlItyoraccuracyofmonItorIngsystems.
2
StandardrequIresqualIfIedpersonneltobepresentIntheoperatIngroomdurInggeneral
anesthesIa,regIonalanesthesIa,andmonItoredanesthesIacaretomonItorthepatIent
contInuouslyandmodIfyanesthesIacarebasedonclInIcalobservatIonsandtheresponses
ofthepatIenttodynamIcchangesresultIngfromsurgeryordrugtherapy.Standard
focuses
P.698
attentIononcontInuallyevaluatIngthepatIent'soxygenatIon,ventIlatIon,cIrculatIon,and
temperature.StandardspecIfIcallymandatesthefollowIng:
1. UsInganoxygenanalyzerwIthalowconcentratIonlImItalarmdurInggeneral
anesthesIa.
2. QuantItatIvelyassessIngbloodoxygenatIondurInganyanesthesIacare.
J. ContInuouslyensurIngtheadequacyofventIlatIonbyphysIcaldIagnostIctechnIques
durIngallanesthesIacare.dentIfIcatIonofexpIredcarbondIoxIdeIsperformedunless
nullIfIedbythetypeofpatIent,procedure,orequIpment.
QuantItatIvemonItorIngoftIdalvolumeandcapnographyIsstronglyencouragedIn
patIentsundergoInggeneralanesthesIa.
4. WhenadmInIsterIngregIonalanesthesIaormonItoredanesthesIacare,suffIcIent
ventIlatIonshouldbeassessedbyqualItatIveclInIcalsIgnsand/ormonItorIngofexhaled
carbondIoxIde.
5. EnsurIngcorrectplacementofanendotrachealIntubatIonorlaryngealmaskaIrway
requIresclInIcalassessmentandqualItatIveIdentIfIcatIonofcarbondIoxIdeInthe
expIredgas.0urInggeneralanesthesIa,capnographyandendtIdalcarbondIoxIde
analysIsIsperformed.
6. WhenusIngamechanIcalventIlator,thereshouldbeadevIcethatIsabletodetecta
dIsconnectIonofanypartofthebreathIngsystem.
7. TheadequacyofcIrculatIonshouldbemonItoredbythecontInuousdIsplayofthe
electrocardIogram,andbydetermInIngthearterIalbloodpressureandheartrateat
leastat5mInuteIntervals.0urInggeneralanesthesIa,cIrculatoryfunctIonIstobe
contInuallyevaluatedbythequalItyofthepulse,eItherelectronIcallyorbypalpatIonor
auscultatIon.
8. 0urIngallanesthetIcs,themeansforcontInuouslymeasurIngthepatIent'stemperature
mustbeavaIlable.WhenchangesInbodytemperatureareIntendedorantIcIpated,
temperatureshouldbecontInuouslymeasuredandrecordedontheanesthesIarecord.
TheASAstandardsemphasIzethemeldIngofphysIcalsIgnswIthInstrumentatIon.
ElectronIcmonItorIng,nomatterhowsophIstIcatedorcomprehensIve,doesnotnecessarIly
reducetheneedforclInIcalskIllssuchasInspectIon,palpatIon,andauscultatIon.
AlthoughtheauthorsbelIevethatelectronIcmonItorsaugmentclInIcaljudgmentswhen
usedproperly,thereIslIttlehIghgradeevIdencethatelectronIcmonItors,bythemselves,
reducemortalItyormorbIdIty.|oreover,thereIsconsIderablecontroversyregardIngthe
needtoapplyspecIfIcmonItorsInunIqueclInIcalsItuatIons,partIcularlythosethatmay
addsIgnIfIcantcost.|onItorIngcanbeclassIfIedasInvasIve,mInImallyInvasIve,or
nonInvasIve.nvasIvemonItorsplacepatIentsatrIskforcomplIcatIonsrelatedtotheIr
applIcatIonanduse.AnesthesIologIstsmustbalancethepotentIalrIskofInstItutIng
InvasIvemonItorIngwIththepresumedbenefItsderIvedfromItsapplIcatIon.
ThevarIetyofdevIcesavaIlableforpatIentmonItorIngIsexpansIveandchangIngas
advancesInbIomedIcalengIneerIngfIndtheIrwayIntothemarketplace.TheAssocIatIon
fortheAdvancementof|edIcalnstrumentatIonhasbeeneffectIveInpromotIngdesIgn
guIdelInestoensurepatIentandoperatorsafetyandreducestressanddIstractIonsoften
assocIatedwIthmedIcalmonItorIng.
J
TheprolIferatIonofalarmtonesdurInganesthesIacarecanbedIsturbIngandmay
paradoxIcallyImpaIrclInIcalvIgIlance.|onItorIngsystemsmaylackadequatesensItIvIty
andspecIfIcItytoapproprIatelyrejecterrors.0urIngroutIneanesthesIacare,amInImum
offIvealarms(InspIredoxygen,aIrwaypressure,pulseoxImetry,bloodpressure,andheart
rate)shouldbeoperatIonal.Unfortunately,spurIouswarnIngsoccurwIthhIghfrequency
durIngroutIneanesthesIamonItorIng.TheIntegratIonofalarmsIgnalsIsanImportantarea
InneedofcontInuIngevaluatIonanddevelopment.Loeb
4
reportedthatanesthesIa
provIdershavedIffIcultyInaccuratelyrecognIzIngthesourceofanalarmtone.Alarm
annuncIatorsusIngunIquesoundandvIsualpromptsareIncorporatedIntonewer
anesthesIaequIpment.WarnIngsIgnalsforventIlatIon,oxygenatIon,drugadmInIstratIon,
temperature,andcardIovascularparametersneedtobedesIgnedsothatproblem
IdentIfIcatIonIsfast,sImple,andrelevant.
Inspiratory and Expired Gas Monitoring: Oxygen
TheconcentratIonofoxygenIntheanesthetIccIrcuItmustbemeasured.|easurIng
InspIredoxygendoesnotguaranteetheadequacyofarterIaloxygenatIon.
5
CasmachIne
manufacturersplaceoxygensensorsontheInspIredlImboftheanesthesIacIrcuIttoensure
thathypoxIcgasmIxturesareneverdelIveredtopatIents.DxygenmonItorsrequIreafast
responsetIme(2to10seconds),accuracy(2oftheactuallevel),andstabIlItywhen
exposedtohumIdItyandInhalatIonagents.
Paramagnetic Oxygen Analysis
DxygenIsahIghlyparamagnetIcgas.ParamagnetIcgasesareattractedtomagnetIcenergy
becauseofunpaIredelectronsIntheIroutershellorbIts.0IfferentIalparamagnetIc
oxImetryhasbeenIncorporatedIntoavarIetyofoperatIngroommonItors.These
InstrumentsdetectthechangeInsamplelInepressureresultIngfromtheattractIonof
oxygenbyswItchedmagnetIcfIelds.SIgnalchangesdurIngelectromagnetIcswItchIng
correlatewIththeoxygenconcentratIonInthesamplelIne.
Galvanic Cell Analyzers
CalvanIccellanalyzersmeettheperformancecrIterIanecessaryforoperatIvemonItorIng.
TheseanalyzersmeasurethecurrentproducedwhenoxygendIffusesacrossamembrane
andIsreducedtomolecularoxygenattheanodeofanelectrIcalcIrcuIt.Theelectronflow
(current)IsproportIonaltothepartIalpressureofoxygenInthefuelcell.CalvanIccell
analyzersrequIreregularreplacementofthegalvanIcsensorcapsule.nthesensor,the
electrIcpotentIalforthereductIonofoxygenresultsfromachemIcalreactIon.DvertIme,
thereactantsrequIrereplenIshment.
6
Polarographic Oxygen Analyzers
PolarographIcoxygenanalyzersarecommonlyusedInanesthesIamonItorIng.nthIs
electrochemIcalsystem,oxygendIffusesthroughanoxygenpermeablepolymerIc
membraneandpartIcIpatesInthefollowIngreactIon:D
2
+2H
2
D+4e
4DH
.Thecurrent
changeIsproportIonaltothenumberofoxygenmoleculessurroundIngtheelectrode.
PolarographIcoxygensensorsareversatIleandareImportantcomponentsofgasmachIne
oxygenanalyzers,bloodgasanalyzers,andtranscutaneousoxygenanalyzers.
Monitoring of Expired Gases
Carbon Dioxide
|onItorIngthepartIalpressureofexpIratoryCD
2
hasevolvedasanImportantphysIologIc
andsafetymonItor.CD
2
Isusually
P.699
sampledneartheendotrachealgasdelIveryInterface.AlteratIonsInventIlatIon,cardIac
output(CD),dIstrIbutIonofpulmonarybloodflow,andmetabolIcactIvItyInfluenceend
tIdalCD
2
concentratIonandthecapnographdIsplayobtaIneddurIngquantItatIveexpIred
gasanalysIs.
Figure 27-1.Thenormalcapnogram.Point DdelIneatestheendtIdalCD
2
(ETCD
2
).
ETCD
2
IsthebestreflectIonofthealveolarCD
2
partIalmeasure.
CapnometryIsthemeasurementandnumerIcrepresentatIonoftheCD
2
concentratIon
durIngInspIratIonandexpIratIon.AcapnogramIsacontInuousconcentratIontImedIsplay
oftheCD
2
concentratIonsampledatapatIent'saIrwaydurIngventIlatIon.
CapnographyIsthecontInuousmonItorIngofapatIent'scapnogram.ThecapnogramIs
dIvIdedIntofourdIstInctphases(FIg.271).ThefIrstphase(A8InFIg.271)representsthe
InItIalstageofexpIratIon.CassampleddurIngthIsphaseoccupIestheanatomIcdeadspace
andIsnormallydevoIdofCD
2
.AtpoInt8,CD
2
contaInInggaspresentsItselfatthesamplIng
sIte,andasharpupstroke(8C)IsseenInthecapnogram.TheslopeofthIsupstrokeIs
determInedbytheevennessofexpIratoryventIlatIonandalveolaremptyIng.PhaseC0
representsthealveolarorexpIratoryplateau.AtthIsphaseofthecapnogram,alveolargas
IsbeIngsampled.Normally,thIspartofthewaveformIsalmosthorIzontal.However,when
ventIlatIonandperfusIonaremIsmatched,PhaseC0maytakeanupwardsslope.PoInt0Is
thehIghestCD
2
valueandIscalledtheend-tidalCD
2
(ETCD
2
).ETCD
2
IsthebestreflectIon
ofthealveolarCD
2
(Paco
2
).AsthepatIentbegInstoInspIre,freshgasIsentraInedand
thereIsasteepdownstroke(0E)backtobaselIne.UnlessrebreathIngofCD
2
occurs,the
baselIneapproacheszero.
TheutIlItyofcapnographydependsonanunderstandIngoftherelatIonshIpbetween
arterIalco
2
(Paco
2
),alveolarco
2
(PACD
2
),andETCD
2
.ThIsconceptassumesthat
ventIlatIonandperfusIonareapproprIatelymatched,thatCD
2
IseasIlydIffusIbleacrossthe
capIllaryalveolarmembrane,andthatnosamplIngerrorsoccurdurIngmeasurement.f
thesecondItIonsaremet,changesInETCD
2
reflectchangesInPaco
2
evenIfItIsassumed
thatallalveolIdonotemptyatthesametIme.nanuprIght,spontaneouslybreathIng
healthyperson,onemayassumethefollowIngIdealIzedmathematIcalmodelof
ventIlatIonperfusIon,ETCD
2
Paco
2
Paco
2
.fthePaco
2
Paco
2
gradIentIsconstantand
small,capnographyprovIdesanonInvasIve,contInuous,realtImereflectIonofventIlatIon.
0urInggeneralanesthesIa,theETCD
2
Paco
2
gradIenttypIcallyIs5to10mmHg.0eadspace
ventIlatIon,amaldIstrIbutIonofventIlatIonandperfusIon([7wIthdotabove]/[QwIthdot
above])whereventIlatIonIsdIsproportIonallyhIghrelatIvetoperfusIonorproblemsIngas
samplIngmayresultInawIdenIngoftheETCD
2
Paco
2
gradIent.0eadspace[7wIthdot
above]/[QwIthdotabove]maldIstrIbutIonIsacommoncauseofanIncreasedPaco
2
Paco
2
gradIent.DtherpatIentfactorsthatmayInfluencetheaccuracyofETCD
2
monItorIngby
wIdenIngthePaco
2
ETCD
2
gradIentIncludeshallowtIdalbreaths,prolongatIonofthe
expIratoryphaseofventIlatIon,orunevenalveolaremptyIng.
0eadspace(wasted)ventIlatIonIstheextremeexample[7wIthdotabove]/[QwIthdot
above]ofmIsmatch,whereacompleteabsenceofperfusIonInthepresenceofadequate
alveolarventIlatIonoccurs.8ecauseonlyperfusedalveolIcanpartIcIpateIngasexchange,
thenonperfusedalveolIhaveaPaco
2
ofzero.TheventIlatIonweIghtedaverageofthe
perfusedandnonperfusedalveolIdetermInestheETCD
2
.Therefore,condItIonsresultIngIn
anIncreaseofdeadspaceventIlatIonlowertheETCD
2
measurementandIncreasethe
Paco
2
ETCD
2
gradIent.ThecommonclInIcalcausesassocIatedwIthawIdenedPaco
2
ETCD
2
gradIentIncludeembolIcphenomena(thrombus,fat,aIr,amnIotIcfluId),
hypoperfusIonstateswIthreducedpulmonarybloodflow,andchronIcobstructIve
pulmonarydIsease.ncontrast,condItIonsthatIncreasepulmonaryshunt(perfusIonInthe
absenceofventIlatIon)resultInmInImalchangesInthePaco
2
ETCD
2
gradIent.
CapnographyIsanessentIalelementIndetermInIngtheapproprIateplacementof
endotrachealtubes.ThepresenceofastableETCD
2
forthreesuccessIvebreathsIndIcates
thatthetubeIsnotIntheesophagus.AcontInuous,stableCD
2
waveformensuresthe
presenceofalveolarventIlatIonbutdoesnotnecessarIlyIndIcatethattheendotracheal
tubeIsproperlyposItIonedInthetrachea.Forexample,thetIpofthetubecouldbe
locatedInamaInstembronchus.naddItIon,acontInuousCD
2
tracIngcanbeevIdent
whenanendotrachealtubeIsproxImallyplacedtothevocalcords.CapnographyIsalsoa
monItorofpotentIalchangesInperfusIonordeadspace,IsaverysensItIveIndIcatorof
anesthetIccIrcuItdIsconnectIonandgascIrcuItleaks,andIsamethodtodetectthequalIty
ofCD
2
absorptIon.ncreasesInETCD
2
canbeexpectedwhenCD
2
productIonexceeds
ventIlatIon,suchasInhyperthermIaorwhenanexogenoussourceofCD
2
Ispresent.Table
271summarIzesthecommonelementsthatmaybereflectedbychangesInETCD
2
durIng
anesthesIacare.
AsuddendropInETCD
2
tonearzerofollowedbytheabsenceofaCD
2
waveformheraldsa
potentIallylIfethreatenIngproblemthatcouldIndIcatemalposItIonofanendotracheal
tubeIntothepharynxoresophagus,suddenseverehypotensIon,massIvepulmonary
embolIsm,acardIacarrest,oradIsconnectIonordIsruptIonofsamplInglInes.Whena
suddendropoftheETCD
2
occurs,ItIsessentIaltoquIcklyverIfythatthereIspulmonary
ventIlatIonandtoIdentIfyphysIologIcandmechanIcalfactorsthatmIghtaccountforthen
ETCD
2
ofzero.0urInglIfesavIngcardIopulmonaryresuscItatIon,thegeneratIonof
adequatecIrculatIoncanbeassessedbytherestoratIonoftheCD
2
waveform.
Table 27-1 Factors that May Change End-Tidal CO
2
(ETCO
2
) During
Anesthesia
INCREASES IN ETCO
2
DECREASES IN ETCO
2
ELE|ENTSTHATCHANCECD
2
PFD0UCTDN
Increases in metabolic rate
HyperthermIa
SepsIs
|alIgnanthyperthermIa
ShIverIng
HyperthyroIdIsm
Decreases in metabolic rate
HypothermIa
HypothyroIdIsm
ELE|ENTSTHATCHANCECD
2
EL|NATDN
HypoventIlatIon
HypoperfusIon
HyperventIlatIon
FebreathIng
PulmonaryembolIsm
P.700
WhereasabruptdecreasesIntheETCD
2
areoftenassocIatedwIthanaltered
cardIopulmonarystatus(e.g.,embolIsmorhypoperfusIon),gradualreductIonsInETCD
2
moreoftenreflectdecreasesInPaco
2
thatoccurwhenthereexIstsanImbalancebetween
mInuteventIlatIonandmetabolIcrate(I.e.,CD
2
productIon),ascommonlyoccursdurIng
anesthesIaatafIxedmInuteventIlatIon.
ThesIzeandshapeofthecapnogramwaveformcanbeInformatIve.
7
AslowrateofrIseof
thesecondphase(8CInFIg.271)IssuggestIveofeItherchronIcobstructIvepulmonary
dIseaseoracuteaIrwayobstructIonasfrombronchoconstrIctIon(asthma)secondaryto
mIsmatchIngInventIlatIontoperfusIon.AnormallyshapedcapnogramwIthanIncreaseIn
ETCD
2
suggestsalveolarhypoventIlatIonoranIncreaseInCD
2
productIon.TransIent
IncreasesInETCD
2
areoftenobserveddurIngtournIquetrelease,aortIcunclampIng,orthe
admInIstratIonofbIcarbonate.
SeveralmethodsforthequantIfIcatIonofCD
2
havebeenapplIedtopatIentmonItorIng
systems.DneofthemostcommonlyusedmethodsIsbasedonInfraredabsorptIon
spectrophotometry.
Infrared Absorption Spectrophotometry
AsymmetrIc,polyatomIcmoleculeslIkeCD
2
absorbInfraredlIghtatspecIfIcwavelengths.
DperatIngroomInfraredabsorptIonspectrophotometry(FAS)devIcescandetectCD
2
,N
2
D,
andthepotentInhaledanesthetIcagents.DperatIngroomInstrumentsaredesIgnedto
measuretheunIqueenergyabsorbedbythegasesandvaporsofInterestwhenasampleof
theInspIredandexpIredgasIsplacedIntotheoptIcalpathofanInfraredbeam.
8
The
mIxturescomplIcatetheanalysIsbecauseofInteractIonsbetweenthegasesandvaporsand
theclosenessofabsorptIonspectraforthegasesofInterest.AllanesthetIcvaporsabsorb
InfraredlIghtatJ.6m.Therefore,manufacturersusIngthIssIgnaturecannotdIsplaywIth
certaIntytheconcentratIonofaspecIfIcanesthetIcagentofInterest.DptIcalfIltersand
unIquedetectIonsystemsenhancethesensItIvItyofFASmonItorIngandpermItestImatIon
ofCD
2
,N
2
D,andthespecIfIcpotentInhalatIonalagentpresentInthemeasurement
chamber.
FASdevIceshavefIvecomponents:anInfraredlIghtsource,agassampler,anoptIcal
path,adetectIonsystem,andasIgnalprocessor.ThelIghtsourceproducestheInfrared
energy.ThelIghtIsfocusedandfIlteredsothatthequalItyofthephotonswIthrespectto
theenergyandfrequencyIsstableovertIme.Narrowwavelengthsarethenpresentedto
thegasstream.Dncethesamplehasenteredthemeasurementchamber,adetectIon
systemcalIbratedtodetermInetheconcentratIonofaspecIfIcgasoragentovertImeIs
actIvated.ChangesIntemperature,pressure,andacoustIccharacterIstIcsInthedetectIon
chambercanbeusedtodetermInetheconcentratIonofthegasoragentsofInterest.
SIgnaldetectorscreateelectrIcalcurrentsanalyzedbythesIgnalprocessor,whIch
transformsthecurrentchangetoameasurement.ThecapnogramoragentwaveformIsan
oscIlloscopIcrepresentatIonoftheelectrIcalcurrentchangesovertIme.ThesIgnal
processIngsectIonofanFASInstrumenthasamemorysectIonthatcorrelatesthe
absorbedenergywIthaconcentratIonaspredIctedbythe8eerLambertlaw.
Multiple Expired Gas Analysis
|ostoperatIngroomgasanalyzersIncorporatemethodssothattheycanmonItor
concentratIonsofatleastD
2
,CD
2
,andtheInhaledanesthetIcagents.Mass spectrometry
systemsbombardthegasmIxturewIthelectrons,creatIngIonfragmentsofapredIctable
massandcharge.ThesefragmentsareacceleratedInavacuum.AsampleofthIsmIxture
entersameasurementchamber,wherethefragmentstreamIssubjectedtoahIgh
magnetIcfIeld.ThemagnetIcfIeldseparatesthefragmentsbytheIrmassandcharge.The
fragmentsaredeflectedontoadetectorplate,andeachgashasaspecIfIclandIngsIteon
thedetectorplate.TheIonImpactsareproportIonaltotheconcentratIonoftheparentgas
orvapor.TheprocessorsectIonofthemassspectrometersystemcalculatesthe
concentratIonofthegasesofInterest.
AnotherunIqueapproachtomonItorrespIratorygasesIsbasedonRaman scattering.
FamanscatterIngresultswhenphotonsgeneratedbyahIghIntensItyargonlasercollIde
wIthgasmolecules.ThescatteredphotonsaremeasuredaspeaksInaspectrumthat
determInetheconcentratIonandcomposItIonofrespIratorygasesandInhaledvapors.D
2
,
N
2
,N
2
D,CD
2
,H
2
DvaporsandInhaledanesthetIcagentsareallmeasurableusIngFaman
scatterIngtechnology.
9
NItrogenmonItorIngprovIdesquantIfIcatIonofwashoutdurIngpreoxygenatIon.Asudden
rIseInN
2
IntheexhaledgasIndIcateseItherIntroductIonofaIrfromleaksInthe
anesthesIadelIverysystemorvenousaIrembolIsm.CrItIcaleventsthatcanbedetectedby
theanalysIsofrespIratorygasesandanesthetIcvaporsarelIstedInTable272.
Arterial Oxygenation Monitoring
TheassessmentofarterIaloxygenatIonIsanIntegralpartofanesthesIapractIce.Early
detectIonandpromptInterventIonmaylImItserIoussequelaeofhypoxemIa.TheclInIcal
sIgnsassocIatedwIthhypoxemIa(e.g.,tachycardIa,alteredmentalstatus,cyanosIs)are
oftenmaskedordIffIculttoapprecIatedurInganesthesIa.ThemechanIsmsresponsIblefor
hypoxemIaaremultIfactorIal.DxygenanalyzersassessoxygendelIverytothepatIent.
DthernonInvasIvetechnologIesdetectthepresenceofarterIalhypoxemIa.ArterIaloxygen
monItorsdonotensureadequacyofoxygendelIveryto,orutIlIzatIonby,thetIssues,and
shouldnotbeconsIderedareplacementforarterIalbloodgasmeasurementswhenmore
defInItIveInformatIonregardIngoxygenatIonIsdesIred.
Pulse Oximetry
PulseoxImetryIsonedevIcesuggestedformonItorIngoxygenatIondurInganesthesIa.
2
PulseoxImetersmeasurepulserateandestImateoxygensaturatIonofhemoglobIn(Hb;
Spo
2
)onanonInvasIve,contInuousbasIs.FIgure272dIsplaystheoxyhemoglobIn
dIssocIatIoncurvethatdefInestherelatIonshIpofhemoglobInsaturatIonandoxygen
tensIon.Dnthesteeppartofthecurve,apredIctablecorrelatIonexIstsbetweenSao
2
and
Pao
2
.nthIsrange,theSao
2
IsagoodreflectIonoftheextentofhypoxemIaandthe
changIngstatusofarterIaloxygenatIon.ShIftsIntheoxyhemoglobIndIssocIatIoncurveto
therIghtortotheleftdefInechangesIntheaffInItyofHbforoxygen.TypIcally,ataPao
2
of75mmHg,theSao
2
plateausandlosesItsabIlItytoreflectchangesInPao
2
.
PulseoxImetryIsbasedonseveralpremIses:
1. ThecolorofbloodIsafunctIonofoxygensaturatIon.
2. ThechangeIncolorresultsfromtheoptIcalpropertIesofHbandItsInteractIonwIth
oxygen.
J. TheratIoofD
2
HbandreducedHbcanbedetermInedbyabsorptIonspectrophotometry.
PulseoxImetrycombInesthetechnologyofplethysmographyandspectrophotometry.
PlethysmographyproducesapulsetracethatIshelpfulIntrackIngcIrculatIon.Dxygen
saturatIonIsdetermInedbyspectrophotometry,whIchIsbasedonthe8eerLambertlaw.
AtaconstantlIghtIntensItyandHb
P.701
concentratIon,theIntensItyoflIghttransmIttedthroughatIssueIsalogarIthmIcfunctIon
oftheoxygensaturatIonofHb.TwowavelengthsoflIghtarerequIredtodIstInguIshD
2
Hb
fromreducedHb.LIghtemIttIngdIodesInthepulsesensoremItred(660nm)andnear
Infrared(940nm)lIght.ThepercentageofD
2
HbandreducedHbIsdetermInedby
measurIngtheratIoofInfraredandredlIghtsensedbyaphotodetector.PulseoxImeters
performaplethysmographIcanalysIstodIfferentIatethepulsatIlearterIalHbsaturatIon
fromthenonpulsatIlesIgnalresultIngfromvenousabsorptIonandothertIssuessuchas
skIn,muscle,andbone.TheabsenceofapulsatIlewaveformdurIngextremehypothermIa
orhypoperfusIoncanlImIttheabIlItyofapulseoxImetertocalculatetheSpo
2
.
TheSpo
2
measuredbypulseoxImetryIsnotthesameasthearterIalsaturatIon(Sao
2
)
measuredbyalaboratorycooxImeter.PulseoxImetrymeasuresthefunctIonal
saturatIon,whIchIsdefInedbythefollowIngequatIon:
Table 27-2 Detection of Critical Events by Implementing Gas Analysis
EVENT GAS MEASURED BY ANALYZER
ErrorIngasdelIvery
D
2
,N
2
,CD
2
,agentanalysIs
AnesthesIamachInemalfunctIon
D
2
,N
2
,CD
2
,agent
0IsconnectIon
CD
2
,D
2
,agentanalysIs
7aporIzermalfunctIonorcontamInatIon AgentanalysIs
AnesthesIacIrcuItleaks
N
2
,CD
2
analysIs
Endotrachealcuffleaks
N
2
,CD
2
PoormaskorL|AfIt
N
2
,CD
2
HypoventIlatIon
CD
2
analysIs
|alIgnanthyperthermIa
CD
2
AIrwayobstructIon
CD
2
AIrembolIsm
CD
2
,N
2
CIrcuIthypoxIa
D
2
analysIs
7aporIzeroverdose AgentanalysIs
L|A,laryngealmaskaIrway.
|odIfIedfromKnopesK0,Hecker8F:|onItorInganesthetIcgases,ClInIcal
|onItorIng.EdItedbyLakeCL.PhIladelphIa,W8Saunders,1990,p24,wIth
permIssIon.
FunctIonalSao
2
=D
2
Hb/(D
2
Hb+reducedHb)100
LaboratorycooxImetersusemultIplewavelengthstodIstInguIshothertypesofHbbytheIr
characterIstIcabsorptIon.CooxImetersmeasurethefractIonalsaturatIon,whIchIs
defInedbythefollowIngequatIon:
Figure 27-2.TheoxyhemoglobIndIssocIatIoncurve.TherelatIonshIpbetweenarterIal
saturatIonofhemoglobInandoxygentensIonIsrepresentedbythesIgmoIdshaped
oxyhemoglobIndIssocIatIoncurve.WhenthecurveIsleftshIfted,thehemoglobIn
moleculebIndsoxygenmoretIghtly.(Feproducedfrom8rown|,7enderJS:Non
InvasIveoxygenmonItorIng.CrItCareClIn1988;4:49J,wIthpermIssIon.)
FractIonalSao
2
=D
2
Hb/(D
2
Hb+reducedHb+CDHb
+|etHb)100
nclInIcalcIrcumstanceswhereotherHbmoIetIesarepresent,theSpo
2
measurementmay
notcorrelatewIththeactualSao
2
reportedbythebloodgaslaboratory.Forexample,
methemoglobInabsorbsredandInfraredwavelengthsoflIghtIna1:1ratIocorrespondIng
toanSpo
2
ofapproxImately85.Therefore,IncreasesIn|etHbproducean
underestImatIonwhenSpo
2
70andanoverestImatIonwhenSpo
2
70.SImIlarly,
carboxyhemoglobInalsoproducesartIfIcIallyhIghandmIsleadIngresults.nfact,onestudy
showedthatat70CDHb,theSpo
2
stIllmeasured90.nmostpatIents,|etHbandCDHb
arepresentInlowconcentratIonssothatthefunctIonalsaturatIonapproxImatesthe
fractIonalvalue.
10
PulseoxImetryhasbeenusedInallpatIentagegroupstodetectandpreventhypoxemIa.
TheclInIcalbenefItsofpulseoxImetryareenhancedbyItssImplIcIty.|odernpulse
oxImetersarenonInvasIve,contInuous,andautocalIbratIng.TheyhavequIckresponse
tImesandtheIrbatterybackupprovIdesmonItorIngdurIngtransport.TheclInIcalaccuracy
IstypIcallyreportedtobewIthIn2toJat70to100saturatIonandJat50to70
saturatIon.PublIsheddatafromnumerousInvestIgatIonssupportaccuracyandprecIsIon
reportedbyInstrumentmanufacturers.
TheapproprIateuseofpulseoxImetrynecessItatesanapprecIatIonofbothphysIologIcand
technIcallImItatIons.0espItethenumerousclInIcalbenefItsofpulseoxImetry,other
factorsaffectItsaccuracyandrelIabIlIty.FactorsthatmaybepresentdurInganesthesIa
careandthataffecttheaccuracyandrelIabIlItyofpulseoxImetryIncludedyshemoglobIns,
dyes(methyleneblue,IndocyanInegreen,andIndIgocarmIne),naIlpolIsh,ambIentlIght,
lIghtemIttIngdIodevarIabIlIty,motIonartIfact,andbackgroundnoIse.Electrocauterycan
InterferewIthpulseoxImetryIftheradIofrequencyemIssIonsaresensedbythe
photodetector.FeportsofburnsorpressurenecrosIsexIstbutareInfrequent.These
complIcatIonscanbereducedbyInspectIngthedIgItsdurIngmonItorIng.
FecentdevelopmentsInpulseoxImetrytechnologyreportedlymaypermItmoreaccurate
measurementsofSpo
2
durIngpatIentmovement,lowperfusIoncondItIons,andInthe
presenceofdyshemoglobIns.SomeoftheseInstrumentsusecomplex
P.702
sIgnalprocessIngofthetwowavelengthsoflIghttoImprovethesIgnaltonoIseratIoand
rejectartIfact.StudIesInvolunteerssuggestthattheperformanceofpulseoxImeters
IncorporatIngthIstechnologyIssuperIortoconventIonaloxImetrydurIngmotIonofthe
hand,hypoperfusIon,andhypothermIa.
11,12,1J
DtherpulseoxImetrydevIcesIncorporate
eIghtwavelengthsoflIghttomoreaccuratelymeasureCDHband|etHb.
11,12,1J
PulseoxImetryhaswIdeapplIcabIlItyInmanyhospItalandnonhospItalsettIngs.However,
therearenodefInItIvedatademonstratIngareductIonInmorbIdItyormortalItyassocIated
wIththeadventofpulseoxImetry.AnolderlargerandomIzedtrIaldIdnotdetecta
sIgnIfIcantdIfferenceInpostoperatIvecomplIcatIonswhenroutInepulseoxImetrywas
used.
14
However,theanesthesIologIstsusIngSpo
2
feltagreaterlevelofcomfortthanthose
whodIdnotuseSpo
2
.AreductIonofanesthesIamortalIty,aswellasfewermalpractIce
claImsfromrespIratoryevents,coIncIdentwIththeIntroductIonofpulseoxImeters
suggeststhattheroutIneuseofthesedevIcesmayhavebeenacontrIbutIngfactor.
Blood Pressure Monitoring
PerIoperatIvemeasurementofarterIalbloodpressureIsanImportantIndIcatorofthe
adequacyofcIrculatIon.SystemIcbloodpressuremonItorIngIscommonlyperformed
IndIrectlyusIngextremItyencIrclIngcuffsordIrectlybyInsertIngacatheterIntoanartery
andtransducIngthearterIalpressure.Today,anesthesIologIstshaveavarIetyof
technIquesavaIlableformeasurIngchangesInsystolIc,dIastolIc,andmeanarterIal
pressure(|AP).
Indirect Measurement of Arterial Blood Pressure
ThesImplestmethodofbloodpressuredetermInatIonestImatessystolIcbloodpressureby
palpatIngthereturnofthearterIalpulsewhIleanoccludIngcuffIsdeflated.|odIfIcatIons
ofthIstechnIqueIncludetheobservanceofthereturnof0opplersounds,thetransduced
arterIalpressuretrace,oraphotoplethysmographIcpulsewaveasproducedbyapulse
oxImeter.
AuscultatIonoftheKorotkoffsoundspermItestImatIonofbothsystolIc(SP)anddIastolIc
(0P)bloodpressures.|APcanbecalculatedusInganestImatIngequatIon(|AP=0P+1/J
[SP0P]).KorotkoffsoundsresultfromturbulentflowwIthInanarterycreatedbythe
mechanIcaldeformatIonfromthebloodpressurecuff.SystolIcbloodpressureIssIgnaledby
theappearanceofthefIrstKorotkoffsound.0Isappearanceofthesoundoramuffledtone
sIgnalsthedIastolIcbloodpressure.
Figure 27-3.0IagramIllustratIngmotIonartIfact,aprematureventrIcularcontractIon
(P7C),andrespIratory(FESP)artIfactassensedbya0InamapnonInvasIveblood
pressure(8P)monItor.(FeproducedfromFamsey|:8loodpressuremonItorIng:
AutomatedoscIllometrIcdevIces.JClIn|onIt1991;7:56,wIthpermIssIon.)
ThedetectIonofsoundchangesIssubjectIveandpronetoerrorsbasedondefIcIencIesIn
soundtransmIssIonorhearIng.CuffdeflatIonratealsoInfluencesaccuracy.QuIck
deflatIonsunderestImatebloodpressure.PalpatIonandauscultatorytechnIquesrequIre
pulsatIlebloodflowandareunrelIabledurIngcondItIonsoflowflow.ThesetechnIquesare
reasonablyaccuratewhenaneroIdgaugesarewIthIncalIbratIon,theencIrclIngcuffIs
approprIatelysIzedandposItIoned,theInflatIonIsabovethetruesystolIcpressure,and
theKorotkoffsoundsorpulseIsproperlyIdentIfIed.
TheAmerIcanHeartAssocIatIonrecommendsthatthebladderwIdthforIndIrectblood
pressuremonItorIngshouldapproxImate40ofthecIrcumferenceoftheextremIty.
8ladderlengthshouldbesuffIcIenttoencIrcleatleast80oftheextremIty.FalselyhIgh
estImatesresultwhencuffsaretoosmall,whencuffsareapplIedtooloosely,orwhenthe
extremItyIsbelowheartlevel.FalselylowestImatesresultwhencuffsaretoolarge,when
theextremItyIsaboveheartlevel,orafterquIckdeflatIons.
SInce1976,mIcroprocessorcontrolledoscIllotonometershavereplacedauscultatoryand
palpatorytechnIquesforroutIneperIoperatIvebloodpressuremonItorIng.Standard
oscIllometrymeasuresmeanbloodpressurebysensIngthepoIntofmaxImalfluctuatIonsIn
cuffpressureproducedwhIledeflatIngabloodpressurecuff.|ostcurrentInstrumentsuse
oscIllometrIctechnIquestomeasuresystolIc,dIastolIc,andmeanbloodpressuresby
determInIngparameterIdentIfIcatIonpoIntsdurIngcuffdeflatIon.
nagenerIcnonInvasIveoscIllometrIcmonItor(noninvasive blood pressure,orN8P),cuff
pressureIssensedbyapressuretransducerwhoseoutputIsdIgItIzedforprocessIng.After
thecuffIsInflatedbyanaIrpump,cuffpressureIsheldconstantwhIleoscIllatIonsare
sampled.fnooscIllatIonsaresensedbythepressuretransducer,themIcroprocessor
swItchesopenadeflatIonvalve,andthenextlowerpressurelevelIssampledforthe
presenceofoscIllatIons.ThemIcroprocessorcontrollIngtheoperatIonoftheN8P
comparestheamplItudeofoscIllatIonpaIrsandnumerIcallydIsplaysthebloodpressure
estImate.FIgure27JdepIctshowatypIcalN8PIsobtaIned.nthIsexample,theeffectof
respIratoryvarIatIon,aprematureventrIcularcomplex,andcuffmovementare
demonstrated.
AutomatedoscIllometryhasbeendemonstratedtocorrelatewellwIthdIrectIntraarterIal
measurementof|APanddIastolIcbloodpressure.AutomatedoscIllometrymay
underestImatesystolIcbloodpressure,wIthmeanerrorsreportedfrom6.9to8.6mmHg
comparedwIthdIrectradIalarterypressuremeasurements.
DscIllometryrequIresthecarefulevaluatIonofseveralcardIaccyclesateachIncrementof
deflatIontosmoothout
P.70J
pronouncedrespIratoryvarIatIonsormotIonartIfacts.CuffmovementorerratIcpulse
transmIssIonInfluencesaccuracy.ntheanesthetIzedpatIent,automatedoscIllometryIs
usuallyaccurateandversatIle.AvarIetyofcuffsIzesmakesItpossIbletouseoscIllometry
Inallagegroups.
Problems With Noninvasive Blood Pressure Monitoring
CuffbasedpressuremonItorIngcontInuestobethestandardmethodusedInthe
perIoperatIveperIod.FaIluretodeflatethecuffIncreasesvenouspressure.Hematomas
havebeendescrIbedbothbeneathanddIstaltothecuff.TremorsorshIverIngcandelay
cuffdeflatIonandprolongthedeflatIoncycle.AcompartmentsyndromeattrIbutedtoa
prolongedInflatIoncyclehasbeendescrIbed.Ulnarneuropathyhasbeenreportedafterthe
useofautomatedcycledbloodpressurecuffs.CompressIonoftheulnarnervecanbe
avoIdedbyapplyIngtheencIrclIngcuffproxImaltotheulnargroove.Automated
sequencIngmayalterthetImIngofIntravenousdrugadmInIstratIonwhentheaccesssIteIs
locatedInthesameextremIty.HydrostatIcerrorsresultwhenbloodpressurecuffsare
placedonextremItIesthatareaboveorbelowtheleveloftherIghtatrIum.The
hydrostatIcoffsetcanbemathematIcallycorrectedbyaddIngorsubtractIng0.7mmHgfor
eachcentImeterthatthecuffIsoffthehorIzontalplaneoftheheart.
Indirect Continuous Noninvasive Techniques
SeveralmethodsformonItorIngbloodpressurecontInuouslyandnonInvasIvelyhavebeen
desIgnedandevaluatedforIntraoperatIvebloodpressuresurveIllance.ThesetechnIques
provIdeclInIcIanswIthacontInuousbloodpressureestImateandanaccuratedIsplayofthe
arterIalbloodpressuretrace.ndIrectcontInuousnonInvasIvetechnIquescontInuetobe
evaluatedtoenablebeattobeatbloodpressuremonItorIngwhIlereducIngtheInherent
rIsksandcostsofdIrectIntraarterIalmonItorIng.SomeclInIcalstudIessuggestthat
accuracyandprecIsIonofIndIrectcontInuousnonInvasIvetechnIquesaresatIsfactory,even
undercondItIonsofrapIdlychangInghemodynamIcs.
15,16
However,onerecentstudyusIng
oneofthesedevIcesIllustratedvarIableagreementwhencomparedwIthdIrectartery
bloodpressuremonItorIngdurInglIvertransplantatIon.
17
Therefore,randomIzedtrIalsare
neededtoIdentIfyInwhIchpatIentpopulatIonandInwhIchsurgIcalenvIronmentthe
IndIrectcontInuousnonInvasIvetechnIqueswIllbemosteffIcacIous.
Invasive Measurement of Vascular (Arterial Blood) Pressure
ndwellIngarterIalcannulatIonpermItstheopportunItytomonItorarterIalbloodpressure
contInuouslyandtohavevascularaccessforarterIalbloodsamplIng.ntraarterIalblood
pressuremonItorIngusesfluIdfIlledtubIngtotransmIttheforceofthepressurepulsewave
toapressuretransducerthatconvertsthedIsplacementofasIlIconcrystalIntovoltage
changes.TheseelectrIcalsIgnalsareamplIfIed,fIltered,anddIsplayedasthearterIal
pressuretrace.ntraarterIalpressuretransducIngsystemsaresubjecttomanypotentIal
errorsbasedonthephysIcalpropertIesoffluIdmotIonandtheperformanceofthe
cathetertransduceramplIfIcatIonsystemusedtosense,process,anddIsplaythepressure
pulsewave.
ThebehavIoroftransducers,fluIdcouplIngs,sIgnalamplIfIcatIon,anddIsplaysystemscan
bedescrIbedbyacomplexsecondorderdIfferentIalequatIon.SolvIngtheequatIon
predIctstheoutputandcharacterIzesthefIdelItyofthesystem'sabIlItytofaIthfullydIsplay
andestImatethearterIalpressureovertIme.ThefIdelItyoffluIdcoupledtransducIng
systemsIsconstraInedbytwopropertIes:damping()andnatural frequency(Fn).Zeta()
descrIbesthetendencyforfluIdInthemeasurIngsystemtoextInguIshmotIon.FndescrIbes
thetendencyforthemeasurIngsystemtoresonate.ThefIdelItyofthetransducedpressure
dependsonoptImIzIngandFnsothatthesystemcanrespondapproprIatelytotherange
offrequencIescontaInedInthepressurepulsewave.AnalysIsofhIghfIdelItyrecordIngsof
arterIalbloodpressureIndIcatesthatthepressuretracecontaInsfrequencIesfrom1toJ0
Hz.
SystemfIdelItyIsoptImIzedwhencathetersandtubIngarestIff,themassofthefluIdIs
small,thenumberofstopcocksIslImIted,andtheconnectIngtubIngIsnotexcessIve.
0ampInglowerstheeffectIvebandwIdthofthetransducersystem,whIchpromotesthe
potentIalforresonance.FIgure274demonstratestheeffectofdampIngonthecharacter
ofthearterIalpressuretrace.nclInIcalpractIce,underdampedcathetertransducer
systemstendtooverestImatesystolIcpressureby15toJ0mmHgandamplIfyartIfact
(catheterwhIp).LIkewIse,excessIveIncreasesInreducefIdelItyandunderestImate
systolIcpressure.ThepresenceofaIrbubblesInthecouplIngfluIdreducesthenatural
frequencyofthetransducIngsystem.ForclInIcaluse,ItIssuffIcIenttoplacethe
transducerattheleveloftherIghtatrIum,openthestopcocktoatmosphere,andbalance
theelectronIcamplIfyIngsystemtodIsplayzero.PerIodIcchecksofthezeroreference
poIntensurethattransducerdrIftIselImInated.
ThefastflushtestIsamethodusedatthebedsIdetodetermInethenaturalfrequency
anddampIngcharacterIstIcsofthetransducIngsystem.
18
ThIstestexamInesthe
characterIstIcsoftheresonantwavesrecordedafterthereleaseofaflush.0ampIngIs
estImatedbytheamplItuderatIoofthefIrstpaIrofresonantwavesandthenatural
frequencyIsestImatedbydIvIdIngthepaperspeedbytheIntervalcycle.
18
Arterial Cannulation
|ultIplearterIescanbeusedfordIrectmeasurementofbloodpressure,IncludIngthe
radIal,brachIal,axIllary,femoral,anddorsalIspedIsarterIes.TheradIalarteryremaIns
themostpopularsIteforcannulatIonbecauseofItsaccessIbIlItyandthepresenceofa
collateralbloodsupply.nthepast,assessmentofthepatencyoftheulnarcIrculatIonby
performanceofanAllen testhasbeenrecommendedbeforecannulatIon.AnAllentestIs
performedbycompressIngbothradIalandulnararterIeswhIlethepatIenttIghtenshIsor
herfIst.FeleasIngpressureoneachrespectIvearterydetermInesthedomInantvessel
supplyIngbloodtothehand.TheprognostIcvalueoftheAllentestInassessIngthe
adequacyofthecollateralcIrculatIonhasnotbeenconfIrmed.
19,20
FadIalarterycannulatIonandbloodpressuremonItorInghavebeenassocIatedwIthseveral
problems.TheradIalarterypulsepressurewaveIssubjecttoInaccuracIesInherenttoIts
dIstallocatIon.AfterseparatIonfromcardIopulmonarybypass,largepressuregradIents
betweenaortIcandradIalarterIeshavebeendescrIbed.
21
Complications of Invasive Arterial Monitoring
TraumatIccannulatIonhasbeenassocIatedwIthhematomaformatIon,thrombosIs,and
damagetoadjacentnerves.AbnormalradIalarterybloodflowaftercatheterremoval
occursfrequently.StudIessuggestthatbloodflownormalIzesInJto70days.FadIalartery
thrombosIscanbemInImIzedbyusIngsmallcatheters,avoIdIngpolypropylenetapered
catheters,andreducIngtheduratIonofarterIalcannulatIon.FlexIbleguIdewIresmay
reducethepotentIaltraumaassocIatedwIthcathetersnegotIatIngtortuousvessels.0urIng
cannularemoval,thepotentIalforthromboembolIsmmaybedImInIshedbycompressIng
theproxImalanddIstalarterIalsegmentwhIleaspIratIngthecannuladurIngwIthdrawal.
P.704
Figure 27-4.TherelatIonshIpbetweenthefrequencyoffluIdfIlledtransducIng
systemsanddampIng.Theshaded arearepresentstheapproprIaterangeofdampIng
foragIvennaturalfrequency(Fn).ThesIzeofthewedgealsodependsonthe
steepnessofthearterIalpressuretraceandheartrate.(FeproducedfromCardnerF|:
0Irectbloodpressuremeasurement:0ynamIcresponserequIrements.AnesthesIology
1981;54:2J1,wIthpermIssIon.)
|anycannulatIonsIteshavebeenusedfordIrectarterIalbloodpressuremonItorIng(Table
27J).ThreetechnIquesforcannulatIonarecommon:dIrectarterIalpuncture,guIdewIre
assIstedcannulatIon(SeldIngertechnIque),andthetransfIxIonwIthdrawalmethod.A
necessarycondItIonforpercutaneousplacementIsIdentIfIcatIonofthearterIalpulse,
whIchmaybeenhancedbya0opplerflowdetectIondevIceInpatIentswIthpoor
perIpheralpulses.
ArterIalcannulatIonIsregardedasanInvasIveprocedurewIthdocumentedmorbIdIty.
schemIaafterradIalarterycannulatIonresultIngfromthrombosIs,proxImalembolI,or
prolongedshock,albeItrare,hasbeendescrIbed.
22
ContrIbutIngfactorsIncludesevere
atherosclerosIs,dIabetes,lowCD,andIntenseperIpheralvasoconstrIctIon.schemIa,
hemorrhage,thrombosIs,embolIsm,cerebralaIrembolIsm(retrogradeflowassocIatedwIth
flushIng),aneurysmformatIon,arterIovenousfIstulaformatIon,skInnecrosIs,andInfectIon
havereportedlyoccurredasthedIrectresultofarterIalcannulatIon,arterIalblood
samplIng,orhIghpressureflushIng.
ContInuousflushdevIcesareIncorporatedIntodIsposabletransducerkItsandInfuseatJto
6mL/hr.nneonates,theInfusIonvolumemaycontrIbutetofluIdoverload.ContInuous
flushdevIceshavelIttleeffectonthebloodpressuremeasurement.However,pressurIzed
flushsystemsmayserveasasourceofanaIrembolIsm.FemovIngaIrfromthepressurIzed
InfusIonbag,stopcocks,andtubIngmInImIzesthepotentIalforaIrembolIsm.
0IrectarterIalpressuremonItorIngrequIresconstantvIgIlance.ThedatadIsplayedmust
correlatewIthclInIcalcondItIonsbeforetherapeutIcInterventIonsareInItIated.Sudden
IncreasesInthetransducedbloodpressuremayrepresentahydrostatIcerrorbecausethe
posItIonofthetransducerwas
P.705
notadjustedafterchangeIntheoperatIngroomtable'sheIght.Suddendecreasesoften
resultfromkInkIngofthecatheterortubIng.8eforeInItIatIngtherapy,thetransducer
systemshouldberezeroedandthepatencyofthearterIalcannulaverIfIed.ThIsensures
theaccuracyofthemeasurementandavoIdstheInItIatIonofapotentIallydangerous
medIcatIonerror.
Table 27-3 Arterial Cannulation and Direct Blood Pressure Monitoring
ARTERIAL CANNULATION
SITE
CLINICAL POINTS OF INTEREST
FadIalartery
PreferredsIteformonItorIng
Nontaperedcatheterspreferred
Ulnarartery
ComplIcatIonsImIlartoradIa
PrImarysourceofhandbloodflow
8rachIalartery
nsertIonsItemedIaltobIcepstendon
|edIannervedamageIspotentIalhazard
Canaccommodate18gaugecannula
AxIllaryartery
nsertIonsIteatjunctIonofpectoralIsanddeltoId
muscles
SpecIalIzedkItsavaIlable
Femoralartery
EasyaccessInlowflowstates
PotentIalforlocalandretroperItonealhemorrhage
Longercatheterspreferred
0orsalIspedIsartery
CollateralcIrculatIon=posterIortIbIalartery
HIghersystolIcpressureestImates
Central Venous and Pulmonary Artery Monitoring
CentralvenouscannulasareImportantportalsforIntraoperatIvevascularaccessandfor
theassessmentofchangesInvascularvolume.CentralvenouscannulaspermIttherapId
admInIstratIonoffluIds,InsertIonofpulmonaryarterycatheters(PACs)orcentralvenous
D
2
(ScvD
2
)catheters,InsertIonoftransvenouselectrodes,monItorIngofcentralvenous
pressure(C7P),andasIteforobservatIonandtreatmentofvenousaIrembolIsm.
TherIghtInternaljugularveInIsthemostcommonsIteforcannulatIonbyanesthesIologIsts
becauseItIsaccessIblefromtheheadoftheoperatIngtable,hasapredIctableanatomy,
andhasahIghsuccessrateInbothadultsandchIldren.
2J
TheleftsIdedInternaljugular
veInIsalsoavaIlablebutIslessdesIrablebecauseofthepotentIalfordamagIngthe
thoracIcductordIffIcultyInmaneuverIngcathetersthroughthejugularsubclavIan
junctIon.AccIdentalcarotIdarterypunctureIsapotentIalproblemwItheItherlocatIon.
ThreetechnIques(posterIor,central,andanterIor)havebeendescrIbedforInternaljugular
cannulatIon.EachInsertIonpoIntIsreferencedtothetrIangleformedbythesternaland
clavIcularheadsofthesternocleIdomastoIdmuscleandtheclavIcle.7enIpunctureusInga
22gaugeseekerneedlemInImIzestraumatoadjacentstructures.WhenthelocatIonof
theInternaljugularveInIsdIffIculttoascertaIn,ultrasonographycanassIstInIdentIfyIng
theproxImItyofInternaljugularveInandthecarotIdartery.SomestudIeshavesuggested
thatultrasoundguIdedplacementofrIghtInternaljugularplacedcentralvenouscatheters
mayreducecomplIcatIonsandImprovefIrstattemptsuccessrates.
24,25
AlternatIvestotheInternaljugularveInIncludetheexternaljugular,subclavIan,
antecubItal,andfemoralveIns.AlthoughtheCentersfor0IseaseControlandPreventIon
suggeststhatthepreferredsIteforcentralvenouscannulatIonshouldbethesubclavIan
sItetopotentIallyreducebloodstreamInfectIons,thIsrecommendatIonmustbetakenIn
contextofthepartIcularclInIcalsItuatIon.
26
TheInternaljugularapproachmaybesuperIor
InthosepatIentswIthcoagulopathIes(wherebleedIngatthesubclavIansItemaybemore
dIffIculttostop)orpatIentswIthsevereacutelungInjury(wheretherIskofpneumothorax
maybeheIghtened).
27
WhencomparIngthesubclavIanapproachwIththefemoral
approach,thereportedreductIonInInfectIonrIskfavorssubclavIan.However,thereIsa
paucItyofprospectIverandomIzeddatawhencomparIngsubclavIantoInternaljugular.
28
Central Venous Pressure Monitoring
ThebenefItofC7PmonItorInghasbeenthesubjectofconsIderabledebate.Proponentsof
C7PmonItorIngbelIevethatC7PpressuresareessentIallyequIvalenttorIghtatrIal
pressuresandserveasareflectIonofrIghtventrIcularpreload.
29
CondItIonsthataffect
rIghtatrIalpressurealsoInfluencetheC7Ppressuretrace.ThenormalC7Pwaveform
consIstsofthreepeaks(a,c,andvwaves)andtwodescents(x,y),eachresultIngfromthe
ebbandflowofbloodIntherIghtatrIum(FIg.275).CorrespondIngeventsoccurIntheleft
atrIumandsImIlarpressurecontoursareobserveddurIngmonItorIngofpulmonaryartery
pressurewhenthePACIsplacedIntheoccludedposItIon.
ThecharacteroftheC7Ptracedependsonmanyfactors,IncludIngheartrate,conductIon
dIsturbances,trIcuspIdvalvefunctIon,normalorabnormalIntrathoracIcpressurechanges,
andchangesInrIghtventrIcularcomplIance.npatIentswIthatrIalfIbrIllatIon,awaves
areabsent.WhenresIstancetotheemptyIngoftherIghtatrIumIspresent,largeawaves
areoftenobserved.ExamplesIncludetrIcuspIdstenosIs,rIghtventrIcularhypertrophyasa
resultofpulmonIcstenosIs,oracuteorchronIclungdIseaseassocIatedwIthpulmonary
hypertensIon.LargeawavesmayalsobeobservedwhenrIghtventrIcularcomplIanceIs
ImpaIred.
Figure 27-5.Thenormalcentralvenouspressure(C7P)trace.ECC,electrocardIogram.
(Fedrawnfrom|arkJ8:CentralvenouspressuremonItorIng:ClInIcalInsIghtsbeyond
thenumbers.JCardIothoracAnesth1991;5:16J,wIthpermIssIon.)
TrIcuspIdregurgItatIontypIcallyproducesgIantvwavesthatbegInImmedIatelyafterthe
QFScomplex.LargevwavesareoftenobservedwhenrIghtventrIcularIschemIaorfaIlure
IspresentorwhenventrIcularcomplIanceIsImpaIredbyconstrIctIveperIcardItIsor
cardIactamponade.ApromInentvwavedurIngC7PmonItorIngmaysuggestrIght
ventrIcularpapIllarymuscleIschemIaandtrIcuspIdregurgItatIon.WhenrIghtventrIcular
complIancedecreases,theC7PoftenIncreaseswIthpromInentaandvwavesfusIngto
formanmorwconfIguratIon.
C7PmonItorIngIsoftenunrelIableforestImatIngleftventrIcularfIllIngpressures,
especIallywhencardIopulmonarydIseaseprocessesalterthenormalcardIovascular
pressurevolumerelatIonshIps.However,C7PmonItorIngIslessInvasIveandlesscostly
thanpulmonaryarterymonItorIngandoffersunIqueunderstandIngofrIghtsIded
hemodynamIceventsandthestatusofvascularvolume.
Pulmonary Artery Monitoring
ThedevelopmentoftheflowdIrected,balloonflotatIonPACwasamajoradvanceIn
hemodynamIcmonItorIng,andIthasbeenanImportanttoolInthequantItatIveassessment
ofcardIopulmonaryfunctIon.NumerousartIcleshaverevIewedthevarIousapplIcatIons
andbenefItsofpulmonaryarterymonItorIng.
J0
UseshouldbeguIdedbytheInformatIon
neededforenhanceddIagnosIsandtherapy.
J1
Today,PACmonItorIngIscommonlyusedIn
surgIcalpatIentstohelpevaluateandtreathemodynamIcalteratIons,whIchcontrIbute
sIgnIfIcantlytothemorbIdItyandmortalItyInherenttothesurgIcalcareofhIghrIsk
patIents.
n199J,theASApublIshedpractIceguIdelInesthatexamInedtheevIdencesupportIngthe
clInIcaleffectIvenessofPACmonItorIng.TheseguIdelIneswereupdatedIn200J.
J2
ssues
suchasthetImIngofPACmonItorIng,ItseffectontreatmentdecIsIons,patIentselectIon
andcasemIx,andevIdenceregardIngPACmonItorIngcontrIbutIontoposItIveornegatIve
outcomeswereevaluatedusIngstrIngentevIdencebasedmethodology.ThIseffort
IdentIfIedmanyflawsInthebodyofevIdence,
P.706
whIchmadeItdIffIculttodrawmeanIngfulconclusIonsregardIngtheeffectIvenessofPAC
monItorIngtoreducemorbIdItyormortalIty.TheconsensusopInIonImplIesthatPAC
monItorIngmayreduceperIoperatIvecomplIcatIonsIfcrItIcalhemodynamIcdataobtaIned
durIngapproprIatePACmonItorIngareaccuratelyInterpretedandapproprIatetreatmentIs
taIloredtothecondItIonsastheychangeovertIme.
J2
Table 27-4 Derived Hemodynamic Variables
NAME ABBREVIATION CALCULATION UNITS
CardIacIndex C CD/8SA 1L/mIn/m
2
SystemIcvascularresIstance S7F (|APC7P/CD)80 dynecm/s
Pulmonaryvascular
resIstance
P7F
(|PAPPCWP/CD)
80
dynecm/s
StrokeIndex S C/heartrate mL/beat/m
2
LeftventrIcularstrokework
Index
L7SW
S(|APPCWP)
0.01J6
g/beat/m
2
FIghtventrIcularstroke
workIndex
F7SW
S(|PAPC7P)
0.01J6
g/beat/m
2
CD,cardIacoutput;8SA,bodysurfacearea;|AP,meanarterIalpressure;C7P,
centralvenouspressure;|PAP,meanpulmonaryarterIalpressure;PCWP,
pulmonarycapIllarywedgepressure.
PACspermItthemeasurementofIntracardIacpressures,thermodIlutIoncardIacoutput
(TCD),mIxedvenousoxygensaturatIon,IntracavItaryelectrocardIograms,andlungwater.
ThIsInformatIoncanhelpdefIneclInIcalproblems,monItortheprogressIonof
hemodynamIcdysfunctIons,andguIdetheresponseofcorrectIvetherapy.
ThemeasurementofIntracardIacpressurescanIndIrectlyassessleftventrIcularpreload,
dIagnosetheexIstenceofpulmonaryhypertensIon,ordIfferentIatecardIacandnoncardIac
causesofpulmonaryedema.PACsallowfortherapIdandreproducIblemeasurementsof
TCD,calculatIonofoxygendelIvery(CDarterIalD
2
content),andassessmentofcardIac
work.HemodynamIcmeasurementsareoftenpredIcatedonthemanIpulatIonofpreload,
afterload,andcontractIlIty.SeveralderIvedIndIcesofhemodynamIcfunctIonnecessItate
measurementscommonlyobtaInedfromPACmonItorIng(Table274).
AccesstomIxedvenousbloodfromthepulmonaryarteryportprovIdesanIndIrect
assessmentofthebalancebetweenD
2
delIveryandD
2
utIlIzatIon.|Ixedvenousoxygen
saturatIon(Svo
2
)measurementsareneededtocalculatemIxedvenousoxygencontent(C[v
wIthbarabove]o
2
).C[vwIthbarabove]o
2
IsanImportantvarIableusedforcalculatIng
Intrapulmonary(fIrstequatIonfollowIng)orIntracardIacshunts(secondequatIon
followIng).
WhereCco
2
=endcapIllaryD
2
content,Cao
2
=arterIalD
2
content,C[vwIthbarabove]o
2
=
mIxedvenousD
2
content,[QwIthdotabove]s/[QwIthdotabove]t=shuntfractIon,Sao
2
=
arterIalD
2
saturatIon,Srao
2
=rIghtatrIalD
2
saturatIon,S[vwIthbarabove]o
2
=mIxed
venousD
2
saturatIon,and[QwIthdotabove]p/[QwIthdotabove]s=pulmonaryto
systemIcshunt.
ThevalIdItyofPACmonItorIngdependsonaproperlyfunctIonIngpressuremonItorIng
system,correctlyIdentIfyIngthetruepulmonary capillary occlusion pressure(PCDP),and
IntegratIonofthevarIousfactorsthataffecttherelatIonshIpofPCDP,andtheother
cardIacpressuresandvolumesthataredetermInantsofventrIcularfunctIon.FIgure276
depIctsthetransducedpressurewavesobservedasaPACIsfloatedtothewedgedposItIon.
CatheterplacementIsmostcommonlyperformedbyobservIngthepressurewavesasthe
catheterIsfloatedfromtheC7PposItIonthroughtherIghtheartchambersIntothe
pulmonaryartery.
PACmonItorIngnecessItatesanapprecIatIonofthevarIousphysIologIcdetermInantsofCD
andoxygendelIvery.ThePACIsusedtocontInuouslymonItorthepulmonaryartery
pressureandIntermIttentlymonItorpulmonarywedgepressure.PCDPIsusedtoassessleft
ventrIcularpreloadIndIrectlybyreflectIngchangesInleftventrIcularenddIastolIc
pressure(L7E0P).FIgure277depIctstherelatIonshIpbetweenthevarIouspressuresInthe
cardIopulmonarysystem.
thasbeenwelldemonstratedthatrIghtsIdedpressuresIntheheartoftenarepoor
IndIcatorsofleftventrIcularfIllIng,eItherasabsolutenumbersorIntermsofthedIrectIon
ofchangeInresponsetotherapy.ThecorrelatIonofthesepressuresasestImatesofL7E0P
(orleftventrIcularenddIastolIcvolume[L7E07])IsdIrectlyrelatedtotheIrproxImItyto
theleftventrIcleandthestatusofventrIcularcomplIance.AssumInganopenconduItfrom
thecathetertIptotheleftventrIcle,whenthePACIsoccluded(wedged),therIghtsIded
heartchambersandvalvesarebypassed.0urIngenddIastole,thereIscessatIonofforward
bloodflow,andastatIcfluIdcolumnIspresumedtoexIstfromtheleftventrIcletothePAC
tIp.deally,changesInL7E0ParereflectedbyallproxImalpressures(leftatrIal,pulmonary
venous,pulmonaryarteryenddIastolIc
P.707
pressure,andPCDP).AlteratIonsofInternalorexternalforcesapplIedtotheopenconduIt
durIngPCDPmeasurementsmayInvalIdatethePCDPL7E0PL7E07relatIonshIp.
Figure 27-6.PressuretracIngobserveddurIngtheflotatIonofapulmonaryartery
catheter.FA,rIghtatrIum;F7,rIghtventrIcle;PA,pulmonaryartery;PCW,pulmonary
capIllarywedgepressure.(Feproducedfrom0IzonCT,8arashPC:Thevalueof
monItorIngpulmonaryarterypressureInclInIcalpractIce.Conn|ed1979;41:622,
wIthpermIssIon.)
Figure 27-7.TheanatomIcposItIonofapulmonaryarterycatheterInthepulmonary
artery.Thedashed lineposItIonstheInflatedballoonInthewedgedposItIon.FA,
rIghtatrIum;F7,rIghtventrIcle;PA,pulmonaryartery;Alv,alveolus;PCap,pulmonary
capIllary;P7,pulmonaryveIn;LA,leftatrIum;L7,leftventrIcle.,,and
characterIzetherelatIonshIpofP
aveolar
,P
arterIal
,andP
venous
asdescrIbedbyWestet
al.
JJ
ThebottomofthefIgureshowsaprogressIvecorrelatIonofvascularpressures.
(Feproducedfrom7enderJS:nvasIvecardIacmonItorIng.CrItCareClIn1988;4:455,
wIthpermIssIon.)
Factors Affecting the Accuracy of Pulmonary Artery Catheter
Data
Pulmonary Vascular Resistance
AnydIseaseprocessorcondItIonthatIncreasespulmonaryvascularresIstancehasthe
potentIaltoreducepulmonarybloodflowandaltertherelatIonshIpbetweenPCDPand
pulmonaryarteryenddIastolIcpressure(PAE0P).PathologIccondItIonssuchasacuteor
chronIclungdIsease,pulmonaryembolI,alveolarhypoxIa,acIdosIs,andhypoxemIa,and
manyvasoactIvedrugsIncreasepulmonaryvascularresIstanceandhavethepotentIalto
modIfythePCDPPAE0PrelatIonshIp.TachycardIashortensventrIculardIastoleandalso
IncreasespulmonaryvascularresIstanceandthemeasureofpulmonaryarterydIastolIc
pressure.
AlveolarPulmonary Artery Pressure Relationships
Westetal.
JJ
descrIbedagravItydependentdIfferencebetweenventIlatIonandperfusIon
Inthelung.ThevarIabIlItyInpulmonarybloodflowIsaresultofdIfferencesInpulmonary
artery(PA),alveolar(Palv),andvenouspressures(P7)andIscategorIzedIntothree
dIstInctzones.DnlyZone(PAP7Palv)meetsthecrIterIaforunInterruptedbloodflow
andacontInuouscommunIcatIonwIthdIstalIntracardIacpressures.ncreasesInalveolar
pressure,decreasesInperfusIon,orchangesIntheposItIonofthepatIentcanconvert
areasofzoneIntoeItherzoneor.FlowdIrectedPACsusuallyadvancetogravIty
dependentareasofhIghestbloodflow.ThefollowIngcharacterIstIcssuggestthatthePAC
tIpIsnotInzone:PCDPPAE0P,nonphasIcPCDPtracIng,andInabIlItytoaspIrateblood
fromthedIstalportwhenthecatheterIswedged.
Respiratory Pattern and Airway Pressure
ChangesInIntrathoracIcandIntrapleuralpressureaffecttransmuralcardIacpressures.
TransmuralpressureIsdefInedasthenetdIstendIngpressureoftheleftventrIcle.Changes
InIntrathoracIcpressureaffectthePCDPL7E0PrelatIonshIp.PosItIveendexpIratory
pressure(PEEP)therapycanInducechangesInbothIntravascularandIntrapleural
pressures.PEEPIncreasesalveolarpressure,potentIallyconvertIngzoneareastozone.
fPEEPIstransmIttedacrossthealveolI,IntrapleuralpressureIncreases.Pulmonary
complIancedetermInestheextentofthIseffect.PEEPaltersventrIculardIstensIbIlItyand
decreasesvenousreturn,whIchcausesadIsproportIonateIncreaseInPCDP(andL7E0P)
comparedwIthchangesInL7E07.
TheeffectofPEEPtherapyonPCDPIsmInImalIfthelevelsofPEEParelow(10cmH
2
D)
andthePACIslocatedInzone.HIgherlevelsofPEEPInfluencethePCDPL7E0P
relatIonshIp,dependIngonpulmonarycomplIanceandtransmIssIonofalveolarpressures.
0urInghIghPEEPtherapy,esophagealpressuremeasurementscanbemeasuredtoreflect
Intrapleuralpressure.AlternatIvely,subtractIng1to2mmHgfromthedIsplayedwedge
pressureforeach5cmH
2
DofPEEPtherapygIvesPCDPestImatewhenPEEPIsabove10cm
H
2
D.
Intracardiac Factors
DbstructIonatthemItralvalvefrommItralstenosIs,atrIalmyxoma,orclotcanInterfere
wIththeabIlItyofleftatrIalpressuretoreflectL7E0P.SImIlarly,mItralregurgItatIon,a
noncomplIantleftatrIum,orlefttorIghtIntracardIacshuntIngoftenIsassocIatedwIth
largevwaves
J4
(seeChapter62).
0ecreasesInleftventrIcularcomplIance,aortIcregurgItatIon,orprematureclosureofthe
mItralvalvemayreversetheleftatrIalpressureL7E0PpressuregradIent.WhenthIs
occurs,PCDPIsnotavalIdreflectIonofL7E07.
FIgure278graphIcallydepIctstherelatIonshIpbetweenL7E0PandL7E07.TheL7E0P
L7E07relatIonshIpIsnotlInear.AfamIlyofL7E0PL7E07complIancecurvescharacterIzes
theeffectofchangIngthestIffnessoftheleftventrIcle.7entrIcularcomplIanceIsa
dynamIcfactorInfluencedbymanyphysIologIcandpathologIcvarIables.TheL7E0PL7E07
complIancecurvessuggestthatatlowpreloads,largerIncreasesInL7E07producesmaller
changesInL7E0P.Conversely,athIgherpreloads,asImIlarchangeInL7E07producesa
greaterpressurechange.ForagIvenL7E07,anydecreaseInventrIcularcomplIance(e.g.,
IschemIa)resultsInanIncreaseInL7E0P.ThIsexplaInsthedevelopmentofhydrostatIc
pulmonaryedemaatnormalL7E07.FactorsthatareassocIatedwIthchangesInventrIcular
complIancearelIstedInTable275.
Complications of Pulmonary Catheter Monitoring
AdverseeffectsfromPACmonItorIngcanbearesultofaccessIngthecentralvenous
cIrculatIon,thecatheterIzatIonprocedure,
P.708
orfromuseofthecatheterafterPACplacement.Centralvenousaccessrepresentsan
InvasIveprocesswIthInherentrIsks,someofwhIcharerarebutarepotentIallylIfe
threatenIng.
Table 27-5 Decreased Left Ventricular Compliance: Common Etiologies
|yocardIalIschemIa CardIactamponade
FestrIctIvemyopathIes |yocardIalfIbrosIs
FIghttoleftIntraventrIcularshunts notropIcdrugs
AortIcstenosIs HypertensIon
Figure 27-8.TypIcalventrIcularcomplIancecurve.L7E0P,leftventrIcularend
dIastolIcpressure;L7E07,leftventrIcularenddIastolIcvolume.(Feproducedfrom
7enderJS:nvasIvecardIacmonItorIng.CrItCareClIn1988;4:455,wIthpermIssIon.)
UnIntentIonalpunctureofnearbyarterIes,bleedIng,neuropathy,andpneumothoraxmay
resultfromneedleInsertIonIntoadjacentstructures.AIrembolIsmmayoccurIfacannula
IsopentotheatmosphereandaIrIsentraIneddurIngorafterC7Pplacement.
0ysrhythmIasarecommondurIngthecatheterIzatIonprocedure,wIthareportedIncIdence
of4.7to68.9.
J2
7entrIculartachycardIaorfIbrIllatIonmaybeInduceddurIngcatheter
advancement.CatheteradvancementhasbeenassocIatedwIthrIghtbundlebranchblock
andmayprecIpItatecompleteheartblockInpatIentswIthpreexIstIngleftbundlebranch
block.Table276summarIzestheadverseeffectsasreportedbytheASATaskForceon
pulmonaryarterycatheterIzatIon.
J2
TherateofIatrogenIcdeathsassocIatedwIthPACmonItorIngIsuncertaIn.Themost
dreadedcomplIcatIonassocIatedwIthPACmonItorIngIspulmonaryarteryrupture.
PulmonaryhypertensIon,coagulopathy,andheparInIzatIonareoftenpresentInpatIents
whohavedIedofpulmonaryarteryrupture.PerforatIonsandsubsequenthemorrhagecan
beavoIdedbyrestrIctIngoverwedgIng,mInImIzIngthenumberofballoonInflatIons,and
usIngpropertechnIquedurIngballoonInflatIons.
nfectIonIsapotentIalcomplIcatIonofthecontInueduseofC7PandPACcatheters.
CuIdelInesforthepreventIonofIntravascularcatheterrelatedInfectIonshavebeen
publIshedbytheCentersfor0IseaseControlandPreventIon.
26
|ethodsrecommendedto
reducetheIncIdenceoflocalandbloodstreamInfectIonsInclude(1)educatIonandtraInIng
ofclInIcIanswhoInsertandmaIntaIncentralcatheters,(2)useofmaxImalsterIlebarrIer
precautIons(mask,cap,sterIleglovesandgown,andlargesterIledrape),(J)useof2
chlorhexIdIneforskInpreparatIon,and(4)avoIdanceofroutInereplacementofC7Pand
PACcatheterssolelyforthepurposeofreducIngtherIskofInfectIon.
SIncetheadventofPACs,severalmodIfIcatIonshavebeenIntegratedIntothedesIgnthat
enhancetheIrmonItorIngcapabIlItIes.ThefIrstsIgnIfIcantdesIgnmodIfIcatIon
IncorporatedathermIstoratthetIp,permIttIngthemeasurementofCD.Dtherfeatures
havebeenIntroducedforclInIcaluseorevaluatIon.TheseIncludemIxedvenousoxImetry,
measurementofrIghtventrIcularejectIonfractIon,pacIngoptIons,andcontInuousCD
monItorIng.
Mixed Venous Oximetry
ContInuousestImatesofSvo
2
provIdeareflectIonoftotaltIssueoxygenbalance.Dxygen
delIvery([0wIthdotabove]o
2
)equalsthearterIaloxygencontentmultIplIedbytheCD(CD
[Hb1J.8Sao
2
+(Pao
2
0.00J1)]),where1J.8representsthevolumeofoxygencarrIedby
HbconvertedtogramsperlIter,Sao
2
representsthearterIaloxygensaturatIon,Pao
2
representsthearterIalpressureofoxygen,and0.00J1representsthe8unsensolubIlIty
coeffIcIentofdIssolvedoxygenpermIllImetersofmercury.DxygenconsumptIon([7wIth
dotabove]o
2
)IsdetermInedbythedIfferencebetweenarterIalandvenousoxygen
delIvery.TherelatIonshIp
P.709
betweenSvo
2
,[7wIthdotabove]o
2
,and[0wIthdotabove]o
2
IsdemonstratedInthe
followIngequatIonderIvedfromtheFIckrelatIonshIp:
Figure 27-9.ThIsSvo
2
recordIngInapostcoronaryarterybypasspatIentdemonstrates
theeffectsofshIverIngandItstreatment,andtherelatIonshIpbetweenSvo
2
,cardIac
output(CD),andmetabolIcrate(S[7wIthdotabove]o
2
).
*PancuronIum,alongactIngmusclerelaxant,usedtoelImInateshIverIngandImprove
S[7wIthdotabove]o
2
.(Feproducedfrom7enderJS:nvasIvecardIacmonItorIng.CrIt
CareClIn1988;4:455,wIthpermIssIon.)
S[vwIthbarabove]o=Sao
2
[7wIthdotabove]o
2
/Hb1J.8CD
Table 27-6 Adverse Effects Associated with Pulmonary Artery Monitoring
COMPLICATION REPORTED INCIDENCE (%)
Centralvenousaccess
ArterIalpuncture 0.11J
PostoperatIveneuropathy 0.J1.1
Pneumothorax 0.J4.5
AIrembolIsm 0.5
FlotatIonofpulmonaryarterycatheter
|InordysrhythmIas 468.9
7entrIculartachycardIaorfIbrIllatIon 0.J62.7
FIghtbundlebranchblock 0.14.J
Completeheartblock(prIorleftbundlebranchblock) 08.5
ComplIcatIonsassocIatedwIthcatheterresIdence
Pulmonaryarteryrupture 0.0J1.5
PosItIveculturesfromcathetertIp 1.4J4.8
SepsIssecondarytocatheterresIstance 0.711.4
ThrombophlebItIs 6.5
7enousthrombosIs 0.566.7
PulmonaryInfarctIon 0.15.6
|uralthrombus 2861
7alvularorendocardIalvegetatIons 2.2100
0eathsattrIbutedtopulmonaryarterycatheter 0.021.5
FromPractIceCuIdelInesforPulmonaryArteryCatherIzatIon:Anupdatedreport
byTheAmerIcanSocIetyofAnesthesIologIstsTaskForceonPulmonary
CatherIzatIon.AnesthesIology200J;99:988,wIthpermIssIon.
ThIsequatIonIndIcatesthatchangesInSvo
2
varydIrectlywIthchangesInCD,Hb,andSao
2
andInverselywIth[7wIthdotabove]o
2
.ThenormalIs75,whIchdenotestIssueoxygen
extractIonof25.
TheoxImetrIcPACusesreflectancespectrophotometryInwhIchseveralwavelengthsare
transmIttedthroughoptIcalfIbersembeddedInthePAC.ThereflectedIntensItyoflIght
IdentIfIesthesaturatIonofbloodsurroundIngthetIpofthePAC.Threewavelengthin vivo
systemscorrelatewellwIthsImultaneoussamplesmeasuredbycooxImetry.
J5
Anexample
oftheutIlItyofmIxedvenousoxImetryIsdepIctedInFIgure279.
Central Venous Oxygen Saturation and its Relation to Mixed
Venous Oxygen Saturation
AlthoughcentralvenousD
2
saturatIon(Scvo
2
)representstheamountofoxygenextractIon
fromtheupperpartofthebodyandbraIn,someclInIcIanssuggesttheuseofScvo
2
asa
surrogatemeasureofSvo
2
.
J6
Scvo
2
measurementsareanappealIngalternatIvebecause
theycanbetakenfromcentralvenouscathetersanddonotrequIrePACInsertIon.Fecent
sepsIsguIdelInessuggestusIngSvo
2
andScvo
2
InterchangeablyforpatIentswIthseptIc
shock.
J7
However,othersarguethatScvo
2
cannotbesynonymouslyusedInplaceofSvo
2
durIngseptIcshock.
J6,J8
TheargumentsagaInsttheuseofScvo
2
statethatdurIngseptIc
shock,regIonaloxygenextractIonInthegastroIntestInaltractIncreases,butcerebralblood
flowIsmaIntaIned.ThIsphenomenonmaycausealesspronounceddropInScvo
2
thanSvo
2
durIngshock.
J6,J7
naddItIon,durIngcardIogenIcorhypovolemIcshock,mesenterIcand
renalflowdecreaseswIthanIncreaseInoxygenextractIonthatmayproducedIscrepancIes
betweenSvo
2
andScvo
2
.
J6
AlthoughstudIesIntheseptIcshockpatIentpopulatIonshow
mIxedresults,recentIntraoperatIvedataIndIcatethatSvo
2
andScvo
2
trendsmay
correlateandthIsmayaIdIntherapeutIcdecIsIonmakIng.
J9
Therefore,furtheroutcome
datamaybeneededtoaddresstheaffectsofdIfferentpatIentpopulatIonsandclInIcal
sItuatIonsontheutIlItyofScvo
2
whenapproxImatIngSvo
2
.
Indicator Dilution Applications
ndIcatordIlutIondetermInatIonofCDIsbasedonaconceptproposedbyStewartand
testedbyHamIltonandcolleagues.
40,41
ThermodIlutIoncardIacoutput(TCD)determInatIon
IsthemostwIdelyusedadaptatIonoftheIndIcatordIlutIonprIncIple,whIchwasfIrst
descrIbedbyFegler
42
In1954.Today,0.9salIneor5dextrosemIxturescanbeused
InterchangeablyastheIndIcator,producIngsImIlarCDmeasurements.AthermIstorlocated
atthePACtIprecordsthedecreaseIntemperatureasthebolusofcooledInjectatepasses
throughthepulmonaryartery.ComputerscontendwIththecomplexItyoftheTCD
equatIon,whIchIncludesthefollowIngfactors:specIfIcheatofthebloodandtheIndIcator
fluId,thevolumeofInjectate,cathetersIze,specIfIcgravItyofthebloodandIndIcator,
andtheareaofthebloodtemperaturecurve.ComparIsonstudIessuggestthatusIngeIther
roomtemperatureorIcedInjectateprovIdesacceptableestImatesofCD.cedInjectateIs
oftenpreferredbecauseItproducesamoreexactIngcurvewIthabettersIgnaltonoIse
ratIo.
4J
Whenproperlyperformed,TCDmeasurementscorrelatewellwIthdIrectFIckordye
dIlutIonestImatesofCD.nclInIcalpractIce,trIplIcatedetermInatIonsareaveragedto
IncreaseprecIsIon.TCDestImatescanvarywIththerespIratorycycle.ThIsvarIabIlItycan
bereducedbyperformIngmeasurementsatpeakInspIratIonorendexpIratIon.PrecIsIonIs
enhancedbyensurIngthattherateofInjectIonandthevolumeareconstant.|ostCD
computersdelaytherepeatmeasurementJ0to90secondstostabIlIzethethermal
envIronmentofthePACthermIstor.
Adaptations for Continuous Cardiac Output Monitoring
ContInuousCDmonItorIngoffersthepotentIaltoIdentIfyacutechangesInventrIcular
performanceastheyoccur.AproperlyposItIonedPACprovIdesaccesstotherIghtatrIum,
rIghtventrIcle,andpulmonaryarteryoutflowtract.TheselocatIonsprovIdemanyoptIons
forassessmentofcontInuousCDmonItorIng.SeveralthermaltechnIqueshavebeen
developed.PulsedthermodIlutIonusesacoIledrIghtventrIcularfIlamentthatapplIesa
lowpowerheatIngsIgnaltotherIghtatrIumandventrIcleInacyclIcalmannerbasedona
proprIetarysequence.
44
AthermIstoratthetIpofthePACdetectschangesInblood
temperatureandsendsthetemperatureInformatIontoamIcrocomputerthatuses
stochastIcanalysIstocreateathermodIlutIoncurve.CDIscomputedcontInuouslyfroma
conservatIonofheatequatIon.
44
AnothertechnIqueapplIesheattoathermIstorlocatedatthetIpofaPAC.TherIght
ventrIcularoutflowsubsequentlycoolsthetIp.ThetemperaturechangesregIsteredare
proportIonaltothedecreasedtemperatureproducedbyrIghtventrIcularbloodflow.8oth
ofthesesystemsrequIrecalIbratIonusIngstandardthermodIlutIonbeforeInItIatIngthe
contInuousCDmonItorIngmode.AlthoughatImelagcanexIst,contInuousCDmonItorIng
comparesfavorablywIthbolusCDmeasurements,evenundercondItIonsofvaryIngpatIent
temperatureandCD.
45
Right Ventricular Ejection Fraction
CalculatIonofrIghtventrIcularejectIonfractIonandenddIastolIcvolumemaybe
performedwIthaspecIalPACthatusesarapIdresponsethermIstorandasophIstIcated
computersystem.ThIssystemanalyzestheexponentIaldecayofthepulmonaryartery
temperatureoverseveralcardIaccyclesandcalculatestheejectIonfractIonbysubtractIng
themeanresIdualfractIonfromtheCD.StudIeshavedemonstratedgoodcorrelatIonwIth
in vitrotechnIquesandclInIcalutIlItyfordetectIngIntraoperatIverIghtventrIcular
IschemIa.
46,47,48,49
DtherstudIessuggestacceptableagreementbetweenrIghtventrIcular
ejectIonfractIongeneratedbythIsnewPACandtransesophagealechocardIographyonly
whenheartrateIsmaIntaInedbelow100beatspermInute.
50
FIghtventrIcularejectIon
fractIonmonItorIngmaybebenefIcIalIncondItIonsofrIghtventrIcular
P.710
dysfunctIon.naddItIon,ItmayalsobeusedforamoreaccurateassessmentofrIght
ventrIcularpreloaddurIngorthotopIclIvertransplant.
51
AccuracyrequIresproper
placement.0ysrhythmIasandtrIcuspIdregurgItatIoncanaffecttheaccuracyofthe
thermaldecaymethodology.
Clinical Benefits and Controversy of Pulmonary Artery
Monitoring
ThedebateregardIngtheclInIcalbenefItofPACmonItorInghaspersIstedsIncethemId
1980s.PerIoperatIveoutcomeshavebeenreportedtobeImproved,worsened,or
unchangedbyPACuse.SeveralartIclescontInuetoIllustrateInsuffIcIentevIdence
supportInganoutcomebenefItfromutIlIzatIonofthePAC.
52,5J,54,55
However,proponents
ofthePACsItethemanyIssuesthatsurroundtheInterpretatIonofPACstudIes,IncludIng
InadequateblIndIng,InadequatesamplesIzeforconclusIonsmade,nonrandomIzatIon,
selectIonbIas,Hawthorneeffect,crossover,vIolatIonofprotocolswIthoutexplanatIon,
debatableendpoIntsofcare,andstatIstIcalflaws.
56
TheproposedbenefItsofthePACrelyonprovIdIngaddItIonaldatathatmayalterpatIent
therapytoImproveoutcome.StIll,thePACIsanInstrumentInterpretedbyhealthcare
staff,whooftentImeslacktheknowledgetocorrectlytranslatethedataIntobenefIcIal
therapIesforpatIents.SeveralstudIeshavemeasuredphysIcIanandnurseknowledgeInthe
UnItedStatesandEurope.Thesesurveysrevealedthatknowledgeofpulmonaryartery
catheterIzatIonIsnotunIformlygoodamongIntensIvecareunItphysIcIans,wIthasmany
ashalfofrespondentsunabletoInterpretthePCWPcorrectlyfromaclearlymarked
tracIng.
57,58
ChangesIntraInIngandcredentIalInghavebeenproposedtoImprovethese
defIcIencIesInknowledge.
59,60,61
fthePACIstobeemployed,ItshouldbeapplIedtotheapproprIatepatIentpopulatIon,
thecorrectclInIcalenvIronment,andusedInatImelyfashIon.Therefore,thepatIents
shouldhavesIgnIfIcantcomorbIdItIesInjeopardyofsustaInIngfurtherorganfaIlureor
death.PhysIologIcderangementsmustbepresentsothatthePACderIvedvarIablescan
guIdetherapytoalteroutcome.FInally,tImelyIdentIfIcatIonofdIseaseprogressIonshould
occursothatthehealthcareprofessIonalInterpretIngthePACdatamayhaveachanceto
useItforpatIentclInIcalbenefItbeforeIrreversIblemorbIdItyoccurs.However,at
present,thepreponderanceofstudIesforvarIousreasonshavehaddIffIculty
demonstratIngoutcomebenefIts.
56
Noninvasive Techniques for Cardiac Output/Fluid
Responsiveness
TheconsummateCDmonItorwouldbenonInvasIve,relIable,andvalIdunderaplethoraof
pathologIchemodynamIccondItIons.naddItIon,Itshouldbeeasytouse,havecontInuous
monItorIngcapabIlItIes,andbeInexpensIve.
Indirect Fick Method
AlmosttwocenturIesago,AdolfFIckreportedthattheuptakeandreleaseofmaterIalfrom
anorganIstheresultofthebloodflowtothatorganandthearterIovenousconcentratIon
dIfferenceofthematerIal.
62
ThIsconceptIsrepresentedastheFIckequatIontoday:
CD=[7wIthdotabove]D
2
/(Cao
2
C[vwIthbarabove]o
2
)
whereCDequalscardIacoutput,7D
2
IsoxygenconsumptIon,Cao
2
IsarterIaloxygen
content,andC[vwIthbarabove]o
2
IsmIxedvenousoxygencontent.
62,6J
SubstItutIng
carbondIoxIdeforoxygencreatestheIndIrectFIckequatIon(CD=7CD
2
/Cvco
2
Caco
2
),
where7CD
2
IsCD
2
produced,Cvco
2
IsthemIxedvenousCD
2
content,andCaco
2
Isthe
arterIalCD
2
content.
6J
0evIceshavebeendevelopedtousetheIndIrectFIckequatIonand
partIalrebreathIngtogeneratenonInvasIveCDmeasurements.
64
ThIsmonItorIncludesa
carbondIoxIdesensor(InfraredlIghtabsorptIon),adIsposableaIrflowsensor,adIsposable
rebreathIngloop,andapulseoxImeter.ParametersthatmayaffectaccuracyIncludesmall
errorsInmeasurementsofPvco
2
andPaco
2
,hyperventIlatIon,largepulmonaryshuntIng,
andIncreasesIn[7wIthdotabove]/[QwIthdotabove]mIsmatchIng.
64
nItIalvalIdatIons
studIesshowedfaIragreement(bIas1.8L/mIn)betweenthermodIlutIonandIndIrectFIck
prIncIplemonItors.
64,65
DtherstudIesthatexamInedpatIentswIthIncreasedpulmonary
shuntlungdIseaseandpostoperatIveatelectasIshaddIsmalstatIstIcalagreement.
64,66,67
Therefore,thIsmonItormaybebestsuItedforcrItIcallyIllpatIentswIthstablelung
functIon.
Impedance Plethysmography
mpedanceplethysmographyIsbasedondetermInIngthepulsatIlechangesInresIstance
occurrIngdurIngventrIcularejectIon.ClassIcally,fourelectrodesareapplIedtotheneck
andthoraxandasmallelectrIccurrentIsapplIed.mpedancemeasurements(dZ/dT)are
madeusIngtwothoracIcelectrodepaIrs.ChangesInImpedancecorrelatewIthstroke
volume.CDIsestImatedbydetermInIngstrokevolumeandventrIcularejectIontIme.
68
ElectrodeplacementandapproprIatecontactwIththeskInareImportantsourcesoferror.
DtherreportedfactorsInfluencIngbIoImpedancemeasurementsIncludeIntrathoracIcfluId
shIfts,thepresenceofaortIcregurgItatIon,extremesofheartrate,cardIacdysrhythmIas,
latelIvercIrrhosIs,andchangesInhematocrIt.
69
|orethan150valIdatIonstudIeshave
beenpublIshed,andbothpoorandgoodcorrelatIonsbetweenImpedanceplethysmography
andareferencemethodhavebeenreported.
70
NewergeneratIonImpedancemonItors
attempttoovercomereportedshortcomIngsofthedevIcewIthupgradedcomputer
technologyandmodIfIedalgorIthmstocalculateCD.0ataareemergIngfromthecrItIcally
IllandcardIacsurgerylIteraturesuggestIngthatthesenewerdevIceshaveacceptable
agreement(wIthIn15)wIththethermodIlutIontechnIque.
64,71
Doppler Ultrasonography
0opplerultrasonographycanmeasurethevelocItyofbloodIntheascendIngordescendIng
aortaoroutflowtractofthepulmonaryartery.CDIscalculatedbymultIplyIngthetIme
weIghtedaveragevelocItyofbloodflowbyanestImateofaortIcorpulmonaryartery
crosssectIonalareathatcanbedIrectlymeasuredorpredIctedfromanomogram.
72
Suprasternal,transtracheal,andtransesophagealprobeshavebeendesIgnedforclInIcal
use.
64,7J
AccuracyandprecIsIondependontheestImateofthevesseldIameterandthe
alIgnmentofthe0opplerprobe.7elocItymeasurementsaremostaccuratewhenthe
0opplerprobeandthebloodflowareparallel.fthealIgnmentexceeds25degrees,
velocItymeasurementsloseprecIsIon.DtherfactorslImItIngtheaccuracyofthIsdevIce
IncludewhenCDIsbasedondescendIngaortIcbloodflowonly,whencrosssectIonalarea
oftheaortaIsdynamIc(andnotcylIndrIcalasthIsdevIceassumesforcalculatIons),when
turbulentflowoccursfromtachycardIa,whenanemIaexIsts,andwhenaortIcvalvedIsease
Ispresent.
64
thasbeenshownthatchangesInhemodynamIcswIththeuseofvasopressors
andInotropescanreducetheaccuracyofthIsdevIcetomeasurestrokevolumechanges.
74
StIll,thedevelopmentofesophageal0opplerprobesallowsforcontInuous,mInImally
InvasIveestImatIonofCD,
P.711
andmayallowforoptImIzatIonofIntravascularvolumestatuswIthouttheuseofaC7Por
PAC.
75,76,77
Figure 27-10.ThefIgurerepresentsbothsystolIcpressure(SP)andpulsepressure(PP)
varIatIonthroughouttherespIratorycycle.ThepulsepressureandsystolIcpressureare
atthepeakdurIngInspIratIonandatmInImumdurIngexpIratIon.8yIncorporatIngan
expIratorypausedurIngposItIvepressuremechanIcalventIlatIon,areferencesystolIc
pressureandpulsepressurecanbeascertaIneddurIngexpIratIontodIfferentIate
betweenexpIratIonandInspIratIon.SP7,systolIcpressurevarIabIlIty;Pa,arterIal
pressurePaw,aIrwaypressure(Feproducedfrom|IchardF:ChangesInarterIal
pressuredurIngmechanIcalventIlatIon.AnesthesIology2005;10J:419,wIth
permIssIon.)
Arterial Pulse Contour Analysis/ Transpulmonary
Thermodilution/Lithium Dilution Technique
PulsecontouranalysIsofthearterIalpressurewaveformallowsclInIcIanstodetermIne
beattobeatmeasurementsofleftventrIcularoutput.ComputeralgorIthmsareusedto
calculatetheareaunderthesystolIcportIonofthearterIalpulsewaveform(fromtheend
ofdIastoletotheendoftheejectIonphase).StrokevolumeIsdetermInedbydIvIdIngthe
resultIngareabytheaortIcImpedance.Therefore,pulsecontourmaynotprovIde
consIstentlyrelIableresultsInthesettIngofdysthymIasorIlldefInedarterIalwaveforms.
64
AnotherlImItatIonofarterIalpulsecontouranalysIsIsthatthetechnIquerequIres
calIbratIonwIthanothermethodofmeasurIngCD.FeferenceCDdetermInatIonsfor
calIbratIoncanbeobtaInedusIngmoderatelyInvasIve(TCDusIngaPACortranspulmonary
thermodIlutIonusIngacentralvenousandarterIallIne)ormInImallyInvasIve(lIthIum
dIlutIonusIngaperIpheralvenousandarterIalcatheter)technology.StudIesshow
reasonableagreementbetweenthetranspulmonarythermodIlutIonandPACthermodIlutIon
technIque.
64,78
However,afemoraloraxIllaryarterIallIneIsoftenrequIredforaccurate
measurementsastheCDIsgeneratedfromthechangeIntemperatureofIcedsalIneInthe
aorta,whenfIrstInjectedIntothecentralveIn.SeveralotherstudIeshavecompared
lIthIumdIlutIon(whIchmeasuresCDInasImIlarfashIontothethermodIlutIontechnIque)
wIthpulmonaryarterythermodIlutIonandsuggestapproprIateagreementaswellbetween
thetwo.
79,80
AnumberofclInIcalstudIeshavedemonstratedthattheprecIsIonandaccuracyofarterIal
pulsecontouranalysIsIsacceptablewhencomparedwIthTCDmeasurementsobtaInedby
PACsandthatItmayalsobeabletopredIctfluIdresponsIveness.
81,82,8J,84
NewdevIces
havebeenconstructedtoelImInatetheneedforcalIbratIonwIththermodIlutIon.ThIs
noveltechnologyhasshowntohavevarIablelevelsofagreementwIthPACmeasurements
ofCDundervarIousclInIcalcondItIons.
85,86,87
LargerrandomIzedcontrolledtrIalsneedto
beperformedtofurthervalIdatetheuseofthesetechnologIes.
Arterial Pulse Pressure/Systolic Pressure Variation
ArterIalpulsepressure/systolIcpressurevarIatIonrecentlyhasbeenusedasarelatIvely
nonInvasIvewaytopredIctfluIdresponsIveness(FIg.2710).StudIeshaveexamInedtheuse
ofpulsepressure/systolIcpressurerespIratoryvarIatIonIndetectIngpatIentswhoare
hypovolemIc.
88
CreaterarterIalpulsepressure/systolIcpressurevarIatIonchangesmay
occurInhypovolemIcpatIentsbecauseofadropInrIghtventrIcularpreload,agreater
IncreaseInrIghtventrIcularafterload,andadecreaseInleftventrIcularafterload.
88
TheclInIcalapplIcatIonofthIsconcepthasbeenexamIned.n1978,FIckand8urke
89
dIscoveredthatasystolIcpressurevarIatIon10mmHgIndIcatedhypovolemIa.n
addItIon,otherstudIeshaveshownthatsystolIcpressurevarIatIonhasacceptable
agreementwIthpulmonaryarteryocclusIonpressures(assystolIcpressurevarIatIon
Increases,PCDPdecreases).
88,90
However,comparIsonswIthechocardIographyhave
producedmIxedresults.AlthoughsomeInvestIgatorsdemonstratedanacceptable
relatIonshIpbetweenleftventrIcularenddIastolIcareaandthemagnItudeofsystolIc
pressurevarIatIondurIngaortIcsurgery,othersshowedweakornocorrelatIonbetween
systolIcpressurevarIatIonandleftventrIcularenddIastolIcareaIncardIovascular
surgery.
88,91
SeveralfactorsmayaffectInterpretatIonofpulsepressure/systolIcpressure
varIatIon,IncludIngcomponentsofthearterIalpressuremonItorIngdevIce,arterIal
complIance,dysrhythmIas,IncreasedchestwallcomplIance,smalltIdalvolumes,
spontaneousbreathIng,andrIght/leftventrIcularfaIlure.Nevertheless,arterIalpulse
pressure/systolIcpressurevarIatIonmaybeusedasapredIctoroffluIdresponsIvenessIn
patIentsundergoIngmostsurgerIesandcrItIcallyIllpatIentswhoaredeeplysedated
undergoIngconventIonalmechanIcalventIlatIon.
88
Temperature Monitoring
TheabIlItytomonItorbodytemperatureIsastandardofanesthesIacare.ThecontInual
observatIonoftemperaturechangesInanesthetIzedpatIentsallowsforthedetectIonof
accIdentalheatlossormalIgnanthyperthermIa.HumansmaIntaIntheIrcoretemperature
bybalancIngheatproductIonfrommetabolIsmandthemanyenvIronmentalfactorsthat
supplyheator
P.712
coolthebody.FegIonaltemperatureInformatIonfromskIn,muscle,thebodycavItIes,
spInalcord,andbraInareIntegratedInthecentralnervoussystem.Conceptually,
thermoregulatIonInvolvestheIntegratIonofsetpoInts,whIch,whenexceeded,trIgger
temperaturedIssIpatIng,temperatureconservIng,orheatproducIngmechanIsms.8oth
generalandregIonalanesthesIaInhIbItafferentandefferentcontrolof
thermoregulatIon.
92,9J
naddItIon,theoperatIngroomenvIronmentandsurgIcalexposure
oftencontrIbutetoexcessIveheatlosses.HeatlossIscommondurIngsurgerybecausethe
surgIcalenvIronmenttransfersheatfromthepatIent,andanesthesIareducesheat
productIonanddImInIshesthecapabIlItyofpatIentstomonItorandmaIntaIn
thermoregulatIon.
HeatIsproducedasaconsequenceofcellularmetabolIsm.nadults,thermoregulatIon
InvolvesthecontrolofbasalmetabolIcrate,muscularactIvIty,sympathetIcarousal,
vasculartone,andhormoneactIvatIonbalancedagaInstexogenousfactorsthatdetermIne
theneedforthebodytocreateheatortoadjustthetransferofheattotheenvIronment.
HeatlossesmayresultfromradIatIon,conductIon,convectIon,andevaporatIon.FadIatIon
referstotheInfraredraysemanatIngfromallobjectsaboveabsolutetemperature.
ConductIonreferstothetransferofheatfromcontactwIthobjects.ConvectIonrefersto
thetransferofheatfromaIrpassIngbyobjects.EvaporatIonrepresentstheheatlossthat
resultswhenwatervaporIzes.Foreverygramofwaterevaporated,0.58kcalofheatIs
lost.
PerIoperatIvehypothermIapredIsposespatIentstoIncreasesInmetabolIcrate(shIverIng)
andcardIacwork,decreasesIndrugmetabolIsmandcutaneousbloodflow,andcreates
ImpaIrmentsofcoagulatIon.ClInIcalstudIeshavedemonstratedthatpatIentsInwhom
IntraoperatIvehypothermIadevelopsareatahIgherrIskfordevelopmentofpostoperatIve
myocardIalIschemIaandwoundInfectIoncomparedwIthpatIentswhoarenormothermIc
IntheperIoperatIveperIod.
94,95
AnesthesIologIstsfrequentlymonItortemperatureand
attempttomaIntaIncentralcoretemperatureatnearnormalvaluesInallpatIents
undergoInganesthesIa.
CentralcoretemperaturescanbeestImatedusIngprobesthatcanbeplacedIntothe
bladder,dIstalesophagus,earcanal,trachea,nasopharynx,orrectum.
96
Pulmonaryartery
bloodtemperatureIsalsoagoodestImateofcentralcoretemperature.
TemperatureIsusuallymeasuredusIngelectrIcalprobescontaInIngcalIbratedthermIstors
orthermocouplesthatserveastemperaturetransducers.ThermIstorsrespondto
temperaturechangesbychangIngtheIrelectrIcalresIstance.Thermocouplesare
constructedbypassIngcurrentthroughacIrcuItwheretheelectrodesaremadeoftwo
dIssImIlarmetals.ThecurrentmeasuredIsdIrectlyproportIonaltothetemperature
dIfferencebetweenthetwometaljunctIons.ThermocoupletemperatureprobesmaIntaIn
onejunctIonataknowntemperatureandplacethesecondjunctIononthetemperature
probetIp.SkIntemperaturecanalsobemonItoredusInglIquIdcrystalthermometry.
However,convenIent,temperaturestrIpsdonotcorrelatewIthcoretemperature
measurements.
97
ThermoregulatoryresponsesarebasedonaphysIologIcallyweIghtedaveragereflectIng
changesInthemeanbodytemperature.|eanbodytemperatureIsestImatedbythe
followIngequatIon:
|eantemperature=0.85Tcore+0.15TskIn
SkIntemperaturemonItorInghasbeenadvocatedtoIdentIfyperIpheralvasoconstrIctIon
butIsnotadequatetodetermInealteratIonsInmeanbodytemperaturethatmayoccur
durIngsurgery.CoretemperaturesIteshavebeenestablIshedasrelIableIndIcatorsof
changesInmeantemperature.0urIngroutInenoncardIacsurgery,temperaturedIfferences
betweenthesesItesaresmall.WhenanesthetIzedpatIentsarebeIngcooled,changesIn
rectaltemperatureoftenlagbehIndthoseofotherprobelocatIons,andtheadequacyof
rewarmIngIsbestjudgedbymeasurIngtemperatureatseverallocatIons.
Future Trends in Monitoring
0IagnostIcandtherapeutIcadvancesInmedIcInehavehadagreatImpactonthestrategIes
andtechnIquesavaIlableforIntraoperatIvemonItorIng.Today'sanesthesIapractIcehas
narrowedthedIstInctIonbetweenlaboratorymedIcIneandpatIentmonItorIng.TechnologIc
advancesInInstrumentdesIgn,computerIzatIon,andengIneerInghavemadeItpossIbleto
havereadyaccesstoserumchemIstrIes,hematologIcprofIles,assessmentofcoagulatIon,
andarterIalbloodgasmeasurements.|odernmonItorIngsystemshavethepotentIalto
transferprocessedandrawdatafromtheoperatIngroomtoInformatIonmanagement
systems,whIchofferthepotentIalforcreatIngmeanIngfulpaperlessanesthesIarecords,
medIcalalerts,decIsIonsupport,andenhancedarchIvIngoftheconductofanesthesIacare
asdepIctedbyrealtImemonItorIngtrends.
TheU.S.0epartmentofHealthandHumanServIcesproposedImplementatIonofpatIent
recordsystemsIn1996.
98
ProprIetarysystemsforautomatedanesthesIarecordsarenowIn
themarketplace.TheseofferfIlesharIngsothatInformatIonthatIstradItIonallyvIewedas
patIentmonItorIngcanalsobeusedforbIllIng,orderIngsupplIes,andqualIty
Improvement.AlthoughcomputerIzatIonofthehospItalenvIronmenthasdIrectand
IndIrectcosts,thebenefItstophysIcIans,patIents,Insurers,andhospItaladmInIstrators
IndIcatethat,lIkeInotherbusInessenvIronments,InformatIonmanagementIscomIngto
operatIngroommonItorIngandanesthesIology.
99,100
TheclInIcalandadmInIstratIvedata
thatcanbeobtaInedfromanesthesIaworkstatIonsIntegratedwIthhospItalInformatIon
systemscouldenhancethequalItyofcareandImprovethevalueofIntraoperatIve
monItorIngofanesthetIzedpatIents.
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2
Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapter28EchocardIography
Chapter28
Echocardiography
Albert C. Perrino JR.
Wanda M. Popescu
Nikolaos J. Skubas
Key Points
1. Understanding the principles of ultrasound and echocardiographic
instrumentation is essential in optimizing image quality.
2. Performing a comprehensive echocardiographic examination ensures
that important pathologies are recognized.
3. Two-dimensional and Doppler techniques have complementary roles
in the assessment of cardiovascular function.
4. Global left ventricular systolic function is influenced by load and
contractility alterations; regional wall motion grading is based on
systolic excursion and thickening.
5. Transmitral flow and pulmonary vein flow Doppler along with tissue
Doppler imaging provide accurate diastolic function assessment.
6. Severity of aortic stenosis is based on the value of the aortic valve
area calculated by continuity equation.
7. The ratio of the width of the regurgitant jet to the diameter of the left
ventricular outflow tract is useful in assessing severity of aortic
insufficiency. Diastolic flow reversal in the descending thoracic aorta
is significant for severe aortic insufficiency.
8. Mitral regurgitation can be of structural or functional etiology. The
jet's vena contracta and the effective regurgitant orifice area by
proximal isovelocity surface area method help grade severity.
9. Aortic atheromas larger than 4 mm are harbingers of thromboembolic
events.
10. The false lumen of aortic dissection does not have diastolic flow.
EchocardIographyIsthefIrstImagIngtechnIquetoenterthemaInstreamofIntraoperatIve
patIentmonItorIng.AremarkablyversatIletool,echocardIographyprovIdesa
comprehensIveevaluatIonofmyocardIal,valvular,andhemodynamIcperformance.These
capabIlItIesattractedtheattentIonofanesthesIologIstsandsurgeonschallengedbythe
unIquedIffIcultIesofperIoperatIvecardIovascularmanagement.DvertheJ0years
followIngthefIrstreportofIntraoperatIveechocardIographytoassessventrIcularfunctIon
by8arashandcolleagues
1
In1978,echocardIographyhasemergedasthetechnIqueof
choIceforawIdevarIetyofIntraoperatIvecasechallenges.
ThebenefItofIntraoperatIveechocardIographyInbothcardIacandnoncardIacsurgIcal
populatIonsIssupportedbyseveralcaseserIes.
2,J,4,5,6,7,8
ApplIcatIonsrangefromguIdIng
theplacementofIntracardIacandIntravascularcathetersanddevIces,totheassessment
oftheseverItyofvalvepathologyandImmedIateevaluatIonofasurgIcalInterventIon,to
therapIddIagnosIsofacutehemodynamIcInstabIlItyanddIrectIngapproprIate
therapIes.
9,10
Consequently,expertIseInIntraoperatIveechocardIographyIshIghlydesIred
amonganesthesIologypractItIoners.TheNatIonal8oardofEchocardIographyhas
establIshedacertIfIcatIonpathwayInperIoperatIvetransesophagealechocardIography
(TEE),http://www.echoboards.org/certIfIcatIon/certexpl.html.TheAmerIcanSocIetyof
AnesthesIologIstsIsconjunctIonwIththeNatIonal8oardofEchocardIographyIsestablIshIng
asecondcertIfIcatIonpathwayInbasIcperIoperatIveechocardIography,
http://www.asahq.org/publIcatIonsAndServIces/standards/TEE.pdfand,http://www.
asahq.org/Newsletters/2008/0108/savage0108.html.TheseeffortsareunIqueIn
IntraoperatIvemonItorIngandattesttothecrItIcalrolethataccurateandthorough
echocardIographIcInterpretatIonplaysIncurrentanesthetIcpractIce.
Principles and Technology of Echocardiography
EchocardIographygeneratesdynamIcImagesoftheheartfromthereflectIonsofsound
waves.TheechocardIographysystemtransmItsabrIefpulseofhIghfrequencysound(I.e.,
ultrasound)thatpropagatesthroughandIssubsequentlyreflectedfromthecardIac
structuresencountered.TheultrasoundtransducerrecordsthetImedelayandsIgnal
IntensItyforeachreturnIngreflectIon.8ecausethespeedofsoundIntIssueIs
P.716
constant,thetImedelayallowstheechosystemtoprecIselycalculatethelocatIonof
cardIacstructuresandtherebycreateanImagemapoftheheart.
Figure 28-1.Soundwave.7IbratIonsoftheultrasoundtransducercreatecyclesof
compressIonandrarefactIonInadjacenttIssue.TheultrasoundenergyIscharacterIzed
byItsamplItude,wavelength,frequency,andpropagatIonvelocIty.nthIsexample,
foursoundwavesareshownInaperIodof0.5s.Thefrequencycanbecalculatedas
fourcyclesdIvIdedby0.5sandequals8|Hz.
Physics of Sound
SoundIsvIbratIonofaphysIcalmedIum.nclInIcalechocardIography,amechanIcal
vIbrator,knownasthetransducer,IsplacedIncontactwIththeesophagus
(transesophagealechocardIography),skIn(transthoracIcechocardIography),ortheheart
(epIcardIalechocardIography)tocreatetIssuevIbratIons.TheresultIngtIssuevIbratIons
createalongItudInalwavewIthalternatIngareasofcompressionandrarefaction(FIg.28
1).
TheamplitudeofasoundwaverepresentsItspeakpressureandIsapprecIatedasloudness.
ThelevelofsoundenergyInanareaoftIssueIsreferredtoasintensity.TheIntensItyof
thesoundsIgnalIsproportIonaltothesquareoftheamplItudeandIsanImportantfactor
regardIngthepotentIalfortIssuedamagewIthultrasound.8ecauselevelsofsoundpressure
varyoveralargerange,ItIsconvenIenttousethelogarIthmIcdecIbel(d8)scale:
0ecIbel(d8)=10log
10
/r=10log
10
A
2
/A
r
2
=20log
10
A/A
r
whereAIsthemeasuredsoundamplItudeandA
r
Isastandardreferencesoundlevel;Is
IntensItyand
r
IsastandardreferenceIntensIty.TheFoodand0rugAdmInIstratIonlImIts
theIntensItyoutputofcardIacultrasoundsystemstobe720W/cm
2
becauseofconcernsof
potentIaltIssueInjury.
11
SoundwavesarealsocharacterIzedbytheIrfrequency(f),orpItch,expressedIncyclesper
second,orHertz(Hz),andbytheIrwavelength().TheseattrIbutessIgnIfIcantlyImpact
thedepthofpenetratIonofasoundwaveIntIssueandtheImageresolutIonofthe
ultrasoundsystem.
ThepropagatIonvelocityofsound(v)IsdetermInedsolelybythemedIumthroughwhIchIt
passes.nsofttIssue,thespeedofsoundIsapproxImately1,540m/s.Astheproductof
wavelengthandfrequencyequalsvelocIty:7=fItbecomesapparentthatthe
wavelengthandfrequencyareInverselyrelated:=v1/fandthat=(1,540m/s)f.HIgh
frequency,shortwavelengthultrasoundIsmoreeasIlyfocusedanddIrectedtoaspecIfIc
targetlocatIon.mageresolutIonalsoIncreaseswIthshortwavelengthsoundwaves;for
thesereasons,ultrasonIcfrequencIesof2to10|HzarepreferredInclInIcal
echocardIography.
Properties of Sound Transmission in Tissue
ThepropagatIonofasoundwavethroughthebodyIsmarkedlyaffectedbyItsInteractIons
wIththevarIoustIssuesencountered.TheseInteractIonsresultInreflectIon,refractIon,
scatterIng,andattenuatIonoftheultrasoundsIgnalanddetermInetheresultIng
appearanceofthetwodImensIonalImage.
EchocardIographIcImagIngrelIesonthetransmIssIonandsubsequentreflectIonof
ultrasoundenergybacktothetransducer.Asoundwavepropagatessmoothlythrough
unIformtIssueuntIlItencounterstheInterfacebetweentwotIssuesvaryIngInacoustIc
Impedance(apropertylargelyrelatedtothedensity[]ofthetIssueandthespeedthat
ultrasoundtravels).AlargeInterfaceorIentedperpendIculartothesoundbeamwIll
produceamIrrorlIkereflectIonofsoundbacktowardthetransducerwIthonlyaportIonof
thesIgnalpassIngthroughtheInterface.8ecausecardIacstructuresaredetectedbytheIr
reflectedechocardIographysIgnal,echocardIographersadjusttheposItIonoftheTEE
transducersothatthedIrectIonofItsbeamIsperpendIculartothecardIacstructureof
Interest.
FefractIoncausesachangeIndIrectIonofpropagatIngsoundandoccurswhenanInterface
lIesoblIquetothesoundbeam.FefractIonIsanImportantfactorIntheformatIonof
artIfactsasthetransducermIstakenlyInterpretsareflectIonfromtherefractedbeamas
orIgInatIngfromacardIacstructurelocatedwIthIntheintendedscannIngfIeld.
Scattering reflectionsoccurwhenanultrasoundbeamencounterssmallorIrregularly
shapedsurfaces,suchasredbloodcells.ThesereflectorsscatterultrasoundenergyInall
dIrectIons,sothatfarlessenergyIsreflectedbacktothetransducer.ThIstypeof
reflectIonIsthebasIsofthe0oppleranalysIsofbloodflow(seefollowIng).
EvenwhentravelIngthroughunIformtIssue,soundundergoesasteadyloss(I.e.,
attenuation)InIntensItyasaconsequenceofdIspersIonandabsorptIon.AttenuatIonresults
InlessenergyreturnIngbacktothetransducerandlowqualItyImageswIthpoorsIgnalto
noIseratIos.TocombatattenuatIonechocardIographersselectbetterpenetratInglow
frequencysIgnals(e.g.,2.5Insteadof7.5|Hz)andchooseanImagIngwIndowthatIsclose
tothestructureofInterest.AdjustIngthegaIncontrolstoamplIfytheweakreturnIng
sIgnalsmakestheIrappearancebrIghteronthedIsplay.Unfortunately,thIsIncreasesthe
brIghtnessofartIfactualnoIse,whIchnegatIvelyImpactstheImageappearance.
Instrumentation
Transducers
UltrasoundtransducersusepIezoelectrIccrystalstocreateabrIefpulseofultrasound.
AlternatIngelectrIcalcurrentstImulatespolarIzedpartIcleswIthInthecrystal'smatrIxto
rapIdlyvIbrate,generatIngultrasound.Conversely,whenasoundreflectIonstrIkesthe
crystal,theImpactvIbratesthepolarIzedpartIclesandgeneratesanelectrIccurrent.ThIs
propertyallowsthepIezoelectrIccrystaltofunctIonasbothatransmItterandareceIverof
ultrasound.
P.717
Theshorterthelengthofthesoundpulses,thebettertheaxIalresolutIonofthesystem.
HIghresolutIonImagIngtransducersemItsoundpulsesofjusttwotofourcyclesofshort
wavelength,hIghfrequencysound.
Beam Shape
TheultrasoundtransduceremItsathreedImensIonalultrasoundbeamsImIlartoamovIe
projectIon(FIg.282).ThebeamIsnarrowInthenearfIeldandthendIvergesIntothefar
fIeldzone.FocusIngofthebeamIsusedtoImprovespatIalresolutIonbynarrowIngthe
ultrasoundbeamatthedesIreddepth.Thedense,narrowbeamIspreferredbecauseIt
provIdesImprovedspatIalresolutIon,produceshIghIntensItyreflectIons,andreduces
artIfact.EchocardIographersadjustfocaldepthandfocustooptImIzetheImageresolutIon.
Resolution
ThreeparametersareevaluatedwhenassessIngtheresolutIonofanultrasoundsystem:the
resolutIonofobjectslyIngalongtheaxIsoftheultrasoundbeam(axial resolution),the
resolutIonofobjectshorIzontaltothebeam'sorIentatIon(lateral resolution),andthe
resolutIonofobjectslyIngvertIcaltothebeam'sorIentatIon(elevational resolution).
ShortpulsesofhIghfrequencyultrasoundofferthegreatestaxIalresolutIonbuthavea
decreasedtIssuepenetratIon.AsresolutIonIshIghestalongtheaxIalplane,
echocardIographIcmeasurementsaremostprecIsewhentakenparalleltothebeam'saxIs.
AccordIngly,echocardIographersselecttransmIttedfrequencybasedonthepartIcular
ImagIngneed.
Figure 28-2.ThreedImensIonalbeam.Theultrasoundprobeprojectsathree
dImensIonalbeam.ThedImensIonsofthIsprojectIonhaveImportanteffectson
ImagIngresolutIonandartIfact.TypIcally,anarrowprofIleIspreferred.A.Unfocused
beam.ThebeamIsnarrowInthenearfIeldandthendIvergesInthefarfIeld.B.
Focusedbeam.FocusInghasresultedInanarrowerbeamInboththelateraland
elevatIonalplanes,sothattheImagIngresolutIonofstructuresInthefocalzoneIs
Improved.0Istaltothefocalzone,thebeamrapIdlydIverges,andtheImagesof
structuresInthIsareawIllbeoflowerqualIty.
8eamsIzedetermInesthelateralandelevatIonalresolutIon.8roadbeamsproducea
smearedImageoftwonearbyobjects,whereasnarrowbeamscanIdentIfyeachobject
IndIvIdually.8eamsIzeIsreducedbyselectInghIghsIgnalfrequencIesandmInImIzIng
ImagIngdepth.
Signal Processing
ToconvertechoesIntoImages,thereturnIngultrasoundpulsesarereceIved,electronIcally
processed,anddIsplayed.TheoscIllatorrepeatedlycyclesthetransducerfromabrIef
transmIssIontoarelatIvelylongreceIvemode.0urIngthereceIvephasethereflected
echocardIographysIgnalsarecapturedandconvertedtoelectrIcalsIgnalsbythe
pIezoelectrIccrystal.TheechocardIographysystememploysaserIesofcontrolsIncludIng
systemgaIn,tImegaIncompensatIon,compressIon,andpostprocessIngsettIngs(notunlIke
thoseavaIlablewIthdIgItalImagIngsoftware)tooptImIzethesIgnalfordIsplay.
Adjustmentsareused,forexample,toemphasIzeedgedetectIonversustIssuetexture,or
toImprovethedelIneatIonofweakerreflectors.ThechoIceofsettIngsIsdIctatedbythe
examInatIonandthepreferencesoftheechocardIographer.
Image Display
UltrasonIcImagIngIsbasedontheamplItudeandtImedelayofthereflectedsIgnals.
8ecausethevelocItyIntIssueIsarelatIvelyconstant1,540m/s,onlythedIstanceofthe
structurefromthetransduceraltersthetImerequIredfortheultrasoundwavetotravelto
andfromthereflectedstructure.SobytImIngtheIntervalbetweentransmIssIonand
returnofthereflectIons,theechocardIographysystemcanprecIselycalculatethedIstance
ofastructurefromthetransducer.
CurrentImagIngIsbasedonbrIghtnessmodeorB-mode technology.WIth8modethe
amplItudeofthereturnIngechoesfromasInglepulsedetermInesthedIsplaybrIghtnessof
therepresentatIvepIxels.M-modeormotIonmodeaddstemporalInformatIonto8mode
bydIsplayIngaserIesofsequentIallycollected8modeImages.|modeechocardIography
provIdesaonedImensIonal,sInglebeamvIewthroughtheheartbutupdatesthe8mode
ImagesataveryhIghrate,provIdIngdynamIcrealtImeImagIng.|moderemaInsthebest
technIqueforexamInIngthetImIngofcardIacevents(FIg.28J).
Two-dimensional (2-D) echocardiographyIsamodIfIcatIonof8modeechocardIographyand
themaInstayoftheechocardIographIcexamInatIon.nsteadofrepeatedlyfIrIngultrasound
pulsesInasIngledIrectIon,thetransducerIn20echocardIographysequentIallydIrectsthe
ultrasoundpulsesacrossasectorofthecardIacanatomy.nthIsway,20ImagIngdIsplays
atomographIcsectIonofthecardIacanatomy,andunlIke|mode,revealsshapeand
lateralmotIon(FIg.284).
TwodImensIonalscannIngIsachIevedusIngphasedarraytechnology,whIchsequentIally
actIvateseachcrystalInthearrayandtherebysteersthebeamwIthoutthetransducer
ItselfbeIngmoved.ThetwocommonlyusedelectronIcscannIngsystemsInmedIcal
ultrasoundarethelInearscannersandsectorscanners.
Thelinear scannerusesalonglIneararray.CroupsofcrystalsareactIvatedsequentIally
fromoneendofthetransducertotheother.ThefIrIngofeachgroupofcrystalscreatesan
ImageofthestructuresdIrectlyInfrontofthem.WIthsequentIalfIrIngtheanatomIc
featuresfromoneendofthetransducertotheotherareImaged(FIg.285).The
dIsadvantageofthIsapproachIsthatthetransducerfacemustbelargetocoverabroad
anatomIcarea.ThelIneararrayIscommonlyusedtoguIdevascularaccessandregIonal
anesthetIcprocedures.
P.718
Figure 28-3.|ethodmode(|mode)echocardIographyofanormalaortIcvalve.The
|modecursorIsplacedatthecenteroftheaortIcvalveandthemotIonoftheaortIc
cuspsovertImeIsshown.0urIngdIastolIccoaptatIontheaortIcvalvecuspsappearas
athIck,brIghtwhItelIne(long arrow),whIleInsystolIcapposItIontheyformashoe
box(short arrow).
Thephasedarraysector scannerIsthemostcommonlyusedInechocardIography.Herethe
ultrasoundscanIssequentIallydIrectedInafanlIkearc.TheresultIngsectorImageknown
asaframeIssImIlarInshapetothatcoveredbyawIndshIeldwIper.The20scannerthen
repeatstheentIreprocesstoupdatetheImageandcapturemotIon.
Figure 28-4.ScanlInes.llustratIonofthearcedsectorfromaphasedarraytwo
dImensIonalechocardIogram.EachdottedlInerepresentsanIndIvIdualbrIghtness
modescanlIne.AnystructurethatInteractswIthascanlInewIllcreatereflectIons
(darkhIghlIght);however,structuresthatlIebetweenthescanlInesarenot
Interrogated,andtheechocardIographysystemaveragestheneIghborIngsIgnalstofIll
InthIsdefect.AccordIngly,thecloserthescanlInes,thebettertheImagequalIty.
Figure 28-5.LInearscannersImagearectangularsectIonofanatomycomparedwIth
thearcedsectorImagedwIthphasedarrayscanners.
Spatial versus Dynamic Image Quality
ExpertechocardIographersselectmachInesettIngstooptImIzepartIcularImagequalItIes
fortheexamInatIonathand.AsdIscussedInthefollowIngsectIons,theseselectIonswIll
determInewhethersectorsIze,spatIalresolutIon,ordynamIcmotIonIsbestdIsplayed.
Thepulse repetition frequencyIstherateatwhIchsoundpulsesaretrIggered.Thegreater
thepulserepetItIonfrequency,thegreaterthenumberofscanlInesthatareemIttedIna
gIvenperIodoftIme.ThIsenhancesmotIondIsplay.Unfortunately,sectordepthmustbe
reducedbecausepulserepetItIonfrequencyIsInverselyrelatedtothesectordepthasa
longerperIodoftImeIsrequIredfortheultrasoundtotraveltheIncreaseddIstances.
Theframe rateIsthefrequencyatwhIchthesectorIsrescanned.AhIghframerate
Improvesthecaptureofmovement.TypIcally,frameratesJ0persecondaredesIred.The
framerateIscrItIcallydependentonthesectordepth,whIchdetermInesthetImerequIred
foreachscanlInetobereceIved,andthesectorwIdth,whIchIncreasesthenumberof
scanlInesthatmustbetransmItted.Consequently,IncreasesInsectorsIzeanddepthcome
atthecostofadecreasedframerateandpoormotIonImagIng.
ThenumberofscanlInesperdegreeofthesector(scan line density)greatlyaffectsthe
ImageresolutIon.0oublIngthescanlInesessentIallydoublesthelateralresolutIon.
However,thecostIsadecreaseIntheframerateandmotIonImagIng.
TheechocardIographermustthoughtfullyselectamongsettIngsthatwIlloftenhave
opposIngeffectsbetweenthesIzeoftheImagIngfIeld,theImagIngresolutIon,andthe
framerate.AcommonapproachIstofocuseachpartoftheexamInatIononagIven
structureofInterestandselecttheImagIngplanethatbestdelIneatesthestructureInthe
nearfIeld.|otIondIsplaycanbethenbeenhancedwIthoutcostsInlateralresolutIonby
decreasIngthesectorangleanddepth.nsItuatIonsInwhIchthemaxImalframerateIs
desIred,|modeIschosen.
Two-Dimensional and Three-Dimensional Transesophageal
Echocardiography Examination
TEEIsthefavoredapproachtoIntraoperatIveechocardIography.ComparedwIth
transthoracIcechocardIography(TTE),TEEoffersaddItIonalwIndowstovIewtheheart,
oftenwIthImprovedImagequalItyfromtheanatomIcproxImItyofthe
P.719
esophagusandheart.ntheoperatIngroom(DF),TEEIsusefulbecausetheprobedoesnot
InterferewIththeoperatIvefIeldandcanbeleftInsItu,provIdIngcontInuous,realtIme
hemodynamIcInformatIonusedtodIagnoseandmanagecrItIcalcardIacevents.TEEIsalso
usefulInsItuatIonsInwhIchthetransthoracIcexamInatIonIslImItedbyvarIousfactors
(obesIty,emphysema,surgIcaldressIngs,andprosthetIcvalves)andforexamInIngcardIac
structuresnotwellvIsualIzedwIthTTE(leftatrIalappendage).However,thedIagnostIc
capabIlItyofTEEdependsonImageacquIsItIonandInterpretatIon.
ThIssectIonIsdesIgnedtoIntroduceTEEImageorIentatIonandthedIagnostIcutIlItyof
eachvIew.naddItIon,examInatIonsequencesusefulforobtaInIngacomprehensIveor
targetedexamInatIonareprovIded.FeadersarereferredtoA Practical Approach to
Transesophageal Echocardiography
12
foramoredetaIleddescrIptIonoftheTEE
examInatIonsdescrIbedInthIssectIon.
Probe Insertion
TheTEEprobeIsInsertedIntheanesthetIzedpatIentInamannersImIlartoInsertIonofan
orogastrIctube.ForImprovedImagequalIty,thestomachIsemptIedofgastrIccontents
andaIrprIortoprobeInsertIon.ThejawIslIftedwIththelefthandandtheTEEprobe,
welllubrIcated,IsInsertedwIththerIghthandbyapplyInggentlebutconstantpressure.f
sIgnIfIcantresIstanceIsencountered,addItIonalforceshouldbestrIctlyavoIdedas
oropharyngealoresophagealInjurymayresult.Father,adecreaseInneckextensIon
and/oruseofalaryngoscopetovIsualIzetheoropharyngealstructuresoftenwIllallow
easypassageoftheprobe.TheTEEprobeIsadvancedbeyondthelarynxandthe
crIcopharyngealmuscle(around25toJ0cmfromteeth)untIlalossofresIstanceIs
apprecIated.AtthIspoInt,theTEEprobelIesIntheupperesophagusandthefIrst
cardIovascularImagesareseen.ExtrInsIccompressIonoftheesophagus(e.g.,osteophytes
oranaortIcaneurysm)mayImpedeprobeplacement.
1J
Transesophageal Echocardiography Safety
TEEIsasemIInvasIveprocedure.WhenperformedbyqualIfIedoperatorsTEEhasalow
IncIdenceofcomplIcatIons.AretrospectIvestudyperformedon846patIentswho
underwentTEEdescrIbedthefollowIngcomplIcatIons:threepatIentswIthpharyngeal
abrasIons,onepatIentwIthachIppedtooth,andfewpatIentswIthtransIentvocalcord
paresIs.
14
AnotherretrospectIvestudyperformedonalargecaseserIesof7,200patIents
showedthatthemorbIdItyassocIatedwIthTEEplacementIs0.2andthemortalItyIs0.
15
ThemostcommoncomplaInt(0.1)waspostoperatIveodynophagIa.7arIousstudIeshave
suggestedanassocIatIonbetweenswallowIngdysfunctIonaftercardIacsurgeryandtheuse
ofIntraoperatIveTEE.
16,17
ThIsfactIsImportantaspostoperatIveswallowIngdysfunctIonIs
assocIatedwIthpulmonarycomplIcatIons.
16
Contraindication to Transesophageal Echocardiography Probe
Placement
TomaIntaInthesafetyprofIleofTEE,eachpatIentshouldbeevaluatedbeforethe
procedureforsIgns,symptoms,orhIstoryofesophagealpathology.Themostfeared
complIcatIonofTEEIsesophagealorgastrIcperforatIon.ForskIlledpractItIonersthIs
complIcatIonIsextremelyrare.PatIentswIthextensIveesophagealandgastrIcdIseaseare
athIghestrIskofperforatIon.ContraIndIcatIonstoTEEprobeplacementarerepresented
byesophagealstrIcture,rIngsorwebs,
18
esophagealmasses(especIallymalIgnant
tumors),
18
recentbleedIngofesophagealvarIces,
18
ZenckerdIvertIculum,
18
statuspost
radIatIontotheneck,
1J
andrecentgastrIcbypasssurgery.ntherarecaseInwhIchTEEIs
essentIalandIstheonlyalternatIve,placementoftheTEEprobecanbeperformedunder
dIrectvIsualIzatIonwIthacombInedgastroscopIcandechocardIographIcexamInatIon.
1J
Probe Manipulation
mageacquIsItIondependsonprecIsemanIpulatIonoftheTEEprobe.8yadvancIngthe
shaftoftheprobe,theprobeposItIoncanbemovedfromtheupperesophagustothe
mIdesophagusandIntothestomach.Theshaftcanalsobemanuallyrotatedtotheleftor
totherIght.8yusIngthelargeknobontheprobehandle,theheadoftheprobecanbe
anteflexed(turnIngtheknobclockwIse)andretroflexed(turnIngtheknobcounter
clockwIse).Thesmallerknob,locatedontopofthelargeknob,IsusedtotIlttheheadof
theprobetotherIghtortotheleft.UsIngtheelectronIcswItchontheprobehandle,the
operatorcanrotatetheultrasoundbeamfrom0degrees(transverseplane)to180degrees
In1degreeIncrements.
Orientation
TheprevIouslymentIonedcontrolsallowtheexperIencedechocardIographerstoperform
comprehensIvecardIacImagIng.However,thedIversItyofImagIngplanescanconfusethe
lessexperIencedechocardIographers,leavIngthemunabletorecognIzethevarIous
anatomIcstructurespresented.Thus,anunderstandIngofthebasIcrulesofImagIng
orIentatIonIsessentIaltoechocardIographIcInterpretatIon.
TheultrasoundbeamIsalwaysdIrectedperpendIculartotheprobeface.The20TEE
ImageIsdIsplayedasasectorscan.TheapexofthesectorIsIncloseproxImItytotheTEE
probeandthestructuresseenInthIsareawIllbetheposterIorones(e.g.,leftatrIum).The
arcofthesectorwIlldIsplaythemoredIstalandtherebymoreanterIorstructures.The
angleofrotatIonoftheImagIngarraydetermInestherIghtandleftorIentatIon.Aneasy
waytounderstandthIsorIentatIonIstoplaceyourrIghthandInfrontofyourchestwIth
thepalmfacIngdown,thethumborIentedleftandthefIngersorIentedanterIorrIght.The
scanlInesthatgeneratetheTEEImagestartatyourfIngersandsweeptowardthethumb.
Consequently,therIghtanatomIcstructureswIllbedIsplayedontheleftsIdeofthe
monItor(sImIlartochestxrayorIentatIon;FIg.286).
P.720
ncreasIngtheImagIngplaneangleproducesclockwIserotatIonofthesectorscan.ThIscan
bevIsualIzedbyrotatIngyourhandInaclockwIsefashIon.Forexample,atthe90degree
ImagIngplanetheleftsIdeofthescreennowdIsplaysposterIorstructures(noteposItIonof
fIngers)andtherIghtsIdeofthescreenanterIorstructures(noteposItIonofthumb;FIg.28
7).
Figure 28-6.DrIentatIonofhand,asdescrIbedInthetext,foranImagIngplaneof0
degrees.TheImagIngplaneIsprojectedlIkeawedgeanterIorlythroughtheheart.The
ImageIscreatedbymultIplescanlInestravelIngbackandforthfromthepatIent'sleft
(greenlIne)tothepatIent'srIght(redlIne).TheresultIngImageIsdIsplayedonthe
monItorasasectorwIththegreenedge(greenlIne)ontherIghtsIdeofthemonItor
andtherededge(redlIne)ontheleft.
Figure 28-7.DrIentatIonofhand,asdescrIbedInthetext,foranImagIngplaneof90
degrees.TheImagIngsectorIsrotatedsothatthegreenedge(greenlIne)hasmoved
clockwIseandIsnowcephaladandtherededgeIsnowcaudad.AsprevIously
descrIbed,thegreenedgeIsdIsplayedontherIghtsIdeofthemonItorandthered
edgeontheleft.
Goals of the Two-Dimensional Examination
EachTEEexamInatIonIsperformedwIththegoalthatnoImportantdIagnosIsIsmIssed.For
thIsreason,acomprehensIveevaluatIonIspreferredwItheachcardIacchamberandvalve
ImagedInatleasttwoorthogonalplanes.However,InanemergencysItuatIon,such
examInatIonmaynotbepossIble.nthesecases,mostechocardIographerswIllfocusthe
TEEexamInatIontothosevIewsmostlIkelytoprovIdeadIagnosIs:thetransgastrIcshort
axIsvIewoftheleftventrIclefordIagnosInghypovolemIa,coronaryIschemIa,oracute
heartfaIlure.
Figure 28-8.|IdesophagealascendIngaortIcshortaxIsvIew.S7C,superIorvenacava.
ToachIevethegoalsoftheIntraoperatIveTEEexamInatIon,theSocIetyofCardIovascular
AnesthesIologIststogetherwIththeAmerIcanSocIetyofEchocardIographyhaspublIshed
guIdelInesforperformIngacomprehensIveIntraoperatIveTEEexamInatIon.
19
These
guIdelInesInclude20standardIzed20echocardIographIcvIews.EachTEEexamInatIon
shouldberecorded(vIdeotapesordIgItalmedIa)alongwIthadetaIledreportofthe
examInatIon.|Illeretal.
20
proposedashortenedversIonofthecomprehensIve
examInatIonthatwouldmeetthegoalsestablIshedbythetheseguIdelInesforbasIc
IntraoperatIveTEEprofIcIencyandIspartIcularlyusefulwhentImeconstraIntsprecludea
moreextensIveexamInatIon.ThesequenceInwhIchthevIewsareacquIreddIffersamong
echocardIographers.nthefollowIngsectIonwedetaIltheacquIsItIonandanatomIc
featuresofthemostcommonlyusedIntraoperatIvevIews.
1. ThemIdesophagealascendIngaortashortaxIsvIew.
ThIsvIewIsobtaInedbyadvancIngtheprobeslIghtlyfromtheupperesophagusuntIlthe
ascendIngaorta(AA)IsseenandthenrotatIngthemultIplaneanglefrom0to45degrees
toobtaInatrueshortaxIs.ThIsgreatvesselvIewImagestheAAInshortaxIsandthe
maInpulmonaryartery(PA)wIthItsbIfurcatIonandrIghtPAInlongaxIs(FIg.288).fthe
multIplaneangleIsrotatedto90degreesthenthemIdesophagealAAlongaxIsvIewIs
obtaIned,InwhIchtheAAIsvIsualIzedInalongItudInalcutandthePAIsvIsualIzedasa
cIrcularcrosssectIonalcut(FIg.289).ThemaInusesofthemIdesophagealascendIng
aortashortaxIsvIewvIewareto:
a. EvaluatetheAAfordImensIonsandpresenceofdIssectIonflaps
b. EvaluatethePA(posItIonofcatheterorruleoutthrombus)
c. AlIgnthe0opplerbeamparalleltothebloodflowInthemaInPA
2. ThemIdesophagealaortIcvalveshortaxIsvIew.
ThIsvIewIsobtaInedfromtheprevIousvIewbyadvancIngtheprobeuntIltheaortIc
valve(A7)IsvIsIble,andthenrotatIngthemultIplaneanglebetweenJ0and60degrees.
ntheclosedposItIon,thethreecuspsoftheA7
P.721
formwhatIsknownasthe|ercedes8enzsIgn(FIg.2810).ThIsvIewIsusedto
evaluate:
Figure 28-9.|IdesophagealascendIngaortIclongaxIsvIew.
a. TheA7cusps
b. AortIcstenosIsandtomeasuretheareaoftheA7orIfIce(planImetry)
c. AortIcInsuffIcIency(A)byapplyIngcolorflow0oppler(CF0)
d. TheInteratrIalseptumforpatentforamenovale(PFD)oratrIalseptaldefect(AS0)
J. ThemIdesophagealaortIcvalvelongaxIsvIew.
ThIsvIewIsobtaInedfromtheprevIousposItIonbyrotatIngthemultIplaneangleto120
to160degrees(FIg.2811).ThevIewIsusedtoassess:
a. TheA7annulus,sInusof7alsalva,sInotubularjunctIonandAAdImensIons
b. AbyusIngCF0
c. 7egetatIonsormassesattachedtotheA7
d. LeftventrIcularoutflowtract(L7DT)pathology(e.g.,hypertrophIcseptumwIth
possIbleL7DTobstructIon)
Figure 28-10.|IdesophagealaortIcvalveshortaxIsvIew.FA,rIghtatrIum;LA,
leftatrIum.
e. ThepresenceofcalcIfIcatIonordIssectIonflapsIntheproxImalAA
4. ThemIdesophagealbIcavalvIew.
ThIsvIewIsobtaInedfromtheprevIousvIewbyturnIngtheprobeshafttothepatIent's
rIght(FIg.2812).ThevIewIsusedto:
a. AssesstheInteratrIalseptumIncludIngCF0todetectapatentforamenovaleorAS0.
ThepassageofaIracrosstheInteratrIalseptumcanbevIsualIzed.
b. CuIdeplacementofcathetersandcannulas(PAcatheter[PAC],pacemakerwIres)or
detectpresenceofthrombusortumors.
5. ThemIdesophagealrIghtventrIcularInflowoutflowvIew.ThIsvIewIsobtaInedfromthe
prevIousvIewbydecreasIngtheInterrogatIonangletoapproxImately60to90degrees
(FIg.281J).ThemaInusesofthevIewaretoevaluatethe:
a. Pulmonaryvalve(P7)bymeasurIngthepulmonaryannulus(requIredforFoss
procedure)andtodetect
P.722
P.72J
pulmonaryInsuffIcIencybyapplyIngCF0ontopof20vIew
Figure 28-11.|IdesophagealaortIcvalvelongaxIsvIew.LA,leftatrIum;L7,left
ventrIcle;L7DT,leftventrIcularoutflowtract;F7DT,rIghtventrIcularoutflow
tract.
Figure 28-12.|IdesophagealbIcavalvIew.7C,InferIorvenacava;LA,left
atrIum,S7C,superIorvenacava;FA,rIghtatrIum.
Figure 28-13.|IdesophagealrIghtventrIcularInflowoutflowvIew.
Figure 28-14.|IdesophagealfourchambervIew,FA,rIghtatrIum;F7,rIght
ventrIcle;LA,leftatrIum;L7,leftventrIcle.
b. F7andF7DTstructureandfunctIon
c. TrIcuspIdvalve(T7);thIsvIewoffersthebest0opplerbeamalIgnment
d. PAClocatIon
6. ThemIdesophagealfourchambervIew.
ThIsvIewIsobtaInedfromtheprevIousvIewbyreturnIngtheImagIngangleto0degree
andslIghtlyadvancIngtheprobetothelevelofthemItralvalve(|7).nthIsvIewthe
fourcardIacchambersarevIsualIzedaswellastheT7and|7(FIg.2814).SlIght
wIthdrawaloranteflexIonoftheprobewIllvIsualIzetheA7andrepresentsthe
mIdesophagealfIvechambervIew.ThemIdesophagealfourchambervIewIsoneofthe
mostrecognIzableandvaluabledIagnostIcvIews.tsmaInusesaretoevaluatethe:
a. LeftatrIum,rIghtatrIum,F7,andtheL7(Inferoseptalandanterolateralwalls)sIze
andfunctIon
Figure 28-15.|IdesophagealtwochambervIew.LA,leftatrIum;|7,mItral
valve;L7,leftventrIcle.
b. T7and|7structureandfunctIon;CF0wIlldetectvalvularpathology
c. 0IastolIcfunctIon
7. ThemIdesophagealtwochambervIew.
ThIsvIewIsobtaInedfromtheprevIousvIewbyrotatIngthemultIplaneangleto90
degrees.nthIsvIewtheleftatrIalappendageIsexamInedforpresenceofthrombus.
SlIghtretroflexIonIsusedtoavoIdaforeshortenedvIewoftheL7soastovIsualIzethe
L7apex(FIg.2815).fthemultIplaneangleIsrotatedtojust60degreesthenthe
mIdesophagealmItralcommIssuralvIewIsobtaIned(FIg.2816).ThemaInusesofthe
mIdesophagealtwochambervIewaretoevaluatethe:
a. L7anterIorandInferIorwallfunctIonb)L7apexaswellastodIagnoseapIcal
thrombus
8. ThemIdesophageallongaxIsvIew.
ThIsvIewIsobtaInedfromtheprevIousvIewbyrotatIngthemultIplaneangleto120to
1J5degrees(FIg.2817).
P.724
ThemaInusesofthemIdesophageallongaxIsvIewaretoevaluatethe:
Figure 28-16.|IdesophagealcommIssuralvIew.
a. L7anteroseptalandposterIorwallfunctIon
b. L7outflowtractpathology
c. |7pathology
9. ThetransgastrIcmIdpapIllaryshortaxIsvIew.
ThevIewIsobtaInedbyadvancIngtheTEEprobefromthemIdesophagealposItIonInto
thestomach,anteflexIngandthenwIthdrawInguntIlcontactIsmadewIththegastrIc
wall.TheL7IsvIsualIzedasadoughnutshapeIncrosssectIonandbothpapIllarymuscles
shouldbeseen(FIg.2818).AddItIonalanteflexIonobtaInsthegastrIcbasalshortaxIs
vIew(FIg.2819).AdvancementoftheprobeallowsvIsualIzatIonoftheL7apexIncross
sectIon.ThetransgastrIcmIdpapIllaryshortaxIsvIewIsunIqueInthatItvIsualIzesall
theL7wallsperfusedbyeachofthethreemajorcoronaryarterIes.ThevIewIs
consIderedtobethemostusefuloneInsItuatIonsofIntraoperatIvehemodynamIc
InstabIlItyasItallowsImmedIatedIagnosIsofhypovolemIcstate,pumpfaIlure,or
coronaryIschemIa.
Figure 28-17.|IdesophageallongaxIsvIew.LA,leftatrIum;L7,leftventrIcle;
F7DT,rIghtventrIcularoutflowtract.
TheprImaryusesofthetransgastrIcmIdpapIllaryshortaxIsvIewIncludeassessmentof
the:
a. L7sIze(enlargement,hypertrophy)andcavItyvolume
b. ClobalventrIcularsystolIcfunctIonandregIonalwallmotIon
10. ThetransgastrIctwochambervIew.
ThIsvIewIsobtaInedfromtheprevIousonebyrotatIngthemultIplaneangleto90
degrees.TheL7IsvIsualIzedInalongItudInalsectIonwIththeapexattheleftofthe
dIsplayand|7attherIght(FIg.2820).TheprImaryuseofthIsvIewIstoassessfunctIon
oftheL7anterIorand,InferIorwalls.
11. ThetransgastrIclongaxIsvIew.
ThIsvIewIsobtaInedfromtheprevIousvIewbyrotatIngthemultIplaneangleto120
degrees(FIg.2821).ThemaInusesofthevIewareto:
P.725
Figure 28-18.TransgastrIcshortaxIsvIew.L7,leftventrIcle.
Figure 28-19.TransgastrIcbasalshortaxIsvIew.A1J,anterIorleafletofmItral
valve,scallops1J;P1J,posterIorleafletofmItralvalve,scallops1J.
Figure 28-20.TransgastrIctwochambervIew.
Figure 28-21.TransgastrIclongaxIsvIew.L7,leftventrIcle;L7DT,leftventrIcular
outflowtract.
P.726
a. PosItIonthe0opplerbeamparalleltobloodflowacrosstheL7DTandA7
b. AssesssystolIcfunctIonoftheanteroseptalandposterIorL7walls
12. ThedeeptransgastrIclongaxIsvIew.
ThIsvIewIsobtaInedbyadvancIngtheprobedeepInthestomach,towardtheL7apex,
andthenanteflexIngandslIghtlywIthdrawIngtheprobe(FIg.2822).ThemaInuseofthe
vIewIs0opplerassessmentofL7DTandaortIcbloodvelocItIes.
1J. 0escendIngshortandlongaxIsvIews.
ThedescendIngaortIcshortaxIsvIewIsobtaInedfromthemIdesophagealfourchamber
vIewbyturnIngtheTEEprobetotheleftuntIlacIrcularvascularstructureIsfound,
representIngthedescendIngaortaIncrosssectIon(FIg.282J).FotatIngthemultIplane
angleto90degreesvIsualIzesthedescendIngaortaInalongItudInalsectIon(tubular
vascularstructure;FIg.2824).nordertoexamInetheentIredescendIngaorta,the
probeIsgraduallyadvancedandwIthdrawnIntheesophagus.ThesevIewsareusedto:
Figure 28-22.0eeptransgastrIclongaxIsvIew.L7,leftventrIcle;L7DT,left
ventrIcularoutflowtract.
a. dentIfypathologyofthedescendIngaorta(atheroma,dIssectIonflaps,aneurysm)
b. AssIstwIthplacementofguIdewIresandcannulas(IntraaortIcballoonpump[A8P],
aortIccannula)
14. UpperesophagealaortIcarchshortaxIsvIew.
ThevIewIsobtaInedfromthedescendIngaortIclongaxIsvIewbywIthdrawIngtheprobe
IntheupperesophagusandrotatIngIttotherIghtuntIlthetubularstructuretransforms
IntoacIrcularone(FIg.2825).ThevIewIsusedtoassessthepresenceofpathologyIn
thedIstalaortIcarchand0opplerassessmentofpulmonaryarterIalbloodvelocItIes.f
themultIplaneangleIsrotatedbackto0degrees,theupperesophagealaortIcarchlong
axIsvIewIsobtaIned(FIg.2826).
P.727
Figure 28-23.0escendIngaortIcshortaxIsvIew.
Three-Dimensional Echocardiography
nordertobetterconceptualIzethemorphologyandpathologyoftheheart,three
dImensIonal(J0)ImagepresentatIonhasbeendeveloped.TherecentIntroductIonofa
realtImeJ0TEEprobemakesthIsgoalarealItyforIntraoperatIveechocardIographers.
ThIstechnologyIscapableofacquIrIngfullvolumesoftheleftventrIcle,ofvIsualIzIng
heartvalvesInthreedImensIons,andassessIngthesynchronyofL7contractIon.
UsesofJ0TEEarejustemergIng.TheutIlItyofJ0ImagIngofthe|7fora|7repaIr
surgeryIsofpartIcularInterest.
21
ThecapacItyofthIsprobetoassessL7contractIon
synchronyInpatIentsundergoIngresynchronIzatIontherapywIthbIventrIcularpacIngmay
offerameanstomaxImIzetheIrcardIacoutput.tIsantIcIpatedthataddItIonal
IntraoperatIveapplIcatIonswIllemergewIththIsexcItIngadvancement.
Figure 28-24.0escendIngaortIclongaxIsvIew.
Doppler Echocardiography and Hemodynamics
Useof20echocardIographycaptureshIghfIdelItymotIonImagesofcardIacstructures,but
notbloodflow.8loodflowIndIcessuchasbloodvelocItIes,strokevolume,andpressure
gradIentsarethedomaInof0opplerechocardIography.UnlIke20ImagIng,whIchrelIeson
thetImedelayandamplItudeofreflectedultrasound,0opplertechnologIesarebasedon
thechangeInfrequencythatoccurswhenultrasoundInteractswIthmovIngobjects.
FeflectIonsfromredbloodcellsareusedtodetermInebloodflowvelocItyandcalculate
hemodynamIcparameters.ThecombInatIonof20ImagesandquantItatIve0oppler
measurementscreateaunIquelypowerfuldIagnostIctool.AccordIngly,0oppler
assessmentsareanessentIalelementoftheechocardIographIcexamInatIon.
22
P.728
Figure 28-25.UpperesophagealaortIcarchshortaxIsvIew.
ThemotIonofanobjectcausesasoundwavetobecompressedInthedIrectIonofthe
motIonandexpandedInthedIrectIonopposItetothemotIon.ThIsalteratIonInfrequency
IsknownastheDoppler effect.8ymonItorIngthefrequencypatternofreflectIonsofred
bloodcells,0opplerechocardIographycandetermInethespeed,dIrectIon,andtImIngof
bloodflow.TheDoppler equationdescrIbestherelatIonshIpbetweenthealteratIonIn
ultrasoundfrequencyandbloodflowvelocIty(FIg.2827)
f=vcos2f
t
/c
wherefIsthedIfferencebetweentransmIttedfrequency(f
t
)andreceIvedfrequency,vIs
bloodvelocIty,cIsthespeedofsoundInblood(1,540m/s),andIstheangleofIncIdence
betweentheultrasoundbeamandbloodflow.Conceptually,theequatIonIssImplIfIedby
observIngthatthechangeInultrasoundfrequencyIsrelatedtojusttwovarIables:blood
velocItyandcos.ForthIsreasonthe0opplersIgnalIsshIftedonlybythecomponentof
thebloodvelocItythatIsInthedIrectIonofthebeampath(I.e.,vcos).Whenthebeam
angledIvergenceIsJ0degreesthevalueofcosdecreasesrapIdlyandthe0oppler
systemwIllmarkedlyunderestImatebloodvelocIty.TherequIrementofnearparallel
orIentatIon(cos0=1)for0opplerexamInatIonscontrastswIththenearperpendIcular
orIentatIonpreferredfor20ImagIng.Consequently,thepreferredImagIngplanesfor
0opplerwIlldIfferfromthoseusedfor20ImagIng.
Figure 28-26.UpperesophagealaortIcarchlongaxIsvIew.
Spectral Doppler
Two0opplertechnIques,pulsed wave(PW)andcontinuous wave(CW),arecommonlyused
toevaluatebloodflow.AthoroughunderstandIngoftheadvantagesanddIsadvantagesof
eachtechnIqueIscrItIcalInselectIngtheonemostapproprIatefortheclInIcalsettIngat
hand.
2J,24
nclInIcalpractIce,PWandCW0opplerarefrequentlyusedInconjunctIonwIth
20ImagIng.The20ImageIsusedtoIdentIfytheareaofInterestandguIdethe
echocardIographerInprecIselylocalIzIngthe
P.729
samplIngvolumeInaPWstudyorIndIrectIngthebeamInaCWstudy.
Figure 28-27.CalculatIngbloodflowvelocIty:the0opplerequatIon.The0oppler
equatIoncalculatesbloodflowvelocItybasedontwovarIables:the0opplerfrequency
shIft(F)andthecosIne(cos)oftheangleofIncIdencebetweentheultrasoundbeam
andthebloodflow.The0opplerfrequencyshIftIsmeasuredbytheechocardIographIc
system,butcosIsunknown,andmanualentrybytheechocardIographerIsrequIred
forItsestImatIon.v,floodflowvelocIty;F
T
,transmIttedsIgnalfrequency;F
F
,
reflectedsIgnalfrequency;F,dIfferencebetweenF
F
,andF
T
;c,speedofsoundIn
tIssue;,angleofIncIdencebetweentheorIentatIonoftheultrasoundbeamandthat
ofthebloodflow.
Pulsed Wave Doppler
PW0opplerofferstheechocardIographertheabIlItytosamplebloodflowfromapartIcular
locatIon.ThePWtransducerusesasInglecrystalasboththeemItterandthereceIverof
ultrasoundwaves.LIkethepulsedechocardIographysystemdescrIbedfor20ImagIng,the
PW0opplersystemtransmItsashortburstofultrasoundtowardthetargetandthen
swItchestoreceIvemodetoInterpretthereturnIngechoes.8ecausethespeedofsound(c)
IntIssueIsconstant,thetImedelayforasIgnaltoreachItstargetandreturntothe
transducerdependssolelyonthedIstance(d)tothetarget.Consequently,reflectedsIgnals
fromlocatIonsmoredIstantfromthetransducerreturnafteragreatertImeInterval.8y
time gating,theelectronIccIrcuItryofthePWtransducerInterpretsreturnIngechoesonly
afterapredetermInedtImedelayfollowIngthetransmIssIonofanultrasoundpulse.nthIs
way,onlythosesIgnalsassocIatedwIthalocatIon,referredtoasthesample volume,are
selectedforevaluatIon.
Figure 28-28.0opplerechocardIographyInaortIcInsuffIcIency.A.Thedeep
transgastrIc(deepTC)vIewoftheleftventrIcle(L7)IsdIsplayed.Acolor0oppler
sectorIsplacedovertheaortIcvalveandL7outflowtractandtheaortIcInsuffIcIency
(A)jetIsImaged.ThecontInuouswave(CW)0opplercursorIsposItIonedInthecenter
oftheAflowandthespectraldIsplayoftheAjetIsshownagaInsttIme.Theslopeof
theAjetIsusedtocalculatethepressurehalftIme(PTIme).AshortPTImeIs
assocIatedwIthsevereA.B.ThedescendIngaortaIsImagedInlongaxIs
(mIdesophageal[|E]aortaLAX).Thesamplevolumeofpulsedwave0opplerIsplaced
upstream.ThereIsasystolIcwaveabovethebaselIne,asthebloodmovestowardthe
transesophagealechocardIographytransducer,andadIastolIcwave(arrow),IndIcatIng
reversalofaortIcflowbecauseofsevereA.0ecel,deceleratIon.
Thepulsed0opplersystemusesarepeatIngpatternofultrasoundtransmIssIonand
receptIon.TherateatwhIchthedevIcerepeatedlygeneratessoundburstsIsknownasthe
pulse repetition frequency.8ecausethespeedofsoundthroughtIssueIsaconstant,the
pulserepetItIonfrequencyIsdIrectlyrelatedtothedepthofthesamplevolume.Thepulse
repetItIonfrequencyIsanalogoustotheframerateofamovIecamera.LIkethemultIple
framesonarollofmovIefIlm,eachultrasoundpulseInteractswIththebloodflowfora
brIefperIodoftIme,andjustasaserIesofmovIeframesdIsplaymotIon,aserIesofpulsed
cyclesareconsecutIvelyanalyzedtodetermInethebloodflow.The0opplerdataIs
frequentlypresentedasavelocItytImeplotknownasthespectral display(FIg.28288).
8ecausethepulsed0opplerdataarecollectedIntermIttently,themaxImalfrequencyand
bloodflowvelocItythatcanbeaccuratelymeasuredbyPW0opplerarelImIted.The
maxImalfrequency,whIchequalsonehalfthepulserepetItIonfrequency,Isknownasthe
Nyquist limit.AtbloodvelocItIesabovetheNyquIstlImIt,analysIsofthereturnIngsIgnal
becomesambIguous,wIththevelocItIesappearIngtobeIntheopposItedIrectIon.AsImIlar
effectIsseenInmovIeanImatIon,InwhIcharapIdlyspInnIngwheelappearstospIn
backwardbecauseoftheslowframerate.TheambIguoussIgnalfromfrequencIesabove
theNyquIstlImIt,knownasaliasing,appearsonthespectraldIsplayasasIgnalonthe
othersIdeofthebaselIne,hencethetermwraparound.ThIsNyquIstlImItatIonhasledto
analternatIveapproachforassessmentofhIghvelocItybloodflows,namelyCW0oppler.
Continuous Wave Doppler
TheCW0opplertechnIqueavoIdsthemaxImalvelocItylImItatIonofPWsystemsbyusIng
twocrystals,onecontInuouslytransmIttIngandtheothercontInuouslyreceIvIngthe
reflectedultrasoundsIgnal.WIthcontInuousreceptIonofthe0opplersIgnal,theNyquIst
lImItIsnotapplIcable,andbloodflowswIthveryhIghvelocItIesarerecordedaccurately.
TheCWmodereceIvesreflectedsIgnals
P.7J0
frombloodflowthroughoutItsbeampathbecauseItIsnottImegatedlIkethePW
technIque(FIg.2828A).TheInabIlItytoselectbloodflowfromaspecIfIclocatIonfavors
theselectIonofCW0opplerprImarIlyfordetectIonofthehIghestvelocItIesalongthe
beampath,whIchIsusefulInapplIcatIonssuchasdetermInIngthehIghvelocItyjetof
aortIcstenosIs.
Figure 28-29.EvaluatIonofaortIcInsuffIcIency(A).Colorflow0oppleroftheaortIc
valve(A7)InthemIdesophageallongaxIsvIew.AIsgradedusIng(1)therelatIveratIo
oftheAjetthIcknesstothedIameterofleftventrIcularoutflowtract(L7DT);both
measurementsareperformedatthesamesIte,usuallywIthIn0.5to1cmproxImalto
theA7plane;and(2)thewIdthoftheAjetasItcrossestheA7cusps(vena
contracta).
Color Flow Doppler
CF0provIdesadramatIcdIsplayofbothbloodflowandcardIacanatomybycombInIng20
echocardIographyandPW0opplermethods(FIg.2829).ThePW0opplerusedforCF0
dIffersfromthatprevIouslydIscussedIntwoImportantways.CF0performsmultiple
samplevolumerecordIngsalongeachscanlIneasthebeamIssweptthroughthesector.
ThIsapproachprovIdesflowdataateachlocatIonInthesector,whIchcanbeoverlaIdon
thestructuraldataobtaInedby20ImagIng.The0opplervelocItydatafromeachsample
volumearecolorcodedandsuperImposedontopofthegrayscale20Image.nthemost
wIdelyacceptedcolorcode,redhuesIndIcateflowtowardthetransducerandbluehues
IndIcatesflowawayfromthetransducer.TheabIlItytoprovIdearealtIme,Integrated
dIsplayofflowandstructuralInformatIonmakesCF0usefulforassessIngvalvularfunctIon,
aortIcdIssectIon,andcongenItalheartabnormalItIes.However,anImportantcaveattoIts
useIntheclInIcalsettIngmustbenoted.8ecauseItrelIesonPW0opplermeasurements,
CF0IssusceptIbletoalIasartIfacts.AlIasIngInthecolorflowmapIsIllustratedInFIgure
28J0.ThIsalIaspatterncanbeusefultocalculatebloodflowInmItralvalvedIseaseusIng
theproxImalIsovelocItysurfacearea(PSA)method(FIg.28J0).
Figure 28-30.0opplerevaluatIonofmItralregurgItatIon(|F)severIty.|FseverItyIs
evaluatedusIngcolor0oppler.A.|FjetIsImagedwIthcolorflow0oppler
(mIdesophagealtwochambervIew).TheNyquIstlImItIsmovedupwardto
demonstrateflowacceleratIonInsIdetheleftventrIcleandtheneck(venacontracta)
ofthe|Fjet.B.ZoomoftheproxImal|FjetallowsmeasurementoftheproxImal
IsovelocItysurfacearea(PSA)radIusandcalculatIonoftheIncompetentmItralvalve
orIfIce.
Hemodynamic Assessments
0opplerechocardIography'sabIlItytoquantItatIvelymeasurebloodvelocItyyIeldsawealth
ofInformatIononthehemodynamIcstate.Strokevolume,chamberpressures,valvular
dIsease,pulmonaryvascularresIstance,ventrIcularfunctIon(systolIcanddIastolIc),and
anatomIcdefectsarecommonlyassessedwIthperIoperatIve0opplerechocardIography.
25
Volumetric Flow Assessments
|easurementssuchasstrokevolumeandcardIacoutputexpressthevolumeofblood
ejectedbytheheartovertIme.7olumetrIcparametersarecalculatedusIngtheprIncIple
thatvolumetrIcflow(Q)equalsbloodflowvelocIty(v)tImesthecrosssectIonalarea(CSA)
oftheconduIt,
P.7J1
thatIsQ=vCSA.TodetermInevolumetrIcflowswIthechocardIography,a0oppler
measurementofthebloodflowvelocItIesanda20measurementoftheCSAarerecorded.
Figure 28-31.0etermInatIonofstrokevolume.7olumetrIcflowcanbedetermIned
fromacombInatIonofareaandvelocItymeasurements.nthIsexample,flowthrough
theascendIngaortaIsusedtodetermInethestrokevolume.ntegratIngthe0oppler
derIvedflowvelocItIesovertIme(knownasthetImevelocItyIntegral)durIngasIngle
cardIaccyclecalculatesthestrokedIstance.ThecrosssectIonalareameasurementIs
obtaInedbytwodImensIonalechocardIography.Theproductofthesetwo
measurements,conceptualIzedasacylInder,Isthestrokevolume.CSA,crosssectIonal
area:Ao7,aortIcvalve.
Stroke Volume and Cardiac Output
TocalculatestrokevolumetheInstantaneousvelocItIesdurIngsystolearetracedfromthe
spectraldIsplayandtheechocardIographIcsystem'sInternalsoftwarepackagecalculates
thetImevelocItyIntegral(7T,IncentImeters).neffectthe7TrepresentsthedIstance(v
t=d)bloodtraveleddurIngsystole(I.e.,strokedIstance).8ymultIplyIngthe7Tbythe
CSA(InsquarecentImeters)oftheconduIt(e.g.,aorta,|7,PA)throughwhIchtheblood
traveled,thestrokevolume(IncubIccentImeters)IsobtaIned:S7=7TCSA(FIg.28
J1).
26,27,28
CardIacoutput,whIchexpressesvolumetrIcflowIncubIccentImetersper
mInute,IsestImatedfromtheproductofS7andheartrate:CD=7TCSAHF.FIgure28
J2demonstratescalculatIonofcardIacoutputandstrokevolumefromtheleftventrIcular
outflowtract.
Figure 28-32.StrokevolumecalculatIon.StrokevolumeIsequaltothebloodflow
crossIngtheleftventrIcularoutflowtract(L7DT).nthedeeptransgastrIcL7vIew,the
L7DTorIfIce(large oval)canbecalculatedfromtheL7DTdIameter(0).Thebloodflow
velocItyacrosstheL7DTIsmeasuredwIthpulsed0oppler,andthevelocItytIme
Integral(7T)bytracIngthevelocItyenvelope.F7,rIghtventrIcle;LA,leftatrIum.
Valve Area
TheContInuItyEquatIon.TheprIncIpleofconservatIonofmassIsthebasIsofthe
continuity equation,whIchIscommonlyusedtomeasuretheaortIcvalvearea.
29
The
contInuItyequatIonsImplystatesthatthevolumeofbloodpassIngthroughonesIteInthe
heart(e.g.,theL7DT)IsequaltothemassorvolumeofbloodpassIngthroughanothersIte
(e.g.,theaortIcvalve).
7olumetrIcFlow
1
=7olumetrIcFlow
2
therefore
CSA
1
7T
1
=CSA
2
7T
2
and
CSA
1
=CSA
2
7T
2
/7T
1
FIgure28JJdemonstratescalculatIonofA7areausIngthIsapproach.
Figure 28-33.EvaluatIonofaortIcstenosIs.CalculatIonofaortIcvalveareausIngthe
doubleenvelopetechnIque.ThecursorofcontInuouswave0opplerIsplacedInthe
mIddleofthebloodflowtraversIngthestenosedaortIcvalve,andtwoenvelopesare
IdentIfIed.TheonewIththeslowervelocItyIsfromtheleftventrIcularoutflowtract
(L7DT)andtheonewIththefastestIsfromtheaortIcvalve(A7).Theenvelopesofthe
velocItIesaretracedtoderIvetherespectIvevelocItytImeIntegrals(7T).TheaortIc
valveareaIscalculatedusIngthecontInuItyequatIon.0dIameter.
P.7J2
Pressure Assessment: The Bernoulli Equation
PressuregradIentsareusedtoestImateIntracavItarypressuresandtoassesscondItIons
suchasvalvulardIsease(e.g.,aortIcstenosIs),septaldefects,outflowtractobstructIon,
andmajorvesselpathology(e.g.,coarctatIon).Asbloodflowsacrossanarrowedor
stenotIcorIfIce,bloodflowvelocItyIncreases.TheIncreaseInvelocItIesrelatestothe
degreeofnarrowIng.ntheclInIcalsItuatIon,thesimplified Bernoulli equationdescrIbes
therelatIonbetweentheIncreasesInbloodflowvelocItyandthepressuregradIentacross
thenarrowedorIfIce
11
:P=47
max
2
wherePInmIllImetersofmercuryIsthepressure
gradIentacrossthenarrowedorIfIceand7
max
4
InmeterspersecondIsthemaxImum
velocItyacrossthatorIfIcemeasuredby0oppler.
ThusInclInIcalechocardIography,pressuregradIentIsobtaInedbythestraIghtforward
processofmeasurIngthepeakvelocItyofbloodflowacrossthelesIonofInterest.
J0,J1
The
measuredpeakvelocItyIsthenenteredIntothesImplIfIed8ernoullIequatIontoestImate
thepressuregradIent.
The8ernoullIequatIonIscommonlyemployedtomeasurethepressuregradIentacrossa
stenotIcvalve.naddItIon,therateofdeclIneInthepressuregradIentacrossthevalveIs
relatedtotheseverItyofdIsease.
J2,JJ
ThIspressure half-timeIsthetImerequIredforthe
peaktransvalvularpressuregradIenttodecreaseby50.TypIcally,alargerorIfIcewIll
haveashorterpressurehalftImeaspressurecanequalIzemorequIckly.
Measurement of Intracavitary Pressures
ntracavItaryandpulmonaryarterIalpressurescanbeestImatedbyobtaInInga0oppler
derIvedpressuregradIentfromaregurgItantjetofthevalveseparatIngtwo
chambers.
J4,J5,J6
ThechamberpressureequalsthepressureoftheneIghborIngchamber
plusthepressuregradIentbetweenthem.Table281provIdescalculatIonsfortheheart
chambersandPA.
Echocardiographic Evaluation of Systolic Function
EvaluatIonofL7systolIcfunctIonIsaprImarycomponentofeveryechocardIographIc
examInatIon.nformatIonaboutglobalaswellregIonalL7performanceIsaccomplIshedby
assessIngtheL7musclecontractIlefunctIonandthesIzeandshapeofL7cavIty.8oth
qualItatIveassessments(whIchareInherentlysubjectIve)andquantItatIvetechnIques
(whIchproducehardnumerIcalestImates)areuseful.|odalItIesusedare20andmotIon
mode(|mode),whIchImagetheL7wallsandcavItyand0opplerechocardIography,whIch
measuresthevelocItyofbloodflowandmovIngtIssue.
Left Ventricular Walls
FromthemIdesophagealposItIon,theTEEImagIngarrayIsrotatedelectronIcallyIna
clockwIsefashIontoscantheentIrecIrcumferenceoftheL7cavItyandwallsIna
longItudInalorIentatIon.FurtheradvancementoftheTEEprobetothetransgastrIcposItIon
combInedwIthanterIorflexIon(anteflexIon)oftheprobesequentIallyImagestheL7short
axIsfromItsbasetoapex.TheL7cavItyandwallsatthebasal,mId,andapIcallevelsare
evaluatedInthemIdesophagealandtransgastrIcvIews.TheechocardIographIcImagIngof
bloodandmyocardIumIsbasedontheIrdIfferentacoustIcpropertIes:muscletIssueIs
reflectIveandImagedInshadesofgray,whIleultrasoundeasIlypropagatesthroughblood,
resultIngIntheL7cavItyappearIngdark.TheIrInterfaceIstheendocardIal
P.7JJ
surface,whIchtypIcallyproducesthebrIghtestsIgnal.TheevaluatIonfocusesontheshape,
sIze,andmotIonofL7walls.
Table 28-1 Calculation of Cardiopulmonary Pressures
pressure equatIon
F7SPorPASP
=4(7
2
TF
)+FAP
PA|P =4(7
early
P)
2
+FAP
PA0P =4(7
late
P)
2
+FAP
LAP =S8P4(7
|F
)
2
L7E0P =08P4(7
Alend
)
2
F7SP,rIghtventrIcularsystolIcpressure;PASP,pulmonaryarterysystolIcpressure;
v,peakvelocIty;TF,trIcuspIdregurgItatIon;FAP,rIghtatrIalpressure;PA|P,
pulmonaryarterymeanpressure;Pl,pulmonIcvalveInsuffIcIency;PA0P,
pulmonaryarterydIastolIcpressure;LAP,leftatrIalpressure;S8P,systolIcblood
pressure;|F,mItralregurgItatIon;L7E0P,leftventrIcularenddIastolIcpressure;
08P,dIastolIcbloodpressure;Al,aortIcInsuffIcIency.
Figure 28-34.LeftventrIcular(L7)walls.ntheesophagus,thetransesophageal
echocardIography(TEE)probeIsrotatedclockwIsefrom0to140degreestoobtaInthe
mIdesophageal(|E)vIews.AdvancementoftheTEEprobeInsIdethestomachobtaIns
thetransgastrIc(TC)mIdpapIllaryshortaxIsvIew.nthe|EvIews,theL7IsdIvIdedIn
basal,mId,andapIcalsegments.4C,fourchamber;2C,twochamber;LA,leftatrIum;
FA,rIghtatrIum;F7,rIghtventrIcle.NotethatthewallslabeledInferolateralInthIs
fIgurearereferredtoInthetextasposterIor.Thesetwotermsareused
InterchangeablyInmanycenters,butarecentconsensuspublIcatIonselected
posterIorastheoffIcIalname.
4J
Shape
TheL7'slongItudInalshapeIsevaluatedInthemIdesophagealvIews(FIg.28J4).tappears
bulletshapedwIththemItralannulusandleafletscomprIsIngItsbroadbase,andthewalls
taperIngtowardItsapex.nthemIdesophagealvIewat0degreesrotatIon(mIdesophageal
fourchamber,mIdesophagealfIvechamber)thelateralwalloftheL7appearsontherIght
oftheTEEmonItorscreenandtheseptalwallontheleft.ClockwIserotatIonoftheTEE
probetoabout90degrees(mIdesophagealtwochamber)wIllImagethelongaxIsoftheL7
anterIorandInferIorwallspresentedontherIghtandleftsIdesofthemonItor,
respectIvely.FurtherrotatIontoapproxImately1J5degreeswIllImagetheL7anteroseptal
andposterIorwallsontherIghtandleftsIdesofthescreen.
TheechocardIographermustbecarefultoImagetheL7alongthetruelongaxIsInthe
mIdesophagealvIews.DftentheImagIngplanemaycutoblIquelyInananterIordIrectIon,
whIchcausesanIncreaseInthewallthIcknessandforeshortenstheL7cavIty.ThIsIs
avoIdedbyconfIrmIngthattheL7axIsIneachvIewapproxImatesthatofthelongestL7
axIsobtaIned(asmeasuredfromthemItralannularplanetotheapex,typIcallyfromthe
mIdesophagealtwochambervIew).nmanycasesslIghtretroflectIonorImagIngplane
rotatIonfromthe0degreeplaneIshelpfultoachIevethebestalIgnment.TheL7wallsare
dIvIdedIntothreesegmentseachbasal,mId,andapIcalasdefInedbylInesdrawn
perpendIculartotheL7longaxIsatthetIpsandbaseofthepapIllarymuscles.
FromthetransgastrIcposItIon,theL7IsseenalongItsshortaxIs,andItsshaperesemblesa
doughnut.ThebasalsegmentsareImagedInshortaxIswIththeTEEprobeInthedIstal
esophagusorveryhIghupInsIdethestomach.AtthIsdepth,themItralleaflets(baseof
heart)areseenenface.CradualadvancementoftheTEEprobeIntothestomachImages
themIdL7segments.Here,theanatomIclandmarkIsthebodyofthepapIllarymusclesat
2o'clock(posteromedIal)and5o'clock(anterolateral).FurtheradvancementoftheTEE
probewIllImagetheL7apex,muchthIckerandwIthsmallercavIty.neIther
mIdesophagealortransgastrIcImagIngplanes,theL7wallsthIckenInsystoleandthInIn
dIastole.AsseenInthemIdesophagealvIews,theL7basedescendstowardtheL7apexand
ascendsatdIastole.
Aneurysms
AneurysmsappearasadIlatedpartoftheL7perImeterwIththInnedwall(s)anddecreased
motIon.AneurysmsarealwayspathologIcandusuallyduetoIschemIarelatednecrosIsand
weakenIngoftheL7wall.AneurysmsareseparatedIntotrueandfalse.fallmyocardIal
layers(epI,mId,andendocardIum)arepresentInthewalloftheaneurysm,ItIscalleda
true aneurysm.TheneckofatrueaneurysmIsusuallywIde,andtheaneurysmalcavIty
shallowwIthasmoothtransItIonfromnormaltoaneurysmalwalls.AnaneurysmIscalled
falseorpseudoIftheL7wallcontaInsonlysomeofthemyocardIallayers(usuallythe
epIcardIumandpartofthemIdwall).FalseaneurysmsarecausedbynecrosIsoftheL7
wall,usuallyfrommyocardIalInfarctIon.SometImes,thewallofafalseaneurysmconsIsts
onlyoftheattachedperIcardIum.FalseaneurysmshaveanarrowerneckandthetransItIon
betweenhealthyanddIseasedwallsegmentsIsabrupt.AfalseaneurysmIsproneto
ruptureandIstreatedsurgIcally.8loodflowIssluggIshwIthInaneurysms.Fedbloodcells
clumptogether,whIchIncreasesechogenIcItyandcreatesspontaneousechocardIography
contrast,asmokelIkeappearanceInsIdetheL7cavIty.Thrombus,appearIngwIth
brIghtnesssImIlartothatofmyocardIumbutclearlyseparatedfromtheL7wall,canalso
developInaneurysms.
Texture
ThetextureoftheL7wallsmayofferaddItIonalInformatIonInpatIentswIthInfIltratIve
cardIomyopathIes,suchasamyloId,wherethethIckenedmyocardIumhasaspeckled
appearance.
Wall Thickness
L7hypertrophyIstermedconcentricIfthecavItyIsnotIncreased(usuallyresultIngfrom
Increasedpressurework)andeccentricwhenthereIsL7dIlatIon(usuallyresultIngfrom
Increasedvolumework).ThedIagnosIsIsmadebysummIngtheenddIastolIc(E0)wall
thIcknessofthe
P.7J4
anteroseptalandposterIorL7segmentsInthebasaltransgastrIcshortaxIsvIew,justatthe
tIpsofthepapIllarymuscles(FIg.28J5).Normalvaluesare182mm(men)and15.51.5
mm(women).
Figure 28-35.TwodImensIonalevaluatIonofleftventrIcular(L7)globalandregIonal
functIon.FegIonalandglobalevaluatIonoftheL7usIngthetransgastrIcshortaxIs
vIewatthemIdpapIllarylevel.|easurementsareperformedatenddIastole(E0)and
endsystole(ES).Top panels:|easurementofdIameters(0),areas(A),andwall
thIckness.WallthIcknessIsmeasuredatE0IntheanteroseptalandInferolateralwall
segments.Bottom panel:0IameterandwallthIcknessmeasuredusIngmethodmode
wIththecursorcrossIngthemIddleofInferIor(top)andanterIor(bottom)segments.
ThepercentchangeofwallthIcknessofthemIdanterIorwallsegmentcanbeusedto
gradeItsregIonalfunctIon.nthIsexample,wallmotIonscore(W|S)Is1(normal)
becausethesegmentthIckensJ0.
Segments and Regional Function
AbnormalmyocardIalwallthIckenIngIsasensItIvemarkerofmyocardIalIschemIathat
appearsearlIerthanelectrocardIographIcandhemodynamIcchanges.
J7,J8,J9
FegIonalL7
systolIcfunctIonreflectstheregIonalmyocardIalbloodflow.
40
TheassocIatIonofthe
regIonalL7wallmotIonwIththeunderlyIngcoronaryarterydIstrIbutIonIsusedtodIagnose
localperfusIondefects.TheL7IsdIvIdedIn17regIonalsegments
41
(FIg.28J4).Alongthe
longItudInalplaneeachwallIsdIvIdedIntobasal,mId,andapIcallevels.Thebasaland
mIdlevelsarefurtherdIvIdedIntoanterIor,InferIor,twoseptal(anteroseptaland
Inferoseptal),andtwolateral(anterolateralandposterIor)segments.TheapIcallevelIs
dIvIdedIntofoursegments(anterIor,InferIor,septal,andlateral)andtheapIcalcapIsthe
seventeenthsegment.TolImItmIsdIagnosIs,evaluatIonofeachsegmentIsdoneInatleast
twodIfferentvIews,ensurIngthatbothendocardIumandepIcardIumarevIsIble.A
mIdesophagealortransgastrIcvIewIsdIgItallystoredandplayedovertIme.Thesegmental
(orregIonal)functIonIsevaluatedbynotIcIngthepresenceorabsenceofendocardIal
excursIon(towardtheL7cavIty)anddegreeofsystolIcwallthIckenIngdurIngoneortwo
consecutIvecardIaccycles(FIg.28J5).TheelectrocardIogramIsusedtodefInesystoleand
dIastole.ThefunctIonofeachwallsegmentIsscoredasshownInTable282.
42
Thewall
motIonscoreIndexIsthesumofallscoresdIvIdedbythenumberofsegmentsevaluated.
TheevaluatIonofsegmentalwallmotIontodetectIschemIaIsnoterrorfree.naddItIon
tobeIngasubjectIveassessment,wallmotIonmaybeaffectedbytetherIng,regIonal
loadIngcondItIons,andstunnIng.
4J
EpIcardIalpacIngofthefreewalloftherIghtventrIcle
(asInpostbypassperIod)producesaleftbundleblockandInducesseptalwallmotIon
abnormalItIes.nterobserverreproducIbIlItyIsbetterfornormallycontractIngsegments
thanfordysfunctIonalsegments.
44
8ecauseoftheseIssues,wallthIckenIngIsamore
relIablemarkerofregIonalfunctIon.
Left Ventricular Cavity
Diameters
TheL7cavItyIsdefInedbyItslongandshortaxes.TheL7major(orlong)axIsdImensIonIs
measuredInthemIdesophagealvIews,fromthebaseofthemItralannulustotheL7apex
(FIg.28J6)whIlethemInor(orshort)axIs
P.7J5
dImensIonIsmeasuredIneItherthemIdesophagealortransgastrIcvIews,perpendIcularto
thelongaxIs,attheheIghtofthepapIllarymuscletIps.ThemInoraxIsIsequaltoonehalf
ofthelongaxIsmeasurement.PropermeasurementoftheL7mInoraxIsIsusedtoquantIfy
theL7E0volume.NormalL7E0dImensIons(E00s)are4.2to5.9cm(men)andJ.9to5.J
cm(women).AnIncreasedL7E00denotesL7dIlatIonandvolumeoverload,whIlea
decreasedL7E00denoteshypovolemIaandInadequatepreload.
Table 28-2 Grading of Wall Function
REGIONAL FUNCTION GRADE INWARD RADIAL MOTION (systolic wall thickening)
Normal 1 J0(marked)
HypokInetIc 2 10toJ0(reduced)
AkInetIc J 10(neglIgIble)
0yskInetIc 4 ParadoxIcalsystolIcmotIon(systolIcthInnIng)
Aneurysmal 5 0IastolIcdeformatIon
Figure 28-36.QuantItatIonofleftventrIcular(L7)systolIcfunctIon.The
mIdesophageal(|E)L7fourchamber(|E4C)andtwochamber(|E2C)vIewsare
obtaIned.TheImagesareexamInedInenddIastole(E0)andendsystole(ES).TheL7
endocardIumIstraced.ThIsautomatIcallydefInestheL7area(A)andlongaxIs(L).
ThesystemsoftwarewIllcalculateL7volumesusIngeItherthemethodofdIscs(|D0)
ortheareaplanemethod(AL).EF,ejectIonfractIon;E07,enddIastolIcvolume,ES7,
endsystolIcvolumeS7,strokevolume.
Global Systolic Function
ThIsfactorIsresponsIblefordelIverIngasuffIcIentamountofbloodtothevesselsatahIgh
enoughpressuretoperfusethetIssuesadequately.AvarIetyofechocardIographIc
measurementsareusedtoevaluatethecomponents(preload,afterload,andcontractIlIty),
whIchcollectIvelydefIneL7globalsystolIcfunctIon.ThetechnIquesforL7evaluatIonare
descrIbedIndetaIlInreferences45and46.
Percent Fractional Shortening (%FS)
FSmeasurestherelatIvechangeoftheL7shortaxIsdIameterbetweenE0andendsystole
(ES;FIg.28J5).FSIsaonedImensIonal,unItlessmeasurementofsystolIcfunctIon.
|easurementsaredoneInthetransgastrIcmIdpapIllaryshortaxIsvIew,justabovethe
papIllarymuscles.AlargernumberoccurswhentheL7hasnormalorIncreasedsystolIc
functIon.FSIsnotasubstItuteforejectIonfractIon(EF)andmayoverestImatesystolIc
functIonIfthereIsL7dIlatIonorabnormalwallmotIonatanotherlevel.FS=(L7E00L7
ES0)/L7E00andIsnormally27to45.
Volumes
L7volumemeasurementsareusedtocalculatepreload(E0volume[E07])aswellasstroke
volume(S7)andEF.TheE0andESL7volumescanbederIvedfrommanuallytracIngofthe
endocardIalborderInE0andES,respectIvely.
L7volumeIscommonlymeasuredusIngthemodIfIedSImpsonorthearealengthmethod.
ThemodIfIedSImpson(ordIscsummatIon)methodconceIvesaserIesofdIsksInsIdetheL7
cavIty,whIchhaveequalthIcknessandarestackedlIkecoInsalongtheL7longaxIs
dImensIon(FIg.28J6).ThedIameterofeachdIskIsdefInedbytheshortaxIsdImensIon
fromtheL7endocardIumtracIng.|easurementsareperformedInthemIdesophagealfour
andtwochambervIews.AlternatIvely,thearealengthmethodcanbeusedtocalculateL7
volume:L7volume=5/6[(area)(length)].ThIsapproachIsperformedInoneofthe
prevIousvIewsandcalculatestheL7volumeusIngtheendocardIalenclosedareaandthe
L7majoraxIs(FIg.28J6).nmostadults,anE0area12cm
2
IndIcateshypovolemIa.
47
FelIableandcorrectvIsualIzatIonoftheendocardIalborderIsparamountforaccurate
measurementofL7volumeswItheIthermethod.ThemethodsunderestImateL7volume
whentheL7cavItyIsforeshortened.
Percent Fractional Area Change (FAC)
FACIsthepercentdIfferencebetweenE0andESL7area(FIg.28J5).TheL7areaIs
measuredbymanuallytracIngtheendocardIalborderInthetransgastrIcmIdpapIllaryshort
axIsvIewInE0andInES.ThepapIllarymusclesarenottraced.UnlIkeL7EF
measurements,FACdoesnottakeIntoaccountthepresenceofwallmotIonabnormalItIes
atadIfferentlevel;forexample,thefunctIonoftheL7apex,whIchIsfrequentlyInvolved
IncoronaryarterydIsease.Therefore,cautIonIsadvIsedwhenInterpretIngFAC.Normal
valuesare56to65.
48
Visual Estimation of FAC
ThemostfrequentlyusedtechnIquetoevaluateglobalL7functIonaswellaspreloadIs
vIsualestImatIonofFAC,oftenreferredtoastheeyeballEF.AlthoughhIghlysubjectIve,It
IspractIcedwIdelyandIsaccurateInexperIencedechocardIographers,especIallyIn
normallycontractIngventrIcles.
49
WIthL7dysfunctIon,vIsualevaluatIonsofFACbecome
lessreproducIbleamongdIfferentobservers.
50
Ejection Fraction
EFIsthemostfrequentlyusedestImateofL7systolIcfunctIon.TheevaluatIonofEF
provIdesprognostIcInformatIonaboutmortalItyandmorbIdIty.
51
EFandstrokevolumeare
affectedbyfactorssuchaspreload,afterload,andheartrate,andthusarenotalways
IndIcatorsofIntrInsIcsystolIcfunctIon.TypIcalclInIcalscenarIosInwhIchEFdoesnot
representL7systolIcfunctIonIncludethehypercontractIleL7InmItralregurgItatIon
(wheremorethanhalfofE0volume
P.7J6
mayregurgItateInsIdetheleftatrIum)orthehypocontractIleL7InaortIcstenosIs(where
L7systolIcperformanceIspoordespItepreservedcontractIlIty).
Stroke Volume
StrokevolumeIscalculatedasthedIfferencebetweenE07andES7,andpercentEFIs
calculatedasEF=S7/E07100=(E07ES7)/E07100.NormalvaluesareE07,67to155
mL(men),56to104mL(women);ES7,22to58mL(men)and19to49mL(women);EF,
55.
Associated Findings
SluggIshflowwIllclumptogetherredbloodcells,producIngspontaneousechocardIography
contrast,whIchIsImagedassmoke.ThrombusIsalsofoundIfthereIsbloodstasIs,such
asInsIdeananeurysmorattheL7apex.ThesefIndIngsareoftenpresentwhenL7functIon
Isdepressed.
Tissue EchocardiographyMyocardial Velocity
TIssue0opplermagIng(T0)measuresthevelocItyofmyocardIalmotIonalongthe
longItudInalaxIsandIsasensItIvemeasurementofregIonalandglobalfunctIonand
outcome.
52
ThemyocardIalvelocItyIsmeasuredfromthebasalL7segmentswIththe
samplevolumeplacednexttothemItralannulus.ThevelocItIesarecomprIsedofa
systolIc(S')followedby,IntheopposItedIrectIon,twodIastolIcwaves,oneearly(E')and
onefollowIngatrIalcontractIon(A').Areduced,ordelayedS'velocItyIsassocIatedwIth
developmentofregIonalIschemIa(FIg.28J7).
5J
Evaluation of Left Ventricular Diastolic Function
AnIncreasedrecognItIonoftheImpactofL7dIastolIcfunctIononcardIacfunctIonand
outcomehasdrIveneffortstobothmonItorandoptImIzedIastolIcperformanceInthe
perIoperatIveperIod.EchocardIographIcstudIeshavesuggestedthatpatIentswIthdIastolIc
dysfunctIonpresentIngforcardIacsurgerymaybepronetoIntraoperatIvehemodynamIc
InstabIlItyandworseoutcomes.
54
ThereadmIssIonandmortalItyrateInpatIentswIth
dIastolIcheartfaIlurearesImIlartothoseobservedInsystolIcheartfaIlurepatIents.
55
0opplerechocardIographyIsthepreferredtechnIquetoassessdIastolIcperformanceand
gradetheseverItyofthedIseaseprocess.
Figure 28-37.TIssue0opplerImagIng.|yocardIalvelocItyofbasalanterolateral
segmentofleftventrIcleIsmeasuredwIthpulsedwavetIssue0oppler.|E,
mIdesophageal;S',systolIcvelocIty;E',earlydIastolIcvelocIty;A',latedIastolIc
velocIty.
0IastolIcdysfunctIonIsdefInedastheInabIlItyoftheL7tofIllatnormalleftatrIal(LA)
pressuresandIscharacterIzedbyadecreaseInrelaxatIonand/orL7complIance.0IastolIc
dysfunctIonmaybepresentIntheabsenceofclInIcalsymptomsofheartfaIlure.When
thesesymptomsoccurInthepresenceofdIastolIcdysfunctIon,thenthedIagnosIsof
dIastolIcheartfaIlureIsmade.
Diastolic Physiology
TradItIonally,thecardIaccyclehasbeendIvIdedIntotwophases:systole,comprIsIng
IsovolumIccontractIonandejectIon,anddIastole,comprIsIngIsovolumIcrelaxatIon,rapId
fIllIng,dIastasIs,andatrIalcontractIon.FatherthanapassIvephaseofthecardIaccycle
whenfIllIngoftheheartoccurs,dIastoleIscurrentlyregardedasbeIngIntImatelycoupled
andInterdependentwIthsystole.nthIsrespect,NIshImuraandTajIk
56
haveproposed
dIvIdIngthecardIaccycleIntothreephases:contractIon,relaxatIon,andfIllIng.
ContractIonencompassestheIsovolumIccontractIonandthefIrsthalfofejectIon.The
crItIcalInsIghtIntotheproposalofNIshImuraandTajIkIsthatrelaxatIonbegInsdurIngthe
secondpartofejection,andthencontInuesdurIngtheIsovolumIcrelaxatIonandrapId
fIllIngphases,IllustratIngtheInterdependencyofsystoleanddIastole.ThefIllIngphase
consIstsoftheearlyrapIdfIllIngphase,dIastasIs,andatrIalcontractIon.TheearlyfIllIng
phasecoIncIdeswIthanddependsonthecontInuatIonofrelaxatIon.
7entrIcularfIllIngIsaffectedbyloadfactors(preloadandafterload)aswellasmechanIcal
factorssuchasventrIcularrelaxatIonandcomplIance,ventrIcularcontractIon,atrIal
contractIonand|7dynamIcs,vIscoelastIcforcesofthemyocardIum,andperIcardIal
restraInt.
TheearlymanIfestatIonofdIastolIcdysfunctIonIscharacterIzedbyanImpaIredrelaxatIon,
ImplyIngthattherateandduratIonofdecreaseInL7pressureaftersystolIccontractIonIs
prolonged.ThIsresultsInanInabIlItyoftheL7tofIll
P.7J7
adequatelydurIngtherapIdfIllIngphase.AcompensatoryIncreaseInfIllIngoccurswIth
atrIalcontractIon.ThIsstageofdIseaseIsknownasgrade I diastolic dysfunction.nmore
advancedstagesofdIsease,gradesandofdIastolIcdysfunctIon,adecreaseInL7
complIanceensues.ComplIanceIsdefInedasachangeofvolumeInrespecttoachangeIn
pressure.Thus,adecreaseInL7complIancewIllleadtoadIsproportIonateIncreaseInL7
pressuresand,ultImately,LApressures.
Echocardiographic Assessment of Left Ventricular Diastolic
Function
EchocardIographyhasbecomethedIagnostIcmodalItyofchoIceforpatIentswIthdIastolIc
dysfunctIon.EchocardIographIcassessmentshavebeenvalIdatedbycardIac
catheterIzatIonandcorrelatewIthclInIcalpresentatIon.
57
AcombInatIonofdIfferent
echocardIographIcmodalItIesIsusedtodIagnosIsdIastolIcdysfunctIon.ThesemodalItIes
arerepresentedby20echocardIography,pulsedwave0oppler,|modecolor0oppler,and
tIssue0oppler.ThIssectIonIslImItedtodIscussIonofthetwomostcommonlyused
methods:pulsedwave0oppleroftransmItralandpulmonaryveInflowsandT0.
Imaging Views and Techniques
TheechocardIographIcacquIsItIonofthedIastolIcparametersIsbestdonewhenIntegrated
InastandardexamInatIon.ThetypIcalvIewusedforbothtransmItralflow0oppler(T|F)
aswellasforthetIssue0opplerImagIng(T0)IsthemIdesophagealfourchambervIew.
nterrogatIonoftheP7IsusuallyperformedInthemIdesophagealcommIssuralor
mIdesophagealtwochambervIews.TheInterrogatIonvolumesampleshouldbeplacedat
thetIpsofthe|7forT|Fassessmentand1to2cmInsIdetheP7forthepulmonaryveIn
flow(P7F)assessment.ForT0ofmyocardIalvelocItyprofIles,thesamplevolumeIs
typIcallyplacedatthejunctIonofthemItralannulusandthelateralwall.
Figure 28-38.0IastolIcphaseofthecardIaccycle.0urIngIsovolumIcrelaxatIon(1)
leftventrIcular(L7)pressurefallsrapIdlyfollowIngaortIcvalveclosure(A7C).When
L7pressuredecreasesbelowleftatrIal(LA)pressure,themItralvalveopens(|7D),
InItIatIngearly,rapIdL7fIllIng(2).EquIlIbratIonofL7andLApressuresresultsIn
dImInIshedtransmItralflowdurIngdIastasIs(J)untIlatrIalcontractIon(4).0Iastole
termInateswIthmItralvalveclosure(|7C).(FeproducedfromPlotnIckC0:ChangesIn
dIastolIcfunctIondIffIculttomeasure,hardertoInterpret.AmHeartJ1989;118:6J7,
wIthpermIssIon.)
Interpretation of Pulsed-Wave Doppler Flow Velocity Curves
FelaxatIon,theactIvephaseofdIastole,commenceswIththedIssocIatIonofactInmyosIn
crossbrIdgesandalowerIngoftheIntracellularcalcIum.L7pressurebegInstofalland
eventuallybecomeslowerthanascendIngaortIcpressure,resultIngInclosureoftheA7.As
theventrIclecontInuestorelax,theL7pressurefallsbelowLApressure,reachIngItsnadIr,
andpromotesopenIngofthe|7.AtthIspoInt,thepressuregradIentbetweentheLAand
L7IsmaxImalandearlyrapIdfIllIngphaseoftheL7occurs.ThIsphaseIsresponsIblefor80
to90ofL7fIllIng.AstheventrIclefIlls,theL7pressuregraduallyrIsesandequatesthe
pressureIntheLA;thus,mInImalflowordIastasIsoccurs.WIthcommencementofthe
atrIalcontractIonphase,thepressuregradIentbetweentheLAandL7rIsesonceagaInand
bloodflowsfromtheLAtotheL7.AttheendoftheLAsystole,thepressureIntheL7rIses
abovetheLApressureandpromotesclosureofthe|7(FIg.28J8).
0opplerassessmentoftheT|FandP7FvelocItyreflectstheInstantaneouspressure
gradIent(seeprevIousdIscussIonof8ernoullIprIncIple).Therefore,thedIsplayedvelocIty
waveformsparallelthechangesInpressuregradIentoccurrIngIntheleftheart.TheT|F
profIleconsIstsoftwowaves,theEandAwaves.ThepeakEwaverepresentsthepeak
earlyfIllIngvelocIty.TherateofdecreaseofvelocItyfollowIngthepeakEvelocItyIs
knownasthedeceleration time(0T).The0TdependsonhowfastthepressurerIsesInL7
durIngtherapIdfIllIngphaseandrepresentsadIrectmeasureofventrIcularcomplIance.
Thus,IftheventrIcularcomplIancedecreases,the
P.7J8
0Tshortens.ThepeakAwaverepresentsthepeakbloodvelocItydurIngatrIalcontractIon.
nanormalIndIvIdualtheEwaveIsslIghtlylargerthantheAwaveandthe0TIs20040
msec(FIg.28J9).
Figure 28-39.TheImpactofprogressIveleftventrIcular(L7)dIastolIcdysfunctIonon
transmItral0opplerflow(T|0F)andpulmonaryvenous0opplerflow(P70F).The
transmItralpressuregradIentIsInItIallyelevatedInnormal,youngIndIvIdualsbecause
ofvIgorousL7relaxatIonandelastIcrecoIl,beforedImInIshIngwhenrelaxatIon
becomesImpaIredandfInallyIncreasIngagaInwhenleftatrIalpressureIncreasesfrom
anelevatedL7enddIastolIcpressureIntherestrIctIvepatternofL7dIastolIc
dysfunctIon.FespectIvechangesarenotedInpulmonaryveIn(P7)profIle.E,Ewave;
A,Awave;7FT,leftventrIcularIsovolumIcrelaxatIontIme;P7
AF
,latedIastolIc
retrogradevelocIty;P7
S1
,fIrstsystolIccomponent;P7
S2
,secondsystolIccomponent;
P7
0
,dIastolIccomponent.
SImIlareventstakeplaceIntheLA.7entrIcularcontractIonlowersthe|7annuluscreatIng
asuctIoneffectandpromotIngbloodflowfromtheP7stotheLA.FIllIngoftheLA
decreasesthepressuregradIentbetweentheP7sandLAandbloodflowplateaus.Asthe
|7opens,anopenconduItformsbetweentheP7s,LA,andL7;thus,addItIonalforward
flowtotheLAoccurs.Subsequently,atrIalcontractIonraIsesLApressureaboveP7
pressureandpromotesbackwardbloodflowIntothem.AnormalP7FvelocItycurve
consIstsofsystolIcforwardflowrepresentIngtheSwave,dIastolIcforwardflow
representIngthe0wave,andareversalofvelocItydurIngatrIalcontractIon
representIngtheawave(FIg.28J6).
AsdIastolIcdysfunctIondevelops,thepatternsoftheflowvelocItycurveschangeIn
concordancewIththepressuregradIentchangesIntheP7LAL7system.ngradedIastolIc
dysfunctIon,astheL7IsIncompletelyrelaxedwhenearlyventrIcularfIllIngoccurs,the
pressuregradIent,andthusEwavevelocIty,Islessthannormal.ThedelayedrelaxatIon
prolongsL7fIllInglateIntodIastole,andthereforethe0TIsprolonged.Acompensatory
IncreaseInT|FdurIngatrIalcontractIon,duetothehIgherresIdualatrIalpreload,
generatesahIghAwavevelocIty.Thus,theT|FcurveofanIndIvIdualwIthabnormal
relaxatIonIsrepresentedbyalowE,hIghA,andprolonged0T.TheIncreasedresIdual
atrIalpreloadgeneratesasmallerpressuregradIentbetweentheP7sandLA;thus,less
flowtotheLAoccursdurIngtheearlyfIllIngphase.ThIsIsrepresentedontheP7Fcurves
asahIgherS/0ratIoascomparedtonormal(FIg.28J9).
ProgressIonofdIastolIcdIseaseleadstogradedIastolIcdysfunctIon,whIchIsmarkedby
decreasesInL7complIance.LApressurerIsesasacompensatorymechanIsmtonormalIze
thepressuregradIentacrossthe|7.nthIsscenarIo,theT|FvelocItIesresemblethe
normalcurve;thus,thIsstageIsknownaspseudonormal.8ecauseofthehIghLApressure,
lessflowfromtheP7soccursdurIngventrIcularsystole,generatIngalowerSwaveonthe
P7Fcurves,andthusalowerS/0ratIo.0urIngatrIalcontractIonalargeramountofblood
IspushedbackIntheP7s,representedbyadeeperawave(FIg.28J9).
CradedIastolIcdysfunctIon,knownastherestrictive phase,IscharacterIzedbya
sIgnIfIcantlydecreasedL7complIance.ThehIghLAL7pressuregradIentproducesafast
acceleratIonofbloodflowIntheL7.ThIsIsrepresentedbyahIghEvelocItyontheT|F
curve.L7pressureIncreasesrapIdlydurIngfIllIngbecauseoftheIncreasedL7stIffness
resultIngInashort0T.TheforwardfIllIngvelocItyatatrIalcontractIonIslow(smallA
wave)becauseofthedecreasedcomplIance.TheelevatedLApressuresInhIbItbloodflow
fromtheP7stotheLAdurIngventrIcularsystole,andtheP7FcurvesshowadecreasedS/0
ratIo(FIg.28J9).DneoftheImportantcaveatstoassessIngdIastolIcfunctIonusIngpulsed
wave0opplerIsthattheflowpatternsdependonpressuregradIentsandthereforeare
affectedbybothpreloadandafterload.nsettIngsInwhIchtheloadcondItIonsvaryata
fastpace,suchastheDF,changesInT|ForP7FvelocItIesmaybedIffIculttoInterpret.
T0,whIchdIrectlymeasuresmyocardIalvelocItIes,provIdesamoreloadIndependent
methodofdIastolIcfunctIonassessment.
58
ThenormalmItralannularT0profIlehasabIphasIcdIastolIccomponent:theearly
dIastolIcwaveErelatedtotheearlyfIllIngandthelatedIastolIcwaveArelatedtoatrIal
contractIon(FIg.28J7).nahealthypatIent,theT0patternmIrrorstheT|Fpattern,
exceptwIthlowervelocItIes.EreflectsL7relaxatIonandvalues8cm/sareconsIdereda
sIgnofdIastolIcdysfunctIon.
59
Thus,InpatIentswIthpseudonormalorrestrIctIvedIsease,
InwhomnormalorelevatedEwaveT|FvelocItIesoccurdespIteadvancedpathology,the
T0EwaveremaInsreduced,makIngItausefulapproachtodIagnosIs.
Pericardial Disease: Constrictive Pericarditis and Pericardial
Tamponade
0IastolIcfIllIngIsalsoImpactedbyperIcardIalrestraInt.PerIcardIalpathologIes,suchas
constrIctIveperIcardItIsorperIcardIaltamponade,ImpededIastolIcflow.
60
DnT|F
0opplerprofIlesthesedIseasesresemblethedIastolIcrestrIctIvefIllIng
P.7J9
pattern.TwodImensIonalechocardIographycanbehelpfulIndIfferentIatIngamongthese
pathologIes.nconstrIctIveperIcardItIstheperIcardIumappearsthIck,fIbrotIc,calcIfIed,
andthusechogenIc;theInferIorvenacavaIsdIlatedandtheventrIcularseptumhasan
abnormalmotIon.
Figure 28-40.EchocardIographIcfIndIngsInperIcardIaleffusIon.A.ClobalperIcardIal
effusIon(asterIsks)surroundIngbothrIghtventrIcle(F7)andleftventrIcle(L7).
TransgastrIcshortaxIs(TCSAX)vIew.B.|modeechocardIographydemonstrates
separatIonoftheepIcardIumfromtheperIcardIum(asterIsks)fromperIcardIal
effusIon.C.FegIonalperIcardIaleffusIon(asterIsks)compressIngtheleftatrIum(LA),
seenInthemIdesophageallongaxIs(|ELAX)vIew.D.|modeechocardIography
revealssystolIccompressIon(asterIsk)ofLA.E.AfterevacuatIonofthefluId
collectIon,theLAsIzeIncreases.
PerIcardIaleffusIonscanbeglobal,surroundIngtheentIreheart,orloculated,asseen
mostlyaftercardIacsurgery(FIg.2840).8ecausetheIntraperIcardIalvolumeIsconstant,
cardIacchambersarecompressedwhenattheIrlowestpressure(atrIaInsystole,ventrIcles
IndIastole).PerIcardIaltamponadeIscharacterIzedbythepresenceofalargeperIcardIal
effusIonseenasanechofree(black)space,aswIngIngmotIonoftheheart,early
dIastolIcF7collapse,andlatedIastolIcrIghtatrIum(FA)collapse.
nsummary,dIastolIcfIllIngIsanactIveprocessandamajorcomponentofeffectIve
cardIacperformance.ThepresenceofdIastolIcdysfunctIon,whetherresultIngfromlossIn
fluIdvolume,L7dIsease,orperIcardIalrestraInt,IsassocIatedwIthpotentIaldeleterIous
surgIcaloutcomes.0opplerechocardIography,InpartIcularT0,provIdesthe
anesthesIologIstthemeanstorapIdlydIagnoseandguIdetherapyofsuchpatIentsInthe
Evaluation of Valvular Heart Disease
TwodImensIonalechocardIographyand0opplerarecomplementarymethodsInvalve
assessment.The20echocardIographyprovIdesevaluatIonofvalveanatomyandfunctIon
and0opplerassessesthephysIologIcconsequencesandseverItyofthelesIon.
Aortic Stenosis
Two-Dimensional and M-Mode Echocardiography
ThenormalaortIcvalve(A7)hasthreecusps,whIchopenwIthoutrestrIctIonInsystole,
yIeldInganA7areaJto4cm
2
.TheappearanceofthevalveandthesystolIcexcursIonof
ItscuspsareImagedwIth20and|modeechocardIography.TheA7IsImagedenfaceIn
themIdesophagealaortIcvalveshortaxIsvIewandItsprofIleInthemIdesophagealaortIc
valvelongaxIsvIew(FIgs.2810,2811).WIththeTEEprobeInsIdethestomach,theA7Is
ImagedInthedeeptransgastrIclongaxIsandtransgastrIclongaxIsvIews(FIgs.2821,28
22).DwIngtotheIncreasedafterload,assocIatedfIndIngsIncludeconcentrIchypertrophy
oftheL7,decreasedEF,aswellasmItralregurgItatIonandleftatrIaldIlatatIon.
Doppler Echocardiography
Jet Velocity, Transvalvular Pressure Gradient.ThetransvalvularpressuregradIentcanbe
calculatedfromtheCW0measuredvelocIty(7)usIngthemodIfIed8ernoullIequatIon:P=
47
2
.ThemeangradIent,calculatedfromthe7TtracIngIscommonlyreportedasIt
correlateswellwIththeangIographIcallydetermInedpressuregradIent.
61
However,forany
gIvenvalvearea,theflowvelocItyandpressuregradIentvarywIthchangesInstroke
volumeandcardIacoutput.AnL7wIthnormalfunctIonwIllgeneratealargepressure
gradIentacrossacrItIcallystenosedA7,andadysfunctIonalL7wIllnot.
62
Valve Area
UsIngthecontInuItyequatIon,flowacrosstheleftventrIcularoutflowtract(L7DT)equals
flowacrossthestenosedA7or7T
L7DT
Area
L7DT
=7T
A7
Area
A7
.8yrearrangIngthe
equatIon,Area
A7
=(7T
L7DT
Area
L7DT
)/(7T
A7
).TheareaL7DTIscalculatedusIngtheL7DT
dIameteratthesIteofthe0opplermeasurement(FIg.28JJ).AnerrorIntheL7DT
dIametermeasurementIsgeometrIcallyIncreasedasArea
L7DT
=(0/2)
2
).The
7T
L7DT
/7T
A7
ratIoIsoftencalculatedtoavoIdthIserrorasflowchangeswIllbereflected
proportIonallyacrossboththeA7andL7DT(0opplerdImensIonlessIndex).AnIndexvalue
0.25IndIcatesanA7area0.75cm
2
.TheechocardIographIccutoffvaluesforgradIng
aortIcstenosIsareshownInTable28J.
6J
Mitral Stenosis
Two-Dimensional Echocardiography
The|7IsImagedInthemIdesophagealvIewsandInthebasaltransgastrIcshortaxIs
vIews.TheleafletscanappearthIckenedandcalcIfIed(thus,stronglyechogenIc),whIle
theremaybefusIonofthe
P.740
chordaeandpapIllarymuscles.ThemajorandmoststrIkIngfIndIngInmItralstenosIs(|S)
IstheInabIlItyofthetwomItralleafletstoseparatefromeachotherIndIastole.nstead,
theIrtIpsremaInopposedwhIlethebodyoftheleafletsbowstowardtheL7cavItybecause
oftheIncomIngblood(FIg.2841).Theareaofthe|7orIfIcecanbetracedbyplanImetry
InthetransgastrIcbasalshortaxIsvIew.
64
AssocIatedfIndIngsIn|SareadIlatedleft
atrIumandleftatrIalappendage(becauseofIncreasedpressure),andpresenceof
thrombusorspontaneousechocardIographIccontrastduetolowflowIntheLA.TheL7
cavItyappearssmall,wIthathIckenedandImmobIleInterventrIcularseptum.TherIght
ventrIclemaybedIlatedand/orhypertrophIed,wIththIckenedwalls,becauseofIncreased
pressurework(FIg.2841andTable284).
Table 28-3 Grading of Aortic Stenosis
Normal AV Mild Moderate Severe
PeakA7velocIty(m/s) 1.7 J.0 J.04.0 4.0
PeaktransvalvulargradIent(mmHg) J6 J664 64
|eantransvalvulargradIent(mmHg) 25 2540 40
A7A(cm
2
) 2.5 1.52.5 1.01.5 1.0
A7,aortIcvalve;A7A,A7area.
Transvalvular Pressure Gradient.TheIncreaseddIastolIcpressuregradIentIsmeasured
wIthcontInuous0opplerInthemIdesophagealfourchamberorlongaxIsvIew.Theearly
dIastolIcvelocItyofthetransmItralflow(Ewave)IsIncreased(usually1.5m/s).ThIsIs
notspecIfIcto|S,asEvelocItywIllalsobeelevatedInthepresenceofIncreasedblood
flow,asInseveremItralregurgItatIon.
65
nsevere|S,themeanpressuregradIentIs10
mmHg(FIg.2842).
Figure 28-41.TwodImensIonalechocardIographIcfIndIngsInmItralstenosIs.A.nthe
mIdesophagealfourchamber(|E4C)vIew,echocardIographIcsIgnsofmItralstenosIs
IncludeadIlatedleftatrIum(LA)wItharIghtwarddIsplacementoftheInteratrIal
septum(IndIcatIngtheelevatedLApressure),andasmallleftventrIcle(L7).B.nthe
mIdesophagealbIcavalvIew,redbloodcellclumpIngcreatesspontaneous
echocardIographycontrast.NotIcetherIghtwarddIsplacementoftheInteratrIal
septumtowardtherIghtatrIum(FA).C.AzoomImageofthemItralvalveand
neIghborIngstructuresInmIdesophagealfourchambervIew.TheanterIormItral
leafletexhIbItsdIastolIcdomIngwhIletheposterIormItralleafletIsImmobIle.D.n
thetransgastrIcmIdpapIllaryshortaxIs(TCmIdSAX)vIew,theL7cavItyIsrelatIvely
small,ascomparedwIththerIghtventrIcle(F7),andInterventrIcularseptumappears
thIckened.
Pressure Half-Time (PHT)
ThedeceleratIonofEvelocItyIsdecreased,becauseIn|StheequalIzatIonoftransmItral
valvepressurestakesalongertIme.PHTIsthetImerequIredforthepeakpressureto
decreasetohalfvalue.ThedecayIngvelocItyIstracedontheCW0sIgnalacrossthe|7In
dIastoleandtheanalysIspackagecalculatesthePHT.|7area(|7A)Iscalculatedas
220/PHT.AprolongedPHT220msIsrelatedtosevere|S(calculated|7A1cm
2
)as
smaller|7orIfIceswIllprolongthepressuredecayacrossthevalve.
66
WhenL7complIance
IsdecreasedorthereIscoexIstIngaortIcregurgItatIon,theIncreasedL7pressureresultsIn
afasterpressureequIlIbratIonacrossthestenosed|7.nsuchcases,PHTwIllbe
shortened,andthecalculated|7AmaybeerroneouslyoverestImated.
67
Associated Findings
CF0wIlldIsplayarIsIngsunpatternofdIastolIcvelocItIesInsIdetheLA,IndIcatIngthe
hIghvelocIty(andIncreasedpressuregradIent)acrossthestenosed|7thatexceedsthe
lImItsofthecolorscale(FIg.2842A).AssocIated
P.741
fIndIngsIncludepulmonaryInsuffIcIencyduetopulmonaryhypertensIonandtrIcuspId
regurgItatIon.
Table 28-4 Grading of Mitral Stenosis
Mild Moderate Severe
|eanpressuregradIent(mmHg) 6 610 10
PressurehalftIme(ms) 100 100220 220
|Itralvalvearea(cm
2
) 1.62.0 1.01.5 1.0
Aortic Regurgitation
Two-Dimensional and M-Mode Echocardiography
TheA7IsImagedInthesamevIewsusedforassessmentofaortIcstenosIs.AssocIated
fIndIngsmayIncludedIlatedaortIcroot(|arfan'ssyndrome),endocardItIslesIons,dIlated
ascendIngaorta,calcIfIedA7,aortIcdIssectIon(maybeassocIatedwIthacuteaortIc
InsuffIcIency(A)),flutterIngoftheanterIormItralleafletandrestrIcteddIastolIcopenIng
ofthe|7fromtheAjet,oradIlatedL7InchronIcA(Table285).
Color Flow.neItherofthemIdesophagealorthetransgastrIcvIewsoftheA7,aCF0
sectorovertheA7andtheL7DTwIlldemonstratethepresenceorabsenceoftheA
regurgItantjet.CF0revealsthecharacterIstIcsoftheAjetasItenterstheL7DTIn
dIastole.ThefollowIngtechnIquesareusedtogradetheseverItyofA:
Ratio of Jet Height to LVOT Diameter
ThemaxImalheIghtoftheAjet(wIthIn1cmfromtheA7plane)IscomparedwIththe
L7DTdIameteratthesamepoInt.TherecommendedvIewIsthemIdesophagealaortIc
valvelongaxIsvIew.AcentraljetusuallyIscausedbyaortIcrootdIlatIon,whereasan
eccentrIcjetImplIesanA7cusplesIon.ThepropagatIonofthejetIntotheL7doesnot
correlatewellwIththeangIographIcdegreeofA,andshouldnotbeusedtogradeA(FIg.
2829).
68
Vena Contracta
7enacontractaIsthenarrowestneckoftheAjetasIttraversestheA7plane,usually
bestapprecIatedInthemIdesophagealaortIcvalvelongaxIsvIew.ThelargestdIameterof
thevenacontractaIndIastoleIsselected(FIg.2829).ThesIzeofvenacontractaIs
relatIvelyloadIndependentandprovIdesarelIablewaytoquantItateAIntraoperatIvely,
InthepresenceoffluctuatInghemodynamIcs.
68
Figure 28-42.0opplerechocardIographyfIndIngsInmItralstenosIs.A.0IastolIcblood
acceleratIonupstreamofthemItralvalveIsseenwIthcolorflow0oppler(rIsIng
sun).B.SpectraldIsplayofthedIastolIcvelocItydecayIsImagedwIthapulsedwave
0opplersamplevolumeplacedatthetIpsofmItralvalve.TracIngofthevelocIty
envelope(white dots)calculatesthemaxImumandmeanpressuregradIent(PC).The
pressurehalftIme(PHT)IscalculatedfromthedeceleratIonofthepeakvelocIty(Evel)
(red dots).ThemItralvalvearea(|7A)IsderIvedfromtheempIrIcformula:|7A=
220/PHT.
Pressure Half-Time
PHToftheAjetIsrecordedInthetransgastrIclongaxIsordeeptransgastrIclongaxIs
vIew.PHTexpressesthepressureequIlIbratIonofthedIastolIcbloodpressure(drIvIng
pressure)andthedIastolIcL7pressure(resIstancepressure).AshortPHT(200ms)Is
assocIatedwIthsevereA.FactorsassocIatedwIthdecreasedL7complIance(e.g.,L7
faIlurewIthrestrIctIvefIllIngpattern)wIllcausethetransaortIcpressuregradIentto
dIssIpatefasterandwIlloverestImatetheseverItyofA(FIg.2828).
Aortic Diastolic Flow Reversal
FetrogradedIastolIcflowInthedescendIngandabdomInalaortaIssensItIveandspecIfIc
forsevereA.ThIsIsImagedwIthPW0InthemIdesophageallongaxIsvIewofthedIstal
descendIngaorta(FIg.2828).
69
Table 28-5 Grading of Aortic Insufficiency (AI)
Trace Mild Moderate Severe
AjetheIght/L7DTdIameter() 25 2545 4664 65
7enacontracta(mm) J 6
PHT(ms) 500 200500 200
AortIcdIastolIcflowreversal HolodIastolIc
L7DT,leftventrIcularoutflowtract;PHT,pressurehalftIme.
P.742
Table 28-6 Carpentier Classification of Mitral Regurgitation (MR)
CARPENTIER TYPE MOTION LEAFLET JET DIRECTION
1 Normal Central
2 ExcessIve(prolapse,flaIl) AwayfromlesIon
Ja FestrIcted,structureIsabnormal 7arIable
Jb FestrIcted,structureIsnormal
Other Findings
SevereArapIdlyelevatesL7dIastolIcpressureandshortenstheearlytransmItralflow
velocIty,resultIngInarestrictive LV filling pattern.Theregurgitant volumeIscalculated
usIngthecontInuItyequatIonandequalsthedIfferencebetweenL7DTflowandthe
dIastolIctransmItralflow.7alues60mLareconsIstentwIthsevereA.
Mitral Regurgitation
Thenormal|7anatomyconsIstsoftwoleaflets(anterIorandposterIor),theIrcoaptatIon
surface,thefIbrousmItralannulus,thesubvalvularapparatuswIththetwopapIllary
muscles(anterolateralandposteromedIal),andtheIrchordaetendInae,whIchattachto
theundersIdeofthemItralleaflets.Thecompetencyofthe|7dependsonadequate
coaptatIonbetweenthe0shapedanterIorleafletandthecrescentshapedposterIor
leaflet.CommoncausesofmItralregurgItatIon(|F)aremyxomatousvalvedegeneratIon,
endocardItIs,andIschemIc,rheumatIcandcongenItalheartdIsease.
TherequIredTEEvIewsforImagIngofthe|7IncludethemIdesophagealfourchamber,
mIdesophagealcommIssural,mIdesophagealtwochamber,mIdesophagealaortIcvalvelong
axIsvIew,andthebasaltransgastrIcshortaxIsandtwochambervIews(FIgs.2814,2815,
2816,2817,2818,2819and2820).
70
EchocardIographIcfIndIngsmayIncludeanyofthe
followIng:abnormaltextureofleaflets(myxomatousdegeneratIon),flaIland/orprolapsIng
leaflet,rupturedchordae,papIllarymuscledysfunctIonorrupture(secondarytoIschemIa),
mItralannuluscalcIfIcatIon,orendocardItIslesIons.TheleafletmotIonIscommonly
reportedusIngCarpentIer'sclassIfIcatIonasdescrIbedInTable286.
Figure 28-43.|ItralregurgItatIon.TheanatomyofmItralvalve(|7)IsdepIctedwIth
twodImensIonal(AandC)echocardIographIcImagIng,andthepresenceofmItral
regurgItatIon(|F)IsImagedwIthcolor0oppler(BandD).The|7IsIncompetent
becauseofposterIorleafletprolapseInsIdetheleftatrIum(LA)durIngsystole(arrows
leftInAandC).LeftventrIcular(L7)systolIccontractIongeneratesandanterIor
dIrected|Fjet,awayfromthe|7lesIonarea.|E4C,mIdesophagealfourchamber
vIew;|E2C,mIdesophagealtwochambervIew.
ColorFlow0oppler.CF0IscommonlyusedasascreenIngtoolforthedetectIonof|F.t
provIdesaneasy,qualItatIvetechnIquebutaddItIonaltestsareadvIsedtogradethe
severItyof|F(FIg.284J).fthe|FjetIs40oftheLAarea,oftentImessevere|FIs
present.
71
ThereareseverallImItatIonstothIstechnIque.tIsdIffIculttovIsualIzethe
entIreLAwIthTEE.Secondly,eccentrIcjetsthatareIncontactwIththeLAwallsare
underestImated(Coandaeffect).
72
ThIrd,machInesettIngssuchasframerateandcolor
0opplerscaleInfluencetheappearanceofthe|Fjet.Fourth,despIteItsappearance,the
colorareaassocIatedwIth|FIsnotequIvalenttoregurgItantvolume.CF0sImplyshows
theareawIthIntheLAwherebloodhasabnormalvelocItyandIsdependentonthesystolIc
pressuregradIentbetweentheL7(adequateL7systolIcfunctIon)andtheLA(chamber
complIance).nacute|F,forexample,the|FjetvelocItIesarelowbecause|FoccursIn
anoncomplIantchamber.
Proximal Isovelocity Surface Area
0urIngsystole,bloodInsIdetheL7cavItyacceleratesasItconvergestowardtheorIfIceof
theIncompetent|7(FIg.28J0).ThIsvelocItypatternresemblesconcentrIchemIspheres,
whosesurfaceshavethe
P.74J
samevelocItyatagIvendIstance(radIus,F)fromthe|7orIfIce.SuchanIsovelocIty
surfaceIscalledproximal isovelocity surface area(PSA).tsvelocItycanbedetermInedby
thecolor0opplersystem'salIasIngvelocIty.
7J
8asedontheprIncIpleofconservatIonof
mass(contInuItyequatIon),theflowthroughthe|ForIfIceIsthesameastheflowofthe
PSAsurface:
|Fflow=PSAflow,
|ForIfIce|FvelocIty=2(F
2
)AlIasIng7elocIty.
|ForIfIce=6.28(F
2
)AlIasIng7elocIty/|F7elocIty.
Table 28-7 Grading of Mitral Regurgitation
Mild Moderate Severe
Qualitative findings
Jetarea/LAarea 20 40
0ensItyofCWsIgnal
0ensecomplete
envelope
Pulmonarybloodflow
Sblunted(S/0
1)
Sreversed(S0)
Quantitative measurements
7enacontracta(mm) J J7 7
EFDA(cm
2
) 0.20 0.200.40 0.40
FegurgItantvolume
(ml)
J0 J060 60
FegurgItantfractIon
()
J0 J050 50
LA,leftatrIum;CW,contInuouswave;S,Swave;S/0,SystolIcwaveofpulmonary
veInflowtodIastolIcwaveofpulmonaryveInflowratIo;EFDAeffectIve
regurgItantorrIfIcearea
AsImplIfIedPSAequatIonyIelds|ForIfIce=(PSAradIus)
2
/2provIdedtheNyquIstlImItIs
setat40cm/sandthatthe|FjethasavelocItyof5m/s.
74
|ostsIgnIfIcantly,asmall
errorInmeasurIngthePSAradIus(F
2
)wIllbesquaredIntheequatIon.
Vena Contracta
7enacontractaIsthenarrowestpartofthe|Fjet,andreflectstheeffectIveor
physIologIcareaofthe|Fjet(FIg.28J0).|FIssevereIfvenacontractaIs7mm.
Pulmonary Vein Inflow Pattern
TheIncreasedvolumeInsIdetheLAwIllaugmentthetransmItraldIastolIcpressure
gradIentandwIllproducearestrIctIvefIllIngpatternInsevere|F(EtoAwaveratIo2).
Forthesamereasons,thesystolIcfIllIngoftheLAvIathepulmonaryveIns(Swave)wIllbe
decreased,Inmoderateandsevere|F(Table287).
Tricuspid Regurgitation
ThetrIcuspIdvalve(T7)IsevaluatedconcomItantwIththerIghtventrIcle,usIngthe
mIdesophagealfourchamber,mIdesophagealrIghtventrIcularInflowoutflow,
mIdesophagealbIcaval,andtransgastrIcF7longaxIsvIews.TheT7planeIsslIghtlyhIgher
thanthe|7plane.TrIcuspIdregurgItatIon(TF)Ismostcommonlysecondarytopulmonary
hypertensIonfromleftsIdedcardIacpathology,whIleendocardItIs,carcInoId,EbsteIn's
anomaly,andrheumatIcheartdIseasearelessfrequentcausesofTF.
TheT7anatomyIsexamInedforabnormalappearance(annulardIlatIon,endocardItIs
vegetatIons,andthrombus)andmotIon(prolapsIngorflaIlIngleaflets).StructuresproxImal
(InferIorvenacava,rIghtatrIum,andInteratrIalseptum)anddIstal(rIghtventrIcleand
InterventrIcularseptum)totheT7areexamInedforsIgnsofvolumeandpressure
overload.
CF0IsapplIedtodetectthepresence,sIze,anddIrectIonofaTFjet,Itsvenacontracta,
andthePSAInsIdetheF7.CW0IsusedtomeasuretheTFjetvelocItyandcalculatethe
F7andPAsystolIcpressure.PW0IsusedtorecordthehepatIcveInflowpattern.CradIng
ofseverItyofTFIsshownInTable288.
Table 28-8 Grading of Tricuspid Regurgitation
Echocardiographic parameter Mild Severe
T7morphology Normal
Prolapse,malcoaptatIon,
endocardItIslesIon,mass
7C/FA/F7sIze Normal 0Ilated/Increased
TFjetarea(cm
2
) 5 10
7enacontractawIdth(mm)
(NyquIstlImIt5060cm/s)
7
PSAradIus(mm)(NyquIstlImIt
-28cm/s)
6 9
TFjetfeatures
Soft,
parabolIc
0ense,trIangular,early
peak
HepatIcveInflowpattern S0
SystolIcwavebelow
baselIne
T7,trIcuspIdvalve;7C,InferIorvenacava;FA,rIghtatrIum;F7,rIghtventrIcle;
PSA,proxImalIsovelocItysurfacearea;TF,trIcuspIdregurgItatIon;S,SystolIc
waveofhepatIcvIewflow;0,dIastolIcwaveofhepatIcveInflow.
P.744
Table 28-9 Grading of Pulmonary Regurgitation
Parameter Mild Severe
P7morphology Normal Abnormal
F7sIze Normal 0Ilated
PFjetsIze Length1cm,narroworIgIn Large,wIdeorIgIn
PFjetfeatures Soft,slowdeceleratIon 0ense,rapIddeceleratIon
P7,pulmonaryveIn;F7,rIghtventrIcle;PF,pulmonaryregurgItatIon.
Pulmonic Valve Regurgitation
PulmonIcvalveregurgItatIon(PF)IsevaluatedInthemIdesophagealrIghtventrIcular
Inflowoutflow,theupperesophagealaortIcarchshortaxIs,andInthemodIfIeddeep
transgastrIcF7vIews(approxImately60to70degrees).PFIsoftenanIncIdentalfIndIng.
PFcandevelopbecauseofrIghtsIdedendocardItIs,orsecondarytopulmonary
hypertensIon.CradIngofseverItyofPFIsdescrIbedInTable289.
Diseases of the Aorta
TheevaluatIonoftheaortaIsanImportantpartofperIoperatIveTEE.nroutInecases
suchascoronaryarterybypasssurgery,evaluatIonoftheaortamayrevealprevIously
unknown,sIgnIfIcantatheromatousdIseaseoftheaortaandalterthesurgIcalplan(off
pumpbypass,alternatIvesItesforcannulatIon).nemergencIes,dIagnosIsofaortIc
pathology(dIssectIon,aneurysm,transsectIon)mayprovelIfesavIng.
Two-Dimensional and Motion-Mode Echocardiography
TheentIrethoracIcaortacanbeImagedwIthTEE,apartfromthedIstalascendIngand
proxImalarchsegments,wheretheInterposItIonoftheleftmaInbronchusbetweenthe
esophagusandtheleftatrIumprohIbItsthepropagatIonofultrasound.ThIsblIndspotcan
beImagedusIngepIaortIcscannIng.
75
ThenormalaortahasasmoothendothelIalsurface,
andbloodflowIslamInar.AtherosclerotIcplaquesareIrregularlyshaped,oftenmobIle
protrusIonsInsIdetheaortIclumen.ThesearchforatheromasshouldbedonebyImagIng
theentIrecIrcumferenceoftheaortIclumen(shortaxIsvIews).DnceapartIcularlesIonIs
found,scannIngInlongaxIsvIewshouldbeperformed(FIg.2844).PlaquesthIckerthan4
mmaremorelIkelytocauseanembolIcevent.
76,77
Figure 28-44.AortIcatheromasImagedIndescendIngthoracIcaortashort(AandC)
andlong(BandD)axIsvIews.
AortIcaneurysmIsadIlatatIonoftheaorta,usually4cm.DncetheaneurysmIs5.5cm,
theprobabIlItyofruptureIncreases(FIg.2845).0IssectIonIsaseparatIonbetweenthe
IntImalandmedIallayeroftheaortIcwall,creatIngafalselumenforbloodflow
78
(FIgs.
2845and2846).8oththetrueandfalselumenfIllwIthblooddurIngsystole,butonlythe
truelumenhasblooddurIngdIastole.ntramuralhematomaIsconsIderedaprecursorof
dIssectIonandshouldbetreatedsImIlarly.ComparedwIthanatheroma,anIntramural
hematomahasasmoothsurface.
Cardiac Masses
CardIactumorscaneItherorIgInatefromtheheartoraremetastasesfromothersItes.
TheycanembolIze,causearrhythmIas,or
P.745
causeheartfaIlure.ThemostcommonprImarytumorIsmyxoma,whIchIslocatedmost
frequentlyattheInteratrIalseptum.ThepotentIalofmyxomastoobstructtheInflowor
outflowregIonofaventrIcleIsdemonstratedwIth0opplerechocardIography.Thenext
mostfrequenttumorIsfIbromaoftheventrIcularwall.FIbromasareusuallycalcIfIed,and
candecreasetheventrIcularvolume.FenalcelltumorsoftenextendIntotheInferIorvena
cavaandrIghtatrIum(FIg.2847).PacemakerwIres,thrombus,andnormalanatomIc
structuresthatmImIctheappearanceofpathology(EustachIanvalve,crIstatermInalIs,
ChIarInetwork,orCoumadInrIdge)shouldbedIfferentIatedfromtumors.
Figure 28-45.AortIcdIsease.AscendIngaortaaneurysmdIstaltothesInotubular
junctIon(mIdesophagealascendIngaortalong[A]andshort[B]axIsvIews).The
dIameteroftheaortaIs5cm.C.AscendIngaortadIssectIon(StanfordtypeA)
orIgInatIngfromthesInotubularjunctIon.Thetruelumen(TL)expandsInsystoleand
theflapIsconvextowardthefalselumen(FL).D.0escendIngaortadIssectIon
(0e8akeytype).
Congenital Heart Disease
ThespectrumofcongenItalheartdIsease(CH0)seenInadultvarIeswIdely.
EchocardIographyIstheprImaryImagIngmodalItyfordIagnostIcassessmentofCH0.
AdvancesInsurgeryhaveIncreasedthesurvIvalrateofchIldrenwIthrepaIredCH0and,as
aconsequence,adultswIthrepaIredCH0areIncreasInglycommonIntheDF.Common
lesIonsevaluatedwIthTEEIncludeAS0,ventrIcularseptaldefect,patentductusarterIosus,
coarctatIonoftheaorta,bIcuspIdA7,andrepaIredtetralogyofFallot(FIg.2848).
79
Figure 28-46.AortIcdIssectIon.ThedescendIngaortaIsseenInshortaxIs.TheaortIc
truelumen(TL)contaInstheaortIcendothelIumandhasasmoothendolumInal
surface.TheIntImalflapusuallybowstowardthefalselumen(FL).Colorflow0oppler
demonstratesbloodflowInsIdethetruelumen(whIchexpandsInsystole)andabsence
offlowInsIdethefalselumen.
P.746
Figure 28-47.CardIacmasses.A.LeftatrIal(LA)myxomaseenInthemIdesophageal
longaxIsvIew.B.FIghtatrIal(FA)myxomaseenInsIdetherIghtatrIum(FA)Inthe
mIdesophagealfourchambervIew.C.FenalcelltumoroccupyIngtheInferIorvena
cava(7C)andextendIngInsIdetheFA.L7DT,leftventrIcularoutflowtract;F7,rIght
ventrIcle;S7C,superIorvenacava.
Echocardiography-Assisted Procedures
naddItIontoItsroleIndIagnostIcs,echocardIographyIsalsoemployedtoassIstvarIous
proceduressuchasplacementofcentralvenouscatheter,IntraaortIcballoonpump(A8P)
catheter,coronarysInuscannula,andguIdewIresforothervenousorarterIalcannulas.
Figure 28-48.AtrIalseptaldefect(AS0).nthemIdesophagealfourchambervIew,a
color0opplersectorIsposItIonedovertheInteratrIalseptum.AnAS0wIthaleftto
rIghtcommunIcatIonIsshownInbluecolor,asthebloodmovesawayfromthe
transducer(toppanel).Pulsedwave0opplerInterrogatIonoftheAS0measuresapeak
velocItygradIentof1m/s.
Ultrasound-Guided Central Vein Cannulation
TheplacementofcentralvenouscathetersIsassocIatedwIthcomplIcatIonsIncludIng
Injurytovascularstructures(carotIdartery),pleura,nervebundles,lymphatIcsystem,and
eventhespInalcanal.HIstorIcally,anatomIclandmarksguIdedneedleorIentatIondurIng
centralvenousaccess.However,multIplestudIeshavedemonstratedthattheanatomIc
relatIonshIpbetweentheInternaljugularveInandcarotIdarteryvarIes,and
P.747
thatevenexperIencedphysIcIansencountercomplIcatIons.
80
7IsualguIdancebyultrasound
provIdesrealtImefeedback,reducIngthecomplIcatIonrateandtheproceduretIme.
81
For
patIentsafetyreasonstheNatIonalnstItuteforClInIcalExcellencehasrecommendedthat
centrallInesbeplacedunderguIdanceof20ultrasoundImagIng.
82
AlIneararrayhandheldtransducerwIthhIghfrequencIes(7.5to12|Hz)Ispreferredfor
ultrasoundguIdedcentrallIneplacement.ThetechnIquerelIesonplacIngthetransducer
overthetradItIonalanatomIclandmarksandIdentIfyIngtheInternaljugularveIn(J)and
carotIdartery(CA)InshortaxIsandtheIranatomIcrelatIonshIp(FIg.2849).The20
crIterIaofdIfferentIatIngtheCAfromtheJveInaredIstensIbIlIty(theJIncreasesInsIze
wIth7alsalvamaneuverandTrendelenburgposItIon)andcompressIbIlIty(theJwIll
decreaseInsIzewIthpressureapplIedoverItbythetransducer).ApplyIngCF0wIththe
transducerorIentedslIghtlycaudaddIsplaystheCAwIthredpulsatIngflowandtheJwIth
acontInuousblueflow(FIg.2849).NotethatIfthetransducerIsorIentedcephaladthe
colorsarereversed.TheneedleInsertIonandvenouspunctureIsperformedunder
ultrasoundguIdance.ThelongItudInalvIew(FIg.2850)IsthenusedtovIewthewIre's
placementInthevessel.TEEcanconfIrmtheguIdewIre'sposItIonInthesuperIorvena
cava(FIg.2850).
Figure 28-49.nternaljugularveIn(J7)andcarotIdartery(CA)andtheIranatomIc
relatIonshIpTop panel.TwodImensIonalexamInatIon,usIngalInearscanner,showIng
theJ7lateraltotheCA.Bottom panel.Colorflow0opplerIsapplIedshowIng
contInuousblueflowIntheJ7andpulsatIngredflowIntheCA(transducerorIented
caudad).
Figure 28-50. A.UltrasoundconfIrmatIonofguIdewIreposItIon.Asectorscanner
transducerIsusedtovIsualIzetheInternaljugularveIn(J7)InlongaxIs.The
guIdewIreIsseenasathInechodenselInearstructureposItIonedInthelumenofthe
veIn.B. TransesophagealechocardIographIcconfIrmatIonofguIdewIreposItIon.The
mIdesophagealbIcavalvIewIsused.TheguIdewIreIsseenInthesuperIorvenacava
(S7C),wIththetIpIntherIghtatrIum(FA);LA,leftatrIum.
ForPACplacement,TEEIsusefulInguIdIngthecatheterthroughtherIghtheartand
confIrmIngproperposItIonInthePA.nthemIdesophagealrIghtventrIcularInflowoutflow
vIew,thePACcanbefollowedfromtheFA,passIngtheT7IntotheF7,andthenpassIng
theP7IntothePA.ThemIdesophagealascendIngaortIcshortaxIsvIewIsusedtoposItIon
thePACsothatItstIplIesIntherIghtPA.
AlthoughultrasoundcanbeavaluabletoolIndecreasIngthenumberofcomplIcatIons,It
doesnotelImInatetherIskoftheprocedure.ExperIenceandtraInIngareessentIalfor
enhancIngpatIentsafetywIthultrasound.
Intra-Aortic Balloon Pump Placement
UseofTEEdurIngA8PplacementallowsposItIonIngofthecathetertothepreferred
locatIon,dIstaltotheleftsubclavIanartery.PrIortoItsInsertIon,theechocardIographer
shouldassessthedescendIngthoracIcaortaforpresenceofmobIleatheromaoraortIc
dIssectIons.ThesesItuatIonsmayrepresentcontraIndIcatIonstocatheterplacement.
0urIngcannulatIon,thepresenceoftheguIdewIreInthedescendIngaortashouldbe
confIrmedwIthTEE.DptImalfunctIonoftheA8PrequIresthatthetIplIes1to10cmdIstal
totheleftsubclavIanartery.TheexactposItIonoftheA8PcathetertIpIsbestvIsualIzed
usIngthedescendIngaortIclongaxIsvIew.
Coronary Sinus Cannulation
TEEIshelpfultoguIdetheplacementofthecannulaandtocheckforproperposItIon.
mproperInsertIonofthecannula
P.748
canresultInInjurytotheInteratrIalseptumortothecruxoftheheart,thefragIlearea
joInIngtheatrIaandventrIcles.7IewofthecoronarysInus(CS)IsobtaInedfromthe
mIdesophagealfourchambervIewbyretroflexIngtheprobe(FIg.2851).Afterthecannula
IsposItIonedIntheCS,themultIplaneangleshouldberotatedto90degreesandtheCS
wIllbeseenIncrosssectIon.ThetIpofthecannulawIllbedIsplayedasasmallechodense
dotInthemIddleoftheCS.ThIsvIewwIllassurethatthecannulaIsposItIonedatan
approprIatedepth.
Figure 28-51.ProberetroflexIonfromthemIdesophagealfourchambervIewIsused
tovIsualIzethecoronarysInus(CS).ThearrowpoIntstotheballoonoftheretrograde
cannula(FCP),rIghtatrIum(FA),andrIghtventrIcle(F7).
Other Cannulation Techniques
TEEIsusefulInverIfyIngtheposItIonofvarIousothercannulas.Forexample,when
femoralarteryfemoralveInbypassIsInstItuted,thevenouscannulacanbevIsualIzedasIt
advancesIntheInferIorvenacavauptotheleveloftheFA.ProperposItIonofguIdewIres
usedtoforaortIccannulatIoncanbeconfIrmedwIthTEE.
Epicardial and Epiaortic Echocardiography
Epicardial Echocardiography
0urIngsurgerIesperformedvIasternotomyorthoracotomy,epIcardIalechocardIography
canbeperformedandIspartIcularlyvaluableInthosecasesInwhIchtheTEEprobecannot
beplacedorIscontraIndIcated.TheepIcardIalvIewsaresImIlartotheonesobtaInedvIa
TTE.TheAmerIcaSocIetyofEchocardIographyIncollaboratIonwIththeSocIetyof
CardIovascularAnesthesIologIstshasrecentlyIssuedguIdelInesfortheperformanceof
epIcardIalechocardIography.
8J
TheepIcardIalprobeuseshIghfrequencytransducers(5to
12|Hz)thatmayrequIreastandoffdevIceand/orsalIneInthemedIastInumforbest
ImagIng.EpIcardIalImagIngofferssuperIorImagequalItyaswellasabetterwIndowtothe
anterIorcardIacstructures(aortaandA7,PAandP7).
Epiaortic Examination
8ecauseoftheInterposItIonoftheleftbronchus,thedIstalAAandtheproxImalaortIcarch
cannotbevIsualIzedwIthTEE.TheascendIngaortIcandproxImalaortIcarchareof
partIcularInterestdurIngcardIacsurgerIesastheyrepresentsItesforaortIccannulatIon.
EpIaortIcscannIngforatheromaIsperformedusIngasmallfootprInt,lIneararray
transducer.CuIdelInesforIntraoperatIveepIaortIcexamInatIonhavebeenpublIshed.
75
Echocardiography Outside the Operating Room
AnunderstandIngofechocardIographyIsalsorelevanttoanesthesIologIstsInthatmany
patIentswIthahIstoryofheartdIseasewIllhaveundergoneanechocardIographIc
examInatIonprIortosurgery.TheechocardIographyreportfromapreoperatIve
examInatIonIsusefulforassessIngsurgIcalrIskanddevelopIngtheanesthetIcplan.
EchocardIographyhasalsoestablIshedItselfaspartIcularlyvaluableInassessmentof
postoperatIvehemodynamIcInstabIlIty.toffersrapIddIagnosIsbydIfferentIatIngamong
thepotentIalcomplIcatIonsfacedInpostoperatIvecare,suchashypovolemIa,perIcardIal
tamponade(FIg.2840),aortIcdIssectIon,myocardIalInfarctIon,endocardItIs,and
pulmonaryembolIsm.
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Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapter29AIrway|anagement
Chapter29
Airway Management
William H. Rosenblatt
Wariya Sukhupragarn
Key Points
1. Management of the airway is paramount to safe perioperative care.
Following a series of evaluation procedures affects outcomes in a
favorable way.
2. The anatomically complex airway undergoes growth, and
development and significant changes in its size, shape, and relation
to the cervical spine between infancy and childhood.
3. A thorough airway-relevant history and physical examination must be
obtained during the preoperative evaluation.
4. Preoxygenation (also commonly termed denitrogenation) should be
practiced in all cases when time permits.
5. The advent of the laryngeal mask airway, as well as other
supraglottic airways, has led some to question the relative safety of
tracheal intubation.
6. The first attempt at laryngoscopy should be the best attempt.
7. Successful laryngoscopy involves the distortion of the normal
anatomic planes of the supraglottic airway to produce a line of direct
visualization from the operator's eye to the larynx.
8. Analysis of laryngeal trauma cases has led some to question whether
direct laryngoscopy is as benign and safe as we have always
assumed.
9. The technique of rapid-sequence induction is performed to gain
control of the airway in the shortest amount of time after the ablation
of protective airway reflexes with the induction of anesthesia.
10. The period of extubation may be far more treacherous than that of
induction and intubation.
11. The American Society of Anesthesiologists (ASA) algorithm for the
approach to the difficult airway stands as a model for
anesthesiologists and other health care specialties.
12. Awake intubation is usually successful if approached with care and
patience.
13. Awake airway management remains a mainstay of the ASA's difficult
airway algorithm.
14. Case studies applying the following technologies help clinicians to
understand the modern airway armamentarium: video laryngoscopy,
flexible and rigid fiberoptics, retrograde wire, and esophageal-
tracheal Combitube.
15. An ever-increasing number of airway-management devices are
commercially available.
16. When access to the airway from the mouth or nose fails, emergency
access via the extrathoracic trachea is a feasible alternative.
Perspectives on Airway Management
nthe20yearssIncepublIcatIonofthefIrstedItIonofthIstext,thefIeldofaIrway
managementhasundergoneavIgorousrevolutIon.AlthoughtheaIrwaymanageroftoday
maystIllemploymanyofthedevIcesavaIlableIn1988,thearrayofdevIces,algorIthms,
andpharmaceutIcalsInthemodernaIrwayarmamentarIumcanbedauntIng.Fortunately,
expertIseInalImIted,albeItcomplementary,numberoftoolsaswellascarefulthought
gIventoplannIng,suffIceInmostcases.AlthoughthefInaldecadeofthelastcenturysawa
resoluteswIngtowardtheapplIcatIonofsupraglottIcaIrways(SCA),amorerecently
IntroducedgeneratIonofdevIcesreflecttheapplIcatIonofvIdeotechnologyIntherealm
oftrachealIntubatIon.TheroleofSCAsIsfIrmlyestablIshedInroutIneanesthetIccareas
wellasaIrwayrescue,buttheadventofvIdeolaryngoscopypromIsestoremovemanyof
thefaIlIngsofatechnIquethathasbeenInuseformorethan100years.
TechnIquesandpractIcesInaIrwaymanagementhavelongbeenanImportantconcernof
theAmerIcanSocIetyofAnesthesIologIsts(ASA),asIllustratedbythepublIcatIonoforIgInal
andrevIseddIffIcultaIrwayguIdelInes.
1
AnalysIsoftheSocIety'sclosedclaImsdatabase,In
theperIodsbeforeandafterthe199JpublIcatIonoftheASAdIffIcultaIrwayguIdelInes,
revealsbothencouragIngaswellasdIsturbIngtrends.
2
AsIgnIfIcantdecreaseInclaIms
relatedtodeath/braIndeathattheInductIonofanesthesIaIsnotmatchedwIthadecrease
durIngemergenceandthepostoperatIveperIod.AlthoughtheclosedclaImsdataare
useful,IthassIgnIfIcantlImItatIons,IncludIngItsretrospectIveandnonrandomnature,and
thelackofadenomInator.
2
P.752
|anagementoftheaIrwayIsparamounttosafeperIoperatIvecare,andthefollowIngsteps
becomenecessarytofavorablyaffectoutcome:(1)athoroughaIrwayhIstoryandphysIcal
examInatIon;(2)consIderatIonoftheeaseofrapIdtrachealIntubatIon,bydIrector
IndIrectlaryngoscopy;(J)formatIonofmanagementplansforuseofasupraglottIcmeans
ofventIlatIon(e.g.,facemask,SCA);(4)weIghIngtherIskofaspIratIonofgastrIccontents;
and(5)estImatIngtherelatIverIsktothepatIentoffaIledaIrwaymaneuvers.
J
ThIs
chapterwIllreflecttheneedtoconsIderthesefIvefactorswhenapproachInganypatIent
whorequIresormayrequIreaIrwaycontrol.
Review of Airway Anatomy
ThetermairwayreferstotheupperaIrwayconsIstIngofthenasalandoralcavItIes,
pharynx,larynx,trachea,andprIncIpalbronchI.TheaIrwayInhumansIsprImarIlya
conductIngpathway.8ecausetheoroesophagealandnasotrachealpassagescrosseach
other,anatomIcandfunctIonalcomplexItIeshaveevolvedforprotectIonofthe
sublaryngealaIrwayagaInstaspIratIonoffoodthatpassesthroughthepharynx.The
anatomIcallycomplexaIrwayundergoesgrowthanddevelopmentandsIgnIfIcantchanges
InItssIze,shape,andrelatIontothecervIcalspInebetweenInfancyandchIldhood.
4
Asare
otherbodIlysystems,theaIrwayIsnotImmunefromtheInfluenceofgenetIc,nutrItIonal,
andhormonalfactors.Table291IllustratestheanatomIcdIfferencesInthelarynxof
Infantsandadult.
ThelaryngealskeletonconsIstsofnInecartIlages(threepaIredandthreeunpaIred);
together,thesehousethevocalfolds,whIchextendInananterIorposterIorplanefromthe
thyroIdcartIlagetothearytenoIdcartIlages.TheshIeldshapedthyroIdcartIlageactsas
theanterIorprotectIvehousIngofthevocalmechanIsm(FIg.291).|ovementsofthe
laryngealstructuresarecontrolledbytwogroupsofmuscles:theextrInsIcmuscles,whIch
movethelarynxasawhole,andtheIntrInsIcmuscles,whIchmovethevarIouscartIlages
InrelatIontooneanother.ThelarynxIsInnervatedbytwobranchesofeachvagusnerve:
thesuperIorlaryngealandrecurrentlaryngealnerves.8ecausetherecurrentlaryngeal
nervessupplyalloftheIntrInsIcmusclesofthelarynx(wIththeexceptIonofcrIcothyroId),
traumatothesenervescanresultInvocalcorddysfunctIon.AsaresultofunIlateralnerve
Injury,aIrwayfunctIonIsusuallyunImpaIred,althoughtheprotectIveroleoflarynxIn
preventIngaspIratIonmaybecompromIsed.
ThecrIcothyroIdmembraneprovIdescoveragetothecrIcothyroIdspace.Themembrane,
whIchIntheadultIstypIcally9mmInheIghtandJcmInwIdth,Iscomposedofayellow
elastIctIssuethatlIesdIrectlybeneaththeskInandathInfacIallayer.tIslocatedInthe
anterIorneckbetweenthethyroIdcartIlagesuperIorlyandthecrIcoIdcartIlageInferIorly.
tcanbeIdentIfIed1to1.5fIngerbreadthsbelowthelaryngealpromInence(thyroIdnotch).
tIsoftencrossedhorIzontallyInItsupperthIrdbytheanastomosIsoftheleftandrIght
superIorcrIcothyroIdarterIes.ThemembranehasacentralportIonknownastheconus
elasticusandtwolateral,thInnerportIons.0IrectlybeneaththemembraneIsthelaryngeal
mucosa.8ecauseofanatomIcvarIabIlItyInthecourseofveInsandarterIesandthe
membrane'sproxImItytothevocalfolds(whIchmaybe0.9cmabovethelIgaments'upper
border),ItIssuggestedthatanyIncIsIonsorneedlepuncturestothecrIcothyroId
membranebemadeInItsInferIorthIrdandbedIrectedposterIorly(aposterIorprobIng
needleswIllstrIkethebacksIdeoftherIngshapedcrIcoIdcartIlage).
Table 29-1 Anatomic Differences Between the Pediatric and Adult Airways
ProportIonatelysmallerInfant/chIldlarynx
NarrowestportIon:CrIcoIdcartIlageInInfant/chIld;vocalfoldsInadult
FelatIvevertIcallocatIon:CJ,C4,C5InInfant/chIld;C4,C5,C6Inadult
EpIglottIs:Longer,narrower,andstIfferInInfant/chIld
AryepIglottIcfoldsclosertomIdlIneInInfant/chIld
7ocalfolds:AnterIoranglewIthrespecttoperpendIcularaxIsoflarynxIn
Infant/chIld
PlIablelaryngealcartIlageInInfant/chIld
|ucosamorevulnerabletotraumaInInfant/chIld
Figure 29-1.ThemajorlandmarksoftheaIrwaymechanIsm.NotethatthecrIcoId
cartIlageIslessthan1cmInheIghtInItsanterIoraspect,butmaybe2cmInheIght
posterIorly(small arrow).
Atthebaseofthelarynx,suspendedbytheundersIdeofthecrIcothyroIdmembrane,Isthe
sIgnetrIngshapedcrIcoIdcartIlage.ThIscartIlageIsapproxImately1cmInheIght
anterIorly,butalmost2cmInheIghtInItsposterIoraspectasItextendsInacephalad
dIrectIoncreatIngthedorsalwallofthelarynxatthelevelofthecrIcothyroIdmembrane
andthethyroIdcartIlage(FIg.291).ThetracheaIssuspendedfromthecrIcoIdcartIlageby
thecrIcotracheallIgament.ThetracheameasuresapproxImately15cmInadultsandIs
cIrcumferentIallysupportedby17to18CshapedcartIlages,wIthamembranousposterIor
aspectoverlyIngtheesophagus.
ntheadultthefIrsttrachealrIngIsanterIortothesIxthcervIcalvertebrae.Thetracheal
cartIlagesareInterconnectedbyfIbroelastIctIssue,whIchallowsforexpansIonofthe
tracheabothInlengthanddIameterwIthInspIratIon/expIratIonandflexIon/extensIonof
thethoracocervIcalspIne.ThetracheaendsatthecarIna(fIfththoracIcvertebra),where
ItbIfurcatesIntotheprIncIpalbronchI.TherIghtprIncIpalbronchusIs
P.75J
largerIndIameterthantheleft,anddevIatesfromtheplaneofthetracheaatalessacute
angle.AspIratedmaterIals,aswellasadeeplyInsertedendotrachealtube(ETT),tendto
gaInentryIntotherIghtprIncIpalbronchus,althoughleftsIdedposItIonIngshouldbe
excluded.CartIlagInousrIngssupportthefIrstsevengeneratIonsofthebronchI.
History of Airway Management
DbstructIonoftheaIrwaywasapoorlyunderstoodphenomenonprIorto1874.DpenIngthe
mouthwIthawoodenscrewanddrawIngthetongueforwardwIthaforcepsorasteel
glovedfIngerwastheheIghtofaIrwaymanagement.
5
FecognItIonthatthebaseofthe
tonguefallIngagaInsttheposterIorpharyngealwallaccountedformostaIrwayobstructIon
dIdnotoccuruntIl1880.CredItforthefIrstuseofatrueSCAIsgIventoJosephThomas
Clover(18251882),althoughItIspossIblethatdevIceswereusedtowardtheendofthe
fIrstmIllennIum.
6
CloverusedanasopharyngealtubeforthedelIveryofchloroform
anesthesIa.TheD'0wyertubewasIntroducedIn1884.ThIsdevIceconsIstedofacurved
metalconduIt,wIthaconIcalendthatcouldsealthelaryngealInletwhenplacedIntothe
oropharynx.AlthoughdesIgnedforthetreatmentofnarcotIcoverdose,Itwaslater
modIfIedtobeusedwIthvolatIleanesthetIcs.Dverthenext50yearsseveralmodIfIcatIons
ofthebasIcoropharyngealaIrwayweredescrIbed.nthe19J0sFalphWatersIntroduced
thenowfamIlIarflattenedtubeoralaIrway.CudelmodIfIedWaters'conceptbyfIttInghIs
aIrwaywIthInastIffrubberenvelopeInanattempttoreducemucosaltrauma.
TrachealIntubatIonwasfIrstdescrIbedIn1788asameansofresuscItatIonofthe
apparentlydead,
7
butwasnotusedforthedelIveryofanesthesIauntIlalmost100years
later.TheforerunnerofthemodernETTwasdesIgnedbytheCermanotolaryngologIst,0r.
FranzKuhn(18661929).KuhndevelopedaflexometallIctubethatresIstedkInkIngand
couldbeshapedtothepatIent'supperaIrwayanatomy.twasInsertedusIngarIgIdstylet,
andthehypopharynxwassealedwIthoIledgauzepackIng.SIrvan|agIllandStanley
FowbothamarecredItedwIththeInItIaldevelopmentofmoderntrachealIntubatIon.
PerformInganesthesIaforreconstructIvefacIalsurgery(durIngWorldWas),they
developedatwotubenasalsystem.Dnenarrowtube(gumelastIcdesIgn)waspassed
throughthenaresandguIdedIntothelarynxusIngasurgIcallaryngoscope.Theothertube
wasblIndlypassedIntothepharynxtoprovIdefortheescapeofgases.0urInguseofthIs
|agIlltube,theexhaustlumenwouldoccasIonalpassblIndlyIntothelarynx,leadIngSIr
vantodescrIbeblIndnasalIntubatIon.
8
CuffedSCAswereInItIallydescrIbedIntheearlypartofthe20thcentury.Threefactorsled
tothedevelopmentofthesedevIces:theIntroductIonofcyclopropane(whIchwas
explosIveandrequIredanaIrtIghtcIrcuItforapproprIategascontaInment),thefactthat
blIndandlaryngoscopIcguIdedtrachealIntubatIonremaInedadIffIculttask,anda
recognIzedneedforprotectIonoftheloweraIrwayfrombloodandsurgIcaldebrIsInthe
upperaIrway.
6
ThePrImrosecuffedoropharyngealtube,theShIpwayaIrway(aCudel
oropharyngealaIrwayfIttedwIthacuff,andacIrcuItconnectordesIgnedbySIrvan
|aCIll)andtheLessIngeraIrwaywerepredecessorsofthemodernsupraglottIcdevIces.n
19J7LeechIntroducedapharyngealbulbgaswaywIthanonInflatablecuffthatfItsnuggly
Intothehypopharynx.
TheuseofSCAsremaIneddomInantuntIltheIntroductIonofcurareIn1942,andthemass
traInIngofanesthesIologIstsIntrachealIntubatIonInantIcIpatIonofcasualtIesdurIng
WorldWar.ThedescrIptIonby|endelson
9
ofgastrIccontentsaspIratIonInobstetrIc
cases(66of44,016patIents,wIth2deaths)furtherpushedthemovetowardtracheal
IntubatIonInmostsurgIcalprocedures.WIthInafewyears,profIcIencyIndIrect
laryngoscopyandtrachealIntubatIonbecameamarkofprofessIonalIsm.Theadventof
succInylcholIne(1951)furtheredthedomInanceoftrachealIntubatIonthroughprovIdIng
rapIdandprofoundmusclerelaxatIon.
8y1981,twotypesofaIrwaymanagementprevaIled:trachealIntubatIonortheanesthesIa
facemask/CudelaIrway.AlthoughbothweretImetested,eachhadItsfaIlIngs(apartfrom
aIrwayfaIlureInasmallnumberofpatIents).TrachealIntubatIonwasassocIatedwIthboth
dentalandsofttIssueInjuryandcardIovascularstImulatIon,andmaskventIlatIonoften
requIredahandsontheaIrwaytechnIque.ThesedIffIcultIesledtothereconsIderatIonof
SCAs.
Limitations of Patient History and Physical Examination
AthoroughaIrwayrelevanthIstorymustbeobtaIneddurIngthepreoperatIveevaluatIon.A
searchfordocumentatIontoconfIrmordIsmIssmanIfestproblemsshouldbeconducted.
SIgnsandsymptomsrelatedtotheaIrwayshouldbesought.(Table292).|anycongenItal
andacquIredsyndromesareassocIatedwIthdIffIcultaIrwaymanagement(Table29J).
Dverthelast2decades,severalphysIcalevaluatIonmeasureshavebecomepopularIzed,
althoughtheIrreproducIbIlItyandpredIctabIlItyaredIsputed.ThedIffIcultyIndevelopIng
theperfectaIrwayevaluatIontoollIesIntwoInterrelatedareas:sImplIcItyand
Interdependency.SImplebedsIdeevaluatIontoolsareuseful,butadequateevaluatIonmay
requIreendoscopIc,radIologIc,orothercurrentlyuncommonexamInatIons.
10,11
nterdependencyreferstothepredIctIvevalueofoneaIrwayexamInatIonmeasurebased
onthefIndIngsofanother.ThIsIsdIscussedlaterIn0IrectLaryngoscopy,underthetopIc
offunctIonalaIrwayassessment(FAA).0etaIlsofthevarIousexamInatIonsandtheIr
InterdependencyaredIscussedInthatsectIon.
HIstorIcally,aIrwayassessmenthasbeensynonymouswIthevaluatIonfortheeaseofdIrect
laryngoscopy(0L),theendpoIntbeIngtheantIcIpateddegreeofvIsualIzatIonofthe
larynx.Unfortunately,theseeffortshavebeenonlymodestlysuccessful.ShIgaetal.
12
performedametaanalysIsofstudIesofthephysIcalpredIctorsofdIffIcult0L.These
authorsconcludedthat,whenusedasIndIvIdualtest,currentlyusedtechnIquesof
evaluatIonhaveonlymodestdIscrImInatIvepower(Tables294and295).
0espItethedIsappoIntIngusefulnessoftheseIndIvIdualIndexesInIdentIfyIngthedIffIcult
toIntubatepatIent(by0L),otherauthorshaverecognIzedthatcombInatIonsoftestscan
provIdeImprovedpredIctabIlIty.ElCanzourIetal.
1J
desIgnedastatIstIcalmodelfor
stratIfyIngrIskofdIffIcult0LInalargepopulatIon.ThIsmultIvarIateIndexassIgned
relatIveweIghtstoeachphysIcalexamInatIonorhIstorIcalfIndIngbasedontheoddsofa
hIghgradelaryngealvIewbeIngachIevedon0LwIthanIncreasIngexamInatIonscore.The
authorsnotedthatwIthIncreasIngmultIvarIateIndexscores,posItIvepredIctIvevalue
Increased,butsensItIvItydecreased(I.e.,hIghermultIvarIateIndexscoresoccurwhen
therearemoreposItIvephysIcalfIndIngs,butnotalldIffIcultlaryngoscopypatIentswIll
manIfestmultIplefIndIngs).ComparedwIththe|allampatIclassIfIcatIonalone,the
multIvarIatecomposIteIndexhadImprovedposItIvepredIctIveandspecIfIcItyvaluesat
equalsensItIvIty.Dfcourse,somepathologywIllonlypresentontheInductIonof
anesthesIaand/orattemptsatlaryngoscopy.
14,15
DthergroupshaveusedsImIlarregImens
toIncreasethepredIctabIlItyofmultIvarIateIndexesbyIncorporatIngImagIng
technologIes.
16
nasmallpopulatIonofpatIents,NaguIb
P.754
etal.
16
wereabletoachIevehIghpredIctIveaccuracy(90orhIgher)whenphysIcal
examInatIonandImagIngscoreswereweIghted.
Table 29-2 Signs, Symptoms and Disorders with Airway Management
Implications
HIstoryrelatedtoaIrwaysproblem
AspIratIonrIsk
HIstoryofvoIcechanges
HIstoryofvocalcordpolyps
HIstoryoffrequentpneumonIas
CoughIngaftereatIng/drInkIng
AcutenarcotIctherapy
Acutetrauma
ntensIvecareunItadmIssIon(current)
Pregnancy(gestatIonalage12weeks)
mmedIatepostpartum(beforesecondpostpartumday)
SystemIcdIseaseassocIatedgastroparesIs:dIabetesmellItus,postvagotomy,
collagenvasculardIsease,ParkInsondIsease,thyroIddysfunctIon,lIverdIsease,
CNStumors,chronIcrenalInsuffIcIency
0IffIcultlaryngoscopy/S6AventIlatIon
HIstoryofsurgIcalmanIpulatIonInoraroundtheaIrway
HIstoryofradIatIontherapyofthehead/neck
7arIouscongenItalandacquIredsyndromes(Table29J)
DbstructIvesleepapnea
8odymassIndexJ5kg/m
2
(IndIcatIve)
LoudsnorIng
PausesInbreathIngdurIngnormalsleep
SleepInterruptIon(wIthchokIng)
0aytImesomnolence/nappIng
AIrwayaffectIngcranIofacIalabnormalItIes
LIngualtonsIlhyperplasIa/supraglottIccystortumors
ChronIcsorethroat
ClobussensatIon
7oIcechange
0ysphagIa
DbstructIvesleepapnea
HIstoryoftonsIllectomy(controversIal)
10
Thyroglossalductcyst
AsymptomatIcanterIorcervIcalmassthatmoveswIthdeglutInatIon
ComplIcatIons:cystsInfectIon,fIstula,spontaneousrupture,voIcechange,
dysphagIa,dyspnea,andsnorIng
SIgnsandsymptomsrelatedtotheaIrway
SnorIng
ChangesInvoIce
0ysphagIa
StrIdor
8leedIng
CervIcalspInepaInorlImItedrangeofmotIon
UpperextremItyneuropathy
TemporomandIbularjoIntpaInordysfunctIon
SequelaeofprevIousIntubatIon
ChIppedteeth
SIgnIfIcantprolongedsorethroat/mandIbleafteraprevIousanesthetIc
|orerecentlysomeauthorshavearguedagaInsttheeffortstodevIsemethodstopredIct
theeaseordIffIcultyof0L,recognIzIngthattheperfecttestIselusIve.8ecausealltests
arelIkelytooverand/orunderpredIcttheeaseordIffIcultyoflaryngoscopyInsome
patIents,andbecauseImpossIbleIntubatIonIsrelatIvelyrare,theutIlItyofthese
examInatIonsIsquestIoned.SImIlarly,becauseoftheprolIferatIonofnewdevIcesfor
supraglottIcventIlatIonandtrachealIntubatIon,therelevanceofapredIcted0LIs
questIoned.
J
FewstudIeshaveobjectIvelydetermInedthosefIndIngsthatIdentIfythedIffIculttomask
ventIlatepatIent.ThIsbasIcaIrwaymaneuverwasexamInedInacontrolstudybyLangeron
etal.
17
Df1,502patIents(excludIngplannedrapIdsequenceInductIonoremergencycases),
5ofpatIentswerecharacterIzedasdIffIculttomaskventIlate.DnlyonepatIentInthe
serIeswasImpossIbletoventIlatebyfacemask.Table296descrIbesthecrIterIafor
defInIngdIffIcultmaskventIlatIonandthefIveIndependentclInIcalpredIctorsfoundby
Langeronetal.
17
ThepresenceoftwopredIctorsIndIctedahIghlIkelIhoodofdIffIcultmask
ventIlatIon.Kheterpaletal.,
18
InvestIgatIng22,660patIentsandusIngdIfferentcrIterIa,
foundadIffIculttomaskventIlateIncIdenceof1.5.naddItIontothecrIterIausedby
Langeronetal.,theseauthorsfoundthatafIndIngofahIgh|allampatIscoreandpoor
mandIbularprotrusIonImprovedthepredIctIonofdIffIcultmaskventIlatIon.
ngeneral,trachealIntubatIonshouldbeconsIderednonroutIneunderthefollowIng
condItIons:(1)thepresenceofequallyImportantprIorItIestothemanagementofthe
aIrway(suchasfullstomach,openglobe),(2)abnormalaIrwayanatomy,(J)an
emergency,or(4)dIrectInjurytotheupperaIrwayandlarynxand/ortrachea.Although
thefIndIngofabnormalanatomyIsnotnecessarIlysynonymouswIththedIffIcultaIrway,It
shouldkIndleaheIghtenedlevelofsuspIcIon.SeveralInvestIgatorshaveIdentIfIed
anatomIcfeaturesashavIngunfavorableInfluencesonthemechanIcsof0L;theseare
explaInableonthebasIsofInabIlItytocreatealIneofsItefromtheoperator'seyetothe
apertureofthelarynx.
PredIctIngdIffIcultyIn0LremaIns,Inalargepart,anenIgma.AsprevIouslyIllustrated,the
commonlyusedIndexesmaynotonlybelesspredIctIvethanorIgInallythought,butmaybe
mIsleadIng.TheadventofvIdeolaryngoscopy(dIscussedlater)maymakethesedefIcIts
Irrelevant;newcrIterIawIllneedtobewrItten.
Clinical Management of the Airway
Preoxygenation
PreoxygenatIon(alsocommonlytermeddenitrogenation)shouldbepractIcedInallcases
whentImepermIts.
19
ThIsprocedureentaIlsthereplacementofthenItrogenvolumeofthe
lung(upwardof69ofthefunctIonalresIdualcapacIty)wIthoxygenInordertoprovIdea
reservoIrfordIffusIonIntothealveolarcapIllarybloodaftertheonsetofapnea.
PreoxygenatIonwIth100D
2
vIaatIghtfIttIngfacemaskfor5mInutesInaspontaneously
breathIngpatIentcanfurnIshupto10mInutesofoxygenreservefollowIngapnea(Ina
patIentwIthoutsIgnIfIcantcardIopulmonarydIseaseandanormaloxygenconsumptIon).n
onestudyofhealthy,nonobesepatIentswhowereallowedtobreathe100D
2
preoperatIvely,subjectssustaInedanoxygensaturatIonof90for60.5mInutes,
whereasobesepatIentsexperIencedoxyhemoglobIndesaturatIonto90In2.70.25
mInutes.
20
UnderIdealcondItIons,thepatIentbreathIngroomaIr(FD
2
=0.21)wIll
P.755
P.756
experIenceoxyhemoglobIndesaturatIontoalevelof90afterapproxImately2mInutesof
apnea.PatIentsInrespIratoryfaIlure,orwIthcondItIonsaffectIngmetabolIsmorlung
volumes,frequentlyevIdencedesaturatIonsooner,owIngtoIncreasedD
2
extractIon,
decreasedfunctIonalresIdualcapacIty,orrIghttolefttranspulmonaryshuntIng.Themost
commonreasonfornotachIevIngamaxImumalveolaroxygenstoredurIngpreoxygenatIon
IsaloosefIttIngmask,allowIngtheentraInmentofroomaIr.
19
Table 29-3 Syndromes Associated with Difficult Airway Management
PATHOLOGIC CONDITION PRINCIPAL PATHOLOGIC CLINICAL FEATURES PERTAINING TO AIRWAY
CONGENITAL
PIerreFobIn
syndrome
|IcrognathIa,macroglossIa,glossoptosIs,cleftsoft
palate
TreacherCollIns
syndrome
AurIcularandoculardefects;malarandmandIbular
hypoplasIa,mIcrostomIa,choanalatresIa
Coldenharsyndrome
AurIcularandoculardefects;malarandmandIbular
hypoplasIa;occIpItalIzatIonofatlas
0ownsyndrome
PoorlydevelopedorabsentbrIdgeofthenose;
macroglossIa,mIcrocephaly,cervIcalspIneabnormalItIes
KlIppelFeIlsyndrome
CongenItalfusIonofavarIablenumberofcervIcal
vertebrae;restrIctIonofneckmovement
Alpertsyndrome
|axIllaryhypoplasIa,prognathIsm,cleftsoftpalate,
tracheobronchIalcartIlagInousanomalIes
8eckwIthsyndrome |acroglossIa
CherubIsm
TumorouslesIonofmandIblesandmaxIllaewIth
Intraoralmasses
CretInIsm
AbsentthyroIdtIssueordefectIvesynthesIsofthyroxIne;
macroglossIa,goIter,compressIonoftrachea,devIatIon
oflarynx/trachea
CrIduchatsyndrome
Chromosome5Pabnormal;mIcrocephaly,mIcrognathIa,
laryngomalacIa,strIdor
|eckelsyndrome |Icrocephaly,mIcrognathIa,cleftepIglottIs
vonFecklInghausen
dIsease
ncreasedIncIdenceofpheochromocytoma;tumorsmay
occurInthelarynxandrIghtventrIcleoutflowtract
Hurler/Hunter
syndrome
StIffjoInts,upperaIrwayobstructIonduetoInfIltratIon
oflymphoIdtIssue;abnormaltracheobronchIalcartIlages
PompedIsease |uscledeposIts,macroglossIa
ACQUIRED
Infections
SupraglottItIs Laryngealedema
Croup Laryngealedema
Abscess(Intraoral,
retropharyngeal)
0IstortIonandstenosIsoftheaIrwayandtrIsmus
PapIllomatosIs ChronIcvIralInfectIonformIngobstructIvepapIllomas
LudwIgangIna 0IstortIonandstenosIsoftheaIrwayandtrIsmus
Arthritis
FheumatoIdarthrItIs
TemporomandIbularjoIntankylosIs,crIcoarytenoId
arthrItIs,devIatIonoflarynx,restrIctedmobIlItyof
cervIcalspIne
AnkylosIngspondylItIs
AnkylosIsofcervIcalspIne;lesscommonlyankylosIsof
temporomandIbularjoInts;lackofmobIlItyofcervIcal
spIne
Benign tumors
CystIchygroma,
lIpoma,adenoma,
goIter
StenosIsordIstortIon
oftheaIrway
Malignant tumors
CarcInomaof
tongue/larynx/thyroId
StenosIsordIstortIonoftheaIrway;fIxatIonoflarynxor
adjacenttIssues(e.g,InfIltratIonorfIbrosIsfrom
IrradIatIon)
Trauma
Head/facIal/cervIcal
spIne
CerebrospInalrhInorrhea,edemaoftheaIrway;
hemorrhage;unstablefracture(s)ofthemaxIllaeand
mandIble;Intralaryngealdamage
Miscellaneous conditions
|orbIdobesIty
Short,thIckneckandlargetonguearelIkelytobe
present
Acromegaly |acroglossIa;prognathIsm
Acuteburns EdemaofaIrway
Table 29-4 Summary of Pooled Sensitivity and Specificity of Commonly
Used Methods of Airway Evaluation
EXAMINATION SENSITIVITY (%) SPECIFICITY (%)
|allampItIclassIfIcatIon 49 86
ThyromentaldIstance 20 94
SternomentaldIstance 62 82
|outhopenIng 46 89
0ataderIvedfromref.12.
Table 29-5 Techniques of Common Airway Indexes Measurement
ThyromentaldIstance:|easuredalongastraIghtlInefromtIpofmentumto
thyroIdnotchInneckextendedposItIon
|outhopenIng:nterIncIsordIstance(orInteralveolusdIstancewhenedentulous)
wIththemouthfullyopened
1J
|allampatIscore(seelegend,FIg.297)
Headandneckmovement:TherangeofmotIonfromfullextensIontofullflexIon
14
AbIlItytoprognath:CapacItytobrIngthelowerIncIsorsInfrontoftheupper
IncIsors
1J
LesstImeconsumIngmethodsofpreoxygenatIonhavealsobeendescrIbed.UsIngaserIesof
fourvItalcapacItybreathsof100D
2
overaJ0secondperIod,ahIgharterIalPao
2
(JJ9
mmHg)canbeachIeved,butthetImetodesaturatIonIsconsIstentlyshorterascompared
wIthtradItIonaltechnIques.
19,21
AmodIfIedvItalcapacItytechnIque,whereInthepatIent
IsaskedtotakeeIghtdeepbreathsIna60secondperIod,showspromIseIntermsof
prolongIngthetImetodesaturatIon.
19,21
Theauthorsofthecurrentchapterpreferthe
technIqueofapplyIngatIghtfIttIngmaskfor5mInutesormoreoftIdalvolumebreathIng;
themaskIsplacedImmedIatelyafterthepatIenthasbeenmadecomfortableonthe
operatIngroomtable,andremaInsInplacedurIngIntravenouscatheterInsertIonandthe
applIcatIonofmonItors.PharyngealInsufflatIonofhasbeendescrIbedtoprolongthe
duratIonofoxyhemoglobInsaturatIon(90)sustaIneddurIngapnea.nthIstechnIque,
oxygenIsInsufflatedatarateofJlIterspermInutevIaacatheterpassedthroughthe
nares.
22
ThIstechnIquerelIesonthephenomenonofapneIcoxygenatIon,aprocessby
whIchgasesareentraInedIntothealveolarspacedurIngapnea,aslongasthereIsapatent
aIrway.ntheobesepatIent,bIlevelposItIveaIrwaypressureaswellasheadupposItIon
(approxImately25degrees)hasbeenadvocatedtobothreachmaxImalpreInductIon
arterIaloxygenatIonandtodelayoxyhemoglobIndesaturatIon.
2J,24
SurprIsIngly,thehead
upposItIonmaynotImprovetheeffIcacyofpreoxygenatIonInthepregnantpatIent.
25
Table 29-6 Assessment and Predictability of Difficult Mask Ventilation
17
Criteria for difficult mask ventilation
nabIlItyforoneanesthesIologIsttomaIntaInoxygensaturatIon92
SIgnIfIcantgasleakaroundfacemask
Needfor4LItespermInutegasflow(oruseoffreshgasflowbuttonmorethan
twIce)
Nochestmovement
TwohandedmaskventIlatIonneeded
ChangeofoperatorrequIred
Independent risk factors for difficult
mask ventilation Odds ratio
Presenceofabeard J.18
8odymassIndex26ng/m
2
2.75
Lackofteeth 2.28
Age55years 2.26
HIstoryofsnorIng 1.84
SomecIrcumstancescanservetodecreasetheeffectIvenessofpreoxygenatIon.For
example,thepatIentwhoexperIencesclaustrophobIawIththeanesthesIafacemask(whIch
canalmostalwaysbeovercomebypatIentsholdIngthemaskthemselves)ortheuseof
selfInflatIngbreathIngbags(whIchdonotdelIveranFD
2
of100durIngspontaneous
breathIng)candecreaseeffectIvenessofpreoxygenatIon.LIkewIse,leaksbetweentheface
maskandpatIent'sfacIalcontoursallowentraInmentofaIr,therebyreducIngtheFD
2
.
Leaksassmallas4mm(crosssectIonal)cancausesIgnIfIcantreductIonsIntheInspIred
oxygencontent.
26
Support of the Airway with the Induction of Anesthesia
WIththeInductIonofanesthesIaandtheonsetofapnea,ventIlatIonandoxygenatIonare
supportedbytheanesthesIologIst.TradItIonalmethodsIncludetheanesthesIafacemask,
andtheETT.0urIngthelast2decadesseveralSCAdevIceshavebeenIntroducedInto
worldwIdeclInIcalpractIce.Dfthese,thelaryngealmaskaIrway(L|A)hasgaIned
sIgnIfIcantacceptanceamonganesthesIologIstsIntheUnItedStates,wIthuseratesashIgh
asJ5ofallgeneralanesthesIacasesInsomesettIngs.
27
Theseandmorerecently
IntroducedSCAs,whIchhavegaInedpopularItyIntheUnItedStates,wIllalsobedIscussed.
The Anesthesia Face Mask
TheanesthesIafacemaskIsthedevIcemostcommonlyusedtodelIveranesthetIcgases
andoxygenaswellastoventIlatethepatIentwhohasbeenmadeapneIc.TheskIllfuluse
ofafacemaskmaybechallengIngand,despItethemanyadvancesInaIrwaymanagement,
remaInsamaInstayInthedelIveryofanesthesIaandInresuscItatIon.WhentheInductIon
ofanesthesIaIsInItIated,thepatIent'slevelofconscIousnesschangesfromtheawake
state,wIthacompetentandprotectedaIrway,totheunconscIousstate,wIthan
unprotectedandpotentIallyobstructedaIrway.ThIsdrugInducedcentralventIlatorydrIve
anddepressIonandrelaxatIonofthemusculatureoftheupperaIrwaycanrapIdlyleadto
hypercapnIaandhypoxIa.FacemaskventIlatIonIsmInImallyInvasIve,vIrtuallyunIversal,
andrequIrestheleastsophIstIcatedequIpment,thusmakIngItcrItIcaltomanagementof
theaIrway.
ThemaskIsgentlyheldonthepatIent'sfacewIththelefthand,leavIngtherIghthandfree
forothertasks(FIg.292).AIrleakaroundtheedgesofthemaskIspreventedbydownward
pressure.|ostmodernmaskscanbedIstortedbytheoperator'sfIngersInordertoseal
aroundthefacIalcontours.ElastIcmaskstrapsmaybeusedtohelpsecurethemaskIn
theawakeoranesthetIzedpatIentwhoIsbreathIngspontaneouslyandwIthoutobstructIon,
ortocomplementthelefthandgrIp.ThemaskstrapscanbepartIcularlyhelpfulforthe
clInIcIanwIthshortfIngers.However,prolongeduseoftIghtfIttIngmaskstrapshasbeen
assocIatedwIthmotorandsensoryneuropraxIas.0urIngapreoxygenatIonphaseof
anesthetIcInductIon,gasleaksmustbeavoIded;durIngInspIratIon,thepatIentmay
entraInaIr,lImItIngtheeffIcacyofthepreoxygenatIonmaneuver.
P.757
Figure 29-2.HoldIngtheanesthesIamaskontheface.ThethumbandthefIrstfInger
grIpthemaskInsuchafashIonthattheanesthesIacIrcuIt(orAmbubag)connectIon
abutsthewebbetweenthesedIgIts.ThIsallowsthepalmofthehandtoapplypressure
totheleftsIdeofthemask,whIlethetIpsofthesethreedIgItsapplypressureoverthe
rIght.ThethIrdfIngerhelpstosecureunderthementum,andtheforthfIngerIsunder
theangleofthemandIbleoralongthelowermandIbularrIdge.|askstraps(onpIllow)
maybeusedtocomplementthehandgrIpbysecurIngtherIghtsIdeofthemask.
npreparatIonforusIngthefacemaskforposItIvepressureventIlatIon(onceapneaIs
Induced),approprIateposItIonIngofthepatIentIsparamount.WIththepatIentInthe
supIneposItIon,theheadandneckareplacedInthesniffingposItIon,whIchIsdIscussed
extensIvelylater.ThIsposItIonImprovesmaskventIlatIonbyanterIorIzIngthebaseofthe
tongueandtheepIglottIs.ThIshasbeendemonstratedInendoscopIcstudIesIn
anesthetIzedpatIents.
28
AfterInductIonofanesthesIa,atIghtfItofthefacemaskIsachIevedbydownward
dIsplacementofthemaskbetweenthethumbandfIrstfIngerwIthconcurrentupward
dIsplacementofthemandIblewIththeremaInIngfIngers.ThIslattermaneuver,commonly
knownasajaw thrust,raIsesthesofttIssuesoftheanterIoraIrwayoffthepharyngealwall
andallowsforImprovedventIlatIon.nthosepatIentswhoareobese,edentulous,or
bearded,twohandsoramaskstrapmayberequIredtoensureatIghtfIttIngmaskseal.
WhentwohandsarerequIredforholdIngthefacemask,asecondoperatorobvIouslywIll
berequIredInordertoventIlatethepatIent.fnecessary,thesecondoperatorcanlenda
thIrdhandtothemaskfIttIng,provIdIngforbothjawthrustandchInlIft.
Dneuseful,albeItpoorlycharacterIzed,maneuverthatcanaIdInfacemaskventIlatIonIs
theexpiratory chin drop.WhenposItIvepressureInspIratIonIssuccessful,butIsnot
followedbypassIvegasescapedurIngexpIratIon,allowIngphasIcheadflexIonandreducIng
chIn/jawlIftIngwIlloftenImprovegasegress.
WhenapatIenthaspresentedwIthremovabledentures,leavIngtheprosthetIcsInplace
canaIdfacemaskventIlatIon.
29
ThepatIentwIthnormallungcomplIanceshouldrequIrenomorethan20to25cmH
2
D
pressuretoInflatethelungs.fmorepressurethanthIsIsrequIred,theclInIcIanshouldre
evaluatetheadequacyoftheaIrway,adjustthemaskfIt,seektheaIdofasecondoperator
Inordertoperformtwoorthreehandedmaskholds,and/orconsIderotherdevIcesthat
aIdInthecreatIonofaopenpassageforaIrflowthroughtheupperaIrway.8othrIgIdoral
aIrwaysandsoftnasalaIrwayscreateanartIfIcIalpassagetothehypopharynx.AvarIetyof
oralandnasalaIrwaysareavaIlable,butwIllnotbedIscussedIndetaIl.NasalaIrwaysare
lesslIkelytostImulatecough,gag,orvomItIngInthelIghtlyanesthetIzedpatIent,butthe
rIskofepIstasIsmustalwaysbeweIghted(especIallyIntheantIcoagulatedpatIent).The
nasalaIrwayIsInsertedalongthefloorofthenose,InadIrectlyanterIorposterIor
dIrectIon,andshouldalwaysbelubrIcated.TheturbInatesofthelateralnasalcavItyare
avoIded.FesIstancetoInsertIonshouldpromptreposItIonIngoftheaIrwaybevel,
reassessmentofthedIrectIonofInsertIonforces,orchangetothecontralateralnarIs.The
aIrwayshouldbelongenoughtoreachfromthenarIstothethyroIdnotchwhenplaced
alongsIdethefaceofthepatIent.DralaIrwaysshouldlIkewIsereachfromtheteeth(or
alveolarrIdge)tothemandIbularangle.ThetypIcalroundedoralaIrwayIsplacedwIthIts
longItudInalconcavItyrotatedInarostraddIrectIon.DncethedIstalendoftheaIrwayhas
beenInsertedtotheleveloftheoropharynx,thedevIceIsrotated180degreesasInsertIon
contInues,toreachItsultImateposItIon.ThIsmaneuveravoIdsdIsplacementofthetongue
Intothehypopharynx.Asmalloralaperture,anIntrapharyngealmassorforeIgnbody,or
lIghtanesthesIamaypreventItsplacement.AswIllbedIscussedlater,someIntubatIngoral
aIrwaysarelargeandhavearectangularcrosssectIon.Thesetendtobetoolargefor
IntraoralrotatIon.TheyareInsertedwIththeconcavItyfacIngcaudadwhIlethetongueIs
stabIlIzedbyatonguedepressororheldbytheoperator.
DbstructIontomaskventIlatIonmaybecausedbylaryngospasm,areflexclosureofthe
vocalfolds.LaryngospasmoccursfromlocalstImulatIonbyaforeIgnbody(e.g.,oralor
nasalaIrway),salIva,blood,orvomItustouchIngtheglottIs,orevenalIghtplaneof
anesthesIa.HypoxIaaswellasnoncardIogenIcpulmonaryedemacanresultIfthereIs
contInuedspontaneousventIlatIonagaInstclosedvocalcords(orotherobstructIon).
TreatmentoflaryngospasmIncludesremovalofanoffendIngstImulus(IfItcanbe
IdentIfIed),contInuousposItIveaIrwaypressure,deepenIngoftheanesthetIcstate,andthe
useofarapIdactIngmusclerelaxant.
ftherearenocontraIndIcatIons(e.g.,afullstomachorotheraspIratIonrIsk),mask
ventIlatIoncanbethetechnIqueemployedfortheduratIonofanesthesIamaIntenance.
DtherwIse,ItIscommonlyusedtoadmInIsteranesthetIcgasesuntIltheanesthetIcstateIs
adequateforuseofanothermeansofaIrwaysupport(e.g.,SCA,ETT).ThIsdecIsIonIs
madeaftercarefulconsIderatIonofthepatIent'scoexIstIngdIseasesandsurgIcal
requIrements.
Supraglottic Airways
TheL|AusheredInthefIrstmajoruseofSCAsIntheUnItedStates.8utbythetImeofIts
InItIalIntroductIonIn1989andapprovalbytheU.S.Foodand0rugAdmInIstratIonIn1991,
ItwasbeIngusedInmorethan500hospItalsIntheUnItedKIngdom.AlthoughInItIally
approvedforuseasasubstItuteforfacemaskventIlatIon,andwhentrachealIntubatIon
wasnotachIevable,ItsoonenjoyedwIdeuseInsurgIcalcasestradItIonallymanagedwIth
trachealIntubatIon.
27
ThoughotherSCAswereavaIlableIntheearly1990s(e.g.,CDPA,|allInckrodt|edIcal,
Athlone,reland),ItwasnotuntIlthepatentoftheorIgInalL|AdesIgnexpIredIn2002that
therewasaprolIferatIonofsImIlardevIces.AwealthofInformatIonexIstsontheL|Aand
ItssubsequentIteratIons(allbytheorIgInalInventor,0r.ArchIe8raIn).|uchofthIs
knowledgemaybeapplIedtonewerdevIces.ThIschapterwIlldevoteconsIderabletextto
thefamIlyofL|As.ThIsIsnotmeanttoInferpreference,butrathertheavaIlabIlItyof
InformatIon.
P.758
TheadventoftheL|AaswellasotherSCAshasledsometoquestIontherelatIvesafetyof
trachealIntubatIon.
J0
ArecentstudybyTanakaetal.
J1
demonstratedvocalcordedema
andIncreasedaIrflowresIstanceInpatIentsundergoIngmInorsurgerywIthanETT.These
changeswerenotseenwIthL|Ause.ThIs,alongwIththeASAclosedclaImsdatabase
InformatIon,lendssupporttothesearchforsafealternatIvestotrachealIntubatIon
wheneverpossIble.
J2
SImIlarly,pharyngealmucosal(traumatIc)changes,asaresultofSCA
useappeartobemarkedlydelayedwhencomparedwIththeaffectsoftheETTInthe
trachea.noneanImalstudy,mucosalInjuryfromtheL|AProSeal(TheLaryngeal|ask
Company,Jersey,UK)dIdnotoccuruntIlmorethan9hoursofcontInuoususe.
JJ
The LMA Classic
TheL|AIscomposedofasmallmaskdesIgnedtosItInthehypopharynx,wIthan
anterIorsurfaceapertureoverlyIngthelaryngealInlet(FIg.29J).TherImofthemaskIs
composedofanInflatablesIlIconecuffthatfIllsthehypopharyngealspace,creatIngaseal
thatallowsposItIvepressureventIlatIonwIthupto20cmH
2
Dpressure.Theadequacyof
thesealdependsoncorrectplacementandapproprIatesIze.tIslessdependentonthe
cufffIllIngpressureorvolume.AttachedtotheposterIorsurfaceofthemaskIsabarrel
(aIrwaytube)thatextendsfromthemask'scentralaperturethroughthemouthandcanbe
connectedtoaselfInflatIngresuscItatIonbagoranesthesIacIrcuIt.
L|AsIzeselectIonIscrItIcaltoItssuccessfuluse,andtotheavoIdanceofmInoraswellas
moresIgnIfIcantcomplIcatIons.NeonataltolargeadultsIzesareavaIlable.The
manufacturerrecommendsthattheclInIcIanchoosethelargestsIzethatwIllfIt
comfortablyIntheoralcavIty,thenInflatetothemInImumpressurethatallows
ventIlatIonto20cmH
2
DwIthoutanaIrleak.TheIntracuffpressureshouldneverexceed60
cmH
2
D(andshouldbeperIodIcallymonItoredIfnItrousoxIdeIsusedaspartofthe
anesthetIc).WhenanadequatesealcannotbeobtaInedwIth60cmH
2
Dcuffpressure,the
L|AmaybemalposItIonedand/orsIzIngshouldbereevaluated.LIghtanesthesIamayalso
contrIbutetopoorsealorpartIalorcompletelaryngospasm.
Figure 29-3.ThefamIlyoflaryngealmaskaIrways(fromtop):ClassIc,FlexIble,
ProSeal,Fastrach,CTrachwIthCTrachmonItor,andSupreme(Inset).
TheInsertIonoftheL|AasdescrIbedbyItsInventor,0r.ArchIeJ..8raIn,hasbeen
modIfIedbyanumberofwrIters.0IscussIonofthesevarIousalternatIvesIsbeyondthe
scopeofthIstext.nordertounderstandtheInsertIontechnIque,werevIewtheprocesses
ofdeglutInatIon,whIchtheproceduremImIcs:lubrIcatIonwIthsalIva;formatIonofaflat
ovalfoodbolusbythetongue;InItIatIonoftheswallowIngreflexbystImulatIonofthe
palate;upwardpressurebythetongueflattenIngthefoodbolusagaInstthepalate;
dIrectIngofthefoodbolustowardtheposterIorpharyngealwallandIntothehypopharynx
bytheshapeofthepalateandpharyngealwall;headextensIonandneckflexIon,whIch
enlargesthespacebehIndthelarynxtoallowpassageofthefoodbolusIntothe
hypopharynx;andfInally,openIngoftheupperesophagealsphInctertoallowesophageal
entryofthefoodbolus.ThesefunctIonsallowthefoodbolustoreachItsmarkblIndly,
whIleavoIdIngtheanterIorpharyngealstructuresandavoIdIngreflexresponsesmeantto
protecttheaIrway.
ThecurrentlyrecommendedInsertIontechnIqueIsIllustratedInFIgure294,andhas98
successrate.nthIstechnIquethemaskIslubrIcatedwIthanonsIlIcone,nonlocal
anesthetIccontaInInglubrIcant(sImulatIngthesalIva),andIsfullydeflatedtoformathIn,
flatwedgeshape(mastIcatedfoodbolus).Theoperator'snondomInanthandIsplacedunder
theoccIputtoflextheneckonthethoraxandextendtheheadattheatlantooccIpItal
joInt(creatIngaspacebehIndthelarynx;thIsactIonalsotendstoopenthemouth).
J4
The
IndexfIngerofthedomInanthandIsplacedInthecleftbetweenthemaskandbarrel.The
hardpalateIsvIsualIzedandthesuperIor(nonaperture)surfaceofthemaskIsplaced
agaInstIt.ForceIsapplIedbytheIndexfIngerInanupwarddIrectIontowardthetopofthe
patIent'shead.ThIswIllcausethemasktoflattenoutagaInstthepalateandfollowthe
shapeofthepalateasItslIdesIntothepharynxandhypopharynx.TheIndexfInger
contInuesalongthIsarc,contInuallyapplyInganoutwardpressureuntIltheresIstanceof
theupperesophagealsphIncterIsmet.ThemostcommonerrormadebyclInIcIansIs
applyIngpressurewIthaposterIorvector.ThIstendstocatchthetIpoftheL|Aonthe
posterIorpharyngealwall,causIngfoldIngwIthresultantmIsplacementandtrauma.
DnceInsertIonIscomplete,removaloftheInsertInghandIsfacIlItatedbygentle
stabIlIzatIonoftheL|AbarrelwIththenondomInanthand.PrIortoattachmentofthe
anesthesIacIrcuIt,theL|AIsInflatedwIththemInImumamountofgastoforman
effectIveseal.SIxtycentImetersofH
2
DpressureIsthemaxImumsuggestedpIlotvalve
pressure.AccompanyIngtheInflatIon,oneshouldbeabletoobservearIsIngofthecrIcoId
andthyroIdcartIlageandlIftIngofthebarreloutofthemouthbyapproxImately1cmas
themaskIslIftedofftheupperesophagealsphIncter.famIdlIneposItIonIsnotpossIble
owIngtothenatureofthepatIentposItIonorsurgIcalprocedure,aflexIbleL|A(dIscussed
later)shouldbeconsIdered.AbIteblockIsrecommendtopreventbItIngandocclusIonof
theL|Abarrel.
AlthoughthedIstaltIpoftheL|AmasksItsIntheesophagealInlet,ItdoesnotrelIablyseal
It.TheL|AwasnotdesIgnedtoprotectagaInsttheaspIratIonofgastrIccontents.0espIte
thIs,whenusedInpatIentsatlowrIskforregurgItatIon,therateofaspIratIondurIngL|A
useIssImIlartothatInallnonL|AgeneralanesthetIcs(approxImately2In10,000cases),
althoughtheIncIdenceofgastroesophagealrefluxmaybeIncreasedwhencomparedwIth
useofthefacemask.
J5
fregurgItatedgastrIccontentsarenotedIntheL|Abarrel,maneuverssImIlartothose
applIedwhenusInganETT
P.759
shouldbeInstItuted:TrendelenburgposItIon,admInIster100oxygen,leavetheL|AIn
placeanduseaflexIblesuctIondevIcedownthebarrel,andIfnecessary,deepenthe
anesthetIc.
Figure 29-4.nsertIonofthelaryngealmaskaIrway(L|A).TheL|AIsInsertedwIth
theIndexfIngerofthedomInanthandpressIngwIthaforcevectoragaInstthehard
palate(AandB).TheoutwardforcevectorIscontInuedfromthehardpalatetothe
pharynxandhypopharynx(C)untIltheIndexfIngermeetsresIstanceagaInsttheupper
esophagealsphIncter(D).
WhenpopulatIonsofpatIentsconsIderedtohaveafullstomacharestudIed(Incontrolled
trIals,prospectIveserIes,oranecdotally),thereIsalowIncIdenceofaspIratIonnotedwIth
electIveoremergencyL|Ause.FeportshaveIncludedpatIentswhoaremorbIdlyobeseor
experIencefrequentgastroesophagealreflux,thoseundergoIngelectIvecesareansectIon
oraIrwayrescuedurInglabor,andthosepresentIngtoemergencydepartmentsor
paramedIccrews.
J6,J7
0urIngcardIopulmonaryresuscItatIon,theIncIdenceof
gastroesophagealregurgItatIonIs4tImesgreaterwIthabagvalvemaskthanwIththe
L|A.
J8
AlthoughfIrstIntroducedforusewIthspontaneousventIlatIon,theL|Ahasproveduseful
forcasesInwhIchposItIvepressureventIlatIonIseItherdesIredorpreferred.
J9
Contraryto
InItIalImpressIon,posItIvepressureventIlatIoncanbesafelyaccomplIshedwIththe
L|A.
40,41
ThereIsnodIfferencefoundIngastrIcInflatIonwIthposItIvepressure(17cm
H
2
D)whencomparIngtheL|AandtheETT.
42
WhenusIngtheL|A,oneshouldlImIttIdal
volumesto8mL/kgandaIrwaypressureto20cmH
2
D.L|AusehasbeendescrIbedwIth
thesupIne,prone,lateral,oblIque,Trendelenburg,andlIthotomyposItIons.Althoughthe
manufacturerrecommendsuseforamaxImumof2toJhours,reportsofuselastIng24
hourscanbefound.
4J
The LMA Flexible
TheIntroductIonoftheL|AFlexIble(TheLaryngeal|askCompany,Jersey,UK)(FIg.29J)
haspermIttedextensIonofL|AusetoavarIetyofcasesInwhIchtheaIrwayIssharedwIth
thesurgIcalteam(e.g.,otolaryngologIcsurgery),orotherwIsewIthInthesurgIcalfIeld
(e.g.,ophthalmologIcsurgery.)TheL|AFlexIbledIffersfromtheorIgInaldesIgnbyvIrtue
ofathInwalled,smalldIameter,wIrereInforced(kInkresIstant)barrel,whIchcanbe
posItIonedoutofthemIdlInewIthoutaffectIngthehypopharyngealposItIonofthemask.t
wasdesIgnedtobeusedwIthatonsIllarmouthgagemployedInsurgeryonthemouthand
pharynx.
44
TheL|AFlexIblehasalsoprovedusefulwhenheavydrapesareplacedoverthe
headandaIrway(e.g.,mastoIdectomy,ophthalmIcprocedures),whenthereIsmovement
oftheheadposItIondurIngsurgery(e.g.,tympanostomytubes),orwhentheL|Abarrel
cannotbesecuredInthemIdlIne(e.g.,mIdorlateralfacIalsurgery).TheuseofthIsmask
Insurgeryabovethelevelofthehypopharynx,IncludIngtonsIllectomy,affordsanumberof
P.760
clInIcallyImportantadvantagesovertrachealIntubatIon(Table297).Whencorrectly
placed,theL|AmaskservestobetterblocktheaIrwayfromblood,secretIons,and
surgIcaldebrIsabovethelevelofthemask,ascomparedwIththetrachealtube,whIchIs
knowntonotprotectthetracheafromlIquIdsInstIlledIntothepharynx.
45
Table 29-7 Advantages of the Laryngeal Mask Airway in Supraglottic
Surgery
mprovedprotectIonoftheaIrwayfrombloodandsurgIcaldebrIs
FeducedcardIovascularresponses
FeducedcoughIngonemergence
FeducedlaryngospasmafteraIrwaydevIceremoval
mprovedoxygensaturatIonafteraIrwaydevIceremoval
AbIlItytoadmInIsteroxygenuntIlcompleterestoratIonofaIrwayreflexes
The LMA and Bronchospasm
AsanSCA,theL|AappearstobewellsuItedtothepatIentwIthahIstoryof
bronchospasm.TheL|ApresentsaunIqueopportunItyfortheclInIcIantoconvenIentlyand
effectIvelycontroltheaIrwaywIthouthavIngtoIntroduceaforeIgnbodyIntothetrachea.
Thus,ItmaybeanIdealaIrwaytoolIntheasthmatIcpatIentwhoIsnotatrIskforreflux
andaspIratIon.
46
8ecausethehalogenatedInhaledanesthetIcsarepotentbronchodIlators,
ItIsatthetImeofemergence,whentheanesthetIcIsdIscontInued,thatthepatIentatrIsk
forbronchospasmIsmostlIkelytowheeze.nthepatIentmanagedwIththeL|A,thereIs
noforeIgnbodyInthesensItIvebronchorespIratorytreeandthepatIentcanbefully
emergedprIortoremovalofthedevIce.ntheeventthatuncontrollablebronchospasm
doesoccurIntraoperatIvely(e.g.,fromvagalstImulIsuchastractIonontheperItoneum),
IntubatIoncanbeperformedthroughtheL|AorafterItsremoval.Whentracheal
IntubatIonIsmandatory(forthesurgIcalprocedure)yetconcernsregardIngbronchospasm
exIst,the8aIleymaneuverIsemployed.
47
nthIsmaneuver,thedeflatedL|AIsplaced
behIndtheInsItuETT.TheETTIsremovedandtheL|AIsInflated.ThepatIentIsthen
emergedontheL|A.
Lma Removal
TImIngoftheremovaloftheL|AattheendofsurgeryIscrItIcal.
47,48
TheL|Ashouldbe
removedeItherwhenthepatIentIsdeeplyanesthetIzedorafterprotectIvereflexeshave
returnedandthepatIentIsabletoopenthemouthoncommand.FemovaldurIng
excItatIonstagesofemergencecanbeaccompanIedbycoughIngand/orlaryngospasm.
|anyclInIcIansremovetheL|AfullyInflated;thus,ItactsasascoopforsecretIons
abovethemask,brIngIngthemoutoftheaIrway.
49
ThIshasbeenpartIcularlyusefulIn
otolaryngologIcsurgery.
Contraindications to LMA Use
TheprImarycontraIndIcatIontoelectIveuseoftheL|AIsarIskofgastrIccontents
aspIratIon(e.g.,fullstomach,hIatushernIawIthsIgnIfIcantgastroesophagealreflux,
IntestInalobstructIon,delayedgastrIcemptyIng,poorhIstory).DthercontraIndIcatIons
IncludepoorlungcomplIanceorhIghaIrwayresIstance,glottIcorsubglottIcaIrway
obstructIon,andlImItedmouthopenIng(1.5cm).
50
LMA Use Complications
ApartfromgastroesophagealrefluxandaspIratIon,reportedcomplIcatIonshaveIncluded
laryngospasm,coughIng,gaggIng,retchIng,bronchospasm,andothereventscharacterIstIc
ofaIrwaymanIpulatIon.TheIncIdenceofsorethroatIsapproxImately10,ascompared
wIthJ0wIthtrachealIntubatIon,buthasbeenreportedwItharangeof0to70.
6
Also
reportedarehoarseness(4to47)anddysphagIa(4to24).TheL|AmaycausetransIent
changesInvocalcordfunctIon.ThIsIspossIblyrelatedtocuffoverInflatIondurIng
prolongedprocedures.
TherehavebeenreportsofnerveInjuryassocIatedwIthL|Ause.AsofSeptember2007,26
casesofnervepalsyhavebeenreported:recurrent,
12
hypoglossal,
7
andlIngual.
7,51
The
InjurIeswerefIrstmanIfestfromemergenceto48hoursaftersurgery.Allbutoneofthese
InjurIesresolvedspontaneouslyIn1hourto18months.PredIsposIngfactorsIncludetheuse
ofsmallmasks,nItrousoxIde,lIdocaInelubrIcatIon,cuffoverInflatIon,dIffIcultor
alternateInsertIontechnIques,andcervIcalboneorjoIntdIsease.
51
PressureneuropraxIa
fromthetubeorcuffIsthemostcommoncause.
The LMA ProSeal
AsIgnIfIcantconcerntotheclInIcIanplacInganysupraglottIcaIrwayIsIdentIfyIngthatItIs
InproperposItIon:thegoldstandardsusedtoIdentIfytrachealIntubatIonbydIrect
laryngoscopy(vIsualIzatIonofthevocalcordsandendtIdalCD
2
detectIon)donotapply.
PoorplacementoftheL|AhasbeenblamedforgastrIcfluIdaspIratIon,neuropraxIas,and
sorethroat.nresponse,theL|AProSealwasdevelopedIn2001by0r.8raInby
IncorporatIngagastrIcdraInpassIngfromthedIstalendofthecufftotheatmosphere.
(FIg.29J).SeveraltestsofL|AProSealplacementhavebeendescrIbedby8raInand
others(Table298).
52,5J,54,55
TheL|AProSealalsoIncreasesthemaxImumaIrwayseal
durIngposItIvepressureventIlatIonascomparedwIthotherL|AdevIces(40cmH
2
D),and
allowspassIve(regurgItatIon)andactIve(gastrIctubeInsertIon)emptyIngofthe
stomach.
5J,54,55
0espItetheabIlItytousehIghaIrwaypressureswIththeL|AProSeal,the
clInIcIanshouldrememberthat,unlessthereIsanobvIouscause(e.g.,obesIty)20cmH
2
D
shouldbeunnecessary.WhenunexpectedlyhIghpressureIsencountered,asearchforthe
causeIsmandatory.AlthoughtheL|AProSealIstypIcallyInsertedwIththesamemethod
asaclassIcL|A,ametallIcInsertIondevIceIsavaIlablefromthemanufacturer.The
advancedcapabIlItIesoftheL|AhaveaddedtoItsuseInaIrwayresuscItatIon.
56,57
|altbyetal.
58
havepIoneeredtheuseoftheL|AProSealdurInglaparoscopIc
cholecystectomyInobesepatIents.ThIssurgIcalprocedurehaslongbeenconsIderedthe
prototypIcalcaseforcontraIndIcatedL|AusebecauseofhIghIntraperItonealpressures,as
wellasIntraoperatIvealImentarytractmanIpulatIon.LaparoscopIccholecystectomywas
performedIn46patIents,12ofwhomhadabodymassIndexofJ0kg/m
2
.ThemedIan
aIrwaypressureatwhIchagasleakoccurredwasJ4cmH
2
D(range,18to45).Fourobese
patIentscrossedovertoacontrol,trachealtubegroup.StomachsIze(e.g.,dIstentIon)was
equalbetweengroups.
The Laryngeal Tube
TheLaryngealTube(78||edIzIntechnIk,CmbH,Sulz,Cermany)consIstsofasInglelumen
tubewIthanapproxImately1J0degreemIdshaftangleandtwo(dIstalandproxImal)low
pressurecuffs(FIg.295).AnovalaperturebetweenthecuffsservesasaventIlatIon
orIfIce.ThedIstalcuffenclosesthedIstalendofthetube.WhenInsertedcorrectly,the
proxImalcuffsealstheoralandnasalpharynxwhereasthedIstalcuffsItswIthIntheupper
esophagealsphIncter.7entIlatIon(spontaneousorposItIvepressure)occursvIaananterIor
surfaceorIfIcemIdwaybetweenthecuffs.ThecuffsareInflatedvIaacommonpIlotvalve.
TheorIgInallaryngealtubeIsavaIlableInsIngleuseorreusablemodels,requIresamouth
openIngofatleast2.Jcm,andIsInsertedeItherblIndlyorwIththeaIdofalaryngoscope.
TheLaryngealTubeSuctIonIsamodIfIcatIonoftheLaryngealTube,wIththeaddItIonofa
P.761
secondlumenforsuctIonandgastrIcdraInage(theorIfIceofwhIchIsatthedIstalaspectof
theesophagealcuff).SIxsIzes(0through5)aresuItableforneonatestolargeadults.UsIng
LaryngealTubeInchIldrenunder10yearsoldIslesseffectIvethantheL|AdurIng
spontaneousorassIstedventIlatIonandforfIberoptIcevaluatIonoftheaIrway.
59
The
LaryngealTubeIsnotrecommendedforchIldrenweIghIng10kgbecauseoftechnIcal
dIffIcultIesandInadequateventIlatIon.
Table 29-8 Features of the Laryngeal Mask Airway Proseal
FEATURE CLINICAL IMPACT
CastrIcdraIn
PosItIonconfIrmatIon
Suprasternalnotchtest
a,52
NogasleakvIagastrIcdraIn
5J
SuccessfullypassInggastrIctube
ActIvegastrIcemptyIng
PassIvegastrIcemptyIng
ProtectIonfromgastrIccontentaspIratIon
PosterIorcuff ncreasedsealpressure
8Iteblock
PreventspatIentbItIng,obstructIon
PosItIonconfIrmatIon
50ormoreofthebIteblockshouldbewIthInthe
oralcavIty
54
WIrereInforcedaIrway
barrel
FeducedoverallsIze
0ecreasedabIlItytotracheallyIntubate
Largebarrel/bIteblock
FIrstInsertIonlesssuccessfulthanL|AclassIc
ConfersrotatIonalstabIlIty
SIzechoIce:sIzedownfromL|AclassIc
L|A,laryngealmaskaIrway.
a
WhenasmallamountoflubrIcantIsusedtooccludethegastrIcdraIn,gentle
pressureonthesuprasternalnotchIsreflectedInmovementofthelubrIcant
menIscus.
ParamedIcsworkIngIntheoperatIngroomfoundInsertIonoftheLTeasy(successwIth
ventIlatIonatfIrstattemptInJ1ofJ4patIents).
60
nsertIontImeoftheLaryngealTube
SuctIonIssImIlartothatoftheL|AProSealandsIgnIfIcantlyshorterthantheCombItube
(dIscussedlater).
61
DnestudyshowedthattheLaryngealTubeSuctIonproducedagreater
andmoresustaInedhemodynamIcandcatecholamInestressresponsethantheL|A
ProSeal.
62
CaItInIetal.
6J
usedtheLaryngealTubeIn175patIentspresentIngforelectIve
surgery.PosItIvepressureventIlatIonwassuccessfulIn96.6ofcases.Successful
ventIlatIonInpatIentswIthunexpecteddIffIcultaIrwaysbecauseofundIagnosedlIngual
tonsIlhyperplasIaandmorbIdobesItywerereported.
Figure 29-5.TheLaryngealTube.
TheLaryngealTubecanbeusedtofacIlItatefIberoptIctrachealIntubatIonwhencombIned
wIththeAIntreeIntubatIoncatheter(CookCrItIcalCare,8loomIngton,ndIana).FotatIon
ofLaryngealTubeandjawthrustmaneuvercanImproveglottIcvIsualIzatIondurIngthIs
procedure.nonereporttheLaryngealTubewasusedforfIberoptIcaIdedIntubatIonIna
patIentInwhomlaryngoscopy,conventIonalfIberoptIcIntubatIon,andInsertIonofanL|A
hadfaIled.
64
AsuccessfuluseoftheLaryngealTubeSuctIonwasreportedInanemergencyaIrway
sItuatIonInapregnantwomanwIthhIstoryofgastroesophagealrefluxwhounderwent
cesareansectIonbutcouldnotbeIntubated.ThedevIceImprovedoxygensaturatIonand
draInedgastrIccontentsdurIngthepatIent'semergencefromrapIdsequenceIntubatIon.
65
AstudyIn15freshcadaversshowedthatmucosalpressuresInlateralpharynx,baseof
tongue,andposterIorpharynxweresImIlarbetweenLaryngealTubeandL|AProSealbut
pressureonposterIorhypopharynxwasalwayshIgherwIththeLaryngealTube.The
InvestIgatorsexpressedconcernthatpressurefromtheLaryngealTubemIghtImpede
pharyngealperfusIonmorethanL|AProSeal.
66
Acaseofacutetongueanduvula
ulceratIonafterusIngLaryngealTubeforhysteroscopyhasbeenreported.
67
The Cobra
TheCobraperIlaryngealaIrway(CobraPLA,EngIneered|edIcalSystems,ndIanapolIs,N)Is
adIsposablesupralaryngealaIrwaydevIce.thasasInglelumenthattermInatesIna
wIdeneddIstalend.ApharyngealcuffservestooccludetheupperaIrwayfromtheoral
cavIty,andaserIesofslotsInthewIdenedendholdtheepIglottIsoutofthebarrel.A
fIberscopeand/orETTmaybepassedthroughthebarrelandtheslots.ThIstechnIquehas
beensuccessfullyusedInpatIentspresentIngwIthdIffIcultIntubatIon/ventIlatIon.Feports
havedemonstratedtheuseoftheCobraPLAInaIrwayrescue,aswellasroutIneanesthetIc
carewIthspontaneousandposItIvepressureventIlatIon.
68
SomestudIeshaveshownthe
CobraPLAprovIdessIgnIfIcantlyhIgheraIrwaysealIngpressuresthantheL|AclassIcaswell
asahIgherfIrstInsertIonsuccessrate,althoughtheIncIdenceofbloodonthedevIceand
P.762
sorethroatwerealsohIgher.
69
nspIratorytIdalvolume,expIratorytIdalvolume,endtIdal
CD
2
concentratIon,andrespIratoryratewerenotdIfferentbetweenpatIentsIntheL|A
andCobraPLAgroups.
69
Cookgas Air-Q Airway
0evelopedby0r.0anIelCook(CookgasLLC,StLouIs,|D),theAIrQperIlaryngealaIrway
functIonsasanelectIveSCA,orasaconduItforblIndorfIberoptIcaIdedIntubatIonofthe
trachea.ThebarreloftheaIrwayIsprecurvedandofwIdedIameter,andwIllaccepta
trachealtubefrom5.0to8.0mmInternaldIameter(0).ThekeyholeshapedaIrwayoutlet
IsdesIgnedtosteertheETTtowardthelarynx.Acuff,grosslytheshapeoftheL|Acuff,
sealstheperIlaryngealspace.ThedevIceIsInserted(cuffdeflated)byatechnIquesImIlar
tothatrecommendedfortheL|A(seeprevIousdIscussIon).f,afterInsertIon,theaIrway
Isobstructed,anupdownmotIonofthebarrelwIlloftenrealIgntheepIglottIs.8lInd
trachealIntubatIonshouldbeundertakenonlyIftheaIrwayIsclearandthepatIentIs
musclerelaxedand/orsuffIcIentlyanesthetIzed.TheETTcuffIscompletelydeflatedand
lubrIcated.tIsInserted12to15cmIntothedevIcebarrel.AdvancementpastthIspoInt
wIllbeIntothelarynx.fresIstanceIsmet,thedevIcecanbereposItIoned.Dncetracheal
IntubatIonIsassured,thedevIcecanberemovedwIththehelpofaspecIalIzedstylet
marketedbythemanufacturer.
Tracheal Intubation
Routine Laryngoscopy
PreparIngforLaryngoscopyandthe8estAttempt.WhetherlaryngoscopyIsundertaken
wIththepatIentInanawakeorunconscIousstate,repeatedattemptsat0LoftenresultIn
traumatotheanterIorupperaIrwaystructures(e.g.,tongue,vallecula,epIglottIs,
laryngealstructures),potentIallyhInderIngsubsequentattemptsatvIsualIzatIonand
causIngIncreasedaIrwayobstructIon.tIsthereforeImportanttoassurethatthefIrst
attemptatlaryngoscopyIsabestattempt.
FIrst,whenfacedwIththecrItIcallyIllpatIent,themostskIlledlaryngoscopIstavaIlable
shouldbeposItIonedtoperformthelaryngoscopy.nlessacutesItuatIons,ItIsnot
InapproprIateforatraInee,clInIcIanextender,orotherskIlledpersonneltoassumethIs
role.Second,theavaIlabIlItyofallthematerIalsneededtoperformlaryngoscopyand
IntubatIonshouldbeassured,asshouldtheavaIlabIlItyofdevIcesneededtomanagea
faIledIntubatIon(Table299).
DtherdevIcesthatcompletetheequIpmentlIst,butmaynotbeunIformlyavaIlable,
Include:endtIdalCD
2
monItorIng(e.g.,capnographyorcolorImetrIcdevIcesuchasEasy
Cap,|allInckrodt),pulseoxImetry,transtrachealjetventIlatIoncatheter,andahIgh
pressureoxygensource.
TheheIghtofthesupInepatIent'saIrwayshouldbeatthelevelofthelaryngoscopIsts'
xyphoIdcartIlage,wIththebedoroperatIngroomtableInanonmovablemode(e.g.,
wheelslocked).TheclInIcIanperformIngtheIntubatIonmusthaveunobstructedaccessto
thehead.
Direct Laryngoscopy
SuccessfullaryngoscopyInvolvesthedIstortIonofthenormalanatomIcplanesoftheupper
aIrwaytoproducealIneofdIrectvIsualIzatIonfromtheoperator'seyetothelarynx;thIs
requIresthecreatIonofanew(nonanatomIc)vIsualaxIs,throughmaxImalalIgnmentof
theaxesoftheoralandpharyngealcavItIes,anddIsplacementofthetongue.
UnantIcIpatedfaIlureof0LIsprImarIlyaproblemoftonguedIsplacement(InabIlItytoalIgn
theaxescanbeantIcIpatedbyphysIcalexamInatIon).
11
SomeInvestIgatorshavefocused
thesearchforthecauseofdIffIcult0LontherelatIveposItIonofthetongue.Chouand
Wu
70
havefoundthatahypopharyngealtongue(e.g.,thegreatermassofthetongueIs
wIthInthehypopharynx)IsaccompanIedbyacaudadlarynx,whIchIsInturndetermInedby
measurementofthemandIbularhyoIddIstance(ameasureofthecephalocaudad
separatIonofthemandIbleandhyoIddurIngfetaldevelopment).8enumof
71
eloquently
explaInsthIsfIndIngIntermsofontogenyandthedescentofthelarynxtocreatethe
phonIcsofthehumanpharyngealspace(ontogenyrecapItulatesphylogeny).Alongdescent
ofthelarynxresultsInalargepartofthetonguebeIngInthehypopharynx.Poordescentof
thelarynxresultsInasmallthyromentaldIstanceandcanIndIcateadIffIcult0L.
Table 29-9 Equipment for Laryngoscopy
a
DxygensourceandselfInflatIngventIlatIonbag(e.g.,Ambubag)
Facemask
b
DropharyngealandnasopharyngealaIrways
b
Trachealtubes
b
Trachealtubestylet
SyrIngefortrachealtubecuffInflatIon
SuctIonapparatus
Laryngoscopehandle(two),testedforworkIngorderandbatteryfreshness
Laryngoscopeblades:CommonbladesIncludethecurved(|acIntosh)andstraIght
(|Iller)
b
PIllow,towel,blanket,orfoamforheadposItIonIng
Stethoscope
a
EquIpmentthatshouldbeImmedIatelyavaIlableIntheIdealclInIcalsettIng.
b
PresumedsIzeaswellasonelargerandonesmallershouldbeImmedIately
avaIlable.
ChouandWu
72
alsonotedthatthelongmandIbulohyoIddIstancecanbepartlyduetoa
shortenedmandIbularramus.AshortramusresultsInthefloorofthemouthbeIngmore
rostradandlesscomplIant,andthereforedIsplacementofthetongueIsmoredIffIcult.fa
smallthyromentaldIstanceaswellasalargethyromentaldIstancecanbothpredIct
dIffIcultlaryngoscopy,thenhowcanthIsmeasurebeusefultotheaIrwayevaluator:As
poIntedoutIntheASA0IffIcultAIrwayPractIceCuIdelInes,noonemeasuremaybe
adequatetodetermInedIffIcultyof0L,andmultIplemeasuresmustbeIntegratedInorder
tomakesensIbleaIrwaymanagementdecIsIons.
1
ShIgaetal.
12
publIshedametaanalysIsof
studIesregardIngaIrwayphysIcalexamInatIonscores,andcautIonedonthepoorsensItIvIty
andonlymodestspecIfIcItyofallroutInetests.
AnothermandIbulardImensIonthathasbeenexamInedIsthemandIbulardepthIndex(the
posterIordepthofthemandIble/mandIbularlength).KIkkawaetal.
7J
havenotedthata
deeporshortmandIble(hIgherIndex)IndIcatesalargehypopharyngealtongue,and
dIffIcultywIthdIsplacement.AlthoughthemandIbularhyoIddIstanceandthemandIbular
depthIndexaredIstInctmeasures,theyapproachtheproblemofdIffIcultywIth0L
sImIlarly:anatomIcrelatIonshIpsofthemandIblemaypredIctadIffIculttodIsplace
hypopharyngealtongue.TheseauthorsalsohIghlIghtthatasInglemeasure(e.g.,
thyromentaldIstance)doesnotyIeldenoughInformatIontobepredIctIve.
EventhoughcongenItalanatomIcvarIatIonmayoccur,pathologIcvarIatIonsmaymImIc
thesameproblemofhypopharyngealtonguemass:DvassapIanetal.
11
haveIdentIfIed
hyperplasIaofthelymphoIdtIssueatthebaseofthetongueastheprIncIplecauseof
unantIcIpateddIffIcultlaryngoscopy.7IsualIzatIonofthIstIssueIscurrentlytheonly
methodofdIagnosIsandmaybedonepreoperatIvely.Dften,lIngualtonsIlhyperplasIamay
bethecauseofthedIffIcult0L,
P.76J
butthedIagnosIsIsnotmadebecauseoftheoverlyIngposItIonofthestandarddIrect
laryngoscope.
0LrequIresthecreatIonofalIneofsItefromtheoperator'seyetotheapertureofthe
larynx.n19448annIsterand|ac8ethproposedathreeaxIsmodeltoexplaIntheanatomIc
relatIonshIpsInvolvedInthIsoperatIon.ThIsexplanatIonhasbeenchallengedbyAdnetet
al.,
74
whonotedthat,whereasextensIonattheatlantooccIpItaljoIntmaxImally
facIlItatedanoralcavIty/pharyngealalIgnment,nosIgnIfIcantImprovementwasachIeved
wIthflexIonofthecervIcalspIneonthethorax.ChouandWu
75
refInedthIsapproachby
notIngthatlaryngealaxIsalIgnmentIsunnecessary.TheendpoIntoftheefforttocreate
anInlInespacefortrachealIntubatIonIstheglottIcaperture:alIgnmentoftheentIre
larynxIsthereforeunnecessary.Theseauthorsproposeatwoaxes/tonguedIsplacement
model.ThIsmodeldoesnotdependonthealIgnmentofallaxestocreateanInlInevIew
ofthelarynx,butrathermaxImIzesthespacesbetweenthealveolarrIdgeandlaryngeal
aperturethroughoropharyngealalIgnmentandtonguedIsplacement.ThIsconceptcanbe
usedtonotonlyunderstandtheproblemsthatmayhInder0L,butalsowhycommon
IndexesofaIrwayassessmentfaIlIntheIrpredIctIvepower.ThIsconcepthasbeen
descrIbedprevIouslyandcanbevIewedasfunctIonalaIrwayassessment(FAA).
76
FAAIsamethodofexamInIngthefunctIonalnatureofeachoftheanatomIccorrelatesof
thecommonlyusedassessmentIndIces.FAAplacesanemphasIsontheInterdependenceof
theseanatomIccharacterIstIcsratherthanontheIrIndIvIdualsIzeorfunctIonalIntegrIty.
AsexplaInedbyChouandWu,
75
whentheheadandneckareIntheneutralposItIon,the
oralandpharyngealaxesareperpendIculartoeachother.WIthmaxImalextensIonofa
normalatlantooccIpItaljoInt,J5degreesormoreofmotIonIsattaIned(FIg.296).ThIs
brIngstheanglebetweentheoralandpharyngealaxIsto125degrees.Althoughan
Improvement,ItIscertaInlynotthe180degreesrequIredforcreatIonofalIneofsIteto
theglottIs.AdIfferentspacemustbecreated.ThIsspaceIscreatedbydIsplacementofthe
tonguewIththelaryngoscope.AlthoughatlantooccIpItalextensIoncannotbyItselfallow
dIrectlaryngealvIsIon,ItdoesprovIdeanterIordIsplacementofthemassofthetongueand
brIngsupthealveolarrIdgeIntoImprovedposItIonrelatIvetothetongueandlarynx.The
extensIonoftheatlantooccIpItalpoIntalsoprovIdesanadvantageInmouthopenIng.
Calderetal.
J4
haveshownthatthemaxImalmouthopenIngIs26greaterInfullatlanto
occIpItalextensIonascomparedwIththeneutralheadposItIon.TemporalmandIbularjaw
functIonalsocontrIbutestothedIsplacementofthetongueawayfromtherequIredvIsual
axIs.FotatIonandtranslatIonofthetemporalmandIbularjoIntresultInarelaxatIonofthe
tongueInsertIon,aswellascreatIonoftheaperturewIdthneededforInstrumentatIon.
Figure 29-6. A.WIththepatIentsupIne,theoralandpharyngealaxesdonotoverlap.
B.ExtensIonattheatlantooccIpItaljoIntmaxImallyoverlapstheoralandpharyngeal
axes.
UsIngtheFAAapproachtoaIrwayevaluatIonalsohelpstoexplaInthevalueofthepopular
yethIghlycrItIcIzed|allampatIandthyromentaldIstanceIndIces.
77
Thesetwomeasures
havehIstorIcallybeenconsIderedImportantbecausetheyapproxImatetherelatIvemassof
thetongue(|allampatI)andtheanterIorposterIorbordersofspaceIntowhIchItwIllbe
dIsplacedbythelaryngoscope(FIg.297).Asnotedelsewhere,theseIndIceshaveshownto
havepoorand/orvarIablepredIctIvepower.TwogroupshaveconsIderedtheInterrelated
natureofthesemeasuresInawaythatrevealswhytheyperformpoorlywhenconsIdered
IndIvIdually.Ayoubetal.
78
foundahIgh|allampatIscoretobepredIctIveofadIffIcult0L
whenthethyromentaldIstancewas4cm.WhenthethyromentaldIstancewas4cm,
relatIvetonguesIze(asdetermInedbythe|allampatIclassIfIcatIon)wasnotpredIctIve.
ohometal.
79
foundsImIlarresultsusIngathyromentaldIstancecutoffof6cm.ThefIndIng
thatthepredIctIvepowerofthe|allampatIImproveswhenthemandIbleIsshortIs
consIstentwIththeconceptofFAA:whenthemandIbularspaceIsrestrIcted,tonguesIzeIs
Important.WhenthespaceIslarge,atongueofanynonpathologIcsIzeshouldbe
accommodated.AnexceptIontothIsmaybehypopharyngealtongue,asdescrIbedbyChou
andWu
70
;althoughaccordIngtothoseauthors,measurementofthemandIbularhyoId
dIstanceshouldhelpIndIagnosIngthIs.
Asnotedabove,acommoncauseofdIffIcultyIn0LIsapathologIcIncreaseIntonguesIze.
DvassapIanetal.
11
haveIdentIfIedlIngualtonsIlhyperplasIaasthemostcommonly
undIagnosedcauseofunantIcIpateddIffIcult0L.TheyrevIewedthecasesofunantIcIpated
dIffIcult0LIntheIrInstItutIonfrom1999to2000.ThIrtythreepatIentswereIdentIfIed.All
patIentswerefoundtohavelIngualtonsIlhyperplasIaonfIberoptIcexamInatIon(FIg.298).
0evIcesthataIdInplacIngthepatIentInasnIffIngposItIonhavebecomeavaIlable.These
IncludethesnIffposItIonpIllow(PopItzPIllow,AlImed,0edham,|A),developedby|Ichael
PopItz,andPI'sPIllow(AmerIcanEagle|edIcal,Holbrook,NY),whIchIscomfortablefor
theawakepatIentbuteasIly
P.764
reconfIguredafteranesthetIcInductIontoprovIdeanIdealposItIonfor0L.
Figure 29-7.|allampatI/SamsoonYoungclassIfIcatIonoftheoropharyngealvIew.
77
A.
Class:uvula,faucIalpIllars,softpalatevIsIble.B.Class:faucIalpIllars,softpalate
vIsIble.C.Class:softandhardpalatevIsIble.D.Class7:hardpalatevIsIbleonly
(addedbySamsoonandYoung).
Figure 29-8.LIngualtonsIlhyperplasIa:thevalleculaIsfIlledwIthhyperplastIc
lymphoIdtIssueInapatIentwhohadanunantIcIpateddIffIcultdIrectlaryngoscopy.
TheobesepatIentmayneedfurtherposItIonIngtomovethemassofthechestawayfrom
theplaneacrosswhIchthelaryngoscopehandlewIllsweepasItIsmanIpulatedIntothe
mouth.ThIsmayrequIreplacIngawedgeshapedlIft(e.g.,theTroopElevatIonPIllow,
|ercury|edIcal,Clearwater,FL)underthescapula,shoulders,andnapeofneck,raIsIng
theheadandneckabovethethoraxandprovIdIngagradeInordertoallowgravItytopull
thepannus'weIghtawayfromtheaIrway.
fdurIngthelaryngoscopy,asatIsfactorylaryngealvIewIsnotachIeved,thebackward
upwardrIghtwardpressure(8UFP)maneuvermayaIdInImprovIngthevIew.nthIs
maneuver,asecondoperatordIsplacesthelarynx(8)backwardagaInstthecervIcal
vertebrae,(U)superIorlyaspossIbleand(F)slIghtlylaterallytotherIght,usIngexternal
pressureoverthecrIcoIdcartIlage.The8UFPmaneuverhasbeenshowntoImprovethe
laryngealvIew,decreasIngtherateofdIffIcultIntubatIonInastudyof1,99JpatIentsfrom
4.7to1.8.
80
WhenalefthandedoperatorIsusIngalefthanded
P.765
laryngoscopeblade,thelateralexternalpressureshoulddIsplacethelarynxtotheleft.
SImIlarly,8enumofandCooper
81
descrIbeoptImalexternallaryngealmanIpulatIon,
whIchconsIstsofpressIngposterIorlyandcephaladoverthethyroId,hyoId,andcrIcoId,as
ImprovInglaryngealvIewbyatleastoneCormackandLehanegrade.
82
DncealIgnmenthasbeenachIeved,themouthIsopenedbyoneoftwotechnIques.The
fIrstmethodaccomplIsheshyperextensIonoftheatlantooccIpItaljoIntbytheuseofthe
domInanthandundertheoccIput.ThIsmaneuverleadstopassIveopenIngofthemouth,
andcanbeaccentuatedbyusIngthefIfthfIngerofthenondomInanthand(holdIngthe
laryngoscope)toapplypressureoverthechInInacaudaddIrectIon.nthesecond
technIque,whIchtendstobemoreeffectIvebutrequIrescontactofthe(gloved)handwIth
theteethand/orgum,caudadpressureIsapplIedwIththethumbofthedomInanthandon
themandIbularcanIne/bIcuspIdsonthepatIent'ssamesIdewhIlethefIrstfInger,crossed
belowthethumb,applIescephaladpressuretotheIpsIlateralmaxIllarycanIne/bIcuspId.
TheultImategoalofbothtechnIquesIsrotatIonandtranslatIonofthetemporomandIbular
joIntInordertoachIevethewIdestInterIncIsorgap,andrelaxatIonofthemandIbular
space.ThepatIent,whetherconscIousornot,Isnowreadyforlaryngoscopy.
Although0LremaInsthemostusedmethodfortrachealIntubatIon,ItIsfarfromsuccessful
InallcasesandnotalwaysbenIgnwhensuccessful.0LmaybedIffIcultorImpossIbleIn8.5
and1.8ofattempts,respectIvely.
8J
TheanalysIsof0omInoetal.
J2
oftheASAClosed
ClaIms0atabaserevealsthatclaImsforlaryngealInjurydurIng0LarIsemoreoftenIn
easyasopposedtodIffIcultlaryngoscopIes.Amongthe4,460casesIntheASAClosed
ClaIm0atabase,87Instancesoflaryngealtraumawererecorded.Dfthese,80occurred
durIngroutIne(nondIffIcult)trachealIntubatIon,InwhIchnoInjurywassuspected.ThIshas
ledsometoquestIonwhetherroutInetrachealIntubatIonIsassafeasassumed.
J0
Use of the Direct Laryngoscope Blade
ProperuseofthelaryngoscopebladeIsvItaltothesuccessofthIsbasIcaIrway
managementtechnIque.TwobladetypesarecommonlyavaIlableandeachIsapplIedIna
unIquemanner.|anyotherbladeshavebeendescrIbedbutwIllnotbedIscussedhere;the
readerIsdIrectedtosomeexcellentrevIews.
84
Thecurved(|acIntosh)bladeIsusedtopulltheepIglottIsoutofthelIneofsIghtbytensIng
theglossoepIglottIclIgament,whereasthestraIghtblade(|Iller)compressestheepIglottIs
agaInstthebaseofthetongue.8othbladesIncludeaflangealongtheleftsIdeoftheIr
length,whIchIsusedtosweepthetonguetotheleftsIdeofthemouth.8ladeswItharIght
sIdedflangeareavaIlableforthelefthandedpractItIoner,buttheyarenotcommonly
foundInpractIce.
HIstorIcally,choIceoflaryngoscopIcbladehashadatheoretIcalbasIsInaIrway
InnervatIon.TheInternalbranchofthesuperIorlaryngealnerve(abranchofthevagus)
provIdessensoryInnervatIonfromthelevelofthevocalcordstotheundersIdeofthe
epIglottIs.StImulatIonofthesestructures(wIththe|Illerblade)wasbelIevedtocause
morevagallyrelatedreactIons(laryngospasm,bradycardIa,hypertensIon).Thevallecula,
stImulatedbythecurved,|acIntoshbladeIsInnervatedbytheglossopharyngealnerve.
nmostavaIlablesystemsthebladeIncorporatesthelIghtsource,eItherabulbplacednear
thedIstalbladeaspectorarIgIdfIberoptIccablethattransmItslIghtproducedwIthInthe
handle(seethehIstorydIscussIon,earlIerInthIschapter).neIthercase,thesebladesmust
belongenoughtoachIevetheIrrespectIveapplIcatIons.Therefore,bladesIzeneedstobe
chosenapproprIatelyand,onoccasIon,exchangedafterafaIledattemptat0L.Asa
generalIzatIon,the|acIntoshbladeIsregardedasadvantageouswheneverthereIslIttle
roomtopassanETT(e.g.,smallmouth),whereasthe|IllerbladeIsconsIderedbetterIn
thepatIentwhohasasmallmandIbularspace,largeIncIsorteeth,oralargeepIglottIs.
85
ThestraIghtagaInstthetonguenatureofthe|IllerbladeaffordsmaxImaltransferof
workforcefromtheoperator'selbowandshoulderontothesurfaceofthetongueInorder
todIsplaceItIntoasmallmandIbularspace.
WIththelefthandholdIngthelaryngoscopehandle,thebladeIsInsertedIntotherIghtsIde
ofthemouth,wIthcaretakennottocompresstheupperlIpagaInsttheteeth.Astheblade
IsadvancedtowardtheepIglottIs,ItIssweptleftward,usIngtheflangetodIsplacethe
tonguetotheleftasthebladecompressesItIntothemandIbularspace.DncereachIngthe
baseofthetongue(the|acIntoshbladetIpInthevallecula,orthe|Illerblade
compressIngtheepIglottIsagaInstthebaseofthetongue),theoperator'sarmandshoulder
lIftInananterIorandcaudaddIrectIon(FIg.299).
mportantly,thelaryngoscopIstmuststrIvetoavoIdrotatIngthewrIstandlaryngoscope
handleInacephaladdIrectIon,brIngIngthebladeagaInsttheupperIncIsorteeth.
ExtendIngeItherbladestyletoodeeplycanbrIngthetIpofthebladetorestunderthe
larynxItself,sothatforwardpressurelIftstheentIreaIrwayfromvIew.
SpecIalconsIderatIonsapplytothetechnIqueoflaryngoscopyandIntubatIonIntheInfant
andchIld.8ecauseofthe
P.766
relatIvelylargersIzeoftheoccIputInchIldren,producIngananatomIcsnIffIngposItIon,
elevatIonofthehead(asdoneIntheadult)IsnotrequIred.
85
DnoccasIon,onemayneed
toelevatethethoraxInstead.TherelatIvelyshortneckgIvestheImpressIonofananterIor
posItIonofthelarynx.PosterIorcrIcoIdpressureIsoftenrequIredtoplacethelaryngeal
InletIntovIew.AstraIghtbladeIsmorehelpfulIndIsplacIngthestIff,omegashaped,and
hIghepIglottIs.8ecausethecrIcoIdcartIlageIsthenarrowestaspectoftheaIrwayuntIl68
yearsofage,theIntubatormustbesensItIvetoresIstancetoadvancementoftheETTthat
haseasIlypassedthevocalfolds.HyperextensIonattheatlantooccIpItaljoInt,asdoneIn
adult,maycauseaIrwayobstructIonfromtherelatIveplIabIlItyofthetrachea.nthe
chIld,thereIsahIgherrIskofendobronchIalIntubatIonoraccIdentalextubatIonwIthhead
movementowIngtotheshortlengthofthetrachea.
Figure 29-9. A.WhenacurvedlaryngoscopebladeIsused,thetIpofthebladeIs
placedInthevallecula,thespacebetweenthebaseofthetongueandthepharyngeal
surfaceoftheepIglottIs.B.ThetIpofastraIghtbladeIsadvancedbeneaththe
epIglottIs.
WIthlaryngoscopy,thevIewofthelarynxmaybecomplete,partIal,orImpossIble.A
laryngealvIewscorIngsystemthathaswongeneralacceptancewasdevelopedbyCormack
andLehane,
82
whodescrIbedfourgradesoflaryngealvIew.Crade1IncludesvIsualIzatIon
oftheentIreglottIcaperture;grade2IncludesvIsualIzatIonofonlytheposterIoraspectsof
theglottIcaperture;gradeJIsvIsualIzatIonofthetIpoftheepIglottIs;andgrade4Is
vIsualIzatIonofnomorethanthesoftpalate(FIg.2910).ACormackLehanegradeJor4Is
expectedIn1.5to8.5ofadultlaryngoscopIes.
86
ThIssystemhasprovedusefulnotonlyasameansofrecordIngthelaryngealvIewon
IndIvIdualpatIents,butalsoasaclInIcalendpoIntIntheevaluatIonofpreoperatIve
aIrwayassessmentstools.AmodIfIcatIonoftheCormackandLehanescorehasbeen
proposedbyKohetal.,
87
whonotedthatwhenapartIalvocalcordvIew(2A)Is
achIeved,trachealIntubatIonwassIgnIfIcantlyeasIerthanwhenonlythearytenoIdsand
epIglottIswerevIsualIzed(28).
Figure 29-10.TheCormackLehanelaryngealvIewscorIngsystem:grade1(A),grade2
(B),gradeJ(C),andgrade4(D).
DncethelarynxIsvIsualIzedwIthaleftsIdeflangedblade,thetrachealtubeIsInserted
fromtherIghthandsIde,carebeIngtakennottoobstructthevIewofthevocalcords.
WheneverpossIble,theactIonoftheETTpassIngthroughthevocalcordsshouldbe
wItnessedbythelaryngoscopIst.ThetrachealtubeshouldbeInsertedtoadepthofatleast
2cmafterthedIsappearanceofthetrachealtubecuffIntothelarynxInorderto
approxImateplacementInthemIdtrachea.ThIsshouldpresentthe21and2Jcmexternal
markIngsattheteethforthetypIcaladultfemaleandmale,respectIvely.
88
ChoIceofadult
trachealtubesIzemaybemadebythegeneralIzatIonthatforwomen,sIze7to80may
beused,andforamale,sIze8to90.ThelargertrachealtubesmaybedesIrableIf
pulmonarytoIletordIagnostIcortherapeutIcbronchoscopyIstobepartoftheclInIcal
course.PedIatrIclaryngoscopebladesandtrachealtubesIzesarepresentedIndetaIlIn
Table2910(SeealsoChapter45).
AnalternatIveapproachto0LhasbeendescrIbedbyHenderson.
88
nthIsapproachto
tonguedIsplacement,astraIghtbladedlaryngoscopeIsIntroducedIntotherIghtsIdeofthe
mouth.ThebladeIsadvancedbetweenthetongueandpalatInetonsIl.Thebladepasses
belowtheepIglottIs,whIchIsthenelevated.ThIsapproachsubjectsthetonguetoless
compressIveforces.thasbeensuggestedthatthIstechnIquemayImprovethevIewofthe
larynxInthepresenceoflIngualtonsIlhyperplasIa.
7erIfIcatIonofsuccessfultrachealtubeplacementIsmadebyavarIetyofmethods.The
goldstandardforconfIrmatIonofplacementIncludesvIsualIzatIonofplacementthrough
thevocalfoldsandsustaIneddetectIonofexhaledcarbondIoxIdeasmeasuredwIth
capnographyoradIsposablechemIcalcolorImetrIc
P.767
devIcesuchastheEasyCap.DtherportabletechnIquesIncludeauscultatIonoverthe
chestandabdomen,vIsualIzatIonofthechestexcursIon,observatIonofcondensatIonIn
theETT,useofaselfInflatIngbulb(TubeChek8,Ambu,LInthIcum,|0),lIghtedstylets
(TrachlIght,Laerdal|edIcal,Armonk,NY;SurchLIte,Aaron|edIcalndustrIes,St.
Petersburg,FL),andstandardanddedIcatedfIberoptIcdevIcesusedtoIdentIfythe
trachealrIngsandcarIna(FoleyFlexIbleAIrwayStylet,Clarus|edIcal,Colden7alley,|N),
ultrasound,orchestxray.
89
Table 29-10 Size and Length of Tracheal Tubes Relative to Airway
Anatomy
AGE INTERNAL DIAMETER (mm)
DISTANCE FROM LIPS TO MIDTRACHEA
a
(cm)
Premature 2.5 8
Fullterm J.0 10
16mo J.5 11
612mo 4.0 12
2yr 4.5 1J
4yr 5.0 14
6yr 5.5 15
8yr 6.5 16
b
10yr 7.0 1718
C
12yr 7.5 1820
14yr 8.09.0 2022
a
Add2toJcmfornasaltubes.
b
Females.
c
|ales.
NPO Status and the Rapid-Sequence Induction
nductIonofanesthesIaInpatIentswhohavefullstomachsorIncompetent
gastroesophagealsphIncterscanresultInregurgItatIonandpulmonaryaspIratIon.
ndIvIdualsatrIskInclude,pregnantwomen,dIabetIcs,orotherswIthgastroparesIsor
IntestInalobstructIon/Ileus/dIstensIon,uppergastroIntestInaltracthemorrhage,thosewho
requIreemergencyoperatIons,patIentspresentIngfromtheIntensIvecareunIt,patIents
receIvIngacuteopIoIdtherapy,patIentswIthgastroesophagealrefluxdIsease,andpatIents
whohaverecentlyeatenorareexperIencIngnausea.ndIvIdualsexperIencIngemotIonal
stresshaveIncreasedgastrIcacIdsecretIonsandarealsoatanIncreasedrIskfor
aspIratIon.
90
AcompletedIscussIonofthepharmacologIctherapyforaspIratIonprophylaxIs
IsavaIlableelsewhereInthIstext.DbesItybyItself,longtaughtasarIskfactorforgastrIc
contentsaspIratIon,maynotdenotearIskInthIsregard.ThoughInItIalstudIestoutedthe
Increasedvolumeof(more)acIdsecretIonsIntheobesefastIngpatIent,ascomparedwIth
theleancontrol,othershaverefutedthIsclaIm.
91,92
ThetechnIqueofrapIdsequenceInductIonIsperformedtogaIncontroloftheaIrwayInthe
shortestamountoftImeaftertheablatIonofprotectIveaIrwayreflexeswIththeInductIon
ofanesthesIa.ntherapIdsequencetechnIque,theadmInIstratIonofanIntravenous
anesthetIcInductIonagentIsImmedIatelyfollowedbyarapIdlyactIngneuromuscular
blockIngdrug.LaryngoscopyandIntubatIonareperformedassoonasmusclerelaxatIonIs
confIrmed.CrIcoIdpressure(SellIckmaneuver)IsapplIedbyanassIstantfromthe
begInnIngofInductIonuntIlconfIrmatIonofETTplacement.CrIcoIdpressureentaIlsthe
downwarddIsplacementofthecrIcoIdcartIlageagaInstthevertebralbodIes.nthIs
manner,thelumenoftheesophagusIsablated,whIlethecompletelycIrcularnatureofthe
crIcoIdcartIlagemaIntaInsthetracheallumen.EarlycadaverIcstudIesshowedthat
correctlyapplIedcrIcoIdpressurewaseffectIveInpreventInggastrIcfluIdsunder100cm
H
2
DpressurefromleakIngIntothepharynx.Unfortunately,theesophagusIslaterally
dIsplacedInamajorItyofnormalpatIents.
9J
8ecausecrIcoIdpressurefurtherlateralIzes
theesophagus,theadequacyofesophagealablatIonhasbeenquestIoned.CrIcoIdpressure
IscontraIndIcatedwIthactIvevomItIng(rIskofesophagealrupture),cervIcalspIne
fracture,andlaryngealfracture.HIstorIcallyfacemaskventIlatIonIsnotundertakenfor
the40to90secondsoftImerequIredtoachIeveadequateneuromuscularrelaxatIon.ThIs
practIceIsbasedonmInImaldataandhasrecentlybeenquestIoned.
fdurIngrapIdsequenceInductIontherearedIffIcultIesInsecurIngtheaIrwayand
oxyhemoglobIndesaturatIonoccurs,gentleposItIvepressureventIlatIonmaybeusedwhIle
maIntaInIngcrIcoIdpressure.ThIsposItIvepressureshouldrequIre25cmH
2
Dpressure.
Someauthorsarguethat,becausecrIcoIdpressureIsofdubIouseffIcacyandmaydIstort
thelaryngoscopIstvIew,ItbereleasedIfdIffIcultIesareencountereddurIngtheIntubatIon
attempt.
94
The Intubating Laryngeal Mask Airway (LMA Fastrach)
8lInd,fIberoptIcaIded,styletguIded,andlaryngoscopydIrectedtrachealIntubatIonvIa
theL|AhasbeenwIdelyreportedInadultsandchIldren.|anylImItatIonstothIstechnIque
havebeendescrIbed.nanefforttoovercometheselImItatIons,8raInetal.
95
Introduceda
versIonoftheL|AwIthalargedIameter(1Jmm0),shortlength(14cm),rIgIdstaInless
steelbarrelcurvedtoalIgnthemaskaperturetotheglottIcvestIbule(FIg.29J).
TheL|AFastrach(Laryngeal|askCompany,Jersey,UK)maskIncorporatesavertIcally
orIented,semIrIgIdbarfIxedattheproxImalendofthebowlapertureandposItIonedtosIt
beneaththeepIglottIsIntheaverageadult.AhandleattheproxImalendofthebarrelIs
usedforInsertIon,reposItIonIng,andremoval.AsecondaryadvantageofthehandleIsthat
theoperatorneverneedstoplacefIngersIntothepatIent'smouth.TheL|AFastrach
barrelcanaccommodateuptoan8.0mm0cuffedETT,whIchcanbeInsertedblIndlyor
overafIberscopeorotherstyletdevIce.TheL|AFastrachIsdesIgnedtobeusedwItha
straIghttrachealtubemanufacturedInbothsIngleandmultIpleusemodels(EuromedIcs,
Kedah,|alaysIa),althoughstandardorParkerFlexTIp(Parker|edIcal,Englewood,CD)
polyvInylchlorIdetrachealtubeshavebeenused.
96
P.768
TheL|AFastrachIsavaIlableInadultsIzeswIthcuffsequIvalenttothesIzeJ,4,and5
L|As.ExperIencehassuggestedthatmostadultsbetween40and70kgarebestmanaged
wIthasIze4L|AFastrach;largerpersonsrequIrethesIze5.
TheL|AFastrachIsIndIcatedforroutIne,electIveIntubatIonsandforantIcIpatedand
unantIcIpateddIffIcultIntubatIons.8ecauseItwasdesIgnedtofacIlItateblIndtracheal
IntubatIon,thepresenceofaIrwaysecretIons,blood,oredema(e.g.,fromprevIous
IntubatIonattemptsortrauma)doesnotInterferewIthItsuse.8ecausethedesIgnofthe
barrelIsbasedonthenormaladultpalatetoglottIsrelatIonshIp,patIentswhoare
evaluatedasbeIngmanageablewIthtrachealIntubatIonby0Lbasedonexternal
examInatIon,butsubsequentlyarefoundtohaveahIghCormackLehanescore(e.g.,
becauseoflIngualtonsIlhyperplasIaorcervIcalspIneImmobIlIty)shouldbesuccessfully
managedwIththeL|AFastrach.
82
nalargetrIaloftheL|AFastrach,ventIlatIonwas
satIsfactoryIn95andunsatIsfactoryIn1of500uses,and96ofpatIentswereIntubated
wIthInthreeattempts(79.8onfIrstattempt,12.4onsecond,4onthIrd).
97
PatIents
whoareassessedasgrosslyabnormalonpreoperatIveaIrwayexamInatIonmayoftenstIll
bemanagedwIththeL|AFastrach.TheL|AFastrachhasbeendemonstratedtobeuseful
asaventIlatoryandIntubatIngdevIceafterfaIledrapIdsequenceIntubatIon.
98
AlargestudyhasshowntheutIlItyoftheL|AFastrachInpatIentswhowereantIcIpatedas
wellasunantIcIpatedtobedIffIculttoIntubate.Fersonetal.
99
successfullyIntubated2J4
patIentsoveraJyearperIodusIngtheL|AFastrach.StudIedpatIentsIncludedthosewIth
normalappearIngaIrwaysonroutIneexamInatIonwhoseaIrwayswereunexpectedly
dIffIculttomanage,patIentswIthaCormackandLehanelaryngealvIewgrade4on
laryngoscopIcexamInatIon,patIentswIthImmobIlIzedortraumatIzedcervIcalspInes,and
patIentswIthaIrwaytumors,prIoraIrwaysurgery,orradIatIon.SuccessfulblIndIntubatIon
vIatheL|AFastrachoccurredIn97ofpatIents;theremaInIngpatIentIntubatIonswere
facIlItatedwIthadjunctuseofafIberoptIcIntubatIonscope.AnewdesIgnoftheL|A
Fastrach,theCTrach(FIg.29J),IntroducedIn2004,IncorporatesafIberoptIccableand
monItorIntotheL|AFastrachdesIgn(dIscussedlater).
ContraIndIcatIonstotheuseoftheL|AFastracharesImIlartothoseoftheL|A.8ecause
theendpoIntofL|AFastrachprocedureIstrachealIntubatIon,Itmayproveusefulforthe
managementofpatIentsatmoderaterIskforgastroesophagealregurgItatIonand
aspIratIon,orforhIghrIskpatIentsonwhomothertechnIqueshavefaIled.
TheL|AFastrachIsInsertedwIththeheadInaneutralposItIon.tcanbeusedInthe
unconscIousorawakepatIent(wIththeuseoftopIcalanesthetIcs).ThemaskoftheL|A
FastrachIstested,deflated,andlubrIcatedasdescrIbedfortheL|A.tIsInsertedIntothe
mouth,wIththehandleheldparalleltothechest,sothemasklIesflatagaInstthepalate.
CentlepressureonthehandleandbarrelreproducesthepalatalpressuredescrIbedfor
InsertIonoftheL|A.AsmoothbackwardrotatIonofthehandletowardthetopofthehead
seatsthetIpofthemaskInthehypopharynx,posterIortothecrIcoIdcartIlage.Dnce
seated,themaskoftheL|AFastrachIsInflatedvIathepIlotcuff.AnAmbubagor
anesthesIacIrcuItIsattachedtotheproxImalendoftheL|AFastrachbarreland
ventIlatIonIsattempted.8yusIngtheL|AFastrachhandle,theposItIonofthedevIcecan
beoptImIzedbylateralandanterIorposterIormanIpulatIon.ThIsactIonIstermedthe
Chandy maneuver(after0r.Chandy7erghese,FeddIngUnItedKIngdom).AseemIngly
commoncauseofaIrwayobstructIonwIththeL|AFastrachIsthedownfoldIngofthe
epIglottIs.ThIscanberelIevedwIthasmoothrotatIonalmovementoftheInflatedL|A
FastrachoutoftheaIrway(6cmalongtheaxIsoftheInsertIon)whIlethecuffremaIns
Inflated,andImmedIatereplacement(theupdownmaneuver).
AfteradequateventIlatIonIsachIeved,theETTIsadvancedthoughthebarrel.AstheETT
exItsthebowlapertureoftheL|AFastrach,thesemIrIgIdelevatIngbarIspushed
anterIorly,carryIngtheepIglottIsoutofthewayoftheaIrway.fposItIonedcorrectly,the
ETTcanfreelyentertheglottIs.
ThesecondpartoftheChandymaneuvermayfacIlItateblIndtrachealIntubatIon.nthIs
maneuverthehandleIsusedtogentlylIft(wIthoutrotatIon)theL|AFastrachanterIorly,
sealIngthebowlagaInstthelarynx.
WhenblIndIntubatIonfaIls(esophagealInsertIonorobstructIon)severalmaneuversare
undertaken.
99
EarlyobstructIonIstypIcallycausedbyadownfoldedepIglottIs.Anupdown
maneuver,asdescrIbedearlIer,canbeemployedandtrachealIntubatIonattempts
repeated.EarlyresIstancemayalsosIgnIfyvallecularentrapmentsecondarytotoolarge
anL|AFastrachsIze.TheoperatormayremovetheL|AFastrachandplaceasmaller
sIzedone.LaterobstructIonmaysIgnIfyentrapmentortoosmalladevIce,andagaIn,a
changeIsIndIcated.
WhenIntubatIonfaIlsdespItetheChandyorupdownmaneuvers,orachangeIntheL|A
FastrachsIze,theclInIcIanshouldrecallthattheL|AFastrachIsaventIlatIondevIcefIrst!
TypIcally,ventIlatIonwIllbeadequatedespItefaIluretoIntubate.AtthIsjuncturethe
clInIcIancan(1)contInuewIthshortsurgIcalproceduresusIngtheL|AFastrachasasImple
SCA(procedureslongerthan15mInutesmaybeIlladvIsedbecauseofthepressureexerted
bytheL|AFastrachontIssues),(2)changetoanotherL|AdevIce,(J)dIagnosethe
IntubatIonImpedImentwIththeaIdofanotherdevIce(e.g.,fIberoptIcbronchoscopeor
FoleyFlexIbleAIrwayStylet),(4)removetheL|AFastrachandemploy0Loranother
technIqueoftrachealIntubatIon,or(5)IntheresuscItatIvesItuatIon,performasurgIcal
aIrwaywhIlecontInuIngventIlatIonwIththeL|AFastrach.ThIslastproceduremaybean
underapprecIatedfacIlItyofalltheSCAs.ThesedevIcesmayserveasabrIdgewhIle
InvasIveaIrwayproceduresareperformed.
DnceIntubatIonIsachIevedandconfIrmed(e.g.,byauscultatIonorcapnography),theETT
cIrcuItadapterIsremovedandtheL|AFastrachIswIthdrawnovertheETT.0urIngthIs
removalprocedure,theETTIsstabIlIzedbyoneoftwomethods.AsIlIconestabIlIzIngrod
(supplIedbythemanufacturer)canbeheldagaInsttheETTastheL|AFastrachIs
retreatedoutofthemouth.nthesecondtechnIque,descrIbedbyFosenblattand
|urphy,
98
a|agIllforcepsIsusedtoholdtheproxImaltIpoftheETTwhIletheL|A
FastrachIsremoved.nthemIdremovalposItIon,afIngerIsplacedInthemouthto
IdentIfyandstabIlIzetheETT,whIlethe|agIllforcepsIsremovedandtheL|AFastrachIs
fullyretreated.
LMA CTrach
TheL|ACTrach(TheLaryngeal|askCompany,8ucks,UK)IsfunctIonallyIdentIcaltothe
IntubatIngL|AFastrach,wIththeaddItIonofIntegratedfIberoptIcchannels(Imageand
lIghtsource)andabatterypoweredmonItorattachedtotheproxImalaIrwaytubevIaa
magnetIclatchconnector,whIchprovIdesavIewoflarynxtofacIlItatetrachealIntubatIon
(FIg.29J).AUS8(unIversalserIalbus)portonthemonItorallowsthevIdeostreamtobe
recordedonapersonalcomputer.8oththeCTrachandL|AFastrachpermItventIlatIon
betweenIntubatIonattempts.
TherearereportsofpatIentswIthknownorunexpecteddIffIcultaIrwayswhowere
successfullyIntubatedvIaCTrachundergeneralanesthesIa.
100,101,102,10J,104
Eventhough
successfulventIlatIonwIththeCTrachIsrelIablyachIeved,InItIalglottIcvIewsareless
certaIn.
105,106
CausesofpoorCTrachvIewareadownfoldIngepIglottIs(57),obstructIon
bythearytenoIds(7),andsecretIons(5).
107
|aneuverstoImprovethevIewIncludethe
Chandymaneuvers,updownmaneuver,bImanual
P.769
mandIbularelevatIon,andmedIallateralmedIalrotatIon.Thesemaneuversallowthe
operatortoseetheglottIsIn80ofcases.
106,107
DverallIntubatIonsuccessrateIsabout
97,
105,106,107
whIchIssImIlartothatoftheL|AFastrach(96.5).
99
Theprocessof
IntubatIonwIththeCTrachIslongerthan0L(57vs.J0seconds)
,
butItprovIdesbetter
oxygenatIonInmorbIdlyobesepatIentscomparedwIth0L.
108
AwakeIntubatIonwIththe
CTrachInthreecasesofunstablecervIcalspIne
109
andthreemorbIdlyobesepatIentswIth
obstructIvesleepapnea
110
hasbeenreported.
Extubation of the Trachea
AlthoughawealthoflIteratureIsfocusedonthefIeldoftrachealIntubatIon,fewrevIews
haveIntenselycontemplatedtheareaofextubatIonaftercompletIonofsurgeryor
prolongedventIlatorysupport.ndeed,theperIodofextubatIonmaybefarmore
treacherousthanthatofIntubatIon(Table29.11,sectIonA).
Routine Extubation
ExtubatIonofthetracheamustnotbeconsIderedabenIgnprocedure.tIsnotsImplythe
elImInatIonorreversaloftrachealIntubatIon.ExtubatIonIsfraughtwIthItsownsetof
potentIalcomplIcatIons(Table2911,sectIon8).ApproprIatelytraInedpersonneland
equIpmentshouldbeImmedIatelyavaIlableatthetImeofextubatIon.ThIsmayrangefrom
apostanesthetIccareunItnurseorrespIratorytherapIstwIthasetoflaryngoscopestoa
surgeonpreparedtoperformanemergencytracheostomy.
Table 29-11 Tracheal Extubation
A. Causes of Ventilatory Compromise During Tracheal Extubation
FesIdualanesthetIc
PoorcentralrespIratoryeffort
0ecreasedrespIratoryrate
0ecreasedrespIratorydrIveInresponsetoCD
2
0ecreasedrespIratorydrIveInresponsetoD
2
FeducedtoneofupperaIrwaymusculature
Feducedgagandswallowreflex
0ecreasedthresholdtolaryngospasm
SurgIcalaIrwaycompromIse
SurgIcalaIrwayedema
7ocalcordparalysIs
ArytenoIdcartIlagedIslocatIon
SupraglottIcedemawIthaIrwayobstructIonbytheepIglottIs
FetroarytenoIdedemawIthlImItedvocalfoldabductIon
SubglottIcedema
TracheomalacIa(fromlongstandIngtrachealIntubatIon)
8ronchospasm
B. Complications of Tracheal Extubation
FespIratorydrIvefaIlure
HypoxIa(e.g.,atelectasIs)
UpperaIrwayobstructIon(e.g.,edema,resIdualanesthetIc)
7ocalfoldrelatedobstructIon(e.g.,vocalcordparalysIs)
TrachealobstructIon(e.g.,subglottIcedema)
8ronchospasm
AspIratIon
HypertensIon
ncreasedIntracranIalpressure
ncreasedpulmonaryarterypressure
ncreasedbronchIalstumppressure(e.g.,afterpulmonaryresectIon)
ncreasedocularpressure
ncreasedabdomInalwallpressure(e.g.,rIskofwounddehIscence)
Table 29-12 Criteria for Routine Awake Extubation
SubjectIveClInIcalCrIterIa
Followscommands
Clearoropharynx/hypopharynx(e.g.,noactIvebleedIng,secretIonscleared)
ntactgagreflex
SustaInedheadlIftfor5seconds,sustaInedhandgrasp
AdequatepaIncontrol
|InImalendexpIratoryconcentratIonofInhaledanesthetIcs
DbjectIveCrIterIa
7ItalcapacIty:10mL/kg
PeakvoluntarynegatIveInspIratorypressure:20cmH
2
D
TIdalvolume6cc/kg
SustaInedtetanIccontractIon(5sec)
T
1
/T
4
ratIo0.7
AlveolararterIalPao
2
gradIent(onFD
2
of1.0):J50mmHg
a
0eadspacetotIdalvolumeratIo:0.6
a
a
UseddurIngweanIngfrommechanIcalventIlatIonIntheIntensIvecaresettIng.
|ostadultpatIentsareextubatedafterthereturnofconscIousnessandspontaneous
respIratIon,theresolutIonofneuromuscularblock,andtheabIlItyofthepatIenttofollow
sImplecommands(Table2912).ThepatIentIsaskedtoopenthemouth,andasuctIon
catheterIsusedtoremoveexcessIvesecretIonsand/orblood.TheaIrwaypressureIs
allowedtorIseto5to15cmofH
2
DtofacIlItateapassIvecough,andtheETTIsremoved
afterthecuff(Ifpresent)Isdeflated.
85
fcoughIngorstraInIngIscontraIndIcatedor
hazardous(e.g.,IncreasedIntracranIalpressure),extubatIonmaybeperformedwhIlethe
patIentIsInasurgIcalplaneofanesthesIa.npatIentsatrIskforgastrIccontents
aspIratIon(e.g.,fullstomach)orupperaIrwayobstructIon,theclInIcIanneedstoassessthe
relatIverIskofeachpotentIalmorbIdIty(e.g.,coughIngvs.obstructIon).|urphyetal.
111
foundthatstandardclInIcalcrIterIaforadequacyofneuromuscularreversalsuchas5
secondheadlIftorhandgrIp,eyeopenIngoncommand,negatIveInspIratoryforcemore
than20cmH
2
D,orvItalcapacItybreathof15cc/kgdoesnotalwaysrepresent
acceptableneuromuscularrecovery.FIftyeIghtpercentofpatIentsInwhomstandard
clInIcalcrIterIawasachIevedhadatraInoffourratIoof0.7and88hadatraInoffour
ratIoof0.9.ToreducetherIsksofstraInIng/coughIng,amaneuverhasbeendescrIbedIn
whIchanL|AIsplacedposterIortotheETT,whIchIsthenremoved.ThIsobvIatesthe
problemofupperaIrwayobstructIon,andmayoffersomeprotectIonagaInstregurgItatIon
andaspIratIon.
47,112
8ecauseoftherIsksofatelectasIsanddIffusIonhypoxIa,theabIlItyto
admInIsteroxygenshouldbeavaIlableatthetImeofextubatIon.
Difficult Extubation
ThepatIentwhopresentedashavIngadIffIcultaIrwayatthetImeofanesthetIcInductIon
mustbeconsIderedashavIngadIffIcultaIrwayatthetImeofextubatIon,evenwhen
correctIvesurgerywasperformedIntheInterIm(e.g.,uvulopalatoplastyIntheobstructIve
sleepapneapatIent).
LaryngospasmatextubatIondeservesspecIalattentIonbecauseofItprevalenceInchIldren
andbecauseItaccountsfor2JofallcrItIcalpostoperatIverespIratoryeventsInadults.
85
LaryngospasmmaybetrIggeredbyrespIratorysecretIons,vomItus,blood,oraforeIgnbody
IntheaIrway;paInInany
P.770
partofthebody;andpelvIcorabdomInalvIsceralstImulatIon.ThecauseofaIrway
obstructIondurInglaryngospasmIsthecontractIonofthelateralcrIcoarytenoIds,the
thyroarytenoId,andthecrIcothyroIdmuscles.|anagementoflaryngospasmconsIstsofthe
ImmedIateremovaloftheoffendIngstImulus(IfIdentIfIable),admInIstratIonofoxygen
wIthcontInuousposItIveaIrwaypressure,andIfothermaneuversareunsuccessful,theuse
ofasmalldoseofshortactIngmusclerelaxants.
85
NegatIvepressurepulmonaryedemamayresultfromanyaIrwayobstructIonInapatIent
whocontInuestohaveavoluntaryrespIratoryeffort.NegatIveIntrathoracIcpressureIs
transmIttedtothealveolI,whIchareunabletoexpandowIngtothemoreproxImal
obstructIon.FluIdIsentraInedfromthepulmonarycapIllarybed.NegatIvepressure
pulmonaryedemaIstreatedasanyotherformofnoncardIogenIcedema.
Identification of Patients at Risk at Extubation
AnumberofwellknownclInIcalsItuatIonsmayplacepatIentsatIncreasedrIskfor
complIcatIonatthetImeofextubatIon(Table291J).However,theclInIcIanshould
evaluateeverypatIentIntermsofpotentIalforproblems,Inthesamemannerthatthe
anesthesIologIstpreparesfortheunantIcIpateddIffIcultIntubatIon.
Approach to the Difficult Extubation
WhenthereIsasuspIcIonthatapatIentmayhavedIffIcultywIthoxygenatIonor
ventIlatIonaftertrachealextubatIon,theclInIcIanmaychoosefromanumberof
managementstrategIes.ThesemayrangefromthepreparatIonofstandbyreIntubatIon
equIpmenttotheactIveestablIshmentofabrIdgeorguIdeforreIntubatIonand/or
oxygenatIon.WhenthepatIent'sIntubatIonIswIthoutdIffIcultyandthereIsnosubstantIal
reasontobelIevethatanInterImInsulttotheaIrwayhasoccurred,extubatIonmaybe
accomplIshedInaroutInefashIon,wIthaheIghtenedstateofreadInessforreIntubatIon.
WhentherehasbeendIffIcultywIthIntubatIonorthereIsaclInIcalsuspIcIonthat
reIntubatIonwIllbedIffIcult,extubatIonoveraguIdIngstyletmaybeasuccessful
technIque.AnynumberofdevIcescanbeusedasastylet(Table2914).
ApopulartestusedtopredIctpostextubatIonaIrwaycompetencyIsthedetectIonofaleak
ondeflatIonoftheETTcuff.ArecentInvestIgatIonhascastdoubtontherelIabIlItyofthIs
testasapredIctorofaIrwayIncompetence:theabsenceofanaIrwayleakoncuffdeflatIon
wasnotpredIctIveofsubsequentventIlatoryfaIlureafterextubatIon.
11J
PatIentswItha
reducedcuffleakvolumeareatrIskforpostextubatIonstrIdor.
114
ArandomIzedcontroltrIalstudyIn2007revealedthatmultIpledosedexamethasone
effectIvelyreducedIncIdenceofpostextubatIonstrIdorInadultpatIentsathIghrIskfor
postextubatIonlaryngealedemawhIlesIngledoseInjectIonofdexamethasonegIven1hour
beforeextubatIondIdnotreducethenumberofpatIentsrequIrIngreIntubatIon.
115
AfIberoptIcbronchoscopemaybeusedtovIewthetrachealstructuresdurIngtheremoval
oftheETT.fextubatIonIstolerated,thefIberoptIcbronchoscopecanbeslowlywIthdrawn
IntothesubglottIcregIon.fsecretIonsdonotobstructtheobjectIvelens,thevocalfolds
andotherstructuresmaybevIsualIzedandevaluated.
AnumberofobturatorsareavaIlableforuseIntrIalextubatIon(wheretheymaybeleftIn
placeIntheaIrwayforextendedperIods)orETTexchange(e.g.,faIlureoftheETTcuff).
|ort
116
foundthatthesuccessoffIrstpassreIntubatIon
P.771
wassIgnIfIcantlyhIgher,andtheIncIdenceofhypoxIalower,InpatIentswItharetaIned
trachealtubeexchangecatheter.
Table 29-13 Clinical Situations Presenting Increased Risk for Complications
at Extubation
a
ParadoxIcalvocalcord
motIon(preexIstIng) PoorlyunderstoodmechanIsm
ThyroIdsurgery 4.JrecurrentlaryngealnerveInjury
Localedema
TracheomalacIa(fromlongstandInggoIter)
Laryngoscopy
(dIagnostIc)
Edema,laryngospasm,especIallywIthbIopsy
Uvulopalatoplasty Palatalandoropharyngealedema
DbstructIvesleepapneasyndrome(uncorrected)
CarotIdendarterectomy Woundhematoma,glottIcedema,nervepalsIes
|axIllofacIaltrauma
Laryngealfracture,reducedlevelofconscIousness,
requIrementsformandIbular/maxIllarywIres
CervIcalvertebrae
decompressIon
ParkInsondIsease
FheumatoIdarthrItI
SupraglottIcandhypopharyngealedema
CeneralIzededema LaryngotrachealnarrowIng
AngIoneurotIcedema LaryngotrachealnarrowIng
AnaphylaxIs LaryngotrachealnarrowIng
Hypopharyngeal
InfectIons
LaryngotrachealnarrowIng
HypoventIlatIonsyndromes
a
HypoxemIcsyndromes
b
nadequateaIrway
protectIvereflexes
AspIratIonrIsk
a
FesIdualanesthetIcorpreoperatIvemedIcatIons(IncludIngalcoholandIllIcIt
drugs),centralsleepapnea,carotIdendarterectomy,polIomyelItIs,CuIllaIn8arr
syndrome,myasthenIagravIs,botulIsm,thoracIcskeletaldeformIty,severepaIn
(wIthdIaphragmatIcsplIntIng),morbIdobesIty,severechronIcobstructIve
pulmonarydIsease.
b
HypoventIlatIon,ventIlatIonperfusIonmIsmatch,IntracardIacorIntrapulmonary
shuntIng,IncreasedoxygenconsumptIon,severeanemIa,ImpaIredalveolaroxygen
dIffusIon.
Table 29-14 Devices Used as Extubating Stylets
DEVICE ADVANTAGE DISADVANTAGE
FIberoptIc
bronchoscope
7IsualIzestructures
Dxygencanbe
Insufflated
ETTcannotbeexchanged
Eschmanncatheter nexpensIve,semIrIgId CannotvIsualIze/oxygenate
Exchangecatheter
Dxygencanbe
Insufflated
CannotvIsualIze,maybeto
short
tIsbeyondthescopeofthIstexttodescrIbeallthecommercIallyavaIlablecatheters.The
CookAIrwayExchangeCatheters(CookCrItIcalCare,8loomIngton,N)aremanufactured
wIthexternaldIametersof2.7,J.7,4.7,and6.JJmm.ThesmallestdIametercatheter
(whIchcanfItwIthInaJ.0mm0ETT)Is45cmlong,whereastheothersare8JcmIn
length.Theyallhaveacentrallumenandrounded,atraumatIcends.Thecathetersare
graduatedfromthedIstalend.TheproxImalendIsfIttedwItheIthera15mmoraLuer
lockFapIFItadapter,whIchcanbequIcklyremovedandreplacedforETTremovalor
exchange.WIththeseadaptersanoxygensourcecanbeusedtoprovIdeInsufflatedorjet
ventIlatedoxygenIfthepatIentfaIlsextubatIonand/orIfreIntubatIonoverthecatheter
faIls.
TheCardIo|edendotrachealventIlatIoncatheter(Cromley,DntarIo,Canada)desIgnedby
FIchardCooper,|0,aCanadIananesthesIologIst,Is85cmInlengthandhasInnerand
outerdIametersofeItherJor4mm.AnIntegralLuerlockfIttIngadapterIsfoundatthe
proxImalend,whereastheblunteddIstalendIncorporateseIghthelIcallyarrangedsIde
holesInaddItIontothedIstalendhole.ThearrangementoftheseholesIsmeanttocenter
thecatheterdurIngoxygenInsufflatIonandpreventtraumatIcwhIppIngwIthInthe
trachea.TheuseofthIscatheterforETTexchange,trachealreIntubatIon,oxygen
InsufflatIon,jetoxygenatIon,andendtIdalCD
2
detectIonafterextubatIonhasbeen
documentedbytheInventor.
85
Figure 29-11.TheAmerIcanSocIetyofAnesthesIologIsts0IffIcultAIrwayAlgorIthm.A.
AwakeIntubatIon.B.ntubatIonattemptsafterInductIonofanesthesIa.
UseofhIghpressureoxygenInsufflatIonvIaanexchangecathetercausIngbIlateral
pneumothoraxhasbeenreported.
117
The Difficult Airway
The Difficult Airway Algorithm
n199JtheASATaskForceonthe0IffIcultAIrwayfIrstpublIshedanalgorIthmthathas
becomeastapleofmanagementforclInIcIans.ThIsalgorIthmwasreIssuedIn200J.
1
AswIll
bedIscussed,themostdramatIcchangeIntheASA0IffIcultAIrwayAlgorIthm(ASA0AA)
wasthereposItIonIngoftheL|AfromtheemergencytotheroutInemanagementpathway
(FIg.2911).TheASAdefInesthedIffIcultaIrwayasthesItuatIonInwhIchthe
conventIonallytraInedanesthesIologIstexperIencesdIffIcultywIthIntubatIon,mask
ventIlatIonorboth.8asedonavaIlabledata,theIncIdenceofdIffIcultIntubatIonby0LIs
4.5to7.5,whereastheIncIdenceoffaIledIntubatIon/InabIlItytoperformmask
ventIlatIonIs0.01to0.0J.
12
TheASAalgorIthmstandsasamodelfortheapproachtothedIffIcultaIrwayfornurse
anesthetIsts,emergencymedIcInephysIcIans,andprehospItalpersonnel,aswellasfor
anesthesIologIsts.AlthoughthealgorIthmlargelyspeaksforItself,ItssalIentfeaturesare
dIscussedhere.DnestatementInthIsdocument
P.772
summarIzesthedIffIcultyofwrItIngandrecommendIngpractIcesInthedIffIcultaIrway
management:ThedIffIcultaIrwayrepresentsacomplexInteractIonbetweenpatIent
factors,theclInIcalsettIngandtheskIllsofthepractItIoner.
1
tshouldbewellrecognIzed
thatthoughtheASA0AAIsastapleIntheUnItedStatesandmuchoftheworld,several
groupsworldwIdehavewrIttentheIrownaIrwayalgorIthmsemphasIzIngtechnIquesand
approachesnatIvetotheIrpractIce.AlthoughthedIfferencesInthesealgorIthmswIllnot
bedIscussedhere,thereaderIsencouragedtoexploretheseImportantalternatIve
approaches.
86,118,119,120,121,122
EntryIntothealgorIthmbegInswIththeevaluatIonoftheaIrway.AlthoughthereIssome
debateastothevalueofpartIcularevaluatIonmethodsandIndIces,theclInIcIanmustuse
allavaIlabledataandhIsorherownclInIcalexperIencetoreachageneralImpressIonas
tothedIffIcultyofthepatIent'saIrwayIntermsoflaryngoscopyandIntubatIon,
supraglottIcventIlatIontechnIques,aspIratIonrIsk,orapneatolerance.
ThIsevaluatIonshoulddIrecttheclInIcIantoentertheASA0AAatoneofItstworoot
poInts:awakeIntubatIon(FIg.2911A)orIntubatIonattemptsaftertheInductIonofgeneral
anesthesIa(FIg.29118).ThIshIghlIghtsthemIsnomerofthealgorIthm:ItIsnotonlyfor
dIffIcultaIrways,butIsrelevanttoallInstancesInwhIchtheaIrwayIsmanaged.FIgure29
118descrIbestheapproachtakenInthemajorItyoftrachealIntubatIons(andIsapplIcable
tofacemaskandSCAmanagedpatIents).ThedecIsIontoenterthealgorIthmvIaeIther
approachIsapreoperatIveone.8oxA(FIg.2911)IschosenwhendIffIcultyIsantIcIpated
thatwIllplacethepatIentatjeopardy,whIlebox8IsforthesItuatIonInwhIchtheremay
beantIcIpateddIffIcultywItheItherventIlatIonortrachealIntubatIon,butan
uncorrectablesItuatIonIsnotexpected.ThIshasbeenfurtherdelIneatedIntoa
preoperatIvedecIsIontreebyFosenblatt
J
:theaIrwayapproachalgorIthm(AAA).FIgure29
12outlInestheAAA,whIchIsssImpleonepathwayalgorIthmforenterIngIntotheASA
0AA.8ranchchoIce,lIketheprevIouslynotedstatementfromtheASApractIceguIdelInes,
IshIghlydependentontheclInIcIan'sskIllandexperIence.0etaIlsoftheAAAcanbefound
elsewhereandaresummarIzedhere.
J,12J
Figure 29-12.TheAIrwayApproachAlgorIthm:adecIsIontreeapproachtoentryInto
theAmerIcanSocIetyofAnesthesIologIsts0IffIcultAIrwayAlgorIthm.TTJ7,
transtrachealjetventIlatIon.
1. saIrwaycontrolnecessary:NomatterhowroutInesedatIonorgeneralanesthesIa
become,whetherornottomakeapatIentapneIcshouldalwaysbeconsIderedserIously
andalternatIvesshouldbecontemplated.
2. CouldtrachealIntubatIonbe(atall)dIffIcult:fthereIsnoIndIcatIonthatrapIdtracheal
IntubatIonby0L,In0L(e.g.,vIdeolaryngoscopyorothermeansfamIlIartotheoperator)
wIllbedIffIcult,theclInIcIanmayproceedwIthanytechnIque(InductIon,0L,L|A,and
soforth)asclInIcallyapproprIate.ThIsIstheessenceofbox8oftheASA0AA
(prototypIcalcase:rapIdsequenceInductIon).fthereIsanIndIcatIon,basedonhIstory
orphysIcalexamInatIon,thattheremaybedIffIcultywIthrapIdtrachealIntubatIon,the
AAAIsfollowedtothenextquestIon.8ychoosIngtocontInuedownthealgorIthm,the
clInIcIanIsnotassumIngtrachealIntubatIondIffIculty,ratherheorsheIsantIcIpatIng
thevIabIlItyofrescuemaneuversshoulddIffIcultlyoccur.
J. CanSCAventIlatIonbeusedIfneeded:ftheclInIcIanthInksthatthereIsaphysIcal
reasonthatSCAventIlatIon(byfacemask,L|A,orotherdevIce)couldbedIffIcult,heor
sheIsprojectIngthepossIbIlItythatajunctureofcannotIntubate(questIon2)cannot
ventIlate(questIonJ)couldbereached.8ecausethIsIsapreoperatIvealgorIthm,boxA
oftheASA0AAmaybethepreferredrootentrypoInt.
4. sthereanaspIratIonrIsk:AsdIscussedearlIer,thepatIentatrIskforaspIratIonIsnota
candIdateforelectIveSCAuse.8ecausetheAAAIsapreoperatIvealgorIthm,and
thereforeallowstheluxuryofdIscretIonarypaths,thejunctureofcannot
Intubate/shouldnotventIlatecanbeavoIdedbyenterIngtheASA0AAatboxA.
5. WIllthepatIenttolerateanapneIcperIod:QuestIonJIsdIffIculttoanswerandIshIghly
dependentontheskIllsandexperIenceoftheclInIcIan.ShouldIntubatIonfaIl,andSCA
ventIlatIonIsInadequate,thepatIent'sabIlItytosustaInoxygensaturatIonwIlldIctate
theabIlItytotolerateanapneIcperIod.Factorssuchasage,pregnancy,pulmonary
status,abnormaloxygenconsumptIon(e.g.,fever),andchoIceofInductIonagentswIll
InfluencethIs.ftImetooxyhemoglobIndesaturatIonIslImIted(lImItedtImetocorrect
hypoxemIa),boxAmaybeprophylactIcallychosen.
6. CanhypoxIaberapIdlycorrectedthroughothermeans:TranstrachealjetoxygenatIon
wIllbedIscussedlaterInthIschapter.ThequestIonthatarIseshereIswIthaccesstothe
patIent'santerIortrachea,theavaIlabIlItyofequIpmentandknowledgeablepersonnel,
andtheexperIenceoftheoperator.Forexample,IfanerrorInjudgmentIsmadeand
theoperatorfIndshImselforherselfInacannotIntubate/cannotventIlatescenarIo,wIll
thesecondItIonsallowforusIngtranstrachealjetventIlatIon(TTJ7)totemporIzethe
sItuatIon.AllcondItIonsmayberIght,butIfthepatIentIsmorbIdlyobeseorhashad
scarrIngorradIatIonoverthelarynx/trachea,thIsoptIonmaynotbeavaIlable.
ThesefactorshavebeendIscussedIndetaIlelsewhere.
J,12J
ToIllustratetheclInIcal
applIcatIonoftheAAA,thepaththroughthIsalgorIthmwIllbetracedfortheclInIcal
scenarIosattheendofthIschapter.
TheexceptIontotheAAAIsthepatIentwhoIsunabletocooperateowIngtomental
retardatIon,IntoxIcatIon,anxIety,depressedlevelofconscIousness,orage.ThIspatIent
maystIllbeapproachedbyboxA(FIg.2911),butawakeIntubatIonmayneedtobe
modIfIedInfavoroftechnIquesthatmaIntaInspontaneousventIlatIon(e.g.,InhalatIon
InductIon).
PreparatIonofthepatIentforawakeIntubatIonIsdIscussedlater.nmostInstances,awake
IntubatIonIssuccessfulIfapproachedwIthcareandpatIence.WhenawakeIntubatIonfaIls,
theclInIcIanhasanumberofoptIons.FIrst,onecanconsIdercancellatIonofthesurgIcal
case.nthIssItuatIon,
P.77J
specIalIzedequIpmentorpersonnelcanbeassembledforareturntotheoperatIngroom.
WherecancellatIonIsnotanoptIon,regIonalanesthetIctechnIquescanbeconsIdered,or
IfdemandedbythesItuatIon,asurgIcalaIrway(e.g.,tracheostomy)maybecalledfor.
Table 29-15 Factors to Consider in Proceeding with Regional Anesthesia
(RA) After the Patient HAS Been Judged to Have A Difficult Airway
MAY CONSIDER RA SHOULD NOT CONSIDER RA
SuperfIcIalsurgery CavItyInvadIngsurgery
|InImalsedatIon
needed SIgnIfIcantsedatIonneeded
LocalInfIltratIon
adequate
ExtensIveneuroaxIal/localanesthetIcrequIredorrIskof
IntravascularInjectIon/absorptIonIshIgh
Accesstothe
aIrway
PooraccesstotheaIrway
Surgerycanbe
haltedatanytIme
Surgerycannotbestoppedoncestarted
ThedecIsIontoproceedwIthregIonalanesthesIabecausetheaIrwaycannotbeassessedor
hasbeenproventobedIffIculttomanagemustbeconsIderedIntermsofrIsksandbenefIts
(Table2915).TheASAClosedClaIms0atabaseprojecthasIdentIfIedfaIlureInregIonal
anesthesIaasasourceofserIouserrorwhennoaIrwaystrategywasprophylactIcally
consIdered.
2
TheASA0AAtrulybecomesusefulIntheunantIcIpateddIffIcultaIrway(box8InFIg.2911,
unabletoIntubateby0LaftertheInductIonofanesthesIa).WhenInductIonagents(wIthor
wIthoutmusclerelaxants)havebeenadmInIsteredandtheaIrwaycannotbecontrolled,
vItalmanagementdecIsIonsmustbemaderapIdly.TypIcally,theclInIcIanhasattempted
dIrectorvIdeolaryngoscopyandtrachealIntubatIonaftersuccessfulorfaIledanesthesIa
maskventIlatIon.EvenIfthepatIent'soxygensaturatIonremaInsadequatethroughout
theseefforts,thenumberoflaryngoscopyattemptsshouldbelImItedtothree.AsdIscussed
earlIer,sIgnIfIcantsofttIssuetraumacanresultfrommultIplelaryngoscopIes,thereby
worsenIngthesItuatIon.FIrst,maskventIlatIonshouldbeInstItuted.ffacemask
ventIlatIonIsadequate,theASA0AAnonemergencypathwayIsentered.TheclInIcIanmay
thenturntothemostconvenIentand/orapproprIatetechnIqueforestablIshIngtracheal
IntubatIon,Ifneeded.ThIsmIghtInclude,butIsnotlImItedtovIdeolaryngoscopy,
IntubatIonfacIlItatedbyafIberoptIcbronchoscope,L|A,L|AFastrach,bougIe,lIghted
stylet,oraretrogradewIre.AsurgIcalaIrwaywIllsometImesbethemostapproprIate
approach.(ThemostwIdelyapplIedoftheseprocedures,aswellasnewtechnIques,wIllbe
dIscussedwIthIntheclInIcalscenarIospresentedlater.)WhenmaskventIlatIonfaIls,the
algorIthmsuggestssupraglottIcventIlatIonvIaanyL|A.fsuccessful,thenonemergency
pathwayoftheASA0AAhasagaInbeenenteredandalternatIvetechnIquesoftracheal
IntubatIonmaybeused,Ifneeded(e.g.,perhapsL|AventIlatIonIsadequateforthe
remaInderofthesurgIcalprocedure).
ShouldL|AventIlatIonfaIltosustaInthepatIentadequately,theemergencypathwayIs
entered.TheASA0AAsuggestsuseofanesophagealtrachealCombItube,rIgId
bronchoscopy,transtrachealoxygenatIon,orasurgIcalaIrway.
Atanyjuncture,thedecIsIontoawakenthepatIentshouldbeconsIderedbasedonthe
adequacyofventIlatIon,therIskofaspIratIon,andtherIskofproceedIngwIthIntubatIon
attemptsorthesurgIcalprocedure.
ThereposItIonIngoftheL|AwIthInthealgorIthm(InIts200JrevIsIon)wasbasedonmore
than12yearsofclInIcaluseIntheUnItedStates(andmorethan20yearsexperIence
worldwIde).FelatIvelyfewcasesofL|AfaIlureInthefaceofthecannotIntubate/cannot
ventIlatesItuatIonhavebeenreported.
15,124,125,126,127,128,129,1J0
ThreebroadcategorIes
accountforthesefaIlures:acuteoropharyngealangle,obstructIonatthelevelofthe
hypopharynx,andobstructIonbelowthevocalfolds.Conversely,manycasesofL|Arescue
ofthefaIledaIrwayhavebeenreported.AlthoughcontrolstudIesarelackIng,Parmetet
al.
124
notedthatallpatIentsfIttIngthecannotIntubate/cannotventIlatescenarIo(wIth
theexceptIonofanIatrogenIcsubglottIcobstructIon)occurrIngIna2yearperIodIna
sInglehospItalwererescuedwIthanL|A.AswIllbedIscussedlater,thereIsevIdencethat
manyoftherecentlyIntroducedSCAswIllfunctIonwIthsImIlarsuccess.
Awake Airway Management
AwakeaIrwaymanagementremaInsamaInstayoftheASA'sdIffIcultaIrwayalgorIthm.
AwakeIntubatIonprovIdesmanyadvantagesovertheanesthetIcstate,IncludIng
maIntenanceofspontaneousventIlatIonIntheeventthattheaIrwaycannotbesecured
rapIdly,IncreasedsIzeandpatencyofthepharynx,relatIveforwardplacementofthebase
ofthetongue,posterIorplacementofthelarynx,andpatencyoftheretropalatalspace.
1J1
TheeffectofsedatIvesandgeneralanesthetIcsonaIrwaypatencymaybesecondaryto
dIrecteffectsonmotoneuronsandontheretIcularactIvatIngsystem.Thesleepapnea
patIentmaybepartIcularlypronetoobstructIonwIthmInImalsedatIon.AddItIonally,the
awakestateconferssomemaIntenanceofupperandloweresophagealsphInctertone,thus
reducIngtherIskofreflux.ntheeventthatrefluxoccurs,thepatIentcanclosetheglottIs
and/orexpelaspIratedforeIgnbodIesbycoughtotheextentthatthesereflexeshavenot
beenobtundedbylocalanesthesIa.
1J2
Lastly,patIentsatrIskforneurologIcsequelae(e.g.,
patIentswIthunstablecervIcalspInepathology)mayundergoactIvesensorymotortestIng
ImmedIatelyaftertrachealIntubatIon.nanemergentsItuatIon,theremaybecautIons
(e.g.,cardIovascularstImulatIonInthepresenceofcardIacIschemIaorIschemIcrIsk,
bronchospasm,IncreasedIntraocularpressure,IncreasedIntracranIalpressure)butno
absolutecontraIndIcatIonstoawakeIntubatIon.ContraIndIcatIonstoelectIveawake
IntubatIonIncludepatIentrefusalorInabIlItytocooperate(e.g.,chIld,profoundmental
retardatIon,dementIa,IntoxIcatIon)orallergytolocalanesthetIcs.
DncetheclInIcIanhasdecIdedtoproceedwIthawakeaIrwaymanagement,thepatIent
mustbepreparedbothphysIcallyandpsychologIcally.|ostadultpatIentswIllapprecIate
anexplanatIonoftheneedforanawakeaIrwayexamInatIonandwIllbemorecooperatIve
oncetheyrealIzetheImportanceof,andratIonalefor,anyuncomfortableprocedures.
PatIentsunderstandsafetyandthedIscussIonshouldemphasIzetheanesthesIologIst's
concerns.DncetheaIrwayhasbeenprepared,patIentswIllrealIzethattheyshould
experIencenofurtherdIscomfortdurIngtheIntubatIon.
P.774
ApartfromapproprIateexplanatIon,medIcatIoncanalsobeusedtoallayanxIety.f
sedatIvesaretobeused,theclInIcIanmustkeepInmIndthatproducIngobstructIonor
apneaInthedIffIcultaIrwaypatIentcanbedevastatIngandanoverlysedatedpatIentmay
notbeabletoprotecttheaIrwayfromregurgItatedgastrIccontents,orcooperatewIth
procedures.AlthoughalmostanysedatIveagentcanbeused,somerulesshouldapplyto
all:judIcIousdosIngInsmallamounts,avoIdpolypharmacy(trytousenomorethattwo
agents),andhavereversalagentsathand.SmalldosesofbenzodIazepInes(dIazepam,
mIdazolam,lorazepam)arecommonlyusedtoallevIateanxIetywIthoutproducIng
sIgnIfIcantrespIratorydepressIon.ThesedrugsmaybegIvenInIntravenousororalforms
(whenavaIlable)andmaybereversedwIthspecIfIcantagonIsts(e.g.,flumazenIl).DpIoId
receptoragonIsts(e.g.,fentanyl,alfentanIl,remIfentanIl)canalsobeusedInsmall,
tItrateddosesfortheIrsedatIveandantItussIveeffects,althoughcautIonmustbe
exercIsed.AspecIfIcantagonIst(e.g.,naloxone)shouldalwaysbeImmedIatelyavaIlable.
KetamIne,droperIdol,anddexmedetomIdInehavealsobeenpopularamongclInIcIans.
0exmedetomIdIne,ahIghlyselectIvecentrallyactIng
2
adrenergIcagonIst,hasbeenused
forsedatIonandanalgesIawIthoutrespIratorydepressIonInpatIentswhounderwentawake
fIberoptIcIntubatIonbecauseofdIffIcultaIrways,
1JJ
cervIcalspIneproblems,
1JJ,1J4
and
InabIlItytocooperatewIthawakeIntubatIon.CombInedwIthtopIcalanesthesIa
dexmedetomIdInesedatIonprovIdedforasmoothIntubatIon.AloadIngdoseof
dexmedetomIdIneIs1g/kgIntravenouslyover10mInutes,andmaIntenanceInfusIondose
Is0.2to0.7g/kg/h.
85
0exmedetomIdInemaycausehypotensIon,whIchcanbecorrected
byphenylephrIneorephedrIne.0eepsedatIonwIthdexmedetomIdIneshouldnotbe
confusedwIthawakeIntubatIon,durIngwhIchtheclInIcIanstrIvestomaIntaInaIrway
protectIvereflexesandpatIentresponsIvenesstoverbalcommandsandcooperatIon.
AdmInIstratIonofantIsIalagoguesIsImportanttothesuccessofawakeIntubatIon
technIques.AswIllbedIscussedlater,clearIngofaIrwaysecretIonsIsessentIaltotheuse
ofIndIrectoptIcalInstruments(e.g.,flexIbleorrIgIdfIberoptIclaryngoscope,
vIdeolaryngoscope)becausesmallamountsofanylIquIdcanobscuretheobjectIvelens.
ThecommonlyuseddrugsatropIne(0.5to1mgIntramuscularlyorIntravenously)and
glycopyrrolate(0.2to0.4mgIntramuscularlyorIntravenously)haveothersIgnIfIcant
effects:byreducIngsalIvaproductIon,thesedrugsIncreasetheeffectIvenessoftopIcally
applIedlocalanesthetIcsbyremovIngabarrIertomucosalcontactandreducIngdrug
dIlutIon.TheclInIcIanmustwaItuntIlthepatIentsubjectIvelyreportsthedryIngactIvIty
oftheInjectedantIsIalagogue.7asoconstrIctIonofthenasalpassagesIsrequIredIfthereIs
tobeInstrumentatIonofthIspartoftheaIrway.DxymetazolIneIsapotentandlonglastIng
vasoconstrIctor.ntheauthors'experIencethenasalpassagesshouldalwaysbeIncludedIn
thepreparatIonforawakeIntubatIon:fIrst,IfdurIngthecourseoftheawakeIntubatIon,
theplanIschangedfromtheoraltonasalroute,preparatIonIscomplete.Second,muchof
thepreparatIonofthenosewIthlocalanesthesIa(seelaterdIscussIon),whIchcanoccur
prIortothepeakonsetofthedesIccant,wIllaffectthepharyngealaIrway.fthepatIentIs
atrIskforgastrIcregurgItatIonandaspIratIon,prophylactIcmeasuresshouldbe
undertaken.tIsalsoprudenttosupplysupplementaloxygentothepatIentbynasal
cannula(whIchcanbeplacedoverthenoseormouth).
LocalanesthetIcsareacornerstoneofawakeaIrwaycontroltechnIques(seeChapter21).
TheaIrway,fromthebaseofthetonguetothebronchI,comprIsesanundenIablysensItIve
serIesofstructures.TopIcalanesthesIaandInjectednerveblocktechnIqueshavebeen
developedtoblunttheprotectIveaIrwayreflexesaswellastoprovIdeanalgesIa.AsIswell
knowntotheanesthetIcpractItIoner,localanesthetIcsarebotheffectIveandpotentIally
dangerousdrugs.TheclInIcIanshouldhaveathoroughunderstandIngofthemechanIsmof
actIon,metabolIsm,toxIcItIes,andacceptablecumulatIvedosesofthedrugsthatheorshe
choosestoemployIntheaIrway.8ecausemuchoftheagentusedwIllbewIthInthe
trachealbronchIaltreeandcantraveltothealveolI,thereIsapotentIalforsIgnIfIcant
IntravascularabsorptIonwIthsometechnIques.nahumanstudyonlIdocaInetoxIcIty,400
or800mgwastopIcallyapplIedtotheupperaIrway.SerIalbloodlIdocaInelevelswere
measuredpeakIng60mInuteslaterat0.5and1.28g/mL,respectIvely.ToxIclevelsof
lIdocaIneareconsIderedtobe4.0g/mL.
1J5
narecentstudyusIngthesamedoseof
lIdocaIneadmInIsteredbynebulIzer,serumlevelsof2.8and6.5g/mLweremeasured
wIthIn10mInutesofdosecompletIon,respectIvely.
1J6
0espItethemyrIadoflocalanesthetIcsavaIlable,onlythosemostcommonlyusedIn
aIrwaypreparatIonwIllbedIscussedhere.nrealIty,thechoIceoflocalanesthetIc
employedhaslIttletodowIthsuccessofthetechnIqueofawakeIntubatIon;IgnorIngthe
otheraspectsofpreparatIonoutlInedhereleadtofaIlurejustasreadIly.
12J
AmongotolaryngologIsts,cocaIneIsapopulartopIcalagent.NotonlyIsItahIghlyeffectIve
localanesthetIc,butalsoItIstheonlylocalanesthetIcthatIsapotentvasoconstrIctor.t
IscommonlyavaIlableIna4solutIon.ThetotaldoseapplIedtothemucosashouldnot
exceed200mgIntheadult.CocaIneshouldnotbeusedInpatIentswIthaknowncocaIne
hypersensItIvIty,hypertensIon,IschemIcheartdIsease,preeclampsIa,orthosetakIng
monoamIneoxIdaseInhIbItors.8ecausecocaIneIsmetabolIzedbypseudocholInesterase,It
IscontraIndIcatedInpatIentswhoaredefIcIentInthIsenzyme.
LIdocaIne,anamIdelocalanesthetIc,IsavaIlableInawIdevarIetyofpreparatIonsand
doses(Table2916).TopIcallyapplIed,peakonsetIswIthIn15mInutes.
TetracaIneIsanamIdelocalanesthetIcwIthalongerduratIonofactIonthaneIther
cocaIneorlIdocaIne.SolutIonsof0.5,1,and2areavaIlable.AbsorptIonofthIsdrug
fromtherespIratoryandgastroIntestInaltractsIsrapId,andtoxIcItyafternebulIzed
applIcatIonhasbeenreportedwIthdosesaslowas40mg,althoughtheacceptablesafe
doseInadultsIs100mgbyotherroutesofapplIcatIon.
1J7
8enzocaIneIspopularamongsomeclInIcIansbecauseofItsveryrapIdonset(1mInute)
andshortduratIon(approxImately10mInutes).tIsavaIlableIn10,15,and20
solutIons.thasbeencombInedwIthtetracaIne(HurrIcaIne)toprolongtheduratIonof
actIon.A0.5secondaerosoladmInIstratIonofHurrIcaInedelIversJ0mgofbenzocaIne,the
toxIcdosebeIng100mg.AnothercommonpreparatIonIsCetacaInespray,whIchcombInes
benzocaInewIthtetracaIne,butylamInobenzoate,benzalkonIumchlorIde,and
cetyldImethylethylammonIumbromIde.8enzocaInemayproducemethemoglobInemIa,
whIchIstreatedbytheadmInIstratIonofmethyleneblue(1to2mgIntravenously).
TherearethreeanatomIcareastowhIchtheclInIcIandIrectslocalanesthetIctherapy:the
nasalcavIty/nasopharynx,
P.775
thepharynx/baseoftongue,andthehypopharynx/larynx/trachea.ThenasalcavItyIs
InnervatedbythegreaterandlesserpalatInenerves(InnervatIngthenasalturbInatesand
mostofthenasalseptum)andtheanterIorethmoIdnerve(InnervatIngthenaresand
anterIorthIrdofthenasalseptum).ThetwopalatInenervesarIsefromthesphenopalatIne
ganglIon,locatedposterIortothemIddleturbInate.TwotechnIquesfornerveblockhave
beendescrIbed.TheganglIoncanbeapproachedthroughanonInvasIvenasalapproach:
cottontIppedapplIcatorssoakedInlocalanesthetIcarepassedalongtheupperborderof
themIddleturbInateuntIltheposterIorwallofthenasopharynxIsreached.Theyareleft
Inplacefor5to10mInutes.ntheoralapproach,aneedleIsIntroducedIntothegreater
palatIneforamen,whIchcanbepalpatedIntheposterIorlateralaspectofthehardpalate,
1cmmedIaltothesecondandthIrdmaxIllarymolars.AnesthetIcsolutIon(1to2mL)Is
InjectedwIthaspInalneedleInsertedInasuperIor/posterIordIrectIonatadepthof2toJ
cm.CaremustbetakennottoInjectIntothesphenopalatIneartery.TheanterIorethmoId
nervecanbeblockedbycottontIppedapplIcatorssoakedInlocalanesthetIcplacedalong
thedorsalsurfaceofthenoseuntIltheanterIorcrIbrIformplateIsreached.TheapplIcator
IsleftInplacefor5to10mInutes.
Table 29-16 Available Lidocaine Preparations
PREPARATION DOSES (%)
njectable/topIcalsolutIon 1,2,4
7IscoussolutIon 1,2
DIntment 1,5
Aerosol 10
TheoropharynxIsInnervatedbybranchesofthevagus,facIal,andglossopharyngeal
nerves.TheglossopharyngealnervetravelsanterIorlyalongthelateralsurfaceofthe
pharynx,ItsthreebranchessupplyIngsensoryInnervatIontotheposterIorthIrdofthe
tongue,thevallecula,theanterIorsurfaceoftheepIglottIs(lIngualbranch),thewallsof
thepharynx(pharyngealbranch),andthetonsIls(tonsIllarbranch).AwIdevarIetyof
technIquesmaybeusedtoanesthetIzethIspartoftheaIrway.ThesImplesttechnIques
InvolveaerosolIzedlocalanesthetIcsolutIon,oravoluntaryswIshandswallow.Aslong
astheclInIcIanhasdevelopedaplantoanesthetIzeallrelevantstructures,hasallowed
enoughtImefordryIngagentstowork,andremaInscontInuallycognIzantofthetotaldose
oflocalanesthetIcsadmInIstered,mostpatIentswIllbeadequatelyanesthetIzedInthIs
way.
SomepatIentsmayrequIreaglossopharyngealnerveblock,especIallywhentopIcal
technIquesdonotadequatelyblockthegagreflex.ThebranchesofthIsnervearemost
easIlyaccessedastheytransversethepalatoglossalfolds.Thesefoldsareseenassoft
tIssuerIdgesthatextendfromtheposterIoraspectofthesoftpalatetothebaseofthe
tongue,bIlaterally(FIg.291J).
AnonInvasIvetechnIqueemploysanesthetIcsoakedcottontIppedapplIcatorsthatare
posItIonedagaInsttheInferIormostaspectofthefolds,andleftInplacefor5to10
mInutes.WhenthenonInvasIvetechnIqueprovesInadequate,localanesthetIccanbe
Injected.StandIngonthesIdecontralateraltothenervetobeblocked,theoperator
dIsplacestheextendedtonguetothecontralateralsIdeanda25gaugespInalneedleIs
InsertedIntothemembranenearthefloorofthemouth.AnaspIratIontestIsperformed.f
aIrIsaspIrated,theneedlehaspassedthroughandthroughthemembrane.fbloodIs
aspIrated,theneedletIpIsredIrectedmoremedIally.ThelIngualbranchIsmostreadIly
blockedInthIsmanner,butretrogradetrackIngoftheInjectatehasalsobeen
demonstrated.
1J2
EventhoughItprovIdesarelIableblock,thIstechnIqueIsreportedtobe
paInfulandmayresultInabothersomeandpersIstenthematoma.
1J8
AposterIorapproach
totheglossopharyngealnervehasbeendescrIbedIntheotolaryngologIclIterature(for
tonsIllectomy).tmaybedIffIculttovIsualIzethesIteofneedleInsertIonasItIsbehInd
thepalatopharyngealarchwherethenerveIsIncloseproxImItytothecarotIdartery.
8ecauseoftherIskforarterIalInjectIonandbleedIng,thetechnIquewIllnotbedescrIbed
here;however,thereaderIsreferredtoamoreauthorItatIvetext.
85
TheInternalbranchofthesuperIorlaryngealnerve,whIchIsabranchofthevagusnerve,
provIdessensoryInnervatIontothebaseofthetongue,epIglottIs,aryepIglottIcfolds,and
arytenoIds.ThebranchorIgInatesfromthesuperIorlaryngealnervelateraltothecornuof
thehyoIdbone.tthenpIercesthethyrohyoIdmembraneandtravelsunderthemucosaIn
thepyrIformrecess.TheremaInIngportIonofthesuperIorlaryngealnerve,theexternal
branch,supplIesmotorInnervatIontothecrIcothyroIdmuscle.SeveralblocksofthIsnerve
havebeendescrIbed.nmanyInstancestopIcalapplIcatIonofanesthetIcsIntheoralcavIty
wIllprovIdeadequateanalgesIa.AnexternalblockIsperformedwIththepatIentsupIne
wIththeheadextendedandtheclInIcIanstandIngonthesIdeIpsIlateraltothenervetobe
blocked.TheclInIcIanIdentIfIesthesuperIorcornuofthehyoIdbonebeneaththeangleof
themandIble.UsIngonehand,medIallydIrectedpressureIsapplIedtothecontralateral
hyoIdcornu,dIsplacIngtheIpsIlateralhyoIdcornutowardtheclInIcIan.CautIonmustbe
takentolocatethecarotIdarteryanddIsplaceItIfnecessary.TheneedlecanbeInserted
dIrectlyoverthehyoIdcornuandthenwalkedoffthecartIlageInananterIorcaudad
dIrectIonuntIlItcanbepassedthroughthelIgamenttoadepthof1to2cm.8eforethe
InjectIonoflocalanesthetIc,anaspIratIontestshouldbeperformedtoensurethatonehas
notenteredthepharynxoravascularstructure.LocalanesthetIcwIthepInephrIne(1.5to
2mL)IsInjectedInthespacebetweenthethyrohyoIdmembraneandthepharyngeal
mucosa.ThesuperIorlaryngealnervecanalsobeblockedwIthanonInvasIveInternal
technIque.ThepatIentIsaskedtoopenthemouthwIdely,andthetongueIsgraspedusIng
agauzepadortongueblade.ArIghtangleforceps(e.g.,JacksonKrauseforceps)wIth
anesthetIcsoakedcottonswabsIsslIdoverthelateraltongueandIntothepyrIformsInuses
bIlaterally.ThecottonswabsorspongeareheldInplacefor5mInutes.
Figure 29-13.Thepalatoglossalarch(arrow)IsasofttIssuefoldthatIsacontInuatIon
oftheposterIoredgeofthesoftpalatetothebaseofthetongue.AlocalanesthetIc
soakedswabplacedInthegutteralongthebaseofthetongueIsleftIncontactwIth
thefoldfor5to10mInutes.
SensoryInnervatIonofthevocalfoldsandthetracheaIsprovIdedbytherecurrent
laryngealnerve.TranstrachealInjectIonoflocalanesthetIccaneasIlybeperformedto
produceadequateanalgesIa,andthetechnIqueIsdescrIbedIndetaIllater(see
FetrogradentubatIon).LIdocaIne,4mLof2or4solutIon,IsInjected.
AneffectIveandnonInvasIvetechnIqueoftrachealandvocalcordtopIcalanalgesIauses
theworkIngchannelofthefIberoptIcbronchoscope.AdIsadvantageofthIstechnIqueIs
thatsolutIonsleavIngtheworkIngchannelcanobscuretheobjectIvelens.ThIscanbe
overcomebyuseofanepIdural
P.776
catheter,InsertedthroughtheworkIngchannel,asdescrIbedbyDvassapIan.
1J9
Notonly
doesthIspreventtheobscurIngofthevIew,butalsoallowsspecIfIcaImIngofthe
anesthetIcstream.|ultIorIfIcecathetersshouldbetrImmedInlengthsoonlythedIstal
orIfIceexIsts.
Clinical Difficult Airway Scenarios
TheclInIcIanapproachIngthepatIentwIthadIffIcultaIrwayhasavastarmamentarIumof
technIquesandInstrumentsthatcanbeapplIedtosecurIngandmaIntaInIngoxygenatIon
andventIlatIon.
140
AlthoughthIsarraycanbeconfusIng,textbookauthorscannotdIctate
specIfIcapproachesIneverysItuatIon;moreover,thevarIabIlItyofpatIentpresentatIon
makesspecIfIcrecommendatIonsdIffIcult.Thus,InordertodIscussmanagement,the
followIngsectIonpresentsanumberofbrIefclInIcalscenarIosandtheauthors'own
approach.ThemajoralternatIveaIrwaymanagementtechnIquesaredIscussedInthIs
manner.AlloftheclInIcalcasesdescrIbedhereInhavebeenmanagedbytheauthorsora
colleague.DthertechnIquesthatmIghtbeapplIedIneachsItuatIonarealsodIscussed,
togetherwIththeauthors'owndecIsIontreeregardIngtheIrapplIcabIlIty.nthesecases,
asInactualpractIce,thefIrsttechnIqueapplIedmaynothavebeenthebestone.The
prIncIpleofflexIbIlIty(andakeeneyetotheneedtochangecoursequIckly)wIllbe
emphasIzedrepeatedly.nvIewofthecrItIcalImportanceoftheactofaIrwaycontrol,the
clInIcIanmustbepreparedtoalterhIsorherapproachasthesItuatIondemands.Table29
17showstheauthors'routethroughtheAAA(FIg.2912)wItheachcase.
When0LandtrachealIntubatIonfaIl,theclInIcIanhasalargearmamentarIumoftoolsto
turnto.8ecausesuccessful0LdependsonsuffIcIenttIssuedIstortIon(Inordertocreatea
lIneofsIte),technIquesthatdonotrequIresImIlaranatomIcalIgnmentmaybesuccessful
afterfaIled0L.FIberoptIc,vIdeocoupled,supraglottIcaIrway(SCA),styletassIsted(e.g.,
lIghtedstylet),andretrogradetechnIquesmayprovIdeasuccessfulalternatIve.8utthese
technIquesalsocalluponalternatIveskIllsets.nadIffIcultorcrItIcalsItuatIonItIs
unlIkelythatturnIngtoanunpractIcedtechnIquewIllbehelpful.
141
Unfortunately,clInIcIansrarelyemployalternatIvetechnIquesuntIladIffIcultsItuatIon
arIses.HeIdeggeretal.
141
IntroducedasImplealgorIthmforIncorporatIngflexIble
fIberoptIcaIdedtrachealIntubatIonIntodaIlypractIceasaroutInealternatIveto0L.
TheIrIncIdenceofdIffIcultIntubatIonwas6In1,J24cases,or0.049,markedlylowerthan
the0.JreportedprevIously.
8J
Case 1: Video laryngoscopy
A46yearoldobesewoman(heIght,15Jcm;weIght,77kg)IsscheduledforcranIotomy.Dn
examInatIonofheraIrwaysheIsfoundtohavea|allampatIgradeof2andathyromental
dIstanceof4.0cm.AfterInductIonofanesthesIaandneuromuscularblockade,0Lwas
performedandrevealedaCormackLehanescoreofJ.FeposItIonIngofthepatIent'shead
andneck,andexternallaryngealmanIpulatIondIdnotImprovethevIewofthelaryngeal
anatomy.AClIdeScopevIdeolaryngoscopewasusedandthearytenoIds,butnotglottIc
aperture,weredIsplayedonthevIdeoscreen.AsecondanesthesIologIstapplIedexternal
laryngealpressureandtheClIdeScopedIsplayclearlyshowedthatthearytenoIdshadbeen
movedtotheleft.8ywatchIngthedIsplay,thesecondanesthesIologIstwasabletoadjust
thedIrectIonandforceofexternallaryngealpressuretobrIngtheglottIsIntovIew.WhIle
observIngthedIsplayedImage,thefIrstanesthesIologIstInsertedagumelastIcbougIeInto
thelarynxoverwhIchaETTwasadvanced.8othanesthesIologIstswereabletovIsually
confIrmETTplacement.CapnographyandauscultatIonofthechestconfIrmedthecorrect
ETTposItIon.
GlideScope
TheClIdeScope(7erathon,8othell,WA;FIg.2914A)provIdesanelectronIcallyprojected
ImageonavIdeomonItoremanatIngfromavIdeochIpsetatthedIstalendofa
conventIonallIkelaryngoscopeblade,butwIthamoreacute(60degrees)dIstal
angulatIon.
142
llumInatIonIslIkewIsegeneratedatthedIstalposItIon.ThIsconfIguratIon
affordsseveraladvantages.(1)tmaybehandledwIthaskIllsetsImIlartothatusedwIth
conventIonal0L.(2)Theoperator'spoIntofsIght(e.g.,thevIdeoapparatus)IsposItIoned
closetothedIstalbladeaspect.(J)ThevIdeoapparatusIsachargedcoupledlIkedevIce
(therebyelImInatIngfragIlefIberoptIcelements).Theoperatorthereforeseesata
posItIonbehIndthetongue,anddIsplacementaswIthconventIonal0LIsnotnecessaryIn
mostcases.SImIlarly,lIngualtonsIlhyperplasIashouldnotaffectthevIsualaxIsasItdoes
wIthconventIonal0L.(4)ThevIdeoImageoftheaIrwayIsdIsplayedonalIghtweIght
portablescreen,andallowsforvIsualIzatIonbymorethanoneIndIvIdual(e.g.,aId,
mentor,student).(5)LessstressmaybeImposedontheaIrwaybyvIrtueofreduced
compressIveforcedIrectedtothetongue.(6)AnexternallIghtsourceIsnotrequIred.
WhenusedbyInexperIencedoperatorstheClIdeScopeprovIdesbetterglottIcexposureas
comparedwIth0L(CormackLehanegrade1vIewIn85.7vs.48.9)andcanobtaIn
CormackLehanegrade1or2In77ofpatIentsInwhomnoglottIcexposurewasachIeved
by0L.
142
AlthoughItcan
P.777
ImprovethelaryngealvIewbyonegradeInmanypatIents,thIsdoesnotautomatIcally
ImplymorerapIdtrachealIntubatIon.nonestudy,placementoftheETTrequIredan
addItIonal16seconds(average).
142,14J
Table 29-17 The Airway Approach Algorithm as Applied to Chapter Clinical
Cases
CASE
a
REQUIRE
CONTROL?
b
DL
DIFFICULT?
b
SGA
POSSIBLE?
b
STOMACH
EMPTY?
b
Tolerance
APNEA
b
BOX
b
1 Yes Yes Yes Yes Yes 8
2 Yes Yes No
C
A
J Yes Yes Yes Yes No A
4 Yes No 8
5 Yes No 8
6 Yes Yes Yes No 8
0L,dIrectlaryngoscopy;SCA,supraglottIcaIrways.
a
FefertoclInIcalcases.
b
FefertoFIgure2911.
c
DnceaNoIsreachedaclInIcaldecIsIon(lastcolumn)Ismade.
Figure 29-14. A.ClIdeScope.(Photographcourtesyof0r.FIchardCooper.)B.C|ac.
(PhotographcourtesyofKarlStorzEndoscopy,CulverCIty,CA).C.The|cCrathSerIes
5vIdeolaryngoscope(Courtesyof|cCrath|edIcal,UK)D.AIrtraq(CourtesyofKIng
Systems).
TheclassIcClIdeScopeInsertIontechnIquefollowsthemIdlIneapproach.AftertheuvulaIs
vIsualIzed,thebladeIsadvancedmIdlIneIntothevalleculaorcanbepassedposterIorto
theepIglottIs.
142
ForpatIentswIthalImItedmouthaperture,analternatIveInsertIonhas
beendescrIbedInwhIchthebladeIsInsertedlIkeaCuedelaIrway;thatIs,theClIdeScope
bladeconcavItyfacIngrostradandrotated180degreescounterclockwIseoncethedIstaltIp
IsIntheoropharynx.ThIsmaneuverdIsplacesthetonguetotheleftandmInImIzesneck
movements.
AlthoughachIevIngagoodlaryngealvIewwIththeClIdeScopeappearsrelatIvelyeasy,ETT
manIpulatIonIntothelarynxmaybemoredIffIcultbecauseoftheacutebladeangulatIon.
TheuseofastyletIsadvIsedtodelIvertheETT.
144,145
0Ifferentauthorshavesuggested
styletshapIngwIthabendof60degree,90degree,adynamIcstylet,J,orgearshIft
shape.FeverseloadIngtechnIqueoruseofagumelastIcbougIehasalsobeendescrIbed.
146
ThereIsonestudythatevIdencedthattheangleoftheETThadgreaterImpactontImeto
IntubatIonthantheCormackandLehanegradeoftheImage.
147
Fecently,adedIcated,
nonmalleablestylet,theClIdescopereusablestylet(7erathon)hasbeenIntroduced.ThIs
stylethasa90degreebend,andmaybe
P.778
usedwIthvarIousvIdeolaryngoscopes.TheClIdeScopehasalsobeenusedtofacIlItate
nasotrachealIntubatIonwIthareducedtImetoIntubatIonwhencomparedwIth0Landa
hIghfIrsttImesuccessrate.
The60degreeangulatIonoftheClIdeScopereducescervIcalspInemotIonby50atthe
C25segmentscomparedwIth|acIntoshlaryngoscopy.TheoretIcally,theaIrwayaxesdo
notneedtobealIgnedtoaffectagoodvIew,butmanIpulatIonoftheClIdeScopetothe
posItIontoachIeveanadequateImagecancausecervIcalsegmentextensIon.thasbeen
successfullyusedtoachIevetrachealIntubatIonInpatIentswIthlImItedcervIcalspIne
movementbecauseofankylosIngspondylItIsandcervIcalspInearthrItIs,butmaybe
dIffIculttouseInpatIentswIthlImItedoralaperture.
148,149
ControlstudIeshaveshownnosIgnIfIcantadvantageoftheClIdeScopeInpreventIng
hemodynamIcresponsestoorotrachealIntubatIonascomparedwIththe|acIntoshdIrect
laryngoscope,althoughothershaveshowncardIovascularresponsessImIlartoIntubatIon
wIthaflexIblefIberoptIcbronchoscope.
150
TraumatIccomplIcatIonsassocIatedwIththeuseoftheClIdeScopevIdeolaryngoscope
havebeenrelatedtoblIndmanIpulatIonoftheETTasItenterstheaIrwaybutIsnotyet
vIsualIzedontheperIlaryngealImage.TraumatIcevents,whIchappeartobemorelIkely
wIththeuseofarIgIdstylet,areprImarIlyreportedtoInvolvethesoftpalate,
palatoglossalarch,rIghtpalatopharyngealarch,andrIghtanterIortonsIllar
pIllar.
151,152,15J,154,155
Video Macintosh
The7Ideo|acIntosh(7|;KarlStorzEndovIsIon,CulverCIty,CA;FIg.29148)consIstsofa
conventIonalappearInglaryngoscopehandleandbladefIttedwIthIllumInatIonandImage
fIberoptIcs.The7|handleInterfaceswIththeKarlStorzproprIetary0Ccamerasystem.
ThevIdeoImageIsdIsplayedonastandardNTSCmonItor.AlthoughtheImageprojected
fromthe7|closelyresemblesthatseenwIththenakedeye,(1)ETTplacementIs
facIlItatedbecausetheoperatordoesnotneedtomaIntaInanunobstructedlIneofsIght
(hIsorhereyeusIngthevIdeomonItor),(2)externallaryngealmanIpulatIoncanbe
observedbyasecondoperator,and(J)useofthe7|IsIdentIcalstandard0L,makIngthe
vIdeofacIlItyunIquelyvaluabledurIngsupervIsedInstructIon.AcomparIsonstudyofdIrect
andvIdeoassIstedvIewsofthelarynxrevealedsIgnIfIcantImprovementoftheglottIcvIew
wIththe7|.
156
ncontrolledtrIals,the7|facIlItatedtrachealIntubatIonInbarIatrIcand
thoracIcsurgerypatIents.
157
Fecently,adIgItalversIon(C|DS)ofthe7Ahasbeen
Introduced(FIg.29148).
McGrath
The|cCrathSerIes5vIdeolaryngoscope(AIrcraft|edIcal,EdInburgh,UK)wasIntroduced
toclInIcalpractIceIn2007(FIg.2914C).AtthetImeofthIswrItIng,nocontrolledclInIcal
trIalswIththIsdevIcehavebeenpublIshedInthelIterature.TheexperIenceamongusers
wasextremelyposItIveforuseasaprImaryorrescuevIdeolaryngoscopydevIce.The
unIquefeaturesofthe|cCrathare(1)selfcontaInedunItIncludInglaryngoscopIcblade,
handle,powersource(1.5vbatterIes),andJ.J2.2cmLC0(lIquIdcrystaldIsplay)screen;
(2)acutedIstalangleblade;(J)adjustablebladelength;and(4)dIsposablepatIentcontact
blade.AswIththeClIdeScope,theacuteanglebladeImprovestheCormackandLehane
gradeofthelaryngealvIewbyaffordIngtheoperatoranoblIquelIneofsIghtaroundthe
baseofthetongue.noneuncontrolledserIes,trachealIntubatIonwassuccessfulIn98of
150electIvesurgerypatIents.
158
8ecause|cCrathvIdeolaryngoscopy,aswIththe
ClIdeScope,doesnotInvolvecreatIonofadIrectlIneofsIghttothelarynx,trachealtube
placementmaybeawkward.UseofasemIornonmalleablestyletIsadvIsablewIthboth
devIces,wItha60to90degreeupwardbendofthedIstaltrachealtube.8ecausetheangle
ofthedIstalETTstyletIsanterIorasItentersthelarynx,a1to2cmwIthdrawalofthe
styletatthIsjuncturefacIlItatesadvancement.
Video laryngoscopes and Education/Supervision
AllowIngsharedglottIcvIsualIzatIonforthepurposeofteachIng,thesupervIsIngand
assIstanceIsaunIqueadvantageofvIdeolaryngoscopeswhencomparedwIthstandard0L.
ThIsmayhavespecIalImpactInchIldren,wherenarrowaIrwayspacesdonotallowdIrect
covIsualIzatIon.WhenfIrstacquIrIng0LskIlls,thestudentcanobserveeachstepofthe
procedurefromInsertIonofthebladeIntothemouth,advancementIntothehypopharynx,
andvIsualIzatIonofthetrachealtubepassIngIntothelarynx.Whentherolesarereversed,
andthenovIceIsattemptIngtheIntubatIon,theInstructorcanobservetheresultsofthe
effortsandcanguIdethenovIcethroughtheentIreprocess,aswellaswItnesslaryngeal
passageoftheETT.
157
7IdeolaryngoscopesmaythereforeprovIdeImportantInformatIon
totheInstructoraboutthetraInee'sdIffIcultIeswIth0LandETTInsertIon.LIkewIse,the
progressIonofexternallaryngealmanIpulatIon,ItsproperapplIcatIon,andeffectIveness
canbedemonstratedandtaughtwIththesedevIces.
159,160
Theuseof7|forteachInglaryngoscopyInthepatIentswIthnormalandantIcIpated
dIffIcultaIrwayshasbeenreported.
161
Fecently,useoftheClIdeScopehasbeendescrIbed
InteachIngfIberoptIcbronchoscopeaIdedtrachealIntubatIon.
162
TheClIdeScopeImage
wasusedbytheInstructortodIrectthenovIceoperators'useofthefIberoptIc
bronchoscope.
Airtraq
TheAIrtraqoptIcallaryngoscope(Prodol|edItecS.A.,7Izcaya,SpaIn;FIg.29140)Isa
sIngleuse,anatomIcallyshapedlaryngoscopeoptIcalprIsmdevIce,wIthalateralguIdIng
channelthatholdsandguIdestheETTthroughthevocalcords.thasabuIltInantIfog
systemandalowtemperaturelIght.
AIrtraqhasbeensuccessfullyusedasarescuedevIceInsevenpatIentsafterfaIled
IntubatIonwIth0L.
16J
FeportsofItsuseInawakepatIents,patIentswIthcervIcalspIne
dIsease,andafterfaIled0LhavebeenpublIshed.
164
Dnestudyshowedtheneedforfewer
maneuverstoImproveglottIcexposureandfeweralteratIonsInbloodpressureandheart
ratewhencomparedwIth0L.
165
Truview
TheTruvIewE7D2optIcallaryngoscope(Truphatek,Netanya,srael),consIstsofaslIm,
straIghtlaryngoscopebladewIthadIstalupwardcurvedtIp(40degrees).TheproxImal
bladeIsfIttedwIthatelescopethatcanbeusedwIththenakedeyeoranendoscopIc
camerahead.AlateralportmaybeconnectedtoanoxygensourcetoprovIde
defoggIng.
166
TwostudIesshowedImprovedglottIcvIewwIthTruvIewcomparedwIth
|acIntoshlaryngoscope,butthetImerequIredforIntubatIonwasprolonged.
166
ntwo
reports,patIentswhofaIledIntubatIonwIththe|acIntoshbladeweresuccessfully
IntubatedwIththeTruvIew.
167
Case 2: Flexible Fiberoptic-Aided Intubation
A50yearoldmanwIthsymptomatIccervIcalvertebraedIskhernIatIonpresentsfordIsk
resectIonandspInalfIxatIon.HehasahIstoryoftobaccouse,alcoholconsumptIon,and
gastroesophagealreflux.nthepreoperatIveholdIngarea,0.4mg
P.779
ofIntravenousglycopyrrolateIsInjected,andoxymetazolIneIsadmInIsteredtothenasal
cavIty(commercIalpreparatIon:AfrInspray).Swabsof5lIdocaIneoIntment(50mg)are
applIedIntothenose.FIfteenmInuteslater,whenthepatIentstatesthathIsoral
secretIonsaremInImIzed,topIcalanesthesIaIsadmInIsteredtotheremaInIngaIrway,as
descrIbed.ThepatIentreceIves4mgofIntravenousmIdazolam.AnIntubatIngoralaIrway
IsplacedwIthoutelIcItIngagagreflexandaflexIblefIberoptIcbronchoscopeIsadvanced
IntotheaIrway.ThevocallIgamentsarevIsualIzed,and4mLof4lIdocaInesolutIonare
InjectedthroughtheaccessorylumenofthefIberscope(usIngtheDvassapIancatheter
technIque),beIngseentobathethelaryngealandsublaryngealstructures.
1J9
ThedIstal
endofthefIberscopeIsadvancedIntothelarynx,anda7.00ETT,whIchhadbeen
threadedontotheInsertIonshaftofthefIberscope,IsadvancedIntothetrachea.The
fIberscopeIsremovedwhIlethestructuresofthecarIna,trachea,andfInallythetracheal
tubeareobserved.TheanesthesIacIrcuItIsattachedtothetrachealtubeandasteady
outputofcarbondIoxIdeIsdetectedbycapnography.AbrIefsensoryandmotorneurologIc
examInatIonIsperformedbytheattendIngsurgeonandgeneralanesthesIaIsInduced.
Use of the Fiberoptic Bronchoscope in Airway Management
ThefIberoptIcbronchoscopeIsaubIquItousInstrumentInanesthesIa,beIngavaIlableto
99ofsurveyedactIveASAmembers.
140
ThetechnIqueoffIberoptIcaIdedIntubatIonwas
fIrstperformedusIngacholedochoscopeInapatIentwIthStIll'sdIsease(IdIopathIc,adult
onsetarthrItIs).
168
8ythelate1980sItwasrecognIzedthattheuseoftheflexIblefIberoptIc
bronchoscoperepresentedsuchasIgnIfIcantadvancementInthemanagementofthe
patIentwIthadIffIcultaIrwaythatexpertsstatedthatnoanesthesIologIstcouldaffordnot
tobefacIlewIththIstechnIque.
169
tIsnowgenerallyacceptedthatforavarIetyof
clInIcalsItuatIons,thefIberoptIcbronchoscopeIsacrItIcaltoolInthearmamentarIumof
theanesthesIologIstdealIngwIththeawakeorunconscIouspatIentwhoIs,orappearsto
be,dIffIculttoIntubate.
1J2
ThefIberoptIcbronchoscopehasproventobethemost
versatIletoolavaIlableInthIsregard.
1J9
ThereIsnotrueorfIrmIndIcatIonforfIberoptIcbronchoscopeaIdedIntubatIon,asthere
mIghtbewIth0L(e.g.,rapIdsequenceInductIonforthefullstomachpatIent).Thereare,
however,manyclInIcalsItuatIonsInwhIchthefIberoptIcbronchoscopecanbeof
unparalleledaIdInsecurIngtheaIrway,especIallyIftheclInIcIanhasmadeaneffortto
masterthenecessaryskIllsbyusIngItInroutIneendotrachealIntubatIons.
1J9,141
These
IncludeantIcIpateddIffIcultIntubatIonbyhIstoryorphysIcalexamInatIonfIndIngs,
unantIcIpateddIffIcultIntubatIon(InwhIchothertechnIqueshavefaIled),lowerandupper
aIrwayobstructIon,unstableorfIxedcervIcalspInedIsease,masseffectIntheupperor
loweraIrways,dentalrIskordamage,andawakeIntubatIon.
1J9
UnlIketheotherdevIces
usedtoIntubatethetrachea,thefIberoptIcbronchoscopecanalsoservetovIsualIze
structuresbelowthelevelofthevocalfolds.Forexample,ItcanIdentIfytheplacementof
thetrachealtubeoraIdInplacementofadoublelumentrachealtube.tmaybehelpfulIn
dIagnosIswIthInthetracheaandbronchIaltreeorInpulmonarytoIlet(FIg.2915).
ContraIndIcatIonstofIberoptIcbronchoscopeaIdedIntubatIonarerelatIve,andrevolve
aboutthelImItatIonsofthedevIce(Table2918).
8ecausetheoptIcalelementsaresmall(theobjectIvelensIstypIcally2mmIndIameteror
smaller),mInuteamountsofaIrwaysecretIons,blood,ortraumatIcdebrIscanhInder
vIsualIzatIon.CaremustbetakentoremovetheseobstaclesfromtheaIrwaybeforehand;
applIcatIonofIntramuscularorIntravenousantIsIalagogues(e.g.,glycopyrrolate,0.2to0.4
mg;atropIne,0.5to1mg)wIllproduceadryIngeffectwIthIn15mInutes,butcautIon
shouldbetakenInpatIentswhomaynotbeabletotolerateanIncreaseInheartrate.
7asoconstrIctIonofthenoseusIngtopIcaloxymetazolIne,phenylephrIne,orcocaIne
reducesthechancesofbleedIngIfthIsrouteIschosen.fanawakeIntubatIonIsplanned
usIngthefIberoptIcbronchoscope,thepatIentmustbeabletocooperateaquIet
aIrway,wIthlIttlemotIonofthehead,neck,tongue,andlarynx,IsvItaltosuccess.FInally,
becausefIberoptIcbronchoscopeaIdedIntubatIonofthetracheacanrequIresIgnIfIcant
tIme,especIallyIftheclInIcIanIsnotfacIlewIththedevIce,hypoxIaorImpendInghypoxIa
IsacontraIndIcatIon,andamorerapIdmethodofsecurInganaIrway(e.g.,L|AorsurgIcal
aIrway)shouldbeconsIdered.
Figure 29-15.ThefIberoptIcbronchoscopemaybeusefulfordIagnosIsandtherapy
belowthelevelofthevocallIgaments,IncludIngbronchIalsegmentsexamInatIonand
toIlet.LaryngealwebIsshownhere.
Elements of the Fiberoptic Bronchoscope
ThefIberoptIcbronchoscopeIsafragIledevIcewIthoptIcalandnonoptIcalelements.The
fundamentalelementconsIstsofaglassfIberbundle.EachfIberIs8to12micronsIn
dIameter,andIscoatedwIthasecondaryglasslayertermedthecladding.ThecladdIng
aIdsInmaIntaInIngtheImagewIthIneachfIberasthelIghtIsreflectedoffthesIdewallat
arateof10,000tImespermeterasItmovesfromtheobjectIvelenstotheeyepIecelensIn
theoperator'shandle.ThetypIcalIntubatIngfIberoptIcbronchoscopehas10,000toJ0,000
suchfIbersencasedIna60cm,waterImpermeableInsertIoncord,wIthgradatIonmarks
every10cm.AlthoughthefIbersareallowedtorotateovereachotherthroughoutthe
lengthofthecord,theyarefusedtogetheratthetwoendsInacoherentpattern;thatIs,
thearrangementofthefIbersattheeyepIeceendIsIdentIcaltothearrangementatthe
objectIvelens,whereadIopterrIngallowsfocusIng.Therefore,onemIghtenvIsIonthat
theImagebeforetheobjectIvelens(I.e.,theobjectIve)IsdIvIdedInto10,000
P.780
IndIvIdualandunIquepIctures,whIchIndependentlytraveldownanunwIeldycordtobe
reassembledInfrontoftheeyepIecelens.8rokenfIbers,whIchmayoccurbecauseof
bendIngoftheInsertIoncord,entrappIngthecordInotherequIpment,anddroppIngthe
fIberoptIcbronchoscope,arereadIlyapparentandaregenerallynomorethananuIsance
untIlthenumberofbrokenfIbersInterfereswIththevIsualfIeld.
Table 29-18 Contraindications to Fiberoptic Bronchoscopy
HypoxIa
HeavyaIrwaysecretIonsnotrelIevedwIthsuctIonorantIsIalagogues
8leedIngfromtheupperorloweraIrwaynotrelIevedwIthsuctIon
LocalanesthetIcallergy(forawakeattempts)
nabIlItytocooperate(forawakeattempts)
TheInsertIoncordalsocontaInsanaccessory lumen(workIngchannel):alumen,upto2
mmIndIameter,whIchtravelsfromthedIstaltIptothehandle.tcanbeusedforapplyIng
suctIon,oroxygen,andInstIllInglavagIngfluIdsordrugs(e.g.,localanesthetIcs).ThereIs
onereportofgastrIcruptureattrIbutedtotheInsufflatIonofoxygenthroughtheworkIng
channelwhenthefIberoptIcbronchoscopewaswIthIntheesophagus.
170
ngeneral,
fIberoptIcbronchoscopesthatare2mmInexternaldIameter(e.g.,pedIatrIc)donothave
aworkIngchannel.
TwowIrestravelIngfromaleverInthehandledownthelengthoftheInsertIoncord
controlmovementofthedIstaltIpInthesagIttalplane.TheentIreInsertIoncordIs
protectedbyametalwrapuntIlthelevelofthedIstaltIp,whIchIshIngedfor
movement.CoronalplanemovementIsaccomplIshedbyacombIneduseofthecontrol
leverandrotatIonoftheentIrefIberoptIcbronchoscopefromhandletodIstalend.8ecause
thefIbersareabletomoveoveroneanother,exceptforwheretheyarefusedatthe
extremeendsoftheoptIccord,rotatIonalcontrolIsmaxImIzedbyreducInganycurvesIn
thefIberoptIcbronchoscopeshaft.
ThefInalelementofthefIberoptIcbronchoscopeIsthelIghtsource.llumInatIonofthe
objectIveIsprovIdedbyoneortwononcoherentbundlesofglassfIbersthattransmItlIght
fromthehandletothedIstaltIp.ThelIghtIsprovIdedeItherbyaunIversalcordthat
emergesfromthehandleandIsInsertedIntoamedIcalgradeendoscopIclIghtsource,or
maybeprovIdedbyabatteryoperatedlIghtsourceonthehandle.
Use of the Fiberoptic Bronchoscope
ThefIberoptIcbronchoscopeIsheldInthenondomInanthand,thethumboverthecontrol
leverandtheIndexfIngerpoIsedovertheworkIngchannelvalve.ThedomInanthandwIll
beusedtosteadyandholdtheInsertIoncordasItIsmanIpulatedInthepatIent.|any
operatorsaretemptedtoswItchhands,butthethumbofthenondomInanthandshould
becapableofcontrollIngthegrossmovementofthecontrollever.AnyexperIenced
endoscopIstwIllrecognIzethatthefInecontrolrequIredtoholdtheshaftoftheendoscope
steady,advancetheobjectIveendIntotheaIrway,andmakedIrectIonaladjustmentsIs
wheretheartofendoscopylIes.
TheInsertIonshaftIslubrIcatedwIthawatersolublelubrIcantandItIsthreadedthrough
thelumenofanETT,theobjectIveendemergIngfromthemaInETTorIfIce.AclInIcally
approprIateETTshouldbechosen,butthelargertheratIobetweentheInternaldIameter
oftheETTandtheexternaldIameteroftheInsertIonshaft,thegreatertherIskofhang
uponaIrwaystructures,asoccursIn20toJ0ofattempts.
1J9
HangupoccurswhenacleftexIstsbetweenthesetwodevIcesbecauseofthedIfferentIal
sIzes.HangupmayInvolveentrapmentoftheepIglottIs,cornIculate/arytenoIdcartIlages,
thearyepIglottIcfolds,orthevocalfolds,andcanoccurwIthanynumberofstyletguIded
technIques(e.g.,fIberoptIc,retrogradewIre,lIghtedstylet),althoughItIsmostthoroughly
descrIbedwIthfIberoptIcaIdedIntubatIon.
171,172
TheorIentatIonofthetrachealtube
bevelIsImportantInthIsregard.norotrachealIntubatIon,thebevelcleftIslIkelyto
entraptherIghtarytenoIdcartIlagewhentheETTIsInItstypIcalconcavItyanterIor
posItIon.FotatIonoftheETTcounterclockwIse90degreesplacesthebevelfacIng
posterIorlyandImprovespassage.0urIngnasotrachealIntubatIon,theepIglottIsmaybe
entrapped,andabevelupposItIon(rotatIonoftheETT90degreesclockwIse)may
facIlItatepassage.
Thetypeoftrachealtubemayalsoaffectpassage.thasbeensuggestedthattheParker
FlexTIpmaypasstheaIrwaystructuresmoreeasIlythanastandardETTbevel.
17J
Theuse
ofsofttIppedETTs,askIngthepatIenttoInspIredeeplydurIngtheETTadvancement,and
thedoublesetupETT,whIchusesasmallETT(e.g.,5.00)wIthInaclInIcallyadequate
ETT(e.g.,7.50)toovercomethecleftscausedbysIzedIfferentIalshavebeen
descrIbed.
171
TheclInIcIanchoosestherouteofIntubatIon,eItheroralornasal,basedonclInIcal
requIrements,surgIcalneeds,operatorexperIence,andotherIntubatIontechnIques
avaIlableshouldfIberoptIcbronchoscopeaIdedIntubatIonfaIl.ThIslastfactorIsImportant
becauseshouldanattemptatnasalIntubatIonfaIl,theremaybesIgnIfIcantbleedIng,
whIchmayhInderotherIndIrectvIsualIzatIontechnIques.ThenasalrouteIsconsIdered
easIerbymanyclInIcIans,althoughothercautIonsapply:vasoconstrIctorsshouldbe
applIedtoreducebleedIng;theturbInates(lateralwalls)mayobstructETTpassage,bleed,
orbepaInfulwhentraumatIzed;small,lubrIcated,andsoftened(bathedInwarmwater)
ETTshouldbeemployed.
AvarIetyofIntubatIngoralaIrwaysarecommercIallyavaIlable.TheIrchIeffunctIonIsto
provIdeaclearvIsualpathfromtheoralaperturetothepharynx,keepthebronchoscope
InthemIdlIne,preventthepatIentfrombItIngtheInsertIoncord,andprovIdeaclear
aIrwayforthespontaneouslyormaskventIlatedpatIent.ThecommoncharacterIstIcofall
IntubatIngoralaIrwaysIsachannelalongthelengthoftheaIrwaylargeenoughtoallow
thepassageofthetrachealtube.TheDvassapIanaIrwayprovIdestwosetsofsemIcIrcular,
IncompleteflexIbleflangesthatstabIlIzetheETT(uptosIze9.00)InthemIdlInebut
allowItsremovalfromtheaIrwayafterIntubatIonhasbeenaccomplIshedsothatthe
IntubatIngoralaIrwaycanberemovedfromthemouth.TheflatlIngualsurfaceofthe
aIrwaygIvesItgoodlateralandrotatIonalstabIlIty.ThePatIlSyracuseendoscopIcaIrway
andtheLuomanenoralaIrwaywerealsodesIgnedforfIberoptIcaIdedIntubatIon.Eachhas
acentralgroove,openatthelIngual(PatIlSyracuse)orpalatal(Luomanen)aspect,whIch
allowseasyremovaloftheETT.TheflatlIngualsurfaceprovIdesgoodstabIlIty.Although
thIsstyleofIntubatIngoralaIrwayprovIdessuperbaccesstothepharynx,ItIslargerthan
otheraIrwaysandIsoftenuncomfortableforthepatIent.TheWIllIamsaIrwayandthe
8ermanaIrwaywerebothdesIgnedforblIndoralIntubatIon.tIsoftendIffIcultto
manIpulatethetIpofthefIberscopewhenItIswIthInthesenarrowaIrways.8othare
moldedplastIcwIthacompletecIrcularInternallumenthatguIdestheETTtowardthe
larynx.TheseaIrwayshaveasmallprofIleandareoftenbettertoleratedbytheawake
patIent,buttendtobelessstableonthetongue.8ecausetheInternallumenIsacomplete
cIrcle,theWIllIamsaIrwaymustberetreatedofftheETTIfItIsgoIngtoberemovedafter
IntubatIon.ThIsmayposedIffIcultyIftheETTInusehasafusedcIrcuItadapter.The
8ermanaIrwaysolvesthIsproblembybeIngsplItalongthelengthofonesIde.TheplastIc
oftheopposItesIdeIsthInandmalleable.ftheInterIncIsorgapIsadequate,theaIrway
canbeopenedlaterallytoallowremovalfromtheETT.
AftersuccessfulnavIgatIonthroughtheoralaIrway,theendoscopIstvIsualIzesthevocal
folds.fglottIcclosure,gag,orcoughIngoccursasthefIberoptIcbronchoscope'sdIstaltIp
stImulatesthestructuresofthelarynx,theoperatorcanchoosetoapplylocalanesthetIc
throughtheworkIngchannel,admInIstermoresedatIon,orwIthdrawthescopeand
reInforcepreparatoryprocedures.TheclInIcIanmIghtalsodecIdetoadvancethe
fIberoptIcbronchoscopeIntothelarynxwIthoutfurtherpreparatIon.TheactIonstaken
mustbedIctatedbytheIndIvIdualclInIcalsItuatIon;IntheelectIvescenarIo,forexample,
theremaybetImeforreInforcedaIrwayanalgesIa,whereas
P.781
InthefaceofImpendIngrespIratoryarrest,patIentdIscomfortmayneedtobetolerated.
DncethelarynxIsentered,theoperatormaychooseastructure,suchasthetracheal
carIna,toserveasanIdentIfyInglandmarkastheETTIsadvanced.SImplybecausethe
fIberoptIcbronchoscopehasenteredthetrachea,thereIsnoguaranteethattheIntubatIon
wIllbesuccessful.AsprevIouslynoted,20toJ0ofETTadvancementsareaccompanIedby
hangup.Therefore,apatIentwIthacrItIcalaIrwayshouldnotbeInducedwIthageneral
anesthetIcwIththeassumptIonthattheETTwIllbeeasytopass.
Table 29-19 AIDS to Fiberoptic-Aided Intubation
TECHNIQUE ADVANTAGE
Endoscopymask
ControlledventIlatIonmaIntaIneddurIngorbetween
attemptsatFD8aIdedIntubatIon
Laryngealmask
ExcellentvIewofthelarynxandabIlItytoventIlate
durIngorbetweenattemptsatFD8aIdedIntubatIon
FIberoptIcaIded
retrogradeIntubatIon
CuIdIngoftheFD8wIthawIreknowntobeenterIng
thetrachea
FetrogradefIberoptIc
IntubatIon
ChangIngatracheostomytoanoralornasaltracheal
tubewhenantegradeIntubatIonIsdIffIcultor
ImpossIble
FD8aIdedIntubatIonwIth
theaIdofarIgId
laryngoscope
HelpfulwIthanobstructIngmassorlargeepIglottIs
FD8,fIberoptIcbronchoscope.
TheprImarylIteraturecontaInsanumberofvarIatIonsandadjunctstofIberoptIc
bronchoscopeaIdedIntubatIon.Table2919,whIchIsnotmeanttobeexhaustIve,lIsts
severalofthesetechnIques.
AlthoughfIberoptIcbronchoscopeaIdedIntubatIonIsaversatIleandvItaltechnIque,there
areseveralpItfalls,mostofwhIchhavebeendIscussed.Table2920lIststhemostcommon
reasonsforfaIlureoffIberoptIcbronchoscopeaIdedIntubatIon.
FlexIblefIberoptIcaIdedIntubatIonIsatechnologyIntensetechnIque.Apartfromthe
delIcatefIberoptIcdevIce,therearecameras,recorders,lIghtsources,andavarIetyof
dIsposableadjunctsthataretypIcallyrequIred.0edIcatedwheeledcarts,desIgnedtocarry
requIredandoptIonalequIpmentInafunctIonalarrangement,areavaIlable.
The Future Technology of the Flexible Fiberoptic
Bronchoscope in Airway Management
TheadventofthechargecoupledevIcetechnologywasembracedInthemanufactureof
endoscopesusedfordIagnostIcpurposes.ThesedevIcesrequIredhIghresolutIonImagesIn
ordertodetectsmalllesIonsorperformdelIcateprocedures(e.g.,venousdIssectIon).ThIs
costlytechnologywasslowtobeIncorporatedIntoIntubatIngflexIblescopes,whIchwork
InamacroenvIronment,notrequIrIngthesamemIcroresolutIon.Althoughsome
manufactureshaveproducedthesedevIcesfortheanesthesIamarket,C|DStechnology,
whIchmaybeproducedatafarlowercosts,promIsestoIncreasethenumberofavaIlable
devIces.
Rigid Fiberoptic Intubation Devices
FIgIdfIberoptIcdevIcesallowIndIrectvIewsofthelarynxandactasanETTguIdefor
IntubatIon.|orethanonethIrdofallanesthesIologIstshaveaccesstothesedevIces.
140
ThemostcommonlyavaIlableofthesedevIcesIncludethe8ullard(AC|,Santa8arbara,
CA)Upshur(|ercury|edIcal,Clearwater,FL)andWuScope(PentaxPrecIsIonnstruments,
Drangeburg,NY)laryngoscopes.AlthoughtheselaryngoscopesmaybeusedInroutIne
clInIcalsItuatIons,theyarepartIcularlyusefulwhenmovementofthepatIent'sheadand
neckIsImpossIbleorcontraIndIcated(e.g.,atlantooccIpItaljoIntdIseaseandthespIne
InjuredpatIent).TheyarealsoapplIcablewhenthereIsalImItedoralaperture(0.64cmIn
thecaseofthe8ullard).ThesedevIcesconsIstofarIgId,staInlesssteellaryngoscopelIke
bladethatencasesafIberoptIccablewIthaproxImaleyepIeceanddIstalobjectIvelens.
ThebladeshaveananatomIccurvetomatchtheneutralposItIonofthehumanoralcavIty
pharynxhypopharynxrelatIonshIp.AlIgnmentoftheoral,pharyngeal,andtrachealaxesIs
notrequIred.llumInatIonIsprovIdedbyasecondfIberoptIccabletransmIttInglIghtfroma
batterypoweredorfreestandInglIghtsource.
The8ullardscope,whIchcomesInadultandpedIatrIcsIzes,hasbeenthebest
InvestIgated.tfeaturesafIxedfIberoptIccablelocatedontheposterIoraspectofthe
blade.TheeyepIecelenshasanadjustabledIopter.AworkIngchannelalsorunsthelength
oftheblade.DncethelarynxIsvIsualIzed,theETTIsadvancedusIngadetachablestylet,
althoughothertechnIqueshavebeendescrIbed.Theadvantagesofthe8ullardscopeover
tradItIonallaryngoscopebladesInmanagIngthespIneInjuredpatIentandtheobese
patIenthavebeenInvestIgated.
174,175,176
AdequateexposurewIththe8ullardlaryngoscope
maybeachIevedafterfaIled0L.
TheUpsherscope(|ercury|edIcal,Clearwater,FL)IsavaIlableInanadultsIzeasofthIs
wrItIng.nsteadofastylet,
P.782
theETTIsheldandadvancedthroughaCshapedlumenIntheblade.ThereIsnoworkIng
channelInthIsscope.TheeyepIeceIsfocusable.
Table 29-20 Common Reasons for Failure During Fiberoptic-Aided
Intubation
LackofexperIence:NotpractIcIngonroutIneIntubatIons
FaIluretoadequatelydrytheaIrway:UnderdoseorrushedtechnIque
FaIluretoadequatelyanesthetIzetheaIrwayoftheawakepatIent:SecretIonsnot
drIed;rushedtechnIque
NasalcavItybleedIng:nadequatevasoconstrIctIon;rushedtechnIque;forcIbleETT
InsertIon
DbstructIngbaseoftongueorepIglottIs:PoorchoIceofIntubatIngaIrway;requIre
chInlIft/jawthrust
nadequatesedatIonoftheawakepatIent
Hangup:ETTtoolarge
FoggIngoftheFD8:SuctIonoroxygennotattachedtoworkIngchannel;cold
bronchoscope
ETT,endotrachealtube;FD8,fIberoptIcbronchoscope.
TheWuScopedIffersfromtheotherdevIcesInthataflexIblefIberoptIcendoscopeIsfItted
IntoapassagewIthInathreepartstaInlesssteelhandleandblade.Asecond,largerlumen
acceptstheETT.AworkIngchannelIsposItIonedalongsIdetheendoscopelumen.Two
adultsIzesaremanufactured.DncethelarynxIsvIsualIzedandtheETTIsadvancedInto
thetrachea,thetwostaInlesssteelpIecesofthelaryngoscopebladearedIsassembledand
removedfromthemouth.UnlIketheothertwodevIces,theWuScopecanalsobeusedfor
nasalIntubatIonbyassemblIngonlytheanterIorbladeportIonandthehandle.AnETT,
prevIouslyplacedInthepharynxvIathenares,canbefIttedIntotheanterIorportIonof
theblade.
AnewgeneratIonoffIberoptIcdevIcesIsfocusedonsImplIcItyandportabIlItyby
IncorporatIngoptIcalandlIghtsourceelementsIntoasInglestyletlIkestaInlesssteel
sheath.ThelackofatonguedIsplacIngbladeandasuctIon/oxygenchannelarepotentIal
dIsadvantages.The8onfIlsntubatIonFIberscope(KarlStorzEndoscopy,TuttIngen,
Cermany;FIg.2916A)Isalong,rIgIdtubulardevIcewIthconventIonaloptIcalandlIght
transmIttIngfIberoptIcelements.
177
AproxImalendeyepIece(wIthadjustabledIopter)can
beusedwIththenakedeyeorfIttedwIthastandardendoscopycamera.Acable(or
batterypoweredattachment)brIngsIllumInatIonfromanexternallIghtsource.ThedIstal
endhasa40degreeangulatIon.SuctIonmaybeapplIedthroughaworkIngchannel.The
technIqueofusereplIcatestheparaglossalapproachoflaryngoscopydIscussedprevIously
InthIschapter.TheShIkanISeeIngDptIcalStylet(SDS;Clarus|edIcal,Colden7alley,|N)
hasasImIlarconfIguratIontothe8onfIls,wIththeexceptIonthatthedIstalhalfofthe
styletIsmalleable(FIg.29168).ThelIghtsourcemaybeselfcontaIned(aproprIetary
poweredhandleoragreenlIne[Fusch|edIcal,0uluth,CA]laryngoscopehandle),or
cabled.UnlIkethe8ofIls,amIdlIneapproachIsrecommended.AsImIlardevIce,the
LevItanFPSscope(Clarus|edIcal,Colden7alley,|N),ashorter(J0cm)versIonofthe
SDS,IsdesIgnedtobeuseddurIng0LwhenahIghlaryngealvIewscoreIsencountered(FIg.
29168).TheshorterlengthallowsmoreergonomIcposItIonIngbythelaryngoscopIst.
178
StudIeshaveInvestIgatedtheuseoftheSDSasasubstItuteforthelaryngoscopeInroutIne
anesthetIccases.
179
ThehypothetIcalbenefItofthIspractIceIsthereductIonof
unantIcIpateddIffIcultIntubatIonsandthemaIntenanceofalternatIvetechnIqueskIllsby
IncorporatIngthIsorsImIlardevIcesIntodaIlypractIce.
141
Figure 29-16. A.The8onfIls(KarlStorzEndoscopy,CulverCIty,CA).nset:DbjectIve
endwIthIntrachealtube.B.TheShIkanISeeIngDptIcalStylet(Clarus|edIcal,
|InneapolIs,|N).
Case 3: Retrograde Wire Intubation
A65yearoldwomanwItha60pack/yearhIstoryofsmokIngandadvancedrheumatoId
arthrItIspresentstotheemergencydepartmentInrespIratorydIstress.Heroxygen
saturatIonwIthanonrebreatheroxygenmaskIs85.ShehasalImItedoralaperture
(approxImately2.5cm)andathyromentaldIstanceof6cm.AlthoughthecrIcothyroId
membranecanbepalpated,thereIslImItedaccesstoItandthetrachealrIngsowIngtoa
sIgnIfIcantcervIcalkyphosIs.ThesputumIsnotedtobebloodtIngedandcontaIns
thIckenedbronchIalsecretIons.AwakeblIndnasalIntubatIonIsattemptedtwIcebythe
emergencymedIcInephysIcIans,Isunsuccessful,andresultsInepIstaxIs.Fetrograde
IntubatIonoftheaIrwayIsperformedwIththepatIentInasIttIngposItIon.AfterInItIal
localanesthetIcInfIltratIonoftheskInoverthemembrane,an18gaugeangIocatheterIs
advancedoverthemIdcrIcothyroIdmembraneataangleof45degreestothechest.After
thefreeaspIratIonofaIrIsnoted,theTeflonsheathofthecatheterIsadvancedIntothe
trachea.A0.0J5InchradIologIcguIdewIre110cmInlengthIsadvancedvIathecatheter
untIltheproxImalendemergesfromthemouth.A7.0ETTIsplacedoverthewIreandIs
guIdedIntothetrachea.ThewIreIsremovedbypushIngItIntothepercutaneouspuncture
sIteandretrIevIngItfromtheproxImalendofthetrachealtube.8reathsoundsare
auscultatedoverthelungfIeldsasventIlatIonIsassIstedwIthposItIvepressure.Dnce
ImprovedoxygensaturatIonIsnoted,thepatIentreceIvessedatIonwIthIntravenous
mIdazolam(IndIvIdeddoses,tItratIngtothesedatIveeffect).
Use of the Retrograde Wire Intubation in Airway Management
FetrogradewIreIntubatIon(FW)InvolvestheantegradepullIngorguIdIngofanETTInto
thetracheausIngawIrethathasbeenpassedIntothetracheavIaapercutaneous
puncturethroughthecrIcothyroIdmembraneor
P.78J
thecrIcotrachealmembrane,andblIndlypassedretrogradeIntothelarynx,hypopharynx,
pharynx,andoutofthemouthornose.n199JthetechnIquewasIncludedIntheASA's
0IffIcultAIrwayAlgorIthm.ThebasIcequIpmentusedIntheretrogradeIntubatIon
technIqueIslIstedInTable2921.
FWhasbeendescrIbedInanumberofclInIcalsItuatIonsasaprImaryIntubatIontechnIque
(electIveorurgent)andafterfaIledattemptsat0L,fIberoptIcaIdedIntubatIon,andL|A
guIdedIntubatIon.
85
ThemostcommonIndIcatIonsareInabIlItytovIsualIzethevocalfolds
owIngtoblood,secretIons,oranatomIcvarIatIons,unstablecervIcalspIne,upperaIrway
malIgnancy,andmandIbularfracture.ContraIndIcatIonsIncludelackofaccesstothe
crIcothyroIdmembraneorthecrIcotracheallIgament(becauseofsevereneckdeformIty,
obesIty,mass),laryngotrachealdIsease(stenosIs,malIgnancy,InfectIon),coagulopathy,
andskInInfectIon.
Table 29-21 Equipment for Retrograde Wire Intubation
18gaugeorlargerangIocatheter
LuerlocksyrInge,JmLorlarger
CuIdewIre:
PreferablyJtypeend
Length:atleast2.5tImesthelengthofastandardETT(typIcally110120cm)
0Iameter:CapableofpassIngvIaangIocatheterbeIngchosen
Dther:Scalpelblade,nervehook,|agIllforceps,J0InchsIlksuture,epIdural
catheter
ETT,endotrachealtube.
TheanatomIcrelatIonshIpstobeconsIderedInFWhavebeendescrIbedelsewhereInthIs
chapter.CommoncomplIcatIonsreportedwIthFWIncludebleedIng,subcutaneous
emphysema,pneumomedIastInum,pneumothorax,breathholdIng,caudaltravelIng
catheter,andtrIgemInalnervetrauma.
Figure 29-17.ThesequenceofretrogradewIreIntubatIonafterthecrIcothyroIdor
crIcotracheallIgamentIsIdentIfIedandapercutaneouspunctureIsperformedwIthaIr
aspIratIon.A.TheretrogradedevIce(twIstedwIre)IsadvanceduntIl(B)Itemerges
fromthemouthornose.C.ThewIreIsclampedattheentrancesIte(arrow)andthe
endotrachealtubeIsadvancedoverthewIreInanantegradefashIon.D.ThewIreIs
removed,leavIngthetrachealtubeInplace.
nthecurrentpatIent(asIncase1),FWwaschosenInasettIngInwhIchthepatIentwas
notapneIcandwasthereforesupportIngherownventIlatIonandoxygenatIon,albeIt
poorly.ThetwocasesdIfferInImpendIngrespIratoryfaIlure(case2)versusfIberoptIc
bronchoscopeaIdedIntubatIonundertakenInastablesItuatIon(case1).nmany
sItuatIons,whereawakeIntubatIonIsapreferredInItIalapproachtosecurIngtheaIrway,
thereIslIttletImeforpatIentpreparatIon(e.g.,theadmInIstratIonofantIsIalagogues,
topIcalanesthetIcs,and/orsedatIon).nthIsregard,FWdoesnotrequIreaclearvIsual
fIeldorsIgnIfIcantpatIentcooperatIonandcanoftenbeperformedwIthlIttleanalgesIaof
theaIrway.ThetechnIqueofFWdIffersgreatlyfromothermethodsoftrachealIntubatIon
famIlIartotheanesthesIologIst.Preferably,FWshouldbelearnedona
sImulator/mannequInmodelbeforebeIngattemptedInapatIent.naddItIon,unlessFWIs
practIcedoften,ItmaybetImeconsumIng.ForthIsreason,FWmaybeapoorchoIcefor
rescueofanacutelycompromIsedaIrway.
Performing Retrograde Wire Intubation
FWIsgenerallyperformedwIththepatIentInasupIneposItIon,althoughthesIttIng
posItIonIsoftenusedforpatIentsInrespIratorydIstress(FIg.2917).ExtensIonofthehead
ortheneckdIsplacesthe
P.784
crIcoIdandtrachealcartIlagesanterIorlyandmovesthesternocleIdomastoIdmuscles
laterally,althoughasIncase2,thIsmaynotalwaysbepossIble.TheskInshouldbe
prepared.fthepatIentIsconscIous,alocalanesthetIcskInwheelIsmadeoverthe
puncturesIte.LocalanesthesIaoftheaIrwayshouldbeadmInIsteredtopreventdIscomfort
andtobluntaIrwayreflexesastImepermIts.ngeneral,topIcalanesthesIaofthetrachea,
larynx,pharynx,andnasalpassagesIsdesIrable.TranslaryngealanesthesIaIsapartIcularly
convenIenttechnIquebecauseapercutaneousentryofthetracheaIsrequIreddurIngthe
FW.StructuresaboveandbelowthevocalfoldsareanesthetIzeddurIngtheensuIng
patIentcoughIfalocalanesthetIcfIlledsyrIngeIsusedtofacIlItatetherecognItIonof
approprIateneedleplacement(wIthtrachealaIrbubbles)andthenIsInjectedtoprovIde
aIrwayanesthesIa.
AsnotedearlIer,thecrIcothyroIdmembraneandcrIcotracheallIgamentarebothpotentIal
sItesfortranslaryngealpuncture.AlthoughthecrIcothyroIdmembranehastheadvantage
ofbeIngdIrectlyanterIortothelargeposterIorsurfaceofthecrIcoIdcartIlage,thereby
protectIngtheesophagusfromapuncturIngneedle,ItplacestheneedleIncloseproxImIty
(0.9to1.5cm)tothevocalfolds,andhenceallowsforasomewhatsmallermargInoferror
atthetImeoftheIntubatIon.
AnatraumatIcJguIdewIreIsthepreferredretrogradedevIce.TheseguIdewIresare
typIcally0.0J2to0.0J8InchesIndIameter,beIngabletopassthoughan18gauge
Intravenouscatheter.ThetypIcallengthIsbetween110and120cm.TheonlyrequIrement
forlengthIsthatthewIrebemorethantwIceaslongasthetrachealtubetobeused.KIts
areavaIlablethatconvenIentlyIncorporateallthenecessaryequIpment(CookCrItIcal
Care).
Theneedle/catheterapproachesthetracheaat90degreestothecoronalandsagIttal
planesIfpossIble(asItwasnotpossIbleIncase2).nthIsorIentatIon,theneedleIslIkely
toImpacttheposterIoraspectofthecrIcoIdcartIlageIfadvancedtoofar,andnot
puncturetheesophagus.AddItIonally,thIsanglewIllhelptoavoIdtraumatothenearlyIng
vocalfolds.
AfterthepercutaneouspunctureIsmadeandthetracheaIdentIfIedbyfreeaIraspIratIon,
thecatheterIsangledcephaladandthewIreIsadvanced(JtIp)IntothetracheauntIlIt
emergesfromthemouthornose.ThewIremayneedtoberetrIevedfromthemouthwIth
asweepIngfInger,|agIllforceps,ornervehook.AnyobstructIontoadvancementofthe
wIreshouldpromptreevaluatIonoftheangleofthecatheterandtheposItIonofthehead
andneck(e.g.,catheterdIrectedposterIorand/orcaudad,neckflexed).CoughIngtypIcally
heraldsacaudadtravelIngofthewIre.fthewIreIsretractedandfoundtobebent,ItIs
prudenttoprocureanewone.WhencomplaIntsofpaInareencounteredabovethelevelof
thelarynx,ItIstypIcallybecauseofthewIrepassIngIntoanInadequatelypreparednasal
cavIty.DptIonsIncluderetractIngthewIremodestlyandaskIngthepatIenttoopenthe
mouthandmaxImallyprotrudethetonguedurIngthereadvancement,reachIngIntothe
oropharynxtoretrIevethewIre,orpatIentlyrepreparIngthenasalpassages.DncethewIre
IssatIsfactorIlyretrIeved,placementofthetrachealtubemaybeperformedusIngthewIre
InanumberoffashIons,dependIngontheoperator'spreferenceandprevIousexperIence.
Table2922lIstscommontechnIques,togetherwIththeIradvantagesanddIsadvantages.
0etaIlsofthesetechnIqueshavebeendescrIbedelsewhere.
85
nthecasereported,othertechnIquesmayhavebeenconsIdered.AlthoughIndIrectvIsual
devIces(flexIblefIberoptIcbronchoscope,rIgIdfIberoptIclaryngoscope)alsomayhave
beenhelpfulInthIscase,threeelementsworkedagaInsttheIruse:(1)tIssuetraumafrom
repeatedattemptsatblIndnasalIntubatIonproducedabloodyaIrway,frustratIngtheuse
ofthesedevIces;(2)thepatIentwasunabletocooperateowIngtoherrespIratorydIstress;
and(J)becauseoftheImpendIngrespIratoryfaIlure,therewaslIttletImeforadequate
aIrwayanalgesIa.AcoughIng,gaggIng,conscIouspatIentmakesfIberoptIctechnIques
nearlyImpossIble.StraInIngandcoughIngdurIngfIberoptIcIntubatIonattemptshave
resultedIn|alloryWeIsstearsoftheesophagus,resultIngInsIgnIfIcanthemorrhage.
Table 29-22 Techniques of Endotracheal Tube (ETT) Advancement Over A
Retrograde Wire
TECHNIQUE ADVANTAGE DISADVANTAGE
WIretravelsthrough
entIremaInlumenofthe
StandardtechnIque
|argInoferror
a
equalsdIstancefrom
vocalfoldsto
puncturesIte
Nostyletafter
ETT removalofwIre
FaIlroadIng
b
can
occur
WIreplacedIntoETT
lumenvIa|urphyeye
WIreentersdIstalendof
ETTandexItsvIa|urphy
eye
ncreasedmargInof
error
0ecreasedraIlroadIng
Cannotusestylet
(below)
|argInoferrorequals
dIstancefromvocal
foldstopuncturesIte
Cannotusestylet
(below)
ETTexchangestyletIs
placedoverwIre,prIor
toplacementofETT
Canusestylettovastly
IncreasemargInof
erroroncewIreIs
removed
Cost
FIberoptIcbronchoscope
IsplacedoverwIreprIor
toplacementofETT
Canusestylettovastly
IncreasemargInof
erroroncewIreIs
removed
7IsualIzatIon
Cost
SIlksuture
NoraIlroadIng
|argInoferrorIssues
reduced
|aybedIffIculttoplace
sIlksuture
SmallETT FeducedraIlroadIng
|aynotbeclInIcally
adequate
a
Margin of errorreferstothedIstancebelowthevocalfoldsthattheendotracheal
tubeextendsatthetImethattheguIdewIreIsremoved.fthIsdIstanceIsnot
adequate,thereIsarIskofImmedIateextubatIon.
b
RailroadingreferstothedIfferentIalsIzeoftheguIdewIreandthetrachealtube.
AlargedIscrepancyInsIzeallowsforacleft,whIchmayentraptheepIglottIs,
arytenoIdcartIlages,aryepIglottIcfolds,orvocalfolds,hInderIngIntubatIon
attempts.
P.785
8lIndnasalIntubatIonwasthefIrsttechnIqueattemptedInthIspatIent.UntIlrecently,
blIndnasalIntubatIonhasbeenastapleofaIrwaycontrol,especIallyIntheemergency
department,whereIthasbeenlargelysupplantedbyrapIdsequenceIntubatIon.ThIs
technIquerequIressIgnIfIcantanalgesIaofthenasalpassagesIntheawakepatIent.Success
IsfarmorelIkelyInthespontaneouslybreathIngpatIent.WIththeheadInthe|agIll
posItIon,theETTIsadvancedIntothenares,nasalpassage(keepIngtheETTbevel
alongsIdethenasalseptum),andIntothepharynx.8reathsoundsareauscultatedfromthe
ETT,andItsposItIonadjustedkeepthemmaxImIzed.ThepatIent'sheadandlarynxcanbe
manIpulatedexternallyasnecessary.
Case 4: Esophageal Tracheal Combitube
A55yearoldmanwIthahIstoryofcIrrhosIsandesophagealvarIcesrequIresaIrway
controlbecauseofacute,recurrentuppergastroIntestInalbleedIng.Apartfromfreshblood
IntheaIrway,physIcalexamInatIonofhIsexternalaIrwayIsconsIstentwItharoutIne
laryngoscopy.Furthermore,hehadbeenIntubatedforsImIlareventsInthepast.Aftera
rapIdsequenceInductIon,thelarynxcannotbevIsualIzedonthreelaryngoscopIesbecause
offreshbloodemanatIngfromtheesophagus.Dnallthreeattempts,theETTIsadvanced
blIndly,andtheabsenceofbreathsoundsoverthethoraxtogetherwIththepresenceof
copIousbloodIntheETTleadstothedIagnosIsofesophagealIntubatIon.Alarge,adult
sIzedEsophagealTrachealCombItube(TycoHealthcare,|ansfIeld,NY)Isrequested,
blIndlyInsertedIntotheaIrway,andthepharyngealanddIstalcuffsareInflated.
7entIlatIonthroughthepharyngealperforatIonslumen(blue)producesbIlateralbreath
soundstoauscultatIon,andtheoxygensaturatIonIncreasesto90.CopIousbloodIs
suctIonedfromtheesophageallumen.ThepatIentIstransportedtotheangIographysuIte
wherehIsesophagealvarIcesareembolIzed.TheesophagealtrachealCombItubeIs
removedandthepatIentIsIntubatedwIth0L.
TheEsophagealTrachealCombItube(CombItube)wasdevelopedby0r.|IchaelFrass,a
crItIcalcarephysIcIanIn7Ienna,AustrIa,In1986.tsdesIgnwasmeanttoImproveand
replacetheesophagealobturatoraIrway,whIchwasarescueaIrwayIntroducedIn1968.
TheCombItubeIsadoublelumenaIrway,thedIstalendofwhIchIsmeanttobeblIndly
placedIntotheesophagus.DnelumenbegInsatthIsdIstalpoIntwIthalargeorIfIce,and
travelstooutsIdethepatIentwhereItopenstotheatmosphere.ThIslumenservesasa
gastrIcdraIn.ThesecondlumentravelsfromoutsIdethepatIenttoapoIntInthe
hypopharynx.ThIslumenhasamultIorIfIceopenIngthatfacesthelarynxandactsasthe
aIrway.TheCombItubehastwocuffs,onewIthIntheesophagusandasecondatthe
oropharynx/pharynxjuncture.TheCombItubeIsfunctIonalIfIntroducedIntotheesophagus
(ventIlatIonbeIngachIevedthroughtheesophageallumen,vIathehypopharyngeal
perforatIons)orInthetrachea(ventIlatIonbeIngachIevedthroughthetracheallumen,vIa
thedIstalaperture).neIthercase,theproxImalballoonsealsboththeoralandnasal
passages,andthedIstalconventIonaltrachealtubecuffIsolatestherespIratorysystem
fromthegastroIntestInalsystem.ThedevIceIsavaIlableIntwosIzes:the41FrenchsIzeIs
usedforlargeradults(heIght168cm)andtheJ7FrenchsIzeIsusedforadults12218Jcm
(FIg.2918).
Use of the Esophageal Tracheal Combitube
TheCombItubeIsInsertedblIndly.TheoperatorlIftsthelowerjawandtongueanterIorly
wIthonehand,andtheCombItubeIsInsertedwIthadownward,caudadcurvedmotIon
untIltheproxImaldepthIndIcator(twoblackrIngsprIntedonthedoublelumentube)come
torestattheleveloftheteeth.TheoropharyngealballoonIsInflatedwIth100mLofaIr
throughablueplastIcpIlotballoon(85mLInthesmalladultsIze)whIlethedIstalcuffIs
InflatedwIth5to15mL(vIaawhItepIlotballoon).AnAmbubagoranesthesIacIrcuItIs
attachedtotheproxImalendoftheesophageallumen(constructedofbluepolyvInyl
chlorIde),andventIlatIonIsconfIrmedbyauscultatIonorothermeans.8ecause90of
CombItubeplacementsresultInanesophagealposItIon,ventIlatIonoccursvIathIslumen's
hypopharyngealperforatIons.fnobreathsoundsareauscultatedand/orgastrIcInflatIonIs
noted,theCombItubehasbeenposItIonedInthetrachea.WIthoutreposItIonIng,
ventIlatIonIschangedtothedIstalendoftracheallumen(clearpolyvInylchlorIde).fno
maneuverImprovesventIlatIon,thedevIceIsmostlIkelyIntheesophagusbuthasbeen
advancedtoodeeply,wIththeoropharyngealcuffobstructIngtheaIrway.nthIscase,the
cuffsshouldbedeflated,thedevIcewIthdrawn2cm,andtheventIlatIonsequence
repeated.
Figure 29-18.TheesophagealtrachealCombItube.nset:ThefIberoptIcportofthe
EasyTube.
AdvantagesoftheCombItubeIncluderapIdaIrwaycontrol,aIrwayprotectIonfrom
regurgItatIon,easeofusebytheInexperIencedoperator,norequIrementtovIsualIzethe
larynx,andtheabIlItytomaIntaIntheneckInaneutralposItIon,althoughcervIcalspIne
movementmaybegreaterthanthatseenwIththeL|A,L|AFastrach,andflexIble
fIberscope.
180
thasbeenshowntobeusefulInthepatIentwIthmassIveupper
gastroIntestInalbleedIngorvomItIng,andasarescuedevIceInfaIledrapIdsequence
InductIonorunantIcIpateddIffIcultIntubatIon.tIsalsousefulInthemorbIdlyobese,In
acutebronchospasm,durIngcardIopulmonaryresuscItatIon,andforprolongedventIlatIon
afteraIrwayrescue.
86,125,126,127,128,129,1J0,1J1,1J2,181,182,18J
SeveralserIeshave
demonstratedtheeffectIvenessCombItubeInprehospItalmanagementoftheaIrway.
184,185
UrtubIaetal.
186
haveusedtheesophagealtrachealCombItubeforelectIvesurgerywItha
hIghsuccessandlowcomplIcatIonrate.
ContraIndIcatIonstouseoftheCombItubeIncludeesophagealobstructIonorother
abnormalIty,IngestIonofcaustIcagents,upperaIrwayforeIgnbodyormass,loweraIrway
obstructIon,heIght4feet,andanIntactgagreflex.8ecausetheCombItubeIncludeslatex
InItsconstructIon,ItshouldnotbeusedInpatIentswIthlatexallergy.
ComplIcatIonsassocIatedwIththeCombItubehaveIncludedlaceratIonstothepyrIform
sInusandesophagealwallresultIngInsubcutaneousemphysema,pneumomedIastInum,
pneumoperItoneum,andesophagealrupture.
187,188,189
AdevIcesImIlartotheCombItubehasbeenavaIlableInmanypartsoftheworldsInce
200J.
190
TheEasyTube(FuschnternatIonal,Kernen,Cermany)IsdIstrIbutedIntwosIzes,
41frforpatIentsabove1J0cmInheIghtand28frforpatIents
P.786
90to1J0cmInheIght.UnlIketheCombItube,thedIstallumenoftheEasyTubeIsdesIgned
toresembleanETT(IncludInga|urphyeye).ThepharyngealapertureIsdesIgnedtoallow
easypassageofafIberscope(orsuctIoncatheter;FIg.2918,Inset).TheEasyTubewas
desIgnedforusedurIngroutIneandemergencyanesthetIcaswellascannot
Intubate/cannotventIlatesItuatIons.
191
ContraIndIcatIonstoEasyTubeuseareIdentIcalto
thosefortheCombItube.AlthoughItmaybeInsertedblIndly,ItIsdesIgnedtobeusedwIth
alaryngoscope(muchlIkeastandardETT).UnlIketheCombItube,ItIslatexfree.
Case 5: Failed Rapid-Sequence Induction and the SGA
AJ9yearoldmanpresentsforelectIveuvulopharyngopalatoplasty.HehasnoprevIous
surgIcalhIstory.HIsmaxImalIncIsorgapIs5cm,thyromentaldIstanceIs7cm,andhIs
oropharyngealvIewIsaSamsoonYoungclass2.ThereIsnolImItatIonInheadandneck
flexIonandextensIon.0urIngasleepapneastudy,hehad15apneIceventseachhour.The
patIenthasasIgnIfIcanthIstoryofgastroesophagealreflux,andrapIdsequenceInductIonIs
planned.AftertheadmInIstratIonofpentothal,succInylcholIne,andcrIcoIdpressure
(SellIckmaneuver),0LwItha|acIntoshnumberJlaryngoscopebladerevealsalarge
epIglottIsobscurIngthevIewofthevocalfolds(CormackLehanegradeJ).
82
SIgnIfIcant
hyperplasIaofthebaseofthetongue,whIchpreventsItsfulldIsplacement,Isalsonoted.
The8UFPmaneuverdoesnotImprovethevIew.
80
A|acIntosh4and|IllerJbladesare
usedanddonotImprovethevIew.DxygensaturatIon,whIchwas100prIortoInductIon,Is
now92,ansdfacemaskventIlatIonIsInItIatedwIththeSellIckmaneuverInplace.
CompleteobstructIontoventIlatIonIsencountered,despItechInand/orjawlIft,two
personventIlatIon,andareductIonInthedegreeofcrIcoIdpressure.Theoxygen
saturatIonfallsto85andasIze5L|A(whIchhadbeenpreparedprIortotheInductIonof
anesthesIa)IsInsertedwIththetechnIqueasdescrIbedbytheInventor.mmedIately,a
clearaIrwayIsestablIshedandtheSellIckpressureremaInsInplace.Aseconddoseof
PentothalIsadmInIstered,andthepatIentIsIntubatedbytheblIndpassageofa7.00ETT
vIatheL|A.TheL|AIsthenremovedusIngaCookaIrwayexchangecatheterasastylet,
andthesurgIcalcaseproceeds.
The SGA in the Failed Airway
DneclearadvantageofSCAuseIsInthefaIledaIrway.Therehavebeenmanyreported
(andunreported)casesoffaIledIntubatIonandfaIluretoventIlatebyfacemaskInwhIch
theaIrwaywasrescuedwIthanL|A,LaryngealTube,CobraPLAoranotherSCA.
192,19J,194
Parmetetal.
124
estImatethat1In800,000patIentscannotbemanagedwIthanL|A,
provIdIngan80foldIncreaseInmargInofsafetyovertheoftnoted1In10,000patIents
whocannotbeventIlatedbymasknorIntubatedbytradItIonalmeans.LIkewIse,awealth
oflIteraturedescrIbestheuseofthevarIousSCAsInelectIvedIffIcultaIrwaymanagement
InawakeandunconscIouspatIents,InantIcIpatedandunantIcIpatedsItuatIons,IncervIcal
spIneInjury,andInpedIatrIcdysmorphIcsyndromes.
56,57,116
ThecharacterIstIcsoftheSCAsthatunderlIetheIrsuperIorItyasatoolInthedIffIcult
aIrwayarmamentarIumarethattheyarewelltoleratedbythepatIent,sImulatIngthe
naturaldIstensIonofthehypopharyngealtIssuesbyfood,andthatItsInsertIonfollowsan
IntrInsIcpathway,requIrIngnotIssuedIstortIon(aswIthlaryngoscopy),whIchmaynotbe
possIbleInallpatIents.FInally,ItIsablIndtechnIquenothInderedbyblood,secretIons,
debrIs,andedemafromprevIousattemptsatlaryngoscopy.
195
8ecausemostoftheeaseof
InsertIonoftheSCAdoesnotdependonanatomythatcanbeassessedonroutInephysIcal
examInatIon,typIcalaIrwayassessmentmeasuresdonotapplytoItsapplIcatIon.
196
The
majordIsadvantageoftheSCAsInresuscItatIonIsthelackofmechanIcalprotectIonfrom
regurgItatIonandaspIratIon.
197,198
LowerratesofregurgItatIondurIngcardIopulmonaryresuscItatIonwIthaL|A(J.5)than
wIththebagvalvemaskventIlatIon(12.4)havebeenshown.
199
EvenInthefaceof
regurgItatIon,pulmonaryaspIratIonIsarareevent.
200
Unfortunately,theuseoftheSellIck
maneuvermaypreventproperseatIngoftheL|AInamInorItyofInstances.
201
ThIsmay
requIrethebrIefremovalofthecrIcoIdpressureuntIltheL|Ahasbeenproperlyseated.
CrIcoIdpressureIseffectIvewIthanL|AInsItu.HadItbeenavaIlable,theL|AFastrack
wouldalsohavebeenanIdealdevIceInthIscasescenarIo.
Case 6: Deviation from the Difficult Airway Algorithm
ThIrteenhoursafteradmIssIontotheIntensIvecareunIt,a76yearoldwomanwhohad
sustaInedtraumatotheface,head,andneckInamotorvehIcleaccIdentIsnotedtohave
progressIvedeclIneInherlevelofconscIousnessandrespIratoryeffort.DnexamInatIon,
thereappearstobeanadequateInterIncIsorgapandthyromentaldIstance.The
oropharyngealvIewandrangeofmotIonoftheheadandneckcannotbeevaluated.
8ecauseoftheInabIlItytofullyevaluatetheaIrwaywIthrespecttoeaseofIntubatIon,an
awakeprocedureIschosen.FIberoptIcdevIcesarenotconsIderedusablebecauseofthe
presenceoffreshandclottedbloodInthemouthasaresultofcontInuedepIstaxIs.Dther
aIrwaytechnIquesthatrequIresIgnIfIcantpatIentpreparatIonarenotconsIderedbecause
oftherapIdprogressIonofthepatIent'srespIratoryfaIlure.AddItIonally,thepresenceof
freshbloodIntheoralandpharyngealcavItIeswIllhInderadequatedryIngandanalgesIa.
8lIndnasalIntubatIonIsconsIderedcontraIndIcatedbasedontheobvIousfacIaltrauma
andtherIskofcrIbrIformplatedIsruptIon.NeItherequIpmentforretrogradeIntubatIonnor
thetrachealesophagealCombItubeIsreadIlyavaIlable.AlIghtedstyletIntubatIonguIdeIs
avaIlable,butnoclInIcIanpresentIsexperIencedwIththIstechnIque.Althoughthemental
statuschangeIsbelIevedtoreflectanIntracranIalprocess(e.g.,IntracranIal
hypertensIon),therIskofcompletelossoftheaIrwayIsjudgedtobetheprImaryclInIcal
hazard.Awake0LIsattemptedwIthmanualInlInestabIlIzatIonoftheneck.AfterclearIng
freshbloodfromthepharynxwIthaYankauersuctIoncatheter,aCormackLehanegradeJ
laryngealvIewIsobtaIned,butbecauseofpatIentresIstance(bItIngonthelaryngoscope
andmovement),trachealIntubatIonIsnotachIeved.ThedecIsIonIsmadetoproceedwIth
rapIdsequenceInductIonandIntubatIon,wIthpreparatIonsmadeforanemergency
tracheostomy.AftersurgIcalpreparatIonoftheneckandpreoxygenatIon,Intravenous
succInylcholIneandetomIdateareadmInIstered,0LIsundertaken,thelarynxIseasIly
vIsualIzed,andthetracheaIsIntubated.
Muscle Relaxants and Direct Laryngoscopy
nthecasedescrIbed,theuseofmusclerelaxantssIgnIfIcantlyImprovedtheabIlItyto
vIsualIzethelarynx.nonestudy,theuseofmusclerelaxantsdurInga0LIncreasedthe
successrateofIntubatIonandwasassocIatedwIthfewerIncIdentsofaIrwaytrauma,
IntubatIonattempts,esophagealIntubatIons,aspIratIon,andevendeath.
202
ntubatIng
condItIonswIthandwIthoutmusclerelaxatIonhavebeenInvestIgatedInfewwell
controlledtrIalsbecausethesuperIorIntubatIngcondItIonsachIevedwIthmusclerelaxants
hasdIscouragedInclusIonofcontrolgroups.
20J
TheeffectsofmusclerelaxatIonthat
ImproveslaryngoscopIcvIewIncludeallowIngcomplete
P.787
temporomandIbularjoIntrelaxatIonandopenIng,anterIormovementoftheepIglottIs,and
wIdenIngofthelaryngealvestIbuleandlaryngealsInus.
204
naddItIon,thefIndIngthat
laryngoscopIcstImulatIonofthepharyngealmusculaturecausestheupperaIrwaylumento
appearsmallIsoffsetbytheuseofrelaxants.
Leaving the Algorithm
ThesItuatIondescrIbedIncase5IsunusualInthatrapIdsequenceInductIonwas
attemptedbecausetheclInIcalsItuatIonhaddevIatedfromtheASA0AowIngtothe
progressIvenatureoftheaIrwaycompromIse.ThesItuatIonwasmoreakIntothecrash
aIrwaydescrIbedbyWalls.
205
nthIscase,theInstItutIonofmusclerelaxatIon,whIchmIght
beconsIderedcontraIndIcatedIntheapparentlydIffIculttoIntubatepatIent,allowedfor
fullvIsualIzatIonofthelarynx.KnowIngthatfaIluretoIntubateInthIscasewouldresultIn
probablelossoftheaIrway,theclInIcIanwaspreparedforcrIcothyroIdotomy.Althoughthe
ASA0AAIsavaluabletoolIntheprocessofapproachIngthedIffIcultaIrway,theclInIcIan
mustalwaysbepreparedforthecasethatdoesnotfItthemold.AsstatedearlIer,
adaptabIlItyInarapIdlychangIngclInIcalsItuatIonIscrItIcaltothesuccessofaIrway
management.AlsoofInterestInthIscasewastheavaIlabIlItyofalIghtedstyletforuseIn
sImIlardIffIcultaIrwayscenarIos.AlthoughthIsdevIcemayhavebeenusefulInthecurrent
case,noclInIcIanpresentwasfamIlIarwIthItsoperatIon.AcrItIcalsItuatIonIsnotan
occasIonfortryInganunfamIlIartechnology.
Other Devices
AneverIncreasIngnumberofaIrwaymanagementdevIcesarecommercIallyavaIlable.
AlthoughencyclopedIccoverageofthesetoolsIsbeyondthescopeofthIschapter,a
revIewofthemoreestablIshedequIpmentfollows.
Lighted Stylets
ThesedevIcesrelyontransIllumInatIonoftheaIrway.AlIghtsourceIntroducedIntothe
tracheawIllproduceawellcIrcumscrIbedglowofthetIssuesoverthelarynxandtrachea.
ThesamelIghtplacedIntheesophaguswIllproducenolIghtoradIffuselIght.Anumberof
devIceshavebecomeavaIlable,IncludIngdIsposable,partlydIsposable,andfullyreusable
systems.AlthoughtherearemanyreportsofsuccessfulIntubatIonusIngthesedevIces,
somecommonproblemshavebeennoted.ngeneral,theoperatIngtheaterlIghtsmustbe
dImmedtobestapprecIatethecIrcumscrIbedglow;astylettIpsuccessfullyplacedInthe
trachea,butnotpoIntIngInananterIordIrectIon,maygIveafalsenegatIveImpressIon;It
IsoftendIffIculttoremovethesemIrIgIdstyletfromtheETTafterIntubatIon.
Airway Bougie
AIrwaybougIesencompassaserIesofsolIdorhollow,semImalleablestyletsthatmaybebe
blIndlymanIpulatedIntothetrachea.AnETTIsthenthreadedoverthebougIeandInto
thetrachea.ThesebougIesaregenerallylowIncostandhIghlyportable.TheEschmann
Introducer(EschmannHealthCare,Kent,England)wasIntroducedIn1949.tIs60cmlong,
15French,andangled40degreesJ.5cmfromItsdIstalend.tIsconstructedfromawoven
polyesterbase,whIchIsmalleable.tcanbeveryhelpfulwhenthelarynxcannotbe
vIsualIzedwIthlaryngoscopy.TheIntroducer(alsoknownasthegum elastic bougie)canbe
manIpulatedundertheepIglottIs,ItsangledsegmentdIrectedanterIorlytowardthelarynx.
DnceIthasenteredthelarynxandtrachea,adIstInctIveclIckIngfeelIselIcItedasthe
tIppassesoverthecartIlagInousstructures.AsImIlardevIce,theFrovantubatIng
ntroducer(CookCrItIcalCare)IsdIsposable,hasanoptIonalstIffenIngstyletanda
hollowbore.TheInternallumenallowsfortheInsufflatIonofoxygen,thedetectIonof
carbondIoxIde,andtheuseofaselfInflatIngbulbtodetectInadvertentesophageal
placement.
Minimally Invasive Transtracheal Procedures
WhenaccesstotheaIrwayfromthemouthornosefaIlsorIsunavaIlable(e.g.,
maxIllofacIal,pharyngeal,orlaryngealtrauma,pathology,ordeformIty),emergency
accessvIatheextrathoracIctracheaIsafeasIbleroutetotheaIrway.TheclInIcIanmust
befamIlIarwIththesealternatIvetechnIquesofoxygenatIonandventIlatIon.ThedecIsIon
toproceedwIthanInvasIveprocedurecanbedIffIcult,andmostclInIcIanswIllhesItate,at
potentIallygraverIsktothepatIent.DneshouldconsIderbecomIngfacIlewIthatleastone
ofthesetechnIquesInelectIvesItuatIons(suchastranstrachealpunctureforadmInIsterIng
aIrwayanalgesIaorelectIveretrogradeIntubatIonor,consIder,forexample,assIstInga
surgIcalcolleagueonatracheostomy).AlthoughtracheostomyandcrIcothyroIdotomyare
beyondthescopeofthIschapter,percutaneoustechnIqueswIllbeconsIdered.
CrIcothyroIdotomy,crIcothyrotomy,conIotomy,andmInItracheostomyaresynonymsfor
establIshInganaIrpassagethroughthecrIcothyroIdmembrane.ThecrIcothyroId
membraneIsafIbroelastIcmembrane,lyIngoverthetrachealmucosa.tIsattachedtothe
InferIorborderofthethyroIdcartIlageandsuperIoredgeofthecrIcoIdcartIlage.Although
crIcothyrotomyIstheprocedureofchoIceInanemergencysItuatIon,Itmayalsoapplyto
anelectIvesItuatIonwhenthereIslImItedaccesstothetrachea(e.g.,severecervIcal
kyphoscolIosIs).CrIcothyrotomyIscontraIndIcatedInneonatesandchIldrenyoungerthan6
yearsofage,andInpatIentswIthlaryngealfractures.
PercutaneousTTJ7,asaformofcrIcothyroIdotomy,IsthemostfamIlIarto
anesthesIologIsts.TheASA0AAlIststranstrachealjetventIlatIonasanoptIonInthecannot
maskventIlate/cannotIntubatesItuatIon.TTJ7IsasImpleandrelatIvelysafemeansto
sustaInthepatIent'slIfeInthIscrItIcalsItuatIon.
85
tprovIdesextratImeforattemptsto
IntubatethetracheaeItherdIrectly,optIcallyorbyasurgIcalaIrway,bymaIntaInIng
arterIaloxygenatIon.
206
Alargeborecatheter,attachedtoa5mLorlargeremptyor
partIallyfluIdfIlled(salIneorlocalanesthetIc)syrInge,shouldbeusedtoentertheaIrway.
ThepatIentIsposItIonedsupIne,wIththeheadmIdlIneorextendedontheneckandthorax
(IfnotcontraIndIcatedbytheclInIcalsItuatIon).AfteraseptIcpreparatIon,localanesthetIc
IsInjectedoverthecrIcothyroIdmembrane(IfthepatIentIsawakeandtImepermIts).The
rIghthandedclInIcIanstandsontherIghtsIdeofthepatIent,facIngthehead.TheclInIcIan
canusehIsorhernondomInanthandtostabIlIzethelarynx.ThecatheterneedleIs
advancedatrIghtanglestoallplanesInthecaudadthIrdofthemembrane.Fromthe
momentofskInpuncturethereshouldbeconstantaspIratIononthesyrIngeplunger.Free
aspIratIonofaIrconfIrmsentranceIntothetracheabutdoesnotIndIcatethedIrectIon
thatthecatchertravelsInthelarynx;cephaladextensIonwIllnotprovIdeadequate
oxygenatIon.UnlessthereIssIgnIfIcantpulmonaryfluId(e.g.,blood,aspIratedgastrIc
contents,orwaterfromdrownIng),theaspIratIonoftrachealaIrshouldbe
IncontrovertIble.TheneedlecatheterassemblyshouldbeadvancedslIghtly,and
subsequentlythecatheteradvancedfullyIntotheaIrwayalone.AlthoughthIstechnIque
hasbeendescrIbedwIthcommonangIocatheters(whIchmaykInkandobstruct),dedIcated
P.788
devIcesmadeofkInkresIstantmaterIalsandwIthaccessoryportsareavaIlablesuchasthe
CookTranstrachealjetventIlatIoncatheter(CookCrItIcalCare,8loomIngton,N).
Figure 29-19.SystemforregulatIonofahIghpressureoxygensourcefortranstracheal
jetventIlatIon.
DncethecatheterhasbeensuccessfullyplacedIntheaIrway,anoxygensourceIs
attached.TheclInIcIanmayhaveseveraloptIonsInthIsregard.fahIghpressuresystemIs
avaIlableforexample,ameteredandadjustableoxygensourcewIthahandcontrolled
valve(FIg.2919)andaLuerlockconnector15toJ0psIofoxygen(centralhospItalsupply
orregulatedcylInder)canbedelIvereddIrectlythroughthecatheter,wIthInsufflatIonsof
1to1.5secondsatarateof12InsufflatIonspermInute.fa16gaugecatheterhasbeen
placed,thIssystemwIlldelIveratIdalvolumeof400to700mL.Lowpressuresystems
cannotprovIdeenoughflowtoexpandthechestadequatelyforoxygenatIonand
ventIlatIon(e.g.,Ambubag,6psI;commongasoutlet,20psI).Hookeretal.
207
recommend
connectIontoanunregulatedoxygensourceofatleast50psI.
LowpressureoxygenflowmeterscanbeusedforTTJ7.Thesesystemsarecapableof
delIverIngabrIef(0.5second)J0psIburstpressure,whIchquIcklydecaysto5psIorless.
208
fthIsoxygensourceIstobeused,anInspIratorytoexpIratoryratIoof1:1wItharateof
J0to60breathspermInuteshouldbeusedtoassureadequateburstpressures.
TheAutomatIcJet7entIlator(|Istralmodel,AcutronIc,HIrzel,SwItzerland)wIthapause
pressurealarmfacIlItyhasbeenusedsafelyforTTJ7IntwopatIentswIthupperaIrway
obstructIon.
209
SpecIalIzedpercutaneouscrIcothyroIdotomysystemshavebeendevelopedthatImprove
theeaseofthIstechnIque.ThesedevIcesgenerallyprovIdealargeboreaccessthatIs
adequateforoxygenatIonandventIlatIonwIthlowpressuresystems.The|elker
emergencycrIcothyroIdotomycatheterset(CookCrItIcalCare)usesaSeldIngercatheter
overawIretechnIquefamIlIartomostanesthesIapractItIoners.ThesetcomesIna
varIetyofcannulasIzes(J.5,4,and6mm0,cuffedanduncuffed).PreparatIonand
posItIonIngofthepatIentarethesameaswIthneedlecrIcothyroIdotomy.A1to1.5cm
vertIcalIncIsIonoftheskInonlyIsmadeoverthelowerthIrdofthecrIcothyroId
membrane.AImIng45degreescaudad,apercutaneouspunctureofthesubcutaneoustIssue
andcrIcothyroIdmembraneIsmadewIththeprovIded18gaugeneedlecatheterassembly
andsyrInge.AfteraIrIsaspIrated,thecatheterIsadvancedIntothetrachea.TheprovIded
guIdewIreIsInsertedthroughthecatheterandIntothetrachea.ThecatheterIsremoved
andthetrachealcannula,fIttedInternallywIthacurveddIlator,IsthreadedontothewIre.
ThedIlatorIsadvancedthroughthemembraneusIngfIrmpressure.SIgnIfIcantresIstance
toItsadvancementmayIndIcatethattheskInIncIsIonneedstobeextended.Dncethe
cannuladIlatorhasbeenfullyInserted,thedIlatorandwIreareremoved.The15mm
cIrcuItadapterendofthecannulaIsnowattachedtoanAmbubagoranesthesIacIrcuIt.
DtherpercutaneoussystemsIncludeNutrake(WeIssEmergencyAIrwaySystem;
nternatIonal|edIcal0evIces)andtheQuIcktrachtranstrachealcatheter(78|
|edIzIntechnIk).NonneedlepuncturetechnIquesarebeyondthecurrentdIscussIon.
SeverecomplIcatIonsofTTJ7arerelatedtobarotraumassuchascervIcomedIastInal
emphysema,pneumothorax,ortensIonpneumothorax.CausesofpenetratIonofaIrInto
paratrachealspaceIncludeInsufflatIonofgasthroughamIsplacedcannulabecauseofpoor
placement,multIpletrachealpunctures,ormIgratIonduetocoughIng.8IlateraltensIon
pneumothoraxwIthhIghfrequencyjetventIlatIonhasbeenreported.
210
TheHunsaker|onJettube(Xomed,JacksonvIlle,FL.)IsaselfcenterIng,nonflammable
subglottIctubethatallowscontInuousmonItorIngofendexpIratoryandpeakaIrway
pressureandperIodIcsamplIngofETCD
2
durInghIghpressure,transglottIcjetventIlatIon.
TheHunsakertubeIsusedforelectIvelaryngealandsupraglottIcsurgery.ThedIstalendof
thetubeshouldbeplaced7to8cmbelowtheglottIs,ensurIngthattheCD
2
/pressure
monItorportIsbelowvocalcords.ThetubeIsselfcenterIngInthetracheabecauseofa
basketshapeddIstalextensIonthatpreventsmalalIgnmentandjetportcontactwIth
trachealmucosa.AnautomatIcjetventIlatorthatwIllautomatIcallyshutdownIftheend
expIratoryorpeakaIrwaypressurerIsesaboveapresetlevelshouldbeemployed.The
HunsakerIscomposedofnonflammablefluoroplastIcmaterIalmakIngItsafetouseIna
100D
2
envIronmentwIthCD
2
,KTP(potassIumtItanylphosphate),andNd:Yag
(neodymIum:yttrIumalumInumgarnet)lasers.Drloffetal.
211
revIewed84patIentsIn
whomtheHunsaker|onJettubewasusedformIcrolaryngealsurgery.AnesthetIc
InductIonandrecoverytImewerecomparablewIthstandardendotrachealIntubatIon,but
therewasImprovedsurgIcalexposureandreducedsurgIcaltIme.0r.J.0avIs(personal
communIcatIon,2007)revIewed552patIentscaredforatWashIngtonStateUnIversIty,In
Seattle,WashIngtonThreepercentofpatIentsrequIredachangetoastandardorlaserETT
durIngtheprocedurebecauseofhypoxIaorhypercarbIa.Nobarotrauma,submucosal
InjectIonofaIr,ortubeIgnItIonoccurredIneItherstudy.
Conclusions
ApartfrommonItorIng,themanagementoftheroutInepatIentaIrwayIsthemost
commontaskoftheanesthesIologIstevendurIngtheadmInIstratIonofregIonal
anesthesIa,theaIrwaymustbemonItoredandpossIblysupported.Unfortunately,routIne
tasksoftenbecomeneglectedastheclInIcIanbecomesdIstracted.8uttheconsequencesof
alostaIrwayaresodevastatIngthattheclInIcIancanneveraffordalackadaIsIcal
approach.
AlthoughtheASA'sTaskForceonthe0IffIcultAIrwayhasgIventhemedIcalcommunItyan
ImmenselyvaluabletoolIntheapproachtothepatIentwIththedIffIcultaIrway,theTask
Force'salgorIthmmustbevIewedasastartIngpoIntonly.Judgment,experIence,the
clInIcalsItuatIon,andavaIlableresourcesallaffecttheapproprIatenessofthechosen
pathwaythrough,ordIvergencefrom,thealgorIthm.TheclInIcIandoesnotneedtobe
expertInalltheequIpmentandtechnIquescurrentlyavaIlable.Father,abroadrangeof
approachesshouldbemasteredsothatthefaIlureofonedoesnotpresentaroadblockto
success.
P.789
Whereasonemayarguethatthelastdecadeofthe20thcenturywasthedecadeofthe
SCA,thefIrstdecadeofthe21stcenturyIswItnessIngtheprolIferatIonofthevIdeo
laryngoscope.AbalancebetweensupraglottIcventIlatIonandvIdeoassIstedIntubatIonIs
thechallengeofthecomIngyears.
ThemedIcalmanufacturIngcommunIty,andthefarsIghtedclInIcIanswhosupplyItwIth
conceptsforaIrwaymanagementproducts,hassupplIedavastarrayofdevIces.|any
representredundancyInconcept,andeachhasItssupportersanddetractors.Noone
devIcecanbeconsIderedsuperIortoanotherwhenconsIderedInIsolatIon.tIsthe
clInIcIanandhIsorherresources(bothequIpmentandpersonnel)andjudgmentthat
determInetheeffectIvenessofanytechnIque.nthemanagementofthedIffIcultaIrway,
flexIbIlIty,andnotrIgIdIty,prevaIls.
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Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJ0PatIentPosItIonIngandFelatednjurIes
ChapterJ0
Patient Positioning and Related Injuries
Mark A. Warner
Key Points
1. Sedated or anesthetized patients should be placed in positions that
are comfortable while they are awake.
2. Padding provided by any number of different materials (e.g., gel or
foam pads, blankets) should be used to widely disperse point
pressure on body parts or tissues.
3. Elevated lower extremity positions (e.g., lithotomy) may reduce
perfusion pressure in the elevated extremities and increase the
opportunity for developing compartment syndromes, especially when
the extremities are elevated for prolonged periods.
4. Brachial plexus neuropathy associated with sternotomy in
anesthetized patients undergoing cardiac procedures may mimic as
peripheral ulnar neuropathy.
5. The etiology of ulnar neuropathy is not always clear. Most commonly
it develops postoperatively in men 40 to 70 years of age who
undergo abdominal or pelvic procedures. There are anatomic and
neurophysiologic reasons for men compared with women to develop
this problem.
6. Excessive flexion or extension of the spine in anesthetized patients
who are placed in unique surgical positions may contribute to spinal
cord ischemia and catastrophic neurologic damage.
7. Perioperative vision loss occurs most frequently in anesthetized
patients undergoing cardiac surgical procedures. Patients undergoing
extensive spine procedures while positioned prone may develop
vision loss, primarily from posterior ischemic optic neuropathy.
8. Neuropathies that result in motor function loss as well as sensory
loss compared with those with isolated sensory loss generally are
associated with more prolonged or permanent nerve dysfunction.
PosItIonIngapatIentforasurgIcalprocedureIsfrequentlyacompromIsebetweenwhatthe
anesthetIzedpatIentcantolerate,bothstructurallyandphysIologIcally,andwhatthe
surgIcalteamrequIresforaccesstotheIranatomIctargets.
1
EstablIshmentoftheIntended
surgIcalposturemayneedtobemodIfIedtomatchthepatIent'stolerance.ThIschapter
presentsthesIgnIfIcanceofvarIousposItIonsInwhIchapatIentmaybeplaceddurIngan
operatIon,brIeflydescrIbesthetechnIquesofestablIshIngtheposItIons,anddIscussesthe
potentIalcomplIcatIonsofeachposture.
tIsveryImportantforclInIcIanstounderstandthephysIologIcandpotentIalpathologIc
consequencesofpatIentposItIonIng.nthepast2decades,anumberofstudIesoflarge
surgIcalpopulatIonshaveprovIdednewInformatIononthefrequencyandnaturalhIstoryof
rareperIoperatIveeventssuchasneuropathIesandvIsIonloss.However,thesestudIes
InfrequentlyhaveprovIdedsuffIcIentdatatoallowspeculatIonastopotentIalmechanIsms
ofInjury.8asedonthefIndIngsofthesestudIes,InvestIgatorsarenowseekIngtoconfIrm
mechanIsmsofInjuryandtheeffIcacyofnovelInterventIonstodecreasethefrequencyof,
ortoprevent,theseperIoperatIveevents.UntIlthesenewInvestIgatIonsarecomplete,the
mechanIsmsformanypotentIalposItIonIngrelatedcomplIcatIonsremaInunknown.
ThelackofsolIdscIentIfIcInformatIononbasIcmechanIsmsofposItIonIngrelated
complIcatIonsoftenleadstomedIcolegalentanglements.NotatIonsonanesthesIaand
operatIngroomrecordsmaybeabsentorunInformatIve.
P.794
P.795
CarefuldescrIptIvenotatIonsaboutposItIonsuseddurInganesthesIaandsurgery,aswellas
brIefcommentsaboutspecIalprotectIvemeasuressuchaseyecareandpressurepoInt
paddIng,areusefultoIncludeontheanesthesIarecord.npotentIallycomplIcatedor
contentIouscIrcumstances,aseparatebrIefdescrIptIonofcaredocumentedInthepatIent's
recordIsadvIsable.DnlyInthIsmannercansubsequentInquIrIesbeproperlyansweredon
behalfofeItherthepatIentortheanesthesIologIst.WhencredIble,expandedknowledge
thatfurtherdelIneatesmechanIsmsofposItIonIngrelatedcomplIcatIonsIsavaIlable,these
IssuesandthecareofpatIentswIllbeImproved.
Figure 30-1. A.SupIneadultwIthmInImalgradIentsInthehorIzontalvascularaxIs.
PulmonarybloodvolumeIsgreatestdorsally.7IsceradIsplacethedorsaldIaphragm
cephalad.CerebralcIrculatIonIsslIghtlyaboveheartlevelIftheheadIsonasmall
pIllow.B.HeaddowntIltaIdsbloodreturnfromlowerextremItIesbutencourages
reflexvasodIlatIon,congestsvesselsInthepoorlyventIlatedlungapIces,andIncreases
IntracranIalbloodvolume.C.ElevatIonoftheheadshIftsabdomInalvIsceraaway
fromthedIaphragmandImprovesventIlatIonofthelungbases.AccordIngtothe
gradIentabovetheheart,pressureInarterIesoftheheadandneckdecreases;
pressureInaccompanyIngveInsmaybecomesubatmospherIc.
Dorsal Decubitus Positions
Variations of the Dorsal Decubitus Position
Supine
Horizontal
nthetradItIonalhorIzontalsupIneposItIon(dubbedlyIngatattentIon),thepatIentlIes
onhIsorherbackwIthasmallpIllowbeneaththehead(FIg.J01A).ThearmsareeIther
comfortablypaddedandrestraInedalongsIdethetrunkorabductedonwellpaddedarm
boards.EItherarm(orboth)maybeextendedventrallyandtheflexedforearmsecuredto
anelevatedframeInsuchawaythatperfusIonofthehandIsnotcompromIsed,noskInto
metalcontactexIststocauseelectrIcalburnsIfacauteryIsused,andthebrachIal
neurovascularbundleIsneItherstretchednorcompressedattheaxIlla.ThelumbarspIne
mayneedpaddedsupporttopreventapostoperatIvebackache(seeComplIcatIonsofthe
0orsal0ecubItusPosItIons).8onycontactpoIntsattheoccIput,elbows,andheelsshould
bepadded.Fortunately,mostmodernsurgIcaltableshavemattresspadsthatare
suffIcIentlybuoyantandthIcktoallowdIspersIonofpoIntpressure.
AlthoughthehorIzontalsupIneposturehasalonghIstoryofwIdespreaduse,Itdoesnot
placehIpandkneejoIntsInneutralposItIonsandIspoorlytoleratedforprolongedperIods
byanImmobIlIzed,awakepatIent.
Contoured
AcontouredsupIneposture(FIg.J02C)hasbeentermedthelawn chair position.
2
tIs
establIshedbyarrangIngthesurfaceoftheoperatIngtablesothatthetrunkthIghhIngeIs
angulatedapproxImately15degreesandthethIghkneehIngeIsangulatedasImIlar
amountIntheopposItedIrectIon.AlternatIvely,arolledtowel,pIllow,orblanketcanbe
placedbeneaththepatIent'skneestokeepthemflexed.ThepatIentofaverageheIght
thenlIescomfortablywIthhIpsandkneesflexedgently.QuIteoftenapersonwhohasbeen
requIredtolIemotIonlessonarIgIdhorIzontaltableandthenIschangedtothecontoured
supIneposItIonoffersanalmostInvoluntaryexpressIonofrelIefandapprecIatIon.
Figure 30-2.EstablIshmentofthecontouredsupIne(lawnchaIr)posItIon.A.
TradItIonalflatsupInetabletop.B.ThIghsflexedontrunk.C.KneesgentlyflexedIn
fInalbodyposItIon.D.TrunksectIonleveledtostabIlIzefloorsupportedarmboard.
(Feproducedfrom|artInJT,Warner|A[Eds]:PosItIonIngInAnesthesIaandSurgery,
JrdedItIon.PhIladelphIa,W8Saunders,1997.p42,wIthpermIssIon.)
Lateral Uterine or Abdominal Mass Displacement
WIthapatIentInthesupIneposItIon,amobIleabdomInalmass,suchasaverylargetumor
orapregnantuterus,canrestonthegreatvesselsoftheabdomenandcompromIse
cIrculatIon.ThIsIsknownastheaortocaval syndromeorthesupine hypotensive syndrome.
AsIgnIfIcantdegreeofperfusIoncanberestoredIfthecompressIvemassIsrolledtoward
thelefthemIabdomenbyleftwardtIltofthetabletoporbyawedgeundertherIghthIp.
J
Lithotomy
Standard
nthestandardlIthotomyposItIon(FIg.J0J),thepatIentlIessupInewItharmscrossedon
thetrunkorwIthoneorbotharmsextendedlaterallyto90degreesonarmboards.Each
lowerextremItyIsflexedatthehIpandknee,andbothlImbsaresImultaneouslyelevated
andseparatedsothattheperIneumbecomesaccessIbletothesurgeon.Formany
gynecologIcandurologIcprocedures,thepatIent'sthIghsareflexedapproxImately90
degreesonthetrunkandthekneesarebentsuffIcIentlytomaIntaInthelowerlegsnearly
paralleltothefloor.|oreacuteflexIonofthekneesorhIpscanthreatentoangulateand
compressmajorvesselsateItherjoInt.naddItIon,hIpflexIonto90degreesonthetrunk
hasbeenshowntoIncreasestretchoftheInguInallIgaments.
4
8ranchesofthelateral
femoralcutaneousnervesoftenpassdIrectlythroughtheselIgamentsandcanbeImpInged
andbecomeIschemIcwIthInthestretchedlIgament.
NumerousdevIcesareavaIlabletoholdlegsthatareelevateddurIngobstetrIcdelIveryor
perInealoperatIons.EachdevIceshouldbefIttedtothestatureoftheIndIvIdualpatIent.
CareshouldbetakentoensurethatangulatIonsoredgesofthepaddedholderdonot
compressthepoplItealspaceortheupperdorsalthIgh.Compartmentsyndromesofoneor
bothlowerextremItIeshaveresultedfromprolongeduseofthelIthotomyposItIonwIth
sometypesofsupportdevIces.
5
WhenthelegsaretobeloweredtotheorIgInalsupIneposItIonattheendofthe
procedure,theyshouldfIrstbebroughttogetheratthekneesandanklesInthesagIttal
planeandthenloweredslowlytogethertothetabletop.ThIsmInImIzestorsIonstresson
thelumbarspInethatwouldoccurIfeachlegwereloweredIndependently.talsopermIts
gradualaccommodatIontotheIncreaseIncIrculatorycapacItance,therebyavoIdIng
suddenhypotensIon.
Low
FormosturologIcproceduresandformanyproceduresthatrequIresImultaneousaccessto
theabdomenandperIneum,thedegreeofthIghelevatIonInthelIthotomyposItIonIsonly
approxImatelyJ0to45degrees(FIg.J04).ThIsreducesperfusIongradIentstoandfromthe
lowerextremItIesandImprovesaccesstoaperInealsurgIcalsIteformembersofthe
operatIngteamwhomayneedtostandatthelateralaspectofeItherleg.
High
SomesurgeonsprefertoImproveaccesstotheperIneumbysuspendIngthepatIent'sfeet
fromhIghpoles.TheeffectIstohavethepatIent'slegsalmostfullyextendedonthethIghs
(FIg.J05)andthethIghsflexed90degreesormoreonthetrunk.Thepostureproducesa
sIgnIfIcantuphIllgradIentforarterIalperfusIonIntothefeet,requIrIngcarefulavoIdance
ofsystemIchypotensIon.LessmobIlepatIentsmaytoleratethIsposturepoorlybecauseof
angulatIonandcompressIonofthecontentsofthefemoralcanalbytheInguInallIgament
(FIg.J05A),orstretchofthescIatIcnerve(FIg.J058),orboth.
P.796
Figure 30-3.StandardlIthotomyposItIonwIthcandycaneextremItysupport.ThIghs
areflexedapproxImately90degreesonabdomen;kneesareflexedenoughtobrIng
lowerlegsgrosslyparalleltothetorsosectIonofthetabletop.ArmsareretaInedon
boards,crossedontheabdomen,orsnuggedatthesIdesofpatIent.(|odIfIedfrom
|artInJT,Warner|A[Eds]:PosItIonIngInAnesthesIaandSurgery,JrdedItIon.
PhIladelphIa,W8Saunders,1997,pp5J,66,wIthpermIssIon.)
Exaggerated
TransperInealaccesstotheretropubIcarearequIresthatthepatIent'spelvIsbeflexed
ventrallyonthespIne,thethIghsalmostforcIblyflexedonthetrunk,andthelowerlegs
aImedskywardsotheyareoutoftheway(FIg.J06).TheresultplacesthelongaxIsofthe
symphysIspubIsalmostparalleltothefloor.ThIsexaggeratedlIthotomyposItIonstresses
thelumbarspIne,producesasIgnIfIcantuphIllgradIentforperfusIonofthefeet,andmay
restrIctventIlatIonbecauseofabdomInalcompressIonbybulkythIghs.tcanbetolerated
underanesthesIabutrarelycanbeassumedbyanawakepatIent.ControlofventIlatIonIs
usuallynecessary.fpreexIstIngpaInfullumbarspInedIseaseIspresent,analternatIve
surgIcalposItIonmayneedtobechosenbeforehandtoavoIdseverelyaccentuatIngthe
lumbardIstressaftersurgery.ThIsposItIonhasbeenassocIatedwIthaveryhIghfrequency
oflowerextremItycompartmentsyndrome.
6
|aIntenanceofadequateperfusIonpressure
InthelegsIsImportant.
Figure 30-4.LowlIthotomyposItIonforperInealaccess,transurethral
InstrumentatIon,orcombInedabdomInoperInealprocedures.(|odIfIedfrom|artInJT,
Warner|A[Eds]:PosItIonIngInAnesthesIaandSurgery,JrdedItIon.PhIladelphIa,W8
Saunders,1997,p99,wIthpermIssIon.)
Tilted
Frequently,somedegreeofheaddowntIltIsaddedtooneofthelIthotomyposItIons.fthe
tIltIsgreatenough,andpartIcularlyIntheInstanceoftheexaggeratedlIthotomyposItIon,
thepatIentmayslIdecephalad.CaremustbetakentoavoIdthIssItuatIon;thereare
severalanecdotesfrommedIcolegalactIonsInvolvIngpatIentswhoslIdoffoperatIngtables
wIthresultIngheadInjurIes.WIthmodernsurgIcaltablesandproceduraltechnIques,steep
headdowntIltIsnotoftenwarranted.TherIskofbrachIalInjurIesassocIatedwIth
cephaladmovementofthepatIentwhIlethearmsorshouldersaresecuredtothetable
wIthretentIonmaterIalsorshoulderbracesIsoftenpresentInthIsposItIon.
0ependIngonthedegreeofheaddepressIon,theaddItIonoftIlttothelIthotomyposItIon
combInestheworstfeaturesofboththelIthotomyandtheheaddownpostures.TheweIght
ofabdomInalvIsceraonthedIaphragmaddstowhateverabdomInalcompressIonIs
producedbytheflexedthIghsofanobesepatIentorofoneplacedInanexaggerated
lIthotomyposItIon.7entIlatIonshouldbeassIstedorcontrolled.
P.797
8ecauseelevatIonofthelowerextremItIesabovetheheartproducesanuphIllperfusIon
gradIent,systemIchypotensIonandcompressIvelegwrappIngmaylImItperfusIontothe
perIphery,andbothcanbefactorsInthedevelopmentofcompartmentsyndromesInthe
legsofpatIentsInthelIthotomyposItIon.
5
ThIsperfusIongradIentoftenIsunpredIctable
andexaggerated,potentIallyIncreasIngtherIskofcompartmentsyndrome.
7,8
Figure 30-5.HIghlIthotomyposItIon.NotepotentIalforangulatIonand
compressIon/obstructIonofcontentsoffemoralcanal(A,inset)orstretchofscIatIc
nerve(B).(Areproducedfrom|cLeskeyCH[Ed]:CerIatrIcAnesthesIology.8altImore,
WIllIamsEWIlkIns,1997,p146,wIthpermIssIon.Breproducedfrom|artInJT,Warner
|A[Eds]:PosItIonIngInAnesthesIaandSurgery,JrdedItIon.PhIladelphIa,W8
Saunders,1997,pp61,6J,wIthpermIssIon.)
CephaladdIsplacementofthedIaphragmandobstructIonofItscaudadInspIratorystroke
accompanyaheaddownposItIonbecauseofgravItyshIftedabdomInalvIscera.
Consequently,theworkofspontaneousventIlatIonIsIncreasedforananesthetIzedpatIent
InaposturethatalreadyworsenstheventIlatIonperfusIonratIobygravItatIonal
accumulatIonofbloodInthepoorlyventIlatedlungapIces.0urIngcontrolledventIlatIon,
hIgherInspIratorypressuresareneededtoexpandthelung.
CranIalvascularcongestIonandIncreasedIntracranIalpressurecanbeexpectedtoresult
fromheaddowntIlt.ForpatIentswIthknownorsuspectedIntracranIaldIsease,the
posItIonshouldbeusedonlyInthoserareInstancesInwhIchasurgIcallyusefulalternate
posturecannotbefound.|aIntenanceoftheposItIonshouldthenbeasbrIefaspossIble.
SteepheaddowntIltposItIons(e.g.,J0to45degreesofheaddowntIlt)mayrequIresome
meansofpreventIngthepatIentfromslIdIngcephaladoutofposItIon.Theuseofbent
kneesIsasatIsfactorymethodofretaInIngthetIltedpatIentInposItIon(FIg.J07)Ifthe
flexedkneejoIntsareplacedsuffIcIentlycaudadofthelegthIghhIngeofthetabletopso
thattheadjacentfIrmedgeofthedepressedlegsectIonofthetablecannotIndenteIther
proxImalcalforobstructstructuresInthepoplItealspace.CompressIveIschemIaand
phlebItIsoracompartmentsyndromemayresultIfeItheroccur.
Figure 30-6.TheexaggeratedlIthotomyposItIon.Shoulderbraces,usuallyneededto
stabIlIzethetorso,areplacedovertheacromIoclavIcularareatomInImIze
compressIonofthebrachIalplexusandadjacentvessels.(FeprIntedfrom|artInJT,
Saunders,1997,p54,wIthpermIssIon.)
HIstorIcally,shoulderbracesalsohavebeenusedtopreventcephaladslIdIngInsteephead
downtIltposItIons.ThesebracesarebesttoleratedIfplacedovertheacromIoclavIcular
joInts,butcaremustbetakentoseethattheshoulderIsnotforcedsuffIcIentlycaudadto
trapandcompressthesubclavIanneurovascularbundlebetweentheclavIcleandthefIrst
rIb.fthebracesareplacedmedIallyagaInsttherootoftheneck,theymayeasIly
compressneurovascularstructuresthatemergefromtheareaofthescalenemusculature.
Fortheseandotherreasons,theuseofshoulderbraceshaswanedInpopularItyandshould
notbeusedIfpossIble.
Formanyofthesereasons,steepheaddownposItIonsshouldbeusedonlywhenaunIque
surgIcalIssuerequIresItforoptImalexposureandonlyforaslongasneededforthat
exposure.
Complications of the Dorsal Decubitus Positions
Postural Hypotension
PosturalhypotensIonmaybeseenwhenaheadelevatedposItIonIsbeIngestablIshed.f
meanarterIalpressureatthecIrcleofWIllIsremaInswIthIntherangeofcerebralblood
flow
P.798
autoregulatIonInapatIentwhoIsnothypertensIve,theposturalhypotensIonmayrequIre
lIttletreatmentotherthantoapproprIatelydecreasetheconcentratIonofanesthetIcdrugs
topreservecompensatoryreflexes.fthedegreeofhypotensIonencounteredIsmore
severe,furtherheadelevatIonshouldbedelayeduntIlthelevelofanesthetIcIsdecreased;
InaddItIon,judIcIoususeoffluIdsandvasopressorscanreestablIsheffectIveperfusIon.
Figure 30-7.HeaddowntIlt.Lower figureshowstradItIonalsteep(J0to45degree)
tIltdescrIbedbyTrendelenburg.LegrestraIntsandkneeflexIonstabIlIzethepatIent,
avoIdIngtheneedforwrIstletsorshoulderbracesthatthreatenthebrachIalplexus.
Upper figureshows10to15degreesofheaddowntIlt,whIchIsmorecommonIn
modernsurgIcalprocedures.(FeprIntedfrom|artInJT,Warner|A[Eds]:PosItIonIng
InAnesthesIaandSurgery,JrdedItIon.PhIladelphIa,W8Saunders,1997,pp98,102,
wIthpermIssIon.)
PosturalhypotensIonmayalsoappearInthepresenceofInadequatelyreplacedbloodloss
whentheIntravascularspacehasbeenfunctIonallyIncreasedeItherbylowerIngthelegsto
horIzontalatthetermInatIonofthelIthotomyposItIonorbyreturnIngaheaddowntIltto
horIzontal.7olumerepletIonIstheIndIcatedtherapy,althoughjudIcIouslysmalldosesof
vasopressorsmaysometImesbeneededInItIally.
Pressure Alopecia
ProlongedcompressIonofhaIrfollIclescanproducehaIrloss.AbelandLewIs
9
descrIbed
patIentswhohadpaIn,swellIng,andexudatIonwheretheoccIputhadbeensupportIngthe
weIghtoftheheadforlongperIodsIntheTrendelenburgposItIon.AlopecIaoccurred
betweentheJrdand28thpostoperatIveday;regrowthwascompletewIthInJmonths.Use
oftIghtheadstrapstoholdanesthetIcfacemasksandprolongedhypotensIonand
hypothermIahavealsobeenassocIatedwIthcompressIonalopecIa.
10
FrequentlyturnIng
thepatIent'sheaddurInglongoperatIons
11
anduseofpadded,softheadsupportsare
recommendedtoreducetherIsksofthIscomplIcatIon.
Pressure-Point Reactions
WeIghtbearIngbonypromInencescanproduceIschemIcnecrosIsofoverlyIngtIssueunless
properpaddIngIsapplIed.HypothermIaandvasoconstrIctIvehypotensIonmayenhancethe
process.Theheels,theelbows,andthesacrumarepartIcularlyvulnerable.Theuseofa
varIetyofpads(e.g.,foamorgel)maydIspersepoIntpressureIfusedforprotectIon.
AlthoughtheIrusemayprotectagaInstskInandsofttIssuecompressIonandIschemIa,
therearenostudIesthathaveproventheIrusetobebenefIcIalInreducIngperIpheral
neuropathIesIntheperIoperatIveperIod.
Brachial Plexus and Upper Extremity Injuries
Brachial Plexus Neuropathy
Root Injuries
ShoulderbracesplacedtIghtagaInstthebaseoftheneckcancompressandInjuretheroots
ofthebrachIalplexus.8races,Ifneededatall,areconsIderedlessharmfulwhenplaced
morelaterallyovertheacromIoclavIcularjoInt.ngeneral,theuseofshoulderbraces
shouldbedIscouraged.
ThedorsaldecubItusposItIonsdonotusuallythreatenstructuresInthepatIent'sneck
unlessconsIderablelateraldIsplacementoftheheadoccurs.nthatposItIon,therootsof
thebrachIalplexusonthesIdeoftheobtuseheadshoulderanglecanbestretchedand
damaged.ftheupperextremItyIsfIxedatthewrIst(e.g.,bywrIstwraporasheetor
towelusedtotuckthearm),thestretchInjuryoftheplexuscanbeaccentuatedasthe
headmoveslaterallyawayfromtheanchorIngpoIntofthewrIst.SImIlarly,exaggerated
rotatIonoftheheadawayfromanextendedarmcanbeassocIatedwIthabrachIalplexus
Injury.
Sternal Retraction
Frequently,thepatIentundergoIngamedIansternotomyhasbotharmspaddedand
securedalongsIdethetorso.AnalternatIveIstohavebotharmsabducted.
12
7anderSalm
etal.
1J,14
descrIbedfIrstrIbfracturesandbrachIalplexusInjurIesassocIatedwIthmedIan
sternotomIes.TheyrelatedtheextentoftheInjurytotheamountofretractor
dIsplacementoftherIb,wIththemostsevereInjurybeIngcausedbydIsplacement
suffIcIenttoproduceafIrstrIbfracture.FoyandassocIates,
15
Inastudyof200consecutIve
adultsscheduledforcardIacsurgeryvIaamedIansternotomy,posItIonedtheleftarm
eItherabductedandpaddedonanarmboardwIththepalmsupInatedorsecuredbyadraw
sheetalongsIdethetrunk;therIghtarmwasalwaysplacedalongsIdethetrunk.Theyfound
a10IncIdenceofupperextremItynerveInjurythatwasnotInfluencedbyInternal
mammaryarteryharvest,InternaljugularveIncatheterIzatIon,orleftarmposItIon.
SurgIcalmanIpulatIonwasmorecontrIbutorythanextremItyposItIonIngInproducIng
traumatothe
P.799
brachIalplexus.JellIshetal.
12
reportedthatthereIslessslowIngofsomatosensoryevoked
potentIals(SSEPs)oftheulnarnervedurIngsternotomywhenbotharmsareabducted
InsteadoftuckedatthesIdes.However,theyfoundnodIfferencesInperIoperatIve
symptomsbetweenpatIentsInthearmabductedversusarmatsIdegroups.
Long Thoracic Nerve Dysfunction
AnumberoflawsuItshavecenteredonpostoperatIveserratusanterIormuscledysfunctIon
andwIngIngofthescapula(FIg.J08)allegedtobetheresultofposItIonrelatedInjurIesto
thelongthoracIcnerveof8ell,whIcharIsesfromnerverootsC5,C6,andC7.8ecauseC5
andC6fIbersofthenervecoursethroughthemIddlescalenemuscleandemergefromIts
lateralbordertojoInthefIbersfromC7,IthasbeenproposedthatneuropathIesofthelong
thoracIcnervearetraumatIcInorIgIn.
16
8ecausethenerveIsnotroutInelyInvolvedIna
stretchInjuryofthebrachIalplexusandbecausetheplexusIsnotroutInelyInvolvedwhen
longthoracIcnervedysfunctIonoccurs,therelatIonshIpbetweenpostoperatIvelong
thoracIcnervepalsyandpatIentposItIonIngremaInsspeculatIve.8asedonevIdenceofFoo
andSwann
17
plusdatafromlItIgatIons,|artIn
18
concludedthatIntheabsenceof
demonstrabletrauma,postoperatIvedysfunctIonsofthelongthoracIcnervewerequIte
lIkelytheresultofcoIncIdentalneuropathIes,possIblyofvIralorIgIn.
Axillary Trauma from the Humeral Head
AbductIonofthearmonanarmboardto90degreesmaythrusttheheadofthehumerus
IntotheaxIllaryneurovascularbundle.ThebundleIsstretchedatthatpoInt,andItsneural
structuresmaybedamaged.nthesamemanner,vesselscanbecompressedoroccluded
andperfusIonoftheextremItycanbejeopardIzed.
Figure 30-8.ScapularwIngIng.TheserratusanterIormuscle(upper right)IssupplIed
solelybythelongthoracIcnervethatbranchesImmedIatelyfromC5,C6,C7,and
sometImesC8(left figure).ArIsIngonthelateralrIbsandInsertIngonthedeepsurface
ofthescapula,themusclekeepstheshouldergIrdleapproxImatedtothedorsalrIb
cage.LongthoracIcnervepalsyallowsdorsalprotrusIonofthescapula(lower right).
SeetextfordetaIls.(Feproducedfrom|artInJT:PostoperatIveIsolateddysfunctIonof
thelongthoracIcnerve:ArareentItyofuncertaInetIology.AnesthAnalg1989;69:
Radial Nerve Compression
TheradIalnerve,arIsIngfromrootsC68andT1,passesdorsolaterallyaroundthemIddle
andlowerportIonsofthehumerusInItsmusculospIralgroove.AtapoIntonthelateral
aspectofthearm,approxImatelythreefIngerbreadthsproxImaltothelateralepIcondyle
ofthehumerus,thenervecanbecompressedagaInsttheunderlyIngboneandInjured.
PressurefromthevertIcalbarofananesthesIascreenorasImIlardevIceagaInstthe
lateralaspectofthearm,excessIvecyclIngofanautomatIcbloodpressurecuff,and
compressIonatthemIdhumeruslevelbyrestrIctIvesheetsortowelsusedtotuckthearms
havebeenImplIcatedIncausIngdamagetotheradIalnerve.
Median Nerve Dysfunction
solatedperIoperatIveInjurIestothemedIannerveareuncommonandthemechanIsmIs
obscure.
19,20
ApotentIalsourceofInjuryIsIatrogenIctraumatothenervedurIngaccessto
vesselsIntheantecubItalfossa,asmIghtoccurdurIngvenIpuncture.Anecdotally,thIs
problemappearstooccurprImarIlyInmen20to40yearsofagewhocannoteasIlyextend
theIrelbowscompletely.ForcedelbowextensIonafteradmInIstratIonofmusclerelaxants
andwhIleposItIonIngthearms,wIthresultantstretchofthemedIannerve,hasbeen
suggestedasonepotentIalmechanIsmforthIsproblem.
Ulnar Neuropathy
mproperanesthetIccareandpatIentmalposItIonInghavebeenImplIcatedascausatIve
factorsInthedevelopmentofulnarneuropathIessIncereportsby8udInger
21
and
CarrIques
22
Inthe1890s.ThesefactorslIkelyplayanetIologIcroleforthIsproblemInsome
surgIcalpatIents.Dtherfactors,however,maycontrIbutetothedevelopmentof
postoperatIve
P.800
ulnarneuropathIes.naserIesof12InpatIentswIthnewlyacquIredulnarneuropathy,
WadsworthandWIllIams
2J
determInedthatexternalcompressIonofanulnarnervedurIng
surgerywasafactorInonlytwopatIents.UlnarneuropathIesdevelopInmedIcalaswellas
surgIcalpatIents.
24
ThemechanIsmsofulnarneuropathyareunclear.
TypIcally,anesthesIarelatedulnarnerveInjuryIsthoughttobeassocIatedwIthexternal
nervecompressIonorstretchcausedbymalposItIonIngdurIngtheIntraoperatIveperIod.
AlthoughthIsImplIcatIonmaybetrueforsomepatIents,threefIndIngssuggestthatother
factorsmaycontrIbute.FIrst,patIentcharacterIstIcs(e.g.,malesex,hIghbodymassIndex
[J8],andprolongedpostoperatIvebedrest)areassocIatedwIththeseulnar
neuropathIes.
25
7arIousreportssuggestthat70to90ofpatIentswhohavethIsproblem
aremen.
19,20,2J,24,25
Second,manypatIentswIthperIoperatIveulnarneuropathIeshavea
hIghfrequencyofcontralateralulnarnerveconductIondysfunctIon.
26
ThIsfIndIngsuggests
thatmanyofthesepatIentslIkelyhaveasymptomatIcbutabnormalulnarnervesbefore
theIranesthetIcs,andtheseabnormalnervesmaybecomesymptomatIcdurIngthe
perIoperatIveperIod.FInally,manypatIentsdonotnotIceorcomplaInofulnarnerve
symptomsuntIl48hoursaftertheIrsurgIcalprocedures.
25,26
AprospectIvestudyofulnar
neuropathyIn1,502surgIcalpatIentsfoundthatnoneofthepatIentshadsymptomsofthe
neuropathydurIngthefIrst2postoperatIvedays.
27
tIsnotclearwhetheronsetof
symptomsIndIcatesthetImethatanInjuryhasoccurredtothenerve.PrIelIppetal.
28
foundthat8of15awakevolunteerswhohadnotablealteratIonsIntheIrulnarnerveSSEP
sIgnalsfromdIrectulnarnervepressuredIdnotperceIveaparesthesIa,evenwhenthe
SSEPwaveformsdecreasedasmuchas72.
ElbowflexIoncancauseulnarnervedamagebyseveralmechanIsms.nsomepatIents,the
ulnarnerveIscompressedbytheaponeurosIsoftheflexorcarpIulnarIsmuscleandcubItal
tunnelretInaculumwhentheelbowIsflexedby110degrees
29,J0
(FIg.J09).nother
patIents,thIsfIbrotendInousroofofthecubItaltunnelIspoorlyformedandcanleadto
anterIorsubluxatIonordIslocatIonoftheulnarnerveoverthemedIalepIcondyleofthe
humerusdurIngelbowflexIon.ThIsdIsplacementhasbeenobservedInapproxImately16
ofcadaversInwhomtheflexormuscleaponeurosIsandsupportIngtIssueshavenotbeen
dIssected.
J1,J2
Ashenhurst
J2
hasspeculatedthattheulnarnervemaybechronIcally
damagedbyrecurrentmechanIcaltraumaasthenerveIsInsubluxatIonoverthemedIal
epIcondyle.
Figure 30-9.|edIaltolateralvIewofrIghtelbow.ThecubItaltunnelretInaculum
(CTF)IslaxInextensIon(A)asItstretchesfromthemedIalepIcondyle(|E)tothe
olecranon(Dl).TheretInaculumtIghtensInflexIon(B)andcancompresstheulnar
nerve(arrow).(FeprIntedfromD'0rIscollSW,HorIIE,CarmIchaelSWetal:ThecubItal
tunnelandulnarneuropathy.J8oneJoIntSurgAm1991;7J:61J,wIthpermIssIon.)
ExternalcompressIonIntheabsenceofelbowflexIonalsomaydamagetheulnar
nerve.
JJ,J4
AlthoughcompressIonwIthInthemedIalepIcondylargroovemaybepossIbleIf
thegrooveIsshallowerthannormal,thebonygrooveusuallyIsdeepandthenerveIswell
protectedfromexternalcompressIon.
J5
ExternalcompressIonmayoccurdIstaltothe
medIalepIcondyle,wherethenerveandItsassocIatedarteryarerelatIvelysuperfIcIal.n
ananatomIcstudy,Contrerasetal.
J6
observedthattheulnarnerveandposterIor
recurrentulnararterypassposteromedIallytothetubercleofthecoronoIdprocess,where
theyarecoveredonlybyskIn,subcutaneousfat,andathIndIstalbandoftheaponeurosIs
oftheflexorcarpIulnarIs.
WhyaremenmorelIkelytohavethIscomplIcatIon:ThereareseveralanatomIc
dIfferencesbetweenmenandwomenthatmayIncreasethelIkelIhoodofperIoperatIve
ulnarneuropathydevelopIngInmen.FIrst,twoanatomIcdIfferencesmayIncreasethe
chanceofulnarnervecompressIonIntheregIonoftheelbow.ThetubercleofthecoronoId
processIsapproxImately1.5tImeslargerInmenthanwomen.
J6
naddItIon,thereIsless
adIposetIssueoverthemedIalaspectoftheelbowofmencomparedwIthwomenof
sImIlarbodyfatcomposItIon.
J6,J7,J8
Second,menmaybemorelIkelytohaveawell
developedcubItaltunnelretInaculumthanwomen,andtheretInaculum,Ifpresent,Is
thIcker.AthIckercubItaltunnelretInaculummayIncreasetherIskofulnarnerve
compressIonInthecubItaltunnelwhentheelbowIsflexed.
ClInIcalmanIfestatIonsofulnarnervedysfunctIonvarywIththelocatIonandextentofthe
lesIon.
J9
NearlyallpatIentshavenumbness,tInglIng,orpaInInthesensorydIstrIbutIonof
theulnarnervesoncetheybecomesymptomatIc.However,therecanbeconsIderable
ulnarnervedysfunctIonbeforesymptomsappear.PrIelIppetal.
28
foundthatonly8of15
malevolunteerswIthsIgnIfIcantulnarnerveconductIonslowIngnotedanysymptoms.|ore
studIesareneededtobetterunderstandthemechanIsmandnaturalhIstoryofulnar
neuropathy.
UlnarnerveInjuryIsrelatIvelycommon.
19,20,27
Also,asIgnIfIcantproportIonofpatIents
havesymptomsofbIlateralulnarnervedysfunctIonsbothbeforeandaftersurgery.
26
Therefore,somehavespeculatedthatItmIghtbehelpfuldurIngthepreanesthetIc
IntervIewtoInquIreaboutahIstoryofulnarneuropathIes(crazyboneproblems)or
prevIoussurgeryattheelbow.fsuchahIstoryIsIndIcated,thefIndIngmustberecorded
andadIscussIonwIththepatIentorfamIlyshouldpresentthepossIbIlItyofapostoperatIve
recurrencedespItespecIalprecautIonsofpaddIngandposItIonIng.
ThetImeofrecognItIonofdIgItalanesthesIaassocIatedwIthulnarnervedysfunctIonmay
bequIteImportantInestablIshIngtheorIgInofthepostoperatIvesyndrome.fulnar
hypesthesIaoranesthesIaIsnotedpromptlyaftertheendofanesthesIa,asIntherecovery
facIlIty,thecondItIonIslIkelytobeassocIatedwItheventsthatoccurreddurInganesthesIa
orsurgery.ftherecognItIonIsdelayedformanyhours,thelIkelIhoodofcauseshIftsfrom
theIntraanesthetIcperIodtopostoperatIveevents.narevIewofclosedclaIms,Krolland
assocIates
19
commentedthatpostoperatIveulnardysfunctIoncanoccurasaresultof
eventsInthepostanesthetIcperIodandthatnerveInjurymaydevelopIncertaIn
susceptIblepatIentsdespIteconventIonallyacceptedmethodsofposItIonIngand
paddIng.
DpIoIdsmaymaskpostoperatIvedysesthesIasandpaIn,butevenstronganalgesIcsdonot
appeartomaskalossofsensatIon
P.801
asaresultofnervedysfunctIon.tmaybehelpfultoassessulnarnervefunctIonandrecord
theseobservatIonsbeforedIschargIngthepatIentfromtherecoveryroom.
Other Dorsal Decubitus Problems
Arm Complications
AnarmthatIshyperabductedcanforcetheheadofthehumerusIntotheaxIllary
neurovascularbundleanddamagenervesandvesselstothearm.AbductIonofthearmto
90degreesfromthetrunkshouldbeavoIded.Anarmboardshouldbesecurelyattachedto
theoperatIngtabletopreventItsaccIdentalrelease.AnarmthatIsnotproperlysecured
canslIpovertheedgeofthetableorarmboard,resultIngInInjurytothecapsuleofthe
shoulderjoIntbyexcessIvedorsalextensIonofthehumerus,fractureoftheneckofan
osteoporotIchumerus,orInjurytotheulnarnerveattheelbow.Conversely,IntheunlIkely
eventthattheretaInIngstrapIsexcessIvelytIghtacrossthesupInatedforearm(FIg.J010),
thepotentIalexIstsforpressuretocompresstheanterIorInterosseousnerve,abranchof
themedIannerveIntheupperforearmthatcourseswIthItsarteryalongthevolarsurface
ofthetoughInterosseousmembrane.TheresultIsanIschemIcInjurytothedIstrIbutIonof
thenerveandarterythatresemblesacompartmentsyndromeInthelowerextremItyand
mayrequIrepromptsurgIcaldecompressIon.
40,41,42
Backache
LumbarbackachecanbeworsenedbythelIgamentousrelaxatIonthatoccurswIthgeneral,
spInal,orepIduralanesthesIa.LossofnormallumbarcurvatureInthesupIneposItIonIs
apparentlytheIssue.PaddIng(FIg.J0J)placedunderthelumbarspInebeforethe
InductIonofanesthesIamayhelpretaInlordosIsandmakeapatIentwIthknownlumbar
dIstressmorecomfortable.HyperlordosIsshouldbeavoIded,however.HyperextensIonof
thelumbarspIne,especIallytoanangulatIonof10degreesattheL2Japexofthelumbar
spIne,mayresultInIschemIaofthespInalnerves.
4J
ElevatIonofthelegscanworsenthepaInofahernIatednucleuspulposus.Whenthe
lIthotomyposItIonIscontemplatedforapatIentwIthahIstoryoflowbackpaInora
hernIatedlumbardIsk,gentlepassIveattemptstohavethepatIentassumetheposture
beforeanesthesIamaybehelpfulIndetermInIngwhethertheposItIoncanbetolerated.
Figure 30-10.ArmrestraInt,IfexcessIvelytIght,cancompresstheanterIor
InterosseousnerveandvesselagaInsttheInterosseousmembraneInthevolarforearm
toproduceanIschemIcneuropathy.(Feproducedfrom|cLeskeyCH[Ed]:CerIatrIc
AnesthesIology.8altImore,WIllIamsEWIlkIns,1997,p155,wIthpermIssIon.)
Perineal Crush Injury
ThesupInepatIentwhoIsplacedonafracturetableforrepaIrofafracturedfemurusually
hasthepelvIsretaInedInplacebyavertIcalpoleattheperIneum(FIg.J011),wIththe
footoftheInjuredextremItyfIxedtoamobIlerest.Awormgearontherestlengthensthe
dIstancebetweenthefootandthepelvIssothatthebonefragmentscanbedIstractedand
realIgned.UnlessthepoleIswellpadded,severepressurecanbeexertedonthepelvIs,
anddamagecanoccurtothegenItalIaandthepudendalnerves.CompletelossofpenIle
sensatIonhasbeenreportedafteruseofthefracturetable.
44,45
ThecorrectposItIonfor
thepoleIsagaInstthepelvIsbetweenthegenItalIaandtheunInjuredlImb.
44
Compartment Syndrome
f,forwhateverreason,perfusIontoanextremItyIsInadequate,acompartmentsyndrome
maydevelop.CharacterIzedbyIschemIa,hypoxIcedema,elevatedtIssuepressurewIthIn
fascIalcompartmentsoftheleg,andextensIverhabdomyolysIs,thesyndromeproduces
extensIveandpotentIallylastIngdamagetothemusclesandnervesInthecompartment.
CausesofacompartmentsyndromethatmaybeassocIatedwIthposItIonIngfactorswhIlea
patIentIsInanyofthedorsaldecubItusposItIonsInclude(1)systemIchypotensIonandloss
ofdrIvIngpressuretotheextremIty(augmentedbyelevatIonoftheextremIty);(2)
vascularobstructIonofmajorlegvesselsbyIntrapelvIcretractors,byexcessIveflexIonof
kneesorhIps,orbyunduepoplItealpressurefromakneecrutch;and(J)external
compressIonoftheelevatedextremItybystrapsorlegwrappIngsthataretootIght,bythe
InadvertentpressureofthearmofasurgIcalassIstant,orbytheweIghtoftheextremIty
agaInstapoorlysupportIvelegholder.AtIghtstraponanarmaswellastIghtdraw
sheetsformaIntaInIngarmsatthepatIent'ssIdesmaycompresstheanterIorInterosseous
neurovascularbundleandmaybeassocIatedwIthananterIorInterosseousneuropathyora
forearmorahandcompartmentsyndrome.
41,42
SeveralclInIcalcharacterIstIcsseemtobeassocIatedwIthperIoperatIvecompartment
syndrome.ProlongedlIthotomypostureInexcessof5hourshasbeenacommonfactorIn
lIteratureanecdotesofpostlIthotomycompartmentsyndromes.ForlengthyproceduresIn
thelIthotomyposItIon,wellpaddedholdersthatImmobIlIzethelImbbysupportIngthe
footwIthoutcompressIngthecalforpoplItealfossaseemtobetheleastthreatenIng
choIce.ThereIsconsIderablevarIabIlItyIntheperfusIonpressureofthelowerextremItyIn
elevatedlegs.HallIwIlletal.
7
andPfefferetal.
8
foundsIgnIfIcantbloodpressurevarIatIon
attheankleInvolunteersplacedInvarIouslIthotomyposItIons.Severalvolunteershad
meanpressuresof20mmHgwhenposItIonedInthehIghlIthotomyposItIon.ThIspressure
IslessthanIntracompartmentpressurescommonlymeasuredInmanylIthotomyposItIons.
Warneretal.
46
haveshownthatperIoperatIvecompartmentsyndromesoccurInpatIentsIn
posItIonsotherthanlIthotomy.ThefrequencyofthIsproblemappearstooccurasoften
(approxImately1In9,000patIents)InanesthetIzedpatIentswhoareposItIonedlaterallyas
InsImIlarpatIentswhoareposItIonedInlIthotomy.ThedIfferencebetweencompartment
syndromesInthesetwogroupsIsthatpatIentsInalateraldecubItusposItIontendtohave
compartmentsyndromesofeItherarm,whIlethoseInalIthotomyposItIonhave
compartmentsyndromesofthelowerextremItIes.
46
P.802
Figure 30-11.TractIontablewIthperInealpoststabIlIzIngpatIentwhIlelegIs
elongatedtoreposItIonboneends.ElevatedlegrIskshypoperfusIon;pelvIcpost
threatensgenItalIa.(Feproducedfrom|artInJT,Warner|A[Eds]:PosItIonIngIn
AnesthesIaandSurgery,JrdedItIon.PhIladelphIa,W8Saunders,1997,p54,wIth
permIssIon.)
Finger Injury
AmputatIonoffIngershasbeenreportedwhentheywerecaughtbetweenthelegandthIgh
sectIonsoftheoperatIngtableasthelegsectIonwasreturnedtothehorIzontalposItIonat
thetermInatIonofanoperatIonperformedInthelIthotomyposItIon.
47
Atowelusedto
createaboxIngglovelIkewraponthehandsoflIthotomIzedpatIentsorcarefully
removIngthepatIent'shandsfromtherIskposItIonbeforeraIsIngthefootofthetablemay
preventsuchatragIcmIsadventure.
Lateral Decubitus Positions
ThereareseveralgeneralposItIonIngconceptstoconsIderwhenplacIngapatIentIntoa
lateraldecubItusposItIon.WrappIngthelegsandthIghsIncompressIvebandageshasbeen
commonlyusedtocombatvenouspoolIng.|arkedflexIonofthelowerextremItIesatknees
andhIpscanpartIallyorcompletelyobstructvenousreturntotheInferIorvenacavaeIther
byangulatIonofvesselsatthepoplItealspaceandInguInallIgamentorbythIgh
compressIonagaInstanobeseabdomen.Asmallsupportplacedjustcaudadofthedown
sIdeaxIllacanbeusedtolIftthethoraxenoughtorelIevepressureontheaxIllary
neurovascularbundleandpreventdIsturbedbloodflowtothearmandhand.However,thIs
chestsupport(InapproprIatelycalledanaxillary rollbysome)hasnotbeenprovento
reducethefrequencyofIschemIa,nervedamage,orcompartmentsyndrometothedown
sIdeupperextremIty.tmay,however,decreaseshoulderdIscomfortpostoperatIvely.Any
paddIngshouldsupportonlythechestwallandItshouldbeperIodIcallyobservedtoensure
thatItdoesnotImpIngeontheneurovascularstructuresoftheaxIlla.
P.80J
Variations of the Lateral Decubitus Positions
Standard (Horizontal) Lateral Position
nthehorIzontallateraldecubItusposItIon(FIg.J012),thepatIentIsrolledontoonesIde
onaflattablesurfaceandstabIlIzedInthatposturebyflexIngthedownsIdethIgh.The
downsIdekneeIsbenttoretaInthelegonthetableandImprovestabIlIzatIonofthe
trunk.ThecommonperonealnerveofthatsIdeIspaddedtomInImIzecompressIondamage
causedbytheweIghtofthelegs.TheupsIdethIghandlegareextendedcomfortably,and
pIllowsareplacedbetweenthelowerextremItIes.TheheadIssupportedbypIllowsora
headrestsothatthecervIcalandthoracIcspInesareproperlyalIgned.Asmallpad,thIck
enoughtoraIsethechestwallandpreventexcessIvecompressIonoftheshoulderor
entrapment/compressIonoftheneurovascularstructuresoftheaxIlla,Isplacedjust
caudadtothedownsIdeaxIlla.ThIspaddIngmaysupportadequateperfusIonofthedown
sIdehandandmInImIzecIrcumductIonofthedependentshoulder,whIchmIghtstretchIts
suprascapularnerve.
Figure 30-12.ThestandardlateraldecubItusposItIon.Properheadsupport,axIllary
roll,andlegpIllowarrangementareshownonlower figure.0ownsIdelegIsflexedat
hIpandkneetostabIlIzetorso.FetaInIngstrapsandpadfordownsIdeperonealnerve
arenotshown.(Feproducedfrom|artInJT,Warner|A[Eds]:PosItIonIngIn
permIssIon.)
Figure 30-13.ThesemIsupIneposItIonwIthdorsalpadssupportIngthetorso,the
extendedarmpaddedattheelbow,andtheelevatedarmrestraInedonawell
cushIoned,adjustableoverheadbar(A).AxIllarycontents(B)arenotundertensIon
andarenotcompressedbytheheadofthehumerus,andapulseoxImeterensuresthat
thedIgItalcIrculatIonIsnotcompromIsed.TheposItIonIssafeonlyIfthearmdoesnot
becomeahangIngmechanIsmtosupportthetorso.(FeproducedfromCollIns7J[Ed]:
PrIncIplesofAnesthesIology,JrdedItIon.PhIladelphIa,LeaEFebIger,199J,p176,wIth
permIssIon.)
ArmsmaybeextendedventrallyandretaInedonasInglearmboardwIthsuItablepaddIng
betweenthem,ortheymaybeIndIvIduallyretaInedonapaddedtwolevelarmsupport
thatcanalsohelptostabIlIzethethorax.AnalternatemethodofarmarrangementIsto
flexeachelbowandplacethearmsonsuItablepaddIngonthetableInfrontofthe
patIent'sface.
ThepatIentIsstabIlIzedInthelateralposItIonbytheuseofoneormoreretaInIngtapesor
strapsstretchedacrossthehIpandfIxedtotheundersIdeofthetabletop.Caremustbe
takentoseethatthehIptapesorstrapslIesafelybetweentheIlIaccrestandtheheadof
thefemurratherthanovertheheadofthefemur.AnaddItIonalrestraInIngtapeorstrap
maybeusedacrossthethoraxorshouldersIfneeded.
Semisupine and Semiprone
ThesemIlateralposturesaredesIgnedtoallowthesurgeontoreachanterolateral
(semIsupIne)andposterolateral(semIprone)structuresofthetrunk.nthesemIsupIne
posItIon,theupsIdearmmustbecarefullysupportedsothatItIsnothyperextendedand
notractIonorcompressIonIsapplIedtothebrachIalandaxIllaryneurovascularbundles
(FIg.J01J).ThesupportIngbarshouldbewellwrappedtopreventelectrIcalgroundIng
contact(FIg.J01JA).SuffIcIentnoncompressIblepaddIngshouldbeplacedunderthedorsal
torso(FIg.J01J,large figure)andhIptopreventthepatIentfromrollIngsupIneand
stretchIngtheanchoredextremIty.ThepulseoftherestraInedwrIstshouldbecheckedto
ensureadequatecIrculatIonIntheelevatedarmandhand(FIg.J01J8).
Flexed Lateral Positions
Lateral Jackknife
ThelateraljackknIfeposItIonplacesthedownsIdeIlIaccrestoverthehIngebetweenthe
backandthIghsectIonsofthetable(FIg.J014).ThetabletopIsangulatedatthatpoIntto
flexthethIghsonthetrunklaterally.AfterthepatIenthasbeensuItablyposItIonedand
restraIned,thechassIsofthetableIstIppedsothattheuppermostsurfaceofthepatIent's
flankandthoraxbecomesessentIallyhorIzontal.Asaresult,thefeetarebelowthelevelof
theatrIa,andsIgnIfIcantamountsofbloodmaypoolIndIstensIblevesselsIneachleg.
ThelateraljackknIfeposItIonIsusuallyIntendedtostretchtheupsIdeflankandwIden
IntercostalspacesasanassettoathoracotomyIncIsIon.However,Intermsoflumbar
stress,restrIctIonbythetautflankofupsIdecostalmargInmotIon,andpoolIngofbloodIn
depressedlowerextremItIes,theposItIonImposesasIgnIfIcantphysIologIcInsult.Actually,
ItsusefulnesstothesurgeonIsbrIef,andItsuseshouldbelImIted.DncetherIbspreadIng
retractorIsplacedIntheIncIsIon,theposItIonhasreducedvaluefortherestofthe
operatIon.
48
P.804
Figure 30-14.ThelateraljackknIfeposItIon,IntendedtoopenIntercostalspaces.Note
theproperlyplacedrestraInIngtapes(large figure)thrustIngcephaladtoretaInthe
IlIaccrestattheflexIonpoIntofthetableandpreventcaudadslIppage,whIch
compressesthedownsIdeflank(inset).(Feproducedfrom|artInJT,Warner|A[Eds]:
PosItIonIngInAnesthesIaandSurgery,JrdedItIon.PhIladelphIa,W8Saunders,1997,
1J0,wIthpermIssIon.)
Kidney
ThekIdneyposItIon(FIg.J015)resemblesthelateraljackknIfeposItIon,butItaddstheuse
ofanelevatedrest(thekidney rest)underthedownsIdeIlIaccresttoIncreasetheamount
oflateralflexIonandImproveaccesstotheupsIdekIdneyundertheoverhangIngcostal
margIn.UnlIkethelateraljackknIfeposItIon,thekIdneyposItIondoesnothaveauseful
alternatIveforaflankapproachtothekIdney.Thus,thephysIologIcInsultsassocIatedwIth
thepostureneedtobelImItedbyvIgIlantanesthesIaandrapIdsurgery.StrIctstabIlIzIng
precautIonsshouldbetakentopreventthepatIentfromsubsequentlyshIftIngcaudadon
thetableInsuchamannerthattheelevatedrestrelocatesIntothedownsIdeflankand
becomesasevereImpedImenttoventIlatIonofthedependentlung.
Complications of the Lateral Decubitus Positions
Eyes and Ears
njurIestothedependenteyeareunlIkelyIftheheadIsproperlysupporteddurIngand
aftertheturnfromthesupInetothelateralposItIon.fthepatIent'sfaceturnstowardthe
mattress,however,andthelIdsarenotclosedortheeyesotherwIseprotected,abrasIons
oftheocularsurfacecanoccur.0IrectpressureontheglobecandIsplacethecrystallIne
lens,IncreaseIntraocularpressureor,partIcularlyIfsystemIchypotensIonIspresent,cause
IschemIa.
nthelateralposItIon,theweIghtoftheheadcanpressthedownsIdeearagaInstarough
orwrInkledsupportIngsurface.CarefulpaddIngwIthapIlloworafoamspongeIsusually
suffIcIentprotectIonagaInstcontusIonoftheear.Theexternalearshouldalsobepalpated
toensurethatIthasnotbeenfoldedoverIntheprocessofplacIngsupportbeneaththe
head.
Neck
LateralflexIonoftheneckIspossIblewhentheheadofapatIentInthelateralposItIonIs
Inadequatelysupported.fthecervIcalspIneIsarthrItIc,postoperatIveneckpaIncanbe
troublesome.PaInfromasymptomatIcprotrusIonofacervIcaldIskcanbeIntensIfIed
unlesstheheadIscarefullyposItIonedsothatlateralorventralflexIon,extensIon,or
rotatIonIsavoIded.
Suprascapular Nerve
7entralcIrcumductIonofthedependentshouldercanrotatethesuprascapularnotchaway
fromtherootoftheneck(FIg.J016).8ecausethesuprascapularnerveIsfIxedboth
paravertebrallyandatthenotch,cIrcumductIoncanstretchthenerveandproduce
troublesome,dIffuse,dullshoulderpaIn.ThedIagnosIsIsestablIshedbyblockIngthenerve
atthenotchandproducIngpaInrelIef.TreatmentmayrequIreresectIngthelIgamentover
thenotchtodecompressthenerve.AsupportIngpadplacedunderthethoraxjustcaudad
oftheaxIllaandthIckenoughtoraIsethechestofftheshouldershouldpreventa
cIrcumductIonstretchInjurytothenerve.
Long Thoracic Nerve
nstancesofpostoperatIvewIngIngofthescapula(FIg.J08)havefolloweduseofthe
lateraldecubItusposItIon.
18
AlthoughcoIncIdentalvIralneuropathIesofthelongthoracIc
nervemayplayamajoretIologIcroleInpostoperatIveappearancesofscapularwIngIngIn
patIentsforwhomonlyadorsaldecubItusposItIonwasused,thepossIbIlItyoftraumato
thenervewhIleestablIshIngthelateralposItIonIsdIffIculttorefute.LateralflexIonofthe
neckmaystretchthelongthoracIcnerveIntheobtuseangleoftheneck.
Ventral Decubitus (Prone) Positions
Variations of the Ventral Decubitus Position
Full (Horizontal) Prone
nthesocalledfullorhorizontal prone position(FIg.J017),therequIrementtoelevate
thetrunkoffthesupportIngsurface
P.805
sothattheventralabdomInalwallIsfreedofcompressIonalmostalwaysresultsInthe
headandlowerextremItIesbeIngbelowthelevelofthespIne.fthetabletopIsangulated
atthetrunkthIghhIngetoremovethelumbarlordosIsandseparatethelumbarspInous
processes,andIfthechassIsIsthenrotatedheadupsuffIcIentlytolevelthepatIent'sback,
asIgnIfIcantperfusIongradIentmaydevelopbetweenthelegsandtheheart.
49
WrappIng
thelegsIncompressIvebandages,ortheuseoffulllengthelastIchosIery,mInImIzes
poolIngofbloodIndIstensIblevesselsandsupportsvenousreturn.
Figure 30-15.Theflexedlateral(kIdney)posItIon.UpperpanelsshowImproper
locatIonsoftheelevatedtransverserest,theflexIonpoIntofthetable,Intheflank
(A)oratthelowercostalmargIn(B)toImpedeventIlatIonofthedownsIdelung.The
IlIaccrestattheproperflexIonpoInt(C),allowIngthebestpossIbleexpansIonofthe
downsIdelung.FestraInIngtapesdeletedforclarIty.(Feproducedfrom|artInJT,
Saunders,1997,1J2,wIthpermIssIon.)
7arIousventralsupports,IncludIngparallelrollsoftIghtlypackedsheets,paddedand
adjustablemetalframes,andfourpIllarframes,havebeendevIsedtofreetheabdomen
fromcompressIon.EachhasmerIt,andnospecIfIcunIthasbeenshowntobebetterthan
theothersforhemodynamIcorrespIratorymaIntenance.However,theuseofframesmay
producemoreopportunItIesforpoIntpressure,andIftheyareused,carefulpaddIngof
contactpoIntsshouldbeconsIdered.ThechoIceofequIpmentIsbasedonthephysIqueof
thepatIent,therequIrementsofthesurgIcalprocedure,andavaIlabIlIty.
PronatedpatIentswIthlImItedmobIlItyoftheneck,ahIstoryofposturalneckpaIn,ora
hIstorysuggestIngasymptomatIccervIcaldIskshouldhavetheIrheadsretaInedInthe
sagIttalplane,eItherwIthaskullpInheadclamporwIthafacerest.
P.806
FacerestshavefluctuatIngpopularIty.ExcessIveperIocularpressuremustbeconsIdered
andavoIdedIfafacerestIsused.ftheneckIspaInfreeandItsmobIlItyIssatIsfactory,
theheadcanbeturnedlaterallyandsupportedtopreventpressureonthedownsIdeeye
andear.However,forcedrotatIonofthepronatedheadshouldbecarefullyavoIdedlestIt
InducepostoperatIveneckpaInorcervIcalnerverootorvascularcompressIon.
Figure 30-16.CIrcumductIonofthearmdIsplacIngthescapulaandstretchIngthe
suprascapularnervebetweenItsanchorIngpoIntsatthecervIcalspIneandthe
suprascapularnotch.(Feproducedfrom|artInJT,Warner|A[Eds]:PosItIonIngIn
permIssIon.)
Figure 30-17.TheclassIcproneposItIon.A.FlattablewIthrelaxedarmsextended
alongsIdepatIent'shead.ParallelchestrollsextendedfromjustcaudadofclavIcleto
justbeyondInguInalarea,wIthpIllowoverpelvIcend.Elbowsandkneesarepadded,
andlegsarebentattheknees.HeadIsturnedontoaCshapedfoamspongethatfrees
thedownsIdeeyeandearfromcompressIon.B.SameposturewItharmssnugly
retaInedalongsIdetorso.C.TableflexedtoreducelumbarlordosIs;subglutealarea
strapsplacedafterthelegsareloweredtoprovIdecephaladthrustandprevent
caudadslIppage.(Feproducedfrom|artInJT,Warner|A[Eds]:PosItIonIngIn
permIssIon.)
WhenapatIentIsscheduledtobepronatedafterInductIonofanesthesIa,ItIsworthwhIle
durIngthepreanesthetIcIntervIewtoobtaInandrecordInformatIonaboutanylImItatIons
thatmayexIstInhIsorherabIlItytoraIsethearmsoverheaddurIngworkorsleep.fthe
patIentIssymptomatIc,ItmaybeprudenttoplacethearmsalongsIdethetorsoafter
pronatIon(seeThoracIcDutletSyndrome).fthearmsareplacedalongsIdethehead
(I.e.,extendedventrallyattheshoulder,flexedattheelbow,andabductedontoarm
boards;thesurrenderposItIon),themusculatureabouttheshouldersshouldbeunderno
tensIon,neItherhumeralheadshouldstretchorcompressItsaxIllaryneurovascularbundle
(I.e.,shouldersshouldbeabducted90degrees),ulnarnervesattheelbowshouldbe
padded,andthepulsesatthewrIstsshouldremaInfull.AnterIor(forward)flexIonofthe
shouldersmayreducetensIonontheneurovascularstructuresoftheaxIlla.
Prone Jackknife
ThepronejackknIfepostureIsusedtoprovIdeaccesstothesacral,perIanal,andperIneal
areasaswellastotheloweralImentarycanal(FIg.J018).ThethIghsareflexedonthe
trunkmorethanIsusualInthefullproneposItIon,wIththetablesurfacehInges
determInIngthedegreeofflexIonachIevable.
Prone Kneeling
KneelIngposItIonshavebeenusedtoImproveoperatIvecondItIonsInthelumbarand
cervIcooccIpItalareas(FIg.J019).Numerousframeshavebeenconstructedtosupportthe
weIghtofakneelIngpatIent,andtheIrusefulnessagaIndependsonthephysIqueofthe
patIent.fthevertebralcolumnIsunstable,kneelIngframesarenotasusefulasparallel
longItudInalsupportsbecausekneelIngrIsksapplIcatIonofshearIngforcesatthefracture
sIte,wIththepotentIalfordamageofthecontentsofthespInalcanal.nmassIvelyobese
patIentswhomustbeoperatedonIntheproneposItIon,kneelIngframestendtoprevent
pressureontheabdomenmoresuccessfullythanlongItudInalframes.However,prolonged
kneelIngcanbefraughtwIthhazardssuchascompartmentsyndromeandsofttIssue
problems.
Complications of the Ventral Decubitus Positions
Eyes and Ears
TheeyesandearsmaysustaInInjuryIntheproneposItIon.TheeyelIdsshouldbeclosed,
andeacheyeshouldbeprotectedInsomemannersothatthelIdscannotbeaccIdentally
separatedandthecorneascratched.nstIllatIonoflubrIcatIonIntheeyesshouldbe
consIdered,althoughthevalueofthIstreatmentIs
P.807
debated.TheeyesshouldalsobeprotectedagaInsttheheadturnIngafterposItIonIngand
pressurebeIngexertedontheglobe.|onItorIngwIresandIntravenoustubIngshouldbe
checkedafterpronatIontoseethatnonehasmIgratedbeneaththehead.ftheheadIs
retaInedInthesagIttalplane,theeyesshouldbecheckedafterposItIonIngtoensurethat
theyaresafefromcompressIonbyanyheadrest.
Figure 30-18.ThepronejackknIfeposItIons.A.LowjackknIfeposItIonwIththetrunk
thIghhIngeofthetableusedastheflexIonposItIonandaugmentedbyapIllowunder
thepelvIs.B.FulljackknIfeposItIonwIththethIghleghIngeofthetableusedasthe
flexIonpoInttoachIevemoreacuteangulatIonofthehIpsonthetorso.(Feproduced
from|artInJT,Warner|A[Eds]:PosItIonIngInAnesthesIaandSurgery,JrdedItIon.
PhIladelphIa,W8Saunders,1997,p16J,164,wIthpermIssIon.)
Figure 30-19.TheAndrewskneelIngframewIthWIltse'sthoracIcjackInuse.
JrdedItIon.PhIladelphIa,W8Saunders,1997,p161,wIthpermIssIon.)
ConjunctIvaledemausuallyoccursIntheeyesofthepronatedpatIentIftheheadIsator
belowtheleveloftheheart.tIsusuallytransIent,InconsequentIal,andrequIresonlyre
establIshmentofthenormaltIssueperfusIongradIentsofthesupIneposItIon,orofaslIght
amountofheaduptIlt,toberedIstrIbuted.TheredoesnotappeartobeanyconnectIon
betweenthIsedemaandtheoccurrenceofposterIorIschemIcoptIcneuropathy.
Blindness
PermanentlossofvIsIoncanoccurafternonocularsurgIcalprocedures,especIallythose
performedInaventraldecubItusposItIon.
50
TheoccurrenceofthIsdevastatIng
complIcatIonIspartIcularlyassocIatedwIthextensIvesurgIcalproceduresdoneInthe
proneposItIon,suchasreconstructIvespInesurgery,wherethereIsassocIatedbloodloss,
anemIa,andhypotensIon.7IsuallossafterneurovascularandcardIopulmonarybypass
proceduresIswellrecognIzedandmayberelatedtoembolIceventsproducedbythe
surgIcalInterventIonItself,hypoperfusIon,orothernonposItIonIngcauses.
51,52,5J,54
7Isual
lossafternoncardIac,nonneurovascularproceduresmayInItIallybenotIcedbyalossof
acuIty,alossofvIsualfIeld,orboth.
SpeculatedcausesofsIgnIfIcantpermanentpostoperatIvevIsuallossusuallyInvolve
compromIseofoxygendelIverytoelementsofthevIsualpathwayandIncludeIschemIc
optIcneuropathy(anterIororposterIor),retInalarteryocclusIon(centralorbranch),and
cortIcalblIndness.
55
NocaseserIesexIsttoprovIdeInformatIonregardIngthefrequencyof
theseeventsafternonocular,noncardIacsurgeryInageneralsurgIcalpopulatIon.8rownet
al.
56
IdentIfIedthreepatIentsInwhompostoperatIveIschemIcoptIcneuropathydeveloped
afternoncardIacsurgeryovera10yearperIodInoneInstItutIon.Warneretal.
57
noted
thatnoneofnearly11,000proneposItIonedpatIentsdevelopedperIoperatIvevIsIonloss.
However,theInstItutIonoftheseauthorssubsequentlyhasexperIencedseveralpatIents
whohavedevelopedcompleteblIndnessafterspInalsurgeryperformedwIthpatIents
posItIonedprone.FeflectIngconcernabouttheapparentIncreasedIncIdenceof
perIoperatIveblIndness,theAmerIcanSocIetyofAnesthesIologIstsCommItteeon
ProfessIonalLIabIlItyhascreatedaformalregIstrytomonItoranddocumenttheIncIdence
ofthIscomplIcatIon.
50
PosItIonIngappearstobearIskfactorforsomeoftheseevents.AvarIetyofstudIesnotIng
arelatIvehIghfrequencyofpostoperatIvevIsuallossInspInalsurgerypatIentshave
ImplIcatedposItIonIngasonecausatIvefactor.UseofthekneechestposItIon,theprone
posItIon,andthehorseshoeheadresthavebeencItedaspotentIalcausesofvIsualloss,
perhapsbydIrectpressureontheglobeIncreasIngtheIntraocularpressurebeyondthe
perfusIonpressureoftheretIna.Dtherreports,IncludIngthoseofspInalsurgerypatIents,
descrIbevIsuallossafterprolongedprocedures,IntraoperatIvehypotensIon,andmassIve
bloodloss,whIchmaypreventadequateoxygendelIverytothevIsualapparatus.The
AmerIcanSocIetyofAnesthesIologIstsTaskForceonPerIoperatIve8lIndnessrevIewed
studIescurrentthrough2005andpublIshedanadvIsory(TableJ01).
58
Table 30-1 Summary of Practice Advisory for Perioperative Visual Loss
Associated with Spine Surgery
ThereIsasubsetofpatIentswhoundergospIneprocedureswhIletheyare
posItIonedproneandreceIvInggeneralanesthesIathathasanIncreasedrIskfor
developmentofperIoperatIvevIsualloss.ThIssubsetIncludespatIentswhoare
antIcIpatedpreoperatIvelytoundergoproceduresthatareprolonged,have
substantIalbloodloss,orboth(hIghrIskpatIents).
ConsIderInformInghIghrIskpatIentsthatthereIsasmall,unpredIctablerIskof
perIoperatIvevIsualloss.
TheuseofdelIberatehypotensIvetechnIquesdurIngspInesurgeryhasnotbeen
showntobeassocIatedwIththedevelopmentofperIoperatIvevIsualloss.
ColloIdsshouldbeusedalongwIthcrystalloIdstomaIntaInIntravascularvolume
InpatIentswhohavesubstantIalbloodloss.
AtthIstIme,thereIsnoapparenttransfusIonthresholdthatwouldelImInatethe
rIskofperIoperatIvevIsuallossrelatedtoanemIa.
HIghrIskpatIentsshouldbeposItIonedsothattheIrheadsarelevelwIthor
hIgherthantheheartwhenpossIble.naddItIon,theIrheadsshouldbe
maIntaInedInaneutralforwardposItIon(e.g.,wIthoutsIgnIfIcantneckflexIon,
extensIon,lateralflexIon,orrotatIon)whenpossIble.
ConsIderatIonshouldbegIventotheuseofstagedspIneproceduresInhIghrIsk
patIents.
FeproducedfromAmerIcanSocIetyofAnesthesIologIstsTaskForceon
PerIoperatIve8lIndness.AnesthesIology2006;104:1J19,wIthpermIssIon.
P.808
Figure 30-20.SourcesofpotentIalInjurytothebrachIalplexusandItsperIpheral
componentswhenthepatIentIsIntheproneposItIon.A.NeckrotatIon,stretchIng
rootsoftheplexus.B.CompressIonoftheplexusandvesselsbetweentheclavIcleand
fIrstrIb.C.njurytotheaxIllaryneurovascularbundlefromtheheadofthehumerus.
D.CompressIonoftheulnarnervebefore,beyond,andwIthInthecubItaltunnel.E.
AreaofvulnerabIlItyoftheradIalnervetolateralcompressIonproxImaltotheelbow.
JrdedItIon.PhIladelphIa,W8Saunders,1997,p185,wIthpermIssIon.)
Neck Problems
AnesthesIaImpaIrsreflexmusclespasmthatprotectstheskeletonagaInstmotIonthat
wouldbepaInfulIfthepatIentwerealert.LateralrotatIonoftheheadandneckofan
anesthetIzed,pronatedpatIent,partIcularlyonewIthanarthrItIccervIcalspIne,can
stretchrelaxedskeletalmusclesandlIgamentsandInjureartIculatIonsofcervIcal
vertebrae.PostoperatIveneckpaInandlImItatIonofmotIoncanresult.ThearthrItIcneck
IsusuallybestmanagedbykeepIngtheheadInthesagIttalplanewhenthepatIentIs
prone.
ExtremesofheadandneckrotatIoncanalsoInterferewIthflowIneIthertheIpsIlateralor
contralateralvesselstoandfromthehead.ExcessIveheadrotatIoncanreduceflowIn
boththecarotId
59
andvertebralsystems.
60
mpaIredcerebralperfusIonIstheobvIous
consequence.
Brachial Plexus Injuries
StretchInjurIestotherootsofthebrachIalplexus(FIg.J020A)onthesIdecontralateralto
theturnedfacearepossIbleIfthecontralateralshoulderIsheldfIrmlycaudadbyawrIst
restraInt.fanarmIsplacedonanarmboardalongsIdethehead,caremustbetakento
ensurethattheheadofthehumerusIsnotstretchIngandcompressIngtheaxIllary
neurovascularbundle(FIg.J0208,C).
WhenanarmIsplacedonanarmboardalongsIdethehead,theforearmnaturally
pronates.Asaresult,theulnarnerve,lyIngInthecubItaltunnel(thegroovebetweenthe
olecranonprocessandthemedIalepIcondyleofthehumerus),IsvulnerabletobeIng
compressedbytheweIghtoftheelbow(FIg.J0200).Consequently,themedIalaspectof
theelbowmustbewellpaddedandItsweIghtborneacrossalargeareatoavoIdpoInt
pressure.
AskIngpatIentsabouttheIrabIlItytoworkorsleepwItharmselevatedoverheadmay
IdentIfypatIentswIththoracic outlet obstruction.AusefulpreoperatIvetestIfthehIstory
IsInquestIonIstohavethepatIentclasphandsbehIndtheoccIputdurIngtheIntervIew
(FIg.J021).fthepatIentdescrIbesdysesthesIas,Itmaybeprudenttokeepthearms
alongsIdethetrunkIntheproneposItIon.AgonIzIng,debIlItatIng,andunremIttIng
postoperatIvepaInhasbeenknowntofollowoverheadarmplacementInpronatedpatIents
whohavehadprIordIscomfortIntheIrarmsInthatposItIon.
Breast Injuries
Thebreastsofapronatedwoman,Ifforcedlaterallybyventralchestsupports,canbe
stretchedandInjuredalongtheIrsternalborders.|edIalandcephaladdIsplacementseems
bettertolerated.0Irectpressureonbreasts(partIcularlyIfbreastprosthesesarepresent)
cancauseIschemIatobreasttIssueandshouldbeavoIded.
Figure 30-21.AssessmentofapotentIalthoracIcoutletsyndrome.A.ThIspatIenthas
ahIstoryofdIstresswhentryIngtoworkorsleepwItharmsoverhead.B.ntervIew
carrIedoutwIththIspatIent'shandsclaspedonoccIputandradIalpulsescheckedfor
dampIng.(Feproducedfrom|cLeskeyCH[Ed]:CerIatrIcAnesthesIology.8altImore,
WIllIamsEWIlkIns,1997,p186,wIthpermIssIon.)
Abdominal Compression
CompressIonoftheabdomenbytheweIghtofthepronepatIent'strunkcancausevIscera
toforcethedIaphragmcephaladenoughtoImpaIrventIlatIon.fIntraabdomInalpressure
approachesorexceedsvenouspressure,returnofbloodfromthepelvIsandlower
extremItIesIsreducedorobstructed.8ecausethevertebralvenousplexusescommunIcate
dIrectlywIththeabdomInalveIns,IncreasedIntraabdomInalpressureIstransmIttedtothe
perIvertebralandIntraspInalsurgIcalfIeldIntheformofvenousdIstentIonandIncreased
dIffIcultywIth
P.809
hemostasIs.AllofthevarIoussupportIvepadsandframes,whenproperlyused,are
desIgnedtoremovepressurefromtheabdomenandavoIdtheseproblems.
Figure 30-22.PosturalsupportscompromIsIngvIsceralstoma.8oththevertIcal
abdomInalsupportofadevIcedesIgnedtomaIntaInapatIentInthelateralposItIon
(A)andthelongItudInalchestrollssupportIngapronatedpatIent(B)cancause
IschemIccompressIonofavIscerocutaneousanastomosIsandsubsequentnecrosIs.
SurgIcalrepaIrofthestomamaybeneeded.(|odIfIedfrom|cLeskeyCH[Ed]:
CerIatrIcAnesthesIology.8altImore,WIllIamsEWIlkIns,1997,pJ40,wIthpermIssIon.)
Figure 30-23. A.ConventIonalneurosurgIcalsIttIngposItIon.Thelegsareat
approxImatelytheleveloftheheartandgentlyflexedonthethIghs;thefeetare
supportedatrIghtanglestothelegs;subglutealpaddIngprotectsthescIatIcnerve.
TheframeoftheheadholderIsproperlyclampedtothesIderaIlsofthebacksectIon
IntheeventofhemodynamIcallysIgnIfIcantaIrembolIsm.B.Improperattachmentof
theheadframetothetablesIderaIlsatthethIghsectIon.nthIsposItIon,the
patIent'sheadcouldnotbequIcklyloweredbecauseItwouldrequIredIsengagIngthe
skullclamp.(Feproducedfrom|artInJT,Warner|A[Eds]:PosItIonIngInAnesthesIa
andSurgery,JrdedItIon.PhIladelphIa,W8Saunders,1997,p72,wIthpermIssIon.)
Viscerocutaneous Stomata
StomatathatdraInvIsceralcontentsIntocontaInersaffIxedtotheabdomInalwallareat
rIskIntheproneposItIonIftheylIeagaInstapartoftheventralsupportIngframeorpad
(FIg.J022).CompressIveIschemIaofthestomalorIfIcecancauseIttoslough.
Head-Elevated Positions
Variations of the Head-Elevated Positions
Sitting
TheclassIcsitting positionforsurgeryplacesthepatIentInasemIreclInIngpostureonan
operatIngtable,wIththelegselevatedtoapproxImatelytheleveloftheheartandthe
headflexedventrallyontheneck(FIg.J02J).HeadflexIonshouldnotbesuffIcIentto
forcethechInIntothesuprasternalnotch(see|IdcervIcalTetraplegIa).ElastIcstockIngs
orcompressIvewrapsaroundthelegsreducepoolIngofbloodInthelowerextremItIes.The
headoftenIsheldInplacebysometypeofafacerestorbyathreepInskullfIxatIon
frame.
SupineTilted Head Up
AdorsalrecumbentposItIonwIththeheadofthepatIentelevatedIsusedformany
operatIonsInvolvIngtheventraland
P.810
lateralaspectsofthehead(FIg.J024)andneck,andoccasIonallywIththeneckflexed,for
transcranIalaccesstothetopofthebraIn.tspurposeIstoImproveaccesstothesurgIcal
targetfortheoperatIngteamaswellastodraInbloodandIrrIgatIonsolutIonsawayfrom
thewound.ThebacksectIonofthesurgIcaltablecanbeelevatedasneededtoproducea
lowsIttIngposItIon(FIg.J024A),ortheentIretablecanberotatedheadhIghwIththe
patIent'sextendedlegssupportedbyafootrest(FIg.J0248).AlthoughthedegreeoftIlt
typIcallyIsnotgreat,smallpressuregradIentsarecreatedalongthevascularaxIsthatcan
poolbloodInthelowerextremItIesorentraInaIrInpatulousvesselsthatareIncIsedabove
theleveloftheheart.
Figure 30-24.HeadelevatedposItIonsoftenusedforoperatIonsabouttheventraland
ventrolateralaspectsofthehead,face,neck,andcervIcalspIne.A.Thelegsareat
approxImatelyheartlevelandthegradIentIntotheheadIsapprecIablebutslIght.B.
TheflattableandfootrestareusefulwhenathyroIdectomyIsplannedunderregIonal
anesthesIa.(Feproducedfrom|artInJT,Warner|A[Eds]:PosItIonIngInAnesthesIa
andSurgery,JrdedItIon.PhIladelphIa,W8Saunders,1997,p89,wIthpermIssIon.)
ForoperatIonsaroundtheshoulderjoInt,thepatIentmaybeplacedInaheadelevated
semIsupIneposItIon,wIththeuppertorsorotatedtowardthenonsurgIcalshoulderand
supportedbyafIrmrollorpad(FIg.J025).
TheuppertrunkIsmovedlaterallyuntIltheraIsedsurgIcalshoulderextendsbeyondthe
edgeoftheoperatIngtable.ThetorsoIssupportedsothatthehIpsareonthetable,the
surgIcalshoulderIsoffandabovethetableedge,andtheheadrestsoneItherapIllow
(FIg.J025A)orahorseshoeheadrest(FIg.J0258).AccessIstherebyprovIdedtoboththe
dorsalandventralaspectsoftheshouldergIrdle.ThesurgIcalarmremaInsontheventral
torsoandIspreparedanddrapedtobemobIleInthesurgIcalfIeld.
LateralTilted Head Up
ThelateraldecubItusposItIonwIththeheadsomewhatelevated,ameansofaccessto
occIpItocervIcallesIons,hasalsobeenreferredtoasthepark bench position.Allthe
stabIlIzIngrequIrementsneededfortheusuallateraldecubItusposItIonapply.Thehead
maybeheldfIrmlyInathreepInskullfIxatIonholder,whIchcanbereadjustedasneeded
durIngsurgery,orsupportedbypIllowsorpaddIng.AlthoughthedegreeofheadelevatIon
usedtypIcallyIs15degrees,theposItIondoesnotcompletelyremovethethreatofaIr
embolIzatIon.TheanesthesIologIsthasgoodaccesstothepatIent'sfaceandventralthorax
forpurposesofmonItorIng,manIpulatIon,andresuscItatIon.ConsIderableattentIonshould
bedIrectedtoavoIdIngcompressIonofneckveIns,whIchcanleadtoanIncreaseIn
IntracranIalpressureandtoedemaofthetongue.
Figure 30-25. A.ThebarberchaIrposItIonforsurgeryaroundtheshoulderjoInt.B.
TheuppertorsoIsrotatedtowardthenonsurgIcalshoulderandsupportedwIthafIrm
rollorpad.
ProneTilted Head Up
TheventraldecubItusposturewIththetablerotatedheadhIgh(FIg.J026)canbeusedto
accessdorsalstructuresoftheheadandneck.UsuallytheperceIvedadvantageofthIs
posItIoncomparedwIthasIttIngposItIonIstheavoIdanceofaIrembolIzatIon.Althoughthe
pressuregradIentsforaIrentraInmentIntopatulousveInsarelessthanInthefullsIttIng
posItIon,thehazardIsnotelImInated.AsaresultoftheposItIvepressureInflatIoncycleof
passIveventIlatIon,abothersomerecurrentfluxofcerebrospInalfluIdIntoandoutofthe
exposedwoundmaybeencountered.TheposturealsorestrIctsresuscItatIveaccesstothe
ventralthorax.
Complications of the Head-Elevated Positions
Postural Hypotension
ntheanesthetIzedpatIent,establIshInganyoftheheadelevatedposItIonsIsfrequently
accompanIedbysomedegreeofreductIonInsystemIcbloodpressure.Thenormal
protectIvereflexesareInhIbItedbydrugsuseddurInganesthesIa.|easurIngmeanarterIal
pressuresatthelevelofthecIrcleofWIllIsIsrecommendedtoassesscerebralperfusIon
pressuresmoreaccurately.
P.811
Figure 30-26.TheskullpInheadrestusedtostabIlIzeapatIentIntheheadelevated
proneposItIon.NotethechestrollsusedtofreetheabdomenfromcompressIonand
theglutealstraptomInImIzecaudadslIppageafterheaduptIlt.(Feproducedfrom
|artInJT,Warner|A[Eds]:PosItIonIngInAnesthesIaandSurgery,JrdedItIon.
PhIladelphIa,W8Saunders,1997,p88,wIthpermIssIon.)
Air Embolus
AIrembolIzatIonIspotentIallylethal(seealsoChapterJ9).nthebloodstream,aIr
mIgratestotheheart,whereItcreatesacompressIblefoamthatdestroysthepropulsIve
effIcIencyofventrIcularcontractIonandIrrItatestheconductIonsystem.AIrcanalsomove
Intothepulmonaryvasculature,wherebubblesobstructsmallvesselsandcompromIsegas
exchange,orItcancrossthroughapatentforamenovaletotheleftsIdeoftheheartand
thesystemIccIrculatIon.
ThepotentIalforvenousaIrembolIzatIonIncreaseswIththedegreeofelevatIonofthe
operatIvesIteabovetheheart.AlthoughtheoccurrenceofaIrembolIIsarelatIvely
frequentphenomenonInheadelevatedposItIons,mostoftheembolIaresmallInvolume,
clInIcallysIlent,andrecognIzableonlybysophIstIcated0opplerdetectIontechnIques.
Nevertheless,thepotentIalfordangerousaccumulatIonsofentraInedaIrrequIres
ImmedIatedetectIonoftheembolIzatIon,acarefulsearchforItsportalofentry,and
prompttreatmentofItsclInIcaleffects.
Pneumocephalus
ntheusualcranIotomy,mostofthebraInlIessubjacenttotheIncIsIon.AftertheduraIs
IncIsed,cerebrospInalfluIdIsremovedtoImproveworkIngcondItIons,andthesurgIcal
fIeldIsopentotheaIr.0urIngclosureofthecranIotomy,mostoftheIntracranIalaIr
escapesfromthewoundandanyresIdualpneumocephalusIsoflIttleconsequence.
However,whenanIncIsIonIsmadethroughtheduraIntheposterIorfossaorcervIcalspIne
ofaseatedpatIent,thebulkofthebraInlIesabovetheIncIsIon.CerebrospInalfluIddraIns
downwardoutofthewound,andtIssueretractIoncanallowaIrtobubbleupoverthe
surfacesofthebraIntobecometrappedIntheupperreachesofthecranIum.
61
WhenbraIn
massIsdecreasedbyventrIculardraInage,steroIds,anddIuresIs,thespaceavaIlabletoa
pneumocephalusIsenlarged.0IffusIonofnItrousoxIdeIntotheaccumulatedaIr,orthe
warmIngoftrappedgas,canproduceatensIonpneumocephaluswIthsIgnsofIncreased
IntracranIalpressureanddelayedawakenIngfromanesthesIa.
Toungetal.
62
foundpostoperatIvepneumocephalusInallofagroupofseatedpatIentsand
InmostofthosewhohadbeenIntheproneortheparkbenchposItIon.ntraventrIcularaIr
waspresentInmostoftheseatedpatIentsandwasrareInthoseIntheotherposItIons.
NoneoftheIrgroupof100patIentshadneurologIcchangesattrIbutabletothetrapped
IntracranIalaIr.Standeferetal.
6J
reportedaJIncIdenceofsymptomatIc(tensIon)
pneumocephalusInseated,anesthetIzedpatIentswhoseduraswereopened.
Ocular Compression
PressurefromapaddedheadrestontheeyesofapatIentwhohasbeenplacedInahead
elevatedposItIoncandIslocateacrystallInelensorrendertheglobeIschemIc.|odern
skullpInheadclampsthatgrIpfIrmlywhenproperlyapplIedhavemadeocularcompressIon
InthesIttIngposItIonararIty.ntheheadelevatedlateraldecubItusorproneposItIon,the
threatstotheeyesarethosedescrIbedIntheprecedIngdIscussIonsofthosenonelevated
postures.
Edema of the Face, Tongue, and Neck
SeverepostoperatIvemacroglossIa,apparentlybecauseofvenousandlymphatIc
obstructIon,canbecausedbyprolonged,markedneckflexIon.
64
PostoperatIveneedfora
tracheostomyhasbeenreported.
65
TrytoavoIdplacIngthepatIent'schInfIrmlyagaInstthe
chestanduseanoralaIrwaytoprotecttheendotrachealtube.ExtremesofneckflexIon,
wIthorwIthoutheadrotatIon,havebeenwIdelyusedtogaInaccesstostructuresInthe
posterIorfossaandcervIcalspIne,buttheIrpotentIalfordamageshouldbeunderstoodand
excessIveflexIonrotatIonavoIdedIfpossIble.|ooreandassocIates
66
havesuggestedthat
theprImarymechanIsmmaybeneurologIcallydetermInedratherthanbeIngtheresultof
eIthervascularobstructIonorlocaltrauma.ThIsproblemalsohasbeendescrIbedwIththe
useoftransesophagealechocardIographyprobes.
Midcervical Tetraplegia
ThIsdevastatIngInjuryoccursafterhyperflexIonoftheneck,wIthorwIthoutrotatIonof
thehead,andIsattrIbutedtostretchIngofthespInalcordwIthresultIngcompromIseofIts
vasculatureInthemIdcervIcalarea.AnelementofspondylosIsoraspondylotIcbarmaybe
Involved.
67,68
TheresultIsparalysIsbelowthegenerallevelofthefIfthcervIcalvertebra.
AlthoughmostreportsInthelIteraturehavedescrIbedthecondItIonasoccurrIngafterthe
useofthesIttIngposItIon,mIdcervIcaltetraplegIahasalsooccurredafterprolonged,
nonforcedheadflexIonforIntracranIalsurgeryInthesupIneposItIon.
Sciatic Nerve
StretchInjurIesofthescIatIcnervecanoccurInsomeseatedpatIentsIfthehIpsare
markedlyflexedwIthoutbendIngtheknees.ProlongedcompressIonofthescIatIcnerveas
ItemergesfromthepelvIsIspossIbleInathIn,seatedpatIentIfthebuttocksarenot
suItablypadded.FootdropmaybetheresultofInjurIestoeItherthescIatIcnerveorthe
commonperonealnerveandcanbebIlateral.
Perioperative Peripheral Neuropathies
Prevention
TheAmerIcanSocIetyofAnesthesIologIstsapprovedanadvIsoryonperIpheralneuropathIes
In1999.
69
ThIsadvIsoryIncludespertInentlIteratureandasummaryoftheopInIonsof
anesthesIaprovIdersonavarIetyofposItIonIngandperIpheralneuropathyIssues.The
paucItyoflIteraturerelatedtotheseIssueslImItedtheadvIsorytorecommendatIonsbased
onopInIonsandcurrent
P.812
practIcesofabroadlyrepresentatIvegroupofanesthesIaprovIdersfromaroundtheUnIted
States.AddItIonalInputandopInIonswereobtaInedfromconsultantsfromaroundthe
world.AsummaryofthefIndIngsoftheadvIsoryIsshownInTableJ02.
Table 30-2 Summary of Perioperative Neuropathy Task Force Consensus
Preoperative assessment:WhenjudgedapproprIate,ItIshelpfultoascertaInthat
patIentscancomfortablytoleratetheantIcIpatedoperatIveposItIon.
Upper Extremity Positioning
ArmabductIonshouldbelImItedto90degreesorlessInsupInepatIents.
PatIentswhoareposItIonedpronemaycomfortablytoleratearmabductIonof90
degreesormore.
ArmsshouldbeposItIonedtodecreasepressureonthepostcondylargrooveof
thehumerus(ulnargroove).WhenarmsaretuckedatthesIde,aneutral
forearmposItIonIsrecommended.Whenarmsareabductedonarmboards,
eIthersupInatIonoraneutralforearmposItIonIsacceptable.
ProlongedpressureontheradIalnerveInthespIralgrooveofthehumerus
shouldbeavoIded.
ExtensIonoftheelbowbeyondacomfortablerangemaystretchthemedIan
nerve.
Lower Extremity Positioning
LIthotomyposItIonsthatstretchthehamstrIngmusclegroupbeyonda
comfortablerangemaystretchthescIatIcnerve.
ProlongedpressureontheperonealnerveatthefIbularheadshouldbeavoIded.
NeItherextensIonnorflexIonofthehIpIncreasestherIskoffemoralneuropathy.
Protective Padding
PaddedarmboardsmaydecreasetherIskofupperextremItyneuropathy.
TheuseofchestrollsInlaterallyposItIonedpatIentsmaydecreasetherIskof
upperextremItyneuropathIes.
PaddIngattheelbowandatthefIbularheadmaydecreasetherIskofupperand
lowerextremItyneuropathIes,respectIvely.
Equipment
ProperlyfunctIonIngautomatedbloodpressurecuffsontheupperarmsdonot
affecttherIskofupperextremItyneuropathIes.
ShoulderbracesInsteepheaddownposItIonsmayIncreasetherIskofbrachIal
plexusneuropathIes.
Postoperative Assessment:AsImplepostoperatIveassessmentofextremItynerve
functIonmayleadtoearlyrecognItIonofperIpheralneuropathIes.
Documentation:ChartIngspecIfIcposItIonIngactIonsdurIngthecareofpatIents
mayresultInImprovementsofcareby(1)helpIngpractItIonersfocusattentIonon
relevantaspectsofpatIentposItIonIngand(2)provIdIngInformatIonthat
contInuousImprovementprocessescanusetoleadtorefInementsInpatIentcare.
FeproducedfromAmerIcanSocIetyofAnesthesIologIstsTaskForceonPreventIon
ofPerIoperatIvePerIpheralNeuropathIes:PractIceadvIsoryforthepreventIonof
perIoperatIveperIpheralneuropathIes.AnesthesIology2000;92:1168,wIth
permIssIon.
Practical Considerations
EffortstopreventperIoperatIveneuropathIesarefrequentlydebated,andthereoftenIs
confusIonoverhowtomanageaneuropathyonceIthasoccurred.ngeneral,thereareno
datatosupportrecommendatIonsonanyoftheseIssues.Therefore,thefollowIngopInIons
havebeenformulatedbypersonalexperIence,guIdedbyadvIcefromneurologIstswhocare
prImarIlyforpatIentswIthperIpheralneuropathIes,andseasonedorsupportedby
speculatIonderIvedfromanecdotalcasereports.
Padding Exposed Peripheral Nerves
|anytypesofpaddIngmaterIalsareadvocatedtoprotectexposedperIpheralnerves.They
oftenconsIstofcloth(e.g.,blanketsandtowels),foamsponges(e.g.,eggcratefoam),
andgelpads.TherearenodatatosuggestthatanyofthesematerIalsIsmoreeffectIve
thananyother,orthatanyIsbetterthannopaddIngatall.Agoodruleofthumbwouldbe
toposItIonandpadexposedperIpheralnervesto(1)preventtheIrstretchbeyondnormally
toleratedlImItswhIleawake;(2)avoIdtheIrdIrectcompressIon,IfpossIble;and(J)
dIstrIbuteoveraslargeanareaaspossIbleanycompressIveforcesthatmustbeplacedon
them.
Prolonged Duration in One Position
ProlongedduratIonInoneposItIonappearstoIncreasetherIskofneuropathyandother
Integumentarydamage.Forexample,prolongedduratIonInlIthotomyposItIonsgreatly
IncreasestherIskoflowerextremItyneuropathy.
70,71
WhenpossIble,Itwouldappear
prudenttolImItasmuchaspractIcalthetImeanypatIentspendsInoneposItIon.
However,IntermIttentmovementofthelImbsorheaddurIngtheIntraoperatIveperIod
mayIncreasetheopportunItyforanumberofdIfferentproblems,IncludIngbutnotlImIted
todIslodgInganendotrachealtube,abradIngacornea,ormovInganextremItyIntoa
suboptImalposItIon.PractItIonersmust
P.81J
judgethebenefItsversusrIsksofanyIntraoperatIvechangesInapatIent'sposItIon.
Course of Action for the Patient with a Neuropathy
AlthougheachsItuatIonIsunIqueandrequIrescarefulassessment,thefollowIngguIdelInes
maysuggestabasIccourseofactIonthatwIllleadtoapproprIatecare
72
:
stheneuropathysensoryormotor:SensorylesIonsaremorefrequentlytransIentthan
motorlesIons.fthesymptomsarenumbnessortInglIngonly,ItmaybeapproprIateto
InformthepatIentthatmanyoftheseneuropathIescanbeexpectedtoresolvedurIng
thefIrst5days.
27
ThepatIentshouldbeInstructedtoavoIdposturesthatmIghtcompress
orstretchtheInvolvednerve.ArrangementsshouldbemadeforfrequentcontactwIth
thepatIent.AcalltoalertaneurologIstIsapproprIate,andIfthesymptomsstIllpersIst
onpostoperatIveday5,theneurologIstshouldbeconsulted.
ftheneuropathyhasamotorcomponent,aneurologIstshouldbeconsulted
ImmedIately.ElectromyographIcstudIesmaybeneededtoassessthelocatIonofany
acutelesIon.ThIsknowledgemaydIrectanapproprIatetreatmentplan.ThestudIesmay
alsodemonstratechronIcabnormalItIesofthenerveor,IfapplIcable,thecontralateral
nerve.
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Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJ1|onItoredAnesthesIaCare
ChapterJ1
Simon C. Hillier
Michael S. Mazurek
Key Points
1. The standards for preoperative evaluation, intraoperative monitoring,
and the continuous presence of a member of the anesthesia care
team, and so forth, are no different from those for general or
regional anesthesia.
3
2. If the level of sedation is deepened to the extent that verbal
communication is lost, most of the advantages of monitored
anesthesia care are lost and the risks of the technique approach
those of general anesthesia with an unprotected and uncontrolled
airway.
3. As a general principle, to avoid excessive levels of sedation, drugs
should be titrated in small increments or by adjustable infusions
rather than administered in larger doses according to predetermined
notions of efficacy.
4. The context-sensitive half-time describes the time required for the
plasma drug concentration to decline by 50% after terminating an
infusion of a particular duration.
5. At the present time, no one inhaled or intravenous drug can provide
all the components of monitored anesthesia care (i.e., analgesia,
anxiolysis, and hypnosis) with an acceptable margin of safety or ease
of titratability.
6. During monitored anesthesia care, the maximum benefit of opioid
supplementation, in terms of potentiation of other administered
sedatives, will accrue when the opioid is used in the analgesic dose
range. Within this dose range there is great potential for adverse
cardiorespiratory interaction.
7. The important mechanisms whereby respiratory function may be
compromised during monitored anesthesia care include the effects of
sedatives and opioids on respiratory drive, upper airway patency, and
protective airway reflexes.
8. If anesthesiologists are not willing or able to provide these services,
others, who are less well qualified, are prepared to assume that role.
0urIngmonItoredanesthesIacarethecontInuousattentIonoftheanesthesIologIstIs
dIrectedatoptImIzIngpatIentcomfortandsafety.|onItoredanesthesIacareusually
InvolvestheadmInIstratIonofdrugswIthanxIolytIc,hypnotIc,analgesIc,andamnestIc
propertIes,eItheraloneorasasupplementtoalocalorregIonaltechnIque.
Terminology
tIsImportanttodIstInguIshbetweenmonItoredanesthesIacareand
sedatIon/analgesIa.nDctober2004,theAmerIcanSocIetyofAnesthesIologIsts(ASA)
Houseof0elegatesapprovedastatemententItled0IstInguIshIng|onItoredAnesthesIa
Carefrom|oderateSedatIon/AnalgesIa.
1
Sedation/analgesiaIsthetermcurrentlyused
bytheASAIntheIrrecentlypublIshedPractice Guidelines for Sedation and Analgesia by
Non-Anesthesiologists.
2
Monitored anesthesia careImplIesthepotentIalforadeeperlevel
ofsedatIonthanthatprovIdedbysedatIon/analgesIaandIsalwaysadmInIsteredbyan
anesthesIologIstprovIder.ThestandardsforpreoperatIveevaluatIon,IntraoperatIve
monItorIng,andthecontInuouspresenceofamemberoftheanesthesIacareteam,andso
forth,arenodIfferentfromthoseforgeneralorregIonalanesthesIa.
J
P.816
Conceptually,monItoredanesthesIacareIsattractIvebecauseItshouldInvokeless
physIologIcdIsturbanceandallowamorerapIdrecoverythangeneralanesthesIa.tIs
InstructIvetorevIewtheASAposItIonstatementthatdefInesmonItoredanesthesIacareas
follows
J
:
Monitored anesthesia care is a specific anesthesia service for a diagnostic or therapeutic
procedure. Indications for monitored anesthesia care include the nature of the
procedure, the patient's clinical condition, and/or the potential need to convert to a
general or regional anesthetic.
Monitored anesthesia care includes all aspects of anesthesia carea preprocedure visit,
intraprocedure care, and postprocedure anesthesia management. During monitored
anesthesia care, the anesthesiologist provides or medically directs a number of specific
services, including but not limited to:
Diagnosis and treatment of clinical problems that occur during the procedure
Support of vital functions
Administration of sedatives, analgesics, hypnotics, anesthetic agents, or other
medications as necessary for patient safety
Psychological support and physical comfort
Provision of other medical services as needed to complete the procedure safely.
Monitored anesthesia care may include varying levels of sedation, analgesia, and
anxiolysis as necessary. The provider of monitored anesthesia care must be prepared and
qualified to convert to general anesthesia when necessary. If the patient loses
consciousness and the ability to respond purposefully, the anesthesia care is a general
anesthetic, irrespective of whether airway instrumentation is required.
Monitored anesthesia care is a physician service provided to an individual patient. It
should be subject to the same level of payment as general or regional anesthesia.
Accordingly, the ASA Relative Value Guide provides for the use of proper base procedural
units, time units, and modifier units as the basis for determining reimbursement.
TheASAalsostatesthatmonItoredanesthesIacareshouldberequestedbytheattendIng
physIcIanandbemadeknowntothepatIent,InaccordancewIthacceptedproceduresof
theInstItutIon.naddItIon,theASAstatesthattheservIcemustIncludethefollowIng:
1. PerformanceofapreanesthetIcexamInatIonandevaluatIon.
2. PrescrIptIonofanesthetIccare.
J. PersonalpartIcIpatIonIn,ormedIcaldIrectIonof,theentIreplanofcare.
4. ContInuousphysIcalpresenceoftheanesthesIologIstor,InthecaseofmedIcaldIrectIon,
oftheresIdentornurseanesthetIstbeIngmedIcallydIrected.
5. ProxImatepresence,orInthecaseofmedIcaldIrectIon,avaIlabIlItyofthe
anesthesIologIstfordIagnosIsandtreatmentofemergencIes.
Furthermore,theASAstatesthatallInstItutIonalregulatIonspertaInIngtoanesthesIa
servIcesshallbeobserved,andalltheusualservIcesperformedbytheanesthesIologIst
shallbefurnIshed,IncludIngbutnotlImItedto:
1. UsualnonInvasIvecardIocIrculatoryandrespIratorymonItorIng.
2. DxygenadmInIstratIon,whenIndIcated.
J. AdmInIstratIonofsedatIves,tranquIlIzers,antIemetIcs,narcotIcs,otheranalgesIcs,beta
blockers,vasopressors,bronchodIlators,antIhypertensIves,orotherpharmacologIc
therapyasmayberequIredInthejudgmentoftheanesthesIologIst.
Preoperative Assessment
ThepreoperatIveevaluatIonIsanessentIalprerequIsItetomonItoredanesthesIacareand
shouldbeascomprehensIveasthatperformedprIortoanygeneralorregIonalanesthetIc
(seeChapter2J).However,InaddItIontotheusualevaluatIonforthepatIentwhoIs
plannedtoundergogeneralanesthesIa,thereareaddItIonalconsIderatIonsunIqueto
monItoredanesthesIacarethatmayultImatelydetermInethesuccessorfaIlureofthe
procedure.tIsImportanttoevaluatethepatIent'sabIlItytoremaInmotIonlessand,If
necessary,actIvelycooperatethroughouttheprocedure.Thus,ItIsImportanttoevaluate
thepatIent'spsychologIcalpreparatIonfortheplannedprocedure.tIsalsoImportantto
elIcItthepresenceofcoexIstIngsensorIneuralorcognItIvedefIcIts.Thesefactorsorthe
InabIlItytocommunIcatewIththepatIentmayoccasIonallymakegeneralanesthesIaa
moreapproprIatealternatIve.7erbalcommunIcatIonbetweenphysIcIanandpatIentIs
veryImportantforthreereasons:(1)asamonItorofthelevelofsedatIonand
cardIorespIratoryfunctIon,(2)asameansofexplanatIonandreassuranceforthepatIent,
and(J)asamechanIsmofcommunIcatIonwhenthepatIentIsrequIredtoactIvely
cooperate.AlthoughcardIorespIratorydIseaseIsoftencItedasanIndIcatIontoperforma
procedureusIngmonItoredanesthesIacareratherthangeneralanesthesIa,thereare
occasIonswhencardIorespIratorydIseasemayreducetheutIlItyofmonItoredanesthesIa
care.Forexample,thepresenceofapersIstentcoughmaymakeItverydIffIcultforthe
patIenttoremaInImmobIle,whIchcanbepartIcularlydangerousdurIngophthalmologIcor
awakeneurosurgIcalprocedures.AttemptstoattenuatecoughIngwIthsedatIontechnIques
arelIkelytobeunsuccessfulandpotentIallyharmfulbecauseasIgnIfIcantlevelof
anesthesIaIsrequIredtoabolIshthecoughreflex.SImIlarly,somepatIentswIthsIgnIfIcant
cardIovasculardIseasemayexperIenceorthopneaandbeunabletolIeflatforanextended
perIod.
Techniques of Monitored Anesthesia Care
AvarIetyofmedIcatIonsarecommonlyadmInIstereddurIngmonItoredanesthesIacare
wIththedesIredendpoIntsbeIngprovIdIngpatIentcomfort,maIntaInIngcardIorespIratory
stabIlIty,ImprovIngoperatIngcondItIons,andpreventIngrecallofunpleasant
perIoperatIveevents.tIshelpfultodelIneateandIndIvIdualIzethegoalsforeachpatIent
InordertoformulateanapproprIateregImen,whIchfrequentlyInvolvestheadmInIstratIon
ofeItherIndIvIdualorcombInatIonsofanalgesIc,amnestIc,andhypnotIcdrugs.There
shouldbeamInImalIncIdenceofsIdeeffects,suchascardIorespIratorydepressIon,nausea
andvomItIng,delayedemergence,anddysphorIa,andthereshouldbearapIdand
completerecovery.deally,thepatIentshouldbeabletocommunIcatedurIngthe
procedure.ClInIcalexperIencesuggeststhatalevelofsedatIonthatallowsverbal
communIcatIonIsoptImalforthepatIent'scomfortandsafety.fthelevelofsedatIonIs
deepenedtotheextentthatverbalcommunIcatIonIslost,mostoftheadvantagesof
monItoredanesthesIacarearelostandtherIsksofthetechnIqueapproachthoseof
generalanesthesIawIthanunprotectedanduncontrolledaIrway.However,because
monItoredanesthesIacareIsprovIdedbyanesthesIologIsts,therangeofsedatIonmaybe
expandedtoIncludesIgnIfIcantlydeepersedatIontechnIquesthanthoseprovIdedby
nonanesthesIologIstsdurIngsedatIon/analgesIa.
ThepreanesthetIcevaluatIonandplanshouldstrIvetoIdentIfyspecIfIccausesofand
provIdespecIfIctherapyforpaIn,anxIety,andagItatIon.PaInmaybetreatedbylocalor
P.817
regIonalanalgesIa,systemIcanalgesIcs,orremovalofthepaInfulstImulus.AnxIetymaybe
reducedbytheuseofananxIolytIcsuchasabenzodIazepIneandreassurancebythe
anesthesIologIst.PatIentagItatIonmaybearesultofpaInoranxIety,butItIsalsovItally
ImportanttoelImInatelIfethreatenIngfactorssuchashypoxIa,hypercarbIa,ImpendIng
localanesthetIctoxIcIty,andcerebralhypoperfusIon.Dther,lessomInous,butoften
overlooked,causesofdIscomfortandagItatIonIncludeadIstendedbladder,hypothermIa,
hyperthermIa,prurItus,nausea,posItIonaldIscomfort,uncomfortableoxygenmasksand
nasalcannulae,Intravenous(7)cannulatIonsIteInfIltratIon,amemberofthesurgIcal
teamleanIngonthepatIent,andprolongedpneumatIctournIquetInflatIon.
Pharmacologic Basis of Monitored Anesthesia Care Techniques
Optimizing Drug Administration
TheabIlItytopredIcttheeffectsofthedrugsInourarmamentarIumdemandsan
understandIngoftheIrpharmacokInetIcandpharmacodynamIcpropertIes.ThIs
understandIngIsafundamentalprerequIsIteforthedesIgnofaneffectIvesedatIonregImen
andgreatlyIncreasestheprobabIlItyofproducIngthedesIredtherapeutIceffect.Context
sensItIvehalftIme,effectsIteequIlIbratIontIme,andanesthetIc/sedatIvedrug
InteractIonsarefundamentalconceptsthatarepartIcularlyusefulInthecontextof
monItoredanesthesIacareandwIllbedIscussedInsomedetaIl.
TheultImateobjectIveofanydosIngregImenIstodelIveratherapeutIcconcentratIonof
drugtoItssIteofactIon,whIchIsdetermInedbytheunIquepharmacokInetIcpropertIesof
thatdrugInthatpartIcularpatIent.ThetherapeutIcresponsetoapartIculardrug
concentratIonIsdescrIbedbythepharmacodynamIcsofthatpartIcularpatIentdrug
combInatIon.ThereIsalargedegreeofpharmacokInetIcandpharmacodynamIcvarIabIlIty,
producIngasIgnIfIcantvarIabIlItyInthedoseresponserelatIonshIpInclInIcalpractIce.
ExcessIvesedatIonmayresultIncardIacorrespIratorydepressIon.nadequatesedatIon
mayresultInpatIentdIscomfortandpotentIalmorbIdItyfromlackofcooperatIon.Asa
generalprIncIple,toavoIdexcessIvelevelsofsedatIon,drugsshouldbetItratedInsmall
IncrementsorbyadjustableInfusIonsratherthanadmInIsteredInlargerdosesaccordIngto
predetermInednotIonsofeffIcacy.nanIdealdosIngregImen,aneffectIveconcentratIon
ofdrugIsachIevedandthenadjustedaccordIngtothemagnItudeofthenoxIousstImulus.
fthenoxIousstImulusIsIncreasedordecreased,theconcentratIonIsIncreasedor
decreasedaccordIngly.8ytheendoftheprocedure,thedrugconcentratIonshouldhave
decreasedtoalevelcompatIblewIthrapIdrecovery.ThIsapproachrequIrestheuseof
drugsthatareeasIlytItratable,suchaspropofol.WhenusIngdrugssuchaspropofol,
adjustableratecontInuousInfusIonsarethemostlogIcalmethodofmaIntaInIngadesIred
therapeutIcconcentratIon.WhenthetradItIonalmethodofIntermIttentbolus
admInIstratIonIsused,sIgnIfIcantfluctuatIonsIndrugconcentratIonoccur.Underthese
cIrcumstances,theplasmaconcentratIonsareeItheraboveorbelowthedesIred
therapeutIcrangeforasIgnIfIcantproportIonoftheprocedure(FIg.J11).ContInuous
InfusIonsaresuperIortoIntermIttentbolusdosIngbecausetheyproducelessfluctuatIonIn
drugconcentratIon,thusreducIngthenumberofepIsodesofInadequateorexcessIve
sedatIon.AdmInIstratIonofdrugsbycontInuousInfusIonratherthanbyIntermIttentdosIng
alsoreducesthetotalamountofdrugadmInIsteredandfacIlItatesamoreprompt
recovery.
4
Figure 31-1.ThechangesIndrugconcentratIondurIngdIfferIngadmInIstratIon
technIques.Thedark linerepresentsacontInuousInfusIonofadrug.nthIssItuatIon
thedrugIsmaIntaInedwIthInthetherapeutIcrangeformostoftheprocedure.The
lighter linerepresentsthedrugconcentratIonresultIngfromIntermIttentbolus
admInIstratIon.ThedrugconcentratIonIssIgnIfIcantlyaboveorbelowthedesIred
therapeutIclevelformostoftheprocedure.
Distribution, Elimination, Accumulation, and Duration of
Action
FollowIngtheadmInIstratIonof7anesthetIcdrugs,theImmedIatedIstrIbutIonphase
causesabrIskdecreaseInplasmalevelsasthedrugIstransportedtotherapIdly
equIlIbratIngvesselrIchgroupoftIssues.ThereIsasImultaneouslyoccurrIngdIstrIbutIonof
drugtothelesswellperfusedtIssuessuchasmuscleandskIn.DvertIme,thedrugIsalso
dIstrIbutedtothepoorlyperfusedtIssuessuchasboneandfat.Althoughthelatter
compartmentsarepoorlyperfused,theymayaccumulatesIgnIfIcantamountsoflIpophIlIc
drugsdurIngprolongedadmInIstratIon.ThIsperIpheraldepotmaycontrIbutetoadelayed
recoverywhenthedrugIseventuallyreleasedbackIntothecentralcompartmentafterIts
admInIstratIonIsdIscontInued.FedIstrIbutIvefactorsareImportantdetermInantsofdrug
effectandInfluencetheplasmaconcentratIonofadrugInatImedependentfashIon.
The Elimination Half-Life
UntIlrecently,theelImInatIonhalftImewasthepredomInantpharmacokInetIcparameter
usedasthepredIctorofananesthetIcdrug'sduratIonofactIon.neverydayclInIcal
practIce,however,thIsparameterhasnotgreatlyenhancedourabIlItytopredIct
anesthetIcdrugdIsposItIon.DnlyInsInglecompartmentmodelsdoestheelImInatIonhalf
tImeactuallyrepresentthetImerequIredforadrugtoreachhalfofItsInItIal
concentratIonafteradmInIstratIon.nasInglecompartmentmodel,elImInatIonIstheonly
processthatcanalterdrugconcentratIon.ntercompartmentaldIstrIbutIoncannotoccur
becausetherearenoothercompartmentsforthedrugtobedIstrIbutedtoandfrom.|ost
drugsIntheanesthesIologIst'sarmamentarIumarelIpophIlIcandarethereforemoresuIted
tomultIcompartmentalmodelIngthansInglecompartmentmodelIng.SImIlarly,other
pharmacokInetIcparameters,suchasdIstrIbutIonhalftIme,dIstrIbutIonvolume,
Intercompartmentalrateconstants,andsoforth,donotprovIdeuswIthapractIcalmeans
ofpredIctIngdrugdIsposItIon.nmultIcompartmentalmodels,themetabolIsmand
excretIonofsome7anesthetIcdrugsmayhaveonlyamInorcontrIbutIontochangesIn
plasmaconcentratIon
P.818
whencomparedwIththeeffectsofIntercompartmentaldIstrIbutIon.
Context-Sensitive Half-Time
TheconceptofcontextsensItIvehalftImewasdevelopedtoImprovethedescrIptIonand
understandIngofanesthetIcdrugdIsposItIon.
5
ThIsconcepthasgreatlyImprovedour
understandIngofanesthetIcdrugdIsposItIonandIsclInIcallyapplIcable.Theeffectof
dIstrIbutIononplasmadrugconcentratIonvarIesInmagnItudeanddIrectIonovertImeand
dependsonthedrugconcentratIongradIentsthatexIstbetweenthevarIouscompartments.
Forexample,durIngtheearlypartofanInfusIonofalIpophIlIcdrug,dIstrIbutIvefactors
wIlltendtodecreaseplasmaconcentratIonsasthedrugIstransportedtotheunsaturated
perIpheraltIssues.Later,aftertheInfusIonIsdIscontInued,drugwIllreturnfromthe
perIpheraltIssuesandreenterthecentralcIrculatIon.TherelatIveeffectonplasma
concentratIonsofdIstrIbutIveprocessesversuselImInatIonvarIesovertImeandfromdrug
todrug.ThecontextsensItIvehalftImedescrIbesthetImerequIredfortheplasmadrug
concentratIontodeclIneby50aftertermInatInganInfusIonofapartIcularduratIon.ThIs
parameterIscalculatedbyusIngcomputersImulatIonofmultIcompartmentalmodelsof
drugdIsposItIon(FIg.J12).ThecontextsensItIvehalftImereflectsthecombInedeffectsof
dIstrIbutIonandmetabolIsmondrugdIsposItIon.ThereareseveralInterestIngaspectsof
thesedata.FIrst,thedataconfIrmtheclInIcalImpressIonthatastheInfusIonduratIon
Increases,thecontextsensItIvehalftImeofallthedrugsIncreases;thIsphenomenonIsnot
descrIbedInanywaybytheelImInatIonhalflIfe.TheIncreaseIncontextsensItIvehalf
tImeIspartIcularlymarkedwIthfentanylandthIopental.nthecaseoffentanyl,drugthat
IsIrreversIblyelImInatedfromtheplasmabyhepatIcclearanceIsImmedIatelyreplacedby
drugreturnIngfromtheperIpheralcompartments.Thus,althoughfentanylhasashorter
elImInatIonhalflIfethanthatofsufentanIl(462vs.577mInutes),ItscontextsensItIvehalf
tImeIsmuchgreaterthanthatofsufentanIlafteranInfusIonoflongerthan2hours.The
storageandlaterreleaseoffentanylfromperIpheralbIndIngsItesdelaysthedeclIneIn
plasmaconcentratIonthatwouldotherwIseoccur.ThecontextsensItIvehalftImesofall
thedrugsbearnoconstantrelatIonshIptotheIrelImInatIonhalftImes.Comparealsothe
contextsensItIvehalftImesofpropofolandthIopental(FIg.J12).Althoughthecontext
sensItIvehalftImesofpropofolandthIopentalarecomparablefollowIngabrIefInfusIon,
thecontextsensItIvehalftImeofthIopentalIncreasesrapIdlyfollowIngallbuttheshortest
InfusIons.ThIsfIndIngconfIrmstheclInIcalImpressIonthatthIopentalIsnotanIdealdrug
forcontInuousInfusIondurIngambulatoryprocedures.ThecontextsensItIvehalftImeof
propofolIsprolongedtoamInImalextentastheInfusIonduratIonIncreases.Afteran
InfusIonofpropofol,thedrugthatreturnstotheplasmafromtheperIpheralcompartments
IsrapIdlyclearedbymetabolIcprocessesandIsthereforenotavaIlabletoretardthedecay
Inplasmalevels.ThIsdIfferencebetweenthIopentalandpropofolIsattrIbutableto(1)the
hIghmetabolIcclearanceofpropofolcomparedwIththIopental,and(2)therelatIvelyslow
rateatwhIchpropofolreturnstotheplasmafromperIpheralcompartments.
Figure 31-2.ContextsensItIvehalftImesasafunctIonofInfusIonduratIon.These
dataweregeneratedfromthecomputermodelofHughesetal.
5
tcanbeseenthat
thecontextsensItIvehalftImeofpropofoldemonstratesamInImalIncreaseasthe
duratIonoftheInfusIonIncreases.AlsonotethatforInfusIonsofshortduratIon,
sufentanIlhasashorterhalftImethanalfentanIl.(FeproducedfromHughes|A,Class
PSA,JacobsJF:ContextsensItIvehalftImeInmultIcompartmentpharmacokInetIc
modelsforIntravenousanesthetIcdrugs.AnesthesIology1992;76:JJ4,wIth
permIssIon.)
AlfentanIlIstheopIoIdthathas,untIlrecently,beenmostfrequentlystudIed,descrIbed,
andpromotedInthecontextofambulatorytechnIques.AlfentanIlhasaveryshort
elImInatIonhalftIme,onefIfththatofsufentanIl(111vs.577mInutes).However,despIte
thelongerelImInatIonhalftImeofsufentanIl,ItscontextsensItIvehalftImeIsactually
lessthanthatofalfentanIlforInfusIonsupto8hoursInduratIon.ThIsphenomenonIs
explaInedInpartbythehugedIstrIbutIonvolumeofsufentanIl.AftertermInatIonofa
sufentanIlInfusIon,thedecayInplasmadrugconcentratIonsIsacceleratednotonlyby
elImInatIonbutalsobythecontInuedredIstrIbutIonofsufentanIlIntoperIpheral
compartments.Dntheotherhand,thesmalldIstrIbutIonvolumeofalfentanIlequIlIbrates
rapIdly;therefore,perIpheraldIstrIbutIonofdrugawayfromtheplasmaIsnotasIgnIfIcant
contrIbutortothedecayInplasmaconcentratIonafteranInfusIon.ThedataderIvedfrom
computersImulatIonbyHughesetal.
5
showthattheplasmadecayofalfentanIlIsslower
thanthatofsufentanIlfollowIngInfusIonsofsImIlarduratIontothoseuseddurIngconscIous
sedatIon.Thus,despIteItsshortelImInatIonhalftIme,alfentanIlmaynotnecessarIlybe
superIortosufentanIlforambulatorysedatIontechnIques.
How Does the Context-Sensitive Half-Time Relate to the Time
to Recovery?
AlthoughthecontextsensItIvehalftImerepresentsasIgnIfIcantadvanceInourabIlItyto
descrIbedrugdIsposItIon,thIsparameterdoesnotdIrectlydescrIbehowlongItwIlltake
thepatIenttorecoverfrom|AC.ThecontextsensItIvehalftImemerelydescrIbeshow
longItwIlltakefortheplasmaconcentratIonofthedrugtodecreaseby50.ThetImeto
recoverydependsonotheraddItIonalfactors.ThedIfferencebetweentheplasma
concentratIonattheendoftheInfusIonandtheplasmaconcentratIonbelowwhIch
awakenIngcanbeexpectedIsanobvIousfactorIndetermInIngtImetorecovery.For
example,IfthedrugconcentratIonIsmaIntaInedataleveljustabovethatrequIredfor
awakenIng,thetImetorecoverywIllbemorerapIdthanafteranInfusIondurIngwhIchthe
drugconcentratIonIsmuchgreaterthanthatrequIredforawakenIng(FIg.J1J).
Furthermore,althoughcontextsensItIvehalftImeIsareflectIonofplasmadrugdecay,
awakenIngfromanesthesIaIsactuallyafunctIonofeffectsIte(I.e.,braIn)concentratIon
decay.ChangesIneffectsIteconcentratIondemonstrateavarIabletImelagbehInd
changesInplasmadrugconcentratIon.EffectsIteequIlIbratIonIsaconceptthatIs
partIcularlyrelevantto7sedatIon.WhenadrugIsadmInIstered7bybolusorInfused
rapIdly,thereIsadelaybeforetheonsetofclInIcaleffect.ThIsdelayoccursbecausethe
plasmaIsnot
P.819
usuallythesIteofactIonbutIsmerelytheroutebywhIchthedrugreachesItseffectsIte.
fsomeparameterofdrugeffectcanbemeasured(e.g.,powerspectrum
electroencephalographIc[EEC]analysIsInthecaseofopIoIds),thehalftImeof
equIlIbratIonbetweendrugconcentratIonInthebloodandthedrugeffectcanthenbe
determIned.
6
ThIsparameterIsabbrevIatedt
1/2
k
e0
.0rugswIthashortt
1/2
k
e0
wIll
equIlIbraterapIdlywIththebraInandhaveashorterdelayInonsetthandrugsthathavea
longert
1/2
k
e0
.ThIopental,propofol,andalfentanIlhaveshortt
1/2
k
e0
valuescomparedwIth
mIdazolam,sufentanIl,andfentanyl.
Figure 31-3.ThecontextsensItIvehalftImeIsnotthesoledetermInantofthetImeIt
takesforthepatIenttoawaken.ThIsparametermerelyreflectsthetImetakenforthe
plasmaconcentratIonofadrugtodecreaseby50.ThetImetoawakenIngIs
determInedInaddItIonbythedIfferenceInconcentratIonattheendoftheprocedure
andtheconcentratIonbelowwhIchawakenIngwIlloccur.
Thet
1/2
k
e0
allowspredIctIonstobemadeofthetImecourseofequIlIbratIonofthedrug
betweenthebloodandthebraIn.AdIstIncttImelagbetweenthepeakserumfentanyl
concentratIonandthepeakEECslowIngcanbeseen.ncontrast,followIngalfentanIl
admInIstratIon,theEECchangescloselyparallelserumconcentratIons.Thet
1/2
k
e0
for
fentanylIs6.4mInutescomparedwIthat
1/2
k
e0
of1.1mInutesforalfentanIl.fanopIoIdIs
requIredtoblunttheresponsetoasInglebrIefstImulus,alfentanIlmIghtrepresenta
logIcalchoIceoverfentanyl.Thet
1/2
k
e0
IsanImportantdetermInantofbolusspacIngwhen
tItratIngdrugstoclInIcaleffect.nthecaseofdrugslIkemIdazolam,whIchhavea
relatIvelylongequIlIbratIontIme(mIdazolamt
1/2
k
e0
=0.97to5.6mInutes),bolusesofdrug
shouldbespacedfarenoughaparttoallowthefullpeakeffecttobeclInIcallyapprecIated
beforefurtherdrugadmInIstratIonInordertoavoIdInadvertentoverdosIng.
7,8
For
example,evenIftheshortestquotedequIlIbratIonhalftImeformIdazolam(0.9mInute)Is
used,ItwIlltake2.7mInutesforeffectsIteconcentratIonstobe87.5equIlIbrated.Dther
factorsarealsoImportantdetermInantsofbolussIzeandspacIng.Forexample,alow
cardIacoutputwIllmarkedlydelaydrugarrIvalatthesIteofactIon.fsuffIcIenttImeIs
notgIvenforthedrugtotakeeffectbeforegIvIngaddItIonaldrugIncrements,sIgnIfIcant
cardIorespIratorycompromIsemayoccur.Furthermore,theeffectsofInItIaldosesofmost
drugsInanesthetIcpractIcearetermInatedbyredIstrIbutIon,whIchdependsonbloodflow
toredIstrIbutIonsItes.fthereIsreducedbloodflowtoredIstrIbutIonsItesbecauseofpre
exIstIngandIatrogenIcdecreasesIncardIacoutput,thedangerousadverseeffectsofthese
drugsarelIkelytobebothdelayedandmarkedlyprolonged.AnexampleofthIsscenarIoIs
thepatIentwIthahemodynamIccompromIsecausedbyatachydysrhythmIawhorequIres
sedatIonforcardIoversIon.Careful,wellspaced,smallbolusesofdrugshouldbegIvento
InducetheapproprIatelevelofsedatIon,bearIngInmIndthatItmaytakeseveralmInutes
forthefulleffectofasmallbolusdosetobecomeapparent.
Drug Interactions in Monitored Anesthesia Care
AtthepresenttIme,nooneInhaledor7drugcanprovIdeallthecomponentsof
monItoredanesthesIacare(I.e.,analgesIa,anxIolysIs,andhypnosIs)wIthanacceptable
margInofsafetyoreaseoftItratabIlIty.Therefore,patIentcomfortIsusuallymaIntaIned
wIthacombInatIonofdrugs.8yactIngsynergIstIcally,combInatIonsofdrugsenable
reductIonsInthedoserequIrementsofIndIvIdualdrugs.Forexample,durInggeneral
anesthesIa,thecombInatIonofpropofolandfentanylbyInfusIonhasbeenshownto
produceamorerapIdrecoveryandbetterstressresponseabolItIonthantheuseof
propofolalone.
9
However,synergIstIcInteractIonmayalsoextendtotheundesIrable
InteractIonsofthedrugssuchascardIorespIratorydepressIon.
0rugInteractIonsmayhavebothapharmacodynamIcandapharmacokInetIcbasIsandmay
varydependIngonthecombInatIonofdrugsbeIngcoadmInIstered,thedoserangeover
whIchthesedrugsareadmInIstered,andthespecIfIcclInIcaleffectthatIsmeasured.For
example,becausefentanylIsprImarIlyananalgesIcratherthanahypnotIc,Itreduces
propofolrequIrementsforsuppressIonofresponsetoskInIncIsIontoamuchgreaterdegree
thanItreducespropofolrequIrementsforInductIonofanesthesIa.
10
Dntheotherhand,
becausemIdazolamhassIgnIfIcanthypnotIcpropertIes,ItdIsplayssIgnIfIcantsynergIsm
wIthpropofolorthIopentalwhenusedtoInducehypnosIs.
11,12
TheplasmaconcentratIonofadrugatsteadystatethatIsrequIredtoabolIshpurposeful
movementatskInIncIsIonIn50ofpatIents(Cp
ss
50)IsameasureofpotencythatIs
analogoustothefamIlIarparameterofmInImumalveolarconcentratIon(|AC)ofthe
volatIleInhaledanesthetIcs.ntravenousanesthetIcInteractIonsmaybeevaluatedbytheIr
effectontheCp
ss
50InamanneranalogoustotheexpressIonoftheeffectsofopIoIdson
volatIleanesthetIcrequIrementsIntermsof|ACreductIon.Forexample,durInggeneral
anesthesIa,opIoIdrequIrementstosuppresstheresponsestonoxIousstImulIaretenfold
hIgherwhenusedasthesoleagentcomparedwIthwhentheyareusedInconjunctIonwIth
anItrousoxIde/potentInhaledvaportechnIque.ThIsInteractIonpersIstsatthelIghter
levelsofanesthesIaencountereddurIng|AC.Therefore,InanambulatoryconscIous
sedatIonsettIng,ItIslIkelythatarapIdrecoverywouldbefacIlItatedbyusIngopIoIdsIn
combInatIonwIthotheragents(e.g.,propofol/mIdazolam)ratherthanasthesoledrug.
0rugInteractIonsaredosedependent.Forexample,whenfentanylIscombInedwIth
Isoflurane,thegreatestreductIonInIsoflurane|ACoccurswIthIntheanalgesIc
concentratIonrangeoffentanyl(I.e.,1to2ng/mL).AtafentanylconcentratIonof1.7
ng/mL,the|ACofIsofluraneIsreducedby50.
1J
DncethefentanylconcentratIonIs
IncreasedbeyondJng/mL,thereappearstobemInImalfurtherreductIonwIthamaxImum
|ACreductIonof80.LIkewIse,the|ACofdesfluraneIsreducedbyapproxImately5025
mInutesafteraJg/kg7bolusoffentanyl.
14
However,whenthefentanylbolusIs
Increasedto6g/kg,thereIsnosIgnIfIcantfurtherdecreaseInthe|ACofdesflurane.The
InteractIonsbetweenpropofolandopIoIdsareImportantbecausetheseagentsare
frequentlyuseddurIng|AC.WhenanalgesIcconcentratIonsoffentanyl(0.6ng/mL)are
usedIncombInatIonwIthpropofolforanesthesIa,theCp
ss
50ofpropofolIsreducedby50
comparedwIthwhenpropofolIsusedasthesoleagent.
12
However,whenthedoseof
fentanylIsIncreased,thereIsno
P.820
sIgnIfIcantfurtherreductIonoftheCp
ss
50forpropofolbeyondafentanylconcentratIonofJ
ng/mL.
AlthoughthedatapresentedherepertaIntopatIentsundergeneralanesthesIa,these
fIndIngshaveImportantImplIcatIonsformonItoredanesthesIacare.ThesestudIes
demonstratethatthepotentIatIngeffectsofopIoIdsoncoadmInIsteredsedatIvesare
pronouncedwIthInthedoserangecommonlyuseddurIng|AC.Furthermore,thedata
suggestthatthedoseresponsecurveIslIkelytobesteepwIthInthIsdoserange,thus
supportIngtheclInIcalImpressIonthatsIgnIfIcantIncreasesIndepthofsedatIoncanoccur
wIthonlymodestIncrementsInopIoIdorhypnotIc/sedatIvedosage.ThefollowIngclInIcal
recommendatIonscanbemade:0urIng|AC,themaxImumbenefItofopIoId
supplementatIon,IntermsofpotentIatIonofotheradmInIsteredsedatIves,wIllaccrue
whentheopIoIdIsusedIntheanalgesIcdoserange.WIthInthIsdoserangethereIsgreat
potentIalforadversecardIorespIratoryInteractIon.
DpIoIdandbenzodIazepInecombInatIonsarefrequentlyusedtoachIevethecomponentsof
hypnosIs,amnesIa,andanalgesIa.ThIsdrugcombInatIondIsplaysmarkedsynergIsmIn
producInghypnosIs.ApproxImately25ofthemedIaneffectIvedoseforeachIndIvIdual
drugIsrequIredIncombInatIontoInducehypnosIsIn50ofpatIents.
15
fthecombInatIon
weresImplyaddItIve,hypnosIswouldbeInducedInonlyapproxImately25ofpatIents.
EvensubanalgesIcdosesofalfentanIl(Jg/kg)produceaprofoundreductIonInmIdazolam
requIrementsforhypnosIs.
16
ThIssynergIsmalsoextendstotheunwantedeffectsofthese
drugs,producIngthelIfethreatenIngcomplIcatIonsofrespIratoryandcardIacdepressIon.
17
SeveralfatalItIeshavebeenreportedaftertheuseofmIdazolam,themajorItyofthese
beIngrelatedtoadverserespIratoryevents.nmanyofthesecases,mIdazolamwasusedIn
combInatIonwIthanopIoId.TheeffectsofmIdazolamandfentanylonrespIratoryfunctIon
InhealthyvolunteershavebeenexamInedby8aIleyetal.
18
WhereasmIdazolamproduced
nosIgnIfIcantrespIratoryeffectsalone,andfentanylaloneproducedhypoxemIa
(oxyhemoglobInsaturatIon95)Inhalfofthesubjects,thecombInatIonofmIdazolam0.05
g/kgandfentanyl2.0g/kgresultedInhypoxemIaIn11of12subjectsandapnea(no
spontaneousrespIratoryeffortfor15seconds)In6of12subjects.ThecombInatIonof
mIdazolamandfentanylplacespatIentsathIghrIskfordevelopInghypoxemIaandapnea.
TherespIratorydepressanteffectsofthIsdrugcombInatIonarelIkelytobeevenmore
sIgnIfIcantInthepatIentwIthcoexIstIngrespIratoryorcentralnervoussystemdIseaseor
attheextremesofage.nclInIcalpractIce,theclInIcaladvantagesofthesynergybetween
opIoIdsandbenzodIazepInesforthemaIntenanceofpatIentcomfortshouldbecarefully
weIghedagaInstthedIsadvantagesofthepotentIallyadverseeffectofthIsdrug
combInatIononthecardIovascularandrespIratorysystems.
Specific Drugs Used for Monitored Anesthesia Care
Propofol
PropofolhasmanyoftheIdealpropertIesofasedatIvehypnotIcforuseIn|AC.ts
pharmacokInetIcprofIle;thatIs,acontextsensItIvehalftImethatremaInsshorteven
afterInfusIonsofprolongedduratIonandashorteffectsIteequIlIbratIontImemakesItan
easIlytItratabledrugwIthanexcellentrecoveryprofIle.ThequalItyofrecoveryandthe
lowIncIdenceofnauseaandvomItIngmakepropofolpartIcularlywellsuItedtoambulatory
monItoredanesthesIacareprocedures.AsIgnIfIcantbodyofexperIencewIththeuseof
propofolformonItoredanesthesIacarehasemerged.PropofolhassIgnIfIcantadvantages
comparedwIthbenzodIazepIneswhenusedasthehypnotIccomponentofamonItored
anesthesIacaretechnIque.AlthoughmIdazolamhasarelatIvelyshortelImInatIonhalf
tIme,ItscontextsensItIvehalftImeIsapproxImatelytwIcethatofpropofol.Whereas
propofolIsnotedfortherapIdreturntoclearheadedness,mIdazolamIsoftenassocIated
wIthprolongedpostoperatIvesedatIonandpsychomotorImpaIrment,partIcularlyInthe
elderly.PropofolIntypIcal|ACdoses(25to75g/kg/mIn)hasmInImalanalgesIc
propertIes.However,theunIqueadvantagesofpropofolcanbeexploItedtothemaxImum
whenpropofolIsusedtoprovIdesedatIonwhentheanalgesIccomponentIsprovIdedbya
localorregIonalanalgesIctechnIque.Theuseofpropofol(50to70g/kg/mIn)toprovIde
sedatIon(defInedassleepwIthpreservatIonoftheeyelashreflexandpurposefulreactIon
toverbalormIldphysIcalstImulatIon)asanadjuncttospInalanesthesIaforlowerlImb
surgeryhasbeenexamIned.
19
AftertermInatIonofInfusIonsofapproxImately100mInutes,
patIentsregaInedconscIousnessInapproxImately4mInutes.Theauthorsalsonotedthe
easewIthwhIchgeneralanesthesIacouldbeInducedIfnecessarybyIncreasIngthe
propofolInfusIon.Thesamegroupalsocomparedpropofol(60.5g/kg/mIn)wIth
mIdazolam(4.Jg/kg/mIn)asanadjuncttospInalanesthesIa.Thepropofolgrouphad
fasterImmedIaterecoverythanthemIdazolamgroup(2.Jvs.9.2mInutestospontaneous
eyeopenIng).Furthermore,psychomotorfunctIonwascomparablewIthbaselInevalues
followIngpropofolsedatIonbutdIdnotreturntobaselIneuntIl2hoursaftermIdazolam
admInIstratIon.SmIthetal.
20
alsocomparedpropofolandmIdazolamsedatIonforlocal
andregIonalanesthesIa.TheseInvestIgatorsexamInedseveralrecoveryparametersand
demonstratedthatpropofolproducedlesspostoperatIvesedatIon,drowsIness,confusIon,
andclumsInessthanmIdazolambutthatdIschargetImesweresImIlar.
TheuseofpropofolforsedatIonhasbeenexamInedInseveraldIverseclInIcalsettIngs,
IncludIngpropofolaloneforuppergastroIntestInalendoscopy
21
andmagnetIcresonance
ImagIngInchIldren,
22
wIthfentanylforextracorporealshockwavelIthotrIpsy,
2J
wIth
alfentanIlfortransvagInaloocyteretrIeval,andforsedatIondurIngthedentalcareto
mentallyandphysIcallyhandIcappedpatIents.
24,25
ThereIsageneralclInIcalImpressIonthatpatIentsrecoverIngfrompropofolnotonly
recoverrapIdlybutoftenexperIenceanIncreasedsenseofwellbeIng.However,astudy
specIfIcallyaddressIngtheIssueofthesubjectIveeffectsoflowdosepropofolInvolunteers
couldfIndnoevIdenceforaeuphorIceffectofpropofol.
26
Theauthorspostulatethatthe
senseofwellbeIngarIsesfromthefeelIngofrelIefthattheprocedureIsover.ThIsfeelIng
ofrelIefmaybeInhIbItedbytheprolongedpsychomotorImpaIrmentthatoftenfollows
otheranesthetIctechnIques.
CeneralanesthesIawIthpropofolIsgenerallyassocIatedwIthlessnauseaandvomItIng
thanmostotheranesthetIctechnIques.ThereIsnowevIdencethatevensubhypnotIcdoses
ofpropofol(asIngle10mgdoseInanadult)alsopossessdIrectantIemetIcpropertIes.
27
Thus,ItIslIkelythatthebenefIcIaleffectsofpropofoluponnauseaandvomItIngwIllbea
featureofmonItoredanesthesIacaretechnIquesusIngthIsdrug.Dntheotherhand,even
durInglowdoseInfusIonsusedforsedatIon,paIndurIngInjectIonofpropofolmaybe
troublesomeInJJto50ofpatIents.
28,29
SeveralstrategIesforreducIngthepaInof
propofoladmInIstratIonaredescrIbedInTableJ11.
J0
Benzodiazepines
8enzodIazepInesarecommonlyuseddurIngmonItoredanesthesIacarefortheIranxIolytIc,
amnestIc,andhypnotIcpropertIes.|IdazolamhasnowdIsplaceddIazepamasthemost
commonly
P.821
usedbenzodIazepIneforconscIoussedatIon.TheImportantdIfferencesbetween
mIdazolamanddIazepamarelIstedInTableJ12.
J1
AlthoughmIdazolamhasashort
elImInatIonhalftIme,thereIsoftensIgnIfIcantandprolongedpsychomotorImpaIrment
followIngsedatIontechnIquesusIngmIdazolamasasIgnIfIcantcomponent.WIththerecent
avaIlabIlItyofpropofol,mIdazolammaybebetterusedInamodIfIedrolebyusInglower
dosesprIortothestartofapropofolInfusIontoprovIdethespecIfIcamnestIcandperhaps
anxIolytIccomponentofabalancedsedatIontechnIqueratherthanasthemajor
hypnotIccomponent.
J2
ThIsstrategyallowsthemoreevanescentandtItratablepropofolto
provIdethedesIredlevelofconscIoussedatIonInanadjustablemanneraccordIngtothe
specIfIcstImulus.TheanalgesIccomponent,IfrequIred,ofabalancedmonItored
anesthesIacaretechnIquecouldbeprovIdedbyregIonal/localtechnIquesoropIoIds.
AgaIn,whenusIngopIoIdswIthbenzodIazepInes,thepotentIalforsIgnIfIcantrespIratory
ImpaIrmentshouldbeconsIdered.
Table 31-1 Published Strategies for Reducing the Pain on Intravenous
Injection of Propofol
UsInglargerveInsInantecubItalfossa
0ecreasIngthespeedofInjectIon
njectIonIntoafastrunnIngIntravenouslIne
0IlutIngwIth5glucoseor10IntralIpId
AddInglIdocaInetopropofol
PretreatIngwIthlIdocaIneandvenousocclusIon
PretreatmentwIthopIoId
PretreatmentwIthpentothal
CoolIngpropofolto4`CprIortoInjectIon
njectIngcooledsalIne(4`C)prIortoInjectIon
0IscontInuIngIntravenousfluIdadmInIstratIondurIngInjectIon
ClInIcalexperIencesuggeststhatthedoseofapartIcularbenzodIazepInerequIredtoreach
adesIredclInIcalendpoIntIsreducedInelderlycomparedwIthyoungerpatIents.ThIs
dIfferenceIndosIngrequIrementsInelderlypatIentsIsmaInlyrelatedtopharmacodynamIc
factors,asdemonstratedbythethreefolddecreaseInplasmaconcentratIonofmIdazolam
atwhIch50ofpatIentswouldbeexpectednottorespondtoverbalcommand(Cp50)Inan
80yearoldpatIentcomparedwItha40yearoldpatIent(FIg.J14).
JJ
8enzodIazepInesarevaluablecomponentsofmonItoredanesthesIacaretechnIques
becausetheyenhancepatIentcomfort,ImproveoperatIngcondItIons,andprovIde
amnesIa.However,recoveryofpsychomotorandcognItIvefunctIonmaybesIgnIfIcantly
prolongedfollowIngbenzodIazepInesedatIon,especIallywhencomparedwIthsedatIve
hypnotIctechnIquesusIngpropofolasthemajorcomponent.
J4
ThespecIfIcbenzodIazepIne
antagonIstflumazenIlprovIdesthepotentIaltoImprovetherecoveryprofIleof
benzodIazepInesbypermIttIngtheactIvetermInatIonoftheIrsedatIveandamnestIc
effectswIthoutInvokIngadversesIdeeffects.However,thepotentIalforresedatIon
remaInsanobstacletotheroutIneuseofbenzodIazepInereversal,partIcularlyInpatIents
undergoIngambulatoryprocedures.TheeffectsofmIdazolammayrecurupto90mInutes
followIngtheadmInIstratIonofflumazenIl.
J5
ThusItIspossIblethatpatIentscouldbe
dIschargedprematurelytoalesswellmonItoredarea,orevenoutofthehospItalInthe
caseofambulatorysurgery,andlaterexperIencerecurrenceofbenzodIazepIneeffects.An
ImportantaddItIonalIssueIsthatofcost.TheroutIneuseofflumazenIlantagonIzed
benzodIazepInesedatIonhasasIgnIfIcantcostdIsadvantage.ChourIetal.
J5
demonstrated
thatflumazenIlantagonIzedmIdazolamsedatIonwasmoreexpensIvethanpropofol
sedatIon(S68.67vs.S27.80).TypIcaldoserequIrementsforuseofflumazenIlarelIstedIn
TableJ1J.
Table 31-2 Comparison of the Important Properties of Midazolam and
Diazepam
MIDAZOLAM DIAZEPAM
Watersoluble,doesnotrequIrepropylene
glycolforsolubIlIzIng
LIpIdsoluble,requIrespropylene
glycolforsolubIlIzIng
NonvenoIrrItant,usuallypaInless 7enoIrrItant,paInonInjectIon
ThrombophlebItIsrare ThrombophlebItIscommon
ShortelImInatIonhalftIme(14h) LongelImInatIonhalftIme(20h)
ClearanceunaffectedbyH
2
antagonIsts ClearancereducedbyH
2
antagonIsts
nactIvemetabolItes(1hydroxy
mIdazolam)
ActIvemetabolItes(desmethyl
dIazepam,oxazepam)
FesedatIonunlIkely FesedatIonmorelIkely
P.822
Table 31-3 Recommended Regimen for the Use of Flumazenil To
Antagonize Benzodiazepine Effects
nItIalrecommendeddoseof0.2mg
fdesIredlevelofconscIousnessIsnotachIevedIn45s,repeat0.2mgdose
0.2mgdosesmayneedtoberepeatedevery60suntIlamaxImumof1mgIs
admInIstered
8eawareofthepotentIalforresedatIon
Figure 31-4.|IdazolamCp50(theconcentratIonatwhIch50ofsubjectswIllfaIlto
respondtoaverbalcommand)asafunctIonofage.ThereIsamarkeddecreaseIn
mIdazolamrequIrementsaspatIentageIncreases.(FeproducedfromJacobsJF,Feves
JC,|artyJetal:AgIngIncreasespharmacodynamIcsensItIvItytothehypnotIceffects
ofmIdazolam.AnesthAnalg1995;80:14J,wIthpermIssIon.)
Opioids
DpIoIdsaremostlogIcallyusedInthecontextofmonItoredanesthesIacaretoprovIdethe
specIfIcanalgesIccomponentofabalancedtechnIqueratherthantoprovIdethe
sedatIvecomponent.DpIoIdanalgesIcsareIndIcatedwhenregIonalorlocalanesthetIc
technIquesareInapproprIateorIneffectIve.DpIoIdsmayalsoplayanImportantroledurIng
theInItIalInjectIonoflocalanesthetIcsolutIonordurIngotherperIodsofIntensepatIent
dIscomfort.PaInrelIefmayberequIredforfactorsotherthantheprocedureItself,suchas
uncomfortableposItIonIng,propofolInjectIon,pneumatIctournIquetpaIn,orotherpaIn
notrelIevedbythelocalanesthetIctechnIque.
AtypIcalcIrcumstanceInwhIchthepatIentmustbrIeflycooperateandremaInmotIonless
IsdurIngtheplacementofaretrobulbarblockprIortoophthalmIcprocedures.PatIent
movementdurIngblockplacementmayIncreasetheIncIdenceofcomplIcatIonssuchas
braInstemanesthesIaandcardIacarrest.Fetrobulbarblockplacementaffordsanexcellent
opportunItytostudytheeffectsofdrugsontheresponsetoastandardIzed,ethIcally
acceptable,brIefpaInfulstImulus.TheIdealdrugforblockplacementwouldprovIdea
brIefperIodofIntenseanalgesIayetallowthepatIenttobeawakeandcooperatIve
wIthoutcausIngcardIorespIratorydepressIonormInImalnauseaandvomItIng,andnot
sIgnIfIcantlyprolongrecovery.
J6
AlfentanIl(20g/kg)hasarapIdonsetandoffsetof
IntenseanalgesIaandwascomparedwIthmethohexItal(0.5mg/kg)forretrobulbarblock
placement.
J6
PatIentsreceIvIngmethohexItalwereunresponsIvetoverbalcommandatthe
tImeofblockplacementanddemonstratedmoremovementonInjectIonthanthose
receIvIngalfentanIl,whoweremostly(87)awakeandcooperatIveatthetImeof
InjectIon.TheauthorsnotethatoneelderlypatIentofthe15whoreceIvedalfentanIl
becameapneIcforJ0seconds,andsuggestedthatthedoseofopIoIdsbereducedInelderly
patIents.TheyalsonotedthatthepersonnelperformIngtheblockwereaccustomedtothe
patIentbeIngasleepdurIngmethohexItalsedatIon,buttooksometImetobecomeat
easewIththeawakeyetcomfortableandcooperatIvepatIentwhohadreceIvedalfentanIl.
ThewelldescrIbedphenomenonofpatIentawarenessandsubsequentrecallof
IntraoperatIveeventsfollowInghIghdoseopIoIdanesthesIaIstakenasevIdencethat
opIoIdslacksIgnIfIcantamnestIcpropertIes.However,whentheeffectsoflowdose
fentanylonmemorywerespecIfIcallyexamInedInvolunteers,Itwasfoundthatalthough
thesubjectsappearedtobeawakedurIngthefentanylInfusIon,therewassIgnIfIcant
memoryImpaIrment.
J7
However,thedegreeofstImulatIonwasprobablylessthanthat
experIencedbyapatIentundergoIngapaInfulsurgIcalprocedure.FecallforapaInful
stImulusmaynotbeImpaIredtothesamedegreeasrecallforthelessnoxIousstImulI
experIencedbythesubjectsofthIsstudy.
AlfentanIlappearstohaveapharmacokInetIcadvantageforthetreatmentofdIscrete
stImulIbecauseofItsshorteffectsIteequIlIbratIontIme,whIchallowsrapIdaccessofthe
drugtothebraInandfacIlItatestItratIon.However,sufentanIlmayhaveamorefavorable
recoveryprofIlewhenusedoveralongerperIodbecauseofItsshortercontextsensItIve
halftIme.nclInIcalpractIce,however,thereIsamarkedInterpatIentvarIabIlItyInopIoId
pharamacokInetIcsanddynamIcs.ThIsInterpatIentvarIabIlItymaybemoresIgnIfIcant
thantheInterdrugdIfferences,makIngItdIffIculttopredIctwIthanyprecIsIontheeffects
ofagIvendrugdoseInanIndIvIdualpatIent.
Remifentanil
nthecontextofmonItoredanesthesIacare,theanalgesIcpropertIesofopIoIdsare
extremelyvaluable.However,theIradverseeffects,IncludIngrespIratorydepressIon,
musclerIgIdIty,andemesIs,areundesIrableInthespontaneouslybreathIngpatIentwIthan
unprotectedaIrwayandsIgnIfIcantlylImIttheabIlItytoconsIstentlyprovIdeeffectIve
analgesIcdoses.AfurthercomplIcatIngIssueIsthattheabIlItytopredIcttheeffectofa
gIvendoseofopIoIdInapartIcularpatIentIslImItedbysIgnIfIcantInterpatIent
pharmacokInetIcandpharmacodynamIcvarIabIlIty.ThIsproblemIsusuallyovercomeIn
practIcebythecautIousIncrementaladmInIstratIonofsmall,carefullyspacedbolusesor
bytItratIngInfusIonstothedesIredeffect.
FemIfentanIlhaspharmacodynamIcpropertIessImIlartothoseofotherpotentopIoId
receptoragonIstssuchasfentanylandalfentanIl.However,remIfentanIlIspredomInantly
metabolIzedbynonspecIfIcesterasesgeneratInganextremelyrapIdclearanceandoffsetof
effect.
J8
ThecontextsensItIvehalftImeofremIfentanIlIsconsIstentlyshort,Jto5
mInutes,IncreasIngtoamInImaldegreewIththeduratIonoftheInfusIon.Furthermore,
remIfentanIlhasashorteffectsIteequIlIbratIontIme(t
1/2
k
e0
)of1.0to1.5mInutes.ThIs
t
1/2
k
e0
IsslIghtlylongerthanthatofalfentanIl(0.6to1.2mInutes)butmuchshorterthan
thatoffentanyl(4to5mInutes)andmorphIne(approxImately20mInutes),andmakesthe
onsetofeffectafterdrugadmInIstratIonveryrapId,thusfacIlItatIngtItratIonofeffect
durIngmonItoredanesthesIacare.
nclInIcalpractIce,remIfentanIlhasbeenusedsuccessfullyastheanalgesIccomponentof
sedatIontechnIquesforregIonalandlocalanesthesIa.tsunIquepharmacokInetIcprofIle
makesItwellsuItedforambulatorymonItoredanesthesIacaretechnIques.PublIshed
experIencewIththeuseofremIfentanIlsuggeststhatItIspossIbletotItrateremIfentanIl
admInIstratIontoprovIdeeffectIveanalgesIawIthmInImalrespIratorydepressIon.The
publIsheddatacanbeusedtogeneratesomepractIcalclInIcalguIdelInes,
J9
whIchare
dIscussedhere.
1. AswIthotherpotentopIoIdsuseddurIngsedatIontechnIques,themostlogIcal
therapeutIcendpoIntforremIfentanIladmInIstratIonIseffectIveanalgesIaandpatIent
comfortratherthansedatIon.WhenopIoIdsaretItratedtopreconceIvedlevelsof
sedatIonratherthanpatIentcomfort,anunacceptabledegreeofrespIratorydepressIon
mayoccur.0rugssuchaspropofolormIdazolamcanbeusedIncombInatIonwIth
remIfentanIltoprovIdethehypnotIcamnestIccomponentofthesedatIontechnIque,
rememberIngthattheconcomItantadmInIstratIonofmIdazolamdecreasesremIfentanIl
doserequIrementsbyupto50.
40
2. PublIsheddatasuggestthatbolusadmInIstratIonofremIfentanIlIsassocIatedwIthan
IncreasedIncIdenceofrespIratory
P.82J
depressIonandchestwallrIgIdIty.8ecausethesesIdeeffectsarelIkelytoberelatedto
hIghpeakconcentratIonsofdrugs,ItIsrecommendedthatremIfentanIlbolusesbe
admInIsteredslowly(overJ0to90seconds)oravoIdedcompletelybyusIngapure
InfusIontechnIque.Furthermore,theadmInIstratIonofremIfentanIlbolusesdurIngthe
concomItantadmInIstratIonofremIfentanIlInfusIonsIsalsoassocIatedwIthanIncreased
IncIdenceofrespIratorydepressIon,themostlIkelymechanIsmagaInbeIngexcessIve
peakdrugconcentratIons.TheseepIsodesofrespIratorydepressIonareofsIgnIfIcant
concern,partIcularlyInthespontaneouslybreathIngpatIentwIthanunprotectedaIrway.
However,IfpromptlyrecognIzedandtheremIfentanIladmInIstratIonIsreducedor
dIscontInued,theyshouldresolvewIthInapproxImatelyJmInutes.Thus,despItethe
pharmacokInetIcadvantagesofremIfentanIl,thelevelofvIgIlancerequIredforIts
admInIstratIonshouldbenodIfferentfromthatforanyotherpotentopIoId.Althoughthe
offsettImeofremIfentanIlIsrapId,ItstIllrequIrestherecognItIonofrespIratory
depressIontotrIggeradownwardadjustmentIndosage.SImIlarly,theshortt
1/2
k
e0
of
remIfentanIlsuggeststhatsuddenrespIratorydepressIonmayoccurInresponseto
upwardadjustmentsIndosage.0espItethepotentIalforrespIratorydepressIon,the
effIcacyofremIfentanIlbolusesdurIngmonItoredanesthesIacarehasbeenInvestIgated
byseveralgroups.ThemostlogIcalscenarIoInwhIchabolusdosecouldbeusedIs
ImmedIatelyprIortoabrIefbutverypaInfulstImulus,suchasplacementofa
retrobulbarblock.
41
Abolusof1g/kgoverJ0secondswasadmInIstered90secondsprIor
toblockplacement.|orethanthreequartersofpatIentsreceIvIngremIfentanIldIdnot
reportanypaIndurIngsubsequentblockplacement.However,15ofthepatIentsgIvena
sInglebolusalonehadsIgnIfIcantrespIratorydepressIon(respIratoryrates8breathsper
mInute),and19ofthosegIvenabolusfollowedbyanInfusIonhadsIgnIfIcant
respIratorydepressIon.
J. TheeffectsofcoadmInIstratIonofbenzodIazepInesandopIoIdsarewelldocumented.
TheaddItIonofmIdazolamtoprovIdetheanxIolytIcsedatIveandamnestIccomponents
ofasedatIontechnIquehasbeenshowntoIncreasepatIentsatIsfactIonandsIgnIfIcantly
reduceremIfentanIldoserequIrements.ThecombInatIonofremIfentanIlwIthmIdazolam
sIgnIfIcantlyreducespatIentanxIetywhencomparedwIththeuseoftheopIoIdalone.
42
EvenrelatIvelylowdosemIdazolam(2mg7)producessIgnIfIcantreductIonsIn
remIfentanIlrequIrementsandpatIentanxIety.0urIngbreastorlymphnodebIopsy,
remIfentanIlInfusIonrequIrementswere0.065g/kg/mInwhenprecededbymIdazolam
comparedwIth0.12Jg/kg/mInwhenusedalone.TheadvantagesofcoadmInIstratIonof
smalldosesofmIdazolamIncludeIncreasedpatIentsatIsfactIon,IncreasedamnesIa,
decreasednauseaandvomItIng,anddecreasedanxIety.ThedIsadvantagesIncludea
tendencytowardIncreasedrespIratorydepressIon,apnea,andexcessIvesedatIon.
4. 8ecausemostpaInfulstImulIareofunpredIctableduratIonandbecausetherIskof
adverserespIratoryeventsIsIncreasedfollowIngbolusadmInIstratIon,themostlogIcal
methodfortheadmInIstratIonofremIfentanIldurIngmonItoredanesthesIacareIsbyan
adjustableInfusIon.ThIsshouldIdeallybeprecededbyasmallbolusofmIdazolam.|ost
InvestIgatorshaveusedInfusIonratesthatstartat0.1g/kg/mInapproxImately5
mInutesprIortothefIrstpaInfulstImulus.ThIsInItIalloadIngInfusIonIsthenweaned
toapproxImately0.05g/kg/mIntomaIntaInpatIentcomfort.ThemaIntenanceInfusIon
IsadjustedupwardInresponsetopaInorhemodynamIcresponseordownwardIn
responsetoexcessIvesedatIon,respIratorydepressIon,orapnea.AtypIcalIncremental
changeInInfusIonrateIs0.025g/kg/mIn.TheuseofremIfentanIlInfusIonsof0.2
g/kg/mInIsassocIatedwIthanIncreasedIncIdenceofrespIratorydepressIonthatIsnot
necessarIlyassocIatedwIthsuperIoranalgesIa.AsInthecaseofpropofoladmInIstratIon,
InadvertentInterruptIonofremIfentanIladmInIstratIonwIllresultInabruptoffsetof
effect,whIchmayresultInpatIentdIscomfort,hemodynamIcInstabIlIty,andeven
morbIdItyduetopatIentmovement.tIsthereforeveryImportanttoensurethatthe
drugdelIverysystemIsmonItoredcarefullydurIngtheprocedure.FemIfentanIlIs
supplIedasapowderthatmustbereconstItutedprIortouse.tIspartIcularlyImportant
whenadmInIsterIngthIsdrugtopatIentswIthanunsecuredaIrwaytoensurethatthere
arenoerrorsIndrugdIlutIonthatwouldresultInInadvertentdosIngerrors.
TypIcaladultdoserecommendatIonsforopIoIdsandotherdrugsdIscussedInthetextare
lIstedInTableJ14.
Table 31-4 Typical Dose Ranges of Sedative, Hypnotic, and Analgesic Drugs
DRUG
TYPICAL ADULT INTRAVENOUS DOSE RANGE (TITRATED TO EFFECT IN SMALL
INCREMENTS)
Benzodiazepines
|Idazolam 12mgprIortopropofolorremIfentanIlInfusIon
0Iazepam
28mgasmajorcomponent
2.510mg
Opioid analgesics
AlfentanIl 520g/kgbolus2mInprIortostImulus
Fentanyl 0.52.0g/kgbolus24mInprIortostImulus
FemIfentanIl
nfusIon0.1g/kg/mIn5mInprIortostImulus
Weanto0.05g/kg/mInastolerated
AdjustupordownInIncrementsof0.025g/kg/mIn
FeducedoseaccordInglywhencoadmInIsteredwIth
mIdazolamorpropofol
AvoIdboluses
Hypnotics
Propofol
250500g/kgboluses
2575g/kg/mInInfusIon
0exmedetomIdIne
LoadIngInfusIon:0.51g/kgover1020mIn
|aIntenanceInfusIon:0.20.71g/kg/h
P.824
Ketamine
KetamIneIsaphencyclIdInederIvatIveandIsanIntenseanalgesIcandIsfrequentlyusedas
acomponentofpedIatrIcsedatIontechnIques.
4J,44
WhenusedInsmalldoses(0.25to0.5
mg/kg)ItsuseIsassocIatedwIthmInImalrespIratoryandcardIovasculardepressIon.
KetamIneproducesadIssocIatIvestateInwhIchtheeyesremaInopenwIthanystagmIc
gaze.However,asthedoseofketamIneIncreases,orwhenusedIncombInatIonwIthother
sedatIves,astateofdeepsedatIonand/orgeneralanesthesIamaybeInadvertently
achIeved.ncreasedoralsecretIonsmakelaryngospasmmorelIkely.Thefearof
laryngospasmIstheunderlyIngratIonaleforthefrequentadmInIstratIonofatropIneor
glycopyrrolate.KetamIneIsfrequentlycombInedwIthabenzodIazepInetoreducethe
IncIdenceofhallucInatIonsassocIatedwIthItsuse.However,thIspractIceIs
controversIal.
45
PatIentmovementmaymakeketamInelessthanIdealforprocedures
requIrIngacompletelymotIonlesspatIent.KetamInecanelevateIntracranIaland
IntraocularpressureandIsthusrelatIvelycontraIndIcatedInpatIentswIthIncreased
IntracranIalpressureandwIthglaucomaoropenglobeInjurIes.AlthoughIthasbeen
suggestedthataIrwayreflexesarerelatIvelypreservedwIthketamIne,thereIsno
convIncIngevIdencetosupportthIsnotIon.
KetamInecanbeadmInIsteredorally,Intramuscularly,orIntravenously.Theoraldoseof
ketamIneIs4to6mg/kg.TheonsetofactIontypIcallyoccurswIthIn20toJ0mInutesand
theduratIonofeffectIsbetween60and90mInutes.TheIntramusculardoseIs2to4mg/kg
wIthanonsetofactIonof5to10mInutesandtypIcallyhasaduratIonofeffectofJ0to120
mInutes.WhenadmInIsteredvIathe7route,ketamIneshouldbegIvenInsmall(0.25to
1.0mg/kg)Increments,tItratIngtoeffectwIthanonsetofactIonof1to2mInutesandan
approxImateduratIonof20to60mInutes.
Dexmedetomidine
0exmedetomIdIneIsaselectIve
2
receptoragonIst.StImulatIonof
2
receptordepresses
centralsympathetIcfunctIonandproducessedatIonandanalgesIa.The
2
agonIsts
potentIateopIoIdInducedanalgesIa,benzodIazepIneInducedhypnosIs,andhavepotent
|ACsparIngeffectswhenadmInIsteredwIthvolatIleagents.Althoughcurrentlyapproved
IntheUnItedStatesforsedatIonofmechanIcallyventIlatedpatIentsInanIntensIvecare
settIng,dexmedetomIdInehasbecomeanImportantaddItIontotheanesthesIologIst's
armamentarIumbothasanadjuncttogeneralanesthesIaandasacomponentof
proceduralsedatIontechnIques.However,thepublIshedexperIencewIthdexmedetomIdIne
remaInsrelatIvelylImItedandItsroleInmonItoredanesthesIacarecontInuestoevolve.
TherehasalsobeenrecentInterestIntheuseofdexmedetomIdIneforsedatIonprovIded
bynonanesthesIaprofessIonals.Toadegree,someofthIsInterestwasgeneratedIn
responsetotheASAstatementonthesafeuseofpropofol,theAmerIcanAssocIatIonof
NurseAnesthetIstsASAjoIntstatementregardIngpropofoladmInIstratIon,theAstra
Zeneca0IprIvanpackageInsert,andprescrIptIveregulatIonsInseveralstates,allofwhIch
promotetheposItIonthattheadmInIstratIonofpropofolshouldbelImItedtothose
IndIvIdualstraInedIntheadmInIstratIonofgeneralanesthesIa.
46
ComparedwIthothersedatIveandanalgesIcdrugs,dexmedetomIdIneappearstohave
relatIvelymInoreffectsonrespIratoryfunctIonwhenusedInthetypIcaldoserange.
47
Df
note,unlIkedurIngopIoIdInducedsedatIon,thehypercapnIcarousalresponse,afeatureof
naturalsleep,appearstobepreserveddurIngdexmedetomIdInesedatIon.However,aIrway
InterventIontorelIeveobstructIonandapneamayberequIreddurIngdexmedetomIdIne
admInIstratIon,partIcularlywhenusedIncombInatIonwIthotherrespIratory
depressants.
48
0exmedetomIdInehasbeenusedforsedatIondurIngInstrumentatIonofthe
dIffIcultaIrway.PatIentsundergoIngfIberoptIcIntubatIonsedatedwIthdexmedetomIdIne
aregenerallycomfortableyetcooperatIve.
49
AdmInIstratIonof
2
agonIstIsassocIated
wIthareductIonofsympathetIcoutflowandanIncreaseIncardIacvagalactIvIty;
therefore,ItIsnotsurprIsIngthathypotensIonandbradycardIamayoccurdurIng
dexmedetomIdIneadmInIstratIon.ClInIcallysIgnIfIcantepIsodesofbradycardIaandsInus
arresthavebeenassocIatedwIthdexmedetomIdIneadmInIstratIonInyoung,healthy
volunteerswIthhIghvagaltone,partIcularlydurIngrapId7orbolusadmInIstratIon.
50
The
2
agonIstsdohaveperIpheralvasoconstrIctIveeffectsthatcanoccasIonallyprecIpItate
hypertensIon.0espItethIsphenomenon,theIncIdenceofhypertensIveepIsodesrequIrIng
InterventIonIslowerwhencomparedwIthanequIvalentpropofolbasedtechnIque.
51
0exmedetomIdInehasbeenusedsuccessfullyInbothadultandpedIatrIcpatIentsfor
monItoredanesthesIacaredurIngtheawakeportIonsofcranIotomIesrequIrIngpatIent
cooperatIonforcortIcalspeechmappIng.
52,5J
0exmedetomIdInehasbeenusedassedatIve
supplementatIontoregIonalanesthesIadurIngcarotIdendarterectomy.Underthese
cIrcumstances,therewerefewerfluctuatIonsfromthedesIredsedatIonlevelwhen
comparedwIththecombInatIonofmIdazolam,fentanyl,andpropofol.
54
0exmedetomIdIne
tendstodecreasecerebralbloodflowbothdIrectlyvIa
2
medIatedconstrIctIonof
cerebralbloodvesselsandIndIrectlyvIaItseffectonsystemIcpressure.However,there
appearstobeaconcomItantdecreaseIncerebralmetabolIcrate.
55
Toaddfurther
reassurance,theuseofdexmedetomIdInedoesnotappeartobeassocIatedwIthan
IncreaseIntheneedforIntracarotIdshuntIngInpatIentsundergoIngawakecarotId
endarterectomy.
56
ThelackofpaInonInjectIonandItsanalgesIcandmInImaladverserespIratorypropertIes
wouldseemtomakedexmedetomIdIneausefulalternatIvetopropofolIncertaIn
cIrcumstances.However,whencomparedwIthpropofol,thetargetsedatIonleveltakes
longertoachIevewIthdexmedetomIdIne(25vs.10mInutes).
57
Furthermore,IfloadIng
bolusesofdexmedetomIdIneareusedtoacceleratetheonsetofsedatIon,bradycardIaand
hypotensIonmayoccur.AlthoughtheuseofdexmedetomIdInemayresultIngreater
sedatIon,lowerbloodpressure,andImprovedanalgesIaIntherecoveryroomwhen
comparedwIthpropofol,thetImetopostanesthesIacareunItdIschargeIsnotsIgnIfIcantly
dIfferent.
57
0exmedetomIdIneIsmostoftendelIveredasanInItIalbolusfollowedbya
contInuousInfusIon.nItIalbolusdosesrangefrom0.5to1.0g/kgover10to20mInutes,
followedbyacontInuousInfusIonof0.2to0.7/kg/h.
TwolargeretrospectIveobservatIonalstudIesfromasInglechIldren'shospItalsuggestthat
dexmedetomIdInemaybeusedforsedatIonforpedIatrIcmagnetIcresonanceImagIngand
computedtomographystudIes.
58,59
nthesestudIes,theloadIngdoseofdexmedetomIdIne
was2toJg/kgover10mInutes,followedbyanInfusIonofbetween1and2g/kg/h.
However,approxImately15ofpatIentsrequIredasecondbolusInordertoachIeve
satIsfactorycondItIonstocompletethescan.TheanalgesIcpropertIesofdexmedetomIdIne
maymakeItausefulalternatIvetotheuseofpropofolasasoleagentdurIngpaInful
procedures.However,thetImetakentodelIvertheloadIngdose,theoccasIonalneedto
rebolus,hypotensIon,bradycardIa,andtherelatIvelylongrecoverytImemaylImItthe
utIlItyofdexmedetomIdIneforverybrIefproceduressuchascomputedtomography
studIes.Dntheotherhand,thepaInonInjectIonofpropofolandthelegIslatIveconstraInts
ontheadmInIstratIonofpropofolbynonanesthesIatraInedprovIdersmaymake
dexmedetomIdIneadvantageousIncertaIncIrcumstances.
P.825
Amnesia During Sedation with Dexmedetomidine or Propofol
0rugswIthsedatIvehypnotIcpropertIesreduceattentIontostImulIdurIngtheIr
admInIstratIonasadIrectconsequenceofdepressIonofconscIousness.Therefore,all
sedatIvehypnotIcshavethepotentIaltoImpaIrmemoryformatIonbecauseattentIonto
stImulIIsacrucIalelementofexplIcItmemoryformatIon.
60
However,lIke
benzodIazepInes,propofolhassIgnIfIcantamnestIceffectsatsubhypnotIcdoses,suggestIng
anaddItIonalamnestIcmechanIsmthatIsseparatefromItssedatIveeffect.nthecaseof
propofol,drugInducedamnesIaappearstobeaconsequenceoflackofretentIonof
InformatIonthatwasalreadysuccessfullystoredIntolongtermmemory.
61
ncontrastto
propofolandbenzodIazepInes,ItIsunlIkelythatdexmedetomIdInehasamnestIcpropertIes
atsubhypnotIcdoses.
60
famnesIaIsdesIredforaprocedureperformeddurIng
dexmedetomIdIneadmInIstratIon,lossofconscIousnesswouldbenecessaryIf
dexmedetomIdIneIsusedasthesoleagent.AlternatIvely,amnestIcdosesofpropofolora
benzodIazepInemaybeusedtosupplementdexmedetomIdIne.ThepropertIesofpropofol
anddexmedetomIdInearecomparedInTableJ15.
Patient-Controlled Sedation and Analgesia
TechnIquesthatallowthedIrectpatIentcontrolofthelevelofsedatIonmayposItIvely
affectpatIentsatIsfactIon.
62
ThedegreeofsedatIondesIredbythepatIentvarIes
sIgnIfIcantlyandtheIndIvIdualresponsetodrugsIsvarIable.PatIentcontrolledsedatIon
appearstobeanattractIvesolutIontothIsproblem.DneapproachtopatIentcontrolled
sedatIonhasbeentouseaconventIonalpatIentcontrolledanalgesIa(PCA)delIverysystem
settodelIver0.7mg/kgbolusesofpropofolwIthaJmInutelockoutperIod.
6J
Dther
approachesIncludefIxeddosecombInatIonsof0.5mgmIdazolamand25gfentanylwItha
5mInutelockoutIntervalbetweendoses.
64
ThIstechnIquewasassafeandeffectIveas
anesthesIologIstcontrolleddrugdelIvery,butmaybeassocIatedwIthgreater
postproceduresedatIon.
65
ThepharmacokInetIcprofIleofalfentanIlIsIdealforthe
treatmentofshort,dIscreteepIsodesofpaIn.ThesepropertIeshavebeenexploIteddurIng
vagInalovumretrIevalprocedures,whenultrasonIcallyguIdedneedlesarepassedthrough
thevagInalwallundermonItoredanesthesIacare.Zelceretal.
66
usedaPCAdelIvery
systemtoallowselfadmInIstratIonofalfentanIldurIngthIsprocedure.AftermIdazolam
premedIcatIonandaloadIngdoseofalfentanIl,patIentsreceIved5g/kgbolusesof
alfentanIlvIathePCApumpwIthamandatoryJmInutelockoutperIod.PatIent
acceptabIlIty,alfentanIldosage,respIratoryvarIables,andpaInscoresweresImIlarto
thoseobtaInedwIthphysIcIancontrolledanalgesIa.FromthelImIteddatathatare
avaIlable,IntraoperatIvePCAdurIngmonItoredanesthesIacareappearstobeaneffectIve
alternatIvetophysIcIanadmInIsteredanalgesIa.
Respiratory Function and SedativeHypnotics
0urIngmonItoredanesthesIacarethereIssIgnIfIcantpotentIalforrespIratorycompromIse
medIatedvIaseveralImportantmechanIsms.TheseIncludeadverseeffectsonrespIratory
drIve,eItherdIrectlyasaresultofsedatIvehypnotIcoropIoIdadmInIstratIonorIndIrectly
asaconsequenceofbraInstemhypoperfusIonresultIngfromhypotensIon,suchasthat
occurrIngdurIngspInalorepIduralanesthesIa.TheremayalsobeamarkedIncreaseInthe
workofbreathIngbecauseofIncreasedupperaIrwayresIstance.
67
0urIngsedatIonItIs
lIkelythatprotectIveaIrwayreflexeswIllbeattenuated.Dntheotherhand,sedatIvedoses
ofbenzodIazepInesappeartohavevarIableeffectsonrespIratorysystemmechanIcs,
eItherdecreasIng,IncreasIng,orhavIngnoeffectonfunctIonalresIdualcapacIty.
68,69
Sedation and Upper Airway Patency
TheupperaIrwayIslocatedoutsIdethethorax.0urIngnormalInspIratIon,thepressure
wIthIntheupperaIrwayIssubatmospherIc;thus,thereIsatendencyfortheupperaIrway
tocollapseundertheInfluenceofthesurroundIngatmospherIcpressure.However,Inthe
normalsubjectthIstendencyforaIrwaycollapseIsopposedbyupperaIrwaydIlatormuscle
tone.ThesemusclesprobablybothIncreasethedIameterandreducethecomplIanceofthe
upperaIrway.AnIncreaseInupperaIrwaydIlatormuscletoneoccursdurIngInspIratIon,
commencIngjustprIortodIaphragmatIccontractIon.
70
SeveralstudIeshaveconfIrmedthe
ImportanceofcoordInatedactIvatIonofthedIaphragmatIcandupperaIrwayrespIratory
musclesInmaIntaInIngaIrwaypatency.UpperaIrwaydIlatormusclecontrolappearstobe
extremelysensItIvetosedatIvehypnotIcdrugadmInIstratIon.
71
Forexample,sedatIve
dosesofmIdazolamhavebeenreportedtoIncreaseInspIratorysubglottIcaIrwayresIstance
bythreetofourfold.
72
SedatIvedosesofdIazepamselectIvelysuppressgenIoglossal
muscleactIvItytoagreaterdegreethandIaphragmatIcactIvIty;furthermore,thIseffectIs
exaggeratedInelderlypatIents.nalltheseexamplestheIncreasedupperaIrway
resIstancemarkedlyIncreasedtheworkofbreathIng.TheresponsetothIsobstructIonIsa
sIgnIfIcantIncreaseInIntercostalandaccessorymuscleactIvIty.
P.826
However,thIsresponseIsonlypartIallyeffectIvebecausetheIncreaseInInspIratoryforce
wIllfurtherdecreaseIntralumInalupperaIrwaypressure,predIsposIngtofurtheraIrway
collapse.tIslIkelythattheseeffectswIllbeofgreatestsIgnIfIcanceInpatIentswIthpre
exIstIngrespIratorycompromIse,suchaselderlypatIentsorthosewIthchronIcobstructIve
pulmonarydIsease.ThesepatIentsoftenhavelImItedrespIratoryreserveandareunableto
IncreasetheIrrespIratorymuscleactIvItyInresponsetotheIncreasedworkofbreathIng
InducedbysedatIonandmaybecomehypercarbIc,acIdotIc,andhypoxIc.
Table 31-5 A Comparison of Some Important Properties of Propofol and
Dexmedetomidine
PROPOFOL DEXMEDETOMIDINE
PaInonInjectIon Yes |InImal
AnalgesIcpropertIesInsubhypnotIcdoses |InImal Yes
AmnestIcpropertIesInsubhypnotIcdoses SIgnIfIcant nsIgnIfIcant
TImeofonsetwIthtypIcaladmInIstratIon FapId 510mIn
FestrIctIveregulatIonsonusebynonanesthesIa
traInedprovIders
Yes No
PotentIalforsIgnIfIcantbradycardIa |InImal SIgnIfIcant
Sedation and Protective Airway Reflexes
CompetentlaryngealandupperaIrwayreflexesarerequIredtoprotecttheloweraIrway
fromaspIratIon.ProtectIvelaryngealandpharyngealreflexesaredepressedbyanesthesIa
andsedatIon.Furthermore,ItIsalsowelldocumentedthatprotectIveaIrwayreflexesare
compromIsedbyadvancedageanddebIlItatIon.Therefore,ItIslIkelythatsIgnIfIcant
depressIonofaIrwayreflexescouldoccurdurIngsedatIonIntheelderlyordebIlItated
patIent.AspIratIonofgastrIccontentscouldoccureItherIntheoperatIngroomordurIng
recovery,partIcularlyIforalIntakeIsallowedbeforethereturnofadequateupperaIrway
protectIvereflexes.ThetImerequIredforthereturnofprotectIvereflexesvarIes
consIderably.CompleterecoveryoftheswallowIngreflexoccursapproxImately15mInutes
afterthereturnofconscIousnessfollowIngpropofolanesthesIa.
7J
However,the7
admInIstratIonof15mgofdIazepamhasbeenshowntodepresstheswallowIngreflexfor
upto4hours.
74
TheswallowIngreflexIssIgnIfIcantlydepressedforupto2hoursfollowIng
theadmInIstratIonofmIdazolamdespItethereturntoanormalstateofconscIousness.
75
n
otherwIsehealthyadultmalevolunteerstheInhalatIonof50nItrousoxIdewasassocIated
wIthmarkeddepressIonoftheswallowIngreflex.
76
tIsapparentfromthesourcesprevIouslyquotedthattheprotectIveaIrwayreflexesalone
cannotberelIedontoprotecttheloweraIrwayfromaspIratIondurIngsedatIon.Thus,
patIentswhoaredeemedtobeatrIskfromaspIratIonofgastrIccontentsshouldbe
maIntaInedatthelIghtestlevelofsedatIonpossIble.deally,thepatIentshouldbeawake
enoughtorecognIzetheregurgItatIonofgastrIccontentsandbeabletoprotecthIsorher
ownaIrway.ftheabIlItyofthepatIenttoprotecthIsorherownaIrwaycannotberelIably
guaranteedandregurgItatIon/aspIratIonIsthoughttobeasIgnIfIcantrIsk,placementofa
cuffedendotrachealtubeundergeneralorlocalanesthesIashouldbeserIouslyconsIdered.
Sedation and Respiratory Control
ClInIcalexperIencewouldleadmostanesthesIologIststopredIctthattheadmInIstratIonof
sedatIvehypnotIcdrugsIsassocIatedwIththedepressIonofrespIratorydrIve.However,
thefIndIngsofscIentIfIcstudIesInthIsareaareoftenconflIctIngandconfusIng,on
occasIonfIndIngmInImal,Ifany,effectsofsedatIvedrugsonventIlatoryresponsIveness.
However,ItIsImportanttonotethatInmanycasesthemethodsusedtomeasure
respIratorydrIvemayaffecttheoutcomeofthestudybystImulatIngthesubject,thus
attenuatIngthenegatIveeffectofthedrugonrespIratorydrIve.nclInIcalpractIceItIs
lIkelythatdurIngregIonalanesthesIathereIsadegreeofdeafferentatIonthatwIll
potentIatetherespIratorydepressanteffectsofsedatIvehypnotIcdrugs.
77
|oststudIes
havedemonstratedthatopIoIdsdepresstheventIlatoryresponsetohypercapnIaand
hypoxIa.
78
FeportsoftheeffectsofsedatIvedosesofbenzodIazepInesoncarbondIoxIde
responsIvenesshaveshownvarIableresults,IncludIngnosIgnIfIcanteffectandclInIcally
sIgnIfIcantdepressIon.
79,80
However,whenopIoIdsandbenzodIazepInesareusedIn
combInatIon,thereappearstoaconsIstentandmarkednegatIveeffectonrespIratory
responsIveness.
17
AlthoughtheaddItIonofsedatIvedosesofpropofoltoopIoIdsshowed
lIttlepotentIatIonoftherespIratoryeffectsofopIoIds,cautIonIsstIllwarrantedwhen
combInatIonsofsedatIvehypnotIcsareused.
Supplemental Oxygen Administration
HypoxIaasaresultofalveolarhypoventIlatIonIsarelatIvelycommonoccurrencefollowIng
theadmInIstratIonofsedatIves,analgesIcs,andhypnotIcs.ntheabsenceofsIgnIfIcant
lungdIsease,theadmInIstratIonofonlymodestconcentratIonsofsupplementaloxygenIs
frequentlyeffectIveInrestorIngthepatIent'soxygensaturatIontoanacceptablelevel.
ThIsconceptIswellIllustratedbyreferencetothefamIlIaralveolargasequatIon.An
extremeexampleIllustratesthepoInt:anotherwIsehealthyadultmalebreathIngroomaIr
receIvesadoseofanopIoIdthatcausesmarkedalveolarhypoventIlatIonsuchthathIs
alveolarPCD
2
IsIncreasedto80mmHg.ThealveolargasequatIonpredIctsthathIsarterIal
PD
2
wIllfalltoapproxImately40mmHgasshownhere:
PAD
2
=PD
2
PACD
2
/F
PD
2
=FD
2
(P
8
PH
2
o)
PD
2
=0.21(76047)=150mmHg
PAD
2
=15080/0.8
PAD
2
=50mmHg
AssumInganormalAagradIent,hIsPao
2
wIllbe40mmHg,correspondIngtoanarterIal
oxygensaturatIonof75.fwhIleInItIatIngdefInItIvetherapyforhypoventIlatIonthIs
patIentweretoreceIveonlyamodestIncreaseInInspIredoxygen,amarkedImprovement
InarterIalsaturatIonwouldbeachIeved:
FD
2
Increasedto28
PD
2
=0.28(76047)=200mmHg
PAD
2
=20080/0.8
PAD
2
=100mmHg
ThIstheoretIcalexampleservestohIghlIghtanImportantpoInt.FIrst,InIsolated
hypoventIlatIonmodestIncreasesInInspIredoxygenareremarkablyeffectIveatrestorIng
oxygensaturatIontoacceptablelevels.However,apatIentwhoIsreceIvIngmInImal
supplementaloxygenandhasanacceptableoxygensaturatIonmayhavesIgnIfIcant
undetectedalveolarhypoventIlatIon.Therefore,beforemakIngthedecIsIontodIscharge
patIentstoalesswellmonItoredenvIronmentwIthoutsupplementaloxygen,ItIsusefulto
measuretheIroxygensaturatIonwhIlebreathIngroomaIr.
Monitoring During Monitored Anesthesia Care
American Society of Anesthesiologists Standards
TheASAstandardsforbasIcanesthetIcmonItorIngareapplIcabletoalllevelsofanesthesIa
care,IncludIngmonItoredanesthesIacare.tIsusefultorevIewthecomponentsoftheASA
P.827
standardsthatarepertInenttomonItoredanesthesIacareasapprovedbytheHouseof
0elegatesonDctober21,1986,andsubsequentlyamendedonDctober25,2005.
81
(See
Chapter2,Table21,forthecurrentASAstandards.)
Communication and Observation
AconscIentIousandwelltraInedanesthesIacaregIverIsthesInglemostvItalmonItorIn
theoperatIngroom.However,hIsorhereffectIvenesswIllbemarkedlyenhancedbythe
useofthebasIcquantItatIveandqualItatIvemonItorIngdevIces,whIchshouldbereadIly
avaIlableInalloperatIngrooms.tIsImportantthattheanesthesIologIstcontInually
evaluatethepatIent'sresponsetoverbalstImulatIontoeffectIvelytItratethelevelof
sedatIonandtoallowtheearlIerdetectIonofneurologIcorcardIorespIratorydysfunctIon.
ContInuousvIsual,tactIle,andaudItoryassessmentofphysIologIcfunctIonshouldInclude
observatIonoftherate,depth,andpatternofrespIratIon;palpatIonofthearterIalpulse;
andassessmentofperIpheralperfusIonbyextremItytemperatureandcapIllaryrefIll.n
addItIon,thepatIentshouldbecontInuallyobservedfordIaphoresIs,pallor,shIverIng,
cyanosIs,andacutechangesInneurologIcstatus.
Auscultation
AuscultatIonofheartandbreathsoundshaslongbeenavItalcomponentofmonItorIng
durInganesthesIa.PlacementofaprecordIalstethoscopenearthesternalnotchofa
nonIntubatedpatIentprovIdesImportantInformatIonconcernIngupperaIrwaypatencyas
wellasacontInuousmonItorofheartsoundsandventIlatIon.ContInuousprecordIal
auscultatIonIsanInexpensIve,effectIve,andessentIallyrIskfreeprocessthatservesan
addItIonalImportantpurposebybrIngIngtheanesthesIacareprovIderclosertothe
patIent.faccesstothepatIentIslImIteddurIngtheprocedure,F|wIrelessorInfrared
remotetransmIssIonsystemsarenowcommercIallyavaIlable.
Pulse Oximetry
NomonItorofoxygentransporthashadagreaterImpactonthepractIceofanesthesIology
thanthepulseoxImeter.
82
PulseoxImetryIsnonInvasIve,safe,andcomfortabletothe
awakepatIent;ItIsalsotechnIcallysImpletoapplyandInterpret,andallowscontInuous
realtImemonItorIngofarterIaloxygenatIon.TheuseofaquantItatIvemeasureof
oxygenatIonIsspecIfIcallymandatedbytheASAstandardsforIntraoperatIvemonItorIng.
TheImportantmechanIsmswherebyrespIratoryfunctIonmaybecompromIseddurIng
monItoredanesthesIacareIncludetheeffectsofsedatIvesandopIoIdsonrespIratorydrIve,
upperaIrwaypatency,andprotectIveaIrwayreflexes.AddItIonalImportantrIskfactorsfor
arterIaldesaturatIonIncludeobesIty,preexIstIngupperaIrwayobstructIonandrespIratory
dIsease,theextremesofage,andthelIthotomyposItIon.
8J
ThefundamentalImportanceof
monItorIngoxygenatIondurIngmonItoredanesthesIacarecanbeapprecIatedfromthe
closedclaImstudyofCaplanetal.,
77
whoexamIned14casesofsuddencardIacarrestIn
otherwIsehealthypatIentswhoreceIvedspInalanesthesIa.ThesemajoranesthetIc
mIshapsoccurredbeforetheroutIneadoptIonofpulseoxImetry.DneofthemajorfIndIngs
ofthIsstudywasthatcyanosIsfrequentlyheraldedtheonsetofcardIacarrest,suggestIng
thatunapprecIatedrespIratoryInsuffIcIencymayhaveplayedanImportantrole.Further
supportfortheuseofpulseoxImetrycomesfromtheASACommItteeonProfessIonal
LIabIlItyanalysIsofclosedanesthesIaclaIms,whIchrevealsthatrespIratoryevents
constItutethesInglelargestsourceofadverseoutcome.Furthermore,revIewofthese
casessuggeststhatpulseoxImetryIncombInatIonwIthcapnometrywouldhaveprevented
theadverseoutcomeInmostcases.
Capnography
AlthoughcapnographyIsmosteffectIveIntheIntubatedpatIent,someusefulInformatIon
maybeobtaInedfromaspontaneouslybreathIng,nonIntubatedpatIent.SIdestream
capnographshavebeenadaptedforusewIthfacemasks,nasalaIrways,andnasalcannulae
andhavebeenusedsuccessfullydurIngmonItoredanesthesIacare.
84,85,86,87
Nasalcannulae
foroxygendelIveryhavebeenmodIfIedtoprovIdeanIntegralportforrespIratorygas
samplIngandareavaIlablecommercIally.AlternatIvely,capnographsamplInglInescanbe
attachedtoshortened7cathetersandInsertedInsIdenasaloxygenprobes.
Cardiovascular System
AtamInImum,theelectrocardIogrammustbecontInuallydIsplayedandthebloodpressure
measuredandrecordedatleastevery5mInutesdurIngmonItoredanesthesIacare.The
pulseshouldbemonItoredbypalpatIon,oxImetry,orauscultatIon.TheselectIonof
addItIonalhemodynamIcmonItorIngIsusuallydetermInedmorebythecardIovascular
statusofthepatIentthanthemagnItudeoftheprocedure.|ostproceduresperformed
undermonItoredanesthesIacaredonotInvolvemajorhemorrhage,fluIdshIfts,ormajor
physIologIctrespass.0ecIsIonsconcernIngchoIceofmonItorIngformyocardIalIschemIa
andotheradversehemodynamIceventswIllneedtobeIndIvIdualIzedonacasebycase
basIs.
Temperature Monitoring and Management During Monitored
Anesthesia Care
ThevalueoftemperaturemonItorIngIswellestablIsheddurInggeneralanesthesIa,the
perIoperatIveperIodbeIngfrequentlycomplIcatedbyhypothermIaandhyperthermIa.
AlthoughsedatIontechnIquesuseddurIngmonItoredanesthesIacaredonotgenerally
trIggermalIgnanthyperthermIa,thereIspotentIalforsIgnIfIcantInadvertenthypothermIa,
partIcularlydurIngneuraxIalanesthesIa.EvenmonItoredanesthesIacaretechnIques
unaccompanIedbyregIonalanesthesIaareassocIatedwIthhypothermIaattheextremesof
age,boththeoldandveryyounghavIngImpaIredthermoregulatorymechanIsms.The
elderlyalsohavemarkedlyreducedmusclemassandthereforebasalheatproductIon.
AlthoughtheanesthesIologIstmaybeabletoexertsomecontrolovertheambIent
temperatureIntheoperatIngroom,heorshemaybeunabletoInfluencethetemperature
atremoteanesthetIzInglocatIons.FadIologysuItesareoftenmaIntaInedatlower
temperaturestoaccommodatethecomputersystemsthatareusedtoreconstructImages.
FadIantheatInglamps,forcedaIrheaters,fluIdwarmers,orwarmIngblankets,allcommon
ItemsInoperatIngrooms,maybeunavaIlableandunsuItableforuseatremotelocatIons.
ForcedaIrheatInghasbeenshowntobeaneffectIvemeansofmaIntaInIngnormothermIa,
andcanbecombInedwIth7fluIdwarmIng.
88
EvenmIldperIoperatIvehypothermIa(I.e.,1
to2`C)accompanyInggeneralanesthesIaIsassocIatedwIthadversemyocardIaloutcomes,
IncreasedbleedIngtendencyandtransfusIonrequIrements,woundInfectIons,anddelayed
P.828
woundhealIngandhospItaldIscharge.
89
ThereIsnoevIdencesuggestIngthatthemorbIdIty
assocIatedwIthperIoperatIvehypothermIaIsanylessdurIngmonItoredanesthesIacare
thandurInggeneralanesthesIa.ThemorbIdItyassocIatedwIthperIoperatIvehypothermIa
IswelldescrIbedInhIghrIskpatIents;thIsIsagroupofpatIentswhoareverylIkelyto
undergoproceduresundermonItoredanesthesIacare.WhenhypothermIaIssIgnIfIcant,
shIverIngmayInterferewIththeplannedprocedureandmarkedlyIncreaseoxygen
requIrementsandpredIsposesusceptIblepatIentstomyocardIalIschemIaorrespIratory
InsuffIcIency.ThemajorthermoregulatorydefensesagaInsthypothermIaInclude
vasoconstrIctIon,shIverIng,andbehavIor.7asoconstrIctIonandshIverIngareImpaIred
durIngmajorconductIonanesthesIa.8ehavIoralthermoregulatIonIsImpaIredevenInthe
conscIouspatIent.FegIonalanesthesIahasmajoreffectsonthermoregulatIon.
90
Lower
extremItyvasodIlatatIoncausescentralcoolIngvIaaredIstrIbutIonofheatfromthecore
totheperIphery.AfferentInputtothehypothalamusfromthewarmperIpheral
compartmentcounteractsconflIctIngInputfromthecoolIngcentralcompartment,thus
delayIngtheInItIatIonofcompensatorythermoregulatIon.ntheabsenceofrelIable
temperaturemonItorIngItIspossIblethatthefIrstIndIcatIonofhypothermIawouldbethe
onsetofshIverIng,bywhIchtImeconsIderablecentralcoolIngmayhaveoccurred.
Frankandcoworkers
91
haveexamInedtheIssueoftemperaturemonItorIngand
managementdurIngneuraxIalanesthesIaandfoundthattemperaturemonItorIngIs
sIgnIfIcantlyunderused,wIthonlyonethIrdofpatIentsbeIngmonItored.Furthermore,the
methodthatwasmostfrequentlyusedtomonItortemperaturemaynotaccuratelyreflect
coretemperature,themostImportantdetermInantofthermoregulatoryresponseand
perIoperatIvemorbIdIty.ForeheadskInsurfacewasthemostcommonlymonItoredsIte.
TheaccuracyofthesedevIcesforperIoperatIvetemperaturemonItorIngremaIns
controversIal;theydonotrelIablydetectmalIgnanthyperthermIaandarenotsuffIcIently
accurateforfeverscreenIngpurposesInchIldren.
92
Sessler
90
recommendstheuseofa
properlyposItIonedaxIllaryprobeorIntermIttentoraltemperaturemonItorIngdurIng
neuraxIalanesthetIcs.
PatIentswIllfrequentlycomplaInoffeelIngtoowarmwhencoveredbyheavydrapes.
AlthoughmalIgnanthyperthermIaIsraredurIngmonItoredanesthesIacare,hyperthermIa
IsstIllpossIbleasaresultofthyroIdstormormalIgnantneuroleptIcsyndrome.The
subjectIvesensatIonofhyperthermIamayalsobethefIrstIndIcatorofImportantadverse
eventsInevolutIonsuchashypoxIa,hypercarbIa,cerebralIschemIa,localanesthetIc
toxIcIty,andmyocardIalIschemIa.
Bispectral Index Monitoring During Monitored Anesthesia Care
ThebIspectralIndex(8S)IsaprocessedEECparameterthatwasdevelopedspecIfIcallyto
evaluatepatIentresponsedurIngdrugInducedanesthesIaandsedatIon.SedatIon
monItorIngIsattractIvebecauseofthepotentIaltotItratedrugsmoreaccurately,avoIdIng
theadverseeffectsofbothoverandunderdosIng.8SmonItorInghassomepotentIal
advantagesoverconventIonalIntermIttenttechnIquesofpatIentassessment.ConventIonal
assessmentInvolvespatIentstImulatIonatfrequentIntervalstodetermInethelevelof
conscIousness,requIrespatIentcooperatIon,andIssubjecttotestIngfatIgue.Anexample
ofaconventIonalassessmenttoolIstheDbserver'sAssessmentofAlertness/SedatIonScale
(TableJ16).
9J
The8ShasbeenshowntobeausefulmonItorofdrugInducedsedatIonand
recallInvolunteersandhasbeenshowntocorrelatewIthDbserver'sAssessmentof
Alertness/SedatIonScalescoresdurIngpropofolInducedsedatIonInpatIentsundergoIng
surgerywIthregIonalanesthesIa.
94
AnIncreasIngdepthofsedatIonwasassocIatedwItha
predIctabledecreaseInthe8S.AbsenceofrecallwasassocIatedwIth8Svaluesbelow80.
ThesefIndIngscorrespondwIththoseofKearseetal.,
95
whofoundnoIntraoperatIverecall
at8Svaluesbelow79durIngmIdazolam,Isoflurane,andpropofolInducedsedatIon.
However,theInabIlItytorecallanonnoxIousstImulussuchasapIcture,asusedInthe
prevIouslymentIonedstudIes,maynotnecessarIlycorrespondtoamnesIatonoxIousevents
suchassurgIcalstImulatIon.0espItethIscaveat,LIuandcoworkers
94
suggestthatusInga
combInatIonofpropofolandmIdazolamtoachIevea8Svaluebelow80wIllmInImIzethe
possIbIlItyofIntraoperatIverecall.Althoughtheuseof8StomonItorsedatIonIs
appealIng,conventIonalassessmentofsedatIonIsanImportantmechanIsmwhereby
contInuouspatIentcontactIsmaIntaIned.deally,8SmonItorIngwIllbeemployedInthe
futureasanadjuncttoclInIcalevaluatIonratherthanastheprImarymonItorof
conscIousness.
Preparedness to Recognize and Treat Local Anesthetic
Toxicity
|onItoredanesthesIacareIsoftenprovIdedInthecontextofregIonalorlocalanesthetIc
technIques.tIsvItallyImportantthattheanesthesIologIstresponsIbleforthepatIenthave
ahIghIndexofsuspIcIonandbefullypreparedtorecognIzeand
P.829
treatlocalanesthetIctoxIcItyImmedIately(seeChapter17).ThIspoIntdeservesspecIal
emphasIs,partIcularlyInvIewofthefactthatmonItoredanesthesIacareIsoftenprovIded
totheelderlyordebIlItatedpatIentwhohasbeendeemedunfItforgeneralanesthesIa;
thesearethepatIentsmostlIkelytosufferadversereactIonstolocalanesthetIcdrugs.
EvenIftheanesthesIologIstdoesnotperformtheblockpersonally,heorsheIsInaunIque
posItIontofulfIllanImportantpreventIverolebyadvIsIngthesurgeonaboutthemost
approprIatevolume,concentratIon,andtypeoflocalanesthetIcdrugortechnIquetobe
used.
Table 31-6 Observer's Assessment of Alertness/Sedation Scale
RESPONSIVENESS SPEECH
FACIAL
EXPRESSION
EYES
COMPOSITE
SCORE
FespondsreadIlyto
namespokenIn
normaltone
Normal Normal Clear,noptosIs 5
(alert)
LethargIcresponse
tonamespokenIn
normaltone
|IldslowIng
or
thIckenIng
|Ild
relaxatIon
ClazedormIld
ptosIs(lessthan
halftheeye)
4
Fespondsonlyafter
nameIscalled
loudlyorrepeatedly
SlurrIngor
promInent
slowIng
|arked
relaxatIon
(slack
jaw)
Clazedand
markedptosIs
(halftheeyeor
more)
J
Fespondsonlyafter
mIldproddIngor
shakIng
Few
recognIzable
words
2
0oesnotrespondto
mIldproddIngor
shakIng

1
(asleep)
SystemIclocalanesthetIctoxIcItyoccurswhenplasmaconcentratIonsofdrugare
excessIvelyhIgh.PlasmaconcentratIonswIllIncreasewhentherateofentryofdrugInto
thecIrculatIonexceedstherateofdrugclearancefromthecIrculatIon.TheclInIcally
recognIzableeffectsoflocalanesthetIcsonthecentralnervoussystemareconcentratIon
dependent.AtlowconcentratIons,sedatIonandnumbnessofthetongueandcIrcumoral
tIssuesandametallIctastearepromInentfeatures.AsconcentratIonsIncrease,
restlessness,vertIgo,tInnItus,anddIffIcultyfocusIngmayoccur.HIgherconcentratIons
resultInslurredspeechandskeletalmuscletwItchIng,whIchoftenheraldtheonsetof
tonIcclonIcseIzures.
TheconductofmonItoredanesthesIacaremaymodIfytheIndIvIdual'sresponsetothe
potentIallytoxIceffectsoflocalanesthetIcadmInIstratIonandadverselyaffectthemargIn
ofsafetyofaregIonalorlocaltechnIque.Forexample,apatIentwIthcompromIsed
cardIovascularfunctIonmayexperIenceafurtherdeclIneIncardIacoutputdurIng
sedatIon.TheresultantreductIonInhepatIcbloodflowwIllreducetheclearanceoflocal
anesthetIcsthataremetabolIzedbythelIverandhaveahIghhepatIcextractIonratIo,
therebyIncreasIngthelIkelIhoodofachIevIngtoxIcplasmaconcentratIons.ApatIent
receIvIngsedatIonmayexperIencerespIratorydepressIonandasubsequentIncreaseIn
arterIalcarbondIoxIdeconcentratIon.HypercarbIaadverselyaffectsthemargInofsafety
Inseveralways.8yIncreasIngcerebralbloodflow,hypercarbIawIllIncreasetheamountof
localanesthetIcthatIsdelIveredtothebraIn,therebyIncreasIngthepotentIalfor
neurotoxIcIty.8yreducIngneuronalaxoplasmIcpH,hypercarbIaIncreasestheIntracellular
concentratIonofthecharged,actIveformoflocalanesthetIc,thusalsoIncreasIngIts
toxIcIty.naddItIon,hypercarbIa,acIdosIs,andhypoxIaallmarkedlypotentIatethe
cardIovasculartoxIcItyoflocalanesthetIcs.Furthermore,theadmInIstratIonofsedatIve
hypnotIcdrugsmayInterferewIththepatIent'sabIlItytocommunIcatethesymptomsof
ImpendIngneurotoxIcIty.However,theantIconvulsantpropertIesofbenzodIazepInesand
barbIturatesmayattenuatetheseIzuresassocIatedwIthneurotoxIcIty.nbothofthese
cIrcumstances,ItIspossIblethatthesymptomsofcardIotoxIcItywIllbethefIrstevIdence
thatanadversereactIonhasoccurred.Thus,approprIatetreatmentIsdelayedor
InadvertentIntravascularInjectIonIscontInuedbecauseoftheabsenceofanyclInIcal
evIdenceofneurotoxIcIty.CardIovasculartoxIcItyusuallyoccursatahIgherplasma
concentratIonthanneurotoxIcIty,butwhenItdoesoccur,ItIsusuallymuchmoredIffIcult
tomanagethanneurotoxIcIty.AlthoughcardIotoxIcItyIsusuallyprecededbyneurotoxIcIty,
ItmayoccurdenovowhenbupIvacaIneIsbeIngused.
Sedation and Analgesia by Nonanesthesiologists
AlthoughanesthesIologIstshavespecIfIctraInIngandexpertIsetoprovIdesedatIonand
analgesIa,InclInIcalpractIcetheseservIcesarefrequentlyprovIdedby
nonanesthesIologIsts.ThespecIfIcreasonsfornonanesthesIologIstInvolvementdIfferfrom
InstItutIontoInstItutIonandfromcasetocaseandIncludeconvenIence,avaIlabIlIty,and
schedulIngIssues;perceIvedlackofanesthesIologIstenthusIasm;perceIvedIncreasedcost;
andaperceIvedlackofbenefItconcernIngpatIentsatIsfactIonandsafetywhensedatIon
andanalgesIaareprovIdedbyanesthesIologIsts.0espIteourfrequentnonInvolvementIn
thesecases,anesthesIologIstsareIndIrectlyInvolvedInthecareofthesepatIentsbybeIng
requIredtopartIcIpateInthedevelopmentofInstItutIonalpolIcIesandproceduresfor
sedatIonandanalgesIa.ToassIstanesthesIologIstsInthIsprocess,anASAtaskforcehas
developedpractIceguIdelInesforsedatIonandanalgesIabynonanesthesIologIsts.
2
FourlevelsofsedatIonaredefInedIntheASApractIceguIdelInesandIncludemInImal
sedatIon,moderatesedatIon,deepsedatIon,andgeneralanesthesIa.ThepractIce
guIdelInesemphasIzethatsedatIonandanalgesIarepresentacontInuumofsedatIon
whereInpatIentscaneasIlypassIntoalevelofsedatIondeeperthanIntended.TheASA
Houseof0elegatesIssuedastatementonthIscontInuumofdepthofsedatIonorIgInallyIn
Dctober1999,andmostrecentlyamendedItInDctober2004.ThIsstatementcontaInsa
chartrepresentIngtheclInIcalprogressIonalongthIscontInuum(TableJ17).
96
When
monItorIngasedatedpatIentdurIngaprocedure,ItIsImportanttorecognIzewhena
patIentbecomesmoredeeplysedatedthanIntendedsothatthecareteamcanact
approprIatelytopreventcardIorespIratorycompromIse.
Table 31-7 Continuum of Depth of Sedation

MINIMAL
SEDATION
MODERATE
SEDATION
DEEP SEDATION
GENERAL
SEDATION
Purposeful
Purposeful
Responsiveness
Normal
response
toverbal
stImulatIon
responseto
verbalor
tactIle
stImulatIon
response
followIng
repeatedor
paInful
stImulatIon
Unarousable,
evenwItha
paInful
stImulus
Airway Unaffected
No
InterventIon
requIred
nterventIon
maybe
requIred
nterventIon
often
requIred
Spontaneous
ventilation
Unaffected Adequate
|aybe
Inadequate
Frequently
Inadequate
Cardiovascular
function
Unaffected
Usually
maIntaIned
Usually
maIntaIned
|aybe
ImpaIred
AdaptedfromASAHouseof0elegates:ContInuumof0epthofSedatIon,
www.asahq.org,2004.
P.8J0
TheguIdelInesemphasIzetheImportanceofpreprocedurepatIentevaluatIon,patIent
preparatIon,andapproprIatefastIngperIods.TheImportanceofcontInuouspatIent
monItorIngIsdIscussedInpartIcular,theresponseofthepatIenttocommandsasaguIde
tothelevelofsedatIon.TheapproprIatemonItorIngofpulmonaryventIlatIon,
oxygenatIon,andhemodynamIcsIsalsodIscussed,andrecommendatIonsaremadeforthe
contemporaneousrecordIngoftheseparameters.Thetaskforcestronglysuggeststhatan
IndIvIdualotherthanthepersonperformIngtheprocedurebeavaIlabletomonItorthe
patIent'scomfortandphysIologIcstatus.EducatIonandtraInIngofprovIdersIs
recommended.SpecIfIceducatIonalobjectIvesIncludethepotentIatIonofsedatIve
InducedrespIratorydepressIonbyconcomItantlyadmInIsteredopIoIds,adequatetIme
IntervalsbetweendosesofsedatIve/analgesIcstoavoIdcumulatIveoverdosage,and
famIlIarItywIthsedatIve/analgesIcantagonIsts.TheroutIneadmInIstratIonof
supplementaloxygenIsrecommended.AtleastonepersonwIthadvancedlIfesupportskIlls
shouldbepresentdurIngtheprocedure.ThIsIndIvIdualshouldhavetheabIlItytorecognIze
aIrwayobstructIon,establIshanaIrway,andmaIntaInoxygenatIonandventIlatIon.The
practIceguIdelInesrecommendthatapproprIatepatIentsIzeemergencyequIpmentbe
readIlyavaIlable,specIfIcallyIncludIngequIpmentforestablIshInganaIrwayanddelIverIng
posItIvepressureventIlatIonwIthsupplementaloxygen,emergencyresuscItatIondrugs,
andaworkIngdefIbrIllator.ThepresenceofrelIableIntravenousaccessuntIlthepatIentIs
nolongeratrIskforcardIorespIratorydepressIonwIllImprovesafety.Adequate
postprocedurerecoverycarewIthapproprIatemonItorIngmustbeprovIdeduntIl
dIscharge.CertaInhIghrIskpatIentgroups(e.g.,uncooperatIvepatIents,extremesofage,
severecardIac,pulmonary,hepatIc,renal,orcentralnervoussystemdIsease,morbId
obesIty,sleepapnea,pregnancy,andpatIentswhoabusedrugoralcohol)wIllbe
encountered,andtheguIdelInesrecommendthatpreprocedureconsultatIonwIth
anesthesIologIsts,cardIologIsts,pulmonologIsts,andsoforthbeperformedbefore
admInIstratIonofsedatIonandanalgesIabynonanesthesIologIsts.
ControversyexIstsregardIngtheleveloftraInIngrequIredfornonanesthesIologIststobe
credentIaledtoprovIdemoderateanddeepsedatIon.TheASAreleasedastatementIn
Dctober2005,amendedInDctober2006,suggestIngaframeworkforgrantIngprIvIleges
thatwIllhelpensurecompetenceofIndIvIdualswhoadmInIsterorsupervIsethe
admInIstratIonofmoderatesedatIon.
97
ThIsstatementsuggeststhatthepractItIoner
shouldcompleteformaltraInIngIn(1)thesafeadmInIstratIonofsedatIveandanalgesIc
drugsusedtoestablIshalevelofmoderatesedatIon,and(2)rescueofpatIentswhoexhIbIt
adversephysIologIcconsequencesofadeeperthanIntendedlevelofsedatIon.FollowIngIs
anexcerptfromseparateASAstatementconcernIngdeepsedatIonreleasedInDctober
2006.
98
Because of the significant risk that patients who receive deep sedation may enter a state
of general anesthesia, privileges to administer deep sedation should be granted only to
practitioners who are qualified to administer general anesthesia or to appropriately
supervised anesthesia professionals.
FInally,ItIsInstructIvetorevIewanexcerptfromthejoIntstatementreleasedIn2004by
theAmerIcanAssocIatIonofNurseAnesthetIstsandtheASA
46
:
Whenever propofol is used for sedation/anesthesia, it should be administered only by
persons trained in the administration of general anesthesia, who are not simultaneously
involved in these surgical or diagnostic procedures. This restriction is concordant with
specific language in the propofol package insert, and failure to follow these
recommendations could put patients at increased risk of significant injury or death.
Conclusion
ThroughtheuseofmonItoredanesthesIacare,anoftenterrIfyIngandpaInfulprocedure
canbemadesafeandcomfortableforthepatIent.|onItoredanesthesIacarepresentsan
opportunItyforourpatIentstoobserveusatwork.FortheanesthesIologIst,monItored
anesthesIacarepresentsanopportunItytoprovIdeamoreprolongedandIntImatelevelof
careandreassurancetoourpatIentsthatIsIncontrasttothemorelImItedexposurethat
occursdurIngandaftergeneralanesthesIa.DuraIrwaymanagementskIllsandourdaIly
practIceofapplIedpharmacologymakeusunIquelyqualIfIedtoprovIdethIsservIce.
|onItoredanesthesIacarepresentsuswIthanopportunItytodIsplaytheseskIllsand
IncreaseourrecognItIonInareasoutsIdetheoperatIngroom.TheavaIlabIlItyofdrugswIth
amorefavorablepharmacologIcprofIleallowsustotaIlorourtechnIquestoprovIdethe
specIfIccomponentsofanalgesIa,sedatIon,anxIolysIs,andamnesIawIthmInImalmorbIdIty
andtofacIlItateapromptrecovery.AsthepopulatIonages,IncreasIngnumbersofpatIents
wIllbecomecandIdatesformonItoredanesthesIacare.SIgnIfIcantadvancesInnonsurgIcal
fIelds(e.g.,InterventIonalradIology)wIllIncreasethenumberofproceduresthatare
IdeallyperformedundermonItoredanesthesIacare.tIsourresponsIbIlItytoclearly
demonstratetoournonanesthesIacolleaguesthatanesthesIologIstprovIdedmonItored
anesthesIacarecontrIbutestothebestoutcomeforourpatIents.fanesthesIologIstsare
notwIllIngorabletoprovIdetheseservIces,others,whoarelesswellqualIfIed,are
preparedtoassumethatrole.
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IntraoperatIverecallanddepthofpropofolInducedsedatIon.AnesthAnalg1997;84:185
95.KearseLA,|anbergP,ChamounNetal:8IspectralanalysIsofthe
electroencephalogramcorrelateswIthpatIentmovementtoskInIncIsIondurIng
propofol/nItrousoxIdeanesthesIa.AnesthesIology1994;81:1J65
96.AmerIcanSocIetyofAnesthesIologIsts:ContInuumofdepthofsedatIon,defInItIonof
generalanesthesIaandlevelsofsedatIon/analgesIa.www.asahq.org,2004
97.AmerIcanSocIetyofAnesthesIologIsts:StatementongrantIngprIvIlegesfor
admInIstratIonofmoderatesedatIontopractItIonerswhoarenotanesthesIa
professIonals.www.asahq.org,2006
98.AmerIcanSocIetyofAnesthesIologIsts:StatementongrantIngprIvIlegesto
nonanesthesIologIstspractItIonersforpersonallyadmInIsterIngdeepsedatIonor
supervIsIngdeepsedatIonbyIndIvIdualswhoarenotanesthesIaprofessIonals.
www.asahq.org,2006
Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJ2AmbulatoryAnesthesIa
ChapterJ2
Ambulatory Anesthesia
J. Lance Lichtor
Key Points
1. Procedures appropriate for ambulatory surgery are those associated
with postoperative care that is easily managed at home and with low
rates of postoperative complications that require intensive physician
or nursing management.
2. Whatever their age, ambulatory surgery is no longer restricted to
patients of ASA physical status I or II. Patients of ASA physical status
III or IV are appropriate candidates, providing their systemic
diseases are medically stable.
3. In the 2006 ASA guidelines, the authors state that for patients with
OSA, if a procedure is typically performed as an outpatient procedure
and local or regional anesthesia is used, that the procedure can also
be performed as an ambulatory procedure.
4. For adults, airflow obstruction has been shown to persist for up to 6
weeks after viral respiratory infections. For that reason, surgery
should be delayed if an adult presents with a URI until 6 weeks have
elapsed.
5. In 1999, the ASA published practice guidelines for preoperative
fasting. The guidelines allow a patient to have a light meal up to 6
hours before an elective procedure and support a fasting period for
clear liquids of 2 hours for all patients.
6. In a meta-analysis of peripheral nerve and centroneuraxial blocks
compared to general anesthesia, time until discharge from the
ambulatory surgery unit was no different for the three groups.
7. Postoperative pain control is best with regional techniques.
8. Nerve blocks using catheters can be placed before surgery that can
be used to provide analgesia after the operation.
9. After induction doses of propofol or thiopental, impairment after
thiopental can be apparent for up to 5 hours, but only for 1 hour
after propofol.
10. Although many factors affect the choice of agents for maintenance of
anesthesia, two primary concerns for ambulatory anesthesia are
speed of wake-up and incidence of postoperative nausea and
vomiting.
11. It is important to distinguish between wake-up time and discharge
time. Patients may emerge from anesthesia with desflurane and
nitrous oxide significantly faster than after propofol or sevoflurane
and nitrous oxide, though the ability to sit up, stand, and tolerate
fluids and the time to fitness for discharge may be no different.
12. Nausea, with or without vomiting, is probably the most important
factor contributing to a delay in discharge of patients and an increase
in unanticipated admissions of both children and adults after
ambulatory surgery.
13. In addition to the PACU, many ambulatory surgery centers in the
United States have another area, often known as a phase II recovery
room, where patients may stay until they are able to tolerate liquids,
walk, and/or void.
Place, Procedures, and Patient Selection
AmbulatorysurgeryoccursInavarIetyofsettIngs.SomecentersarewIthInahospItalorIn
afreestandIngsatellItefacIlItythatIseItherpartoforIndependentfromahospItal.The
IndependentfacIlItIesareoftenforprofItandnotlocatedInruralorInnercItyareas.Some
prIvatecompanIesacquIreorbuIldambulatoryfacIlItIesandthenworkusuallywIthlocal
surgeonswhobecomethecompany'saffIlIatedstaff.PhysIcIans'offIcesmayalsoservefor
procedures.FreestandIng,IndependentfacIlItIeswIllcontInuetogrowInnumberand
popularIty,althoughsomeconsumersprefercareInunItsaffIlIatedwIthhospItals.
AmajorconcernoffreestandIngambulatorysurgerygrowthIsthatthesurgerycentersmay
forcesomehospItalsoutofbusIness.ThIsIssuecanbepartIcularlyproblematIcInareasIn
whIchpopulatIondensItyormedIanIncomeIslow.HospItalsusuallyarenonprofItandcare
forpatIentswhobothcanandcannotpay.FreestandIngambulatoryfacIlItIesmayalsobe
nonprofItbutusuallydonotprovIdecharItycare.
SomesurgeonsmayworkexclusIvelyInafreestandIngfacIlItyandnotbeonthestaffofa
hospItal.ArequIrementforhospItalstaffprIvIlegesfrequentlyIsthataphysIcIanprovIdes
coverageforthehospItal'semergencydepartment.SomehospItalshavelostemergency
departmentcoverageforanentIresurgIcalspecIaltybecausethatsurgIcalspecIaltyworks
exclusIvelyInafreestandIngfacIlIty.
P.8J4
TheCentersfor|edIcareand|edIcaIdServIces(C|S)IstheU.S.federalagencythat
admInIsters|edIcare.C|S,InasetofregulatIonsthatweredIsclosedInJuly2007,
generallywIllpayambulatorycenters65ofwhathospItaloutpatIentsurgIcalfacIlItIes
receIve.FordevIceIntensIveprocedures,though,ambulatorysurgerycenterswIllbepaId
thesameashospItals.ForproceduresthatusuallyareperformedInanoffIce,ambulatory
surgerycenterswIllreceIvethelesserof65or|edIcare'sstandardphysIcIanpractIcefee.
ThIspaymentratewIllbephasedInfrom2008to2011.Thepaymentsystemmayforce
someambulatoryfacIlItIestodecIdewhethertheyaccept|edIcarepatIents.AtthattIme
also,C|Saddedmorethan700procedurestotheacceptablelIstofambulatory
procedures,makIngthetotalnumberofcoveredproceduresaboutJ,J00.
ProceduresapproprIateforambulatorysurgeryarethoseassocIatedwIthpostoperatIve
carethatareeasIlymanagedathomeandwIthlowratesofpostoperatIvecomplIcatIons
thatrequIreIntensIvephysIcIanornursIngmanagement.EstablIshIngalowrateof
postoperatIvecomplIcatIondependsontherelatIveaggressIvenessofthefacIlIty,surgeon,
patIent,andpayer.Forexample,proceduresthatpostoperatIvelyresultInIntensepaIn
maybetreatedwIthcontInuousregIonaltechnIquesthatarecontInuedathome,whereas
InothersettIngstheseproceduresarelImItedtoInpatIents.
ScorIngsystemshavebeendevelopedtohelpdetermInethelIkelIhoodofhospItal
admIssIonafterambulatorysurgery.DnesystemIsbasedonpatIentswhowerehospItalIzed
afterambulatorysurgery.
1
PatIentsreceIveonepoIntIftheyareolderthan65years,have
anoperatIngtImelongerthan120mInutes,cardIacdIagnoses,perIpheralvasculardIsease,
cerebrovasculardIsease,malIgnancy,posItIvehumanImmunodefIcIencyvIrusstatus;andIf
regIonalanesthesIaIsused.PatIentswhoreceIvegeneralanesthesIaget2poInts.PatIents
wIthascoreofJhave21tImestheoddsofhospItaladmIssIonofthosewIthascoreof0or
1,andpatIentswIthscoresJhaveJ2tImestheodds.
|anyfacIlItIesseta4hourlImItasacrIterIonforperformIngaprocedure.PatIents
undergoInglongerproceduresshouldhavetheIroperatIonsearlIerIntheday,prImarIly
becauseInmostfreestandIngfacIlItIes,theanesthesIologIstcannotleaveuntIlthelast
patIentIsdIscharged.TheneedfortransfusIonIsalsonotacontraIndIcatIonfor
ambulatoryprocedures.SomepatIentsundergoIngoutpatIentlIposuctIon,forexample,are
gIvenautologousblood.8ecauseofbloodbankIngIssues,though,ambulatoryprocedures
thatrequIretheuseofabloodbankaremorecommonlyperformedInlargerfacIlItIes.
FreestandIngdIalysIsfacIlItIescommonlyreceIvebloodshIppedfromabloodbanklocated
elsewhereandthesamecanbesetupwIthfreestandIngambulatorysurgeryfacIlItIes.The
keyIstohaveproperproceduresestablIshed.
SomehavewonderedaboutthesafetyofperformInglIposuctIonInanoffIce,followIng
reportsofdeathaftertheprocedureInFlorIda.ThrombophlebItIswasthecauseofdeathIn
9of11patIentswhodIedInFlorIdafrom2000to2006afterabdomInoplastyand
lIposuctIon.
2
nasurveyof7,010patIentsundergoIngabdomInallIposuctIon,theIncIdence
ofdeepveInthrombosIswas0.04andthatofpulmonaryemboluswas0.02.
J
tIshoped
thatorganIzatIonswIllsoonprovIdebetterguIdelInesforstratIfyIngrIskandstrategIesto
preventvenousthromboembolIsmafterlIposuctIonsurgery.
nfantswhosepostconceptualageIs46weeks,orIftheIrageIs60weeksbuttheyalso
haveahIstoryofchronIclungorneurologIcdIsease,orwhohaveanemIa(hemoglobIn6
mmol/L)shouldbemonItoredfor12hoursaftertheIrprocedurebecausetheyareatrIskof
developIngapneaevenwIthoutahIstoryofapnea.
4
nfantsolderthan46weeksand60
weekswIthoutdIseaseshouldbemonItoredfor6hoursaftertheIrprocedure.Somehave
foundthatspInalanesthesIawIthouttheuseofotherdrugsIntraoperatIvelyor
postoperatIvelyIsnotassocIatedwIthapnea;althoughInonestudyof62prematureand
formerprematureInfantswhounderwentsurgeryusIngspInalanesthesIa,postoperatIve
apneawasseenIn5of55prematureInfants.
5
ntravenouscaffeIne,10mg/kg,mayhelp
preventapneaInInfants(seealsoChapter44).
AttheotherextremeoflIfe,advancedagealoneIsnotareasontodIsallowsurgeryInan
ambulatorysettIng.Age,however,doesaffectthepharmacokInetIcsofdrugs.Evenshort
actIngdrugssuchasmIdazolamandpropofolhavedecreasedclearanceInolder
IndIvIduals.naddItIon,asprevIouslymentIoned,Increasedagemaybeafactorthat
affectsthelIkelIhoodofunantIcIpatedadmIssIon.
AdmIssIon,byItself,IsnotnecessarIlybadIfItresultsInabetterqualItyofcareor
uncoverstheneedformoreextensIvesurgery.WIthproperpatIentselectIonfor
ambulatoryprocedures,whIchareusuallyelectIve,theIncIdenceofreadmIssIonshouldbe
verylow.|ostmedIcalproblemsthatolderIndIvIdualsmayexperIenceafterambulatory
proceduresarenotrelatedtopatIentage,buttospecIfIcorgandysfunctIon.Forthat
reason,allIndIvIduals,whetheryoungorold,deserveacarefulpreoperatIvehIstoryand
physIcalexamInatIon.
WhatevertheIrage,ambulatorysurgeryIsnolongerrestrIctedtopatIentsofAmerIcan
SocIetyofAnesthesIologIsts(ASA)physIcalstatusor.PatIentsofASAphysIcalstatus
or7areapproprIatecandIdates,provIdIngtheIrsystemIcdIseasesaremedIcallystable.n
arevIewofASApatIentswhowerecomparedwIthASAorpatIentsundergoIng
outpatIentsurgery,nosIgnIfIcantIncreaseInunplannedadmIssIons,unplannedcontact
wIthhealthprofessIonals,andpostoperatIvecomplIcatIonswasfound.
6
CertaInly,notall
lIfethreatenIngdIseaseshavebeenstudIedastohowapproprIatesuchpatIentswIththese
dIseasesmIghtbeIftheyweretoundergoambulatorysurgery.Yet,ofthosepatIentswIth
suchdIseaseswhohavebeenstudIed,thedIseaselabelItselfdoesnotseemtoprecludean
ambulatorysurgIcalprocedure.
PatIentswhoareobeserepresentaspecIalsItuatIon.TheyarenotmorelIkelytohave
adverseoutcomes,althoughtheyhaveahIgherIncIdenceofobstructIvesleepapnea(DSA).
narevIewof258morbIdlyobesepatIentswhounderwentoutpatIentsurgery,compared
wIthpatIentswhowerenotmorbIdlyobese,therewasnotagreaterIncIdenceof
unplannedadmIssIons,mInorcomplIcatIons,orunplannedcontactwIthhealthcare
professIonals.
7
nanotherstudy,J,900patIentsreceIvedarIskfactorquestIonnaIreafter
ambulatorysurgery;symptomswerenotrelatedtobodymassIndex.
8
TheASAhas
publIshedpractIceguIdelInesfortheperIoperatIvemanagementofpatIentswIthDSA.
9
n
thoseguIdelInes,theauthorsstatethatforpatIentswIthDSA,IfaprocedureIstypIcally
performedasanoutpatIentprocedureandlocalorregIonalanesthesIaIsused,the
procedurecanalsobeperformedasanambulatoryprocedure.YetforpatIentswhoareat
IncreasedrIskforperIoperatIvecomplIcatIons,theprocedureshouldnotbeperformedIna
freestandIngambulatorysurgeryfacIlIty.TableJ21presentsamorecompletelIstof
recommendedambulatoryproceduresforpatIentswIthDSA,basedontheASAguIdelInes.
PatIentswhoundergoambulatorysurgeryshouldhavesomeonetotakethemhomeand
staywIththemafterwardtoprovIdecare.8eforetheprocedure,thepatIentshould
receIveInformatIonabouttheprocedureItself,whereItwIllbeperformed,laboratory
studIesthatwIllbeordered,anddIetaryrestrIctIons.ThepatIentmustunderstandthathe
orshewIllbegoInghomeonthedayofsurgery.ThepatIent,orsomeresponsIbleperson,
mustensureallInstructIonsarefollowed.Dnceathome,thepatIentmustbeableto
toleratethepaInfromtheprocedure,assumIngadequatepaIntherapyIsprovIded.The
majorItyofpatIentsaresatIsfIedwIthearlydIscharge,althoughafewpreferalongerstay
InthehospItal.PatIentsforcertaInproceduressuchaslaparoscopIccholecystectomyor
transurethralresectIonoftheprostateshouldlIveclosetotheambulatory
P.8J5
facIlItybecausepostoperatIvecomplIcatIonsmayrequIretheIrpromptreturn.
FeasonabledIstanceandtImeforthepatIenttogetcareIfproblemsarIsearenoteasIly
defIned.ThIsIssuemustbeaddressedbyeachfacIlItyandbyeachpatIent,andalso
dependsonthetypeofsurgerytobeperformed.
Table 32-1 Consultant Opinions Regarding Procedures that may be
Performed Safely on an Outpatient Basis for Patients at Increased
Perioperative Risk From Obstructive Sleep Apnea
Type of Surgery/Anesthesia Consultant Opinion
SuperfIcIalsurgery/localorregIonalanesthesIa Agree
SuperfIcIalsurgery/generalanesthesIa EquIvocal
AIrwaysurgery(adult,e.g.,UPPP) 0Isagree
TonsIllectomyInchIldrenJyearsold 0Isagree
TonsIllectomyInchIldrenJyearsold EquIvocal
|InororthopaedIcsurgery/localorregIonalanesthesIa Agree
|InororthopaedIcsurgery/generalanesthesIa EquIvocal
CynecologIclaparoscopy EquIvocal
LaparoscopIcsurgery,upperabdomen 0Isagree
LIthotrIpsy Agree
UPPP,uvulopalatopharyngoplasty.
FromCrossJ8,8achenbergKL,8enumofJLetal:PractIceguIdelInesforthe
perIoperatIvemanagementofpatIentswIthobstructIvesleepapnea:Areportby
theAmerIcanSocIetyofAnesthesIologIstsTaskForceonPerIoperatIve
|anagementofpatIentswIthobstructIvesleepapnea.AnesthesIology2006;104:
1081,wIthpermIssIon.
Preoperative Evaluation and Reduction of Patient Anxiety
EachoutpatIentfacIlItyshoulddevelopItsownmethodofpreoperatIvescreenIngtobe
conductedbeforethedayofsurgery.ThepatIentmayvIsItthefacIlItyorstaffmembers
maytelephonetoobtaInnecessaryInformatIonaboutthepatIent,IncludIngacomplete
medIcalhIstoryofthepatIentandfamIly,themedIcatIonsthepatIentIstakIng,andthe
problemsthepatIentorthepatIent'sfamIlymayhavehadwIthprevIousanesthetIcs.na
studyoftheusefulnessofapreoperatIvescreenIngtelephonecall,patIentswerelesslIkely
tocancelsurgeryIftheyhadbeenscreenedbeforehand.
10
ThescreenIngmayuncoverthe
needfortransportatIontothefacIlItyortheneedforchIldcare.TheprocessalsoprovIdes
thestaffwIthanopportunItytoremIndpatIentsofarrIvaltIme,suItableattIre,and
dIetaryrestrIctIons(e.g.,nothIngtoeatordrInkaftermIdnIght,nojewelryormakeup).
StaffmemberscandetermInewhetheraresponsIblepersonIsavaIlabletoescortthe
patIenttoandfromthefacIlItyandcareforthepatIentathomeaftersurgery.The
screenIngIstheIdealtImefortheanesthesIologIsttotalkwIththepatIent,butIfthatIs
notpossIble,theanesthesIologIstmayrevIewthescreenIngrecordtodetermInewhether
addItIonalevaluatIonbyotherconsultantsIsnecessaryandwhetherlaboratorytestsmust
beobtaIned.PatIentswhodonotshowupfortheIrclInIcappoIntmentmaybemorelIkely
nottoshowupfortheIroperatIon.
11
AutomatedhIstorytakIngmayalsoprovebenefIcIaldurIngthescreenIngofapatIent.
ComputerIzedquestIonnaIresorchecklIstswIthplastIcoverlaysautomatethetakIngof
patIenthIstorIes,flagproblemareas,andsuggestlaboratoryteststobeordered.Such
devIcescanalsobeusedInasurgeon'soffIce,bothtoguIdethesurgeonIntheselectIonof
laboratorytestsandtoserveasamedIcalsummaryfortheanesthesIologIst.SuchdevIces
arepartIcularlyusefultocontrolthecostofpreoperatIvetestIng.Theyenabletest
orderIngbasedonInformatIonobtaInedfromapatIent'sresponsestohealthquestIons,thus
elImInatIngrequestsforteststhatarenotwarrantedbyhIstoryorphysIcalexamInatIon.
Upper Respiratory Tract Infection
Foradults,aIrflowobstructIonhasbeenshowntopersIstforupto6weeksaftervIral
respIratoryInfectIons.Forthatreason,surgeryshouldbedelayedIfanadultpresentswIth
anupperrespIratoryInfectIon(UF)untIl6weekshaveelapsed.nthecaseofchIldren,
whethersurgeryshouldbedelayedforthatlengthoftImeIsquestIonable.nonestudyof
1,078chIldren1monthto18yearsofage,rIskfactorsforadverserespIratoryeventsIn
chIldrenwIthUFswereexamIned.
12
TheauthorscouldfIndnodIfferenceInlaryngospasm
orbronchospasmIfthechIldrenhadactIveUFs,aUFwIthIn4weeks,ornosymptoms.8ut
chIldrenwIthactIveorrecentUFshadmoreepIsodesofbreathholdIng,IncIdencesof
desaturatIon90,andmorerespIratoryeventscomparedwIthchIldrenwIthoutsymptoms
(FIg.J21).AlthoughacasemaybecancelledbecauseachIldIssymptomatIc,thechIld
maydevelopanotherUFwhentheprocedureIsrescheduled.nchIldren,UFhasnotbeen
showntobeassocIatedwIthanIncreasedlengthofstayInthehospItalafteraprocedure.
ndependentrIskfactorsforadverserespIratoryeventsInchIldrenwIthUFsIncludeuseof
anendotrachealtube(versususeofalaryngealmaskaIrway[L|A]orfacemask),hIstoryof
prematurIty,hIstoryofreactIveaIrwaydIsease,hIstoryofparentalsmokIng,surgery
InvolvIngtheaIrway,presenceofcopIoussecretIons,andnasalcongestIon.Cenerally,Ifa
patIentwIthaUFhasanormalappetIte,doesnothaveafeveroranelevatedrespIratory
rate,anddoesnotappeartoxIc,ItIsprobablysafetoproceedwIththeplannedprocedure.
Restriction of Food and Liquids Before Ambulatory Surgery
TodecreasetherIskofaspIratIonofgastrIccontents,patIentsareroutInelyaskednotto
eatordrInkanythIng(nonperos[NPD]
P.8J6
ornothIngbymouth)foratleast6to8hoursbeforesurgery.However,prolongedfastIng
canbedetrImentaltoapatIent.ndeed,InonestudyInfantswhofastedlongerhadgreater
dropsInIntraoperatIvebloodpressure(FIg.J22).
1J
NotrIalhasshownthatashortened
fluIdfastIncreasestherIskofaspIratIon.CastrIcvolumesareactuallylesswhenpatIents
areallowedtodrInksomefluIdsbeforesurgery.AdmIttedly,though,themajorItyof
studIeshavenotbeenspecIfIcallyperformedInIndIvIdualswhoareatanIncreasedrIskfor
aspIratIon.AnexcellentrevIewofthIstopIchasbeenpublIshed.
14
Figure 32-1.AdverserespIratoryeventsaresImIlarbetweenchIldrenwIthanupper
respIratoryInfectIon(UF)andarecentUF,andthIssImIlarItypersIstsforatleast4
weeksaftertheUF.
12
*p0.05versusnoUF.(FeprIntedfromTaItAF,|alvIyaS,
7oepelLewIsTetal:FIskfactorsforperIoperatIveadverserespIratoryeventsIn
chIldrenwIthupperrespIratorytractInfectIons.AnesthesIology2001;95:299,wIth
permIssIon.)
Figure 32-2.8loodpressureIslowerInchIldren1to6monthsofagewhofastmore
than8hours,comparedwIththosewhofastforlessthan4hours.
1J
llustratedare
changesInsystolIcbloodpressurefrombaselInetothetImewhen2mInImumalveolar
concentratIonhalothanewasreachedIn250InfantsandchIldren.*p0.05versus0to
4hourfastInggroup.(FeprIntedfromFrIesenFH,WurlJL,FrIesenF|:0uratIonof
preoperatIvefastcorrelateswItharterIalbloodpressureresponsetohalothaneIn
Infants.AnesthAnalg2002;95:1572,wIthpermIssIon.)
n1999,theASApublIshedpractIceguIdelInesforpreoperatIvefastIng.TheguIdelInes
allowapatIenttohavealIghtmealupto6hoursbeforeanelectIveprocedureandsupport
afastIngperIodforclearlIquIdsof2hoursforallpatIents.CoffeeandteaareconsIdered
clearlIquIds.CoffeeandteadrInkersshouldfollowfastIngguIdelInesbutshouldbe
encouragedtodrInkcoffeeprIortotheIrprocedurebecausephysIcalsIgnsofwIthdrawal
(e.g.,headache)caneasIlyoccur.tIsnotclearIftheguIdelInesshouldapplytopatIents
wIthdIabetesordyspepsIa.ThereIssomeevIdencethatshorterperIodsofpreoperatIve
fastIngareaccompanIedbylesspostoperatIvenauseaandvomItIng(PDN7).Yet,ItIs
unclearwhetherrehydratIondurIngsurgeryIsequIvalenttoashorterfastbeforesurgeryIn
relatIontoPDN7.
ToensurepatIentsareoptImallymedIcallymanagedbeforetheIroutpatIentsurgery,gIven
thefactthatclearlIquIdscanbetakenupto2hoursbeforesurgery,patIentsshouldbe
encouragedtotaketheIrchronIcmedIcatIons.
Anxiety Reduction
Clearly,somepatIentsscheduledtoundergosurgeryareanxIous,andtheyareprobably
anxIouslongbeforetheycometotheoutpatIentarea.PreoperatIvereassurancefrom
nonanesthesIastaffandprovIdIngbookletswIthInformatIonabouttheprocedurealso
reducepreoperatIveanxIety.However,useofbookletsIslesseffectIvethanapreoperatIve
vIsItbytheanesthesIologIst.AudIovIsualInstructIonsalsoreducepreoperatIveanxIety.
However,notalloutpatIentsareanxIous.Forexample,althoughInsomnIaandanxIetyare
related,InastudyofsleepcharacterIstIcsofoutpatIentsbeforeelectIvesurgery,no
dIfferencesInsleepqualItywerefoundbetweenpatIentsbeforesurgeryandacommunIty
controlgroup,
15
ndeed,physIcIansoftentendtooverestImatethelevelofanxIetythat
patIentsareactuallyexperIencIng.
16
SomeoperatIonscancertaInlygeneratemoreanxIety
thanothers.fIndoubtaboutpatIentanxIety,askthepatIent.
LIkeadults,chIldrenshouldhavesomeIdeaofwhattoexpectdurIngaprocedure.8ut
muchofachIld'sanxIetybeforesurgeryconcernsseparatIonfromaparentorparents.A
chIldIsmorelIkelytodemonstrateproblematIcbehavIorfromthetImeofseparatIonfrom
parentstoInductIonofanesthesIaIfaprocedurehasnotbeenexplaInedpreoperatIvely.
ParentsandchIldrenneedtobeInvolvedInsomepreoperatIvedIscussIonstogethersothe
anxIetyoftheparentsIsnottransmIttedtothechIld.ThetransmIssIonofanxIetyIsat
leastasproblematIcasIstheseparatIonItself(e.g.,experIencesofchIldrenbeIngleftwIth
babysItters).ftheparentsarecalmandcaneffectIvelymanagethephysIcaltransfertoa
warmandplayfulanesthesIologIstornurse,premedIcatIonIsnotnecessary.SemIsedatIon
maybeawkward,andrecoveryafterpremedIcatIonmaybeprolonged.
fachIldIsaccompanIedbyaparentdurIngtheInductIonofanesthesIa,thechIld'sanxIety
canbereduced.SomeparentscanbecomeupsetwhentheyseetheIranesthetIzedchIld,
whoappearstobedead,albeItbreathIngandwIthabeatIngheart.SeparatIonanxIetyon
thepartoftheparentsIsprobablynodIfferentIfthechIldIsawakeorasleep.Those
chIldrenwhohavepreoperatIveInstructIonsandcoachIngbothforthemselvesandtheIr
famIlIes,andtheIrparent/spresentdurIngInductIonhavelessanxIetypreoperatIvely,less
postoperatIvedelIrIum,shorteneddIschargetImeaftersurgery,andreducedanalgesIc
consumptIonaftersurgery.
17
FamIlycenteredcarehasbecomepopularandIsusefulfordecreasIngpreoperatIveanxIety
InchIldren.nonestudy,408chIldrenundergoIngelectIveambulatorysurgeryreceIved
eItherstandardcare,hadaparentpresentdurIngInductIon,receIvedoralmIdazolamprIor
tosurgery,orreceIvedfamIlycenteredcareprIortosurgery.
17
FamIlycenteredtherapy
consIstedofprovIdIngthefamIlIesofchIldrenwIthavIdeotape,threepamphlets,anda
maskpractIcekItdurIngtheIrpreoperatIvevIsIt.DnepamphletwasdesIgnedtohelp
parentsunderstandwhattoexpectonthedayofsurgeryandsomerecommendatIonsfor
themtodecreasetheIranxIetyandtheIrchIld'sanxIety.AnothergavethemInstructIonsfor
dIstractIngtheIrchIldonthedayofsurgery.AthIrdgaveInstructIonstoteachthechIld
whattodowhenIntheoperatIngroom(DF),suchasgettIngontheDFbed,andusIngthe
maskforInductIon.ParentswerealsogIvenanInductIonmask,andahaIrnet.Dntheday
ofsurgery,chIldrenInthefamIlycenteredtherapygroupweregIventoys,desIgnedtobe
ageapproprIateanddIstractIng(e.g.,puzzles,braInteasers),unlIketheotherchIldrenwho
weresImplygIventoys.PatIentsInthefamIlycenteredgroup,comparedwIththeother
threegroups,preoperatIvelywerelessanxIous.ParentswerealsolessanxIous.naddItIon,
thepatIentshadlesssevereemergencedelIrIumsymptoms,neededlessfentanyl
postoperatIvely,andweredIschargedearlIer.
Managing the Anesthetic: Premedication
TheoutpatIentIsnotthatdIfferentfromtheInpatIentundergoIngsurgery.nboth,
premedIcatIonIsusefultocontrolanxIety,postoperatIvepaIn,nauseaandvomItIng,and
toreducetherIskofaspIratIondurIngInductIonofanesthesIa.8ecausetheoutpatIentIs
goInghomeonthedayofsurgery,thedrugsgIvenbeforeanesthesIashouldnothInder
recoveryafterward.
P.8J7
|ostpremedIcantsdonotprolongrecoverywhengIvenInapproprIatedosesfor
approprIateIndIcatIons,althoughdrugeffectsmaybeapparentevenafterdIscharge.
Benzodiazepines
AlthoughhIstorIcallymanyclassesofdrugs(e.g.,barbIturates,antIhIstamInes)havebeen
usedtoreduceanxIetyandInducesedatIon,benzodIazepInesarecurrentlythedrugsmost
commonlyused.|IdazolamIsthebenzodIazepInemostcommonlyusedpreoperatIvely.t
canbeusedIntravenouslyandorally.nadults,ItcanbeusedtocontrolpreoperatIve
anxIetyand,durIngaprocedurealoneorIncombInatIonwIthotherdrugs,forIntravenous
sedatIon.ForchIldren,oralmIdazolamIndosesassmallas0.25mg/kgproduceseffectIve
sedatIonandreducesanxIety.
18
WIththIsdose,mostchIldrencanbeeffectIvelyseparated
fromtheIrparentsafter10mInutesandsatIsfactorysedatIoncanbemaIntaInedfor45
mInutes.0Ischargemaybedelayed,though,whengIvenbeforeashortprocedure.Dral
dIazepamIsusefultocontrolanxIetyInadultpatIents,eItherthedaybeforesurgeryorthe
dayofsurgeryandbeforeanIntravenouslInehasbeenInserted.
FatIgueassocIatedwIththeeffectsofanxIolytIcsmaydelayorpreventthedIschargeof
patIentsonthedayofsurgery,althoughmorefrequentlypatIentsarenotdIscharged
becauseoftheeffectsoftheoperatIon.WIthregardtoanesthesIaeffects,patIents
normallystayInthehospItalnotbecausetheyaretoosleepybutbecausetheyare
nauseous.nadults,partIcularlywhenmIdazolamIscombInedwIthfentanyl,patIentscan
remaInsleepyforupto8hours(FIg.J2J).
19
AlthoughchIldrenmaybesleepIerafteroral
mIdazolam,dIschargetImesarenotaffected.
Figure 32-3.PatIentscanremaInsleepyafterreceIvIngmIdazolamandfentanyl,even
8hoursafterdrugadmInIstratIon.
19
TheabscIssarepresentstIme(hours)after
sedatIon.TheordInaterepresentssleeplatency(I.e.,tImetofallasleep).0ataarethe
meantImetofallasleep.AnIndIvIdualIssleepIerIflesstImeIsrequIredtofallasleep.
SubjectsreceIvIngthemIdazolamandfentanylcombInatIonweremuchsleepIerthan
thesamesubjectsreceIvIngothertypesofsedatIon.AlthoughnotseenInthefIgure,
upto8hoursaftersedatIon,somesubjectswerestIllsleepIerthanbeforethey
receIveddrug.(FeprIntedfromLIchtorJL,AlessIF,Lane8S:Sleeptendencyasa
measureofrecoveryafterdrugsusedforambulatorysurgery.AnesthesIology2002;96:
Atproperdoses,neIthermIdazolamnordIazepamplacepatIentsatanyaddItIonalrIskfor
cardIovascularandrespIratorydepressIon.0ecreasedoxygensaturatIonhasbeenreported
afterInjectIonofmIdazolam.FoutIneadmInIstratIonofsupplementaloxygenwIthor
wIthoutcontInuousmonItorIngofarterIaloxygenatIonIsrecommendedwhenever
benzodIazepInesaregIvenIntravenously.ThIsprecautIonIsImportantnotonlywhen
mIdazolamIsgIvenasapremedIcant,butalsowhenItIsusedaloneorwIthotherdrugsfor
conscIoussedatIon.ThepotentIalforamnesIaafterpremedIcatIonIsanotherconcern,
especIallyforpatIentsundergoIngambulatorysurgery.AnterogradeamnesIacertaInly
occurs.AlthoughbenzodIazepInesfacIlItateretrogradememory,Inonestudytherewasno
ImmedIateretrogradeamnesIaafterIntravenousmIdazolam,2to10mg.
20
For
benzodIazepInes,theeffectsonmemoryareseparatefromtheeffectsonsedatIon.n
addItIon,amnesIaIsnotsImplyaneffectofdrugadmInIstratIonbut,amongotherfactors,
ItIsalsoafunctIonofstImulusIntensIty.
Opioids and Nonsteroidal Analgesics
DpIoIdscanbeadmInIsteredpreoperatIvelytosedatepatIents,controlhypertensIondurIng
trachealIntubatIon,anddecreasepaInbeforesurgery.|eperIdIne(butnotmorphIneor
fentanyl)IssometImeshelpfulIncontrollIngshIverIngIntheDForthepostanesthesIacare
unIt(PACU),althoughtreatmentIsusuallyInstItutedatthetImeofshIverIngandnotIn
antIcIpatIonoftheevent.TheeffectIvenessofopIoIdsInrelIevInganxIetyIscontroversIal
andprobablynonexIstent,partIcularlyInadults.
DpIoIdsareusefulIncontrollInghypertensIondurIngtrachealIntubatIon.DpIoId
premedIcatIonpreventsIncreasesInsystolIcpressureInadosedependentfashIon.After
trachealIntubatIon,systolIc,dIastolIc,andmeanarterIalbloodpressuressometImes
decreasebelowbaselInevalues.
PreoperatIveadmInIstratIonofopIoIdsornonsteroIdalantIInflammatorydrugs(NSA0s)
maybeusefulforcontrollIngpaInIntheearlypostoperatIveperIod.nonestudy,
controlledreleaseoxycodone,10mg,whengIvenbeforesurgery,waseffectIveIn
managIngpaInafterlaparoscopIctuballIgatIonsurgeryandwasevenassocIatedwIthless
PDN7.
21
nasImIlarstudyofpatIentsundergoInglaparoscopIctuballIgatIonsurgery,
though,premedIcatIonwIthcontrolledreleaseoxycodone,15mg,dIdnotImprovethe
postoperatIvepaInmanagement.
22
CelecoxIb,upto400mg,IseffectIveInreducIngpostoperatIvepaIn.
2J
buprofenor
acetamInophencanbegIvenrectallytochIldrenaroundthetImeofInductIon.frectal
acetamInophenIsusedInchIldren,anInItIalloadIngdoseof40mg/kgIsapproprIate;
subsequentdosesof20mg/kgevery6hourscanbeused.
24
And,whenpreoperatIverectal
acetamInophenIscombInedwIthketoprofen,partIcularlyformorepaInfulprocedures,
postoperatIvepaInIslessthanwhenthedrugsaregIvenIndIvIdually.
25
PreoperatIvesedatIonIsnotneededforeverypatIent.ThefollowIngIsourpractIcewhen
patIentsrequIredrugstorelIeveanxIety.ForthepatIentwhohasbeenseenatleast24
hoursbeforeascheduledprocedureandexpressesadesIreformedIcatIontorelIeve
anxIetyorhasanxIetythatcannotberelIevedwIthcomfortIng,oraldIazepam,2to5mg
per70kgbodyweIght,IsprescrIbedforthenIghtbeforeandat6:00A|onthedayof
surgery(evenIfsurgeryIsscheduledfor1:00P|orlater).ForpatIentsseenforthefIrst
tImeInthepreoperatIveholdIngareawhoseemtoneedmedIcatIon,mIdazolam,0.01
mg/kg,IsadmInIsteredIntravenously,orthepatIentIsbroughtIntotheDFandpropofol,
0.7mg/kg,IsInjectedIntravenously.ForchIldren,whennecessary,oralmIdazolam,0.25
mg/kg,Is
P.8J8
admInIsteredInthepreoperatIveholdIngarea.WhenthechIldIsasleep,acetamInophen,
40mg/kgrectally,andketorolac,0.5mg/kgIntravenously,areadmInIsteredprIorto
InItIatIonofsurgery.
Intraoperative Management: Choice of Anesthetic Method
ThereareseveralchoIcesamonganesthetIcmethods:generalanesthesIa,regIonal
anesthesIa,andlocalanesthesIa.FegIonalandlocalanesthesIacanbeusedwIthorwIthout
sedatIon.ExceptforobstetrIccases,forwhIchregIonalanesthesIamaybesaferthan
generalanesthesIa,allthreetypesareotherwIseequallysafe.However,evenfor
experIencedanesthesIologIsts,thereIsafaIlurerateassocIatedwIthregIonalanesthesIa.
CertaInly,someproceduresarepossIbleonlywIthageneralanesthetIc.Forothers,the
preferenceofpatIents,surgeons,oranesthesIologIstsmaydetermIneselectIon.Thecostof
sedatIonIsusuallylessthanthecostofageneralorregIonalanesthetIc.nacomparIsonof
costsforpatIentsundergoIngInguInalhernIasurgeryIntenhospItalsInSweden,for
example,IntraoperatIveandpostoperatIvecostswereleastInpatIentswhoreceIvedlocal
anesthesIa.
26
ThosepatIentswhoreceIvedlocalanesthesIaalsospentlesstImeIntheDF,
hadlesspostoperatIvepaIn,andtheleastproblemswIthurInatIon.Thethreetypesof
anesthesIa,though,arenotanoptIonforalloperatIons.
TImetorecoverymayalsoInfluencethechoIceofanesthetIcmethod.nastudyof
patIentsundergoIngprostatebIopsy,dIschargeaftergeneralanesthesIawasfasterthan
afterspInalanesthesIa.
27
Conversely,InastudyofpatIentsundergoIngshouldersurgery
whoreceIvedeIthergeneralorregIonalanesthesIa,patIentswhoreceIvedregIonal
anesthesIaweremoreoftenabletobypassfIrststagerecovery,hadlesspaIn,wereableto
ambulate,andwereelIgIblefordIschargeearlIerthanthegeneralanesthesIagroup.
28
na
metaanalysIsofperIpheralnerveandcentroneuraxIalblockscomparedwIthgeneral
anesthesIa,tImeuntIldIschargefromtheambulatorysurgeryunItwasnodIfferentforthe
threegroups.
29
nterestInglyalso,postoperatIvenauseaInthecentroneuraxIalblockgroup
wasnotdIfferentfromthegeneralanesthesIagroup.nastudyofpatIentsundergoIng
spInalorgeneralanesthesIaforkneesurgery,recoverytImeswereequIvalent,butafter
spInalanesthesIa,postoperatIvesIdeeffectswerefewer.
J0
WhenapplyIngstudIesof
regIonalanesthesIatoeverydaypractIce,rememberthatthestudIescomefromcenters
wheretheauthorsareexperIencedInperformIngregIonalanesthesIaandthatmIghtnotbe
thecaseInotherpractIces.
Forsomeproceduressuchasarthroscopy,patIentsmIghtpreferaregIonalanesthetIc
sImplybecausetheyarecurIousandwanttowatchthesurgery.
J1
PostoperatIvepaInIsless
afterregIonalanesthesIa,whIchIsdIscussedInmoredetaIllaterInthIssectIon.Also,wIth
regIonalanesthesIaorsedatIon,someofthesIdeeffectsofgeneralanesthesIacanbe
avoIded,althoughnoformofmedIcalcareIswIthoutsIdeeffects.Wheneverdrugsare
gIventhataffectmemory,patIentsmIghtcomplaInthattheydonotremembereventsthat
occuraftertheprocedure.AlthoughwIthregIonalanesthesIamoretImeIsrequIredto
placeablockthanIttakestoInduceageneralanesthetIc,ametaanalysIsofseveral
studIesshowedthIsIncreasedtImetobeonaveragenomorethan8to9mInutes.
29
none
surveyoforthopaedIcsurgeons,themajorItyofsurgeonswhodIrecttheIrpatIents'choIce
ofanesthetIcchooseregIonalanesthesIa,althoughthepotentIaldelayInestablIshInga
blockandperceIvedunpredIctablesuccessdetractedfromtheIrenthusIasmwIthregIonal
anesthesIa(FIg.J24).
J2
Figure 32-4.DperatIngroom(DF)delaysarethemajorreasonsorthopaedIcsurgeons
donotfavorregIonalanesthesIa.
J2
CA,generalanesthesIa.(FeprIntedfromDldman|,
|cCartneyCJ,LeungAetal:AsurveyoforthopedIcsurgeons'attItudesandknowledge
regardIngregIonalanesthesIa.AnesthAnalg2004;98:1486,wIthpermIssIon.)
DneadverseeffectassocIatedwIthspInalanesthesIaIsheadache,butheadachesarealso
experIencedbypatIentsaftergeneralanesthesIa.TheIncIdenceofheadacheaftereIther
technIquemaybesImIlarespecIallywhensmallerspInalneedlesareused.PatIentsmay
experIencebackacheafterspInalanesthesIa,althoughsorethroatandnauseaarehIgher
aftergeneralanesthesIathanspInaltype.LargerstudIesofpatIentsundergoIngambulatory
surgeryareneededthatcomparesedatIonwIthregIonalandgeneralanesthesIa.
Regional Techniques
LocalanesthesIaandregIonalanesthesIahavelongbeenusedforambulatorysurgery.As
earlyas196J,forexample,56ofambulatoryprocedureswereperformedwIththeuseof
thesetechnIques.
JJ
FegIonaltechnIquescommonlyusedforambulatorysurgery,InaddItIon
tospInalandepIduralanesthesIa,IncludelocalInfIltratIon,brachIalplexusandother
perIpheralnerveblocks,andIntravenousregIonalanesthesIa.CeneralanesthesIacanalso
besupplementedwIthregIonalnerveblocks.
PerformIngablocktakeslongerthanInducInggeneralanesthesIa,andtheIncIdenceof
faIlureIshIgher.UnnecessarydelayscanbeobvIatedbyperformIngtheblockbeforehand
InapreoperatIveholdIngarea.8ecauseapostoperatIvenursIngInterventIon,usually
assocIatedwIthgeneralanesthesIa,IsassocIatedwItha27to45mInutedelay,the
IncreasedsetuptImeforaregIonalanesthetIcmaybeassocIatedwIthashortertImeto
dIscharge.
J4
PostoperatIvepaIncontrolIsbestwIthregIonaltechnIques.
AnoccasIonalpatIentmayexperIencesyncopewhentheneedlefortheregIonalblockIs
Inserted.ntheexperIenceoforalandmaxIllofacIalsurgeonsIn|assachusettsInthelate
1990s,1of160patIentsfaIntedwhenlocalanesthesIawasInjected.
J5
WhensedatIon
accompanIeslocalanesthesIaInjectIon,theIncIdenceofsyncopeIsreduced.PatIents
usuallyexperIencelesspostoperatIvepaInwhenlocalorregIonalanesthesIahasbeenused.
PatIentsmaystIllhaveanumbextremIty(e.g.,afterabrachIalplexusblock)butotherwIse
meetallcrIterIafordIscharge.nsuchInstances,theextremItymust
P.8J9
bewellprotected(e.g.,wIthaslIngforanupperextremItyprocedure)andpatIentsmust
becautIonedtoprotectagaInstInjurybecausetheyarewIthoutnormalsensatIonsthat
wouldwarnthemofvulnerabIlIty.FeassurancethatsensatIonwIllreturnshouldbe
provIded.
Spinal Anesthesia
Children
SpInalanesthesIaIsusedInsomecenterspartIcularlyforchIldrenundergoIngInguInal
hernIarepaIr.DnegroupdescrIbedaserIesof1,000patIentswherespInalanesthesIawas
usedforchIldrenaged6monthsto14yearsforproceduresonthelowerpartofthebody.
J6
|usclerelaxatIonwIththetechnIquewasexcellent.nthIsserIes,allchIldrenlefttheDF
awakeandpaInfree.TheanesthesIologyteamused0.5hyperbarIcbupIvacaIneatadose
of0.2mg/kg.TheoretIcally,PDN7shouldbelessafterspInalanesthesIa.Thatwasthecase
Inonestudy,althoughdIschargetImesorpatIentsatIsfactIonwerenodIfferentwhen
comparedwIthpatIentswhoreceIvedgeneralanesthesIa.
J7
Adults
TheuseofspInalneedleswIthpencIlpoInt,noncuttIngtIpshaspromptedaresurgenceof
spInalanesthesIaforambulatorysurgeryInadults.SpInalanesthesIaIssuItableforpelvIc,
lowerabdomInal,andlowerextremItysurgery.DnegroupdescrIbeduseofspInal
anesthesIaforambulatorylaparoscopIccholecystectomywIthspInalneedleInsertIonat
L10,althougheventheseauthorsrecommendedtheIrtechnIquenotbeusedroutInely
becauseofthepotentIalfordIrectcontactofneuraltIssuebythespInalneedle.
J8
|otorblockofthelegsmaydelayapatIent'sabIlItytowalk.However,theuseofashort
actInglocalanesthetIcwIllmInImIzethIsproblem.NauseaIsmuchlessfrequentafter
epIduralorspInalanesthesIathanaftergeneralanesthesIa.
0IfferentdrugsanddrugconcentratIonshavebeenusedforspInalanesthesIa.LIdocaIne
andmepIvacaIneareIdealforambulatorysurgerybecauseoftheIrshortduratIonof
actIon,althoughlIdocaIneusehasbeenproblematIcbecauseoftransIentneurologIc
symptoms.TransIentneurologIcsymptomscanbeseenafterotherlocalanesthetIcs,but
therIskIs7tImesmoreafterIntrathecallIdocaInethanafterbupIvacaIne,prIlocaIne,or
procaIne.
J9
ChloroprocaInespInalanesthesIahasrapIdonsetandoffset.nastudyofnonpatIent
volunteers,after40mgof2chloroporcaIne,thestudypartIcIpantscouldvoIdafter110
mInutes.
40
nthatstudy,when20goffentanylwasIncluded,regressIontImetoL1was
lengthenedandtournIquettolerancewasImproved,althoughoverallblocklengthwas
mInImallyaffected.FortymIllIgramsofpreservatIvefree2chloroporcaIneproducesa
sImIlaronsettImeandblockheIghtwhencomparedwIth40mgoflIdocaIne.
41
nonestudy,
theauthorsshowedthat40and50mgof2chloroprocaIneprovIdedadequatespInal
anesthesIaforoutpatIentprocedureslastIng45to60mInutes,whereasafterJ0mg,the
duratIonofblockwasInadequate.
42
8othropIvacaIneandbupIvacaInehavebeenusedforambulatorysurgIcalprocedures,but
recoverytImeIsrelatIvelylong.nastudycomparIng7.5mgbupIvacaIneand15mg
ropIvacaIneforspInalanesthesIaforkneearthroscopy,tImetoambulatIonforbothdrugs
wasabout5hours.
4J
AlthoughheadacheIsacommoncomplIcatIonoflumbarpuncture,smallergaugeneedles
resultInalowerIncIdenceofpostduralpunctureheadache.ForthosepatIentswhodo
receIvespInalanesthesIa,ItIsIncumbentontheanesthesIologIstandthefacIlItytohave
followupwIthtelephonecallstoensurenodIsablIngsymptomsofheadachehave
developed.ftheheadachedoesnotrespondtobedrest,analgesIcs,andoralhydratIon,
thepatIentmustreturntothehospItalforacourseofIntravenouscaffeInetherapyoran
epIduralbloodpatch.
SpInalanesthesIashouldnotbeavoIdedInambulatorysurgerypatIentssImplybecause
theymaybemoreactIvepostoperatIvelythanInpatIents.8edrestdoesnotreducethe
frequencyofheadache.ndeed,earlyambulatIonmaydecreasetheIncIdence.Further
studyIsneededtoassesstherelatIverIskbenefItratIoofspInalanesthesIaasatechnIque
fortheambulatorysurgerypatIent.
Epidural and Caudal Anesthesia
EpIduralanesthesIatakeslongertoperformthanspInalanesthesIa.DnsetwIthspInal
anesthesIaIsmorerapId,althoughrecoverymaybethesamewItheIthertechnIque.none
studyofpatIentsundergoIngkneearthroscopy,spInalanesthesIawIthsmalldoselIdocaIne
andfentanylwascomparedwIthJ2chloroporcaIneadmInIsteredIntheepIduralspace:
IntraoperatIvecondItIons,dIschargecharacterIstIcsandtImes,andrecoveryprofIleswere
sImIlar.
44
Also,faIlureratesforthetwotechnIques,althoughlow,werethesame.Some
studIessuggestthatbIcarbonatecanbeaddedtosolutIonsforfasteronsetofepIdural
anesthesIa.AnadvantageoftheepIduralblockIsthatItcanbeperformedoutsIdetheDF,
andafterthesurgIcalprocedureIscompleted,theproblemofpostduralpunctureheadache
IsusuallyavoIded.
CaudalanesthesIaIsaformofepIduralanesthesIacommonlyusedInchIldrenbefore
surgerybelowtheumbIlIcusasasupplementtogeneralanesthesIaandtocontrol
postoperatIvepaIn.8upIvacaIne,0.175to0.25,orropIvacaIne,0.2,Inavolumeof0.5to
1.0mL/kg,maybeused;asafemaxImaldoseIs2.5mg/kg.EpInephrIne,1:200,000,when
addedtotheanesthetIcsolutIon,mayallowearlIerdetectIonofIntravenous,ratherthan
epIdural,InjectIon.DtherusefulalbeItcontroversIaladdItIvesforIncreasIngduratIonof
blockadeIncludeopIoIds,ketamIne,clonIdIne,andneostIgmIne.
45
Theblockmaybemore
dIffIcultInchIldren,partIcularlythosewhoweIgh10kgandareobese,Iflandmarksfor
theblockaredIffIculttolocate.TheblockIsusuallyadmInIsteredwhIlethechIldIs
anesthetIzed.AfterInjectIon,thedepthofgeneralanesthesIacanbereduced.8ecauseof
betterpaIncontrolafteracaudalblock,chIldrencanusuallyambulateearlIerandbe
dIschargedsoonerthanwIthoutacaudalblock.PaIncontrolanddIschargetImesareno
dIfferentwhetherthecaudalblockIsplacedbeforesurgeryorafterItIscompleted.
Nerve Blocks
nasurveymaIledtomembersoftheSocIetyforAmbulatoryAnesthesIaIn2001,therewas
showntobewIdespreaduseofaxIllaryandInterscaleneblocksforsurgeryIntheupper
extremIty,andofankleandfemoralblocksforlowerextremItysurgery.
46
Nerveblocks
ImprovepostoperatIvepatIentsatIsfactIonPDN7andpostoperatIvepaInareless.Costs
arealsoless.DnenonrandomIzedstudyofoutpatIentsInaunIversItysettIngshowedthat
PACUadmIssIons,hospItalcost,andunexpectedhospItaladmIssIonwereallreducedwhen
nerveblockwasusedforanterIorcrucIatelIgamentrepaIrreconstructIon.
47
Forknee
arthroscopy,psoascompartmentblockorspInalanesthesIaIssuperIortogeneral
anesthesIaIntermsofpostoperatIvepaInmanagementandpatIentsatIsfactIon.
48
After
morecomplexkneesurgery,patIentswhoreceIvedfemoralscIatIcnerveblockrequIred
fewernursIngInterventIonsforpaIn;and,IfpatIentsreceIvedeItherthatblockoronlya
femoralnerveblock,unplannedhospItaladmIssIonswerelesscomparedwIthpatIentswho
underwenttheprocedurewIthoutablock.
49
nacomparIsonofpatIentswhounderwent
eItherInfraclavIcularbrachIalplexusblockorgeneralanesthesIaforupperextremIty
surgery,afterbrachIalplexusblockmorepatIentswereabletobypassphasePACUcare,
hadlesspaInonPACUarrIval,andweredIschargedmuchsooner(FIg.J25).
50
P.840
Figure 32-5.FecoverywasfasterwhenanInfraclavIcularbrachIalplexusblockwItha
shortactInglocalanesthetIcwasused,comparedwIthgeneralanesthesIaandwound
InfIltratIonforoutpatIentsundergoInghandandwrIstsurgery.
50
TImesarecalculated
fromtheendofanesthesIa.(FeprIntedfromHadzIcA,ArlIssJ,KerImoglu8etal:A
comparIsonofInfraclavIcularnerveblockversusgeneralanesthesIaforhandandwrIst
daycasesurgerIes.AnesthesIology2004;101:127,wIthpermIssIon.)
CertaInprocedurescanbequItepaInful,andhospItalIzatIonmayberequIredtocontrol
paIn.NerveblocksusIngcathetersthatcanbeusedtoprovIdeanalgesIaafterthe
operatIoncanbeplacedbeforesurgery.ParavertebralsomatIcnerveblockcanbeusedfor
breastsurgery,followedbyacontInuousperIneuralInfusIonoflocalanesthetIcathomefor
24to48hours.
51
PerIneuralcathetersInthescIatIcnervethroughthepoplItealfossacan
beusedtocontrolpaInafterfootsurgeryforbothadultsandchIldren.
52,5J
Femoralnerve
cathetersleftInforabout2daysafteranterIorcrucIatelIgamentreconstructIonsurgery
afterpatIentsweredIschargedhavebeenshowntodecreasepostoperatIvepaInupto4
daysaftersurgery.
54
nterscaleneperIneuralcatheters,keptInfor4daysaftersurgery,
havebeenusedforpatIentsundergoIngmoderatelypaInfulshouldersurgery.
55
Compared
wIthpatIentswhohaveregIonalanesthesIaforsurgeryandthentreatmentafterwardwIth
narcotIcs,patIentswhogohomewIththeInterscaleneperIneuralcathetersattachedtoan
InfusIonpumpwIthropIvacaInecanleavethehospItalearlIerthedayaftersurgery,and
oncehomehavelesspaInandrequIrelessnarcotIcs(FIg.J26).ContInuouscervIcal
paravertebralblockmayalsobeusefulforanalgesIaaftershouldersurgery.
56
PoplIteal
cathetershavebeenusedforlowerextremItysurgerysuchashalluxvalgussurgery.
57
PatIentswhogohomewIthcathetersInsertedmustbetaughtaboutpumpfunctIon,
understandsIgnsoflocalanesthesIatoxIcIty,andhavesomeoneelseathomewhocan
provIdeassIstance.naddItIon,thepatIentsmustbeabletocommunIcatewIthsomeone
byphone.ThenumberofpatIentswhohavebeensenthomewIthcathetersIsIncreasIng
butIsnotlarge.|orestudyIsneededInordertodemonstratepatIentsafety.
Sedation and Analgesia
|anypatIentswhoundergosurgerywIthlocalorregIonalanesthesIaprefertobesedated
andtohavenorecollectIonoftheprocedure.SedatIonIsImportant,Inpart,because
InjectIonwIthlocalanesthetIcscanbepaInfulandlyIngonahardDFtablecanbe
uncomfortable.LevelsofsedatIonvaryfromlIght,durIngwhIchapatIent'sconscIousnessIs
mInImallydepressed,toverydeep,InwhIchprotectIvereflexesarepartIallyblockedand
responsetophysIcalstImulatIonorverbalcommandmaynotbeapproprIate.When
patIentsareunsuItableforoutpatIentgeneralanesthesIa,surgerycanoftenbeperformed
IflocalorregIonalanesthesIaIssupplementedwIthconscIoussedatIon.However,serIous
rIsk,suchasdeath,IsprobablynodIfferentaftersedatIonthanaftergeneralanesthesIa.
ChIldrenwhohavesurgeryusuallywIllnotremaInImmobIleunlesstheyaredeeplysedated
orreceIvegeneralanesthesIa.
Figure 32-6.PatIentswhocontInuedtoreceIveanInterscaleneInfusIonofropIvacaIne
aftersurgerycouldbedIschargedhomemuchearlIercomparedwIthpatIentswho
receIvedpostoperatIvenarcotIcs.
55
0IschargecrIterIaIncludedadequateanalgesIa,
IndependencefromIntravenousopIoIds,andtheabIlItytotolerateatleast50of
passIveshouldermotIontargetsdurIngphysIcaltherapy.(FeprIntedfromlfeld,8|,
7andenborne,K,0uncan,PW,etal:AmbulatorycontInuousInterscalenenerveblocks
decreasethetImetodIschargereadInessaftertotalshoulderarthroplasty:A
randomIzed,trIplemasked,placebocontrolledstudy.AnesthesIology2006;105:999,
wIthpermIssIon.)
Foradults,theproperdosemIghtbeselectedbyhavIngthepatIentcontrolthedosage.
Yet,atleastforambulatorysurgIcalprocedures,patIentcontrolledsedatIonIsnotpopular.
ThIsmaybebecauseamemberoftheanesthesIacareteammustbecontInuouslypresent
anyway.
General Anesthesia
ThedrugsselectedforgeneralanesthesIadetermInehowlongpatIentsstayInthePACU
aftersurgery,andforsomepatIents,whethertheycanbedIschargedtogohome.
Induction
ThepopularItyofpropofolasanInductIonagentforoutpatIentsurgeryInpartrelatestoIts
halflIfe:theelImInatIonhalflIfeofpropofolIs1toJhours,shorterthanthatof
methohexItal(6to8hours)orthIopental(10to12hours).Althoughtheeffectofdrugs
gIvenforInductIonseemstobetransIent,thesedrugscandepresspsychomotor
performanceforseveralhours.AfterInductIondosesofpropofolorthIopental,ImpaIrment
afterthIopentalcanbeapparentforupto5hours,butonlyfor1hourafterpropofol.
PaInonInjectIoncanbeaproblemwIthpropofol.PaInIsmorelIkelyonInjectIonInto
dorsalhandveInsandIsmInImIzedIfforearmorlargerantecubItalveInsareused.Some
IndIvIduals,though,experIencepaInIfthedrugIsInjectedIntoproxImallargerveIns.
Nonetheless,thrombophlebItIsdoesnotappeartobeaproblemafterIntravenous
admInIstratIonofthIsagent,whereasItcanbeevIdentafterthIopental.
P.841
ntravenouslIdocaIne,0.2mg/kg,canbeusedtodecreasetheIncIdenceandseverItyof
paIn;othertechnIqueshavebeentrIed,IncludIngketamIne,0.1mg/kg,ImmedIatelybefore
propofolInjectIonorlIdocaIne,20mg,plusmetoclopramIde,10mg.
58,59
Somehave
questIonedthestabIlItyofmIxIngmorethan20mglIdocaInewIth20mLpropofol.
60
|ostchIldrenandsomeadultsprefernottohaveanIntravenouscatheterInsertedbefore
thestartofanesthesIa.SevofluranehasarelatIvelylowbloodgaspartItIoncoeffIcIentand
thespeedofInductIonIssImIlarto,albeItsomewhatslowerthan,thatofpropofol.
nductIonwIthsevofluranecanbehastenedwhenthepatIentIstoldtobreatheoutto
resIdualvolume,takeavItalcapacItybreaththroughaprImedanesthesIacIrcuIt,andthen
holdthebreath.
Forshortprocedures,somepatIentsmaynotrequIreneuromuscularblockIngdrugs;others
mayneedbrIefparalysIs(e.g.,wIthsuccInylcholIne)tofacIlItatetrachealIntubatIon.
NondepolarIzIngdrugscanbeusedtofacIlItateIntubatIonandalsodurIngtheprocedure.
NondepolarIzIngdrugssuchasrocuronIumhaverapIdonsettImesthataresImIlartothose
wIthsuccInylcholIne.Dfcourse,paralysIsIsnotneededtoInsertanendotrachealtube;
drugcombInatIonssuchaspropofol,alfentanIlorremIfentanIl,andlIdocaIneobvIatethe
needforparalysIs.
61
SuccInylcholIneshouldbeusedwIthcautIonInchIldrenbecauseofthe
possIbIlItyofcardIacarrestrelatedtomalIgnanthyperthermIaorunsuspectedmuscular
dystrophy,partIcularly0uchennedIsease.
Maintenance
AlthoughmanyfactorsaffectthechoIceofagentsformaIntenanceofanesthesIa,two
prImaryconcernsforambulatoryanesthesIaarespeedofwakeupandIncIdenceofPDN7.
Anesthesia Maintenance and Wake-Up Times
TImetorecoverymaybemeasuredbyvarIouscrIterIa;however,foranambulatorycenter,
apatIentmaybeconsIderedawakewhenheorsheIsabletoleavethecenter.Actual
dIschargefromanambulatorycenter,though,maydependonadmInIstratIveIssuessuchas
awrIttenorderfromasurgeonoranesthesIologIst.ThetImenecessarybeforeapatIent
canbetakenfromtheDFaftercompletIonofsurgery,orapatIent'sabIlItytoskIpthe
PACUandgodIrectlytoastepdownunIt,maybedIrectlyrelatedtotheanesthetIcand
mayresultIncostsavIngsforanInstItutIon.0oeschoIceofmaIntenanceagentaffect
recoveryafteranesthesIa:Propofol,desflurane,andsevofluranehavecharacterIstIcsthat
makethemIdealformaIntenanceofanesthesIaforambulatorysurgery.Propofolhasa
shorthalflIfeand,whenusedasamaIntenanceagent,resultsInrapIdrecoveryandfew
sIdeeffects.0esfluraneandsevoflurane,halogenatedetheranesthetIcswIthlowbloodgas
partItIoncoeffIcIents,seemtobeIdealforgeneralanesthesIaforambulatorysurgery.
Sevoflurane,unlIkedesflurane,facIlItatesasmoothInhalatIonInductIonofanesthesIa,the
preferredtechnIquetoensurerapIdrecoveryofchIldrenInambulatorysurgerycenters.
tIsImportanttodIstInguIshbetweenwakeuptImeanddIschargetIme.PatIentsmay
emergefromanesthesIawIthdesfluraneandnItrousoxIdesIgnIfIcantlyfasterthanafter
propofolorsevofluraneandnItrousoxIde,althoughtheabIlItytosItup,stand,and
toleratefluIdsandthetImetofItnessfordIschargemaybenodIfferent.Whenthe
bIspectralIndex(8S)orotherguIdeofanesthetIcdepthIsused,thedIfferencebetween
drugsandwakeuptImesmaynotbeasgreat.
62
Conversely,IffastwakeuptImescan
translatetobypassofphase,theremaybecostsavIngs.
Intraoperative Management of Postoperative Nausea and
Vomiting
Nausea,wIthorwIthoutvomItIng,IsprobablythemostImportantfactorcontrIbutIngtoa
delayIndIschargeofpatIentsandanIncreaseInunantIcIpatedadmIssIonsofbothchIldren
andadultsafterambulatorysurgery.PatIentshatevomItIng.StudIeshavebeenperformed
InwhIchpatIentsareaskedhowmuchtheywouldpaytoavoIdPDN7orpostoperatIvepaIn.
PatIentsarewIllIngtopaythemosttopreventeItheroftheseoutcomes,althoughthe
actualamountIsafunctIon,Inpart,onpatIentIncome.
6J
Women,especIallythosewhoare
pregnant,haveahIgherIncIdenceofPDN7.DtherrIskfactorsIncludeaprevIoushIstoryof
motIonsIcknessorpostanesthetIcemesIs,surgerywIthIn1to7daysofthemenstrualcycle,
notsmokIng,andproceduressuchaslaparoscopy,lIthotrIpsy,majorbreastsurgery,and
ear,nose,orthroatsurgery.ThegreaterthenumberofrIskfactors,thegreaterrIskfor
nauseaorvomItIngaftersurgery.nhalatIonagentsareassocIatedwIthanIncreasedrIskof
PDN7,partIcularlyIntheearlystagesofrecovery;postoperatIvenarcotIcuseIsassocIated
wIthPDN72hoursaftersurgery.
64
ThevomItIngpathwaystartsperIpherally,whereemerogenesthroughenterochromaffIn
cellsInthegastroIntestInaltractand/orothersensoryneuronsactIvatevagalafferentsto
thegroupofbraInstemnucleIIntheareapostrema,thenucleustractussolItarIus,andthe
dorsalmotornucleusofthevagus.ThIsareaInthebraInIsotherwIseknownasthe
vomiting center.AlthoughthepathwaysforvomItIngarenotcompletelyunderstood,the
areapostremaIshIghlyvascular,lacksacompletebloodbraInbarrIer,andhasreceptors
forneurotransmIttersandhormones.
65
FeceptorantagonIsts,specIfIcallyselectIve
serotonInantagonIsts(ondansetron,dolasetron,andgranIsetron),havebeenshowntohave
sImIlareffIcacytohelpallevIatenauseaandvomItIng.0opamIneantagonIsts,
antIhIstamInes,andantIcholInergIcdrugsareusefulandaregenerallylessexpensIve,but
areassocIatedwIthextensIvesIdeeffects.NeurokInIn(NK1)receptorantagonIstsmayalso
beusefultocontrolPDN7.TherapIesusefulIncontrollIngPDN7Includeacupuncture(FIg.
J27).
66
supplementalfluIdtherapy,
67
clonIdIne(perhapsInpartbecauseItdecreases
anesthesIarequIrement),
68
anddexamethasone.
69,70
nonestudy,acupuncturetherapywas
effectIveIncontrollIngbothPDN7andpostoperatIvepaIn.
71
AcupressureIsmosteffectIve
whenItIsadmInIsteredaftersurgery,
72
althoughIf,IntraoperatIvely,leadsto
P.842
monItorpatIentparalysIsareplacedattheP6acupuncturepoInt,PDN7Isreduced.
7J
Figure 32-7.TheP6acupuncturepoIntInrelatIontootherhandstructuresIs
Illustrated.
87
(1)P6acupuncturepoInt,(2)palmarIslongtendon,(J)flexorcarpI
radIalIstendon,(4)medIannerve,and(5)palmaraponeurosIs.(FeprIntedfromWang
S|,KaInZN:P6acupoIntInjectIonsareaseffectIveasdroperIdolIncontrollIngearly
postoperatIvenauseaandvomItIngInchIldren.AnesthesIology2002;97:J59,wIth
permIssIon.)
CombInatIontherapyIsprobablythemosteffectIvewaytocontrolPDN7.TherapyIncludes
avoIdanceofnItrousoxIde;avoIdanceofInhalatIonagents;avoIdanceofmusclerelaxant
reversal,IfclInIcallyIndIcated;avoIdanceofnarcotIcs;fluIdhydratIon;andadmInIstratIon
ofa5HTJantagonIst,anantIemetIcfromadIfferentdrugclass,anddexamethasone.FIsk,
ofcourse,IsafunctIonofotherfactors,asprevIouslydescrIbed.nonestudyInwhIch
combInatIontherapywasused,nauseaIncIdencewas10andwasevenlowerforcertaIn
proceduresandtypesofpatIents.
74
8ecauseofItsabIlItytodecreasePDN7,propofolIsthebestgeneralanesthetIcfor
ambulatoryanesthesIa.Forexample,Inastudyof5,161patIents,propofol,comparedwIth
avolatIleanesthetIc,reducednauseaandvomItIngby19;andnItrogencomparedwIth
nItrousoxIdereducedtheIncIdenceby12(FIg.J28).
70
PropofolIsnowgenerIcsothe
decIsIontousethedrugshouldnotbebasedoncost.
TheuseofnItrousoxIdeforambulatoryanesthesIaIsanIssuebecausetheIncIdenceof
emesIsmaybegreaterafternItrousoxIdethanafterotherInhalatIonagents.Although
manystudIeshaveshownthatnItrousoxIdecanbeusedsuccessfullyforambulatory
anesthesIa,thereIsevIdencethatnItrousoxIdeshouldbeavoIded,exceptforInhalatIon
InductIonofanesthesIa.nonestudyofpatIentsundergoIngmajor,albeItnotambulatory,
surgery,avoIdanceofnItrousoxIdereducedpostoperatIvecomplIcatIons,IncludIng
postoperatIvefever,woundInfectIon,pneumonIa,pulmonaryatelectasIs,andsevere
nauseaorvomItIng.
75
WhetherthechangesfoundInthatstudywouldbeasdramatIcIn
ambulatorypatIentsIsnotclear.Yet,manywouldarguethatnItrousoxIdeIsnolonger
neededexceptforInhalatIonInductIonofanesthesIa.
Paralysis
|uscleparalysIsforambulatoryanesthesIaextendsbeyondthetImeofparalysIsfor
IntubatIon,partIcularlywhennondepolarIzIngdrugsareused.TheduratIonofactIonof
rocuronIum,vecuronIum,rapacuronIum,andatracurIumrangesfrom25to40mInutes.
FeversalagentsmustbeusedunlessthereIsnodoubtthatmusclerelaxatIonhasbeenfully
reversed.
Figure 32-8.PostoperatIvenauseaandvomItIng(PDN7)Isleastafterapropofol
anesthetIcwIthaIr.
70
llustratedIstheIncIdenceofPDN7whendIfferentanesthetIcs
anddIfferentnumbersofprophylactIcantIemetIctreatmentsareadmInIstered.
(FeprIntedfromApfelCC,KorttIlaK,Abdalla|etal:AfactorIaltrIalofsIx
InterventIonsforthepreventIonofpostoperatIvenauseaandvomItIng.NEnglJ|ed
2004;J50:2441,wIthpermIssIon.)
Intraoperative Management of Postoperative Pain
DpIoIds,whengIvenIntraoperatIvely,areusefultosupplementbothIntraoperatIveand
postoperatIveanalgesIa.FentanylIsprobablythemostpopulardrug,althoughallother
avaIlablenarcotIcshavebeentrIed.AllnarcotIcscancausenausea,sedatIon,and
dIzzIness,whIchcandelayapatIent'sdIscharge.NonsteroIdalanalgesIcsarenoteffectIve
assupplementsdurInggeneralanesthesIa,althoughtheyareusefulIncontrollIng
postoperatIvepaIn,partIcularlywhengIvenbeforeskInIncIsIon.TocontrolpostoperatIve
paIn,combInatIontherapyIsmostuseful.(SeealsotheprevIousdIscussIononopIoIdsand
nonsteroIdalanalgesIcsInDpIoIdsandNonsteroIdalAnalgesIcs.)
Depth of Anesthesia
Useof8S,andentropy,oraudItoryevokedpotentIalmonItorscandecreaseanesthesIa
requIrementwIthoutsacrIfIcIngamnesIadurInggeneralanesthesIa.8ecauselessanesthesIa
Isused,tItratIonofanesthesIawIththesemonItorsresultsInearlIeremergencefrom
anesthesIa.nametaanalysIsof8SmonItorIngforambulatoryanesthesIa,8SmonItorIng
wasshowntoreduceanesthetIcuseby19,wIthmoremodestdecreasesInPACUduratIon
(4mInutes)andPDN7(6;FIg.J29).
76
Fesultsareevenmoremodest,albeItmIxed,In
termsoflaterrecoveryendpoInts.SympatholytIcdrugs,InsteadofanesthesIa,canbeused
tocontrolautonomIcresponsestoanesthesIa.nfact,recoveryIsfasterandsIdeeffects
arefewerInambulatorypatIentswhosebloodpressureIscontrolledbysympatholytIcs
InsteadofInhalatIonagents.
77
nastudyofalmost5,000patIentswhounderwentgeneral
anesthesIaandwhowereparalyzedand/orwereIntubated,awarenesswassIgnIfIcantly
reducedInthegroupofpatIentswhoweremonItoredwItha8ScomparedwIththegroup
whowerenotmonItoredwIththe8S.
78
Entropy,audItoryevokedpotentIal,andcerebral
statemonItorsaresImIlarto8S.8ecausethesemonItorsresultInlessuseofanesthesIa,
thereIsthepossIbIlItythatIntraoperatIveawarenessandmyocardIalIschemIamIghtbe
Increased.
Airways
TheuseofanL|A,orsImIlartypeofaIrway,provIdesseveraladvantagesforallowInga
patIenttoreturntobaselIne
P.84J
statusquIckly.|usclerelaxantsrequIredforIntubatIoncanbeavoIded.CoughIngIsless
thanwIthtrachealIntubatIon.AnesthetIcrequIrementsarereduced.Hoarsenessandsore
throatarealsoreduced.Dverall,costsavIngsresultwIththeuseofL|As.8ecauseof
gastrIcInsufflatIon,though,nauseaandvomItIngmaybegreater.TheuseoftheL|Ahas
beendescrIbedforlaparoscopIcprocedures,althoughthepotentIalforaspIratIonexIsts
becauseofanInflatedabdomendurInglaparoscopy.
Figure 32-9.8IspectralIndex(8S)(Aspect|edIcalSystems,nc.,Norwood,|A),
monItorIngreducesanesthetIcconsumptIon,costtotreatpostoperatIvenauseaand
vomItIng(PDN7),andpostanesthesIacareunIt(PACU)tIme;thecostoftheelectrode
reversescostsavIngs.
76
TheordInaterepresentscostdIfferencepercasepooledfrom
threestudIes(I.e.,costsforthecontrolgroupmInuscostforthegroupthatused8S).
ThecapItalcostforthe8SmonItorwasnotIncluded.(AdaptedfromLIuSS:Effectsof
bIspectralIndexmonItorIngonambulatoryanesthesIa:AmetaanalysIsofrandomIzed
controlledtrIalsandacostanalysIs.AnesthesIology2004;101:J11,wIthpermIssIon.)
Management of Postanesthesia Care
|anyrecoveryIssuesarepartofpatIentselectIonandperIoperatIvemanagementand
mustbeconsIderedbeforethepatIententersthePACU.|anagIngcommonproblemsInthe
PACUquIcklyandeffectIvelyIsasImportantasapproprIatepatIentselectIonandchoIceof
anesthetIctechnIqueIfthepatIentIstoreturnhomeonthedayofsurgery.Thethreemost
commonreasonsfordelayInpatIentdIschargefromthePACUaredrowsIness,nauseaand
vomItIng,andpaIn.AllthreeareafunctIonofIntraoperatIvemanagement,butnausea,
vomItIng,andpaInalsocanbetreatedInthePACU.
Reversal of Drug Effects
FeversalofmusclerelaxantsIsnotunIquetotheambulatorysurgerypatIentandIsnot
dIscussedhere.FeversalofopIoIdsmaysometImesbenecessary.FlumazenIl,a
benzodIazepInereceptorantagonIst,hasprImarIlybeenusedtoreversetheeffectsof
sedatIonafterendoscopyandspInalanesthesIa.FeversalofpsychomotorImpaIrmentwIth
flumazenIlIsnotcomplete,andthesubjectIveexperIenceofsedatIonIsnotnecessarIly
attenuated.FeversalofamnesIawIthflumazenIlIsonlypartIal,andtheduratIonofthe
reversaleffectmaynotbelongenoughtobeclInIcallysIgnIfIcant.FlumazenIlshouldnot
beusedroutInelyasabenzodIazepIneantagonIst,butmaybeusedwhensedatIonappears
tobeexcessIve.naddItIon,reversalofbenzodIazepIneInducedsedatIonbyflumazenIl
shouldnotreplaceapproprIateventIlatoryassIstanceand,Ifnecessary,placementofan
endotrachealtube.
Nausea and Vomiting
NauseaandvomItIngarethemostcommonreasonsbothchIldrenandadultshave
protractedstaysInthePACUorunexpectedhospItaladmIssIonduetoanesthesIa.Nausea
andvomItIngarealsothemostcommonadverseeffectInpatIentsInthePACU.|uch
researchhasbeenundertakentostudyprophylactIctreatmentofthIsproblembefore
surgery,aswellastechnIquesIntheDFthatcanmInImIzenauseaandvomItIngInthe
PACU.ThetreatmentofthIsproblem,onceItoccursInthePACU,hasnotreceIvedasmuch
study.Yet,thereareavarIetyofdrugsthatareeffectIveIntreatIngtheproblem.The5
HTJantagonIstsseempartIcularlyeffectIve.Forexample,InonestudyofchIldrenwho
underwentstrabIsmussurgeryandwerethennauseousdurIngthefIrstJhoursafter
recoveryfromanesthesIa,emesIsfreeepIsodesweregreateraftergranIsetron,40g/kg
(88),comparedwIthdroperIdol,50g/kg(6J),ormetoclopramIde,0.25mg/kg(58).
79
n
adults,granIsetron,40g/kg;metoclopramIde,0.2mg/kg;orhydroxyzIne,25mg,arealso
effectIve.0examethasone,8mg,gIvenwIthotherantIemetIcscanenhancetreatmentof
establIshedPDN7InthePACU.
80
|Idazolamandpropofol,althoughmorecommonlyusedforsedatIon,haveantIemetIc
effectsthatarelongerInduratIonthantheIreffectsonsedatIon.Forexample,when
patIentsInthePACUwerenauseousandthenreceIvedeItherpropofol,15mg,or
mIdazolam,1or2mg,subsequentnauseawasnodIfferentthanwIthondansetron,4mg.
81
AcupressurebandsoracupressurestImulatIonIntheregIonoftheP6acupuncturepoIntcan
helpreducePDN7.WhenaFelIef8and(Neurowave|edIcalTechnologIes,ChIcago,L)
acustImulatIondevIcewascomparedwIthondansetronforpatIentswhowerenauseousIn
thePACUafterreceIvIngmetoclopramIdeordroperIdolandundergoInglaparoscopIc
surgery,nauseawasmosteffectIvelytreatedwIthboththeFelIef8andandondansetron,
althoughboththerapIeswereequallyeffectIveIndIvIduallyIntreatIngPDN7.
82
fpatIents
havealreadyreceIvedondansetronprophylaxIsIntheDF,andthenarenauseousInthe
PACU,anotherrepeatdosemIghtnotbeeffectIve.8asedonaretrospectIveanalysIsof
patIentswIthnauseaafterreceIvIngprophylactIcondansetron,establIshedPDN7wasmore
effectIvelytreatedwIthpromethazInethanondansetron;andpromethazIne,6.25mg
Intravenously,ratherthanhIgherdoseswasmosteffectIve.
8J
|oreworkIsobvIously
neededtostudyeffectIvetherapIesfortreatmentPDN7InthePACU.FInally,becausepaIn
maybeassocIatedwIthnausea,treatmentofpaInfrequentlydecreasesnausea.
Pain
PostsurgIcalpaInmustbetreatedquIcklyandeffectIvely.tIsImportantforthe
practItIonertodIfferentIatepostsurgIcalpaInfromthedIscomfortofhypoxemIa,
hypercapnIa,orafullbladder.|edIcatIonsforpaIncontrolshouldbegIvenInsmall
Intravenousdoses(e.g.,1toJmg/70kgmorphIneor10to25g/70kgfentanyl).
ntramuscularInjectIonofopIoIdforpaIncontrolInthePACUIsprobablynotnecessary.
DnsetofactIonofdrugsIsfasterafterIntravenouscatheteradmInIstratIonthanafteroral
admInIstratIon.ControlofpostoperatIvepaInmayIncludeadmInIstratIonofopIoId
analgesIcsorNSA0s,whIcharenotassocIatedwIthrespIratorydepressIon,nausea,or
vomItIng.FentanylIsthenarcotIcfrequentlyusedtocontrolpostoperatIvepaInthat
ambulatorysurgerypatIentsexperIence,althoughtheeffectsofmorphInelastlonger.
PatIentswhoreceIvefentanylforpaIncontrolmayrequIreaddItIonalInjectIonsandgo
homenosoonercomparedwIthpatIentswhoreceIvemorphIne.NonsteroIdalmedIcatIons,
suchasketorolacorIbuprofen,canalsoeffectIvelycontrolpostoperatIvepaInand,
comparedwIthnarcotIcs,cangIvepaInrelIefforalongerperIodandareassocIatedwIth
lessnauseaandvomItIng.NSA0scanIncreasebleedIng,althoughthereIsnoevIdenceat
thIstImeofsuchadangerformostambulatorysurgeryprocedures.WhenswellIngandpaIn
areproblematIcpostoperatIvely,NSA0scanbemoreeffectIvethanopIoIdsInrelIevIng
both.
WemanagepaInInbothadultsandchIldrenInItIallyeItherwIthashortactIngopIoId
analgesIcsuchasfentanyl(25g/70kg),orwIthanInjectIonofketorolac,J0to60mg/70
kgIntramuscularlyorIntravenously.FentanylIsrepeatedat5mInuteIntervalsuntIlpaInIs
controlled.ForchIldren,wealsouseanelIxIrofacetamInophencontaInIngcodeIne(120
mgacetamInophenand12mgcodeIne,Ineach5mLofsolutIon).FIvemIllIlItersIs
admInIsteredtochIldrenbetweentheagesofJand6,and10mLtochIldrenbetweenthe
agesof7and12.ChIldrenarereturnedtoparentalcareassoonastheyareawake.WefInd
frequentlythatInfantsyoungerthan6monthsofageusuallyneedtobereunItedwIththeIr
mothersfornursIngorbottlefeedIngafteraprocedurenotassocIatedwIthseverepaIn.
ForolderInfantsandyoungchIldrenInthePACU,acetamInophen,60mgperyearofage
(gIvenorallyorrectally),IscommonlyusedtorelIevemIldpaIn.ntravenousfentanyl(up
toadoseof2g/kg)Ispreferredformoresevere
P.844
paIn.|eperIdIne(0.5mg/kg)andcodeIne(1to1.5mg/kg)canbegIvenIntramuscularlyIf
anIntravenousroutehasnotbeenestablIshed.
Preparation for Discharging the Patient
naddItIontothePACU,manyambulatorysurgerycentersIntheUnItedStateshave
anotherarea,oftenknownasaphaserecoveryroom,wherepatIentsmaystayuntIlthey
areabletotoleratelIquIds,walk,and/orvoId.WIththeanesthetIcsthataretypIcallyused
InambulatorysurgeryDFs,patIentswhoareawakenedIntheDFandareevaluatedas9or
10accordIngtothemodIfIedAldretescorIngsystemmaybetransferreddIrectlytophase
recoveryfromtheDF.PatIentswhoundergoproceduresundermonItoredanesthesIacare
canusuallygostraIghttothephaseareafromtheDF.AftergeneralanesthesIa,L|Ause
andpaIncontrolusIngnonopIoIdanalgesIcsfacIlItatesfasttrackIng.nonestudy,J5to5J
ofpatIentswhounderwentlaparoscopIcgynecologIcsurgerywereabletobypassthe
PACU.
84
nthatstudy,resIdualsedatIonwasthemostcommonreasonthePACUwasnot
bypassed.nanotherstudyofpatIentswhounderwentoutpatIentkneesurgerybypassed
thePACUandwereInthephaserecoveryarea,J1requIrednursIngInterventIonsand
wereJtImesmorelIkelytoneedanursIngInterventIon,comparedwIth16whorequIred
anursIngInterventIonwhofIrstwenttothePACU.Yet,dIschargetImeswerefasterand
unplannedhospItaladmIssIonswerefewerIfpatIentswereabletobypassthePACU.
85
na
sImIlarstudy,thoseauthorsfoundthateventhoughdIrecttransfertophaserecovery
maydecreasetImespentInthehospItal,nursIngworkloadwasnodIfferentthanIfpatIents
fIrstwenttophaserecovery.
86
SomecrIterIafordIschargetohomewerecreatedwIthoutscIentIfIcbasIs.DnecrIterIonIs
theabIlItytotoleratelIquIdsbeforebeIngdIscharged.PostoperatIvenauseamaybe
greaterIfpatIentsarerequIredtodrInklIquIdsprIortodIscharge.EventhoughItIs
warrantedafterspInalorepIduralanesthesIa,therequIrementthatlowrIskpatIentsvoId
beforedIschargemayonlylengthenstayInthehospItal,partIcularlyIfpatIentsarewIllIng
toreturntoamedIcalfacIlItyIftheyareunabletovoId.PractIcalcrIterIaforpatIent
dIschargefromtheDF,fromthePACU,andfromthephaserecoveryareaareneeded
thatInnowaycompromIsepatIentsafety.Thevalueofpsychomotorteststomeasure
dIfferentphasesofrecovery(exceptforresearchpurposes)IsquestIonable.
AlthoughscorIngsystemsmaybeusedtoguIdetransferfromthePACUtothephase
recoveryroomandfromphaserecoverytohome,theydolIttletotesthIgherlevelsof
functIon,suchastheabIlItytouseone'shands,todrIveacar,ortoremaInalertlong
enoughtodrIve.PatIentsmayfeelfIneaftertheyleavethehospItal,buttheyshouldbe
advIsedagaInstdrIvIngforatleast24hoursafteraprocedure.PatIentsandresponsIble
partIesshouldberemIndedthatthepatIentshouldnotoperatepowertoolsorbeInvolved
InmajorbusInessdecIsIonsforupto24hours.DncethepatIentleavesthemedIcalfacIlIty,
supervIsIonmaynotbeasgoodasItwasInthehospItal.Therefore,beforeapatIentIs
dIscharged,dressIngsshouldbechecked.tIswIsetoIncludetheresponsIblepersonInall
dIschargeInstructIons,whIcharebestmadeavaIlableonprIntedforms.
PatIentsshouldalsobeInformedthattheymayexperIencepaIn,headache,nausea,
vomItIng,ordIzzInessand,IfsuccInylcholInewasused,muscleachesandpaInsapartfrom
theIncIsIonforatleast24hours.ApatIentwIllbelessstressedIfthedescrIbedsymptoms
areexpectedInthecourseofanormalrecovery.WrIttenInstructIonsareImportant.The
addItIonofwrIttenandoraleducatIontechnIquesatdIschargehasasIgnIfIcantImpacton
ImprovIngcomplIance.
ForpatIentswIthalanguagebarrIer(e.g.,InapopulatIonwIthahIghpercentageof
ImmIgrants),consentforms,proceduralexplanatIon,anddIschargeInformatIonmayhave
tobewrIttenInlanguagesotherthanEnglIshandtheservIcesofanInterpretermaybe
necessary.NursIngstaffshouldassesstheadultwhowIlltakethepatIenthometo
determInewhetherheorsheIsaresponsIbleperson.AresponsIblepersonIssomeonewho
IsphysIcallyandIntellectuallyabletotakecareofthepatIentathome.FacIlItIesshould
developamethodoffollowupafterthepatIenthasbeendIscharged.AtsomefacIlItIes,
staffmemberstelephonethepatIentthenextdaytodetermInetheprogressofrecovery;
othersusefollowuppostcards.
WheneverwebecomeInnovatIveInthemanagementofouroutpatIents,wemustassess
howacosteffectIve,nofrIllsapproachtocareaffectspatIentsafety.Wemust
determInewhatwecandoforthepatIentwholIvesalone,forthepatIentwhose
responsIblepersonIsunabletomanagehIsorherneeds,forthepatIentwIthoutmeansof
transportatIon,andforthepatIentwIthlImItedInsurancecoverage.HospItalbedscanbe
setasIdeforpatIentswhorequIreobservatIon.PatIentsInthesebedsafteranambulatory
surgIcalprocedurearestIllconsIderedoutpatIents.TheyarechargedforthehoursspentIn
theobservatIonarea.SomehospItalshavejoInedwIthmanagementfIrmstobuIlda
hospItalhotelormedIcalmotelclosetothehospItalItself.Thehotel,usuallyanonmedIcal
facIlIty,offerstheoutpatIentacomfortable,InexpensIve,andconvenIentplaceto
recuperatewhIlebeIngcaredforbyfamIlyornurses.HomehealthcarenursIngmaybe
approprIateaftersurgIcalproceduressuchasreductIonmammoplasty,abdomInoplasty,
vagInalhysterectomy,andmajoropenlIgamentrepaIrsoftheknee.ThevarIousservIces
formanagementand/orobservatIonofoutpatIentsaftersurgerystandtodaywhere
technIquesformanagementofoutpatIentsdurIngsurgerystoodInthehealthcaredelIvery
system20yearsago.ProspectIvestudIesareneededtoassessthequalItyofcareandthe
effectthattheseInnovatIveapproacheshaveonpatIentsafety.
PatIent,procedure,avaIlabIlItyandqualItyofaftercare,andanesthetIctechnIquemustbe
IndIvIduallyandcollectIvelyassessedtodetermIneacceptabIlItyforambulatorysurgery.A
delIcatebalancemustbemaIntaInedbetweenthephysIcalstatusofthepatIent,the
proposedsurgIcalprocedure,andtheapproprIateanesthetIctechnIque,towhIchmustbe
addedtheexpertIseleveloftheanesthesIologIstcarIngforapatIent.
AnesthesIaforambulatorysurgeryIsarapIdlyevolvIngspecIalty.PatIentswhowereonce
belIevedtobeunsuItableforambulatorysurgeryarenowconsIderedtobeapproprIate
candIdates.DperatIonsoncebelIevedunsuItableforoutpatIentsarenowroutInely
performedInthemornIngsopatIentscanbedIschargedIntheafternoonorevenIng.The
approprIateanesthetIcmanagementbeforethesepatIentscometotheDF,durIngtheIr
operatIon,andthenafterwardIsthekeytosuccess.TheavaIlabIlItyofbothshorteractIng
anesthetIcsandlongeractInganalgesIcsandantIemetIcsenablesustocareforpatIentsIn
ambulatorycenterseffectIvely.
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nauseaandvomItIng:AquantItatIvesystematIcrevIew.AnesthAnalg2000;90:186
70.ApfelCC,KorttIlaK,Abdalla|etal:AfactorIaltrIalofsIxInterventIonsforthe
preventIonofpostoperatIvenauseaandvomItIng.NEnglJ|ed2004;J50:2441
71.CanTJ,JIaoKF,Zenn|etal:ArandomIzedcontrolledcomparIsonofelectro
acupoIntstImulatIonorondansetronversusplaceboforthepreventIonofpostoperatIve
nauseaandvomItIng.AnesthAnalg2004;99:1070
72.WhItePF,Hamza|A,FecartAetal:DptImaltImIngofacustImulatIonfor
antIemetIcprophylaxIsasanadjuncttoondansetronInpatIentsundergoIngplastIc
surgery.AnesthAnalg2005;100:J67
7J.Arnberger|,StadelmannK,AlIscherPetal:|onItorIngofneuromuscularblockade
attheP6acupuncturepoIntreducestheIncIdenceofpostoperatIvenauseaand
vomItIng.AnesthesIology2007;107:90J
74.SkledarSJ,WIllIams8A,7allejo|Cetal:ElImInatIngpostoperatIvenauseaand
vomItIngInoutpatIentsurgerywIthmultImodalstrategIesIncludInglowdosesof
nonsedatIng,offpatentantIemetIcs:szerotoleranceachIevable:ScIentIfIcWorldJ
2007;7:959
75.|ylesPS,LeslIeK,Chan|Tetal:AvoIdanceofnItrousoxIdeforpatIentsundergoIng
majorsurgery:ArandomIzedcontrolledtrIal.AnesthesIology2007;107:221
76.LIuSS:Effectsof8IspectralndexmonItorIngonambulatoryanesthesIa:Ameta
analysIsofrandomIzedcontrolledtrIalsandacostanalysIs.AnesthesIology2004;101:
J11
77.WhItePF,Wang8,TangJetal:TheeffectofIntraoperatIveuseofesmololand
nIcardIpIneonrecoveryafterambulatorysurgery.AnesthAnalg200J;97:16JJ
78.EkmanA,LIndholm|L,LennmarkenCetal:FeductIonIntheIncIdenceof
awarenessusIng8SmonItorIng.ActaAnaesthesIolScand2004;48:20
79.FujIIY,TanakaH,to|:TreatmentofvomItIngafterpaedIatrIcstrabIsmussurgery
wIthgranIsetron,droperIdol,andmetoclopramIde.DphthalmologIca2002;216:J59
80.Fusch0,ArndtC,|artInHetal:TheaddItIonofdexamethasonetodolasetronor
haloperIdolfortreatmentofestablIshedpostoperatIvenauseaandvomItIng.
81.UnlugencH,CulerT,CunesYetal:ComparatIvestudyoftheantIemetIceffIcacyof
ondansetron,propofolandmIdazolamIntheearlypostoperatIveperIod.EurJ
82.Coloma|,WhItePF,DgunnaIke8Detal:ComparIsonofacustImulatIonand
ondansetronforthetreatmentofestablIshedpostoperatIvenauseaandvomItIng.
8J.HabIbAS,FeuvenIJ,TaguchIAetal:AcomparIsonofondansetronwIth
promethazInefortreatIngpostoperatIvenauseaandvomItIngInpatIentswhoreceIved
prophylaxIswIthondansetron:AretrospectIvedatabaseanalysIs.AnesthAnalg2007;
104:548
84.Coloma|,ZhouT,WhItePFetal:FasttrackIngafteroutpatIentlaparoscopy:
FeasonsforfaIlureafterpropofol,sevoflurane,anddesfluraneanesthesIa.AnesthAnalg
2001;9J:112
85.WIllIams8A,Kentor|L,WIllIamsJPetal:PACUbypassafteroutpatIentknee
surgeryIsassocIatedwIthfewerunplannedhospItaladmIssIonsbutmorephase
nursIngInterventIons.AnesthesIology2002;97:981
86.Song0,ChungF,Fonayne|etal:FasttrackIng(bypassIngthePACU)doesnot
reducenursIngworkloadafterambulatorysurgery.8rJAnaesth2004;9J:768
87.WangS|,KaInZN:P6acupoIntInjectIonsareaseffectIveasdroperIdolIn
controllIngearlypostoperatIvenauseaandvomItIngInchIldren.AnesthesIology2002;
97:J59
Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJJDffIce8asedAnesthesIa
ChapterJJ
Office-Based Anesthesia
Laurence M. Hausman
Meg A. Rosenblatt
Key Points
1. There is an increased risk of morbidity and mortality associated with
an office-based anesthetic when compared with one performed in a
freestanding ambulatory surgery center.
2. The Closed Claims Project database reveals that injuries during
office-based procedures occur throughout the perioperative period
and are multifactorial in etiology.
3. Patient selection remains a controversial topic among practicing
office-based anesthesiologists because little morbidity and mortality
data exist to support the inclusion or exclusion of specific
populations.
4. Outpatient facilities have developed specific policies regarding
acceptable patients for the outpatient setting, possibly excluding
patients with obstructive sleep apnea syndrome.
5. The anesthesiologist should function as a zealous patient advocate in
assuring that an anesthetic is performed only in a safe location.
6. Destinations for a patient in need of hospital admission must be
identified.
7. The American Society of Plastic Surgeons has recommended that
procedures be limited to 6 hours and be completed by 3 PM, thus
allowing for a full patient recovery with maximum office staffing. In
addition, when determining the suitability of a procedure one must
consider the possibility of hypothermia, blood loss, or significant fluid
shifts.
8. Although no minimum age requirement for a child to undergo an
office-based anesthetic has been established, patients >6 months of
age and American Society of Anesthesiologists physical status 1 or 2
may be reasonable candidates.
9. The drugs should have a short half-life, be inexpensive, and not be
associated with undesirable side effects such as nausea and vomiting.
10. There should be at least one Advanced Cardiac Life Support/Pediatric
Advanced Life Support-certified member of the health care team
present until the last patient has left the office.
11. Every anesthetic administered should be designed to maximize
postoperative patient alertness and mobility and minimize the risks of
the need for a prolonged postanesthesia care unit stay.
12. The anesthesiologist maintains the role of a zealous patient advocate
and helps to educate the surgeon as to what constitutes a safe
anesthetizing location.
13. Ignorance of the law offers no protection or excuse, and one should
seek the advice of expert billing agencies even if one chooses not to
outsource this responsibility.
ThefIeldofoffIcebasedanesthesIa(D8A)hasbecomeanIntrInsIcandvItalaspectwIthIn
thefIeldofanesthesIology.AnoffIcebasedanesthetIcIsonethatIsperformedIna
locatIon,usuallyanoffIceorprocedureroom,thatIsnotaccredItedbythestateasan
ambulatorysurgerycenter(ASC)orasahospItal.nfact,Insomepartsofthecountry,the
surgIcaloffIcemayhavenoaccredItatIonatall.AddItIonally,theoffIcemustalsohouse
nonsurgIcalactIvItIessuchaspatIentconsultatIonandpractIceadmInIstratIon.
0urIngthe1970s,10ofallsurgIcal/dIagnostIcprocedureswereperformedonan
ambulatorybasIs,andofthese,vIrtuallyallwereperformedInhospItals.8y1987,
approxImately25mIllIon,or40ofallprocedures,wereperformedasambulatory.nthe
UnItedStatesbetween1984and1990,thenumberofoffIcebasedproceduresIncreased
from400,000to1.2mIllIon,andby1994,8.5ofallprocedureswereperformedInoffIces.
1
nthesameyear,asurveyofthemembershIpoftheAmerIcanSocIetyofPlastIcSurgeons
(ASPS),revealedthat55oftherespondentsperformedthemajorItyoralloftheIr
proceduresInanoffIce.
2
8ytheyear2000,approxImately75ofallprocedureswere
performedonanoutpatIentbasIs;17InfreestandIngASCs,and14to25(approxImately8
to10mIllIon)InphysIcIans'offIces.
J,4,5
TherearelIttleexactdataavaIlable;howeverIt
wasestImatedthatIn2005approxImately82ofallsurgIcalprocedureswereoutpatIent
andofthese,24wereoffIcebased.
J,6
AlthoughanD8ApractIcemaybeanexcItIngalternatIvetothetradItIonalhospItalbased
one,ItrequIrestheanesthesIologIsttoexpandhIsorherrolewIthInthehealthcare
delIverysystem.AlongwIthprovIdIngsafeanesthetIcsacrossthespectrumofhealthyto
medIcallychallengedpatIentsundergoIngIncreasInglycomplexprocedures,the
anesthesIologIstmustunderstandoffIcesafetyandpolIcy,aswellaslegalandfInancIal
IssuessuchasbIllIngandcollectIon.
5,7
ThesearerelatIvelynewresponsIbIlItIesfor
anesthesIologIsts,whohIstorIcallyhaveworkedasmemberswIthInahospItaldepartment
eItherInthe
P.848
prIvateoracademIcsettIng.AfurtherchallengetotheoffIcebasedpractItIonerIsthat
thereIspresentlylIttletonotraInIngInD8AwIthInthestandardanesthesIaresIdency
program.
8
Advantages/Disadvantages
TherearemanyadvantagestoanoffIcebasedprocedurewhencomparedwItha
tradItIonalhospItalbasedone.ThemostobvIousoftheseadvantagesIscostcontaInment.
SeveralcomponentsmakeuptheactualcostofagIvensurgIcalprocedure.naddItIonto
surgIcalandanesthesIafees,whIchareusuallynegotIatedprIortoanelectIveprocedure,
thereIsafacIlItyfeechargedbythehospItalorASC.ThIsfeegenerallycoversthe
assocIatedcoststothehospItal/ASC,andIncludesoverheadsuchasmaIntenance,
equIpment,andstaff.toftenconstItutesalargecomponentofthepatIent'soverall
charge.nanoffIce,thIsamountcaneasIlybepredIctedandIsoftenmInImalwhen
comparedwIththatofahospItalthat,becauseofgreateroverheadcosts,canbeboth
enormousandunpredIctable.
J,4,9,10
n1994,Schultz
10
determInedthecostofa
laparoscopIcInguInalhernIarepaIr,whendoneInahospItal,tobeS5,494.Whenthesame
procedurewasperformedInanoffIce,theprIcewasdecreasedtoS1,5JJ.84.SImIlarly,the
averagecostofanInhospItalopenInguInalhernIarepaIrwasfoundtobeS2,2J7,whIlethe
sameprocedureperformedInaprIvateoffIcecostS894.79.AddItIonally,Ithasbeen
reportedthatoffIcebasedocularsurgeryperformedundermonItoredanesthesIacare
(|AC)cancost70lessthansImIlarproceduresperformedInahospItal.
11
FealIzIngthIs
costsavIngs,someInsurancecompanIesbeganofferIngIncentIvestosurgeonswhousedan
offIcelocatIonastheIrsurgIcalvenue.DtherclearadvantagesofoffIcebasedprocedures
IncludeeaseofschedulIng(oftenwIthlesspaperwork),patIentandsurgeonconvenIence,
decreasedpatIentexposuretonosocomIalInfectIons,andImprovedpatIentprIvacyand
contInuItyofcare(anoffIceIsusuallystaffedbyasmall,consIstentgroupof
personnel).
4,5,7,12,1J
TherearepotentIaldIsadvantagestooffIcebasedsurgery,whIchusuallyrelatetoIssues
regardIngpatIentsafetyandpeerrevIew.nsomepartsofthecountry,thereareno
regulatIonsgovernIngoffIcebasedsurgeryandD8A.Therefore,theremaybelIttletono
oversIghtregardIngthecertIfIcatIon/qualIfIcatIonofeItherthesurgeonoranesthesIologIst,
thesurgIcaloffIce'spolIcyregardIngpeerrevIew,performanceImprovement,
documentatIon,generalpolIcIesandprocedures,andthereportIngofadverseoutcomes.
However,thenumberofstateswIthoutsuchregulatIonsIsrapIdlydecreasIng(TableJJ
1).
14
Table 33-1 States that Have Regulations Regarding Office-Based Surgery
and Anesthesia as of December 1, 2007
Alabama |IssIssIppI
ArIzona
a
NewJersey
CalIfornIa NewYork
Colorado NorthCarolIna
ConnectIcut DhIo
0IstrIctofColumbIa Dklahoma
FlorIda Dregon
llInoIs PennsylvanIa
ndIana Fhodesland
Kansas SouthCarolIna
Kentucky Tennessee
LouIsIana Texas
|assachusetts WashIngton
a
ndevelopment.
WhetherornotmandatoryregulatIonsexIst,ItIsvItalthattheanesthesIologIstconsIderall
oftheseIssuesbeforeselectInganoffIcefacIlItyInwhIchtodelIvercare.
Office Safety
|edIareportsandnewspaperartIclesraIsedtheearlIestquestIonsregardIngthesafetyof
offIcebasedprocedures.
7,15,16
0atarevealthatInjurIesanddeathsoccurrIngInoffIcesare
oftenmultIfactorIalIncausatIon.FeasonsIncludeoverdosagesoflocalanesthetIcs,
prolongedsurgerywIthoccultbloodloss,pulmonaryembolIsm,accumulatIonofmultIple
anesthetIcswIthoversedatIon,hypovolemIa,hypoxemIa,andtheuseofreversaldrugswIth
shorthalflIves.
15,17,18
8oththeAnesthesIaPatIentSafetyFoundatIonandtheAmerIcan
SocIetyofAnesthesIologIsts(ASA)haveemergedasleadersInthefIeldofD8Asafetyand
haveadvocatedthatthequalItyofcareInanoffIcebasedpractIcebenolessthanthatof
ahospItalorASC.
19,20
Thus,ItIsImperatIvetoensurethatallsafetyprecautIonsonemay
takeforgrantedInahospItalarepresentInthesurgIcaloffIce.
15
n1990themortalItyratefromanesthesIawasapproxImately1/100,000.8ytheyear2000,
theratehaddecreasedto1/250,000InhospItalsand1/400,000InfreestandIngASCs.
5,15,21
AlthoughtheprecIsIonofthesefIguresIsopentodebate,thedecreaseInmortalItycanbe
attrIbuted,Inpart,toImprovementsInthetraInIngoftheanesthesIaprovIders,thesafety
profIlesoftheneweranesthetIcs,ImprovedperIoperatIvemonItorIngcapabIlItIes,and
IntrInsIcsafetymechanIsmsInplacewIthIntheanesthetIzInglocatIon.8ecausethe
majorItyofoffIcebasedpatIentsareyoungandhealthy,onewouldexpectthatan
anesthetIcperformedInanoffIcewouldbeatleastequallyassafeasananesthetIc
performedInahospItal,Ifnotsafer.However,reportsofmorbIdItyandmortalItywIthIn
offIcebasedpractIcesexIstandvarydramatIcally.n1997,|orelloetal:
22
conducteda
surveyqueryIngtheoffIcepersonnelof418accredItedplastIcsurgeons.Theyhada57
responserateandfoundthatovera5yearperIod,400,675offIceprocedureswere
conducted;6J.2werecosmetIcandJ6.8werereconstructIve.Severaloutcomeswere
revIewedIncludInghemorrhage,hypertensIon,hypotensIon,woundInfectIon,needfor
hospItaladmIssIon,andreoperatIon.TherewasanoverallcomplIcatIonrateof0.24,and
sevendeathsoccurred.ThecausesofmortalItywerebothsurgeryandanesthesIarelated.
ThesedeathswerefromtwocasesofmyocardIalInfarctIon,onefollowInganaugmentatIon
mammaplastyandtheother4hoursafterarhInoplasty;onecaseofcerebralhypoxIa
durInganabdomInoplasty;onecaseofatensIonpneumothoraxdurIngabreast
augmentatIon;onecaseofacardIacarrestdurIngcarpaltunnelsurgery;onecaseofa
strokeJdaysfollowIngarhytIdectomyandbrowlIft;andoneunexplaIneddeath.ThIs
representsanoverallmortalItyrateof1In57,000.AreportbyHoefflInetal,
2J
however,
foundnocomplIcatIonsafter2J,000plastIcsurgIcalproceduresthatoccurredInanoffIce
undergeneralanesthesIa.SImIlarly,SullIvanandTattInI
24
retrospectIvelyrevIewedthe
resultsInanoffIceperformIng5,000surgIcalproceduresbyfIveIndependentplastIc
surgeons.TheanesthesIadurIngthIstImeconsIstedofdeepsedatIonInconjunctIonwIth
localanesthesIaorregIonalblock,andwasperformedbyananesthesIologIstsupervIsInga
certIfIedregIsterednurseanesthetIst.NomortalItIesoccurreddurIngthe5yearperIod.
8Itaretal:
25
retrospectIvelystudIedadverseoutcomesInJ,615consecutIvepatIents
undergoIng4,778plastIcsurgeryproceduresInoffIcesbetween1995and2000,|ACwIth
mIdazolam,propofolandanopIoId,andnodeathswerereported.0yspneaoccurredIn
0.05ofpatIents,nauseaandvomItIngIn0.2,andtherewasa0.05rateofhospItal
admIssIons.WhenanalyzIng
P.849
theseoutcomes,ItmustbeapprecIatedthatbecausethemortalItyratefromanesthesIaIs
solow,anextremelylargecohortgroupwouldbenecessarytoprovIderealdataregardIng
therelatIverIskofanoffIcebasedanesthetIc.Fecentdataevensuggestsa10fold
IncreasedrIskofmorbIdItyandmortalItyassocIatedwIthanoffIcebasedanesthetIcwhen
comparedwIthoneperformedInafreestandIngASC.
17
DtherstudIesrevealasIgnIfIcantrIskassocIatedwIthanoffIcebasedprocedure.Faoet
al:
26
reportedthataccordIngtoclosedmalpractIceclaImsInFlorIda,8J0deathsand4,000
InjurIeswereassocIatedwIthD8Abetween1990and1999.TheseclaImsaccountedforJ0
ofallmalpractIceclaImsInthatstate.nahospItaloperatIngroom,therIsksofan
anesthetIcareusuallylImItedtotheunderlyIngmedIcalcondItIonofthepatIent,whereas
InanoffIcetheymaybeIncreasedbecauseoffactorssuchasInadequatestandardsand
safeguards.
15
|orerecentFlorIdadatahaveshownthatoffIcebasedmorbIdItyand
mortalItyareusuallytheresultofInadequateperIoperatIvepatIentmonItorIng,
oversedatIon,andthromboembolIcevents.
18,27,28
ThechallengeofacquIrIngaccurate
morbIdItyandmortalItydataforoffIcebasedanesthesIaIscomplIcatedbythefactthat
manyoffIcesarenotrequIredtoreportadverseevents.naddItIon,althoughan
anesthesIologIstmaynotevenbeadmInIsterIngtheanesthetIcInanoffIce,many
complIcatIonsmaystIllbereportedasanesthetIcrelated.
29
TradItIonalcredentIalIngprocedures,suchasboardcertIfIcatIonandthegrantIngor
renewIngofhospItalprIvIlegesbasedoncompetencyandproofofcontInuIngmedIcal
educatIon,maynotberequIredInanoffIce.
21
WIthInandamongoffIces,healthcare
provIdersofanesthesIamayalsohavevaryIngdegreesofbotheducatIonandexpertIse.
TheprovIdermaybeananesthesIologIst,anurseanesthetIst,adentalanesthetIst,ora
surgeonwIthlIttleornotraInIngInanesthesIa.
J0
Furthermore,safetywIthInan
anesthetIzInglocatIonprobablydependsontheperIoperatIvepatIentmonItorIng
capabIlItIes.AlthoughhospItalpatIentsreceIvedefInedstandardofcareformonItorIngIn
theoperatIngroomsandpostanesthesIacareunIts(PACUs),theymaybelackIngInan
InadequatelypreparedsurgIcaloffIce.
25
TherehavebeenInjurIestopatIentsdurIngoffIce
basedproceduresresultIngfromtheuseofobsoleteand/ormalfunctIonInganesthesIa
machInes,aswellasfromalarmsthathavenotbeenservIcedand/orarenotfunctIonIng
properly.
4
TheASAcreatedguIdelInesfordefInIngobsoleteanesthesIamachInes;the
guIdelInesprohIbIttheuseofanyanesthesIamachInethatlacksessentIalsafetyfeatures
(e.g.,oxygenratIodevIce,oxygenpressurefaIlurealarm),hasthepresenceof
unacceptablefeatures(e.g.,copperkettles,orvaporIzerswIthrotaryconcentratIondIals
thatIncreasevaporconcentratIonwhenthedIalIsturnedclockwIse),orforwhIchroutIne
maIntenanceIsnolongerpossIble.
J1
ArevIewofASAClosedClaImsProjectdata,whIchIncorporatesInformatIonfromtheJ5
lIabIlItyInsurersthatIndemnIfyapproxImately50ofthepractIcInganesthesIologIstsIn
theUnItedStates,revealssafetyconcernsInoffIcebasedpractIcesaremorethan
theoretIcal.
21
Asof2001therewere75J(1J.7)claImsforambulatoryproceduresand14
(0.26)foroffIcebasedones.ThIssmallnumberofclaImsmostlIkelybecauseoftheJto
5yeartImelagInreportIngtothedatabase.
21
ASAphysIcalstatus1or2femalepatIents
whohadundergoneelectIvesurgeryundergeneralanesthesIamakeupthemajorItyof
claImsfIled.ThIsstatIstIcparallelstheprofIlesoftrendsseenInoperatIngroomsand
freestandIngASCs.TheInjurIesthatoccurInoffIcestendtobeofgreaterseverItythan
thosethatoccurInASCs.TwentyonepercentofthereportedInjurIessustaInedInoffIces
weretemporaryandnondIsablIngInnatureand64werepermanentorledtodeath,whIle
62oftheInjurIessustaInedInASCsweretemporaryandnondIsablIngandonly21were
permanentorledtodeath.
21
AstudybyCotetal:
J2,JJ
revealedthatthecausesfor
InjurIesInanoffIcerangedfromhumanerrortomachIneandequIpmentmalfunctIon
(TableJJ2).
Table 33-2 Causes of Injury in the Office-Based Practice
1. nadequateresuscItatIonequIpment
2. nadequatemonItorIng
a.|ostcommonlynopulseoxImetry
J. nadequatepreoperatIveorpostoperatIveevaluatIon
4. Humanerror
1. SlowrecognItIonofanevent
2. Slowresponsetoanevent
J. LackofexperIence
4. 0rugoverdosage
0ataderIvedfromCotCJ,KarlHW,Notteman0Aetal:AdversesedatIonevents
InpedIatrIcs:AnalysIsofmedIcatIonsusedforsedatIon.PedIatrIcs2000;106:66J;
andCotCJ,Notteman0A,KarlHWetal:AdversesedatIoneventsInpedIatrIcs:A
crItIcalIncIdentanalysIsofcontrIbutIngfactors.PedIatrIcs2000;105:8
TheClosedClaImsProjectdatabaserevealsthatInjurIesdurIngoffIcebasedprocedures
occurthroughouttheperIoperatIveperIodandaremultIfactorIalInetIology.ThemajorIty,
64,occurredIntraoperatIvely,14occurredInthePACU,and21afterdIscharge.
21
Half
oftheseadverseeventswererespIratoryInnatureandIncludedaIrwayobstructIon,
bronchospasm,InadequateoxygenatIonandventIlatIon,andunrecognIzedesophageal
IntubatIon.Thesecondmostcommongroupofeventsweredrugrelated,occurrIng25of
thetIme.TheseIncludedIncorrectagentordosage,allergy,andmalIgnanthyperthermIa.
CardIovascularInjuresandequIpmentrelatedInjurIeseachoccurredIn8ofIncIdents.
21
AnImportantpoInttoconsIderwhenlookIngatadverseeventsIswhetherornottheywere
preventable.AgaIn,accordIngtotheInformatIonIntheClosedClaImsProjectdatabase,
1JoftheeventsthatoccurredInASCswereconsIderedpreventable,whereas46ofthe
offIcebasedonesweredeemedaspreventable.Furthermore,alloftheadverserespIratory
eventsthatoccurredInthePACUofoffIcescouldhavebeenpreventedhadpulseoxImetry
beenused.CarewasconsIderedtobesubstandardIn50ofD8AclaImsandInJ4ofASC
ones.n2001,claImsorIgInatIngfromanoffIcebasedprocedureresultedInamonetary
award92ofthetIme,wIthamedIanpaymentofS200,000(rangIngbetweenS10,000and
S2,000,000),whereasclaImsorIgInatIngfromASCbasedprocedureswerecompensatedonly
59ofthetIme,wIthamedIanpayoutofS85,000(rangIngbetweenSJ4andS14,700,000).
21
EnsurIngoffIcebasedpractIcesafetyIscrItIcal.AfterseveralhIghlypublIcIzedoffIce
lIposuctIonInjurIesanddeathsInAugust2000,theStateofFlorIdaattemptedtoaddress
thIsproblembyplacInga90daymoratorIumonalloffIcebasedproceduresthatused
anesthetIcdepthsgreaterthanconscIoussedatIon.0urIngthat90dayperIodasafetypanel
composedofsurgeons,anesthesIologIsts,andotherhealthcareprofessIonalswasformed
andchargedwIththetaskofdevelopIngrecommendatIonstoImprovethesafetyrecordof
offIcebasedprocedures.Thepanel'srecommendatIonsconcernedfactorsIncludIngpatIent
selectIon,preoperatIveevaluatIonandtestIng,procedurestobeexcluded,surgeon
qualIfIcatIon,andfacIlItystandards.
1J,J4
DthermajororganIzatIonsthathaveplayeda
leadIngroleIndevelopIngstandardsfortheoffIcebasedpractItIonerIncludetheASA,
ASPS,theAmerIcanAssocIatIonofNurseAnesthetIsts,andtheAmerIcan|edIcal
AssocIatIon.
1J,19,24,J4,J6
P.850
Patient Selection
PrIortopresentIngforanoffIcebasedprocedure,thepatIent'smedIcalcondItIonshouldbe
optImallymanaged.HeorsheshouldhaveapreoperatIvehIstoryandphysIcalexamInatIon
recordedwIthInJ0days,andallpertInentlaboratorytestsandanymedIcallyIndIcated
specIalIstconsultatIon(s)mustbereadIlyavaIlable.Consentfortheprocedureandthe
anesthetIcmustbeInthechart.TheanesthesIologIstshouldhaveaccesstoallofthIs
InformatIonpreoperatIvelyand,whenpossIble,shouldcontactthepatIentprIortothe
scheduledprocedure.
PatIentselectIonremaInsacontroversIaltopIcamongpractIcIngoffIcebased
anesthesIologIstsbecauselIttlemorbIdItyandmortalItydataexIsttosupporttheInclusIon
orexclusIonofspecIfIcpopulatIons.Astudyby|erIdy
J7
In1982concludedthatpatIents
shouldnotbeexcludedfromundergoIngambulatoryproceduresbasedsolelyontheIrage,
thetypeofprocedure,ortheduratIonoftheplannedprocedure.SImIlardataareyetto
exIstregardIngoffIcebasedpractIces;however,somerecommendatIonshavebeenmade.
TheASPShasacknowledgedthattheIdealpatIentforanoffIcebasedprocedurehasanASA
physIcalstatusof1or2.TheyrecommendedthatASAphysIcalstatusJpatIentsundergoan
offIcebasedprocedureonlyafterananesthesIaconsultatIon,andpatIentsassIgnedanASA
physIcalstatusJshouldhaveanoffIcebasedprocedureperformedonlyunderlocal
anesthesIawIthoutsedatIon.
14
TheASAalsohasdevelopedrecommendatIonsregardIng
patIentselectIon.
J8
tIsImportanttorealIzethattheoffIceIsoftenremote,andthe
anesthesIologIstmaybeunabletogetassIstanceshouldItberequIred.Thus,groupsof
patIentsInwhomantIcIpatedanesthetIcproblemsmaydevelopshouldbeavoIded(Table
JJJ).ndIvIdualanesthesIologIstsshouldthereforeconsIderexcludIngcertaInpatIentswIth
sIgnIfIcantcomorbIdcondItIonsInordertoavoIdunantIcIpatedproblems.
15,J9
ThemorbIdlyobeseandpatIentswIthobstructIvesleepapneasyndrome(DSAS)present
unIqueandIncreasInglyfrequentchallengestotheoffIcebasedpractItIoner.ndeed,they
areusuallythesamepopulatIon,wIthestImatesof60to90ofallDSApatIentsbeIng
obese(bodymassIndexJ0kg/m
2
).
40,42
ConfoundIngthIsproblemIsthatthemajorItyof
thepatIentswIthDSAShaveyettobeformallydIagnosed.
4J,44,45
ThesepatIentsarelIkely
topresentmajoranesthetIcproblemsthroughouttheperIoperatIveperIod.
46
Theremaybe
faIluretoIntubateorventIlate,theymayhaverespIratorydIstresssoonafterextubatIon,
orsufferfromrespIratoryarrestwIthpreoperatIvesedatIonorpostoperatIveanalgesIa.
40
ThesepatIentstendtobeexquIsItelysensItIvetotherespIratorydepressanteffectsofeven
smalldosagesofsedatIonoranalgesIcs.
42,46,47
Furthermore,respIratorydepressIonmay
notbereversIblewIthpharmacologIcantagonIsm.
48
DneofthefIrststepsIntheASA
algorIthmformanagementofthedIffIcultaIrwayIstocallforhelp.nanoffIce,thIs
usuallyIsnotpossIble.thasbeenrecommendedthatapostoperatIveobservatIonalunIt
wIthclosemonItorIngofoxygensaturatIonoranIntensIvecareunItsettIngbeusedfor
monItorIngtheDSASpatIentpostoperatIvely.
49
thasalsobeensuggestedthatoutpatIent
facIlItIesdevelopspecIfIcpolIcIesregardIngacceptablepatIentsfortheoutpatIentsettIng,
possIblyexcludIngpatIentswIthDSAS.
4J
TheserecommendatIonswouldalsoclearlybe
relevanttotheoffIcebasedpractItIoner.
Table 33-3 Patients WHO may not be Good Candidates for an Office-Based
Procedure
1. PoorlycontrolleddIabetes
2. ExpectedsIgnIfIcantbloodlossorpostoperatIvepaIn
J. HIstoryofsubstanceabuse
4. SeIzuredIsorder
5. |alIgnanthyperthermIasusceptIbIlIty
6. PotentIaldIffIcultaIrway
1. |orbIdobesIty
2. DbstructIvesleepapneasyndrome
7. NPD8hours
8. Noescort
9. PrevIousadverseoutcomefromanesthesIa
10. SIgnIfIcantdrugallergIes
11. AspIratIonrIsk
NPD,nothIngbymouth.
Table 33-4 Risk Factors for the Development of Deep Vein Thrombosis
(DVT)
Age40
AntIthrombIndefIcIency
CentralnervoussystemdIsease
FamIlyhIstoryof07T
HeartfaIlure
HIstoryofa07T
Hypercoagulablestates
LupusantIcoagulant
|alIgnancy
DbesIty
DralcontraceptIveuse
PolycythemIa
PrevIousmIscarrIage
FadIatIontherapyforpelvIcneoplasms
SevereInfectIon
Trauma
7enousInsuffIcIency
PulmonaryembolIsmIsasIgnIfIcantcauseofperIoperatIvemorbIdItyandmortalItyfrom
anoffIcebasedsurgIcalprocedure.
50,51
FeInIschetal:
52
foundthat0.J9(J7/9,49J)of
patIentswhounderwentrhytIdectomydevelopedadeepveInthrombosIs.Dfthese,40.5
(15/J7)wentontoformapulmonaryembolIsm.AlthoughgeneralanesthesIahad
accountedforonly4JoftheanesthetIctechnIquesusedfortheprocedure,8J.7ofthe
embolIceventswereassocIatedwIththepatIenthavIngundergoneageneralanesthetIc
(CA).FIskfactorsforthedevelopmentofdeepveInthrombosIsappearInTableJJ4.
5J
The
ASPSrecommendsthatpatIentsbestratIfIedaccordIngtorIskandthattheprophylactIc
treatmentbedIrectedbyrIsk(TableJJ5).
AsmorepersonsInsubspecIaltIesbegIntoperformoffIcebasedprocedures,theywIlltreat
olderandsIckerpatIents.TheanesthesIologIstmustbethepatIent'sadvocateInthe
matterofsafety.ThIsadvocacycanresultonlyfromatrueunderstandIngofhowto
adequatelyselectapproprIatepatIentsforthIsunIquesurgIcalvenue.
Surgeon Selection
TherelatIonshIpbetweenthesurgeonandanesthesIologIstmustbeoneofmutualtrustand
understandIng.8ecausethesurgeonperformIngtheproceduremayalsoowntheoffIce,he
orshemustnotputpressureontheanesthesIologIsttoperformananesthetIcIfthe
anesthesIologIstbelIevesthatthepatIentorprocedureIsnotapproprIate.
P.851
Table 33-5 Recommended Treatment for Prevention of Deep Vein
Thrombosis (DVT) in Patients, Stratified by Risk
COHORT TREATMENT
LowFIsk
NorIskfactors
UncomplIcatedsurgery
ShortduratIon
ComfortableposItIon
Kneesflexedat5degrees
AvoIdconstrIctIonandexternalpressure
|oderateFIsk
Age40wIthnoother
rIsksforthe
developmentof07T
ProcedureJ0mIn
ProperposItIonIng
ntermIttentpneumatIccompressIonofcalfor
ankle(prIortosedatIonandcontInueduntIlpatIent
IsawakeandmovIng)
FrequentalteratIonsoftheDFtable
HIghFIsk
Age40wIthotherrIsk
factorsforthe
developmentof07T
ProcedureJ0mIn
undergeneral
anesthesIa
TreatmentasperpatIentswIthmoderaterIsk
PreoperatIvehematologyconsultatIonwIth
consIderatIonofperIoperatIveantIthrombotIc
therapy
DF,operatIngroom.
ThesurgeonmusthaveavalIdmedIcallIcense,regIstratIon,and0rugEnforcement
AdmInIstratIon(0EA)certIfIcate.HeorsheshouldbeeItherboardelIgIbleorboard
certIfIedbyarecognIzedmemberoftheAmerIcan8oardof|edIcalSpecIaltIes,
J4
and
eItherhaveprIvIlegestoperformtheproposedprocedureInalocalhospItal,orhave
traInInganddocumentedcompetencycomparabletoapractItIonerwhodoeshavesuch
prIvIlegesInahospItal.AlthoughthIsrequIrementmaysoundIntuItIve,therehavebeen
casesreportedofsurgeonsperformIngproceduresforwhIchtheyhavelIttleornotraInIng.
4
naddItIon,thesurgeonmusthaveadequatelIabIlItyInsurance,atleastequaltothat
carrIedbytheanesthesIologIst.falawsuItshouldarIseandthesurgeonIsInadequately
Insured,theanesthesIologIstmaybeheldfInancIallyresponsIbleandbecomethedeep
pocket.SImIlarly,thefacIlItyItselfshouldhaveadequatelIabIlItyInsurance.
naddItIon,thereshouldbeasystemInplaceformonItorIngcontInuIngmedIcaleducatIon
aswellaspeerrevIewandperformanceImprovement,forboththesurgeonand
anesthesIologIst.ThIsIsoftennotthecaseInanoffIcebasedpractIce.
4
fananesthesIa
groupprovIdescareatmorethanoneoffIce,anoverallpeerrevIewforthepractIcemay
beused;ItneednotbespecIfIctoeachIndIvIdualoffIcesIte.SoloanesthesIapractItIoners
shouldnotbeexemptfromthIsprocess.HeorsheneedstoalIgnwIththeoffIcesInwhIch
heorsheprovIdesservIces,andeItherpartIcIpateIntheoffIce'sprocessorhelpto
organIzeanongoIngone.ThepeerrevIewcommItteeshouldIncludesurgeons,
anesthesIologIsts,andnursIngstaff.tshouldmeetregularlyandmaIntaInawrIttenrecord
ofmInutesandrecommendatIons.SImIlarly,contInuIngmedIcaleducatIonshouldalsobe
documentedand,atamInImum,shouldbesuffIcIenttomeetrelIcensIngrequIrements.
WhenformulatIngaqualItyassuranceprogram,thereshouldbekeysentIneleventsthat
trIggeracaserevIew(TableJJ6).tIsImperatIvethatthIsrevIewbeanopenforumto
ensurecontInuedqualItyImprovementofcare,andnotbebIasedorhInderedbyfearof
lItIgatIon.LegalcounselshouldbesoughttodetermInewhetherInformatIondIsclosedat
thesemeetIngsIsdIscoverableInacourtoflaw,shouldamalpractIceclaImarIse.
Office Selection
TheanesthesIologIstshouldfunctIonasazealouspatIentadvocateInassurIngthatan
anesthetIcIsperformedonlyInasafelocatIon.
J0
TheoffIceneedstobeapproprIately
equIpped,stocked,andmaIntaInedtoperformaCA(TableJJ7).AllsupplIesmustbeage
andsIzeapproprIateforthepatIentpopulatIon.fananesthesIamachIneorventIlatorIs
present,ItmustberegularlyservIcedandcalIbrated.fpotentInhaledvolatIleagentsor
nItrousoxIde(N
2
D)areused,theremustbeafunctIonIngwastegasscavengIngsystem.
ThIssystemmaybeexhaustedvIaawIndoworroofvent.However,theexhaustmustnot
beventedbackIntotheoffIceorIntoanyotherInhabItedspaceandmustbeInaccordance
wIthDccupatIonal
P.852
SafetyandHealthAdmInIstratIonstandards.AIrtestIngshouldalsobedoneonaregular
basIs.nanoffIcewIthoutanexhaustsystem,totalIntravenousanesthesIatechnIques
shouldbeemployed.SImIlarly,allmedIcalandhazardouswastemustbedIsposedofIn
accordancewIthstateandlocallaws.
Table 33-6 Adverse outcomes Signaling Case Review
a
1. 0entalInjury
2. CornealabrasIon
J. PerIoperatIve|orstroke
4. AspIratIon
5. FeIntubatIon
6. FeturntotheoperatIngroom
7. PerIpheralnerveInjury
8. AdversedrugreactIon
9. UncontrolledpaInornausea/vomItIng
10. UnexpectedhospItaladmIssIon
11. CardIacarrest
12. 0eath
1J. ncompletecharts
14. ControlledsubstancedIscrepancy
15. PatIentcomplaInts
|,myocardIalInfarctIon.
a
SentIneleventsthatshouldtrIggeracaserevIewandbepresentedata
performanceImprovement/qualItyassurancemeetIng.
Table 33-7 Equipment Required for the Safe Delivery of Office-Based
Anesthesia
|onItors
NonInvasIvebloodpressurewIthanassortmentofcuffsIzes
Heartrate/ECC
PulseoxImeter
Temperature
Capnography
AIrwaysupplIes
Nasalcannulas
DralaIrways
Facemasks
SelfInflatIngbagmaskventIlatIondevIce
LaryngoscopesmultIplesIzesandstyles(|acIntoshand|Iller)
Handles
7arIoussIzesoftrachealtubes
Stylettes
EmergencyaIrwayequIpment(L|As,crIcothyrotomykIt,transtrachealjet
ventIlatIonequIpment)
SuctIoncathetersandsuctIonequIpment
CardIacdefIbrIllator
Emergencydrugs
ACLSdrugs
0antroleneandmalIgnanthyperthermIasupplIes
AnesthetIcdrugs
7ascularcannulatIonequIpment
ECC,electrocardIogram;L|A,laryngealmaskaIrway;ACLS,AdvancedCardIacLIfe
Support.
AlloffIces,especIallythosewIthoutventIlatorsoranesthesIamachInes,requIreamethod
todelIverposItIvepressureventIlatIontothepatIent'slungs.ThIscanbeachIevedusInga
selfInflatIngresuscItatIondevIce.Anadequatesupplyofcompressedoxygenmustbe
presentaswellasabackupsupplyforuseInanemergency.noffIcesthatdonothavea
pIpelInesupplyofoxygen,HcylIndersareusuallyusedandseveralEcylIndersshouldbe
keptInreserve.ApolIcymustbeInplacedescrIbIngthetransport,storage,anddIsposalof
medIcalgases,consIstentwIthstateandlocallaws.AllequIpmentdescrIbedIntheASA
algorIthmformanagementofthedIffIcultaIrwayshouldbepresent.
54
AreadIlyavaIlable
meanstocreateanemergencysurgIcalaIrwayandjetventIlatIoncapabIlItymaybe
lIfesavIng.
PerIoperatIvemonItorIngmustadheretotheASAstandardsforbasIcanesthetIc
monItorIng.
55,56
TheseIncludecontInuousmonItorIngofheartrateandoxygensaturatIon,
IntermIttentnonInvasIvebloodpressuremonItorIng,endtIdalCD
2
monItorIngandthe
capacItyforbothtemperaturemonItorIngandcontInuouselectrocardIogram.|onItors
mustberoutInelyservIced,calIbrated,andrepaIredasnecessary.AllmonItorsshouldhave
abackupbatterysupplyandthereshouldbeanextramonItoravaIlableforanemergency.
AllemergencydrugsappearIngontheAmerIcanHeartAssocIatIonAdvancedCardIacLIfe
Support(ACLS)protocolshouldbeavaIlable.TheexpIratIondatesfortheseagentsshould
becheckedonaregularbasIsandoutdateddrugsreplacedasnecessary.AcardIac
defIbrIllatorwIthabatterybackupmustbeImmedIatelyavaIlableandroutInelychecked,
asshouldasourceofsuctIonIncludIngapharyngealsuctIoncatheter.TheoffIcebased
anesthesIologIstshouldbepreparedtobegIntheInItIaltreatmentofmalIgnant
hyperthermIa,whIchrequIreshavIngatleast12bottlesofdantrolene.AcompletelIstIngof
malIgnanthyperthermIasupplIesIsavaIlableonlIneatwww.mhaus.org.
AprotocolforthedelIveryandsecurestorageofcontrolledsubstancesmustbeInplace.A
lIcensedanesthesIologIstmaysupplythesedrugsInaccordancewIth0EAregulatIons,as
mayanylIcensedphysIcIanwIthacurrent0EAregIstratIoncertIfIcate.nsteadof
transportIngdrugs,ItIsoftenmoreconvenIenttostorethemInthesurgIcaloffIce.nthIs
sItuatIon,theymustbestoredInadoublelockedstoragecabInet,InstalledInasecure
locatIon,InaccordancewIthstateandlocalregulatIons.TheoffIceInwhIchthecontrolled
substanceswIllbedIspensedmustalsobeproperlyregIsteredwIththe0EA.0rug
accountIngmustbeperformedInaccordancewIthstateandfederalregulatIons.ndIvIdual
stateshavedIfferentprovIsIonsandregulatIonsregardIngthedIspensIngofcontrolled
substances,andItIstheresponsIbIlItyofthedIspensIngphysIcIantoassurethattheoffIce
basedpractIceIsIncomplIance.
AmedIcaldIrector,responsIbleforoveralloperatIons,shouldbeIdentIfIedforeveryoffIce.
TheremustalsobeapolIcyandproceduresmanualthatoutlInestheresponsIbIlItIesof
eachstaffmember,IncludIngnurses(cIrculatIng/scrubandpostoperatIve),physIcIan
assIstants,surgIcaltechnIcIans,offIcestaff,andadmInIstrators.ThemanualshouldInclude
adescrIptIonoftheInfectIoncontrolpolIcyaswellasanesthesIapolIcIes.Allnursesshould
belIcensedbythestateandhavetraInIngandeducatIonconsIstentwIththeIr
responsIbIlItIes.8asIccardIaclIfesupportcertIfIcatIonshouldbemandatory,andACLS
certIfIcatIonIspreferable.naddItIon,eIthertheanesthesIologIstorthephysIcIanwho
supervIsestheanesthesIacareprovIdermustbecertIfIedInACLSorPedIatrIcAdvanced
LIfeSupport(PALS),dependIngonthepatIentpopulatIon.Thereshouldalwaysbeatleast
onememberofthehealthcareteamwIthACLS/PALScertIfIcatIonpresentIntheoffIce
untIlthelastpatIenthasbeendIscharged.
EmergencIescan,anddo,occurInanoffIcebasedsettIng(TableJJ8).EachoffIcemust
haveaplanInplacedelIneatIngtheresponsIbIlItIesofeachstaffmemberIntheeventof
suchanoccurrence.ThephysIcalstructureoftheoffIceIsanImportantconsIderatIon.
ThereshouldbeaclearegressthatwouldeasIlyaccommodateastretchercarryInga
mechanIcallyventIlated
P.85J
patIent.AdequateclearanceandroomfortransportInanelevatormustalsobe
consIdered.
Table 33-8 Emergencies that Require Contingency Plans
1. FIre
2. 8omb/bombthreat
J. Powerloss
4. EquIpmentmalfunctIon
5. Lossofoxygensupplypressure
6. CardIacorrespIratoryarrestInthewaItIngroom,DF,orPACU
7. Earthquake
8. HurrIcane
9. ExternaldIsturbancesuchasarIot
10. |alIgnanthyperthermIa
11. |assIvebloodloss
12. EmergencytransferofpatIenttoahospItal
DF,operatIngroom:PACU,postanesthesIaunIt.
0estInatIonsforapatIentInneedofhospItaladmIssIonmustbeIdentIfIed.0evelopIngan
offIcehospItalrelatIonshIpIschallengIng,ashospItalsmaybereluctanttobeInvolvedIn
offIcemIshaps.However,ItIsofutmostImportancetohaveaformalwrIttenarrangement.
TelephonIngtheemergencyservIcesnumber(911)IsanacceptableplanfortransportatIon,
provIdedtheresponsetImeIsrapId.f911IsunavaIlableInaspecIfIccItyorhasaslow
responsetIme,theoffIceshouldhaveacontractualagreementwIthanambulance
company.
deallya1hourfIrewallshouldbeInplace.ThIswallwouldprovIdeenoughtImetoawaken
andescortapatIenttosafetyIntheeventofafIre.fa1hourfIrewallIsnotpresent,the
offIceshould,atamInImum,beIncomplIancewIthlocalfIrecodes.AddItIonally,the
offIcemustbeIncomplIancewIthcommercIalconstructIoncodesandwIthmaxImum
occupancyregulatIons.
TheremustbecontIngencyplansIntheeventofapowersupplyInterruptIonorelectrIcal
faIlure.EachoffIceshouldhaveanemergencygeneratorcapableofrunnIngnecessary
equIpmentandmonItors;monItorsshouldhavebatterybackuppowerthatIsroutInely
checked.8atteryreservepowerwIllusuallylastfor11/2hours,butthIsneedstobe
verIfIedforeachpIeceofelectrIcallypoweredequIpment.
TheoffIceshouldkeeppatIentrecords(IncludInganesthesIarecords)InaccordancewIth
locallaws,whIchIsusuallyforamInImumof5years.SImIlarly,theanesthesIologIstshould
maIntaInhIsorherownrecords,whIchIncludethepreanesthesIahIstoryandphysIcal,
Informedconsent,IntraoperatIvedocumentatIon,andpostoperatIvecarerecord,aswellas
dIschargeorders.
Accreditation
DnewaytoobjectIvelyevaluateanoffIceIstohaveItbeaccredItedbyanatIonally
recognIzedaccredItIngagency.TheASAhasdevelopedaclassIfIcatIonofoffIcesthat
stratIfIesthembythelevelofanesthetIcdepththatmaybeadmInIstered(TableJJ9).
J8
|anystatesrequIreoffIcestobeaccredIted,andmorestatesarefollowIngsuIt(TableJJ
1).nstatesthatdonotrequIreaccredItatIon,therearebenefItstovoluntarIlyobtaInIng
It.DftentImesaccredItatIonwIllallowthefacIlItyfeetobereImbursedbyathIrdparty
payerInmedIcallynecessaryprocedures.
57
naddItIon,thepatIentmayfeelmore
comfortableundergoIngaprocedureInanoffIcethathasbeenaccredIted.FInally,asmore
statesrequIreaccredItatIon,Ifasurgeon'soffIceproactIvelybecomesaccredItedInastate
thatsubsequentlyrequIresIt,therewouldbenoInterruptIonofservIces.
7
Table 33-9 American Society of Anesthesiologists Classification of Surgical
Procedures
ClassA
|InorsurgIcalprocedures
Local,topIcal,orInfIltratIonoflocalanesthetIc
NosedatIonpreoperatIvelyorIntraoperatIvely
Class8
|InorormajorsurgIcalprocedures
SedatIonvIaoral,rectal,orIntravenoussedatIon
AnalgesIcordIssocIatIvedrugs
ClassC
|InorormajorsurgIcalprocedures
CeneralanesthesIa
|ajorconductIonblockanesthesIa
0ataderIvedfromAmerIcanSocIetyofAnesthesIologIstsCommItteeonAmbulatory
SurgIcalCareandtheAmerIcanSocIetyofAnesthesIologIstsTaskForceonDffIce
8asedAnesthesIa:DffIcebasedanesthesIa:consIderatIonsforanesthesIologIstsIn
settIngupandmaIntaInIngasafeoffIceanesthesIaenvIronment.ParkFIdge,L,
AmerIcanSocIetyofAnesthesIologIsts,2000,wIthpermIssIon.
CurrentlytherearethreemajoraccredItIngbodIesforoffIcebasedsurgeryoffIces,
althoughseveralotheragencIesarealsorecognIzed.TheAccredItatIonAssocIatIonfor
AmbulatoryHealthCare(AAAHC)wasthefIrstmajoraccredItIngbody,offerIng
certIfIcatIonsInce1998.TheAmerIcanAssocIatIonforAccredItatIonofAmbulatorySurgIcal
FacIlItIes(AAAASF),orIgInallytheAccredItatIonAssocIatIonforAmbulatoryPlastIcSurgIcal
FacIlItIes,wasthesecondgroup,followedbytheJoIntCommIssIonforAccredItatIonof
HealthcareDrganIzatIons(JCAHD).Todate,themostactIveorganIzatIonIstheAAAASF.ts
requIrementsaresImplerthanthoseofAAAHCandJCAHDandaccredItatIonIsless
expensIve;however,changesareunderwaytoallowAAAHCandJCAHDtobemore
competItIve.
7
EachagencyhasdIfferentcrIterIaforelIgIbIlItyanddIfferentaccredItatIon
cyclespertaInIngtothetImelImItofacertIfIcate.
58
TheagencIesdealwIthsurgIcal
condItIonsrangIngfromphysIcaloffIcedesIgntopatIentIssues(TableJJ10).naddItIon
theAAAHCcanaccredItnotonlythesurgIcaloffIce,butalsoananesthesIagroupthat
provIdesD8A.
Table 33-10 Factors to be Considered in Accrediting an Office for Surgical
Procedures
a
1. PhysIcallayoutoftheoffIce
2. EnvIronmentalsafety/InfectIoncontrol
J. PatIentandpersonnelrecords
4. SurgeonqualIfIcatIon
1. TraInIng
2. LocalhospItalprIvIleges(surgIcalandadmIssIon)
5. DffIceadmInIstratIon
6. AnesthesIologIstrequIrements
7. StaffIngIntraoperatIvelyandpostoperatIvely
8. |onItorIngcapabIlItIesbothIntraoperatIvelyandpostoperatIvely
9. AncIllarycare
10. EquIpment
11. 0rugs(emergency,controlledsubstances,routInemedIcatIons)
12. 8LS,ACLS/PALScertIfIcatIon
1J. Temperature
14. NeuromuscularfunctIonIng
15. PatIentposItIonIng
16. PreandpostanesthesIacare/documentatIon
17. QualItyassurance/peerrevIew
18. LIabIlItyInsurance
19. PACUevaluatIon
20. 0IschargeevaluatIon
21. Emergencyprocedure(e.g.,fIre/admIssIon/transfer)
8LS,basIccardIaclIfesupport;ACLS,AdvancedCardIacLIfeSupport;PALS,
PedIatrIcAdvancedLIfeSupport;PACU,postanesthesIacareunIt.
a
AcompletelIstIngofcrIterIacanobtaInedfromtheIndIvIdualagencIes.
P.854
TheaccredItIngagencIesweredeveloped,Inpart,toreducesomeofthevarIabIlItythat
exIstsamongoffIcesInregardtosafetyIssues.SeveralprofessIonalsocIetIesare
encouragIngtheIrmemberstoperformproceduresonlyInaccredItedfacIlItIes.TheSocIety
forAesthetIcPlastIcSurgeonsmandatesthatallofItsmembersperformproceduresonlyIn
offIcesthathaveeItherbeenaccredItedbyoneofthenatIonallyrecognIzedaccredItIng
agencIes,havebeencertIfIedtopartIcIpateInthe|edIcareprogramunderTItleX7,or
arelIcensedbythestate.TheactualImprovementInsafetyconferredbyperformIng
surgeryInanaccredItedoffIcehasyettobedetermIned,andtherearethosewhosuggest
thatItprovIdesnoadvantage.
22,59
AslongasthereIsnomandatoryreportIngsystemIn
place,ItwIllbeImpossIbletodetermInetruemorbIdItyratesassocIatedwIthanoffIce
basedpractIce.Clearlythough,safetyInanoffIcedependsonmorethanjust
accredItatIon;theremustbeconstantvIgIlancebyallmembersofthehealthcareteam.
Procedure Selection
EarlyInthedevelopmentofoffIcebasedsurgery,proceduresweregenerallynonInvasIve
andofshortduratIon.However,asnewersurgIcalandanesthetIctechnIqueshaveevolved,
longerandmoreInvasIveprocedureshavebeensuccessfullyperformed.
J0,60,61,62,6J,64,65
SuItableoffIcebasedproceduresrangethegamutfromIncIsIonanddraInageofabscesses
tomIcrolaparoscopIes.
0uratIonofprocedurehaslongbeencorrelatedwIththeneedforhospItaladmIssIon,wIth
procedureslastIng1hourbeIngassocIatedwIthahIgherIncIdenceofunplanned
admIssIon.
67
DtherdatahaveshownthatlongerproceduresarealsooftenassocIatedwIth
anIncreasedIncIdenceofpostoperatIvenauseaandvomItIng(PDN7),postoperatIvepaIn,
andbleedIng,
68,69
whIchmaywarranthospItaladmIssIon.ForthesereasonstheASPShas
recommendedthatproceduresbelImItedto6hoursandbecompletedbyJP|,thus
allowIngforafullpatIentrecoverywIthmaxImumoffIcestaffIng.
J4
naddItIon,when
determInIngthesuItabIlItyofaprocedure,onemustconsIderthepossIbIlItyof
hypothermIa,bloodloss,orsIgnIfIcantfluIdshIfts.
J4
Specific Procedures
Liposuction
LIposuctIonIsthesecondmostcommonlyperformedcosmetIcprocedureafterbreast
augmentatIon,andIsperformedprImarIlybyplastIcsurgeonsanddermatologIsts.
70
tIs
accomplIshedbyInsertInghollowrodsIntosmallIncIsIonsIntheskInandsuctIonIng
subcutaneousfatIntoanaspIratIoncanIster.SuperwetandtumescenttechnIques,
IntroducedInthemId1980s,uselargevolumes(1to4mL)ofInfIltratesolutIon(0.9salIne
orFIngerlactatewIthepInephrIne1:1,000,000andlIdocaIne0.025to0.1)foreach1cm
J
offattoberemoved.8loodlossIsgenerally1oftheaspIratewIththesetechnIques.
71
ThepeakserumlevelsoflIdocaIneoccur12to14hoursafterInjectIonanddeclIneoverthe
subsequent6to14hours.
72,7J
AlthoughthemaxImumdoseoflIdocaInehasbeen
tradItIonallylImItedto7mg/kg,dosesofJ5to55mg/kghavebeenusedsafelybecausethe
tumescenttechnIqueresultsInasInglecompartmentclearancesImIlartothatofa
sustaInedreleasemedIcatIon.
7J,74
LIposuctIonIsnotabenIgnprocedure.n2000,acensussurveyofthe1,200membersofthe
AmerIcanSocIetyofAesthetIcPlastIcSurgeonsrevealedanoverallmortalItyrateof
19.1/100,000lIposuctIonprocedures,wIthpulmonaryembolIsmthedIagnosIsIn2J.1of
deaths.DthercausesofmortalItyIncludedabdomInalvIscousperforatIon,anesthesIa
causes,fatembolIsm,InfectIon,andhemorrhage;28.5ofalldeathsInthIsstudywere
reportedasofunknownorconfIdentIaletIology.
75
FIskfactorsIdentIfIedIncludedtheuse
ofmultIlIterwettIngsolutIonInfIltratIon,megavolumeaspIratIoncausIngmassIvethIrd
spacIng,multIpleconcurrentprocedures,anesthetIcsedatIveeffectsyIeldIng
hypoventIlatIon,andpermIssIvedIschargepolIcIes.ThemanagementofthepostoperatIve
perIod,wIthattentIontofluIdandelectrolytebalanceandpaIncontrol,IscrItIcaltoan
optImaloutcomeafterlIposuctIon.ThepatIent'sfluIddefIcIt,maIntenance,IntraoperatIve
loss,andthIrdspacIngshouldguIdefluIdmanagementthroughouttheperIoperatIveperIod.
Cenerally,anoffIcelIposuctIonshouldbelImItedto5,000mLoftotalaspIrant,whIch
IncludessupernatantfatandfluId.
J4
tIsalsorecommendedthatlargevolumelIposuctIon
notbedoneInconjunctIonwIthotherprocedures.
versonetal:
1J,J4
developedthefollowIngconsIderatIonsandrecommendatIonsregardIng
offIcebasedlIposuctIon:
1. PlastIcsurgeonsshouldfollowthecurrentASACuIdelInesforSedatIonandAnalgesIa.
2. CAcanbeusedsafelyIntheoffIcesettIng.
J. CAhasadvantagesformorecomplexlIposuctIonproceduresthatIncludeprecIsedosIng,
controlledpatIentmovement,andaIrwaymanagement.
4. EpIduralandspInalanesthesIaIntheoffIcesettIngIsdIscouragedbecauseofthe
possIbIlItyofvasodIlatatIon,hypotensIon,andfluIdoverload.
5. |oderatesedatIon/analgesIaaugmentsthepatIent'scomfortandIsaneffectIveadjunct
totheanesthetIcInfIltratesolutIons.
TwohundredsIxtyonerespondentstoasurveysenttothemembershIpofTheAmerIcan
SocIetyfor0ermatologIcSurgeryreportednomortalItIesamong66,570lIposuctIon
proceduresperformedInhospItals,ASCs,andoffIces.Theauthorsreportedadverseevents,
whIchmIrroredthoseIntheAmerIcanSocIetyofAesthetIcPlastIcSurgeons.Theyfound
thatserIousadverseeventsoccurredmorefrequentlywIthproceduresperformedIn
hospItalandASCsthanthoseInoffIces.ThIsmaybepartlybecauselIposuctIonInhospItals
IsperformedonsIckerpatIentsorthattheproceduresareassocIatedwIthremovalofa
largeramountoffat.nterestIngly,71oftheoffIcessurveyedwerenonaccredIted.
Further,theauthorsreportedthatmorbIdItycorrelatedbetterwIththeareaofthebody
suctIoned(abdomenandbuttocks)thanthefacIlItyInwhIchtheproceduretookplace.
76
Aesthetics
|anyfacIalaesthetIcproceduressuchasblepharoplasty,rhInoplasty,andmeloplastyare
routInelyperformedInoffIces,usuallyundervaryIngdepthsof|AC,butoccasIonallywIth
CA.FacIalplastIcproceduresthatrequIreuseofalaserorevenroutIneelectrocautery
poseaproblemfortheanesthesIologIst.SupplementalnasaloxygenInpatIentsreceIvIng
sedatIonIsafIrehazard.AnysupplementaloxygenmustbeturnedoffdurIngperIodsof
laserorelectrocauteryuseabouttheface,andthIsrequIresvIgIlancebythe
anesthesIologIstwhomustbeInconstantcommunIcatIonwIththesurgeon.|ethodsfor
delIverIngsupplementaloxygentoapatIenthavIngafacIalprocedureIncludenasal
cannula,anoxygenhood,orplacementofoxygentubIngInanoral/nasalaIrway.The
latterusuallyrequIresadeeperlevelofsedatIon.TheavoIdanceofsupplementaloxygen
whenmedIcallyapproprIateIsIdeal.
Breast
ProceduressuchasbreastbIopsyoraugmentatIon,Implantexchanges,andcompletIonof
transverserectusabdomInalmuscleflaps(e.g.,nIppleconstructIonorrevIsIons)are
routInelyperformedInoffIcesettIngs.8reastaugmentatIonentaIls
P.855
separatIngthepectoralIsmusclesfromthechestwall,whIchIspaInfulandusuallyrequIres
CA.ThIscanbeaccomplIshedbyusIngeItheralaryngealmaskaIrwayortrachealtube.
TheuseofregIonalanesthesIawIthparavertebralnerveblockshasalsobeenreported.
77
8reastsurgeryhasahIghIncIdenceofPDN7,thusItIslIkelythatpatIentsundergoIng
breastsurgerywIllrequIreantIemetIcmedIcatIonInaddItIontopostoperatIveanalgesIcs.
78
Gastrointestinal Endoscopy
ProceduresperformedbygastroenterologIstsIncludeesophageal,gastrIc,andduodenal
endoscopIesandcolonoscopIes.ThIspatIentpopulatIontendstobeolder,wIthsIgnIfIcant
comorbIdcondItIons.UppergastroIntestInalproceduresrarelyrequIreendotracheal
IntubatIonbecause,althoughmanyofthesepatIentshavegastroesophagealreflux,the
stomachIsemptIedunderdIrectvIsualIzatIon.TheendoscopIstrequIrespatIent
partIcIpatIontoaIdInInsertIonoftheendoscope,whIchcanusuallybeaccomplIshedwIth
sedatIonusIngsmalldosesofpropofolwIthorwIthoutmIdazolam.
ColonoscopyIspaInfulsecondarytotheInsertIonandmanIpulatIonoftheendoscope,and
maybeassocIatedwIthcardIovasculareffects,IncludIngdysrhythmIa,bradycardIa,
hypotensIon,hypertensIon,myocardIalInfarctIon,anddeath.ThemechanIsmofthese
cardIovasculareffectsIsnotknown,butthereIsevIdencethattheymaybemedIatedby
theautonomIcnervoussystemwhenstImulatedbyanxIetyordIscomfort.
79
AddIngan
opIoIdtomIdazolamdurIngcolonoscopyhasbeenshowntoImprovepatIenttoleranceof
theprocedureanddecreasepaInwIthoutIncreasIngthefrequencyofrespIratoryevents.
80
nterestIngly,anesthetIctechnIquesconsIstIngofmIdazolam,
81
remIfentanIl/propofol,and
fentanyl/propofol/mIdazolam
82
potentIatethelowfrequencycomponentsofheartrate
varIabIlIty,whIchreflectssympathetIcactIvatIonasseenoncontInuous
electrocardIography,andmaycontrIbutetothenumberofcardIovasculareventsthat
occurdurIngcolonoscopy.
Fecently,thegastroenterologycommunItyhassoughttobeabletoprovIdemoderateor
evendeepsedatIonwIthpropofolwIthouttheassIstanceofatraInedanesthesIologIst.
8J
However,becauseofsafetyconcernspropofolmaystIllonlybegIvenbyananesthesIologIst
asIndIcatedIntheproductInsert.AddItIonally,thenstItuteforSafe|edIcalPractIceshas
IndIcatedthatpropofolmaybeadmInIsteredonlybyIndIvIdualswhoaretraInedInthe
admInIstratIonofdrugsthatcausedeepsedatIonandCAandwhoprovIdeonlythe
sedatIon(notalsoperformIngtheprocedure)andareprofIcIentattrachealIntubatIon.
84
TheAAAASFhaslIkewIseIndIcatedthatanesthesIaprofessIonalsarebestqualIfIedto
admInIsterpropofolsedatIon.
Dentistry and Oral and Maxillofacial Surgery
NItrousoxIdehasbeenusedformostoftheworld'soffIcebaseddentalanesthetIcssInce
1884,whenHoraceWells,hImselfadentIst,hadN
2
DadmInIsteredforawIsdomtooth
extractIonbyacolleague.twasHarryLanga,anotherdentIst,whopIoneeredtheconcept
ofusInglowerconcentratIonsofN
2
DIncombInatIonwIthlocalanesthetIcs.ThIsIdeaof
relatIveanalgesIawastheforbearerofconscIoussedatIon.
85
TheAmerIcanAssocIatIonofDraland|axIllofacIalSurgeonsstudIedaprospectIvecohort
studyofpatIentswhounderwentoralandmaxIllofacIalsurgerybetweenJanuaryand
0ecember2001.DftheJ4,191patIentsIncluded,71.9receIveddeepsedatIon/CA,15.5
conscIoussedatIons,and12.6localanesthesIa.TheoperatIngsurgeonprovIdedanesthesIa
servIcesIn96ofcases;theanesthesIaspecIfIchospItalIzatIonratewas4/100,000,wIthno
reportedmortalItIes.TheauthorsattrIbutedthIssafetyleveltotheuseofpulseoxImetry,
bloodpressureandventIlatIonmonItorIng,aswellasadmInIstratIonofsupplemental
oxygen.
86
AsanesthesIologIstsIncreasetheIrpresenceInthedental/oralandmaxIllofacIal
surgeryarena,onecanexpectanIncreasedutIlIzatIonofnontradItIonalagentsfor
procedures.
Orthopaedics and Podiatry
TheorthopaedIcoffIceprovIdesanexcellentlocatIonfortheanesthesIologIstwho
practIcesregIonalanesthesIa.AlthoughkneearthroscopIescanbeperformedwIthIntra
artIcularlocalanesthesIaand|AC,athreeInoneblockofthelumbarplexuswIth
bupIvacaIneorropIvacaIne,supplementIngtheIntraartIcularlocalanesthetIcInan
arthroscopIcallyassIstedanterIorcrucIatelIgamentrepaIrwIllprovIdelongactIng
postoperatIveanalgesIa.nterscaleneandaxIllaryregIonalanesthetIcsavoIdaIrway
manIpulatIonsInpatIentsundergoIngupperextremItyprocedures,whIleankleblocksor
blocksofthescIatIcnerveInthepoplItealfossaprovIdeanesthesIaforoperatIonsonthe
lowerextremIty.AlloftheseblockscanbesupplementedwIthshortactInganxIolytIc
agents.
SpInalanesthetIcsIntheoffIcebasedsettIngmustbeofshortduratIon,secondaryto
lImItedPACUspace.LIdocaIne,whIchprovIdesrelIableshortactInganalgesIa,maybe
assocIatedwIthanIncreasedrIskoftransIentneurologIcsymptomsIntheambulatory
patIentpopulatIon,
87
whereasusIngprocaInefentanylspInalsareassocIatedwIthnausea
andvomItIngaswellasprurItus.
88
WhentheneuraxIalanesthetIcwearsoff,Issuesof
postoperatIvepaInmanagementarIse;therefore,thepatIentmustbedIschargedwIthoral
analgesIcsaswellascontactInformatIonforboththesurgeonandtheanesthesIologIst.
Gynecology and Genitourinary
|anyprocedures,suchasdIlatIonandcurettage,vasectomy,andcystoscopyhavebeen
performedInoffIcesformanyyears.FecentlytherehasbeenanIncreaseInmoreInvasIve
proceduressuchasmInIlaparoscopIes,ovumretrIeval,prostatebIopsIes,andlIthotrIpsy,
necessItatIngananesthesIologIst'sexpertIse.AvarIetyofanesthetIcoptIonsareavaIlable
fortheseproceduresandtheanesthetIcchoIcedependsonthesurgeon,patIent,and
anesthesIologIst'spreferences.
Ophthalmology and Otolaryngology
DphthalmologIcproceduressuItablefortheoffIceIncludecataracts,lacrImalductprobIng,
andocularplastIcs.TopIcalanesthesIaandperIorbItalorretrobulbarblocksarefrequently
usedtoprovIdeanalgesIa.SupplementalsedatIonmayberequIred.Dtolaryngology
proceduresIncludeendoscopIcsInussurgery,turbInateresectIon,septoplasty,and
myrIngotomy.AgaIn,combInatIonsoftopIcalandregIonalnerveblockswIthsupplemental
sedatIonarecommonlyemployed,butoccasIonallyCAIsused.
Pediatrics
AlthoughnomInImumagerequIrementforachIldtoundergoanoffIcebasedanesthetIc
hasbeenestablIshed,patIents6monthsofageandASAphysIcalstatus1or2maybe
reasonablecandIdates.
89
ApproprIateD8ApedIatrIccasesareusuallydental,andchloral
hydratewIthN
2
DhashIstorIcallybeentheanesthetIcchoIceofmanydentIsts.However,
theuseoftheseagentsIsassocIatedwIthsIgnIfIcantmorbIdIty.FossandEck
9
foundthatIn
chIldrenbetweentheagesof1and9years,70mg/kgofchloralhydratewIthJ0N
2
D
resultedInhypoventIlatIonIn94ofpatIents,whIchIncreasedto97ofpatIentswhenthe
chloralhydratewascombInedwIth50N
2
D.ThIsIncreaseIssIgnIfIcantInvIewofthe
fIndIngsofCotetal:,
J2,JJ
whorevIewed95adversesedatIonrelatedeventsIn
P.856
pedIatrIcpatIents.nthe9JofthesecasesthatresultedInpermanentneurologIcInjuryor
death,theanesthetIcwasdelIveredbyeItheranoralsurgeon,perIodontIst,orcertIfIed
regIsterednurseanesthetIstsupervIsedbyadentIst.
Table 33-11 Guidelines for the Pediatric Perioperative Anesthesia
Environment
PatIentCareFacIlItyand|edIcalStaffPolIcIes
0esIgnatIonofoperatIveprocedures
CategorIzatIonofpedIatrIcpatIentsundergoInganesthesIa
AnnualmInImalcasevolumetomaIntaInclInIcalcompetence
ClInIcalPrIvIlegesofAnesthesIologIsts
FegularprIvIleges
SpecIalclInIcalprIvIleges
PaInmanagement
PatIentCareUnIts
PreoperatIveevaluatIonandpreparatIonunIts
DperatIngroom
AnesthesIologIsts
DtherhealthcareprovIdersInvolvedInperIoperatIvecare
ClInIcallaboratoryandradIologIcservIcesavaIlabIlItyandcapabIlItIes
PedIatrIcanesthesIaequIpmentanddrugs,IncludIngresuscItatIoncart
PACU
NursIngstaff
AnesthesIologIst/physIcIanstaff
PedIatrIcanesthesIaequIpmentanddrugs
PostoperatIventensIveCare
ThereareIncreasIngnumbersofophthalmologIc(examInatIonunderanesthesIa,lacrImal
ductprobIng),otolaryngology(myrIngotomy),cast/dressIngchanges,andmInorplastIcs
proceduresbeIngperformedonchIldrenInoffIces.TheAmerIcanAcademyofPedIatrIcs
SectIononAnesthesIologyhasdevelopedguIdelInesforthepedIatrIcperIoperatIve
envIronmentthatshouldbeadheredtoIntheD8AsettIng(TableJJ11).
90
Anesthetic Techniques
TheASArecommendsthatanesthetIcsbeprovIdedorsupervIsedbyafullylIcensed
anesthesIologIst.
J8
fananesthesIologIstIsdIrectInganesthesIacare,heorshemustbe
ImmedIatelyavaIlablethroughouttheentIreperIoperatIveperIod.FegulatIonsInseveral
stateshavequestIonedtheneedforthIslevelofanesthesIatraInIngInthedelIveryofD8A.
SomestatesallowforananesthetIctobeperformedbyanonphysIcIananesthesIaprovIder
supervIsedbyalIcensedphysIcIan.nthIssItuatIon,thesupervIsIngphysIcIanmustbe
qualIfIedtoperformapreanesthetIcfocusedhIstoryandphysIcalexamInatIonaswellasbe
ImmedIatelyavaIlablethroughouttheperIoperatIveperIod.Heorshemustknowhowto
handleanesthetIcrelatedemergencIesandcomplIcatIons.ThesupervIsIngphysIcIanmust
beACLScertIfIed.
D8AmayentaIlanytypeofanesthesIafrom|ACthroughregIonalandCA.
90
AnesthesIaIs,
however,acontInuumandItIsoftenImpossIbletopredIcthowapatIentwIllreact.The
ASAhasdevelopeddefInItIonsregardIngdepthsofanesthesIa(TableJJ12).PatIentswIll
routInelydrIftbetweentheanesthetIcdepths,thusItIsImperatIvethattheanesthesIa
provIderorsupervIsorbeabletorescueapatIentfromadeeperlevelofanesthetIcthan
wasantIcIpated.
WhenformulatIngananesthetIcplan,onemustconsIderthatallagentsandtechnIques
usedshouldbeshortactIng,andthusthepatIentshouldbereadyfordIschargehomesoon
afterthecompletIonoftheprocedure.
5,91
Furthermore,anyagentsusedshouldhavea
hIghsafetyprofIleaswellasbecosteffectIve.
92
nchoosIng|ACoverCA,onemustnotbe
underthefalseImpressIonthat|ACanesthesIaIsInherentlysaferthanCA.n1988,Cohen
etal:
9J
revIewedthedatafrom100,000anesthetIcs.TheyfoundthatthegroupwIththe
greatestnumberofmortalItIeshadundergoneprocedureswIth|AC,whereas|AC
constItutedonly2ofallcases.ThecomplIcatIonraterelatedto|ACanesthetIcsIs
IncreasIngasItsuseexpands.TheClosedClaImsProjectdatabaserevealsthatInthe1970s
|ACcasesaccountedfor1.6oftheclaIms,Inthe1980s,1.9,andbythe1990s,6ofthe
caseswere|ACanesthetIcs.
94
narecentrevIewby8hanaker,etal,Itwasfoundthat
InjurydurIng|ACrangesfromtemporaryandnondIsablIngthroughdeath,wIthdeath
accountIngforJJofallclaImsdurIng|AC.
94a
ThecausesforInjurIesdurIng|ACare
varIed(TableJJ1J).ThepercentageofclaImsresultIngfrommortalItywasIdentIcalfor
both|ACandCAcases.nthe1990s,whenInjurIesotherthandeathoccurreddurIng|AC
anesthetIcs,theyweremorelIkelytobepermanent,whereasInjurIesoccurrIngdurIngCA
weremorefrequentlytemporary.
94
|ACanesthetIcsalsotendtoleadtolItIgatIon.SuIts
werefIledIn90ofthe|ACclaIms;65weresettled,20wenttojudgment,and15were
dIscontInued.TherangeofpayoutwasS2,000toS6,J00,000wIthamedIanofS75,000.
94
P.857
Table 33-12 Definitions of Levels of Sedation/Analgesia by the American
Society of Anesthesiologists
1. |InImalsedatIon(anxIolysIs)
1. 0rugInducedsedatIon
2. PatIentrespondsnormallytoverbalcommands
J. CognItIveandmotorfunctIonmaybeImpaIred
4. 7entIlatoryandcardIovascularfunctIonmaIntaInednormally
2. |oderatesedatIon/analgesIa(conscIoussedatIon)
2. PatIentrespondspurposefullytoverbalcommandseItheraloneorwIthlIght
tactIlestImulatIon
J. PatIentmaIntaInsapatentaIrwayandspontaneousventIlatIon
4. CardIovascularfunctIonmaIntaIned
J. 0eepsedatIon/analgesIa
2. PatIentcannotbeeasIlyarousedbutcanrespondpurposefullytorepeatedor
paInfulstImulatIon
J. 7entIlatoryfunctIonmaybeImpaIred,requIrIngassIstanceInmaIntaInInga
patentaIrway,andspontaneousventIlatIonmaybeInadequate
4. CardIovascularfunctIonIsusuallymaIntaIned
4. CeneralanesthesIa
1. 0rugInducedlossofconscIousness
2. PatIentscannotbearousedbypaInfulstImulatIon
J. 7entIlatoryfunctIonIsoftenImpaIred;patIentmayrequIreassIstanceIn
maIntaInIngapatentaIrway.
4. SpontaneousventIlatIonmaybeImpaIredaswellasneuromuscular
functIonIng
5. PosItIvepressureventIlatIonIsoftenrequIred
6. CardIovascularfunctIonmaybeImpaIred.
AdaptedfromAmerIcanSocIetyofAnesthesIologIstsTaskForceonSedatIonand
AnalgesIabyNonAnesthesIologIsts.PractIceguIdelInesforsedatIonandanalgesIa
bynonanesthesIologIsts.AnesthesIology2002;96:1004
Table 33-13 Causes of Injuries During Monitored Anesthesia Care (n = 121)
FespIratory29(24)
EquIpmentFaIlure/|alfunctIon25(21)
CardIovascularEvent17(14)
nadequateAnesthesIa/PatIent|ovement1J(11)
|edIcatIonFelated11(9)
FelatedtoFegIonal8lock2(2)
DtherEvents24(20)
a
a
ncludIngsurgIcaltechnIque/patIentcondItIon,wrongoperatIon/locatIon,
posItIonIng,faIluretodIagnose.
Adaptedfrom8hanankerS|,PosnerKL,CheneyFW,etal.njuryandlIabIlIty
assocIatedwIthmonItoredanesthesIacare.AclosedclaImsanalysIs.
Anesthetic Agents
ntravenoussedatIon(propofol,barbIturates,mIdazolam,fentanyl,meperIdIne)Isthe
mostoftenusedanesthetIctechnIqueIntheD8AsettIng.
J0
WhenselectIngananesthetIc
foranoffIcebasedprocedure,onemustconsIderfactorssuchasduratIonofactIon,cost
effectIveness,andsafetyprofIle.ThedrugsshouldhaveashorthalflIfe,beInexpensIve,
andnotbeassocIatedwIthundesIrablesIdeeffectssuchasnauseaandvomItIng.
AlthoughfentanylhasbeenthemaInstayforshortactIngnarcotIcs,recentlytheuseof
remIfentanIlhasIncreasedInpopularIty.ThIsultrashortactIngopIoId,whencombIned
wIthpropofolforconscIoussedatIon,hasbeenshowntoprovIdedIschargereadInesswIthIn
15mInutesaftercolonoscopy.ThIstImeframeIsamarkedreductIonfromthe48to80
mInutesreportedafterthetradItIonalmeperIdIne/mIdazolamtechnIque.
95
FemIfentanIlIs
alsoanIdealdrugforusedurIngmanyoffIcebasedprocedures,suchasfacIalcosmetIc
procedures,whIchcanbequItepaInfulwhIlethelocalanesthetIcIsbeIngInjectedand
afterwhIchItIsrelatIvelypaInless.AnImportantcaveattotheuseofremIfentanIlIsthat
ItmaycausenauseaandvomItIngaswellasapnea.AddItIonally,ItoftenrequIrestheuse
ofanInfusIonpump.
KetamIne,aphencyclIdInederIvatIve,hasexperIencedaresurgenceoverthepastseveral
yearsIntheD8ApractIce.
9
TheuseofketamInepropofolsedatIonhasbeendescrIbedasan
excellentwaytoprovIdearelaxedsurgIcalfIeldInaquIet,ImmobIlepatIent,often
elImInatIngtheneedforsupplementaloxygen.
96
KetamInefunctIonsasbothananesthetIc
andananalgesIc.tdoesnotdepressrespIratIonandwIllIncreaselaryngealreflexes,thus
decreasIngtherIskofaspIratIon.Furthermore,ItIsnotassocIatedwIthnauseaand
vomItIng.
97
KetamInecan,however,causeanIncreaseInsecretIonsaswellascause
hallucInatIons.ThelattercanbedecreasedorelImInatedbyaddIngpropofoland
mIdazolam.
97,98,99,100
ClycopyrrolatecanbeusedasanantIsIalagogue.Anotheradvantage
ofketamIneIsthatItIsrelatIvelyInexpensIve.
ClonIdInehasalsobeenfoundtobeusefulInanoffIce.8ecauseItIsan
2
agonIst,
clonIdInewIllhelpcontrolbloodpressurethroughouttheperIoperatIveperIod,thus
potentIallymInImIzIngbloodloss.
101,102
naddItIon,Itmaydecreasethetotalpropofol
usage.
100
However,ItsusemayprecIpItatehypotensIonandoversedatIondurIngthe
AnytypeofanesthesIafromsedatIonthroughCAcanbeadmInIsteredsafelyInanoffIce
settIng.However,becauseanesthesIaIsacontInuum,ItIsvItalthattheoffIcebe
adequatelyequIppedandstaffedtorescueapatIentfromadeeperstageofanesthesIa.
Thus,If|ACIsplanned,CAmustbeantIcIpated.
0epthofanesthesIamonItorInghasbeenshowntodecreasethetImetoextubatIonand
dIschargereadIness.
10J,104,105
AdepthofanesthesIamonItorhasbeendescrIbedasusefulIn
theoffIcedurIng|ACprocedures,wIthapossIbledecreaseIntotalpropofolusage.
106
WhetherthIstypeofmonItorIngwIllprovetobecosteffectIveIntheoffIcebasedsItuatIon
remaInstobeseen.
Postanesthesia Care Unit
FollowInganoffIcebasedprocedure,thepatIentshouldbeabletosItInachaIror
ambulatetoanexamInatIonroomtodress,almostImmedIatelypostoperatIvely.Aformal
PACUmaynotbepresent,andthepatIentmayberequIredtorecoverInthesurgIcalsuIte.
FegardlessofwherethepatIentrecovers,ItIsImportanttoadheretoalltheASAstandards
formonItorInganddocumentatIonthroughoutthepostoperatIveperIod.
56
StaffIngInthe
recoveryareamustbeadequate,andtheuseofapulseoxImeterIsImperatIve.
21,107
tIs
recommendedthattherebeatleastoneACLS/PALScertIfIedmemberofthehealthcare
teampresentuntIlthelastpatIenthaslefttheoffIce.
8ecausePACUspaceInanoffIceIsoftenlImItedandtheanesthesIologIstmayhave
multIplelocatIonstoattendInasIngleday,problemsofPDN7andpaInareofpartIcular
concern.TheeffectofthesephysIologIcoccurrencesarenotlImItedtothepatIentand
anesthesIologIst,butmayalsohaveaprofoundeconomIcImpactonanoffIcesurgIcal
unIt.
108
tIsImperatIvethateveryanesthetIcadmInIsteredbedesIgnedtomaxImIze
postoperatIvepatIentalertnessandmobIlItyandmInImIzetherIsksoftheneedfora
prolongedPACUstay.
109
TwerskyhasrecommendedthatthepostanesthesIadIscharge
scorIngsystemandclInIcaldIschargecrIterIausedInambulatorysurgerybealsousedIn
theoffIcebasedsettIng.
J0
nterestIngly,thereIsatrendtodIschargepatIents,partIcularly
aftercolonoscopy,wIthoutescorts.ThIshasbeensanctIonedInsomestates.nNewYork,
regulatIonsrequIrethatallpatIentsundergoIngaprocedurewIthanesthesIabedIscharged
InthecompanyofaresponsIbleadult,unlessexemptedbyaphysIcIan.
110
SpecIfIcdata
confIrmIngthesafetyofthIspractIcedonotexIst.
LocalanesthesIa,conscIoussedatIonsupplementedbywoundInfIltratIonwIthlocal
anesthetIcs,orperIpheralnerveblocksoftenformsthebasIsforamultImodalstrategyfor
postoperatIvepaInmanagement.TheseeffectIvepaInrelIeftechnIquesnotonlydecrease
theanesthetIcandanalgesIcrequIrementsdurIngsurgerybutalsoreducetheneedfor
opIoIdanalgesIcsInthepostoperatIveperIod,thusfacIlItatIngtherecoveryprocess.
111
NonopIoIdanalgesIcs(e.g.,acetamInophen)andnonsteroIdalantIInflammatorydrugs(e.g.,
ketorolac)areroutInelyused.KetorolacdecreasestheIncIdenceofPDN7,andpatIents
receIvIngIttolerateoralfluIdsandmeetdIschargecrIterIaearlIerthanthosereceIvIng
opIoIds.
112
nanefforttomInImIzethepotentIalforpostoperatIvebleedIngandrIskof
gastroIntestInalcomplIcatIons,morespecIfIccyclooxygenase2InhIbItorsarebeIng
IncreasInglyusedasnonopIoIdadjuvantsformInImIzIngpostoperatIvepaIn.
11J
AnoptImalantIemetIcregImenforD8AhasyettobeestablIshed,butasthecausesof
PDN7aremultIfactorIal,combInatIontherapIesmaybemorebenefIcIalInhIghrIsk
patIents.|anyofthetradItIonalfIrstlInetherapIesareassocIatedwIthsedatIon,
drowsIness,andextrapyramIdalsIdeeffects,andhavebeensupplantedby5
hydroxytryptamInetypeJ(5HT
J
)antagonIstssuchasondansetron,dolasetron,
P.858
andgranIsetron.
114
0examethasonehasbeenshowntoImprovetheeffIcacyofboth5HT
J
antagonIsts
115
aswellasdopamIneantagonIsts
116
FoutIneprophylaxIs,though,hasnot
beenshowntoofferanyadvantageoversymptomatIctreatment
117
andhasdIrectcosts
assocIatedwIthIt.EnsurIngadequatehydratIon(upto20mL/kg),toavoIdorthostatIc
hypotensIonandthuspreventthereleaseofemetogenIcchemIcalsbydecreasedbloodflow
tothemIdbraInemetIccentersIsanInterventIonthatmaybeusefulInthepreventIonof
PDN7.
114
Regulations
CovernmentaloversIghtofoffIcebasedsurgeryvarIesamongstates;currentlyregulatIons
exIstInmanystates,andothersarefollowIngInthIsdIrectIon.WhereasaccredItatIonIs
oftenavoluntarycertIfIcatIonofanoffIce,regulatIonsaregovernmentalmandates
Imposedbythelocalorstategovernment.tIsImperatIvethatanyanesthesIologIst
embarkIngonanoffIcebasedpractIcefamIlIarIzehImselforherselfwIthanyrulesand
regulatIonsthatgovernpractIceInhIsorherpartIcularstate.
n1994,CalIfornIawasthefIrststatetoadoptlegIslatIonregardIngD8A,followedbyNew
Jersey.
4
AcloserlookatthesetwostatesprovIdesanexampleofthevarIedrequIrements
beIngenforcedbystatesthroughoutthecountry.CalIfornIa'sregulatIonspertaIntopatIents
undergoIngaCAanddonotaddressproceduresperformedunderlocalanesthetIc,
perIpheralnerveblock,orsedatIon/anxIolysIsadmInIsteredIndosesthatdonotaffecta
patIent'slIfepreservIngreflexes.
118
TheregulatIonsdealwIthIssuesrangIngfromoffIce
polIcyandmandatoryreportIngofadverseoutcomes,tosurgeonandanesthesIaprovIder
qualIfIcatIons.
119
CalIfornIaHealthandSafetyCode12481248.85mandatesthatsurgIcal
proceduresoccuronlyInoffIcesthathavebeenaccredItedorhavebeencertIfIedto
partIcIpateInthe|edIcareProgramunderTItleX7(42U.S.C.Sec.1J95etseq.),wIth
veryfewexceptIons.
120
naddItIon,theoffIcemusthaveawrIttenplanInplacethatdeals
wIthIssuesregardIngemergencyadmIssIons.ThesurgeonmusthaveadmIttIngprIvIlegesat
alocallIcensedoraccredItedacutecarehospItalorhaveawrIttentransferagreement
wIthaphysIcIanwhodoeshavesuchprIvIleges.TheoffIcemusthaveanagreementwIth
thehospItalfortheadmIssIon,InaccordancewIththehospItal'ssystemofqualIty
assuranceandpeerrevIew.CalIfornIalawalsorequIresthatoffIceshaveadequatepatIent
monItorIngthroughouttheperIoperatIveperIod,andhaveasystemInplaceforthestorage
andmaIntenanceofpatIentrecords.AnoffIcethatfaIlstocomplywIththeregulatIonsIn
placerIskssanctIonsrangIngfromreprImandwIthorwIthoutmonetarypenaltIesthrough
crImInalprosecutIon.
NewJersey'sadmInIstratIveCode1J:J54A.11J:J54A.18developscrIterIaforpatIent
selectIon.DnlyASAphysIcalstatus1and2patIentsmayundergogeneralorregIonal
anesthesIa.ASAphysIcalstatusJpatIentscanundergoonlyconscIoussedatIon.The
provIderofCAmusthavecredentIalstodosobyahospItal,andonlyaphysIcIanwIth
approprIatecredentIalsmaysupervIseacertIfIedregIsterednurseanesthetIst.NewJersey
lawestablIshesguIdelInesregardIngmandatorymonItorIng,emergencysupplIesthatmust
bepresent,physIcIancredentIalIng,andpeerrevIew.ncontrasttoCalIfornIa,New
Jersey'sregulatIonspertaIntoallpatIentsundergoIngasurgIcalprocedure,regardlessof
thedepthofanesthetIc.However,sImIlartoCalIfornIa,vIolatIonsmayresultInfInes
rangIngfromreprImandtolIcenserevocatIonandcrImInalprosecutIon.
121
AlthoughmanystateshaveregulatIonsInplaceregardIngoffIcebasedsurgIcalprocedures,
somestIllhavenone.Consequently,anyphysIcIanwhoholdsavalIdmedIcallIcenseInan
unregulatedstatemayperformanyprocedurethatheorshesochooseswIthInanoffIce.A
surgeonmayperformaprocedureforwhIchheorshemayhavehadlIttletonotraInIng,
andmaysedateapatIentwIthoutanytraInIngInanesthesIaoraIrwaymanagement.n
fact,therehavebeenreportedcasesofpatIentsundergoIngaprocedurewIthouta
preoperatIveevaluatIon,pertInentlaboratorytests,Informedconsent,IntraoperatIveor
postoperatIvemonItorIng,oroperatIvereport,andwIthoutregardforsterIletechnIque.
4
t
IsthereforeImperatIvethattheanesthesIologIstcontInuestomaIntaIntheroleofa
zealouspatIentadvocateandhelptoeducatethesurgeonastowhatconstItutesasafe
anesthetIzInglocatIon.
Business and Legal Aspects
tIsIntheanesthesIaprovIder'sbestInteresttoseeklegalcounselandcreateavalId
busInessmodelbeforeembarkIngonacareerInD8A.ThIsmodelmustconsIderthe
overheadcostsassocIatedwIthstaffIngandrunnIngasafesurgIcaloffIceaswellasthe
potentIalandprobablecaseloadandpatIentInsurancemIx.AnD8AdIvIsIonwIthIna
departmentmayprovIdeotherbenefItstoanacademIcpractIceInaddItIontothe
monetaryones.TheremaybeanIntangIblebenefIttothecommunItyItserves,aswell
enhancIngtheanesthesIatraInIngprogram.
8
However,Itwouldbecomenecessaryto
InvolvetheAmerIcan8oardofAnesthesIologyaswellastheAmerIcanCollegeofCraduate
EducatIon(ACC|E)toensurethatanyresIdentrotatIonoutsIdetheACC|Eapproved
hospItalsettIngIsacceptable.
|anyD8AgroupshaveformedeItherprofessIonalcorporatIonsorlImItedlIabIlIty
companIes.AlthoughnotelImInatIngtheneedforlIabIlItyInsurance,bothofthese
arrangementsservetoprotecttheprIvateassetsoftheanesthesIologIstInthecaseofa
malpractIceclaIm.
7
LegalrepresentatIonIsthusanessentIalcomponentformulatIngan
D8Agroup.LegalcounselmayalsoprovetobebenefIcIalIncreatIngabusInessplansthat
followsallstateandfederallawsregardIngbIllIng/collectIonandantItrust.
122
tIsImperatIvetohaveanaboveboardandlegalrelatIonshIpwItheveryoffIceInwhIcha
patIentIssedated.8IllIngstrategIesmustbelegalandethIcal.nthIscomplexenvIronment
ofthIrdpartypayersItIsquIteeasytomakelegalerrors.gnoranceofthelawoffersno
protectIonorexcuse,andoneshouldseektheadvIceofexpertbIllIngagencIesevenIfone
choosesnottooutsourcethIsresponsIbIlIty.ncalculatIngprIcIngonemustIncludeall
overheadchargessuchasdrugs,equIpment,tIme,andbusInessexpensesIncludIng
malpractIceInsurance.AprIcIngstructurewIththesurgeonmustexIstbeforeembarkIngon
abusInessrelatIonshIp.DnemustoutlInespecIfIcallywhatwIllbeprovIdedbytheoffIce
(e.g.,IntravenousequIpment,antIbIotIcs,monItors)andwhattheanesthesIologIstwIll
supply.ThesedecIsIonstakeonfurtherlegalImplIcatIonswhentheoffIceIschargInga
facIlItyfee.
Conclusions
D8AcontInuestorapIdlyexpandandposeunIquechallengestoanesthesIologIsts,whomust
notonlyprovIdemedIcalcareInnewenvIronmentsbutalsohaveagoodbusInesssense
andanunderstandIngofoperatIngroommanagement.tIsImperatIvethat,although
regulatIonshavenotkeptpacewIththegrowthofD8A,anesthesIaprovIdersmakeIttheIr
responsIbIlItytohelpensurethateverypossIblesafetymeasureIsaffordedtotheIr
patIents.0ecIsIonsaboutapproprIatepatIent/procedureselectIonandequIppIng
anesthetIzInglocatIonsmustbemadeInconjunctIonwIththesurgeon.AllclInIcaldecIsIons
musttakeIntoconsIderatIontheneedforrapIdturnoverandlImItedPACUavaIlabIlIty.Any
depthofanesthesIamaybedelIvered
P.859
aslongasthepropersafeguardsareInplace.ThemanyadvantagesaffordedbyoffIce
basedsurgeryarefuelIngItsevolutIon,andasmorecomplexproceduresareconductedon
patIentswIthIncreasIngnumbersofcomorbIdItIestheanesthesIologIst'sroleaspatIent
advocateIsvItal.
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Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJ4AnesthesIaProvIdedatAlternateSItes
ChapterJ4
Anesthesia Provided at Alternate Sites
Karen J. Souter
Key Points
1. Alternate sites are locations remote from the operating room.
2. The number of requests for anesthetic services in alternate sites is
increasing.
3. A three-step approach is useful in considering an anesthetic at an
alternate site: the patient, the procedure, and the environment.
4. The American Society of Anesthesiologists (ASA) has defined
guidelines to be applied to the administration of anesthesia at
nonoperating room locations.
5. Environmental considerations include hazards such as radiation and
the side effects of contrast media.
6. Procedural considerations are both general (e.g., duration, position,
and level of discomfort) and specific to individual specialties.
7. Patient considerations include whether the patient will tolerate
sedation or require general anesthesia, the ASA classification,
significant comorbidities, and the level of monitoring.
8. Patients should receive the same standard of care at an alternate site
as they do in the operating room.
9. The anesthetic and monitoring equipment must meet the same
standards as equipment provided in the operating room.
10. Following anesthesia at an alternate site, the patient should be
transported to an appropriate postanesthesia care unit, accompanied
and monitored by anesthesia personnel.
ThIschapterdIscussesthechallengesfacIngtheanesthesIologIstregardIngtheprocedures,
thepatIents,andtheenvIronmenttobetterunderstandanddevelopasystematIcapproach
toprovIdInganesthesIaatalternatesItes.ThIschapteralsodescrIbesthespecIal
consIderatIonsthatapplytoadmInIsterInganesthesIaatsItesotherthantheoperatIng
room.ThesesItesmaybelocatedwIthInalargehospItal,suchasInaradIology
department,endoscopysuIte,ordentalclInIc,wheretheresourcesoftheoperatIngrooms
arewIthInthefacIlItybutarenotcloseathand.AdIscussIonoftheprovIsIonofanesthesIa
forsurgIcalproceduresperformedInstandaloneambulatorycenters,oroffIces,appearsIn
ChaptersJ2andJJ.
General Principles
nrecentyears,thenumberofanesthetIcsbeIngdelIveredtopatIentsInareasotherthan
theoperatIngroomhassteadIlyIncreased.ThIsIsmaInlyrelatedtothedevelopmentof
large,complexequIpmentthatcannotbetransportedtotheoperatIngroomforboth
dIagnostIcandtherapeutIcprocedures.StandardsIntroducedbytheJoIntCommIssIonon
AccredItatIonofHealthcareDrganIzatIonsrequIrethattheanesthesIologyservIcesofa
hospItalpartIcIpatewIthotherdepartmentsInsettIngupaunIformqualItyofcarefor
patIentsundergoIngsedatIonInallpartsofthehospItal.
1
ToassIstInthIsprocessThe
AmerIcanSocIetyofAnesthesIologIsts(ASA)hasdevelopedpractIceguIdelInesforsedatIon
andanalgesIabynonanesthesIologIsts.
2
AnesthesIologIstsundertakemostoftheIrtraInIngIntheoperatIngroom,surroundedby
famIlIarequIpmentandstaffexperIencedInthecareoftheanesthetIzedpatIent.Away
fromtheoperatIngroom,theanesthesIologIstmaynothavethIssupport.AsImplethree
stepparadIgmcanbeusedtoapproachananesthetIcassIgnmentInanalternatesIte(FIg.
J41andTableJ41).
P.862
Figure 34-1.AthreestepparadIgmforanesthesIaatalternatesItes.
The Environment
TheASAhasdevelopedstandardstoapplytoanesthesIaInremotelocatIons
J
(TableJ42).
8eforecommencIngananesthetIcInanalternatesIte,ItIsvItaltoconfIrmthepresence
andproperfunctIonIngofallequIpmentananesthesIologIstwouldexpecttohaveInthe
operatIngroom.ThIsequIpmentIncludesacentraloxygensupply,spareoxygencylInders,
wallsuctIon,overheadlIghtIng,gasscavengIngsystems,andelectrIcaloutlets.
FeplacementbatterIesshouldbeavaIlableforanyequIpmentthatIsbatterypowered.The
locatIonofImmedIatelyavaIlableresuscItatIonequIpmentshouldbenotedandprotocols
developedwIththelocalstafffordealIngwIthemergencIes,IncludIngcardIopulmonary
resuscItatIonandthemanagementofanaphylaxIs.
Table 34-1 A Three-Step Approach to Anesthesia at Alternate Sites
1.EnvIronment
AnesthetIcequIpment
AnesthesIamonItors
SuctIon
FesuscItatIonequIpment
Personnel
TechnIcalequIpment
FadIatIonhazard
|agnetIcfIelds
AmbIenttemperature
WarmIngblankets
2.Procedure
0IagnostIcortherapeutIc
0uratIon
LevelofdIscomfort/paIn
PosItIonofpatIent
SpecIalrequIrements(e.g.,functIonalmonItorIng)
PotentIalcomplIcatIons
SurgIcalsupport
J.PatIent
AbIlItytotoleratesedatIonversusgeneralanesthesIa
ASAgradeandcomorbIdIty
AIrwayassessment
AllergIes7contrast
|onItorIngrequIrementssImpleversusadvanced
ASA,AmerIcanSocIetyofAnesthesIologIsts;7,Intravenous.
Anesthesia Equipment and Monitors
nsomealternatesItes,anesthesIamachInesandmonItorsareprovIded;Inothers,Itmay
benecessarytobrInganesthesIaequIpmenttothelocatIon.8othsItuatIonscanpresent
problems.AnesthesIamachInesandmonItorsthatremaInInanoutsIdelocatIonneedto
undergoroutInemaIntenance,asdoesanesthesIaequIpmentusedInthemaInoperatIng
rooms.ThIsequIpmentIsnotoftenusedonadaIlybasIs;therefore,beforeusIngthe
equIpment,ItIsvItaltoconductathoroughcheck.Forexample,attentIonshouldbepaId
tothefreshnessofthesodalImeandwhetheranypIecesofequIpmentormonItorshave
beenremovedormIsplaced.|onItorIngequIpmentfoundInalternatesItesIsoftenusedby
thestafftomonItorpatIentswhoarenotbeInganesthetIzed.ThesemonItorsmaybe
dIfferentfrommonItorsusedIntheoperatIngroom.AnesthesIologIstsshouldbeawareof
thesedIfferences.fmoreadvancedmonItors(e.g.,anarterIallIne,centralvenous
pressureorIntracranIalpressure[CP]monItorIng)arerequIred,thesedevIcesshouldbe
readIlyavaIlable.Small,portableanesthesIamachInesandmonItorsareavaIlable.Apre
preparedcartcontaInIngessentIalequIpmentthatIscheckedandrestockedaftereach
caseIsrecommendedtoelImInatetheneedforanesthesIapersonneltomovebetween
locatIonstocollectequIpmentthathasbeenforgottenorthatIsneededurgently.
Technical Equipment
ThecomplextechnIcalequIpmentusedInalternatesItes,partIcularlyInradIologysuItes,Is
oftenbulkyandfIxedtothefloorsotheanesthesIateamhastoworkaroundIt(FIg.J42).
onIzIngradIatIonrelatedtobothImagIngandtherapeutIcproceduresIsahazardtoboth
staffandpatIents.|agnetIcresonanceImagIng(|F)createsItsownenvIronmental
concernsrelatedtomagnetIcfIelds.nalltheseareas,theequIpmentIskeptatlow
temperatures,andpatIentsmayeasIlydevelophypothermIa.PatIentwarmIngdevIces
shouldbeavaIlable.FadIatIontherapyroomsareheavIlyshIelded,andstaffareexcluded
fromtheroomdurIngtreatment,requIrIngtheanesthesIologyteamtomonItorpatIents
remotely,oftenwIthsurveIllancecameras.
4
Procedures
CommonprocedurescarrIedoutInalternatesItesforwhIchthepatIentmayrequIre
anesthesIaorsedatIonarelIstedInTableJ4J.tIsvItalfortheanesthesIologIstto
understandthenatureoftheprocedure,theposItIonofthepatIent,howpaInfulthe
procedurewIllbe,andhowlongtheprocedurewIlllast.ThIswIllallowthedevelopmentof
ananesthesIaplantoprovIdesafepatIentcareandfacIlItatetheprocedure.0IscussIons
wIthphysIcIans,dentIsts,andothersperformIngInterventIonalproceduresmustInclude
contIngencIesforadverseoutcomes.
Patients
PatIentsmayrequIreanesthesIaatalternatesItesforanumberofreasons(TableJ44).
ThepatIentmayhavebeenunableto
P.86J
toleratetheprocedurewIthoutsedatIonorhasfaIledwIthsImplesedatIonadmInIsteredby
anonanesthesIologIst.ChIldrenrepresentaspecIalgroupofpatIentswhoaremorelIkelyto
requIresedatIonoranesthesIaforvarIousdIagnostIcandtherapeutIcprocedures.Theterm
pediatric procedural sedationhasbeencoInedtodescrIbethIsemergIngfIeldofpractIce.
5
AnothergroupofchallengIngpatIentsarethosewhoaretooIlltotolerateamajorsurgIcal
procedure,butwhomaybeabletoundergopallIatIve,lessInvasIveproceduresat
alternatesItes.ThesepatIentsrequIreathoroughpreanesthetIcassessmentandoftenneed
InvasIvemonItorIng.
Table 34-2 American Society of Anesthesiologists (ASA) Guidelines for
Nonoperating Room Anesthetizing Locations
1. Dxygen
FelIablesource
8ackupEcylInderfull
2. SuctIon
AdequateandrelIable
J. ScavengIngsystemIfInhalatIonalagentsareadmInIstered
4. AnesthetIcequIpment
8ackupselfInflatIngbagtodelIverposItIvepressureventIlatIon
AdequateanesthetIcdrugsandsupplIes
AnesthesIamachInewIthequIvalentfunctIontothoseIntheoperatIngrooms
andmaIntaInedtothesamestandards
AdequatemonItorIngequIpmenttoallowadherencetotheASAStandardsfor
8asIc|onItorIng
9
5. ElectrIcaloutlets
SuffIcIentforanesthesIamachIneandmonItors
solatedelectrIcalpowerorgroundfaultcIrcuItInterruptersIfwetlocatIon
6. AdequateIllumInatIon
8atteryoperatedbackups
7. SuffIcIentspacefor
PersonnelandequIpment
EasyandexpedItIousaccesstopatIent,anesthesIamachIne,andmonItorIng
8. FesuscItatIonequIpmentImmedIatelyavaIlable
0efIbrIllator
Emergencydrugs
CardIopulmonaryresuscItatIonequIpment
9. AdequatelytraInedstafftosupportanesthesIateam
10. AllbuIldIngandsafetycodesandfacIlItystandardsshouldbeobserved
11. PostanesthesIacarefacIlItIes
7
AdequatelytraInedstafftoprovIdepostanesthesIacare
ApproprIateequIpmenttoallowsafetransporttomaInpostanesthesIacare
unIt
P.864
Table 34-3 Common Procedures Requiring Anesthesia at Alternate Sites
FadIology
Computedtomography
|agnetIcresonanceImagIng
nterventIonalradIology(vascularandnonvascular)
nterventIonalneuroradIology
FunctIonalbraInImagIng
PosItronemIssIontomography
FadIofrequencyablatIon
FadIotherapy
FadIatIontherapy
ntraoperatIveradIotherapy
FadIosurgery
Castroenterology
Uppergastroenterologyendoscopy
EndoscopIcretrogradecholangIopancreatography
Colonoscopy
LIverbIopsy
TransjugularIntrahepatIcportosystemIcshunt
CardIology
CardIaccatheterIzatIon
FadIofrequencyablatIon
CardIoversIon
TransesophagealechocardIography
PsychIatry
ElectroconvulsIvetherapy
Figure 34-2.AradIologysuIteshowIngamazeofequIpmentandthenecessItyforthe
anesthesIologIsttoberemotefromthepatIent'shead.
Anesthesia Care
Thetermsanesthesia, sedation, conscious sedation,anddeep sedationarecommonlyused.
TheyspanacontInuumthatstartswIthafullyawakepatIentwIthaprotected,patent
aIrwayandendswIthgeneralanesthesIaandtheneedforInterventIonstomaIntaInand
protecttheaIrway.TheJoIntCommIssIononAccredItatIonofHealthcareDrganIzatIons
defInesanesthesia careastheadmInIstratIonofIntravenous,Intramuscular,orInhalatIonal
agentsthatmayresultInthelossofthepatIent'sprotectIvereflexes.PatIentswhoreceIve
anesthesIaorsedatIonatalternatesItesshouldexpectthesamestandardofcarethatthey
wouldreceIveIntheoperatIngroom.TheASAhaspublIshedguIdelInesandstandardsof
care,IncludIngthoseforpreanesthesIaandpostanesthesIacare,aswellasmonItored
anesthesIacare,
6,7,8
anddefInItIonsofgeneralanesthesIaandlevelsofsedatIon
2
(TableJ4
5).ApatIent'slevelofsedatIonfrequentlyvarIesdurIngthecourseofaprocedure,andItIs
ImportantthatIndIvIdualsadmInIsterIngagIvenlevelofsedatIonareabletorescuethe
patIentwhoselevelbecomesdeeperthanInItIallyIntended.TheASAbasIcstandardsof
monItorIngshouldbeadheredtoInanylocatIonwhereanesthesIaorsedatIonIsbeIng
performed.
9
StandardrequIresaqualIfIedanesthesIaprovIdertobepresentIntheroom
throughouttheconductofanesthesIa.StandardcallsforcontInualevaluatIonofthe
patIent'soxygenatIon,ventIlatIon,cIrculatIon,andtemperature.ThedegreeofInvasIve
monItorIngthatshouldbeusedwIlldependonthepatIent'sstatusandtheprocedurebeIng
undertaken.
AttheconclusIonoftheprocedure,patIentsshouldrecoverfromanesthesIaorsedatIonIn
apostanesthesIacareunIt(PACU)orsImIlarsettIng.
7
CareshouldbesupervIsedby
personnelwhoaretraInedtotakecareofunconscIouspatIents,wIthapproprIate
monItorIngandresuscItatIonequIpmentImmedIatelyathand.
Table 34-4 Patient Factors Requiring Sedation or General Anesthesia at
Alternate Sites
AnxIetyandpanIcdIsorders
ClaustrophobIa
0evelopmentaldelayandlearnIngdIffIcultIes
Cerebralpalsy
SeIzuredIsorders
|ovementdIsorders
SeverepaIn
AcutetraumawIthunstablecardIovascular,respIratory,orneurologIcfunctIon
SIgnIfIcantcomorbIdIty
ChIldage
Radiology and Radiation Therapy
0evelopmentsIntechnologyhavemeantthatInterventIonalradIologIstsnowperforman
IncreasIngnumberofproceduresthatwereonceInthedomaInofsurgeons.
AnesthesIologIstsareIncreasInglyrequIredtotakecareofpatIentsundergoIngboth
dIagnostIcandtherapeutIcInterventIonalprocedures.TwoImportantaspectsofthe
radIologIcenvIronmentarethesIdeeffectsofcontrastmedIa,whIcharecommonlyusedto
enhanceradIologIcImages,andthehazardsofIonIzIngradIatIon.
Intravenous Contrast Agents
ntravenouscontrastagentsareIodInatedcompoundsusedformanyradIologIc
procedures.
10
|FcontrastmedIaarealsonowwIdelyused;theseagentsarechelated
metalcomplexescontaInInggadolInIum,Iron,andmanganese.
ContrastmedIaareelImInatedvIathekIdneys,andcontrastInducednephropathy(CN)Isa
recognIzedcomplIcatIonoftheIruse.CNIsthethIrdleadIngcauseofhospItalacquIred
acuterenalfaIlure,accountIngfor12ofcases.
11
PatIentswIthchronIcrenaldIsease,
dIabetes,andhypovolemIaaremostatrIskforCN,andpatIentstakIngmetformInareat
rIskofdevelopInglactIcacIdosIs;adequatehydratIon,monItorIngofurIneoutput,andthe
useoflowosmolarItyandnonIonIccontrastmedIahelpreducetherIsk.
12
CNmaybe
preventedbytheuseofadequatehydratIonandsodIumbIcarbonateInfusIons1hour
beforetheprocedure.
1J
AntIoxIdantssuchasNacetylcysteIne,ascorbIcacIdmaybeuseful
InpreventIngCN.However,thevasodIlatorsdopamIneandfenoldopamhavenotbeshown
tobeeffectIve.
12
n1990,theoverallIncIdenceofadversedrugreactIonswIthnonIonIc
contrastmedIawasreportedasJ.1JandtheIncIdenceofseverereactIons
P.865
Is0.04.
14
ThesefactsareshownInmoredetaIlInTableJ46.FeactIonsaredescrIbedas
mIld(e.g.,urtIcarIa,chIlls,fever,facIalflushIng,nausea,vomItIng),moderate(e.g.,
edema,bronchospasm,hypotensIonseIzures),andsevere(e.g.,dyspnea,prolonged
hypotensIon,cardIacarrest,lossofconscIousness,anaphylactIcreactIons).PatIentswIth
atopyorallergytoshellfIsharemorepronetocontrastrelatedadversereactIons.
15
PretreatmentwIthoralmethylprednIsoloneprIortoIntravenousadmInIstratIonofcontrast
medIum
16
canreducetheIncIdenceofadversereactIons.TreatmentofseverereactIons
shouldIncludedIscontInuIngthecausatIveagentandsupportIvetherapy,suchasoxygen
admInIstratIon,securIngtheaIrway,andcardIovascularsupportwIthfluIds,vasopressors,
andInotropes.8ronchospasmshouldbetreatedwIthapproprIatebronchodIlators.Low
osmolarIty,nonIonIccompoundswIthosmolarItIesrangIngfrom290to650mDsm/kghavea
lowerIncIdenceofadversereactIonscomparedwIththeolder,hIghosmolarItyagents.
14,17
AdversereactIonsto|FcontrastmedIaaresImIlartothoseasothercontrastmedIaand
haveasImIlarIncIdence.
18
nsomecases,thereIscrosssensItIvItybetweengadolInIum
contaInIngagentsandIodInatedones.
Table 34-5 Definition of General Anesthesia and Levels of
Sedation/Analgesia

MINIMAL
SEDATION
ANXIOLYSIS
MODERATE
SEDATION/ANALGESIA
CONSCIOUS
SEDATION
DEEP
SEDATION/ANALGESIA
GENERAL
ANESTHESIA
FesponsIveness
Normal
response
toverbal
stImulatIon
Purposeful
responseto
verbalor
tactIle
stImulatIon
Purposeful
response
followIng
repeatedor
paInful
stImulatIon
Unarousable
evenwIth
paInful
stImulus
AIrway Unaffected
NoInterventIon
requIred
nterventIon
maybe
requIred
nterventIon
requIred
Spontaneous
ventIlatIon
Unaffected Adequate
|aybe
Inadequate
Frequently
Inadequate
CardIovascular
functIon
Unaffected
Usually
maIntaIned
Usually
maIntaIned
|aybe
ImpaIred
Protection From Ionizing Radiation
PatIents,physIcIans,andotherhealthcareworkersarefrequentlyexposedtoIonIzIng
radIatIon,usuallyIntheformofxrays.ExposuretogammaradIatIon,orrarely,alphaor
betaradIatIonfromradIoactIveIsotopes,mayalsooccurdurIngImplantatIonorremoval
procedures.onIzIngradIatIonexposuremayoccurdIrectlyfromthesource,asleakage
fromtheIonIzIngdevIce,orasscatterfromtheequIpment.0Irectexposuremustbe
avoIded.Arad(radIatIonabsorbeddose)IsameasureofanabsorbeddoseofradIatIon.
ThetotaldoseofxraysIsmeasuredInroentgens,andarem(roentgenequIvalentman)Is
thedoseofIonIzIngradIatIonwIththesamebIologIcaltIssueeffectas1radofxrays.
19
ThedoseofradIatIon
P.866
receIveddurIngachestradIographIsIntheorderof8mrem,aheadcomputedtomography
(CT)scanIs170mrem,andanabdomInalCTIs680mrem.
20
FadIatIonexposurewIth
fluoroscopymaybe75,000mrem.
19
TheeffectIvedosereceIvedbythepatIentdurIng
IntraoperatIvedIgItalsubtractIonangIographywascalculatedas76.7mrem.
20
The
exposureofhealthcareworkerstotheradIatIonemIttedfromxrayequIpmentIsseveral
ordersofmagnItudelower.
20
TheNatIonalCouncIlonFadIatIonProtectIonand
|easurementshasestablIshedguIdelInesgovernIngmedIcalradIatIon.
21
Therecommended
annualoccupatIonalexposureIs5,000mrem.WIththeroutIneuseofaleadapron,
protectIvegoggles,andthyroIdshIeld,exposuretoradIatIoncanbekepttoalowlevel.
However,thIsprotectIveclothIngIscumbersomeandcanresultInfatIgueanddIscomfort,
whIchcandIstractfrompatIentcare.
Table 34-6 Incidence of Contrast-Related Adverse Reactions
IODINATED CONTRAST MEDIA
HIGH-OSMOLARITY
CONTRAST MEDIA (%)
ADVERSE REACTIONS
LOW-OSMOLARITY
CONTRAST MEDIA (%)
6.0 NauseaandvomItIng 1.0
J.0 UrtIcarIa 0.5
2.6
Hoarseness,sneezIng,cough,
dyspnea,facIaledema
0.5
0.1 HypotensIon 0.01
MAGNETIC RESONANCE IMAGING CONTRAST MEDIA
CONTRAST MEDIA ADVERSE REACTIONS INCIDENCE (%)
CadolInIum
chelates
|Ild(nauseaand/orvomItIng) 2.0
|oderate 0.1
Severe 0.01
FerrousoxIde
AchIngmuscles 8.0
Dthers(IncludIngallergIclIke
reactIons)
J.0
|anganesefodIpIr
njectIonsItedIscomfort 67.0
Nauseaand/orvomItIng 14.0
Headache 5.0
Dthers 1.0
FeprIntedfromKIng8F:ntravascularcontrastmedIaandpremedIcatIon,
FadIologyLIfeSupport.EdItedby8ushWH,KreckeKN,KIng8F,etal.London,
Arnold,1999,p1J,wIthpermIssIon.
Specific Radiologic Procedures
CerebralandspInalangIographycausemInImaldIscomfortandmaybeperformedunder
localanesthesIawIthorwIthoutlIghtsedatIonadmInIsteredbynonanesthesIologIsts.
PatIentsarerequIredtoremaIncompletelymotIonlessdurIngtheseprocedures,whIchmay
belengthy,partIcularlyspInalangIography.NeurologIcdIsorderssuchasrecent
subarachnoIdhemorrhage,stroke,anddepressedlevelofconscIousnessorraIsedCPmay
makeItImpossIbleforpatIentstotoleratetheseproceduresunsedated.0eepsedatIonor
generalanesthesIawIthaIrwayprotectIonIsoftenrequIred.AngIographyIsusually
performedvIathefemoralartery;thefemoralveInmayalsobeaccessedwhenImagIng
arterIovenousmalformatIonsorduralvenousabnormalItIes.LIberaluseoflocalanesthetIc
atthepuncturesIteprecludestheneedforIntravenousanalgesIa.TheInjectIonofcontrast
medIaIntothecerebralarterIesmaycausedIscomfort,burnIng,orprurItusaroundthe
faceandeyes.HypotensIonandbradycardIamayalsooccur.ComplIcatIonsfollowIng
angIographyaredescrIbedasneurologIcandnonneurologIc,andvarybetween1and
2.5.
22
0urIngcerebralangIography,thepatIentIsplacedonamovInggantryandtheradIologIst
posItIonsthepatIenttotrackcathetersastheypassfromthegroInIntothecerebral
vessels.tIsvItaltohaveextensIonsonallanesthesIabreathIngcIrcuIts,InfusIonlInes,
andmonItorstopreventthesefrombeIngaccIdentallydIslodgedastheradIologIstswIngs
thexraytablerapIdlybackandforth.CareshouldbetakenwIthposItIonIngofradIopaque
pIecesofequIpment.TheelectrocardIogramelectrodesmayInterferewIthImagIngdurIng
spInalangIography,andlIttlemetallIccoIlsInthecuffsofendotrachealtubescancause
InterestIngandannoyIngartIfactsIftheylIeovertheareabeIngImaged.
Interventional Neuroradiology
AnumberofneurosurgIcalcondItIonsmaybetreatedbyInterventIonalneuroradIologIc
technIques.
2J
ThedIseasesamenabletoendovasculartreatmentmaybeclassIfIedas
emergentorelectIve,hemorrhagIcorocclusIve,anddefInItIve,adjunctIve,orpallIatIve.
EndovasculartreatmentofIntracranIalaneurysmswIthdetachableplatInumcoIls
(CuglIelmIdetachablecoIls)
24
hasbecomeanacceptablealternatIvetosurgeryfor
reducIngtherIskofspontaneousrecurrenthemorrhagefollowIngsubarachnoId
hemorrhage.
25
EndovasculartreatmentavoIdstheneedforcranIotomyandIsoftenoffered
topatIentswIthsIgnIfIcantcomorbIdItyorpoorprognoses
26,27
;ItmayalsoreducecognItIve
ImpaIrmentandfrontotemporalbraIndamageassocIatedwIthcranIotomy.
28
ArterIovenous
malformatIons(A7|s)areIncreasInglybeIngtreatedendovascularly,eItherasthesole
therapyorInconjunctIonwIthsurgIcalresectIonorstereotactIcradIosurgery.
29
|aterIals
usedforInterventIonalneuroradIologIctechnIquesIncludeocclusIveagents;detachable
balloons,polyvInylalcoholpartIcles,coIls(pushable,flowdIrected,anddetachable),and
lIquIdagents;andacrylIcglues(Nbutylcyanoacrylates),nonadhesIvepolymerIzIngagents,
andsclerosIngagents.
29
FormostInterventIonalneuroradIologIcprocedures,arterIal
accessIsgaInedusInga6or7FrenchgaugesheathvIathefemoralor,rarely,thecarotId
oraxIllaryartery
29,J0
(FIg.J4J).TheumbIlIcalvesselsareanalternatIverouteIn
neonates.AcontInuousInfusIonofheparInIzedsalIneIsInfusedIntothesheathvIaasIde
armdurIngtheprocedure.ContInuousmonItorIngofbloodpressureandsamplIngof
arterIalbloodmaybeperformedvIathesheath,althoughmostanesthesIologIstspreferto
InsertadedIcatedarterIalcatheterformonItorIngthepatIent.TheradIologIcImagIng
technIquesIncludehIghspeedfluoroscopyanddIgItalsubtractIonangIography.Dncethe
sheathIsInplace,aguIdecatheterIsadvancedthroughthesheathandaroadmappIng
technIqueIsemployed,wherebyabolusofcontrastmedIumIsInjectedtooutlInethe
vascularanatomy.ThIsImagemaybesuperImposedontothelIvefluoroscopIcImagIngto
guIdetheadvancementofthemIcrocathetersforplacementofembolIcmaterIalsIntoan
aneurysmorthefeedIngvesselsofanA7|.
Figure 34-3.FepresentatIonofasuperselectIvecatheter.(FeprIntedfromYoungWL,
PIleSpellmanJ:AnesthetIcconsIderatIonsforInterventIonalneuroradIology.
Anticoagulation
AntIcoagulatIonwIthheparInIsrequIreddurIngandupto24hoursafterInterventIonal
radIologIcprocedurestopreventthromboembolIsm.TheusualdoseIsbetweenJ,000and
P.867
5,000UasanInItIalbolus,followedbyanInfusIon.TheactIvatedclottIngtImeIsthe
preferredmethodofmonItorIngtheeffectsofheparInandIsgenerallymaIntaInedbetween
1.5and2.5tImesthepatIent'sbaselIne.
J1
Complications
nterventIonalneuroradIologIcproceduresarenonstImulatIngandgenerallywelltolerated.
PartIcularcareshouldbeexertedtopreventaIrembolIsmvIathefemoralsheath.
Hematomaorhemorrhagemayresultfromfemoralarterypuncture.Therehavealsobeen
reportsofpulmonaryembolIcphenomenaduetoacrylIcglues.
J2
0urIngangIoplastyor
stentIngofcarotIdarterystenosIs,theanesthesIateamshouldbepreparedtotreatsevere
bradycardIasortransIentasystole.ThetwomostcatastrophIccomplIcatIonsthatcanoccur
areIntracranIalhemorrhageorthromboembolIcstroke.TheIncIdenceofthesedurIng
coIlIngofcerebralaneurysmsIs2.4andJ.5,respectIvely.
JJ
0urIngembolIzatIonofA7|s,
theIncIdenceofcatastrophIccomplIcatIonsIsbetween1and8.
J4
TheanesthesIateamIs
vItalIntheexpedIenttreatmentoftheselIfethreatenIngevents(TableJ47).
Anesthetic Technique
CeneralanesthesIaandconscIoussedatIonarebothsuItabletechnIquesforInterventIonal
neuroadIologydependIngonthecomplexItyoftheprocedure,theneedforbloodpressure
manIpulatIon,andtheneedforIntraproceduralassessmentofneurologIcfunctIon.
J5
CeneralanesthesIaIsusuallyconductedwIthendotrachealIntubatIonandIntermIttent
posItIvepressureventIlatIon,althoughthelaryngealmaskaIrway(L|A)IsasuItable
alternatIve.
JJ
ConscIoussedatIontechnIquesvary.PropofolInfusIonsarewIdelyused,as
arecombInatIonsofabenzodIazepIne(usuallymIdazolam)andopIoId(usuallyfentanyl).
|orerecently,dexmedetomIdInehasbeenevaluatedasasedatIveagentthatdoesnot
causesIgnIfIcantrespIratorydepressIonInpatIentsrequIrIngneurologIctestIng.
J5
0exmedetomIdInehasmanyadvantagesasasedatIveagent
J6,J7
;however,onestudy
demonstratedImpaIrmentofcognItIvetestIngInpatIentsundergoIngendovascular
embolIzatIonofcerebralA7|swIthdexmedetomIdIneasthesedatIveagent.nvasIve
monItorIngIsusedlessoftenInpatIentsundergoIngInterventIonalneuroradIology
comparedwIththosehavIngneurosurgIcalprocedures.TheanesthesIacareteammay
facIlItatetheneuroradIologIstInanumberofwaysbymanIpulatIngsystemIcblood
pressureandcontrollIngendtIdalcarbondIoxIdetensIon.
J0,JJ
ControlledhypotensIonIs
oftenrequestedtofacIlItateembolIzatIonofA7|s.Esmolol,labetalol,metoprolol,and
hydralazInearecommonlyused.|oderatehypertensIonmayhelpreducecerebralIschemIa
bymaIntaInIngcerebralperfusIon;InthIscase,phenylephedrIneIstheagentofchoIce.
CertaInproceduresrequIrepatIentstobeawakeatleastforpartoftheprocedure.A
superselectIveanesthesIafunctIonalexamInatIon,orSAFE,
J0
maybeperformedprIorto
therapeutIcembolIzatIontodetermInewhetherthecatheterhasbeenplacedInavessel
thatsupplIesaneloquentareaofthebraInorspInalcord,suchasspeechorlanguage
areas.FollowIngbaselIneneurologIcexamInatIon,amobarbItalJ0mg(forInvestIgatIngthe
graymatterareas)orlIdocaIneJ0mg(toevaluatetheIntegrItyofthewhItemattertracts)
mIxedwIthcontrastagentIsInjectedvIathecatheter.ThepatIentIsthenreassessedfor
neurologIcdefIcItsIntheareasatrIsk;IftheassessmentIsnegatIve,embolIzatIonmay
proceed.AsleepawakesleepanesthetIctechnIqueusIngapropofolInfusIonallowsthe
patIenttoberapIdlyawakenedforapproprIateneurologIctestIng;oncethIsIscomplete,
thepatIentIsagaInsedatedoranesthetIzedwhIlethedefInItIveprocedureIscarrIedout.
Table 34-7 Acute Management of Neurologic Catastrophes
nItIalresuscItatIon
CommunIcatewIthradIologIsts
CallforassIstance
SecuretheaIrwayandhyperventIlatewIth100D
2
0etermIneIfproblemIshemorrhagIcorocclusIve
HemorrhagIc:ImmedIateheparInreversal(1mgofprotamIneforeach100unItsof
heparIngIven)andlownormalpressure
DcclusIve:delIberatehypertensIon,tItratedtoneurologIcexamInatIon,
angIography,orphysIologIcImagIngstudIes(e.g.,TC0,C8F)
FurtherresuscItatIon
Headup15`InneutralposItIon
TItrateventIlatIontoaPaCD
2
of2628mmHg
0.5g/kgmannItol,rapIdIntravenousInfusIon
AntIconvulsants:0IlantIn(gIveslowly,50mg/mIn)andphenobarbItal
TItratethIopentalInfusIontoelectroencephalogramburstsuppressIon
AllowbodytemperaturetofallasquIcklyaspossIbletoJJJ4`C
ConsIderdexamethasone,10mg
TC0,transcranIal0oppler;C8F,cerebralbloodflow.
FeprIntedfromYoungWL,PIleSpellmanJ:AnesthetIcconsIderatIonsfor
InterventIonalneuroradIology.AnesthesIology1994;80:427
Computed Tomography, Radiofrequency Ablation, and
Magnetic Resonance Imaging
CTscannIngand|FareusedforawIdearrayofdIagnostIcImagIngandanIncreasIngly
largenumberoftherapeutIcprocedures.TheproceduresaresImIlarInthattheyare
relatIvelypaInlessandmostadultscantoleratethemwIthouttheneedforsedatIonor
anesthesIa.However,thereIsanabsoluterequIrementforthepatIenttoremaIn
motIonlesswhIlethestudyIsbeIngperformed.ChIldrenandadultswIthavarIetyof
psychologIcalorneurologIcdIsordersmayrequIresedatIonoranesthesIatoenablethemto
toleratetheprocedures(TableJ44).
PatIentswIthacutethoracIc,abdomInal,andcerebraltraumaoftenrequIreurgentImagIng
tofacIlItatedIagnosIs.tIsnotunheardofforthesepatIentstodevelophemorrhagIc
shock,raIsedCP,depressIonofconscIousness,andcardIacarrestIntheCTscanner.
PatIentsmustbeadequatelyresuscItatedandstabIlIzedbeforetransportatIontothe
radIologydepartment.
Computed Tomography
|odernCTscannersobtaInacrosssectIonalImageInjustafewseconds,andspIral
scannerscanImageaslIceofthebodyIn1second,mInImIzIngtheproblemswIthmotIon
artIfacts.ContrastmedIamayberequIreddurIngCTImagIng,andthIsIsoften
admInIsteredorally.AnesthesIologIstsneedtobeawarethattheIrpatIentmayhavejust
receIvedalargevolumeoforalcontrastmedIaprIortotheexamInatIon.Also,a
nasogastrIctubemayberequIredtofacIlItateadmInIstratIonofthecontrastmedIumIn
sedatedoranesthetIzedpatIents.DccasIonally,CTscannIngmaybeemployedtofacIlItate
InvasIveproceduressuchasabscesslocalIzatIonanddraInage,ablatIon
P.868
ofbonymetastases,andradIofrequencyablatIonoflungorothermalIgnancIes.
Radiofrequency Ablation
PercutaneousradIofrequencyablatIonIscarrIedoutIntheradIologysuItefortreatmentof
prImaryandmetastatIchepatIctumors,aswellastumorsInthelung,adrenalgland,
kIdney,breast,thyroId,prostate,kIdney,andspleen.ThemajorItyoftheseproceduresare
toleratedwIthoutsedatIon.fananesthesIologIstdoesbecomeInvolvedInthecareof
thesepatIents,theyneedcarefulevaluatIon.ThesepatIentsmaybeInthelaterstagesof
theIrdIsease,haveoftenfaIledsurgIcaltreatment,andmaywellhaveundergone
extensIveradIatIontherapyand/orchemotherapy.PercutaneousradIofrequencyablatIon
ofpulmonarylesIonsmaybeperformedbyradIologIstsasanoutpatIentprocedureunder
conscIoussedatIonorgeneralanesthesIa.
J8
TheIncIdenceofcomplIcatIonsIslow;
however,theoffsIteanesthesIologIstshouldbeawareofpotentIalproblemssuchas
hemorrhage,pneumothorax,pleuraleffusIon,InfectIon,andbronchopleuralfIstula.0urIng
theprocedurethesurroundIngtIssuesheatup,andthepresenceofacardIacpacemakerIs
anabsolutecontraIndIcatIontotheprocedure.
J9
Magnetic Resonance Imaging
ThephysIcalprIncIplesof|FaredescrIbedIndepthelsewhere.
40
8rIefly,whenatomswIth
anoddnumberofprotonsIntheIrnucleI,notablyhydrogen,aresubjectedtoapowerful
statIcmagnetIcfIeld,theyalIgnthemselveswIththemagnetIcfIeld.ftheyarethen
IntermIttentlyexposedtoaradIofrequencywave,thenucleIchangetheIralIgnment.As
theradIofrequencypulsesaredIscontInued,theprotonsreturntotheIrorIgInalalIgnment
(I.e.,theyrelax)wIthIntheorIgInalmagnetIcfIeldand,astheydo,theyreleaseenergy.
ThereleaseofenergyovertIme(therelaxatIontIme)IsspecIfIcforgIventIssuesandIs
usedtogeneratethe|FsIgnal.ThemagnetIcfIeldstrengthsaremeasuredIntesla(T;1T
=10,000gauss).Theearth'smagnetIcfIeldIsapproxImately0.5gauss.|Fscannersused
forclInIcalpurposesgenerateafIeldof0.15to2.0T,
41
andmachInesgeneratIngmagnetIc
fIeldsfrom4to8TareusedInresearch.0espIteextensIverevIew,
42
noadverseeffects
havebeendescrIbedfromhumanexposuretomagnetIcfIelds.0eathsandadverse
outcomesIn|FscannersareentIrelyrelatedtothepresenceofferrometallIcforeIgn
bodIessuchascerebralaneurysmclIpsorImplanteddevIcessuchaspacemakers.8efore
enterIngthevIcInItyofthemagnet,patIentsandstaffneedtocompletearIgorous
checklIsttoensuretheyhavenoferrometallIcobjectsIntheIrbodIes.ThemagnetIcfIeld
takesseveraldaystoestablIshandIsconstantlypresent.tdecreasesInstrengthwIth
dIstancefromthecenterofthemagnet,quantIfIedasanumberofconcentrIcrIngstermed
gauss lines.ThIsperIpheralorfrIngefIeldaroundthemagnetIsresponsIbleformalfunctIon
ofelectrIcalequIpment.The5gausslIne,forexample,IsthepoIntbeyondwhIch
pacemakerswIllmalfunctIon.FerromagnetIcanesthetIcgascylInders,IfbroughtwIthInthe
50gausslIne,becomepotentIallylethalprojectIles;anumberofnearmIssIncIdentshave
beendocumented.
4J
|FcompatIbleanesthesIamachInesandmonItorsareavaIlable.The
electrocardIogramIssensItIvetothechangIngmagnetIcsIgnals,andItIsnearlyImpossIble
toelImInateallartIfacts.Theelectrodesshouldbeplacedclosetogetherandtowardthe
centerofthemagnetIcfIeld.TheleadsshouldbeInsulatedfromthepatIent'sskInbecause
theymayheatupandcausethermalInjury.AllcablesandwIresshouldrunastraIghtpath
andnotbewoundInloopstoavoIdInductIonheatIngeffects.NonInvasIvebloodpressure
monItorsandtransducersforInvasIvepressuremonItorIngareavaIlable.ntheabsenceof
|FcompatIblemonItors,longsamplIngtubescanbeconnectedtostandardcapnographs
andanesthetIcagentmonItors.|ostInfusIonpumpscanbeusedoutsIdetheJ0gauss
lIne,
44
andextralengthsofextensIontubIngshouldbeavaIlable.
|FtakesupwardofJ0mInutes,andmanypatIentsfIndItdIffIculttostaystIllforlong
perIods.tmaybecomeverywarmwIthInthecoIlofthemagnet,oftenreachIng80`F,
addIngtopatIentdIscomfort.The|FscanneremItsaconsIderableamountofnoIse,upto
90d8,andboththepatIentandtheanesthesIologIstshouldwearhearIngprotectIon.tIs
ImportanttorememberthatonceascansequenceIsInItIated,noonemayenterorleave
thescanroom.nthecaseofanemergency,the|FtechnIcIansshouldbenotIfIed,the
scansequencestopped,andthepatIentrapIdlyremoved.FesuscItatIonattemptsshould
takeplaceoutsIdethescannerbecauseequIpmentsuchaslaryngoscopes,oxygencylInders,
andcardIacdefIbrIllatorscannotbetakenclosetothemagnet.
Anesthetic Technique
ThIrtypercentofadultpatIentsexperIencesomedegreeofanxIetydurIng|FscannIng,
45
andupto10experIenceseverepanIcandclaustrophobIa.FourpercentofadultpatIents
wIlltermInatetheprocedureprematurely,
46
and14requIresomeformofsedatIonto
tolerate|FscannIng.
47
nmostcases,thIsmaybeprovIdedaseItheroralsedatIonwIth
benzodIazepInesorIntravenoussedatIonadmInIsteredunderthesupervIsIonofthe
radIologIst.AnesthesIologIstsareusuallyInvolvedonlywIthmorecomplexpatIents,suchas
thosewIthobesIty,obstructIvesleepapnea,raIsedCP,movementdIsorders,
developmentaldelay,andthepotentIalforadIffIcultaIrway.
|ostchIldrenyoungerthantheageof5yearsandmanyasoldasage11
48
requIresedatIon
orgeneralanesthesIatotolerate|FandCTscannIng.TwentytwopercentofchIldren
undergoIngsedatIonfor|ForCTscanshavebeenfoundtoexperIencesomesortof
adverseevent;oxygendesaturatIonoccurredIn2.9,andsedatIonwasInadequateIn
15.
49
AdverseeventsaremorecommonInchIldrenwIthahIgherASAclassIfIcatIonwho
areundergoIngsedatIon,andpreselectIngchIldrenwhoareunsuItablefororalsedatIon
ImprovestheeffIcIencyoforalsedatIonprograms.DralsedatIontechnIques,If
approprIatelyadmInIstered,haveasuccessrateof9J.
48,49
ChIldrenwhoundergogeneral
anesthesIaforscanshaveaverylowIncIdenceofadversereactIons(0.7).
48,49
Dral
chloralhydrateIsapopularagentforsedatIonbynonanesthesIologIsts,anddosesbetween
80and100mg/kghaveshowntobeeffectIveforchIldrenyoungerthanJyearsofagewho
areundergoIngCTscan.
50
ChloralhydratecancauseexcessIvesedatIon,agItatIon,
51
and
respIratorydepressIon;ItmayalsohaveaprolongedeffectInneonates.
52
Fecently,a20
faIlureratewIthchloralhydrateasasoleagentforsedatIonofneurologIcallyImpaIred
chIldrenfor|Fhasbeenreported
5J
althoughrescuesedatIonwIthsevoflurane,
pentobarbItal,mIdazolam,orketamInewassuccessfulInmostcases.8enzodIazepInessuch
asmIdazolamadmInIsteredeItherorally(0.25to0.75mg/kg)orIntravenously(0.05to0.15
mg/kg)arealsocommonlyusedforsedatIon.0eepsedatIonwIthpropofolInfusIon,oxygen
admInIstratIonvIanasalcannula,andendtIdalcarbondIoxIdemonItorIngIsasuccessful
technIque.
48
ChIldrenareInItIallysedatedwIthIncrementalpropofolbolusesuptoJmg/kg
wIthorwIthoutmIdazolam,0.2to0.5mg/kg,andthenmaIntaInedwIthanInfusIonrateof
propofol,1toJmg/kg/hr,wIthsupplementalbolusesof1mg/kgformovement.
Radiation Therapy
TwodIfferenttypesofradIatIontherapycommonlyrequIreanesthesIacare:externalbeam
radIatIontreatments,usuallyforchIldrenwIthmalIgnancIes,andIntraoperatIveradIatIon
P.869
totumormassesthatcannotbecompletelyresected.FadIosensItIvemalIgnancIes
occurrIngInchIldrenareshownInTableJ48.
Table 34-8 Common Radiosensitive Tumors in Children
PrImaryCNStumorneuroblastoma,medulloblastoma
AcuteleukemIaCNSleukemIa
FadIosensItIveoculartumorsretInoblastoma
ntraabdomInaltumorsWIlmstumor
Fhabdomyosarcoma
DthertumorsLangerhanscellhIstIocytosIs
CNS,centralnervoussystem.
TumorsmayInvolveavarIetyofvItalareas,IncludIngtheaIrway,thorax,medIastInum,
andheart.PatIentswIthcentralnervoussystem(CNS)tumorsshouldbeassessedforsIgns
ofraIsedCP.|anychIldrenreceIvecytotoxIcorImmunosuppressIvechemotherapyaswell
asradIotherapy.ThIsmayresultInIncreasedrIskofsepsIs,thrombocytopenIa,andanemIa.
PatIentsaretypIcallyscheduledforaserIesoftreatmentsoverseveralweeks.FadIatIon
dosesarehIgh,Intherangeof180to250cCy,andallmedIcalpersonnelmustleavethe
roomdurIngthetreatment.0IrectobservatIonofthepatIentIsnotpossIble;anInterfaced
systemofclosedcIrcuIttelevIsIonandtelemetrIcmIcrophonesIsusedwIthstandard
monItorIng.
4
ntheeventofaproblem,shutdownoftheradIatIonbeamandImmedIate
accesstothepatIent(wIthIn20toJ0seconds)arecrucIal.
ThegoalsofanesthesIaforpedIatrIcradIotherapyhavebeendefInedas
54
:
1. AssuranceofImmobIlIty
2. FapIdonset
J. 8rIefduratIonofactIon
4. NotpaInfultoadmInIster
5. Promptrecovery
6. |InImalInterferencewItheatIngordrInkIngandplayIng
7. AvoIdanceoftolerancetotheanesthetIcagents
8. |aIntenanceofapatentaIrwayInavarIetyofbodyposItIons
CeneralanesthesIa
54
ordeepsedatIontechnIqueswIthpropofol
55
arepreferabletoprevent
patIentmovementandtoallowchIldrentotoleratewhatcanbefaIrlylengthprocedures,
somelastIngatleastJ0mInutes.|ostchIldrenwIllhaveIndwellIngIntravenousaccess,
avoIdIngtheneedforrepeatedIntravenouspunctureandInhalatIonalInductIon.
ntraoperatIveradIatIontherapytreatmentsareprovIdedafterthemassesareexposedto
vIew.PatIentswIthpancreatIc,colon,andrectalcancers;radIatIonsensItIvesarcomas;
andspecIfIctypesofovarIancancersreceIvethIsformoftreatment.0osesof5,000to
6,000cCymaybeuseddurIngasIngle,IntraoperatIvetreatment.ThesepatIentstypIcally
sufferfromadvancedcancersandmayhavetheattendantnutrItIonaldefIcIency,
dehydratIon,electrolyteImbalances,andcoagulopathIesthatcancomplIcateanesthetIc
management.SomehospItalsareequIppedwIthcombInatIonradIatIontherapy/operatIng
roomsuItes;however,mostcentersrequIrethatsurgIcalexploratIonbeperformedInthe
tradItIonaloperatIngroom.TheanesthetIzedpatIentIssubsequentlytransportedtothe
radIologysuIte,whIchmaybeataconsIderabledIstance.PortablemonItorsandmethods
fordelIveryofoxygenandagentstomaIntaIngeneralanesthesIadurIngtransportare
requIred.
56
FequIrementsforpatIentmonItorIngforIntraoperatIveradIatIonare
comparabletothosedescrIbedforexternalbeamradIatIon.Personnelmustleavetheroom
durIngtheactualtreatment.Aftertreatment,patIentsmustbetransportedbacktothe
operatIngroomforsurgIcalclosure.DccasIonally,closurecanbeperformedInthe
radIologysuIteandthepatIenttakendIrectlytothePACU.
Cardiac Catheterization
CommonInterventIonsInthecardIaccatheterIzatIonlaboratoryInclude
57
:
0IagnostIccardIaccatheterIzatIon
CoronaryangIographyandstentIng
ElectrophysIologystudIesandablatIons
PlacementofpacInganddefIbrIllatordevIces
nrecentyearsthenumberandcomplexItyofproceduresperformedhaveexpanded
rapIdly.
58
Newprocedureshavebeendeveloped,IncludIng,balloondIlatIonandstentIng
forvalvularandsubvalvularlesIons,electrophysIologIcalstudIes,andablatIonofspecIfIc
pathways(e.g.,WolffParkInsonWhItesyndrome)orareas(e.g.,atrIalfIbrIllatIon),and
bIventrIcularpacIngforheartfaIlure.|anypatIentswIlltoleratetheseprocedureswIth
lIghtormoderatesedatIon;however,generalanesthesIaIsbecomIngmorewIdely
practIced,partIcularlyasproceduresbecomelongerandmorecomplex.
CardIaccatheterIzatIonIsperformedInchIldrenwIthcongenItalheartdIseaseforboth
hemodynamIcassessmentandInterventIonalprocedures.
59
CarefulcardIacassessmentIs
essentIal,andthepresenceofatraInedpedIatrIcanesthesIologIstIsdesIrable.PatIents
oftenpresentwIthcyanosIs,dyspnea,congestIveheartfaIlure,andIntracardIacshunts.
HypoxIa,hypercarbIa,andsympathetIcstImulatIonasaresultofanxIetymayexacerbate
cardIopulmonaryabnormalItIes.npatIentswIthapatentductusarterIosIs,hIghoxygen
tensIoncanleadtoprematureclosureandshouldbeavoIded.ProstaglandInInfusIonsare
oftenusedtomaIntaInductpatency.|etIculousattentIonmustbepaIdtopreventIngaIr
bubblesenterIngIntravenouslInesbecausetheymaycrosstothearterIalcIrculatIonvIaa
rIghttoleftshunt.0IagnostIc,nonInterventIonalstudIesareoftenperformedwIth
sedatIon,andlocalanesthetIcIsInjectedatthesIteoffemoralpuncture.DralsedatIon
technIquesIncludechloralhydrate,75to100mg/kg,oramIxtureofmeperIdIne,
promethazIne,andchlorpromazIne.
59
ntravenousagentsIncludemIdazolam,morphIne,
andketamIne.CeneralanesthesIaIsnecessarywhenchIldrencannottoleratesedatIon
technIquesand/orhavesIgnIfIcantcardIacorothermorbIdIty,andwhentheprocedure
InvolvesseverehemodynamIcdIsturbancessuchasventrIcularseptaldefectocclusIon.
KetamIneIsusefulInchIldrenwIthmyocardIaldepressIonandcanbeusedasanInfusIon
togetherwIthpropofol.
60
Fentanyl,mIdazolam,andetomIdatearealternatIves.
Electrophysiological Procedures
ElectrophysIologIcstudIesandablatIonofabnormalconductIonpathwaysareperformedfor
treatmentofdysrhythmIascausedbyaberrantconductIonpathways.CardIaccathetersare
InsertedvIathefemoralandsometImesInternaljugularroutes,andmultIplestImulatIons
ofthecardIacconductIngsystemarecarrIedout.DnceIdentIfIed,theabnormalconductIon
pathwaysareablatedusIngradIofrequencytechnIques.ThevolatIleanesthetIcagentsand
propofolhavebeenshownnottoInterferewIthcardIacconductIondurIngthese
procedures.
61
ElectrophysIologIcstudIesarelengthyandcanbepaInful;chIldrenusually
requIregeneralanesthesIa.ChIldrenundergoIngradIofrequencyablatIonexperIenceahIgh
IncIdenceofnauseaandvomItIng,
62
andthIsmaybereducedusIngapropofolInfusIon
technIqueratherthanvolatIleanesthesIa.ThepatIent'santIdysrhythmIctherapyIsstopped
prIortothe
P.870
procedure,andcardIacdysrhythmIasgeneratedbytheprocedureareusuallytermInated
usIngoverdrIvepacIngvIathecathetersor,Ifunsuccessful,byexternalcardIoversIon.
ExternaldefIbrIllatIonpadsshouldbeapplIedbeforetheprocedure.
Automatic Implantable Cardioverter-Defibrillators
nthelate1990s,anumberoftrIalsprovedthebenefItofautomatIcImplantable
cardIoverterdefIbrIllatorsInreducIngmortalItyofpatIentswIthventrIcular
tachyarrhythmIasandleftventrIculardysfunctIonfollowIngmyocardIalInfarctIonor
cardIacarrest.
6J,64
AutomatIcImplantablecardIoverterdefIbrIllatorsareusuallyImplanted
IntheelectrophysIologIclaboratoryratherthanIntheoperatIngroom,undergeneral
anesthesIaorsedatIon.TheprocedureItselfIsnotpartIcularlypaInful;however,
ventrIcularfIbrIllatIonIsInducedtotestthedevIcedurIngImplantatIon,whIchIs
dIstressIngforthepatIent.
Cardioversion
AtrIalfIbrIllatIon(AF)affectsapproxImately0.4ofthegeneralpopulatIon,Itsprevalence
IncreasIngwIthage.
65
AFIsassocIatedwIthanumberofcondItIons,partIcularly
hypertensIon,chronIcheartfaIlure,andvalvularandIschemIcheartdIsease,andIsa
frequentsequelaofcardIothoracIcsurgery.
66
TransthoracIc0CcardIoversIonIsan
accepted,oftenusedtreatmentforatrIaldysrhythmIasIncludIngAFandatrIalflutter,
67
andInpatIentsundergoIngoutpatIentcardIoversIon;thesuccessrateforconversIonto
sInusrhythmIs90.
68
AFIsassocIatedwIthsIgnIfIcantmorbIdItyandmortalItyfrom
thromboembolIcstroke.TwostrategIesareemployedtopreventthromboembolIsm
followIngcardIoversIonInpatIentswhohavebeenInAFforlongerthan48hours.The
conventIonalapproachIstoInItIateantIcoagulatIonJweeksbeforecardIoversIon,usually
wIthCoumadIn,andtocontInuefor4weeksaftercardIoversIon.
67,69
|orerecently,
transesophagealechocardIography(TEE)hasbeenrecommendedtodetermInewhether
patIentsareatloworhIghrIskofthromboembolIsm.
70,71
nlowrIskpatIents,thedoseof
antIcoagulantscanbereduced,whereasInpatIentsconsIderedtobehIghrIsk,
cardIoversIonmaybepostponedtoallowadequateantIcoagulatIon.
72
SImplecardIoversIon
takesafewseconds;however,ItIsdIstressIng,andsedatIonIspreferableexceptInlIfe
threatenIngsItuatIons.ThecomplIcatIonrateforcardIoversIonIsreportedas2.6.
68
ComplIcatIonsassocIatedwIthcardIoversIonIncludethromboembolIcphenomena,
pulmonaryedema,aspIratIonpneumonItIs,andbradycardIa.
68
ElectIvecardIoversIonIs
oftenperformedInareasneartheoperatIngroom,usuallyInthePACU.AlternatIvely,
theremaybearequIrementfortheanesthesIologIsttoprovIdesedatIonIntheIntensIve
careunIt(CU)forurgentcardIoversIonInanunstablepatIent.
AsmallbolusofIntravenousInductIonagentIsusuallysuffIcIenttosedateapatIentfor
cardIoversIon.AllcurrentlyavaIlableInductIonagentsareeffectIve.EtomIdateproduces
lesshypotensIonthanpropofolmakIngItabetterchoIceInpatIentswIthsIgnIfIcantcardIac
dIsease,althoughhypotensIoncanbeattenuatedbyusIngsmallerdosesofpropofol(1
mg/kg).
7J,74
Fecently,propofolhasbeenshowntoprovIdemorerapIdrecoverythan
mIdazolamfollowIngcardIoversIonInelderlypatIents,
74
andapropofol/remIfentanIl
technIqueprovIdedmorehemodynamIcstabIlItyandfasterrecoverythanmIdazolamIn
patIentsundergoIngcardIoversIonforAFfollowIngcardIacsurgery.
75
WhenTEEIs
performedprIortocardIoversIon,theproceduretakes15toJ0mInutesandvarIous
sedatIonagentsmaybeusedtohelpthepatIenttoleratetheprocedure.AIrwaycontrolIs
Important,andInmostcasesnasalcannulasaresuffIcIenttoprovIdesupplemental
oxygenatIonwhIlethepatIentmaIntaInshIsorherownaIrway.
AtechnIqueusIngdeeppropofolsedatIontogetherwIthaL|AtosupporttheaIrwayand
allowventIlatIonhasalsobeendescrIbed.
76
nthIsstudytheL|AwasInsertedeItheratthe
begInnIngoftheprocedureormIdwaythroughIfrespIratoryproblemsoccurred.The
presenceoftheL|AwasnotfoundtoInterferewIththeTEEprocedure.ThoroughaIrway
evaluatIonIsImportantprIortoTEE,andoccasIonally,endotrachealIntubatIonmaybethe
mostprudentapproach.8eforeTEE,localanesthetIc,eIther4lIdocaIneor20
benzocaIne,IssprayedIntotheoropharynxtoalloweasypassageoftheTEEprobe.AbIte
blockIsInsertedtopreventthepatIentfrombItIngdownontheprobe,damagIngboththe
teethandtheprobe.
Gastroenterology
ThegastroenterologysuIteIsanotherlocatIonwheretechnologyIsexpandIng,andwhere
anIncreasIngnumberofdIagnostIcandtherapeutIcproceduresarebeIngperformed.
ProcedurescommonlyperformedInthegastroIntestInal(C)endoscopysuIteareshownIn
TableJ49.
ArevIewIn2007bytheAmerIcanCastroenterologIcalAssocIatIonreportsthat98of
endoscopIstsIntheUnItedStatesadmInIstersedatIonforupperandlowerendoscopIes.
77
A
wIdevarIetyofsedatIontechnIquesareused,andthecomplIcatIonratesforsedatIonare
reported0.54to0.1.
78
ThemortalItyrateIs0.0J.
79
CastroenterologIstsareIncreasIngly
usIngpropofolsedatIontechnIques,andmanyhavefoundIttobeaneffectIveandsafe
technIque.
80
However,theAmerIcanCastroenterologIcalAssocIatIonrecommendatIonscall
forapproprIatetraInIngofendoscopIstsandtheInvolvementofananesthesIologIstfor
patIentsInASAcategorIes7and7orwIthhIstorIesofadverseorInadequateresponsesto
sedatIon.
78
Upper Gastrointestinal Endoscopy
UpperCendoscopyIsperformedfordIagnostIcprocedures,suchasbIopsy,andfor
therapeutIcprocedures,suchasretrIevalofforeIgnbodIes,treatmentofesophageal
varIceswIthsclerotherapyorbandlIgatIon,dIlatIonofesophagealstrIctures,and
placementofapercutaneousendoscopIcgastrostomy.PatIentsmayhaveanumberof
comorbIdItIes,IncludIngdIseaseoftheesophagusandstomach,wItharIskofreflux,
bIlIary,andhepatIcdIseasewIthesophagealvarIces,hepatIcdysfunctIon,coagulopathy,
andascItes.TheprocedureIstoleratedwIthoutsedatIonIn66to81ofpatIents,
81
and
conscIoussedatIonIsusuallysuffIcIentIntheremaInder.WIthgeneralanesthesIa,patIents
usuallyrequIreendotracheal
P.871
IntubatIontoprotecttheaIrwayandfacIlItatepassageoftheendoscope.TheL|Ahasalso
beenusedsuccessfullyInadults
82
andchIldren
8J
asanalternatIvedevIceforaIrway
management.LocalanesthetIcIssprayedIntotheoropharynxtofacIlItatepassageofthe
endoscope;thIscanabolIshthegagreflex,IncreasIngtherIskofaspIratIon.AbIteblockIs
InsertedtopreventthepatIentfrombItIngdownontheendoscopeanddamagIngboththe
teethandtheendoscope.fthepatIenthasreceIvedgeneralanesthesIa,caremustbe
takenthatthebIteblockandendoscopedonotdIslodgeorobstructtheendotrachealtube.
ProceduresareperformedIntheproneorsemIproneposItIonwIththepatIent'shead
rotatedtothesIde.ThIsposItIonmakestheaIrwaylessaccessIble.CareandattentIon
shouldalsobepaIdtopressureareas,partIcularlytheeyes,lIps,andteeth.Extreme
rotatIonoftheneckshouldbeavoIded.|ostproceduresarebrIef,lastIng10toJ0mInutes,
andaregenerallypaInless.
Table 34-9 Common Gastroenterologic Procedures
Upperendoscopy
SIgmoIdoscopy
Colonoscopy
EndoscopIcretrogradecholangIopancreatography
EsophagealdIlatatIon
EsophagealstentIng
PercutaneousendoscopIcgastrostomytubeplacement
TransjugularIntrahepatIcportosystemIcshunt
Endoscopic Retrograde Cholangiopancreatography
EndoscopIcretrogradecholangIopancreatography(EFCP)IsImportantInthedIagnosIsand
treatmentofbothbIlIaryandpancreatIcdIsease.0urIngtheprocedure,theendoscopeIs
advancedvIathemouthIntothestomach,andthenIntotheduodenumwheretheampulla
of7aterIsvIsualIzed.ThebIlIaryandpancreatIcductsystemsmaythenbeInstrumented,
andtherapeutIcmaneuverssuchasthepassageofstentsorremovalofstonescarrIedout.
SphIncterofDddImanometrymayalsobeperformed.PatIentsusuallyexperIence
dIscomfortdurIngEFCP,partIcularlywIthInstrumentatIonandstentIngofthebIlIaryand
pancreatIcducts.ConscIousordeepsedatIontechnIquesarerecommendedforthe
procedure,whIchusuallylastsbetween20and80mInutes.
84
Dnly5to8ofpatIents
requIregeneralanesthesIa.
82,85
TheaIrwayandpatIentposItIonIngconsIderatIonsaresImIlartothoseforCendoscopy.
EFCPIntheproneposItIoncanbepartIcularlyproblematIcIfcarefulattentIonIsnotpaId
tomaIntenanceofapatentaIrway.fsphIncterofDddImanometryIsbeIngperformed,
glycopyrrolate,atropIne,andglucagonshouldbeavoIded
84
becausetheyeffectsphIncter
pressure.DpIoIds,partIcularlymorphIne
86
andfentanyl,causespasmofthesphIncterof
DddI,whIchmayberelIevedwIthnaloxone.
87
|eperIdIne,Incontrast,reducesthe
frequencyofsphIncterofDddIcontractIons.
86
PatIentspresentIngforemergencyEFCPmayhavesIgnIfIcantcomorbIdIty,
85
IncludIng
acutecholangItIswIthseptIcemIa,jaundIcewIthlIverdysfunctIonandcoagulopathy,
bleedIngfromesophagealvarIcesresultIngInhypovolemIa,orbIlIarystrIcturefollowIng
majorhepatobIlIarysurgery,IncludInglIvertransplantatIon.TransIentbacteremIamay
occurdurIngendoscopy,andantIbIotIcprophylaxIsIsrecommendedforpatIentswIth
cardIacvalvularabnormalItIes.CastroenterologIstsfrequentlyuseantIspasmodIcsto
ImproveoperatIngcondItIonsdurIngendoscopy.
88
ntravenoushyoscyamInegIvenasa0.5
mgbolusbeforetheprocedurehasbeenshowntoreducetheIncIdenceofspasm,shorten
theprocedure,andImprovepatIentcomfort
88
;sInustachycardIamayoccur.
Transjugular Intrahepatic Portosystemic Shunt
ThetransjugularIntrahepatIcportosystemIcshunt(TPS)IscreatedvIaacatheterInserted
IntheInternaljugularveInanddIrectedIntothelIver.tconnectstherIghtorleftportal
veInthroughthelIverparenchymatooneofthethreehepatIcveIns.
89
TheTPSfunctIons
todecompresstheportalcIrculatIonInpatIentswIthportalhypertensIonandIsoften
performedInpatIentswhohavefaIledtorespondtomedIcaltherapy.TheTPShasbeen
foundtobeequallyeffectIveasothertherapIesInthesecondaryprophylaxIsofbleedIng
varIcesandcontrolofrefractorycIrrhotIcascItes,
90
butwIthnoImprovementInmortalIty
andanIncreasedrIskofdevelopmentofencephalopathy.TheTPShasbeenusedIn
chIldrenandfoundtobefeasIbleandsafeInprovIdIngtemporaryrelIefofportal
hypertensIonwhIleawaItInglIvertransplantatIon.
91
TheTPSprocedurecausesmInImal
stImulatIon,lastsbetween2andJhours,andmaybeperformedundersedatIonorgeneral
anesthesIa.
92
Table 34-10 Preoperative Considerations in Patients Presenting for the
Transjugular Intrahepatic Portosystemic Shunt Procedure
AIrwayrIskof
aspIratIon
FecentgastroIntestInalbleedIng
FaIsedIntragastrIcpressureduetoascItes
0ecreasedlevelofconscIousnessduetohepatIc
encephalopathy
FespIratorysystem
0ecreasedfunctIonalresIdualcapacItyduetoascItes
PleuraleffusIon
ntrapulmonaryshunts
PneumonIa
CardIovascularsystem
AssocIatedalcoholIccardIomyopathy
Alteredvolumestatus
AcutehemorrhagefromesophagealvarIces
ntraperItonealhemorrhage
HematologIcsystem
Coagulopathy
ThrombocytopenIa
NeurologIcsystem HepatIcencephalopathy
PatIentspresentIngforaTPSprocedure,Ingeneral,havesIgnIfIcanthepatIcdysfunctIon
andrequIrecarefulpreoperatIveassessment.ConsIderatIonsareoutlInedInTableJ410
(seealsoChapter48).ChronIclIverdIseasehasanumberofeffectsonthe
pharmacokInetIcsofanesthetIcagents,
92
andtheresponsetoanesthetIcagentsmaybe
unpredIctable.7olumeofdIstrIbutIonIsIncreased,andproteInbIndIng,drugmetabolIsm,
andelImInatIonarealldecreased.CNSsensItIvItyIsvarIablyaffected.PatIentsneed
carefulmonItorIng;theuseofanarterIalcathetertomonItorbloodpressureandtoallow
frequentbloodgasandchemIstryanalysIsIsrecommended.8loodglucoseshouldbe
monItoredfrequentlyaspatIentswIthhepatIcdIseaseareatrIskforhypoglycemIabecause
ofdepletedlIverglycogenstores.PreoperatIveuseofdIuretIcsandIntraoperatIvefluId
shIftsmakethesepatIentsvulnerabletoelectrolyteabnormalItIes.UrIneoutputshouldbe
closelymonItoredtopreventworsenIngofrenalfunctIonanddevelopmentofthe
hepatorenalsyndrome.
Electroconvulsive Therapy
ElectroconvulsIvetherapy(ECT)hashadanImportantroleInthemanagementof
psychIatrIcdIsorderssIncethe19J0s.ECTIsusedtotreatdepressIon,manIa,andaffectIve
dIsordersInschIzophrenIcpatIents,aswellasanumberofotherpsychIatrIcdIsorders.
TypIcally,ECTIsperformedJtImesperweekfor6to12treatments,followedbyweeklyor
monthlymaIntenancetherapytopreventrelapses.
9J
P.872
Physiologic Response to Electroconvulsive Therapy
ThephysIologIcresponsetoanelectrIcalcurrentapplIedtothebraInIncludesgeneralIzed
motorseIzuresandanacutecardIovascularresponse.ThegrandmalseIzurelastsseveral
mInutesandIncludesashort,10to15secondtonIcphase,followedbyamoreprolonged
clonIcphase,lastIngJ0to60seconds.AmInImumseIzureduratIonof25secondsIs
recommendedtoensureadequateantIdepressanteffIcacy.
94
ThecardIovascularresponse
IncludesIncreasedcerebralbloodflowandCP.CeneralIzedautonomIcnervoussystem
stImulatIonresultsInanInItIal10to15secondsofbradycardIaandoccasIonalasystole,
followedbyamorepromInentsympathetIcresponseofhypertensIonandtachycardIa.
DccasIonally,cardIacdysrhythmIas,myocardIalIschemIa,InfarctIon,orneurologIcvascular
eventsmaybeprecIpItated.ShorttermmemorylossIsalsocommonfollowIngECT.Dther
sequelaeIncludemuscularaches,fracture/dIslocatIons,headache,emergenceagItatIon,
statusepIleptIcus,andsuddendeath.
Anesthetic Considerations
ECTIsusuallycarrIedoutInthePACUneartheoperatIngroom;alternatIvely,psychIatrIc
InstItutIonsmayhaveanareasetasIdefortreatments.PsychIatrIstsplacescalpelectrodes
tomonItortheelectroencephalogramdurIngtheseIzure,andabloodpressurecuffIs
applIedtoanextremItyandInflatedbeforethemusclerelaxantIsadmInIsteredtomonItor
theseIzure.PatIentswIthdepressIonpresentIngforECTareoftenelderly,wIthanumber
ofcoexIstIngcondItIons;therefore,athoroughpreoperatIveassessmentandworkupshould
beperformedbeforethepatIentbegInstreatment.
95
FIrstlInepharmacotherapeutIcagents
forthetreatmentofdepressIonIncludetrIcyclIcantIdepressants,monoamIneoxIdase
InhIbItors,andselectIveserotonInreuptakeInhIbItors.PatIentsmaybetakIngavarIetyof
drugs,whIchcanhaveImportantInteractIonswIththeanesthetIcagent.ThemonoamIne
oxIdaseInhIbItorshavethemostsIgnIfIcantInteractIons,althoughmoremoderndrugsare
supersedIngthese.TheanesthetIcrequIrementsforECTIncludeamnesIa,aIrway
management,preventIonofbodIlyInjuryfromtheseIzure,controlofhemodynamIc
changes,andasmooth,rapIdemergence.
9J,95
|ostoftheIntravenousInductIonagentshavebeenusedtoInduceanesthesIaforECT.
|ethohexItal(1to1.5mg/kg)IsconsIderedthegoldstandard,
9J
althoughItdecreases
seIzureduratIonInadosedependantway.EtomIdate(0.15to0.Jmg/kg)Isgenerally
assocIatedwIthlongerseIzureduratIon,myoclonus,anddelayedrecovery,andIs
consIderedbysomepsychIatrIststobesuperIortopropofolormethohexItal.
96,97
EtomIdate
doesnotdepressthecardIovascularsystem,sohypertensIveandtachycardIcresponses
maybeaccentuated.
9J
PropofolIsmoreeffectIveatattenuatIngtheacutehemodynamIc
responsestoECT
98
andrecoveryIsrapId.Propofol,however,hasantIconvulsanteffects,
althoughwIthasmalldose(0.75mg/kg)seIzureduratIonIsusuallyacceptable,
96
and
studIeshavefoundthatreductIonInseIzureduratIonbypropofoldoesnotadverselyaffect
theoutcomeofECTtherapy.
99
|ostotherInductIonagentsdecreaseseIzureactIvIty.
ShortactIngopIoIds,suchasremIfentanIl,canbeusedtodecreasethedoseofInductIon
agentandprolongseIzureduratIonwIthoutreducIngthedepthofanesthesIa.
100
|uscle
relaxantsareusedtopreventmusculoskeletalcomplIcatIonssuchasfracturesor
dIslocatIonsdurIngtheseIzure.SuccInylcholIne,0.75to1.5mg/kg,Isthemostcommonly
usedagentandIspreferabletothelongeractIngnondepolarIzIngagents.
9J
AnesthesIaIsInducedandthepatIentIsventIlatedwIth100oxygenusInganoralaIrway
andaselfInflatIngbagandmask.|oderatehyperventIlatIonIsbenefIcIalprIortotheECT
toImprovethequalItyandduratIonofseIzures,andIthasbeensuggestedthattheL|A
maybeusefultoImproveventIlatIondurIngECT.
101
8eforeadmInIsterIngtheseIzure,a
bIteguardIsplacedtoprotecttheteeth.nyoungerpatIents,15toJ0mgofIntravenous
ketorolachelpstoreduceECTInducedmyalgIa.DlderpatIents,orthoseInwhomketorolac
IscontraIndIcated,mayreceIveaspIrInoracetamInophenorallybeforetheIrtreatment.
9J
TheparasympathetIceffectsofECT,salIvatIon,transIentbradycardIa,andasystolecanbe
preventedbypremedIcatIonwIthglycopyrrolateoratropIne.Anumberofdrugshavebeen
usedtoattenuatethehypertensIveandtachycardIcresponsesthataccompanyECT.
Labetalol(0.Jmg/kg)andesmolol(1mg/kg)bothhavebeenshowntoamelIoratethe
hemodynamIcresponses,althoughesmololhasalessereffectonseIzureduratIonthan
labetalol.
102
ThecalcIumchannelantagonIstsnIfedIpIne,dIltIazem,andnIcardIpIneall
attenuatethehemodynamIcresponsestoECT,partIcularlyIncombInatIonwIthlabetalol.
The
2
adrenergIcreceptoragonIstsclonIdIne,
9J
andmorerecently,dexmedetomIdIne
10J
(1
g/kgadmInIsteredover10mInutesjustbeforeInductIonofanesthesIa)havebeenshown
tobeeffectIveIncontrollIngbloodpressurewIthoutaffectIngseIzureduratIon.
Dental Surgery
|ostdentalproceduresareperformedIntheoffIcewIthnosedatIonandonlylocal
anesthesIa.CeneralanesthesIamayberequIreddurIngmorecomplIcatedorprolonged
casesandwhenpatIentsareuncooperatIve,phobIc,ormentallychallenged.PatIentsmay
alsopresentfordentalclearanceprIortoundergoIngcardIacsurgeryorheart
transplantatIonwIthseverecardIomyopathyorvalvularabnormalItIes.Anumberof
genetIcdIseasesresultInmentaldefIcIency,psychIatrIcdIagnoses,andaberrantbehavIor.
ThesepatIentscommonlyrequIresedatIonorgeneralanesthesIatotoleratedental
procedures.CenetIcdIseasesarecommonlyassocIatedwIthothermedIcalproblems,
partIcularlythoserelatedtothecardIovascularsystemandtheaIrway.
104
0ownsyndrome
Iscommonlyencountered,andtheanesthesIologIstshouldbeawareofcardIac
abnormalItIes,IncludIngconductIonabnormalItIesandstructuraldefects,therIskof
atlantooccIpItaldIslocatIon,andavarIetyofpotentIalaIrwayproblems,IncludIng
macroglossIa,hypoplastIcmaxIlla,palatalabnormalItIes,ormandIbularprotrusIon.fthe
patIentIsposItIonedheadupInthedentalchaIr,vasodIlatIonandmyocardIaldepressant
effectsofanesthetIcscanbepronounced,especIallyInpatIentswIthcardIovascular
dIseases.PatIentswIthneuromusculardIseasesmayhaveahIstoryofaspIratIonand
epIsodesofchronIcrecurrentpneumonItIsthatmustbeaddressedbeforedentalsurgery.
ThemostchallengIngpartofanesthesIafordentalsurgeryIsInductIon.|anypatIents,
partIcularlychIldren,areunabletocooperatebecauseoflearnIngdIsabIlItIesormental
retardatIon.KetamIneIsausefulInductIonagent.tmaybegIvenalonebyavarIetyof
routes(orally,Intramuscularly,Intravenously),orIncombInatIonwIthatropIneand
mIdazolam.
105
0osesareasfollows:Intravenously,1to2mg/kg;orally,5to10mg/kg;and
Intramuscularly,2to4mg/kg,wIthanonsettImeof5to10mInutes.Therectaland
Intranasalrouteshavealsobeenused.KetamIneIsalsoadvantageousInthatItdoesnot
abolIshupperaIrwayreflexes.DralmIdazolamIsalsopopular.Adoseof0.5mg/kgIs
dIssolvedInasmallamountoflIquId.nchIldrenandneedlephobIcadults,theuseoflocal
anesthetIccreamfacIlItatestheplacementofIntravenouslInes.AlternatIvely,an
InhalatIonInductIonmaybeattempted.
0urIngandafterdentalsurgeryblood,salIva,anddentaldebrIsarepresentIntheupper
aIrway.AthroatpackIsusedtohelpprotecttheaIrway,andthIsmustberemovedatthe
endof
P.87J
surgery.TrachealIntubatIon,oftenvIathenasalroute,IsrequIredtoprotecttheaIrway,
althoughtheL|Ahasbeenusedsuccessfullyforbothadults
106
andchIldren
107
undergoIng
dentalsurgery.AnesthesIacanbemaIntaInedwIthIntravenousInfusIonsorInhalatIon
anesthesIa.PatIentsneedcloseobservatIondurIngemergenceandrecovery.The
ImmedIatepostoperatIvecomplIcatIonsIncludebleedIng,aIrwayobstructIon,andlaryngeal
spasm.FeanesthetIzIngthepatIentfortreatmentofdentalhemorrhagecanbevery
dIffIcultbecauseofthepresenceofbloodIntheaIrwayandtherIskofpulmonary
aspIratIon.LatercomplIcatIonsInambulatorypatIentsIncludedrowsIness,nauseaand
vomItIng,andpaIn.
108
Transport of Patients
PatIentswhoreceIveanesthesIaorsedatIonatalternatesItesmayneedtobetransported
tothePACUattheendoftheprocedure;thIsmaybesomedIstanceaway.0urIng
transport,patIentsshouldbeaccompanIedbyamemberoftheanesthesIateam,who
shouldcontInuetoevaluate,monItor,andsupportthepatIent'smedIcalcondItIon.
9
Dther
patIentstransportedwIthInahospItalmayrequIrethecareofananesthesIologIstfora
varIetyofreasons.Forexample,surgerypatIentsmaybetransferredtotheCUorthe
radIologydepartmentforImagIngattheendofsurgery,orcrItIcallyIllpatIentsmaybe
transferredtotheoperatIngroomfromtheCUortheemergencydepartmentforurgent
surgery.nthesesItuatIons,theanesthesIologIstshouldmonItorthepatIentsclosely.These
patIentsareoftenventIlatedandreceIvInganumberofdrugInfusIonsforbothsedatIon
andhemodynamIcsupport.PortableventIlatorsareusefulfortransport;however,these
areoftenoxygenpowered,andadequatesupplIesofoxygenmustbeavaIlableforthe
transfer,aswellasamanualselfInflatIngbagtoallowhandventIlatIonIntheeventof
ventIlatorfaIlure.SImIlarly,theInfusIonpumpsandportablemonItorsshouldhave
adequatebatterypowertoallowthemtocontInueworkIngIntransIt.TheanesthesIologIst
shouldcarryspareanesthetIcandemergencydrugs,equIpmentforIntubatIonor
reIntubatIon,portablesuctIon,andIfthepatIent'scondItIonrequIres,aportable
defIbrIllator.tIsusefultonotIfypersonsInthedestInatIonareathatthepatIentIsIn
transItsoapproprIatepreparatIonstoreceIvethepatIentcanbemadeInadvance.tIs
alsousefultosendpersonnelaheadtosecuretheelevatorstopreventdelaysdurIng
transfer.
Summary
ThenumberandcomplexItyofproceduresthatareperformedatalternatesItesIssteadIly
IncreasIng.ThIshasledtoanexpansIonofanesthesIaservIcesInareasremotefromthe
operatIngroomthatmaynotbefamIlIartoanesthesIaprovIders.npreparIngto
admInIsteranesthesIaorsedatIonInanalternatesIte,asImplethreestepapproachcanbe
followed.ThIsInvolvesgIvIngcarefulconsIderatIontotheneedsofthepatient,the
partIcularproblemsposedbytheprocedure,andthehazardsandlImItatIonsofthe
environment.nallcases,thestandardsofanesthesIacareandmonItorIngshouldbeno
dIfferentthanthoseprovIdedIntheconventIonaloperatIngroom.
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Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJ5AnesthesIafortheDlderPatIent
ChapterJ5
Anesthesia for the Older Patient
G. Alec Rooke
Key Points
1. The aging of America presents a medical and economic challenge to
the entire health care system, including anesthesiologists, as older
patients present for surgery in ever-increasing numbers.
2. The aging process affects connective tissue and cellular function,
including the mitochondria, and inevitably leads to decreased function
and, ultimately, frailty.
3. The rate at which diminished function and frailty develop is highly
variable and lends credence to the concept of a measure of
physiologic age.
4. Decreased organ reserve and increased sensitivity to anesthetic
agents result from generalized body composition changes such as
connective tissue stiffening and decreased muscle mass, plus central
nervous system dysfunction including impaired swallowing, impaired
autonomic reflexes, and increased sensitivity to drugs.
5. Preoperative preparation will more often involve evaluation of how
best to enhance recovery of function after surgery, and discussions
surrounding informed consents, living wills, and ethical treatment of
the older patient.
6. Intraoperative management must take into account the increased
sensitivity to drugs in the elderly patient, as well as an increased
likelihood of hemodynamic, pulmonary, and thermoregulatory
instability.
7. Analgesia is an important component of postoperative care, but is
made more difficult by the increased likelihood of adverse
consequences from the analgesic regimen.
8. Perioperative complications, most notably pulmonary, cardiac, and
central nervous system complications such as delirium or cognitive
decline, occur more commonly in the elderly patient because of an
interaction between comorbid disease and the decreased
physiological reserve of aging.
Age is not a particularly interesting subject. Anyone can get old. All
you have to do is live long enough.
Don Marquis
TheabovequotesuggeststhatagIngIsdull.TomanymedIcalpractItIoners,ItIsfarworse
thandull.tIsoverwhelmIngfromthemagnItudeofcarerequIredbyourevergrowIng
olderpopulatIon,frustratIngfromItscomplexItyofcare,anddIscouragIngInItsmonetary
reImbursement.Nevertheless,theImpactoftheagIngpopulatIononthepractIceof
medIcIneIsfarreachIngandprofound,andthereforecannotbeIgnored.JustaschIldren
arenotlIttleadults,theolderpatIentIstrulydIfferentfromtheyoungeradult
counterpart.AllcaregIvers,IncludInganesthesIologIsts,shouldbeknowledgeableofat
leastsomeaspectsofagIngInordertoprovIdeIntellIgentmodIfIcatIonoftheIrstandard
practIce.|oreInformatIonIsavaIlablethaneverbefore,muchofItelectronIcallyfrom
theAmerIcanSocIetyofAnesthesIologIsts(www.asahq.org),theSocIetyforthe
AdvancementofCerIatrIcAnesthesIa(www.sagahq.org),andtheAmerIcanCerIatrIcs
SocIety(www.amerIcangerIatrIcs.org).ThepolItIcs,economIcs,andsocIetalattItudes
towardtheelderlypopulatIonmustbereckonedwIthaswell.Lastly,carIngforanolder
patIent,althoughchallengIng,IsusuallyfunandInterestIng.AnyonewIthapassIngInterest
InphysIologyshouldenjoytheapplIcatIonofagIngphysIologytoanesthetIcmanagement.
DlderpatIentsareusuallymorerelaxedabouttheprospectofsurgery(oftenmoresothan
theIradultchIldren!),andInvarIablyhavefascInatIngstorIestotellabouttheIrlIves.Yes,
theIrcareIsoftentImeconsumIngandstressful,butmoreoftenthannotItprovIdesthe
anesthesIacaregIvertheopportunItytotrulypractIcemedIcIneandmakeaposItIve
ImpactonavulnerablepatIent'slIfe.
Demographics and Economics of Aging
WhenSocIalSecurItywasInItIatedIn19J5,only6.1oftheU.S.populatIonwasolderthan
65years.
a
8y2005thatpercentagehadmorethandoubledto12.4,andby20J5ItIs
P.877
expectedtobeover20oftheU.S.populatIon.Thepercentageofpeopleolderthan85Is
expectedtodoublefrom2005(1.7)to20J5(estImatedJ.J).Thegrowthoftheolder
populatIonIsshownInFIgureJ51.TheImpactofthesestatIstIcsIsenormouswIthrespect
tomedIcalcare.Theelderlyaccountforover44ofallInpatIentdays,anaverageper
capItaratemorethan5tImesgreaterthanpeopleunderage65.
1
n1996,therewerean
estImated72mIllIonsurgIcalandnonsurgIcalproceduresperformedIntheUnItedStates.
2
Dfthese,47wereonpatIentsolderthan65years.AlthoughItIsnotclearIfthat
percentageapplIestothe47mIllIontotalsurgIcalInpatIentandoutpatIentprocedures,of
the26.6mIllIonInpatIentsurgIcalproceduresIn2004,JJwereperformedonelderly
patIents.
1
Eventhelowerpercentagemeansthatpeopleoverage65havesurgeryJ.5
tImesmoreoftenthanpeopleunderage65.
Figure 35-1.TheactualandestImatedU.S.populatIonfrom1940to2040Isshown
brokendownbyagerange.Yellowbar=age65;purplebar=age65to74;greenbar=
age75foryears1940to1970,andage75to84from1980on;redbar=age85.0ata
source:StatIstIcalAbstractoftheUnItedStates(www.census.gov).
FederalspendIngfor|edIcareIn2005wasS286bIllIon.
b
ThIsamountrepresentsaJJ
IncreaseIntotalexpendItureanda29IncreaseperenrolleeIncomparIsontotheyear
2000.
c
AsImpressIveasthatvaluemaybe,federalspendInglIkelyunderestImatesthetotal
costofallhealthcarespendIngforpeopleoverage65toaconsIderabledegree.tIs
estImatedthatpeopleoverage65accountfornearlyhalfofthenatIon'shealthcarecosts.
For2007,totalU.S.healthcostsareestImatedatS2.JtrIllIon,orapproxImately16ofthe
grossnatIonalproduct.
d
nconsequence,thereIsconsIderablepressuretocontaInhealth
carecostsInthIscountry,IncludIngphysIcIanreImbursement,bybothprIvateInsurance
companIesandthefederalgovernment.Unfortunately,federalreImbursementto
anesthesIologIstsIsespecIallypoor.n2002,|edIcarereImbursedanesthesIacareat
approxImatelyJ9ofwhatcommercIalInsurancecompanIespaId.ThIspercentageIsIn
sharpcontrasttoallotherspecIaltIes,forwhIch|edIcarereImbursementIsapproxImately
8JofcommercIalrates.
J
8y2007,theconversIonfactorhadfallentoS16.19,andnow
representedonly29ofprIvatepayreImbursement.
e
Eventherecent(late2007)Increase
ofJ2,aswelcomeasItIs,doesnotrestore|edIcarepaymenttothe2002relatIvelevel.
ThereductIonInreImbursementformedIcaldIrectIonIsespecIallyegregIousforteachIng
InstItutIons.Although|edIcarewIllreImburseat50levelforuptofourconcurrent
medIcallydIrectedprocedures,academIcprogramsarenotpermIttedtostaffmorethan
twoproceduressImultaneouslyIfanyInvolveanesthesIaresIdents.Fortunately,asof2010,
|edIcarewIllreImburseacademIcInstItutIonsat100fortwoconcurrentcases.
The Process of Aging
You can't help getting older, but you don't have to get old.
George Burns
TherearemanytheorIesofagIng,andItIsquIteprobablethateachcouldplayaroleIn
thephysIologIcalchangeswIthageandwhydeathIsInevItable.SometheorIesof
programmedagIngsuggestthattherearegenetIccodesthatdIctatehowlongacell(and
theorganIsmasawhole)wIlllIve.ThIskIllergenetheorywouldhavetoconferan
advantagetospecIessurvIvalforevolutIontoresultInprogrammeddeath.AlthoughthIs
phenomenondoesoccurInnature(e.g.,femalesofcertaInspecIesofoctopI),thereIslIttle
evIdencethatsuchamechanIsmapplIestomammals.AnothertheoryoflImItedcell
vIabIlItyIstheattractIvehypothesIsoftelomereshortenIng.EachtImeacelldIvIdes,a
telomereIscleavedoffthe0NA.Whenthe0NArunsoutoftelomeres,thecellcannot
dIvIdeandwIlleventuallydIe.
4
SuchlImItedcelldIvIsIonoccursInculturedmammalIan
cells,andalthoughspecIeslIfespancorrelatesroughlywIththenumberofallowablecell
dIvIsIons,thereIslIttleevIdencethattelomereshortenIngaffectshumanlIfespan.
Furthermore,agIngInvolvesmorethanjustthedeathoftheorganIsm.
|ammalIanagIngclearlyInvolvesagradual,cumulatIveprocessofdamageand
deterIoratIon.ThequestIoncouldbeposed:WhyIssuchaprocessallowedInnature:
TeleologIcalreasonIngwouldsuggestthatonceoffsprInghavebeenraIsed,thereIsno
furtherneedforcontInuedsurvIvaloftheIndIvIdual.ProtectIvemechanIsmsagaInstagIng
arecostlytotheorganIsm,sothedIsposablesomatheoryofagIngstatesthatantIagIng
mechanIsmsonlyneedtobegoodenoughtogIvethenextgeneratIonthebestopportunIty
toreproduce.nfact,mostofthegaInsInaveragehumanlIfespanhavebeenastheresult
ofreducIngthosefactorsthatcauseprematuredeath:predatIon,accIdents,anddIsease.
TheInabIlItytothwartagIngcompletelyImplIesthattheaveragehumanlIfespanIs
lImIted,andthatIfeveryonedIedonlyofoldage,theageatdeathwouldendupbeInga
bellshapedcurvecenteredatacertaInvalue,probablyaroundage85.
5
Nevertheless,ItIs
possIblethatthebellshapedcurvecouldbeshIftIngtoahIghervalue,buthowfarItcan
beshIftedIsunclear.
AvarIetyofdeleterIousprocessescontInuallyattack0NA,proteIns,andlIpIds(seeChapter
6).TheprImaryculprItsarefreeradIcalsandnonenzymatIcglycosylatIonofsugarsand
amInes.FreeradIcalsareabyproductofoxIdatIvemetabolIsm,whereasglycosylatIonIs
enhancedbyelevatedglucoselevels.|anyofthechangesassocIatedwIthagIngarethe
resultofdamagetoproteIn.CollagenbecomesstIfferfromaromatIcrIngcleavageandby
crosslInkIngtoothercollagenmolecules.ElastIn,oncedamagedandremoved,Isusually
replacedbythestIffercollagen.nthecardIovascularsystem,arterIes,veIns,andthe
myocardIumallstIffenwIthage.ncontrast,lungparenchymabecomeslessstIffbecause
oflossofelastInwIthoutcollagensubstItutIon.0NAdamageoccursaswelland,curIously,
mItochondrIal0NAsuffersmoredamagethannuclear0NA.nfact,onehypothesIsof
termInalagInganddeathIsthatwerunoutofenergyasthemItochondrIabecomelessand
lesseffectIve.0amagetolIpIdsalsoappearstoplayamajorroleInsenescenceandlIfe
span.
6
CalorIcrestrIctIonwelldocumentedtoIncreaselIfespanInsmallmammals
probablydoessobydecreasIngtherateofoxIdatIvedamage.
P.878
Functional Decline and the Concept of Frailty
Old age is no place for sissies.
Bette Davis
FunctIonalreserverepresentsthedegreetowhIchorganfunctIoncanIncreaseabovethe
levelnecessaryforbasalactIvIty.ForhealthyIndIvIduals,reservepeaksatapproxImately
ageJ0,graduallydeclInesoverthenextseveraldecades,andthenexperIencesmorerapId
declInebegInnIngaroundtheeIghthdecade.AssessmentofreserveIssomethIng
anesthesIologIstsperformallthetIme.Forexample,theabIlItytoachIevethedesIred
mInImumoffourmetabolIcequIvalentspresumablyprovIdesenoughcardIovascular
reservetotoleratethestressofmostsurgIcalprocedures.
7
EvenwIthoutformal
assessment,anIntuItIvesenseofreserveIsoftenobtaInedthroughsImpleobservatIon.A
personwholooksandactsoldpresumablyhassufferedmorefromtheagIngprocess,
regardlessofchronologIcage.ThelossofsubcutaneoustIssue,unsteadyorslowedgaIt,
decreasedcognItIonormemory,astoopedbodyhabItus,andmInImalmusclemassproduce
theImpressIonoffraIlty.tturnsoutthatsomeofthesetraItsmaywellcorrelatewIth
reserve.SarcopenIaIsaserIousproblemfortheveryoldpatIent,andwhensevereenough,
canleadtoanaccelerateddeterIoratIonwIthfurtherweIghtloss,mentalandphysIcal
declIne,andIncreasedmortalIty.
8
0ImInIshedmentatIonIsarIskfactorforpostoperatIve
delIrIum.
9
DftentImestheanesthesIologIstIstheonlycaregIverprIortosurgerytolookat
thepatIentasawhole.WheneverpossIble,weneedtobeawareofpreoperatIverIsk
factorsandprobableperIoperatIveadverseoutcomesandassIstthesurgIcalteamIn
handlIngIdentIfIedIssues.
Physiologic Age
If you didn't know how old you were, how old would you be?
James Hubert Eubie Blake
AlthoughtheeffectsofagIngareInevItableandeveryonewIllbecomefraIlIftheylIve
longenough,therateatwhIchagIvenIndIvIdualagesIshIghlyvarIable.SomeagerapIdly
andsufferaddItIonaldecrementsfromchronIcdIseasesthatInteractwIththeeffectsof
agIng,whereasothersremaInremarkablyactIveandvIgorouslateInlIfe.Perhapsthe
greatestchallengefacIngthemedIcalprofessIonandsocIetyIngeneralIsnotsImplyto
keeppeoplealIveforalongertIme,buttomaIntaInfunctIonforaslongaspossIble.
SuccessfulagIngshouldbethegoal,andItImplIesthatphysIcalandmentalabIlItIesremaIn
atalevelsuffIcIenttomaIntaInalIfestylethatIsenjoyableandproductIve.tIsthe
antIthesIstotheoldadagethatwehave20yearstolearn,40yearstoearn,andtherestof
thetImetojustsItaroundandwaIt.Unfortunately,howfastweageIstoagreatextent
determInedbyourgenetIcsandluckatavoIdIngIllnesses,trauma,orenvIronmental
exposurethatmaycontrIbutetofunctIonalloss.Nevertheless,successfulagIngcanbe
promotedvIagoodnutrItIon,regularexercIse,andtheavoIdanceofobesIty.
PerhapsthemostImportantpoInttobemadeaboutagIngIsthatItIshIghlyvarIablefrom
oneIndIvIdualtothenext.Theolderweget,thelesslIkelyourchronologIcagereflectsour
physIologIcalstatusandfunctIonalreserve.deally,anIndexofphysIologIcalagewouldbe
avaIlable.DneInterestIngapproachtothIsobjectIvethatIsavaIlabletothelaypublIcIsto
quantIfymanyoftheknownmodIfIableandnonmodIfIablefactorsthatInfluencelIfe
expectancy.
f
8ypluggIngone'sIndIvIdualdataIntotheprogram,ameasureofhowoldyou
arerelatIvetoyourchronologIcageIsprovIded,plustIpsonhowyoucanImproveyour
healthstatusandloweryourage.SuchanapproachmaybeusefulforpromotInga
healthylIfestyle,butdoesnotaddresstheneedforanIndexthatwouldquantIfythe
reserveofeachorgansystem,IncludIngthebraIn,andpredIcttherIskofcommon
perIoperatIvecomplIcatIons.
The Physiology of Organ Aging
0efInIngwhatconstItutesnormalagIngIsproblematIc.0Ifferencesbetweengroupsof
youngandelderlysubjectsmaynotstrIctlyreflectagIng,astheelderlysubjectsmayhave
experIencedamuchdIfferentdIet,lIfestyle,andenvIronmentalexposurethanwhatthe
younggroupwIllexperIencebythetImetheybecomeold.FollowIngagroupofhealthy
subjectsoveralongperIodIsmorelIkelytodefInetheeffectsofagIng,butnotall
avaIlabledatacomefromsuchlongItudInalstudIes.StudIesthatexamIneonlytheveryold
personsmayactuallyunderestImatethetypIcaleffectsofagIngbecauseIndIvIduals
generallydonotachIeveoldageunlessthereIssomethIngIntrInsIcallyrobustaboutthem.
Lastly,thereaderIsremIndedthat,aswIththedIscussIonofphysIologIcalage,theeffects
ofagIngdescrIbedInthIssectIonwIllvarIablyapplytoanygIvenpatIent,andthatdIsease
wIllInteractwIthagIngtofurtherdImInIshfunctIonalorganreserve.
Changes in Body Composition, and Liver and Kidney Aging
ChangesInbodycomposItIonareprImarIlycharacterIzedbyagraduallossofskeletal
muscleandanIncreaseInbodyfat,althoughthelatterIsmorepromInentInwomen(FIg.
J52).
P.879
8asalmetabolIsmdeclIneswIthage,wIthmostofthedeclIneaccountedforbythechange
InbodycomposItIon.
10
ThereIsareductIonIntotalbodywaterthatreflectsthereductIon
IncellularwaterthatIsassocIatedwIthalossofmuscleandanIncreaseInadIpose
tIssue.
11
AgIngcausesasmalldecreaseInplasmaalbumInlevels;IfanythIng,thereIsa
smallIncreaseIn
1
acIdglycoproteIn.
12
TheeffectofthesechangesondrugproteIn
bIndInganddrugdelIvery,however,appeartobemInImal.
Figure 35-2.AgerelatedchangesInbodycomposItIonaregenderspecIfIc.nwomen,
totalbodymassremaInsconstantbecauseIncreasesInbodyfat(upper shaded
segment)offsetboneloss(middle segment)andIntracellulardehydratIon(lower
shaded segment).nmen,bodymassdeclInesdespItemaIntenanceofbodylIpIdand
skeletaltIssueelementsbecauseacceleratInglossofskeletalmuscleandother
componentsofleantIssuemassproducesmarkedcontractIonofIntracellularwater
(lower shaded segment).
LIvermassdecreaseswIthage,andaccountsformost,butnotall,ofthe20to40
decreaseInlIverbloodflow.
1J
ThereIsalsoamodestreductIonInphasedrugmetabolIsm
andbIlesecretIonwIthage.EvenIntheveryoldperson,lIverreserveshouldbemorethan
adequateIntheabsenceofdIsease,otherthanfortheeffectofagIngondrugmetabolIsm.
FenalcortIcalmassalsodecreasesby20to25wIthage,butthemostpromInenteffectof
agIngIsthelossofuptohalfoftheglomerulIbyage80.
14
ThedecreaseIntheglomerular
fIltratIonrateofapproxImately1mL/mIn/yrafterage40typIcallyreducesrenalexcretIon
ofdrugstoalevelwheredrugdosageadjustmentbecomesaprogressIvelyImportant
consIderatIonbegInnIngatapproxImatelyage60.Nevertheless,thedegreeofdeclIneIn
glomerularfIltratIonrateIshIghlyvarIableandIslIkelytobemuchlessthanpredIctedIn
manyIndIvIduals,especIallythosewhoavoIdexcessIvedIetaryproteIn.
15
TheagedkIdneydoesnotelImInateexcesssodIumorretaInsodIumwhennecessaryas
effectIvelyasthatofayoungadult.
15
PartofthefaIluretoconservesodIumwhen
approprIatemaybebecauseofreducedaldosteronesecretIon.SImIlarly,theagedkIdney
doesnotretaInorelImInatefreewaterasrapIdlyasyoungkIdneyswhenchallengedby
waterdeprIvatIonorfreewaterexcess.Lastly,thesensatIonofthIrstdeclIneswIthage.n
short,fluIdandelectrolytehomeostasIsIsmorevulnerableIntheolderpatIent,
partIcularlywhenanolderpatIentsuffersacuteInjuryordIseaseandeatInganddrInkIng
becomesmoreofachore.
Forthemostpart,functIonalendocrInedeclInedoesnotInteractwIthanesthetIc
managementtoanysIgnIfIcantdegree.However,agIngIsassocIatedwIthdecreasedInsulIn
secretIonInresponsetoaglucoseload,andalsoIncreasedInsulInresIstance,partIcularly
Inskeletalmuscle.
16
Thus,evenhealthyelderlypatIentsmayrequIreInsulIntherapymore
oftenperIoperatIvelythanyoungadults.AgIngalsoresultsIndecreasesIntestosterone,
estrogen,andgrowthhormoneproductIon.
17
Theuseofhormonaltherapytoreduce
sarcopenIa,fraIltyIngeneral,andcognItIvedeclIneanddementIaIsthesubjectof
consIderablecurrentInvestIgatIon,buthasnocurrentapplIcatIontoanesthetIc
management.
Central Nervous System Aging
8raInmassbegInstodecreaseslowlybegInnIngatapproxImatelyage50anddeclInesmore
rapIdlylater,suchthatan80yearoldbraInhastypIcallylost10ofItsweIght.
18
NeurotransmItterfunctIonssuffermoresIgnIfIcantly,IncludIngdopamIne,serotonIn,
amInobutyrIcacId,andespecIallytheacetylcholInesystem.
19
ThelatterIsespecIally
ImportantbecauseofItsconnectIontoAlzheImer'sdIsease.FesponsetImesIncrease,and
learnIngIsmoredIffIcult,butvocabulary,wIsdom,andpastknowledgearebetter
preserved.
18
Nevertheless,ofthoseIndIvIdualsage85andolder,nearlyhalfhave
sIgnIfIcantcognItIveImpaIrment.naddItIon,somedegreeofatherosclerosIsappearstobe
InevItable.Fortunately,andcontrarytoprIorbelIef,theagedbraIndoesmakenew
neuronsandIscapableofformIngnewdendrItIcconnectIons.
20
PerhapsthebestknowneffectofbraInagIngasItapplIestoanesthesIaIsthe
approxImately6decreaseIn|AC(mInImumalveolarconcentratIon)perdecadeafterage
40.
21
ThIseffectofagIngIsrelatIvelysImpletodealwIthIntheclInIcalarena.|uchmore
dIffIcultIsthepotentIalInteractIonofanesthesIa,thestressofsurgery,andabraInwIth
mInImalreserve.AgeIsamajorrIskfactorforpostoperatIvedelIrIumand/orcognItIve
declIne(seePerIoperatIveComplIcatIons).TheotherpertInentbraInagIngphenomenon
IspharmacodynamIc(seenextsectIon).
Drug Pharmacology and Aging
TheeffectofadrugInanolderpatIentIsoftenthatofamorepronouncedeffect(see
Chapter7).ThecausecanbeeItherpharmacodynamIc,InwhIchcasethetargetorgan
(oftenthebraIn)IsmoresensItIvetoagIvendrugtIssuelevel,orthecausecanbe
pharmacokInetIc,InwhIchcaseagIvendoseofdrugcommonlyproduceshIgherblood
levelsInolderpatIents.
|ostIntravenousanesthetIcdrugsfollowapredIctablepatternwhenadmInIsteredasa
bolus.fthedrugwasdIstrIbutedonlytotheplasmaonInjectIon,thentheInItIaldrug
concentratIonwouldbedefInedbytheamountofdruggIvendIvIdedbytheplasma
volume.However,evenasthedrugIsmIxIngIntotheplasma,somedrugIsleavIngthe
plasmaandenterIngtIssue.TherateoftransferIntoagIvenpIeceoftIssuedependsonthe
rateofdelIvery(concentratIontImesbloodflowpergramoftIssue),theconcentratIon
gradIentofthedrugbetweenthebloodandthetIssue(obvIouslyahIghgradIentInItIally),
theeasewIthwhIchthedrugcrossesthebloodandtIssuemembranes,andthesolubIlItyof
thedrugInthetIssue.Thus,thevesselrIchgroup(braIn,heart,kIdney,muscle)wIll
acquIredrugmuchmorerapIdlythanthevesselpoorgroup(fat,bone).ProteInbIndIng
mayaffecttherateoftIssuetransfer.0rugsthatarehIghlyproteInboundwIllhavea
lowerfreeconcentratIonandaslowerrateoftransfer.
CIventhIsdIscussIon,therearemanywaysforabolusofdrugtohaveamorepronounced
InItIaleffectonolderpatIents.TypIcally,theInItIalbloodconcentratIonofbolusdrugsIs
hIgherInolderpatIents,partlybecauseofamIldlycontractedbloodvolume.Early
redIstrIbutIonofthedrugfrombloodIntotIssueIsoftenslowerInolderadults,perhaps
partlybecauseofthereductIonInmusclemass.8ydIvertInglessdrugIntomuscleand
therebykeepIngthedrugbloodconcentratIonhIgherforalongertIme,moredrugwIllbe
drIvenIntotheotherorgansofthevesselrIchgroupsuchasthebraIn(oftenthetarget
organ)orheart.AprImeexampleofthIsphenomenonIssodIumpentothal,andtoalesser
degree,propofol.
22
fthedrugIsboundtoalbumIn,theloweralbumInlevelmayIncrease
thefreedrugconcentratIonandfurtherenhancetargetorgandrugdelIvery.
0espItethetypIcallyenhancedeffectofbolusdrugsonolderpatIents,thereIsageneral
ImpressIonthatbolusdrugstakelongertoachIevethatgreatereffect.tIsnotentIrely
clearwhythIsIsso.SlowercIrculatIonIssometImeshypothesIzed,buttotalbloodflowto
anyorgandoesnotappeartodecreasebeyondthatexpectedfromthedecreaseInorgan
mass.AnotherpossIbIlItyIsaslowerrateoftransferIntothetargetorgan.Theeffectofa
drugdependsonItsconcentratIonInthetargetorgan,notthebloodlevel.ttakestIme,
forexample,forbraIndruglevelstoequIlIbratewIthbloodlevels.fadrugdIffusesInto
thebraInmoreslowly,ortakesmoretImetoalterthebraIn'sfunctIononceInthetIssue,
thenthepeakdrugeffectwouldlagevenfurtherbehIndthetImeofpeakblood
concentratIon.TheeaseoftransferIsoftenmodeledasthevarIablek
eo
.8loodtarget
organequIlIbratIonhalflIfeIstherefore0.69J/k
eo
.Proofthatk
eo
decreases(and
equIlIbratIontImeIncreases)wIthageIslImIted,buthasbeendocumentedfor
remIfentanIl.
2J
Whyk
eo
shoulddecreasewIthageIsnotunderstood.
UltImately,though,thedrugwIlldIstrIbutethroughoutthebodybasedontIssuemassand
solubIlIty.8ecausemostIntravenousdrugsusedInanesthesIaarehIghlylIpIdsoluble,most
P.880
ofthedrugwIllendupInfat.HowcompletelythedrugIsdIspersedoutofthebloodand
IntothetIssueIsreflectedby7d
ss
,thedrug'svolumeofdIstrIbutIonatsteadystate.ThIs
varIableIsexpressedasthelItersofplasmathatwouldbenecessarytodIlutetheamount
ofdrugadmInIstereddowntotheconcentratIonobservedIntheplasma.Assuch,drugs
thatareveryfatsolublecanhaveavaluefor7d
ss
thatIsseveraltImesgreaterthantotal
bodywater.0urIngtheprocessofredIstrIbutIon,drugwIlldIffuseoutofvesselrIchgroup
tIssuebackIntotheblood,onlytobesoakedupbyfat.nsodoIng,thetargetorgan(e.g.,
braIn)druglevelwIllfallbecausethetargetorganIsalwaysInthevesselrIchgroup.Dnce
asIngletherapeutIcdoseofadrughasfullydIstrIbutedthroughoutthebody,thebloodand
targetorgandruglevelsaretypIcallytoolowtohaveameanIngfulclInIcaleffect.
However,verylargedoses,repeateddoses,orInfusIonswIlleventuallydelIverenoughdrug
toyIeldresIdualdruglevelsthatproducetherapeutIceffects.AtthIspoInt,theonlywayto
decreasebloodandtargetorganlevelsandelImInatethedrug'seffectsIsthrough
metabolIsm.TheelImInatIonormetabolIchalflIfeofadrugInthebloodequalsthe
volumeofdIstrIbutIonatsteadystate(7d
ss
)dIvIdedbytheclearance,whereclearance
representstheamountofbloodfromwhIchdrugIselImInatedpermInute.
Figure 35-3.TheeffectofageonthevolumeofdIstrIbutIonatsteadystate(7d
ss
)for
pentothalInwomen.(FeprIntedfromJung0,|ayersohn|,PerrIer0etal:ThIopental
dIsposItIonasafunctIonofageInfemalepatIentsundergoIngsurgery.AnesthesIology
1982;56:26J,wIthpermIssIon.)
Unfortunately,themostpromInentpharmacokInetIceffectofagIngIsadecreaseIndrug
metabolIsmfrombothadecreaseInclearanceandanIncreaseIn7d
ss
(FIg.J5J).The
IncreaseIn7d
ss
wIthageIslIkelyduetotheIncreaseInbodyfat.ClearancedecreaseswIth
ageforanydrugmetabolIzedbythelIverorkIdney.WhendrugmetabolIsmIsvIathelIver,
decreasedlIvermassandbloodflowwIlldecreaseclearanceforbothhIghandlow
extractIondrugs.naddItIon,elderlypatIentsareoftenonahostofchronIcmedIcatIons,a
setupfordrugInteractIonsaswellasforInhIbItIonofdrugmetabolIsm.0rugswIth
prImarIlyrenalelImInatIonwIllexperIencedecreasedmetabolIsmbecauseofreductIonsIn
glomerularfIltratIonratewIthagIng.TheneteffectondrugmetabolIsmIstypIcallya
doublIngoftheelImInatIonhalflIfebetweenoldandyoungadults.However,wIthsome
drugs,theeffectonhalflIfecanbedramatIc.nthecaseofdIazepam,thehalflIfeIn
hoursIsroughlyequaltothepatIent'sage(FIg.J54).
24
Fora72yearoldperson,Itwould
thereforerequIreJdaystometabolIzehalfofadoseofdIazepam.SuchpharmacokInetIcs
clearlyIllustratewhythereIsnoplaceInmodernmedIcIneforthechronIcuseofdIazepam
andotherdrugswIthsImIlarhalflIveswhenthedesIredeffectIssupposedtobetransIent
(e.g.,asasleepIngaId).
Figure 35-4.TheeffectofageontheelImInatIonhalflIfeofdIazepam.ThehalflIfe
InhoursIsequaltoapproxImatelythepatIent'sageInyears.(FeprIntedfromKlotzU,
AvantCF,HoyumpaAetal:TheeffectsofageandlIverdIseaseonthedIsposItIonand
elImInatIonofdIazepamInadultmen.JClInnvest1975;55:J47,wIthpermIssIon.)
WhendealIngwIthInfusIonsorforthatmatteraserIesofbolusInjectIonsthetImeIt
takestodecreasethebloodandtargetorgandruglevelstobelowthetherapeutIc
thresholdwIlldependonmanyfactors.ThIsIswheretheconceptofthecontextsensItIve
halftImeprovesuseful;thatIs,thetImenecessaryfora50(oranydesIredpercent)
decreaseInplasmaconcentratIonfollowIngtermInatIonofanInfusIon.Atoneextreme,If
theresIduallevelproducedbythecumulatIvedrugadmInIstratIonIsstIllverylow,and
onlyamodestdecreaseInbloodlevelIsnecessarytoreversethedrugeffect,thentheto
rapIdredIstrIbutIonofthemostrecentlyadmInIstereddrugwIllleadtoarapIddecreaseIn
thebloodlevelandtermInatIonofeffect.Attheotherextreme,Iftherehasbeen
sIgnIfIcantaccumulatIonofdrugInthebody,and/orthemaIntenancebloodlevelwashIgh,
thenalongtImemayberequIredtodecreasethedruglevelsenoughtotermInatethedrug
effect.Asageneralrule,thetImetodecreasetheeffectsItedrugconcentratIonIs
IncreasedmostdramatIcallybyagIngwhenalargepercentagedecreaseInplasmalevelIs
necessarytodIpbelowthetherapeutIcthreshold.
25
FevIewofthelIteraturecanyIeldaconfusIngpIcturewhentryIngtosortoutwhat
pharmacologIcvarIableIsresponsIbleforagIvenclInIcaleffect.Fortunately,onedoesnot
needtoknowsuchdetaIlsInordertouseanesthetIcdrugsInanIntellIgentfashIonwIth
olderpatIents.TableJ51summarIzessomeofthIsInformatIonformanyofthecommon
anesthetIcdrugs.
25,26,27,28
TheeffectofagIngonsedatIvehypnotIcagentsvarIably
InvolvesbothpharmacodynamIcandpharmacokInetIcchanges(TableJ51).Forthe
opIoIds,theolderbraInappearstobemoresensItIvethanthatofyoungadults,whereas
thepharmacokInetIcsofopIoIdsarelargelyunaffectedbyage.
0espItethelossofmuscleandmotorneuronswIthage,musclerelaxantsdonotappearto
bemorepotentIntheolderpatIentwhensteadystatebloodlevelsforagIvenlevelof
paralysIsarecompared.|usclerelaxantsoftenhaveadecreasedInItIalvolumeof
dIstrIbutIon,butthIspharmacokInetIcchangedoesnotseemtotranslateIntosmaller
doses.FordrugselImInatedbythelIverorkIdney,andwheretheeffectofabolusIs
elImInatedprImarIlybyredIstrIbutIon,multIpledoseswIllresultIndrugaccumulatIon,and
eachsubsequentdosewIllhaveamoreprolongedeffect.ThIsphenomenonwIllbe
exaggeratedInelderlypatIentsbecauseofdecreasedmetabolIcelImInatIon,andwIllbe
mostpromInentwIththelongactIng
P.881
P.882
agents.CIventherIskofresIdualneuromuscularblockadewIthlongactIngdrugssuchas
pancuronIum,coupledwIththemuscleandnervoussystemchangesofagIngthatIncrease
therIskofventIlatoryfaIlureoraspIratIonpostoperatIvely,Itcanbearguedthatlong
actIngneuromuscularblockIngagentsshouldbeusedverycarefullyInanolderpatIent,If
atall.
Table 35-1 Effect of Age on Drug Dosing
DRUG
BOLUS
ADMINISTRATION
MULTIPLE BOLUSES OR
INFUSION
COMMENTS
a
Propofol
2060
reductIon,dose
onleanbody
mass,1mg/kg
Inveryold
50reductIon,
InfusIonsbeyond50
mInprogressIvely
IncreasethetIme
requIredtodecrease
thebloodlevelby
50(buteffectsIte
levelsmaydecrease
fasterInelderly)20
reductIon
braInsensItIvIty
(bysomereports),
decreased7
cen
,
slowed
redIstrIbutIon
ThIopental 20reductIon 20reductIon
=braIn
sensItIvIty,
decreased7
cen
,
slowed
redIstrIbutIon
EtomIdate 2550reductIon =braInsensItIvIty
|Idazolam
Comparedto
age20,modest
reductIonatage
60,75
reductIonatage
90
SImIlartobolus
(metabolIct
1/2
longer,butnot
meanIngfulunless
verylargedosesare
braIn
sensItIvIty
used)
|orphIne
Probably50
reductIon.Peak
morphIneeffect
Is90mIn
(thoughhalfof
peakeffectat5
mIn)
LongeffectsIte
equIlIbratIontIme
translatesIntovery
slowreductIonIn
effecton
termInatIonof
InfusIon(4hrfor50
reductIon)
|etabolIte
morphIne6
glucoronIdebuIld
uprequIres
prolonged
morphIneuse,but
ItsrenalexcretIon
wIllmakeItvery
longactIng
Fentanyl 50reductIon 50reductIon
braIn
sensItIvIty,
mInImalchanges
In
pharmacokInetIcs;
delayed
absorptIonfrom
fentanylpatch
AlfentanIl,
sufentanIl
50reductIon 50reductIon
ProbablybraIn
sensItIvIty,
mInImalchanges
In
pharmacokInetIcs
FemIfentanIl 50reductIon 50reductIon
Slowerblood
braIn
equIlIbratIon,
suggestIngslower
onsetandoffset,
modestdecreased
7
cen
Hydromorphone
NostudIeson
agIngexIst,but
assume
Increased
potencyIn
elderly
Assume50
reductIon
ComparedwIth
morphIne,no
actIve
metabolIte,faster
onset
|ethadone
NostudIeson
agIngexIst,but
assume
Increased
potencyIn
elderly
Assume50
reductIon
|eperIdIne
Useonlyfor
postoperatIve
shIverIng
0onotuse
ToxIcmetabolIte
normeperIdIne,
whoserenal
excretIon
decreaseswIth
age
7ecuronIum
Sloweronset
(JJ)
Slowerrecovery
tImes
SlIghtlygreater
lIvermetabolIsm
thanrenal,age
nearlydoubles
metabolIct
1/2
|IvacurIum
Equallyfast
onsetInyoung
andold
|odestdose
reductIonfor
InfusIon,longer
recoverytImeon
repeatedboluson
repeatedboluson
repeatedboluson
repeatedbolus
ElImInatIonby
plasma
cholInesterase,
modest
prolongatIonof
metabolIct
1/2
by
age
CIsatracurIum
Sloweronset
(JJ)
NosIgnIfIcant
changeswIthage
|ostlyHoffmann
elImInatIon,
modest
prolongatIonof
metabolIct
1/2
by
age
FocuronIum
|InImally
sloweronset
LIvermetabolIsm
slIghtlygreater
thanrenal,
modestIncrease
InmetabolIct
1/2
byage
PancuronIum
PrImarIlyrenal
elImInatIon,agIng
doublesmetabolIc
t
1/2
PIpecuronIum
Sloweronset
(50),elderly
maybeless
sensItIve
PrImarIlyrenal
elImInatIon,no
apparentchange
InmetabolIct
1/2
SuccInylcholIne
Sloweronset
(40)

EdrophonIum
SImIlardosIng
andonset
7
cen
,prImarIly
renalelImInatIon,
modestIncrease
InmetabolIct
1/2
byage
NeostIgmIne
0espIte
pharmacokInetIc
changes,some
studIesIndIcate
needfor
Increaseddose
wIthage
7
cen
,hepatIc
elImInatIon,
modestIncrease
InmetabolIct
1/2
byage
a
7
cen
,centralvolumeofdIstrIbutIonorInItIalvolumeofdIstrIbutIon.Although7
cen
doesnothaveananatomIccorrelate,asmaller7
cen
wIllIncreaseInItIalplasma
levelsandenhancetransferofthedrugInthetargetorgan(e.g.,braIn,muscle).
Cardiovascular Aging
A man is as old as his arteries.
Thomas Sydenham
7IrtuallyallcomponentsofthecardIovascularsystemareaffectedbytheagIngprocess.
ThemajorchangesInclude(1)decreasedresponsetoreceptorstImulatIon;(2)stIffenIng
ofthemyocardIum,arterIes,andveIns;(J)changesIntheautonomIcnervoussystemwIth
IncreasedsympathetIcactIvItyanddecreasedparasympathetIcactIvIty;(4)conductIon
systemchanges;and(5)defectIveIschemIcprecondItIonIng(seeChapter10).Although
atherosclerosIsappearstoaffecteveryonebyvIrtueofthefactthatthemechanIsmsof
agIngcontrIbutetothedevelopmentofatherosclerosIs,ItIsnotclearthatItInevItably
leadstofunctIonalImpaIrmentordIsease.
AutonomIcImbalanceanddysfunctIondevelopswIthage
29
(seeChapter15).SympathetIc
nervoussystemactIvItyIncreasesandvagaloutflowdecreases.TheIncreasedsympathetIc
actIvItyIspresentatrestandthereIsoftenanexaggeratedresponsetostImulIthat
IncreasesympathetIcactIvIty.AlthoughthereIssomeevIdenceofdecreased
responsIvenessofreceptorswIthage,ItapparentlyIsnotenoughtopreventexcessIve
changesInvascularresIstancefrommakIngasIgnIfIcantcontrIbutIontothelabIlItyIn
bloodpressureobserveddurInganesthesIaorcontrIbutetothedecreaseInbloodpressure
whenanesthesIaremovesthatsympathetIctone.
J0
ThedecreaseInvagaltonemaylImIt
theIncreaseInheartrateafteradmInIstratIonofatropIneorglycopyrrolate.
AgIngleadstoadecreaseIntheresponsetoreceptorstImulatIon.
J1
ThemechanIsmdoes
notappeartobeadownregulatIonofreceptorsontheheart,butadefectInthe
IntracellularcouplIng.HeartrateIncreaseslessInresponsetoendogenousreleaseor
exogenousadmInIstratIonofcatecholamInes.TheheartrateIncreasetoexercIseIs
thereforeaffected,asIsmaxImalheartrate(oftenquotedas220age),andthedecrement
contrIbutestothedecreasedexertIonalcapacItywIthage,evenIntraInedIndIvIduals.
8aroreflexcontrolofheartrateIsdecreasedandcontrIbutestoImpaIredregulatIonof
bloodpressure.
J2
ChronIchypertensIonfurtherdecreasesthebaroreflexcontrolofheart
rateatanyage.
Conductanceartery(aortatoarterIoles)stIffenIngtypIcallyleadstosystolIchypertensIon
vIatwomechanIsms.
JJ
FIrst,muchofthestrokevolumeIsstoredInthethoracIcaorta
durIngejectIon.PressuremustIncreasemoretostretchoutthestIffenedaortato
accommodatethatvolume.Secondly,allarterIalstIffenIngcausesthepressurewaveto
transmItmorerapIdlyInthearterIes.neveryone,thewavereflectsoffthearterIalwalls
andbranchpoInts,andthereflectedwavestravelbacktotheheartmorequIcklyInan
olderperson.nyoungpeople,thereflectedwavesdonotreachtheheartuntIlafter
ejectIonIscomplete.ThesewavesareresponsIbleforthemodestbumpInpressureInthe
aortIcrootjustafterthedIcrotIcnotch.8utInolderpeople,thereflectedwavesreturnto
theheartInlateejectIonandIncreasethepressureagaInstwhIchtheleftventrIclemust
pumptocompletethestrokevolume.NormallyattheendofejectIontheventrIcular
contractIonIsweakenIng,soIdeallytheventrIclewouldlIketopushagaInstanever
decreasIngpressure.WhentheventrIclemustnowpumpagaInstahIgherpressure,thIs
IncreasedstresstothemusclestImulateshypertrophy.
Figure 35-5.YoungandelderlyadultsaresubjectedtoapassIvetIlttestIntheIr
euvolemIcstateandafteranapproxImate2kgofwaterand100mEqofsodIumloss.
WIthtIlt,bloodpoolsInthelegs.AlthoughyoungsubjectstoleratetIltunderboth
cIrcumstances,thecombInatIonofhypovolemIaandtIltexceedsthecompensatory
mechanIsmsoftheoldersubjects.(FeprIntedfromShannonFP,WeIJY,FosaF|etal:
TheeffectofageandsodIumdepletIononcardIovascularresponsetoorthostasIs.
HypertensIon1986;8:4J8,wIthpermIssIon.)
HypertrophyInandofItselfstIffenstheventrIcle,butevenworse,hypertrophyslows
dIastolIcrelaxatIonthat,Inturn,ImpaIrsventrIcularfIllIngInearlydIastole.Theleft
ventrIcleIsnowmoredependentontheatrIalkIckandleftatrIalpressurethatcontrollate
dIastolIcfIllIng.TheIncreaseInatrIalpressureIspresentatrest,butcanbequItedynamIc
wIthacuteIncreasesdurIngstresssuchastachycardIa.ThIsphenomenon,termeddiastolic
dysfunction,IncreasesInseverItywIthage.ThemajorItyofcasesofcongestIveheart
faIlureInveryoldpersonsareduetodIastolIcdysfunctIonandoccurIntheabsenceof
clInIcallysIgnIfIcantsystolIcdysfunctIon.
J1,J4
7entrIcularfIllIngbecomesmorecrItIcalwIthage.Thedecreasedresponsetoreceptor
stImulatIonrequIrestheventrIclestodependmoreonadequateenddIastolIcvolumeto
generateenoughcontractIlestrengthvIathelengthtensIon(FrankStarlIng)relatIonshIp.
ThedIastolIcdysfunctIonrequIresanIncreaseIncentralbloodvolumeandatrIalpressure
tomaIntaInthatenddIastolIcvolume.Therefore,maIntenanceofanadequatecentral
bloodvolumetomyocardIalperformancebecomesmorecrItIcalwIthage.
Unfortunately,theveInsstIffenwIthage.
J5
neveryone,theveInsserveasareservoIrfor
bloodandservetobufferchangesInbloodvolumeInordertomaIntaIncentralblood
volumeandventrIcularfIllIngatanapproprIatelevel.7enousstIffenIngImpaIrsthIs
bufferIngcapacItyandcreatesasItuatIonInwhIchmodestchangesInvenousbloodvolume
mayproducemoredramatIcchangesInvenousandcardIacfIllIng.nshort,thesystemhas
becomeInherentlymoreunstableasIllustratedbythedevelopmentofpostural
hypotensIonInelderlypersonsbutnotInyoungadultswIthmIldhypovolemIa(FIg.J55).
J6
FhythmdIsturbancesmaydevelopwIthage.FIbrosIsoftheconductIonsystemmayleadto
conductIonblocks,andlossofsInoatrIalnodecellsmaymaketheolderpatIentmoreprone
tosIcksInussyndrome.TheprevalenceofatrIalfIbrIllatIonexponentIallyclImbswIthage,
perhapspartlybecauseofatrIalenlargementwIthage.
P.88J
Lastly,agIngappearstodImInIshorevenelImInateanyprotectIveeffectofIschemIc
precondItIonIng,aphenomenonwherebyabrIefperIodofmyocardIalIschemIawIlllessen
theadverseeffectsofasubsequent,moreprolongedIschemIcevent.WarmupangInaIs
theabIlItytoachIeveahIgherlevelofexertIonafterfIrstexercIsIngtothepoIntofangIna.
StartIngaroundage65theIncrementInthelevelofexertIonprogressIvelydImInIsheswIth
age.nyoungeradults,deathorheartfaIlureIsalessfrequentcomplIcatIonofa
myocardIalInfarctIonIfthepatIenthadbeenexperIencIngangInawIthIn2weeksofthe
myocardIalInfarctIon.ThIsprotectIveeffectofangInaIsnotpresentInolderadults.
J1
Pulmonary Aging
ThemostpromInenteffectsofagIngonthepulmonarysystemarestIffenIngofthechest
wallandadecreaseInelastIcItyofthelungparenchyma
J7,J8
(seeChapter11).Chestwall
stIffenIngIncreasestheworkofbreathIngandItalsoproducesamorebarrelshapedthorax
thatleadstoflattenIngofthedIaphragm.LessdIaphragmatIccurvatureprovIdesa
mechanIcaldIsadvantageforthegeneratIonofnegatIvepressureIntheIntrapleuralspace.
ThestIffenedchestwall,flatteneddIaphragm,andthelossofmusclemassfromagIngall
combInetomaketheolderpatIentmorepronetofatIguewhenchallengedbyanIncrease
InmInuteventIlatIon,andthusmorelIkelytoexperIencerespIratoryfaIlure.
AlthoughthedecreaseInlungtIssueelastIcItymakesthelungseasIertoInflate,thereare
severaladverseeffectsofthIsIncreaseIncomplIance.SmallaIrwaysdonothaveenough
InherentstIffnessanddependontetherIngbythesurroundIngtIssuetoremaInopen.The
degreeofoutwardpullbythetIssuedependsonthestIffnessofthetIssueandthedegree
ofstretchofthetIssue.AsthetIssuelosesItssprIngIness,greaterlungInflatIonIsneeded
toproducethesameamountofoutwardpullontheaIrways.Theneedforgreaterlung
InflatIontopreventsmallaIrwaycollapseIsreflectedbytheIncreaseInclosIngcapacIty
wIthage(FIg.J56).ClosIngcapacItytypIcallyexceedsfunctIonalresIdualcapacItyInthe
mId60s,andwIlleventuallyexceedthetIdalvolumeatsomelaterage.Thesechanges,
plusamodestreductIonInalveolarsurfaceareawIthage,contrIbutetoamodestdeclIne
InrestIngPao
2
.
J9
LesseffectIvesmallaIrwaytetherIngalsoleadstogreaterlImItatIonsdurIngforced
exhalatIonsuchasIspresentdurIngexercIse.Atallages,forcedexhalatIonproduces
posItIvepressuresIntheIntrapleuralspacethattendtocompressIntrathoracIcaIrways.
DnlytheaIrwayconnectIvetIssueandlungtIssuetetherIngopposethatcompressIon.WIth
lesslungtIssuetetherIng,aIrwayscompressatalargerlungvolumeInoldersubjectsand
producealImItatIonInaIrflowdurIngexhalatIonoveramuchlargerpercentageofthe
exhaledtIdalvolume(e.g.,thelast45Ina70yearoldperson)thanInayoungersubject
(e.g.,20InaJ0yearoldperson).
40
ChangeswIthInthenervoussystemfurtherInfluencetherespIratorysystem.AgIngleadsto
anapproxImate50decreaseIntheventIlatoryresponsetohypercapnIa,andaneven
greaterdecreaseIntheresponsetohypoxIa,especIallyatnIght.
41
CeneralIzedlossof
muscletonewIthageapplIestothehypopharyngealandgenIoglossalmusclesand
predIsposeselderlypersonstoupperaIrwayobstructIon.AhIghpercentage,perhapseven
75,ofpeopleoverage65havesleepdIsorderedbreathIng,aphenomenonthatmayor
maynotbethesameassleepapnea,butcertaInlyplacestheelderlypeopleatIncreased
rIskofhypoxIapostoperatIvely.
42
AgIngalsoresultsInlesseffectIvecoughIngandImpaIred
swallowIng.AspIratIonIsasIgnIfIcantcauseofcommunItyacquIredpneumonIaandmay
wellplayaroleInthedevelopmentofpostoperatIvepneumonIa.
4J
Figure 35-6.EffectofagIngonlungvolumes.WIthage,InspIratorycapacIty(C)Is
compromIsedbecauseofthecombInedeffectofmodestdecreasesIntotallung
capacIty(TLC)andmodestIncreaseInfunctIonalresIdualcapacIty(FFC).7Ital
capacIty(7C)decreasesbecauseofthedecreaseInCandtheIncreaseInresIdual
volume.However,themostdramatIcchangewIthagIngIstheIncreaseInclosIng
volume(C7)andclosIngcapacIty(CC)suchthatInveryoldpersons,closIngcapacIty
exceedsfunctIonalresIdualcapacIty.(FeprIntedfromSmIthTC:FespIratorysystem:
AgIng,adversIty,andanesthesIa,CerIatrIcAnesthesIology,1stedItIon.EdItedby
|cLeskeyCH.8altImore,WIllIamsEWIlkIns,1997,p85,wIthpermIssIon.)
Thermoregulation and Aging
nthepastdecadeorsotherehasbeenheIghtenedawarenessoftheadverseconsequences
ofperIoperatIvehypothermIaaswellasImprovedmethodstopreventhypothermIa.Even
outsIdetheoperatIngroom,elderlyIndIvIdualsarepronetohypothermIawhenstressedby
modestlycoldenvIronmentsthatwouldnotaffectyoungerIndIvIduals.TheInItIalresponse
toacoldenvIronmentIsvasoconstrIctIon,andIfthatresponseIsInsuffIcIentandthe
subjectbecomescolder,thenshIverIngIsthesecondresponse.8othmechanIsmsare
trIggeredbydecreasesIncoreand/orskIntemperature.ThetwotemperaturesInteract
suchthatadecreaseInskIntemperatureof1degreewIllInItIatevasoconstrIctIonor
shIverIngatacoretemperatureapproxImately0.2degreeshIgherthanwouldhave
otherwIseoccurred.
44
AgInghasavarIableeffectonvasoconstrIctIonandshIverIng,wIth
someelderlyIndIvIdualsdemonstratIngresponsesIdentIcaltoyoungIndIvIdualsandother
elderlyIndIvIdualsdemonstratInganearabsentresponse.Dverall,however,
vasoconstrIctIonandmetabolIcheatproductIonaredImInIshedInmagnItudeInthe
communItydwellIngelderlypopulatIon.
45
Atallages,bothInhalatIonalandsomeIntravenousagents(e.g.,propofolandalfentanIl
butnotmIdazolam)altertheregulatorythresholdssuchthatbodytemperaturemustfall
byasmuchas4`C(7`F)beforeInItIatIonofvasoconstrIctIonorshIverIng.AgIngfurther
ImpaIrsthethresholds,byapproxImately1`C(2`F),notonlydurInggeneralanesthesIabut
durIngspInalanesthesIaaswell.
44
TheIncreasedrIskofIntraoperatIvehypothermIaInanelderlypatIentbylesseffectIve
vasoconstrIctIonIscompoundedbythedecreasedbasalmetabolIsm(heatproductIon)In
elderlyIndIvIduals.tIsthereforenotsurprIsIngthat
P.884
hypothermIahasbeenobservedmorefrequentlyInolderpatIentsthantheIryounger
counterparts.
46
TherIsksofhypothermIaIncludemyocardIalIschemIa,surgIcalwound
InfectIon,coagulopathywIthIncreasedbloodloss,andImpaIreddrugmetabolIsm.
44
ShIverIngplacesasIgnIfIcantmetabolIcstressonapatIentandmaynotbewelltolerated
byapatIentwIthborderlInecardIacorpulmonaryreserve.However,shIverIngInelderly
adultsIsnotassevereasInyoungadults,anddoesnotappeartoplacetheelderlyadults
atgreaterrIskofatleastmyocardIalIschemIa.ThepreventIonandtreatmentof
hypothermIaInanelderlypatIentdoesnotappeartobeanydIfferentthanforyounger
adults.
Conduct of Anesthesia
The Preoperative Visit
twouldbeIdealIfasImplechecklIstcouldbeofferedonhowtoadmInIsteranesthesIato
anolderpatIent.Unfortunately,thevarIabIlItyInresponsefromonepatIenttoanotherIs
moreextremeInelderlythanInyoungadults.Therefore,whenmanagIngtheolderpatIent,
theartofanesthesIaIsanessentIalcomponentofgoodcare.
ThepreoperatIvevIsItcanbeextremelyImportantInthecareoftheelderlypatIent.The
vIsItshouldbegInwIthadetaIledunderstandIngofthepatIent'smedIcalhIstory,current
functIonalstatusofallvItalorgans,andmedIcatIonlIst(seeChapter2J).PreoperatIve
evaluatIonInvolvesasearchforfactorsthatareassocIatedwIthadverseoutcomes,
obtaInIngapproprIatepreoperatIvetests,andpreparIngthepatIentasmuchaspossIbleIn
afashIontoreducethelIkelIhoodofadverseoutcomes.StudIesthathaveexamInedonly
olderpatIentshavefoundpreoperatIverIskfactorsthataresImIlartoresultsfromstudIes
thatexamInedthegeneralpopulatIon;forexample,emergencysurgery,AmerIcanSocIety
ofAnesthesIologIstsclassIfIcatIonofJorhIgher,lowfunctIonalstatus,orclInIcalevIdence
ofcurrentcongestIveheartfaIlure.
47
WIthrespecttobasIclaboratorytestIng,thereIs
growIngevIdencethatforthegeneralpopulatIonsuchtestshavelIttleprognostIcvalue
andshouldbeorderedbasedontheantIcIpatedsurgeryoronmedIcalIssuesIdentIfIedat
thepreoperatIvevIsIt.ThatbasIclaboratorytestIngIsalsonotwarrantedforolderpersons
hasstrongsupportfromseveralstudIes,andIthasbeenarguedthatthesubsequent
InvestIgatIonofIncIdentalabnormaltestresultsmayleadtomoreharmthangood.
48
TherearesomeaddItIonalIssuesmoreprevalentamongtheelderlypopulatIonthatshould
beraIsed.Forexample,IsthepatIent'slIvIngsItuatIoncapableofprovIdIngthesupport
necessaryforasuccessfulrecovery:AnagedspousemaynotbephysIcallycapableof
helpIngthepatIentIfthesurgerytemporarIlypreventsthepatIentfromselfmanagement
ofsomeofthebasIcactIvItIesofdaIlylIvIngsuchasdressIngandbathIng.Furthermore,
elderlypatIentsmayrequIrealongtImetoreturntotheIrpreoperatIveleveloffunctIon.
Forexample,aftermajorabdomInalsurgery,mostpatIentswIllneedatleastJmonthsfor
actIvItIesofdaIlylIvIng(A0Ls)andIndependentA0LstoreturntobaselIne.
49
PersIstent
dIsabIlItyat6monthswIllbepresentatanIncIdencethatdependsonthetask,wIthonlya
9IncIdenceofpersIstentA0LdefIcIts,a19IncIdenceofdefIcItInIndependentA0Ls,and
a52IncIdenceofdImInIshedgrIpstrength.
DlderpatIentsoftenrecognIzethattheendoftheIrlIvesIsnolongerthetheoretIcal
consIderatIonofyouth,sotheyaremorelIkelytohavelIvIngwIlls,healthcareproxIes,
andhealthcaredIrectIvesInplaceatthetImeofsurgery.TheolderpatIent'sexpectatIons
fromsurgerymaybemuchdIfferentthanthatoftheIryoungercounterparts,andthe
anesthesIologIstmustbecarefulnottojudgeapatIent'sdecIsIonmakIngonthebasIsof
moretypIcalgoals.ThIsIspartIcularlyImportantwhenquestIonsofcompetencearIseand
thephysIcIancanbetemptedtoquestIoncompetencewhenthepatIent'sdecIsIondoesnot
coIncIdewIththatofthephysIcIan.
50
AdIscussIonofrIsksandbenefItsneedstoIncludethe
probabledegreeoffunctIonalrecoveryandthespeedwIthwhIchthatrecoveryIslIkelyto
occur.fhealthcaredIrectIvesprohIbItvarIouslIfesustaInIngorresuscItatIveprocedures,
thepatIent/proxyandanesthesIologIstmustcometoamutualunderstandIngofwhatwIll
orwIllnotbeperformedIfanuntowardeventoccurs.
AlthoughbeyondthescopeofasInglechapterongerIatrIcpatIents,thereareseveralother
IssuesthatthepractItIonershouldbealerttodurIngthepreoperatIvevIsIt.Polypharmacy
anddrugInteractIonIsahugeproblemforolderpatIents.nfact,oneofthemajorgoalsof
gerIatrIcconsultservIcestosurgIcalpatIentsIstoparedownthosemedIcatIonswhenever
possIble.TheanesthesIologIstcanhelpbyalertIngtheprImarycareteamtothIsIssueand
suggestaconsult.0ehydratIon,elderabuse,andmalnutrItIonareallmorecommonInthe
veryoldpopulatIonthanIsgenerallyapprecIated.nthecaseofmalnutrItIon,thedefIcIt
maybelImItedtoIsolateddefIcIencIessuchasvItamIn0or8
12
,orItmaybemoreglobal
andIncludeInadequatecalorIcIntakefrompoororalhygIeneortheanorexIaofagIng,In
whIchneuroendocrInechangesleadtoearlysatIetyanddImInIshedsenseoftaste.
51
NutrItIonalstatusIsunderapprecIatedasarIskfactorforsurgery.nfact,the7eterans
AffaIrsNatIonalSurgIcalQualItymprovementProgramfoundalbumIntobeassensItIvean
IndexformortalItyormorbIdItyasanyothersIngleIndIcator,IncludIngtheAmerIcan
SocIetyofAnesthesIologIstsstatus.
52
Intraoperative Management
TherearenomagIcbulletsfortheInductIonofgeneralanesthesIaInolderpatIents.The
effectsoftheInItIaldoseonasInglepatIentarehIghlyvarIable,soadmIttedlythereIsa
certaInamountofguesswork.Clearly,smallerdosesareneededIncomparIsonwIthyoung
adults,andtheeffIcacyofusInglessdrugbecomesmoreapparentIfmoretImeIsallowed
forthedrugtogetclosertoItspeaktargetorgan(braIn)effect.AgIvenbloodlevelof
propofolcausesagreaterdecreaseInbraInactIvItyInanolderpatIent,butthedecreaseIn
bloodpressureIsevenmoredramatIcIncomparIsontothedecreaseobservedInyoung
adults.
5J
|anystrategIescanbeusedtomInImIzethedecreaseInbloodpressure,butmost
attempttoreducetheamountofpropofolwIththeuseofadjunctssuchasopIoIds,or
combInIngsmalldosesofpropofolwIthetomIdate.SomeadvocateInductIonwItha
propofolInfusIonof400g/kg/mIntolessentherIskofoverdose.
27
EtomIdatehasbeen
observedtoproducelesshypotensIonthanpropofolInolderpatIents.
54
Nevertheless,most
anystandardtechnIqueIssafeIfperformedcarefully.HypoorhypertensIon,orboth,may
occurdurIngInductIon,IntubatIon,andthepostIntubatIon,preIncIsIonperIod.CyclIngthe
bloodpressurecuffeverymInuteshouldalertthepractItIonertothesechangessoonerthan
wouldlessfrequentcyclIng.AlthoughswIngsInbloodpressuremaynotbedesIrable,there
IsnoevIdencethatevenmajor,butbrIef,changesInbloodpressureleadtoadverse
outcomes.
WhethergeneralorneuraxIalanesthesIaIsused,InductIonandmaIntenanceofanesthesIa
wIllcommonlyresultInasIgnIfIcantdecreaseInsystemIcbloodpressure,moresothan
typIcallyoccursInyoungerpatIents.
55
AlthoughdecreasesInbothsystemIcvascular
resIstanceandcardIacoutputlIkelyoccur,thedecreaseInvascularresIstanceIsprobably
thelargestcontrIbutor,althoughthIsobservatIonhasreallybeenconfIrmedonlydurIng
spInalanesthesIa.
J0
FIgureJ57demonstratesthIslargedecreaseInvascularresIstanceand
furthershowsthatvenouspoolIngIsresponsIbleforadecreaseInpreloadthatInturn
decreasescardIacoutput.However,theafterloadreductIonfromthedecreaseInblood
pressurepresumablyallowedthe
P.885
ejectIonfractIontoIncrease,therebyamelIoratIngtheeffectthedecreaseInenddIastolIc
volumehadonstrokevolume.8ecausevascularresIstancecontrIbutessIgnIfIcantlytothe
decreaseInbloodpressuredurInganesthesIa,IthasbeenarguedthattheuseofagonIsts
IsanapproprIatetherapyandmaybemoreeffectIvethanvolumealone.
J1
AgonIstsalso
tendtopromotevenoconstrIctIon,therebyshIftIngbloodbacktothecentralcIrculatIon
andreducIngthedecreaseInventrIcularpreloadbyvenouspoolIng,andpresumably
reducIngtheneedforatleastsomevolumeadmInIstratIon.Althoughnoonewould
advocatevasoconstrIctIonasatreatmentforhypovolemIa(exceptasastopgapmeasure),
theventrIclecanonlygetsobIg;therefore,ItIsImpossIbleforvolumeadmInIstratIon
alonetoraIsecardIacoutputenoughtocompensateforalargedecreaseInvascular
resIstance.Furthermore,whensympathetIcnervoussystemactIvItyreturns
postoperatIvely,bloodwIllshIftfromtheperIpherytothecentralcIrculatIon.Excess
perIpheralvolumenowbecomesexcesscentralvolumeandcouldpushanelderlyheart
IntodIastolIcheartfaIlure.nshort,volumeadmInIstratIontoanolderpatIentmaybe
problematIc,wIthaveryfInelInebetweentoomuchandtoolIttle,andwhatwasjust
rIghtatonepoIntmaybecometoomuchlateron.
Figure 35-7.TheresponsetototalsympathectomyfromspInalanesthesIaIsIllustrated
InoldermenwIthcardIacdIsease.Dver70ofthedecreaseInmeanarterIalblood
pressure(|AP)wasduetoadecreaseInsystemIcvascularresIstance(S7F).CardIac
fIllIngwasmarkedlydImInIshed,butItseffectonstrokevolume(S7)andcardIac
output(CD)wasamelIoratedbyanIncreaseInejectIonfractIon(EF).Althoughheart
rate(HF)IncreasedInsomesubjectsanddecreasedInothers,theoveralleffectwasno
change.E07,enddIastolIcvolume.(FeprIntedfromFookeCA,FreundPF,Jacobson
AF:HemodynamIcresponseandchangeInorganbloodvolumedurIngspInalanesthesIa
InelderlymenwIthcardIacdIsease.AnesthAnalg1997;85:99,wIthpermIssIon.)
ThechoIcebetweenanendotrachealtubeversusalaryngealmaskaIrwayInvolvesmany
consIderatIons,IncludIngbodyhabItus,apparentfraIlty,surgIcalposItIonIng,andduratIon
ofsurgery(seeChapter29).AnendotrachealtubewIlllIkelyhavemoreadverseeffectson
mucocIlIaryclearanceandpossIblyonswallowIngthanalaryngealmask,butan
endotrachealtubewIllguaranteetheabIlItytoprovIdeeItheralargetIdalvolumeor
posItIveendexpIratorypressure,thetwomaneuversmostlIkelytopreventIntraoperatIve
atelectasIs.
Postoperative Care
ThegoalsofemergenceandtheImmedIatepostoperatIveperIodarenodIfferentforan
elderlythanforayoungpatIent,theyarejustmoredIffIculttoachIeve.AnalgesIaIsa
majorgoal,andItshouldbestatedupfrontthatthereIsnoevIdencethatpaInIsanyless
severeoranylessdetrImentalInanolderpatIentthanInyoungpatIents(seeChapter57).
LessdrugmayberequIred(ornot),butgIventhatthestandardapproachtoanalgesIaIsto
tItratetothedesIredeffect,theoutcomeshouldbegoodpaInrelIefforpatIentsofall
ages.ThereareImpedImentstoachIevIngadequateanalgesIaInanolderpatIent,
however.
56
ElderlypatIentssometImesunderreporttheIrpaInlevelandmaybemore
tolerantoftheIracutepaIn,perhapspartlybecauseoftheexIstenceofchronIcpaInIn
theIrlIfe.DlderpatIentshavemoredIffIcultywIthvIsualanalogscorIngsystemsthan
verbalornumerIcsystems.fthepatIentIscognItIvelyImpaIred,communIcatIonofpaInIs
furtherImpaIred;Indeed,dementedpatIentsoftenexperIenceseverepaInafterhIp
surgery,butevenmIldcognItIveImpaIrmentcanleadtoproblemswIthpaInassessmentor
wIthuseofapatIentcontrolledanalgesIamachIne.
FaIluretoachIeveadequatelevelsofanalgesIaIsassocIatedwIthnumerousadverse
outcomes,IncludIngsleepdeprIvatIon,respIratoryImpaIrment,Ileus,suboptImal
mobIlIzatIon,InsulInresIstance,tachycardIa,andhypertensIon.TheconsequencesInclude
longerhospItalIzatIonandIncreasedIncIdenceofdelIrIum.
56,57
Theapparentparadoxof
adequateanalgesIaIsthatopIoIdsarethemaInstayofpostoperatIveanalgesIa,andopIoIds
arecapableofproducIngmanyofthosesameadverseoutcomes,IncludIngrespIratory
depressIon,sedatIon,Ileus,anddelIrIum,andthoseoutcomesmaybemorefrequentInthe
olderpatIent.Therefore,aswIthallmedIcalcareofelderlypatIents,goodjudgment,
cautIon,andfrequentmonItorIngofanalgesIaandadverseeffectsareessentIal.Afew
studIeshaveexamInedthechoIceofopIoIdInolderpatIents,wIththemostpromInent
conclusIonbeIngtoavoIdtheuseofmeperIdInebecauseofItsassocIatIonwIth
delIrIum.
57,58
nfact,theonlyapproprIateroleofmeperIdIneInelderlypatIentsIsthe
smalldoseusedtotreatpostoperatIveshIverIng.AdjunctIvemedIcatIonssuchas
nonsteroIdalantIInflammatorydrugshavebeenshowntoreduceopIoIdrequIrementsand
someoftheopIoIdadverseeffects,butoftencarrytheIrownrIskssuchasrenaldamageor
gastroIntestInaltoxIcIty.
56
EpIduralanalgesIaIswellknowntoprovIdeanalgesIathatIs
superIortoIntravenoustherapy,afIndIngthathasbeenspecIfIcallyreplIcatedInthe
elderly.
59,60
AlthoughImprovedcardIopulmonaryoutcomeswereequIvocal,morerapId
returnofbowelfunctIon,earlIermobIlIzatIon,andnutrItIonalstatuswerebetterwIth
epIduralanalgesIa.
AlthoughmostotheraspectsofpostoperatIvecarearegenerallymorethepurvIewofthe
surgeonortheInternIst,therearesomethIngsthattheanesthesIologIstcouldandprobably
shouldbewatchfulforwhenperformIngapostoperatIvevIsItonanolderpatIent.fa
patIenthadasurgerywIthmajorfluIdrequIrements,ItIsImportanttolookforsIgnsof
fluIdoverload,IncludIngrales,dyspnea,tachypnea,andorthopnea.AtImely
admInIstratIonofadIuretIcmaypreventthepatIentfrommoreflorIdpulmonaryedema
andtheaccompanyIngescalatIonoftherapyandrIsk.AskIfthepatIenthasexperIenced
anychestpaIn.7ItalsIgnscanberevIewedwIthapartIculareyetotachycardIa.Feelthe
pulse:atrIalfIbrIllatIonIsoftenIntermIttentandthemoreoftensomeonelooksforIt,the
morelIkelyItwIllbedetected.0elIrIumoftengoesundetectedInolderpatIents,Inpart
becausetheolderpatIentIslesslIkelytoexhIbItagItatIonthanayoungdelIrIouspatIent.
TakethetImetochatwIththepatIentforafewmInutes.tshouldnotbedIffIcultto
becomesuspIcIousIfthepatIentdemonstrateswaxIngandwanIngalertness,IsInattentIve
ordIstractIble,dIsplaysrambledorIncoherentspeech,IsdIsorIented,orhasperceptual
dIsturbances.thasbeendemonstratedthatoverallrecoveryandavoIdanceof
complIcatIons,IncludIngdelIrIum,pneumonIa,uncontrolledpaIn,InfectIon,andlengthof
stay,canbeenhancedbycomprehensIveevaluatIonandmanagementofeachpatIent'srIsk
factors.
61,62
AnesthesIologIstsshouldbepreparedtosupportsuchprogramsasmuchas
possIble.
P.886
Perioperative Complications
My diseases are an asthma and a dropsy and, what is less curable,
seventy-five.
Samuel Johnson
TheolderpatIentIsatIncreasedrIskforcomplIcatIonsIntheperIoperatIveperIod.Partof
thatrIskIscertaInlyrelatedtothosecomorbIddIseasesthatarecontrIbutedtobythe
agIngprocess.TheothercomponentofrIskIstypIcallythoughtofasthereductIonInorgan
systemreservedIrectlyduetotheagIngprocess.WhethertheagIngprocesscanbethought
ofasmeredecreasedreserveorsubclInIcaldIseaseIsamatterofsemantIcs.TheresultIs
thesame:theelderlyareatIncreasedrIskforalmosteverypossIbleperIoperatIve
complIcatIonIncludIngcardIovascular,pulmonary,renal,centralnervoussystem,wound
InfectIon,anddeath(FIg.J58).
6J,64
8ecausethemechanIsmsofagIngcontrIbutenotonlytonormalagIngbuttothe
developmentandseverItyofdIsease,onemIghtexpectthatageanddIseasewouldInteract
IntheIrcontrIbutIontoperIoperatIverIsk.ConfIrmatIonofsuchahypothesIsIsprovIdedby
aprospectIvesurveyofnearly200,000anesthetIcsInFrance.
65
8othageandthenumberof
chronIcdIseaseswereassocIatedwIthanIncreasedrateofcomplIcatIons,butwhatIs
partIcularlyInterestIngIsanapparentInteractIonofthesetwofactors.FIgureJ59
demonstratesthat,foranygIvenagegroup,thenumberofcomplIcatIonsIncreaseswIth
thenumberofcomorbIddIseases.NotethattheJ4yearoldgroupIssomewhatofan
outlIerIfthatrIskIncreasesespecIallydramatIcallythreeormorecomorbIddIseasesare
present.tcouldbesurmIsedthattobethatsIckatsuchayoungagerepresentsaspecIal
degreeofrIsk.ConnectIngthedotsofequalnumberofcomorbIddIseaserevealsamodest
IncreaseInrIskwIthageforpatIentswIthzerocomorbIddIsease,butexamInatIonofpoInts
ofone,two,orthreeormoredIseasesrevealsaneffectofagethatbecomesIncreasIngly
larger.notherwords,ageappearstoInteractwIthcomorbIddIseasetoIncreaserIsk.
ComplIcatIonsofthecardIovascularandpulmonarysystemsareassocIatedwIththe
greatestperIoperatIvemortalIty.ThebestdatabaseIsprovIdedbythe7eteransAffaIrs
NatIonalSurgIcalQualItymprovementProject,andmuchofthedatabaseInvolves
examInatIonofpatIentsolderthan80(TableJ52).
64
AlthoughtheperIoperatIve
complIcatIonsofmyocardIalInfarctIonorcardIacarrestcarryhIgherassocIatedmortalIty
ratesthanpneumonIa,prolongedIntubatIon,orreIntubatIon,thehIgherIncIdencesofthe
pulmonarycomplIcatIonssuggestthatgreatermortalItyresultsfrompulmonary
complIcatIonsthancardIaccomplIcatIons.ThatpulmonarycomplIcatIonsaresosIgnIfIcant
underscorestheneedforabetterunderstandIngofthemechanIsmofpostoperatIve
pneumonIa,partIcularlythelIkelycontrIbutIonofsIlentaspIratIon.
66
Figure 35-8.ShowstherelatIonshIpbetweenageandmortalItyandmorbIdItyamonga
7eteransAffaIrspopulatIon.(|odIfIedfromTurrentIneFE,WangH,SImpson78etal:
SurgIcalrIskfactors,morbIdIty,andmortalItyInelderlypatIents.JAmCollSurg2006;
20J:865,wIthpermIssIon.)
Figure 35-9.0etaIlstheInteractIonbetweenageandcomorbIddIsease.Foreachage
bracket,ascomorbIddIseaseIncreases,sodoestherateofcomplIcatIons.Theeffect
ofageonthecomplIcatIonrateIsbestvIsualIzedbyexamInIngpoIntsofequal
comorbIddIsease.AtzerodIsease,onlyamodestIncreaseIncomplIcatIonsIsobserved
wIthIncreasIngage.AteverIncreasIngdegreesofcomorbIddIsease,however,the
IncreaseIncomplIcatIonswIthagebecomesmoreandmorepronounced.(FeprInted
fromTIretL,0esmontsJ|,HattonFetal:ComplIcatIonsassocIatedwIthanaesthesIa:
AprospectIvesurveyInFrance.CanAnesthSocJ1986;JJ:JJ6,wIthpermIssIon.)
AlthoughanesthesIologIstsfrequentlyfocusoncardIovascularandpulmonary
complIcatIons,centralnervoussystemcomplIcatIonsarealsoamajorsourceofmorbIdIty
andmortalIty.TheIncIdenceofstrokeInthegeneralsurgIcalpopulatIonIsapproxImately
0.5(TableJ52).
64,67,68
AgeIsarIskfactor,asIsatrIalfIbrIllatIon,andahIstoryofaprIor
strokeIncreasestherIskofperIoperatIvestrokebyasmuchas10fold.StrokestypIcally
occurwellaftersurgery,onaverage7dayslater.naddItIontocomaorstroke,
postoperatIvecognItIvedeclIneandpostoperatIvedelIrIumarereceIvIngIncreased
attentIonassIgnIfIcantsourcesofdebIlItatIngmorbIdIty.AlthoughthesetwoentItIesmay
yetprovetoberelatedtoeachother,atpresenttheyappeartobedIstInctclInIcal
syndromes.
PostoperatIvedelIrIumIsanacuteconfusIonalstatemanIfestedbyanacuteonset(hoursto
days)andvacIllatInglevelsofattentIonandcognItIveskIll.
9,69
0IsorIentatIon,perceptual
dIsturbances(frommIsInterpretatIonofthesItuatIontohallucInatIons),dIsorganIzed
thInkIng,andproblemswIthmemorymaybemanIfested.EmergencedelIrIumdoesnot
qualIfyaspostoperatIvedelIrIum.nfact,patIentswhogoontoexperIencepostoperatIve
delIrIumhaveadefInedperIodofnormalItyafterInItIalrecoveryfromanesthesIa.Several
methodsofdIagnosIshavebeenpopularIzed,wIththeConfusIonAssessment|ethodused
mostoften,atleastInresearchstudIes.
70
TherIskofpostoperatIvedelIrIumaftermajor
surgeryInolderpatIentsIssomewhereontheorderof10;however,therIskvarIeswIth
thesurgIcalprocedure.HIghestrIskIshIpsurgery,wIthanapproxImateIncIdenceofJ5.
ThecauseofdelIrIumIsmultIfactorIal.PatIentrIskfactorsIncludepatIentage,baselIne
lowcognItIvefunctIon(IncludIngdementIa),depressIon,andpossIblygeneraldebIlIty
IncludIngdehydratIonorvIsual/audItoryImpaIrment.
9,69
7IrtuallyanydrugwIthcentral
nervoussystemeffectshasbeenImplIcated,IncludIngnarcotIcs(especIallymeperIdIne),
benzodIazepInes(especIallylorazepam),anddrugsthatpossessantIcholInergIcpropertIes
(exceptglycopyrrolate).
P.887
DtherfactorsthatlIkelycontrIbutetodelIrIumIncludesleepdeprIvatIon,beIngInan
unfamIlIarenvIronment,postoperatIvepaIn,andperIoperatIvebloodloss.ChoIceof
regIonalversusgeneralanesthesIadoesnotappeartobeafactor,especIallyIfsedatIonIs
usedInconjunctIonwIththeregIonaltechnIque.Dncedetected,managementfocuseson
reversIblerIskfactorssuchascurrentmedIcatIons,paInmanagement,andabettersleep
envIronment.HaloperIdolIndosesnogreaterthan1.5mgcanbehelpful,especIallyfor
agItateddelIrIum,andwhenapplIedprophylactIcally,mayreducetheseverItyand
duratIonbutnottheIncIdenceofdelIrIum.
71
SpecIalcareprogramsdesIgnedtolImItthe
reversIblerIskfactorsappeartoreducetheIncIdenceofdelIrIumby50.
62
PreventIonIs
notjustanacademIcexercIse.0elIrIumIsassocIatedwIthanIncreasedduratIonof
hospItalIzatIonandItsattendantcosts,poorerlongtermfunctIonalrecovery,and
IncreasedmortalIty.
Table 35-2 Effect of Age on Selected Perioperative Complications and
Associated Mortality
a
COMPLICATION COMPLICATION RATE
MORTALITY RATE FROM THE
COMPLICATION
Age
80
Age
80
Age80 Age80
|yocardIalInfarctIon 0.4 1.0 J7.1 48.0
CardIacarrest 0.9 2.1 80.0 88.2
PneumonIa 2.J 5.6 19.8 29.2
48hoursonventIlator 2.1 J.5 J0.1 J8.5
FequIredreIntubatIon 1.6 2.8 J2.J 44.0
Cerebrovascular
accIdent
0.J 0.7 26.1 J9.J
Coma24hours 0.2 0.J 65.9 80.9
ProlongedIleus 1.2 1.7 9.2 16.0
a
AlldIfferencesbetweenpatIentslessthan80versus80andolderaresIgnIfIcantat
p0.001,exceptforcomamortalIty(p=.004).
|odIfIedfromHamel|8,HendersonWC,KhurISFetal:SurgIcaloutcomesfor
patIentsaged80andolder:morbIdItyandmortalItyfrommajornoncardIac
surgery.JAmCerIatSoc2005;5J:424,wIthpermIssIon.
PostoperatIvecognItIvedysfunctIonIscharacterIzedbyalongtermdecreaseInmental
abIlItIesaftersurgery.tIsInherentlymoredIffIculttodIagnosethandelIrIumbecauseIt
usuallyrequIressophIstIcatedneuropsychologIcaltestIng,IncludIngbaselInetestsprIorto
surgery.SelectIonoftests,theIrtImIng,andwhatdefIcItsarerequIredtoqualIfyfor
cognItIvedeclInehaveprovenproblematIcInthelIterature.Nevertheless,somebasIc
observatIonscanbemade.
72
ncomparIsontononsurgIcalcontrolsubjects,thecognItIve
declInelessensovertImewIthperhapsa10IncIdenceatJmonthsIncomparIsonwItha
25IncIdenceat1week.
7J
At6monthsandbeyondtheremaybeaprevalenceof1of
subjectswIthdeclIne,butthereIslIttleevIdenceofdeclIneIncomparIsonwIthcontrol
subjects.AnesthetIcmanagementdoesnotappeartoaffectcognItIvedeclInewhen
comparIsonsaremadebetweengeneralversusregIonalanesthesIa,controlledhypotensIon
versusnormotensIon,orIntravenousversusInhalatIonanesthesIa.
72
PatIentrIskfactors
Includeage,lowerlevelsofeducatIon,andprIorhIstoryofstrokeevenwIthoutresIdual
defIcIt.
74
ncreasedmortalItyat1yearIsassocIatedwIthpatIentswhodemonstrate
cognItIvedeclIneatbothhospItaldIschargeandatJmonthspostoperatIvely.nterestIngly,
postoperatIvedelIrIumwasnotfoundtobearIskfactorforcognItIvedysfunctIonatJ
months.CognItIvedeclIneIsacomplIcatIonthatIsstIllInItsInfancywIthrespecttoan
understandIngoftheunderlyIngmechanIsm(s)andtheImplIcatIonsforpatIentqualItyof
lIfe.
The Future
I will never be an old man. To me, old age is always 15 years older
than I am.
Francis Bacon
mprovementsInsurgIcalandanesthetIctechnIquesthatreducetheoverallstresstothe
patIentarepermIttIngmoresurgerIestobeperformedonolderandsIckerpatIentsthan
everbefore.Nevertheless,theolderpatIentwIllcontInuetoexperIencethemajorItyof
theadverseoutcomesfromsurgeryandanesthesIa.|uchremaInstobeaccomplIshedIn
thequesttofIndwaystodecreasetheIncIdenceandseverItyofthoseadverseoutcomes.
66
ThemostpressIngIssuesarearguablythepreventIonofpostoperatIvedelIrIum,cognItIve
declIne,pneumonIa,andrespIratoryfaIlure.mprovedpaIncontroltechnIquesthatalso
dImInIshsIdeeffects,especIallytothebraInandbowels,wouldbewelcome.However,
otherrealmsofcarearejustIntheIrInfancy,mostnotablywhetherthefunctIonalstatus
offraIlpatIentscanbeImprovedprIortosurgery.Forexample,canshortcoursesofbetter
nutrItIon,exercIseregImens,orevenmedIcatIonsreducecomplIcatIonsorspeedrecovery
andImprovefunctIonalrecovery:WhencarIngfortheelderly,especIallythefraIlelderly,
theoverrIdInggoalshouldbetoproduceaslIttlestresstothepatIentaspossIbledurIng
bothsurgeryandthesubsequenthospItalIzatIonandrecovery.CompletecarewIlloftenbe
multIdIscIplInary.NosInglespecIaltypossessesthetotalperspectIve,andthe
anesthesIologIst'sexpertIseIsanImportantcomponentofthatcare.
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47.LeungJ|,0zankIcS:FelatIveImportanceofpreoperatIvehealthstatusversus
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54.FeIch0L,HossaInS,Krol|etal:PredIctorsofhypotensIonafterInductIonof
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Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJ6AnesthesIaforTraumaand8urnPatIents
ChapterJ6
Anesthesia for Trauma and Burn Patients
Levon M. Capan
Sanford M. Miller
Key Points
1. Initial evaluation of the trauma patient involves rapid overview,
primary survey, and secondary survey.
2. Airway management is tailored to the type of injury, the nature and
degree of airway compromise, and the patient's hemodynamic and
oxygenation status.
3. Fast computed tomography technology with the capability of sagittal
image reconstruction is replacing conventional multiple-view plain
radiographic evaluation of cervical spine injury. Further, magnetic
resonance imaging is replacing flexion/extension plain radiographic
evaluation of the relatively infrequent ligamentous injuries of the
cervical spine.
4. Morbidity and mortality of flail chest are primarily related to
underlying pulmonary contusion that develops over a period of a few
hours after injury. A too liberal indication for tracheal intubation of
patients in this condition may be associated with increased morbidity
and mortality.
5. Lethal triad or bloody vicious circle refers to the development of
acidosis, hypothermia, and coagulopathy that, if untreated, may lead
to death.
6. Approximately 10% of patients with hemorrhagic shock may have
severe coagulopathy at the time of admission and the early operative
phase, requiring hemostatic resuscitation with plasma, platelets, and
coagulation factors.
7. Head injury and hemorrhagic shock are the most common causes of
traumatic death.
8. The most important therapeutic maneuvers in head-injured patients
are normalization of intracranial pressure, cerebral perfusion
pressure, and oxygen delivery.
9. Brain ischemia is the most threatening consequence of head injury.
By causing cerebral vasoconstriction, hyperventilation further
aggravates ischemia.
10. Penetrating neck injuries usually present with obvious clinical
manifestations, whereas blunt cervical trauma may be more subtle.
11. The term blunt cardiac injury has replaced myocardial contusion and
encompasses varying degrees of myocardial damage, coronary artery
injury, and rupture of the cardiac free wall, the septum, or a valve.
12. Extraperitoneal or preperitoneal pelvic packing may be helpful in
diminishing the rate of severe pelvic fracture bleeding. Angiography
and embolization may follow pelvic packing if there is arterial
bleeding from a pelvic fracture.
13. Deep anesthesia and high airway pressures should be avoided before
evacuation of the hemopericardium.
14. Hypermetabolism caused by major burn injuries can be reduced by
early decompressive escharotomies and skin grafting. Other
measures to decrease metabolism and catabolism include low-dose
insulin infusion, beta-blockade, and anabolic oxandrolone.
15. Persistent hypotension following trauma is usually the result of one of
four mechanisms: bleeding, tension pneumothorax, neurogenic
shock, and cardiac injury.
16. Death is a much greater threat during emergency trauma surgery
than it is in any other operative procedure.
AccordIngtodatafromtheNatIonalSafetyCouncIl,
1
IntentIonalandunIntentIonalInjurIes
kIlled167,000AmerIcansIn2004.ntentIonalInjurIes(suIcIde,homIcIde,andassault)
claImed55,000lIvesandunIntentIonalmortalIty(e.g.,motorvehIcle,falls,drownIng,and
poIsonIng)accountedfor112,000deaths,makIngtraumathethIrdleadIngcauseofdeath
afterheartdIseaseandcancer.UnIntentIonalInjurIeswerethefIfth,suIcIdestheeleventh,
andassaultthefIfteenthleadIngcausesofdeathoverall.Fortheagerangebetween15and
J1,accIdents,suIcIde,andhomIcIdewerethethreeleadIngcausesofdeath.|orbIdIty
causedbyInjurIesIsfarInexcessofmortalIty;In2005,atotalof27,156,7J4emergency
departmentvIsItswererelatedtounIntentIonalInjurIes.n2006,theestImatedcostof
unIntentIonalInjurIesalonewasS652bIllIon,IncludIngthecostsoffatalandnonfatal
InjurIes,employercosts,vehIcledamage,andfIrelosses.TheaddItIonalcostoflostqualIty
oflIfeIsestImatedasSJ,080bIllIon,brIngIngthetotalannualcostoftraumatoSJ,7J2
bIllIon.
1
ApproxImately75ofthehospItalmortalItyfromtraumaoccurswIthIn48hoursafter
admIssIon,
2
mostcommonly
P.890
fromcentralnervoussystem(CNS),thoracIc,abdomInal,retroperItoneal,orvascular
InjurIes
2
;CNSInjuryandhemorrhagearethemostcommoncausesofearlytrauma
mortalIty.NearlyonethIrdofthesetraumapatIentsdIewIthInthefIrst4hoursafter
admIssIon,representIngthemajorItyofoperatIngroom(DF)traumadeaths.DfthehospItal
deaths,5to10occurbetweenthethIrdandseventhdayofadmIssIon,usuallyfromCNS
InjurIes,
2
andtheremaInderInsubsequentweeks,mostcommonlyasaresultofmultIorgan
faIlure.
2
PulmonarythromboembolIsmandInfectIouscomplIcatIonsmayalsocontrIbuteto
mortalItydurIngthIsphase.
2
Figure 36-1.ClInIcalsequenceforInItIalmanagementofthemajortraumapatIent.
CT,computedtomography;EF,emergencyroom;CU,IntensIvecareunIt.
Initial Evaluation and Resuscitation
ThestrategyofInItIalmanagementcanbedefInedasacontInuous,prIorItydrIvenprocess
ofpatIentassessment,resuscItatIon,andreassessment.Thegeneralapproachto
evaluatIonoftheacutetraumapatIenthasthreesequentIalcomponents:rapIdovervIew,
prImarysurvey,andsecondarysurvey(FIg.J61).FesuscItatIonIsInItIated,Ifneeded,at
anytImedurIngthIscontInuum.Rapid overviewtakesonlyafewsecondsandIsusedto
determInewhetherthepatIentIsstable,unstable,dyIng,ordead.Theprimary survey
InvolvesrapIdevaluatIonoffunctIonsthatarecrucIaltosurvIval.TheA8CsofaIrway
patency,breathIng,andcIrculatIonareassessed.ThenabrIefneurologIcexamInatIonIs
performedandthepatIentIsexamInedforanyexternalInjurIesthatmIghthavebeen
overlooked.
Thesecondary surveyInvolvesamoreelaboratesystematIcexamInatIonoftheentIrebody
toIdentIfyaddItIonalInjurIes.FadIographIcandotherdIagnostIcproceduresmayalsobe
performedIfthestabIlItyofthepatIentpermIts.WIthInthIsgeneralframeworkthe
anesthesIologIst,asIdefrommanagIngtheaIrway,contrIbutesaspartoftheteamto
evaluatIonandresuscItatIon,whIlegatherIngInformatIonneededforpossIblefuture
anesthetIcmanagement.
njurIesmaybemIsseddurIngInItIalevaluatIonandevendurIngemergencysurgery,
resultIngInsIgnIfIcantpaIn,complIcatIons,resIdualdIsabIlIty,delayoftreatment,or
death.
J
FeportedmIsseddIagnosesIncludecervIcalspIne,thoracoabdomInal,pelvIc,
nerve,andexternalsofttIssueInjurIes,andextremItyfractures.SomeoftheseInjurIes
maypresentdurInganesthesIa,suchasspInalcorddamageInapatIentwIthunrecognIzed
cervIcalspIneInjury,massIveIntraoperatIvebleedIngfromanunrecognIzed
thoracoabdomInalInjurydurIngextremItysurgery,orsuddenIntraoperatIvehypoxemIaIn
apatIentwIthunrecognIzedpneumothorax.Atertiary surveywIthInthefIrst24hoursafter
admIssIon(whIchmayIncludeaperIodofanesthesIa)canpotentIallydIagnosethemajorIty
ofclInIcallysIgnIfIcantInjurIesmIsseddurIngInItIalevaluatIon
J
byrepeatIngtheprImary
andsecondaryexamInatIonsandrevIewIngtheresultsofradIologIcandlaboratorytestIng.
Airway Evaluation and Intervention
AIrwayevaluatIonInvolvesthedIagnosIsofanytraumatotheaIrwayorsurroundIng
tIssues,recognItIonandantIcIpatIonof
P.891
therespIratoryconsequencesoftheseInjurIes,andpredIctIonofthepotentIalfor
exacerbatIonoftheseorotherInjurIesbyanycontemplatedaIrwaymanagement
maneuvers(seeChapter29).AlthoughnontraumatIccausesofaIrwaydIffIculty,suchas
preexIstIngfactors,maybepresent,onlythemanagementoftraumarelatedproblemsIs
dIscussedInthIssectIon.Cenerally,theAmerIcanSocIetyofAnesthesIologIstsdIffIcult
aIrwayalgorIthmcanbeapplIedwIthcertaInmodIfIcatIonstovarIoustraumaaIrway
managementscenarIos.ForInstance,cancellatIonofaIrwaymanagementwhendIffIculty
arIsesmaynotbeanoptIon.LIkewIse,awakeratherthanasleepIntubatIonorasurgIcal
aIrwayfromtheoutsetmaybethepreferredtechnIqueInsomesItuatIons.TheAmerIcan
SocIetyofAnesthesIologIstsdIffIcultaIrwayalgorIthmasmodIfIedforvarIoustrauma
condItIonsIsavaIlable.
4
Airway Obstruction
AIrwayobstructIonIsprobablythemostfrequentcauseofasphyxIaandmayresultfrom
posterIorlydIsplacedorlaceratedpharyngealsofttIssues,hematoma,bleedIng,secretIons,
foreIgnbodIes,ordIsplacedboneorcartIlagefragments.8leedIngIntothecervIcalregIon
mayproduceaIrwayobstructIonnotonlybecauseofcompressIonbythehematoma,but
alsofromvenouscongestIonandupperaIrwayedemaasaresultofcompressIonofneck
veIns.SIgnsofupperandloweraIrwayobstructIonIncludedyspnea,cyanosIs,hoarseness,
strIdor,dysphonIa,subcutaneousemphysema,andhemoptysIs.CervIcaldeformIty,edema,
crepItatIon,trachealtugand/ordevIatIon,orjugularvenousdIstentIonmaybepresent
beforethesesymptomsappearandmayhelpIndIcatethatspecIalIzedtechnIquesare
requIredtosecuretheaIrway.
TheInItIalstepsInaIrwaymanagementarechInlIft,jawthrust,clearIngofthe
oropharyngealcavIty,placementofanoropharyngealornasopharyngealaIrway,andIn
InadequatelybreathIngpatIents,ventIlatIonwIthaselfInflatIngbag.mmobIlIzatIonofthe
cervIcalspIneandadmInIstratIonofoxygenshouldbeapplIedsImultaneously.8lInd
passageofanasopharyngealaIrwayoranasogastrIcornasotrachealtubeshouldbe
avoIdedIfabasIlarskullfractureIssuspected;ItmayentertheanterIorcranIalfossa.A
cuffedoropharyngealaIrwayoralaryngealmaskaIrway(L|A)maypermItventIlatIonwIth
aselfInflatIngbag,althoughneItherprovIdesprotectIonagaInstaspIratIonofgastrIc
contents.Theymaybeusedastemporarymeasures,andIftheydonotprovIdeadequate
ventIlatIon,thetracheamustbeIntubatedImmedIatelyusIngeItherdIrectlaryngoscopyor
acrIcothyroIdotomy,dependIngontheresultsofaIrwayassessment.
|axIllofacIal,neck,andchestInjurIes,aswellascervIcofacIalburns,arethemost
commontraumarelatedcausesofdIffIculttrachealIntubatIon.AIrwayassessmentshould
IncludearapIdexamInatIonoftheanterIorneckforfeasIbIlItyofaccesstothecrIcothyroId
membrane.TracheostomyIsnotdesIrabledurIngInItIalmanagementbecauseIttakes
longertoperformthanacrIcothyroIdotomyandrequIresneckextensIon,whIchmaycause
orexacerbatecordtraumaInpatIentswIthcervIcalspIneInjurIes.ConversIontoa
tracheostomyshouldbeconsIderedlatertopreventlaryngealdamageIfa
crIcothyroIdotomywIllbeInplaceformorethan2toJdays.PossIblecontraIndIcatIonsto
crIcothyroIdotomyIncludeageyoungerthan12yearsandsuspectedlaryngealtrauma;
permanentlaryngealdamagemayresultIntheformer,anduncorrectableaIrway
obstructIonmayoccurInthelattersItuatIon.
Full Stomach
AfullstomachIsabackgroundcondItIonInacutetrauma;theurgencyofsecurIngthe
aIrwayoftendoesnotpermItadequatetImeforpharmacologIcmeasurestoreducegastrIc
volumeandacIdIty.Thus,ratherthanrelyIngontheseagents,theemphasIsshouldbe
placedonselectIonofasafetechnIqueforsecurIngtheaIrwaywhennecessary:rapId
sequenceInductIonwIthcrIcoIdpressureforthosepatIentswIthoutserIousaIrway
problems,andawakeIntubatIonwIthsedatIonandtopIcalanesthesIa,IfpossIble,forthose
wIthantIcIpatedserIousaIrwaydIffIcultIes.
TheprobabIlItyofafullstomachprecludestheuseofanL|AoranyotherdevIcethatdoes
notprotectthetrachea,asadefInItIveaIrwayIntraumapatIents.However,thesedevIces
canserveasabrIdgeforabrIefperIodtoreestablIshaIrwaypatencyortofacIlItate
IntubatIonaIdedbyaflexIblefIberoptIcbronchoscope(FD8).npatIentswIthmaxIllofacIal
InjurIes,aspIratIonofpharyngealbloodorsecretIonsIsmorelIkelythanaspIratIonof
gastrIccontents.fItcanbeInsertedInthesecIrcumstances,anL|Amayprotectthe
lungs.AlthoughposItIvepressureventIlatIonmaybeusedwIththeL|A,patIentswIth
pulmonarycontusIon,edema,oraspIratIonmaybedIffIculttoventIlatewIththIsdevIce.
AnIntubatInglaryngealmaskorsImIlarlaryngealaIrwaysmaypermItrapIdblIndorFD8
guIdedtrachealIntubatIonwhIleallowIngtemporaryventIlatIon.AnImportant
dIsadvantageoftheIntubatInglaryngealmaskIsthatItsmetalpartmayexertconsIderable
pressureagaInstthecervIcalvertebrae,potentIallyexacerbatInganunstableInjuryInthIs
regIon.nagItatedanduncooperatIvepatIents,topIcalanesthesIaoftheaIrwaymaybe
ImpossIble,whereasadmInIstratIonofsedatIveagentsmayresultInapneaoraIrway
obstructIon,wIthanIncreasedrIskofaspIratIonofgastrIccontentsandInadequate
condItIonsfortrachealIntubatIon.AfterlocatIngthecrIcothyroIdmembraneand
denItrogenatIngthelungs,arapIdsequenceInductIonmaybeusedtopermItsecurIngthe
aIrwaywIthdIrectlaryngoscopyor,Ifnecessary,wIthImmedIatecrIcothyroIdotomy.
PersonnelandmaterIalnecessarytoperformtranslaryngealventIlatIonor
crIcothyroIdotomymustbeInplacebeforeInductIonofgeneralanesthesIa.
Head, Open Eye, and Contained Major Vessel Injuries
TheprIncIplesoftrachealIntubatIonaresImIlarfortheseInjurIes.Apartfromtheneedto
ensureadequateoxygenatIonandventIlatIon,patIentswIththeseInjurIesrequIredeep
anesthesIaandprofoundmusclerelaxatIonbeforeaIrwaymanIpulatIon.ThIshelpsprevent
hypertensIon,coughIng,andbuckIng,andtherebymInImIzesIntracranIal,Intraocular,or
IntravascularpressureelevatIon,whIchcanresultInhernIatIonofthebraIn,extrusIonof
eyecontents,ordIslodgmentofahemostatIcclotfromanInjuredvessel,respectIvely(see
Chapter51).ThepreferredanesthetIcsequencetoachIevethIsgoalIncludes
preoxygenatIonandopIoIdloadIng,followedbyrelatIvelylargedosesofanIntravenous
anesthetIcandmusclerelaxant.HemodynamIcresponsestotheopIoIdshouldbecarefully
monItoredandpromptlycorrected.SystemIchypotensIon,IntracranIalpressure(CP)
elevatIon,anddecreasedcerebralperfusIonpressure(CPP=meanarterIalpressureCP)
mayoccurwhethercerebralautoregulatIonIspresentorabsentInpatIentswIthhead
InjurIes,andIfuntreatedcanproducesecondaryIschemIcInsults.
5
KetamIneIsusually
contraIndIcatedInpatIentswIthheadandvascularInjurIesbecauseItmayIncreaseboth
IntracranIalandsystemIcvascularpressures;however,nosIgnIfIcantIncreaseIn
Intraocularpressure(DP)hasbeendocumented.Anymusclerelaxant,IncludIng
succInylcholIne,maybeusedaslongasthefascIculatIonproducedbythIsagentIsInhIbIted
byprIoradmInIstratIonofanadequatedoseofanondepolarIzIngmusclerelaxant.
AlternatIvely,rocuronIumcanprovIdeIntubatIngcondItIonswIthIn60secondswIthadose
of1.6to2.0mg/kg,althoughtheneuromuscularblockadeproducedbythIsdoselasts
approxImately2hours.
6
ntravenouslIdocaInehasanattenuatIngeffectonthepressor
responsetoaIrwayInstrumentatIon,butItIsmIldandunpredIctable.Dfcourse,neIther
P.892
musclerelaxantsnorIntravenousanesthetIcsareIndIcatedwhenInItIalassessment
suggestsadIffIcultaIrway.AsInanyothertraumapatIent,hypotensIondIctateseIther
reducedornoIntravenousanesthetIcadmInIstratIon.
Cervical Spine Injury
Dverall,2to4ofblunttraumapatIentshavecervIcalspIneInjurIes.
7
Themostcommon
causesIncludehIghspeedmotorvehIcleaccIdents,falls,dIvIngaccIdents,andgunshot
wounds.HeadInjurIes,especIallythosewIthlowClasgowComaScores(CCS)andfocal
neurologIcdefIcIts,arelIkelytobeassocIatedwIthcervIcalspIneInjurIes.ApproxImately2
to10ofheadtraumapatIentshavecervIcalspIneInjurIes,whIle25to50ofpatIents
wIthcervIcalspIneInjurIeshaveanassocIatedheadInjury.
7
TheIncIdenceofassault
relatedInjurIesdependsonthemechanIsm,beInghIghestaftergunshotwounds(1.J5),
lowestafterstabwounds(0.12),andIntermedIateafterblunttrauma(0.4)tothe
cervIcothoracIcregIon.nconscIouspatIents,neckpaIn,tenderness,andextremIty
paresthesIasarestrongIndIcatorsofspIneInjury.AccurateandtImelyevaluatIonIs
ImportantbecauseapproxImately2to10ofblunttraumaInducedcervIcalspIneInjury
patIentsdevelopneworworsenIngneurologIcdefIcItsafteradmIssIon,attrIbutablepartly
todelayeddIagnosIsandImpropercervIcalspIneprotectIonand/ormanIpulatIon.
7
Dften
thereIsnotImetoevaluatetheInjurywhenemergencyaIrwaymanagementIsneeded
durIngtheInItIalphaseofmanagement.
mmobIlIzatIonoftheneckInneutralposItIonIsIndIcatedbeforeaIrwaymanagementIn
allacutetraumapatIentssuspectedtohavecervIcalspIneInjurybasedonmechanIsmand
clInIcalpresentatIon.ntubatIonmaytheoretIcallycausespInalcorddamagedurIng
manIpulatIonoftheneck,althoughtheavaIlablelIteratureatteststotherare,possIbly
nonexIstent,occurrenceofthIsevent.
7,8
Nevertheless,ItIsaprIorInecessarytoprotect
theneckdurIngaIrwaymaneuversInanypatIentwIthapossIblyunstablecervIcalspIne.
7,8
Initial Evaluation
ApatIentwhoarrIvesInthehospItalwItharIgIdcollarandotherneckstabIlIzIngdevIces
thatareroutInelyplacedbytheemergencymedIcalservIce,butwhoIsnotInneedof
emergencyaIrwaymanagement,shouldbeevaluatedforcervIcalspIneInjury.Clearance
oftheneckshouldbeperformedattheearlIestpossIbletIme,notnecessarIlytofacIlItate
aIrwaymanagement,buttomInImIzetherIskofpressureulceratIonbythecollar.
TheproceduresforcervIcalspIneclearancevaryaccordIngtothepatIent'scondItIon.n
theconscIouspatIentwIthasuspectedInjury,dIagnosIsIsrelatIvelyeasy.TheAmerIcan
NatIonalEmergencyXFadIographyUtIlIzatIonStudy(NEXUS)suggeststhatIf,bycareful
clInIcalexamInatIon,thepatIentmeetsallofthefollowIngcrIterIa,theInjurymaybe
ruledout:(1)nomIdlInecervIcaltenderness,(2)nofocalneurologIcdefIcIt,(J)normally
alert,(4)notIntoxIcated,and(5)nodIstractIngpaInfulInjury.
11
DfthesecrIterIa,
dIstractIngInjuryIsthemostdIffIculttoevaluate.SpInalpaInIsnotalwayslocalIzedtothe
levelofInjury,andnotalldIstantpaInfulInjurIesmaskcervIcalpaIn.Forexample,upper
torsoInjurIesmaybemorepaInfulandmorelIkelytodIstractfromrelIablecervIcalspIne
examInatIonthanlowertorsoInjurIes.
9
TheCanadIanCSpIneFuleforFadIographyafter
TraumaIsanothertooldesIgnedtodetermInelowrIskpatIents.
10,11
Properanswerstothe
followIngthreequestIonselImInatethepossIbIlItyofInjuryandtheneedforradIographIc
studIes:(1)sthereanyhIghrIskfactormandatIngradIography:(2)AretherelowrIsk
factorsthatpermItsafeevaluatIonoftherangeofmotIonoftheneck:(J)CanthepatIent
rotatethenecklaterallyfor45degreesIneachdIrectIonwIthoutpaIn:ComparIsonof
thesetwosetsofcrIterIashowedthattheCanadIanFuleIsmorerelIablethanNEXUSIn
dIagnosIngcervIcalspIneInjuryInresponsIvepatIents.
11
nawakepatIentswIthsuggestIvefIndIngsbytheNEXUSorCanadIancrIterIa,andthose
whoareIncomaorobtunded,thedIagnosIsofcervIcalspIneInjurynecessItatestheuseof
radIographIcstudIesInaddItIontotheclInIcalexamInatIon.TheEasternAssocIatIonforthe
SurgeryofTrauma(EAST)guIdelInesrecommendastandardthreevIew(anteroposterIor,
lateral,andopenmouth)serIesandexamInatIonofsuspectorsuboptImallyvIsualIzed
areaswIthlImIted,focusedcomputedtomography(CT)scans.
12
WIththedevelopmentof
fast,sophIstIcatedCTscanners,ItIsclearthatthedIagnostIccapabIlItyoftheplaInfIlms
recommendedbytheEASTguIdelInesIsInferIortohelIcalCTscanswIthsagIttaland
coronalreconstructIon.
1J,14,15
CTscansperformedInthIsfashIonprovIderelIable
InformatIonaboutfracturesandareabletodIfferentIatefracturesthatcancause
vertebralInstabIlItyfromthosethatarenotlIkelytocausespInalcorddamage.Stable
fracturesofthespInearespInousprocessfractures;Isolatedosteophyte,trabecular,
transverseprocess,andavulsIonfractureswIthoutlIgamentInjury;andwedgecompressIon
fractureswIthlossof25ofvertebralbodyheIght.
7
TheadvantagesofCTexamInatIon
IncludelessrelIanceonplaInfIlms,whIcharefrequentlyInadequateanddIffIculttoobtaIn
InuncooperatIvepatIents,almost100sensItIvItyIndetectInganInjury,theabIlItytoscan
otheranatomIclocatIonsInthesamesessIon,andpossIblyreducedcost.Currentlythe
EASTguIdelInesarestIllbeIngupdated;theywIllprobablyrecommendCTscannIngasa
prImarydIagnostIcmeasure.TheabIlItyofaCTscantodIagnoselIgamentousInjuryIsless
thanthattodetectfractures.
16
ThestandardmeasurefordIagnosInglIgamentousInjuryIs
aflexIon/extensIonserIes.ThIsapproachIscumbersome,notcosteffectIve,andperhaps
hazardous.naddItIon,ItIsInadequatewhen,asInmanyacutetraumapatIents,therange
ofmotIonoftheneckIslImIted.|agnetIcresonanceImagIng(|F)canbeusedInsteadfor
thIspurpose.
19,20,21
Althoughuseful,|FtendstooverreadtheInjurybeyondtheclInIcally
sIgnIfIcantrange.
21
tIsalsoImpossIbletoperformInpatIentswIthmultIpletrauma
patIentswhohavemetallIcskeletalfIxators.Fortunately,clInIcallysIgnIfIcantlIgamentous
InjurIesarerelatIvelyrare,andthustheneedfor|FIsInfrequent.
TwogroupsoftraumapatIentswIthnormalCTresultsaredIffIculttoevaluate:conscIous
patIentswIthneckpaInandobtundedorcomatosepatIents.DbvIously,theusualapproach
todIagnoselIgamentousInjuryInthesepatIentsIsevaluatIonbyflexIon/extensIonserIesor
by|F.thasbeendemonstratedthatdIagnosIsmaynotrequIretheseaddItIonalstudIes,
aslongasconscIouspatIentsareneurologIcallyIntact,obtundedorcomatosepatIentsare
abletomovealloftheIrextremItIesonadmIssIon,andtheCTscanIsperformedwIthJ
mmcutsandsagIttalreconstructIonoftheentIrecervIcalspIne.
22,2J
AlthoughthIs
approachlImItstheneedfor|FonlytothosewhohaveneurologIcdefIcIts,Italso
emphasIzestheImportanceofobservInganddocumentIngmotorfunctIonbefore
admInIstratIonofanesthetIcormusclerelaxantagentsforaIrwaymanagement.FamIlIarIty
wIththesedIagnostIcstrategIesmayhelptheanesthesIologIstassesspatIentsclearedfor
cervIcalspIneInjurybeforeaIrwaymanagement.
Airway Management
AlmostallaIrwaymaneuversIncludIngjawthrust,chInlIft,headtIlt,andoralaIrway
placementresultInsomedegreeofcervIcalspInemovement
7
(seeChapter29).
StabIlIzatIonofthehead,neck,andtorsoInneutralposItIonforaIrwaymanagementIn
patIentswhosecervIcalspIneIsyettobeclearedIsbestaccomplIshedbymanualInlIne
ImmobIlIzatIon.AhardcervIcalcollaralone,whIchIsroutInelyplaced,doesnotprovIde
absoluteprotectIon,especIallyforrotatIonalmovementsoftheneck.|anualInlIne
ImmobIlIzatIonIsbestaccomplIshedbyhavIngtwooperatorsInaddItIontothephysIcIan
whoIsactuallymanagIngtheaIrway.ThefIrstoperator
P.89J
stabIlIzesandalIgnstheheadInneutralposItIonwIthoutapplyIngcephaladtractIon,and
thesecondoperatorstabIlIzesbothshouldersbyholdIngthemagaInstthetableor
stretcher.TheanterIorportIonofthehardcollar,whIchlImItsmouthopenIng,maybe
removedafterImmobIlIzatIon.
AnexcellentrevIewofaIrwaymanagementaftercervIcalspIneInjuryIsprovIdedby
Crosby
7
;thereaderIsreferredtoItformoredetaIledInformatIon.Althoughcontroversy
exIstsaboutthechoIceoftechnIqueInthesepatIents,theselectIonshouldgenerallybe
basedonthetImIngofaIrwaymanagementInrelatIontotheInjuryandthefamIlIarItyof
theoperatorwIththespecIfIctechnIque.FD8guIdedIntubatIonproducestheleast
dIstractIonofthecervIcalspIne,butIntheacutephaseoftraumafactorssuchasfull
stomach,lackofpatIentcooperatIon,andtImeconstraIntsmayInfluencetheoperatorto
selectconventIonaldIrectlaryngoscopy,preferablyafterInductIonofanesthesIa,In
patIentswIthoutantIcIpatedaIrwaydIffIcultIes.nlInestabIlIzatIon,however,decreases
thevIsIbIlItyofthelarynxInasIgnIfIcantproportIonofpatIents.TheIncIdenceof
InadequateexposureofthelarynxIncreasesfromJInthegeneralpopulatIonto
approxImately10wIthImmobIlIzatIonoftheneck.
24
Furthermore,aIrwaymanagement
maybedIffIcultInsomepatIentsbecauseofenlargementoftheprevertebralspacebya
hematomafromvertebralfracture.LateralneckfIlmsmayhelpdIagnosearetropharyngeal
hematoma,whIchmaycausetrachealdevIatIonandcomplIcateaIrwaymanagement.UsIng
analternatetechnIqueIncludIngcrIcothyroIdotomyshouldbeconsIdered,Ifnecessary,
ratherthancausIngexcessIvemanIpulatIonoftheneck.CrIcoIdpressureshouldbeapplIed
wIthgreatcareInthepatIentwIthapossIblecervIcalspIneInjuryasItmayproduceundue
motIonofthespIneIfexcessIveforceIsused.
DtherdevIcesandtechnIques,IncludIngthe|cCoylaryngoscope(PenlonAmerIca,
|Innetonka,|N),rIgIdfIberoptIclaryngoscopes(8ullard,AC|Cyrus,Southborough,|A;
ClIdeScope,7erethon,8othell,WA;orWuScope,AchICorporaton,SanJose,CA),flexIble
fIberoptIcendoscope,lIghtwand,translaryngeal(retrograde)IntubatIon,and
crIcothyroIdotomy,canbeusedtosecuretheaIrwayIntheacutephaseInpatIents
requIrIngcervIcalspIneImmobIlIzatIon.The|cCoylaryngoscopeIsabletolIftthe
epIglottIsandmayImprovethelaryngealvIew:thecuffofaFogartycatheterattachedto
thetIpofthIsdevIcemayfurtherImproveexposure.AgumelastIcbougIepassedthrough
theendotrachealtube,orasatInsheathedstyletplacedthroughIts|urphyaperture,may
alsobehelpful;theycanbeInsertedthroughthelarynxmoreeasIlythanthetubeItself
becausetheIrsmalldIameterdoesnotblockthevIewoftheglottIsdurIngdIrect
laryngoscopy.TheWuScopeprovIdesaconsIstentlygoodlaryngealvIewwIthahIghrateof
successfulIntubatIonandmInImalneckmovement.
25
FlexIblefIberoptIclaryngoscopyand
translaryngealguIdedIntubatIon(see|axIllofacIalnjurIes)causealmostnoneck
movement,butbloodorsecretIonsIntheaIrway,alongpreparatIontIme,anddIffIcultyIn
theIruseIncomatose,uncooperatIve,oranesthetIzedpatIentsreducetheIrutIlItydurIng
InItIalmanagement.
NasotrachealIntubatIoncarrIestherIsksofepIstaxIs,faIlureofIntubatIon,andthe
possIbIlItyofentryoftheendotrachealtubeIntothecranIalvaultortheorbItIfthereIs
damagetothecranIalbaseorthemaxIllofacIalcomplex.AbsenceoftheusualsIgnsof
cranIalbasefracture(8attlesIgn,raccooneyes,orbleedIngfromtheearorthenose)
cannotberelIedontoexcludethepossIbIlItyofItsoccurrencebecausethesesIgnsmaynot
beImmedIatelyapparentwIthrapIdprehospItaltransport.
nthesubacutephaseofcervIcalspIneInjurywhentImeconstraInts,fullstomach,and
patIentcooperatIonIssuesdonotexIst,theuseofFD8Intheawake,sedatedpatIentwIth
approprIatetopIcalanesthesIaIspreferred.AdvantagesofthIstechnIquearemInImal
movementoftheneck,posItIonIngofthepatIentawake,maIntenanceofprotectIve
reflexes,andtheabIlItytoassesstheneurologIcstatusafterIntubatIon.
Direct Airway Injuries
0IrectaIrwaydamagecanoccuranywherebetweenthenasopharynxandthebronchI;
sometImesmorethanonesItemaybeInvolved,resultIngInpersIstentaIrwaydysfunctIon
afteroneoftheproblemsIscorrected.
26
Maxillofacial Injuries
naddItIontosofttIssueedemaofthepharynxandperIpharyngealhematoma,bloodor
debrIsIntheoropharynxmayberesponsIbleforpartIalorcompleteaIrwayobstructIonIn
theacutestageoftheseInjurIes.DccasIonally,teethorforeIgnbodIesInthepharynxmay
beaspIratedIntotheaIrway,causIngsomedegreeofobstructIon,whIchmayoccurorbe
recognIzedonlydurIngattemptsattrachealIntubatIon.AnotherproblemIsthedynamIc
natureofsofttIssueInjurIesInthIsregIon.AhematomaoredemaIntheface,tongue,or
neckmayexpanddurIngthefIrstseveralhoursafterInjuryandultImatelyoccludethe
aIrway.SerIousaIrwaycompromIsemaydevelopwIthInafewhoursInupto50ofpatIents
wIthmajorpenetratIngfacIalInjurIesormultIpletraumaasaresultofprogressIve
InflammatIonoredemaresultIngfromlIberaladmInIstratIonoffluIds.Theface,head,and
neckarevulnerabletomIssIleandexplosIonInjurIes.
27
Althoughrare,massIve
hemorrhage,mostfrequentlyfromtheInternalmaxIllaryarteryorItsbranches,maybe
lIfethreatenIng,requIrIngangIoembolIzatIon.
28
ProphylactIcIntubatIonofthetracheamay
avertaIrwaycompromIseInthesecIrcumstances.
FractureInducedencroachmentontheaIrwayorlImItatIonofmandIbularmovement,
paIn,andtrIsmusmaylImItmouthopenIng.FentanylIntItrateddosesofupto2to4g/kg
overaperIodof10to20mInutesmayproduceanImprovementInthepatIent'sabIlItyto
openthemouthIfmechanIcallImItatIonIsnotpresent.
TheselectIonofanaIrwaymanagementtechnIqueInthepresenceofamaxIllofacIal
fractureIsbasedonthepatIent'spresentIngcondItIon.|ostpatIentswIthIsolatedfacIal
InjurIesdonotrequIreemergencytrachealIntubatIon.Surgerymaybedelayedforaslong
asaweekwIthnoadverseeffectontherepaIr.PatIentswhopresentwIthaIrway
compromIsemaybeIntubatedusIngdIrectlaryngoscopy;thedecIsIonabouttheuseof
anesthetIcsandmusclerelaxantsIsbasedontheresultsofaIrwayevaluatIon.Whenthere
IsbleedIngIntotheoropharynx,aflexIblefIberoptIclaryngoscopemaybeuselessbecause
ofobstructIonofthevIew.AretrogradetechnIque,usIngawIreorepIduralcatheter
passedthrougha14gaugecatheterIntroducedIntothetracheathroughthecrIcothyroId
membrane,maybeusedIfthepatIentcanopenhIsorhermouth.AsurgIcalaIrwayIs
IndIcatedwhenthereIsaIrwaycompromIse,whendIrectlaryngoscopyhasfaIledorIs
consIderedImpossIble,whenthejawswIllbewIred,orwhenatracheostomywIllbe
performedanywayafterdefInItIverepaIrofthefracture.NasogastrIcornasotracheal
IntubatIonshouldbeavoIdedwhenabasIlarskullormaxIllaryfractureIssuspected
becauseofthepossIbIlItythatthetubemayenterthecranIumortheorbItalfossa.
HemorrhagIcshockandlIfethreatenIngcranIal,laryngotracheal,thoracIc,andcervIcal
spIneInjurIesmayaccompanymajorfacIalfractures
9,29
;aIrwaymanagementmustbe
taIloredaccordIngly.ThelIkelIhoodofcranIalInjuryIncreasesInmIdfacefractures
InvolvIngthefrontalsInus,aswellastheorbItozygomatIcandorbItoethmoIdcomplexes.
Cervical Airway Injuries
njurytothecervIcalaIrpassagescanresultfrombluntorpenetratIngtrauma.The
IncIdenceofbluntandpenetratInglaryngotrachealInjurIesadmIttedtomajortrauma
centersIs0.J4and4,respectIvely.
9
SImIlarlytomaxIllofacIalInjurIes,wartIme
laryngotrachealInjurIesaremoresevereandoccurmorefrequently(5to6)than
peacetImeInjurIes(0.91).
J0
AlthoughthepharynxandesophagusareclosetothecervIcal
aIrpassages,theIrInvolvementInpeacetIme
P.894
traumaIslesslIkelythanaIrwayInjurIes(0.08afterblunttraumaand0.9after
penetratIngtrauma).
9
ClInIcalsIgnssuchasescapeofaIr,hemoptysIs,andcoughIngare
presentInalmostallpatIentswIthpenetratIngInjurIes,facIlItatIngthedIagnosIs.n
contrast,majorbluntlaryngotrachealdamagemaybemIssed,eItherbecausethepatIentIs
asymptomatIcorunresponsIve,orbecausesuggestIvesIgnsandsymptomsaremIssedInthe
InItIalevaluatIon.
26
ThetypIcalpresentatIonIncludeshoarseness,muffledvoIce,dyspnea,
strIdor,dysphagIa,odynophagIa,cervIcalpaInandtenderness,ecchymosIs,subcutaneous
emphysema,andflattenIngofthethyroIdcartIlageprotuberance(Adam'sapple).Whether
thetraumaIsbluntorpenetratIng,attemptsatblIndtrachealIntubatIonmayproduce
furthertraumatothelarynxandcompleteaIrwayobstructIonIftheendotrachealtube
entersafalsepassageordIsruptsthecontInuItyofanalreadytenuousaIrway.
J1
Thus,
wheneverpossIble,IntubatIonofthetracheashouldbeperformedusInganFD8,orthe
aIrwayshouldbesecuredsurgIcally.ACTscanoftheneckprovIdesvaluableInformatIon
andshouldbeperformedbeforeanyaIrwayInterventIonInallstablepatIentswIthneck
InjuryandwIthoutrespIratoryandhemodynamIccompromIse.
ThestrategyfortrachealIntubatIondependsontheclInIcalpresentatIon.
J1
Thetracheasof
somepatIentswIthpenetratIngaIrwayInjurIes,especIallystabwounds,maybeIntubated
throughtheaIrwaydefectwIthouttheneedforanesthetIcsoroptIcalequIpment.The
presenceofcartIlagInousfracturesormucosalabnormalItIesnecessItatesawakeIntubatIon
wIthaFD8orawaketracheostomy.LaryngealdamageprecludescrIcothyroIdotomy.
TracheostomyshouldbeperformedwIthextremecautIonbecauseupto70ofpatIents
wIthbluntlaryngealInjurIesmayhaveanassocIatedcervIcalspIneInjury.
J1
UncooperatIve
orconfusedpatIentsmaynottolerateawakeaIrwaymanIpulatIon.tmaybebestto
transportthesepatIentstotheDF,InduceanesthesIawIthInhalatIonalagents,and
IntubatethetracheawIthoutmusclerelaxants.
J1
EpIsodesofaIrwayobstructIondurIng
spontaneousbreathIngunderanInhalatIonalanesthetIccanbemanagedbyposItIonIngthe
patIentuprIghtInaddItIontotheusualmaneuvers.CompletetransactIonofthetracheaIs
rare,butwhenItoccursItIslIfethreatenIng;thedIstalsegmentofthetrachearetracts
Intothechest,causIngaIrwayobstructIoneItherspontaneouslyordurIngaIrway
manIpulatIon.SurgeryInvolvespullIngupthedIstalendandperformInganendtoend
anastomosIstotheproxImalsegmentorsuturIngIttotheskInasapermanent
tracheostomy.nextremesItuatIons,suchascompleteornearcompletetransectIonofthe
larynxandtrachea,femorofemoralbypassorpercutaneouscardIopulmonarysupportmay
beconsIderedIftImepermIts.
J2
Thoracic Airway Injuries
WhereaspenetratIngtraumacancausedamagetoanysegmentoftheIntrathoracIc
aIrway,bluntInjuryusuallyInvolvestheposterIormembranousportIonofthetracheaand
themaInstembronchI,usuallywIthInapproxImatelyJcmofthecarIna.AsIgnIfIcant
numberoftheseInjurIesresultfromIatrogenIccausessuchastrachealIntubatIon.
JJ
Pneumothorax,pneumomedIastInum,pneumoperIcardIum,subcutaneousemphysema,and
acontInuousaIrleakfromthechesttubearetheusualsIgnsofthIsInjury;theyoccur
frequentlybutarenotspecIfIcforthoracIcaIrwaydamage.npatIentsIntubatedwIthout
thesuspIcIonofatrachealInjury,dIffIcultyInobtaInIngasealaroundtheendotracheal
tubeorthepresenceonachestradIographofalargeradIolucentareaInthetrachea
correspondIngtothecuffsuggestsaperforatedaIrway.DtherradIographIcfIndIngsInclude
aradIolucentlInealongtheprevertebralfascIaduetoaIrtrackIngupfromthe
medIastInum,perIbronchIalaIrorsuddenobstructIonalonganaIrfIlledbronchus,andthe
droppedlungsIgnwhencompleteIntrapleuralbronchIaltransectIoncausestheapexof
thecollapsedlungtodescendtothelevelofthehIlum.AIrwaymanagementIssImIlarto
thatofcervIcalaIrwayInjury.AnesthetIcs,andespecIallymusclerelaxants,mayproduce
IrreversIbleobstructIon,presumablybecauseofrelaxatIonofstructuresthatmaIntaInthe
aIrwaypatentIntheawakepatIent;however,aIrwaylossmayalsooccurdurIngattempts
atawakeIntubatIon,oftenasaresultoffurtherdIstortIonoftheaIrwaybythe
endotrachealtube,patIentagItatIon,orrebleedIngIntotheaIrway.
J4
AfterIntubatIonof
thetrachea,theadequacyofaIrwayInterventIonIsevaluatedmaInlybyauscultatIonand
capnography.PulmonarycontusIon,atelectasIs,dIaphragmatIcrupturewIththoracIc
mIgratIonoftheabdomInalcontents,andpneumothoraxmaycomplIcatethe
InterpretatIonofchestauscultatIon.LIkewIse,CD
2
elImInatIonmaybedecreasedorabsent
InshockandcardIacarrest.
TheoutcomeaftersurgIcalrepaIroftheseInjurIesIsoftensuboptImalandcomplIcatedby
stumpleakandempyema,suturelInestenosIs,ortheneedfortracheostomyor
pneumonectomy.TherecenttrendIsselectIveconservatIvemanagement.PatIentswIth
lesIonslargerthan4cm,cartIlagInousratherthanmembranousInjurIes,concomItant
esophagealtrauma,progressIvesubcutaneousemphysema,severedyspnearequIrIng
IntubatIonandventIlatIon,dIffIcultywIthmechanIcalventIlatIon,pneumothoraxwIthan
aIrleakthroughthechestdraIns,and/ormedIastInItIsarestIllmanagedsurgIcally.Those
wIthouttheseproblemsmaybetreatednonoperatIvelywIthareasonableoutcome.
JJ
Management of Breathing Abnormalities
DftheseveralcausesthatmayalterrespIratIonaftertrauma,tensIonpneumothorax,flaIl
chest,andopenpneumothoraxareImmedIatethreatstothepatIent'slIfeandtherefore
requIrerapIddIagnosIsandtreatment.Hemothorax,closedpneumothorax,pulmonary
contusIon,dIaphragmatIcrupturewIthhernIatIonofabdomInalcontentsIntothethorax,
andatelectasIsfromamucousplug,aspIratIon,orchestwallsplIntIngcanalsoInterfere
wIthbreathIngandpulmonarygasexchangeanddeterIorateIntolIfethreatenIng
complIcatIons.
AlthoughcyanosIs,tachypnea,hypotensIon,neckveIndIstentIon,trachealdevIatIon,and
dImInIshedbreathsoundsontheaffectedsIdearetheclassIcsIgnsoftensIon
pneumothorax,neckveIndIstentIonmaybeabsentInhypovolemIcpatIentsandtracheal
devIatIonmaybedIffIculttoapprecIate.ThedefInItIvedIagnosIsIsestablIshedbychest
radIograph;however,InhypoxemIcandhypotensIvepatIents,ImmedIateInsertIonofa14
gaugeangIocatheterthroughthefourthIntercostalspaceInthemIdaxIllarylIneor,at
tImes,throughthesecondIntercostalspaceatthemIdclavIcularlIneIsessentIal.ThereIs
notImeforradIologIcconfIrmatIonInthIssettIng.
AflaIlchestresultsfromfracturesofmorethantwosItesofatleastthreeadjacentrIbsor
rIbfractureswIthassocIatedcostochondralseparatIonorsternalfracture.AnunderlyIng
pulmonarycontusIonwIthIncreasedelastIcrecoIlofthelungandworkofbreathIngIsthe
maIncauseofrespIratoryInsuffIcIencyorfaIlureandresultInghypoxemIa.
J5
toften
developsoveraJto6hourperIod,causInggradualdeterIoratIonofthechestradIograph
andarterIalbloodgases.
J5
CoexIstInghemopneumothorax,paradoxIcalchestwall
movement,and/orpaInInducedsplIntIngmaycontrIbutetothegasexchange
abnormalItIes.FepeatedevaluatIonbyphysIcalexamInatIon,chestradIograph,and
arterIalbloodgasdetermInatIonsIsessentIalforearlyrecognItIonofthesecomplIcatIons.
ThefractIonoflungvolumecontused,asdetermInedbychestradIographorCTscan,may
bepredIctIveofthesubsequentdevelopmentofacuterespIratorydIstresssyndrome
(AF0S);thelIkelIhoodIncreasesabruptlyoncethecontusIonvolumeexceeds20oftotal
lungvolume
J6
(seeChapter56).WIthoutsIgnIfIcantgasexchangeabnormalItIes,chestwall
InstabIlItyaloneIsnotan
P.895
IndIcatIonforrespIratorysupport.ThereIsevIdencethatlIberaluseoftrachealIntubatIon
andmechanIcalventIlatIonInthepresenceofaflaIlchestorpulmonarycontusIon
IncreasestherateofpulmonarycomplIcatIonsandmortalIty,andprolongsthehospItal
stay.
J5
EffectIvepaInrelIefbyItselfcanImproverespIratoryfunctIonandoftenavoIdthe
needformechanIcalventIlatIon.ForthIspurpose,contInuousepIduralanalgesIawIthlocal
anesthetIcsandopIoIds,preferablydIrectedtothoracIcsegments,provIdesbetterpaIn
relIefandventIlatoryfunctIonthanparenteralopIoIds,reducIngmorbIdItyandmortalItyIn
elderlypatIentswIthchestwalltrauma
J7
(seeChapter57).DthertherapeutIcmeasures
Includesupplementaloxygen,contInuousposItIveaIrwaypressureof10to15cmH
2
Dby
facemask,aIrwayhumIdIfIcatIon,chestphysIotherapy,IncentIvespIrometry,
bronchodIlators,aIrwaysuctIonIng(usIngfIberoptIcbronchoscopy,Ifnecessary),and
nutrItIonalsupport.
J5
DverzealousInfusIonoffluIdsandtransfusIonofbloodproductsmay
resultIndeterIoratIonofoxygenatIonbyworsenIngtheunderlyIngpulmonaryInjury.
J5,J8
npatIentswIthpulmonarycontusIon,respIratoryInsuffIcIency,orfaIluredespIteadequate
analgesIa,clInIcalevIdenceofsevereshock,assocIatedsevereheadInjury,orInjury
requIrIngsurgery,aIrwayobstructIon,andsIgnIfIcantpreexIstIngchronIcpulmonary
dIseaseareIndIcatIonsfortrachealIntubatIonandmechanIcalventIlatIon.PosItIveend
expIratorypressure(PEEP)wIthlowtIdalvolumes(6to8mL/kg)andlowInspIratory
alveolarorplateaupressuresshouldbeusedtodecreasethelIkelIhoodofAF0SIf
ventIlatIonIscontrolled.nIntubated,spontaneouslybreathIngpatIents,aIrwaypressure
releaseventIlatIon,InwhIchspontaneousbreathIngIssuperImposedonmechanIcal
ventIlatIonbyIntermIttentsudden,brIefdecreaseofcontInuousposItIveaIrwaypressure,
provIdesImproved[7wIthdotabove]/[QwIthdotabove]matchIngandsystemIcblood
pressure,lowersedatIonrequIrements,greaterD
2
delIvery,andshorterperIodsof
IntubatIon.
J5,J9
SevereunIlateralpulmonarycontusIonthatIsunresponsIvetothese
measuresmaybetreatedbydIfferentIallungventIlatIonvIaadoublelumenendobronchIal
tube.nbIlateralseverecontusIonswIthlIfethreatenInghypoxemIa,hIghfrequencyjet
ventIlatIonmayenhanceoxygenatIonandcardIacfunctIon,whIchmaybecompromIsedby
concomItantmyocardIalcontusIonorIschemIa.
40
SystemIcaIrembolIsmoccursmaInlyafterpenetratInglungtraumaandblastInjurIes,and
lessfrequentlyafterbluntthoracIctraumathatproduceslaceratIonsofbothdIstalaIr
passagesandpulmonaryveIns
41
;posItIvepressureventIlatIonaftertrachealIntubatIon
maythenresultInentraInmentofaIrIntothesystemIccIrculatIon.HemoptysIs,
cIrculatory,andCNSdysfunctIonImmedIatelyafterstartIngartIfIcIalventIlatIon,aswellas
detectIonofaIrInbloodfromtheradIalartery,establIshesthedIagnosIs.AIrbubblesmay
alsobeseenInthecoronaryarterIesdurIngthoracotomy.SurgIcalmanagementInvolves
ImmedIatethoracotomyandclampIngofthehIlumofthelaceratedlung.FespIratory
maneuversthatmInImIzeorpreventaIrentryIntothesystemIccIrculatIonInclude
IsolatIngandcollapsIngthelaceratedlungbymeansofadoublelumentube,orventIlatIon
wIththelowestpossIbletIdalvolumesvIaasInglelumentube.
41
Transesophageal
echocardIography(TEE)oftheleftsIdeoftheheartmaypermItvIsualIzatIonofaIrbubbles
andtheIrdIsappearancewIththerapeutIcmaneuvers.
Management of Shock
HemorrhageIsthemostcommoncauseoftraumatIchypotensIonandshock.Dthercauses
areabnormalpumpfunctIon(myocardIalcontusIon,perIcardIaltamponade,preexIstIng
cardIacdIsease,orcoronaryarteryorcardIacvalveInjury),pneumothoraxorhemothorax,
spInalcordInjury,and,rarely,anaphylaxIsorsepsIs(TableJ61).
EvaluatIonoftheseverItyofhemorrhagIcshockIntheInItIalphaseIsbasedonafew
relatIvelyInsensItIveandnonspecIfIcclInIcalsIgns.Forexample,tachycardIa,whIchIs
tradItIonallyusedasanIndexofhypovolemIa,maybeabsentInuptoJ0ofhypotensIve
traumapatIentsbecauseofIncreasedvagaltone,chronIccocaIneuse,orotherreasons.
42
ncontrast,byIncreasIngcatecholamIneoutput,tIssueInjuryandassocIatedpaInmay
maIntaIntachycardIaandnormalorelevatedsystemIcbloodpressureInthepresenceor
absenceofhypovolemIawIthoutnecessarIlyIncreasIngthecardIacIndexortIssueoxygen
delIvery.nfact,InthIssItuatIonanIncreaseInIntestInalvascularresIstanceanda
decreaseInsplanchnIcbloodflowmayoccur,andIfprolonged,mayallowentryof
IntestInalmIcroorganIsmsIntothecIrculatIonandIncreasethelIkelIhoodofsubsequent
sepsIsandorganfaIlure.
4J,44,45
Thus,equatInganormalheartrateandsystemIcblood
pressurewIthnormovolemIadurIngInItIalresuscItatIonmayleadtolossofvaluabletIme
fortreatIngunderlyIngocculthypovolemIaorhypoperfusIon.Nevertheless,heartrate,
systemIcbloodpressure,pulsepressure,respIratoryrate,urIneoutput,andmentalstatus
remaIntheavaIlableearlyclInIcalIndIcatorsoftheseverItyofhemorrhagIcshock
4J,46
(TableJ62).
SomeoftheprovenmarkersoforganperfusIoncanbeuseddurIngearlymanagementto
setthegoalsofresuscItatIon.Dfthese,thebasedefIcItandbloodlactatelevelarethe
mostusefulandpractIcaltoolsdurIngallphasesofshock,IncludIngtheearlIest.Thebase
defIcItreflectstheseverItyofshock,theoxygendebt,changesInD
2
delIvery,the
adequacyoffluIdresuscItatIon,andthelIkelIhoodofmultIpleorganfaIlureandsurvIval
wIthreasonableaccuracyInpreviously healthyadultandpedIatrIctraumapatIents.
47,48
A
basedefIcItbetween2and5mmol/LsuggestsmIldshock,between6and14mmol/L
IndIcatesmoderateshock,whereas14mmol/LIsasIgnofsevereshock.AnadmIssIonbase
defIcItInexcessof5to8mmol/LcorrelateswIthIncreasedmortalIty.
47,48
Thus,
normalIzatIonofthebasedefIcItIsoneoftheendpoIntsofresuscItatIon.
49,50
ElevatIonofthebloodlactatelevelIslessspecIfIcthanbasedefIcItasamarkeroftIssue
hypoxIabecauseItcanbegeneratedInwelloxygenatedtIssuesbyIncreasedepInephrIne
InducedskeletalmuscleglycolysIs,acceleratedpyruvateoxIdatIon,decreasedhepatIc
clearanceoflactate,andearlymItochondrIaldysfunctIon.
51
AllthesecondItIonsmaybe
presentInthetraumapatIent.Nevertheless,InmosttraumapatIentsanelevatedlactate
levelcorrelateswIthothersIgnsofhypoperfusIon,renderIngItanImportantmarkerof
dysoxIaandanendpoIntofresuscItatIon.ThenormalplasmalactateconcentratIonIs0.5
to1.5mmol/L;levelsabove5mmol/LIndIcatesIgnIfIcantlactIcacIdosIs.ThehalflIfeof
lactateIsapproxImatelyJhours;thus,theleveldecreasesrathergraduallyafter
correctIonofthecause.FaIluretoclearlactatewIthIn24hoursafterreversalof
cIrculatoryshockIsapredIctorofIncreasedmortalIty.
52
TheresponseofthepulseandbloodpressuretoInItIalfluIdtherapyalsoaIdsInthe
assessmentofhypovolemIa.
4J
nhypotensIveandtachycardIcpatIents,admInIstratIonof
lactatedFInger(LF)solutIon,2,000mLover15mInutesInadultsor20mL/kgInchIldren,
shouldnormalIzethevItalsIgnsIfhemorrhageIsmIld(10to20).AtransIentImprovement
afterfluIdInfusIonsuggestsa20to40decreaseIncIrculatIngvolumeorcontInuIngblood
loss.|orecrystalloIdsandpossIblybloodtransfusIonarerequIredInthesepatIents.fthe
vItalsIgnsdonotrespondtoInItIalfluIdresuscItatIon,therehasprobablybeensevere
(40)bloodand/orvolumeloss,whIchmustbereplacedbyrapIdInfusIonofcrystalloIds,
colloIds,andblood.TradItIonally,asystolIcbloodpressure90mmHgIsusedtodefIne
shockdurIngtheearlyphaseoftraumamanagement,IncludIngtheIntraoperatIveperIod.
FecentdatafromtwotraumacentersrevIewIngtherelatIonshIpbetweenInItIalsystolIc
bloodpressureandmortalIty,basedefIcIt,lengthofstay,andInfectIonratesuggestthata
valueof
P.896
P.897
110mmHgshouldbeconsIderedforthIspurpose
5J,54
(FIg.J62).
Table 36-1 Guidelines For Management of Traumatic Shock

ETIOLOGY
Hemorrhage or
Extensive Tissue
Injury
Cardiac Tamponade
Myocardial
Contusion
Pneumothorax or
Hemothorax
PrImary
mechanIsms
HypovolemIa
7entrIcularInflow
restrIctIon
0ImInIshed
ventrIcular
performance
and
elevated
pulmonary
vascular
resIstance
Lungcollapse
|edIastInal
shIft,causIng
Inflowand
outflow
obstructIonof
theheart
TypIcal
sIgnsand
symptoms
TachycardIa
Narrowpulse
pressure
Cold,clammy
skInfrom
vasoconstrIctIon
TachycardIa
HypotensIon
0Ilatedand
engorgedneck
veIns
|uffledheart
sounds
0ImInIshed8P
responsetofluId
challenge
0ysrhythmIa
TachycardIa
HypotensIon
TachycardIa
HypotensIon
0Ilatedand
engorgedneck
veIns
Absentbreath
sounds
Hyperresonance
topercussIon
TrachealshIft
0yspnea
Subcutaneous
emphysema
Treatment
contInuum,
fromleast
tomost
Intense
CrystalloIds
InItIally
TransfusIonIf
2,000mLof
crystalloIdIn15
mIndoesnot
restore8P
PerIcardIocentesIs
PerIcardIal
wIndow
Emergency
department
thoracotomy
FluIds
FluIdsand
vasodIlators
FluIdsand
Inotropes
FeleaseofaIr
wIth14gauge
catheter
Chesttube
8P,bloodpressure.
Table 36-2 Advanced Trauma Life Support Classification of Hemorrhagic
Shock
a
CLASS I CLASS II CLASS III CLASS IV
8loodloss(mL) 750 7501,500 1,5002,000 2,000
8loodloss(blood
volume)
15 15J0 J040 40
Pulserate(permIn) 100 100 120 140
8loodpressure Normal Normal 0ecreased 0ecreased
Pulsepressure
Normalor
Increased
0ecreased 0ecreased 0ecreased
FespIratoryrate
(breaths/mIn)
1420 20J0 J040 J5
UrIneoutput
(mL/hr)
J0 20J0 515 NeglIgIble
|entalstatus
SlIghtly
anxIous
|Ildly
anxIous
AnxIousand
confused
Confused,
lethargIc
FluIdreplacement
(J:1rule)
b
CrystalloId CrystalloId
CrystalloId+
blood
CrystalloId
+blood
a
Fora70kgmalepatIent,basedonInItIalpresentatIon.
b
TheJ:1ruleIsbasedonempIrIcobservatIonthatmostpatIentsrequIreJ00mL
balancedelectrolytesolutIonforeach100mLbloodloss.WIthoutotherclInIcal
andmonItorIngparameters,thIsguIdelInemayresultInexcessIveorInadequate
fluIdresuscItatIon.
AdaptedfromAmerIcanCollegeofSurgeons,CommItteeonTrauma:Shock,
AdvancedTraumaLIfeSupportCourseforPhysIcIans.ChIcago,AmerIcanCollegeof
Surgeons,1997,p108.wIthpermIssIon.
8Ickelletal.
55
showedthatdelayIngfluIdresuscItatIonuntIlsurgIcalcontrolofbleedIngIn
patIentswIthpenetratIngtraumaImprovedsurvIvaltohospItaldIschargeanddecreased
thelengthofhospItalstay.7IgorousfluIdtherapyIncreasesarterIalandvenouspressures,
dIlutesclottIngfactorsandplatelets,anddecreasesbloodvIscosIty,andthusmay
reInItIatebleedIngalreadystoppedbyasoftthrombus.AlthoughmanyexperImental
studIeshaveconfIrmedthesefIndIngs,IthasalsobecomeclearthatwIthholdIngfluIds
completelycanresultInasmuchharmasvIgorousresuscItatIon.
56
ncontrast,slow
InfusIonofIsotonIcorhypertonIccrystalloIds,andpreferablyofpackedredbloodcells
(PF8Cs),tItratedtolowerthannormalsystemIcpressure,hadbenefIcIaleffectsonanImal
survIvalwIthouttIssueInjuryororganfaIlure.AclInIcalstudyconductedsubsequentto
thatof8Ickelletal.faIledtodemonstrateanydecreaseInmortalIty.
57
Nevertheless,
althoughthIspractIceIscontraIndIcatedIntraumatIcbraInandspInalcordInjurIesIn
whIchadequateperfusIonIscrucIal,ItemphasIzestheusefulfactthatfluIdadmInIstratIon
InexcessofthatneededforachIevIngnormovolemIaprIortocontrolofhemorrhagemay
bedeleterIous.
AreasonabletransfusIonthresholdIsahematocrIt25foryoung,healthypatIentsand
J0forolderpatIentsorthosewIthcoronaryorcerebrovasculardIsease.TransfusIonof
PF8CsIsshowntobeanIndependentrIskfactorformortalItyandIntensIvecareunIt(CU)
andhospItallengthofstayIntraumapatIents;thIsfIndIngwastrueIndependentofthe
severItyofshock.
58
Nevertheless,thIsconcernshouldnotprecludetImelyandadequate
admInIstratIonofbloodproducts.Normally,typespecIfIccrossmatchedbloodcanbe
avaIlableInmostcentersInaboutJ0mInutes,IncludIngtransporttIme.TypespecIfIc
uncrossmatchedbloodcanbeavaIlableInevenlesstImeforpatIentswIthsevere
hemorrhage.However,IfthesItuatIondIctatesImmedIatetransfusIon,typeDFh+bloodIs
satIsfactoryInmostsItuatIons.ControversyexIstsabouttheuseofuncrossmatchedtypeD
PF8CsbecauseofconcernaboutthedevelopmentofalloantIbodIesandallergIcreactIons.
0uttonetal.,
59
revIewIngtheIrexperIenceIn161patIentsreceIvIng581unItsofunIversal
donorblood,demonstratedthatonlyoneofthe10FhmalepatIentsreceIvIngDFh+blood
developedalloantIbodIes.AllfourfemalepatIentsIntheserIesreceIvedtypeDFhblood
wIthoutapparentproblem.
Figure 36-2.FelatIonshIpbetweenemergencydepartment(E0)systolIcblood
pressure,basedefIcIt,andoverallmortalItyrateoftraumapatIents;headInjury
patIentsarenotIncluded.NotethatmortalItyandbasedefIcItdecreaseassystolIc
bloodpressureIncreases,stabIlIzIngat110mmHgratherthanatthegenerally
accepted90mmHg.(AdaptedfromEastrIdge8J,SalInasJ,|c|anusJCetal:
HypotensIonbegInsat110mmHg:redefInInghypotensIonwIthdata.JTrauma2007;
6J:291,wIthpermIssIon.)
DneoftheprIncIpalgoalsdurIngearlymanagementofthehemorrhagIngtraumapatIentIs
toavoIdthedevelopmentofthesocalledvIcIouscycleorlethaltrIad,consIstIngof
acIdosIs,hypothermIa,andcoagulopathy(FIg.J6J).8othacIdosIsandhypothermIaare
majorfactorsIntheInductIonofcoagulopathy.FesuscItatIonwIthfluIdsandPF8Cs,whIch
havenohemostatIcactIvIty,furtheraddstothIseffectbydIlutIngplateletsalready
reducedInnumberanddysfunctIonalandcoagulatIonfactors(seeChapter16).8leedIng
andIntravascularcoagulatIonfurtheraugmentcoagulopathyvIalossorconsumptIonof
damagedordepletedplateletsandcoagulatIon
P.898
factors.AugmentedcoagulopathyfurtherIncreasesthebloodloss,necessItatIngaddItIonal
fluIdreplacementandmaIntaInIngthevIcIouscycle.
Figure 36-3.SchematIcrepresentatIonofbloodyvIcIouscycleorlethaltrIad.
TraumaInducedhemorrhagecausesacIdosIs,hypothermIa,andcoagulopathy.AcIdosIs
andhypothermIaproducefactorandplateletdysfunctIonenhancIngcoagulopathy,
whIchInturncausesIncreasedbleedIng.ThecyclecontInuesuntIldeathensues,unless
effectIvetreatmentbytImelycontrolofbleedIngandcorrectIonofacIdosIs,
hypothermIa,andcoagulopathyIsInstItuted.
ThecurrentpractIceofadmInIsterInglargevolumesofcrystalloIds,colloIds,andPF8Cs
wIthnohemostatIccomponentsforInItIalresuscItatIonIsconsIderedtobethemajor
factorInthedevelopmentofoftenlethalcoagulopathy.|osttraumapatIentsare
hypercoagulablewhenadmIttedtotheemergencydepartmentanddonotdevelop
coagulopathywhenadmInIstratIonofhemostatIcagentsIsdelayed.However,Inthe
estImated10ofpatIentswIthseveretraumaandshockwhoenterthehospItalIna
hypocoagulablestate
60
orrapIdlydevelophypocoagulatIon,resuscItatIvefluIdsandPF8Cs
mayfurtherworsenthecoagulopathyandfacIlItatethevIcIouscycle.Acomputer
sImulatIonstudybyHIrshbergetal.
61
clearlydemonstratedthatwIthcurrentfluId
resuscItatIontechnIques,mostmajortraumapatIentsarecoagulopathIcatthetImethey
arrIvetotheDF.ntheIrstudy,theprothrombIntIme(PT)wouldIncreasetobelow
hemostatIclevelsafterreplacementofonebloodvolume,fIbrInogenwoulddecayat
replacementof1.25bloodvolumes,andfInally,plateletsatalossof1.75bloodvolumes.
ExperIencegaInedfromtheraqandAfghanIstanwarsatteststotheaccuracyofthe
fIndIngsofHIrshbergetal.;Holcombetal.
62
stronglyrecommendstartInglIquIdplasma
replacementalongwIthfluIdsandPF8CsassoonasthepatIentarrIvesIntheemergency
department,andcontInuIngItthroughoutsurgery.
LIquIdplasmadIffersfromfreshfrozenplasma(FFP)InthatItIsfrozenat180`CwIthIn8
to24hours,whereasFFPIsfrozenwIthIn8hours.tcontaInsallofthestableproteIns
foundInFFP,althoughInslIghtlylowerconcentratIons.ThemajordIfferenceIsa25
reductIonoffactor7.DneunItofFFPcontaInsapproxImately7ofthecoagulatIon
factoractIvItyofa70kgman.ThawIngofFFPorlIquIdplasmatakesaboutJ0mInutes.
TherecommendedratIoofFFPandplateletstoPF8CsvarIeswIdely,rangIngfrom1:10to
2:JforFFPtoPF8Csandfrom6:10to12:10forplateletstoF8Cs.
6J
Nevertheless,recent
mIlItarydatademonstratethatthedeathratewas65whentheplasmatoPF8CsratIo
was1:8,J4whenItwas1:2.5,and19whenItwas1:1.4.
64
Currently,manytraumacentersusehemostatic resuscitation protocolsdurIngInItIal
resuscItatIonofmajortraumatIchemorrhageIntheemergencydepartmentandDF.These
InvolveadmInIsterIngarelatIvelylImItedquantItyofcrystalloIdsolutIonsandvolume
replacementwIthlIquIdplasmaandPF8Cs.naddItIon,plateletsandcryoprecIpItateare
gIvenregularlyand,InspecIalsItuatIons,recombInantfactor7a(rF7a)IsadmInIstered.
ProthrombIncomplexconcentratesarealsolIkelytobeaddedtothIsprotocolInthenear
future.
Dnesuchprotocol,usedInParkland|emorIalHospItalIn0allas,Texas,Involvesregular
shIpmentfromthebloodbankofpackagedbloodproducts,IncludIng5unItsofPF8Cs,2
unItsofthawedplasma,5unItsofplatelets,and10unItsofcryoprecIpItateIneach
package.PlasmaandPF8CsaresenteveryJ0mInutes,andplateletsandcryoprecIpItate
everyhour.FecombInantfactor7a,Ifdeemednecessary,IsprovIdedearlydurIng
resuscItatIon.ThenumberofunItsIneachpackagecanbedoubledonrequest,If
necessary.
65
FapIdestablIshmentofvenousaccesswIthlargeborecannulasplacedIn
perIpheralveInsthatdraInbothaboveandbelowthedIaphragmIsessentIalforadequate
fluIdresuscItatIonInthepatIentwhoIsseverelyInjured.Whenvascularcollapseand
extremItyInjuryImpaIraccesstoarmorlegvessels,percutaneouscannulatIonofthe
Internaljugular,subclavIan,orfemoralveInscanbeperformed.UltrasoundguIdancemay
facIlItatecannulatIonoftheInternaljugularveInandpreventneedleentryandInfusIonof
fluIdsIntothepleuralspaceInpatIentswIthalargehemothorax.
66
Ultrasoundmayalsobe
usedforInfraclavIcularaccesstotheaxIllaryveIn,
67
ortothecephalIcorbasIlIcveInsat
themIdarmlevel.
68
fnecessary,acutdowntoasaphenousorarmveIncanberapIdly
performedInolderchIldrenandadults.nchIldrenyoungerthan5yearsofage,
IntraosseouscannulatIonhasahIghsuccessrateandalowIncIdenceofcomplIcatIons.
nfusIonratescomparablewIththoseobtaInedwIthIntravenouslInesarepossIbleInsmall
chIldren,althoughapressureInfusIondevIcemaybenecessarytoachIeveadequateflow.
69
AspecIalscrewtypeneedleortheneedleofa16or18gaugeangIocatheterIsIntroduced
IntothebonemarrowofthedIstalfemurorproxImaltIbIaatthelevelofItstuberosIty.
CareshouldbetakennottoInjuretheepIphysealplatedurIngpuncture.Properplacement
IsIndIcatedbylossofresIstancetofluIdInjectIonoraspIratIonofmarrow.
PatIentswhoarrIveIntheemergencydepartmentIncardIacarrestrequIreadvanced
cardIaclIfesupport(seeChapter59).However,thesuccessrateofexternalcardIac
massageInhypovolemIctraumapatIentsIslIkelytobelow.
70
Emergencydepartment
thoracotomynotonlypermItsperformanceofopencardIacmassage,butalsoaIds
resuscItatIoneffortsbyallowIngdraInageofperIcardIalblood,controlofcardIacandgreat
vesselbleedIng,applIcatIonofacrossclamptotheaorta,andrapIdadmInIstratIonof
fluIdsthroughasmallFoleycatheterIntroducedIntotherIghtatrIum,orIndesperate
sItuatIons,throughalargeborecatheterorIntroducerInthedescendIngaorta.ThIs
procedureIsnotIndIcatedInblunttorsotrauma;themortalItyrateIssImIlarregardlessof
whetherItIsattempted.
71
npenetratIngInjurIes,dependIngonthepresentIngcondItIonof
thepatIent,theInItIalsuccessratemaybeashIghas70,buttheneurologIcallyIntact
hospItaldIschargerateIsonly10to15.
71,72
Early Management of Specific Injuries
Head Injury
ApproxImately40ofdeathsfromtraumaarecausedbyheadInjury,andIndeed,evena
moderatebraInInjurymayIncreasethemortalItyrateofpatIentswIthotherInjurIes.n
nonsurvIvors,progressIonofthedamagedareabeyondthedIrectlyInjuredregIon
(secondarybraInInjury)canbedemonstratedatautopsy.
7J
ThemajorfactorInsecondary
InjuryIstIssuehypoxIa,whIchresultsInlactIcacIdosIs,freeradIcalgeneratIon,
prostaglandInsynthesIsandreleaseofexcItatory
P.899
amInoacIds(prImarIlyglutamate),lIpIdperoxIdatIonandbreakdownofcellmembranes,
entryoflargequantItIesofsodIum,calcIum,andwaterIntothecells,andleakageoffluId
fromthebloodvesselsIntotheextracellularspace.
74,75
ThIsprocessresultsInbraInedema
andbothregIonalandglobaldIsturbancesofthecerebralcIrculatIon.Thus,ofallthe
possIblesecondaryInsultstotheInjuredbraIn,decreasedoxygendelIveryasaresultof
hypotensIonandhypoxIahasthegreatestdetrImentalImpact
76,77
(TableJ6J).
Table 36-3 Effects on Outcome of Secondary Insults Occurring from Time
of Injury Through Resuscitation
a
Secondary Insults
No. of
Patients
% of TOTAL Patients
6-MONTH OUTCOME (%)
Good/Moderate Severe/Vegetative Dead
Totalcases 717 100 4J.0 20.2 J6.8
NeIther J08 4J.0 6J.9 10.2 26.9
HypoxIa 161 22.4 50.J 21.7 28.0
HypotensIon 62 11.4 J2.9 17.1 50.0
8oth 166 2J.2 20.5 22.J 57.2
a
0atafromhospItalemergencydepartmentsenrolledInTraumatIcComa0ata
8ank.
FeprIntedfromPrough0S,LangJ:TherapyofpatIentswIthheadInjurIes:Key
parametersformanagement.JTrauma1997;42(Suppl):10S,wIthpermIssIon.
8raInInjurybyItselfdoesnotcausehypotensIonInadultsexceptasapretermInalevent.
However,morethanhalfofpatIentswIthsevereheadtraumahaveotherInjurIesthat
renderapproxImately15ofthemhypotensIve;approxImatelyJ0arehypoxIcon
admIssIonasaresultofcentralrespIratorydepressIonorassocIatedchestInjurIes.
Furthermore,exposuretotheseInsultsIslIkelytooccurdurInganyphaseofthecontInuum
ofhospItalcare:IntheradIologyunIt,theDF,therecoveryroom,theCU,orelsewhere.
ThemostcommonearlycomplIcatIonsofheadtraumaareIntracranIalhypertensIon,braIn
hernIatIon,seIzures,neurogenIcpulmonaryedema,cardIacdysrhythmIas,bradycardIa,
systemIchypertensIon,andcoagulopathy.
Diagnosis
|entalImpaIrmentaftertraumamayhaveanyofseveraletIologIes.However,the
possIbIlItyofhypoxIaandshockmustalwaysbeconsIderedfIrst.fconscIousnessremaIns
depresseddespIteventIlatIonandfluIdreplacement,aheadInjuryIsassumedtobe
presentandthepatIentIsmanagedaccordIngly.Asnoted,hypotensIonIsthemost
ImportantcauseofdeathIntheheadInjuredpatIent.Chesnut
77
demonstratedthatasIngle
epIsodeofsystolIcbloodpressure90mmHgIsassocIatedwItha50IncreaseInmortalIty,
andsubsequentepIsodesorlowerpressures
78
IncreasemortalItyevenfurther.Therefore,
everyeffortshouldbemadetosupportthebloodpressurewIthfluIdsandvasopressors
(preferablyphenylephrIne,whIchdoesnotconstrIctcerebralvessels),andensureadequate
oxygenatIonbeforetheunconscIouspatIentIsevaluated.AbaselIneneurologIc
examInatIonshouldbeperformedafterInItIalresuscItatIon,butbeforeanysedatIveor
musclerelaxantagentsareadmInIstered,andshouldberepeatedatfrequentIntervals
becausethepatIent'scondItIonmaychangerapIdly.AnesthetIcandadjunctdrugsmay
renderanadequateneurologIcexamInatIonImpossIble;thus,longactIngmusclerelaxants,
opIoIds,sedatIves,orhypnotIcsshouldbegIvenselectIvely.
76,79
ConscIousnesscanbeInItIallyassessedwIthInafewsecondsusIngtheA7PUsystem(alert;
respondstoverbalstImulI;respondstopaIn;unresponsIve;TableJ64).|oreprecIse
InformatIonIsprovIdedbytheCCSscore(TableJ64),whIchprovIdesastandardmeansof
evaluatIngthepatIent'sneurologIcstatus.nthIstest,thesumofthescoresobtaInedfor
eyeopenIng,verbalresponse,andmotoractIvItycorrelateswIththestateof
conscIousness,theseverItyoftheheadInjury,andtheprognosIs.
79
Assessmentofmotor
functIonshouldbeperformedontheextremItythatrespondsbest.ThelImbaffectedby
neurologIcInjuryIsexamIned,buttheresultIsnotconsIderedIntheCCSscore.
0IlatatIonandsluggIshresponseofthepupIlIsasIgnofcompressIonoftheoculomotor
nervebythemedIalportIonof
P.900
thetemporallobe(uncus).AmaxImallydIlatedandunresponsIveblownpupIlsuggests
uncalhernIatIonunderthefalxcerebrI.ThepresenceofsImIlarfIndIngsInocularInjurIes
makesInterpretatIonofpupIllaryfIndIngsdIffIcultwheneyeandheadInjurIescoexIst.
However,thepupIllaryreactIontolIghtIsusuallymoresluggIshIntheheadInjured
patIent.
Table 36-4 Two-Level Initial Evaluation of Consciousness
LEVEL 1. AVPU SYSTEM
A=Alert
7=FespondstoverbalstImulI
P=FespondstopaInfulstImulI
U=UnresponsIve
LEVEL 2. GLASGOW COMA SCALE (GCS)
a
EyeopenIng(E)
Spontaneous,alreadyopenandblInkIng 4
Tospeech J
TopaIn 2
None 1
7erbalresponse(7)
DrIented 5
Answersbutconfused 4
napproprIatebutrecognIzablewords J
ncomprehensIblesounds 2
None 1
8estmotorresponse(|)
Dbeysverbalcommands 6
LocalIzespaInfulstImulus 5
WIthdrawsfrompaInfulstImulus 4
0ecortIcateposturIng(upperextremItyflexIon) J
0ecerebrateposturIng(upperextremItyextensIon) 2
Nomovement 1
a
CCS8=deepcoma,severeheadtrauma,pooroutcome.
CCS912=conscIouspatIentwIthmoderateInjury.
CCS12=mIldInjury.
CTscannIngIsusedforthedIagnosIsofmostacuteheadInjurIes.PosItIveCTfIndIngsafter
acuteheadInjuryIncludemIdlIneshIft,dIstortIonoftheventrIclesandcIsterns,
effacementofthesulcIIntheunInjuredhemIsphere,andthepresenceofahematomaat
anylocatIonInthecranIalvault.Subduralhematomasusuallyhaveaconcaveborder,
whereasepIduralhematomaspresentwIthaconvexoutlIneclassIcallytermedalenticular
confIguratIon.PatIentsInseverecoma(CCSscore8)havea40lIkelIhoodofan
IntracranIalhematoma.ThosewIthhIgherCCSscoresarelesslIkelytohavehad
IntracranIalbleedIng,althoughItIsevIdentthatthesIgnIfIcantIncIdenceofthIs
complIcatIonevenInthesepatIentsnecessItatesaCTstudy,preferablywIthcontrast
enhancement.DtherbenefItsofCTscannIngIncludedetectIonofIntracranIalaIrand
depressedskullfractures.
Management
TheprImaryobjectIveoftheearlymanagementofbraIntraumaIstopreventorallevIate
thesecondaryInjuryprocessthatmayfollowanycomplIcatIonthatdecreasestheoxygen
supplytothebraIn,IncludIngsystemIchypotensIon,hypoxemIa,anemIa,raIsedCP,
acIdosIs,andpossIblyhyperglycemIa(serumglucose200mg/dL;seeChapter49).These
InsultscauseexacerbatIonoftraumaInducedcerebralIschemIaandmetabolIc
derangements,worsenIngtheoutcome.
80,81
The most important therapeutic maneuvers in
these patients are aimed at normalizing ICP, CPP, and oxygen delivery.The8raInTrauma
FoundatIonandtheAmerIcanAssocIatIonofNeurologIcalSurgeonshavepublIshed
evIdencebasedguIdelInesforthetreatmentofheadInjuredpatIents.
76
PrImarytherapy
IncludesnormalIzatIonofthesystemIcbloodpressure(meanbloodpressure80)and
maIntaInIngthePao
2
95,theCP20to25mmHg,andtheCPP50to70mmHg.
|aIntaInIngtheCPPatlevelsabove70mmHg,theformerstandard,IsnolongeradvIsedas
ItmaybeassocIatedwIthanIncreasedIncIdenceofAF0S.
76
ThepatIentIskeptatJ0
degreesheadelevatIon,sedatIonandneuromuscularblockersaregIvenasnecessary,and
cerebrospInalfluIdIsdraInedthroughaventrIculostomycatheter,IfavaIlable.FapIdand
adequaterestoratIonoftheIntravascularvolumewIthIsotonIccrystalloIdand,If
necessary,wIthcolloIdsolutIonsshouldbeaImedatmaIntaInIngtheCPPbetween50and
70mmHgwhIleattemptIngtomInImIzefurtherbraInswellIng.LFsolutIon,whIchIs
slIghtlyhypotonIc(Na
+
=1J0mEq/L,osmolalItyapproxImately255mDsm/L),maypromote
swellIngInunInjuredareasofthebraInIfItIsgIvenInlargequantItIes;edematendsto
occurInInjuredbraInregIonsregardlessofthetypeofsolutIonadmInIsteredbecauseof
IncreasedpermeabIlItyofthebloodbraInbarrIer.TomInImIzeedemaformatIon,ItIswIse
tomonItorserumosmolalItyandtoreplaceLFsolutIonwIthIsotonIcnormalsalIne.f
serumosmolalItycannotbemeasured,thIschangecanbemadeempIrIcallyafterJlItersof
LFsolutIon.
EffectIvereductIonInCPcanbeprovIded,oratleastaIded,byadmInIstratIonof
mannItol,anImportantpartofthemanagementofsevereheadInjury.tIsadmInIsteredIn
bolusesof0.25to0.5g/kg,repeatedevery4to6hoursasneededtocontroltheCP.
76
n
addItIontoItsosmotIcdIuretIceffect,thIsagentmayImprovecerebralbloodflow(C8F)
andD
2
delIverybyreducIngthehematocrItandthusthebloodvIscosIty,ImprovIngC8Fand
oxygendelIvery.
76
ThereIsarIskofhypovolemIaandresultanthypotensIonwhen
therapeutIcdosesofmannItolareused.ftheCPelevatIonpersIsts,addItIonaldosesof
mannItolshouldbegIvencautIously.AcutemannItoltoxIcIty,manIfestedbyhyponatremIa,
hIghserumosmolalIty,andagapbetweencalculatedandmeasuredserumosmolalIty10
mDsm/L,mayresultwhenthedrugIsgIvenInlargedoses(2toJg/kg)ortopatIentswIth
renalfaIlure.|annItolshouldbeusedwIthgreatcareInthepresenceofhypotensIon,
sepsIs,nephrotoxIcdrugs,orpreexIstIngrenaldIseaseasthesemayalsoprecIpItaterenal
faIlure.
76
Further,theeffectsofmannItolresultfromItsactIvItyInregIonsofthebraIn
wherethebloodbraInbarrIerIsIntact.tmayexacerbateedemaInInjuredareasInwhIch
ItmayeasIlyenterthetIssues.
HyponatremIaInthesepatIentsresultsfromIntravascularvolumeexpansIonratherthan
sodIumloss;thus,treatmentwIthsalInesolutIonsIsnotapproprIate.8ecauseofa
synergIstIcactIonbetweenmannItolandloopdIuretIcsInImprovIngtheCP,addItIonof
furosemIdemaybeasaferandmoreeffectIvetreatmentthanIncreasIngthedoseof
mannItolwhenIntracranIalhypertensIonpersIsts.UntIlabout1995,hyperventIlatIontoa
Paco
2
of25toJ0mmHgwasamaInstayofthetherapyofheadInjury.However,braIn
IschemIa,whIchIsprobablythemostthreatenIngconsequenceofheadInjury,IslIkelyto
occurdurIngthefIrst6hoursaftertraumaevenwhentheCPPIsmaIntaInedabovethe
generallyrecommended50to70mmHg.
82
ThIshypoperfusIonseemstobecausedlargely
byIncreasedcerebralvascularresIstance,whIchmaybeenhancedbyhyperventIlatIon.
However,somedegreeofhyperventIlatIonmaybenecessaryforshortperIodsoftImeIn
patIentswhohavesevereInjurIesandelevatedCPthatdoesnotrespondtonormal
ventIlatIonanddIuretIcs,althoughthIsshouldnotbeuseddurIngthefIrst24hours
followIngInjury.
76
tsuseaftertheInItIalphaseshouldbebasedonmonItorIngoftheCP
and,IfavaIlable,thejugularbulbD
2
saturatIon(Sjvo
2
)andarterIovenousD
2
dIfference
(A70o
2
).tshouldbenotedthathyperventIlatIonIntheseverelybraInInjuredpatIentmay
alsobeassocIatedwIthacutelungInjury.
8J
|easurementoftheSjvo
2
IsusedInsomecentersasaguIdetotherapyoftheheadInjured
patIent.
84
AcatheterIspassedretrogradeIntothejugularbulbunderfluoroscopIccontrol.
TheD
2
saturatIonmaybemeasuredwIthacooxImeterorcontInuouslybymeansofa
fIberoptIcsensor.
84
AnSjvo
2
of50IsconsIderedcrItIcaldesaturatIon.TheA70o
2
Isa
standardmeasureofthebraIn'soxygensupply/demandratIo.tIsequalto1.J4Hgb
(Sao
2
Sjvo
2
),wIththesaturatIonsexpressedasdecImalvalues,andnormallyIs
approxImately6.AnIncreaseInthIsvalueIsasIgnofInsuffIcIentbloodflow,whereasa
subnormallevelIndIcateshyperemIa.AreductIonInCPwIthelevatIonofCPPdurIng
treatmentIsreflectedbyarIseInSjvo
2
andanarrowIngoftheA70o
2
,presumably
reflectInganImprovementInthecIrculatIontothebraIn.Unfortunately,several
shortcomIngsofthetechnIquehavehInderedItsunIversalacceptance.8ecauseallofthe
cerebralveInsdraInIntothecavernoussInusandfromthereIntothejugularbulbs,A70o
2
measuresonlyglobalD
2
consumptIon,whIchmaywellbeverydIfferentfromthesItuatIon
IntheInjuredregIon.ndeed,Coles
82
hasdemonstratedbyposItronemIssIontomography
scannIngthatasIgnIfIcantIncreaseIntheregIonofcrItIcalhypoperfusIonresultIngfrom
hyperventIlatIonwasnotnecessarIlyassocIatedwIthacorrespondInglyabnormalSjvo
2
or
A70o
2
(FIg.J64).PatIentorcathetermovementmayalsoalterthemeasuredPjvo
2
.Thus,
theremaybeahIghproportIonofInaccuratevaluesashIghasnearlytwothIrdsalthough
recentadvancesInthetechnIquehaveprobablyreducedtheseerrors.Cruz
85
hassuggested
thatjugularvenousmonItorIngshouldbeusedonlyInsedated,paralyzedpatIents.
ftheCPremaInselevateddespIteallofthesemeasures,pentobarbItal(Jto10mg/kg
gIvenover0.5to2.5hours,followedbyamaIntenanceInfusIonof0.5toJ.0mg/kg/hr,
aImedataserumconcentratIonbetween2.5and4.0mg/dL)mayberequIred.HIghdose
barbIturatesareofnovalueIntheroutIne
P.901
therapyofheadInjury,andshouldbeusedonlyforrefractoryCPelevatIon.Whether
actIvenormalIzatIonofelevatedserumglucose(acommonoccurrenceIntheheadInjured
patIent)hasanysalutaryeffectonoutcomeIsnotknown.Dfcourse,ImmedIatesurgIcal
decompressIon,especIallyofepIduralhematomas,IsanImportantfactorInreducIng
morbIdItyandmortalIty.
Figure 36-4.EffectsofhyperventIlatIononcerebralbloodflow(C8F).TheleftImage
IsacomputedtomographyscanofthepatIentwhoseposItronemIssIontomography
scansareshownIntheothertwoImages.NotethatthereIsasIgnIfIcantdecreaseIn
theC8FandanIncreaseIntheareasofhypoperfusIondespIteImprovementInthe
IntracranIalpressure(CP),andnormalSjvo
2
andA70o
2
.CPP,cerebralperfusIon
pressure.(AdaptedfromColesJP:FegIonalIschemIaafterheadInjury.CurrDpInCrIt
Care2004;10:120,wIthpermIssIon.)
fthepatIentIshemodynamIcallystable,aCTscanIsperformed;thestrIctestattentIon
shouldbepaIdtoensurIngadequateoxygenatIon,ventIlatIon,bloodpressure,andCP
controldurIngtheprocedure.fthepatIentIshemodynamIcallyunstableorrequIres
emergencysurgeryforassocIatedInjurIes,andhasahIstorysuggestIngaheadInjuryeven
thoughasIgnIfIcantIntracranIalhematomaIsunlIkelyonclInIcalgrounds,IntraoperatIve
CPmonItorIngIsIndIcatedtopermItrapIddetectIonofCPelevatIon.8othIntracranIal
hematomasandhemorrhageInotherregIonshaveahIghsurgIcalprIorIty.nthepatIent
wIthmultIpletraumas,prIorItIzatIonbetweenthetwoIsbasedontheseverItyofeach
Injury.8ecausethereIsnotImetoobtaInaCTscanoftheheadInpatIentswIthboth
profusehemorrhageandbraInhernIatIon,thepatIentIsbroughtdIrectlytotheDFfor
sImultaneouscontrolofthebleedIngsIteandevacuatIonoftheIntracranIalhematoma.
ThesIteofthecranIotomycanbedetermInedbyaventrIculogramoranultrasound
examInatIonwIthapencIltIpprobe;bothtestsmaybeperformedunderlocalanesthesIa
throughafrontalburrhole.
TheaddItIonofrelatIvelysmallvolumesofhypertonIcsalIneInconcentratIonsbetweenJ
(6to8mL/kg)and7.5(4mL/kg)followedbyInfusIonofLFmaybebenefIcIalInmultIple
traumapatIentswIthheadInjury.
86
LIkemannItol,hypertonIcsalInedrawsfluIdfromthe
Intracellularspaceand,thus,InaddItIontorestorIngthebloodvolume,ItreducesbraIn
edemaandpreventselevatIonoftheCP.
87
Dntheotherhand,hypertonIcsalInemay,also
lIkemannItol,IncreaseedemaIntheInjuredregIonofthebraIn.
88
TheIntravascular
volumeexpansIonproducedbyhypertonIcsalIneIstransIent;Itcanbeprolongedbythe
addItIonof6dextran70orhetastarchtothesolutIon.However,admInIstratIonof
hypertonIcsalInecannotbemaIntaInedforlongperIods.tmaycausehypernatremIa,
hyperosmolalIty,orhyperchloremIcacIdosIs,probablyfromrenalbIcarbonateloss
secondarytoIncreasedlevelsofCl
.SerumconcentratIonsofNa
+
andCl
andthepatIent's
acIdbasestatusshouldbefollowed,andtheadmInIstratIonofhypertonIcsalIneshouldbe
dIscontInuedIfplasmaNa
+
reaches160mEq/L.8ecauseoftheseconsIderatIons,andthe
factthattherehasbeennostandardIzatIonoftheconcentratIon,thedose,ortheduratIon
oftreatment,theuseofhypertonIcsalIneshouldstIllbeconsIderedexperImental
therapy.
76,89
FesuscItatIonwIthcolloIdsolutIons(hetastarch,pentastarch,pentafractIon,
humanalbumIn5and25,ordextran)provIdesasustaInedImprovementInvItalsIgns,
buttheIncreaseIncolloIdosmotIcpressureproducedbythesesolutIonsmaynothavean
ImportantroleInreducIngbraInedema.
tmaybepossIbletoImprovetheoutlookforbraInInjuredpatIents:
1. Cruz
90
andtheLundgroup
91
usedwIdelydIfferentapproaches,butthecommonfactorIn
theIrtreatmentswasnotonlymaIntenanceoftheCPP,butalsoavoIdance,oratleast
lImItatIon,ofbraInswellIng.CruzaccomplIshedthIsbystandardtherapyaugmentedby
monItorIngthecerebralD
2
extractIon(Ceo
2
=Sao
2
Sjvo
2
).HyperventIlatIonwasused
whenthIsvaluedecreasedbelowthenormalrangeof24to42,InordertoconstrIctthe
cIrculatIonandthusdecreasetheCP,whIlemannItolwasusedforIncreasedCeo
2
to
decreaseCPandImprovetheC8F.TheLundtreatmentInvolvedarathercomplex
pharmacologIcapproach,bothtocontrolbloodpressureandCP,andtolImItedema
formatIon.ThereportedoutcomeswereverypromIsIng(TableJ65).Unfortunately,
becausebothoftheseapproacheswerereportedIn1998,theyhaveneItherbeen
confIrmedbyothergroupsnorfollowedupbytheorIgInalauthors.
2. TheearlIerdefInItIvetreatmentIsInItIated,thebettertheoutcomeIslIkelytobe.
FudehIlletal.
92
havedemonstratedImprovementInoutcomesInalargeserIesof
patIentswhencarewasInItIatedbyanesthesIologIstsattheaccIdentscene.
J. |eanwhIle,thewIdevarIetyoftypesandseverItIesofInjury,andofresponsesto
treatmentbothamongdIfferentpatIentsandInthesamepatIentatdIfferenttImes
ImplythattherapeutIcInterventIonsmustbeIndIvIdualIzed.
9J,94
TheseaImsmaybe
met,atleastpartly,bycarefullystructuredIntensIvecare.
95,96
TherapeutIcgoalsshould
besetexplIcItlyandrevIewed,andalteredIfnecessary,ateverychangeofshIft.
ndeed,earlyInterventIonandcontrolledmanagementmayexplaInmuchofthe
ImprovementInoutcomesthathasbeenobtaInedoverthepast10years,IncludIngthe
resultsobtaInedbyCruz
90
andtheLundgroup,
91
byPalmeretal.
95
usIngthe8raInTrauma
FoundatIon1995guIdelInes,andbyWattsetal.
96
usIngthe2000guIdelInes(TableJ65).
Spine and Spinal Cord Injury
Initial Evaluation
TheobjectIveIntheevaluatIonofspInaltraumaIstodIagnoseInstabIlItyofthespIneand
theextentofneurologIcInvolvement(seeChapterJ9).NotstabIlIzIngthespIneInthefIrst
hoursafteramajoraccIdentuntIladefInItIvedIagnosIsIsestablIshedcarrIestherIskof
convertInganeurologIcallyIntactpatIentIntoaparaplegIcorquadrIplegIc.0urIng
transporttothehospItal,thepatIentshouldbeImmobIlIzedwIthahardcollar,aspIne
board,andtape.AfteradmIssIon,patIentsshouldnotbeleftonarIgIdspIneboardfor
longerthan1hour,especIallywhentheyareparalyzed,becauseoftherIskofdecubItus
ulcers.
ntheconscIouspatIent,thedIagnosIsIsrelatIvelyeasy:ahIstoryofamotorvehIcle,
IndustrIal,orathletIcaccIdent,anactofvIolence,orafall;penetratIngtraumaresultIng
InaneurologIcdefIcItbelowaspecIfIcspInallevel;orpaInandtenderness
P.902
overtheInvolvedvertebraestronglysuggestaspIneInjury.tshouldbenoted,however,
thatspInalpaInIsnotalwayslocalIzedtothelevelofInjury.
97
DbvIously,thesesymptoms
aredIffIculttoelIcItInthecomatosepatIent.nthesecIrcumstances,flaccIdareflexIa,
lossofrectalsphInctertone,paradoxIcalrespIratIon,andbradycardIaInahypovolemIc
patIentsuggestthedIagnosIs.ncervIcalspInetrauma,anabIlItytoflexbutnottoextend
theelbowandresponsetopaInfulstImulIabovebutnotbelowtheclavIclealsoIndIcate
neurologIcInjury.CurrentguIdelInesconsIderabsenceofneckpaInorparesthesIaanda
negatIvefIndIngsonphysIcalexamInatIonlackoftendernesswIthpalpatIonanddurIng
voluntaryflexIonandextensIonoftheneckInaneurologIcallyIntact,conscIouspatIentas
adequateIndIcatIonsforrulIngoutacervIcalspIneInjurywIthoutfurtherradIologIc
studIes.AlcoholIntoxIcatIonanddIstractIngassocIatedInjurIesdonotseemtoalterthese
crIterIaaslongasthepatIentIsalert,conscIous,andabletoconcentrate.
Table 36-5 Six-Month Outcomes for Patients with Brain Injury in Various
Studies
a
Name of Study N
Year
Published
6-MONTH OUTCOME (%)
Good/Moderate Severe/Vegetative Dead Comments
Three
country
(Jennettet
al.
b
)
700 1977 J8 11 51
7arIous
treatments,
some
untreated
|Illeret
al.
C
158 1981 47 12 40
7ent,
surgery,CP
monItorIng,
andFx
TraumatIc
Coma0ata
8ank
(TC08)
86
717 1997 4J 20 J7
Total
patIents,
standard
therapy
TC08
86
J08 1997 54 19 27
PtswIthout
hypotensIon
orhypoxIa
FudehIllet
al.
92
1,508 2002 69 11 20
Standard
protocol
Cruz
90
178 1998 74 17 9
Ceo
2
group
Ekeret
al.
91
5J 1998 79 1J 8
Lund
treatment
a
FesultsofvarIoustreatmentprotocolsforbraInInjurIes.Thethreecountrystudy
surveyedpatIentswhohadreceIvedawIdevarIetyoftreatment;somewere
untreated.|Illeretal.relIedonhyperventIlatIonand,whennecessary,
barbIturates.TheTC80patIentsweretreatedsImIlarly;notethedIfferenceIn
outcomeofthepatIentswhodIdnotexperIencehypotensIonorhypoxIa(seeTable
J6J).ThefInalthreestudIesaredescrIbedInthetext.
b
Jennett8,TeasdaleC,CalbraIthS:SevereheadInjurIesInthreecountrIes.J
NeurolNeurosurgPsychIatry1977;40:291.
c
|IllerJ0,8utterworthJF,CudemanSKetal:FurtherexperIenceInthe
managementofsevereheadInjury.JNeurosurg1981;54:289.
0ependIngonthedegreeofdefIcIt,spInalcordInjurIesarecategorIzedascompleteor
incomplete.ntactsensoryperceptIonoverthesacraldIstrIbutIonandvoluntary
contractIonoftheanus(sacralsparIng)arepresentInIncomplete,butnotIncomplete,
InjurIes.ThereIspractIcallynopossIbIlItyofsIgnIfIcantneurologIcrecoveryIncomplete
Injury,whereasfunctIonalrestoratIonmayoccurInupto50ofpatIentsafterIncomplete
InjurIes.nsomepatIentsthedevelopmentofspinal shock,whIchIsmanIfestedbyabsolute
flaccIdItyandlossofreflexes,precludesdIstInguIshIngbetweencompleteandIncomplete
InjurIesdurIngtheInItIalphaseoftreatment.Therefore,evenIntheabsenceofsacral
sparIng,thepossIbIlItyofneurologIcrecoverydIctatesthatallpossIbleeffortsbemadeat
thIstImetopreventfurtherdamageandtopreservecordfunctIon.AsImIlarprIncIple
applIestotheevaluatIonofthelevelofInjury.AfterthefIrstfewdays,spInalcordedema
subsIdesandthefInallevelIscommonlyafewsegmentslowerthanonInItIalpresentatIon.
Thus,earlytherapeutIceffortsshouldnotbeabandonedevenInthepatIentwIthahIgh
levelInjury,whIchcarrIesagrImfunctIonalprognosIs.
SpInalshockIsprobablycausedbydIrecttraumatothespInalcord,andusuallysubsIdes
wIthIndaystoweeks.ThetermIsfrequentlyusedasamIsnomerforneurogenic shock,
whIchIsdefInedashypotensIonandbradycardIacausedbythelossofvasomotortoneand
sympathetIcInnervatIonoftheheartasaresultoffunctIonaldepressIonofthedescendIng
sympathetIcpathwaysofthespInalcord.tIsusuallypresentafterhIghthoracIcand
cervIcalspIneInjurIesandImproveswIthInJto5days.
Initial Management
ThespInalcord,amIcrocosmofthebraIn,IsalsovulnerabletoasecondaryInjuryprocess
thatmaybeaproductofhypotensIon,hypoxIa,andprobablyotherphysIologIc
complIcatIons.
98
PromptrecognItIonandaggressIvetreatmentoftheseInsults,whIchmay
alsoresultfromassocIatedtrauma,maymInImIzeexacerbatIonofspInalcordlesIonsand
ImprovethelongtermoutlookofthesepatIents.
80,99
Immobilization and Intubation
|aIntenanceofImmobIlIzatIonoftheInjuredspIneIsofparamountImportance.fa
cervIcalspInefractureIssuspected,ImmobIlIzatIonormanualInlInestabIlIzatIonofthe
neckIsnecessarybeforethepatIentIsmoved.fthepatIenthasathoracIcorlumbar
Injury,acarefullogrollIngmaneuvershouldbeused.
98,100
AboutonethIrdofparaplegIcpatIentsrequIreaIrwaymanagement,mostlywIthInthefIrst
24hoursafterInjury.SIgnsofrespIratorydIstressorfatIgue,orarIsIngrespIratoryrateor
Paco
2
,aremajorIndIcatIonsforventIlatoryassIstance.SeverebradycardIaordysrhythmIas
mayresultfromunopposedvagalactIvItydurIngtrachealIntubatIonorsuctIonIng:the
patIentmustbepreoxygenatedandatropIne(0.4to0.6mg)shouldbegIvenbeforeany
InstrumentatIon.fbradycardIadevelopsdurIngaIrwaymanagement,treatmentIncludes
addItIonalatropIne,glycopyrrolate,Isoproterenol,or,Ifnecessary,cardIacpacIng.
ThetechnIquesofIntubatIonInspIneInjuredpatIentsaredIscussedInthesectIonAIrway
|anagement.
Steroids
Forthepastseveralyears,hIghdosemethylprednIsolonehasbeenusedInmanycentersIn
anattempttoImprovetheoutcomefromspInalcordInjurIes.ThedrugIsgIvenasabolus
ofJ0mg/kgwIthIn8hoursofInjury,followedIn1hourbyanInfusIonof5.4mg/kg/hrfor
thenext2Jto
P.90J
47hours.TheNatIonalAcuteSpInalCordnjuryStudIes(NASCS2andNASCSJ)
101,102
IndIcatedsomeImprovementInmotorfunctIonIntreatedpatIentswhohadpartIalsensory
andmotorloss.TheresultsseemedtohavebeenbestInpatIentswhoreceIved24hoursof
therapystartIngwIthInJhoursofInjury,andthosereceIvIng48hoursoftreatmentstartIng
wIthInJto8hoursofInjury.TherewasvIrtuallynoImprovementInsensoryscoresInany
ofthegroups.TherewaslIttleornodIfferencefromuntreatedpatIentsIngroupswIth
moresevereInjurIesorInthosewhoweretreatedafter8hours,andthelongterm
ImprovementInthefunctIonalstatusofmostofthepatIentswasatbestmoderate.
However,thefIndIngsofthesestudIeshavenotbeenduplIcatedInanyotherprospectIve
orretrospectIvetrIals,
10J
andhavebeencrItIcIzedbecauseofmultIplemajordefIcIencIes
IntheanalysIsofthedata.
Furthermore,steroIdtherapyIsassocIatedwIthanIncreasedrateofsepsIs,pneumonIa,
anddaysofIntensIvecareandposItIvepressureventIlatIon,
104
andIsalsoassocIatedwIth
IncreasedmortalItyIntheJ6to74ofpatIentswIthspIneInjurIeswhoalsohavehead
InjurIes.
105
CIventheseresults,theGuidelines for the Management of Acute Cervical Spine
and Spinal Cord Injuries,
106
states,TreatmentwIthmethylprednIsoloneforeIther24or48
hoursIsrecommendedasanoptIonInthetreatmentofpatIentswIthacutespInalcord
InjurIesthatshouldbeundertakenonlywIththeknowledgethattheevIdencesuggestIng
harmfulsIdeeffectsIsmoreconsIstentthananysuggestIonofclInIcalbenefIt.SImIlarly,
theNatIonalAssocIatIonofEmergency|edIcalPhysIcIansstatesthattreatmentwIth
steroIdsshouldnotbeconsIderedthestandardofcare,andthatroutIneuseofsteroIdsIn
emergencymedIcalservIcesIsnotsupported.
107
Respiratory Complications
FespIratorycomplIcatIonsarecommonInallphasesofthecareofspInalcordInjured
patIentsandarethemostfrequentcauseofdeathIntheacutestage.
108,109
ntheInItIal
perIodtheseproblemsmaybeaugmentedbyassocIatedbraIn,neck,chest,orabdomInal
Injury,alcoholIntoxIcatIon,ortheeffectsofselfadmInIsteredorIatrogenIcdrugs.njurIes
atC5orlowerareusuallyassocIatedwIthnormaltIdalvolumesbecausethefunctIonofthe
dIaphragmIsIntact,whereaspatIentswIthlevelsatC4orabovemayrequIrepermanent
ventIlatoryassIstance.Nevertheless,accessoryrespIratorymuscleparesIsmaycausea
sIgnIfIcantlossofexpIratoryreserveevenwhentheInjuryInvolvesthelowerspInal
segments.
110
PulmonaryedemaIsanothersIgnIfIcantcauseofrespIratorydysfunctIon.A
severecatecholamInesurgefollowsacutetraumatothespInalcord.
111
Althoughthe
resultantseverehypertensIonlastsforonlyafewmInutes,ItseffectspersIst;Itmay
producebothpulmonarycapIllarydamage,asaresultofshIftIngofalargeportIonofthe
bloodvolumeIntothepulmonarycIrculatIon,andleftventrIculardysfunctIon.Dverzealous
fluIdtherapytotreatthepatIent'sInItIalhypotensIonmayleadtoacutepulmonaryedema
whenthesympathetIcactIvItyreturnsapproxImatelyJto5daysaftertheInjury.
ParadoxIcalrespIratIonInthequadrIplegIcpatIentresultsfrompartIalchestwallcollapse
durIngInspIratIon;ItmayproducelImItatIonofthetIdalvolumeandanIncreasedrIskof
hypoventIlatIon.
110
ThesItuatIonIsaggravatedwhenthepatIentIsInanuprIghtposItIon.
ThedIaphragmcannotmaIntaInItsnormaldomedshape,theonlywayItcancontract
effIcIently,becausetheweIghtofthethoracIccontentsIsnotopposedbythenormaltone
oftheabdomInalmuscles.Thus,IncontrasttootherdIseasesthatproducerespIratory
InsuffIcIency,thesupIneposItIonImprovesrespIratIonInpersonswIthquadrIplegIa
110
(FIg.
J65).
DthercausesofInadequaterespIratIonIntheearlyphaseofspInalcordInjuryare
aspIratIonofgastrIccontents,atelectasIs,pneumonIa,andbronchoconstrIctIon.
|anagementIncludescarefulobservatIonofthepatIent'sbreathIngandpreparatIonto
ventIlatethelungsandIntubatethetracheaatthefIrstsIgnofrespIratorydepressIon.
110
Figure 36-5.EffectofsemIFowlerposItIononventIlatIonInquadrIplegIcpatIents.
(FeprIntedfromWInslowC,8odeFK,Felton0etal:mpactofrespIratory
complIcatIonsonlengthofstayandhospItalcostsInacutecervIcalspIneInjury.Chest
2002;121:1548,wIthpermIssIon.)
Hemodynamic Management
HemodynamIcmanagementofquadrIplegIcpatIentsIncludesacompleteassessment,wIth
apulmonaryarterycatheterIfnecessary,asearlyaspossIbleafterInjury.nasmanyas
25ofpatIentswIthcervIcalspInalcordInjurIes,leftventrIculardysfunctIonmay
contrIbutetothehypotensIon.
112
0ecreasedpreloadcanbetreatedwIthfluIdInfusIon
usIngcardIacfunctIoncurvesasaguIde.ngeneral,volumemaybesafelyreplacedtoa
centralvenousorpulmonarycapIllarywedgepressure(PCWP)of18mmHg.
112
ThIsavoIds,
oratleastlImIts,theseverItyofthepulmonaryedemadescrIbedprevIously.HypotensIon
despIteadequatefluIdInfusIon,acIdosIs,orlowmIxedvenousPo
2
requIrestreatmentwIth
InotropessuchasdopamIne.
Anesthetic Considerations
AnyanesthetIctechnIquecompatIblewIththepatIent'sgeneralcondItIonIssatIsfactoryfor
thespInalcordInjuredpatIent.HypotensIonIsverycommondurInganesthesIaIn
quadrIplegIcpatIents.Placementofacentralvenousorpulmonaryarterycathetermay
facIlItatemanagementofthepatIent'svolumeandbloodpressurestatus.
SuccInylcholInemayproduceasudden,severeIncreaseInserumK
+
InspIneInjured
patIents(seeChapter20).LevelsashIghas14mEq/Lmaybereached:theresultmaybe
IrreversIbleventrIculardysrhythmIasandcardIacarrest.AlthoughsuccInylcholIneIs
probablysafedurIngthe4to7daysafterInjury,ItIsprobablybesttoavoIdItaltogetherIn
theparaplegIcpatIentandtouserapIdonsetnondepolarIzIngagentssuchasrocuronIum
whenarapIdsequenceInductIonIsrequIred.
Neck Injury
8othpenetratIngandblunttraumamayInjurethemajorstructuresIntheneck:vessels,
respIratoryanddIgestIvetracts,andnervoussystem.Hemorrhage,asphyxIa,medIastInItIs,
paralysIs,stroke,ordeathmayresultIftheseInjurIesarenotpromptlyrecognIzedand
treated.
P.904
PenetratIngneckInjurIesusuallypresentwIthobvIousclInIcalmanIfestatIons;blunt
cervIcaltraumamaybemoresubtle.AIrwaycompromIseorobstructIon,brIskbleedIng
fromthewoundsIte,anexpandIngpulsatIlehematoma,andshockwIthorwIthoutexternal
bleedIngareobvIoussIgnsofcervIcalvascularInjuryanddIctateImmedIateaIrway
managementandvascularcontrol.0ecreasedorabsentupperextremItyordIstalcarotId
pulses,aswellascarotIdbruItorthrIll,arepathognomonIcforcervIcalarterIalInjury;
however,theseoftendonotrequIreImmedIatesurgery.Hemothorax,pneumothorax,and
sIgnsofaIrembolIsmarealsosuggestIve.FespIratorydIstress,cyanosIs,orstrIdorare
obvIoussIgnsofaIrwayInjuryandrequIreImmedIatetrachealIntubatIon.DthersIgnsthat
stronglysuggestaIrwayInjuryaredysphonIa,hoarseness,cough,hemoptysIs,aIrbubblIng
fromthewound,subcutaneouscrepItus,laryngealtenderness,pneumothorax,and
hemothorax.8ecauseoftheIrdynamIcnature,cervIcalaIrwayInjurIesmayrapIdly
progresstoobstructIon;therefore,thepatIentshouldbeobservedcarefullyandthe
tracheaIntubatedatthefIrstsIgnofproblems.
EsophagealInjurIes,whetherIntheneckorthechest,areInsIdIousanddIffIcultto
dIagnose.0ysphagIa,odynophagIa,hematemesIs,subcutaneouscrepItus,prevertebralaIr
onalateralcervIcalradIograph,andmajorconcomItantInjurIestoothercervIcal
structuressuggestanesophagealInjuryandcallforconfIrmatIonwIthanesophagram.
TheneurologIcmanIfestatIonsofapenetratIngneckInjuryvarydependIngontheInjured
structure.PartIalspInalcordtransectIonproducesthe8rownSequardsyndromewIth
IpsIlateralmotorandcontralateralsensorydefIcItbelowtheInjury.CompletespInalcord
transectIon,dependIngonthelevelofInjury,producesparaplegIaorquadrIplegIa,usually
wIthneurogenIcshock.DccasIonally,lumInalocclusIonofthecarotIdandvertebral
arterIesmayleadtoahemIspherIccerebrovascularaccIdent;assocIatedhypotensIon
IncreasesthelIkelIhoodofthIsevent.
PatIentswIthsevereactIvebleedIng,persIstenthypotensIon,andaIrbubblIngthroughthe
woundrequIreImmedIatesurgerywIthoutfurtherdIagnostIcstudIes.
11J
ControversyexIsts
overtheIndIcatIonsforsurgIcalmanagementofstablepenetratIngneckInjurIes.
|andatoryexploratIonIsassocIatedwIthnegatIvefIndIngsInapproxImately70of
patIents.
11J
Thus,Inmanycenters,patIentsareevaluatedwIthnonInvasIvedIagnostIc
testsandundergosurgeryonlywhenthereareposItIvefIndIngs.
11J
8luntcervIcalvascularInjurIesusuallypresentwIthahematomathatmaycompressthe
cervIcalveIns,dIsplacetheaIrway,andproducepharyngealandlaryngealcongestIon.
njurytoanarterymayproduceanIntImaltear,pseudoaneurysm,fIstula,orthrombosIs.f
acarotIdorvertebralarteryIsInvolved,cerebralIschemIamayoccur.ThrombosIsoften
developsgraduallyovermInutestoafewhours,thustheappearanceofneurologIc
symptomsIsdelayedInapproxImately40ofpatIents.SymptomatIcpatIentsmaypresent
wIthacervIcalbruIt,alteredmentalstatus,orlateralIzIngneurologIcdefIcItsIncludIng
hemIparesIs,transIentIschemIcattacks,amaurosIsfugax,orHornersyndrome.The
mortalItyrateassocIatedwIthbluntcarotIdInjuryvarIesbetween15and28,and15to
50ofsurvIvorshaveneurologIcdefIcIts.
114
dentIfIcatIonofabluntcarotIdInjuryInan
asymptomatIcpatIentusIngCT,magnetIcresonanceangIography,orfourvessel
arterIographynotonlyallowsearlyInstItutIonofantIplatelettherapy,systemIc
antIcoagulatIon,endovascularInterventIon,orsurgIcalrepaIr,
114,115
butalsooccasIonally
preventstheneurologIcdefIcItsthatmayfollowsurgeryforassocIatedInjurIesInan
unprotectedpatIent.
AIrwayInjurIesafterblunttraumaarerare,butcarryanoverallmortalItyrateof2.
115
TheIrseverItyvarIesfromasImplemucosaltearorhematomatoacommInutedlaryngeal
cartIlagefractureorcompletecrIcotrachealseparatIon.TheyfrequentlyrequIreprImary
laryngealrepaIrortracheostomy.AnesthetIcmanagementIsnotonlycomplIcatedby
relatIvelycomplexaIrwaymanagementproblems
J1,J2
(dIscussedInAIrwayEvaluatIonand
nterventIon),butalsowIthassocIatedskullbase,IntracranIal,openneck,cervIcalspIne,
esophageal,orpharyngealInjurIes.
115
Chest Injury
AlthoughahIghpercentageofthoracIcInjurIescanbetreatedconservatIvely,patIents
whoneedsurgerymayhavemajorIntraoperatIvephysIologIcdIsturbances.
Chest Wall Injury
FIb,scapula,andsternalfractures,InaddItIontoInterferIngwIthadequaterespIratIon,
maybeassocIatedwIthsevereunderlyIngthoracIc,abdomInal,andcranIalInjurIes.The
managementprIncIplesfortheseInjurIesaresImIlartothoseprevIouslydescrIbedforflaIl
chest,althoughtheneedformechanIcalventIlatIonIslesslIkelyInsInglerIbfracturesthan
InaflaIlchest.EffectIvepaInrelIef,preferablywIthcontInuousthoracIcepIdural
anesthetIcsoropIoIds,Iscentraltomanagement.
J7
Pleural Injury
ClosedpneumothoraxIseasytobemIssedInmajortrauma.Thepresenceofsubcutaneous
emphysema,pulmonarycontusIon,andrIbfracturesshoulddrawsuspIcIonofcoexIstIng
pneumothorax.
116
TensIonpneumothoraxInvolvIng50ofahemIthoraxpresentswIth
dyspnea,tachycardIa,cyanosIs,agItatIon,dIaphoresIs,neckveIndIstentIon,tracheal
devIatIon,anddIsplacementofthemaxImalcardIacImpulsetothecontralateralsIde.
AlthoughanuprIghtplaInchestradIographprovIdesthebestopportunItyfordetectIonof
pneumothorax,thIsposItIonmaybeImpossIbleorcontraIndIcatedInpatIentswhoare
experIencIngmajorhemorrhageorthosewIthsuspectedspIneInjury.AIrInthepleural
spacetendstoaccumulateanterIorlyInsupIneorsemIrecumbentpatIents,oftenInthe
anteromedIalsulcus.|orerecently,transthoracIcultrasoundhasbeenusedforthe
dIagnosIsofpneumothorax.Normally,movementofthelungbeneaththechestwall
producescomettaIlartIfactsfromechodenseareasonthelungsurface.nthepresence
ofpneumothorax,neItherlungmotIonnorcomettaIlscanbeseen.nonestudyofblunt
andpenetratIngtraumapatIents,ultrasoundwasmoresensItIvethanasupInechestfIlm,
butdIdnotdetectallpneumothoraces.Further,ultrasounddetectIonofrIbandsternal
fracturesalsoappearedtobemoreaccuratethanthechestradIograph.twas
recommendedthatachestfIlmandtheultrasoundcancomplementeachother,butthat
chestCTbeusedasthedefInItIvetest.
117
UltrasoundexamInatIonmayalsobehelpfulIn
detectIngresIdualpleuralaIrafterplacementofthoracostomytube.However,after24
hoursoftubeplacement,theaccuracyofthIstechnIquedecreases,probablybecauseof
adhesIonsbetweenthelungandthepleura.
118
8raseletal.suggestedthatasmallclosedpneumothoraxcanbesafelymanagedby
observatIonalone,wIthoutachesttube,evenInthosepatIentswhorequIreposItIve
pressureventIlatIon,aslongascontInuIngvIgIlanceIsmaIntaIned.
118a
However,basedon
anearlIerstudy
119
andourownexperIence,westronglybelIevethatoncedIagnosed,a
traumatIcpneumothorax,nomatterhowsmall,shouldbetreatedwIththoracostomy
draInagebeforetrachealIntubatIonandposItIvepressureventIlatIon.
P.905
8leedIngIntercostalvesselsareresponsIbleformosthemothoraces.SevereaIrway
devIatIonmaybeproducedbyahemothorax,althoughItIsnotascommonasItIsaftera
pneumothorax.TreatmentconsIstsofdraInagewIthaJ0to40Frenchchesttube(26toJ2
FrenchIsusedforpneumothorax).nItIaldraInageof1,000mLofblood,orcollectIonof
200mL/hrforseveralhours,IsanIndIcatIonforthoracotomy.AddItIonalIndIcatIonsfor
thoracotomyareawhItelungappearanceontheanteroposterIorchestradIograph,ora
contInuousmajoraIrleakfromthechesttube,whIchmayresultfromadIrectaIrway
InjuryormajorlunglaceratIon.HemodynamIcallystablepatIentswIthpersIstentbleedIng
of150mL/hraremanagedwIthvIdeoassIstedthoracoscopIcsurgery(7ATS)tocontrol
bleedIng.ThIsprocedurerequIresplacementofadoublelumentubetocollapsethelung
ontheInvolvedsIde;ItcanalsobeusefulIndIagnosIsofsuspecteddIaphragmatIc,cardIac,
ormedIastInalInjurIes;evaluatIonofsomebronchopleuralfIstulas;andevacuatIonof
clottedbloodoranempyemathatdoesnotdraInwIthachesttube.Useof7ATSdecreases
theneedforopenthoracotomyandthenumberofnegatIveexploratIonsInstabletrauma
patIents.
120
Pulmonary Contusion
ThIsentItyoftenaccompanIeschestwallInjury,butmayalsodevelopInIsolatIon.ts
managementIsdIscussedInthesectIononflaIlchest.
Penetrating Cardiac Injury
PerIcardIaltamponade,cardIacchamberperforatIon,andfIstulaformatIonbetweenthe
cardIacchambersandthegreatvesselsaretheconsequencesofthIstypeoftrauma.Any
penetratIngwoundofthechest,especIallyonewIthInthecardIacwIndow(mIdclavIcular
lIneslaterally,clavIclessuperIorly,andcostalmargInsInferIorly),cancausethIsInjury.
PneumoperIcardIumvIsIbleonaplaInchestradIographafterpenetratIngchesttrauma
shouldIncreasethesuspIcIon,althoughItIsnotseenInallpatIents.UnstablepatIents
requIreImmedIatesternotomyorleftthoracotomy.TransthoracIcechocardIographycanbe
usedforscreenIngstablepatIents,
121
butItmaybeInconclusIveInobesepatIentsandIn
thosewIthpneumothorax;TEEprovIdesanaccuratedIagnosIsInthesepatIents,butItIs
ImpractIcaldurIngtheInItIalevaluatIonphaseoftrauma
122
(seeChapter28).Dfthe
alternatIvedIagnostIcmeasures,thecentralvenouspressure(C7P)Isnotalwaysaccurate,
andasubxIphoIdperIcardIalwIndowIsInvasIve,mustbeperformedIntheDFunder
generalanesthesIa,takeslonger,andcannotdetectanIntracardIacshunt.
Figure 36-6.AlgorIthmformanagementofvarIousclInIcalscenarIosproducedby
severebluntcardIacInjury(8C).EvaluatIonofseveremultIpletraumaInduced8C
useselectrocardIogram(ECC),troponIn,andtransesophagealechocardIography
(TEE).ArrowsrepresentthefrequencyofoccurrenceofeachscenarIoandthe
frequencyofmanagementmeasures.Thick arrowsrepresenthIghfrequency,thin
arrowsrepresentlowfrequency,anddotted arrowsrepresentveryrareoccurrences.
CU,IntensIvecareunIt;CA8C,coronaryarterybypassgraft;HFJ7,hIghfrequencyjet
ventIlatIon.(AdaptedfromDrlIaguetC,FerjanI|,FIou8:TheheartInblunttrauma.
Pericardial Tamponade
TheclassIcfIndIngsofperIcardIaltamponadetachycardIa,hypotensIon,dIstantheart
sounds,dIstendedneckveIns,pulsusparadoxus,orpulsusalternansaredIffIcultto
apprecIateormaybeabsentInahypovolemIctraumapatIent.TransthoracIc
echocardIographyorTEEcandemonstratebloodIntheperIcardIalsacandthepresenceof
ventrIculardIastolIccollapse,whIchIndIcatesatleasta20reductIonIncardIacoutput.
nItIalmanagementconsIstsofIntravenousfluIdsand,Ifnecessary,carefulselectIonand
tItratIonofanesthetIcagents,suchasketamIneandetomIdate,whIchproducerelatIvely
lIttlemyocardIaldepressIon.EvacuatIonoftheperIcardIalbloodbyperIcardIocentesIsor
surgeryshouldbeperformedassoonaspossIble.fanesthesIaIscontemplatedforsurgery,
ItsadmInIstratIonshouldbedelayeduntIlpatIentdrapIngandpreparatIonarecompleted.
Blunt Cardiac Injury
Thetermblunt cardiac injuryhasreplacedmyocardial contusionandencompassesvaryIng
degreesofmyocardIaldamage,coronaryarteryInjury,andruptureofthecardIacfree
wall,septum,oravalvefollowIngblunttrauma.
12J
|yocardIalInjuryconsIstsof
myofIbrIllardIsIntegratIon,edema,bleedIng,ornecrosIsthat,dependIngonItsseverIty,
presentsasmInorelectrocardIogram(ECC)orenzymeabnormalItIes,complex
dysrhythmIas,orcardIacfaIlurecausedbydIrectmechanIcalImpactorIndIrectlyby
coronaryocclusIon.0ysrhythmIaslastnomorethanafewdays;ventrIcularwallmotIon
abnormalItIesmaypersIstforupto1year,butanyIncreasedrIskofperIoperatIvecardIac
complIcatIonsappearstolastfornomorethanamonth.
ThepromInentclInIcalfIndIngsareangIna,sometImesrespondIngtonItroglycerIn,
dyspnea,chestwallecchymosIsand/orfractures;dysrhythmIasofanytype;andrIghtsIded
orleftsIdedcongestIveheartfaIlure.DrlIaguetetal.
12J
proposedanalgorIthmforthe
dIagnosIsandtreatmentofseveralclInIcalscenarIoscausedbythIsInjury(FIg.J66).The
dIagnosIsIsbasedonthe12leadECC,troponInlevel,andechocardIography.TheECCIs
verysensItIve,althoughnotspecIfIc.AnormaltracecannotruleoutthedIagnosIs,butItIs
thebestscreenIngtest.CommonECCabnormalItIesIncludealmostanytypeof
dysrhythmIa,STorTwavechanges,andconductIon
P.906
delays.PatIentswIthanormalECCundergoIngmInorsurgerydonotrequIreanyfurther
testIng.PatIentswIthsevereInjurIesneedmeasurementoftroponInandTEEtodIagnose
anyabnormalItIescausedbythecardIacInjury(FIg.J66).TroponInhasreplacedserum
creatInekInaseandItsmyocardIalbandfractIonbecauseofItsgreaterspecIfIcItyfor
cardIacmuscledamage.EchocardIographycandemonstratewallmotIonabnormalItIes,
valvemalfunctIon,hemoperIcardIum,IntracardIacthrombI,venousorsystemIcembolIsm,
andenddIastolIcandfractIonalventrIcularwallareachanges.ThusItaIdsnotonlyInthe
dIagnosIsofbluntcardIacInjury,butalsoInhemodynamIcmanagement.Treatment
optIonsdependonthedIagnosIs(FIg.J66).TheseoptIonsIncludeantIarrhythmIcagents,
Inotropes,fluIdloadIng,hIghfrequencyjetventIlatIontooptImIzecardIacfunctIon,and
surgeryforhemoperIcardIum,valvularorseptallesIons,orcoronaryarteryInjuryor
dIsease.
Table 36-6 Common Clinical, Radiographic, and Ultrasound Features of
Thoracic Aortic Injuries
CLINICAL RADIOGRAPHIC
SPIRAL COMPUTED
TOMOGRAPHY
ULTRASOUND
ncreasedarterIal
pressureand
pulseamplItude
Inupper
extremItIes
0ecreased
arterIalpressure
andpulse
amplItudeIn
lowerextremItIes
Absentorweak
leftradIalartery
pulse
Dsler'ssIgn:
dIscrepancy
betweenleftand
rIghtarmblood
pressure
Fetrosternalor
Interscapular
paIn
Hoarseness
SystolIcflow
murmuroverthe
precordIumor
medIaltotheleft
scapula
NeurologIc
defIcItsInthe
lowerextremItIes
WIdened
medIastInum
8lurrIngofthe
aortIccontours
WIdened
paraspInal
Interfaces
LeftapIcalcap
DpacIfIed
aortopulmonary
wIndow
8roadened
paratracheal
strIpe
0Isplacementof
theleftmaIn
stembronchus
0IsplacedS7C
FIghtward
devIatIonofthe
esophagusand
trachea
NasogastrIctube
shIft
Lefthemothorax
Sternaland/or
upperrIb
fractures
LungcontusIon
Pneumothorax
|edIastInal
hematoma
AortIcwall
IrregularIty
ntImalflap
Falseaneurysm
PseudocoarctatIon
ntramural
hematoma
ntralumInalclot
ormedIalflap
ntImalflap
Turbulentflow
0IlatedaortIc
Isthmus
Acutefalse
aneurysm
ntralumInal
medIalflap
Hemothorax
HemomedIastInum
S7C,superIorvenacava.
Thoracic Aortic Injury
ThIsInjuryoccursattheIsthmusthejunctIonbetweenthefreeandfIxedportIonsofthe
descendIngaortaIn90ofcases,andcarrIesan80mortalItyInthefIrsthourfollowIng
Injury.TheremaybenoclInIcalfIndIngsIntheemergencydepartment(TableJ66).Dnly
20toJ0ofpatIentswIthmedIastInalwIdenIngactuallyhavethoracIcaortIcInjury,
althoughthenegatIvepredIctIvevalueofthefIndIngIs98.|easurIngtheleftmedIastInal
wIdth(6cm)andItsfractIonofthetotalmedIastInalwIdth(0.6)mayIncreasethe
specIfIcItyandposItIvepredIctIvevalueoftheplaInfIlm.
124
ContrastenhancedspIralCT
wIthvolumerenderedImagereconstructIontechnIquesandultrasoundtechnologIespermIt
relIablenonInvasIvedIagnosIsandhavesubstantIallydecreasedtheneedforbIplanar
aortography.8othCTandTEEareequallycapableofdIagnosIngsubadventItIalaortIc
InjurIesthatrequIresurgIcalInterventIon
125
(seeChapter28).CTIsmorelIkelytobeused
fordIagnosIsbecauseIntroducIngaTEEprobeunderthesecIrcumstancesmaybe
undesIrable.LesIonsoftheIntImaandmedIathatcanbetreatedconservatIvelyand
concomItantbluntcardIacInjurIesaremuchmorelIkelytobedetectablebyTEEand
CT.
125
TEEIsespecIallyusefulfortheanesthesIologIstwhenotherInjurIesrequIre
ImmedIatesurgerywIthouttImeforCTexamInatIonofthechest.
8asedonTEEfIndIngs,traumatIcaortIcInjurycanbeclassIfIedIntothreecategorIes:grade
1InjuryconsIstsofanIntramuralhematoma,lImItedIntImalflapand/ormuralthrombus;
grade2InjuryconsIstsofsubadventItIalrupture,InjurytothemedIa,alteredaortIc
geometryand/orsmallhemomedIastInum;gradeJInjuryconsIstsoftranssectIonwIth
massIvebloodextravasatIon,IntralumInalobstructIoncausIngpseudocoarctatIon,and
IschemIa
126
(FIg.J67).Dfthese,grade1InjurIescanbetreatednonoperatIvelywIthserIal
followupsusIngTEE.Crade2andJ
P.907
InjurIesrequIreImmedIateordelayedsurgerybasedonclInIcalfIndIngs.
126,127
SeverIty
gradIngmayalsobedonebycrIterIaInvolvIngmeasurementbyTEEofmaxImumaortIc
dIameter,theratIobetweenInjuredandnormalaortIcdIameter,depthof
pseudoaneurysm,esophagustoaortIcIsthmusdIstance,aortIcIsthmustoleftvIsceral
pleuraldIstance,andthepresenceofhemothorax.
127
Figure 36-7.TypIcaltransesophagealechocardIographIcappearancesofthreegrades
oftraumatIcaortIcInjury.A.CradeJInjury.AdventItIaoftheaortIcwallIsdamaged
andafalseaneurysm(FA)IscommunIcatIng(arrow)wIththeaortIclumen(Ao).B.
Crade2Injury.LargemedIalflapmovesbackandforthdurIngeachcardIaccycle.
AdventItIaIsIntact.C,D.Crade1Injury.ntImalflap(C)andIntramuralhematoma(D,
shownwItharrows)wIthouthemomedIastInumoralteratIonofaortIcgeometry.
TreatmentchoIcesaredIfferentforeachgrade:grades2andJInjurIesusuallyrequIre
rapIdordelayedsurgery;grade1InjuryIsusuallytreatedconservatIvelywIthout
surgery.(FeprIntedfromCoarInJP,CluzelP,Cosgnachetal:EvaluatIonof
transesophagealechocardIographyfordIagnosIsoftraumatIcaortIcInjury.
AnesthesIology2000;9J:1J7J,wIthpermIssIon.)
SurgIcalprIorItIzatIonwhenmultIpleInjurIesarepresentdependsonthehemodynamIcand
neurologIcstatusofthepatIent.AlthoughtheaortashouldberepaIredasearlyaspossIble,
controlofactIvehemorrhagefromothersItesandsurgeryforIntracranIalhematomashave
ahIghersurgIcalprIorIty,unlesstheaortaIsleakIng.nmostInstances,abloodclot
betweentheaortaandthemedIastInalpleuraoccludesthevessel.AnydIsturbanceofthe
tamponadedregIonmayreInItIatebleedIng.ArapIdflowofbloodInalargearterytendsto
pullItsendothelIumwIthItandthusmayruptureanInjuredvesselthatIssealedwItha
clotorahematoma.SuchanIncreaseIntheaortIcbloodflowIsusuallycausedby
IncreasedmyocardIalcontractIlIty;everyeffortshouldbemadetopreventIncreased
cardIaccontractIlItyandhypertensIon.EndovascularstentgraftshavebeenusedInmany
centersforrepaIrofthoracIcaortIcInjurIes,wIthnorIskofparaplegIa,sImpleranesthetIc
technIques,andmanyfewerofthecomplIcatIonsassocIatedwIththoracotomy.
128
Diaphragmatic Injury
njurytothedIaphragmmaypermItmIgratIonofabdomInalcontentsIntothechestwhere
theymaycompressthelung,producIngabnormalItIesofgasexchange,ortheheart,
resultIngIndysrhythmIasand/orhypotensIon.8ecausethedefectproducedbybluntInjury
IslargerthanthatresultIngfromapenetratIngInjury,mIgratIonofabdomInalcontents,
whIchrequIresadefectofatleast6cmIndIameter,Isalsomorecommonafterblunt
trauma.
129
ThelIverprotectstherIghtsIdeofthedIaphragm,thustraumatIchernIatIonIs
morecommonontheleftsIde.
129
ThebestmethodofdIagnosIngadIaphragmatIchernIaIslaparoscopy,orInselectedcases,
7ATS.Nevertheless,notIngthattheendofanasogastrIctubeIsabovethedIaphragmon
thechestradIographIsacertaInsIgnthatthestomachIsdIsplacedIntothechest.Achest
radIographthatshowsIntestInalmarkIngsandlungcompressIon,oracontrastenhanced
abdomInalCTscanthatIncludesthelowerthIrdofthethorax,alsocanprovIdeImportant
InformatIon.FaIluretoretrIevetheInstIlledfluIddurIngdIagnostIcperItoneallavage(0PL)
ordraInageof0PLfluIdfromathoracostomytubealsoIndIcatesthIsInjury.
Abdominal and Pelvic Injuries
TableJ67summarIzesthestrengthsandweaknessesofthecurrentlyavaIlabledIagnostIc
toolsusedforabdomInalInjurIes.
1J0
8ecauseoftheunpredIctablecourseofbulletsInthe
body,exploratorylaparotomyor,Inselectedcases,laparoscopyIsrequIredInmost
patIentsafteragunshotwoundoftheabdomen.DccasIonallyInhemodynamIcallystable
patIents,abdomInalandflankgunshotwoundsmaybeevaluatedwIthanInItIalCTscan.
StabwoundsmaybemanagedwIthtractotomytodetermInewhethertheperItoneumIs
Involved.Laparoscopy,laparotomy,or0PLmaybeIndIcatedafteraposItIvetractotomy.
PatIentswIthbluntabdomInaltraumaareevaluatedbyCTscanunlesstheyare
hemodynamIcallyunstableandthereareovertabdomInalsIgnssuchastenderness,
guardIng,andgrossdIstentIon.AbsenceofabdomInaldIstentIon,however,doesnotrule
outIntraabdomInalbleedIng.Atleast1lIterofbloodcanaccumulatebeforethesmallest
changeIngIrthIsapparent,andthedIaphragmcanalsomovecephalad,allowIngfurther
sIgnIfIcantbloodlosswIthoutanychangeInabdomInalcIrcumference.
ThedIagnostIcabIlItyoffocusedassessmentwIthsonographyfortrauma(FAST),
popularIzeddurIngthepastdecade,IsInferIortoCTscanevaluatIon,whIchhasrecently
realIzedsIgnIfIcanttechnologIcImprovements.FASTIsoperatordependent,hasgood
specIfIcItybutmoderatesensItIvIty,candIagnoseInjurIesassocIatedwIthIntraperItoneal
fluIdbutnotthosewIthoutIt,andcannotdetermInetheseverItyoforganInjury.
Currently,manylowgradeIntraabdomInalsolIdorganInjurIesthat
P.908
canbeevaluatedbyCTbutnotFASTaretreatedconservatIvelywIthoutsurgery.Arecent
CochranerevIewreportedthatcurrentdataareInsuffIcIenttodevelopultrasoundbased
clInIcalpathwaystodIagnosebluntabdomInalInjury.DntheotherhandFASTrequIresone
thIrdofthetImeandIslessexpensIvetoperformthanCT,andIswIthoutthehazardof
radIatIon.
ScreenIngwIthabdomInalultrasonographyIsperformedbyplacIngaJ.0to5.0|Hzprobe
onfourdIstInctareasoftheabdomen:subxIphoId,todetectperIcardIalblood;rIghtupper
quadrant,forbloodInthehepatorenalpouch;leftupperquadrant,todetectperIsplenIc
blood;andjustabovethepubIcsymphysIs,forbloodIntherectovesIcalpouch.
Table 36-7 Diagnostic Tools in Abdominal Trauma: Strengths and
Weaknesses
DIAGNOSTIC TOOL STRENGTH WEAKNESS
PhysIcal
examInatIon
ExpedItIous,safe,and
InexpensIve;potentIalfor
serIalexamInatIon
0IagnosIsofspecIfIcInjury(e.g.,
dIaphragm)
0IagnostIc
perItoneal
0IagnosIsofdIaphragmatIc
Injury,hollowvIscusInjury,
lavage InexpensIve retroperItonealInjury;canbe
oversensItIveandnonspecIfIc
Computed
tomography
EvaluatIonofperItoneum
andretroperItoneum
Injury,hollowvIscusInjury
StagIngofsolIdorgan
Injury
ExpensIve;controversIalneed
forcontrast
Ultrasonography
InexpensIve;accuratefor
freeperItonealfluId
Injury,hollowvIscusInjury,
penetratIngInjury,good
specIfIcIty,butmoderate
sensItIvIty
PotentIalforserIal
examInatIons
LessaccurateInthepresenceof
largeretroperItoneal
hematomas
Laparoscopy
0IagnosIsofperItoneal
penetratIon,
dIaphragmatIcInjury
0IagnosIsofhollowvIscus
Injury,retroperItonealInjury
EvaluatIonofbleedIngor
solIdorganInjury
PotentIalfortherapy
ExpensIve
7IdeoassIsted
thoracIcsurgery
EvaluatIonoflung,
dIaphragm,medIastInum,
chestwall,and
perIcardIum;potentIalfor
treatment
FequIresoperatIngroom;
expensIve
0IagnosIsofabdomInalInjurIes
FeprIntedfrom7IllavIcencIoFT,AucarJA:AnalysIsoflaparoscopyIntrauma.JAm
CollSurg1999;189:11,wIthpermIssIon.
LaparoscopyIsanexcellentscreenIngtoolInabdomInaltraumapatIents.AnanalysIs
showedthatthIsmethodavoIdedlaparotomyIn6JofpatIentsandmIssedonly1ofthe
InjurIes.
1J0
tIsalsopossIbletorepaIrdIaphragmatIc,bladder,andsolIdorganInjurIeswIth
thIstechnIque.ThecomplIcatIonrateoflaparoscopyIntraumaIsapproxImately1,
IncludIngpneumothorax,smallbowelInjury,IntraabdomInalvascularInjury,and
extraperItonealCD
2
InsufflatIon.
1J0
Fractures of the Pelvis
PelvIcfracturesoccurInwIdelyvarIedanatomIcformsandphysIologIcseverIty.|ajor
hemorrhageoccursIn25andexsanguInatIonIn1ofpatIents.TheyareusuallyassocIated
wIthchest,braIn,IntraabdomInal,andlongboneInjurIes,whIchIncreasethemorbIdIty
andmortalItyofpelvIcfractures.AlargedatabaseshowedthattheJmonthcumulatIve
mortalItyofpatIentswIthpelvIcfractures(14.2)wasalmostJtImeshIgherthanthose
wIthoutthem(5.6).nmostofthesefractures,bleedIngresultsfromvenousdIsruptIonby
fragmentsofbone.FetroperItonealpelvIcbleedIngIsselflImItedInmostpatIentswIth
venousInjurIesbecauseoftamponadIng,exceptthosewIthopenfractures.ApproxImately
18to20ofpatIentshavearterIalbleedIng,whIchdoesnotstop.TheretroperItoneal
spaceInthesepatIentsmayserveasadIstensIblecontaIner,whIchexpandssuperIorlyand
anterIorlyandmaytotallyoblIteratethelowerpartoftheabdomInalcavIty.Thus,0PL,as
InpregnanttraumapatIents,shouldbeperformedabovetheumbIlIcus.Large
retroperItonealhematomasmayalsocauserespIratorydIffIcultybecauseofpressureon
thedIaphragm.
FollowIngexternalpelvIcfIxatIon,whIchdecreasesthemobIlItyofthebonefragmentsand
thushelpscontrolbloodloss,angIographycanIndIcatethetypeandlocatIonofbleedIng.
ArterIalbleedIngIstreatedwIthembolIzatIon;theangIographysuIteshouldbepreparedIn
advancenotonlyforanesthesIa,butalsoforInvasIvemonItorIngandresuscItatIon.n
hemodynamIcallyunstablepatIents,decIdIngwhethertotransportthepatIenttotheDFto
controlbleedIngfromassocIatedInjurIes,ortoproceedtoInterventIonalradIologyfor
angIographyandpossIbleembolIzatIonIsdIffIcult.nmostcentersIttakesatleast45
mInutestobegInangIography,durIngwhIchtImeaconsIderableamountofbloodmaybe
lost.PrelImInarydatafromEuropesuggestthatexternalfIxatIonandextraperItoneal
packIngofthepelvIsIntheDFfollowedbyangIographyandpossIbleembolIzatIonIsmore
benefIcIalthanonlyexternalfIxatIonandangIography.
1J1,1J2
nthIsmanner,anyIntra
abdomInalInjurIesmayalsobecontrolled.ThIsconceptcontrastswIththetradItIonal
understandIngthatopenIngaretroperItonealhematomaInducedbyafracturedpelvIsmust
beavoIded.PelvIcfracturesmayalsoInjurethebladderandtheurethra.Thus,a
urethrogramshouldbeperformedbeforeInsertIonofaurInarycatheter.
Extremity Injuries
SurgIcalrepaIrofextremItyfractures,whetheropenorclosed,shouldbeperformedas
soonaspossIble(seeChapter5J).0elayedfracturerepaIrIsassocIatedwIthanIncreased
rIskofdeepveInthrombosIs(07T),pneumonIa,sepsIs,andthepulmonaryandcerebral
complIcatIonsoffatembolIsm.nopenfractures,anaddItIonalImportantconcernIs
InfectIon.WoundsleftunrepaIredformorethan6hoursarelIkelytobecomeseptIc.
AssocIatedvasculartraumamustberecognIzedearly.|ostvascularInjurIesexhIbItat
leastsomepartoftheclassIcsyndromeofpain, pulselessness, pallor, paresthesias,and
paresis.ThedefInItIvedIagnosIsIsmadewItharterIography;InselectedpatIents,aduplex
ultrasoundstudymaybeusedasascreenIngtest.PatIentswIthvasculartraumashouldbe
operatedonexpedItIously,oftenwIthoutpreoperatIveangIography.ThesepatIentsmay
bleedslowlybutsubstantIallybothpreandIntraoperatIvely;thus,delayedsurgeryand
prolongedskeletalrepaIrmayleadtounrecognIzedhemorrhagIcshock,whIchmayattImes
becomeIrreversIble.0amagecontrol,thatIs,controllIngbleedIngandexternalfIxatIonof
thefractures,maybethemanagementofchoIce.
Compartment syndrome,whIchIscharacterIzedbyseverepaInIntheaffectedextremIty,
shouldberecognIzedearlysothatemergencyfascIotomycanbeeffectIveInpreventIng
IrreversIblemuscleandnervedamage.nunconscIouspatIents,swellIngandtensenessof
theextremItyIndIcatethepresenceofthIscomplIcatIon.ThedefInItIvedIagnosIsIsmade
bymeasurIngcompartmentpressuresusIngatransducerattachedtoafluIdfIlledextensIon
tubeandaneedleInsertedIntothevarIouscompartmentsoftheextremIty.Apressure
exceedIng40cmH
2
DIsanIndIcatIonforImmedIatesurgery.CautIonmustbeexercIsed
whenusIngepIduralornerveblockanalgesIaforperIoperatIvepaInrelIefInthepresence
ofextremItyfractures.AbsenceofpaIncandelaythedIagnosIsofcompartmentsyndrome.
Burns
0etermInatIonofthesIzeanddepthofaburnsetstheguIdelInesforresuscItatIon,aswell
astheIndIcatIonsforsurgIcalInterventIon.
1JJ
ApartIalthIcknessburnIsred,blanchesto
touch,andIssensItIvetopaInfulstImulIandheat.SuperfIcIalpartIalthIckness(fIrst
degree)burnsInvolvetheepIdermIsandupperdermIs,andhealspontaneously.0eep
partIalthIckness(seconddegree)burnsInvolvethedeepdermIsandrequIreexcIsIonand
graftIngtoensurerapIdreturnoffunctIon.AfullthIckness(thIrddegree)burndoesnot
blanchevenwIthdeeppressureandIsInsensate.CompletedestructIonofthedermIs
requIreswoundexcIsIonandgraftIngtopreventwoundInfectIonthatmayleadtolocal
sepsIsandsystemIcInflammatIon.FourthdegreeburnsInvolvemuscle,fascIa,andbone,
necessItatIngcompleteexcIsIonandleavIngthepatIentwIthlImItedfunctIon.Laser
0opplerImagIngcanbeusedasanaIdtojudgeburnwounddepth.
1J4
ThesIzeofthe
burnedareaasafractIonofthetotalbodysurfacearea(T8SA)IsestImatedbytheruleof
nInes.nanadult,theheadcontrIbutesto9;theupperextremItIes,18;thetrunk,J6;
andthelowerextremItIes,J6oftheT8SA.TheseproportIonsaresomewhatdIfferentIn
chIldren,dependIngontheageandsIze.ToestImatethesIzeofaburn,thepalmarsurface
ofachIld(excludIngthedIgIts)representsabout0.5oftheT8SAoverawIderangeof
ages.
nformatIonaboutthemechanIsmofInjuryfacIlItatesthedIagnosIsofassocIatedclInIcal
abnormalItIes.Forexample,thermaltraumacausedbyflamesInaclosedspaceIslIkelyto
beassocIatedwIthaIrwaydamage.8urnsresultIngfrommotorvehIcle,aIrplane,or
IndustrIalaccIdentsmaybecomplIcatedbyothertraumatIcInjurIes.FInally,burnscaused
byelectrocutIonmayshowlIttleexternalevIdencebutmaybeassocIatedwIthsevere
fractures,hematomas,vIsceralInjury,andskeletalandcardIacmuscleInjuryresultIngIn
paIn,myoglobInurIa,anddysrhythmIasorotherECCabnormalItIes.
FullthIcknessburnsInvolvIng10oftheT8SA;partIalthIcknessburnscoverIng25of
T8SAInadultsandover
P.909
20attheextremesofage;burnsInvolvIngtheface,hands,feet,orperIneum;InhalatIon,
chemIcal,andelectrIcalburns;andburnsInpatIentswIthseverepreexIstIngmedIcal
dIsordersareconsIderedtobemajorburns.
1JJ
AsevereburnIsasystemIcdIseasethat
stImulatesthereleaseofmedIatorssuchasInterleukIns,tumornecrosIsfactor,and
neopterIns,locallyproducIngwoundedemaandIntothecIrculatIon,resultIngInImmune
suppressIon,hypermetabolIsm,proteIncatabolIsm,sepsIs,andmultIsystemorganfaIlure.
8urns40T8SAconsIstentlydevelopcatabolIsmandweIghtlossthatmaylastupto1
year.PreventIonofsepsIs,maIntenanceofnormalbodytemperature,andpaIn
managementmaydecreasetheextentofcatabolIsm.PharmacologIcally,lowdoseInsulIn
InfusIon,betablockade,andthesynthetIctestosteroneanalogueoxandrolonecandecrease
catabolIsmorImproveanabolIsm.
1J5
Airway Complications
FespIratorydIstressIntheInItIalphaseofaburnIsusuallycausedbyaIrwayInjury
InvolvIngthepharynxorthetrachea.SIngedfacIalhaIr,facIalburns,dysphonIaor
hoarseness,cough,sootInthemouthornose,andswallowIngdIffIcultIesInpatIents
wIthoutrespIratorydIstressshouldIncreasethesuspIcIonofupper(frequent)andlower
(occasIonal)aIrwayInjury.ntheupperaIrway,glottIcandperIglottIcedemaandcopIous,
thIcksecretIonsmayproducerespIratoryobstructIon.ThIsmaybeaggravatedbyfluId
resuscItatIonevenIntheabsenceofsIgnIfIcantInhalatIonInjury.
1J6
nloweraIrwayburns,
decreasedsurfactantandmucocIlIaryfunctIon,mucosalnecrosIsandulceratIon,edema,
tIssuesloughIng,andsecretIonsproducebronchIalobstructIon,aIrtrappIng,and
bronchopneumonIa.ThedevelopmentofparenchymallungInjurytakesapproxImately1to
5daysandpresentswIththeclInIcalpIctureofadultrespIratorydIstresssyndrome.
PneumonIaandpulmonaryembolIsm(PE)arelatecomplIcatIonsthatoccur5ormoredays
afterburns.ThepresenceofalungInjurymarkedlyIncreasesthemortalItyratefrom
thermalInjurIes.
1J7
AdmInIstratIonofthehIghestpossIbleconcentratIonofD
2
byfacemask
IsthefIrstprIorItyInmoderatelytoseverelyburnedpatIentswIthapatentaIrway.n
patIentswIthmassIveburns,strIdor,respIratorydIstress,hypoxemIa,hypercarbIa,lossof
conscIousness,oralteredmentatIon,ImmedIatetrachealIntubatIonIsIndIcated.The
IntubatIontechnIqueselecteddependsontheoperator'sexperIence,theageofthe
patIent,andtheextentofaIrwaycompromIse.nadults,awakefIberoptIcIntubatIonunder
adequatetopIcalanesthesIaIsprobablythesafestapproach,butothertechnIques
(WuScope,AIrtraq(KIngSystems,NobelsvIlle,N),ClIdeScope,IntubatIngL|A,retrograde
IntubatIon,ortranstrachealjetventIlatIon)maybeused.nmostpedIatrIcpatIents,
awakeIntubatIonIsnotpossIble(seeChapter29).AnInhalatIonInductIonwIthD
2
and
sevoflurane,followedbyIntubatIonusInganFD8orconventIonallaryngoscopeIs
approprIate.
1JJ
AsurgIcalaIrwayentaIlsasIgnIfIcantrIskofpulmonarysepsIs,lateupper
aIrwaysequelae,anddeathInburnedpatIents;Itshouldbereservedforthosewhose
aIrwaymanagementcannotbehandledInanyotherway.
1JJ,1J8
mmedIatelyaftersecurIng
theaIrway,ventIlatIonwIthlowlevelsofPEEPwIllpreventthepulmonaryedemathatmay
developsecondarytolossoflaryngealautoPEEPInpatIentswIthsIgnIfIcantaIrway
obstructIonbeforeIntubatIon.AIrwayhumIdIfIcatIon,bronchIaltoIlet,andbronchodIlators
IfneededforbronchospasmarealsoIndIcated.
ThepedIatrIcaIrwayIspartIcularlychallengIngbecauseItmaybeoccludedbymInImal
amountsofswellIngbecauseofItssmalldIameter.ProphylactIcIntubatIonmaytherefore
berequIredInchIldrenwhoaresuspectedofhavInganInhalatIonInjury,eventhoughthey
arenotyetInrespIratorydIstress.ProphylactIctrachealIntubatIonmayalsobeIndIcated
InadultswhentheresourcesforcarefulfollowupareInsuffIcIent.nformatIonobtaIned
fromradIologIc,arterIalbloodgas,andendoscopIcexamInatIonsandpulmonaryfunctIon
testIngmaybeusefultopredIctwhIchpatIentwIllneedtrachealIntubatIonandpossIbly
decreasetherIsksofaIrwaymanIpulatIon.
1J9
FIberoptIclaryngoscopyIseasytoperformandcanprovIdedIrectInformatIonaboutthe
glottIcandperIglottIcstructures.tmayavoIdtrachealIntubatIonInpatIentswhowould
otherwIsebeconsIderedcandIdatesforthIsprocedure.
1J9
FIberoptIcbronchoscopyhasthe
addItIonaladvantageofprovIdIngInformatIonabouttheloweraIrway,althoughItIsmore
uncomfortableforthepatIentandrequIrestopIcalanesthesIaofthetracheobronchIaltree.
ThesestudIesshouldbeperformedeveryJto4hoursforthefIrst12hoursafterInjury.n
cooperatIvepatIents,pulmonaryfunctIontestIngmayaIdIntheevaluatIonofaIrway
obstructIon.AsawtoothedorflattenedInspIratoryflowandanextrathoracIcobstructIon
patternontheflow/volumeloopsuggestupperaIrwayobstructIon.0ecreasedpeak
expIratoryflow,forcedvItalcapacItyandpulmonarycomplIance,andIncreasedaIrway
resIstancesuggestloweraIrwayInjury.
ThechestradIograph,arterIalbloodgases,andpulmonaryfunctIontestsareusually
normalIntheImmedIatepostburnperIod,evenInpatIentswIthpulmonary
complIcatIons.
17
However,thesetestsshouldbeperformedatthIstImeforlater
comparIson.Asexpected,themoreextensIvethepulmonaryedema,themoresevereare
thefunctIonalabnormalItIesofthelungs.ThetreatmentofsmokeInhalatIonInburns
InvolvesventIlatorymanagement,IntensIvecare,andtreatmentofcarbonmonoxIde(CD)
andcyanIde(CN
)toxIcIty.
Ventilation and Intensive Care
HypoxemIamaypersIstdespItetrachealIntubatIon,ventIlatIonwIthPEEP,bronchodIlators,
andsuctIonofaIrwaysecretIons(seeChapter56).nthefIrstJ6hours,thIsIscausedby
acutepulmonaryedema.FromthesecondtothefIfthday,hypoxIamayresultfrom
atelectasIs,bronchopneumonIa,andaIrwayedemafollowIngmucosalnecrosIsand
sloughIng,vIscoussecretIons,anddIstalaIrwayobstructIon.LatertheremaybenosocomIal
pneumonIa,hypermetabolIsmInducedrespIratoryfaIlure,andAF0S.Treatmentofthese
complIcatIonsIsIndIvIdualIzed,usIngventIlatorymaneuverssuchaslowtIdalvolume(5to
6mL)wIthtItratedPEEP,bronchoscopIclavage,antIbIotIcs,chestphysIotherapy,andother
supportIvemeasures.ProphylactIcmeasuresagaInst07T,gastrIculcers,andhypothermIa
shouldbeusedroutInely.LackofresponsetotherapybecauseofsevereventIlatIon
perfusIonmIsmatchIngorshuntmaybeanIndIcatIonfortheuseofnItrIcoxIde,apotent,
shortactIngvasodIlator,vIatheaIrway.
18
PatIentswIthAF0SmaybenefItfromhIgh
frequencyoscIllatoryventIlatIonbothIntraoperatIvelyandIntheCU.mprovementIn
oxygenatIonhasbeenreportedInburnpatIentswIththIsmodeofventIlatIon;the
benefIcIaleffectonoxygenatIonwasslowerandlessInpatIentswIthsmokeInhalatIonthan
InthosewIthburnInjuryonly.
140
Carbon Monoxide Toxicity
nburnvIctIms,CDInhalatIonIsalmostalwaysassocIatedwIthsmokeInhalatIon,whIch
IncreasesthemorbIdItyandmortalItycomparedwIthCDtoxIcItyalone.CDproducestIssue
hypoxIaprImarIlybyIts200foldgreateraffInItyforhemoglobInthanoxygenandbyIts
abIlItytoshIftthehemoglobIndIssocIatIoncurvetotheleft,ImpaIrIngD
2
unloadIngtothe
tIssues.talsoInterfereswIthmItochondrIalfunctIon,uncouplIngoxIdatIve
phosphorylatIonandreducIngadenosInetrIphosphateproductIon,thuscausIngmetabolIc
acIdosIs.ProbablybecauseofthIseffectonthemItochondrIa,CDcanbeadIrect
myocardIaltoxIn,preventIngsurvIvalInpatIentswhosuffercardIacarrest,eventhough
theyhavebeenresuscItatedandtreatedwIthhyperbarIcoxygen.
AnormaloxygensaturatIononapulseoxImeterdoesnotexcludethepossIbIlItyofCD
toxIcIty,althoughlowarterIal
P.910
D
2
saturatIonmeasuredbyacooxImetershouldraIsethesuspIcIon
141
(seeChapter26).
FecentlyIntroducedportabledevIces(|asImoFad5,|asImoCorporatIon,rvIne,CA)are
capableofmeasurIngcarboxyhemoglobInandmethemoglobInlevelsnonInvasIvelyvIaa
fIngersensoralongwIthpulseoxImeterreadIng,alertIngtheclInIcIanforhIghD
2
saturatIonvalues.ThemIxedvenousoxImetercathetersthatareusedforcontInuousIn
vIvomeasurementofSvo
2
overestImateoxyhemoglobInconcentratIonInthepresenceof
CD.fCDtoxIcItyIsnotaccompanIedbyalungInjuryandthusbydecreasedPao
2
,
tachypneaIsabsent;thecarotIdbodIesaresensItIvetothearterIalD
2
tensIonandnotto
theD
2
content.TheclassIccherryredcolorofthebloodIsalsoabsentInmostpatIents
becauseItoccursonlyatcarboxyhemoglobIn(CDHb)concentratIonsabove40,andItmay
alsobeobscuredbycoexIstenthypoxIaandcyanosIs.
Table 36-8 Symptoms of Carbon Monoxide Toxicity as A Function of the
Blood Carboxyhemoglobin (COHb) Level
BLOOD COHbc LEVEL (%) SYMPTOMS
1520 Headache,dIzzIness,andoccasIonalconfusIon
2040 Nausea,vomItIng,dIsorIentatIon,andvIsualImpaIrment
4060 AgItatIon,combatIveness,hallucInatIons,coma,andshock
60 0eath
ThepatIent'sInspIredoxygenshouldbemaIntaInedatthehIghestpossIbleconcentratIon,
evenwhenthereIsnoevIdenceofsIgnIfIcantsmokeInducedlungInjury,untIlCDtoxIcIty
IsruledoutbymeasurementofbloodCDHb.AhIghFD
2
notonlyImprovesoxygenatIon,but
alsopromoteselImInatIonofCD;anFD
2
of1.0decreasesthebloodhalflIfeofCDHbfrom
the4hoursseenInroomaIrto60to90mInutes,andto20toJ0mInutesatJatmIna
hyperbarIcchamber.
1JJ
ThegreaterthebloodconcentratIonsofCDHb,themoresevereare
thepresentIngsymptoms(TableJ68).0elayedneuropsychIatrIcdIsordershavebeen
descrIbedInpatIentsexposedtotoxIclevelsofCD,andthereIsevIdencetosuggestthat
earlyhyperbarIcD
2
treatmentmaypreventthesesymptoms.
1JJ
ThedecIsIontoInstItute
thIstreatmentshouldbebasedoncomparIngtherIsksoftransport,decreasedpatIent
access,anddelayInemergencytreatmentagaInstthepossIbleneurologIcsequelae.
Currently,hyperbarIcD
2
IsrecommendedforpatIentswIthCDHbJ0atadmIssIonIfthe
treatmentoflIfethreatenIngproblemsshock,neurologIcInjury,metabolIcacIdosIs,
myocardIalIschemIa,InfarctIon,orarrhythmIaswIllnotbecompromIsed.
Cyanide Toxicity
AnothercauseoftIssuehypoxIaInburnedpatIentsIsCN
toxIcIty.CyanIdeorhydrocyanIc
acIdIsproducedbyIncompletecombustIonofsynthetIcmaterIals,andmaybeInhaledor
absorbedthroughmucousmembranes.AsInCDtoxIcIty,theusualclInIcalpresentatIonIs
unexplaInedmetabolIcacIdosIs.NonspecIfIcneurologIcsymptomssuchasagItatIon,
confusIon,orcomaarealsocommonfIndIngs.ElevatedplasmalactatelevelsInsevere
burnsmayresultfromhypovolemIa,CDtoxIcIty,orCN
toxIcIty.However,lactIcacIdosIs
aftersmokeInhalatIonInapatIentwIthoutamajorburnsuggestsCN
toxIcIty.
142
The
defInItIvedIagnosIscanbemadeonlybydetermInatIonofthebloodcyanIdelevel,whIchIs
toxIcabove0.2mg/Landlethalatlevelsbeyond1mg/L.AspectrophotometrIcassayusIng
methemoglobInasacolorImetrIcIndIcatorprovIdesatImelyandrelIabledetermInatIonof
bloodCN
.
14J
ThepulseoxImetryreadIngwIllbeaccurateIntheabsenceofCDtoxIcItyand
nItratetherapyInducedmethemoglobInemIa.
ncreasedCN
InthebloodcancausegeneralIzedcardIovasculardepressIonandcardIac
rhythmdIsturbances,especIallyInpatIentswIthlactIcacIdosIs.Fortunately,thehalflIfeof
CN
Isshort(approxImately1hour),
142
andrapIdImprovementofhemodynamIcsshouldbe
expectedafterrescueofthevIctImfromthetoxIcenvIronment.mmedIateadmInIstratIon
ofD
2
,whIchIsrequIredforallburnvIctIms,maybelIfesavIngforthIscomplIcatIon.
AlthoughtherearespecIfIctherapIesforCN
toxIcIty(e.g.,amylnItrate,sodIumnItrIte,
thIosulfate),gIventheshorthalflIfeoftheIon,ItIsnotclearwhetherthesemeasures
offersIgnIfIcanthelptothepatIentwhosebloodCN
usuallydecreasestolowlevelsdurIng
transportfromthefIeldtothehospItal.
144
Dfcourse,IfcIrcumstancespermIt,hyperbarIc
D
2
treatmentcanbeusedforallthecomplIcatIonsofthermalInjury:CDandCN
poIsonIng,
smokeInducedlungdamage,andcutaneousburns.
Fluid Replacement
mmedIatelyafteraserIousburn,mIcrovascularpermeabIlItyIncreases,causIngthelossof
asubstantIalamountofproteInrIchfluIdIntotheInterstItIalspace.Amajorburn,adelay
InInItIatIonofresuscItatIon,oranInhalatIonInjuryIncreasesthesIzeoftheleak.
1JJ
Further,thereseemstobeacorrelatIonbetweenInhalatIonInjuryandcutaneousburnsIn
theproductIonofedema.PulmonaryedemaIncreasescutaneousedemaandvIceversa.
145
fresuscItatIonIssuccessful,edemaformatIonstopswIthIn18to24hours.
145
ThIsfluIdflux
IsenhancedbyIncreasedIntravascularhydrostatIcandInterstItIalosmotIcpressuresand
decreasedInterstItIalhydrostatIcpressure.naddItIon,cardIaccontractIlItymaydecrease
becauseofcIrculatIngmedIators,adImInIshedresponsetocatecholamInes,decreased
coronarybloodflow,andIncreasedsystemIcvascularresIstance.
1JJ
ThIsmayresultIn
shock,whoseorIgInIsprImarIlyhypovolemIcand,toamuchsmallerextent,
cardIogenIc.
146
fthehypotensIonIstreatedapproprIatelywIthfluIds,thehemodynamIc
pIctureIsreplacedwIthIn24to48hoursbyoneresemblIngsepsIsorseptIcshock,wIth
IncreasedcardIacoutputanddImInIshedsystemIcvascularresIstancecausedbytherelease
ofInflammatorymedIators.
146
FluIdresuscItatIonIsessentIalIntheearlycareoftheburnedpatIentwIthanInjury15
oftheT8SA.SmallerburnscanbemanagedwIthreplacementat150ofthecalculated
maIntenancerateandcarefulmonItorIngoffluIdstatus.ntravascularvolumeshouldbe
restoredwIthutmostcaretopreventexcessIveedemaformatIonInbothdamagedand
IntacttIssuesresultIngfromthegeneralIzedIncreaseIncapIllarypermeabIlItycausedby
theInjury.EdemafromoveraggressIveresuscItatIonhasmanydeleterIousandpotentIally
lIfethreatenIngeffects.|entIonhasalreadybeenmadeofthefacIlItatIonofupperaIrway
edemaafterrapIdfluIdInfusIonInlargecutaneousburnswIthorwIthoutsmoke
InhalatIon.
1J6
LIkewIse,chestwalledemamaydevelopafteradmInIstratIonoflarge
quantItIesoffluId,causIngrespIratorydIffIcultIesandnecessItatIngexcIsIonofburned
tIssuefromtheanterIoraxIllarylInetoImprovebreathIng.AbdomInaledemamayalso
occur,andwhenresuscItatIonvolumeexceedsJ00mL/kgover24hours,IncreasedIntra
abdomInalpressuremayproduceabdomInalcompartmentsyndromewIthImpedanceof
venousreturn.
147,148
EdemaformatIonmayalsoIncreasethetIssuepressureIntheburned
area,resultIngInreductIonofbloodflowtodIstalsItes.ThIs,togetherwIthdecreased
tIssueoxygentensIon,mayproducenecrosIsofdamagedbutvIablecells,IncreasIngthe
extentofInjuryandtherIskofInfectIon.
P.911
CrystalloIdsolutIonsarepreferredforresuscItatIondurIngthefIrstdayfollowIngaburn
Injury;leakageofcolloIdsdurIngthIsphasemayIncreaseedema.Nevertheless,crystalloId
resuscItatIon,especIallyInchIldren,maycausearapIddeclIneInplasmaproteIn
concentratIonandnecessItateadmInIstratIonof5albumInInLFafterthefIrstday
followIngaJ0burnand/orsIgnIfIcantInhalatIonInjury,whenthecapIllaryleakstops.
149
tIsbelIevedthatthIswIllmoderatethetendencytoedemaformatIonassocIatedwIththe
admInIstratIonoflargeamountsofIsotonIc(0.9salIneorLF)solutIons,eventhougha6
IncreaseIntherIskofmortalItyhasbeenreportedwIththeuseofcolloIdsInpatIentswho
arecrItIcallyInjuredandburned.SomecentersuseplasmawIthcrystalloIdroutInelyand
attrIbutethegoodoutcomeoftheIrpatIentspartlytothIspractIce.
150
AdmInIstratIonof
fluIdsInexcessoftheamountrecommendedbytheParklandformulaappearstobe
relatIvelyfrequentInmodernburnmanagementandIstermedfluIdcreep.AvoIdanceof
earlyoverresuscItatIon,useofcolloIdroutInely,adherencetoprotocolsarerecommended
strategIestopreventfluIdcreep.
151
AlternatIvely,hypertonIcsalInesolutIonsdraw
IntracellularwaterIntothebloodstreamandthusdecreasethefluIdvolumeneededto
maIntaInperfusIon,maIntaInextracellularvolume,andlImIttheseverItyofedemaIn
patIentswIthburnsoccupyIng50oftheT8SA,cIrcumferentIalextremItyburns,or
InhalatIonalInjury.
1JJ
Unfortunately,hypertonIcsolutIonscausehypernatremIaand
IntracellularwaterdepletIon;patIentsandexperImentalanImalsreceIvIngthesefluIdsfor
burntherapyoftendIdnotshowanoverallfluIdsparIngeffect,andhadanunacceptably
hIghIncIdenceofrenalfaIlureanddeathcomparedwIththosereceIvIngLF.
152,15J
DfthemanyresuscItatIonformulasavaIlable,theParkland(8axter)andmodIfIed8rooke
formulasaretaIloredtotheclInIcalcondItIonofthepatIentandareacceptedInmost
centers
149
(TableJ69).TheaddItIonofglucoseIsnotnecessaryexceptInchIldren,
especIallythoseweIghIng20kg.AlbumIn5maybeadmInIsteredafterthefIrstday
followIngInjuryatarateof0.J,0.4,or0.5mL/kgperpercentburnper24hoursforburns
ofJ0to50,50to70,or70to100ofT8SA,respectIvely.TheseformulasareguIdelInes
only,andnonecanbeexpectedtoprovIdeadequaterestoratIonofIntravascularvolumeIn
allburnvIctIms,especIallysmallchIldrenandpatIentswIthInhalatIonInjurIes.Therefore,
admInIstratIonoffluIdsdurIngtheInItIalphaseshouldbetItratedtospecIfIcgoals
descrIbedInTableJ69;andIfapulmonaryarterycatheterIsplaced,acceptablecardIac
output,fIllIngpressures,andamIxedvenousoxygentensIon(Pvo
2
)ofJ5to40mmHg.
CarefulmonItorIngofthehematocrItmayalsoguIdefluIdmanagement.AnIncreaseIn
hematocrItdurIngthefIrstdaysuggestsInadequatefluIdresuscItatIonbecausehemolysIs
andsequestratIonareactuallyexpectedtocauseadecreaseInthIsparameter.Acute
anemIa,asmayoccurdurIngexcIsIonandgraftIngofburns,Isusuallywelltolerated.8lood
replacementIsusuallynotInItIateduntIlthehematocrItIsbelow15to20Inhealthy
patIentsrequIrInglImItedoperatIons,approxImately25Inthosewhoarehealthybutneed
extensIveprocedures,andJ0ormorewhenthereIsahIstoryofpreexIstIng
cardIovasculardIsease.
154
Table 36-9 Guidelines for Initial Fluid Resuscitation After Thermal Injury
AdultsandchIldren20kg
Parkland formula
a
4.0mLcrystalloIdperkgperburnperfIrst24hr
Modified Brooke formula
a
2.0mLlactatedFIngerperkgperburnperfIrst24hr
ChIldren20kg
CrystalloId2JmL/kgperburnper24hr
a
CrystalloIdwIth5dextroseatmaIntenancerate
100mL/kgforthefIrst10kgand50mL/kgforthenext10kgfor24hr
Clinical end points of burn resuscitation
UrIneoutput:0.51mL
Pulse:80140permIn(agedependent)
SystolIc8P:60mmHg(Infants);chIldren7090plus2ageInyearsmmHg;
adults|AP60mmHg
8asedefIcIt:2
8P,bloodpressure;|AP,meanarterIalpressure.
a
50ofcalculatedvolumeIsgIvendurIngthefIrst8hours,25IsgIvendurIngthe
second8hours,andtheremaInIng25IsgIvendurIngthethIrd8hours.
AlthoughthereIsevIdencethatthestandardclInIcalendpoIntsofresuscItatIonoften
provIdeInadequateInformatIonInmajorburnsandthatbetterInformatIonmaybe
obtaInedfrompulmonaryarterycatheterdata,
155
therearealsopractIcaland
methodologIcproblemsassocIatedwIththelatter,especIallytherIsksofInfectIous
complIcatIonsandtherequIrementforaddItIonalvascularaccess.
WhenInrareInstancesfluIdresuscItatIonfaIlsdespIteadmInIstratIonofcrystalloIdsIn
excessof6mL/kg/T8SA,andInvasIveorsemIInvasIvemonItorIngsuggestsadequate
Intravascularvolume,vasopressorand/orInotropIcagentsmaybeIndIcated.0opamIneIn
smalldoses(5g/kg/mIn)and/oradrenergIcagentsmayImproveurIneoutputwIthout
furtherneedforfluIds.
149
ElectrolyteabnormalItIesmayoccurafterthefIrstdayfor
severalreasonsbutareprImarIlyaresultoftopIcalagentsapplIedtocontrolpaIn,
decreasevaporloss,preventdesIccatIon,andslowbacterIalgrowth.
149
Nonaqueous
topIcals(sIlversulfadIazIne),IfadmInIsteredwIthoutprovIdIngfreewatersuchas5
dextrose,mayresultInhypernatremIaandItsCNSconsequences,IncludIngIntracranIal
bleedIng.ncontrast,aqueoustopIcalagentssuchas5sIlvernItratesolutIonmaycause
hyponatremIaandItsconsequencesofcerebraledemaandseIzuresecondarytoelectrolyte
leachIng.CentralpontInedemyelInatIonmayoccurIfthehyponatremIaIscorrected
rapIdlywIthsaltsolutIons.SerumIonIzedcalcIumandmagnesIumshouldalsobe
monItored.
Operative Management
Dverall,nearly25oftraumapatIentspresentwIthpreexIstIngcondItIonssuchas
cIrrhosIs;cardIovascular,pulmonary,andrenaldIseases;coagulatIondIsorders;dIabetes;
andalcoholordrugabusethatmayIncreasetraumarelatedmorbIdItyandmortalItyand
requIreaddItIonalcare.
156
PremedIcatIonIsrarelyIndIcated,especIallyInthosewhoare
hypovolemIc,headInjured,orIntoxIcated.fneeded,smalldosesofopIoId(morphIne,1to
2mg;fentanyl,25to50g)orsedatIve(mIdazolam,0.5to1.0mg)maybeadmInIstered
wIthclosemonItorIngofvItalsIgns.FegIonalanalgesIamaybeprovIdedforstablepatIents
wIthskeletalInjurIesawaItIngsurgery.Femoralnerveblock,forexample,provIdes
excellentanalgesIaforfemoralshaftfractures.EvaluatIonofthemultIpletraumapatIent
emergentlytransportedtotheDFInvolvesrevIewIngpreexIstIngcondItIons,thevItal
sIgns,oxygenatIon,andpreoperatIvefluIdreplacement,andconfIrmatIonofcorrect
posItIonandpatencyofaprevIouslyInsertedendotrachealtube.
Monitoring
TableJ610lIstsmonItorIngtechnIquescurrentlyusedIntheDFandIndIcatestheIrrelatIve
ImportanceIntheIntraoperatIve
P.912
P.91J
careofthetraumapatIent.Clearly,valuabletImecanbelostIftheplacementofInvasIve
monItorstakesprecedenceoverresuscItatIon.
Table 36-10 Techniques to Monitor Physiologic Parameters and Their
Importance in Intraoperative Management of the Trauma Patient
PHYSIOLOGIC
PARAMETER
DEGREE OF
IMPORTANCE
MONITORING EQUIPMENT
SPECIFIC INTRAOPERATIVE
USES IN THE TRAUMA PATIENT
CardIacrate,
rhythm,and
myocardIal
IschemIa
EssentIal
FIvelead
electrocardIogram
systemwIth
oscIlloscope,dIgItal
dIsplay,recorder,and
prInter(threelead
systemcanbeused)
FoutIne
ArterIalblood
pressure
EssentIal
ndIrect
8loodpressurecuff
0opplersystem
Programmable
oscIllometrIcsystem
0Irect
Pressuretransducer
wIthcalIbrated
oscIlloscopeand
recorder
FoutIne
Centralvenous Useful
Pressuretransducer
wIthcalIbrated
oscIlloscopeand
recorder
HypovolemIa
PerIcardIal
tamponade,
myocardIalcontusIon
AIrembolIsm
PulmonarycontusIon
Pulmonaryartery
EssentIal
In
multIple
trauma
Pressuretransducer
wIthcalIbrated
oscIlloscopeand
recorder
8luntchestInjury
(perIcardIal
tamponade,
myocardIalcontusIon)
AdultrespIratory
dIstresssyndrome
0IfferentIatIonoflow
pressureandhIgh
pressurepulmonary
edema;traumatIc
(cardIaccontusIon)or
preexIstIngheart
faIlure
CardIacoutput
UsefulIn
some
patIents
ThermodIlutIon
cardIacoutput
computerwIth
recorderandprInter
Sameaspulmonary
arterypressure
measurement
CardIacwall
motIon
abnormalItIes,
myocardIal
IschemIa,flow
throughvalvesor
septaldefects
UsefulIn
some
patIents
Transesophageal
echocardIograph
CardIaccontusIon
Coronaryartery
InjurIes:
SeptalInjurIes
AIrembolIsm
ThoracIcaortIc
rupture
Shock
7entIlatIon EssentIal
EndtIdalCD
2
monItor
wIthwaveform
dIsplayandrecordIng
FoutIne
HeadInjury
AIrembolIsm
ArterIal
oxygenatIon
EssentIal
AIrwaypressure
PulseoxImeter
ArterIalbloodgases
(IntermIttentor
contInuous)
FoutIne
TIssue
oxygenatIon
Useful
Pulmonaryartery
catheter(P[7wIthdot
above]o
2
)
ArterIal/venous
lactateanalyzer
8asedefIcIt
LowperfusIonstates
FenalfunctIon EssentIal
Foleycatheterand
graduatedcontaIner
nallmajortrauma
patIents
Temperature EssentIal
Esophagealorrectal
probe
FoutIne
Neuromuscular
functIon
EssentIal
PerIpheralnerve
stImulator
electromyograph
HeadInjury
Dpenglobe
Sealedmajorvessel
Injury
NeurologIc
functIon
Useful
ntracranIalpressure
measurementwIth
bolt,catheter,or
fIberoptIcsensor
JugularbulbD2
saturatIon
HeadInjury
0epthof
anesthesIa
8IspectralIndex
monItor
ntraoperatIve
awareness
8loodcoagulatIon Useful
ProthrombIn
tIme/partIal
thromboplastIn
tIme/platelet
count/fIbrInogen,
tubetest,
thrombelastograph
Shock
|assIvetransfusIon
PreexIstIng
coagulatIon
abnormalItIes
Figure 36-8.ArterIalpressurerecordsofamechanIcallyventIlatedpatIentbefore
(left)andafter(right)1,000mLbloodloss.NotetheIncreaseInsystolIcpressure
varIatIonanddowncomponentfollowInghemorrhage.0ecreaseInbloodpressure
occursdurIngexhalatIonwIthmechanIcalventIlatIonandInspIratIonInspontaneously
breathIngsubjects(upgoing arrowdefInesInhalatIon).UpIsthedIfferencebetween
theendexpIratorysystolIcpressureandthemaxImumsystolIcpressureovera
respIratorycycle.SeetextfordefInItIonofsystolIcpressurevarIatIonanddown
component.(FeprIntedfromFookeCA,SchwIdHA,ShapIraY:Theeffectofgraded
hemorrhageandIntravascularvolumereplacementonsystolIcpressurevarIatIonIn
humansdurIngmechanIcalandspontaneousventIlatIon.AnesthAnalg1995;80:925,
wIthpermIssIon.)
Hemodynamic Monitoring
0IrectIntraarterIalpressuremonItorIng,whIchpermItsbeattobeatdataacquIsItIonand
samplIngformeasurementofbloodgases,shouldbeInplacebeforesurgery(seeChapter
27).AnultrasoundguIdedtechnIqueorasurgIcalcutdownmaybenecessarytofacIlItate
access.TheradIalarteryIsthevesselofchoIceInabdomInalorchesttraumaInwhIchthe
aortamaybecrossclamped,makIngafemoralordorsalIspedIscannulanonfunctIonal.The
rIghtradIalarteryIspreferredIncasesofchesttraumaInwhIchcrossclampIngofthe
descendIngaortamIghtresultInocclusIonoftheleftsubclavIanartery.nmechanIcally
ventIlatedpatIents,themagnItudeofsystolIcpressurevarIatIon(thedIfferencebetween
themaxImumandmInImumsystolIcpressureovertherespIratorycycle)andItsdown
component(thedIfferencebetweensystolIcpressureatendexpIratIonandthelowest
valuedurIngtherespIratorycycle)canprovIderelIableInformatIonaboutthe
Intravascularvolumestatus(FIg.J68).AsystolIcpressurevarIatIon5mmHganda
down2mmHgsuggesthypovolemIa.
157
0elayIngemergentsurgerytoplaceacentralvenouslIneIsrarelyIndIcatedunlessalarge
borecatheterIsneededforvolumeresuscItatIon.However,IfthepatIentIselderly,If
thereIsalIkelIhoodofmyocardIaldamage,orIfthereIsmultIpleorgandamagewIth
requIrementforprolongedsurgeryandmassIvefluIdreplacement,earlyplacementofa
C7PorpulmonaryarterycatheterIsIndIcatedbeforethedevelopmentofcoagulopathy
rendersIthazardous.
SeveralrecentlydescrIbeddynamIcmeasurementtechnIquesmaybeusefulInassessIng
hypovolemIaandtheresponsetofluIdloadIng.
158
Dfthese,pulsecontouranalysIs,usInga
mathematIcalalgorIthm,candetermInethestrokevolume,cardIacoutput,andsystemIc
vascularresIstance.Theesophageal0opplermonItorcandetermInestrokevolumeand
cardIacoutput;byusIngtheseparametersonecancalculateaortIcflowtIme,whIch
correlateswIthpreload,andpeakvelocItyofbloodflow,whIchcorrelateswIthmyocardIal
contractIlIty,enablIngtheclInIcIantoassessIntravascularvolume,responsetofluId
loadIng,andmyocardIalperformance.ThesetechnIquescannotbedefInItIvely
recommended,however,astheyhavenotbeentestedIntraumapatIents.
7olumetrIcassessmentofpreloadappearstocorrelatebetterwIthcardIacIndexthanthe
C7PorPCWP.
159
ApulmonaryarterycatheterequIppedwItharapIdresponsethermIstor
andIntracardIacelectrodesIscapableofmeasurIngrIghtventrIcular(F7)cardIacoutput
andejectIonfractIon,andcalculatIngF7enddIastolIcvolumeIndex.Thelatterappearsto
correlatewIthcardIacoutputbetterthanC7PandPCWPIntraumapatIents.AnF7end
dIastolIcvolumeIndex1J0mL/m
2
IsconsIderedoptImalfororganperfusIon.
159
ThemIxedvenousD
2
saturatIoncanalsoconveyImportantInformatIonaboutorgan
perfusIon;ItcanbedetermInedbyanalyzIngbloodfromthepulmonaryarteryor
contInuouslyvIaafIberoptIcsensoratthejunctIonofthesuperIorvenacavaandtherIght
atrIum.Dftheseparameters,systolIcpressurevarIatIonandstrokevolumeappearto
correlatebestwIthIntravascularvolumestatus.
TheTEEprovIdesvaluabledIagnostIcInformatIonInbluntcardIacInjury,cardIacseptalor
valvulardamage,coronaryarteryInjury,perIcardIaltamponade,andaortIcrupture.
160
t
alsopermItsassessmentofcardIacfunctIon,IncludIngrIghtandleftventrIcularvolume,
ejectIonfractIon,wallmotIonabnormalItIes,pulmonaryhypertensIon,andcardIacoutput,
anddetectsacuteIschemIamoreaccuratelythaneItherECCorpulmonaryarterypressure
monItorIng.|onItorIngleftventrIcularvolumealonecanprovIdeInformatIonaboutthe
adequacyoftheIntravascularvolume.ThIstechnIquealsoallowsvIsualIzatIonoffatand
aIrentryIntotherIghtheart,ortheleftheartthroughapatentforamenovale,durIng
InternalfIxatIonoflowerextremItyfractures.
161
nthetraumasettIng,ItIspossIblethat
theTEEprobemaybeIntroducedIntoanunrecognIzedesophagealtearbecausethe
InsIdIousnatureofesophagealInjurymakesdIagnosIsdIffIcultdurIngthefIrst24hours
aftertrauma.
P.914
Urine Output
UrIneoutputIsroutInelymonItoredasanIndIcatoroforganperfusIon,hemolysIs,skeletal
muscledestructIon,andurInarytractIntegrItyaftertrauma.tsrelIabIlItyformonItorIng
perfusIonIsdecreasedbyprolongedshockprIortosurgeryandosmotIcdIuresIscausedby
admInIstratIonofmannItolorradIopaquedye.0ark,colacoloredurIneInthetrauma
patIentsuggestseItherhemoglobInurIaresultIngfromIncompatIblebloodtransfusIon,or
myoglobInurIacausedbymassIveskeletalmuscledestructIonafterbluntorelectrIcal
trauma.AlthoughthedefInItIvedIagnosIsIsmadebyserumelectrophoresIs,rapId
dIfferentIaldIagnosIscanbemadebycentrIfugatIonofabloodspecImen.PInkstaIned
serumsuggestshemoglobInurIa,whereasunstaInedserumIndIcatesmyoglobInurIa.8othof
thesecondItIonsmayresultInacuterenalfaIlure.PreventIonInvolvesInducIngdIuresIs
wIthfluIdsandmannItoland,InmyoglobInurIa,althoughcontroversIal,addItIonal
alkalInIzatIonoftheurInewIthsodIumbIcarbonatetopH5.6.FedcoloredurIneusuallyIs
causedbyhematurIa,whIchInthetraumatIzedpatIent,suggestsurInarytractInjury.t
shouldbeInvestIgatedwIthIntravenouspyelography.
Oxygenation
Frequently,mostcurrentlyusedoldergeneratIonpulseoxImetersfaIltoprovIdeaccurate
measurementsInpatIentswIthD
2
saturatIon90,hypothermIa,hypotensIon,decreased
perIpheralperfusIon,orexcessIvehandmotIon,andwhenexcessIveambIentlIght
InterfereswIthsensorfunctIon.
162
TraumapatIentsfrequentlydevelopthesecondItIons,
decreasIngtheusefulnessofnonInvasIveD
2
saturatIon(Spo
2
)monItorIng.NewgeneratIon
pulseoxImetersaredesIgnedtobemoreaccurateInthesecIrcumstances,althoughthey
arenotabsolutelyexact.TwocategorIesofthesedevIcesareavaIlable:forehead
oxImeterswIthreflectancemodesensors,producedprImarIlybyNellcorPulseDxImetry,
NellcorTycoHealthcare,8oulder,CD;andfIngerorearlobepulseoxImeterswIth
transmIssIonmodesensors,prIncIpallymanufacturedby|asImo.WIththetransmIssIon
modesensor,theoptIcalemItteranddetectorareposItIonedopposItetoeachotherason
thefInger,whereasInreflectancemode,theemItteranddetectorareposItIonedsIdeby
sIde.TheforeheadpulseoxImeterIslessaffectedbydecreasedperfusIonbecauseItsenses
thepulsatIonofthesupraorbItalartery,abranchofthecarotIdartery,whIchIs
presumablylessaffectedbyshockorhypothermIa.HoweverSpo
2
resultswIththIsmonItor
maybeaffectedbyvenouspulsatIon,especIallyInpatIentsreceIvIngposItIvepressure
ventIlatIonorInanysItuatIonthatdIstendsthetrIbutarIesofthesuperIorvenacava.
16J
t
hasbeensuggestedthatusIngthesesensorswIthaheadbandthatexerts10to20mmHg
pressuremaymInImIzetheInaccuracy.
16J
ThenewgeneratIon|asImotransmIssIonmode
pulseoxImeterscomeInseveraltypes.Dfthese,the|asImo8lueSensorattachedtoa
|asImoSetFadIcalpulseoxImeterappearstoprovIdethemostaccurateresults,
comparabletothoseobtaInedwIththeforeheadoxImeter.
164,165
WIthrecentadvancesIntechnology,multIwavelengthpulsecooxImetersarealsocapable
ofprovIdIngotherphysIologIcdataIncludIngpulserate,Spo
2
,perfusIonIndex,
carboxyhemoglobIn,andmethemoglobIn.ThesemonItorscanalsomeasurenonInvasIve
contInuoushemoglobInconcentratIon(SpHb)wIthreasonableaccuracy.
166
TheabIlItyof
thesenewmonItors(|asImoFad7andFad57PulseCDoxImeter)tomeasure
methemoglobInandcarboxyhemoglobInconcentratIonnonInvasIvelyrendersthemhIghly
usefulInacuteburnInjurymanagement.AbuIltInalgorIthmalsoallowsthesemonItors
automatIcallytoestImatetherespIratoryvarIatIonsofthepulseoxImetrycurve,provIdIng
InformatIonaboutIntravascularvolume.
167
AlthoughthesemonItorsprovIdemoreaccurate
InformatIonthanconventIonalpulseoxImeters,tothebestofourknowledgetheyhavenot
yetbeentestedInmajortraumapatIents.
Organ Perfusion and Oxygen Utilization
AsdIscussedprevIously,unrecognIzedhypoperfusIonmayleadtosplanchnIcIschemIawIth
resultIngacIdosIsIntheIntestInalwall,permIttIngthepassageoflumInalmIcroorganIsms
IntothecIrculatIonandreleaseofInflammatorymedIators,causIngsepsIsandmultIorgan
faIlure.
4J,44,45
DxygentransportvarIables,basedefIcIt,bloodlactatelevel,andgastrIc
IntramucosalpH(pHI)areconsIderedacceptablemarkersoforganhypoperfusIonInthe
apparentlyresuscItatedpatIentandmaybeusedtosettheoptImalendpoIntsof
resuscItatIon.
45
CastrIcIntramucosalpHmonItorIngIstoocumbersometousedurIng
surgeryandIntheImmedIatepostoperatIveperIod.|onItorIngofbasedefIcItandblood
lactatelevelhasalreadybeendIscussedInthesectIon|anagementofShock.
DxygentransportvarIablesconsIstofoxygendelIvery(0o
2
),D
2
consumptIon(7o
2
),andD
2
extractIonratIo(seeChapter11).A0o
2
Index(0o
2
)of500mL/mIn/m
2
hasbeenshownto
beanacceptablegoalforoptImalshockresuscItatIon,
168
performIngaseffectIvelyasthe
prevIouslyrecommended0o
2
of600mL/mIn/m
2
.SelectIonofthesespecIfIcnumbersIs
basedontheresultsofstudIesInwhIchcrItIcallyIllpatIentswhocouldIncrease0o
2
above
thIslevelsurvIved.At0o
2
500mL/mIn/m
2
,patIentsreceIvedapproxImatelyJ0less
crystalloIdsandbloodtransfusIonsthanwererequIredtoattaInthehIgherlevel.A
computerIzedCUbedsIdedecIsIonprotocoldevelopedtostandardIzeshockresuscItatIon
Insomecentersuses0o
2
500mL/mIn/m
2
asagoal.
168
ThIsIsapartIcularlyusefulend
poIntbecauseItIntegratesthreeImportantvarIables:hemoglobInconcentratIon,arterIal
oxygensaturatIon,andcardIacoutput.TheoxygenconsumptIonIndex(7o
2
)Isalsoan
ImportantvarIable.SubsequentorganfaIluremayoccurIfItdecreasesbelowavalueof
170mL/mIn/m
2
,IndIcatIngaflowdependentphaseofD
2
utIlIzatIon.
45
ncreasIng0o
2
untIl
7o
2
attaInsflowIndependencemaypreventorganfaIlure;however,thIsapproachIsnot
practIcalclInIcally,maInlybecausetherearealso0o
2
Independentregulatorsof7o
2
.
168
FInallyaglobalD
2
extractIonratIo0.25to0.JsuggestsabsenceofdysoxIa.However,ItIs
possIblethatdysoxIamaybepresentInanIndIvIdualorganInthepresenceofanormal
overallD
2
extractIonratIo.|onItorIngofD
2
transportvarIables,themostusefulofwhIch
Is0o
2
,IsusuallydoneIntheCUwhenInvasIvemonItorIngpermItsmeasurementof
cardIacoutputandmIxedvenousD
2
.ThesevaluescanalsobemonItoredIntheDF
wheneverarterIalandpulmonaryarterylInesarepresent.
AparameterthathasbeenmorerecentlyusedIntraoperatIvelyasaguIdetoresuscItatIon
durIngemergencysurgeryfortraumapatIentsIstheendtIdalarterIalCD
2
dIfference(Pa
ET)CD
2
.7alues10mmHgafterresuscItatIonpredIctmortalIty.
169
tmayalsobeusefulIn
thedecIsIonaboutwhentoperformdamagecontrolsurgeryand,IntraoperatIvely,In
guIdIngresuscItatIonwIthfluIds,Inotropes,andvasopressors.
Coagulation
ConventIonalbloodcoagulatIonmonItorIngIncludesabaselIneandsubsequentserIal
measurementsofPT,actIvatedpartIalthromboplastIntIme(aPTT),plateletcount,blood
fIbrInogenlevel,andfIbrIndegradatIonproducts(F0P;seeChapter16).Althoughtrauma
centerlaboratorIescannotprovIderesultsofthestandardcoagulatIontestswIthInanhour,
abloodsampleshouldbesenttothelaboratorytodetermIne,atleastretrospectIvely,the
etIologyofanycoagulatIonabnormalIty.Thetubetest,whIchInvolvesobtaInIngatube
ofbloodwIthnoantIcoagulantandobservIngcoagulatIon,clotretractIon,andclotlysIs,Is
apractIcalIntraoperatIvemethod
P.915
ofcoagulatIonmonItorIng.fagoodqualItyclotdoesnotform,ordoessoonlyafter10to
20mInutes,clottIngfactordefIcIencyIsthemostlIkelycause.FaIlureofclotretractIon
wIthIn1hourafterbloodsamplIngsuggestsplateletdepletIonordysfunctIon.ClotlysIs
earlIerthan6hoursIndIcatesfIbrInolysIs,whIchIsInfrequentIntraumapatIents.
0IssemInatedIntravascularcoagulatIon(0C)occursfrequentlyaftertraumaandIs
assocIatedwIthabsenceofspontaneousclottIngInthetubetest.naddItIontocausIng
bleedIng,ItmaypreventtypIngandcrossmatchIngofblood.
Figure 36-9.CalculateddosereductIonofvarIousanesthetIcsadmInIsteredasabolus
orInfusIonInmoderatehemorrhagIcshock.CalculatIonIsbasedonpharmacokInetIc
andpharmacodynamIcstudIesperformedInexperImentalhemorrhagIcshock.
(FeprIntedfromShaferSL:Shockvalues.AnesthesIology2004;101:567,wIth
permIssIon.)
Thrombelastography(TEC)IssImIlarInprIncIpletothetubetestbutprovIdesa
quantItatIve,graphIcevaluatIonofclottIngfunctIon.
170
TECdetermInesthetIme
necessaryforInItIalfIbrInformatIon,therapIdItyoffIbrIndeposItIon,clotconsIstency,the
rateofclotformatIon,andthetImesrequIredforclotretractIonandlysIs.
170
8asIcally,the
FandKvaluesareIndIcesofformatIon,buIldup,andcrosslInkIngoffIbrIn,anddependon
thefunctIonofcoagulatIonfactors.ThemaxImumamplItudeIsthewIdestportIonofthe
curveandIndIcatestheabsolutestrengthofthefIbrInclot.trepresentsplateletfunctIon.
Thea-angleIstheslopeoftheexternaldIvergenceofthetracIngfromtheFvaluepoInt,
IndIcatIngthespeedofclotformatIonandfIbrIncrosslInkIng.ThevalueofthIsparameter
IsdetermInedbybothcoagulatIonfactorsandplatelets.HypothermIacancause
coagulopathybyInterferIngwIthbothplateletsandcoagulatIonfactors.
171
Whentheblood
ofacoldandcoagulopathIcpatIentIsplacedIntheTECcuvette,whIchIsnormallyheated
toJ7`C,anearnormaltracemaybeobtaIned.NewerTECdevIcesaretemperature
adjustable.Thus,thetemperatureInthecuvettecanbeadjustedtothatofthepatIent.
Anesthetic and Adjunct Drugs
ApartfromregIonalanesthesIatechnIques,whIchareusedInpatIentswIthmInor
extremItyInjurIesandstablehemodynamIcs,anesthetIcandadjunctdrugsforgeneral
anesthesIaneedtobetaIloredtofIvemajorclInIcalcondItIons.ThevaryIngcontrIbutIonof
thesecondItIonstotheclInIcalpIctureofagIvenpatIentnecessItatesprIorItyorIented
plannIng.
Airway Compromise
AnesthetIcsandmusclerelaxantsshouldbeavoIdedbeforetheaIrwayIssecuredIfthereIs
sIgnIfIcantaIrwayobstructIonorIfthereIsdoubtastowhetherthepatIent'stracheacan
beIntubatedbecauseofanatomIclImItatIons.ftImepermIts,lateralneckradIographs,CT
scannIng,andendoscopycanbeusedtobetterdefInetheproblem.TopIcalanesthesIawIth
mIldsedatIoncanbeusedtosecuretheaIrwaywIthaconventIonalbladeorflexIbleFD8.
farapIdsequenceInductIonIscontemplated,ketamIneandetomIdatemayconfer
advantagesoverthIopentalandpropofol.nequIpotentdosesInnormovolemIcpatIents,
theyproducelesscardIovasculardepressIon.AlthoughsuccInylcholIne,wIthItsshortonset
tImeandduratIon,IsstIllthemusclerelaxantofchoIceforrapIdsequenceInductIon,
rocuronIum(0.9to1.2mg/kg)hasalmostthesameonsettImeanddoesnothavethe
undesIrablesIdeeffectsassocIatedwIthsuccInylcholIne(e.g.,IncreasedIntragastrIc
pressure,Intraocularpressure,andCP;potassIumreleaseInpatIentswIthburnsand
neurologIcdIseases),ItslongerduratIonofactIonmaybedIsadvantageousandmayleadto
hypoxIaIfbothventIlatIonandIntubatIonprovetobeImpossIble(seeChapter29).Under
thesecIrcumstances,a8ullardblade,ClIdeScope,WuScope,AIrtraqorotheraIdscanbe
employedtoovercometheproblem;surgIcalstandbyforcrIcothyroIdotomymaybe
consIderedIfothertechnIquesfaIl.
172
8radycardIa,dysrhythmIas,andcardIacarresthave
beendescrIbedaftersuccInylcholIneInthepresenceofhypoxIaandhypercarbIa;someof
thesecomplIcatIonsmayalsofollowanapparentlyuneventfulIntubatIonperformed
wIthoutsuccInylcholIne.
Hypovolemia
AnesthetIcagentsnotonlyhavedIrectcardIovasculardepressanteffects,butalsoInhIbIt
compensatoryhemodynamIcmechanIsmssuchascentralcatecholamIneoutputand
baroreflex(neuroregulatory)mechanIsms,whIchmaIntaInsystemIcpressureIn
hypovolemIa.HemorrhageandhypovolemIaleadtoahIgherthannormalblood
concentratIonfollowIngagIvendoseofIntravenousagents,IncreasedsensItIvItyofthe
braIntoanesthetIcs,preferentIaldIstrIbutIonofthecardIacoutputtothebraInandthe
heart,cerebralhypoxIa,dIlutIonalhypoproteInemIa,andacIdosIs,allofwhIchIncreasethe
effectsofdrugsonthebraInandtheheart.
ThepharmacokInetIcandpharmacodynamIcresponsesofIntravenousagentto
experImentalhemorrhagIcshockvary(seeChapter18).8ecauseofthedecreaseInsIzeof
thecentralcompartmentandInsystemIcclearance,plasmaconcentratIonsoffentanyland
remIfentanIlareIncreased.
17J
AdecreasedvolumeofdIstrIbutIonalsoIncreasestheblood
levelofetomIdateby20Inshock,
174
andforpropofolthIseffectIssubstantIal.ThereIs
alsovarIatIonIntheextentofbraInsensItIvItytotheseagents.AlthoughetomIdate
pharmacodynamIcsareunchanged,
175
asIgnIfIcantIncreaseInthesensItIvItyofthebraIn
andhearttopropofolIsnotedInanImals,
174
evenafterfluIdresuscItatIon.
174
8asedon
theseexperImentalfIndIngs,Shafer
176
calculatedthatInpatIentswIthshock,thedoseof
propofolshouldbeonly10to20ofthatgIventoahealthypatIent.Althoughhecalculated
thatetomIdatedoseshouldnotrequIreadjustmentforshock,wedecreasethedosebyat
least25to50whenwesuspecttreatedoruntreatedhypovolemIa.DftheopIoIds,the
calculateddoseforfentanylandremIfentanIlIsapproxImatelyonehalfofthatgIvento
healthypatIents
176
(FIg.J69).DftheremaInIngIntravenousagents,thIopentaland
mIdazolamarealsoknowntohavesIgnIfIcantcardIovasculardepressantactIvIty,whereas
ketamInehasstImulatoryeffectswhentheautonomIcnervoussystemIsIntact.
TherearealsodIfferencesamonganesthetIcsInthedIrectIonandextentoftheIreffectson
compensatorymechanIsms.Forexample,thebaroreceptordepressIonproducedby
IntravenousagentsIsusuallymIlderthanthatofInhalatIonalagents(seeChapter18).
DpIoIdagentshavelIttledIrectcardIovascularorbaroreflexdepressanteffect;however,
theseagentscan
P.916
causehypotensIonbyInhIbItIngcentralsympathetIcactIvIty,especIallyInthehypovolemIc
traumapatIentwhoseapparenthemodynamIcstabIlItyIsmaIntaInedbyhyperactIve
sympathetIctone.
TwoImportantprIncIplesIntheuseofanesthetIcagentsareaccurateestImatIonofthe
degreeofhypovolemIaandreductIonofdosesaccordIngly.ThepresenceofhypotensIon
suggestsuncompensatedhypovolemIa,InwhIchcaseanesthetIcsalmostInvarIablyproduce
furtherdeterIoratIonofsystemIcbloodpressureandsometImescardIacstandstIll.
ntravascularvolume,totheextentpossIble,mustberestoredbeforetheIruse.WhentIme
constraIntsorcontInuInghemorrhagepreventrestoratIonofbloodvolume,theaIrway
mustbesecuredwIthoutthebenefItofanesthesIa(perhapsusIngonlyrapIdlyactIng
musclerelaxantsandsmalldosesofopIoIds,etomIdate,orketamIne),eventhoughthIs
approachmayresultInrecallofInductIonandIntraoperatIveeventsInupto40of
patIents.
177
HypothermIa,alcoholIntoxIcatIon,drugusebeforeanesthesIa,andmetabolIc
dIsturbancesIntheacutetraumapatIentcannotrelIablypreventrecall.However,sco
polamIne,0.6mg,gIvenbeforeaIrwaymanagementmaydecreasethelIkelIhoodofthIs
complIcatIon.ntraoperatIveuseofthebIspectralIndexmonItorand,wheneverpossIble,
tItratInganesthetIcstobIspectralIndexlevels60maypreventrecallIntrauma
patIents.
178
nnormotensIvebuthypovolemIcpatIents,restoratIonofvolumeandselectIonofanagent
wIththeleastcardIovasculardepressanteffectappearslogIcal.KetamIneandetomIdate
arethepreferredInductIonagents,
175
althoughatlowdosesotherIntravenousanesthetIcs
arealsounlIkelytoproducehypotensIon(seeChapter18).Therefore,theuseofanyof
thesedrugsInreduceddosesIsprobablymoreImportantthanthepartIcularagentchosen.
TheseprIncIplesmaybecomeespecIallyImportantfortheanesthesIologIstIftheconcept
ofdelayedfluIdresuscItatIon,wIthhypovolemIaprolongeduntIlhemorrhageIscontrolled
surgIcally,becomeswIdelyaccepted.
55
|aIntenanceofanesthesIaInthehypovolemIctraumapatIentraIsesconcernssImIlarto
thosepertaInIngtoInductIon.FecentexperImentaldatahasshownthatdependIngonIts
severItyhemorrhagIcshockdecreasesmInImumalveolarconcentratIon(|AC)by
approxImately25(seeChapter17).FestoratIonofIntravascularvolumedIdnot,but
admInIstratIonofnaloxonedId,normalIze|ACIntheanImals,suggestIngthatshock
InducedreleaseofendorphInsIsprImarIlyresponsIbleforreductIonofIsoflurane|AC.
179
AlthoughthemyocardIaldepressanteffectofnItrousoxIde(N
2
D)Isnormallysomewhat
counterbalancedbyItsabIlItytoIncreasesympathetIcoutflow,Inacutehemorrhagethere
IsalreadyadramatIcIncreaseInsympathetIcactIvItyandstImulatIonofbaroreceptors.
UnderthesecIrcumstances,patIentsareunlIkelytorespondtothesympathetIceffectof
N
2
D,andthecardIovasculardepressantpropertIesofthegasareunmasked;thesemaybe
sImIlartothoseofotherInhalatIonagents.naddItIon,byreducIngFD
2
,useofN
2
DIncurs
arIskofhypoxemIaInpatIentswIthreducedcardIacoutputorpulmonarycompromIse.
0espItecausInglIttleImpaIrmentofreflextachycardIaandhavIngavasodIlatoryactIon
thatpreservesorganbloodflowInnormovolemIcpatIents,IsofluranecanImpaIrcardIac
outputandorganbloodflowInhypovolemIathatIs,ItcancausecardIovascular
depressIon.0esfluraneandsevofluranearenotsIgnIfIcantlybetterthanIsofluraneInthIs
regard.However,becauseoftheIrlowsolubIlItyInblood,severehemodynamIcdepressIon
producedbytheseagentscanberapIdlyreversed,preventIngsuboptImalperfusIonfora
sIgnIfIcantperIodoftIme.nsummary,InthehypovolemIcpatIentallInhalatIonalagents
mayreducebothglobalandregIonalbloodflows,andtherefore,shouldbeusedonlyIn
smallconcentratIons(1|AC).DpIoIdsupplementatIonIsusuallywelltoleratedandoften
IndIcated.
Head and Open Eye Injuries
TheImportanceofdeepanesthesIaandadequatemusclerelaxatIondurIngaIrway
managementofpatIentswIthheadoropeneyeInjurIeshasalreadybeendIscussed.
AnesthetIcagentsselectedformanagementofbraInInjuryshouldproducetheleast
IncreaseInCP,theleastdecreaseInmeanarterIalpressure,andthegreatestreductIonIn
cerebralmetabolIcrate(C|FD
2
;seeChapter56).AsdemonstratedbyIntraoperatIveSjvo
2
measurementsInpatIentswIthacuteheadInjury,themostImportantfactorIncausIng
cerebralIschemIaIsIncreasedCPfromIntracranIalhematoma.PromptdecompressIonIs
themostcrucIalmeansofensurIngcerebralwellbeIng.HypotensIoncausedbyanesthetIcs
orotherfactorscontrIbutestothedevelopmentorprogressIonofcerebralIschemIa.
UtmostattentIonshouldbepaIddurInganesthesIatoavoIdanceofhypotensIon(mean
arterIalpressure60mmHg)and,moreImportant,IfrelIableSjvo
2
monItorIngIsInplace,
toavoIdvalues55to60.WIththepossIbleexceptIonofketamIne,allIntravenous
anesthetIcscausecomparabledegreesofcerebrovascularconstrIctIon.
180
ThIopental,
mIdazolam,propofol,andetomIdatethereforealsoproduceadosedependentreductIonIn
cerebrospInalfluIdformatIon.AgaIn,wIththeexceptIonofketamIne,C|FD
2
Isalso
reducedbyalltheavaIlableIntravenousanesthetIcs.
180
AnImportantdrawbacktothese
agentsIsthattheIrcardIovasculardepressanteffectsmayreduceCPP.
180
ThIsproblemcan
beamelIoratedbyadmInIsterIngpretreatmentdosesofopIoIds(fentanyl,2toJg/kg),
whIchpermItreductIonoftheanesthetIcdose.ThIsmayalsopreventthemyoclonIc
movementsassocIatedwIthetomIdateandoccasIonallywIthpropofol,andthusreducethe
rIsksofCPandDPIncrease.Nevertheless,myoclonusIsbestpreventedbycarefultImIng
ofthedoseofmusclerelaxants.
181
AnothermeasuretopreserveCPPdurInganesthesIaIsto
admInIstervasopressors,beIngawarethathypovolemIamaybemaskedbytheIruse.
DrdInarIly,admInIstratIonofsuccInylcholIneshouldfollowpretreatmentdosesof
nondepolarIzIngagentstopreventfascIculatIonInducedelevatIonofCPandDP
182
(see
Chapter20).AvoIdIngsuccInylcholIneusuallydoesnotallevIatetheproblembecause
laryngoscopyandtrachealIntubatIonproduceagreaterandlongerlastIngIncreaseInDP
andCP.
18J
FocuronIum,0.9to1.2mg/kg,hasanonsettImecomparablewIththatof
succInylcholIne.
184
|IvacurIumhasalongeronsettImethanrocuronIumand,unlIke
rocuronIum,cancausevasodIlatatIonandhypotensIon.NoneofthenondepolarIzIngmuscle
relaxantscauseselevatIonofCPorDPIntheabsenceofassocIatedtrachealIntubatIon.
AllInhalatIonanesthetIcsmayIncreaseC8F,cerebralbloodvolume,andthustheCP.
CerebralautoregulatIon,CD
2
responsIveness,andC|FD
2
arereduced.UnlIkethIopental,
whIchdecreasesbothC8FandC|FD
2
Inparallel,InhalatIonalanesthetIcsdecreaseC|FD
2
whIleIncreasIngtheC8F.TheextentofthIsuncouplIngvarIeswIththeagentandthedose.
sofluranehastheleastvasodIlatoryeffectandthusIsthemostwIdelyusedInhalatIon
anesthetIc,althoughdesfluraneandsevofluranehavecomparableeffectsonthecerebral
cIrculatIon.nhyperventIlatedpatIentswIthcerebraltumorsormIldedema,Isoflurane
doesnotraIsetheCPIfItIsadmInIsteredatanInspIredconcentratIonof1|AC.nthe
presenceofsevereheadInjury,whencerebralautoregulatIonandCD
2
responsIvenessare
ImpaIred,IsofluranehasthepotentIaltoIncreaseC8FandCPevenatlevels1|ACand
wIthhyperventIlatIon.Therefore,ItmaybeprudentnottousethIsagentathIgh
concentratIonsInthepresenceofelevatedCP,atleastuntIltheskullIsopenedandthe
CPIscontrolled.nthesepatIents,anesthesIacanbemaIntaInedInItIallywIthopIoIdsplus
thIopental,propofol,mIdazolam,oretomIdate.
NItrousoxIdemayIncreaseC8F,cerebralbloodvolume,andCPwhenadmInIsteredwIth
InhalatIonanesthetIcsIfthe
P.917
Paco
2
IsnormalorIncreased.ThIseffectmaybeelImInatedwhenthIsagentIs
admInIsteredwIthadequatedosesofbarbIturatesorhyperventIlatIon.Theeffecton
C|FD
2
IsvarIable:bothanIncreaseandadecreasehavebeenobserved.Thus,N
2
D
probablyIsnotdeleterIousInpatIentswIthheadInjurywIthmInImalCPelevatIon,IfItIs
usedafterabolusdoseordurIngInfusIonofIntravenousanesthetIcs.
naspontaneouslybreathIngpatIent,opIoIdsmayproducehypoventIlatIonwIthan
assocIatedIncreaseInC8FandCP;therefore,theyshouldbeusedInheadtraumaonlyIn
mechanIcallyventIlatedpatIents(seeChapterJ9).SomereportssuggestthatopIoIdsand,
toasmallerextent,opIatesmayInterferewIthCPPbyIncreasIngCP,decreasIngmean
arterIalpressure,orboth.
5,185
FentanylandsufentanIlaremostImplIcated,andItappears
thatthIsphenomenonoccurswhentheheadInjuryIssevere.
186
AlthoughtheclInIcal
sIgnIfIcanceofthesefIndIngsIsnotyetclear,ItIsprudenttoadmInIsterfentanylorIts
analogsslowly,whenthearterIalpressureIsnormalorslIghtlyelevated,ensurIng
preservatIonofsystemIcbloodpressurewIthvasoactIveagents,Ifnecessary.
Cardiac Injury
fthereIsperIcardIaltamponade,preloadandmyocardIalcontractIlItyshouldbe
maIntaIned(seeChapter41)asanydecreaseIntheseparametersmayexacerbatean
alreadyexIstIngF7InflowocclusIon.AdecreaseInheartrateshouldalsobetreated
promptlytomaIntaInadequatecardIacoutput.8ecausealltheavaIlableanesthetIcscan
depressmyocardIalcontractIlItyandcausevasodIlatIon,ItIspreferabletoadmInIster
theseagentsafterevacuatIonofperIcardIalbloodunderlocalanesthesIa.fgeneral
anesthesIaIsrequIredtorelIevethetamponade,InductIonshouldbedelayeduntIlthe
patIentIspreparedanddraped.8othanesthetIcsandcontrolledventIlatIon,partIcularly
wIthPEEP,ImpaIrcardIacoutput.0eepanesthesIaandhIghaIrwaypressuresshouldbe
avoIdedbeforeevacuatIonofthehemoperIcardIum.nchronIcperIcardIaleffusIon,
ketamInesupportsthecardIacIndexbetterthandIazepam.nacuteperIcardIal
tamponade,evenmInorInsultscanbrIngcardIacactIvItytoahalt.KetamInethusremaIns
theagentofchoIce.tshouldbegIvenInsmalldosesafteradequatefluIdInfusIon.SImIlar
prIncIplesapplytotheuseofmaIntenanceagents,whIchshouldbegIvenInthesmallest
possIbledosesuntIltheheartIsdecompressed.TEEmonItorIngmayaIdmanagement
betweenInductIonandperIcardIotomy.
nbluntmyocardIalInjury,theobjectIveIsnotonlytomaIntaIncardIaccontractIlIty,but
alsotolowertheelevatedpulmonaryvascularresIstancethatmayresultfrom
concomItantpulmonarycontusIon,atelectasIsoraspIratIon.Preferably,allanesthetIcs
shouldbeadmInIsteredafterrestoratIonofIntravascularvolumeandtItratedtomaIntaIn
adequatesystemIcbloodpressureandcardIacoutput.fnecessary,Inotropes,preferably
amrInoneormIlrInone,whIchproducesomepulmonaryvasodIlatIon,maybeused.
AnesthetIcmaIntenancebyInfusIonofIntravenousanesthetIcsandopIoIdstoavoIdthe
myocardIaldepressIonproducedbyInhalatIonalagentsshouldalsobeconsIdered.
Burns
AhypermetabolIcstatecharacterIzedbytachycardIa,tachypnea,catecholamInesurge,
IncreasedD
2
consumptIon,andaugmentedcatabolIsmfollowstheInItIalfewhoursofa
burnandcontInuesIntotheconvalescentphase,necessItatIngIncreasedoxygen,
ventIlatIon,andnutrItIon.
1JJ
EarlyextensIveandrepeatedescharotomIeswIthcoverageof
skIngraftsattenuatepostburnhypermetabolIcresponse,decreasefluIdloss,andImprove
survIval.tIsusuallyperformedbetweentheseconddayandthesecondweek,often
necessItatIngmassIvetransfusIon,temperaturecontrol,andmanagementoffluId,
electrolyte,andcoagulatIonabnormalItIes.UsuallyeItheranautograftharvestedfromthe
patIent,allograftfromacadaver,orboth,Isused.Fecently,artIfIcIalskIn,ntegra(ntegra
LIfeScIences,PlaInsboro,NJ)consIstIngofdermalInnerlayermadeofbovInecollagenand
chondroItIn6sulfateandneoepIdermalouterlayermadeofpolysIloxanepolymerIsalso
usedwIthmorefavorablereductIonofrestIngenergyexpendItureandelevatIonofserum
proteInsascomparedwIthcadaverIcskIn.
187
AnesthetIcmanagementofescharotomIespresentsseveraldIffIcultIes.8urnedtIssuemay
preventaccessforECC,pulseoxImeter,neuromuscularfunctIon,andnonInvasIveblood
pressuremonItorIng;needleelectrodesorsurgIcalstaples,areflectancepulseoxImeter,
andanarterIalcathetermaybenecessary.LargeboreIntravenouscathetersareessentIal.
HyperthermIaoccurs,buthypothermIaIsmorelIkelyIntheDFandIstobeavoIded.
ExposureandevaporatIvefluIdlossnecessItatemaIntenanceoftheDFtemperature
between28andJ2`C,useofcountercurrentfluIdandbloodwarmIngdevIces,surface
heatIngwIthforceddry,warmaIr,andhumIdIfIedInspIredgases.8loodlosscanbe
controlledbyrestrIctIngtheescharotomyto15to20ofT8SA,useofextremIty
tournIquets,admInIsterIngtopIcalthrombInandfIbrInsealantsontheexcIsedarea,
188
applyIngdIluteepInephrInesolutIontopIcally(1:10,000)orbyInjectIon(0.5mgper1,000
mL),andusIngcompressIonbandages.EpInephrInedosesofupto6.7mgtopIcallyor0.8mg
byInjectIonIntothesurgIcalareaarewelltolerated;theaffInItyofadrenergIcreceptors
tolIgandsIsdecreasedafterburns.TheadmInIstratIonofalargeamountofbloodand
bloodproductssubjectsthepatIenttocomplIcatIonsoftransfusIonsuchascoagulopathy.
AlthoughcItrateInducedhypocalcemIaIsarelatIvelyrarecomplIcatIonoftransfusIon,
189
monItorIngofCa
2+
andadmInIstratIonofcalcIumchlorIde(2.5to5.0mg/kg)orgluconate
(7.5to10.0mg/kg)shouldbeconsIderedwhenbloodproductsareadmInIsteredrapIdly.
Shock,hyperdynamIccIrculatIon,decreasedserumalbumInconcentratIon,Increased
1
acIdglycoproteInconcentratIon,andalteredreceptorsensItIvItyaltertheresponseto
varIousdrugsdurIngtheresuscItatIveandconvalescentphases.
1JJ
ThedosesofIntravenous
anesthetIcsshouldbereduceddurIngtheresuscItatIonphasetopreventexcessIve
hemodynamIcdepressIon.8urnpatIentshaveexcrucIatIngpaInandexceedInglyhIghopIoId
requIrements.AprovenanesthetIcregImenforexcIsIonandgraftIngofburnsIsIsoflurane
pluslargedosesofopIoId.TheresponsetodepolarIzIngandnondepolarIzIngmuscle
relaxantsremaInsunaltereddurIngthefIrst24hoursafterburnInjury.However,afterthe
fIrstday,succInylcholIneshouldbeavoIdedforatleast1yearbecauseItcanresultIna
potentIallylethalIncreaseofserumK
+
whentheburnsIzeexceeds10ofT8SA.The
mechanIsmofthIsresponseIsrelatedtoupregulatIon(Increase)ofacetylcholIne
receptors,whIchultImatelyoccupytheentIremusclemembrane,theaddItIonalexpressIon
oftwonewIsoformsofacetylcholInereceptor,andtherecentlydescrIbednIcotInIc
(neural)7acetylcholInereceptors.ThelattercanbedepolarIzednotonlyby
acetylcholIneandsuccInylcholIne,butalsobycholIne,whIchthusplaysanImportantrole
InthedevelopmentofhyperkalemIa.
190
FesIstancedevelopstoallnondepolarIzIngmuscle
relaxants,exceptmIvacurIumInpatIentswIthburnsofJ0T8SAstartIngapproxImately1
weekandpeakIng5to6weeksafterInjury,probablyfrompharmacodynamIccauses.
1JJ,1J4
ncreasIngthedosecanpartlyovercomethIsresIstance.ForInstance,rocuronIum,whIchIs
ImportantforrapIdsequenceInductIonandtreatmentoflaryngospasmwhen
succInylcholIneIscontraIndIcated,hasanonsettImedelayedbyabout50seconds(J0
longerthanpatIentswIthoutburn)whena0.9mg/kgdoseIsused.ncreasIngthedoseto
1.2mg/kgdecreasesthedelaybyJ0secondsbuttheonsettImeremaInsabout25toJ0
secondslongerthanthatobservedInpatIentswIthoutburn.
P.918
ntubatIngcondItIonsalsoImprovebyIncreasIngthedose.FecoverytImefromblockIs
shorterInburnpatIentsthanInnormalIndIvIduals.
191
ForserIalwounddebrIdement,ketamIneInIntermIttentdoses,neuraxIalorperIpheral
nerveblocksvIaanIndwellIngcatheter,orsedatIonwIthopIoIdsandIntravenousagents
maybeemployed.
Management of Intraoperative Complications
Persistent Hypotension
PersIstenthypotensIonfollowIngtraumaIsusuallytheresultofoneoffourmechanIsms:
bleedIng,tensIonpneumothorax,neurogenIcshock,andcardIacInjury.Althoughmany
othercauses,suchascItrateIntoxIcatIon(hypocalcemIa),hypothermIa,coronaryartery
dIsease,allergIcreactIons,orIncompatIbletransfusIonmayberesponsIbleforthIs
complIcatIon,theyoccurInfrequently.
HypotensIonIsmostlIkelyduetobleedIng.ThesourcemaybeobvIous,suchasexternal
bleedIngfromtheskulloranopenvesselIntheextremItIes,orhIdden.ThethoracIcand
abdomInalcavItIesandthepelvIcretroperItonealspacearethemostcommonsItesof
occulthemorrhagethatresultsInhypotensIon.|anagementIncludesearlydIagnosIsand
controlofthebleedIngsItepluseffectIvefluIdresuscItatIon.Thelattercanbestbe
accomplIshedusInganInfusIonsystemwIthlargedIametertubIng(5mm)anda
countercurrentheatexchanger.Upto1,000mL/mInofcrystalloIdsolutIonor600mL/mIn
ofpackedcellscanbegIvenIfaboxtypepressurepumpandalargeboreIntravenous
cannulaareused.Thesystemshouldbeconnectedto14gaugeorlargercannulas,
preferablyInsertedIntoveInsbothaboveandbelowthedIaphragm.TherapIdInfusor
system(8elmontnstrumentCorp.,8ellerIca,|A),whIchconsIstsofareservoIr,
countercurrentheatIngsystem,androllerpump,IscapableofdelIverIngupto1,600
mL/mInofwarmfluIdsoncetherateofInfusIonIsprogrammed.
DftheIsotonIccrystalloIdsolutIons,LFIspreferredovernormalsalIne.ExperImental
evIdenceshowsthatresuscItatIonwIthnormalsalInedurInguncontrolledhemorrhageIs
assocIatedwIthgreaterurIneoutputandthusgreaterfluIdrequIrementcomparedwIthLF,
resultIngInhyperchloremIcacIdosIsanddIlutIonalcoagulopathy.
192
AcIdosIsdoesnotoccur
wIthLF,buttIssueedemamayresultfromItsslIghthypotonIcIty(27JmDsm/L),and
neutralIzatIonofthecItrateantIcoagulantInPF8CsmayoccurbecauseofItsCa
2+
content.
HumanserumalbumIn(5and25)andhydroxyethylstarcharethemostcommonlyused
colloIds.Hetastarch,ahIghmolecularweIght(670k0a)polymerIcglucosecompound,Is
currentlythemostcommonlyusedhydroxyethylstarchIntheUnItedStates.8ecauseofIts
molecularweIght,ItremaInswIthInthebloodvesselsandcanrestorethebloodvolume.
However,ItalsohasanadverseeffectoncoagulatIon,especIallyonplatelets,factor7,
andvonWIllebrandfactor.Thus,therecommendeddoseshouldnotexceed20mL/kg,
althougharevIewsuggeststhatthereIslIttlesupportforthIsrecommendatIon.
19J
ts
IntravascularretentIonandadverseeffectsoncoagulatIonarenotonlyrelatedtoIts
molecularweIghtbutalsotomolarsubstItutIon,whIchIsdefInedasthenumberof
hydroxyethylgroupsperglucosesubunIt;thehIgherthemolarsubstItutIon,thehIgherthe
IntravascularretentIonandthusthemoreseverethecoagulopathy.Effortstoreduce
molecularweIghtandmolarsubstItutIonInordertomaIntaInIntravascularretentIonand
yetmInImIzecoagulopathyrecentlyresultedInthedevelopmentofanewcompound,
hydroxyethylstarch1J0/0.4(7oluven;FresnIusKabI,8adHomburg,Cermany),InEurope
wIthamolecularweIghtof1J0k0aandmolarsubstItutIonof0.4.AlthoughItsuseInmajor
traumapatIentsremaInstobeInvestIgated,ItappearstoprovIdeadequatevascular
volumeexpansIonwIthlesscoagulatIonabnormalItyInpatIentsundergoIngmajor
orthopaedIcsurgery.
AlthoughhIghlyexperImental,anewconceptInhemorrhagIcshockmanagementIsthe
combIneduseoffluIdandvasopressortreatment.TheoretIcally,thIsstrategymayrapIdly
restorebloodpressuretonormallevelswhIlelImItIngthefluIdvolumeInfused.Amoderate
doseofnorepInephrInewIthfluIdshasbeenshowntoImproveshorttermsurvIvalIn
experImentalanImals.
194
NeurogenIcshockfromspInalcordInjurymaybemIsseddurIng
InItIalevaluatIon,especIallyInunconscIouspatIents.However,dIfferentIatIonof
neurogenIcshockfromhemorrhagIcshockIsImportant
195
:patIentswIthspInalcordInjury
areoftenbradycardIcandreadIlyrespondtocatecholamIneadmInIstratIon.|IstakIng
neurogenIcshockforhemorrhagIcshockmayleadtoexcessIvefluIdInfusIonandpulmonary
edema.Thereverseerrormayalsooccur:deprIvIngpatIentswIthhemorrhagIcshockof
fluIdsbecauseofmIsdIagnosIsofneurogenIcshock.nvasIvecentralhemodynamIc
monItorIngmaybeIndIcatedInsuchpatIents.
112
nsomepatIents,ofcourse,hemorrhagIc
shockandneurogenIcshockmaycoexIst.
CardIaccausesofpersIstenthypotensIonIncludebluntcardIacInjuryandperIcardIal
tamponade.ntraoperatIveTEEcanbeusefulInthedIfferentIaldIagnosIs.TheF7Ismost
commonlyInvolvedInbluntcardIacInjury.fthereIsaconcomItantIncreaseInpulmonary
vascularresIstance(e.g.,fromanassocIatedpulmonarycontusIon),theF7pressure
IncreaseswhIleItsoutputdecreases,resultIngInanIncreasedC7P.TheraIsedF7pressure
causestheInterventrIcularseptumtoshIfttowardtheleft,decreasIngleftventrIcular
complIance,IncreasIngItsdIastolIcpressure,anddecreasIngcardIacoutput(ventrIcular
Interdependence).ThesealteratIonsIncardIacanatomyandventrIculardynamIcscanbe
dIsplayedbyTEE,InformatIonthatcanbeusefuldurIngInterpretatIonofelevatedcardIac
fIllIngpressures.
ntheabsenceofTEE,apulmonaryarterycathetermaybehelpful.EqualIzatIonof
pressuresacrossthecardIacchambersdurIngdIastolesuggestsperIcardIaltamponade.A
sImIlarpIcturemayalsobeseenInseverebluntcardIacInjury,causIngdIffIcultyIn
dIfferentIaldIagnosIs.ThIseffect,however,IsrareandIsusuallyassocIatedwIthcrItIcal
hemodynamIcInstabIlIty.0IfferentIaldIagnosIsIntheseInstancescanbeestablIshedby
perIcardIocentesIs.SeptalencroachmentIntotheleftventrIclefromF7contusIonresults
InanIncreaseInpulmonaryarterywedgepressure.0ecreasIngtherateoffluIdInfusIonIn
thesepatIentsresultsInafurtherdecreaseIncardIacoutput.TreatmentIncludesfluId
InfusIon,pulmonaryvasodIlatorsIfthesystemIcbloodpressureIsnormal,andInotropIc
supportIfthesystemIcbloodpressureIslow.AbsenceofresponsetothIstreatmentIsan
IndIcatIonforplacementofanIntraaortIcballoonpump.PulmonaryarterycatheterIzatIon
mayalsohelpdetectanoxygenstepupfromseptalInjury.0urIngthoracotomy,a
dIstendedF7shouldalsoraIsethesuspIcIonofaseptaldefect.
Hypothermia
Shock,alcoholIntoxIcatIon,exposuretocold,fluIdresuscItatIon,andabnormalItIesIn
thermoregulatorymechanIsmsrenderthemajortraumapatIenthypothermIcdurIngthe
InItIalphaseofInjury.AdmIssIonhypothermIa,whIchIspresentInapproxImately50of
patIents,IsanIndependentrIskfactoraftermajortrauma,
196
andthemortalItyrate
IncreaseswIthdecreasIngtemperature.SeverehypothermIa,whIchInthetraumapatIent
IsdefInedascoretemperaturebelowJ2`C,
197
wasassocIatedwItha100mortalItyrateIn
onestudy.
198
TheIntraoperatIverIskofhypothermIaIsalsohIgherforthetraumapatIent
thanforelectIvelyoperatedpatIents.
199
HeatlossIncreasesespecIallyInpatIentswIth
spInalcord,extensIvesofttIssue,andburnInjurIes,andInthosewhoconsumedethanol
beforesurgeryorpatIentsundergoIngbodycavItysurgery.
P.919
Figure 36-10.TherateofrIseIncoretemperaturewIthcIrculatIngwaterandforced
aIrdevIcesusedInhealthyanesthetIzedvolunteers.CIrculatIngwaterdevIceswarm
thebodyfasterthanforcedaIrdevIces.(FeproducedfromWadhwaA,KomatsuF,
DrhanSungur|etal:NewcIrculatIngwaterdevIceswarmmorequIcklythanforced
aIrInvolunteers.AnesthAnalg2007;105:1681,wIthpermIssIon.)
HypothermIacausescardIacdepressIon,myocardIalIschemIa,dysrhythmIas,perIpheral
vasoconstrIctIon,ImpaIredtIssueoxygendelIvery,elevatedoxygenconsumptIondurIng
rewarmIng,bluntedresponsetocatecholamInes,IncreasedbloodvIscosIty,metabolIc
acIdosIs,alteredplateletandclottIngfunctIon,abnormalItIesofK
+
andCa
2+
hemostasIs,
reduceddrugclearance,andIncreasedrIskofInfectIon.
196,197,198,199
FewarmIngafter
hypothermIa,especIallyatarapIdrate,mayreleaseaccumulatedmetabolIcproductsInto
thecentralcIrculatIoncausIngfurthermyocardIaldepressIon,hypotensIon,andIncreased
acIdosIs.8ecauseoftheseadverseeffects,delIberatehypothermIa,althoughItIsbelIeved
tobeprotectIveoforganfunctIon,hasnoIndIcatIondurIngresuscItatIonfromhemorrhagIc
shockandthemanagementofheadInjury.
PreventIonofhypothermIaandcorrectIonofbodytemperaturetonormalappearto
decreasemortalItyrate,bloodloss,fluIdrequIrement,organfaIlure,andlengthofCU
stay.
200
ConvectIvewarmIngwIthforceddryaIrat4J`CcanpreventatemperaturedropIn
mosttraumapatIentsbutcannoteffectIvelytreatseverehypothermIa;becausethelow
specIfIcheatofaIrhaslIttleheatcontenttogIvetothecoldtraumapatIent,andoften
becauseofthenatureofthesurgIcalprocedure,onlyalImItedbodysurfaceareaIs
exposedtowarmIng.
200
NewlydevelopedcIrculatIngwaterwarmersthatoccupya
relatIvelysmallerbodysurfaceareathanforcedaIrwarmersmayproducefaster
rewarmIng
201
(FIg.J610).AIrwaywarmIngcanreducetheheatlosscausedbythelatent
heatofvaporIzatIon,butthIstechnIquealsotransfersverylIttleheat.
200
AdmInIstratIonof
warmIntravenousfluIdsIsthemosteffectIvewaytopreventandtreathypothermIaInthe
traumapatIent,provIdedthattheyareadmInIsteredatarelatIvelyrapIdrate.Foreach
lIteroffluIdgIvenat40`CtoapatIentwIthabodytemperatureofJJ`C,29.JJkJofheat
energyIsgaIned;thespecIfIcheatofwaterIs4.19kJ/L/`C.Countercurrentheat
exchangIngsystemsaremoreeffectIvethandryheatorstIllwaterbathwarmers.They
warmthefluIdto40`C,andthedelIveredfluIdtemperatureIsnotaffectedbytherateof
admInIstratIon.ThemosteffectIvemethodthatmaybeusedwhenrapIdwarmIngIs
Intended,however,IscontInuousarterIovenousrewarmIng,whIchcanbeachIevedusInga
modIfIedlevel1countercurrentsystem(FIg.J611).ThebloodexItsthebodyfroma
percutaneouslyplacedfemoralarterIalcatheteratthepatIent'spressure,andthenIs
warmedIntheInfusIonsystemandreturnedtothebodythroughavenouscannula.8ecause
thecIrcuIttubIngIsheparInbonded,thereIsnoneedforheparInIzatIon.ThIstechnIque
canbeusedIntheCUandcanrewarmahypothermIcpatIent(TJ5`C)InapproxImately
40mInutes.
200,202
Figure 36-11.SchematIcdrawIngofthesystemusedforcontInuousarterIovenous
rewarmIng.7,Intravenous;F,French;njectIon(FeprIntedfromCentIlelloL|,
CobeanF,DffnerPJetal:ContInuousarterIovenousrewarmIng:FapIdreversalof
hypothermIaIncrItIcallyIllpatIents.JTrauma1992;J2:J16,wIthpermIssIon.)
Coagulation Abnormalities
ntrauma,multIplefactorsmayberesponsIbleforcoagulopathy:dIlutIonofcoagulatIon
factorsandplatelets,dIsturbanceoffIbrInogen/fIbrInpolymerIzatIonbyhydroxyethyl
starchInfusIon,
20J
tIssuehypoperfusIon,andhypoxIa,hypothermIa,acIdosIs,and0C(see
Chapter16).0CresultsfromacutereleaseofthromboplastInfromInjuredbraIn,fat,
amnIotIcfluId,orothersources,orsubacutelyfromendothelIalInflammatIonorfaIlure
InterferIngwIthclearanceofactIvatedcoagulatIonfactors,causIngmIcrothrombIand
consumptIoncoagulopathy.
204
tIsalsosuggestedthatearlycoagulopathy,beforefluId
admInIstratIon,IscausedbytIssuehypoperfusIon,whIchIncreasesthrombomodulInand
dIvertsthrombInfromfIbrIngeneratIontoactIvatIonofproteInC.
205
HypothermIaaffects
plateletmorphology,functIon,andsequestratIonandretardsenzymeactIvIty,slowIngthe
InItIatIonandpropagatIonofplateletplugsandfIbrInclot,aswellasenhancIngfIbrInolytIc
actIvIty.
60,6J
ThemechanIsmofhypothermIaInducedcoagulopathyIscomplexanddepends
ontheextentoftemperaturedecrease.0owntoJJ`CthereIslIttlealteratIonIn
coagulatIonenzymeactIvIty,explaInIngthepractIcallyunchangedvaluesreportedfor
aPTT.
206
WIthInthIstemperaturerange,coagulopathyresultsfromalteredplatelet
P.920
aggregatIon/adhesIon.
206
8othenzymatIcactIvItyandplateletaggregatIonareabnormal
belowJJ`C.
206
Thus,theaPTTattemperaturesfromJJtoJ7`CdoesnotprovIdeany
meanIngfulInformatIonaboutcoagulatIonstatus,evenwhenthetestIsperformedatthe
hypothermIcpatIent'stemperature,becauseItdoesnotmeasureplateletadhesIon.n
contrast,thrombelastographyatthepatIent'stemperaturemaybereflectIveofthedegree
ofcoagulopathy.
20J
Figure 36-12.ThrombIngeneratIonrateInnormal,acIdotIc,hypothermIc,and
acIdotIcandhypothermIcswIne.ThrombIngeneratIonwasdetermInedbymeasurIng
thrombInantIhrombIn(TAT)concentratIonInbloodsamplesobtaInedat1mInute
IntervalsIneachcondItIon.NotethatacIdosIsandhypothermIadecreasethrombIn
generatIonrate.(Feproducedfrom|artInIWZ,PusaterIAE,UscIlowIczJ|etal:
ndependentcontrIbutIonsofhypothermIaandacIdosIstocoagulopathyInswIne.J
Trauma2005;58:1002,wIthpermIssIon.)
|etabolIcacIdosIsIsprobablyastrongercoagulatIonenzymeInhIbItorthanhypothermIa:It
InterfereswIthgeneratIonofthrombIn,afactoressentIalInactIvatIngcofactors,platelets,
andenzymes,InaddItIontoconvertIngfIbrInogentofIbrIn.ThIseffectofacIdosIsIs
potentIatedbyhypothermIa.FIgureJ612showsthe(IndIrectlydetermIned)thrombIn
generatIonratebymeasurementofthrombInantIthrombIn(TAT)complex
concentratIonsInswIne.
207
PerIoperatIvedIagnosIsofcoagulopathyIsoftenmadeby
observIngbleedIngfromwoundsorpuncturesItes,ratherthanbyInterpretatIonof
laboratorytests.However,thedIfferentIaldIagnosIsbetweenconsumptIveanddIlutIonal
coagulopathyrequIreslaboratorytestIng,althoughtheresultsofthesetestsareusually
delayed.ngeneral,theInabIlItytodetermInethetypeofcoagulopathydoesnotpresenta
problembecausetheInItIaltreatmentIssImIlarforbothcondItIons.Nevertheless,the
dIagnosIsof0ChasprognostIcsIgnIfIcancebecauseItstreatmentInvolveselImInatIonof
Itscause(s).ThepresenceofelevatedcIrculatIngfIbrIndegradatIonproducts(F0P/fdp),
especIallywhen40mg/mL,IssuggestIveof0C,buttheresultofthIsstudywIllreachthe
clInIcIanlongafterthecompletIonofInItIalresuscItatIon.AfIbrInogenlevel100mg/dLIs
alsosuggestIveof0C,butreductIontothIsvalueoftentakesalongtIme,decreasIngthe
dIagnostIcvalueofthetest,althoughserIalmeasurementsmaybeuseful.AcombInatIonof
plateletcount,PTandpartIalthromboplastIntIme,fIbrInogen,afewclottIngfactorsand
InhIbItorsandF0P/fdpmeasurementmaybemoreusefulthanIndIvIdualtests.AdIagnostIc
scorIngsystemconsIstIngofplateletcount,PT,fIbrInogenlevel,andF0P/fdp
measurementshasbeensuggestedtorule0CInorout.
208
thasbeenshownthat
transfusIonofPF8CsInelectIvesurgeryresultsInearlIerdepletIonofcoagulatIonfactors
thanofplatelets.
209,210
ThusItIsnotunreasonabletoadmInIsterFFP,lIquIdplasma,or
cryoprecIpItatebeforeorsImultaneouslywIthplateletsdurIngemergencytraumasurgery.
AsprevIouslydIscussed,InseverecasesthesebloodproductsshouldcometotheDFat
regularIntervals.ThemInImumdoseofFFPforadultsIs2unIts(approxImately600mL)
gIvenwIthIn1hour.AfIbrInogenconcentratIon80mg/dLIsanIndIcatIonfor
cryoprecIpItate.TenunItsIncreaseplasmafIbrInogenconcentratIonbyapproxImately100
mg/dL.
211
EachunItofplateletconcentratecontaIns55bIllIonplatelets,whIchnormally
Increasetheplateletcountby5,000to10,000/L.nseveretraumatheseproductsmustbe
startedveryearlyIntheemergencydepartmentbecauseoncetheadmInIstratIonoffactor
defIcIentPF8CsandfluIdsexceedsonebloodvolume,clInIcalcoagulopathyIslIkelyevenIn
theabsenceofshock,hypothermIa,orotheraggravatIngfactors.
211,212
Thus,plateletor
factoradmInIstratIonIsalmostalwaysIndIcatedIntraumapatIentswhoreceIve
replacementofbetweenoneandtwobloodvolumes.ntheabsenceofabnormalbleedIng
ormassIvetransfusIon,prophylactIcadmInIstratIonofplatelets,FFP,orcryoprecIpItateIs
unwarranted,evenIfcoagulatIontestsIndIcateplateletandfactordepletIon.Also,In
hypothermIcpatIentswIthclInIcalcoagulopathy,thecrItIcaltreatmentIsrewarmIng
ratherthanplateletandcoagulatIonfactoradmInIstratIon,althoughsomecIrcumstances
mayrequIreboth.
FecombInantfactor7amaybeIndIcatedforofflabeluseInselectedpatIentswIth
hemorrhageInducedcoagulopathy.8yactIvatIngfactorXthIsagentproducesathrombIn
burst,whIchInturnconvertsfIbrInogentofIbrIn.ThethrombInburstIsaugmentedby
plateletactIvatIonbyfactorX.SevereacIdosIs,hypothermIa,andhemodIlutIonblockthe
effectoffactor7a.Thus,toobtaInbenefIt,ItshouldbeadmInIsteredaftercorrectIonof
pHandhypothermIaatleastto7.2andJJ`C,respectIvely.
21J
Althoughnumerous
retrospectIveserIesandcasereportssuggesttheusefulnessofthIsagentIntraumaInduced
coagulopathy,sofarthereIsonlyonephase,multIcenter,randomIzedcontrolledtrIalof
rF7aInmajortrauma,usIngmuchhIgher(200g/kg)thanusualdoses(90g/kgfor
patIentsInshockand1.2mgInthosenotInshock).
214
ThedrugwasabletoreducePF8C
transfusIonby2.6unItsInsurvIvIngvIctImsofblunttrauma,butfaIledtoproduceany
effectInpenetratIngtraumapatIents.NeIther48hournorJ0daysurvIvalwasaffectedby
rF7aand,whenallsurvIvIngandnonsurvIvIngpatIentswereconsIdered,thereductIonIn
PF8CreplacementwasInsIgnIfIcant.
8ecauseofItshIghcost,rF7aIsusedunderstrIctprotocolInmanycenters,InpatIents
wIthsurvIvableInjuryand/ormedIcaldIsease,whoarenotIntermInalshockasevIdenced
bypH7.0andK
+
6.0mEq/L,norIncardIacarrestorrequIrIngvasoactIveagents.
215
8asedontheseguIdelInes,patIentsmustreceIvealargequantItyofbloodproductsbefore
rF7aIsconsIdered.
215
ThIsconcept,however,recentlyhasbeenchallengedIna
prelImInarystudyconductedInraqandAfghanIstanwarvIctIms,comparIngearly(after8
UofPF8Cs)andlate(after8UofPF8Cs),admInIstratIonoftheagent.Early
admInIstratIonreducedtheoverallrequIrementforPF8Csby20comparedwIthlateuse
ofrF7a.SurvIvaluptoJ0dayswasnotdIfferentbetweenthegroups,norwastheuseof
FFP,cryoprecIpItate,platelets,andcrystalloIds.
216
ThromboembolIccomplIcatIonsoccurIn
aboutJto5ofpatIentsreceIvIngthedrug,usuallynotImmedIately,butwIthInafew
hoursordaysafteradmInIstratIon.8otharterIalandvenoussystemsarevulnerable,andIn
fact,thrombosIscanoccurIncentrallIneorbypasscIrcuIttubIng.
215
FecombInantfactor7aalsomaybebenefIcIalInpatIentsreceIvIngwarfarIntherapywIth
traumatIcbraInInjurIesandIntracranIalhematomas.nthesepatIentstheagentmay
successfullycontrolpotentIallydevastatIngbleedIngandlowertheInternatIonal
normalIzedratIoIntoarangepermIttIngsurgery,andInsomecases,mayobvIatetheneed
forsurgery.
217
AmultIcenterstudyIsunderwaytoclarIfyfurthertheIndIcatIonsforrF7lla
Intrauma.
P.921
Electrolyte and Acid-Base Disturbances
ntraoperatIvehyperkalemIamaydevelopasaresultofthreemechanIsms.FIrst,In
patIentswIthIrreversIbleshock,cellmembranepermeabIlItyIsaltered,thusmassIveK
+
effluxresultsInseverehyperkalemIa;InthIssItuatIon,survIvalIsunlIkely(seeChapter14).
Second,afterrepaIrofamajorvessel,subsequentreperfusIonoftheIschemIctIssues
resultsInasuddenreleaseofK
+
IntothegeneralcIrculatIon.ThIrd,transfusIonatarate
fasterthan1Uevery4mInutestoanacIdotIcandhypovolemIcpatIentmaycausean
IncreaseInplasmaK
+
levels.FrequentmonItorIngofserumK
+
,gradualandIntermIttent
unclampIngofvascularshunts,andavoIdIngtransfusIonathIgherratesthanneededhelp
reducetherateofK
+
Increase.farIseInK
+
Isdetected,treatmentwIthregularInsulIn,10
UIntravenously,wIth50dextrose,50mL,andsodIumbIcarbonate,8.4,50mL,Is
IndIcated.fthereIsadysrhythmIa,CaCl
2
,500mg,shouldalsobeadmInIstered.nsulInand
dextrosecanberepeated2orJtImesatJ0to45mInuteIntervals,Ifnecessary.
HemodIalysIsmaybeIndIcatedIndesperatesItuatIons.
|etabolIcacIdosIsIscausedbyshockInmosttraumapatIents.Dtherrarecausesof
metabolIcacIdosIsInthIspopulatIonarealcoholIclactIcacIdosIs,alcoholIcketoacIdosIs,
dIabetIcketoacIdosIs,andCDorCN
poIsonIngafterInhalatIonInjurIes.ThedIfferentIal
dIagnosIsbetweenhypovolemIc,dIabetIc,andalcoholIcacIdosIs,allofwhIchhaveanIon
gaps,requIresmeasurementofbloodlactate,urInaryketonebodIes,bloodsugar,and
InvasIvemonItorIngtoassessIntravascularvolume.AlcoholIcketoacIdosIsIstreatedwIth
Intravenousdextrose,whereasdIabetIcketoacIdosIsIsmanagedwIthInsulIn.NospecIfIc
treatmentexceptIntravenousnormalsalIneexIstsforalcoholIclactIcacIdosIs.
TreatmentofmetabolIcacIdosIsInvolvescorrectIonoftheunderlyIngcause:management
ofhypoxemIa,restoratIonofIntravascularvolume,optImIzatIonofcardIacfunctIon,or
treatmentofCDorCN
toxIcIty.SymptomatIctreatmentwIthsodIumbIcarbonatehas
serIousdIsadvantages,IncludIngleftwardshIftoftheoxyhemoglobIndIssocIatIoncurve
causIngdecreasedD
2
unloadIng,ahyperosmolarstatesecondarytotheexcessIvesodIum
load,hypokalemIa,furtherhemodynamIcdepressIon,overshootalkalosIsafewhoursafter
gIvIngthedrug,andIntracellularacIdosIsIfadequateventIlatIonorpulmonarybloodflow
cannotbeprovIded.Nevertheless,becauseofthepossIbIlItythatsevereacIdosIscancause
dysrhythmIas,myocardIaldepressIon,hypotensIon,andresIstancetoexogenous
catecholamInes,someclInIcIansadmInIsterbIcarbonatetobuytImeIfthepHIs7.2.
Intraoperative Death
0eathIsamuchgreaterthreatdurIngemergencytraumasurgerythanItIsInanyother
operatIveprocedure.ApproxImately0.7ofpatIentsadmIttedforacutetraumadIeInthe
DF,accountIngforapproxImately8ofpostInjurydeaths.
218
UncontrollablebleedIngIsthe
causeofapproxImately80ofIntraoperatIvemortalIty;braInhernIatIonandaIrembolIsm
arethemostcommoncausesofdeathIntheremaInIngpatIents.
218
AmultIcenter,
retrospectIvestudyhasdefInedcertaInfeaturesthatIncreasethelIkelIhoodofDFdeath
218
(TableJ611).FapIdtransporttotheDF,rapIdlystabIlIzInglIfethreatenIngInjurIeswhIle
deferrIngdefInItIvesurgery(damagecontrol),sImultaneousthoracotomyandlaparotomy
forthoracoabdomInalInjurIes,approprIatemanagementofretroperItonealhematoma,and
earlycorrectIonofhypothermIaandshockmayreduceIntraoperatIvemortalItyrates.
218
Dfthesemeasures,thedamagecontrolprIncIplehasreducednotonlytheIntraoperatIve,
butalsotheoverallmortalItyfromtraumasurgery,althoughmorbIdItyfromsepsIs,abscess
formatIon,andgastroIntestInalfIstulasmayIncrease.
219
DrIgInallydescrIbedInthree
stages,thecurrentsuggestIonIsthatItshouldbemanagedInfourphases.nthefIrst
phase,attentIonIsdIrectedIntheemergencydepartmenttorecognItIonofthepatternof
Injury,aswellastothedecIsIontoInItIatedamagecontrolbyactIvatIngrewarmIngand
bloodcomponentreplacement.ThesecondphaseoccursIntheDFwhere,InaddItIonto
effortstomaIntaInthepatIent'sIntravascularvolume,nearnormaltemperature,acIdbase
status,andcoagulatIon,surgeonsrapIdlycontrolbleedIngandleavetheabdomInalcavIty
temporarIlycoveredbya7acPacdressIng,whIchallowsanenlargedspaceforedematous
organsandcontrolledegressoffluId.ThethIrdphasetakesplaceIntheCUwhere
Intravascularvolume,hypothermIa,acIdosIs,andcoagulatIonabnormalItIesarecorrected.
nthefourthphase,thestabIlIzedpatIentIsreturnedtotheDFfordefInItIvesurgeryand
abdomInalclosure.ThedamagecontrolprIncIple,orIgInallyproposedforabdomInal
trauma,IsnowapplIedtoInjurIesatotheranatomIcsItesIncludIngthechest,pelvIs,
extremItIes,andInsofttIssues.
220
Table 36-11 Clinical Features Associated with Intraoperative Mortality
CATEGORY CLINICAL FEATURES
|echanIsmofInjury
Cunshotwound
PedestrIanInjurIes
njuryseverIty
|eanInjuryseverItyscore41
|eanrevIsedtraumascoreJ.0
PreoperatIvephysIologIc
profIle
|ean8PInthefIeld50mmHg
|ean8PonarrIvaltoE060mmHg
8estsystolIc8PIntheE090mmHg
CIrculatoryshocktIme10mIn
8estmeanpH7.18
|eanpreoperatIvecrystalloIdresuscItatIonJ,850
mL;meanredcelltransfusIon8J4mL
TypeofInjury
SIgnIfIcanthead,chest,abdomInal,andpelvIc
InjurIesIndIvIduallyorIncombInatIonafterblunt
trauma
SIgnIfIcantchestandabdomInalInjurIesIndIvIdually
orIncombInatIonafterpenetratIngtrauma
DrganInjury
8raIn
LIver
AortaorothermajorvascularInjury
CardIacInjury
DperatIngroom
resuscItatIonand
physIologIcstatus
SystolIc8P90mmHgdurIngfIrsthour
SystolIc8P90mmHgforJ0mIn
0eterIoratIonofmeanpHfrom7.19to7.01
|eanIntraoperatIvebloodloss5,172
mL;meanbloodreplacement4,541mL
|eanplatelettransfusIon784mL
|eanfreshfrozenplasma1,418mL
|eanIntraoperatIvetemperatureJ2.2`C
ntraoperatIvecardIacarrest
8P,bloodpressure;E0,emergencydepartment.
0atafromHoyt08,8ulgerE|,Knudson||etal:0eathIntheoperatIngroom:An
analysIsofamultIcenterexperIence.JTrauma1994;J7:426.
P.922
Early Postoperative Considerations
TheconcernsIntheearlypostoperatIveperIodaresImIlartothoseoftheIntraoperatIve
phase.FeevaluatIonandoptImIzatIonofthecIrculatIon,oxygenatIon,temperature,CNS
functIon,coagulatIon,electrolyteandacIdbasestatus,andrenalfunctIonarethe
hallmarksofpostoperatIvemanagement.PaIncontrolInthIsgroupofpatIentsmayhave
morethanahumanItarIanpurpose;ItcanImprovepulmonaryfunctIon,ventIlatIon,and
oxygenatIonInpatIentswIthchestInjuryoralongabdomInalIncIsIon(seeChapter57).For
sedatIonInmechanIcallyventIlatedpatIents,bothpropofol(25to75g/kg/mIn)and
mIdazolam(0.1to20g/kg/mIn)InfusIonsaloneorIncombInatIonareequallyeffectIve
andsafe,althoughwakeuptImeInpatIentsreceIvIngmIdazolamIslonger(660400
mInutes)thanInthosereceIvIngpropofolalone(11050mInutes)orInbothagents
combIned(190200mInutes).
221
|orphIne,0.02to0.04mg/kg/hr,orfentanyl,1toJ
g/kg/hr,maybeaddedforanalgesIa.SmallbolusesofmIdazolam(Jto5mg),propofol(50
mg),morphIne(2toJmg),orfentanyl(25to50g)mayalsobegIvenasrequIred
221
(see
Chapter57).
Acute Renal Failure
AcuterenalfaIlureIsapossIbIlItyIfprolongedshockorcrushsyndromeoccurdurIngearly
management.nastudyaImedatfIndIngthepredIctorsofacuterenalfaIlureafter
emergencynoncardIacsurgery,whIchIncludestrauma,prolongedhypotensIonwasoneof
thesevenIndependentpredIctorsofthIscomplIcatIon.
222
FollowInganepIsodeofshockIn
patIentswhohavenotreceIvedanosmotIcload(radIopaquematerIal,mannItol)or
dIuretIc,determInatIonof2or6hourcreatInIneandfreewaterclearancesmayhelp
predIctthedevelopmentofposttraumatIcrenaldysfunctIon.
22J
CreatInIneclearance25
mL/mInandfreewaterclearance15mL/hrsuggestthelIkelIhoodofacuterenalfaIlure.
0ecreasedurIneflowrateIsnotagoodpredIctor,andthebloodureanItrogendoesnotrIse
untIlatleast24hoursaftersurgeryortrauma.
22J
ThecauseofrenalfaIlureIncrushsyndromeIsprobablyrhabdomyolysIsInducedmyoglobIn
releaseIntothecIrculatIon.SerumcreatInekInaselevelsIncreaseInthesepatIents;levels
above5,000U/LareassocIatedwIthrenalfaIlure.
224
ThedIfferentIatIonofmyoglobInurIa
fromhemoglobInurIaIsdescrIbedInUrIneDutput..Aclearsupernatantofthe
centrIfugedbloodsamplesuggestsmyoglobIn,whereasarosecolorIndIcateshemoglobIn.
ThetradItIonalprophylaxIsforrenalfaIlureafterrhabdomyolysIsIncludesfluIds,mannItol,
andbIcarbonate.However,morerecentdatasuggestthatbIcarbonateandmannItolare
IneffectIve.
224
Abdominal Compartment Syndrome
AbdomInalcompartmentsyndromeresultsfromIntraabdomInalhypertensIonwIthorgan
dysfunctIonaftermajorabdomInaltraumaandsurgery(prImarysyndrome);patIentsalso
maydevelopthesyndromewIthoutsurgery;forexample,durIngmassIvefluIdresuscItatIon
followIngmajortraumaorburns(secondarysyndrome).
225,226,227,228
tfrequentlyfollows
hemorrhage.
227
ThesyndromeresultsfrommassIveedemaofIntraabdomInalorgans
producedbyshockInducedInflammatorymedIators,fluIdresuscItatIon,andsurgIcal
manIpulatIon.ThesIgnIfIcantcardIac,pulmonary,renal,gastroIntestInal,hepatIc,andCNS
dysfunctIoncausedbythIssyndromeresultsInahIghmortalItyrate
226
(FIg.J61J).A
damagecontrolprocedurewIthtowelclIpclosureofthefascIaafterlaparotomymay
IncreaseItsIncIdencefromthe17seenwIthbogatabagclosureto80.
228
Figure 36-13.PhysIologIceffectsofabdomInalcompartmentsyndrome.mageInthe
centerIsofapatIentwhoseabdomenwasleftopenbutcoveredwIthnonadhesIve
dressIng.CD,cardIacoutput;PADP,pulmonaryarteryocclusIonpressure;C7P,central
venouspressure;S7F,systemIcvascularresIstance;CP,IntracranIalpressure;CPP,
cerebralperfusIonpressure;PP,peakInspIratorypressure;Paw,meanaIrway
pressure;Cdyn,dynamIcpulmonarycomplIance;Qsp/Qt,Intrapulmonaryshunt;7d/7t,
deadspaceventIlatIon;S|A,superIormesenterIcartery;pHI,IntramucosalpH;CFF,
glomerularfIltratIonrate.(AdaptedfromCheatham|L:ntraabdomInalhypertensIon
andabdomInalcompartmentsyndrome.NewHorIz1999;7:96,wIthpermIssIon.)
ClInIcally,atense,dIstendedabdomenshoulddIrecttheclInIcIantomeasurethe
IntravesIcalpressurevIaaFoleycatheter,whIchreflectstheIntraabdomInalpressure.
226
7alues20to25mmHgIndIcateInadequateorganperfusIonandnecessItateabdomInal
decompressIon,whIch,Ifdelayed,resultsInprogressIontomultIorganfaIlureand
death.
225,228
UseofavolumetrIcpulmonaryarterycatheterforassessmentofpreloadby
leftventrIcularenddIastolIcvolumeIndexdetermInatIonmaybemoreaccuratethan
measurIngC7PorPCWPInthesepatIents.
226
AlmostallthesepatIentsrequIremechanIcal
ventIlatIon.AttrIbutIngarelatIvelyhIghPCWPtotheventIlatorandcontInuInghIgh
volumefluIdInfusIonmayfurtherIncreaseIntraabdomInaledemaandIncrease
mortalIty.
229
nterestIngly,patIentswhowIlldevelopabdomInalcompartmentsyndrome
oftendonotrespondtofluIdadmInIstratIonwIthelevatedcardIacoutputdespItean
IncreasIngPCWP.
229
Thromboembolism
TheoverallIncIdenceof07TIntheproxImalfemoralveIns,themajorsourceofPE,Is
approxImately18IntraumapatIents.
2J0
However,07ToccursIn24oflowerextremIty
InjurIes,27ofspIneInjurIes,20ofmajorheadInjurIes,and15ofserIousInjurIesofthe
face,chest,orabdomen.
2J0
WhenInjurIesInvolvemorethanoneofthesehIghrIskregIons,
thelIkelIhoodof07TIsevenhIgher.
2J0
Fortunately,onlyarelatIvelysmallfractIon
(approxImately0.Jto2)ofseverelyInjuredpatIentshavePE.
2J0,2J1,2J2
Almosthalfofall
casesofPEoccurwIthInthefIrstweek,andInonestudy,J7ofthecasesoccurredwIthIn
thefIrst4days,suggestIngthat07Tdevelopsshortlyaftertrauma.
2J1,2J2
nmostInstances,
07TIsasymptomatIc,andInmanyofthoseInwhomlegswellIngdevelops,concurrent
lowerextremItyInjurIesmaybeImplIcated.ThedIagnosIsofproxImal07TInsymptomatIc
patIentscanbemadebyduplexultrasonography,butthIsmethodhaslowsensItIvItyInthe
absenceofsymptoms.
2JJ
7enography,whIchIsthegoldstandard,canbeperformedIn
equIvocalcases,
P.92J
althoughItIsassocIatedwIthcomplIcatIonsandInherentlogIstIcalproblems.HypoxemIa,
evenveryearlyafterInjury,especIallywhensuddenandassocIatedwIthdyspneaand
hemodynamIcabnormalItIes,IshIghlysuggestIveofPE.ThedefInItIvedIagnosIsIs
establIshedbyspIralCTandpulmonaryangIography.nhemodynamIcallyunstable
patIents,resuscItatIontakesprecedenceoverradIologIcdIagnosIs.|anagementIs
symptomatIc,andIncludestrachealIntubatIon,posItIvepressureventIlatIonwIthFD
2
of
1.0,admInIstratIonoffluIdsandInotropes(amrInoneormIlrInone),andcontInuousarterIal
andC7PorpulmonaryarterymonItorIng.TEEIshelpfulbecauseItmaydemonstrateF7
performance,trIcuspIdregurgItatIon,or,Insomecases,thethrombuswIthInthe
pulmonaryartery,therIghtheartchambers,orIntransItthroughapatentforamenovale
totheleftatrIum.
npatIentswIthrelatIvelymInorInjurIes,PEIstreatedwIthantIcoagulants.Low
molecularweIghtheparInmaybeusedIfbleedIngIsunlIkelytoexacerbatetheInjury.
ConsIderatIonshouldbegIventoplacementofavenacavafIlterIftherIskofbleedIngIs
unacceptablyhIgh.FemovablevenacavafIltersarenowavaIlable
2J4
andarelIkelytobe
usedprophylactIcallyInhIghrIskpatIentsmoreoftenthanpermanentfIlters,whIchare
assocIatedwIthlongtermcomplIcatIons.npatIentswIthseverehemodynamIcdepressIon
orcardIacarrestthatIsunresponsIvetoresuscItatIvemeasures,thrombolytIcagentsmay
beconsIdereddespItetherIskofhemorrhage.ThecurrentrecommendatIonforprophylaxIs
InmosttraumapatIentsIslowmolecularweIghtheparIn.
2JJ
LowdoseunfractIonated
heparInappearstobeIneffectIveIntraumapatIents.
2J5
|echanIcaldevIcessuchas
sequentIalcompressIonbootsshouldbeapplIedasearlyaspossIbleafterInjury.Late
InItIatIonofprophylaxIs(4daysafterInjury)becauseofmassIvetransfusIon,low
antIcIpatedrIskbecauseofabsenceofcomorbIdIty,orbecauseoffearofIntracranIal
bleedIngaftersevereheadInjury,hasbeenshowntotrIpletherIskofvenous
thromboembolIsm.
2J6
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Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJ7EpIduralandSpInalAnesthesIa
ChapterJ7
Epidural and Spinal Anesthesia
Christopher M. Bernards
Key Points
1. Clinicians must develop a three-dimensional mental picture of the
spinal anatomy so that when they contact bony structures during
attempted epidural or spinal needle placement they can redirect the
needle in a reasoned and systematic manner and not subject the
patient to random needle pokes in an effort to place the block.
2. The epidural fat and the epidural venous plexus do not form a
continuous cylinder surrounding the spinal cord, as is often depicted.
Rather, the epidural fat lies in discrete pockets in the posterior and
lateral epidural space and the epidural veins travel primarily in the
anterior and lateral epidural space and are normally absent in the
posterior epidural space.
3. Serious systemic toxicity during attempted epidural block is almost
always the result of inadvertent local anesthetic injection directly into
the vasculature. Consequently, an appropriate test dose designed to
identify intravascular injection is critical.
4. Physical characteristics (e.g., height, weight, cerebrospinal fluid
volume) and age do have an effect on spinal and epidural block
characteristics. However, the magnitude of the effects are relatively
small and of such low predictive power that these characteristics are
not useful predictors of local anesthetic dose in any individual patient.
5. The risk of hemodynamic complications of epidural and spinal
anesthesia increases with increasing block height.
6. Lidocaine appears to be worse than other local anesthetics in terms
of the risk of neurologic toxicity (i.e., cauda equina syndrome and
transient neurologic symptoms).
7. Human studies suggest that the preservative-free formulation of
chloroprocaine may offer a viable alternative to lidocaine for short-
duration spinal anesthesia.
8. Administration of drugs that impair coagulation can put patients at
increased risk of spinal hematoma. Our understanding of the relative
risk of different classes of drugs affecting the clotting system is
constantly evolving. Clinicians are directed to the consensus
statement from the American Society for Regional Anesthesia and
Pain Medicine for the most recent recommendations.
TherearenoabsoluteIndIcatIonsforspInalorepIduralanesthesIa.However,thereare
clInIcalsItuatIonsInwhIchpatIentpreference,patIentphysIology,orthesurgIcal
proceduremakescentralneuraxIalblockthetechnIqueofchoIce.ThereIsalsoevIdence
thatthesetechnIquesmayImproveoutcomeInselectedsItuatIons.SpInalandepIdural
anesthesIahavebeenshowntobluntthestressresponsetosurgery,
1
todecrease
IntraoperatIvebloodloss,
2,J
tolowertheIncIdenceofpostoperatIvethromboembolIc
events,
2,J,4,5
andtodecreasemorbIdItyandmortalItyInhIghrIsksurgIcalpatIents.
6,7
n
addItIon,bothspInalandepIduraltechnIquescanbeusedtoextendanalgesIaIntothe
postoperatIveperIod,wheretheIrusehasbeenshowntoprovIdebetteranalgesIathancan
beachIevedwIthparenteralopIoIds.
8
naddItIon,centralneuraxIalanalgesIahasbecome
anIndIspensabletechnIquetoprovIdeanalgesIatononsurgIcalpatIents.Thus,these
technIquesarean
P.928
IndIspensablepartofmodernanesthetIcpractIce,andeveryanesthesIologIstshouldbe
adeptatperformIngthem.
Figure 37-1.PosterIor(A)andlateral(C)vIewsofthehumanspInalcolumn.Notethe
Inset(B),whIchdepIctsthevarIabIlItyInvertebrallevelatwhIchthespInalcord
termInates.
Anatomy
ProfIcIencyInspInalandepIduralanesthesIarequIresathoroughunderstandIngofthe
anatomyofthespIneandspInalcord.TheanesthesIologIstmustbefamIlIarwIththe
surfaceanatomyofthespInebutmustalsodevelopamentalpIctureofthethree
dImensIonalanatomyofdeeperstructures.naddItIon,onemustapprecIatethe
relatIonshIpbetweenthecutaneousdermatomes,thespInalnerves,thevertebrae,andthe
spInalsegmentfromwhIcheachspInalnervearIses.
Vertebrae
ThespineconsIstsofJJvertebrae(7cervIcal,12thoracIc,5lumbar,5fusedsacral,and4
fusedcoccygeal;FIg.J71).WIththeexceptIonofC1,thecervIcal,thoracIc,andlumbar
vertebraeconsIstofabodyanterIorly,twopediclesthatprojectposterIorlyfromthebody,
andtwolaminaethatconnectthepedIcles(FIg.J72).Thesestructuresformthevertebral
canal,whIchcontaInsthespInalcord,spInalnerves,andepIduralspace.ThelamInaegIve
rIsetothetransverse processesthatprojectlaterallyandthespinous processthatprojects
posterIorly.ThesebonyprojectIonsserveassItesformuscleandlIgamentattachments.
ThepedIclescontaInasuperIorandInferIorvertebral notchthroughwhIchthespInal
nervesexItthevertebralcanal.ThesuperIorandInferIorarticular processesarIseatthe
junctIonofthelamInaandpedIclesandformjoIntswIththeadjoInIngvertebrae.ThefIrst
cervIcalvertebra(atlas)dIffersfromthIstypIcalstructureInthatItdoesnothavea
bodyoraspInousprocess.
ThefIvesacralvertebraearefusedtogethertoformthewedgeshapedsacrum,whIch
connectsthespInewIththeIlIacwIngsofthepelvIs(FIg.J71).ThefIfthsacralvertebraIs
notfusedposterIorly,gIvIngrIsetoavarIablyshapedopenIngknownasthesacral hiatus.
DccasIonally,othersacralvertebraedonotfuseposterIorly,gIvIngrIsetoamuchlarger
sacralhIatus.Thesacral cornuarebonypromInencesoneIthersIdeofthehIatusandaIdIn
IdentIfyIngIt.ThesacralhIatusprovIdesanopenIngIntothesacralcanal,whIchIsthe
caudaltermInatIonoftheepIduralspace.ThefourrudImentarycoccygealvertebraeare
fusedtogethertoformthecoccyx,anarrowtrIangularbonethatabutsthesacralhIatus
andcanbehelpfulInIdentIfyIngIt.ThetIpofthecoccyxcanoftenbepalpatedInthe
proxImalglutealcleft,andbyrunnIngone'sfIngercephaladalongItssmoothsurface,the
sacralcornucanbeIdentIfIedasthefIrstbonypromInenceencountered.
dentIfyIngIndIvIdualvertebraeIsImportantforcorrectlylocatIngthedesIredInterspace
forepIduralandspInalblockade.ThespIneofC7IsthefIrstpromInentspInousprocess
encounteredwhIlerunnIngthehanddownthebackoftheneck.ThespIneofT1Isthemost
promInentspInousprocessandImmedIatelyfollowsC7.The12ththoracIcvertebracanbe
IdentIfIedbypalpatIngthe12thrIbandtracIngItbacktoItsattachmenttoT12.AlIne
drawnbetweentheIlIaccrestscrossesthebodyofL5orthe45Interspace.
Figure 37-2.0etaIlofthelumbarspInalcolumnandepIduralspace.Notethatthe
epIduralveInsarelargelyrestrIctedtotheanterIorandlateralepIduralspace.
P.929
Ligaments
ThevertebralbodIesarestabIlIzedbyfIvelIgamentsthatIncreaseInsIzebetweenthe
cervIcalandlumbarvertebrae(FIg.272).FromthesacrumtoT7,thesupraspinous
ligamentrunsbetweenthetIpsofthespInousprocesses.AboveT7thIslIgamentcontInues
astheligamentum nuchaeandattachestotheoccIpItalprotuberanceatthebaseofthe
skull.Theinterspinous ligamentattachesbetweenthespInousprocessesandblends
posterIorlywIththesupraspInouslIgamentandanterIorlywIththelIgamentumflavum.The
ligamentum flavumIsatough,wedgeshapedlIgamentcomposedofelastIn.tconsIstsof
rIghtandleftportIonsthatspanadjacentvertebrallamInaeandfuseInthemIdlIneto
varyIngdegrees.
7,8
ThelIgamentumflavumIsthIckestInthemIdlIne,measurIngJto5mm
attheL2JInterspaceofadults.ThIslIgamentIsalsofarthestfromthespInalmenIngesIn
themIdlIne,measurIng4to6mmattheL2JInterspace.
9
Asaresult,mIdlIneInsertIonof
anepIduralneedleIsleastlIkelytoresultInunIntendedmenIngealpuncture.TheanterIor
andposterIorlongitudinal ligamentsrunalongtheanterIorandposterIorsurfacesofthe
vertebralbodIes.
Epidural Space
TheepIduralspaceIsthespacethatlIesbetweenthespInalmenIngesandthesIdesofthe
vertebralcanal(FIg.J7J).tIsboundedcranIallybytheforamenmagnum,caudallybythe
sacrococcygeallIgamentcoverIngthesacralhIatus,anterIorlybytheposterIorlongItudInal
lIgament,laterallybythevertebralpedIcles,andposterIorlybyboththelIgamentum
flavumandvertebrallamIna.TheepIduralspaceIsnotaclosedspacebutcommunIcates
wIththeparavertebralspacebywayoftheIntervertebralforamIna.
10
TheepIduralspace
IsshallowestanterIorlywheretheduramayInsomeplacesfusewIththeposterIor
longItudInallIgament.ThespaceIsdeepestposterIorly,althoughthedepthvarIesbecause
thespaceIsIntermIttentlyoblIteratedbycontactbetweentheduramaterandthe
lIgamentumflavumorvertebrallamIna.ContactbetweentheduramaterandthepedIcles
alsoInterruptstheepIduralspacelaterally.Thus,theepIduralspaceIscomposedofa
serIesofdIscontInuouscompartmentsthatbecomecontInuouswhenthepotentIalspace
separatIngthecompartmentsIsopenedupbyInjectIonofaIrorlIquId.ArIchnetworkof
valvelessveIns(8atsonplexus)coursesthroughtheanterIorandlateralportIonsofthe
epIduralspaceandonlyveryrarelyIntheposterIorepIduralspace(FIg.J72).
11
The
epIduralveInsanastomosefreelywIthextraduralveIns,IncludIngthepelvIcveIns,the
azygoussystem,andtheIntracranIalveIns.TheepIduralspacealsocontaInslymphatIcs
andsegmentalarterIesrunnIngbetweentheaortaandthespInalcord.
Figure 37-3.ThecompartmentsoftheepIduralspace(pink areas)aredIscontInuous.
AreaswherenocompartmentsareIndIcatedrepresentapotentIalspacewherethe
duramaternormallyabutsthesIdesofthevertebralcanal.(FeprIntedfromHoganQ:
LumbarepIduralanatomy:AnewlookbycryomIcrotomesectIon.AnesthesIology1991;
75:767,wIthpermIssIon.)
Epidural Fat
ThemostubIquItousmaterIalIntheepIduralspaceIsfat,whIchIsprIncIpallylocatedIn
theposterIorandlateralepIduralspace(FIg.J7J).
10
nterestIngly,theepIduralfatappears
tohaveclInIcallyImportanteffectsonthepharmacologyofepIdurallyandIntrathecally
admInIstereddrugs.Forexample,usIngapIgmodel,8ernardsetal.
12
showedthatthereIs
alInearrelatIonshIpbetweenanopIoId'slIpIdsolubIlItyandItstermInalelImInatIonhalf
tImeIntheepIduralspace,ItsmeanresIdencetImeIntheepIduralspace,andIts
concentratIonInepIduralfat.naddItIon,nettransferofopIoIdfromtheepIduralspaceto
theIntrathecalspacewasgreatestfortheleastlIpIdsolubleopIoId(morphIne)andleast
forhIghlylIpIdsolubleopIoIds(fentanyl,sufentanIl).neffect,IncreasInglIpIdsolubIlIty
resultedInopIoIdsequestratIonInepIduralfat,therebyreducIngthebIoavaIlabIlItyof
drugIntheunderlyIngsubarachnoIdspaceandspInaltIssue.
EpIduralfatalsoappearstoplayaroleInthepharmacokInetIcsofepIdurallyadmInIstered
localanesthetIcs.SpecIfIcally,sequestratIonInepIduralfatlIkelyexplaInswhyahIghly
lIpIdsolublelocalanesthetIclIkeetIdocaIneIsonlyapproxImatelyequIpotentwIth
lIdocaIneIntheepIduralspacedespItethefactthatetIdocaIneIsroughly7tImesmore
potentthanlIdocaIneInvItro.8ecauseofItsmuchgreaterlIpIdsolubIlIty,etIdocaIneIs
morelIkelythanlIdocaInetobesequesteredInepIduralfat,therebyreducIngtheamount
ofdrugavaIlabletoproduceblockInthespInalnerverootsandspInalcord.ConsIstent
wIththIshypothesIs,Tuckerand|ather
1J
showedthatafteradmInIsterIng80mgof
etIdocaIneand50mgoflIdocaIneIntotheepIduralspaceofsheep,theamountof
etIdocaInestIllpresentInepIduralfat12hourslaterwasmorethan100tImesgreaterthan
theamountoflIdocaIne.Thus,sequestratIonInepIduralfatappearstoplayanImportant
roleInthepharmacokInetIcsoflocalanesthetIcsjustasItdoesforepIduralopIoIds.
Meninges
ThespInalmenIngesconsIstofthreeprotectIvemembranes(duramater,arachnoIdmater,
andpIamater),whIcharecontInuouswIththecranIalmenInges(FIg.J74).
Dura Mater
TheduramaterIstheoutermostandthIckestmenIngealtIssue.ThespInalduramater
begInsattheforamenmagnumwhereItfuseswIththeperIosteumoftheskull,formIngthe
cephaladborderoftheepIduralspace.Caudally,theduramaterendsatapproxImatelyS2,
whereItfuseswIththefIlumtermInale.TheduramaterextendslaterallyalongthespInal
nerverootsandbecomescontInuouswIththeconnectIvetIssueoftheepIneurIumat
approxImatelytheleveloftheIntervertebralforamIna.TheduramaterIscomposedof
randomlyarrangedcollagenfIbersandelastInfIbersarrangedlongItudInallyand
cIrcumferentIally.
14
TheduramaterIslargelyacellularexceptforalayerofcellsthat
formstheborderbetweentheduraandarachnoIdmater.0espItethelackofcellular
elements,theInneredgeoftheduramaterIshIghlyvascular,
15
whIchlIkelyresultsInthe
duramaterbeInganImportantrouteofdrugclearancefromboththeepIduralspaceand
thesubarachnoIdspace.
ThereIscontroversyregardIngtheexIstenceandclInIcalsIgnIfIcanceofamIdlIne
connectIvetIssueband,theplica medianis
P.930
dorsalis,runnIngfromtheduramatertothelIgamentumflavum.AnatomIcstudIesusIng
epIduroscopy
16
andepIdurography
17
havedemonstratedthepresenceoftheplIcamedIanIs
dorsalIsandhaveledtospeculatIonthatthIstIssuebandmayonoccasIonberesponsIble
fordIffIcultyInInsertIngepIduralcathetersandforunIlateralepIduralblock.However,
usIngcryomIcrotomesectIonstoInvestIgatetheepIduralspace,Hogan
10
faIledtofInd
evIdenceofasubstantIalconnectIonbetweentheduramaterandthelIgamentumflavum.
HespeculatedthattheInjectIonofeItheraIrorcontrastrequIredfortheearlIerstudIes
mayhavecompressedepIduralcontents(e.g.,fat)andproducedanartIfactmImIckInga
connectIvetIssueband.naddItIon,Hogan
18
hasshownInaclInIcalstudythatthereIsno
sIgnIfIcantImpedImenttospreadofInjectateacrossthemIdlIne.Thus,theplIcamedIanIs
dorsalIsdoesnotappeartobeclInIcallyrelevantwIthrespecttoclInIcalepIdural
anesthesIa.
Figure 37-4.ThespInalmenIngesofthedog,demonstratIngthepIamater(P|)In
apposItIontothespInalcord,thesubarachnoIdspace(SS),thearachnoIdmater(A|),
trabeculae(fIbersstretchIngfromarachnoIdmatertopIamater),andtheduramater
(0|).TheseparatIonbetweenthearachnoIdmaterandtheduramaterdemonstrates
thesubduralspace.ThesubduralspaceIsonlyapotentIalspacein vivobutIscreated
hereasanartIfactofpreparatIon.(FeprIntedfromPetersA,PalaySL,WebsterH(Eds):
TheFIneStructureoftheNervousSystem:TheNeuronsandSupportIngCells.
PhIladelphIa,W8Saunders,1976,wIthpermIssIon.)
TheInnersurfaceoftheduramaterabutsthearachnoIdmater.ThereIsapotentIalspace
betweenthesetwomembranescalledthesubdural space(FIg.J74).DccasIonally,adrug
IntendedforeIthertheepIduralspaceorthesubarachnoIdspaceIsInjectedIntothe
subduralspace.
19
SubduralInjectIonhasbeenestImatedtooccurIn0.82ofIntended
epIduralInjectIons.
20
TheradIologylIteraturesuggeststhattheIncIdenceofsubdural
InjectIondurIngIntendedsubarachnoIdInjectIonformyelographymaybeashIghas10.
21
Arachnoid Mater
ThearachnoIdmaterIsadelIcate,avascularmembranecomposedofoverlappInglayersof
flattenedcellswIthconnectIvetIssuefIbersrunnIngbetweenthecellularlayers.The
arachnoIdcellsareInterconnectedbyfrequenttIghtjunctIonsandoccludIngjunctIons.
ThesespecIalIzedcellularconnectIonslIkelyaccountforthefactthatthearachnoIdmater
IstheprIncIpalanatomIcbarrIerfordrugsmovIngbetweentheepIduralspaceandthe
spInalcord.
22
ntheregIonwherethespInalnerverootstraversetheduraandarachnoIdmembranes,
thearachnoIdmaterhernIatesthroughtheduramaterIntotheepIduralspacetoform
arachnoIdgranulatIons.AswIththecranIalarachnoIdgranulatIons,thespInalarachnoId
granulatIonsserveasasIteformaterIalInthesubarachnoIdspacetoexItthecentral
nervoussystem(CNS).AlthoughsomehavepostulatedthatthearachnoIdgranulatIonsare
apreferredroutefordrugstomovefromtheepIduralspacetothespInalcord,the
avaIlableexperImentaldatasuggestthatthIsIsnotthecase.
2J
Thesubarachnoid spacelIesbetweenthearachnoIdmaterandthepIamaterandcontaIns
thecerebrospInalfluId(CSF).ThespInalCSFIsIncontInuItywIththecranIalCSFand
provIdesanavenuefordrugsInthespInalCSFtoreachthebraIn.naddItIon,thespInal
nerverootsandrootletsrunInthesubarachnoIdspace.
Pia Mater
ThespInalpIamaterIsadherenttothespInalcordandIscomposedofathInlayerof
connectIvetIssuecellsInterspersedwIthcollagen.TrabeculaeconnectthepIamaterwIth
thearachnoIdmaterandthecellsofthesetwomenIngesblendtogetheralongthe
trabeculae.UnlIkethearachnoIdmater,thepIamaterIsfenestratedInplacessothatthe
spInalcordIsIndIrectcommunIcatIonwIththesubarachnoIdspace.ThepIamaterextends
tothetIpofthespInalcordwhereItbecomesthefilum terminale,whIchanchorsthe
spInalcordtothesacrum.ThepIamateralsogIvesrIsetothedentatelIgaments,whIch
arethInconnectIvetIssuebandsextendIngfromthesIdeofthespInalcordthroughthe
arachnoIdmatertoduramater.TheselIgamentsservetosuspendthespInalcordwIthIn
themenInges.
Cerebrospinal Fluid
CSFIsacomplexsolutIoncontaInInganarrayofmoleculesIncludIngelectrolytes,proteIns,
glucose,neurotransmItters,neurotransmIttermetabolItes,cyclIcnucleotIdes,amInoacIds,
amongmanyothers.CSFIsproducedbyultrafIltratIonofplasmaInthechoroIdplexusand
thecerebral/spInalcapIllarIesandbyoxIdatIonofglucose,whIchproduceswaterasaby
product.TheCSFvolumeIsapproxImately100to160mLInadulthumansandItIs
producedattherateof20to25mL/hr.Consequently,theentIreCSFvolumeIsreplaced
roughlyevery6hours.CSFIsremovedbyarachnoIdvIllIpresentInthesuperIorsagIttal
sInusandalongmanyspInalnerveroots.
ContrarytowIdelytheheldvIew,CSFdoesnotfloworcIrculatethroughthe
subarachnoIdspace.ThedevelopmentofcInemagnetIcresonanceImagIngandcIne
computedtomographytechnIqueshaveshownthatCSFoscIllatesInthecephalocaudalaxIs
wIthafrequencyequaltotheheartrate.
24,25
CSF
P.9J1
oscIllatesbecausecerebralexpansIondurIngsystoledIsplacesCSFcaudallyIntothespInal
canalandcerebralcontractIondurIngdIastolecausestheCSFdIsplacedIntothespInal
canaltoretreatbackIntothecranIalvault.NetCSFmovementIsestImatedat0.04per
oscIllatIon.
TheclInIcalsIgnIfIcanceofthIsunderstandIngofCSFmotIonIsthatCSFcannotberelIedon
todIstrIbutedrugsInthesubarachnoIdspace.ThIsIsoflIttleImportanceInsIngleshot
spInalanesthesIabecausethekInetIcenergyoftheInjectIonandthebarIcItyofthe
solutIonservetodIstrIbutedrug.However,thelackofsIgnIfIcantnetCSFmotIonexplaIns
whydrugdIstrIbutIondurIngtheveryslowInfusIonsusedforchronIcIntrathecalanalgesIa
resultsInverylImIteddrugdIstrIbutIon.
26
Spinal Cord
nthefIrsttrImesterfetus,thespInalcordextendsfromtheforamenmagnumtotheend
ofthesacrum.Thereafter,thevertebralcolumnlengthensmorethanthespInalcordso
thatatbIrththespInalcordendsataboutthelevelofthethIrdlumbarvertebra.nthe
adult,thecaudadtIpofthespInalcordtypIcallylIesatthelevelofthefIrstlumbar
vertebra.However,InJ0ofIndIvIdualsthespInalcordmayendatT12,whIleIn10It
mayextendtoLJ(FIg.J71).
27
AsacralspInalcordhasbeenreportedInanadult.
27
FlexIon
ofthevertebralcolumncausesthetIpofthespInalcordtomoveslIghtlycephalad.
ThespInalcordgIvesrIsetoJ1paIrsofspinal nerves,eachcomposedofananterior motor
rootandaposterior sensory root.ThenerverootsareInturncomposedofmultIple
rootlets.TheportIonofthespInalcordthatgIvesrIsetoalloftherootletsofasIngle
spInalnerveIscalledacord segment.TheskInareaInnervatedbyagIvenspInalnerveand
ItscorrespondIngcordsegmentIscalledadermatome(FIg.J75).TheIntermedIolateral
graymatteroftheT1throughL2spInalcordsegmentscontaInsthecellbodIesofthe
preganglionic sympathetic neurons.ThesesympathetIcneuronsrunwIththecorrespondIng
spInalnervetoapoIntjustbeyondtheIntervertebralforamenwheretheyexIttojoInthe
sympathetIcchaInganglIa.
Figure 37-5.Humansensorydermatomes.
ThespInalnervesandtheIrcorrespondIngcordsegmentsarenamedfortheIntervertebral
foramenthroughwhIchtheyrun.nthecervIcalregIon,thespInalnervesarenamedfor
thevertebraformIngthecaudadhalfoftheIntervertebralforamen;forexample,C4
emergesthroughanIntervertebralforamenformedbyCJandC4.nthethoracIcand
lumbarregIon,thenerverootsarenamedforthevertebraeformIngthecephaladhalfof
theIntervertebralforamen;forexample,L4emergesthroughanIntervertebralforamen
formedbyL4andL5.8ecausethespInalcordusuallyendsbetweenL1andL2,thethoracIc,
lumbar,andsacralnerverootsrunIncreasInglylongerdIstancesInthesubarachnoIdspace
togetfromtheIrspInalcordsegmentoforIgIntotheIntervertebralforamenthroughwhIch
theyexIt.ThosenervesthatextendbeyondtheendofthespInalcordtotheIrexItsIteare
collectIvelyknownasthecauda equina(FIg.J71).
Technique
SpInalandepIduralanesthesIashouldbeperformedonlyafterapproprIatemonItorsare
applIedandInasettIngwhereequIpmentforaIrwaymanagementandresuscItatIonare
ImmedIatelyavaIlable.8eforeposItIonIngthepatIent,allequIpmentforspInalblock
shouldbereadyforuse;forexample,localanesthetIcsmIxedanddrawnup,needles
uncapped,skInantIseptIcsolutIonavaIlable,andsoon.PreparIngallequIpmentaheadof
tImewIllmInImIzethetImerequIredtoperformtheblockandtherebyenhancepatIent
comfort.
P.9J2
Needles
SpInalandepIduralneedlesareclassIfIedbythedesIgnoftheIrtIps(FIg.J76).The
WhItacre,Eldor,|arx,andSprottespInalneedleshaveapencIlpoInttIpwIthoneortwo
(Eldor)aperture(s)onthesIdeoftheshaftproxImaltothetIp.TheCreene,Atraucan,and
QuInckeneedleshavebeveledtIpswIthcuttIngedges.ThepencIlpoIntneedlesrequIre
moreforcetoInsertthanthebeveltIpneedlesbutprovIdeabettertactIlefeelofthe
varIoustIssuesencounteredastheneedleIsInserted.naddItIon,thebevelhasbeen
showntocausetheneedletobedeflectedfromtheIntendedpathasItpassesthrough
tIssueswhIlethepencIlpoIntneedlesarenotdeflected.
28
EpIduralneedleshavealarger
dIameterthanspInalneedlestofacIlItatetheInjectIonoffluIdoraIrwhenusIngtheloss
ofresIstancetechnIquetoIdentIfytheepIduralspace.naddItIon,thelargerdIameter
allowsforeasIerInsertIonofcathetersIntotheepIduralspace.TheTuohyepIduralneedle
hasacurvedtIptohelpcontrolthedIrectIonthatthecathetermovesIntheepIdural
space.TheHusteadneedletIpIsalsocurved,althoughsomewhatlessthantheTuohy
needle.TheCrawfordneedletIpIsstraIght,makIngItlesssuItableforcatheterInsertIon.
Figure 37-6.SomeofthecommercIallyavaIlableneedlesforspInalandepIdural
anesthesIa.NeedlesaredIstInguIshedbythedesIgnoftheIrtIps.
TheoutsIdedIameterofbothepIduralandspInalneedlesIsusedtodetermInetheIrgauge.
Largergauge(I.e.,smallerdIameter)spInalneedlesarelesslIkelytocausepostdural
punctureheadaches(P0PH),butaremorereadIlydeflectedthansmallergaugeneedles.
EpIduralneedlesaretypIcallysIzed16to19gaugeandspInalneedles22to29gauge.SpInal
needlessmallerthan22gaugeareofteneasIertoInsertIfanIntroducerneedleIsused.
TheIntroducerIsInsertedIntotheInterspInouslIgamentIntheIntendeddIrectIonofthe
spInalneedleandthespInalneedleIsthenInsertedthroughtheshaftoftheIntroducer.
TheIntroducerpreventsthespInalneedlefrombeIngdeflectedorbentasItpassesthrough
theInterspInouslIgament.
28
NeedlesofthesameoutsIdedIametermayhavedIfferent
InsIdedIameters.ThIsIsImportantbecauseInsIdedIameterdetermIneshowlargea
cathetercanbeInsertedthroughtheneedleanddetermIneshowrapIdlyCSFwIllappearat
theneedlehubdurIngspInalneedleInsertIon.AllspInalandepIduralneedlescomewItha
tIghtfIttIngstylet.ThestyletpreventstheneedlefrombeIngpluggedwIthskInorfatand,
Importantly,preventsdraggIngskInIntotheepIduralorsubarachnoIdspaces,wherethe
skInmaygrowandformdermoIdtumors.
Sedation
fthepatIentdesIres,lIghtsedatIonIsapproprIatebeforeplacementofspInalorepIdural
block.Cenerally,thepatIentshouldnotbeheavIlysedatedbecausesuccessfulspInaland
epIduralanesthesIarequIrespatIentpartIcIpatIontomaIntaIngoodposItIon,evaluate
blockheIght,andtoenablecommunIcatIonwIththeanesthesIologIstshouldaparesthesIa
occurwhentheneedlecontactsneuralelements.naddItIon,patIentcooperatIonIs
requIredtoproperlyevaluateanepIduraltestdose;sedatIonwIthaslIttleas1.5mgof
mIdazolamplus75goffentanylhasbeenshowntoreducetherelIabIlItyofpatIent
reportsofsubjectIvesymptomsofIntravenous(7)localanesthetIcInjectIon.
29
Dncethe
blockIsplacedandadequateblockheIghtassured,thepatIentcanbesedatedasdeemed
approprIate.
Spinal Anesthesia
Position
CarefulattentIontopatIentposItIonIngIscrItIcaltosuccessfulspInalpuncture.Poor
posItIonIngcanturnanotherwIseeasyspInalanesthetIcIntoachallengeforboththe
anesthesIologIstandthepatIent.SpInalneedlesaremostoftenInsertedwIththepatIentIn
thelateraldecubItusposItIonandthIstechnIqueIsdescrIbedIndetaIllater.However,both
thepronejackknIfeandsIttIngposItIonsofferadvantagesunderspecIfIccIrcumstances.
ThesIttIngposItIonIssometImesusedInobesepatIentsbecauseItIsofteneasIerto
IdentIfythemIdlInewIththepatIentsIttIng.naddItIon,thesIttIngposItIonallowsoneto
restrIctspInalblocktothesacraldermatomes(saddle block)whenusInghyperbarIclocal
anesthetIcsolutIons.SpInalblockIsgenerallyperformedInthepronejackknIfeposItIon
onlywhenthIsIstheposItIontobeusedforsurgery.TheuseofhypobarIclocalanesthetIc
solutIonswIththepatIentInthepronejackknIfeposItIonproducessacralblockfor
perIrectalsurgery.
nthelateraldecubItusposItIon,thepatIentlIeswIththeoperatIvesIdedownwhenusIng
hyperbarIclocalanesthetIcsolutIonsandwIththeoperatIvesIdeupwhenusInghypobarIc
solutIons,thusassurIngthattheearlIestandmostdenseblockoccursontheoperatIve
sIde.ThebackshouldbeattheedgeofthetablesothatthepatIentIswIthIneasyreach.
ThepatIent'sshouldersandhIpsarebothposItIonedperpendIculartothebedtohelp
preventrotatIonofthespIne.Thekneesaredrawntothechest,theneckIsflexed,andthe
patIentIsInstructedto
P.9JJ
actIvelycurvethebackoutward.ThIswIllspreadthespInousprocessesapartand
maxImIzethesIzeoftheInterlamInarforamen.tIsusefultohaveanassIstantwhocan
helpthepatIentmaIntaInthIsposItIon.UsIngtheIlIaccrestsasalandmark(alInedrawn
betweentheIlIaccrestscrossesthebodyofL5orthe45Interspace),theL2J,LJ4,and
L45InterspacesareIdentIfIedandthedesIredInterspacechosenforneedleInsertIon.
nterspacesaboveL2JareavoIdedtodecreasetherIskofhIttIngthespInalcordwIththe
needle.SomefIndIthelpfultomarkthespInousprocessesflankIngthedesIredInterspace
wIthaskInmarker.ThIsobvIatestheneedtoreIdentIfytheIntendedInterspaceafterthe
patIentIspreparedanddraped.
TheskInIspreparedwIthanapproprIateantIseptIcsolutIonanddraped.AllantIseptIc
solutIonsareneurotoxIc,andcaremustbetakennottocontamInatespInalneedlesor
localanesthetIcswIththeantIseptIcsolutIon.ChlorhexIdInealcoholantIseptIcprevents
colonIzatIonofpercutaneouscathetersbetterthandoes10povIdoneIodIne.
Consequently,theAmerIcanSocIetyofFegIonalAnesthesIacurrentlyrecommends
chlorhexIdIneforskInantIsepsIsprIortoregIonalanesthesIaprocedures.
a
Howonedrapes
Isamatterofpersonalpreference,butclearplastIcdrapesoffertheImportantadvantage
ofpermIttIngvIsualIzatIonoftheentIreback,whIchmakesIteasIertoIdentIfyarotated
orInadequatelyflexedspIne.
Midline Approach
ForthemIdlIneapproachtothesubarachnoIdspace,theskInoverlyIngthedesIred
InterspaceIsInfIltratedwIthasmallamountoflocalanesthetIctopreventpaInwhen
InsertIngthespInalneedle.DneshouldavoIdraIsIngtoolargeaskInwhealbecausethIs
canobscurepalpatIonoftheInterspace,especIallyInobesepatIents.AddItIonallocal
anesthetIc(1to2mL)IsthendeposItedalongtheIntendedpathofthespInalneedletoa
depthof1to2Inches.ThIsdeeperInfIltratIonprovIdesaddItIonalanesthesIaforspInal
needleInsertIonandhelpsIdentIfythecorrectpathforthespInalneedle.nfIltratInglocal
anesthetIclateraltothemIdlIneIspaInfulandgenerallyunnecessary.
ThespInalneedleorIntroducerneedleIsInsertedInthemIddleoftheInterspacewItha
slIghtcephaladangulatIonof10to15degrees(FIg.J77).TheneedleIsthenadvanced,In
order,throughthesubcutaneoustIssue,supraspInouslIgament,InterspInouslIgament,
lIgamentumflavum,epIduralspace,duramater,andfInallyarachnoIdmater.The
lIgamentsproduceacharacterIstIcfeelstheneedleIsadvancedthroughthem,andthe
anesthesIologIstshoulddeveloptheabIlItytodIstInguIshaneedlethatIsadvancIngthrough
thehIghresIstancelIgamentsfromonethatIsadvancIngthroughlowerresIstance
paraspInousmuscle.ThIswIllallowearlydetectIonandcorrectIonofneedlesthatarenot
advancIngInthemIdlIne.PenetratIonoftheduramateroftenproducesasubtlepopthat
IsmosteasIlydetectedwIththepencIlpoIntneedles.0etectIonofduralpenetratIonwIll
preventInsertIngtheneedleallthewaythroughthesubarachnoIdspaceandcontactIng
thevertebralbody.naddItIon,learnIngtodetectduralpenetratIonwIllallowoneto
InsertthespInalneedlequIcklywIthouthavIngtostopeveryfewmIllImetersandremove
thestylettolookforCSFattheneedlehub.
DncetheneedletIpIsbelIevedtobeInthesubarachnoIdspace,thestyletIsremovedto
seeIfCSFappearsattheneedlehub.WIthsmalldIameterneedles(26to29gauge)thIs
generallyrequIres5to10seconds,butmayrequIre1mInuteInsomepatIents.Centle
aspIratIonmayspeedtheappearanceofCSF.fCSFdoesnotappear,theneedleorIfIce
maybeobstructedbyanerverootandrotatIngtheneedle90degreesmayresultInCSF
flow.AlternatIvely,theneedleorIfIcemaynotbecompletelyInthesubarachnoIdspace
andadvancInganaddItIonal1to2mmmayresultInbrIskCSFflow.ThIsIspartIcularly
trueofpencIlpoIntneedles,whIchhavetheIrorIfIceonthesIdeoftheneedleshaft
proxImaltotheneedletIp.FInally,faIluretoobtaInCSFsuggeststhattheneedleorIfIceIs
notInthesubarachnoIdspaceandtheneedleshouldbereInserted.
Figure 37-7.|IdlIneapproachtothesubarachnoIdspace.ThespInalneedleIsInserted
wIthaslIghtcephaladangulatIonandshouldadvanceInthemIdlInewIthout
contactIngbone(B).fboneIscontacted,ItmaybeeItherthecaudad(A)orthe
cephaladspInousprocess(C).TheneedleshouldberedIrectedslIghtlycephaladand
reInserted.fboneIsencounteredatashallowerdepth,theneedleIslIkelywalkIngup
thecephaladspInousprocess.fboneIsencounteredatadeeperdepth,theneedleIs
lIkelywalkIngdowntheInferIorspInousprocess.fboneIsrepeatedlycontactedatthe
samedepth,theneedleIslIkelyoffthemIdlIneandwalkIngalongthelamIna.
(FeprIntedfrom|ulroy|F:FegIonalAnesthesIa:AnllustratedProceduralCuIde.
8oston,LIttle8rown,1989,wIthpermIssIon.)
fboneIsencountereddurIngneedleInsertIon,theanesthesIologIstmustdevelopa
reasoned,systematIcapproachtoredIrectIngtheneedle.SImplywIthdrawIngtheneedle
andrepeatedlyreInsertIngItIndIfferentdIrectIonsIsnotapproprIate.WhencontactIng
bone,thedepthshouldbeImmedIatelynotedandtheneedleredIrectedslIghtlycephalad.
fboneIsagaInencounteredatagreaterdepth,thentheneedleIsmostlIkelywalkIng
downtheInferIorspInousprocessandItshouldberedIrectedmorecephaladuntIlthe
subarachnoIdspaceIsreached.fboneIsencounteredagaInatashallowerdepth,thenthe
needleIsmostlIkelywalkIngupthesuperIorspInousprocessandItshouldberedIrected
morecaudad.fboneIsrepeatedlyencounteredatthesamedepth,thentheneedleIs
lIkelyoffthemIdlIneandwalkIngalongthevertebrallamIna(FIg.J77).
WhenredIrectInganeedleItIsImportanttowIthdrawthetIpIntothesubcutaneoustIssue.
fthetIpremaInsembeddedInoneofthevertebrallIgaments,attemptsatredIrectIngthe
needlewIllsImplybendtheshaftandwIllnotrelIablychangeneedledIrectIon.WhenusIng
anIntroducerneedle,ItalsomustbewIthdrawnIntothesubcutaneoustIssuebeforebeIng
redIrected.ChangesInneedledIrectIonshouldbemadeInsmallIncrementsbecauseeven
smallchangesInneedleangleattheskInmayresultInfaIrlylargechangesInposItIonof
theneedletIpwhenItreachesthespInalmenIngesatadepthof4to6cm.Careshouldbe
exercIsedwhengrIppIngtheneedletoensurethatItdoesnotbow.nsertIonofacurved
needlewIllcauseIttoveeroffcourse.
fthepatIentexperIencesaparesthesIa,ItIsImportanttodetermInewhethertheneedle
tIphasencounteredanerverootIntheepIduralspaceorInthesubarachnoIdspace.When
theparesthesIaoccurs,ImmedIatelystopadvancIngtheneedle,removethestylet,and
lookforCSFattheneedlehub.ThepresenceofCSFconfIrmsthattheneedleencountered
acauda
P.9J4
equInanerverootInthesubarachnoIdspaceandtheneedletIpIsIngoodposItIon.CIven
howtIghtlypackedthecaudaequInanerverootsare,ItIssurprIsIngthatallspInal
puncturesdonotproduceparesthesIas.fCSFIsnotvIsIbleatthehub,thentheparesthesIa
mayhaveresultedfromcontactwIthaspInalnerveroottraversIngtheepIduralspace.
ThIsIsespecIallytrueIftheparesthesIaoccursInthedermatomecorrespondIngtothe
nerverootthatexItsthevertebralcanalatthesamelevelthatthespInalneedleIs
Inserted.nthIscasetheneedlehasmostlIkelydevIatedfromthemIdlIneandshouldbe
redIrectedtowardthesIdeopposItetheparesthesIa.DccasIonally,paInexperIencedwhen
theneedlecontactsbonemaybemIsInterpretedbythepatIentasaparesthesIaandthe
anesthesIologIstshouldbealerttothIspossIbIlIty.
DncetheneedleIscorrectlyInsertedIntothesubarachnoIdspace,ItIsfIxedInposItIonand
thesyrIngecontaInInglocalanesthetIcIsattached.CSFIsgentlyaspIratedtoconfIrmthat
theneedleIsstIllInthesubarachnoIdspaceandthelocalanesthetIcslowlyInjected(0.5
mL/sec).AftercompletIngtheInjectIon,asmallvolumeofCSFIsagaInaspIratedto
confIrmthattheneedletIpremaInedInthesubarachnoIdspacewhIlethelocalanesthetIc
wasdeposIted.ThIsCSFIsthenreInjectedandtheneedle,syrInge,andanyIntroducer
removedtogetherasaunIt.fthesurgIcalprocedureIstobeperformedInthesupIne
posItIon,thepatIentIshelpedontohIsorherback.TopreventexcessIvecephaladspread
ofhyperbarIclocalanesthetIc,careshouldbetakentoensurethatthepatIent'shIpsare
notraIsedoffthebedastheyturn.
DncetheblockIsplaced,strIctattentIonmustbepaIdtothepatIent'shemodynamIcstatus
wIthbloodpressureand/orheartratesupportedasnecessary.8lockheIghtshouldalsobe
assessedearlybypInprIckortemperaturesensatIon.TemperaturesensatIonIstestedby
wIpIngtheskInwIthalcohol,andmaybepreferabletopInprIckbecauseItIsnotpaInful.
f,afterafewmInutes,theblockIsnotrIsInghIghenoughorIsrIsIngtoohIgh,thetable
maybetIltedasapproprIatetoInfluencefurtherspreadofhypobarIcorhyperbarIclocal
anesthetIcs.
Paramedian Approach
TheparamedIanapproachtotheepIduralandsubarachnoIdspacesIsusefulInsItuatIons
wherethepatIent'sanatomydoesnotfavorthemIdlIneapproach,suchasInabIlItytoflex
thespIneorheavIlycalcIfIedInterspInouslIgaments.ThIsapproachcanbeusedwIththe
patIentInanyposItIonandIsprobablythebestapproachforthepatIentIntheprone
jackknIfeposItIon.
ThespInousprocessformIngthelowerborderofthedesIredInterspaceIsIdentIfIed.The
needleIsInsertedapproxImately1cmlateraltothIspoIntandIsdIrectedtowardthe
mIddleoftheInterspacebyanglIngItapproxImately45degreescephaladwIthjustenough
medIalangulatIon(approxImately15degrees)tocompensateforthelateralInsertIon
poInt.ThefIrstsIgnIfIcantresIstanceencounteredshouldbethelIgamentumflavum.8one
encounteredprIortothelIgamentumflavumIsusuallythevertebrallamInaofthe
cephaladvertebraandtheneedleshouldberedIrectedaccordIngly.AnalternatIvemethod
IstoInserttheneedleperpendIculartotheskInInallplanesuntIlthelamInaIscontacted.
TheneedleIsthenwalkedoffthesuperIoredgeofthelamInaandIntothesubarachnoId
space.ThelamInaprovIdesavaluablelandmarkthatfacIlItatescorrectneedleplacement;
however,repeatedneedlecontactwIththeperIosteumcanbepaInful.
Lumbosacral Approach
Thelumbosacral(orTaylor)approachtothesubarachnoIdandepIduralspacesIssImplya
paramedIanapproachdIrectedattheL5S1Interspace,whIchIsthelargestInterlamInar
space.ThIsapproachmaybeusefulwhenanatomIcconstraIntsmakeotherapproaches
unfeasIble.ThepatIentmaybeposItIonedlaterally,prone,orsIttIng,andtheneedle
InsertedatapoInt1cmmedIaland1cmInferIortotheposterIorsuperIorIlIacspIne.The
needleIsangledcephalad45to55degreesandjustmedIalenoughtoreachthemIdlIneat
theleveloftheL5spInousprocess.AswIththeparamedIanapproach,theInterspInous
lIgamentIsbypassedandthefIrstsIgnIfIcantresIstancefeltshouldbethelIgamentum
flavum.
Continuous Spinal Anesthesia
nsertIngacatheterIntothesubarachnoIdspaceIncreasestheutIlItyofspInalanesthesIa
bypermIttIngrepeateddrugadmInIstratIonasoftenasnecessarytoextendthelevelor
duratIonofspInalblock.AcommonandreasonablerecommendatIonforsubsequentdosIng
ortoppIngupofcontInuousspInalblocksIstoadmInIsterhalftheorIgInaldoseoflocal
anesthetIcwhentheblockhasreachedtwothIrdsofItsexpectedduratIon.
ThetechnIqueIssImIlartothatdescrIbedforsIngleshotspInalanesthesIaexceptthata
needlelargeenoughtoaccommodatethedesIredcathetermustbeused.AfterInsertIng
theneedleandobtaInIngfreeflowIngCSF,thecatheterIssImplythreadedIntothe
subarachnoIdspaceadIstanceof2toJcm.tIsofteneasIertoInsertthecatheterIfItIs
dIrectedcephaladorcaudadInsteadoflaterally.fthecatheterdoesnoteasIlypass
beyondtheneedletIp,rotatIngtheneedle180degreesmaybehelpfuloranother
Interspacemaybeused.ThecathetershouldnotbewIthdrawnbackIntotheneedleshaft
becauseoftherIskofshearIngthecatheteroffIntothesubarachnoIdspace.
AvarIetyofcathetersandneedlesareavaIlableforcontInuousspInalanesthesIa.
Commonly,18gaugeepIduralneedlesand20gaugecathetersareused.However,needles
andcathetersthIssIzecarryahIgherrIskofP0PH,especIallyInyoungpatIents.8ecauseof
thIsrIsk,smallerneedleandcathetercombInatIonshavebeendevelopedwIthcatheters
rangIngInsIzefrom24toJ2gauge.AlthoughsmallercathetersdecreasetherIskofP0PH,
theyhavealsobeenassocIatedwIthmultIplereportsofneurologIcInjury,specIfIcally,
caudaequInasyndrome(seeComplIcatIons).ForthIsreason,theUnItedStatesFoodand
0rugAdmInIstratIonhasadvIsedagaInstusInganycathetersmallerthan24gaugefor
contInuousspInalanesthesIa.
Epidural Anesthesia
ForthenovIce,correctplacementofanepIduralneedlecanbetechnIcallymore
challengIngthanspInalneedleplacementbecausethereIslessroomforerror.However,
wIthexperIence,epIduralneedleplacementIsofteneasIerthanspInalneedleplacement
becausethelargergaugeneedlesusedforepIduralanesthesIaarelesslIkelytobe
deflectedfromtheIrIntendedpathandtheyproducemuchbettertactIlefeelofthe
InterspInousandflavallIgaments.naddItIon,thelossofresIstancetechnIqueprovIdesa
muchclearerendpoIntwhenenterIngtheepIduralspacethandoesthesubtlepopofa
spInalneedlepIercIngtheduramater.
PatIentpreparatIon,posItIonIng,monItors,andneedleapproachesforepIduralanesthesIa
arethesameasforspInalanesthesIa.UnlIkespInalanesthesIa,epIduralanesthesIamaybe
performedatanyIntervertebralspace.However,atvertebrallevelsabovethetermInatIon
ofthespInalcord,theepIduralneedlemayaccIdentallypuncturethespInalmenIngesand
damagetheunderlyIngspInalcord.TopreventaccIdentalmenIngealpuncture,the
anesthesIologIstmustlearntoIdentIfytheInterspInouslIgamentsandthelIgamentum
flavumbytheIrfeel.naddItIon,epIduralneedlesmustbeadvancedslowlyand,most
Importantly,undercontrol.
AfterproperposItIonIng,sterIleskInpreparatIon,anddrapIng,thedesIredInterspaceIs
IdentIfIedandalocalanesthetIcskIn
P.9J5
whealIsraIsedatthepoIntofneedleInsertIon.8ecauseepIduralneedlesarerelatIvely
blunt,ItIssometImeshelpfultopIercetheskInwItha18gaugehypodermIcneedlebefore
InsertIngtheepIduralneedle.ForepIduralanesthesIausIngthemIdlIneapproach,the
epIduralneedleIsInsertedthroughthesubcutaneoustIssueandIntotheInterspInous
lIgament.TheInterspInouslIgamenthasacharacterIstIcgrIttyfeel,muchlIkeInsertInga
needleIntoabagofsand.ThIsIsespecIallytrueofyoungerpatIents.ftheInterspInous
lIgamentIsnotclearlyIdentIfIed,thenoneshouldbesuspIcIousthattheneedleIsnotIn
themIdlIne.AfterengagIngtheInterspInouslIgament,theneedleIsadvancedslowly
throughItuntIlanIncreaseInresIstanceIsfelt.ThIsIncreasedresIstancerepresentsthe
lIgamentumflavum.
TheepIduralneedlemustnowtraversethelIgamentumflavumandstopwIthInthe
epIduralspacebeforepuncturIngthespInalmenInges.NumeroustechnIquesforIdentIfyIng
theepIduralspacehavebeenusedsuccessfully;however,thelossofresIstancetofluIdhas
theadvantageofsImplIcIty,relIabIlIty,and,mostImportantly,ahIghersuccessratewhen
comparedtotheuseofaIrforlossofresIstance.
J0
naddItIon,useoffluIdInsteadofaIrfor
lossofresIstancedecreasestherIskofP0PHIntheeventofaccIdentalmenIngeal
puncture.
J1
AglasssyrIngeoraspecIallydesIgnedlowresIstanceplastIcsyrIngeIsfIlledwIth2toJmL
ofsalIneandasmall(0.1to0.JmL)aIrbubble.ThesyrIngeIsattachedtotheepIdural
needleandtheplungerIspresseduntIltheaIrbubbleIsvIsIblycompressed.ftheneedle
tIpIsproperlyembeddedwIthInthelIgamentumflavum,ItshouldbepossIbletocompress
theaIrbubblewIthoutInjectIngfluId.nthIswaytheaIrbubbleservesasagaugeofthe
approprIateamountofpressuretoexertonthesyrIngeplunger.ftheaIrbubblecannotbe
compressedwIthoutInjectIngfluId,thentheneedletIpIsmostlIkelynotInthe
lIgamentumflavum.nthIscase,theneedletIpmaystIllbeIntheInterspInouslIgament,
orItmaybeoffthemIdlIneIntheparaspInousmuscles.TodIfferentIatebetweenthese
possIbIlItIes,onecancarefullyadvancetheneedleandsyrIngeafewmIllImetersInan
efforttoengagethelIgamentumflavum.fItIsstIllnotpossIbletocompresstheaIr
bubble,wIthdrawtheneedleIntothesubcutaneoustIssueandreInsertIt.
DncethelIgamentumflavumIsIdentIfIed,theneedleIsslowlyadvancedwIththe
nondomInanthandwhIlethedomInanthandmaIntaInsconstantpressureonthesyrInge
plunger(FIg.J78).0onotadvancetheneedlewIththehandcompressIngtheplunger
becausethIsdoesnotallowforadequatecontrolofneedlemovement.AstheneedletIp
enterstheepIduralspace,therewIllbeasuddenanddramatIclossofresIstanceasthe
salIneIsrapIdlyInjected.SalIneInjectIonIntotheepIduralspacecanbemoderately
paInfulandpatIentsshouldbeforewarned.ftheneedleIsadvancIngoblIquelythroughthe
lIgamentumflavum,ItIspossIbletoenterIntotheparaspInousmusclesInsteadofthe
epIduralspace.nthIscasethelossofresIstancewIllbelessdramatIc.TohelpverIfythat
theneedlehasenteredtheepIduralspace,0.5mLofaIrcanbedrawnIntothesyrIngeand
Injected.TherewIllbevIrtuallynoresIstancetoaIrInjectIonIntheepIduralspace,whIle
IntheparaspInousmusclesaIrInjectIonwIllencounterdemonstrableresIstance.
AfterenterIngtheepIduralspace,stopadvancIngtheneedle.8ecausetheduramater
abutsthelIgamentumflavumInmanyplaces,theduramaynowbetentedovertheneedle
tIpandadvancIngtheneedleanyfartherthannecessaryheIghtenstherIskofaccIdental
menIngealpuncture,thatIs,wet tap.WhenthesyrIngeIsdIsconnectedfromtheneedle,
ItIscommontohaveasmallamountoffluIdflowfromtheneedlehub.ThIsIsusuallythe
salIneflowIngbackoutoftheepIduralspacebutItcouldbeCSFIftheneedleaccIdentally
enteredthesubarachnoIdspace.CSFcanoftenbedIstInguIshedbythefactthatCSFwIll
usuallyflowoutInavolumegreatlyexceedIngthatusedforthelossofresIstance,CSFwIll
bewarmcomparedwIthsalIne,andCSFwIlltestposItIveforglucose.
fasIngleshottechnIqueIstobeused,thenalocalanesthetIctestdoseshouldbe
admInIsteredtohelpruleoutundetectedsubarachnoIdor7needleplacement.Aftera
negatIvetestdose,thedesIredvolumeoflocalanesthetIcshouldbeadmInIsteredInsmall
Increments(e.g.,5mL)atarateof0.5to1mL/sec.Slow,IncrementalInjectIondecreases
therIskofpaIndurIngInjectIonandallowsdetectIonofadversereactIonstoaccIdental7
orsubarachnoIdplacementbeforetheentIredoseIsadmInIstered.
Figure 37-8.ProperhandposItIonwhenusIngthelossofresIstancetechnIqueto
locatetheepIduralspace.AfterembeddIngtheneedletIpInthelIgamentumflavum,a
syrIngewIth2toJmLofsalIneandanaIrbubbleIsattached.Thelefthandrests
securelyonthebackandthefIngersofthelefthandgrasptheneedlefIrmly.Theleft
handadvancestheneedleslowlyandundercontrolbyrotatIngatthewrIst.The
fIngersoftherIghthandmaIntaInconstantpressureonthesyrIngeplungerbutdonot
aIdInadvancIngtheneedle.ftheneedletIpIsproperlyengagedInthelIgamentum
flavum,ItshouldbepossIbletocompresstheaIrbubblewIthoutInjectIngthesalIne.
AstheneedletIpenterstheepIduralspace,therewIllbeasuddenlossofresIstance
andthesalInewIllbesuddenlyInjected.(FeprIntedfrom|ulroy|F:FegIonal
AnesthesIa:AnllustratedProceduralCuIde.8oston,LIttle8rown,1989,wIth
permIssIon.)
Continuous Epidural Anesthesia
UseofacatheterforepIduralanesthesIaaffordsmuchgreaterflexIbIlItythanthesIngle
shottechnIquebecausethecathetercanbeusedtoprolongablockthatIstooshort,to
extendablockthatIstoolow,ortoprovIdepostoperatIveanalgesIa.DnthedownsIde,
cathetersmaymIgrateIntoanepIduralveIn,IntothesubarachnoIdspace,oroutan
Intervertebralforamen.CatheteruseIsalsomorelIkelytoresultInunIlateralepIdural
block,aclInIcalfactshowntoresultfromcathetertIpsthatendupIntheanterIorepIdural
spaceormIgrateoutanIntervertebralforamIna.
18,J2
AneverchangIngselectIonof
epIduralcathetersIscommercIallyavaIlable.TheydIfferIndIameter,stIffness,locatIonof
InjectIonholes,presenceorabsenceofastylet,constructIonmaterIal,andthelIke.
WhIchevercatheterIschosen,ItIsImportanttoverIfythatItpasseseasIlythroughthe
epIduralneedlebeforetheneedleIsplacedIntheepIduralspace.EpIduralcathetersare
usuallyInsertedthrougheItherTuohyorHusteadneedlesbecausetheIrcurvedtIpshelp
dIrectthecatheterawayfromtheduramater.TheneedlebevelshouldbedIrectedeIther
cephaladorcaudad,althoughthedIrectIonofthebeveldoesnotguaranteethatthe
catheterwIlltravelInthatdIrectIon.ThecatheterwIlltypIcallyencounterresIstanceasIt
reachesthecurveatthetIpoftheneedle,butsteadypressurewIllusuallyresultIn
passageIntotheepIduralspace.fthecatheterwIllnotpassbeyondtheneedletIp,ItIs
possIblethattheneedleopenIngIsnotcompletelyIntheepIduralspaceorthatsome
structureIntheepIduralspaceIspreventIngcatheter
P.9J6
InsertIon(e.g.,epIduralfat).nthIsInstance,theneedlecanbecarefullyadvanced1to2
mmmoreorrotated180degreesandthecatheterreInserted.AlthougheItherofthese
maneuversmayresultInsuccessfulcatheterplacement,theyalsoIncreasetherIskof
accIdentalmenIngealpuncture.AlternatIvely,theprocedurecanberepeatedatanother
InterspaceorwIthadIfferentneedleapproach,forexample,paramedIan.DccasIonallya
catheterwIlladvanceonlyashortdIstancepasttheneedletIp.ThIsraIsesthepossIbIlIty
thattheneedletIpIsnotIntheepIduralspaceandneedstobereposItIoned.nthIscase,
thecathetershouldnotbewIthdrawnbackIntotheepIduralneedlebecauseoftherIsk
thatthecathetertIpwIllbeshearedoffbythebevel'ssharpedge.Father,theneedleand
cathetershouldbepulledoutIntandemandtheprocedurerepeated.AnalternatIve
explanatIonfortheInabIlItytothreadanepIduralcatheterIsthatthetIpoftheepIdural
needlewasbentdurIngbonycontactandnowpartIallyoccludestheneedlelumen.
ThecathetershouldbeadvancedonlyJto5cmIntotheepIduralspace.PlacIngalonger
lengthofcatheterIntheepIduralspaceIncreasestherIskthatItwIllformaknot,
JJ,J4
enteranepIduralveIn,puncturethespInalmenInges,exItanIntervertebralforamen,wrap
aroundanerveroot,orwIndupInsomeotherdIsadvantageouslocatIon.Dncethecatheter
IsapproprIatelyposItIonedIntheepIduralspace,theneedleIsslowlywIthdrawnwIthone
handasthecatheterIsstabIlIzedwIththeother.AftertheneedleIsremoved,thelength
ofcatheterIntheepIduralspaceIsconfIrmedbysubtractIngthedIstancebetweentheskIn
andtheepIduralspacefromthelengthofcatheterbelowtheskIn.0ocumentIngthIs
dIstanceIsImportantwhentryIngtodetermIneIfcathetersusedInthepostoperatIve
perIodhavebeendIslodged.
AnepIduraltestdosemustbeadmInIsteredthroughthecathetertotestfor7or
subarachnoIdplacementbeforeIncrementallydelIverIngtheentIreepIduraldrugdose.n
addItIon,becauseoftherIskofundetected7orsubarachnoIdmIgratIonofthecatheter
overtIme,addItIonaltestdosesmustbeadmInIsteredbeforeeachtopupdoseIsgIven
throughthecatheter.AswIthcontInuousspInalanesthesIa,areasonableguIdelInefortop
updosesIstoadmInIsterhalftheInItIallocalanesthetIcdoseatanIntervalequaltotwo
thIrdstheexpectedduratIonoftheblock.
Epidural Test Dose
TheepIduraltestdoseIsdesIgnedtoIdentIfyepIduralneedlesorcathetersthathave
enteredanepIduralveInorthesubarachnoIdspace.FaIluretoperformthetestmayresult
In7InjectIonoftoxIcdosesoflocalanesthetIcortotalspInalblock.AspIratIngthe
catheterorneedletocheckforbloodorCSFIshelpfulIfposItIve,buttheIncIdenceof
falsenegatIveaspIratIonsIstoohIghtorelyonthIstechnIquealone.
J5
ThemostcommontestdoseIsJmLoflocalanesthetIccontaInIng5mg/mLofepInephrIne
(1:200,000).ThedoseoflocalanesthetIcshouldbesuffIcIentthatsubarachnoIdInjectIon
wIllresultInclearevIdenceofspInalanesthesIa.ntravenousInjectIonofthIsdoseof
epInephrInetypIcallyproducesanaverageJ0beatspermInuteheartrateIncrease
between20and40secondsafterInjectIon.
J6,J7
HeartrateIncreasesmaynotbeasevIdent
InsomepatIentstakIngbetablockIngdrugs;reflexbradycardIausuallyoccursInthese
patIents.
J6,J8
nbetablockedpatIents,asystolIcbloodpressureIncreaseof20mmHgmay
beamorerelIableIndIcatorof7InjectIon.
J6,J8
mportantly,thesensItIvItyofthestandard15gepInephrInetestdosehasbeenshownto
bemarkedlydImInIshedbypreexIstInghIghthoracIcepIduralanesthesIaand/orconcurrent
generalanesthesIa.
J9
LargerepInephrInedosesmaybeeffectIveatdetectIng7InjectIon
InthesesettIngs,butthathasnotbeenshownexperImentally.
soproterenolhasalsobeenusedtodetectIntravascularInjectIon.
40
naddItIon,aIr
InjectIoncombInedwIthaprecordIal0opplertodetectthecharacterIstIcmurmurhasbeen
usedsuccessfullytotestfor7placementofepIduralcatheters.
J5
ThesetechnIqueshave
beendevelopedforuseInlaborIngwomenInwhomthesensItIvItyofepInephrIneasatest
doseIsdIsturbInglylowbecausematernalheartrateIncreasesdurIngcontractIonsare
oftenaslargeasthoseproducedbyepInephrIne.
41
TheclInIcalIndIcatIonsforthese
alternatIvetestsof7InjectIonawaItaddItIonallargerstudIes.
Combined Spinal-Epidural Anesthesia
CombInedspInalepIduralanesthesIa(CSEA)IsausefultechnIquebywhIchaspInalblock
andanepIduralcatheterareplacedsImultaneously.ThIstechnIqueIspopularbecauseIt
combInestherapIdonset,denseblockofspInalanesthesIawIththeflexIbIlItyaffordedby
anepIduralcatheter.TherearespecIalepIduralneedleswIthaseparatelumento
accommodateaspInalneedleavaIlableforCSEA(FIg.J76).However,thetechnIqueIs
easIlyperformedbyfIrstplacIngastandardepIduralneedleIntheepIduralspaceandthen
InsertInganapproprIatelysIzedspInalneedlethroughtheshaftoftheepIduralneedleand
IntothesubarachnoIdspace.ThedesIredlocalanesthetIcIsInjectedIntothesubarachnoId
space,thespInalneedleIsremoved,andacatheterplacedIntheepIduralspacevIathe
epIduralneedle.ThecathetercanthenbeusedtoextendtheheIghtorduratIonof
IntraoperatIveblockorcanbeusedtoprovIdepostoperatIveepIduralanalgesIa.
AnInterestIngpharmacologIcaspectofCSEAIstheobservatIonthatafterthepeakspInal
blockheIghtIsestablIshed,bothsalIneandlocalanesthetIcInjectedIntotheepIdural
spaceareeffectIveatpushIngtheblocklevelhIgher.
42,4J,44
ThIsobservatIonhasbeen
InterpretedtoIndIcatethatthemechanIsmbywhIchtheepIduraltopupIncreasesblock
heIghtIsbyavolumeeffect(I.e.,compressIonofthespInalmenIngesforcIngCSFcephalad)
aswellasalocalanesthetIceffect.
ApotentIalrIskofthIstechnIqueIsthatthemenIngealholemadebythespInalneedlemay
allowdangerouslyhIghconcentratIonsofsubsequentlyadmInIsteredepIduraldrugsto
reachthesubarachnoIdspace.AnecdotalcasereportsandInvItroanImalstudIessuggest
thatthIsmaybealegItImateconcern.
41,45,46,47
AlthoughCSEAIsadvantageousInsome
cIrcumstances,addItIonalprospectIvestudIesarenecessarytoIdentIfytherelatIverIsks
andlImItatIonsofthetechnIque.
Pharmacology
SuccessfulspInalorepIduralanesthesIarequIresablockthatIshIghenoughtoblock
sensatIonatthesurgIcalsIteandlastfortheduratIonoftheplannedprocedure.However,
becausevarIabIlItybetweenpatIentsIsconsIderable(FIgs.J79andJ710),relIably
predIctIngtheheIghtandduratIonofcentralneuraxIalblockthatwIllresultfroma
partIcularlocalanesthetIcdoseIsdIffIcult.Thus,recommendatIonsregardInglocal
anesthetIcchoIceanddosemustbevIewedasapproxImateguIdelInes.TheclInIcIanmust
understandthefactorsgovernIngspInalandepIduralblockheIghtandduratIonto
IndIvIdualIzelocalanesthetIcchoIceanddoseforeachpatIentandprocedure.
Spinal Anesthesia
Block Height
TableJ71lIstssomecommonsurgIcalproceduresthatarereadIlyperformedunderspInal
anesthesIaandtheblockheIght
P.9J7
thatIsusuallysuffIcIenttoensurepatIentcomfort.AlsolIstedaretechnIquesthatare
approprIatetoachIevethedesIredblockheIght.TheratIonalefortheserecommendatIons
IsexplaInedInthefollowIngsectIon.
Figure 37-9.PeakspInalblockheIghtfollowIng10and15mgdosesofhypobarIc,
IsobarIc,andhyperbarIctetracaInesolutIonsInjectedatLJ4wIthpatIentsInthe
lateralhorIzontalposItIon.NotethatdosehasnoInfluenceonblockheIghtandthat
thereIsconsIderableInterIndIvIdualvarIabIlItyInpeakblockheIght,especIallywIth
thehypobarIcsolutIon.(Adaptedfrom8rown0T,WIldsmIthJA,CovIno8Cetal:Effect
ofbarIcItyonspInalanaesthesIawIthamethocaIne.8rJAnaesth1980;52:589,wIth
permIssIon.)
Figure 37-10.PeakepIduralblockheIghtfollowIng20mLof0.75bupIvacaIneor1.5
etIdocaIneInjectedvIaacatheterattheL12Interspace.NotethatdespIteawell
controlledtechnIque,theInterIndIvIdualvarIabIlItyInblockheIghtIsconsIderableand
demonstratesthedIffIcultyInaccuratelypredIctIngblockheIghtInanIndIvIdual
patIent.(AdaptedfromSInclaIrCJ,Scott08:ComparIsonofbupIvacaIneand
etIdocaIneInextraduralblockade.8rJAnaesth1984;56:147,wIthpermIssIon.)
Baricity and Patient Position
TheheIghtofspInalblockIsthoughttobedetermInedbythecephaladspreadoflocal
anesthetIcwIthIntheCSF.TableJ72lIstssomeofthemanyvarIablesthathavebeen
proposedtoInfluencethespreadoflocalanesthetIcswIthInthesubarachnoIdspace.|any
ofthesevarIableshavebeenshowntobeofneglIgIbleclInIcalImportance.Dfthosefactors
thatdoexertsIgnIfIcantInfluenceonlocalanesthetIcspread,thebarIcItyofthelocal
anesthetIcsolutIonrelatIvetopatIentposItIonIsprobablythemostImportant.BaricityIs
defInedastheratIoofthedensIty(mass/volume)ofthelocalanesthetIcsolutIondIvIded
bythedensItyofCSF,whIchaverages1.000J0.000Jg/mLatJ7`C.SolutIonsthathave
thesamedensItyasCSFhaveabarIcItyof1.0000andaretermedisobaric.SolutIonsthat
aremoredensethanCSFaretermedhyperbaric,whereassolutIonsthatarelessdensethan
CSFaretermedhypobaric.
TableJ7JlIststhebarIcItyoflocalanesthetIcsolutIonscommonlyusedforspInal
anesthesIa.ForpractIcalpurposes,solutIonswIthabarIcIty0.9990canbeexpectedto
relIablybehavehypobarIcallyInallpatIents.HypobarIcsolutIonsaretypIcallypreparedby
mIxIngthelocalanesthetIcsolutIonwIthdIstIlledwater.SolutIonswIthabarIcItyof
1.0015canbeexpectedtorelIablybehavehyperbarIcally.HyperbarIcsolutIonsare
typIcallypreparedbymIxIngthelocalanesthetIcIn5to8dextrose.ThebarIcItyofthe
resultantsolutIondependsontheamountofdextroseadded;however,dextrose
concentratIonsbetween1.25and8resultInequIvalentblockheIghts.
48,49
Lowerdextrose
concentratIonshavebeenshowntohaveaconcentratIondependenteffectonblock
heIght,wIth0.JJproducIngablocktoT9.5onaverage,0.8JproducIngablocktoT7.2,
and8producIngablocktoTJ.6.
50
8arIcItyIsImportantIndetermInInglocalanesthetIcspreadandthusblockheIghtbecause
gravItycauseshyperbarIcsolutIonstoflowdownwardInCSFtothemostdependentregIons
ofthespInalcolumn,whereashypobarIcsolutIonstendtorIseInCSF.ncontrast,gravIty
hasnoeffectonthedIstrIbutIonoftrulyIsobarIcsolutIons.Thus,theanesthesIologIstcan
exertconsIderableInfluenceonblockheIghtbychoIceofanesthetIcsolutIonandproper
patIentposItIonIng.SpInalblockcanberestrIctedtothesacralandlowlumbar
dermatomes(saddle block)byadmInIsterIngahyperbarIclocalanesthetIcsolutIonwIth
thepatIentInthesIttIngposItIon
51
orbyadmInIsterIngahypobarIcsolutIonwIththe
patIentInthepronejackknIfeposItIon.SImIlarly,hIghthoracIctomIdcervIcallevelsof
anesthesIacanbereachedbyadmInIsterInghyperbarIcsolutIonswIththepatIentInthe
horIzontalandTrendelenburgposItIons
52,5J
orbyadmInIsterInghypobarIcsolutIonswIth
thepatIentInasemIsIttIngposItIon.However,thIsuseofhypobarIcsolutIonsIsnot
recommendedbecausethehIghblockachIevedandthedImInIshedvenousreturn
assocIatedwIththeuprIghtposturecanleadtosIgnIfIcantcardIovascularcompromIse.
ThesIttIng,Trendelenberg,andjackknIfeposItIonshavemarkedInfluencesonthe
dIstrIbutIonofhypobarIcandhyperbarIcsolutIonsbecausetheseposItIonsaccentuatethe
effectofgravIty.However,mostspInalanesthetIcsareadmInIsteredashyperbarIc
solutIonsInjectedwhIlepatIentsareInthehorIzontallateralposItIon,afterwhIchtheyare
turnedtothehorIzontalsupIneposItIon.nthIssItuatIontheInfluenceofgravItyIsmore
subtlebecausethedependentareasofthespInalcolumndonotdevIateasmuchfromthe
horIzontal.WhIlethepatIentIsturnedlaterally,gravItyhasasmallbutmeasurableeffect
onlocalanesthetIcdIstrIbutIonInthathyperbarIcsolutIonswIllproduceadenser,longer
lastIngblockonthedependentsIde,whIlehypobarIcsolutIonswIllhavetheopposIte
effect.
54
ThIs
P.9J8
P.9J9
makeshypobarIcsolutIonsIdealforunIlateralproceduresperformedInthelateralposItIon
(e.g.,hIpsurgery).HyperbarIcsolutIonscanbeusedtoadvantageforunIlateralprocedures
performedInthesupIneposItIonIftheoperatIvesIdeIsdependentdurIngdrugInjectIon
andthepatIentIsleftInthelateralposItIonforatleast6mInutes.
54
0espItedIfferencesIn
blockdensItyandduratIon,peakblockheIghtwIllbecomparablebetweenthedependent
andnondependentsIdes.
Table 37-1 Representative Surgical Procedures Appropriate For Spinal
Anesthesia
SURGICAL
PROCEDURE
SUGGESTED
BLOCK
HEIGHT
TECHNIQUE COMMENTS
PerIanal
PerIrectal
L12
HyperbarIc
solutIon/sIttIng
posItIon
HypobarIc
solutIon/jackknIfe
posItIon
sobarIcsolutIon/
horIzontalposItIon
PatIentsmustremaInIn
relatIveheaduporhead
downposItIonwhenusIng
hypobarIcandhyperbarIc
solutIonstomaIntaIn
restrIctedspreaddurIngthe
procedure
Lower
extremIty
HIp
Transurethral
resectIonof
theprostate
T10 sobarIcsolutIon
HypobarIcandhyperbarIc
solutIonsarealsosuItablebut
mayproducehIgherblocks
thannecessary
7agInal/cervIcal
HernIorrhaphy
PelvIc
procedures
Appendectomy
T68
HyperbarIc
solutIon/horIzontal
posItIon
sobarIcsolutIonsInjectedat
L2JInterspacemayalsobe
suItable
AbdomInal
Cesarean
sectIon
T46
HyperbarIc
solutIon/
horIzontalposItIon
UpperabdomInalprocedures
usuallyrequIreconcomItant
generalanesthesIatoprevent
vagalreflexesandpaInfrom
tractIonondIaphragm,
esophagus,andthelIke
Table 37-2 Factors that Have Been Suggested as Possible Determinants of
Spread of Local Anesthetic Solutions Within the Subarachnoid Space
CHARACTERISTICS OF THE LOCAL
ANESTHETIC SOLUTION
8arIcIty
LocalanesthetIcdose
LocalanesthetIcconcentratIon
7olumeInjected
PATIENT CHARACTERISTICS
Age
WeIght
HeIght
Cender
Pregnancy
PatIentposItIon
TECHNIQUE
SIteofInjectIon
SpeedofInjectIon
8arbotage
0IrectIonofneedlebevel
AddItIonofvasoconstrIctors
DIFFUSION
AdaptedfromCreeneN|:0IstrIbutIonoflocalanesthetIcsolutIonswIthInthe
subarachnoIdspace.AnesthAnalg1985;64:715,wIthpermIssIon.
Table 37-3 Baricity of Solutions Commonly Used for Spinal Anesthesia

BARICITY
a
HYPERBARIC
TetracaIne:0.5In5dextrose 1.01JJ
8upIvacaIne:0.75In8.25dextrose 1.0227
LIdocaIne:5In7.5dextrose 1.0265
ProcaIne:10Inwater 1.0104
ISOBARIC
b
TetracaIne:0.5InnormalsalIne 0.9997
8upIvacaIne:0.75InsalIne 0.9988
8upIvacaIne:0.5InsalIne 0.998J
LIdocaIne:2InsalIne 0.9986
HYPOBARIC
TetracaIne:0.2Inwater 0.9922
8upIvacaIne:0.JInwater 0.9946
LIdocaIne:0.5Inwater 0.9985
a
|easuredatJ7`C,exceptforhypobarIc0.5lIdocaInemeasuredat25`C.AtJ7`C,
thIssolutIon'sbarIcItyIsless.
b
ThesesolutIonsareslIghtlyhypobarIcbutareusedclInIcallyasIftheywere
IsobarIc.
0atafromHorlockerTT,Wedel0J:0ensIty,specIfIcgravIty,andbarIcItyofspInal
anesthetIcsolutIonsatbodytemperature.AnesthAnalg199J;76:1015;Lambert0,
CovIno8:HyperbarIc,hypobarIcandIsobarIcspInalanesthesIa.FesIdentStaff
PhysIcIan1987;JJ:79;CreeneN|:0IstrIbutIonoflocalanesthetIcsolutIonswIthIn
thesubarachnoIdspace.AnesthAnalg1985;64:715;and8odIlyN,CarpenterF,
Dwens8:LIdocaIne0.5spInalanaesthesIa:AhypobarIcsolutIonforshortstay
perIrectalsurgery.CanJAnaesth1992;J9:770.
Figure 37-11.nthehorIzontalsupIneposItIon,hyperbarIclocalanesthetIcsolutIons
InjectedattheheIghtofthelumbarlordosIs(circle)flowdownthelumbarlordosIsto
poolInthesacrumandInthethoracIckyphosIs.PoolIngInthethoracIckyphosIsIs
thoughttoexplaInthefactthathyperbarIcsolutIonsproduceblockswIthanaverage
heIghtofT46.
WhenthepatIentIsturnedsupInefollowInghyperbarIcdrugInjectIonInthelateral
posItIon,thenormalspInalcurvaturewIllInfluencesubsequentmovementoftheInjected
solutIon.HyperbarIcsolutIonsInjectedattheheIghtofthelumbarlordosIswIlltendtoflow
cephaladtopoolInthethoracIckyphosIsandcaudadtopoolInthesacrum(FIg.J711).
PoolIngofhyperbarIclocalanesthetIcsolutIonsInthethoracIckyphosIshasbeenevokedto
explaIntheclInIcalobservatIonthathyperbarIcsolutIonstendtoproduceblockswIthan
averageheIghtInthemIdthoracIcregIon(FIg.J79).naddItIon,hyperbarIcsolutIonshave
alsobeenobservedtoproduceblockswIthabImodaldIstrIbutIon;thatIs,onegroupof
patIentswIthblockscenteredInthelowthoracIcregIonandasecondgroupofpatIents
wIthblockscenteredInthehIghthoracIcregIon.
55,56
ThepresumedexplanatIonforthIs
observatIonIsthatthelumbarlordosIsproducessplIttIngofthelocalanesthetIcsolutIon
wIthsomeportIonflowIngcaudadtowardthesacrumandtheremaInderflowIngcephalad
IntothethoracIckyphosIs.ThecephaladextentoftheblockthendependsonwhatfractIon
oftheInjecteddrugflowscephalad.ConsIstentwIththIshypothesIsIsthefactthat
elImInatIngthelumbarlordosIsbymaIntaInIngthehIpsflexedhasbeenshownto
sIgnIfIcantlyreduce
56
orelImInate
55
thebImodaldIstrIbutIonofblockswIthoutaffectIng
maxImalblockheIght.
DbvIously,gravItyInfluencesthedIstrIbutIonofhyperbarIcandhypobarIcsolutIonsonly
untIltheyaresuffIcIentlydIlutedInCSFsothattheybecomeIsobarIc.AtthIspoInt,the
localanesthetIcsolutIonnolongermovesInresponsetochangesInpatIentposItIonand
theblockIssaIdtobefIxed.nterestIngly,thetImerequIredforalocalanesthetIc
solutIontobecomefIxedmaybeconsIderable.Poveyetal.
51,52
showedthathyperbarIc
bupIvacaIneInjectedInthesIttIngposItIonproducesasaddleblockthatIsrestrIctedtothe
lumbarsegmentsforaslongasthesubjectsremaInedsIttIng.However,even60mInutes
afterbupIvacaIneInjectIontheblockspreadtomIdthoracIclevelsafterturnIngthe
patIentssupIne.SImIlarly,8odIlyetal.
57
foundthathypobarIclIdocaIneadmInIsteredIn
thejackknIfeposItIonroseasmanyassIxdermatomeswhenpatIentswereallowedtosIt
uprIghtIntherecoveryroomaslongas60mInutesafterlIdocaIneInjectIon.WhetherItIs
alsopossIbletoaffectspreadsolongafterInjectInghyperbarIcorhypobarIcsolutIonsIn
thehorIzontalposItIonIsunclear.Nonetheless,thesefIndIngsdemonstratethatInsome
sItuatIonsItmaybepossIbletoexertInfluenceonblockheIghtbyadjustIngpatIent
posItIonforatleast60mInutesafterlocalanesthetIcInjectIon.
ncontrasttothesItuatIonwIthhyperbarIcsolutIons,patIentposItIonhasnoeffectonthe
dIstrIbutIonofIsobarIcsolutIonsbecausethesesolutIonsarenotInfluencedbygravIty.
Consequently,IsobarIcsolutIonstendnottospreadasfarfromthesIteofInjectIonand
produceblockswIthanaverageheIghtInthelowthoracIcregIon(FIg.J79).
49,58
The
obvIouscaveatIsthatthelocalanesthetIcsolutIonmustbetrulyIsobarIcInthepatIentIn
whomItIsused.8ecauseofthevarIabIlItyInCSFdensItyamongpatIents,ItIsdIffIcultto
producerelIablyIsobarIclocalanesthetIcsolutIons.Nonetheless,asIndIcatedInTableJ7
J,severallocalanesthetIcsolutIonsareusedasIftheywereIsobarIc.tIsnoteworthythat
whIleIsobarIcsolutIonsproduceanaverageblockheIghtthatIslowerthancomparable
hyperbarIcsolutIons,
49,58,59,60
theIsobarIcsolutIonsproduceblockswIthamuchgreater
varIabIlItyInheIght.
61,62,6J
Loganetal.
61
havetermedplaInbupIvacaIneanunpredIctable
spInalanesthetIcagent.ThegreatervarIabIlItyInspreadmaystemInpartfromthefact
thatthesesolutIonsareactuallyslIghtlyhypobarIcandtheIrspreadhasbeenshowntobe
affectedbypatIentposItIon.
64,65
TemperaturerelatedchangesInbarIcItymayalsoplaya
roleInthevarIabIlItyIndIstrIbutIonofthesenearlyIsobarIcsolutIons.Forexample,
SteInstraandvanPoorten
66
haveshownthatthedIstrIbutIonofplaInbupIvacaIneIs
sIgnIfIcantlyalteredbychangesIntemperatureoftheInjectedsolutIon.naddItIon,
|cClureetal.
67
haveshownthatIncreasIngthevolumeanddecreasIngtheconcentratIon
ofIsobarIctetracaInealsoIncreasesthevarIabIlItyInblockheIght.Theseandother
unknownfactorsmayplayaroleIntheunpredIctabIlItyofthesenearlyIsobarIcsolutIons.
AlthoughunpredIctabIlItyIscauseforconcern,ItshouldbepoIntedoutthatthelower
averageblockheIghtachIevedofferspotentIaladvantagesforsurgIcalproceduresbelow
theumbIlIcusbecauseofthedecreasedIncIdenceofcardIovascularsIdeeffectsassocIated
wIthlowerblocks.TheIsobarIcsolutIonthathasbeenshowntomostrelIablyproducea
lowthoracIcblockIs10mgoftetracaInecrystalsdIlutedIn1or2mLroomtemperature
salIneandInjectedInthehorIzontalposItIon.
67
Dose, Volume, and Concentration
StudIesaImedatdetermInIngtheeffectofthesethreeInterdependentvarIablesonblock
heIghtaredIffIculttoconductandInterpretbecauseItIsnotpossIbletochangeone
varIablewIthoutsImultaneouslychangInganother.Nonetheless,ItIspossIbletodrawsome
conclusIonsregardIngtheeffectofthesevarIablesonblockheIght.SeveralstudIeswIth
IsobarIctetracaIneandbupIvacaInesolutIonshavefoundthatneItherInjectedvolumenor
drugconcentratIonaffectsblockheIghtwhendoseIsheldconstant.
67,68,69,70,71
0rugdose
doesappeartoplayasmallroleIndetermInIngblockheIghtwIthIsobarIcbupIvacaIne.
TwostudIeshavefoundthat10mgofIsobarIcbupIvacaIneresultsInsIgnIfIcantly
P.940
lowerblocksthandoes15or20mg,butthereIsnodIfferenceInblockheIghtbetweenthe
twohIgherdoses.
72,7J
ncontrast,twostudIesthatexamInedtheeffectofdIfferentdoses
ofIsobarIctetracaInefoundthatdosesbetween5and15mghadnoeffectonblockheIght,
producIngblockswIthanaverageheIghtofT9T10.
58,74
0rugdoseandvolumeappeartoberelatIvelyunImportantInpredIctIngthespreadof
hyperbarIclocalanesthetIcsolutIonsInjectedInthehorIzontalposItIon.ncreasIngthe
doseandvolumeofhyperbarIctetracaIne,whIleholdIngconcentratIonconstant,doesnot
affectblockheIghtwhendosesbetween7.5and15mgareused.
58,74,75
SImIlarly,IncreasIng
thedoseandvolumeofhyperbarIc0.5bupIvacaInedoesnotIncreaseblockheIghtwhen
dosesbetween10and20mgareused.
76,77
However,dosesofhyperbarIc0.5bupIvacaIne
10mghavebeenshowntoresultInblocksthatareapproxImatelytwoandonehalf
dermatomeslowerthanthoseachIevedwIthdoses10mg.
76
ThefactthatbupIvacaIne
doseaffectsblockheIghtonlyattheextremelowendoftheusualdoserangeIsconsIstent
wIththeexperIencewIthIsobarIcbupIvacaInereportedearlIer.ThefactthatdrugdoseIs
relatIvelyunImportantIndetermInIngblockheIghtwIthhyperbarIcsolutIonslIkelyresults
fromanoverwhelmIngeffectofbarIcItyandpatIentposItIonIndetermInIngspreadof
thesesolutIons.
Injection Site
ThesIteofInjectIoncanhaveanImportanteffectonblockheIghtInsomesItuatIons.n
partIcular,sensoryblockheIghtresultIngfromIsobarIc0.5bupIvacaIneIsreducedbytwo
dermatomesperInterspacewhencomparIngdIfferentgroupsofpatIentswhoreceIved
InjectIonsattheL2J,LJ4,orL45Interspaces.
78,79
nanevenmoreconvIncIngstudy,thIs
groupofInvestIgatorsperformedrepeatedblocksInthesamepatIentandfoundthatby
movIngfromtheLJ4totheL45InterspacemeansblockheIghtcouldbereducedfromT6
toT10whenusIngIsobarIc0.5bupIvacaIne.
80
ncontrast,Sundnesetal.
76
foundno
relatIonshIpbetweenInjectIonsIteandblockheIghtwhenusIngahyperbarIcbupIvacaIne
solutIon,presumablybecauseoftheoverwhelmIngeffectofgravItyandpatIentposItIonon
dIstrIbutIonofhyperbarIclocalanesthetIcs.WhetherIsobarIcandhyperbarIcsolutIonsof
otherlocalanesthetIcswIllbehavesImIlarlyIsnotclear.
Patient Characteristics
nyoungadults,ItwasdetermInedthatthemostImportantvarIablegovernIngblockheIght
wIthhyperbarIclocalanesthetIcsolutIonsmaybelumbosacralCSFvolume.
81
However,ItIs
unclearIfthesefIndIngscanbeextrapolatedtootherlocalanesthetIcsorpatIentages.
HIguchIandcolleagues
82
performedadetaIledexamInatIonoftheeffectoflumbarCSF
volume,CSFdensIty,lumbarCSFmotIon,patIentage,patIentweIght,patIentheIght,and
patIentbodymassIndex(8|)onspInalblockwIthIsobarIcbupIvacaIne.|ultIplelInear
regressIondemonstratedthatneItherpatIentagenorheIghtcorrelatedwIthanyclInIcal
characterIstIcofspInalblock.However,CSFvolumeandweIghtwerecorrelatedwIthpeak
blockheIght.CSFvolumewastheonlyvarIabletocorrelatewIthtImetovoIdIng.8|was
theonlysIgnIfIcantpredIctoroftImetoonsetofcompletesensoryblock.
AlthoughthesevarIableswerestatIstIcallysIgnIfIcantpredIctorsofseveralImportant
aspectsofspInalblock,thecoeffIcIentsofdetermInatIon(F
2
)weregenerallysmall
(average,0.2J;range,0.08to0.46),IndIcatIngthatthesevarIablesaccountforarelatIvely
smallamountofthevarIabIlItyIneachoftheblockoutcomesexamIned.Clearly,other
factorscontrIbutesIgnIfIcantlytotheclInIcalcharacterIstIcsofspInalblockwIthIsobarIc
bupIvacaIne.
AlthoughthesestudIesaremechanIstIcallyImportant,theIrclInIcalapplIcatIonIs
necessarIlylImItedbythedIffIcultyIndetermInInganIndIvIdualpatIent'sCSFvolume,CSF
densIty,andvelocItyofCSFmovement.
mportantly,severalInvestIgatorshavefoundthatpatIentage,weIght,8|,andheIghtare
eIthernotpredIctIveofclInIcalcharacterIstIcsofspInalblock
8J,84,85,86,87
orareofsuchlow
predIctIvepowerastobeunrelIablepredIctorsInanyIndIvIdualpatIent.
6J,78,88,89,90
Onset
|ostpatIentscansensetheonsetofspInalblockwIthInaveryfewmInutesafterdrug
InjectIonregardlessofthelocalanesthetIcused.However,thereIsasIgnIfIcantdIfference
amongdrugsInthetImetoreachpeakblockheIght.LIdocaIneandmepIvacaInetendto
reachpeakblockheIghtbetween10and15mInutes,whereastetracaIneandbupIvacaIne
mayrequIre20mInutesbeforepeakblockheIghtIsreached.
Duration
SpInalblocksdonotendabruptlyafterafIxedperIodoftIme.Father,theyrecede
graduallyfromthemostcephaladdermatometothemostcaudad.Asaresult,surgIcal
anesthesIalastssIgnIfIcantlylongeratsacrallevelsthanatthoracIclevels.Therefore,
whendIscussIngtheduratIonofspInalblockItIsnecessarytodIstInguIshbetweenduratIon
atthesurgIcalsIteandthetImerequIredfortheblocktocompletelyresolve.Theformer
IsImportantforprovIdIngadequatesurgIcalanesthesIa,andthelatterIsImportantfor
assurIngatImelyrecovery.AthoroughunderstandIngofthefactorsthatgovernblock
duratIonIsnecessaryIftheclInIcIanIstochoosetechnIquesthatresultInanapproprIate
duratIonofspInalblockade.
Local Anesthetic
TheprIncIpaldetermInantofspInalblockduratIonIsthelocalanesthetIcdrugemployed.
ProcaIneIstheshortestactInglocalanesthetIcforsubarachnoIduse,lIdocaIneand
mepIvacaIneareagentsofIntermedIateduratIon,andbupIvacaIneandtetracaInearethe
longestactIngdrugs.TableJ74lIststherangeoftImesrequIredforsensoryblockto
regresstwodermatomesandtocompletelyresolvewIththelocalanesthetIcsmost
commonlyusedforspInalanesthesIa.AlthoughdrugchoIceIstheprIncIpaldetermInantof
blockduratIon,othervarIablesareresponsIbleforthewIderangeofblockduratIonfound
InTableJ74.
Drug Dose
ncreasInglocalanesthetIcdoseclearlyIncreasestheduratIonofspInalblock.
72,7J,75,91,92
Forexample,8rownetal.
58
demonstratedthatduratIonofsensoryblockatL1followIng15
mgoftetracaInewasapproxImately20greaterthanfollowIng10mg.Sheskeyetal.
7J
demonstratedanapproxImate40IncreaseInblockduratIonatL2whencomparIng10mg
ofbupIvacaInewIth15mg.SImIlarly,Axelssonetal.
91
foundthatduratIonofsensoryblock
atL2wasnearlydoubledwhencomparIng10mgofbupIvacaInewIth20mg.
Block Height
fdrugdoseIsheldconstant,hIgherblockstendtoregressfasterthanlowerblocks.
92
Consequently,IsobarIclocalanesthetIcsolutIonswIllgenerallyproducelongerblocksthan
hyperbarIcsolutIonsusIngthesamedose.TheconventIonalwIsdomIsthatgreater
cephaladspreadresultsInrelatIvelylowerdrugconcentratIonIntheCSFandspInalnerve
roots.Asaresult,IttakeslesstImeforlocalanesthetIcconcentratIontodecreasebelow
themInImallyeffectIveconcentratIon.
Adrenergic Agonists
AdrenergIcagonIsts,suchasepInephrIne,phenylephrIne,andclonIdIne,areaddedtolocal
anesthetIcsInanefforttoprolongtheduratIonofspInalanesthesIa.TheIreffectIveness
dependsonthelocalanesthetIcwIthwhIchtheyarecombIned.naddItIon,theyaremore
effectIveatprolongIngblockInthelumbarandsacraldermatomesthanInthoracIc
dermatomes.
P.941
Table 37-4 Dose and Duration of Local Anesthetics Used for Spinal
Anesthesia
DRUG DOSE(mg)
a
DURATION OF SENSORY BLOCK
TWO-DERMATOME
REGRESSION (min)
b
COMPLETE
RESOLUTION
(min)
b
PROLONGATION BY
ADRENERGIC AGONISTS
(%)
c
ProcaIne 50200 J050 90120 J050
ChloroprocaIne J0100 J050 70150 NF
LIdocaIne 25100 40100 140240 2050
8upIvacaIne 520 90140 240J80 2050
TetracaIne 520 90140 240J80 50100
NF:Notrecommended;seetextforexplanatIon.
a
ThelowestdosesareusedprImarIlyforveryrestrIctedblocks(e.g.,saddleblock),
lesttheybecometoodIlutetobeeffectIve.
b
0uratIonIsInfluencedbydoseandblockheIght.TheduratIonofsurgIcal
anesthesIawIllobvIouslydependonthesurgIcalsIte.
c
TheeffectofadrenergIcagonIstsdependsonthedoseandchoIceofagonIst.
ProlongatIonIsgreatestatlumbarandsacraldermatomesandleastatthoracIc
dermatomes.
EpInephrIneIstypIcallyadmInIsteredIndosesof0.2to0.JmgandphenylephrIneIndoses
of2to5mg.ThereIsevIdencetosuggestarelatIonshIpbetweenthedoseof
vasoconstrIctoraddedandtheduratIonofspInalanesthesIa;however,therelatIonshIpIs
notstrong.
9J,94,95,96
AtthemaxImaldosesusedclInIcally,phenylephrIne(5mg)prolongs
spInalblocktoagreaterdegreethanepInephrIne(0.5mg).
97,98
Atlowerdoses,epInephrIne
(0.2to0.Jmg)andphenylephrIne(2toJmg)appeartobeequallyeffectIveInprolongIng
spInalblock.
96,99
Thus,bothchoIceofadrenergIcagonIstanddoseadmInIsteredappearto
playaroleIndetermInIngblockduratIon.ClonIdIne,mostcommonlyInadoseof75to150
mg,IsatleastaseffectIveasmoderatedosesofphenylephrIneandepInephrIneat
prolongIngsensoryblockbuthasbeenassocIatedwIthgreaterdecreasesInbloodpressure
Insome
100
butnotallstudIes.
101
nterestIngly,clonIdInealsoprolongsspInalblockwhen
admInIsteredorally.
102,10J,104
TetracaIneIsthelocalanesthetIcthatIsmostdramatIcallyprolongedbyaddItIonof
adrenergIcagonIsts.TheduratIonoftetracaInespInalblockmaybeIncreased70to100at
lumbarandsacraldermatomesbyaddItIonofphenylephrIne.EpInephrInemayprolong
tetracaInespInalanesthesIaby40to60.ClonIdIneprolongstetracaInespInalblockby50
to70,wIththelargereffectoccurrIngatlumbardermatomes.
8upIvacaInespInalblockIsalsoprolongedbyadrenergIcagonIsts,althoughtheeffectIs
somewhatlessthanthatseenwIthtetracaIne(TableJ74).EpInephrIneIndosesof0.2mg
prolongsbupIvacaInespInalblockby20toJ0,butonlyInlumbardermatomes.Larger
dosesofepInephrIne(0.Jto0.5mg)prolongsensoryblockInthoracIcdermatomesaswell
byJ0to50.ClonIdIneprolongsbupIvacaInespInalblockbyJ0to50aswell.
TheeffectofadrenergIcagonIstsontheduratIonoflIdocaInespInalblockIscontroversIal.
SomeclInIcalstudIeshavedemonstratedthatadrenergIcagonIstsclearlyprolonglIdocaIne
spInalblock,
94,105,106,107
whereasothershaveconcludedthatadrenergIcagonIstsdonot
produceclInIcallyusefulprolongatIon.
108,109
ThIsdIscrepancymaybeexplaIned,Inpart,by
thefactthatspInalblockduratIonIssovarIablethatstudIesusIngsmallnumbersof
patIentsmaylacksuffIcIentstatIstIcalpowertodetectrealdIfferencesInmeanblock
duratIonbetweengroups.ThIsproblemwasobvIatedInanInterestIngstudybyChIuet
al.,
110
whousedacrossoverstudydesIgntodemonstratethat0.2mgofepInephrIne
sIgnIfIcantlyprolongedlIdocaInesensoryblockInlumbarandsacraldermatomes.Thus,the
avaIlabledatasuggestthataddIngepInephrInetolIdocaInewIllresultInasomewhat
longerblock,atleastInlumbarandsacraldermatomes,thanwouldbeachIevedIf
epInephrInewerenotadded.
ThemechanIsmbywhIchadrenergIcagonIstsprolongspInalblockIsnotclear.DrIgInally,
epInephrIneandphenylephrInewereaddedtolocalanesthetIcswIththeIntentofreducIng
localspInalcordbloodflowandtherebyslowIngtherateofdrugelImInatIonfromthe
spInalcordandCSF.ThereareanImalstudIesthatsupportthIsmechanIsm
111,112
and
othersthatdonot.
11J,114
AnImalstudIeswIthclonIdIneIndIcatethatItdoesreduce
regIonalspInalcordbloodflow.
115
TherearenohumanstudIesthathaveInvestIgatedthe
effectofIntrathecaladrenergIcagonIstsonspInalcordbloodflow.However,thereare
humanstudIesthatdemonstratethatepInephrInedecreasestherateoflocalanesthetIc
clearancefromtheCSF
116,117
andalsoslowstherateatwhIchsubarachnoIdlocal
anesthetIcappearsIntheplasma.
105
ThesefIndIngshavebeenInterpretedasevIdenceofa
vasoconstrIctormedIateddecreaseIndrugclearancefromthespInalcord;however,they
arenotproofthatthIsIstheonly,oreventheprIncIpal,mechanIsmbywhIchadrenergIc
agonIstsprolongspInalanesthesIa.AlternatIvely,Kozodyetal.
118
haveshownthat
IntrathecalepInephrInedecreasesbloodflowIntheduramaterwIthoutalterIngspInalcord
bloodflow,afIndIngmostconsIstentwIthdecreaseddrugclearancevIathedural
vasculature.
AdrenergIcagonIstsarepotentanalgesIcagentsIntheIrownrIghtwhenadmInIsteredInto
thesubarachnoIdspace.
119
AnalgesIaresultsfromInhIbItIonofnocIceptIveafferents,an
effectthatIsmedIatedbystImulatIonofadrenergIcreceptorsInthespInalcorddorsal
horn.naddItIon,largeIntrathecaldosesofadrenergIcagonIstshavebeenshownto
produceflaccIdItyInanImalmodelsbyhyperpolarIzIngmotorneurons.
120
Thus,
prolongatIonofmotorandsensoryblockbyadrenergIcagonIstsmaybepartlybecauseof
dIrectInhIbItoryeffectsofthesedrugsonsensoryandmotorneurons.
Epidural Anesthesia
AnyprocedurethatcanbeperformedunderspInalanesthesIacanalsobeperformedunder
epIduralblockandrequIresthesameblockheIght(TableJ71).AswIthspInalanesthesIa,
thereIsagreatdealofvarIabIlItyamongpatIentsInspread
P.942
(FIg.J710)andduratIonofepIduralblock(TableJ75).Therefore,tochoosethemost
approprIatelocalanesthetIcanddoseforapartIcularclInIcalsItuatIon,the
anesthesIologIstmustbefamIlIarwIththevarIablesthataffectspreadandduratIonof
epIduralanesthesIa.
Table 37-5 Local Anesthetics Used for Surgical Epidural Block
DRUG
a
DURATION OF SENSORY BLOCK
TWO-DERMATOME
REGRESSION (min)
COMPLETE
RESOLUTION (min)
PROLONGATION BY
EPINEPHRINE (%)
ChloroprocaIne
J
4560 100160 4060
LIdocaIne2 60100 160200 4080
|epIvacaIne2 60100 160200 4080
FopIvacaIne
0.51.0
90180 240420 No
EtIdocaIne1
1.5
120240 J00460 No
8upIvacaIne
0.50.75
120240 J00460 No
a
TheseconcentratIonsarerecommendedforsurgIcalanesthesIa;moredIlute
concentratIonsareapproprIateforepIduralanalgesIa.
Block Spread
Injection Site
UnlIkespInalanesthesIa,epIduralanesthesIaproducesasegmentalblockthatspreadsboth
caudallyandcranIallyfromthesIteofInjectIon(FIg.J712).Thus,InjectIonsIteIsarguably
themostImportantdetermInantofthespreadofepIduralblock.CaudalepIduralblocksare
largelyrestrIctedtosacralandlowlumbardermatomes.LowthoracIclevelscanbe
reachedwIthcaudalInjectIonsIflargevolumesareused(e.g.,J0mL).However,theblock
atthoracIcdermatomestendstobepatchyandshortlIvedfollowIngcaudalInjectIon.
121
LumbarlocalanesthetIcInjectIonswIthvolumesof10mLoftenextendcaudadtoInclude
allsacraldermatomes,althoughtheonsetofblockIntheL5andS1rootsIsoftendelayed
andmaybepatchy.
122
TwentymIllIlItervolumesproducebetterqualItysacralanesthesIa
followInglumbarInjectIon.TheslowonsetatL5andS1IsthoughttoresultfromtheIr
largerdIameterandconsequentslowerdrugpenetratIon.LumbarInjectIonscanbe
extendedtomIdthoracIclevels(T46)when20mLvolumesoflocalanesthetIcareused.
ThoracicInjectIonsproduceasymmetrIcsegmentalbandofanesthesIa,thewIdthofwhIch
dependsonthedoseoflocalanesthetIcadmInIstered.WhenusIngamIdtoupperthoracIc
InjectIonsIte,ItIsprudenttoreducethelocalanesthetIcdosesbyapproxImatelyJ0to50
relatIvetolumbardosestopreventexcessIvecephaladspread.tIsgenerallynotfeasIble
toproducesurgIcalanesthesIaInlowlumbarandsacraldermatomeswIthmIdthoracIcor
hIgherInjectIonsItes.ThoracIcepIduralblockIsIdeallysuItedforanesthesIaofthechest
andabdomen.
Figure 37-12.SpreadofepIduralsensoryblockovertImefollowIngInjectIonofvarIous
localanesthetIcsolutIonsattheL2JInterspace.AllsolutIonscontaInedepInephrIne
1:200,000.SensoryblockspreadsbothcephaladandcaudadfromthesIteofInjectIon
wIthtIme.NotethedelayInonsetofblockattheL5andS1dermatomeswIthall
solutIonstested.(FeprIntedfrom8romagePF:EpIduralAnalgesIa.PhIladelphIa,W8
Saunders,1978,wIthpermIssIon.)
Dose, Volume, and Concentration
WIthIntherangetypIcallyusedforsurgIcalanesthesIa,drugconcentratIonIsrelatIvely
unImportantIndetermInIngblockspread.However,drugdoseandvolumeareImportant
varIablesdetermInIngbothspreadandqualItyofepIduralblock.fdrugconcentratIonIs
heldconstant,IncreasIngthevolumeoflocalanesthetIc
P.94J
(andtherebythedose)wIllresultInsIgnIfIcantlygreateraveragespreadandgreaterblock
densIty.However,therelatIonshIpIsnonlInear.Forexample,doublIngthevolumeand
doseof1.5lIdocaIneor0.75bupIvacaInefrom10to20mLhasbeenshowntoIncrease
spreadbyonlythreetofourspInalsegments.
122,12J
7olumeappearstobeImportantIn
determInIngblockspreadIndependentofdrugdose,butagaIntherelatIonshIpIsnonlInear.
ErdemIretal.
124
showedthattrIplIngtheInjectedvolumeoflIdocaInefrom10toJ0mL
whIleholdIngthedoseconstant(J00mg)Increasedthecephaladextentofblockbyonly4.J
dermatomes.ThIstendencytowardgreaterspreadIsthoughttobeexplaInedbythe
observatIonthatIncreasIngthevolumeofsolutIonInjectedIntotheepIduralspace
IncreasescephaladdIstrIbutIon.
125
Position
WhenusIngasIngleshottechnIque,maIntaInIngpatIentsInthelateralposItIondurIngand
afterepIduralInjectIonofsurgIcaldosesoflocalanesthetIcsdoesnotseemtohavea
clInIcallyImportanteffectonspreadoftheblockfromsIdetosIde.
126
SImIlarly,studIes
examInIngtheeffectofpatIentposItIononcephaladspreadofepIduralblockhave
generallyfoundthattheeffectofpostureonspreadIsnotclInIcallyImportant.
127
nterestIngly,Ponholdetal.
128
demonstratedthatmaIntaInIngaJ0degreeheadup
posItIonsIgnIfIcantlyIncreasedthefrequencyofadequateblockattheL5andS1nerve
rootseventhoughtherewasnoeffectonthecephaladextentofanesthesIa.
Patient Characteristics
Age
|ost,
122,12J,129,1J0,1J1,1J2
butnotall,
1JJ
studIesthathaveexamInedtheeffectofageon
epIduralblockhavedemonstratedgreaterspreadInolderpatIents.However,theeffectof
ageIsprobablyclInIcallysIgnIfIcantonlywhencomparIngadultswhoseagesdIfferbyJ
decades.Evenso,thedIfferenceInblockheIghtIsnotlIkelytobemorethanthreeorfour
dermatomes.CreaterspreadInolderpatIentsIsthoughttoberelatedtoalesscomplIant
epIduralspaceanddImInIshedabIlItyforepIduralsolutIonstoleakoutofIntervertebral
foramIna.
125,1J4
8othoftheseagerelatedchangeswouldbeexpectedtoresultInmore
extensIvespreadofsolutIonswIthIntheepIduralspace.
Height and Weight
ThecorrelatIonbetweenpatIentheIght
122,12J,1J2,1JJ
orweIght
1J2,1JJ
andspreadofepIdural
blockIsweakandoflIttleclInIcalsIgnIfIcanceexceptperhapsInpatIentswhoare
extremelytall,extremelyshort,ormorbIdlyobese.
Pregnancy
StudIesexamInIngtheeffectofpregnancyonspreadofepIduralblockareconflIctIng.Some
studIeshavedemonstratedgreaterspreadatterm
1J5
anddurIngearlypregnancy,
129
suggestIngthatgreaterspreaddurIngpregnancyIsnotsImplytheresultofanatomIc
changesassocIatedwIthpregnancy.However,otherstudIeshavenotfoundasIgnIfIcant
dIfferenceInspreadofepIduralblockbetweenpregnantandnonpregnantwomen.
1J6,1J7,1J8
Atherosclerosis
AtherosclerosIswassuggestedasanImportantdetermInantofthespreadofepIdural
block
1J5
;however,subsequentstudIeshavefaIledtoconfIrmthIsrelatIonshIp.
12J,129,1J9
CIventhemyrIadfactorsthathavesomeeffectonspreadofepIduralanesthesIa,how
shouldanesthesIologIstschooseanapproprIatelocalanesthetIcdoseforasIngleshot
epIduralblock:AusefulrecommendatIonIstoassumethata20mLvolumeofalllocal
anesthetIcsIntendedforsurgIcalanesthesIawIllproduceamIdthoracIcblockonaverage
afterlumbarInjectIon.ftherearemultIplereasonstoexpectthattheblockmayspread
excessIvelyInanIndIvIdualpatIent(e.g.,advancedage,obesIty,veryshortstature,hIgh
InjectIonsIte)orIftheproceduredoesnotrequIreahIghblock,thenreducethedose
accordIngly.ftherearemultIplereasonstoexpectthatthespreadmaybereducedfrom
theaverage,thenIncreasethevolumeaccordIngly.DbvIously,choIceoftheapproprIate
localanesthetIcdoseIsobvIatedIfanepIduralcatheterIsused.nthIssItuatIon,begIn
wIthalowerdosethanoneantIcIpateswIllbeneededandadmInIsteraddItIonallocal
anesthetIcasnecessarytoextendtheblocktothedesIredlevel.
Onset
TheonsetofepIduralblockwIthalllocalanesthetIcscanusuallybedetectedwIthIn5
mInutesInthedermatomesImmedIatelysurroundIngtheInjectIonsIte.ThetImetopeak
effectdIfferssomewhatamonglocalanesthetIcs.ShorteractIngdrugsgenerallyreachtheIr
maxImumspreadIn15to20mInutes,whereaslongeractIngdrugsrequIre20to25mInutes.
ncreasIngthedoseoflocalanesthetIcspeedstheonsetofbothmotorandsensoryblock.
Duration
Local Anesthetic
AswIthspInalanesthesIa,choIceoflocalanesthetIcIsthemostImportantdetermInantof
theduratIonofepIduralblock.ChloroprocaIneIstheshortestduratIondrugusedfor
epIduralanesthesIa;lIdocaIneandmepIvacaIneprovIdeblocksofIntermedIateduratIon;
andbupIvacaIne,ropIvacaIne,andetIdocaIneproducethelongestlastIngepIduralblock.
TableJ75lIstslocalanesthetIcscommonlyusedforepIduralblockandapproxImate
duratIonofsurgIcalanesthesIa.Dfnote,tetracaIneandprocaInearenotgenerallyusedfor
epIduralblockbecauseofthepoorqualItyblockthatthesedrugsproduce.
mportantly,whenusedepIdurallysomelocalanesthetIcsexhIbItconsIderableseparatIon
InboththeIntensItyandduratIonofsensoryandmotorblock.EtIdocaIneproducesthe
mostIntensemotorblockandIsunusualamonglocalanesthetIcsInthatmotorblockmay
consIderablyoutlastsensoryblock.
140
ThephenomenonofthepostoperatIvepatIentwhoIs
InpaInyetstIllunabletomovehIsorherlegshasledsomeanesthesIologIststoabandon
etIdocaIneforepIduraluse.ThIsIsunfortunatebecauseetIdocaIne'ssuperIormuscle
relaxatIonIssometImesbenefIcIalIntraoperatIvely.8upIvacaInehastheopposIte
sensorImotorprofIleInthatlowconcentratIonsofbupIvacaIneproducesensoryblockthat
IsrelatIvelymoreIntensethanmotorblock.ThIsseparatIonofsensoryandmotorblock
underlIesthecommonpractIceofusIngdIlutebupIvacaInesolutIonsforepIduralanalgesIa.
Dose
ncreasIngthedoseoflocalanesthetIcadmInIsteredresultsInIncreased
duratIon
122,141,142,14J
anddensIty
122,142,14J
ofepIduralblock.
Age
StudIesthathaveevaluatedtheeffectofageonepIduralblockduratIonareInconclusIve.
7eerIngetal.
1J1
foundthatduratIonofepIduralblockwIthplaInbupIvacaInewasnot
sIgnIfIcantlyaffectedbyage.Nydahletal.
1J0
foundthatepIduralblockusIngbupIvacaIne
wIthepInephrInewasactuallyshorterInolderpatIents.ncontrast,Parketal.
129
found
thatepIduralblockusInglIdocaInewIthepInephrInewasslIghtlybutsIgnIfIcantlylongerIn
olderpatIents.AddItIonalstudIesarenecessarytoclarIfytheeffectofageonduratIonof
epIduralblock.
Adrenergic Agonists
EpInephrIne,InaconcentratIonof5g/mL(1:200,000),IsthemostcommonadrenergIc
agonIstaddedtoepIdurallocalanesthetIcs.thasbeenshowntoprolongtheduratIonof
lIdocaIneandmepIvacaIneepIduralblockbyasmuchas80.
144
8lockIsprolongedby
decreaseddrugclearancefromtheepIduralspace,
145
probablyasaresultof
P.944
reducedbloodflowIntheduramater.AsdIscussedearlIerforspInalanesthesIa,
prolongatIonofmotorandsensoryblockmaybepartlyduetodIrectInhIbItoryeffectsof
epInephrIneonsensoryandmotorneurons.
EpInephrInedoesnotsIgnIfIcantlyprolongtheduratIonofanesthesIawhenaddedto
concentratedsolutIonsofbupIvacaIne,
146,147
etIdocaIne,
142,147
orropIvacaIne
148
thatare
generallyusedforsurgIcalanesthesIa,probablybecausetheInherentduratIonofthese
drugsexceedstheduratIonofepInephrIne'seffects.However,epInephrInedoesappearto
prolonganalgesIaandImprovethequalItyofblockwhenaddedtomoredIlutesolutIonsof
theselocalanesthetIcs,suchasthoseusedforlaboranalgesIa.
149,150,151
Summary
TheextentandduratIonofbothspInalandepIduralblockareInfluencedbyanumberof
varIables,someofwhIchareunderthecontroloftheanesthesIologIst.UnderstandIngthe
ImpactofthesevarIableswIllallowtheanesthesIologIsttoratIonallyselectthemost
approprIatedruganddoseforanyclInIcalsItuatIon.However,eventhemostexperIenced
anesthesIologIstwIllstIllhaveblocksthatarenotadequatefortheplannedprocedure.The
frequencyoffaIledblockscanbekepttoamInImumIftheclInIcIanaImstoproduceblocks
thatarealIttlehIgherandalIttlelongerthanseemsnecessary.tIsofteneasIertodeal
wIthablockthatIstoohIghortoolongthantocoverupforablockthatIstoolowortoo
brIef.
Physiology
Neurophysiology
ThephysIologyoflocalanesthetIcneuralblockadeIsdIscussedIndetaIlInChapter21.ThIs
sectIonbrIeflypresentsaspectsofthephysIologyofneuralblockadethatareunIqueto
spInalandepIduralanesthesIa.
Site of Action
ThesIteofactIonofspInalandepIduralanesthesIaIsnotprecIselyknown.FollowIng
epIduraladmInIstratIon,localanesthetIcIsfoundInthespInalnerveswIthIntheepIdural
space,InspInalnerverootletswIthIntheCSF,andInthespInalcord.SImIlarly,followIng
IntrathecaladmInIstratIonInanImals,localanesthetIcIsfoundInallsItesbetweenthe
spInalnerverootletsandtheInterIorofthespInalcord.
152,15J
Thus,neuralblockadecan
potentIallyoccuratanyorallpoIntsalongtheneuralpathwaysextendIngfromthesIteof
drugadmInIstratIontotheInterIorofthespInalcord.
nanInterestIngstudyInhumans,8oswelletal.
154
demonstratedthatpatIentsareableto
feelparesthesIasdurIngdIrectelectrIcalstImulatIonofthespInalcordunderspInal
anesthesIa.CortIcalevokedpotentIalsfromdIrectspInalcordstImulatIonwerealso
maIntaInedunderspInalanesthesIa,althoughamplItudesweredecreased.ncontrast,
paresthesIasandcortIcalevokedpotentIalsfromtIbIalnervestImulatIonwereabolIshedby
spInalanesthesIa.TheseInvestIgatorsconcludedthatneuralpathwayswIthInthespInal
cordwerelargelyIntactdurIngspInalanesthesIaandthatthespInalnerverootletswere
theprIncIpalsIteofneuralblockade.
ThesIteofepIduralblockIslesswelllocalIzed.|onkeystudIessuggestthatepIduralblock
occurslargelyatsIteswIthInthespInalmenInges,IncludIngthecaudaequInanerveroots,
dorsalrootentryzone,andthelongtractsofspInalcordwhItematter.
155
However,these
fIndIngsarenotentIrelyconsIstentwIththesegmentalonsetofepIduralanesthesIa(FIg.
J712)orwIththelImItedsegmentalblocksthatcanbeproducedwIthsmalldosesof
lumbarepIdurallocalanesthetIcsInhumans.TheseclInIcalobservatIonsaremostreadIly
explaInedbyblockofthesegmentalspInalnervesastheytraversetheepIduralor
paravertebralspaces.nrealIty,epIduralblocklIkelyoccursatbothextraduraland
subduralsIteswIthextraduralradIcularblockpredomInatIngearlyandsubduralspInal
blockpredomInatInglater.ThIssupposItIonIsconsIstentwIthhumanstudIesbyUrban,
156
whorIgorouslyexamInedtheanatomIcpatternofanalgesIathatoccurreddurIngonsetand
regressIonofepIduralblock.HeconcludedthatlocalanesthetIcsInItIallyactedon
radIcularstructuresfollowedlaterbyactIonswIthInthespInalcord.
nterestIngly,humanstudIesdemonstratethatsomatosensoryevokedpotentIalsare
maIntaIneddurIngepIduralanesthesIa,althoughamplItudesaredecreasedandlatencIes
areIncreased.ThIscontrastswIthspInalblockInwhIchevokedpotentIalsarecompletely
elImInatedandsupportstheclInIcalImpressIonthatepIduralblockIsgenerallylessdense
thanthatachIevedwIthspInalanesthesIa.
Differential Nerve Block
Differential blockreferstoaclInIcallyImportantphenomenonInwhIchnervefIbers
subservIngdIfferentfunctIonsdIsplayvaryIngsensItIvItytolocalanesthetIcblockade.
SympathetIcnervefIbersappeartobeblockedbythelowestconcentratIonoflocal
anesthetIcfollowedInorderbyfIbersresponsIbleforpaIn,touch,andmotorfunctIon.ThIs
observatIonhasledtothewIdelyheldbelIefthatdIfferencesInsensItIvItytolocal
anesthetIcblockadeIsexplaInedsolelybydIfferencesInfIberdIameter,wIthsmaller
dIameterneuronsexhIbItInggreatersensItIvItythanlargerdIameterneurons.Althoughthe
mechanIsmfordIfferentIalblockInspInalandepIduralanesthesIaIsnotknown,ItIsclear
thatfIberdIameterIsnottheonly,orperhapsnoteventhemostImportant,factor
contrIbutIngtodIfferentIalblock.
157,158
0IfferentIalblockoccurswIthbothperIpheralnerveblocksandcentralneuraxIalblocks.n
theperIpheralnervoussystem,dIfferentIalblockIsatemporalphenomenonwIth
sympathetIcblockoccurrIngfIrstfollowedIntImebysensoryandmotorblock.ncontrast,
wIthspInalandepIduralanesthesIadIfferentIalblockIsmanIfestasaspatIalseparatIonIn
themodalItIesblocked.ThIsIsseenmostclearlywIthspInalanesthesIaInwhIch
sympathetIcblockmayextendasmanyastwotosIxdermatomeshIgherthanpInprIck
sensatIon,
159
whIchInturnextendstwotothreedermatomeshIgherthanmotorblock.ThIs
spatIalseparatIonIsbelIevedtoresultfromagradualdecreaseInlocalanesthetIc
concentratIonwIthIntheCSFasafunctIonofdIstancefromthesIteofInjectIon.WIth
epIduralanesthesIa,sImIlarzonesofdIfferentIalsensoryandsympathetIcblockare
found.
160
PerhapsthemosttroublesomeconsequenceofdIfferentIalblockIstheoccasIonalpatIent
whohasIntacttouchandproprIoceptIonatthesurgIcalsItedespIteadequateblockadeof
paInsensatIon.EventhemoststoIcpatIentsarelIkelytofIndthIsunpleasantandmaylIe
InfearthattheprocedurewIllsoonbecomepaInful.nnoInstanceshouldthe
anesthesIologIstdownplaythedIstressthIsmaycausepatIents.FeassuranceandjudIcIous
sedatIonasnecessaryareusuallysuffIcIenttoovercomethIsproblem.
AnotherImportantneurophysIologIcaspectofcentralneuroaxIalblockIsthatItproduces
sedatIon,
161
potentIatestheeffectofsedatIvehypnotIcdrugs,
162,16J,164
andmarkedly
decreasesmInImumalveolarconcentratIonofvolatIleanesthetIcs.
165
ThemechanIsm(s)
underlyIngtheseeffectsIsnotknownbutdeafferentatIon,thatIs,thelossofascendIng
sensoryInputtothebraIn,IscommonlyInvokedascausatIve.
P.945
Cardiovascular Physiology
CardIovascularsIdeeffects,prIncIpallyhypotensIonandbradycardIa,arearguablythemost
ImportantandmostcommonphysIologIcchangesdurIngspInalandepIduralanesthesIa.
UnderstandIngthehomeostatIcmechanIsmsresponsIbleforcontrolofbloodpressureand
heartrateIsessentIalforunderstandIngandtreatIngthecardIovascularchanges
assocIatedwIthspInalandepIduralanesthesIa.
Spinal Anesthesia
8lockadeofsympathetIcefferentsIstheprIncIpalmechanIsmbywhIchspInalanesthesIa
producescardIovascularderangements.Aswouldbeexpected,theIncIdenceofsIgnIfIcant
hypotensIonorbradycardIaIsgenerallyrelatedtotheextentofsympathetIcblockade,
whIchInturnparallelsblockheIght.
166,167
However,theseverItyofcardIovascularchanges
hasbeenshownnottocorrelatewIthpeakblockheIghtInonestudy
168
andtocorrelate
poorlyInanother(FIg.J71J).
166
AddItIonalrIskfactorsassocIatedwIthhypotensIonInclude
age40to50years,concurrentgeneralanesthesIa,obesIty,hypovolemIa,andaddItIonof
phenylephrInetothelocalanesthetIc.
166,169
HypotensIondurIngspInalanesthesIaIstheresultofbotharterIalandvenodIlatIon.
7enodIlatIonIncreasesvolumeIncapacItancevessels,therebydecreasIngvenousreturn
andrIghtsIdedfIllIngpressures.
168,170,171,172
ThIsfallInpreloadIsthoughttobethe
prIncIpalcauseofdecreasedcardIacoutputdurInghIghspInalanesthesIa.ArterIaldIlatIon
durIngspInalanesthesIaresultsInsIgnIfIcantdecreasesIntotalperIpheralresIstance(FIg.
J714).
171,17J
Thus,thehypotensIonthataccompanIesJ0to
P.946
40ofspInalanesthetIcsmaybetheresultofreductIonsInafterload,reductIonsIncardIac
output,orboth(FIg.J714).HumanandanImalstudIesIndIcatethatanIntactrenIn
angIotensInsystemhelpstooffsetthehypotensIveeffectsofsympathetIcblockade.
174,175
ThIssuggestsextracautIonwhenadmInIsterIngcentralneuraxIalblocktopatIentstakIng
antIhypertensIvesthatImpaIrtheangIotensInsystem(e.g.,angIotensInconvertIngenzyme
InhIbItorsorangIotensInreceptorblockers).
Figure 37-13.TherelatIonshIpbetweenpeakblockheIghtandchangeInsystolIcblood
pressure(S8P)durIngspInalanesthesIa.AlthoughthereIsastatIstIcallysIgnIfIcant
correlatIonbetweenblockheIghtanddecreaseInsystolIcbloodpressure,the
InterIndIvIdualvarIabIlItyIssogreatthattherelatIonshIphaslIttlepredIctIvevalue.
ThIsIsreflectedIntheF
2
of0.07forthelInearregressIonlIne.(FromCarpenterFL,
CaplanFA,8rown0Letal:ncIdenceandrIskfactorsforsIdeeffectsofspInal
anesthesIa.AnesthesIology1992;76:906,wIthpermIssIon.)
Figure 37-14.ThecardIovasculareffectsofspInalandepIduralanesthesIaIn
volunteerswIthT5blocks.TheeffectsofspInalanesthesIaandepIduralanesthesIa
wIthoutepInephrIneweregenerallycomparableandarebothqualItatIvelyand
quantItatIvelydIfferentfromtheeffectsofepIduralanesthesIawIthepInephrIne.
(|odIfIedfrom8onIcaJJ,KenneduWFJr,WardFJetal:AcomparIsonoftheeffects
ofhIghsubarachnoIdandepIduralanesthesIa.ActaAnaesthesIolScand1966;2J
(Suppl):429.)
HeartratedoesnotchangesIgnIfIcantlydurIngspInalanesthesIaInmostpatIents(FIg.J7
14).However,clInIcallysIgnIfIcantbradycardIaoccasIonallyoccurswIthareported
IncIdenceof10to15.AswIthhypotensIon,therIskofbradycardIaIncreaseswIth
IncreasIngblockheIght.
166
AddItIonalrIskfactorsassocIatedwIthbradycardIaIncludeage
youngerthan50years,AmerIcanSocIetyofAnesthesIologIsts1physIcalstatus,and
concurrentuseofbetablockers.
166,169
ThemechanIsmresponsIbleforbradycardIaIsnot
clear.8lockadeofthesympathetIccardIoacceleratorfIbersorIgInatIngfromT14spInal
segmentsIsoftensuggestedasthecause.ThefactthatbradycardIaIsmorecommonwIth
hIghblockssupportsthIsmechanIsm.However,sIgnIfIcantbradycardIasometImesoccurs
wIthblocksthatareseemInglytoolowtoblockcardIoacceleratorfIbers.0ImInIshed
venousreturnhasalsobeenproposedasacauseofbradycardIadurIngspInalanesthesIa.
ntracardIacstretchreceptorshavebeenshowntoreflexIvelydecreaseheartratewhen
fIllIngpressuresfall.
176
ConsIstentwIththIsmechanIsm,Jacobsenetal.
177
demonstrateda
sIgnIfIcantreductIonInleftventrIcularvolumesandheartratedurInghypotensIveepIsodes
IntwopatIentsdurIngepIduralanesthesIa.TheyconcludedthatcentralvolumedepletIon
elIcItedavagallymedIatedreflexslowIngofheartrate.SImIlarly,8aronetal.
178
demonstratedthatvagalactIvItyIsenhancedbydecreasedvenousreturndurIngepIdural
anesthesIa.However,thIsmechanIsmdoesnotoperateatalltImesInallpatIents.AnzaI
andNIshIkawa
172
demonstratedsIgnIfIcantheartrateIncreasesIn40patIentswhohadtheIr
fIllIngpressuressuddenlydecreasedbybodytIltdurIngspInalanesthesIa.nrealIty,both
blockadeofcardIoacceleratorfIbersanddecreasedfIllIngpressuresaswellasother
unrecognIzedfactorslIkelycontrIbutetobradycardIadurIngspInalanesthesIa.
AlthoughbradycardIaIsusuallyofmoderateseverItyandwelltolerated,therehavebeen
reportsofsudden,unexplaIned,severebradycardIaandasystoledurIngbothspInaland
epIduralanesthesIa.
179,180
naddItIon,multIplecasereportsdocumentthatspInal
anesthesIacanalsoproducesecondandthIrddegreeheartblock
181,182,18J
andthatpre
exIstIngfIrstdegreeblockmaybearIskfactorforprogressIontohIghergradeblocksdurIng
spInalanesthesIa.
181
ThesereportsdocumenttheneedforcontInuedvIgIlancewIthprompt
and,Ifneeded,aggressIvetreatmentofthecardIovascularchangesthataccompany
centralneuraxIalblockade.
Epidural Anesthesia
ThehemodynamIcchangesproducedbyepIduralanesthesIaarelargelydependenton
whetherornotepInephrIneIsaddedtothelocalanesthetIcsolutIon(FIg.J714).
184
HIgh
epIduralblockwIthlocalanesthetIcsolutIonsthatdonotcontaInepInephrIneresultsIn
decreasedstrokevolume,cardIacoutput,totalperIpheralresIstance,andarterIal
pressure.ThemagnItudeofthesechangesIsgenerallylessthanthatseenwIthcomparable
levelsofspInalblock.
184
AswIthspInalanesthesIa,thesehemodynamIcchangesare
belIevedtoresultfromvenousandarterIaldIlatIonInducedbysympathetIcblockade.n
contrast,whenepInephrInecontaInIngsolutIonsareusedforepIduralanesthesIa,stroke
volumeandcardIacoutputIncreasesIgnIfIcantly(FIg.J714).
184
However,perIpheral
resIstancefallsdramatIcally,resultIngInadecreaseInarterIalpressuregreaterthanthat
seenwIthnonepInephrInecontaInIngsolutIons.
2
adrenergIcmedIatedvasodIlatatIon
producedbylowdosesofabsorbedepInephrIneaccountsforthegreaterdecreaseIn
perIpheralvascularresIstanceandbloodpressure.0ecreasedperIpheralresIstancemay
alsocontrIbutetothemarkedIncreaseIncardIacoutput.However,epInephrIneInduced
venoconstrIctIonwItharesultantIncreaseInvenousreturnmayalsoplayanImportant
roleInIncreasIngcardIacoutput.
185
Treating Hemodynamic Changes
TreatmentofhypotensIonsecondarytospInalandepIduralblockmustbeaImedattheroot
causes:decreasedcardIacoutputand/ordecreasedperIpheralresIstance.8oluscrystalloId
admInIstratIonhasoftenbeenadvocatedasameansofrestorIngvenousreturnandthus
cardIacoutputdurIngcentralneuraxIalblockade.However,theeffectIvenessofthIs
therapyInnormovolemIcpatIentsIscontroversIal.PrehydratIngpatIentswIth500to1,500
mLofcrystalloIddoesnotrelIablypreventhypotensIon,butIthasbeenshowntodecrease
theIncIdenceofhypotensIondurIngspInalanesthesIaInsome,
186,187
butnotall,
studIes.
167,188
Thus,althoughjudIcIouscrystalloIdpreloadIngofpatIentsbeforecentral
neuraxIalblocksmaybenefItsomepatIents,thIspractIcecannotberelIedontoprevent
clInIcallysIgnIfIcanthypotensIonInall,orevenmost,patIents.ThereasonforthIsIsthat
IncreasIngpreloadcanonlyIncreasestrokevolume,whIchhaslImItedabIlItytorestore
bloodpressureIfheartrateorsystemIcvascularresIstanceremaInslow.nthIsregard
colloIdsolutIonsofferanInterestIngalternatIvetocrystalloIdsforpreloadIngbefore
centralneuraxIalblocks.|arhoferandcolleagues
189
haveshownthat500mLof6
hetastarchactuallyIncreasessystemIcvascularresIstanceIndexInelderlypatIentshavIng
spInalanesthesIa,and1,500mLofcrystalloIdsIgnIfIcantlydecreasessystemIcvascular
resIstanceIndex.
7asopressorsareamorerelIableapproachtotreatInghypotensIonsecondarytocentral
neuraxIalblockade.0rugswIthbothandadrenergIcactIvItyhavebeenshowntobe
superIortopureagonIstsforcorrectIngthecardIovascularderangementsproducedby
spInalandepIduralanesthesIa.
190,191
EphedrIneIsthedrugmostcommonlyusedtotreat
hypotensIon.EphedrInebolusesof5to10mgIncreasebloodpressurebyrestorIngcardIac
outputandperIpheralvascularresIstance.0opamIne,Inlowtomoderatedoses,hasalso
beenshowntocorrectthehemodynamIcchangesInducedbycentralneuraxIalblock.
192,19J
0opamInemaybepreferabletoephedrIneforlongtermInfusIonbecausetachyphylaxIscan
developtorepeatedephedrIneboluses.PureadrenergIcagonIsts,mostcommonly
phenylephrIne,arealsousedtocorrecthypotensIondurIngspInalanesthesIa.However,
agonIstsIncreasebloodpressurelargelybyIncreasIngsystemIcvascularresIstance,
sometImesattheexpenseoffurtherdecreasIngcardIacoutput.
191
naddItIon,
phenylephrIneboluseshavebeenshowntoproducetransIentleftventrIculardysfunctIon
durIngepIduralanesthesIawIthnonepInephrInecontaInInglocalanesthetIcs.
194
A
potentIal,butasyetunstudIed,roleforagonIstsmaybetotreathypotensIonthatoccurs
durIngepIduralanesthesIawIthepInephrInecontaInInglocalanesthetIcs.8ecausethe
prIncIpalderangementInthIssItuatIonIsamarkeddecreaseInsystemIcvascular
resIstance,agonIstsmaybeanapproprIatechoIcefortreatInghypotensIonInthIs
settIng.
0ecIdIngwhentotreathemodynamIcderangementsdurIngspInalandepIduralanesthesIa
IsperhapsmoredIffIcultthandecIdInghowtotreatthem.TherearecurrentlynostudIes
thatclearlydefInethelowerlImItofacceptablebloodpressureorheartrateforanygroup
ofpatIents.ntheabsenceofsuchdata,severalauthorshaverecommendedtreatIngblood
pressureIfItdecreasesmorethan25toJ0belowbaselIneorInnormotensIvepatIents,If
systolIcpressurefallsbelow90mmHg.FecommendatIonsregardIngbradycardIasuggest
InItIatIngtreatment
P.947
Ifheartratefallsbelow50to60beatspermInute.TheserecommendatIonsarereasonable,
althoughnotunIversallyapplIcable.UltImately,anesthesIologIstsmustdecIdewhatIsan
acceptablebloodpressureandheartrateforanIndIvIdualpatIentbasedonthatpatIent's
underlyIngmedIcalcondItIon.
Respiratory Physiology
SpInalandepIduralblockstomIdthoracIclevelshavelIttleeffectonpulmonaryfunctIonIn
patIentswIthoutpreexIstInglungdIsease.0rugsusedperIoperatIvelyforsedatIondurIng
spInalorepIduralblocklIkelyhavealargerImpactonpulmonaryfunctIonthantheblock
perse.npartIcular,lungvolumes,restIngmInuteventIlatIon,deadspace,arterIalblood
gastensIons,andshuntfractIonshowlIttleornochangedurIngspInalorepIdural
anesthesIa.nterestIngly,theventIlatoryresponsetohypercapnIaIsactuallyIncreasedby
spInalandepIduralblock.
195,196
HIghblocksassocIatedwIthabdomInalandIntercostalmuscleparalysIscanImpaIr
ventIlatoryfunctIonsrequIrIngactIveexhalatIon.Forexample,expIratoryreservevolume,
peakexpIratoryflow,andmaxImummInuteventIlatIonmaybesIgnIfIcantlyreducedby
hIghspInalandepIduralblocks.ThenegatIveImpactofhIghblocksonactIveexhalatIon
suggestscautIonwhenusIngspInalorepIduralanesthesIaInpatIentswIthobstructIve
pulmonarydIsease,whoneedtocoughtoclearsputum,orwhootherwIserelyontheIr
accessorymusclesofrespIratIontomaIntaInaclearaIrwayand/oradequateventIlatIon.
PatIentswIthhIghspInalorepIduralblocksmaycomplaInofdyspneadespItenormalor
elevatedmInuteventIlatIon.ThIslIkelyresultsfromthepatIent'sInabIlItytofeelthechest
wallmovewhIlebreathIng.ThIsIsunderstandablyfrIghtenIngtothepatIent,but
reassuranceIsusuallyeffectIveInallevIatIngthefear.TheanesthesIologIstmustbealert
tothepossIbIlItythatthecomplaIntofdyspneastemsfromIncIpIentrespIratoryfaIlure
secondarytorespIratorymuscleparalysIs.AnormalspeakIngvoIce,asopposedtoafaInt
gaspIngvoIce,suggestsventIlatIonIsnormal.
Gastrointestinal Physiology
ThegastroIntestInaleffectsofspInalandepIduralanesthesIaarelargelytheresultof
sympathetIcblockade.TheabdomInalorgansderIvetheIrsympathetIcInnervatIonfrom
T6L2.8lockadeofthesefIbersresultsInunopposedparasympathetIcactIvItybywayofthe
vagusnerve.Consequently,secretIonsIncrease,sphInctersrelax,andthebowelbecomes
constrIcted.SomesurgeonsbelIevethIsImprovessurgIcalexposure.NauseaIsacommon
complIcatIonofspInalandepIduralanesthesIa.TheetIologyIsunknownbutanIncreased
IncIdenceofnauseadurIngspInalanesthesIaIsassocIatedwIthblockshIgherthanT5,
hypotensIon,opIoIdpremedIcatIon,andahIstoryofmotIonsIckness.
166,169
Endocrine-Metabolic Physiology
SurgeryproducesnumerousendocrIneandmetabolIcchanges,IncludIngIncreasedproteIn
catabolIsmandoxygenconsumptIonaswellasIncreasesIncIrculatIngconcentratIonsof
catecholamInes,growthhormone,renIn,angIotensIn,thyroIdstImulatInghormone,
endorphIn,glucose,andfreefattyacIds,amongothers.
1
TheseendocrInemetabolIc
changeshavecollectIvelybeentermedthesurgical stress response.
ThemechanIsmsresponsIbleforthestressresponsearecomplexandIncompletely
understood.However,afferentsensoryInformatIonfromthesurgIcalsIteplaysan
ImportantroleInInItIatIngandmaIntaInIngthesechanges.
1
NotsurprIsIngly,spInaland
epIduralanesthesIahavebeenshowntoInhIbItmanyoftheendocrInemetabolIcchanges
assocIatedwIththestressresponse.TheInhIbItoryeffectIsgreatestwIthlowerabdomInal
andlowerextremItyproceduresandleastwIthupperabdomInalandthoracIcprocedures.
ThesalutaryeffectofspInalandepIduralanesthesIaIsbelIevedtoresultfromblockadeof
theafferentsensoryInformatIonthathelpsInItIatethestressresponse.
AlthoughsomeaspectsofthesurgIcalstressresponsemaybebenefIcIal,ItIsgenerally
vIewedasmaladaptIveandpossIblyacontrIbutortopostoperatIvemorbIdItyand
mortalIty.
1
0espItetheabIlItyofcentralneuraxIalblocktodecreasethestressresponse,
thereIsasyetnoclearevIdencethatthIsresultsIndecreasedmorbIdItyormortalIty.
Complications
Backache
AlthoughpostoperatIvebackacheoccursfollowInggeneralanesthesIa,ItIsmorecommon
followIngepIduralandspInalanesthesIa.
197
ComparedwIthspInalanesthesIa,backpaIn
followIngepIduralanesthesIaIsmorecommon(11vs.J0)andoflongerduratIon.
198
mportantly,backpaInhasbeencItedInonestudyasthemostcommonreasonforpatIents
torefusefutureepIduralblock.
198
TheetIologyofbackacheIsnotclear,althoughneedle
trauma,localanesthetIcIrrItatIon,andlIgamentousstraInsecondarytomusclerelaxatIon
havebeenofferedasexplanatIons.
Postdural Puncture Headache
P0PHIsacommoncomplIcatIonofspInalanesthesIawIthareportedIncIdenceashIghas
25InsomestudIes.TherIskofP0PHIslesswIthepIduralanesthesIa,butItoccursInupto
50ofyoungpatIentsfollowIngaccIdentalmenIngealpuncturewIthlargedIameter
epIduralneedles.TheheadacheIscharacterIstIcallymIldorabsentwhenthepatIentIs
supIne,butheadelevatIonrapIdlyleadstoaseverefrontooccIpItalheadache,whIchagaIn
ImprovesonreturnIngtothesupIneposItIon.DccasIonally,cranIalnervesymptoms(e.g.,
dIplopIa,tInnItus)andnauseaandvomItIngarealsopresent.TheheadacheIsbelIevedto
resultfromthelossofCSFthroughthemenIngealneedlehole,resultIngIndecreased
buoyantsupportforthebraIn.ntheuprIghtposItIonthebraInsagsInthecranIalvault,
puttIngtractIononpaInsensItIvestructures.TractIononcranIalnervesIsbelIevedto
causethecranIalnervepalsIesthatareseenoccasIonally.
TheIncIdenceofP0PHdecreaseswIthIncreasIngage(FIg.J715)andwIththeuseofsmall
dIameterspInalneedleswIthnoncuttIngtIps.
199,200
nsertIngcuttIngneedleswIththebevel
alIgnedparalleltothelongaxIsofthemenIngeshasalsobeenshowntodecreasethe
IncIdenceofP0PH.
200,201
SomeauthorshavesuggestedthatparallelInsertIonspreadsdural
fIbers,whereasperpendIcularInsertIoncutsthefIbers,resultIngInalargermenIngeal
hole.However,thecollagenfIbersoftheduramaterarearrangedrandomly;therefore,as
manyfIberswIllbecutwIthparallelInsertIonaswIthperpendIcularInsertIon.Amore
lIkelyexplanatIonarIsesfromthefactthattheduramaterIsunderlongItudInaltensIon.
Thus,aslItlIkeholeorIentedperpendIculartothIslongItudInaltensIonwIlltendtobe
pulledopen,andaholeorIentedparalleltothIstensIonwIllbepulledclosed.SomestudIes
havesuggestedthatwomenareatgreaterrIskofdevelopIngP0PH.However,Ifage
dIfferencesareaccountedfor,theredoesnotappeartobeagenderdIfferenceInthe
IncIdenceofP0PH.
200
FolkloreasIde,remaInIngsupInefollowIngmenIngealpuncturedoes
notdecreasethe
P.948
IncIdenceofP0PH.FInally,useoffluId,InsteadofaIr,forlossofresIstancedurIng
attemptedepIduralanesthesIadoesnotaltertherIskofaccIdentalmenIngealpuncture,
butdoesmarkedlydecreasetherIskofsubsequentlydevelopIngP0PH.
J1
P0PHusually
resolvesspontaneouslyInafewdaystoaweekformostpatIents.However,thereare
reportsofP0PHpersIstIngformonthsfollowIngmenIngealpuncture.nItIaltreatmentIs
approprIatelyconservatIveIfthIsmeetsthepatIent'sneeds.8edrestandanalgesIcsas
necessaryarethemaInstayofconservatIvetreatment.CaffeInehasalsobeenshownto
produceshorttermsymptomatIcrelIef.
202
Figure 37-15.TheIncIdenceofpostduralpunctureheadachedecreasesaspatIentage
Increases.WhenusIngbeveledneedles,theIncIdenceIshIgherthanaverageatany
gIvenageIftheneedleIsInsertedperpendIculartothespInalmenIngesandlowerIf
InsertedparalleltothespInalmenInges.(|odIfIedfromLybeckerH,|ollerJT,|ayD
etal:ncIdenceandpredIctIonofpostduralpunctureheadache:AprospectIvestudyof
1021spInalanesthesIas.AnesthAnalg1990;70:J89.)
Epidural Blood Patch
PatIentswhoareunableorunwIllIngtoawaItspontaneousresolutIonofP0PHshouldbe
offeredepIduralbloodpatch.EpIduralbloodpatchIsbelIevedtoformaclotoverthe
menIngealhole,therebypreventIngfurtherCSFleakwhIlethemenIngealrentheals.Ten
to20mLofautologousbloodIsaseptIcallyInjectedIntoepIduralspaceatornearthe
InterspaceatwhIchthemenIngealpunctureoccurred.ThIsIseffectIveInrelIevIng
symptomswIthIn1to24hoursIn85to95ofpatIents;approxImately90ofpatIentswho
faIlanInItIalbloodpatchwIllrespondtoasecondpatch.ThemostcommonsIdeeffectsof
bloodpatcharebackacheandradIcularpaIn,althoughtransIentbradycardIaandcranIal
nervepalsIeshavealsobeenreported.
ThetImIngofepIduralbloodpatchhasbeencontroversIal.EarlystudIessuggestedthat
prophylactIcbloodpatchInpatIentsathIghrIskforP0PHwasIneffectIve.ThIsledseveral
authorstosuggestthatbloodpatchshouldnotbeperformedbeforepatIentsdevelop
symptomsofP0PH.SubsequentstudIes,whIchusedlargervolumesofbloodIntheepIdural
space(15to20mL),haveshownthatprophylactIcbloodpatchIseffectIveInpreventIng
P0PHInpatIentsInwhomthemenIngeswereaccIdentallypunctureddurIngattempted
epIduralanesthesIa.
20J,204
ProphylactIcbloodpatchIsnotapproprIateformostpatIents
butIsworthconsIderIngInhIghrIskoutpatIentsforwhomareturntrIptothehospItalfor
epIduralbloodpatchwouldbedIffIcult.
EpIdurallyadmInIsteredfIbrIngluehasbeenshowntobeaneffectIvealternatIvetoblood
admInIstratIonfortreatmentofP0PH.
205
WhetherItIssuperIortobloodrequIresfurther
studybutItmaybeanattractIvealternatIveforsomepatIents.
Hearing Loss
Lambergetal.
206
demonstratedthatatransIent(1toJdays)mIlddecreaseInhearIng
acuIty(10d8)IscommonafterspInalanesthesIa,wIthanIncIdenceofroughly40anda
J:1femaletomalepredomInance.SImIlarly,CultekInetal.
207
demonstrateda45
IncIdenceofhearIngImpaIrmentInsubjectsundergoIngprIlocaInespInalanesthesIabuta
muchlowerIncIdence(18)InpatIentshavIngbupIvacaInespInalanesthesIa.The
mechanIsmofhearInglossInthesestudIesIsunclear,butthemarkedfemale
predomInance,theabsenceofP0PH,andthedIfferenceInIncIdencebetweenprIlocaIne
andbupIvacaInesuggestthatCSFleakIsnotthecause.
Systemic Toxicity
SystemIctoxIcItyoflocalanesthetIcsIsdIscussedIndetaIlInChapter21.SystemIctoxIcIty
doesnotoccurwIthspInalanesthesIabecausethedrugdosesusedaretoolowtocause
toxIcreactIonsevenIfInjectedIntravenously.8othCNSandcardIovasculartoxIcItymay
occurdurIngepIduralanesthesIa.CNStoxIcItymayresultfromlocalanesthetIcabsorptIon
fromtheepIduralspacebutmorecommonlyoccursfollowIngaccIdentalIntravascular
InjectIonoflocalanesthetIc.ncontrast,cardIovasculartoxIcItyfromlocalanesthetIcscan
probablyonlyoccurfromunIntendedIntravascularInjectIonbecausetheplasma
concentratIonsoflocalanesthetIcsrequIredtoproduceserIouscardIovasculartoxIcItyare
veryhIgh.Anadequate7testdoseandIncrementalInjectIonoflocalanesthetIcsarethe
mostImportantmethodstopreventbothCNSandcardIovasculartoxIcItydurIngepIdural
anesthesIa.
Total Spinal Anesthesia
TotalspInalanesthesIaoccurswhenlocalanesthetIcspreadshIghenoughtoblockthe
entIrespInalcordandoccasIonallythebraInstemdurIngeItherspInalorepIdural
anesthesIa.ProfoundhypotensIonandbradycardIaarecommonsecondarytocomplete
sympathetIcblockade.FespIratoryarrestmayoccurasaresultofrespIratorymuscle
paralysIsordysfunctIonofbraInstemrespIratorycontrolcenters.|anagementIncludes
vasopressors,atropIne,andfluIdsasnecessarytosupportthecardIovascularsystem,plus
oxygenandcontrolledventIlatIon.fthecardIovascularandrespIratoryconsequencesare
managedapproprIately,totalspInalblockwIllresolvewIthoutsequelae.
Neurologic Injury
SerIousneurologIcInjuryIsararebutwIdelyfearedcomplIcatIonofepIduralandspInal
anesthesIa.|ultIplelargeserIesofspInalandepIduralanesthesIareportthatneurologIc
InjuryoccursInapproxImately0.0Jto0.1ofallcentralneuraxIalblocks,althoughInmost
oftheseserIestheblockwasnotclearlyproventobecausatIve.
208
PersIstentparesthesIas
andlImItedmotorweaknessarethemostcommonInjurIes,althoughparaplegIaanddIffuse
InjurytocaudaequInaroots(cauda equina syndrome)dooccurrarely.njurymayresult
fromdIrectneedletraumatothespInalcordorspInalnerves,fromspInalcordIschemIa,
fromaccIdentalInjectIonofneurotoxIcdrugsorchemIcals,fromIntroductIonofbacterIa
IntothesubarachnoIdorepIduralspace,orveryrarelyfromepIduralhematoma.
208
mportantly,localanesthetIcsIntendedforepIduralandIntrathecalusecanthemselvesbe
neurotoxIcInconcentratIonsusedclInIcally.
209
npartIcular,hyperbarIc5lIdocaInehas
been
P.949
ImplIcatedasacauseofmultIplecasesofcaudaequInasyndromefollowIngsubarachnoId
InjectIonthroughsmallbore(mIcrospInal)cathetersdurIngcontInuousspInal
anesthesIa.
210
HyperbarIcsolutIonsInjectedthroughthesehIghresIstancecathetershave
beenshowntoproduceverylIttleturbulenceandthuspoormIxIngofthelocalanesthetIc
wIthInCSF.
211
NerveInjuryIsbelIevedtoresultfrompoolIngoftoxIcconcentratIonsof
undIlutedlIdocaInearounddependentcaudaequInanerveroots.Consequently,theU.S.
Foodand0rugAdmInIstratIonhasbannedtheuseofthesesmallgaugecathetersfor
contInuousspInalanesthesIa.AlthoughthecombInatIonofmIcrospInalcathetersandhIgh
concentratIonsoflIdocaInehaveclearlybeenImplIcatedIncausIngcaudaequIna
syndrome,thIscomplIcatIonhasalsooccurredwhenusInglarger(20gauge)catheters,
210
2lIdocaIne,
212
and0.5tetracaIne.
210
AcommonthreadInallofthesereportshasbeen
theapparentmaldIstrIbutIonofthelocalanesthetIcwIthIntheCSF.|aldIstrIbutIonshould
besuspectedwheneverspInalblockIsunexpectedlyrestrIcted,andmaneuverssuchas
alterIngpatIentposItIonordrugbarIcItyshouldbeemployedtoImprovedrugdIstrIbutIon
beforeaddItIonaldrugIsInjectedthroughacontInuousspInalcatheter.fthesemaneuvers
faIltoImprovedrugdIstrIbutIon,analternatIveanesthetIctechnIqueshouldbeemployed.
ThemechanIsmbywhIchlocalanesthetIcsproducecaudaequInasyndromeIsnotyetclear;
however,InvItroevIdencesuggeststhatlocalanesthetIcscanproduceexcItotoxIcdamage
bydepolarIzIngneuronsandIncreasIngIntracellularcalcIumconcentratIons.
21J
Dther
studIesdemonstratethatlocalanesthetIcscancauseneuronalInjurybydamagIngneuronal
plasmamembranesthroughdetergentlIkeactIons
214,215
orbyactIvatIonofphospholIpase
C.
216
tIsalsounclearasyetwhetheradjunctsaddedtolocalanesthetIcs(e.g.,
epInephrIne)contrIbutetocaudaequInasyndrome.However,basedonanImalstudIes,It
hasbeenarguedthatepInephrIneshouldnotbeaddedtoIntrathecallIdocaIne.
217
Father,
IfaprolongedduratIonofspInalanesthesIaIsnecessary,thenalongeractIngdruglIke
bupIvacaIneshouldbeused.
Transient Neurologic Symptoms
naddItIontocaudaequInasyndrome,theoccurrenceoftransient neurologic symptoms
(TNS)ortransient radicular irritation(TF)hasalsoemergedasaconcernfollowIngcentral
neuraxIalblockade.TFIsdefInedaspaIn,dysesthesIa,orboth,Inthelegsorbuttocks
afterspInalanesthesIaandwasfIrstproposedasarecognIzableentItybySchneIderet
al.
218
AlllocalanesthetIcshavebeenshowntocauseTF,althoughtherIskappearstobe
greaterwIthlIdocaInethanotherlocalanesthetIcs.
219,220,221,222,22J,224,225
nalargeepIdemIologIcstudyofnearly2,000patIents,Freedmanetal.
226
characterIzed
theclInIcalpIctureofTF.TheyfoundthatpatIentsreceIvInglIdocaIneweresIgnIfIcantly
morelIkelytodevelopTFthanwerepatIentsreceIvIngspInaltetracaIneorbupIvacaIne,
althoughTFdIdoccurwIththeselattertwodrugsaswell.DtherrIskfactorsforTF
IncludeaddItIonofphenylephrIneto0.5tetracaIne,
227
surgeryInthelIthotomyposItIonor
wIththelegflexedattheknee(asformenIscectomy),andoutpatIentstatus.
228
Evronet
al.
229
reportedtheuseofadoubleorIfIcepencIlpoIntneedlewasshowntosIgnIfIcantly
reducetherIskofTFcomparedwIthasIngleorIfIceneedle.7arIablesshownnotto
IncreasetherIskofTFIncludedlIdocaInedose,addItIonofepInephrInetolIdocaIne,
presenceofdextrose,paresthesIa,hypotensIon,andbloodtIngedCSFamongothers.
PaInfromTFisnottrIvIal,wIththemajorItyofpatIentsratIngItasmoderate(vIsual
analoguescale=4to7/10).ThepaInusuallyresolvesspontaneouslywIthIn72hours,buta
fewpatIentshaverequIredupto6months.
226
ThemechanIsmresponsIbleforTFIsunknown;however,ItIsnotsImplyamIlder
manIfestatIonofcaudaequInasyndrome.0IfferencesInclInIcalpresentatIonandrIsk
factorssuggestthatthesearenotsImplytwopoIntsalongacontInuumofthesame
process.
Chloroprocaine
ChloroprocaInewasIntroducedIntoclInIcalpractIceIn1951andwasusedforspInal
anesthesIabegInnIngthatyear.ntheearly1980s,however,clInIcIansreportedmultIple
casesofneurologIcInjuryfollowIngIntrathecalInjectIonofchloroprocaIne.mportantly,
thechloroprocaInesolutIonavaIlableatthetImecontaInedeIthermethylparabenasan
antImIcrobIalorbIsulfIteasanantIoxIdant.SubsequentanImalstudIesaImedat
determInIngthemechanIsmforspInalInjuryhavebeenconfusIng,wIthsomeauthors
reportIngthatchloroprocaIneItselfdoesnotcauseneurologIcInjurybutthatbIsulfItedoes,
andothersreportIngthatchloroprocaInecancauseneurologIcInjurybutthatbIsulfIteIs
neuroprotectIve.
2J0,2J1,2J2
Nonetheless,concernaboutthepotentIalforchloroprocaIne
medIatedneurotoxIcItyledtoItsnearlycompleteabandonmentasaspInalanesthetIc,In
largepartbecauselIdocaInewasperceIvedasasaferalternatIve.
However,wenowrecognIzethatlIdocaIneIsnotwIthoutrIskofneurologIctoxIcIty;In
fact,ItmaybethemostneurotoxIcspInalanesthetIc.ThIsobservatIon,coupledwIththe
factthatapreservatIvefreechloroprocaIneformulatIonIsnowavaIlable,hasledtoare
evaluatIonofchloroprocaIneasashortactIngspInalanesthetIc.n2004,KourIand
Kopacz
2JJ
comparedtheblockcharacterIstIcsof40mgofplaIn2lIdocaInewIth40mgof
plaIn2preservatIvefreechloroprocaIneInhumansusIngadoubleblInd,randomIzed
crossoverstudydesIgn.TheyfoundthatbothdrugsproducedIdentIcalaverageblock
heIghts(T8),butthatchloroprocaIneresultedInmorerapIdresolutIonofsensoryblock(10J
1Jvs.12616mInutes.)andfasterattaInmentofdIschargecrIterIa(10412vs.1J414
mInutes).naddItIon,sevenofeIghtvolunteersexperIencedTNSfollowIngIntrathecal
lIdocaIneandnoneexperIencedTNSfollowIng2chloroprocaIne.notherstudIesfromthe
sameresearchgroup,chloroprocaInespInalblockheIghtandduratIonwereshowntobe
posItIvelycorrelatedwIthchloroprocaInedose
2J4
andaddItIonofdextrosewasshownnot
toalterspInalblockcharacterIstIcs,exceptthatItIncreasedpostvoIdbladdervolume.
2J5
ThIsgroupalsoperformedstudIestodetermInetheeffectofepInephrIneandfentanylas
blockprolongIngadjuvantstospInalchloroprocaIne.7athandKopacz
2J6
foundthatthe
addItIonof20goffentanylto40mgofchloroprocaIneIncreasedaveragepeakblock
heIght(T5vs.T9),prolongedthetImeforsensoryblockregressIontoL1(787vs.5J19
mInutes),andmodestlyIncreasedthetImetocompleteregressIon(1047vs.959
mInutes).nterestIngly,SmIthetal.
2J4
foundthatepInephrIne(0.2mg)Increased
chloroprocaIneblockduratIonbutthatItsusewasassocIatedwIthahIghIncIdenceof
myalgIa,arthralgIa,malaIse,andanorexIathatlastedupto48hours.Theauthorshadno
explanatIonfortheepInephrIneassocIatedsIdeeffects,butrecommendedagaInstItsuse
wIthIntrathecalchloroprocaIne.naretrospectIverevIewoftheIrexperIencewIthspInal
chloroprocaIneIn600patIents,HejtmanekandPollock
2J7
reportedcomparableclInIcal
pharmacology,andnoneurologIccomplIcatIons.
Thus,thesestudIes,coupledwIthconcernsaboutthepotentIalforlIdocaInemedIated
neurotoxIcIty,raIsethepossIbIlItythatchloroprocaInewIllreenterthemaInstreamasa
spInalanesthetIc,especIallyforambulatoryanesthesIa.
mportantly,asofthIswrItIng,chloroprocaIneIsnotspecIfIcallyIndIcatedforspInal
anesthesIa;therefore,ItsuseIsofflabel.8utthen,soIstheuseofmultIpledrugsthat
are
P.950
routInelyadmInIsteredIntrathecally,IncludIngplaInbupIvacaIne,plaInlIdocaIne,
hydromorphone,fentanyl,andsufentanIl,amongothers.
Spinal Hematoma
SpInalhematomaIsararebutpotentIallydevastatIngcomplIcatIonofspInalandepIdural
anesthesIa,wIthanIncIdenceestImatedtobe1In150,000.PatIentsmostcommonly
presentwIthnumbnessorlowerextremItyweakness,afactthatcanmakeearlydetectIon
dIffIcultInpatIentsreceIvIngperIoperatIvespInallocalanesthetIcsforpaIncontrol.Early
detectIonIscrItIcalbecauseadelayofmorethan8hoursIndecompressIngthespIne
reducestheoddsofgoodrecovery.
2J8
CoagulatIondefectsaretheprIncIpalrIskfactorforepIduralhematoma.ThIsraIsesthe
legItImatequestIonastohowtotreatpatIentswhoareorwhowIllbeantIcoagulated.ThIs
IssuehasbeenaddressedInaConsensusStatementfromtheAmerIcanSocIetyforFegIonal
AnesthesIaandPaIn|edIcIne
2J9
andtherecommendatIonspresentedherearetakenfrom
thIsconsensusstatement.nbrIef,patIentstakIngnonsteroIdalantIInflammatorydrugs
wIthantIplateleteffects(e.g.,cyclooxygenase1InhIbItors)orreceIvIngsubcutaneous
unfractIonatedheparInfordeepveInthrombosIsprophylaxIsarenotvIewedasbeIngat
IncreasedrIskofspInalhematoma.
ncontrast,otherclassesofantIplateletdrugs,lIkethIenopyrIdInederIvatIves(e.g.,
tIclopIdIne,clopIdogrel)andglycoproteInb/aantagonIsts(e.g.,abcIxImab,eptIfIbatIde,
tIrofIban)haveamorepotenteffectonplateletaggregatIon,andneuraxIalblockshould
generallynotbeperformedInpatIentstakIngtheseorsImIlarmedIcatIons.Further,the
consensusstatementrecommendsthattIclopIdInebedIscontInuedfor2weeksand
clopIdogrelfor1weekbeforeperformIngcentralneuraxIalblocks.TheglycoproteInb/a
antagonIstshaveashorterduratIonofactIon;thus,ItIsrecommendedthatabcIxImab
shouldbedIscontInued24to48hoursbeforecentralneuraxIalblock,andeptIfIbatIdeand
tIrofIbanshouldbedIscontInued4to8hoursbeforehand.
PatIentsreceIvIngfractIonatedlowmolecularweIghtheparIn(e.g.,enoxaparIn,
dalteparIn,tInzaparIn)areconsIderedtobeatIncreasedrIskofspInalhematoma.PatIents
receIvIngthesedrugspreoperatIvelyatthromboprophylactIcdosesshouldhavethedrug
heldfor10to12hoursbeforecentralneuraxIalblock.AthIgherdoses,suchasthoseused
totreatestablIsheddeepveInthrombosIs,centralneuraxIalblockshouldbedelayedfor24
hoursafterthelastdose.ForpatIentsInwhomlowmolecularweIghtheparInIsbegun
aftersurgery,sIngleshotcentralneuraxIalblocksarenotcontraIndIcatedprovIdedthat
thefIrstlowmolecularweIghtheparIndoseIsnotadmInIstereduntIl24hours
postoperatIvelyIfusIngatwIcedaIlydosIngregImenand6to8hoursIfusIngaoncedaIly
dosIngregImen.fanIndwellIngcentralneuraxIalcatheterIsInplace,Itshouldnotbe
removeduntIl10to12hoursafterthelastlowmolecularweIghtheparIndose,andthe
subsequentdosesshouldnotbegInuntIlatleast2hoursaftercatheterremoval.
PatIentswhoarefullyantIcoagulated(I.e.,haveelevatedprothrombIntImeorpartIal
thromboplastIntIme)orwhoarereceIvIngthrombolytIcorfIbrInolytIctherapyare
consIderedtobeatIncreasedrIskofspInalhematoma.ThesepatIentsshouldnotreceIve
centralneuraxIalblockexceptInveryunusualcIrcumstanceswhenotheroptIonsarenot
vIable.
mportantlyforthosepatIentswhomayhaveanepIduralorIntrathecalcatheterplaced,
ItsremovalIsnearlyasgreatarIskforspInalhematomaasItsInsertIon,andthetImIngof
removalandantIcoagulatIonshouldbecoordInated.Also,drugs/regImensnotconsIdered
toputpatIentsatIncreasedrIskofneuraxIalbleedIngwhenusedalone(e.g.,mInIdose
unfractIonatedheparInandnonsteroIdalantIInflammatorydrugs)mayInfactIncreaserIsk
whencombIned.
Contraindications
TheonlyabsolutecontraIndIcatIontospInalorepIduralanesthesIaIspatIentrefusal.
However,severalpreexIstIngcondItIonsIncreasetherelatIverIskofthesetechnIquesand
theanesthesIologIstmustcarefullyweIghtheexpectedbenefItsbeforeproceedIng.Some
condItIonsthatIncreasetheapparentrIskofcentralneuraxIalblockIncludethefollowIng:
1. HypovolemIaorshockIncreasetherIskofhypotensIon.
2. ncreasedIntracranIalpressureIncreasestherIskofbraInhernIatIonwhenCSFIslost
throughtheneedle,orIfafurtherIncreaseInIntracranIalpressurefollowsInjectIonof
largevolumesofsolutIonIntotheepIduralorsubarachnoIdspaces.
J. CoagulopathyorthrombocytopenIaIncreasetherIskofepIduralhematoma.
4. SepsIsIncreasestherIskofmenIngItIs.
5. nfectIonatthepuncturesIteIncreasestherIskofmenIngItIs.
PreexIstIngneurologIcdIsease,partIcularlydIseasesthatwaxandwane(e.g.,multIple
sclerosIs),havebeenconsIderedacontraIndIcatIontocentralneuraxIalblockbysome
authors.Unfortunately,therearenowellcontrolledstudIesthatanswerthequestIonasto
whetherspInalorepIduralanesthesIaaltersthecourseofanypreexIstIngneurologIc
dIsease.However,Hebletal.
240
conductedanuncontrolledretrospectIvechartrevIewof
567patIentswIthpreexIstIngsensorImotorneuropathyordIabetIcpolyneuropathywho
underwentspInalanesthesIa.TwoofthesepatIents(0.4;confIdenceInterval:0.1to1.J)
developedsIgnIfIcantandpersIstentnewneurologIcsymptoms:paInfulexacerbatIonof
dIabetIcneuropathyandlumbarplexopathysuperImposedonpreexIstIngsensorImotor
neuropathy.nbothcases,theroleofspInalanesthesIaInthepatIent'snewsymptomswas
unknown;thus,ItIsdIffIculttousethesedatatoInformthedecIsIonwhetherornottouse
centralneuraxIalblockInpatIentswIthpreexIstIngperIpheralneuropathy.UntIlmoreand
betterdataareavaIlable,ItIsprudenttoInformpatIentsthattheremaybeasmallrIsk
thattheIrneuropathymayworsensothattheycanconsIderthatwhendIscussIngtheIr
anesthetIcchoIce.
Spinal or Epidural Anesthesia?
SpInalandepIduralanesthesIaeachhaveadvantagesanddIsadvantagesthatmaymake
oneortheothertechnIquebettersuItedtoapartIcularpatIentorprocedure.Controlled
studIescomparIngbothtechnIquesforsurgIcalanesthesIahaveconsIstentlyfoundthat
spInalanesthesIatakeslesstImetoperform,producesmorerapIdonsetofbetterqualIty
sensorImotorblock,andIsassocIatedwIthlesspaIndurIngsurgery.0espItetheseImportant
advantagesofspInalanesthesIa,epIduralanesthesIaoffersadvantagestoo.ChIefamong
themarethelowerrIskofP0PH,lesshypotensIonIfepInephrIneIsnotaddedtothelocal
anesthetIc,theabIlItytoprolongorextendtheblockvIaanIndwellIngcatheter,andthe
optIonofusInganepIduralcathetertoprovIdepostoperatIveanalgesIa.
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104.DtaK,NamIkIA,wasakIHetal:0osIngIntervalforprolongatIonoftetracaIne
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105.AxelssonK,WIdman8:8loodconcentratIonoflIdocaIneafterspInalanaesthesIa
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106.LeIchtCH,CarlsonSA:ProlongatIonoflIdocaInespInalanesthesIawIthepInephrIne
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107.|oore0C,ChadwIckHS,FeadyL8:EpInephrIneprolongslIbocaInespInal:PaInIn
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108.ChambersWA,LIttlewood0C,Logan|Fetal:EffectofaddedepInephrIneon
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109.SpIvey0L:EpInephrInedoesnotprolonglIdocaInespInalanesthesIaInterm
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110.ChIuAA,LIuS,CarpenterFLetal:TheeffectsofepInephrIneonlIdocaInespInal
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111.KozodyF,SwartzJ,PalahnIukFJetal:SpInalcordbloodflowfollowIng
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114.0enson00,8rIdenbaughPD,TurnerPAetal:Neuralblockadeand
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115.CrosbyC,Fusso|,Szabo|etal:SubarachnoIdclonIdInereducesspInalcordblood
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116.ConverseJC,LandmesserC|,Harmel|H:TheconcentratIonofpontocaIne
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122.ParkWY,HagInsF|,FIvatELetal:AgeandepIduraldoseresponseInadultmen.
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124.ErdemIrHA,SoperLE,SweetF8:StudIesoffactorsaffectIngperIduralanesthesIa.
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126.ApostolouCA,ZarmakoupIsPK,|astrokostopoulosCT:SpreadofepIdural
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127.ParkWY,HagInsF|,|assengale|0etal:ThesIttIngposItIonandanesthetIc
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141.KerkkampHE,CIelen|J,WattwIl|etal:AnopenstudycomparIsonof0.5,0.75
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142.8uckleyFP,LIttlewood0C,CovIno8Cetal:EffectsofadrenalIneandthe
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144.8romagePF,8urfoot|F,Crowell0Eetal:QualItyofepIduralblockade.:
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145.8ernardsC|,Shen00,SterlIngESetal:EpIdural,cerebrospInalfluId,andplasma
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146.KIerL:ContInuousepIduralanalgesIaInprostatectomy:ComparIsonofbupIvacaIne
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148.Cederholm,AnskarS,8engtsson|:Sensory,motor,andsympathetIcblockdurIng
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149.AbboudT,SheIkolEslamA,YanagITetal:SafetyandeffIcacyofepInephrIne
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150.EIsenachJC,CrIceSC,0ewan0|:EpInephrIneenhancesanalgesIaproducedby
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151.FInucane8,|cCraneyJ,8ush0:0oubleblIndcomparIsonoflIdocaIneand
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152.CohenE:0IstrIbutIonoflocalanesthetIcagentsIntheneuroaxIsofthedog.
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154.8oswell|,aconoF,CuthkelchA:SItesofactIonofsubarachnoIdlIdocaIneand
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155.CusIckJ,|yklebustJ,AbramS:0IfferentIalneuraleffectsofepIduralanesthetIcs.
156.Urban8:ClInIcalobservatIonssuggestIngachangIngsIteofactIondurIngInductIon
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157.FInk8F:|echanIsmsofdIfferentIalaxIalblockadeInepIduralandsubarachnoId
158.FInk8F,CaIrnsA|:LackofsIzerelateddIfferentIalsensItIvItytoequIlIbrIum
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159.ChamberlaIn0,ChamberlaIn8:ChangesInskIntemperatureofthetrunkandtheIr
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160.8rullSJ,CreeneN|:ZonesofdIfferentIalsensoryblockdurIngextradural
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166.CarpenterFL,CaplanFA,8rown0Letal:ncIdenceandrIskfactorsforsIdeeffects
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169.TarkkIlaP,solaJ:AregressIonmodelforIdentIfyIngpatIentsathIghrIskof
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175.PetersJ,SchlagheckeF,ThouetHetal:EndogenousvasopressInsupportsblood
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181.8ernardsC|,HymasNJ:ProgressIonoffIrstdegreeheartblocktohIghgrade
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186.CravesCL,UnderwoodPS,KleInFLetal:ntravenousfluIdadmInIstratIonas
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192.LundbergJ,NorgrenL,Thomson0etal:HemodynamIceffectsofdopamInedurIng
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194.CoertzAW,SeelIngW,HeInrIchHetal:EffectofphenylephrInebolus
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225.8ergeronL,CIrard|,0roletPetal:SpInalprocaInewIthandwIthoutepInephrIne
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226.FreedmanJ|,LI0K,0rasnerKetal:TransIentneurologIcsymptomsafterspInal
anesthesIa:AnepIdemIologIcstudyof1,86JpatIents[publIshederratumappearsIn
AnesthesIology89(6)1614,1998].AnesthesIology1998;89:6JJ
227.SakuraS,SumI|,SakaguchIYetal:TheaddItIonofphenylephrInecontrIbutesto
thedevelopmentoftransIentneurologIcsymptomsafterspInalanesthesIawIth0.5
tetracaIne[seecomments].AnesthesIology1997;87:771
228.PollockJE,NealJ|,StephensonCAetal:ProspectIvestudyoftheIncIdenceof
transIentradIcularIrrItatIonInpatIentsundergoIngspInalanesthesIa[seecomments].
229.EvronS,CurstIeva7,EzrITetal:TransIentneurologIcalsymptomsafterIsobarIc
subarachnoIdanesthesIawIth2lIdocaIne:theImpactofneedletype.AnesthAnalg
2007;105:1494
2J0.CIssenA,0attaS,Lambert0:ThechloroprocaInecontroversy:.schloroprocaIne
neurotoxIc:FegIonalAnesthesIa1984;9:1J5
2J1.FavIndranFS,Turner|S,|ullerJ:NeurologIceffectsofsubarachnoId
admInIstratIonof2chloroprocaIneCE,bupIvacaIne,andlowpHnormalsalIneIndogs.
2J2.TanIguchI|,8ollenAW,0rasnerK:SodIumbIsulfIte:scapegoatforchloroprocaIne
neurotoxIcIty:AnesthesIology2004;100:85
2JJ.KourI|E,Kopacz0J:SpInal2chloroprocaIne:AcomparIsonwIthlIdocaIneIn
2J4.SmIthKN,Kopacz0J,|c0onaldS8:SpInal2chloroprocaIne:adoserangIngstudy
andtheeffectofaddedepInephrIne.AnesthAnalg2004;98:81
2J5.Warren0T,Kopacz0J:SpInal2chloroprocaIne:Theeffectofaddeddextrose.
2J6.7athJS,Kopacz0J:SpInal2chloroprocaIne:Theeffectofaddedfentanyl.Anesth
Analg2004;98:89
2J7.Hejtmanek|,PollockJ:ChloroprocaIneforDutpatIentSurgeryExperIencewIth
600cases.AnesthesIology2008(InPress)
2J8.7andermeulenEP,7anAkenH,7ermylenJ:AntIcoagulantsandspInalepIdural
anesthesIa.AnesthAnalg1994;79:1165
2J9.HorlockerTT,Wedel0J,8enzonH:FegIonalanesthesIaIntheantIcoagulated
patIent:0efInIngtherIsks(thesecondASFAConsensusConferenceonNeuraxIal
AnesthesIaandAntIcoagulatIon).FegAnesthPaIn|ed200J;28:172
240.HeblJF,KoppSL,Schroeder0Fetal:NeurologIccomplIcatIonsafterneuraxIal
anesthesIaoranalgesIaInpatIentswIthpreexIstIngperIpheralsensorImotorneuropathy
ordIabetIcpolyneuropathy.AnesthAnalg2006;10J:1294
Stock, M. Christine
TableofContentsSectIon7AnesthetIc|anagementChapterJ8PerIpheralNerve8lockade
ChapterJ8
Peripheral Nerve Blockade
Ban C.H. Tsui
Richard W. Rosenquist
Key Points
1. Peripheral nerve blocks provide effective anesthesia and analgesia in
a site-specific manner with the potential for effects of long duration.
2. Accurate identification of target nerves and precise and adequate
local anesthetic placement are paramount for performing safe and
successful peripheral nerve blocks.
3. Ultrasound imaging has renewed interest in peripheral nerve
blockade because it allows the needle to be directed toward the
nerve structure(s) with real-time visualization, potentially avoiding
critical structures in the path of the needle and reducing
complications. Although highly desirable as an aid to the performance
of regional anesthesia, this technology requires considerable training
in addition to thorough knowledge of the equipment and regional
nerve block anatomy.
4. Peripheral nerve stimulators are useful tools to facilitate nerve
blockade, but they do not eliminate the risk of nerve injury. In the
adult patient, maintenance of responsiveness may allow reporting of
nerve contact or pain during injection.
5. Nerve blocks associated with bony or vascular landmarks are more
reliable and easy to perform than those that depend on surface
landmarks alone.
6. Larger volumes of local anesthetic may increase the potential success
of peripheral nerve blocks, but the total milligram dosage must be
limited to avoid systemic toxicity. Higher concentrations of local
anesthetics increase the degree of motor block, but larger volumes of
more dilute solutions can be used with less risk of toxicity. Ultrasound
imaging, through more accurate nerve localization and visualization
of local anesthetic spread, may enable successful blocks to be
performed with reduced volumes of local anesthetics, but this has yet
to be proven.
FegIonalanesthesIaenablessItespecIfIc,longlastIng,andeffectIveanesthesIaand
analgesIa.tIssuItableformanysurgIcalpatIentsandcanImproveanalgesIa,
1
reduce
morbIdIty,mortalIty,andtheneedforreoperatIonaftermajorsurgIcalprocedures.
2
PerIpheralnerveblocks(PN8)canbeusedastheonlysurgIcalanesthetIc,asa
supplementtoprovIdeanalgesIaandmusclerelaxatIonalongwIthgeneralanesthesIa,or
astheInItIalstepIntheprovIsIonofprolongedpostoperatIveanalgesIasuchaswIth
IntercostalblocksorcontInuousperIpheralnervecatheters.ComparedwIthparenteral
analgesIcs,sIngleshotorcontInuousPN8canprovIdesuperIoranalgesIaandalower
IncIdenceofsIdeeffects.
J,4,5
DptImalpaInrelIefandmInImalsIdeeffects(e.g.,nauseaand
vomItIng)aftersurgerycanhaveamajorImpactonpatIentoutcome,IncludIngpatIent
satIsfactIonandearlIermobIlIzatIon,aswellasfulfIllIngthecurrentneedforstreamlIned
surgIcalservIceswIthlowercosts.
6
However,thesafetyandsuccessofPN8technIquesare
hIghlydependentonaccuratedelIveryofthecorrectdoseoflocalanesthetIc.
Unfortunately,thereIsanInherentfaIlurerateassocIatedwIthregIonalanesthesIaeven
whenapplIedInexperIencedhands,
7
wIththe(albeItrare)potentIalforsystemIctoxIcIty,
InfectIon,bleedIng,permanentnerveInjury,orotherphysIcalInjury.naddItIontothe
benefItsofPN8,advancesInknowledge(e.g.,physIologIccharacterIstIcsofsolutIonsdurIng
electrIcalnervestImulatIon)andtechnology(e.g.,theIntroductIonofanatomIcallybased
ultrasoundImagIng)areattractIngmanyanesthesIologIstsandsurgeonstousePN8ona
morefrequentbasIs.
|edIcIneandthetechnIquesassocIatedwIthItareforeverchangIng.Eachnewadvance
provIdesopportunItIesforImprovementbutweneedtostudythesenewadvancesand
comparethemtoprevIouslyacceptedtechnIques.ncontrasttotherapIdchangesIn
medIcIneandspecIfIcallyanesthesIologyanatomIcstructuresarestatIc,andhavInga
basIcunderstandIngofanatomIcknowledgecannotbereplacedbyexcellenttechnIcalskIlls
andknowledgeofthetechnIquewhenperformIngregIonalanesthesIa.Thus,thIschapter
provIdesanIndepthdIscussIonofregIonalanatomy,whIleprovIdInganovervIewoftoday's
twomostuptodatetechnIquesfornervelocalIzatIonandblockperformance:nerve
stImulatIon(NS)andultrasound(US)ImagIng.SpecIfIctechnIquesthatarepractIcally
usefulfortheanesthesIologIstaredescrIbedInsectIonsgroupedbyanatomIclocatIon.
General Principles and Equipment
FegIonalanesthesIahaslongbeenregardedasanart,andoutstandIngsuccesswIththese
technIqueswasconfInedtoa
P.956
smallnumberofgIftedIndIvIduals.TheIntroductIonofNSsomeJ0yearsagowasthefIrst
steptowardtransformIngregIonalanesthesIaIntoascIence.ThIstechnIquerelIeson
physIologIcalresponsesofneuralstructurestoelectrIcalImpulses.ThereIsconsIderable
InterIndIvIdualvarIatIonInphysIologIcalresponsestoNS.Furthermore,anumberofother
factorsInfluenceresponsestoNS,IncludIngInjectates,physIologIcsolutIons(e.g.,blood),
anddIsease.0espItetheselImItatIonsNSwasoneofthefIrstobjectIvemethodsavaIlable
InregIonalanesthesIatoplace,wIthsomerelIabIlIty,aneedleIncloseproxImItytoa
targetnerve.DneofthemostexcItIngadvancesIntechnologyInrelatIontoregIonal
anesthesIaInrecentyearshasbeentheIntroductIonofanatomIcallybasedUSImagIng.For
thefIrsttImeInnearly100yearsofregIonalanesthesIapractIce,wecanactuallyvIsualIze
thetargetnerve.ThIsquantumleapIntechnologymayencouragemanyanesthesIologIsts
whohadprevIouslyabandonedthesetechnIquestoresumeorIncreasetheIruseofregIonal
anesthesIa.
However,despIteInItIalexcItementoverthIsadvancement,USvIsualIzatIonIsstIll
IndIrectandImagesaresubjecttoIndIvIdualInterpretatIondependIngonexperIence,
traInIng,andwherethatexperIenceandtraInIngwasobtaIned.SomeIndIvIdualsaregIfted
IntheIrabIlItytoInterpretUSImages;however,thIsIsnotthecasewIththemajorIty.
ThereIsasubstantIallearnIngcurveassocIatedwIthUSguIdedregIonalanesthesIa.
Consequently,InmanysItuatIons,ItIsprudenttocombInethetwotechnologIesofNSand
USImagIngInordertoachIevethegoalof100successwIthregIonalblocks.USmayallow
goodvIsualIzatIonoftheneedleandnerveaswellasareasonableestImateofthespread
ofthefulldoseofthelocalanesthetIc,yetthecorrectIdentItyofthenervemaybe
unknown.
8
8ystImulatIngthatnervewecanobjectIvelydetermIneItsIdentItybyobservIng
themotorresponsetoNS.
PatIentmonItorIngandotherfactorsrelatedtooptImIzIngpatIentcareandpreventIonof
complIcatIonsaresImIlartothoseforgeneralanesthesIa,wIthsomeImportantdIfferences.
SafeandsuccessfulperformanceofPN8requIrescarefulselectIonofpatIents,
admInIsterInganapproprIatetypeanddoseoflocalanesthetIcInthecorrectlocatIon,and
monItorIngthepatIentdurIngtheprocedure,prIortodIscharge,andInthecaseof
ambulatorypatIentswIthhomegoIngcatheters,observIngthemremotelyuntIlthecatheter
hasbeenremovedandtheblockhascompletelyregressed.
Setup and Monitoring
Setup
AlthoughregIonalblockscanbeperformedIntheoperatIngroomsettIngjustlIkegeneral
anesthesIa,ItIspreferableanddesIrabletoperformthesetechnIquesInadesIgnatedroom
orareaoutsIdetheImmedIateoperatIngroomenvIronment(FIg.J81).8ecauseofthe
varIabletImerequIredforregIonalanesthesIatowork,aseparateroomallowsvarIable
soaktIme,whIchIsthetImeIttakesforlocalanesthetIcstocrossthecellmembraneand
blockactIonpotentIalswIthoutdelayIngtheoperatIngroom.ThIsdesIgnatedareamust
contaInthenecessaryequIpmentforsafemonItorIngandresuscItatIon,butmustalso
contaInallofthesupplIesandequIpmenttoperformcommonandsophIstIcatedregIonal
blocktechnIques.SomeImportantconsIderatIonsforthIsblockroomaredescrIbedhere.
AllsupplIeslocatedInthIsareamustbereadIlyIdentIfIableandaccessIbletothe
anesthesIologIst.
TheareashouldbeofamplesIzetoallowblockperformanceandmonItorIngand
resuscItatIonofpatIents.
ThereshouldbeequIpmentforoxygendelIvery,emergencyaIrwaymanagement,and
suctIon,andtheareashouldhavesuffIcIentlIghtIng.
Figure 38-1.0esIgnatedregIonalblockroomwIthlabeledstoragecart.
ApractIcallyorganIzedequIpmentstoragecart(FIg.J81)IsdesIrableandshouldcontaIn
allofthenecessaryequIpment(IncludIngthatrequIredforemergencyprocedures),
supplIes,localanesthetIcs,needles,nervestImulators,blocktrays,dressIngs,and
resuscItatIondrugs.
tIsIdealtohaveapreparedspecIaltytrayIncludIngItemsforsterIleskInpreparatIon
anddrapIng,amarkIngpenandrulerforlandmarkIdentIfIcatIon,needlesandsyrInges
forskInInfIltratIon,andspecIfIcblockneedlesandcatheters.
AselectIonofsedatIves,hypnotIcs,andIntravenousanesthetIcsshouldbeImmedIately
avaIlabletopreparepatIentsforregIonalanesthesIa.ThesedrugsshouldbetItratedto
maxImIzebenefItsandmInImIzeadverseeffects(hIghtherapeutIcIndex);shortactIng
drugswIthahIghsafetymargInaredesIrable.
EmergencydrugsshouldIncludeatropIne,epInephrIne,phenylephrIne,ephedrIne,
propofol,thIopentoneandsuccInylcholIne,andamrInoneandIntralIpId.
Monitoring
0urIngtheperformanceofregIonalanesthesIa,ItIsvItaltohaveskIlledpersonnelmonItor
thepatIentatalltImes.AtamInImum,standardmonItorIngshouldInclude
electrocardIogram,nonInvasIvebloodpressure,andpulseoxImetry.naddItIon,thelevel
ofconscIousnessofthepatIentshouldbegaugedfrequentlyusIngverbalcontactbecause
vasovagalepIsodesarecommonwIthmanyregIonalprocedures.Atpresentthereareno
practIcaloreffectIvedevIcesthatcandetectrIsIngbloodlevelsoflocalanesthetIc,
althoughwecanIndIrectlymonItorlocalanesthetIcbloodlevelsbyaddIngpharmacologIc
markerssuchasepInephrInetothelocalanesthetIcs.CloseobservatIonforsystematIc
toxIcItysecondarytorapIdIntravenousInjectIon(wIthIn2mInutes)aswellasdelayed
(approxImately20mInutes)absorptIonIsessentIal.ThepatIentshouldbemonItoredforat
leastJ0mInutespostprocedurally.
StandardelectrocardIogramandpulseoxImetryareessentIalmonItorswhIleperformIng
regIonalanesthesIa.
CarefulmonItorIngofthepatIent'sheartrate(alongwIthelectrocardIogram
measurement)IsImportanttodetectthetachycardIaseenwIthepInephrInewhenItIs
IncludedInatestdose.tIsalsousefulasanIndIcatorofsystemIctoxIcItywIth
bupIvacaIneandotherpotentlocalanesthetIcs.
8eforeperformIngblockswIthsIgnIfIcantsympathetIceffects,abaselInebloodpressure
readIngshouldbeobtaIned.DncetheregIonalanesthesIaprocedureIs
P.957
complete,themonItorsshouldremaInattached.nconscIouspatIents,endtIdalcarbon
dIoxIdemonItorIngIsnotrequIred;however,therearespecIalnasalprongsavaIlablefor
monItorIngpatIentswhensupplementalD
2
IsIndIcated.
AtamInImum,stablevItalsIgnsmustbepresentfollowIngregIonalanesthesIatofulfIll
dIschargecrIterIafromtherecoveryarea.ftheblockhasnotbeguntoregress,
approprIateprotectIonfortheanesthetIzedlImbandcompleteInstructIonsshouldbe
provIdedtothepatIentandhIsorherfamIlyIfthepatIentIsbeIngdIschargedhome.For
InpatIents,approprIateordersshouldbewrIttentoassurelImbprotectIon.
PatIentsreceIvIngperIneurallocalanesthetIcInfusIonsshouldbevIsItedregularly
postoperatIvelybyaqualIfIedphysIcIan(I.e.,acutepaInservIce).
Common Techniques: Nerve Stimulation and Ultrasound
Imaging
Nerve Stimulation
Basics of Technique and Equipment
ElectrIcalstImulatIonofnervestructureswasIntroducedtoregIonalanesthesIaInthe
mIddleofthe20thcentury.
9,10
AlowcurrentelectrIcalImpulseapplIedtoaperIpheral
nerveproducesstImulatIonofmotorfIbersandtheoretIcallyIdentIfIesproxImItytothe
nervewIthoutactualneedlecontactorrelatedpatIentdIscomfort.WhenNStechnIques
areusedItIsnotnecessarytomakeactualcontactwIththenerve(Incontrasttothe
paresthesIamethod).ThIsnotIontheoretIcallyInfersthattherIskofnerveInjuryshouldbe
lesswhenusIngNSmethods.However,thIstheoryhasnotbeenproved.StImulatIng
cathetershaverecentlybeenIntroducedandhaveIncreasedourabIlItytoaccurately
advancecathetersalongnervestructuresforgreaterdIstances.
11,12
UsIngmotorresponsestoNSasaprImarynervelocalIzatIontechnIquehasdrawbacks.The
maInlImItatIonswIthNSarerelatedtotheInconsIstentresultsofthIstechnIque
1J,14
and
thevarIanceInelectrIcalpropertIesofdIfferentnervestImulators.
15
|anyvarIablesaffect
theabIlItytostImulatenerves,IncludIngconductIveareaoftheelectrode(needleor
stImulatIngcathetertIp),electrIcalImpedanceofthetIssues,electrodetonervedIstance,
currentflow,andpulseduratIon.
16
UltImately,thetechnIquerelIesonthephysIologIc
responsesofneuralstructurestothestImulatIngcurrent,whIchIssubjecttoconsIderable
InterIndIvIdualvarIatIon.
Today'snervestImulatorshavefeaturestoImproveeaseofuseandsuccess,suchas
maIntaInIngaconstantcurrentwIthadjustablefrequency,pulsewIdth,andcurrent
IntensIty(InmIllIamperes[mA]).ThIsconsIstencyenablesastablecurrentoutput(an
Importantsafetyfeature)InthepresenceofvarIedresIstancesfromtheneedle,tIssues,
andconnectors.AcleardIgItaldIsplayIndIcatIngtheactualcurrentdelIveryIsImportant,
asIsregularcalIbratIonandtestIng.SomenervestImulatorsareequIppedwIthlow(upto6
mA)andhIgh(upto80mA)currentoutputranges.ThelowerrangeIsprImarIlyfor
localIzIngperIpheralnerves,andthehIgherrangeIsmaInlyusedformonItorIng
neuromuscularblockade.Fecently,hIgherrangeshavebeenusedfortranscutaneousNS
technIques
17
(2to5mA)IncludIngpercutaneouselectrodeguIdance
18
andsurfacenerve
mappIng,
11,19
andtheepIduralstImulatIontest(1to10mA).
20,21
|ostnervestImulators
delIveranelectrIcalpulsewIdthof100sor200sforstImulatIngmotornerves.SImIlarto
currentamplItude,thelengthoftImeoverwhIchthecurrentIsdelIvered(pulsewIdth)Is
usuallyconsIderedImportantbecausecurrentsofshorterduratIoncanselectIvelystImulate
motorcomponentsofmIxednerveswhIlesparIngthedIscomfortcausedbysensory
components.SomesophIstIcateddevIcesallowvarIablepulsewIdthsfrom50sto1msIn
anattempttoprovIdesuchselectIvestImulatIon.ThegeneralruleIstouseshortduratIon
currentof100sforperIpheralNS,althoughthereIssomeevIdencethatduratIondoes
notImpactpatIentdIscomfort
22
andthatIntensIty(numberofmIllIamperes)ofthe
stImulatIonIsperhapsthemostImportantvarIable.
2J
Practical Guidelines
0urIngInItIaladvancementoftheneedle,thenervestImulatorshouldbesettodelIvera
currentof1to2mAInordertogaugetheapproxImatedIstancetothenerve.
0epolarIzatIonofthenervecanalsobeImprovedbyusIngtheposItIve(anode;red)poleof
thestImulatorastheground(referenceorsurfaceelectrode)electrodeandthenegatIve
(cathode;black)leadastheconnectIontotheneedleItself(knownascathodal
preference).TheactuallocatIonofthegroundIsoflIttleImportancewIththeuseof
constantcurrentnervestImulators.
2J
Cenerally,theneedleIsIncloseproxImItytothe
nervewhenthethresholdformotorresponseIsbetween0.Jand0.5mA;placIngtheneedle
tothepoIntwhereamotorresponseonlyrequIres0.1to0.2mAmayIncreasethechance
ofnervepunctureandshouldbeavoIded.
24
DncealowthresholdresponseIsobtaIned,2to
JmLoflocalanesthetIcIsInjectedandtheoperatorwatchesfordIsappearanceofthe
motortwItch,whIchIsasIgnaltoInjecttheremaInderoftheproposeddoseIndIvIded
alIquots.ThIsFajtest
25
wasorIgInallythoughttoresultfromthephysIcaldIsplacement
ofthetargetednervebytheInjectIonsolutIon,butthIsresponsehasrecentlyalsobeen
attrIbutedtoachangeIntheelectrIcalfIeldattheneedletIssueInterface.ElectrIcally
conductIngsolutIons(e.g.,localanesthetIcorsalIne)reducesthecurrentdensItyatthe
needletIp,therebyIncreasIngthecurrentthresholdformotorresponse,whIle
nonconductIngsolutIons(e.g.,dextrose5Inwater[05W])IncreasethecurrentdensItyand
maIntaInoraugmentthetwItchresponse(FIg.J82).
26
AfternervelocalIzatIonusIngastImulatIngneedle,IntroductIonofastImulatIngcatheter
wIthcontInuousstImulatIonofthenerveIssuItableforprovIsIonofcontInuousanalgesIa.
SImIlarcurrentthresholdsareapplIcablewIththeuseofstImulatIngcatheters.fan
attempttodIlatetheperIneuralspaceIsundertaken,InjectIonof05WIspreferableIn
ordertomaIntaInthemotorresponsetostImulatIon.
27
ThereaderIs
P.958
referredtothesectIonDtherFelatedEquIpmentforoptImalfeaturesofstImulatIng
catheters.
Figure 38-2.ThecurrentdensItyIslocalIzedtotheneedletIpwhenusIng
nonconductIngsolutIons(e.g.,dextrose5Inwater[05W]),therebymaIntaInIngthe
motorresponsetothethresholdcurrentleveldurIngnervestImulatIon.
Ultrasound Imaging
Basics of Technique and Equipment
USImagIngIsrapIdlyemergIngasaverypromIsIngregIonalanesthesIatoolasthesIze,
depth,andprecIselocatIonofmanynervesIntheIrsurroundIngenvIronmentcanbe
determInedwIthcorrectInterpretatIonofthevIsualImage.7IsualIzatIonofthemovIng
needle,onceInsertedatanapproprIateangleandwIthIntheplaneoftheUSprobe,aswell
asthespreadoflocalanesthetIc,provIdesvaluableassIstancetotheanesthesIologIst
performIngregIonalanesthesIa.WIthUSguIdedPN8technIques,theoperatorcanadjust
theneedleorcatheterplacementunderIndIrectvIsIon(I.e.,USImagIng),whIchmaylead
tofewerneedleattemptsandultImatelyImprovedmotorandsensoryblock.Furthermore,
vIsIbIlItyofvItalstructures(e.g.,vesselsandpleura)IsadvantageousInthequesttoavoId
complIcatIons.Today,technologIcaladvanceshaveledtothedevelopmentofUSsystems
thatcandelIverhIghfrequency(10|HzorhIgher)soundwavesofferIngthehIghaxIal
resolutIonrequIredforvIsualIzatIonofnerves,whIchdIstInguIshesthemfromthe
surroundInganatomIcstructures(e.g.,tendons,muscles).TheproposedbenefItsofUS
guIdance,ascomparedwIthNS,forupperextremItyblocksIncludeImprovedblock
success
28
andcompleteness,
29
reducedblockperformanceandonsettImes,
28,29,J0,J1
prolongedduratIonofblocks,
J0
andreductIonIncomplIcatIons.
J2
AlthoughthecumulatIve
evIdencemayappearconvIncIng,manyofthestudIesshowconflIctIngresultsforcertaIn
parameters,andthelargevarIabIlItyIntrIalmethodsandapplIcatIonofdIfferentoutcome
measuresaccountformanyofthedIscrepancIes.ndeed,thevarIousendpoIntsused
durIngresearchInregIonalanesthesIamaybIasoutcomeswhencomparIngmultIple
regIonaltechnIques.
USIsdefInedasanysoundwIthafrequency20kHz,althoughmedIcalImagInggenerally
requIresbetweenJand15|Hz.WIthInthebody,USscannersemItsoundwavesthat
produceanechowhentheyencounteratIssueInterface.Therefore,USImagesreflect
contours,IncludIngthoseofanatomIcstructures,basedondIfferIngacoustIcImpedancesof
tIssueorfluIds.SIgnIfIcantreflectIonofsoundwavesoccursatInterfacesbetween
substancesofdIfferentacoustIcImpedance,resultIngIngoodcontourdefInItIonbetween
dIfferenttIssues.HIghUSbeamreflectIon,fromhIghImpedance/densestructures(e.g.,
bone,connectIvetIssue),resultsInabrIght(hyperechoIc)Image,oftenwIthdorsal
shadowIngunderneath;lowImpedancestructuresreflectbeamstoasmallerextentand
appeargrey(hypoechoIc);mInImalImpedancestructures/spaces(e.g.,fluIdInvessels)
appearblack(anechoIc).
HIgherfrequencIesofferthebestspatIalresolutIonatsuperfIcIallocatIons(e.g.,brachIal
plexusatsupraclavIcularfossa),andlowerfrequencIesareoftenrequIredforstructure
delIneatIonatdeeplocatIons(e.g.,scIatIcnerveatsubglutealregIon).8locklocatIonand
depthoftargetnervestructuresdetermInewhIchtransduceroffersthebestImagIngand
resolutIon.SeveralfunctIonsoftheUSsystemwIllbeImportanttobecomefamIlIarwIth,
IncludIngfIeldandgaInfunctIonsaswellas0opplereffect.0opplereffectcanbevery
usefulforIdentIfyIngbloodvesselsdurIngnervelocalIzatIonusIngUSguIdanceasmany
nervesaresItuatedIncloseproxImItytovascularstructures.
Practical Guidelines
8oththeprobeandtheskInofthepatIentshouldbepreparedformaxImumsterIlItyand
optImalImagIng.ProbesterIlItyIsparamountIfperformIngrealtIme,ordynamIc,US
guIdancedurIngblockperformance.SterIlItycanbemaIntaInedbystandardsleevecovers
butthesecanbeexpensIveandcumbersome.ForsIngleshotblocks,ItIspractIcaltousea
sterIletransparentdressIng(e.g.,Tegaderm;J|HealthCare,St.Paul,|N)wIthoutthefull
coverofasterIlesleeve(FIg.J8JA).
JJ
AnIssuewhenusIngstandardlongcoversIsthe
potentIalforaIrtotrackbetweentheprobeandskIn,whIchreducesImagequalIty.The
targetareashouldbesurveyed(scanned)usIngagenerousamountofUSgel(watersoluble
conductIvItygelIsoptImal)prIortosterIlepreparatIon.Dneofthemostcommonreasons
forpoorvIsualIzatIonIslackofsuffIcIentgelforskInprobecontact.
FornervelocalIzatIondurIngUSguIdedPN8,ItIseffectIvetofIrstIdentIfyoneormore
relIableanatomIclandmarks(boneorvessel)wIthaknownrelatIonshIptothenerve
structure.TheoperatorcanthenlocalIzethenerveatalocatIonnearthelandmark,and
proceedtofollowalongortracethenervetotheoptImalblocklocatIon(TableJ8
1).
J4,J5
Cenerally,nervestructuresaremostvIsIblewhentheangleofIncIdenceIs
approxImately90degreestotheUSbeam.DbtaInIngatransverseaxIsvIewofthenerve
usuallyallowsthebestapprecIatIonoftheanatomIcrelatIonshIpofnervewIthIts
surroundIngstructure.ToobtaInthebestpossIblevIewoftheshaftandtIpoftheneedle,
ItIsImperatIvetoalIgntheneedleshafttothelongItudInalaxIs(Inplane[P])oftheUS
transducer(probe)(FIg.J8J8).ThenervestructureIsoftenplacedattheedgeoftheUS
screentoensureadequatevIewIngdIstancefortheneedleshaft.AnalternatIveapproach
usesatransverseortangentIal(outofplane[DDP])alIgnment,whIchonlyallows
apprecIatIonoftheneedleIncrosssectIonandusuallyonlydurIngmovement(FIg.J8J8).
ThenervestructureIsoftenplacedInthecenterofthescreentoguaranteethatalIgnIng
theneedlepuncturewIththecenteroftheprobewIllensurecloseneedletIpnerve
alIgnment.ThIsapproachcanbebenefIcIalIncertaInblocklocatIons(compactareas)and
forInsertIngcatheters(e.g.,atthesubglutealarea),butshouldneverbeusedInareas
whereneedletIpvIsIbIlItyInrelatIontovItalstructuresIscrItIcal(e.g.,supraclavIcular
fossanearthepleura).
AfteroneobservesthattheneedleIsclosetothenerve(s),a1to2mLtestdoseoflocal
anesthetIcor05WcanbeInjectedtovIsualIzethespreadandperformaFajtestIfa
stImulatIngneedleIsbeIngused.ThesolutIonwIllbeseenasahypoechoIcexpansIonand
wIlloftenIllumInatethesurroundIngarea,enablIngbettervIsIbIlItyofthenervesand
blockneedle.fNSIsbeIngusedtoconfIrmnerveIdentIty,ItIsusefultoadmInIster05WIn
ordertomaIntaInaccuratemotorresponses.
27
ThIsresponsewIllbeespecIallyImportant
durIngcatheterIntroductIonandadvancement.fthetestshowsundesIredapplIcatIon
nearorwIthInvesselsorcavItIes,subsequentInjectIonoflocalanesthetIcshouldbe
postponeduntIlbetterneedlelocalIzatIonIsachIeved.fsuboptImalspreadofInjectateIs
observed,theneedlecanbereposItIonedtoallowanotherInjectIon.
TherecanbealengthylearnIngcurveforUSguIdednerveblocks,andtechnIquesto
ImproveneedleandcathetervIsIbIlItydurIngadvancementareImportantInorderto
ImprovetraInIngforthIstechnology.TwosuchapproacheshavebeendescrIbed
experImentally:
ThefIrstmethodIsthewalkdownapproachtofacIlItateneedletIpIdentIfIcatIon
durIngDDPneedlIng.
J4,J6
ThIstechnIqueInvolvescalculatIngtherequIreddepthof
puncture(wIthmeasurementtothedesIredneuralstructurerecordedusIngUSprIorto
theblock)andusIngtrIgonometrywIththeshaftangleandlengthtocalculatea
reasonablelocatIontoplacetheInItIalneedlepuncturesIte.TheInItIalshallow
puncturewIllbeeasIlyseenasabrIghtdotonthescreen,andtheneedletIpcanbe
followedasItIswalkeddowntothefInalcalculateddepth.Forexample,IfthefInal
depthofpenetratIonfortheblockIs2cm,theneedlewIllultImatelyobtaIna45degree
angleIftheInItIalpuncturesIteIs2cmfromtheprobeandtheneedleIsIncrementally
angledtothIslevel.
AmethodofneedleprobealIgnmentusIngalaserattachmentfortheprobehasbeen
reported;thelaserlIne
P.959
wIllprojectontoboththeneedleshaftandthemIdlIneoftheprobe,IndIcatInganP
posItIon.
J4,J7
AlIgnIngthevIsIbleoptIcallaserlInewIththelongItudInalaxIsoftheUS
probewIllmImIctheInvIsIblebeamfromtheUSprobeandallowImprovementswIth
PneedlealIgnment.WIththelaserunItattachment,anymIsalIgnmentoftheneedleto
theUSbeamcanbeeasIlydetectedandadjustedInrealtIme.
Figure 38-3. A.ProbesterIlItyusIngasterIletransparentdressIng(e.g.,Tegaderm;J|
HealthCare,St.Paul,|N)wIthoutthefullcoverofasterIlesleeve.DtherdressIngs
maycreatemultIplesmallwellsovertheprobesurfacebecauseofadhesIvepockets
andleadtopoorImagequalIty.
J4
B.nplaneandoutofplaneneedlealIgnmentand
thesubsequentvIsIbIlItyoftheneedle.
Other Related Equipment
Needles
NeedlesusedforregIonaltechnIquesareoftenmodIfIedfromstandardInjectIonneedles.
AlthoughreportsmayspeculatethatneedledesIgnIsadetermInantofnerveorother
tIssueInjury,thereIsInsuffIcIentevIdencetosubstantIatethIsclaIm.ForperIpheralnerve
blocks,theshortbevel(I.e.,J0to45degrees)or8bevelIsoftenusedtoreducethe
potentIalforInjurytonerves.
J8
DthermodIfIcatIons,suchasthepencIlpoIntneedle,
havebeenIntroducedInattemptstoreducenerveInjury.SIngleshotPN8technIques
generallyrequIreusIng22to24gaugeInsulatedneedleswIthshortbevels.fsuperfIcIal
andfIeldblocksareperformed,smallergauge(e.g.,25to26gauge)sharpneedlescanbe
used.ContInuousblocksrequIrelargerboreneedlestofacIlItatecatheterIntroductIon
(e.g.,18gaugeneedlesfor20gaugecatheters).8lunttIppedTuohydesIgnedneedlesare
commonlyusedforcontInuousPN8wIthsuccess.
J9
ShortbevelandTuohyneedlesoffer
moreresIstanceandgIveabetterfeelwhentraversIngdIfferenttIssues.0esIredneedle
lengthwIlldependoneachspecIfIcblockandIndIvIdualpatIentcharacterIstIcs.Clear
markIngsthroughouttheentIrelengthoftheneedleareImportantformeasurIngdepthof
penetratIon,partIcularlyforcorrespondencetoUSmeasurements.
Practical Tips
TechnIquesanddevIceshavebeenproposedtolImItInjectIonpressure,asthereIs
consIderablevarIatIonamonganesthesIologIstsIntheamountofpressuretheyapplydurIng
InjectIons
40
andhIghpressureInjectIonsIntothenerve(especIallyIntrafascIcular)have
beenassocIatedwIthdamageInanImals.
41,42
0Isposable,InlIneInjectIonpressure
monItorsareavaIlable,althoughtheIrabIlItytopreventlongtermInjuryIsnotwell
documented.AlternatIvely,acompressedaIrInjectIontechnIquehasbeendescrIbedto
lImItthegeneratIonofexcessIvepressuredurIngInjectIon.WIththIsmethod,aIrIsdrawn
IntothesyrIngeandcompressedby50durIngtheentIreInjectIontomaIntaInpressuresof
approxImately760mmHg(8oyle'slaw:pressurevolume=constant).
4J
Catheters
ContInuousInfusIoncatheterkItssuItableforPN8areavaIlablethatIncludeastandard
polyamIdecatheter,suchasthose
P.960
prevIouslyusedforepIduralanalgesIa,combInedwIthanInsulatedTuohyneedlewIthNS
capabIlIty.Fecently,cathetershavebeenadvancedtothepoIntofmakIngthemamenable
tostImulatIon(anelectrodeIsplacedIntothecathetertIp).AstImulatIngcathetertIpmay
enablemoreaccurateadvancementofcathetersforsubstantIaldIstancestoprovIde
contInuousanalgesIa.SomestudIeshavesuggestedthatItmaybehelpfultoInjecta
solutIontodIlatetheperIneuralcompartmenttofacIlItatetheadvancementofcatheter.
ThereaderIsreferredtothedIscussIonofpractIcalguIdelInesofNSInthesectIon
CommonTechnIques:NerveStImulatIonandUltrasoundmagIngfordIscussIonof
InjectIonsolutIonsforperIneuraldIlatIon.ThereareanumberofcontInuousInfusIon
devIcesnowavaIlableforbothInpatIentandoutpatIentusethatallowdelIveryofdIlute
localanesthetIcconcentratIonsforaslongas72hoursaftersurgery.StandardprecautIons
arerequIredtomaIntaInsterIlItyofthecatheterandInsertIonsIte,butcomplIcatIonshave
beenrarewIththesetechnIquesandnewdevIces.
Table 38-1 Anatomical Landmarks Useful for Localizing Nerves During
Common Ultrasound-Guided Peripheral Nerve Blocks
PERIPHERAL
NERVEBLOCK
LOCATION
ANATOMIC LANDMARK(S) APPROACH FOR ULTRASOUND IMAGING
nterscalene
SubclavIanartery
andscalene
muscles
Locatetheplexustrunks/dIvIsIons
superolateraltothearteryatthe
supraclavIcularfossaandtrace
proxImallytowheretheroots/trunkslIe
betweenthescalenusanterIorand
medIusmuscles(FIg.J815).
SupraclavIcular SubclavIanartery
ScanfromlateraltomedIalonthe
superIoraspectoftheclavIcletolocate
thepulsatIleartery;theplexus
trunks/dIvIsIonslIelateralandoften
superIortotheartery(FIg.J816).Color
0oppleruseful.
nfraclavIcular
SubclavIan/axIllary
arteryandveIn
Placethearteryatthecenterofthe
fIeldandlocatethebrachIalplexus
cordssurroundIngtheartery(FIg.J817).
AxIllary
PerIpheral
nerves:
AxIllaryartery
ThetermInalnervessurroundtheartery
(FIg.J818).
|edIannerve
atantecubItal
fossa
8rachIalartery
ThelargeanechoIcarterylIes
ImmedIatelylateraltothenerve(FIg.
J821).
FadIalnerve
atanterIor
elbow
HumerusatspIral
grooveanddeep
brachIalartery
ToconfIrmthenerve'sIdentItyatthe
elbow,tracethenerveproxImallyand
posterIorlytowardthespIralgrooveof
thehumerus,justInferIortothedeltoId
muscleInsertIon.ThenerveIslocated
hereadjacenttothedeepbrachIal
arteryandcanbefollowedbacktothe
anterIorelbow(FIg.J819).
Ulnarat
medIalforearm
Ulnarartery
ScanattheanteromedIalsurfaceofthe
forearmapproxImatelyatthejunctIon
ofItsdIstalthIrdandproxImaltwo
thIrdstocapturetheulnarnerveasIt
approachestheulnararteryonIts
medIalaspect(FIg.J822).
Lumbarplexus
Transverse
processes
TheplexuslIesbetweenandjustdeepto
thelateralaspect(tIps)oftheprocesses
(FIg.J8J0).
Femoral Femoralartery
ThenervelIeslateraltotheartery(veIn
mostmedIal)(FIg.J8J1).nsertthe
needleabovethebranchIngofthedeep
femoralartery.
ScIatIc
ClassIc/Labat
schIalboneand
InferIorglutealor
pudendalvessels
ThenervelIeslateraltothethInnest
aspectoftheIschIalbone.TheInferIor
glutealarterygenerallylIesmedIalto
andatthesamedepthasthenerve(FIg.
J8J4).
Subgluteal
Creatertrochanter
andIschIal
tuberosIty
ThenervelIesbetweenthetwobone
structures.
PoplIteal PoplItealartery
TracethetIbIalandcommonperoneal
nervesfromthepoplItealcreaseto
wheretheyformthescIatIcnerve.At
thecrease,thetIbIalnervelIesadjacent
tothepoplItealartery.ScannIng
proxImallytothescIatIcbIfurcatIon,the
arterybecomesdeeperandatagreater
dIstancefromthenerve(FIg.J8J7).
Ankle
TIbIal
(posterIor
PosterIortIbIal
artery
NervelIesposterIortotheartery(FIg.
J8J8).
tIbIal)
0eep
peroneal
AnterIortIbIal
artery
NervelIeslateraltotheartery(FIg.J8
J9).
Avoiding Complications
0espItetheexcellentsafetyrecordofregIonalanesthesIaIngeneralwIthcomplIcatIon
ratesaslowas8per10,000forseIzures,
2
0.1to1fornerveInjury
7,44
andrarecase
reportsofseverechronIcpaInsyndromes.
45
theIncIdenceofsomecomplIcatIonsIsoften
hIgherInPN8thanotherregIonalanesthesIa/analgesIatechnIques,andresultscanbe
devastatIng.ChoosIngasuItablepatIentandapplyIngtherIghtdoseoflocalanesthetIcIn
thecorrectlocatIonaretheprImaryconsIderatIons.FollowupprIortoandafterdIscharge
IsequallyImportant,althoughoftenoverlooked.
Patient Selection
PatIentselectIonIsacrItIcalelementfortheperformanceofsafeandeffectIvePN8.Not
allpatIentsaresuItablecandIdatesforPN8.ngeneral,patIentsscheduledforextremIty,
thoracIc,abdomInal,orperInealsurgeryshouldbeconsIderedpotentIal
P.961
candIdatesforperIpheralregIonalanesthetIctechnIques.AdamantrefusalofregIonal
anesthesIabyapatIentIsacontraIndIcatIontotheprocedure.
DthercontraIndIcatIonsIncludelocalInfectIon,systemIcantIcoagulatIon,andsevere
systemIccoagulopathy.nmostcases,schIzophrenIcpatIentsshouldreceIveregIonal
technIquesonlyIfgeneralanesthesIaIsalsoperformed.ThepresenceofpreexIstIng
neurologIcdIseaseIsacontroversIaltopIc.AlImItedamountofdataIsavaIlableInthe
caseofspInalanesthesIa,butthesafetyofPN8Isunclear.DnemustbecognIzantofthe
potentIaltocompoundexIstIngneurologIcdefIcIt.Therefore,cleardocumentatIonofthe
defIcItsprIortotheprocedureandacarefuldIscussIonofthepotentIalrIsksandbenefIts
arecrItIcal.ForeveryclInIcalsItuatIon,theuseofregIonalanesthesIamustbecarefully
evaluatedasamatterofrIskversusbenefIt.tIsImperatIvetofollowapplIcablenatIonal
andInternatIonalguIdelInes,suchasthoseformonItorIngbytheAmerIcanSocIetyof
AnesthesIologIsts,andforantIcoagulatedpatIentsbytheAmerIcanSocIetyforFegIonal
AnesthesIaandPaIn|edIcIne.
Local Anesthetic Drug Selection, Toxicity, and Doses
ThIssectIonwIllprovIdeanovervIewofdrugselectIonandtoxIcItydurIngPN8.Foramore
detaIleddIscussIonofthepharmacologyandtoxIcItyoflocalanesthetIcs,thereaderIs
referredtoChapter21.
FatesofsystemIcandlocaltoxIcItyInaddItIontonerveInjurywIthPN8aregenerallylow.
However,useofavaIlablemethodstoreduceInadvertentIntravascularandIntraneural
InjectIonsIsclearlywarranted.tIsImportanttonotethatlowerconcentratIonsoflocal
anesthetIc(e.g.,1to1.5lIdocaIne,0.125to0.5bupIvacaIne)thanthoseusedfor
epIduralanesthesIaareapproprIateforperIpheralnerves.NeuraltoxIcItyofthese
anesthetIcsappearstobeconcentratIondependent.
46
TheuseofhIghlyconcentrated
solutIonsmaybeusefultoIncreasemotorblock,butthIsIncreasesthetotalmIllIgramdose
oflocalanesthetIc.LowerconcentratIonsareusuallyIndIcatedwhenlargervolumesare
requIredtoanesthetIzepoorlylocalIzedperIpheralnervesortoblockaserIesofnerves.
Nevertheless,thereIsnoclInIcalevIdencethatprolongedexposure(aswIthcontInuous
PN8)ofnervestolocalanesthetIcsolutIonsofapproprIateconcentratIonpredIsposesto
neurotoxIcInjury.
47
SystemIctoxIcItyIsmostoftenrelatedtoaccIdentalIntravascularInjectIonandrarelyto
theadmInIstratIonofanexcessIvequantItyoflocalanesthetIctoanapproprIatesIte.The
rIskofsystemIctoxIcreactIonsIsoftenrelatedtothedrugused.FopIvacaIne(generallyat
0.5)IsarecentexampleofadrugIntroducedIntoclInIcalpractIceInordertoreduce
centralnervoussystemandcardIovasculartoxIcItythroughItsphysIochemIcaland
stereoselectIvepropertIes
48,49
;despItethIs,thereareexamplesofropIvacaInetoxIcIty
durIngPN8.
50,51,52,5J
DnestrategytopotentIallyreducethevolumeandconcentratIonof
localanesthetIcsolutIonrequIredtoproduceasuccessfulblockIsusIngUSImagIngtomore
accuratelyposItIontheneedleIncloseproxImItytothenerveandtovIsualIzethespread
ofsolutIontoensureadequateexposure.
54,55
DfgreatestImportanceIstheabIlItytoavoId
IntravascularInjectIon.ThIsrIskmaybereducedwhenusIngUS,especIallyIfcombIned
wIthcolor0opplerforvessellocalIzatIon.
ThedegreeofsystemIcdrugabsorptIonandtheduratIonofanesthesIacanalsovary
dependIngonthesIteofInjectIon(I.e.,levelofvascularIzatIon)andaddItIonof
vasoconstrIctors.ThehIghestbloodlevelsoflocalanesthetIcoccurafterIntercostalblocks,
followedbycaudal,epIdural,brachIalplexus,IntravenousregIonal,andlowerextremIty
blockade.EquIvalentdosesoflocalanesthetIcmayproduceonlyJto4hoursofanesthesIa
whenplacedIntheepIduralspace,but12to14hoursInthearmand24toJ6hourswhen
InjectedalongthescIatIcnerve.|anybelIevethattheaddItIonofepInephrIne,1:200,000
to1:400,000,IsadvantageousInprolongIngtheduratIonofblockandInreducIngsystemIc
bloodlevelsoflocalanesthetIc.tsuseIsnotapproprIateInthevIcInItyoftermInal
bloodvessels,suchasInthedIgIts,penIs,orear,orwhenusInganIntravenousregIonal
technIque.PN8usIngsIgnIfIcantquantItIesoflocalanesthetIcshouldnotbeperformed
unlessoxygen,suctIon,andapproprIateresuscItatIonequIpmentIsImmedIatelyavaIlable.
WhenperformIngPN8,atestdoseofanepInephrInecontaInIngsolutIonandsmall
IncrementalInjectIonsarerecommendedtoreducetherIskofunrecognIzedIntravascular
InjectIon.ToxIcItycanalsooccurfromperIpheralabsorptIonofexcessIvedosesoflocal
anesthetIc.PatIentsshouldbeobservedcarefullyforatleastJ0mInutesfollowIngInjectIon
becausepeakbloodlevelsmayoccuratthIstIme.
AnImalstudIes
56
andrecentcasereports
57,58
haveshownsuccessfulresuscItatIonfrom
localanesthetIctoxIcItybyIntravenousadmInIstratIonofntralIpId(20lIpId;not10lIpId
ofpropofol),usIngoneormoreboluses(eachof1to2mL/kgor100mL)followedbyaJ0
mInuteInfusIon(0.5mL/kg/mIn).tIsImportanttousethIsstrategyasanacute
resuscItatIonagent,afterstandardmeasureshaveprovenIneffectIve.
Nerve Damage and Other Complications
PerIpheralnerveInjuryInhumansmayresultfromIntraneuralInjectIon
59,60
ordIrect
needletrauma,
61
althoughthereareothercausesIncludIngthoserelatedtothesurgIcal
procedures(e.g.,patIentposItIonIng,proxImItyofnervetosurgIcalsIte,andtournIquet
applIcatIon).
62
NeedlerelatedtraumawIthoutInjectIonmayresultInInjuryofalesser
magnItudethanthatfromInjectIonInjury.
6J
nanImalstudIes,nerveInjuryappearsto
occurwhenhIghInjectIonpressuresareapplIedIntrafascIcularlyandpartIcularlywhen
hIghlyconcentratedlocalanesthetIcsolutIonsortheIrpreservatIvesareused.
41,42,64
Dne
majorsequelfromIntrafascIcularInjectIonIsendoneuralIschemIa.
65
AlthoughInsome
casesthesesyndromesresolveuneventfully,fullrecoveryofsomeperIpheralInjurIesmay
neveroccurormayrequIreseveralmonthsasaresultofslowregeneratIonofInjured
perIpheralnerves.
66
DthermInorcomplIcatIonsarereportedfollowIngPN8,suchaspaInatthesIteofInjectIon
andlocalhematomaformatIon,buttheseareselflImItedsIdeeffectsandarebestdealt
wIthbycommunIcatIonwIththepatIentandreassurancebytheanesthesIologIst.
HematomaaroundaperIpheralnerveIsnotofthesamesIgnIfIcanceasthatoccurrIngIn
theepIduralorsubarachnoIdspace.tIsImportanttoaddressconcernsexpressedby
patIentsandtomakeeveryefforttorelIeveanypaInordIscomfortresultIngfromvarIous
InterventIons.
Discharge Criteria
StablevItalsIgnsmustbepresentInordertofulfIllcrIterIafordIschargefromtherecovery
area.nsomecases,acceptableevIdenceofregressIngsensoryandmotorblockadeshould
bepresent;however,IfalonglastInglocalanesthetIcwasusedtoperformtheblockora
contInuouscatheterwIthanInfusIonoflocalanesthetIcIspresent,theblockmaynotshow
evIdenceofregressIonatthetImeofdIscharge.PostoperatIvefollowupIsImportantIn
confIrmIngthatneurologIcfunctIonhasreturnedtonormal.fadefIcItIssuspected,early
neurologIcassessmentIscrItIcaltodetermInetheapproprIatecourseofmanagement.
PatIentsshouldhavewellcontrolledpaInondIscharge;IncorporatIngastandardlevelof
paInrelIef(e.g.,onaverbalratIngscale)prIortodIschargehomeortothewardIs
prudent.SpecIfIccommonrIsksforcertaInblocksshouldbedIscussedwIththepatIentprIor
todIscharge.WhendIschargIngpatIentsfrompostanesthesIacareunItswhIleanextremIty
IsstIll
P.962
anesthetIzed(e.g.,theblockwasperformedtoprovIdeextendedanalgesIa),ItwIllbe
necessarytoprovIdeIndepthInstructIonrelatedtotherIsksandtheIrpreventIon(e.g.,
rIskofburnstoanesthetIzedareaswIllrequIreavoIdanceofcertaInformsofcookIng,
potentIalfordevelopIngpressureneuropathIes).AclearunderstandIngoftheInformatIon
provIdedIsImportantforboththepatIentandthecaregIvers.WrIttenInstructIons
IncludIngexpectedcourse,commonsIdeeffects,and24hourcontactInformatIonshouldbe
provIded.
Premedication and Sedation
ThebestpreparatIonforaregIonaltechnIqueIscarefulpatIentselectIonaswellas
ensurIngthatthepatIentIsadequatelyeducatedandInformedabouttheanesthetIcand
surgIcalprocedures.SupplementalmedIcatIonIsoftenhelpful.ApproprIatesedatIonand
analgesIaareanessentIalpartofsuccessfulregIonalanesthesIaInordertoproduce
maxImumbenefItwIthmInImalsIdeeffects.EffectIvesedatIoncanbeachIevedwItha
varIetyofmedIcatIonsIncludIngbutnotlImItedtopropofol,mIdazolam,fentanyl,
ketamIne,remIfentanIl,alfentanIl,oracombInatIonofthesedrugs.Thedosagesshouldbe
tItratedtoreachanapproprIatelevelofsedatIonfortheIndIvIdualpatIent,specIfIcnerve
blockprocedure,andlengthofsurgery.SomeexamplesofadultdosagesarelIstedhereIn
bolusamounts:
|Idazolam,1to2mg(tItratedupto0.07mg/kg)
Fentanyl,0.5to1g/kg
AlfentanIl,7to10g/kg
KetamIne,0.1to0.5mg/kg
naddItIontothegeneralcommentsaboutpremedIcatIondIscussedInearlIerchapters,
regIonalanesthesIatechnIqueshavespecIalrequIrements.SedatIonmustbeadjustedto
therequIredlevelofpatIentcooperatIon.nthecaseofelIcItatIonofaparesthesIa(as
durIngseveralblocksIntheheadandneckregIon)orelectrIcalstImulatIontechnIques,
medIcatIonmustbejustsuffIcIentenoughtoallowthepatIenttoIdentIfyandreportnerve
contact.AlthoughalowdoseofopIoId(50to100goffentanylorequIvalent)wIllhelp
easethedIscomfortofnervelocalIzatIon,patIentresponsIvenessmustbemaIntaIned.ThIs
goalforsedatIondoesnotprecludetheuseofanamnestIcagent.Smalldosesofpropofol
ormIdazolammayprovIdeexcellentamnesIaatlevelsofconscIousnessthatstIllallow
cooperatIon.
Specific Techniques
TheremaInderofthIschapterIsdevotedtotheanatomIcandproceduraldetaIlsofthe
performanceofspecIfIcblocks,arrangedbyanatomIcregIonsofthebody.nthesectIons
dIscussIngupperextremIty,trunk,andlowerextremIty,detaIlsforusIngNSandUSImagIng
durIngtheblocksareIncluded.ThenervestImulatorIssettodelIvervarIablecurrentswIth
afrequencyof2HzandpulsewIdthof0.1msunlessstatedotherwIse.Thevolumesoflocal
anesthetIcIncludedarethosesuggestedforblocksdurIngwhIchNSwasusedfornerve
localIzatIon;USguIdancemayreducetherequIredvolumeInsomeInstances.ThefIgures
InthesesectIonswIllfocuspredomInantlyonusIngacombInedUSandNSstImulatIon
guIdedtechnIque,althoughproceduresforblIndtechnIquesusIngNSarealsodescrIbed.t
IsImportanttonotethatthefIguresIllustratIngtechnIqueInhumansarerepresentatIveof
theclInIcalscenarIo,butwIthoutallofthesterIlepreparatIonrequIredsoastofacIlItate
observatIonofproperprobeandneedlehandlIng.WItheachtechnIque,thereare
comments,whIchIncludepractIcaltIpsandevIdencebasedrecommendatIons.naddItIon,
mostsuggestIonsrelatedtovolumeoflocalanesthetIcwerebasedonconventIonal
technIque.AlthoughItIsnotyetwellestablIshed,manyexpertsspeculatethattheuseof
USguIdancemayreducethevolumeoflocalanesthetIcrequIredtoachIeveadequate
block.
Head and Neck Blocks
FegIonalanesthesIafortheheadandneckIsdIverse,wIthmanyheadandnecksurgIcal
proceduresbeIngamenabletosomeformofregIonalanesthesIa.AregIonaltechnIquemay
bethesolemodeofanesthesIaormaybeIncorporatedIntoabalancedgeneralanesthetIc
offerIngoptImalpostsurgIcalanalgesIa.8lockscanbeusedforophthalmIc,neurologIc,
ear/nose/throat,plastIc,andendocrInesurgery.FegIonalanesthesIatechnIques,suchas
trIgemInaloroccIpItalnerveblock,mayalsobeusedfordIagnostIcandtherapeutIc
purposesInacuteandchronIcpaInsyndromes.8locktechnIquesrangefromlocal
InfIltratIontofIeldblocktospecIfIcnerveblocks.TheabsenceofdefInItIveaIrwaycontrol
IsafrequentsourceofconcernwIthregIonaltechnIques,asIntraoperatIveaIrwaycontrol
canbechallengIng.
FegIonalanesthesIaoftheheadandneckprImarIlydependsonlocalInfIltratIonand/or
specIfIcnerveblocksplacedwIthrelIableanatomIclandmarks.ElIcItatIonofaparesthesIa
IsthemaInstayofnervelocalIzatIon,whIleNSorUSImagInghasnotyetbeenperformed
orreportedtoanyextentfortheseblocks.Therefore,thedescrIptIonoftechnIquesInthIs
sectIonwIlldevIatefromotherareaswherethereIsgreaterrelIanceonnervelocalIzatIon
modalItIesusIngNSandUSImagIng.
Clinical Anatomy
Trigeminal Nerve
SensoryandmotorInnervatIonofthefaceIsprovIdedbythebranchesofthefIfthcranIal
(trIgemInal)nerve(FIgs.J84andJ85).
TherootsofthIsnervearIsefromthebaseoftheponsandsendsensorybranchestothe
largesemIlunar(trIgemInalorgasserIan)ganglIon,whIchlIesonthedorsalsurfaceofthe
petrousbone.tsanterIormargIngIvesrIsetothreemaInbranches:theophthalmIc,
maxIllary,andmandIbularnerves.
AsmallermotorfIbernucleuslIesbehIndthemaIntrIgemInalganglIonandsendsmotor
branchestoonetermInalnerve,themandIbularnerve.
ThethreemajorbranchesofthetrIgemInalnerveeachhaveaseparateexItfromthe
skull.
TheuppermostophthalmicbranchpassesthroughthesphenoIdalfIssureIntotheorbIt.
ThemaIntermInalfIbersofthIssensorynerve,thefrontal nerve,runbehIndthecenter
oftheorbItalcavItyandbIfurcateIntothesupratrochlearandsupraorbItalnerves.The
supratrochlearbranchtraversestheorbItalongthesuperIorborderandexItsonthefront
ofthefaceIntheeasIlypalpatedsupraorbItalnotch;thesupraorbital nerverunsIna
medIaldIrectIontowardthetrochlea.
ThemaxillarynervecontaInsonlysensoryfIbers.texItstheskullthroughtheround
foramen(foramenrotundum),passesbeneaththeskullanterIorly,andentersthe
sphenopalatInefossa.AtthIspoInt,ItlIesmedIaltothelateralpterygoIdplateoneach
sIde.AttheanterIorendofthIschannel,ItagaInmovessuperIorlytoreentertheskull
IntheInfraorbItalcanalIntheflooroftheorbIt.tbranchestoformthezygomatIc
nervetotheorbItandtheshortsphenopalatIne(pterygopalatIne)nerves,andtogIveoff
theposterIordentalbranches.TheanterIordentalnervesarIsefromthemaIntrunkasIt
passesthroughtheInfraorbItalcanal.ThetermInalInfraorbItalnervepenetratesthrough
theInferIororbItalfIssureto
P.96J
thebaseoftheorbIt,totheInfraorbItalgrooveandcanal(justbelowtheeyeandlateral
tothenose),andreachesthefacIalsurfaceofthemaxIlla.tthendIvIdesIntothe
palpebral(lowereyelId),nasal(wIngofthenose),andlabIalnerves(upperlIp).
Figure 38-4.|ajorbranchesofthetrIgemInalnerve.TherootsofthIsnervearIse
fromtheponsandformthelargegasserIan(orsemIlunar)ganglIon.Thethreemajor
brancheshaveseparateexItsfromtheskull.ThemaIntermInalfIbersofthe
ophthalmIcnerve,thefrontalnerve,termInateasthesupraorbItaland
supratrochlearnervesandexIttheIrrespectIveforamen.ThemaxIllaryand
mandIbularbranchesemergefromtheskullmedIaltothelateralpterygoIdplate;
themaxIllarytermInatIngastheInfraorbItalnerve(throughtheInfraorbItal
foramen)andthemandIbularprovIdIngtheInferIoralveolarnerve(aswellasmotor
branches),whIchexItsatthementalforamenasthementalnerve.
ThemandibularnerveIsthethIrdandlargestbranchofthetrIgemInal,andtheonlyone
toreceIvemotorfIbers.texItstheskullposterIortothemaxIllarynervethroughthe
ovalforamen(foramenovale),formsashortthIcktrunk,andthendIvIdesIntoan
anterIortrunk,maInlymotor,andaposterIortrunk,whIchIsmostlysensory.ThemaIn
branch(posterIortrunk)contInuesastheInferIoralveolarnervemedIaltotheramusof
themandIbleandInnervatesthemolarandpremolarteeth.ThIsnervecurvesanterIorly
tofollowthemandIbleandexItsasatermInalbranch(mentalnerve)throughthemental
foramen.ThementalnerveprovIdessensatIontothelowerlIpandchIn.DthertermInal
nervesIncludethelIngualnerve(floorofmouthandanterIortwothIrdsoftongue)and
theaurIculotemporalnerve(earandtemple).
Cervical Plexus
SensoryandmotorfIbersoftheneckandposterIorscalparIsefromtheanterIorramI
(branches)ofthefIrstfourcervIcal(C14)spInalnerves.ThereaderIsreferredtothe
ClInIcalAnatomyoftheupperextremItysectIonforadescrIptIonofthespInalnerve
anatomy.ThecervIcalplexusIsunIqueInthatItdIvIdesearlyIntocutaneousbranches
(penetratIngthecervIcalfascIa)(FIgs.J85andJ86)andmuscularbranches(deeper
branchesthatInnervatethemusclesandjoInts),whIchcanbeblockedseparately(FIg.
J87).ThedermatomesofthecervIcalnervesC24areIllustratedInFIgureJ88.
Figure 38-5.LateralvIewofthesurfaceofhead,showIngthecutaneousInnervatIon
ofthesuperfIcIal/dIstaltrIgemInalnervebranchestothefaceandtheanatomyand
blockneedleInsertIonangleofthesuperfIcIalcervIcalblock.TheneedleIsInItIally
InsertedperpendIculartotheskInatthemIdpoIntofthelateralborderofthe
sternocleIdomastoIdmuscle(whereItIscrossedbytheexternaljugularveIn).
Subsequently,theneedlecanbeInsertedInsuperIorandInferIorangulatIonsto
reachtheentIreplexus.SD,supraorIbtalnerve;ST,supratrochlearnerve;D,
InfraorbItalnerve;|,mentalnerve.
ClassIccervIcalplexusanesthesIaalongthetuberclesofthevertebralbodyproduces
bothmotorandsensoryblockade.ThetransverseprocessesofthecervIcalvertebrae
formpeculIarelongatedtroughsfortheemergenceoftheIrnerveroots.Thesetroughs
lIeImmedIatelylateraltoamedIalopenIngforthecephaladpassageofthevertebral
artery(FIg.J87).ThetroughatthetermInalendofthetransverseprocessdIvIdesInto
ananterIorandaposterIortubercle,whIchoftencanbeeasIlypalpated.
ThesetuberclesalsoserveastheattachmentsfortheanterIorandmIddlescalene
muscles,whIchformacompartmentforthecervIcalplexusaswellasthebrachIalplexus
ImmedIatelybelow.ThecompartmentatthIslevelIslessdevelopedthantheone
formedaroundthebrachIalplexus.
ThedeepmuscularbranchescurlanterIorlyaroundthelateralborderoftheanterIor
scaleneandproceedcaudallyandmedIally.|anybranchesservethedeepanterIorneck
muscles,butotherbranchesIncludetheInferIordescendIngcervIcalnerve,thetrapezIus
branchoftheplexus,andthephrenIcnerve.TheygIveanterIorbranchestothe
sternocleIdomastoIdmuscleastheypassbehIndIt.
P.964
Figure 38-6.SchematIcofthecervIcalplexus,whIcharIsesfromtheanterIor
prImaryramIofC24.Themotorbranches(IncludIngthephrenIcnerve)curl
anterIorlyaroundtheanterIorscaleneandtravelcaudadandmedIallytosupplythe
deepmusclesoftheneck.ThesensorybranchesexItatthelateralborderofthe
sternocleIdomastoIdmuscletosupplytheskInoftheneckandshoulder.
Figure 38-7.NeedleInsertIonpoIntsandanglesforthedeepcervIcalplexus
blockade.ThenerverootsexItthevertebralcolumnvIathetroughsformedbythe
transverseprocesses.TheneedleIsInsertedateachofnerverootsofC2throughC4
usIngacaudadandposterIordIrectIon.
ThesensoryfIbersemergebehIndtheanterIorscalenemusclebutseparatefromthe
motorbranchesandcontInuelaterallytoemergesuperfIcIallyundertheposterIorborder
ofthesternocleIdomastoIdmuscle.Thebranches,IncludIngthelesseroccIpItalnerve,
greataurIcularnerve,transversecervIcalnerve,andthesupraclavIcularnerves
(anterIor,medIal,posterIorbranches),InnervatetheanterIorandposterIorskInofthe
neckandshoulder.
Occipital Nerve
TheophthalmIcbranchofthetrIgemInalnerveprovIdessensoryInnervatIontothe
foreheadandanterIorscalp.TheremaInderofthescalpIsInnervatedbyfIbersofthe
greaterandlesseroccIpItalnerves(FIg.J89).
Thelesser occipital nervearIsesfromthesuperfIcIal(cutaneous)cervIcalplexus(FIg.J8
5)andtraversescephaladfromtheposterIoredgeofthesternocleIdomastoIdmuscle
towardthetopofthehead,dIvIdIngIntoseveralbranches.Thegreater occipital nerve
arIsesfromtheposterIorramusofthesecondcervIcalspInalnerve(thecervIcalplexus
arIsesfromtheanterIorramI)andtravelsInacranIaldIrectIontoreachtheskInInthe
areaofthesuperIornuchallInewhIlegIvIngbranchestosupplytheheadandlaterally
towardtheear.
ThesenervescanbeblockedbysuperfIcIalInjectIonatthepoIntontheposterIorskull
wheretheyemergefrombelowthemusclesoftheneck.
Techniques
Foreveryprocedure,preparetheneedleInsertIonsIteandotherapplIcableskInareaswIth
anantIseptIcsolutIonandusesterIleequIpment.
P.965
Figure 38-8.ThecervIcal,thoracIc,lumbar,andsacraldermatomesofthebody.
Trigeminal Nerve Blocks
AlloftheblocksdescrIbedInthIssectIonusetheextraoralroute,althoughalternatIve
IntraoralroutesmaybesuItableInmanycases.
1. SemIlunar(gasserIan)ganglIonblock.ThemostcomprehensIveblockadeofthe
trIgemInalnervetargetsthecentralganglIon(FIg.J84).ThIsblockIsusuallyperformed
byneurosurgeonsunderfluoroscopIcguIdancefortreatmentofdIsablIngtrIgemInal
neuralgIa.FewanesthesIologIstsperformthIstechnIcallydIffIcultblockandItwIllnotbe
descrIbedIndetaIlhere.
2. SuperfIcIaltrIgemInalnervebranchblock.TrIgemInalblockcanbeeasIlyperformedby
InjectIonofthethreeIndIvIdualtermInalsuperfIcIalbranches(supraorbItal,InfraorbItal,
mentalnerves).EachnerveIscloselyassocIatedwIthItsrespectIveforamIna,andall
foramInalIeInthesamesagIttalplaneoneachsIdeoftheface(approxImately2.5cm
lateraltothemIdfacIallInepassIngthroughthepupIl)(FIg.J810).TheseforamInaare
readIlypalpable,andthesenervescanbeblockedwIthsuperfIcIalInjectIonsofsmall
quantItIesoflocalanesthetIc.ThebonylandmarksareusuallysuffIcIentthemselvesfor
routIneanesthetIcpurposes.However,paresthesIasaredesIrablewhenperformIng
neurolytIcblockswIthalcohol.AnaddItIonalblockofthesupratrochlearnerveIs
requIredIfthefIeldofanesthesIaIstocrossthemIdlIne(FIg.J85).Cenerally,fIne,short
needles(e.g.,24to26gauge,2toJcm)andsmallsyrInges(1to5mL)wIllbesuItablefor
theseblocks.TheblockIsusuallyperformedwIththepatIentInthesupIneposItIon.
Figure 38-9.CreaterandlesseroccIpItalnervedIstrIbutIon,supply,andblock
needleInsertIonsItes(X).
Figure 38-10.LocatIonsofforamenforthesuperfIcIal/dIstaltrIgemInalnerve
blocks.ThesupraorbItal,InfraorbItal,andmentalforamenalllayapproxImately2.5
cmlateraltothemIdlIneoftheface,InlInewIththemIddleofthepupIl.SD,
supraorIbtalnerve;ST,supratrochlearnerve;D,InfraorbItalnerve;|,mental
nerve.
P.966
Procedure
SupraorbItalnerve(termInalnerveofophthalmIcbranch).ThesupraorbItalnotchIs
easIlypalpatedatthemedIalupperangleoftheorbIt.TheneedleIsInsertedandlocal
anesthetIc(seeComments)IsslowlyInjectedafteraspIratIon,slIghtlyoutsIdethe
notchandproducesanesthesIaoftheIpsIlateralforehead.
Supratrochlearnerve(termInalnerveofophthalmIcbranch).AnesthesIaofthe
supratrochlearnerveIsobtaInedwIthsuperfIcIalInfIltratIonoftheupperInternal
angleoftheorbItalrIm.ThIsIsneededIfthefIeldofanesthesIaIstocrossthemIdlIne.
nfraorbItalnerve(termInalbranchofmaxIllarynerve).TheInfraorbItalforamenlIes
about1cmbelowthemIddleofthelowerorbItalmargIn.ftheforamencannotbe
palpateddIrectly,ItcanbesoughtbygentlyprobIngwIthasmallgaugeneedle.The
needleshouldbeIntroducedInacranIaldIrectIonthroughaskInwhealapproxImately
0.5cmbelowtheexpectedopenIng.AftermakIngcontactwIththeboneand
wIthdrawIngslIghtly,InjectIonofasmallquantItyoflocalanesthetIcIsperformed.
ThIsblockproducesanesthesIaofthemIddlethIrdoftheIpsIlateralface.
|entalnerve(sensorytermInalbranchofmandIbularnerve).Thementalnerve
emergesfromItsforamen,whIchlIesInferIortotheouterlIpatthelevelofthe
secondpremolar,mIdwaybetweentheupperandlowerbordersofthemandIble.The
mentalcanalanglesmedIallyandInferIorlysothat,InthIscase,needleInsertIon
shouldstartapproxImately0.5cmaboveand0.5cmlateraltotheantIcIpatedlocatIon
oftheorIfIceIfItcannotbepalpateddIrectly.SlowInjectIonafteraspIratIonatthe
openIngofthecanalproducesanesthesIaofthemandIbulararea.njectIondIrectly
IntothecanalshouldbeavoIdedtoreducetherIskofneuralInjury.
Comments
ChoIceoflocalanesthetIcforallblockswIlldependonthepurposeoftheblockand
theduratIonofanesthesIarequIred(e.g.,1mepIvacaIneforshorterand0.75
ropIvacaIneforlongerprocedures).ForsurgIcalanesthesIa,2to5mLoflocal
anesthetIcmaybeused,whIledIagnostIcortherapeutIcvolumeswIllbemuchsmaller
(0.5to1mL).
TheblocksshouldbefollowedbylocalcompressIontopreventhematomaformatIon.
PN8ofthetermInalbranchesofthetrIgemInalnerveoffersasafeandeffectIve
alternatIvetolocalInfIltratIonforsofttIssueInjuryoftheface.0espItethIs,local
InfIltratIonIsoftenrequIredtorectIfyIncompleteanesthesIa,especIallyofthe
supraorbItalandInfraorbItalnerves.
67
nfraorbItalnerveblockmaybeperformedforpostoperatIveanalgesIaaftercleftlIp
repaIr.PalpatInganatomIclandmarksforthIsblockcanbedIffIcultIntheneonate
becauseofthedevelopIngfacIalconfIguratIon.
SkullnerveblockscanbeusedforcranIotomyproceduresandarealsorecommended
toattenuatepostoperatIvepaIn.
68
ThenervesblockedtoachIevesuccessful
anesthesIaforcranIotomyIncludethesupraorbItalandsupratrochlearnerves,the
greaterandlesseroccIpItalnerves,theaurIculotemporalnerves,andthegreater
aurIcularnerves.
SupraorbItalnerveblockshavebeenassocIatedwIthahIghrequIrementfor
supplementatIon,perhapsbecauseoftheanatomIcvarIatIonofthenerve.Thenerve
mayexIttheskullundIvIdedorItsmedIalandlateralbranchesmayexItseparately.
ForframepInplacementdurIngstereotactIcneurosurgery,faIluretoblockthelateral
branchmayaccountforInadequatecoverage.
69
0urIngmentalnerveblockInolderpatIents,resorptIonofthesuperIormargInofthe
mandIblewIllmaketheforamenappeartolIemoresuperIorlyalongtheramus.
J. |axIllarynerveblock.ThIsblockshouldbeperformedbypractItIonerswIthrelatedand
adequateexperIence.tIsrequIredwhenthesuperfIcIalblockoftheInfraorbItalnerve
doesnotproduceadequateanesthesIaorwhenanesthesIaofthemoreproxImalsuperIor
dentalnervesIsrequIred.ThIsblockcanbeperformedbyalateralapproachtothe
sphenopalatInefossa.
Procedure
ThepatIenteIthersItswIththemouthslIghtlyopenorlIessupInewIthasmalltowel
undertheoccIputandtheheadturnedslIghtlyawayfromthesIdetobeblocked.
AbovethezygomatIcarch.ThecenteroftheupperzygomatIcarchIsmarked.A6cm
needleIsIntroducedat45degrees,caudallyandmedIally,towardthecontralateral
molarteeth.AfteraparesthesIaIselIcItedatthenostrIl,upperlIp,andcheek,slow
IncrementalInjectIonoflocalanesthetIcIsperformedafterslIghtneedlewIthdrawal
andwIthfrequentaspIratIon.
8elowthezygomatIcarch(FIg.J811).ThezygomatIcarchIsmarkedalongItscourse,
andthepatIentIsaskedtoopenandclosethemouthslowlysothatthecurvedupper
borderofthemandIblecanbeIdentIfIed.ThemandIbularfossaIspalpatedbetween
thecondylarandcoronoIdprocesses.ThelowestpoIntofthemandIbularnotchIs
palpated,andanXIsmarkedatthIsspot,whIchIsusuallyatthemIdpoIntofthe
zygoma.AlocalanesthetIcskInwhealIsraIsedattheXafterapproprIateskIn
preparatIon.
WIththepatIent'sjawIntheopenposItIon,a6to9cmneedleIsIntroducedthrough
theXata45degreeangletowardthedorsalpartoftheeyeball(cephaladandslIghtly
anterIor).
Figure 38-11.LateralvIewoftheskullshowIngthebonylandmarksandfInal
needleInsertIonanglesforthemaxIllary(red needle)andmandIbular(blue
needle)nerves.EachblockprocedureInvolvesfIrstreachIngthelateralpterygoId
plate(seetextfordetaIls).
P.967
TheneedleshouldcontactthelateralportIonofthepterygoIdprocess(pterygoId
plate)atadepthof4to5cm.tIsthenwIthdrawnandredIrectedslIghtlycephalad
andanterIorlyuntIlItpassesbeyondthepterygoIdplateandentersthe
pterygopalatInefossaatanaddItIonaldepthofnomorethan1cm.AparesthesIaIn
thenoseortheupperteethconfIrmsnervelocalIzatIon.ThepterygopalatInefossaIs
hIghlyvascular,socaremustbeexercIsedtoavoIdIntravascularInjectIon.
AnesthesIacanbeachIevedbyInjectIng5mlIntothepterygopalatInefossa,eItheron
obtaInIngtheparesthesIaorblIndlybyadvancIng1cmbeyondtheplate.
Comments
DneconcerndurIngthIsblockIsspreadoflocalanesthetIctoadjacentstructures,
especIallytothenervesIntheorbIt.fpaInoccursIntheregIonoftheorbItdurIngthe
procedure,theInjectIonshouldbestoppedandtheneedleshouldbewIthdrawn.
AlthoughthemaInstayoftreatmentfortrIgemInalneuralgIacontInuestobe
pharmacologIcorneuroablatIve,maxIllarynerveblockwIthextraoralmandIbular
nerveblockhasbeenreportedtoprovIderelIefInsomesettIngs.
70
4. |andIbularnerveblock(FIg.J811).ThIsnervecanbeblockedfordentalandmaxIllary
surgeryorforInferIordentalpaIn,trIgemInalneuralgIaInthethIrdbranch,or
temporomandIbularjoIntdysfunctIon.tIstheonlybranchofthetrIgemInalnervewhere
anesthesIacarrIestherIskoflossofmotor(mastIcatIon)functIon.
Procedure
ThepatIentlIessupInewIththefaceInprofIle.LandmarksforlocatIonofthe
mandIbularfossaarethesameasthosedescrIbedformaxIllarynerveblockade.
A6to9cmneedleIsIntroducedthroughtheskInwhealanddIrectedperpendIcularly
totheskIn,wIthoutthecephaladangulatIonrequIredformaxIllarynerveanesthesIa.
ThedepthshouldbenotedwhenthepterygoIdplateIscontacted.TheneedleIsthen
redIrectedposterIorlyuntIlItpassesbeyondthepterygoIdplate.tshouldcontactthe
nerve0.5to1cmdeeptothepoIntwherethepterygoIdplateIscontacted.
ParesthesIaofthelowerjaw,lowerlIp,andlowerIncIsorsatadepthofapproxImately
4to4.5cmconfIrmsproxImItytothenerve.CentleexploratIonInacephaladand
caudaddIrectIon,fromtheInItIalpoIntwheretheneedlepassesposterIortotheplate,
mayberequIred.AfterslIghtneedlewIthdrawal,5to10mLofsolutIonIsInjected
IncrementallywIthrepeatedaspIratIontoavoIdIntravascularInjectIon.AswIth
maxIllaryblockade,paresthesIascanbepaInfultothepatIent.
Comments
AnesthesIaoftheaurIculotemporalnerveIsoftendelayed.
FacIalnerveanesthesIaoccasIonallycanbeseenwhenlargevolumesareInjectedto
blockthemandIbularnerve.ThIsIsoflIttleconsequenceunlessneurolytIcagentsare
used.
AmoreserIouscomplIcatIonIsthepossIbIlItyofIntravascularInjectIonInthIshIghly
vascularIzedarea.njectIonshouldbeperformedIncrementallywIthsmallquantItIes
andthereshouldbeconstantobservatIonforsIgnsoftoxIcIty.
Cervical Plexus Blocks
AnesthesIaofeItherthedeeporsuperfIcIalcervIcalplexus,orboth,canbeusedfor
proceduresofthelateraloranterIornecksuchasparathyroIdectomyandcarotId
endarterectomy.ncarotIdsurgery,localInfIltratIonofthecarotIdbIfurcatIonmaybe
necessarytoblockreflexhemodynamIcchangesassocIatedwIthglossopharyngeal
stImulatIon.
1. 0eepcervIcalplexusblock
Procedure
ThepatIentIsplacedsupInewIthasmalltowelunderthehead,whIchIsturned45
degreestotheopposItesIdewIthslIghtneckextensIon.
LandmarksIncludetheposterIoredgeofthesternocleIdomastoIdmuscle,thecaudal
portIonofthemastoIdprocess,theangleofthejaw,andthetransverseprocessesof
cervIcalvertebraeC2throughC5(about1.5cmapart).falltransverseprocesses
cannotbepalpated,themostpromInenttubercleofC6(ChassaIgnac)Ismarked.AlIne
IsdrawnfromthemastoIdprocessalongthesternocleIdomastoIdmuscletoreachthe
transverseprocessofC6.EachtransverseprocessofC2throughC5Ismarked
approxImately0.5to1cmbehIndthelIne;thatofC2lIesabout1.5cmInferIortothe
mastoIdprocess.
SkInInfIltratIonIscarrIedoutattheXmarksofC2throughC4,andthreeneedles(22
gauge,J.5to5cm)areIntroducedperpendIculartotheskInandadvancedaboutJ0
degreescaudallywIthaslIghtposterIororIentatIon(FIg.J87).
AfterconfIrmIngcontactwIththetransverseprocess,theneedleIswIthdrawnslIghtly
andasyrIngeIsconnectedtotheneedle.TwotoJmLoflocalanesthetIcsolutIonIs
InjectedpersegmentfortherapeutIcordIagnostIcpurposes;5to10mLpersegment
maybesuffIcIentforsurgIcalblock(lImItIngthetotaltoapproxImately20mLIf
superfIcIalblocksarealsoperformed).
Comments
ThedeepblockmaybeperformedbysIngleInjectIonatCJorC4asorIgInally
descrIbedbyWInnIeetal.
71
orbyastandardthreeInjectIontechnIque.
ParesthesIaoccurrIngdurIngtheseblockshasbeenassocIatedwIthmoreeffectIve
anesthesIa.
72
AnesthesIaforcarotIdendarterectomymayInvolveperformIngcombInedsuperfIcIal
anddeepcervIcalplexusblocks,yetthebenefItofcombInedoversuperfIcIalblock
alonehasbeenquestIoned.
7J,74
ThereappearstobenodIfferencebetweenthesetwo
approachesIntheamountofsupplementallocalanesthesIarequIred.
ThereareseverallIfethreatenIngcomplIcatIonsthatmayarIsefromdeepcervIcal
plexusblock.njectIonmayoccurIntothevertebralartery.SubarachnoIdorepIdural
InjectIonsarepossIbleIftheneedleIsadvancedtoofarmedIallyIntothevertebral
foramen.ThIsIsmorelIkelyInthecervIcalregIonbecauseofthelongerduralsleeves
thataccompanythesenervebranches.CarefulmonItorIngofthepatIentshould
contInuefor60mInutesaftertheblockhasbeenperformed.
PhrenIcnervepalsyleadIngtohemIdIaphragmatIcparesIsIsacommonoccurrence
wIththIsblock.
75,76
ThIsblockIsnotIndIcatedInanypatIentwhodependsonthe
dIaphragmfortIdalventIlatIon,norIsbIlateralblockadeeverrecommended.
DtherwelldescrIbedsIdeeffectsIncludeHornersyndrome(IfthesuperIorcervIcalor
cervIcothoracIcganglIonIsblocked),
77
stellateganglIonblock,
78
andhoarseness
becauseofrecurrentlaryngealnerveblock.
2. SuperfIcIalcervIcalplexusblockIsperformedInasImIlarposItIonasdeepcervIcal
plexusblockandresultsInanesthesIaonlyofthesensoryfIbersoftheplexus.
P.968
Procedure
AnXIsmadeatthemIdpoIntoftheposterIorborderofthesternocleIdomastoId
muscle(FIg.J85).
LocalskInInfIltratIonIsperformedwIthafanlIkeInjectIonusIng10to20mLoflocal
anesthetIcalongtheposterIorborderofthesternocleIdomastoIdmuscle4cmabove
andbelowthelevelofthemIdpoInt.
Comments
ThemostcommonapproachformInImallyInvasIveparathyroIdectomy(InvolvInga
smallunIlateralIncIsIonratherthanbIlateralneckexploratIon)IncludesacombInatIon
ofC2throughC4superfIcIalcervIcalplexusblock,InfIltratIonalongtheIncIsIonlIne,
andInfIltratIonoftheupperthyroIdpedIcle.
79
ThIsapproachcanresultInshorter
anesthetIcandoperatIvetImes,leadIngtoearlIerhospItaldIschargeaswellas
sIgnIfIcantlybetterpostoperatIvepaInrelIef.
79,80
ThyroIdsurgeryhasbeenperformed,usIngamodIfIedsurgIcalapproach,under
superfIcIalcervIcalplexusblockIncombInatIonwIthanterIorfIeldblock.
81
|InImallyInvasIvesurgerymayrequIreconversIontogeneralanesthesIawhenthereIs
dIffIcultyensurIngadequateprotectIonoftherecurrentlaryngealnerveorwhen
IntraoperatIvedIagnosIsofparathyroIdcarcInomaormultIglandularparathyroId
hyperplasIaoccurs.
PhrenIcnerveparalysIsleadIngtodIaphragmatIcdysfunctIon,
72
vagusnerveblockwIth
resultantrecurrentnerveparalysIs
82
andInadvertentIntravascularInjectIonhaveall
beenreported.
8J
Occipital Nerve Blocks
ThegreaterandlesseroccIpItalnervescanbeblockedbysuperfIcIalInjectIonatthepoInts
ontheposterIorskullwheretheyemergefrombelowthemusclesoftheneck.ThIsblockIs
rarelyusedforsurgIcalprocedures;ItIsmoreoftenapplIedasadIagnostIcstepIn
evaluatIngheadandneckpaIncomplaInts.
Procedure (Fig. 38-9)
ThepatIentsItswIththeheadtIltedforwardslIghtlytoexposethepromInentnuchal
rIdgeofboneattheposterIorbaseoftheskull.
ThesuperIornuchallIneIspalpatedatonethIrdofthedIstancebetweentheexternal
occIpItalprotuberanceandtheforamenmagnum.AmarkIsplacedonthenuchallIneat
thelateralborderoftheInsertIonoftheerectormusclesoftheneck,usually2.5cm
fromthemIdlIne.ThebranchesofthegreateroccIpItalnerveusuallypasslaterallyfrom
behIndthemuscletocrossthenuchallIneatthIspoInt.ThenerveIslocateddIrectly
lateraltotheeasIlypalpatedoccIpItalartery.0urIngItsascentontheposterIorskull,
thelesseroccIpItalnervecanbelocatedatanaddItIonal2.5cmdIstancefromthe
greateroccIpItalnervealongthesuperIornuchallIne;amarkshouldbeplacedhereas
well.
Ashort,fIneneedle(e.g.,2.5cm,25gauge)IsIntroducedwIthaslIghtcranIalangulatIon
ateachmarktothedepthoftheskullItself.AfterslIghtwIthdrawal,localanesthetIcIs
Injected(e.g.,0.5to1mLof1lIdocaInefordIagnostIcproceduresor1toJmLof0.75
ropIvacaInefortherapeutIcprocedures).ParesthesIasareoccasIonallyencounteredbut
arenotessentIalforobtaInIngsImpleskInanesthesIa.
fmoreanterIoranesthesIaofthescalpIsrequIred,thelesseroccIpItalnervebranches
arealsoblockedbyadvancIngtheneedlesubcutaneouslyfromthIspoIntInananterIor
dIrectIontowardthemastoIdprocess.AbandofanesthetIcsolutIonIsdeposItedalong
thelInebetweenskInentryandthemastoIdprocessusIng2toJmLoflocalanesthetIc.
Comments
8lockIngthelesseroccIpItalandthegreataurIcularnerve(bothblockedbysubcutaneous
InjectIonfromtheangleofthemandIbletothemastoIdprocess)hasbeensuccessfulIn
provIdIngpostoperatIveanalgesIaafterotoplasty.
84
FeducIngtherequIrementforopIoId
analgesIa(wIthItsassocIatednauseaandvomItIng)IsessentIalbecauseofthehIgh
IncIdenceofpaInandvomItIngonthefIrstpostoperatIvedayrelatedtothesurgIcal
procedurealone.
ThegreateroccIpItalnerveblockIscommonlyusedforprImaryheadachesyndromes;for
chronIcsyndromes,theanterIorregIonInvolvIngthetrIgemInalnerveIsalsoblocked.
85
thasbeenreportedforusewIthcervIcogenIcheadache,occIpItalneuralgIa,mIgraIne,
andclusterheadache.
86
ComplIcatIonswIththIstechnIquearerare.Caremustbetakennottoadvancethe
needleanterIorlyundertheskullastheforamenmagnummIghtbeentered
unIntentIonallywIthalongneedle.LocalhematomamaybeproducedwIthsuperfIcIal
InjectIon,butthIsIsonlyatemporaryproblem.
Upper Extremity Blocks
AlthoughmanyapproachestothebrachIalplexushavebeendescrIbed,thereare
tradItIonallyfouranatomIclocatIonswherelocalanesthetIcsareplaced:(1)the
InterscalenegroovenearthecervIcaltransverseprocesses,(2)thesubclavIansheathat
thefIrstrIb,(J)nearthecoracoIdprocessIntheInfraclavIcularfossa,and(4)surroundIng
theaxIllaryarteryIntheaxIlla.TheIntroductIonofUSImagInghasgreatlyIncreaseduseof
blocksatthesupraclavIcularfossa.7IsualIzatIonofthesubclavIanarteryandlungmake
thesecrItIcalstructureseasIertoavoId.tIsImportanttostressthatclearvIsIbIlItyofthe
needleIsessentIalforthIsblock(andgenerallyforallblocksofthebrachIalplexus).The
approprIatechoIceofapproachdependsnotonlyonthepatIent'sanatomybutonthesIte
ofsurgeryandthelocalIzatIonmethod.
ThetermInalbranchescanalsobeanesthetIzedbylocalanesthetIcInjectIonalongtheIr
perIpheralcoursewheretheylIeIncloseproxImItytoeasIlyIdentIfIablestructures(Table
J81),orbytheInjectIonofadIlutelocalanesthetIcsolutIonIntravenouslybelowa
pneumatIctournIquetontheupperarm(IntravenousregIonalor8Ierblock).Theuseof
USmayIncreasethenumberoflocatIonswherethetermInalnervescanbesuccessfully
blocked.Forexample,theulnarnervecanbeblockedeffectIvelyatthemedIalsurfaceof
themIdforearm,whIchmayreducetherIskofulnarnervepalsycomparedwIthblockat
theelbownearthecubItaltunnel.AsstatedIntheIntroductIontoSpecIfIcTechnIques,
theuseofacombInedUSandNSguIdedtechnIqueIsstressedInthefIgures,andtheuseof
allnecessarysterIleprecautIonwasnotIncludedforsImplIcItyofvIewIng.
Clinical Anatomy
Spinal Nerves
ThespInalnervesarepartoftheperIpheralnervoussystem,alongwIththecranIaland
autonomIcnervesandtheIrganglIa.
ThereareJ1paIrsofspInalnerves:8cervIcal(C1throughC8),12thoracIc(T1through
T12),5lumbar(L1throughL5),5sacral(S1throughS5),and1coccygeal.ThesespInal
nervesareformedbytheunIonoftheventral(anterIor)anddorsal(posterIor)spInal
roots.
ThespInalnervesaremIxednervesconsIstIngofbothmotorandsensoryfIbers.n
addItIon,allspInalnervescontaInsympathetIcfIbersforsupplyIngbloodvessels,smooth
muscle,andglandsIntheskIn.ThenervesgIveoff
P.969
sympathetIcbranchesImmedIatelyafterleavIngtheIntervertebralforamen.Crayand
whIteramIcommunIcantesconnectthespInalnervestothesympathetIcchaInganglIato
allowpreganglIonIcsympathetIcfIbersleavIngthespInalcord(T1throughL2/J)toenter
thechaInandleaveItagaIntobedIstrIbutedwIthspInalnervesatalllevels.
SoonafterexItIngtheIntervertebral(spInal)foramIna,eachspInalnerveInturndIvIdes
Intoalargerventralandasmallerdorsalramus(branches).TheventralramIcourse
laterallyandanterIorlytosupplythemuscles,subcutaneoustIssues(superfIcIalfascIa),
andskInoftheneck,trunk,andtheupperandlowerextremItIes(thedermatomesofthe
bodyareshownInFIg.J88).ThedorsalramIcourseposterIorlyandsupplythe
paravertebralmuscles,subcutaneoustIssues,andskInofthebackclosetothemIdlIne.
tIsImportanttorealIzethatthefIrstcervIcal(C1)nerveleavesthespInalcordand
coursesabovetheatlas(C1vertebra);hence,thecervIcalnervesarenumbered
correspondIngtothevertebraeInferIortothem;forexample,theC8nerveexItIngbelow
C7andaboveT1.FromthIspoInton,allthespInalnervesarenamedcorrespondIngto
thevertebrallevelabove.Forexample,TJandL4spInalnervesexItbelowtheTJandL4
vertebrae,respectIvely.
Brachial Plexus
ThebrachIalplexus(FIg.J812)classIcallyarIsesfromtheanterIorprImaryramIofC58
andT1spInalnerves.
TheplexusconsIstsoffIveroots,threetrunks,sIxdivisions(twopertrunk),threecords,
andfIvemajortermInalnerves.
TheC5T1nerverootsemergefromtheIrcorrespondIngIntervertebralforamInaandthen
travelalongthegroovesbetweentheanterIorandposterIortuberclesofthe
correspondIngtransverseprocess.TheyfInallyemergebetweenthescalenusanterIorand
medIusmuscles,abovethesecondpartofsubclavIanarteryandposterIortovertebral
artery.
C5and6nerverootsunItetoformtheupper (superior) trunk,C7contInuesasthemiddle
trunk,andC8andT1convergeIntothelower (inferior) trunk.
Figure 38-12.SchematIcofthebrachIalplexus.|anybranches,IncludIngthe
medIalcutaneousnervesoftheforearmandarm,whIcharIsefromthemedIalcord
arenotshown.
FIbroussheaths(aspartoftheprevertebralfascIa)surroundtheanterIorandposterIor
partsoftheplexusandcontInuetoenvelopetheplexusbetweenthescalenemuscles
moredIstally(calledtheinterscalene fascial sheathproxImallyandtheaxillary sheath
dIstally).
ThethreetrunkstravelInferolaterallyandcrossthebaseoftheposterIortrIangleofthe
neck(superfIcIal)andthefIrstrIb(upperandmIddletrunksabovesubclavIanarteryand
lowertrunkbehIndorbelowtheartery).AtthelateralborderoffIrstrIb,eachtrunk
bIfurcatesIntoanteriorandposterior divisions.
ApproxImatelyatthelevelwherethenervescourseunderthepectoralIsmInormuscle,
thedIvIsIonsconvergetoformthreecords:lateral cordanterIordIvIsIonsofupperand
mIddletrunks(C57);medial cordanterIordIvIsIonoflowertrunk(C8,T1);andposterior
cordposterIordIvIsIonsofallthreetrunks(C5T1).
ThecordsaregroupedaroundthesecondpartoftheaxIllaryartery(wIthIn2.5cmfrom
Itscenter).
87
TherearethreepartsoftheaxIllaryarterynamedfortheIrposItIonsabove
(medIalto),behInd,andbelow(lateralto)thepectoralIsmInormuscle.TypIcally,wIth
anUSprobeplacedtovIewthetransverseaxIsofthecords,themedIalcordlIesInferIor,
thelateralcordsuperIor,andtheposterIorcordposterIortothefIrstpartoftheaxIllary
artery.
mmedIatelybeyondthepectoralIsmInormuscle,thethreecordsdIvergeIntothe
termInalbranches;theseIncludethemedIan,ulnar,radIal,axIllary,and
musculocutaneousnerves.
ThephrenIcnervenormallydescendsanterIortothescalenusanterIormuscle;Itcrosses
themusclefromlateraltomedIalasItdescendsandpassesundertheclavIcleand
throughthesuperIorthoracIcapertureIntothesuperIormedIastInumjustmedIaltothe
externaljugularveIn.However,thereIsanatomIcvarIatIonofthecourseofthephrenIc
nerveandItIsnotalwaysanterIortothescalenusanterIormuscle.
Terminal Nerves
TheanatomyoftheperIpheralnervesIsoutlInedhere,althoughtheclInIcallyrelated
InnervatIonpatternsareIncludedInthedIscussIonofeachblock'stechnIque.FIgureJ81J
P.970
IllustratesthecoursesofthesenerveswIthIntheupperextremIty.FIgureJ814Illustrates
thecutaneousInnervatIonofthetermInalnervesoftheupperextremIty.TheaxIllary
nerveIsanaddItIonaltermInalnerveoftheupperextremIty,buttheanatomyand
blockIngofthIsnervewIllnotbedIscussedhere.
Figure 38-13.CoursesofthetermInalnervesoftheupperextremIty.TheposterIor
vIew(A)IllustratesthebranchesfromtheposterIorcord(axIllaryandradIalnerves),
andtheanterIorvIew(B)Illustratesthebranchesfromthelateral(musculocutaneous
andmedIannerves)andmedIal(medIanandulnarnerves)cords.
1. FadIalnerve(orIgInatesfromC58andT1roots,upperandmIddletrunks,posterIor
dIvIsIons,andposterIorcord).
torIgInatesdeep(oftenposteromedIal)
88
totheaxIllaryartery,descendswIthInthe
axIlla(gIvIngoffbranchestolongheadofthetrIcepsbrachII),passesbetweenthe
medIalandlateralheadsofthetrIceps,andthendescendsoblIquelyacrossthe
posterIoraspectofthehumerusalongthespIral(radIal)grooveatthelevelofthe
deltoIdInsertIon.
Figure 38-14.CutaneousInnervatIonoftheupperextremItynerves.
ttravelsposterIorandmedIaltothedeepbrachIalarteryofthearmandreachesthe
lateralmargInofthehumerus5to7cmabovetheelbowbeforecrossIngoverthe
lateralepIcondyleandenterIngtheanterIorcompartmentofthearm.
nfrontoftheelbow,thenervedIvIdesandcontInuesasthesuperfIcIalradIal
(sensory)andthedeepposterIorInterosseous(motor)nerves.
P.971
J. |edIannerve(orIgInatesfromC58,T1,alltrunks,andlateralandmedIalcords).
ntheaxIlla,thenerveoftenlIesanterolateraltotheaxIllaryartery.
88,89
Thenerve
descendsalongthemedIalaspectofthearmlateraltothebrachIalarteryandcrosses
theartery,usuallyanterIorly,atthemIdpoIntofthearmattheInsertIonofthe
coracobrachIalIsmuscle.
ThenervecrossestheelbowlyIngmedIallyonthebrachIalIsmuscleandjustmedIalto
thebrachIalarteryandveIn(allofthesemedIaltothebIcepsbrachIItendon).
0IstaltotheantecubItalfossa,thenervegIvesofftheanterIorInterosseousnerveand
cutaneoussensorybranches.
4. |usculocutaneousnerve(orIgInatesfromC57roots,upperandmIddletrunks,anterIor
dIvIsIons,lateralcord).
ThIsnerveleavesthefascIalsheathoftheplexusapproxImatelyatthelevelofthe
coracoIdprocess,thustheInfraclavIcularlocatIonforbrachIalplexusblockIsgenerally
themostdIstalblocksIteforthIsnerve.
JustdIstal(2toJcm)tothepectoralIsmajormuscleattachment,thenerveusually
pIercesthecoracobrachIalIsmuscle,afterwhIchItexItsthIsmuscleandcomestolIe
betweenthecoracobrachIalIsmuscleandtheshortandlongheadsofthebIceps
brachIImuscle.
AlthoughItIsdIffIculttoobserveusIngUS,thenervecontInuesasthelateral
cutaneousnerveoftheforearmattheantecubItalfossaandcoursesalongthelateral
aspectoftheforearmprovIdIngsubsequentanterIorandposterIorbranches.
5. Ulnarnerve(orIgInatesfromC78,T1roots,lowertrunk,anterIordIvIsIon,medIalcord).
nItIallythenerveoftencoursesbetweentheaxIllaryarteryandveIn(ItmaylIe
anteromedIaltothearteryandveIn)andthenalongthemedIalaspectofthebrachIal
arterytothemIdpoIntofthehumerusbeforepassIngposterIorlyandfollowIngthe
anterIorsurfaceofthemedIalheadofthetrIceps.
tthenpassesbehIndthemedIalepIcondyleofthehumerus(Inthecondylargroove),
dIvIdesbetweenthehumeralandulnarheadsoftheflexorcarpIulnarIs,andlIeson
themedIalaspectoftheelbowjoInt.
0urIngItsdescentthroughtheforearm,thenervecoursesanterIorly,toapproachthe
ulnararterydIrectlyanterIortotheulnaatthejunctIonofthelowerthIrdandupper
twothIrdsoftheforearm.
AtthewrIstItcrossessuperfIcIaltotheflexorretInaculumanddIvIdesIntosuperfIcIal
anddeepbranches;theulnararterylIesanterolateraltothenerveatthewrIst.
Anatomic Variation
TherearemanyvarIatIonsInformatIonofthebrachIalplexus,
90
aswellasInthecourseof
thetermInalnervesandthevascularelements.SomeofthesevarIatIonsmaycontrIbuteto
dIffIcultywhenperformIngPN8astheremaybeerroneousNSresponses(e.g.,Iftwonerves
areconjoIned)orpoorlocalIzatIonbyNSorbyUSImagIng(e.g.,Ifthenervefollowsa
substantIallydIfferentpath).SomeexamplesaredescrIbedhere.
TheplexusmayIncludeanterIorramIfromC4toC8(prefIxed)or,lesscommon,from
C5toT2(postfIxed.)
TheexIstenceand/orcharacterIstIcsoftheconnectIvetIssuesheaththatInveststhe
plexusatvarIousregIonsarecontroversIal.AcontInuous,tubularsheathhasbeenshown
unlIkely,especIallyIntheaxIllaryregIon.Amoreconvolutedandseptatedstructuremay
bethecauseofnonunIformdIstrIbutIonoflocalanesthetIcInmanycases,whIchsupports
thefIndIngsthatmultIpleInjectIontechnIquesmaybesuperIor.
91
USguIdancecanbe
veryvaluableInthIslocatIontoensurecIrcumferentIalspreadoflocalanesthetIcaround
thenerves.
TheInterscalenegroovemayhavevarIatIonIntherelatIonshIpbetweentheplexusroots
andtrunksandthemuscles.Forexample,theC5and/orC6nerverootsmaytraverse
eItherthroughoranterIortotheanterIorscalenemuscle.
92
nmanycadaverIcspecImens,noInferIortrunkexIsts.
9J
AsInglecordorapaIrofcords
maydevelop.thasbeenobservedthatnodIscreteposterIorcordformsInsomecases,
wIththeposterIordIvIsIonsdIvergIngtoformtermInalnerves.
90
ThetermInalnervesmaylIeInvarIousrelatIonstotheaxIllaryvessels.Theuseofa
combInedNSandUSguIdedtechnIquetobothconfIrmthenervelocalIzatIon(NS)and
obtaIncIrcumferentIalspreadoflocalanesthetIcaroundeachofthenerves(US)may
Improveblocksuccess.
8
Themusculocutaneousnervemayfusetoorhave
communIcatIonswIththemedIannerve,whIchcanresultInItsabsencefromwIthInthe
coracobrachIalIsmuscle.
94,95
CommunIcatIonbetweenthemedIanandulnarnervesIn
theforearmarecommon,wIththemedIannervereplacIngtheInnervatIontovarIous
musclesnormallysupplIedbytheulnarnerve.
96
TheremayalsobelargevarIatIonswIthrespecttothevesselswIthInthearm,wIth
aberrantformatIonsIncludIngdoubleaxIllaryveIns,hIghorIgInoftheradIalartery,and
doublebrachIalarterIes.
97,98,99
Techniques
Brachial Plexus Blockade
1. nterscaleneblockasdescrIbedbyWInnIe
100
In1970,IsIndIcatedmostlyforsurgIcal
anesthesIatotheshoulder,upperarm,andforearm,butIsoftenInsuffIcIentforthe
hand.tfrequentlysparesthelowestbranchesoftheplexus,theC8andT1fIbers,whIch
Innervatethecaudad(ulnar)borderoftheforearm.ThepatIentIsposItIonedsupIne,
wIththeheadfacedslIghtlytothecontralateralsIde.ThemaInsurfacelandmark
(sternocleIdomastoIdmuscle)usedforthIsblockcanbeaccentuatedbyaskIngthe
patIenttoreachfortheIpsIlateralkneeandbyrotatIngtheheadapproxImately45
degreestothenonoperatIvesIde.TheheadshouldalsobeslIghtlyelevated,andthe
patIentshouldbeInstructedtotakeadeepbreathbecausecontractIonofthescalenus
musclesaccentuatestheInterscalenegroove.ThIsgroovelIesImmedIatelybehIndthe
lateralborderoftheclavIcularheadofthesternocleIdomastoIdmuscleatthelevelof
thecrIcoIdcartIlage(C6).AsforallproceduresoftheupperextremIty,preparethe
needleInsertIonsIteandotherapplIcableskInareaswIthanantIseptIcsolutIonand,If
usIngUSImagIng,obtaInsterIlItyoftheUSprobewIthastandardsleevecoveror
transparentdressIng.
Procedure Using Nerve Stimulation Technique
Landmarks:UsIngthemaneuversdescrIbed,theInterscalenegrooveIspalpatedby
rollIngthefIngersposterIorlyoffthelateralborderofthesternocleIdomastoIdmuscle;
markthegrooveashIghaspossIble.AfterthepatIentrelaxes,thepromInent
transverseprocessofC6canoftenbefeltdIrectlyInthegrooveandshouldbemarked.
NeedlIng:AskInwhealIsraIsedIntheInterscalenegrooveatthelevelofthecrIcoId.A
22gauge,2.5cm(orless)InsulatedneedleIsIntroducedthroughthewheal.The
needleIsdIrectedmedIally,caudally,andslIghtlyposterIorlyInthedIrectIonoftheC6
transverseprocess.ThecaudadtIltoftheneedleIsImportanttoavoIdeItherenterIng
theneuralforamenorInjectIonIntotheduralnerverootsheath,andthushIghspInal
anesthesIaorspInalcordInjury.
101
AvoIdIngmedIalplacement,by
P.972
usIngamostlycaudadandposterIordIrectIon,mayreducetherIsksevenmore.The
superfIcIalstructuresoftheplexushavebeenshowntobelocatedatanaverage,
shallowdepthof5.5mm.
102
Figure 38-15.UltrasoundguIdedInterscaleneblockusInganInplaneneedle
alIgnmenttoalInearhIghfrequencyprobe.TheneedleIsdIrectedfromlateralto
medIalwIthaslIghtcaudalangletoavoIdtheIntervertebralforamen.The
roots/trunksoftheplexusareusuallyseenasthreeormoreroundorovalshaped
hypoechoIcstructuressandwIchedbetweenscalenusanterIorandmedIusmuscles
IntheInterscalenegroove.
NervelocalIzatIon:ApplyInganInItIalcurrentof0.8mAIssuffIcIentforstImulatIonof
theplexus(usuallyatadepthof1toJcm),andthecurrentIsreducedtoaImfora
thresholdcurrentof0.4mAbeforeInjectIonafterobtaInInganapproprIatemotor
response.0IaphragmatIcortrapezIustwItchesshouldbeavoIded,astheyare
assocIatedwIthcervIcalplexusstImulatIon;adIaphragmatIcresponseIndIcatesthat
thephrenIcnerveIsbeIngstImulatedandthattheneedleIstooanterIor.
njectIon:AftercarefulaspIratIon,25toJ0mLoflocalanesthetIcIsInjectedInsmall
IncrementstodetectIntraneuralorIntravascularplacementoftheneedle.
Procedure Using Ultrasound Guidance
ScannIng:TwoscannIngtechnIquesarerecommendedforvIewIngthebrachIalplexus
attheInterscalenelevel:(1)begInnInganterIorlyatthecrIcoIdcartIlagelevel(C6)
wIthmovementfromanterIorandmedIaltoposterIorandlateraltowardsthe
Interscalenegroove,and(2)scannIngproxImallyfromthesupraclavIcularfossatothe
InterscalenelocatIon(FIg.J815).
Figure 38-16.UltrasoundguIdedsupraclavIcularblockusInganInplaneneedle
alIgnmenttoasmallfootprIntcurvedprobe,anddIrectIngtheneedlefromlateral
tomedIalInaslIghtlysagIttalplane.Color0opplercanalsobeveryvaluableIn
locatIngthesubclavIanarteryquIckly,Inordertolocatetheplexustrunks/
dIvIsIonsImmedIatelysuperolateraltothevessel.
Appearance:AtthesupraclavIcularfossa,thebrachIalplexus(trunks/dIvIsIons)canbe
seenInshortaxIsasatIghtlyenclosedcluster(I.e.,ahoneycomb)superIorandlateral
tothesubclavIanartery(FIg.J816).AftertracIngthenervesInaproxImalfashIon
towardtheInterscalenegroove,thenervestructures(roots/trunks)InasagIttal
oblIquesectIonarevIsualIzedasthree(usually)oruptofIveroundorovalshaped
hypoechoIc(seeCommonTechnIques:NerveStImulatIonandUltrasoundmagIng)
structures,sometImeswIthfewInternalpunctateechoes,lyIngbetweenthescalenus
anterIorandmedIusmuscles.C8andT1rootsmaybedIffIculttoIdentIfybecauseof
theIrdepth.
10J,104
NeedlIng:AskInwhealIsraIsedInthegrooveatthelevelofthecrIcoIdcartIlage.A
22gauge,5cm(orless)needle(InsulatedIsrecommended)IsIntroducedeItherDDP
(seeCommonTechnIques)orPtotheprobe(FIg.J815)andadvancedtoa
maxImumofJcmformostpatIents.ForDDPneedleInsertIontechnIque,theclInIcIan
standsbesIdeorcephaladtotheprobeandplacestheInItIalneedlepuncturesIte
cranIaltotheprobe.The
P.97J
needleIstypIcallyangledsomewhatcaudallytowardtheUSbeamplane.ForPneedle
InsertIontechnIque,theneedleIsmovedfromlateraltomedIal(stIllslIghtlycaudad)
andwIllfIrstpenetratethescalenusmedIusmusclebeforeenterIngtheInterscalene
groove.tIsrecommendedtouseNStoprovIdefurthernervelocalIzatIon.
LocalanesthetIcspread:AtestInjectIonof05WIsrecommendedandwIllhelpconfIrm
nervelocalIzatIonandestImatethepatternoflocalanesthetIcspread.Local
anesthetIcshouldbedeposItedInthemIdstoftheneuralstructuressothatItspreads
tosurroundthenervescIrcumferentIally.LocalanesthetIcdIstentIonInthIs
compartmentcanbeseenbyUSasahypoechoIc(fluId)expansIon.
Comments
TheuseoflongactInglocalanesthetIcsmayprovIdeanalgesIafor12to14hours.For
longeranalgesIa,InsertIonofacontInuouscatheterIseffectIveforproceduressuchas
totalshoulderreplacement,althoughsecurIngthecathetersInthemobIlenecktIssues
Isachallenge.
EqualsuccesshasbeenachIevedwhenanyoftheapproprIatemuscleresponsesIs
elIcItedasaposItIvestImulatIngtest.PalpatIonofthemusclemayconfIrmthe
response.
0espItethefactthatsubarachnoIdInjectIoncanoccurevenwhenthethreshold
currentIs0.4mA,ItIsadvIsabletoavoIdInjectIngwhenthecurrentresponsesare
presentat0.4mA.
ThemostcommonlyobservedmIstakeIsplacementoftheneedletooanterIortothe
optImalskInInsertIonsIte.However,notInfrequentlytheneedlemaybeplacedtoo
posterIorlyaswell.
nadequateanesthesIaIsmostlIkelytooccurIntheulnardIstrIbutIon.ThIsmaybe
reducedbyusInghIghervolumes(J5to40mL)oflocalanesthetIc.
facontInuousblockIsIndIcated,theneedleentrypoIntmaybemovedacentImeter
cephaladandthecorrespondIngangleofInsertIonIsalIttlesteeperandmore
tangentIaltothecourseoftheplexus.TheopenIngofthetIpoftheIntroducIngneedle
shouldbedIrectedlaterally.WhenusIngastImulatIngcatheter,theperIneuralspace
maybedIlatedIfnecessarytofacIlItatecatheterplacementwIth05WtomonItorIts
advancementtoalocatIonwheremotorresponseIsmaIntaInedat0.5mA.
SecurIngcathetersInthefreelymobIleneckIsachallenge.Someprefertosecurethe
catheterbytunnelIngJto4cmbelowtheskInbypassIngItbackthroughan
IntravenouscatheterthathasbeenIntroducedsubcutaneouslyneartheentrysIte.
0urIngDDPUSguIdedtechnIque,anglIngtheneedlemorethan45degreesshouldbe
avoIdedastheneedlemaybeInsertedtoodeepanddIrectedtowardthespInalcord.
ComplIcatIonsfromthIsapproacharerelatedtothestructureslocatedInthevIcInIty
ofthetubercle.ThecupolaofthelungIsclose,partIcularlyontherIghtsIde,andcan
becontactedIftheneedleIsdIrectedtoofarcaudally.Pneumothoraxshouldbe
consIderedIfcoughorchestpaInIsproducedwhIleexplorIngforthenerve.fthe
needleIsallowedtopassdIrectlymedIally,ItmayentertheIntervertebralforamen,
andInjectIonoflocalanesthetIcmayproducespInalorepIduralanesthesIa.The
vertebralarterypassesposterIorlyatthelevelofthesIxthvertebratolIeInItscanal
Inthetransverseprocess;dIrectInjectIonIntothIsvesselcanrapIdlyproducecentral
nervoussystemtoxIcItyandconvulsIons.CarefulaspIratIonandIncrementalInjectIons
areImportanttohelpavoIdbothofthesepotentIalproblems.
EvenwIthapproprIateInjectIon,localanesthetIcsolutIoncanspreadtocontIguous
nerves.tmayproducecervIcalplexusblock,IncludIngmotorfIberstothedIaphragm,
whIchmaybeaproblemInpatIentswIthrespIratoryInsuffIcIency.HornersyndromeIs
commonbecauseofspreadtothesympathetIcchaInontheanterIorvertebralbody.
NeuropathyoftheC6rootIsapotentIalproblembecausetheneedlemay
unIntentIonallypInthenerverootagaInstthetubercleandpredIsposetoIntraneural
InjectIon.TheneedleshouldbewIthdrawnslIghtlyIfthefIrstInjectIonproducesthe
characterIstIccrampypaInsensatIon.
AnalternatIvetechnIqueforblockIngtherootsofthebrachIalplexusIstoperforma
cervIcalparavertebralblock,
105
whIchcanusethebonylandmarksofthevertebral
column.ThIsIsahIghqualItyblock,whIchIsreadIlyperformedusIngUSguIdance.A
lateralUSvIewofthebrachIalplexusatthelevelofC6allowsvIsualIzatIonofthe
needleasItpasseslateraltotheC6transverseprocessandIntotheInterscalene
space.ThIsvIewavoIdsthechallengesofattemptIngtovIewthebrachIalplexusfrom
aposterIorapproachInwhIchthebonystructuresmayobscurethevIewoftheneedle
andplexus.
2. SupraclavIcularblocktargetsthetrunksand/ordIvIsIonsofthebrachIalplexus
dependIngonthelocatIonoftheInjectIonsIteandthepatIent'sanatomy.SImIlartothe
Interscaleneblock,thepatIentIsposItIonedsupInewIththeheadturnedapproxImately
45degreestothecontralateralsIde.PreparetheneedleInsertIonsIteandother
applIcableskInareaswIthanantIseptIcsolutIonandobtaInsterIlItyoftheUSprobewIth
astandardsleevecoverortransparentdressIng.
Landmarks:TheoutlIneoftheclavIcleIsdrawnontheskInandthemIdpoIntofthe
clavIcleIsmarked.AnXIsplacedposterIortothIsmIdpoIntIntheInterscalenegroove,
usually1cmbehIndtheclavIcle.ThesubclavIanarterypulseservesasarelIable
landmarkInthInnerIndIvIdualsastheplexuslIesImmedIatelycephaloposterIortothe
subclavIanartery.
NeedlIng:LocalInfIltratIonIsperformedatthesIteofthenerveanda2.5to5cm,22
gaugeneedleIsIntroducedIntheparasagIttalplaneatthesuperIorborderofthe
clavIcleatthelateraledgeofthesternocleIdomastoIdmuscleInsertIon.AnInItIal
InsertIonangleof45degreescephaladIsrecommended,wIthsubsequentreductIonsIn
angleasnecessary.
106
Lessthan20degreesmayleadtotheneedlecontactIngthe
pleuraand/orsubclavIanveInprIortotheplexus.TherIbmaybecontacted,wIth
subsequentanteroposterIorneedleadjustmenttocontacttheplexus,butavoIdIngrIb
contactmaybemostprudent.CarefullateralormedIalexploratIonmaybeneeded,
butthegreatestdangerofcontactIngthepleuraoccurswhenprobIngtoomedIally.
NervelocalIzatIon:TheresponsestoNScanbeveryusefulforconfIrmatIonofneedle
proxImItytotheseparatetrunks.TwItchesofpectoralIs,deltoId,bIceps(uppertrunk),
trIceps(upper/mIddletrunk),forearm(upper/mIddletrunk),andhand(lowertrunk)
muscleswIthcurrentIntensItyof0.4mA(0.1to0.Jms)areacceptable.0Istal
responses(handorwrIstflexIonorextensIon)arebesttoconfIrmplacementwIthInthe
fascIa.|ultIplenerveresponsesarenotrequIred.
njectIon:fanerveresponseIsproduceddurIngthecourseofexploratIon,the
anesthetIcsolutIonIsInjectedwhIletheneedleIsfIxedInposItIon.TwentyfIveto40
mLoflocalanesthetIcwIllproduceadequateanalgesIa.
Procedure Using Ultrasound Imaging
ScannIng:TheprobeIsfIrstplacedInacoronaloblIqueplaneatthelateralendofand
justabovetheupperborder
P.974
oftheclavIcle(FIg.J816).tIsthenmovedmedIallyuntIlanImageofthesubclavIan
arteryappearsonthescreen.SomedorsalandventralrotatIonoftheprobemaybe
necessary.WIththesubclavIanarteryInthemIddleofthescreen,theplexusIslocated
superolateraltothearteryandtheneurovascularstructuresarelyIngabovethefIrst
rIb.
Appearance:ThesubclavIanarteryIsanechoIc,hypodense,pulsatIle,andround;Its
IdentItycanbefurtherconfIrmedbycolor0oppler.Trunks/dIvIsIonsofthebrachIal
plexusappearasaclusterofhypoechoIcgrapelIkestructuresconsIstIngofusually
three(moreasonemovesdIstally)hypoechoIcnodules,allsurroundedbya
hyperechoIclInIng(presumablytheconnectIvetIssues).WIththeprobeInacoronal
oblIqueplane,theplexusdepthhasbeenshownwIthmagnetIcresonanceImagIngto
equal1.65cmInmalepatIentsand1.45cmInfemalepatIents.
106,107
|edIalanddeep
totheartery,therIbmaybeseenasahyperechoIclInewIthdorsalshadowIng.The
anechoIcsubclavIanveInmaybeseenInferomedIaltotheartery.
NeedlIng:TheselectedneedleInsertIonsIteIsoftenmorelateralwIththeUSguIded
technIquethanwhenusIngNStechnIques.TheskInIsInfIltratedwIthlocalanesthetIc
anda22gauge,5cm(orless)needle(InsulatedIsrecommended)IsIntroducedwIthP
needlealIgnmenttoasmallfootprIntcurved(FIg.J816)orlInearprobe.TheneedleIs
InsertedImmedIatelyabovetheclavIcleInalateraltomedIaldIrectIonwIthaslIght
cephaladangle.tIsrecommendedtofollowNSprocedureforaddItIonalconfIrmatIon
ofnervelocalIzatIon.
LocalanesthetIcspread:tIsbesttodeposItlocalanesthetIcnexttothenerve
structuresImmedIatelylateraltothesubclavIanarteryontopofthefIrstrIb.njectIon
InthIslocatIonwIlloftenlIftthenervestructuressuperIorlyawayfromthefIrstrIb
andsubclavIanartery.ThehypoechoIcspreadoflocalanesthetIcsurroundIngthe
nervesmaybeseenontheUSscreen.
Comments
tIsrecommendedtouseUSImagIngInaddItIontoNStechnIquedurIngthIsblockto
helpavoIdpuncturIngthepleura.tIscrItIcaltomeasuretheskInpleuradIstancewIth
USprIortoneedleInsertIon.TheresponsestoNScanbeusefulforconfIrmatIonof
needleproxImItytotheseparatetrunks.
ThemajorchallengewIthUSImagIngInthIsregIonIsthepresenceofabony
promInence(clavIcle)andcurvedsofttIssuecontourthatcanInterferewIthImagIngof
thebrachIalplexusInshortaxIs.0espItedIsadvantageswIthcurrentlowtomoderate
frequencycommercIallyavaIlablecurvedarrayprobes(e.g.,C11,TItanor|Icro|axx,
SonosItenc.,8othell,WA);acurvedarrayprobewIthasmallfootprIntIsextremely
usefulInthIscompactarea.
ThelateraltomedIalPneedleapproachwIllensuretheneedleapproachesthenerve
structuresprIortoreachIngthesubclavIanartery(I.e.,lesschanceofInadvertent
vascularpuncture).0espItethIs,usIngaslIghtlysagIttalplane(FIg.J816)mayreduce
therIskofpleuralpuncture.TheneedleshouldbevIewedatalltImeswhenusInga
lateraltomedIaldIrectIon.
ThegreatestfearwhenusIngthIstechnIqueIstherIskofpneumothoraxasthecupola
ofthelunglIesjustmedIaltothefIrstrIb,notfarfromtheplexus.TherIskof
pneumothoraxIsgreaterontherIghtsIdeasthecupolaofthelungIshIgheronthat
sIde.TherIskIsalsogreaterIntall,thInpatIents.
DthercomplIcatIonsofPN8ofthebrachIalplexusdonotoccurwIthanygreater
frequencywIththIsblockthanwIthothermethodsofbrachIalplexusblock.
J. nfraclavIcularblocktargetsthecordsofthebrachIalplexus,andthenervescanbe
blockednexttothesecondpartoftheaxIllaryarteryatthelevelofthecoracoId
process.8rachIalplexusblockIntheInfraclavIcularareaoffersexcellentanalgesIaofthe
entIrearmandallowsIntroductIonofcontInuouscatheterstoprovIdeprolonged
postoperatIvepaInrelIef.TheInfraclavIcularapproachblocksthemusculocutaneousand
axIllarynervesmoreconsIstentlybecausethesetwonervesoftenbranchoffhIghInthe
axIllaandareoftenmIssedwIththeaxIllaryblockapproach.However,multIple
InjectIonsmayberequIredforsuccessfulInfraclavIcularandaxIllaryblocks.
nfraclavIcularblocksareIndIcatedforforearm,elbow,andhandsurgery.ThepatIentIs
supInewIththeheadturnedapproxImately45degreestothenonoperatIvesIde;thearm
mayeItherbeatthesIdewIthhandontheabdomenorabductedwIththepalmplaced
behIndthehead.WhenpreparIngforthIsblock,ItIscommontoperformtheblockwIth
thepatIent'selbowflexedandthehandrestIngontheabdomentofacIlItateobservatIon
ofmotorresponsesgeneratedwIthNS.AlternatIvely,externallyrotatIngthearmand
placIngthehandbehIndtheheadstretchesthecordsandbrIngsthenervescloseraround
theaxIllaryartery,whIchmayfacIlItatelocalanesthetIcspreadaroundthenerves.As
always,preparetheneedleInsertIonsIteandotherapplIcableskInareaswIthan
antIseptIcsolutIonandobtaInsterIlItyoftheUSprobewIthastandardsleevecoveror
transparentdressIng.
Procedure Using Nerve Stimulation Technique.Severalapproacheshavebeen
descrIbedforInfraclavIcularblock,allwIthvarIousneedlepuncturesItesandanglesof
InsertIon.
108,109,110,111,112,11J
HerewedescrIbealateralapproach,
109
whIchmayImprove
plexuscordlocalIzatIonandreducerIskofpuncturetoboththepleuraandaxIllary
artery.
114,115
Landmarks:WIththepatIent'sarmadductedandthehandrestIngontheabdomen,the
medIalaspectofthecoracoIdprocessIspalpatedasoneslIpsthefIngeroffthe
clavIcle.
NeedlIng:AfterskInpreparatIonandskInwheal,a5to9cm,18to22gaugeneedleIs
InsertedwheretheclavIclemeetsthemedIalaspectofthecoracoIdprocess,dIrected
generallyat0to15degreesposterIortothehorIzontalplane(FIg.J817IllustratesthIs
needleInsertIonwhenusIngUSguIdance).The15degreetrajectorywIlllIkelyIncrease
thechancesofcontactIngthemoreposterIorlylocatedposterIorormedIalcords,
whIchmayImproveanalgesIa.AgreateranglemayberequIredtoachIeveadequate
responsestoNSbecauselocalanesthetIcInjectIonatmorethanonecordmaybe
benefIcIal.ThecordsshouldbereachedatapproxImately4to6cmdepth(morethan
7.5cmmayrIskpleuralpuncture).
109
TheneedlepuncturesItemaybeadjusted
slIghtlycaudadtothIslocatIon,aswIththetechnIqueofKapraletal.
108
ftheneedle
Isplacedat2.5cmcaudadtothecoracoIdprocess,alaterallyprojectedneedle
dIrectedtowardtheaxIllaryarterymaybeeffectIve.
109
NervelocalIzatIon:ThefIrstresponse(elbowflexIon)obtaInedIsusuallythe
musculocutaneousnervearIsIngfromthelateralcord.ForcompleteanesthesIaofthe
hand,aseparatedIstalresponseneedstobeobtaInedfromthemedIal(dIstalflexors)
andposterIor(dIstalandproxImalextensors)cords.
116
AsImplIfIedapproachto
determInIngthespecIfIccorddIstalresponsesdurIngInfraclavIcularblockhasbeen
descrIbed.
117
AcloseexamInatIonofthemovementsofthefIfthdIgItcanbeusefulto
dIfferentIatethecords,wIthlateralmovement(I.e.,pronatIon)representIngthe
lateralcord,medIalmovement(I.e.,flexIon)representIngthemedIalcord,
P.975
anddorsalmovement(I.e.,extensIon)representIngtheposterIorcord.
117
Somealso
advocatethatelIcItIngaforearmresponse(pronatIonvIathelateralcord)IsessentIal
foracompleteblock.
118
ThearterymaybepuncturedeasIlyatthIspoInt,andcareful
aspIratIonIsrequIredtopreventIntravascularInjectIon.
Figure 38-17.UltrasoundguIdedInfraclavIcularblockusInganInplaneneedle
alIgnmenttoalInearprobe,anddIrectIngtheneedle15degreesposterIorlyIna
cephaladtocaudaddIrectIon.ncontrasttothemoreproxImalblocks,thenerves
(cords)appearhyperechoIcnowbecauseoftheIrhIgherfascIalcontentand
becausethesurroundIngtIssue(muscle)IslargelyhypoechoIc.
njectIon:famusculocutaneousnerveresponseIsfIrstobtaIned,thenerveorlateral
cordcanbeblockedbyanInjectIonof5to10mLoflocalanesthetIc.Dnceresponses
InthehandareobtaIned,afurther25mLoflocalanesthetIccanbeInjectedalongthe
posterIorandmedIalcords.
ScannIng:mmedIatelymedIalandInferIortothecoracoIdprocess,posItIonalInearor
curvedlowerfrequencytransducer(4to7|Hz)InaparasagIttalplaneandcapturethe
bestpossIbleshortaxIsvIewofthebrachIalplexuscordsandaxIllaryvessels(FIg.J8
17).fthepatIentIsquItethInorIfusIngamoremedIallocatIon(notdescrIbedhere)
wherethenervesaremoresuperfIcIal,ahIgherfrequencyprobemaybeused.
Appearance:ThepectoralIsmajorandmInormusclesareseparatedbyahyperechoIc
lInIng(perImysIum);thepectoralIsmajorlIessuperfIcIalandlateraltothepectoralIs
mInormuscle.0eeperatadepthofapproxImately4to5cmlIestheaxIllary
neurovascularbundle;thelargeaxIllaryveInlIesmedIallyandcaudallytotheartery.
ThelateralcordoftheplexusIsoftenreadIlyvIsualIzedasahyperechoIcoval
structure;themedIalandposterIorcordsmaynotbereadIlyIdentIfIedbecausethe
medIalcordlIesbetweentheaxIllaryarteryandveIn,andtheposterIorcordcanbe
hIddendeeptoanaxIllaryarteryacoustIcshadow.naddItIon,themedIalcordcanbe
posterIororevenslIghtlycephaladtotheaxIllaryartery.tIsImportanttorealIzethat
thereIsagreatdealofIndIvIdualanatomIcvarIatIonInthecordlocatIonaroundthe
artery.ThenervestructuresnowappearhyperechoIc,ratherthanhypoechoIcasseen
moreproxImally,presumablybecauseofanIncreaseInthenumberoffascIclesand
amountof(hyperechoIcappearIng)connectIvetIssue.
90
NeedlIng:TheskInIsInfIltratedwIthlocalanesthetIc.A5to9cm,18to22gauge
Insulatedneedle,IfusIngNS,IsusedforsIngleshottechnIque;a9cm,17to20gauge
needleIssuItableforcatheterplacement.UsInganPneedlealIgnmentwIllbemost
suItableInmostcases;theblockneedleIsInsertedcephaladtotheprobe.tIsthen
advancedcaudallyandposterIorlyatapproxImatelyJ0degreestotheskIn.Thecords
shouldbereachedatadepthof4to6cm,sImIlartoblIndtechnIque.
119
tIs
recommendedtocombIneUSwIthNSforaccuratenervelocalIzatIon(e.g.,
musculocutaneousnerveorspecIfIccord)becauseofthehIghvarIabIlItyofcord
locatIon.
LocalanesthetIcspread:AImtoplacetheneedleandlocalanesthetIcposterIortothe
axIllaryarterynexttotheposterIorcord(spreadfromthIslocatIonIsmostoptImalfor
completeblocksuccess).PerformIngatestdosewIth05WIsrecommendedprIorto
localanesthetIcapplIcatIontovIsualIzespreadandconfIrmnervelocalIzatIon.nject
20to25mLoflocalanesthetIcaroundtheposterIorcord.flocalanesthetIcspreadIs
deemedInadequatetosurroundallcords,reposItIontheneedleprIortoInjectIngany
addItIonallocalanesthetIc.
Comments
nthepast,numeroustechnIquesweredevelopedwIthmodIfIcatIonstolocalIzenerves
andavoIdvesselandpleuralpunctures.FealtImeguIdancewIthUSwIlladdresssome
oftheseIssues,althoughUSguIdedblocksaregoIngthrougharapIddevelopment
processtodetermInethesafestandmostsuccessfulapproaches.
TechnIquesthatIncorporatemultIpleInjectIonsmaybeeasIerandpotentIallysafer
undercombInedUSandNSguIdance,whIchprovIdesdIrectvIsualIzatIonofthe
anatomIcstructures.
facatheterIstobethreaded,theaImshouldbetoelIcItmotorresponsesInthehand
Itself.ThetIpoftheTuohyneedle(9cm,17to20gauge)shouldbedIrectedlaterally
toallowthecathetertorunInthedIrectIonofthenerves.
AscomparedwIthblocksatmoreproxImallocatIons,theInfraclavIcularblockhasthe
advantageoflowerrIskofblockIngthephrenIcnerveorstellateganglIon.However,In
somecases,contInuouscathetersmaylIealongonecordandfaIltoprovIdecomplete
anesthesIaandanalgesIaoftheentIrebrachIalplexuswIthsmallvolumeInfusIons.
ThIsmayoftenbeovercometosomedegreebyIntermIttentbolusesoflargervolumes
oflocalanesthetIc.
7esselpunctureIsapotentIalcomplIcatIon;therefore,frequentaspIratIonshouldbe
performed.ThelateralneedleInsertIonwIllhelpavoIdtherIskofpneumothorax.
P.976
Figure 38-18.UltrasoundguIdedaxIllaryblockusInganInplaneneedlealIgnment
toalInearhIghfrequencyprobe.TypIcally,theblockneedleIsadvancedIn
sequencetoreacheachofthemedIan,ulnar,andradIalnerves.
4. AxIllary8lock,ThenervestargetedfortheaxIllaryblockcoursedIstallywIththeaxIllary
arteryandveInalongthehumerusfromtheapexoftheaxIlla(FIg.J81J).ThIsblockIs
usefulforsurgeryoftheelbow,forearm,andhand.Theulnar,medIan,andradIalnerves
aretheprImarytargets;themusculocutaneousnerveoftenleavestheplexus(vIathe
lateralcord)proxImaltothIspoIntandmaybeblockedseparatelydurIngtheaxIllary
block(InthecoracobrachIalIsmuscle)orseparatelyatmIdhumerallocatIons(alongIts
dIagonalcoursethroughorbeyondthecoracobrachIalIsmuscle).FelatIvetothethIrd
partoftheaxIllaryartery,thIsIstheusualcourseofthetermInalnerves:themedIan
nervelIesanterIorandmedIal,theulnarnervelIesposterIorandmedIal,the
musculocutaneousnervelIesanterIorandlateral,andtheradIalnervelIesposterIorand
lateral.8ecauseoftheobservatIonthatthesInglesheathmaybebrokenupInto
separatecompartmentsbyfascIalseptasurroundIngIndIvIdualnervesIntheaxIlla,some
advocatethatlocalanesthetIcshouldbeInjectedatmultIplesItesIntheaxIllaIn
contrasttothesIngleInjectIonspossIblewIthproxImalapproaches.ThepatIentIs
posItIonedsupInewIththearmabductedat70to80degreesandexternallyrotated,the
elbowflexedat90degrees,andthedorsumofthehandfacIngthetable.
Landmarks:TheaxIllaryarteryIsmarkedashIghInItscourseIntheaxIllaasIs
practIcal.tIsusuallyfeltIntheIntramusculargroovebetweenthecoracobrachIalIs
andthetrIcepsmuscles.talsopassesbetweentheInsertIonsofthepectoralIsmajor
andthelatIssImusdorsImusclesonthehumerus.
NeedlIng:AJ.5to5cm,22gaugeInsulatedneedleIssuItableforthIsblock.After
aseptIcpreparatIon,askInwhealIsraIsedovertheproxImalportIonoftheartery.The
IndexandmIddlefIngersofthenondomInanthandstraddlethearteryjustbelowthIs
poInt,bothlocalIzIngthepulsatIonandcompressIngtheneurovascularbundlebelow
theIntendedsIteofInjectIon.TheneedleIsInsertedInaslIghtcephaladdIrectIon,In
atwostep,fourInjectIonprocesswIthpunctureatlocatIonsjustsuperIorandInferIor
totheartery.
NervelocalIzatIon:WIthNStechnIque,Ideally,thenervesservIngtheareaofproposed
surgeryaresoughtfIrst.ThemedIanandthemusculocutaneousnerveslIeonthe
superIoraspectoftheartery(asvIewedbytheoperator),whereastheulnarandradIal
nerveslIebelowandbehIndthevessel.DbtaInIngadIrectmusculocutaneousnerve
response(elbowflexIon)IndIcateslocalIzatIonofthIspartIcularnerve,butnot
necessarIlyallnerves.
njectIon:ExperIencehasshownthatamultIpleInjectIontechnIquearoundeach
IndIvIdualnerveIsthemostrelIableapproach(10to15mLateachnervelocatIon);It
mayrequIrelessvolumebutthemInImumrequIreddose/volumepernerveIsnot
knownatthIstIme.
ScannIng:HIghfrequency,lInearprobesaregenerallyrecommended(10to15|Hz)for
ImagIngbecausethenervesaresuperfIcIal(1to2cm)belowtheskIn(FIg.J818).The
mostproxImallocatIonattheapexoftheaxIllamaybethebestforvIewIngallofthe
termInalbranchesofthebrachIalplexus.TheprobeIsposItIonedperpendIculartothe
anterIoraxIllaryfoldandIncrosssectIontothehumerusatthebIcIpItalsulcus(andat
theleveloftheaxIllarypulse)tocapturethetransverse,orshortaxIs,vIewofthe
neurovascularbundle.
Appearance:ncrosssectIon:
ThebIcepsbrachIIandcoracobrachIalIsmusclesareseenlaterally;thetrIceps
brachIImuscleIsmedIally,deeperthanthebIcepsbrachIImuscle
TheanechoIcandcIrcularaxIllaryarterylIescentrally,adjacenttoboththebIceps
brachIIandcoracobrachIalIsmuscles;ItIssurroundedbythenerves
ThenervesappearroundtoovalInshortaxIs;generallytheyappearashyperechoIc
massesbecauseofthelargeamountofconnectIvetIssue(epIandperIneurIum)
InterspersedwIthInthehypoechoIcnervefascIcles
ThemediannerveIsoftenlocatedsuperfIcIalandbetweenthearteryandbIceps
brachIImuscle;theulnarnerveIsusuallylocatedmedIalandsuperfIcIaltothe
artery;theradialnervelIesdeeptothearteryatthemIdlIne(clockwIse:medIan,
ulnar,radIal,buttherearemanyvarIatIons)
ThemusculocutaneousnerveIscommonlylocatedInthehyperechoIcplanebetween
thebIcepsbrachIIandcoracobrachIalIsmuscles
NeedlIng:A5cm,22gaugeInsulated(combInedUSandNStechnIqueIsrecommended)
needleIssuItable.8othPandDDPneedleapproachescanbeusedforaxIllary
P.977
block.AnDDPapproach,wIththeneedledIstaltotheprobeandIntransverseaxIsto
thenerve,IssImIlartothetradItIonalblIndprocedure,exceptthattheneedlewIllbe
alIgnedatanangletooptImIzeneedlevIsIbIlItyratherthanmoreperpendIculartothe
skIn.UsInganangleofJ0to45degreesfromtheskIn,wIththeneedleplaced
approxImately1to2cmcaudallytotheprobemayallowoptImalneedlevIsIbIlIty(see
thedescrIptIonofthewalkdowntechnIqueInCommonTechnIques:Nerve
StImulatIonandUltrasoundmagIng).
J4,J6
ThePapproachInvolvesInsertIngthe
needleatanacuteangle(20toJ0degrees)totheskInInalateraltomedIaldIrectIon
(FIg.J818).TypIcally,theblockneedleIsadvancedtocontactthemedIannerve.tIs
thencrossedovertheaxIllaryarterytocontacttheulnarnervesuperfIcIallyandthen
fInallybehIndthearterytothedeeperradIalnerve.FollowtheNSprocedureIfusIng
thIstechnIque.
LocalanesthetIcspread:PerformIngatestdosewIth05WIsrecommendedprIorto
localanesthetIcapplIcatIontovIsualIzespreadandconfIrmnervelocalIzatIon.A
properInjectIonIsIndIcatedbyfluIdspreadcompletelyaroundthenervestructure,
wIthnervemovementawayfromtheneedletIp.mproperInjectIon,suchasInjectIon
outsIdethesheath,IsIndIcatedbyapartIalasymmetrIcalfluIdexpansIonnot
ImmedIatelyadjacenttothenervestructure.
Comments
AlthoughthemultIpleInjectIonNStechnIquehasbeenusedextensIvelyforthIsand
otherblocks,ItIsImportanttoconsIderthatsomespreadofthelocalanesthetIc
solutIonwIlloccurandhypesthesIacanoccurInanunpredIctablefashIon,lImItIngthe
IdentIfIcatIonofsubsequentnerves.
fforearmanesthesIaIsrequIredandthemusculocutaneousnervewasnotlocalIzed
prevIously,supplementaryanesthesIaofthemusculocutaneousnerveshouldbe
attaInedusIngsomerelIablemeansofnervelocalIzatIon(I.e.,NSand/orUSguIdance)
ratherthanblIndInjectIonIntothecoracobrachIalIsmuscle.USImagIng1to2cm
dIstaltotheaxIllaryblocklocatIoncanclearlyIdentIfythemuscleandusuallythe
nerve.
ntercostobrachIalandmedIalantebrachIalcutaneousnerveblockscanbeachIevedby
subcutaneousInjectIons(5mL)onthemedIalsurfaceoftheupperarmalltheway
fromthebIcepstotrIcepsmuscles.
PerIvascularInfIltratIonandtransarterIalapproachesarealsodescrIbedforaxIllary
block.
ForcontInuousnerveblocks,acathetercanbethreadedcentrallyafternerve
localIzatIon.A17to18gaugeneedleIsrequIredtofacIlItatecatheterplacement.
SecurIngthecatheterIntheaxIllamaybechallengIngandmayrequIreashorttunnel
tostabIlIzethecatheter.
AxIllaryapproachestothebrachIalplexusareassocIatedwIthmInImalcomplIcatIons
comparedwIthmoreproxImalbrachIalplexusblocks.Neuropathyfromneedle
punctureorIntraneuralInjectIonoflocalanesthetIcIstheforemostconsIderatIon,
althoughthIsmaybereducedwIthUSImagIngandcarefulattentIontoInjectIon
pressuresdurIngtheblock.HematomacanoccurIftheaxIllaryarteryIspunctured,but
thIsIsselflImItIngcomplIcatIon.
Terminal Upper Extremity Nerve Blocks
PN8sIntheupperextremItyareofpartIcularvalueasrescueblockstosupplement
IncompletesurgIcalanesthesIaandtoprovIdelonglastIngselectIveanalgesIaInthe
postoperatIveperIod.TheperIpheralnervesmaybeIndIvIduallyblockedatmIdhumeral,
elbow,orwrIstlocatIons,dependIngonthespecIfIcnerve.fusIngUSguIdance,theelbow
andforearmregIonsappeartobethemostsuItableblockregIonsandblocksatthesesItes
mayImprovetheaccuracyofnervelocalIzatIonandlocalanesthetIcspread.ThewrIstIs
hIghlypopulatedwIthtendonsandfascIaltIssues(e.g.,flexorandextensorretInaculae),
whIchcanbedIffIculttodIstInguIshfrom,andmayobscuretheImagesof,thenerves.WIth
thehelpofcolor0oppler,UScanbeusedtoclearlyIdentIfythenervesatmanydesIrable
locatIonsastheyareoftensItuatednearbloodvessels(TableJ81).ThIssectIonwIllfocus
onthoseblockswhereNSandUSImagIngaremostamenable,butwIllcommentonnerve
blocksatthewrIstforcompletIon.8lockofthemusculocutaneousnerveatthemIdhumeral
levelIsdIscussedInthesectIononaxIllaryblock.FIguresJ81JandJ814Illustratethe
coursesandcutaneousInnervatIonofthetermInalnervesoftheupperextremIty.
1. FadIalnervecanbeblockedattheanterosuperIoraspectofthelateralepIcondyleofthe
humerus.TheradIalnervesupplIestheposterIorcompartmentsofthearmandforearm
IncludIngskInandsubcutaneoustIssues.talsosupplIesskInontheposterIoraspectof
thehandlaterallynearthebaseofthethumbandthedorsalaspectoftheIndexandthe
lateralhalfoftherIngfIngeruptothedIstalInterphalangealcrease.ThepatIentIs
posItIonedsupInewIththearmslIghtlyabductedandlaterallyrotatedandwIththe
elbowextended.
Landmarks:AlIneIsdrawnontheanterIorelbowbetweenthemedIalandlateral
epIcondylesofthehumerus.TheradIalnerveIslocatedbeneaththIsIntracondylar
lIne,approxImately1to2cmlateraltothebIcepstendon.ThIsposItIonshouldbe
markedwIthanX.
NeedlIng:AJ.5to5cm,22to24gaugeInsulatedneedleIsusedandaskInwhealIs
raIsedattheX.TheneedleIsthenInsertedperpendIculartotheplanepassIngthrough
thehumeralepIcondyles.
NervelocalIzatIon:ThecorrectresponsetoradIalNSatthIslocatIonIsextensIon
(dorsIflexIon)ofthewrIstanddIgItsontheoperatIvesIde.ElbowextensIonshouldnot
beelIcItedasthebranchtothelongheadofthetrIcepshasbranchedoffproxImally.
njectIon:ApproxImately5mLoflocalanesthetIcIsInjectedunderlowpressure.
ScannIng:AlInearprobeInthefrequencyrangeof5to10|HzIssuItableforscannIng
Inmostcases(FIg.J819).TheradIalnervecanfIrstbelocatedproxImallyatthelevel
ofthespIral(radIal)grooveofthehumeruswhereItlIesImmedIatelyadjacentthe
humerusandposteromedIaltothedeepbrachIal(profundabrachII)arteryofthearm.
ThepatIent'sarmshouldbeInternallyrotatedandplacedwIththehandoverthe
abdomenontheopposItesIdeofthebody.ThespIralgroovelIesImmedIatelydIstal
andposterIortothedeltoIdtubercle.SubsequenttracIngofthenervefromthIs
humerallocatIontotheanterolateralelbowmayfacIlItateItsprecIselocalIzatIon.The
probecanberotatedslowlytoscanthenervebothInthelongItudInalandtransverse
planesattheelbowforconfIrmatIonofItslocatIon.
Appearance:AtthespIralgrooveofthehumerus,thehumerusIsquItesuperfIcIaland
appearsdeeptothehypoechoIctrIcepsbrachIImuscleasaclearlydemarcated
hyperechoIcovalshapewIthdarkshadowIngInItsInterIor(notshownInFIg.J819).
ThenerveappearsovalandpredomInantlyhyperechoIc;ItIslocatedIntheposterIor
aspectofthehumerusandImmedIatelyadjacenttothesmall,pulsatIledeepbrachIal
(profundabrachII)artery(asverIfIedwIth0oppler).AtapoIntjustproxImaltothe
anterIorcompartmentoftheelbow,the
P.978
humerushaschangedInshapeandappearssmallerandalmostrectangularIncross
sectIon.ThehyperechoIcradIalnervenowlIesatsomedIstancefromthehumerusand
IssandwIchedbetweenthebrachIalIsandbrachIoradIalIsmuscles;ItremaInsovalIn
shape.
Figure 38-19.UltrasoundguIdedradIalnerveblockusInganoutofplaneneedle
alIgnmenttoalInearprobeattheanterolateralelbow.TheIdealplacementwIll
beafewcentImetersabovetheelbow,wherethenervehasnotyetdIvIdedInto
superfIcIalanddeepbranches.
NeedlIng:AJ.5to5cm,22gaugeInsulatedneedleIssuItableIfusIngNS.Theneedle
canbealIgnedbothPandDDP(FIg.J819)totheprobetoblockthenerveatthe
anterosuperIoraspectofthelateralepIcondyleofthehumerus.Thenerveshouldbe
blockedslIghtlyabovetheelbowbecauseItdIvIdesIntodeepandsuperfIcIalbranches
approxImately2cmabovethatsIte.TheblockneedleIsadvancedtoapproachthe
targetnerveonItssIde,preferablyavoIdIngdIrectneedlecontactwIththenerve.
localanesthetIcapplIcatIontovIsualIzespreadandconfIrmnervelocalIzatIon.The
aImIstoInjectapproxImately5mLoflocalanesthetIcandseespreadaroundthe
nervecIrcumferentIally.
Comments
NeedlecontactwIththehumerusIndIcatesthattheneedleIstoodeep,whIledeep
needlepenetratIonwIthoutbonecontactIndIcatesthattheneedleIslateraltothe
humerus(beyondthebone).
TheradIalnervecanbeblockedatthewrIstorevenlateraldIstalforearmadjacentto
theradIalartery.AtthewrIst,JmLofsolutIonIsInjectedIntotheanatomIc
snuffboxformedbythetendonsoftheextensorpollIcIslongusandextensorpollIcIs
brevIstendons.AsubcutaneouswhealIsthenraIsedfromthIspoInt,extendIngover
thedorsumofthewrIstJto4cmontothebackofthehand.ThIsapproachIs
suboptImalformostproceduresbecausethenervedIvIdesImmedIatelybeyondthe
elbowandcontInuesasthesuperfIcIalradIal(sensory)andthedeepposterIor
Interosseous(motor)nerves.
2. |edIannervecanbeblockedatthemIdlIneoftheanterIorelboworatthemIdtodIstal
aspectoftheanterIorforearm(FIg.J820).ThenerveIslocatedadjacent(medIal)tothe
brachIalarteryattheelbow,facIlItatIngItslocalIzatIonhere.ntheforearm,thenerve
canbelocatedatItsposItIonlateraltotheulnarnerve.ThenervesupplIestheskIn,
anterIorly,onthemedIalsurfaceofthethumb,palm,anddIgItstwothroughfourand
posterIorlyonthedIstalthIrdofthesecondthroughforthdIgIts.tcausesflexIonatthe
metacarpophalangealjoIntsandextensIonattheInterphalangealjoIntsofdIgItstwoand
three.ThenerveInnervatesmuscles,whIchproduceflexIonandopposItIonofthethumb,
mIddleandIndexfIngers,andpronatIonandflexIonofthewrIst.Forblocksatthe
anterIorwrIstoranterIordIstalforearm,thepatIent'sarmshouldbeposItIonednextto
thetorso,wIththeelbowflexedslIghtlyandthehandfreetoallowawrIstorthumb
flexIonresponseelIcItedbyNS.
Figure 38-20.AnIllustratIonoftheanterIorforearmshowIngthecoursesofthe
medIanandulnarnerves.TheulnararteryIsarelIablelandmarktolocalIzethe
ulnarnervewhenusIngultrasoundImagIng.
P.979
Procedure Using Nerve Stimulation Technique at the Elbow
Landmarks:ThesameIntracondylarlIneIsdrawnaswIththeradIalnerveblock,and
thenerveIslocatedwherethIslInecrossesthepulsatIonofthebrachIalartery,usually
1cmtotheulnarsIdeofthebIcepsbrachIItendon.
NeedlIng:UsIngaJto5cmInsulatedneedle,askInwhealIsraIsedatthepoInt
desIgnatedwIthlandmarkIng(above)andtheneedleIsIntroducedperpendIcularlyat
thIspoInt.
NervelocalIzatIon:NerveresponsestoelectrIcalstImulatIonaresoughtImmedIately
adjacenttotheartery.TheoptImalNSresponseformedIannerveblockattheelbow
locatIonIsanyoneofthefollowIngoracombInatIonthereof:flexIonandopposItIonof
thethumb,mIddleandIndexfIngers,flexIonofthewrIst,andpronatIonofthe
forearm.
njectIon:njectIonof5mLoflocalanesthetIcshouldsuffIceforblockIngthIsnerve.
CareshouldbetakentoavoIdIntravascularandIntraneuralInjectIon.
Procedure Using Nerve Stimulation Technique in the Forearm.tmaybedIffIcultto
blIndlylocatethIsnerveIntheforearmusIngNS,althoughthetechnIqueof
transcutaneouselectrIcalstImulatIon,
17
orsImIlarlypercutaneouselectrode
guIdance,
18,120
canbeusedtolocatethenerveusIngaprobeplacedonorIndentIngthe
skIn'ssurface.DncethenervehasbeenlocalIzed,anInsulatedneedleIsInserted
perpendIculartotheplaneoftheforearmandNSresponsesaresought.AsImIlarvolume
oflocalanesthetIcshouldsuffIce.
Procedure Using Ultrasound Imaging (Elbow and Forearm)
ScannIng:AhIghfrequency(10to15|Hz)lInearprobecanbeusedtocapturea
transversevIewofthenerveandlocalIzethebrachIalartery(1)attheelbowwhere
thenervelIesmedIaltoboththearteryandthenthetendonofthebIcepsbrachII
muscle(FIg.J821),and(2)IntheanterolateralforearmwhereItlIeslateraltothe
ulnarnerveandartery(localIzIngtheulnarnervefIrstwIllhelpIdentIfythemedIan
nerve)(FIg.J822).Color0opplermaybeusedtoconfIrmthelocatIonofthese
arterIes.
Appearance:Attheelbow,themedIannervecanbeIdentIfIedatapproxImately1to2
cmdepthasahyperechoIc,yetdIstInctlyhoneycombstructure,lyIngmedIaltothe
anechoIcpulsatIlebrachIalartery.0eeptotheneurovascularstructureslIesthe
musculatureofthesuperIoraspectoftheelbow(pronatorteresandbrachIalIs
muscles)asahypoechoIchomogeneousmass.Attheforearm,thenerveappearsoval
shapedandlateraltotheulnarnerveandartery.
Figure 38-21.UltrasoundguIdedmedIannerveblockusInganoutofplaneneedle
alIgnmentatthemedIalaspectoftheanterIorelbow.ThenervelIesmedIaltothe
largeanechoIcbrachIalartery.
NeedlIng:8othDDPandPtechnIquescanbeusedforeItherblocklocatIon.ForDDP
needlIngattheelbow(FIg.J821),afteradjustIngtheUSImagetohavethenerve
locatedInthemIddleofthescreen,InsertaJ.5to5cmInsulatedneedle
perpendIculartothetransverselyplacedprobeata45to60degreeangle.TheNS
procedureshouldbefollowedIfusIngacombInedtechnIque.ThePtechnIque,wIth
theneedleInamedIaltolateraldIrectIon,maybeadvantageousattheelbowto
alloweasytrackIngoftheneedletoensureItavoIdspuncturIngthebrachIalartery.
LocalanesthetIcspread:AfterperformIngatestdosewIth05W,theaImIstospread
approxImately5mLoflocalanesthetIcaroundthenerveInacIrcularfashIontoavoId
nervecontactandobtaIncompleteblock.
Comments
ThemedIannervelIesdeeptotheflexorretInaculumatthewrIst,andthereIsalways
thepotentIalrIskofcausIngcarpaltunnelsyndromefromelevatedpressurewIthInthe
tunnelfromtheInjectIonsolutIon.ForthIsreason,theelboworforearmlocatIonsfor
blockIngthemedIannervearethemorelogIcalchoIces.
AtthewrIst,themedIannervelIesbetweenthetendonsofthepalmarIslongusand
theflexorcarpIradIalIsmuscles.fonlythepalmarIslongusmusclecanbefelt,the
nervelIesjusttotheradIalsIdeofthIstendon.AskInwhealIsraIsed,andaneedleIs
InserteduntIlItpIercesthedeepfascIa.AnInjectIonofJmLoflocalanesthetIcIs
suffIcIenttoproduceanesthesIa.
8loodaspIratedIntothetubIngdurIngelbowblockIndIcatesbrachIalarterypuncture
andtheneedleshouldbereInsertedafterapplyIngpressuretothepuncturesIte;
contactwIththehumerusIndIcatesthattheneedleIstoodeep;localIzedcontractIon
ofthearmmuscles(e.g.,elbowflexIonand/orforearmpronatIon)IndIcates
stImulatIonofthelocalmusclesandthattheneedleIsalsolIkelytoodeep.
J. Ulnarnerve.ntheperIphery,theulnarnervecanbeblockedattheelbow,forearm,or
wrIst.UlnarnerveblockmaybeusedforrescueanalgesIaorblockofthefIfthdIgItfor
surgery.AtthejunctIonofthedIstalthIrdandproxImaltwothIrdsofthemedIal
forearm,thenerveIscommonlylocatedjustmedIaltothepulsatIleulnarartery(FIg.J8
20).
P.980
USguIdedtechnIqueIsadvIsedwhenusIngthIsblocklocatIonInordertoavoIdthe
arteryandlocalIzethenervemoreaccurately.TheulnarnerveInnervatesmusclesthat
produceflexIonoftherIng(fourth)andlIttle(fIfth)fIngersandulnardevIatIonofwrIst.
tsupplIestheskInoverthemedIalsurface(anterIorandposterIor)ofthehandand
dIgItsfourandfIve.ThepatIent'sarmIsflexedattheelbowbyJ0degrees,wIththe
shoulderexternallyrotatedandtheforearmsupInated.Theforearmcanrestonan
armboardwIthanaddItIonalpIllowunderthewrIst.PreparetheneedleInsertIonsIte
andskInsurfacewIthanantIseptIcsolutIon.PreparetheUSprobesurfacebyapplyInga
sterIlesheathoradhesIvedressIngtoItprIortoneedlIng.
Procedure Using Nerve Stimulation Technique at the Elbow
8lockIngtheulnarnerveattheelbowmaybeuncomfortableforpatIent.NSIsnot
routInelyusedforlocalIzIngtheulnarnerveattheelbowasthenerveIseasIlylocated
(andpalpated)InthecubItaltunnel(ulnargroove)betweenthemedIalepIcondyleof
thehumerusandtheolecranonprocessoftheulna.Asmallvolume(1to4mL)oflocal
anesthetIcshouldbeInjectedIfperformIngtheblockatthIslocatIon.
Procedure Using Nerve Stimulation Technique in the Forearm
SImIlartothemedIannerve,ItmaybedIffIculttoblIndlylocatethIsnerveInthe
forearmusIngNS.TranscutaneouselectrIcalstImulatIon
17
orpercutaneouselectrode
guIdance
18,19
canbeusedtolocatethenerve.DncethenervehasbeenlocalIzed,an
InsulatedneedleattachedtoanervestImulatorIsInsertedperpendIculartotheplane
oftheforearmandapproprIatemotorresponsesaresought.Thecorrectresponsesfor
ulnarnerveblockatthIslocatIonareflexIonoftherIng(fourth)andlIttle(fIfth)
fIngersandulnardevIatIonofthewrIst.njectIonof5mLoflocalanesthetIcIs
suffIcIenttoblockthenerveattheforearm.CombInedUSandNSguIdedtechnIque
provIdesgoodlocalIzatIonandaccuracywIthlocalanesthetIcspread.
Procedure Using Ultrasound Imaging (Forearm)
ScannIng:AhIghfrequency(10to15|Hz)lInearprobeIsoftenusedforthIsblock.The
probeIsplacedtransverselyjustabovethemIdforearmleveltovIewtheulnarnerve
InshortaxIsasItapproachestheulnarartery(FIg.J822).tIsposItIonedabovethe
ulnaandthebellyoftheflexorcarpIulnarIs,ontheanterIorsurfaceofthearm,
ratherthanmedIallytocontactthebone.TheoperatorscansdownwardslowlyuntIl
thepulsatIlearteryandnervearevIewedadjacenttoeachother(0opplermaybevery
valuablehere),andretractsthescanheadslIghtlysothearteryandnerveare
separatedsomewhat(FIg.J822).
Figure 38-22.UltrasoundguIdedulnarnerveblockInthemIddIstalforearmusIng
anInplaneneedlealIgnmenttoasmallfootprIntlInear(hockeystIck)probe.
TheIdealblocklocatIon,therebyavoIdIngarterIalpuncture,Iswherethenerve
hasyettofullyapproachtheulnarartery.
Appearance:ThenerveInshortaxIsIsseenasahoneycomb,ovalshapedstructure,
IncludInghypoechoIcfascIcularstructuressurroundedsIgnIfIcantlybyhyperechoIc
tIssue.TheadjacentulnararteryappearsanechoIcandIsroughlysImIlarInsIzetothe
nerveandlateraltoIt.ThemedIannervemaybeseenatthelateraledgeofthe
ImageandappearssImIlartotheulnarnerveInsIzeandshape.
NeedlIng:0urIngPneedlIng,theImageshouldbeadjustedtomovetheImageofthe
nervetothemostlateraledgeofthescreenforgoodvIsIbIlItyoftheneedleshaft(not
shownInFIg.J822).Ashort(2toJcm)needlecanbeusedInamedIaltolateral
dIrectIontoreducetherIskofvascularpuncture.
LocalanesthetIcspread:TheaImIstospreadapproxImately5mLoflocalanesthetIc
aroundthenerveInacIrcularfashIonInordertoavoIdnervecontactbutobtaIna
completeblock.ThelocalanesthetIcInjectIonwIllappearasanexpansIonof
hypoechogenIcItysurroundIngthenerve,whIchmayseparatethenervefromthe
artery.
Comments
0urIngtheelbowblock,dIrectInjectIonafterelIcItIngaparesthesIaordIrectlyInto
thegrooveunderpressureIsnotadvIsedbecauseoftherIskofdamagetothenerve.
Smallvolumes(Jto5mL)oflocalanesthetIcshouldbeused.
0urIngnerveblockIntheforearm,bloodwIthdrawalIntothetubIngsuggestsulnar
arterypunctureandtheneedleshouldbereInsertedafterholdIngpressure.Contact
wIththeulnaIndIcatesthattheneedleIstoodeep.
USImagIngfacIlItatestheunIqueapproachofblockIngtheulnarnerveIntheforearm.
ThIstechnIquemayreducecomplIcatIonssuchasulnarnerveneurItIsorneurapraxIa
whencomparedwIthblocksatthecubItaltunnelbehIndthemedIalepIcondyle.
AlInearorcurvedarrayUSprobewIthasmallfootprInt(26mm;forexamplea
hockeystIckprobe)maybeused.ThIssIzeprobeIshelpfulforeasymanIpulatIonon
theforearmandforgoodalIgnmentoftheneedleusIngPtechnIque.
AtthewrIst,theulnarnervelIesbetweentheulnararteryandthetendonoftheflexor
carpIulnarIsmuscle.AskInwhealIsraIsedatthelevelofthestyloIdprocessonthe
palmarsIdeoftheforearmbetweenthesetwolandmarks.
P.981
AsmallgaugeneedleIsInserted,andJmLofsolutIonIsInjectedIntothearea,wIthor
wIthoutparesthesIas.
Intravenous Regional Anesthesia (Bier Block)
WIthoutusIngNSorUS,armanesthesIacanbeprovIdedbytheInjectIonoflocalanesthetIc
IntothevenoussystembelowanoccludIngtournIquet.
Procedure
Asmallgauge(20or22)IntravenouscatheterIsInsertedandtapedonthedorsumofthe
handInthearmtobeblocked.AheparInlockorsmallsyrIngeIsattachedandsalIneIs
InjectedtomaIntaInpatency.ApneumatIctournIquetIsapplIedovertheupperarm.
ThetournIquetpressureshouldbesetto2.5tImesthesystolIcbloodpressure.The
tournIquetshouldbeInflatedtoconfIrmthatthepressureIssuffIcIenttooccludedIstal
arterIalbloodflowanddeflatedprIortostartIngtheblock.
ThearmIselevatedtopromotevenousdraInage.AnEsmarchbandageIsthenwrapped
tIghtlyaroundthelImbfromdIstaltoproxImaltoproducefurtherexsanguInatIon.After
exsanguInatIon,thetournIquetIsInflatedtoJ00mmHgor2.5tImesthepatIent'ssystolIc
bloodpressureandIsagaIntestedforadequateocclusIonofthedIstalradIalpulse.
ThearmIsreturnedtothehorIzontalposItIon,a50mLsyrIngewIth0.5lIdocaIneIs
attachedtotheprevIouslyInsertedcannula,andthecontentsareInjectedslowly.The
forearmdIscolors,andthepatIentperceIvesatransIentpInsandneedlessensatIonand
warmthasanesthesIaensuesoverthefollowIng5mInutes.EpInephrIneshouldnotbe
addedtothelocalanesthetIcsolutIon.
Forshortprocedures,thecannulacanberemovedatthIspoInt.fsurgerymayextend
beyond1hour,thecannulacanbeleftInplaceandreInjectedafter90mInutes.
8eyond45mInutesofsurgery,manypatIentsexperIencedIscomfortatthelevelofthe
tournIquet.SpecIaldoublecufftournIquetsareavaIlableforthIsblocktoallevIatethIs
problem.ThedIstalcuffIsInflatedfIrst,followedbytheproxImalcuff.ThedIstalcuffIs
thendeflated,allowInganesthesIatobeInducedIntheareaunderthedIstalcuff.f
dIscomfortensues,thedIstalcuffIsInflatedovertheanesthetIzedareaofskIn,andthe
uncomfortableproxImalcuffIsreleased.ThIsstepIscrItIcalbecausethemajorrIskof
thIsprocedureIsprematurereleaseofthelocalanesthetIcsolutIonIntothecIrculatIon.
fadoublecuffIsused,bothcuffsshouldbetestedbeforestartIngandtheproper
sequenceforInflatIonanddeflatIonmetIculouslyfollowed.ThepotentIalforleakageof
anesthetIcIntothecIrculatIonIsgreaterwIththenarrowercuffsusedInthedouble
setup.8ecausetheshIftIngprocessalsoIncreasesthepotentIalforunIntentIonalrelease
ofanesthetIc,theuseofasIngle,wIdercuffmaybebetterforshortprocedures.
fsurgeryIscompletedIn20mInutes,thetournIquetIsleftInflatedforatleastthat
totalperIodoftIme.f40mInuteshaselapsed,thetournIquetcanbedeflatedasasIngle
maneuver.8etween20and40mInutes,thecuffcanbedeflated,reInflatedImmedIately,
andfInallydeflatedafter1mInutetodelaythesuddenabsorptIonofanesthetIcIntothe
systemIccIrculatIon,althoughthIsmaynottrulylowertheeventualpeakplasmalocal
anesthetIclevelsachIeved.
0uratIonofanesthesIaIsmInImalbeyondthetImeoftournIquetrelease.Although
bupIvacaInemayproduceaslIghtprolongatIonofanalgesIa,thecardIotoxIcItyof
systemIclevelsofbupIvacaInemakesthIsdrugcontraIndIcatedfora8Ierblock.
Comments
ThesImplIcItyofthIstechnIqueIsoffsetbythepotentIallysIgnIfIcantrIskofsystemIc
localanesthetIctoxIcItyIfthetournIquetfaIlsorIsreleasedprematurely.CarefultestIng
ofthetournIquetandslowInjectIonofsolutIonIntoaperIpheral(notantecubItal)veIn
wIllreducethechanceofleakageunderthetournIquet.SystemIcbloodlevelsaretIme
dependent,andcarefulattentIonshouldbepaIdtothesequenceoftournIquetrelease
andtopatIentmonItorIngdurIngthIsperIod.AseparateIntravenoussIteforInjectIonof
resuscItatIondrugsIsneededaswellasreadyavaIlabIlItyofallapproprIateresuscItatIve
equIpment.WIthcarefulattentIontothesedetaIls,thIstechnIqueIsoneofthemost
effectIveandrelIableavaIlabletotheanesthesIologIst.
Trunk Blocks
AnesthesIaoftheabdomenandchestIsoftenmostsImplyobtaInedwIthspInaland
epIduralInjectIonsoflocalanesthetIcs,butperIpheralblockofthespInalnervesInthe
paravertebralspaceoroftheIntercostalorInguInalnervesIsquItesuItableformanyuses.
PerIpheralnerveblocksarepartIcularlyrelevantwheneItheranarrowerbandof
anesthesIa(Intercostalorparavertebral)orwhenreducedmotorblockIspreferable.
AddItIonally,epIduralInjectIonmaybehazardousbecauseofthepresenceofInfectIonor
coagulopathy.EpIduralanesthesIaalsocarrIesconcernsofsystemIchypotensIonand
epIduralhematoma,whIchcanlImItItsuseforsomepatIents.
121
nmanyclInIcal
sItuatIons,ItmaybedesIrabletouseIntercostalblockstoseparateanesthesIaofthe
somatIcandsympathetIcfIbersthatoccursIncombInatIonwhenneuraxIalblocksare
performed.ThesympathetIcnervesseparatefromtheIrsomatIccounterpartsearlyIntheIr
course,whIchmakesIndependentsomatIcandsympathetIcblockadeapractIcal
consIderatIon.LIkewIse,althoughparavertebralblocksmayresultInbothsomatIcand
sympathetIcblock,hemodynamIcresponsesareoftenlessthanfromepIduralblock.
SympathetIcblocksarecommonlyperformedatthemajorganglIa,partIcularlythe
stellate,celIac,andlumbarplexus.TheseblocksoftenrequIremultIpleInjectIonsandare
technIcallymoredIffIcultthanaxIalanesthesIa,buttheyofferadvantagesIncertaIn
clInIcalsItuatIons.TheseblocksarenotconsIderedhere,andthereaderIsreferredto
Chapter56.
lIoInguInalandIlIohypogastrIcnerveblocksareusedforproceduresIntheInguInalarea,
IncludInghernIarepaIrandorchIdopexy.AseparateblockfromthatofthelumbarplexusIs
requIredbecausethesenervesexIttheplexusmorecranIally(L1toL2)thanthosenerves
targetedbythelumbarplexusblock(LJtoL5).TransversusabdomInIsplaneblock
122,12J
andrectussheathblock
124,125
canalsobeperformedforabdomInal,umbIlIcal,orother
mIdlInesurgIcalproceduresandareoftenperformedbIlaterally.Theapproachestothe
rectussheathaImtoblockthetermInalbranchesofthe9th,10th,and11thIntercostal
nerveswIthIntherectussheath.deally,theInjectIonIsbetweentheposterIorrectus
sheathandtherectusabdomInusmuscle.ThetransversusabdomInIsplaneblockaImsto
blocktheInnervatIonoftheabdomInalwalluptothelevelofT8byInjectInglocal
anesthetIcbetweenthetransversusabdomInIsandInternaloblIquemuscles.8ecausethe
perItoneumIsImmedIatelybeyondtheposterIorrectussheathandtransversusabdomInIs
muscle,thesetwoblockshavenotbeenwIdelyused.However,USImagInghasbeen
exploredwIthsuccessfortheseblocks.
126
AlthoughpromIsIng,theseblocksarenotwell
establIshedandarenotdescrIbedfurtherhere.
TradItIonally,theseblocksareperformedblIndly,wItheIthersoleuseoflandmarks,
IncludIngalossofresIstancetoneedlepenetratIonofthecostotransverselIgamentfor
paravertebral
P.982
block,oracombInedlandmarkandNSstImulatIontechnIque.USImagIngmaybebenefIcIal
fortheseblocks,partIcularlyparavertebralblock,InordertofacIlItatelandmark
localIzatIon.Forexample,preproceduralscannIngcanIdentIfythetIpsofthetransverse
processesInordertoIdentIfycorrectneedleInsertIonsIte.USmaybepartIcularlyuseful
forperformIngblocksInobesepatIents(wherethedepthofneedleInsertIonwIllbe
modIfIed)orthosewIthanatomIcvarIatIon(e.g.,scolIosIs).ThIssectIonprovIdesa
detaIleddescrIptIonofthetechnIqueusIngNSguIdance,alsoprovIdesIllustratIonsInthe
sectIonsonparavertebralandInguInalblocksofUSImagIngprIortoblockperformance.
Clinical Anatomy
AnovervIewoftheanatomyofthespInalnervesIsdescrIbedInUpperExtremIty,ClInIcal
Anatomy.ThedermatomalInnervatIonofthethoracIcandlumbarnervesIsIllustratedIn
FIgureJ87.
Orientation of the Vertebral Body Processes
TherearevarIatIonstotheanatomyofthevertebralcolumnthatshouldbeconsIdered
whendetermInIngthedesIredlocatIonforneedleInsertIonforblocksofthetrunk.
ThespInousprocesseslIeInthemIdlIne,wIthT7atthedIstaltIpsofthescapulaeandL4
attheleveloftheIlIaccrests.
ThetransverseprocessesapproxImately2.5cmlateraltothespInousprocesses:atT1,
thetransverseprocessIsdIrectlylateraltoItscorrespondIngspInousprocessbut
subsequenttransverseprocessesareextendedtoIncreasInglycephaladlocatIons(I.e.,T7
transverseprocessIslateraltoT6spInousprocess).
nthelumbarregIon,thespInousprocessesarestraIght,andthetransverseprocesseslIe
opposItetheIrownrespectIvespInousprocess.
Paravertebral Space
TheparavertebralspaceIsabIlateralwedgeshapedspacebetweentheIndIvIdual
vertebrae,oneIthersIdeofandextendIngtheentIrelengthofthevertebralcolumn.The
spInalnervespassthroughthIsspace,gIvIngofftheIrsympathetIcbranchandalsoasmall
dorsalsensorybranchafterexItIngfromtheIntervertebralforamIna.nthethoracIc
regIon,ItsboundarIesareasfollows:
|edIallyItconsIstsofthevertebralbody,IntervertebraldIscandforamen,andspInous
processes(angulatIondecreasesfromT1toL45);
AnterolaterallyItIstheparIetalpleura;and
PosterIorlylIesthecostotransverseprocess,approxImately2.5cmfromthetIpofthe
spInousprocess,oftenInaslIghtlycaudalorIentatIon.
TheIntervertebralforamInaateachlevellIebetweenthetransverseprocessesand
approxImately1to2cmanterIortotheplaneformedbythetransverseprocessesIntheIr
assocIatedfascIae.AtthIspoInt,thesympathetIcganglIalIeclosetothesomatIcnerves,
andcoIncIdentalsympathetIcblockadeIsusuallyattaIned.
Intercostal Nerves and Articulations
1. ntercostalNerves.
AtthethoracIclevel,theanterIorprImaryramIenteraneurovascularbundlewIthIts
respectIvearteryandveInandtravelalongtheIntercostalgroovealongtheventral
caudadsurfaceofeachrIb.
ThefascIaeoftheInternalandexternalIntercostalmusclesprovIdeInterIorand
externalbordersofthIsIntercostalgroove.
AstheIntercostalnervestravelbeyondthemIdaxIllarylIne,theygIveoffalateral
sensorybranchwhIlethemaIntrunkcontInuesontotheanterIorabdomInalwallto
provIdesensoryandmotorInnervatIonforthetrunkandabdomendowntothelevelof
thepubIs.
TheIntercostalgroovebecomesmuchlesswelldefInedanterIortothemIdaxIllary
lIne,andthenervebegInstomoveawayfromItsprotectedposItIon.Thelowermost
Intercostalnerve(subcostal,the12th)IsmuchlesscloselyapplIedtoItsaccompanyIng
rIbandIsnotaseasytoIdentIfyandanesthetIzeusIngaclassIcIntercostalblockade
technIque.
2. CostovertebralArtIculatIons.TherIbsartIculatethroughtwosynovIaljoIntswIththe
vertebralcolumn,eachenclosedInfIbrouscapsulesthatarereInforcedbylIgaments:
Costovertebral jointIsasynovIalartIculatIonoftheheadoftherIbwIththe
demIfacetsontheadjacentthoracIcvertebralbodIesandthecorrespondIng
IntervertebraldIscoftheuppervertebraljoInt(exceptfor1st,10th12thrIbs,whIch
artIculatewIthasInglevertebralfacet).
Costotransverse jointIsasynovIaljoIntbetweentheartIcularfacetsonthetubercles
oftherIbsandthetransverseprocessesofthethoracIcvertebrae(the11thand12th
rIbslackthIsartIculatIonbecausetheydonotpossesstubercles).PenetratIonofthe
costotransverselIgamentmayoccurdurIngparavertebralblock.
Lumbar Spinal Nerves and Plexus
ThespInalnervesatthelumbarlevelfollowthesamecourseasthoseofthethoracIclevel
whenleavIngtheIntervertebralforamen,yettheanterIor(ventral)ramIformthelumbar
plexusInsteadofcontInuIngasIntercostalnerves.Thelumbarplexus(FIg.J82J)Isformed
bytheunIonoftheanterIorprImaryramIofL1JandpartofL4.
TheuppernerverootsemergefromtheIrforamInaIntoacompartmentlInedbythe
fascIaeofmusclesanterIorandposterIortoIt.nthIscase,thequadratuslumborumIs
posterIor,whIletheposterIorfascIaofthepsoasmuscleprovIdestheanterIorborderof
thecompartmentbeforethenervesmoveIntothebodyofthemuscle.
ThelumbarplexussupplIestheskInandmusclesofthelowerpartoftheanterIor
abdomInalwall(IncludIngtheexternalgenItalIa)andtheskInandmusclesofthe
anterIorandmedIalcompartmentsofthethIgh.L1bIfurcatesIntoanupperpart
(IlIohypogastrIcandIlIoInguInalnerves)andlowerpart,whIchjoInswIthabranchfrom
L2toformthegenItofemoralnerve.LJ,wIthportIonsofL2andL4,dIvIdesIntoanterior
andposterior divisions:theanterIordIvIsIonformstheobturator(L24)andaccessory
obturator(LJ4,whenpresent)nervesandtheposterIordIvIsIonformsthelateral
(femoral)cutaneousnerveofthethIgh(L2J)andthefemoralnerve(L24).
nanatomIcrelatIontothepsoasmajormuscle,theobturator(L24)andaccessory
obturatornervesemergefromItsmedIalborder;thegenItofemoral(L12)pIercesthe
muscletolIeonItsanterIorsurface;allothersemergefromItslateralborder.
Inguinal Nerves
TheIlIohypogastrIcnervepenetratesthetransverseabdomInIsmusclejustabovetheIlIac
crest,supplIesIt,anddIvIdesIntoanterIorandlateralcutaneousbranches:(1)theanterIor
branchpIercesandsupplIestheInternaloblIquemusclejust2cmmedIaltotheanterIor
superIorIlIacspIne;ItthencoursesdeeptotheexternaloblIquemuscleandsuperIortothe
InguInalcanalandpIercestheexternaloblIqueaponeurosIsabout2toJcmabovethe
superfIcIalInguInalrIng,termInatIngsubcutaneouslyIntheskInofthesuprapubIcregIon;
and(2)thelateralcutaneousbranchsupplIestheanterolateralportIonoftheglutealskIn
afterpIercIngboththeoblIquemuscles.TheIlIoInguInalnervepIercesandsupplIesthe
InternaloblIquemuscleandthenenterstheInguInalcanal,InwhIchIt
P.98J
traversesoutsIdethespermatIccord,toemergethroughthesuperfIcIal(external)InguInal
rIng(theexternaloblIqueaponeurosIs)whereItprovIdescutaneousInnervatIontotheskIn
ofthescrotum(orlabIummajus)andadjacentthIgh.
Figure 38-23.Lumbar(L1throughL4)andsacral(L4throughS4)plexuses.
Techniques
Intercostal Nerve Blockade
AnesthesIaoftheIntercostalnervesprovIdesbothmotorandsensoryanesthesIaofthe
abdomInalwallfromthexIphoIdtothepubIs.ntercostalnerveblockadeIsusedfor
varIouscondItIonsofacuteandchronIcpaIneffectIngthethoraxandupperabdomen(e.g.,
postoperatIveanalgesIaafterthoracotomIes,varIouscardIacsurgerIes,andbothopenand
laparoscopIccholecystectomIes).tcanbeperformedthroughseveralmeans,IncludIng
contInuousInfusIonsIntothesubpleuralspace,throughInterpleuralcatheters,andby
dIrectIntercostalnerveblock.ThesurgIcalsIte(I.e.,IntraoperatIveanatomIcaccess)
determInestheavaIlableoptIons.
ThesenerveblocksInvolveInjectIonsalongtheeasIlypalpatedsharpposterIorangulatIon
oftherIbs,whIchoccursbetween5and7cmfromthemIdlIneIntheback.Theblocksmay
beperformedmorelaterally(8to10cmfromthemIdlIne)
127
ormoremedIally
(ImmedIatelybeyondthetransverseprocesses).ThelevelsofT1throughT5maybemost
amenabletoparavertebralblockbecauseoftheoverlyIngscapulaandbulkyparaspInal
musculatureatthIsregIon.EstablIshIngblockoffIveorsIxlevelsofIntercostalnervesIsa
usefulanesthetIcprocedureforprovIdInganalgesIaandmotorrelaxatIonforupper
abdomInalproceduressuchascholecystectomyandgastrIcsurgery.UnIlateralblockadeof
thesenervesIsausefultreatmentforthepaInofrIbfractureandalsoservestoreduce
postoperatIveanalgesIarequIrementsInpatIentswIthsubcostalIncIsIons.Several
segmentsmustbeblockedIneachoftheseapplIcatIonsbecauseoftheoverlapInsupplyof
theIntercostalnerves.ThIstechnIqueIsalsousefulInreducIngthepaInassocIatedwIth
theInsertIonofchesttubesorpercutaneousbIlIarydraInageprocedures.
ForIntercostalblocks,thepatIentmaybeInthelateral,sIttIng,orproneposItIon.For
operatIveanesthesIa,theproneposItIonIsmostpractIcal.ApIllowIsplacedunderthe
abdomentoprovIdeslIghtflexIonofthethoracIcspIne.Thearmsaredrapedovertheedge
ofthestretcheroroperatIngtablesothatthescapulafallsawaylaterallyfromthe
mIdlIne.TheanesthesIologIststandsatthepatIent'ssIde.|ostanesthesIologIstspreferto
standonthesIdethatallowstheIrdomInanthandtoholdthesyrIngeatthecaudadendof
thepatIent.
Procedure Using Landmark-Based Technique
Landmarks:ThereaderIsreferredtotheprevIousClInIcalAnatomysectIonfor
descrIptIonsofthelocatIonsoftherelevantlandmarks.ThespInousprocessesInthe
mIdlInefromT6throughT12aremarked.TherIbsarethenIdentIfIedalongthelIneof
theIrmostextremeposterIorangulatIon.The6thand12thrIbsaremarkedfIrstattheIr
InferIorbordersandalIneIsdrawnbetweenthesetwopoInts.TherestoftherIbs
betweenthemareIdentIfIed,andamarkIsplacedontheInferIorborderofeachrIb
alongtheangledparasagIttalplaneIdentIfIedbythefIrstlInebetweenthe6thand12th
rIbs.
NeedlIng:AfteraseptIcpreparatIon,lIghtsedatIonIsprovIdedforthepatIent,andaskIn
whealIsraIsedateachmarkontheInferIorborderofeachrespectIverIb.StartIngwIth
thelowestrIb,theIndexfIngerofthecephaladhandretractstheskInabovethe
IdentIfyIngmarkInacephaladdIrectIon.TheanesthesIologIst'sotherhandInsertsa
needle(22gauge,J.75cm)dIrectlyontotherIb,maIntaInIngaconstant10degree
cephaladangulatIon.AftercontactIsmadewIththerIb,thecephaladtractIonIsslowly
released,thecephaladhandtakesovertheneedleandsyrInge,andtheneedleIs
allowedtowalkdowntobelowtherIbatthesameangle.TheneedleIsthenadvanced
approxImately4mmundertherIb.
njectIon:DnceInthegroove,aspIratIonIsperformedandJto5mLofalocalanesthetIc
solutIonIsInjected.TheneedlIngandInjectIonprocedureIsrepeatedforeachsegmental
levelandforbothsIdesIfapplIcable.8ecausetheIntercostalspaceIshIghly
vascularIzed,localanesthetIcsareabsorbedrapIdlyandtoxIclevelsoflocalanesthetIc
maybeencounteredwhenusInglargevolumesandcanquIcklyleadtoneurologIcor
cardIovascular
P.984
sequelae.|axImumdosesshouldbecalculatedandfollowedcarefullyfortheseblocks.
Figure 38-24.ProbeplacementandultrasoundImagedurIngparavertebralblockIn
thethoracIcspIne.TheprobeIsfIrstplacedInthemIdlIneofthespInetocapturea
transversevIewofthevertebralandcostal(IfthoracIcspIne)elements.
Cenerally,theIntercostalnervesarewelllocalIzedwIththeblIndlandmarkbased
technIque.AlternatIvely,therIbcanbeeasIlyvIsualIzedwIththeuseofUS(FIgs.J824and
J825).TheremaInderoftheprocedurewIllbesImIlartothatofblIndtechnIque.famore
medIal(proxImal)IntercostalnerveblockIsdesIred,suchastorelIevethepaInofherpes
zosterorofproxImalrIbfractures,USImagIngofthecostotransversejoIntandrIbsmaybe
helpful.ThelatersectIononparavertebralblockdescrIbesandIllustratesthIsImagIng.
Comments
ntercostalnerveblockscanbesupplementedbyanumberofsomatIcparavertebral
nerveblocksorsympathetIcblockofthecelIacplexus.Careshouldbetakentoadjust
thetotaldoseofdrugInthesecombInedtechnIquessothatthemaxImalrecommended
amountsarenotexceeded.
TheadvantageswIthIntercostalblockoversoleIntravenousopIoIduseIncludesuperIor
analgesIa,opIoIdsparIng,ImprovedpulmonarymechanIcs(IncludIngearlIerextubatIon),
reducedcentralnervoussystemdepressIon,andavoIdanceofurInaryretentIon.
127
ntercostalblocksareoftenusedInaddItIontosystemIcanalgesIa(e.g.,Intravenous
patIentcontrolledanalgesIa).
0espItefrequentconcernabouttheIncIdenceofpneumothoraxwIthIntercostalblocks,
thIscomplIcatIonIsrareInexperIencedhands.ThIsdependsprImarIlyonmaIntaInIng
strIctsafetyfeaturesofthedescrIbedtechnIque.EmphasIsshouldbeplacedonabsolute
controlofthesyrIngeandneedleatalltImes,partIcularlydurIngInjectIon.
Figure 38-25.UltrasoundImagesfromscannIngInamedIaltolateraldIrectIonwIth
acurvedultrasoundprobeplacedInthelongItudInalaxIs.
AcommoncomplIcatIonIsrelatedtothesedatIonrequIredtoperformthIsblockInthe
proneposItIon.DverdosecanleadtoaIrwayobstructIonandrespIratorydepressIonIn
theproneposItIon.AttentIonmustbepaIdtothepatIent'smentalstatusbecausethIs
blockproducesthehIghestbloodlevelsoflocalanesthetIcswhencomparedwIthany
otherregIonalanesthetIctechnIque.WhentheblockIsperformedforpostoperatIvepaIn
relIef,thedoseshouldbereducedto0.25bupIvacaIneorropIvacaInetomInImIzethe
chancefortoxIcIty.
tIspossIbletoproducepartIalspInalorepIduralanesthesIaIftheInjectIonIsmade
closetothemIdlIneandtheanesthetIctracksalongaduralsleevetotheepIduralor
subarachnoIdspace.FespIratoryInsuffIcIencycanalsobeseenIftheIntercostalmuscles
areblockedInapatIentwhodependsonthemforventIlatIon.PatIentswIthchronIc
obstructIvedIseasewIthIneffectIvedIaphragmmotIonarenotgoodcandIdatesforthIs
technIque.
Paravertebral Block
ThIsblocktechnIqueIsusefulforsegmentalanesthesIa,partIcularlyoftheupperthoracIc
segments.tIsalsousefulIfamoreproxImal(central)blockadethanthatoftheIntercostal
nervesIsneeded,suchastorelIevethepaInofherpeszosterorofaproxImalrIbfracture.
ThethoracIcparavertebralblockIsusedforbreastsurgeryandperIoperatIvelyforthoracIc
surgery.Thoracolumbarparavertebral
P.985
anesthesIaIscommonlyusedforInguInalhernIorrhaphyandpostoperatIveanalgesIa
followInghIpsurgery.Lumbarparavertebralblockadehasbeenusedsuccessfullyfor
outpatIenthernIaoperatIons,provIdIngsIgnIfIcantpostoperatIveanalgesIa.
SIngleInjectIonparavertebralblockusedforsurgIcalanesthesIahasbeenshowntosurpass
generalanesthesIawIthrespecttopostoperatIvepaInrelIef,IncIdenceofvomItIngand
paIndurIngmobIlIty.
128
ParavertebralblocksareconsIderedunIlateralepIduralsbecause
theyselectIvelyblockspInalnervesonthesIdeofanesthetIcapplIcatIon,althoughthey
alsohavethepotentIalforepIduralspread(I.e.,theycanbebIlateralIfdesIred).The
anesthesIaIncludesbothsomatIcandsympathetIceffects,wIthareducedhemodynamIc
response(e.g.,hypotensIon)ascomparedwIthepIduralanesthesIa.ThIsnerveblock
requIresexcellentknowledgeofparavertebralanatomy,butcanbeeasIlyperformedwIth
experIence.
TheupperfIverIbsaremoredIffIculttopalpatelaterally,andblocksoftheIrassocIated
IntercostalnervesIsbestperformedwIthaparavertebralInjectIon.ThIsapproachIs
technIcallymoredIffIcultandhasslIghtlygreaterpotentIalforcomplIcatIonsbecauseof
theproxImItyofthelungandoftheIntervertebralforamIna.Theparavertebralblockcan
beusedatanylevel.AtthelumbarspIne,someprefertoperformlumbarplexusblockto
reducethenumberofInjectIonsandavoIdsympathetIcblock.Theparavertebralblock
InjectIonIsmadeIntothetrIangularparavertebralspacewherethespInalnervehasjust
lefttheIntervertebralforamen.ThenervemaybedIffIculttolocalIzeusIngbony
landmarksInablIndfashIon,andlargervolumesoflocalanesthetIcareoftenrequIred.NS
hasbeenusedtolocalIzethenerve.UScanbeperformedprIortotheblocktoImprove
bonylandmarkIdentIfIcatIon,partIcularlyforpatIentswhohaveanobesehabItusora
spInaldeformIty.However,realtImeUSguIdancecanbechallengIngandmayofferlImIted
addItIonalvaluefrompreprocedurallandmarkIdentIfIcatIon,astheoverrIdIngbonetIssue
reflectstheUSbeamandprovIdesdorsalshadowIng,whIchobscuresImagIng(especIallyof
theneedle)tothedepthoftheparavertebralspace.
ThIsblockIsperformedwIththepatIentInthelateral,sIttIng,orproneposItIon,thelatter
usIngapIllowplacedunderthepatIent'sabdomentoproduceflexIonofthethoracIcand
lumbarspIne.
Procedure Using Nerve Stimulation or Loss-of-Resistance Technique
Landmarks(FIg.J826):TheparavertebralapproachvarIessomewhat,dependIngonthe
spInallevelandtherespectIveorIentatIonofthevertebralspInousandtransverse
processes(seeClInIcalAnatomy).Thus,paravertebralblocksIntheupperthoracIc
regIonareperformedateachlevelbyIdentIfyIngthespInousprocessofthevertebra
abovetheleveltobeblocked;InthelumbarregIon,thespInousprocessofthelevelto
beblockedIsusedtolocatethetransverseprocess.TheapproprIatespInousprocessesIn
theregIontobeblockedaremarkedandtransverselInesaredrawnacrossthecephalad
borderofthespInousprocessesandextendedlaterallytooverlIethetransverseprocess
(approxImately2.5cm).FInally,thetransverseprocessesaremarkedIndIvIduallyorby
drawIngavertIcallIneparalleltothespInejoInIngtheendsofthetransverselInes.Fora
dIagnostIcblock,asInglenervemayneedtobeanesthetIzed.ForpaIncontrol,several
levelsmustbeIdentIfIed.TheInjectIonofatleastthreesegments(asInIntercostal
blockade)IsrequIredtoproducerelIablesegmentalblockbecauseofsensoryoverlap
frommultIplenerves.
NeedlIng:AfteraseptIcskInpreparatIonandpatIentsedatIon,skInwhealsareraIsedat
themarkedtransverseprocesses.A22gauge,7.5cmInsulatedneedleIsIntroduced
throughtheskInwhealInthesagIttalplaneanddIrectedslIghtlycephaladtocontactthe
transverseprocess(usuallyatadepthof2to4cmInthethoracIcregIonand5to8cmIn
thelumbarregIon),oroftentImes,lIkelythecostotransverselIgament.Centlecephalad
orcaudadexploratIonmayberequIredtoIdentIfythebone.Thedepthofthetransverse
processshouldbecarefullynotedontheneedleshaft.TheneedleIsnowwIthdrawnfrom
thetransverseprocesstotheskInlevelandreInserted10degreessuperIorly(totarget
thespInalnervecorrespondIngtothespInousprocess)orInferIorly(correspondIngtothe
vertebrallevelbelowthespInousprocess)and1cmdeeperthanthepoIntofbone
contact.TheneedleshouldbeangledslIghtlymedIallytoavoIdcausIngpneumothorax.
TherewIllbeasubtlegIveatthemIdpoIntbetweentheselandmarks(spInousand
transverseprocesses)IndIcatIngentranceIntotheparavertebralspace.
Figure 38-26.LandmarksfortheparavertebralblockatthethoracIcspIne.The
spInousprocessofthelevel(e.g.,T6)belowtheblock(e.g.,T7)IsIdentIfIedanda
lIneIsdrawnhorIzontallyfromthecranIalaspectofthespInousprocesstomarkthe
transverseprocess.TheneedleIsInsertedatapproprIatespInallevelsatthelateral
lInemarkIngthetransverseprocesses.
NervelocalIzatIon:ForNS,anInItIalcurrentof2.5to5mAIsusedandtheneedleIs
advanceduntIlcontractIonsoftheapproprIatemuscles(e.g.,abdomInalmuscleswIth
lumbarparavertebralblock)areobserved,andthecurrentIntensItyIsthenreducedto
localIzethenervesat0.5to0.6mA.AtestdoseoflocalanesthetIcwIllconfIrmnerve
localIzatIonwIthabolIshmentofthenerveresponse,resultIngfromthecurrent
dIssIpatIonattheneedletIpfromtheconductIngsolutIon.
26
ForlossofresIstance,a22
gaugeTuohyneedleIsused.AfterwalkIngoffthetransverseprocesses,apoporlossof
resIstancemaybefeltwhenenterIngtheparavertebralspace.
njectIon:Whentheneedlehasenteredtheparavertebralspace,Jto7mLoflocal
anesthetIcIsInjectedaftercarefulaspIratIonateachsIte,dependIngonnumberofsItes
andpatIentsIze.AttentIonmustbepaIdtothetotalmIllIgramdoseInjected.The
volumerequIredtoblockeachlevellImItstheconcentratIonthatcanbeusedandthe
totalnumberoflevelsthatcanbeblocked.flumbarparavertebralInjectIonsare
combInedwIthIntercostalblocks,theconcentratIonandtotalvolumeforbothblocks
mayhavetobereduced.
magIngfortheseblocksIsoftenusedbeforeblockperformance(I.e.,preprocedural,
supported,orofflIneImagIng)ratherthandurIng(I.e.,realtImeoronlIne
ImagIng)toIdentIfythedeepbonylandmarks,IncludIngtheartIcularandtransverse
processes.
ScannIng:PlacIngtheprobetransverselyatthemIdlInewIllprovIdeanovervIewofthe
vertebrallamInaand
P.986
processes,aswellascostalstructuresIfvIewIngthethoracIcspIne(FIg.J824).AmedIal
tolateralscanusIngalongItudInallyplacedprobecanthenbeusedtolocateandmark
Importantbonylandmarks(FIg.J825).ForthIs,a5to7|HzcurvedarrayUSprobe
(lowerfrequencyforobesepatIentsandhIgherfrequencylInearprobesforthInadultor
pedIatrIcpatIents)IsposItIonedInthesagIttalplaneontopofthespInousprocessesof
thetargetthoracIcorlumbarregIon.SubsequentlateralscannIngwIllallowconsecutIve
IdentIfIcatIonofthelamIna,artIcularandtransverseprocessesand(InthethoracIc
spIne)therIbs.
Appearance:TheInItIaltransversescanwIllshowahyperechoIcoutlIneofthevertebral
spInousandtransverseprocesses,thelamIna,and(InthethoracIcspIne)assocIatedrIb.
0urIngthelateralscanwIththeprobeplacedlongItudInallytothespIne,thelamInae
wIllappearfIrst,aslargelyoverlappInglInearstructures.TheartIcularprocessesInlong
axIsappearasmultIplelumpsjustlateraltothespInousprocessesandareshort
rectangularstructureswIthhyperechoIclIneswIthunderlyInghypoechoIcbony
shadowIng.|ovInglaterally,thetransverseprocessesappearandlooksImIlartothe
artIcularprocesses;theywIlldIsappearfromthevIewwhentheprobeIsmovedbeyond
theIrtIps,whIchcanhelpdIstInguIshthemfromtheartIcularprocessesandmarkthe
lateralblocklocatIon.8eyondthetransverseprocesses,therIbheadsappearaslong
shadowswIthInhyperechoIcborders,deeptothelInearhyperechoIcmusclefIbersofthe
paravertebralmuscles.TheparavertebralspacelIesdeeptothetransverseprocesses
andthepleuracanoftenbeIdentIfIedbetweenanddeeptothetransverseprocessas
wellasdeeptotherIbs.
NeedlIng:8ecausemultIpleInjectIonsaregenerallyneededtocompletelycoverallthe
dermatomesofthesurgIcalareaInclInIcalpractIce,USImagIngIsmoresuItablefora
preblockassessment(supportedUS)tovIsualIzeandmeasurethedepthofneedle
penetratIonrequIredfortheneedletocontactthetransverseprocesses.NeedlIngwIllbe
IdentIcaltothatforblIndtechnIque,wIththeexceptIonthatthedepthtothetransverse
processwIllbemoreaccuratelyknown.tIspossIbletoperformrealtImeUSguIdance
usIngeItherPorDDPneedlealIgnment.ThereaderIsreferredtotheComments
sectIonforadvIcerelatedtoImportantprecautIonswhenusIngUSguIdance.
LocalanesthetIcspread:LocalanesthetIcspreadwIllbedIffIculttovIewIfusIngreal
tImeguIdancedurIngthIsblock.TheoverlyIngboneslargelyreflecttheUSbeamand
obstructvIsIbIlItybeyondIntotheparavertebralspace.
Comments
8ecausetheparavertebralspaceIswellvascularIzed,InadvertentvascularpuncturewIll
oftenoccur,whIchhIghlIghtstheneedforfrequentaspIratIonandInjectIonInsmall
alIquots.
129
ThecomplIcatIonofpneumothoraxIsmorelIkelywIthaparavertebraltechnIquethan
wIthIntercostalblock.TheneedleshouldbedIrectedmedIallyasItpassesbelowthe
transverseprocessandnevermorethan2cmbeyondthetransverseprocess.fcoughor
chestpaInoccurs,achestradIographshouldbeperformedtoruleoutpneumothorax.
SubarachnoIdInjectIonIsalsomorelIkelyInthethoracIcareabecauseoftheextensIon
oftheduralsleevestotheleveloftheIntervertebralforamIna.CarefulaspIratIonIs
ImportantbutmaynotpreventtheunIntentIonalInjectIonoflocalanesthetIcIntothe
subduralspace.TotalspInalanesthesIacanresultwItha5to10mLInjectIon.SystemIc
toxIcItyIsalsoapossIbIlItybecauseoftheneedforrelatIvelylargevolumesoflocal
anesthetIc.
fattemptIngrealtImeUSguIdanceofparavertebralblock,angulatIonoftheneedleIs
ImportanttocarefullyobserveandusInganPneedlealIgnmenttoalongItudInalprobe
maybemostprudent.TheneedleshouldnotbeInsertedwIthasIgnIfIcantmedIal
dIrectIonasthereIsarIskofspInalcordInjuryfromIntraforamInalInsertIonand
InjectIon.LIkewIse,alateraldIrectIonbearstherIskofpneumothorax.fchoosIngtouse
realtImeUSguIdancedurIngblockprocedure,pleasenote:(1)wIththeprobeplacedIn
thesagIttal/longItudInalplane,DDPneedlIngmaybemorerIskyasItoftenrequIresthe
medIalorlateralangulatIonsprevIouslydescrIbed;and(2)anPneedlIngapproachcan
bemorerIskywhentheprobeIsplacedInthecoronal/transverseplane.
Inguinal Nerve Block
ThIsblockIsperformedeasIlywIthblIndtechnIque,althoughUSImagIngmaybeperformed
tohelpImprovethesuccessrateofnervelocalIzatIonandpotentIallyreducelocal
anesthetIcrequIrementsandtherIskoftoxIcItyandotheradverseeffects.
55,1J0
The
patIentlIessupInewIththeIpsIlateralhandplacedunderthehead.
Procedure Using Blind Technique (Single-Shot Fascial Click)
Landmarks:TheInjectIonsIteIslocatedatabout1to2cmmedIaland1to2cmInferIor
totheanterIorsuperIorIlIacspIne.
NeedlIngandInjectIon:A25gaugeJ.75to5cmneedleIsapproprIate;a22gauge,5cm
InsulatedneedleIsusedIfusIngNS.TheneedleIsInsertedfromtheanterIorabdomen
(vertIcally)untIlafascIalclIckIsdetected,presumablyatthejunctIonoftheInternal
oblIqueandtransverseabdomInusmuscles.AnInjectIonofabout10to15mLlocal
anesthetIc(0.Jto0.5mL/kg)Isperformed.
ThIsprocedurehasonlybeenreportedfromstudIesInchIldren.
ScannIng:TwodIfferentapproacheshavebeenusedforUSscannIngoftheIlIoInguInal
andIlIohypogastrIcnerves.
55,1J1
ntheIrclInIcalstudy,WIllschkeetal.
55
usedasmall
footprInt(hockeystIck),5to10|Hzprobe,placedIntransverseaxIs,justmedIaland
superIortotheanterIorsuperIorIlIacspIne.ThecrosssectIonalvIewoftheIlIoInguInal
nervecanbecapturedlyIngbetweentheInternaloblIqueandtransverseabdomInus
muscles.ntheIrcadaverIcstudy,EIchenbergeretal.
1J1
foundaprobewIth7.5|Hzto
besuperIortoonehavIng10|Hzfrequency.TheyusedaposItIonabout5cmcranIaland
slIghtlyposterIortotheanterIorsuperIorIlIacspIne,wherebothnerveshavebeenshown
tobepresentbetweentheprevIouslymentIonedmuscleswItha90probabIlIty.These
authorsvIsualIzedbothnervesasdIstInctentItIes.
Appearance:ThenervesappearhypoechoIcwIthmanyhyperechoIcdotsandadIstInct
hyperechoIcrIm.Theyhaveanoval,somewhatboomerangshape,andappearembedded
betweenthefascIcularhypoechoIcappearIngmuscles.nthemorecranIalposItIon,the
IlIacbonemaybecaptured,wIthItshyperechoIcborderanddorsalshadowIng,onthe
medIalaspectofthescreen.ThethInexternaloblIquemusclelIessuperfIcIalatthe
cranIalposItIon,butItseventhInnercomponentmaynotbevIsIblemoreInferIorly.
NeedlIng:8othgroupsofauthorsusedanDDPneedlIngalIgnment,wIththeneedleplaced
caudadtotheprobeInItscenter.ThIsapproachwIllonlyprovIdeavIewofthe
P.987
needletIp,makInggoodneedletrackIngwIthInthetIssuecrItIcal.Presumably,anP
alIgnmentcouldbeusedasanalternatIve.
LocalanesthetIcspread:EItheroneortwoInjectIonscanbemade,dependIngonthe
numberofdIstInctnerveslocalIzed.ThedoseoflocalanesthetIcmaybelower(0.075
mL/kghasbeenshowneffectIveforasIngleInjectIontechnIque)
1J0
whenusIngUS
ImagIng,asthenervesarewelllocalIzed.AhypoechoIcareaofsolutIonshouldbe
vIsualIzedadjacenttothenerve(s).
Comments
TheIlIoInguInalandIlIohypogastrIcnervesmayexIstasacommontrunkatthelevelof
theanterIorsuperIorIlIacspIne,whIchfurthersupportstheuseofUSguIdancefor
localIzIngthesInglenerve.
1J1
8ecausethereIshIghvarIabIlItyIntheskInInnervatIonfromthesenerves,ItIs
ImpossIbletoconfIrmwIthclInIcaltestswhIchnerveIsblocked.njectInglateraltothe
mostlaterallyposItIonedIlIoInguInalnerve,ormedIaltotheIlIohypogastrIcnerve,has
beenreportedInanattempttodIstInctlyblockthesenerves.
1J1
ComplIcatIonsofthIsblockaregenerallyvolumerelatedandIncludesystemIctoxIcIty
andtransIentfemoralnervepalsy.
Penile Blocks
ApenIleblockIsusedInchIldrenandadultsforsurgIcalproceduresoftheglansandshaft
ofthepenIs.Thedorsalnerves(termInalbranchesofpudendalnerve;S2throughS4)lIe
bIlaterallyontheouteraspectofthedorsalarterIesofthepenIs.Fromthebaseofthe
penIs,theydIvIdeseveraltImesandencIrcletheshaftofthepenIsbeforereachIngthe
glans.ThIsblockIsoftenperformedasacIrcumferentIalInfIltratIonoftherootofthepenIs
(rIngblock).TwoskInwhealsareraIsedatthedorsalbaseofthepenIs,oneoneachsIde
justbelowandmedIaltothepubIcspIne.A25gauge,J.75cmneedleIsIntroducedoneach
sIde,and5mLofanesthetIc(0.5to1mLforInfants)IsdeposItedsuperfIcIallyanddeep
alongthelowerborderofthepubIcramustoanesthetIzethedorsalnerve.Foracomplete
rIngofInfIltratIon,anaddItIonal5mL(adults)IsInfIltratedInthesubcutaneoustIssue
aroundtheundersIdeoftheshaft.AlargerneedleorasecondInjectIonsItemaybeneeded
tocompletetherIng.Twentyto25mLof0.75lIdocaIneor0.25bupIvacaIneusually
suffIcesInadults.EpInephrInecontaInIngsolutIonsshouldnotbeusedtoavoId
compromIsIngpenIlecIrculatIon.
Lower Extremity Blocks
CombInedblocksofthelumbarandscIatIcplexusesprovIdeeffectIvesurgIcalanesthesIato
theentIrelowerextremIty.PrIortothe1990sananterIorlumbarblockapproach(aka,
femoralthreeInoneapproach),fIrstdescrIbedbyWInnIeandcolleaguesIn197J,
1J2
was
commonlyperformed,basedontheassumptIonthatalargevolumelocalanesthetIc
InjectIonIntothefemoralnervesheathwouldproducespreadofthesolutIonproxImallyto
anesthetIzetheobturatorandlateralfemoralcutaneousnervesaswell.Laterreportsof
faIlurestoobtaInobturatornerveblockwIththIsapproach,
1JJ,1J4
however,haveledtothe
femoralblockbeIngconsIderedasanIndIvIdualnerveblock,andhaveadvocatedthe
posterIorlumbarblockapproachforaccessIngthewholelumbarplexus.
PN8IsIndIcatedwhenspInal,caudal,orepIduraltechnIquesarecontraIndIcatedorwhen
selectIveanesthesIaofonelegorfootIsneeded.8ecausetheanatomIclandmarks
IdentIfyIngthefascIalsheathsorcompartmentsoftheplexusesarenotasclearlydefIned
asthoseIntheupperextremIty,lowerextremItyblocksareoftenperformedmoredIstally,
wherethenerveshavealreadyseparatedIntotermInalbranches.Thus,InaddItIontothe
fascIalcompartmentapproach(psoasblock),thereareperIpheralapproachesdescrIbedat
theanterIorandposterIorhIp,knee,andankle.
Figure 38-27.CutaneousInnervatIonfromthetermInalnervesofthelowerextremIty.
Clinical Anatomy
Together,thelumbarandsacralplexuses(FIg.J82J)supplythelowerlImb.TheformatIon
ofthelumbarplexusIsdIscussedInTrunk8lock.mportantlandmarksthatcontaInthe
plexusdurIngItscourseIncludethepsoascompartment,borderedposterIorlybythe
quadratuslumborummuscleandanterIorlybytheposterIorfascIaofthepsoasmuscle,and
moredIstally,thesubstanceofthepsoasmajormuscle.TheanatomyofthetermInal
nervesIsexamInedInthefollowIngsectIon,asaretheformatIonandbranchesofthe
sacralplexus.ThecutaneousInnervatIonInthelowerextremItyIsshownInFIgureJ827.
ThelowerextremItydermatomesareshownInFIgureJ88.
Terminal Nerves of the Lumbar Plexus
1. CenItofemoralnerve(L1,2).ThIsnerveleavesthelumbarplexusatthelowerborderof
theLJvertebrae.tpIercesandthenlIesanterIortothepsoasmajormuscle,before
descendIngsubperItoneallyandbehIndtheureterwhereItdIvIdesIntotwobranches
(genItalandfemoral),atavarIabledIstanceabovetheInguInallIgament.ThegenItal
branchcrossestheexternalIlIacarteryandtransversestheInguInalcanal.tsupplIesthe
cremastermuscleandskInoverthescrotumandadjacentthIgh(males)ortheskInover
anterIorpartoflabIummajusandmonspubIs(females).Thefemoralbranchdescends
lateraltotheexternalIlIacartery,passesundertheInguInallIgament,entersthe
femoralsheathlateraltothefemoralartery,andpIercestheanterIorlayerofthe
femoralsheathandfascIalata.tInnervatestheskInImmedIatelybelowthecreaseof
groInanterIortotheupperpartofthefemoraltrIangle.
2. LateralcutaneousnerveofthIgh(aka,lateralfemoralcutaneousnerve;L2,J).ThIsnerve
passesoblIquelyfromthelateralborderofthepsoasmajormuscleovertheIlIacusto
enterthethIghbeloworthroughtheInguInallIgament,varIablymedIaltotheanterIor
superIorIlIacspIne(FIg.J828).DntherIghtsIdeofthebody,thenervepasses
posterolateraltothececumandontheleftIttraversesbehIndthelowerpartofthe
descendIngcolon.ThenervelIesontopofthesartorIusmusclebeforedIvIdIngInto
anterIor(supplIesskInovertheanterolateralaspectofthethIgh)
P.988
andposterIor(supplIesskInonthelateralaspectofthIghfromthegreatertrochanterto
themIdthIgh)branches.DccasIonally,thIsnerveIsabranchofthefemoralnerverather
thanItsownnerve.
Figure 38-28.llustratIonoftheanterIorthIghshowIngneuromuscularanatomyand
blockneedleInsertIonsItes(X)alongtheInguInalcreaseforthemajorbranchesof
thelumbarplexus.ASS,anterIorsuperIorIlIacspIne.
J. Femoralnerve(L24).ThefemoralnerveIsthelargestnerveofthIsplexus,supplyIng
musclesandskInontheanterIoraspectofthethIgh.tdescendsthroughthepsoasmajor
muscleandemergeslowatItslateralborder,coursIngInferIorlybetweentheIlIacusand
psoasmajormusclestoenterthethIghundertheInguInallIgament(FIg.J828).Atthe
InguInallIgament(runnIngbetweenanterIorsuperIorIlIacspIneandthemedIalpubIc
tubercle)andjustdIstaltoIt(InthefemoraltrIangle),thenervelIesslIghtlydeeper(0.5
to1cm)andlateral(approxImately1.5cm)tothefemoralartery;theveInIsmedIalto
theartery(7ANIsthemnemonIcfortheanatomIcalrelatIonshIp,startIngmedIally).At
thefemoral(InguInal)crease(afewcentImeterscaudadtotheInguInallIgament)the
nervelIesunderneaththefascIaIlIaca(IlIopectInealfascIa),deeptothefascIalata.
8eyondthefemoraltrIangle,ItbranchesIntoanterIor(quIteproxImally)andposterIor
dIvIsIons.TheanterIordIvIsIongIvesmuscularbranchestothepectIneusandsartorIus
musclesandcutaneousbranches(IntermedIateandmedIalcutaneousnervesofthIgh)to
theskInontheanterIoraspectofthethIgh.TheposterIordIvIsIonsendsmuscular
branchestothequadrIcepsfemorIsmuscleandgIvesrIsetothesaphenous nerve,Its
largestcutaneousbranch.Thesaphenousnervefollowsthefemoralartery,lyInglateral
toItwIthIntheadductor(Hunter,subsartorIal)canalandthencrossIngItanterIorlytolIe
medIaltotheartery.0IstaltothecanalItleavesthearterytolIesuperfIcIalatthe
medIalaspectoftheknee;thenervethencontInuesInferIorly(subcutaneously)wIththe
long(great)saphenousveInalongthemedIalaspectofthelegdowntothetIbIalaspect
oftheankle.ThesaphenousbranchsupplIestheskInonthemedIalaspectoftheleg
belowthekneeandtheskInonthemedIalaspectofthefoot;ItprovIdesartIcular
branchestothehIp,kneeandanklejoInts.
4. Dbturatornerve(L24).TheobturatornerveemergesfromthemedIalborderofthe
psoasmajormuscleatthepelvIcbrImtopassbehIndthecommonIlIacvesselsand
lateraltotheInternalIlIacvessels.tthencoursesInferIorlyandanterIorlyalongthe
lateralwallofthepelvIccavItyontheobturatorInternusmuscletowardtheobturator
canal,throughwhIchItenterstheupperpartofthemedIalaspectofthethIghabove
andanterIortotheobturatorvessels.tdIvIdesIntoItsanterIorandposterIorbranches
neartheobturatorforamen(FIg.J828).TheanterIorbranchpassesIntothethIgh
anterIortotheobturatorexternus,descendsInfrontoftheadductorbrevIs,behIndthe
pectIneusandadductorlongusmuscle,wIthItstermInalcutaneousbranchesemergIngas
ItcoursesalongsIdethefemoralartery.tsupplIestheadductorlongus,gracIlIs,adductor
brevIs(usually),andpectIneus(often)muscles.tscutaneousbranchessupplytheskInon
themedIalaspectofthethIghandperhapstothemedIalknee.Thenerve'sposterIor
branchpIercestheobturatorexternusmuscleanterIorlyandsupplIesIt,thenpasses
behIndtheadductorbrevIsmuscle(sometImessupplIesIt)todescendontheanterIor
aspectoftheadductormagnusmuscle(medIaltotheanterIorbranch),whIchItsupplIes.
ThereIsnoapparentcutaneoussupplyfromthIsnerve.tthentraversestheadductor
canalwIththefemoralarteryandveIntoenterthepoplItealfossa,whereIttermInates
asanartIcularbranchtothebackofthekneejoIntcapsule(oblIquepoplIteallIgament).
5. Accessoryobturatornerve(LJ,4).ThIsnerveIspresentInaboutJ0ofIndIvIduals;It
descendsalongthemedIalborderofthepsoasmajormuscle,crossesthesuperIorpubIc
ramusbehIndthepectIneusmuscle,supplIesItandgIvesartIcularbranchestothehIp
joInt.
Sacral Plexus: Formation and Branches
AtthemedIalborderofthepsoasmajormuscle,thelumbosacraltrunkIsformedbythe
unIonofabranchofL4andtheanterIorramusofL5.AfterexItIngthroughtheanterIor
sacralforamIna,theanterIor
P.989
prImaryramIofS14joInthelumbosacraltrunktoformthesacralplexus(FIg.J82J).The
nervesoftheplexusconvergetowardthegreaterscIatIcforamenanterIortothepIrIformIs
muscleontheposterIorpelvIcwall.ThemaIntermInalnervesarethescIatIcnerve
(contInuatIonoftheplexus)andthepudendalnerves(termInalbranches);severalother
smallbranchesaregIvenoff,IncludIngmuscularbranches(e.g.,InferIorandsuperIor
glutealnervesandnervestoquadratusfemorIs,pIrIformIs,obturatorInternus,and
externalsphInctermuscles),cutaneousbranches(e.g.,posterIorcutaneousnerveofthe
thIgh),andvIsceralbranches(pelvIssplanchnIcnerves).Theglutealvessels(superIorand
InferIor)generallyfollowthecourseofthesacralnervesIntheanterIorplaneandcanbe
usedtohelpIdentIfythescIatIcnerveatItsproxImalcourse.AddItIonalvascularstructures
thatmaybeIdentIfIedunderUSImagIngarethepudendalvessels,whIchpassfromthe
greatertolesserscIatIcforamenbetweenthescIatIcandpudendalnerves.
Sciatic, Tibial, and Common Peroneal Nerves
ThescIatIcnerveIsthelargestnerveofthebodyandIsusuallytheconjunctIonoftwo
trunksInItIallyenvelopedInacommonsheath:alateraltrunk(L4throughS2),whIch
eventuallyemergesasthecommonperonealnerveandamedIaltrunk(L4throughSJ),
whIchlaterbecomesthetIbIalnerve.ThesecombInednervesexItthroughthescIatIc
notchandpassanterIorlytothepIrIformIsmuscletothenlIebetweentheIschIal
tuberosItyandthegreatertrochanterofthefemur.TheycurvecaudallyanddescendInthe
posterIorthIghadjacenttothefemur.AtavarIabledIstancewIthIntheposterIorthIgh
(oftenhIghInthepoplItealfossa),thescIatIcnervebIfurcatesIntocommonperonealand
tIbIalnerves.ThecommonperonealnervedescendsalongthemedIalborderofbIceps
femorIsmuscleandthenonthelateralborderofthegastrocnemIusmuscle.AtthefossaIt
gIvesoffthelateralsuralnerve,whIchformsthelateralsuralcutaneousnervebyjoInIng
themedIalsuralnervesupplIedbythetIbIalnerve.twIndsaroundtheneckofthefIbula
andtermInatesasthedeepandsuperfIcIalperonealnerves.ntheposterIorthIgh,the
tIbIalnerveIscoveredmedIallybythesemItendInosusandsemImembranosusmusclesand
laterallybythebIcepsfemorIsmuscle.8eyondthekneejoInt,ItIscoveredbybothheads
ofthegastrocnemIusmuscleandthendeeptothesoleusmuscle,beforecomIngtoanend
onthetIbIalIsposterIormuscleandfInallyontheposterIorsurfaceofthetIbIalshaft
medIaltothemedIalmalleolus.WIthInthefossa,ItgIvesoffmuscularbranches
(gastrocnemIus,soleus,poplIteus,andplantarIsmuscles)aswellasthemedIalsuralnerve
(tojoInItslateralcounterpartfromthecommonperonealnerve).nthelowerlegand
foot,ItgIvesoffmuscular,artIcular(ankle),andcutaneousbranches,andtermInatesas
medIalandlateralplantarnerves.ThenerveIsoftencalledtheposterior tibial nerveIn
thelowerleg.
Nerves at the Ankle
8ythetImethefemoral,tIbIal,andcommonperonealnervesreachtheankle,thereare
fIvebranchesthatcrossthIsjoInttoprovIdeInnervatIonfortheskInandmusclesofthe
foot.
1. 0eepperonealnerve(L5,S1).ThIsnervelIesanterIortothetIbIaandInterosseus
membraneandlateraltotheanterIortIbIalarteryandveInattheankle.ttravelsdeep
toandbetweenthetendonsoftheextensorhallucIslongusandextensordIgItorum
longusmuscles.8eyondtheextensorretInaculumItbranchesIntomedIalandlateral
termInalbranches:themedIalbranchpassesoverthedorsumofthefootandsupplIes
thefIrstwebspacethroughtwotermInaldIgItalbranchesandthelateralbranch
traverseslaterallyandtermInatesasthesecond,thIrd,andfourthdorsalInterosseus
nerves.
2. TIbIalnerve(aka,posterIortIbIalnerve;S1J).DntheposterIoraspectofthekneejoInt,
thetIbIalnervejoInstheposterIortIbIalarteryandthenrunsdeepthroughtothelower
thIrdoftheleg,whereItemergesatthemedIalborderofthecalcanealtendon(AchIlles
tendon).8ehIndthemedIalmalleolusItlIesbeneathseverallayersoffascIaandIs
separatedfromtheAchIllestendononlybythetendonoftheflexorhallucIslongus
muscle.ThenerveIsposteromedIaltotheposterIortIbIalarteryandveIn,whIchareIn
turnposteromedIaltothetendonsoftheflexordIgItorumlongusandtIbIalIsposterIor
muscles.JustbelowthemedIalmalleolus,thenervedIvIdesIntothelateralandmedIal
plantarnerves.ThenerveInnervatestheanklejoIntthroughItsartIcularbranchesand
theskInoverthemedIalmalleolus,theInneraspectoftheheel(IncludIngAchIlles
tendon),andthedorsumofthefoot(throughthemedIalandlateralplantarnerves)wIth
Itscutaneousbranches.
J. SuperfIcIalperonealnerve.ThesuperfIcIalperoneallIeslateraltothedeepperoneal
nerveIntheupperleg.ntheanterolateralaspectoflowerleg,ItbecomessuperfIcIal
about7to8cmabovethelateralmalleolusanddIvIdesIntomedIalandlateraldorsal
cutaneousnervestosupplythedorsumofthefoot.
4. Suralnerve.ThIsnervearIsesfromtIbIal(medIalsuralnerve)andcommonperoneal
(lateralsuralnerve)nerves.temergestothesuperfIcIalcompartmentatasImIlarbut
posterIorleveltothesuperfIcIalperonealnerve,7to8cmabovethelateralmalleolus
andcurvesaroundthemalleolusatsomedIstance(1to1.5cm)toenterandInnervate
thelateralaspectofthedorsalsurfaceofthefoot.
5. Saphenousnerve.ThesaphenousnerveIsthesuperfIcIaltermInusofthefemoralnerve,
whIchsupplIestheskInoverthelowermedIalleg(FIg.J827).tleavesthefemoral
nerveproxImallyInthefemoraltrIangle(ScarpatrIangle),descendswIthIntheadductor
canal,andcoursesbeneaththesartorIusmusclewIththefemoralartery(begInnIng
lateralofthevesselatfIrstandthencrossIngtothemedIalsIdesuperIortotheartery
justproxImalofthelowerendoftheadductormagnusmuscle).FurtherdIstally,the
femoralarterydepartsawayfromthesartorIusmuscle,travelIngdeeptocontInueasthe
poplItealarteryattheadductorhIatus.AtthIslocatIon,thesaphenousnervecontInues
ItscourseunderthesartorIusmuscle,travelIngadjacenttothesaphenousbranchofthe
descendInggenIcularartery.trunssuperfIcIalatthemedIalsurfaceofthelowerlegand
Infrontoftheheel.
Techniques
Psoas Compartment Block
SeveraltechnIquesforblockIngthelumbarplexususIngaposterIorapproachhavebeen
descrIbed,althoughtheapproachatthepsoascompartment,descrIbedfIrstbyChayenet
al.
1J5
In1976,remaInspopular.ThIsblockIsperformed,oftenwIthasIngleInjectIon,ata
poIntsomedIstancelateraltothespInousprocessofL4,asthenervesofthelumbarplexus
areIncloseproxImItybetweenthetransverseprocessesofL4andL5.ContInuouspsoas
compartmentblockshavealsobeenshowntobeeffectIveforanesthesIa(wIthscIatIc
nerveblock)andperIoperatIveanalgesIaInpatIentswIthhIpfractures
1J6
andafterhIp
arthroplasty.
1J7
Amorecephaladapproach,nearLJ,asdescrIbedbyParkInsonetal.
1J4
maybeused,althoughtherehavebeenreportsofrenalsubcapsularhematomaswIth
blocksperformedatthIslevel.
1J8
ThIsblockhastheadvantageofblockIngtheentIre
lumbarplexusandthereforeprovIdesanesthesIa/analgesIaoftheanterolateralandmedIal
thIgh,theknee,andthecutaneousdIstrIbutIonofthesaphenousnervebelowtheknee.
AlthoughthesacralnerverootsmaybeanesthetIzed,thIsblockwIlllIkelynotbecomplete
andscIatIcnerveblockwIllusuallyneedtobeperformedaswell.ThepatIentIsplacedIn
thelateralposItIon,wIththeoperatIvesIdeup.AdequatesedatIonshouldbeprovIded
becausetheplexuslIesdeepandtheneedlewIllpenetrateseveralmuscles.Preparethe
needleInsertIon
P.990
sIteandskInsurfacewIthanantIseptIcsolutIon.PreparetheUSprobesurfacebyapplyIng
asterIlesleeveoradhesIvedressIngtoItprIortoneedlIng.
Figure 38-29.SurfacelandmarkIngforthepsoascompartmentblock.Theneedle
InsertIonsIteIsonethIrdthedIstancealongahorIzontallIneextendIngfromtheL4
transverseprocesstowhereItcrossesavertIcallInedIssectIngtheposterIorsuperIor
IlIacspIne(PSS).PS,posterIorInferIorIlIacspIne.
Landmarks:ThelandmarksdevelopedbyCapdevIlaetal.
1J7
usIngcomputedtomography
areIllustratedhere(FIg.J829).AscomparedwIththedepthofthelumbarplexusor
transverseprocesses,thedIstancebetweentheL4spInousprocessandthelumbarplexus
wasnotaffectedbybodymassIndex.ThespInousprocessofL4IsestImatedtolIe
approxImately1cmcephaladtoalInebetweenthetopsoftheIlIaccrests(IntercrIstal
lIne);ahorIzontallIneIsdrawnlaterallyfromtheL4spInousprocessestothefarsIdeof
thebody.AvertIcallIne,runnIngparalleltothespIne,IsthendrawnatthepoIntofthe
posterIorsuperIorIlIacspIne,toIntersectthehorIzontallIne.ThelumbarplexusIsthen
locatedwIthanXbelowapoIntonthehorIzontallIne,atthejunctIonbetweenthe
lateralthIrdandmedIaltwothIrdsbetweenthespIneandPSS.ThemeanskIntolumbar
plexusdepthatthelevelofL4Is8.4cmInadultmenand7.1cmInadultwomen,based
oncomputedtomographyassessment.ThedIstancebetweentheposterIoredgesofthe
transverseprocessesofthelumbarvertebraeandthelumbarplexusIsabout1.8cm.
NeedlIng:AskInwhealIsraIsedatthemarkedblocksIte.AnInsulatedneedle(17to20
gauge,9to10cmlong)IsInsertedperpendIculartoallplanesattheXuntIlcontactwIth
theL4transverseprocessIsobtaIned(approxImately5to6cmdeep).Aftercontact,the
needleIswIthdrawnandredIrectedcaudadbelowtheprocesstoamaxImumdepthof2
cmdeeptothetransverseprocess.
Figure 38-30.UltrasoundassIstedpsoascompartmentblockade.Thecurvedarray
probecanbeplacedtransverselytocaptureanovervIewofthespInalcolumn(left
image),whIlethelongItudInalscan(right image and clinical picture)wIllhelpmark
theblocklocatIon:thetIpsofthetransverseprocesses.fattemptIngrealtIme
needleInsertIon,thesafestneedlealIgnmentwIllbeInplanetoalongItudInally
placedprobeovertheLJ5transverseprocesses.
NervelocalIzatIon:WIththenervestImulatorsettodelIveranoutputcurrentof1to1.5
mA,acontractIonofthequadratusfemorIsmuscle(patellartwItch)Issought.Theplexus
IslocalIzedwhenthemotorresponseIsmaIntaInedat0.Jto0.5mA.famotorresponse
IsnotobtaInedatfIrst,cautIouslymovIngtheneedleInaslIghtmedIaldIrectIon,
wIthoutaImIngtowardthespInalcord,orIna15degreecaudadorcephaladdIrectIon
mayhelp.
njectIon:AftertheplexusIslocalIzed,J0to40mLoflocalanesthetIcIsInjected,usIng
carefulaspIratIonandadmInIstratIonofatestdosetoruleoutIntravascular,epIdural,
orsubarachnoIdplacement.FIfteento20mInutesmayberequIredforspreadofthe
anesthetIctoalltherootsofthelumbarplexus.twIlltakelongertoproduceanesthesIa
ofthecaudadbranches(thelowersacralfIbersthatformthetIbIalnerve)andtheymay
notbeanesthetIzedatall.
ThelumbarplexusIsdIffIculttovIewadequatelyasthetargetstructuresarelocateddeep.
SImIlartoparavertebralblock,USImagIngmaybebestforIdentIfyIngtheexactlocatIon
anddepthofthetransverseprocessesprIortotheblockprocedure.fthereIsdesIreto
performtheblockatLJL4,vIewIngthekIdneysprIortoand/ordurIngtheblockmayhelp
preventrenalInjuryandhematoma.
ScannIng:Acurvedarrayprobe(5to8|Hz)IsplacedInthetransverseplaneInthe
mIdlIneattheleveloftheL4spInousprocesstoprovIdeanovervIewoftheL4vertebra
(FIg.J8J0).TheprobeshouldberotatedtothelongItudInalaxIs,paralleltothespIne,
whIchwIllallowalateralscantobeperformedtoIdentIfythetIpsofthetransverse
processes.WIthoutthecontInuatIonofrIbs,thetIpsofthetransverseprocessesarefaIrly
easIlydelIneated.
Appearance:ThedeeplocatIonofthIsblockprecludesclearvIsIbIlItyofthelumbar
plexus.ndeed,thetransverseprocesses(whIcharetheprImarylandmarks)arestIll
oftenveryvaguelydelIneated.Therefore,ItIsImportanttoswItchbetweentransverse
andlongItudInalscannIngbetweenthespInousprocessesandthetIpofthetransverse
processestosurveythearea.nthetransversescan,thespInousprocessesappear
hypoechoIc(lIkelyfromthedorsalshadowIngeffect)andextendsuperfIcIally,whIlethe
transverseprocessesarehyperechoIcmasses/lInesatthelateraledgeofthevertebra.
ThefascIcularappearIngmusculatureIsevIdentsurroundIngthevertebra,yetpoorly
delIneatedbymostcompactUSmachInes.nthelongItudInalscan,thelateraltIpsofthe
transverseprocesseswIllbeIdentIfIedatthemostlateralpoIntwhereahyperechoIc
noduleIsvIewed.
P.991
NeedlIng:NeedlIngwIllbeIdentIcaltothatforblIndtechnIque,wIththeexceptIonthat
thedepthtothetransverseprocesswIllbemoreaccuratelyknown.fchoosIngto
performamorecephaladapproachaboveL4,realtImeImagIngmaybehelpfultovIew
thekIdneys(especIallydurIngInspIratIonwhentheyfalltowardLJL4).AnPneedle
alIgnmenttoalongItudInalprobemaybemostsuItabletoavoIdexcessIvemedIalor
lateralneedleangulatIon(seeParavertebral8lockadecomments).
LocalanesthetIcspread:twIllbedIffIculttovIewlocalanesthetIcspreadwhenusIngUS
guIdance.fseen,ahypoechoIcmasswIllspreadwIthInthemusclemasslateralanddeep
tothetransverseprocess.
Comments
ThepsoascompartmentblockcanbebenefIcIalforplacIngacathetertoprovIdelong
lastInganalgesIa;thecatheterIssecurelyfIxedbythepsoasmusclesandkeptawayfrom
anyactIvejoIntregIon.AfterobtaInInggoodlocalIzatIonwIththestImulatIngneedle
(bevelfacIngcaudadandlateral),astImulatIngcatheterIsadvancedJto5cm.nsome
cases,InjectInganonconductIngsolutIonsuchas05WtoexpandtheperIneuralspace,
whIlemaIntaInIngtheelectrIcalcharacterIstIcs,Ishelpful.
27
ThequadrIcepsmuscle
contractIonshouldbemaIntaIneddurIngcatheteradvancementwIthastImulatIng
catheter.
ComplIcatIonsofthIstechnIqueIncludehematomaInthemusclesheath,retroperItoneal
space,orkIdney,InfectIon,andcatheterplacementwIthIntheperItoneum.Neuropathy
ofthenervesIspossIble.UnIntendedspreadtotheepIduralorevensubarachnoIdspace
hasalsobeenreported.nadequateanesthesIaofsomeofthebranchesmayoccurmore
frequentlythantheserarecomplIcatIons.
Separate Blocks of the Terminal Nerves of the Lumbar Plexus
AnesthesIacanbeperformedforfourtermInalnerves(lateralfemoralcutaneous,femoral,
obturator,andsaphenous),althoughalumbarplexusblockIspreferableIfanesthesIaofall
thesenervesIsrequIred.AnesthesIaofthelateralfemoralcutaneousnerveIsoccasIonally
usedtoprovIdesensoryanesthesIaforobtaInIngaskIngraftfromthelateralthIgh.tcan
alsobeblockedasadIagnostIctooltoIdentIfycasesofmeralgIaparesthetIca.Dbturator
nerveblockcanbeeffectIvetopreventobturatorreflexdurIngtransurethralbladder
tumorresectIons,fortreatmentofpaInInthehIparea,foradductorspasm(asseenIn
multIplesclerosIspatIents),orasadIagnostIctoolwhenstudyInghIpmobIlIty.
1J9
SaphenousnerveblockoftencomplementsscIatIcnerveblockwhenanesthesIaofthe
medIalaspectoftheankleandfootarerequIred.ProceduresonthekneerequIre
anesthesIaofthefemoralandtheobturatornerves,althoughpostoperatIveanalgesIaof
thekneecanusuallybeprovIdedbyfemoralnerveblockalone.SIngleshotfemoralnerve
blockprovIdessuItablepostoperatIveanalgesIaaftertotalkneearthroplasty,whIlesparIng
thesIdeeffectswhencomparedwIthIntrathecalmorphIne
140
;theuseofacontInuous
technIquecanalsoreducesIdeeffectsascomparedwIthcontInuousepIdurals
141
and
facIlItaterehabIlItatIon.
142
AUSguIdedInfrapatellarnerveblockhasbeendescrIbedfor
useforpostoperatIveanalgesIaafteroutpatIentarthroscopIcsurgery,
14J
butwIllnotbe
Includedhere.8ecauseseparatefemoralnerveblockIsusedextensIvelyforanalgesIaand
USguIdancehasbeendescrIbedforthIsblock,thIschapterwIllprovIdecomprehensIve
descrIptIonofthIsblock.USguIdanceforobturatornerveblockhasbeendescrIbedandwIll
beexamInedhere.TheothertwonerveblockswIllonlybebrIeflydIscussed.Theblock
sItesforthefemoral,lateralfemoralcutaneous,andobturatornervesareIllustratedIn
FIgureJ828.
1. FemoralNerve/FascIalIacus8lock:ProcedureUsIngNerveStImulatIon.
Landmarks:ThepatIentIsplacedInthesupIneposItIon,wIthslIghtexternalrotatIon
ofthefemur.ApIllowcanbeplacedunderthepatIent'shIptofacIlItatepalpatIonof
thefemoralpulseandaccentuateotherpertInentlandmarksforeaseofpalpatIon.
7lokaetal.
144
studIedcadaversusIngfourcommonneedleInsertIonsItesforfemoral
nerveblockandfoundthatthepoIntwherethenervelIesbeneaththeInguInalcrease,
ImmedIatelylateraltothefemoralartery,bestlocalIzedthenerve.Theartery
descendsatthemIdInguInalpoInt,atthejunctIonbetweenthemedIalthIrdand
lateraltwothIrdsoftheInguInallIgament,althoughItIsmostsuperfIcIalatthe
femoralcrease.tlIesapproxImately1to1.5cmmedIaltothenerve.TheInguInal
creaseIstheskInfoldlocatedcaudally,approxImately2.5cm,andparalleltothe
InguInallIgament(seeClInIcalAnatomyoflowerextremIty).
NeedlIng:AskInwhealIsraIsedabovethefemoralnerveanda5cm,22gauge
InsulatedneedleIsInsertedperpendIculartotheskInorusIngacephaladangleof
approxImatelyJ0degrees.AspIratIonIsperformedfrequentlybecausethefemoral
arteryIssItuatedclosetothenerve.
NervelocalIzatIon:ForthefemoralnerveusIngNS,aquadrIcepsfemorIsmuscle
response(patellartwItchpreferably)Issought,wIthanendpoIntof0.5mAusedfor
accuratelocalIzatIon.8ranchestothesartorIusmusclearIsejustInferIortothe
InguInallIgamentandleavethefemoralnerveproxImaltothemaInblocklocatIon
sIte.AresponsetostImulatIonofthIsmuscleoftenIndIcatesthattheneedleIstoo
superfIcIalandmedIaltothemaInfemoralnerve.ForafasIcaIlIacusblock,lossof
resIstancetechnIqueIsusedInsteadofNS.TheneedleIsplacedvertIcally5cmlateral
tothearteryattheInguInalcrease.Twopopsarefeltwhentheneedletraversesthe
fascIalataandIlIacusandenterstheIlIopsoasmuscle.
njectIon:njectIonof20mL(orless)oflocalanesthetIcshouldsuffIceforsolefemoral
nerveanesthesIa.ntermIttentInjectIonwIthIntervalaspIratIonshouldbeperformed.
Femoral Nerve/Fascia Iliacus Block: Procedure Using Ultrasound Imaging
ScannIng:A10|HzorhIghertransducercanbeusedforbothblocksIfthe
neurovascularstructuresarenotlocatedtoodeep(I.e.,thInIndIvIduals)asthIswIll
showgooddIstInctIonbetweenthenerveandthesurroundIngstructures(vesselsand
muscles).AmIdrange5to8|HzlIneartransducerIsrecommendedIfthenerveand
arteryaredeep(4cm).PosItIontheprobetransversetothenerveaxIsatthelevelof
theInguInalcrease(FIg.J8J1).ThenerveshouldappearapproxImately1cmdeepand
1.5cmlateraltothefemoralartery(color0opplermaybeusedtoIdentIfythefemoral
arteryandveIn).
Appearance:ThenervelIesabout1cmlateralanddeeptothelarge,cIrcular,and
anechoIcfemoralartery.toftenappearstrIangularInshapeandofvarIablesIze,
becauseofItsIrregularcourse;earlybranchIngabovetheInguInallIgamentcan
IncreasethetransversedIameterofthenerve.ThefascIalata(mostsuperfIcIal)and
IlIaca(ImmedIatelyadjacenttothenerveandInfactseparatIngthenervefromthe
artery)maybeseensuperfIcIaltothefemoralnerveandoftenappearbrIghtand
longItudInallyangled.
NeedlIng:PlacethenerveatthemedIaledgeofthescreen,wIththeprobecapturInga
transversevIewoftheneurovascularstructures.A5cm,22gaugeneedle(forsIngle
shot)canbeInsertedusIngeItherPorDDP(FIg.J8J1)needlealIgnment,although
DDPalIgnmentwIllbebenefIcIalIfInsertIngacatheter.TheneedleshouldbeInserted
usInganacute(J0to45degree)angletomaxImIzevIewIng.ForIlIacusblock,the
needleIsgenerallyplacedmorelaterallythanwIththefemoralnerveblock.
P.992
localanesthetIcapplIcatIontovIsualIzethespreadandconfIrmnervelocalIzatIon.
LocalanesthetIcspreadshouldoccurwIthInthefascIalspacesurroundIngthenerve.
ThesolutIonmaydIsplacethenervemedIallytowardorlaterallyawayfromthe
artery.
Figure 38-31.UltrasoundguIdedfemoralnerveblock.TheprobeIsplacedIna
slIghtlyoblIqueplane(atthelevelofandparalleltotheInguInalcrease)tocapture
thenerveInshortaxIslateraltothefemoralartery.Theneedlecanbeseen(not
shown)asIttransectsthefascIalataandIlIaca.nplaneneedlIngshouldoccurIna
lateraltomedIaldIrectIon.
Comments
WhenInsertIngacatheter,ItIsdebatablewhetherastImulatIngcatheterImproves
placement,
145,146
butusIngasolutIontoexpandtheperIneuralspacehasshown
benefIcIalInsomecases.
147
fusIngstImulatIngcatheters,usIng05WfortIssue
expansIonwIllmaIntaInmotorresponsestoNS.
26,27
ThelateraltomedIalneedleInsertIonwhenusIngthePneedlealIgnmentwIllensure
thatthenerveIsreachedprIortoreachIngthefemoralvessels.
tIsImportanttoensurethattheUSbeamIsperpendIculartothenerve'stransverse
axIstomInImIzeanIsotropIcaffectschangIngtheechogenIcpropertIesofthe
structure.thasbeenshownthatanapproxImate10degreescephaladorcaudadtIltof
thetransducercanmakethenerveIsoechoIc(sImIlarappearIng)totheunderlyIng
IlIopsoasmuscle.
148
2. LateralFemoralCutaneousNerve.UsIngNStechnIque,Shannonetal.
149
foundthatthe
lateralfemoralcutaneousnervecanbelocalIzedattheInguInalcrease,approxImately0
to1cmmedIaltotheanterIorsuperIorIlIacspIne(FIg.J828),althoughthIsmarkmay
behIghlyvarIant(someuse2.5cmInferIorand2.5cmmedIaltothespIne)andshouldbe
confIrmedwIthNS.AnInsulatedneedle(5cm,22gaugeIssuItable)IsInserted,usInga
perpendIcularapproachIfthepunctureIsclosetotheanterIorsuperIorIlIacspInebuta
lateraldIrectIonIfItIsatadIstance.Apopmaybefeltastheneedlepenetratesthe
fascIalata.TheprImaryendpoIntforNSwIththIsnerveIsparesthesIaoverthelateral
thIgh(FIg.J827)wIthacurrentofapproxImately0.5to0.6mA.ThesensorydIstrIbutIon
maynotextendproxImaltothegreatertrochanter.FIveto10mLofalocalanesthetIcIs
usuallysuffIcIenttoobtaInablock.
J. DbturatorNerve.8ecausetheobturatornervebranchesearlyafterItsdescentfromthe
obturatorforamen,blockIngthIsnervebeforeItbranches,wIthIntheforamennearthe
superIorpubIcramus,IsoftendescrIbedforblIndtechnIques.ThepatIentIsplaced
supInewIththehIpslIghtlyexternallyrotated;thehIpmayalsobeslIghtlyflexedand
abducted.fusIngUSImagIngastraIghtleghasbeenshowntobethebestposItIon.The
publIctubercleIslocatedandamarkIsplaced1.5cmbothInferIorandlateraltoIt(thIs
markshouldresemblethatshownInFIg.J828).
AnInsulatedneedle(18to22gauge,9to10cm)IsInsertedperpendIcularlyuntIl
contacttotheInferIorpubIcramusIsobtaIned.TheneedleIsthenredIrectedlaterally
andcaudallytoentertheobturatorforamenandadvanced2toJcm.NSusIng0.5mA
foracurrentendpoInt,wIthadductormusclecontractIon,hasbeenshowntogreatly
ImprovenervelocalIzatIon.
1J9
Procedure Using Ultrasound Imaging.TheuseofUStoblocktheobturatornervewas
recentlyIntroduced,althoughexperIencewIththIstechnIqueIslImIted.Soongetal.
150
usedtheAcusonSequoIaC256machInefromSIemens|edIcalSolutIons(|ountaIn7Iew,
CA)andfoundthattheanterIorandposterIorbranchesmaybemosteasIlyvIsualIzed
wIththeprobeplaced2cmlaterallyanddIstallytothepubIctubercle.Thebranches
maybelocalIzedoneIthersIdeoftheadductorbrevIsmuscle,IfthefascIalplanesofthe
musclesarehIghlyvIsIble(hyperechoIc).ThedepthsoftheanterIorandposterIor
branchesasmeasureddurIngUSguIdancewere15.5mmand29.Jmm,respectIvely;
tIssuecompressIonbytheprobemayInfluencethIsdepth.ThemaIn(common)obturator
nervemaybehardtovIewwIthUSImagIng.PneedlIngtechnIquewIllbeImportantto
use,aswIllcolor0oppler,InordertoavoIdadjacentvessels.
Comment
AspIratIonIsessentIalwhenInjectIngneartheunbranchedobturatornerveasthe
obturatorarterylIesadjacenttothenerve,andhemorrhageInvolvIngthIsarterycan
belIfethreatenIng.
151
4. SaphenousNerve.|anyapproachestoblockIngthesaphenousnervehavebeen
descrIbed,wIthneedleplacementatvarIouslocatIonsIncludIngthemIdthIgh,
surroundIngthekneeorattheankle(asdIscussedInAnkle8lock).UsIngblInd
technIque,atransarterIalblockdescrIbedfIrstbyvanderWaletal.
152
hasshowntobe
moreeffectIveascomparedwIthblockatthemedIalfemoralcondyle(paracondylar
block)
P.99J
ortIbIaltuberosIty(belowthekneefIeldblock)forproducInganesthesIatothemedIal
aspectofthefoot
15J
andwIllbedescrIbedhere.USguIdancehasbeenusedsuccessfully
wItheItheratranssartorIusperIfemoralapproach
154
oraperIvenous(saphenousveIn)
approach
155,156
;theprIorwIllbeIntroducedhere.UsIngthemoreproxImallylocated
largerfemoralartery(ratherthanthemoredIstalsaphenousbranchofthedescendIng
genIcularartery)asahIghlyvIsIblelandmarkseemstohelpIdentIfythesartorIusmuscle
andnerve.
Figure 38-32.UltrasoundguIdedsaphenousnerveblockusIngatranssartorIus
perIfemoralapproach.TheprobeIsplacedInthecoronalplaneatthelocatIon
wherethefemoralnervehasyettobecomethepoplItealartery,approxImately10
to12cmproxImalandJto4cmmedIaltothemIdpoIntofthepatella.UsIngthe
largefemoralarteryasalandmarkmaybebenefIcIaltomoredIstalapproaches
wherethenervelIesadjacenttothesmallersaphenousbranchofthedescendIng
genIcularartery.
148
Procedure Using Nerve Stimulation Technique (Transsartorial)
Landmarks:ThesartorIusmuscleIspalpatedatthemedIalaspectofthekneejoIntby
askIngthepatIenttoraIsetheextendedleg5to10cmoffthetable.Theblock
locatIonIsmarkedbytheendofa4cmvertIcallInedrawnfromthIspoIntIna
proxImaldIrectIon.(8enzonetal.
15J
useaslIghtlymorecephaladpoIntJto4cm
superIorand6to8cmposterIortothesuperomedIalborderofthepatella.)
NeedlIng:AnInsulated22gaugeneedleIsInsertedusInganangleof45degreeswItha
slIghtposterIorangleadvancedfromthemedIalaspectoftheknee,InaslIght
posterIorandcaudadangle,topenetratethesartorIusmuscleatadepthof
approxImately2toJcm.
NervelocalIzatIon:ParesthesIareferredtothemedIalmalleolusshouldbeelIcIted
wIththenervestImulatorat0.6mAorlessatadepthofJto5cm.
njectIon:FollowIngcarefulaspIratIon,10mLoflocalanesthetIc(e.g.,1.5to2
lIdocaIne)IsInjected.
Procedure Using Ultrasound Imaging.UsIngUS,
154
thesartorIusmusclecaneasIlybe
IdentIfIedasbeIngasuperfIcIalrooftotherelatIvelylargelandmarkofthefemoral
arterybeforethearterytravelsdeepandbecomesthepoplItealarteryvIatheadductor
hIatus.ThenerveIslocatedbetweenthesartorIusmuscleandthearteryInthethIgh.
ScannIng:AhIghfrequencylInearUStransducer(e.g.,LJ8,|Icro|axx,SonosIte,
8othell,WA)IsplacedtransverselytothelongItudInalaxIsoftheextremItyatthe
mIdthIgh,approxImately10to12cmproxImalandJto4cmmedIaltothemIdpoIntof
thepatella(FIg.J8J2).ThefemoralarterycanbeIdentIfIedherewIthcertaIntyby
power0oppler;whIchInturnconfIrmstheIdentItyoftheoverlyIngsartorIusmuscle.
TheprobeIsthenusedtoscandIstallyuntIlItcapturesthepoIntjustprIortowhere
thefemoralarterybecomesthepoplItealartery.
Appearance:UsIngcolor0opplerIsImportanttovIsualIzethefemoralartery,asa
largehypoechoIc(beneaththecolor)structureatadepthofapproxImately2toJcm
InaveragesIzedIndIvIduals.ThesartorIusmusclecanthenbeIdentIfIedasahIghly
delIneatedmuscleImmedIatelysuperfIcIaltotheartery,wIthhyperechoIcborders.
ThenervecanbeblockedasItlIessandwIchedbetweenthearteryandmuscleatthIs
level.AlternatIvely,thenervecanbeblockedmoredIstallyattheknee.
NeedlIng:A22gaugeneedleIsInsertedIneItheranPorDDPfashIontopenetratethe
sartorIusmuscletodeposItlocalanesthetIcImmedIatelybeneaththemuscleand
medIaltotheartery.FIveto10mLoflocalanesthetIcInjectedbythenerveshould
suffIce.
LocalanesthetIcspread:AsmallhypoechoIcmassonthemedIalsurfaceofthefemoral
arteryshouldappeardurIngInjectIon.
Sciatic Nerve Blockade Using Posterior, Anterior and Posterior
Popliteal Approaches
AscIatIcnerveblockcanbeusedwIthlumbarplexusblockforanesthesIaofthelower
extremIty.TogetherwIthsaphenousnerveblock,theblockproducesadequateanesthesIa
tothesoleofthefootandthelowerleg.ThelargescIatIcnerveIsdeepwIthInthegluteal
regIonandmaybedIffIculttolocateblIndlyorwIthUS.DfbenefItdurIngUSguIded
blockadeofthescIatIcnerveandItstermInalbranches(tIbIalandcommonperoneal
nerves)arethenumerousbonyandvascularlandmarksthatcanbeusedforeaseof
IdentIfIcatIon.KnowledgeofanatomyIsparamountwIththeseblocks,andtheblock
locatIonandapproachwIllultImatelydependonthesurgIcalrequIrement.Forallblocks,
preparetheneedleInsertIonsIteandotherapplIcableskInareaswIthanantIseptIc
solutIonandobtaInsterIlItyoftheUSprobewIthastandardsleevecoverortransparent
dressIng.
1. PosterIorScIatIcNerve8lock:ClassIcClutealApproach.PosItIonthepatIentsemIprone
(SImposItIon)wIththehIpandkneeflexedandtheoperatIvesIdeuppermost.
Procedure Using Nerve Stimulation
Landmarks(FIg.J8JJ):AnoblIquelIneIsdrawnjoInIngtheposterIorsuperIorIlIac
spInetothemIdpoIntofthegreatertrochanter
P.994
(onItsmedIalaspect).Next,ahorIzontallIneIsdrawnjoInIngthegreatertrochanter
(atabovelocatIon)tothesacralhIatus.AperpendIcularlInedrawnatthemIdpoIntof
theoblIquelIneandreachIngtheparahorIzontallIneIsthetradItIonalpuncturesIte
(thIsIntersectIonshouldbeapproxImately5cmcaudadalongtheperpendIcularlIne).
Figure 38-33.LandmarksforthescIatIcnerveblockusIngaposterIorgluteal
approachwhenusIngnervestImulatIonprocedure.ThIslocatIonwIllserveasa
referencepoIntwhenapplyIngultrasoundImagIng.PSS,posterIorsuperIorIlIac
spIne.
NeedlIng:FaIsealocalanesthetIcskInwhealafteraseptIcpreparatIon.A9to10cm,
22gaugeneedle,InsulatedIfNSIsdesIred,IsInsertedperpendIculartoallplanes.
NervelocalIzatIon:Nerveresponsesofthelowerlegandfootaresought.ftheyare
notobtaInedatthefulldepthoftheneedle,theneedleIswIthdrawntotheskInand
reIntroducedatalocatIonperpendIculartothecourseofthenerve.8onecontact
typIcallyrequIreslateralneedleadjustment.
njectIon:njectIonof20toJ0mLoflocalanesthetIc(e.g.,0.75ropIvacaIne,1
mepIvacaIne,0.5bupIvacaIne)Isperformed.fseveralblocksarerequIred(I.e.,
lumbarplexusand/orsaphenousnerve),areducedconcentratIonoflocalanesthetIc
maybenecessary.
ScannIng:Acurved,lowerfrequency2to5|HzprobeIsgenerallyusedforscannIng
theglutealregIon(FIg.J8J4).|ovIngtheprobecephaladandcaudadInthegluteal
regIonwIllhelpexamInetheIschIalbone(ahyperechoIclInewIthbonyshadowIng
underneath),andthewIdestportIonofthIsbonewIththeIschIalspInemedIallyshould
belocated.ThebulkygluteusmaxImusmusclewIllbeseensuperfIcIalandposterIorto
thescIatIcnerve.7ascularstructuresthatmaybeusefultoIdentIfyusIngcolor
0oppleraretheInternalpudendalvessels(arteryandveIn)thatareadjacenttothe
IschIalspInethatIsmedIaltothescIatIcnerveandtheInferIorglutealartery
ImmedIatelyadjacenttothescIatIcnerve.AlternatIvely,thenervecanbelocated
fIrstatthesubglutealregIon,ataboutthemIdpoIntbetweenthegreatertrochanter
andIschIaltuberosIty,andtracedproxImally.
Figure 38-34.UltrasoundguIdedscIatIcnerveblockusIngaposterIorgluteal
approachandanInplaneneedlealIgnmenttoacurvedlowfrequencyprobe.The
lateraltomedIalneedledIrectIonmayhelpavoIdpunctureoftheInferIorgluteal
orInternalpudendalvessels.
Appearance:ThescIatIcnerveIntheglutealregIonIsfoundlateraltotheIschIalspIne
andsuperfIcIaltotheIschIalbone.tappearspredomInantlyhyperechoIc(brIght)and
IsoftenwIdeandflatInshortaxIsonUS.DverlyIngthescIatIcnervelIesthelarge
gluteusmaxImus,whIchIsquItedIstInctwIththeusualstarrynIghtappearance;the
Innermusclelayers(superIorandInferIorgemellusmuscles,obturatorInternusmuscle,
andquadratusfemorIsmuscle)areoftenIndIstInct.
NeedlIng:8oththePandDDPapproachesareapproprIateforUSguIdedscIatIcnerve
blockIntheglutealregIon.ForDDPneedlIng,theneedleIsInsertedInferIortothe
probeInacephaloanterIordIrectIon.AfaIrlysteepangleofInsertIonwIllberequIred,
butplacIngtheneedleslIghtlyInferIortotheprobewIllreducetheanglesomewhatfor
bettervIsIbIlItyoftheneedle.WIththePapproach,theneedlemaybemovedIna
lateraltomedIaldIrectIontopenetratethegluteusmaxImusmuscleprIortoreachIng
thescIatIcnerveabovetheIschIalbone(FIg.J8J4).
localanesthetIcapplIcatIontovIsualIzethespreadandconfIrmnervelocalIzatIon.t
IsgenerallyrecommendedtodeposItthelocalanesthetIcsolutIonsothatItspreads
completelyaroundthescIatIcnerve.
Comments
ForbothPandDDPneedlIngapproaches,scannIngprIortoneedlIngwIlldetermIne
theangle,dIstance,anddepthofneedlepenetratIon.
TheDDPapproachIsoftenusedforcatheterInsertIonandItIsImportanttolIneupthe
sIteofneedleInsertIonattheskInwIththetargetnerve.
P.995
J. PosterIorScIatIcNerve8lock:SubglutealApproach.ThepatIentIsposItIonedsemIprone
(SImposItIon)wIththehIpandkneeflexedandthefootrestIngonthedependentknee.
nsomepatIents,thesupIneposItIonwIththehIpflexedandkneebentIseIthermost
comfortableornecessItatedbecauseoffractureorpaInatthehIp.ThIslatterposItIon
requIresanassIstanttosupportthebentleg.
Landmarks:AhorIzontallIneIsdrawnjoInIngthemedIalaspectofthegreater
trochantertotheIschIaltuberosIty.ThetradItIonalpuncturesIteIslocatedonthIs
lInejustmedIaltoItsmIdpoInt.
NeedlIng:A5to10cmInsulatedneedleIsused,dependIngonpatIentsIze.Theneedle
IsInsertedperpendIculartoallskInplanes.
NervelocalIzatIon:ConfIrmIngscIatIcnervelocalIzatIonwIthNSIsImportantprIorto
localanesthetIcapplIcatIon.SImIlarresponsesasthatfortheclassIcglutealapproach
aresought,wIthankleresponsespreferable.tIsImportanttodIstInguIshthetIbIal
(InversIonorplantarflexIon)andcommonperoneal(eversIonordorsIflexIon)
componentsofthenerve,andeItherobtaInbothormostImportantlythetIbIal
response.
njectIon:njectIonof20toJ0mLoflocalanesthetIcIssuffIcIent.faddItIonalblocks
ofthelowerextremItyarealsoperformed,asolutIonwIthlowerconcentratIonshould
beconsIdered.
ScannIng:Acurved,lowerfrequency2to5|HzprobeoralInear4to7|HzprobeIs
suItableforscannIngthesubglutealregIon(FIg.J8J5).Thecenteroftheprobeshould
bealIgnedwIththemIdpoIntofalInebetweentheIschIaltuberosItyandthegreater
trochanter.fthescIatIcnerveIsdIffIculttolocalIzeatthesubglutealregIon,Itcan
betracedproxImallyfromthebIfurcatIonpoIntatorneartheapexofthepoplIteal
fossa.
Appearance:DnthelateralsIdeofthescreen,themedIalaspectofthegreater
trochanterappearsalmostpearshapedandhypoechoIcwhenusIngacurvedarray
probe.ThescIatIcnerveInthesubglutealregIonappearspredomInantlyhyperechoIc
(brIght)andIsoftenellIptIcalInashortaxIsvIewusIngUS.
NeedlIng:SImIlartotheclassIcglutealapproach,bothPandDDPplaneneedlIngcan
beperformed,wIththeneedledIrectedfromlateraltomedIalforthePtechnIque.
UsInganangleofInsertIonofapproxImately45degreestotheskInwIllprovIdethe
bestvIewoftheneedleandreachthenerve,although60to70degreesmaybe
requIredIncertaInobeseIndIvIduals.
Figure 38-35.UltrasoundguIdedscIatIcnerveblockfromthesubglutealapproach
usIngoutofplaneneedlIngtoacurvedprobe.ThemedIallyposItIonedIschIal
tuberosItyIsnotcapturedInthIsImage,butwIllserveasagoodbonylandmarkIn
mostcIrcumstances.DutofplaneapproachesoftenwIllbeusedasthIsblockIs
oftenusedforIndwellIngcatheterplacement.
LocalanesthetIcspread:ThegoalIstodeposItlocalanesthetIc(20toJ0mL)nextto,
butnotdIrectlywIthIn,thescIatIcnervestructureInthesubglutealregIon.A
hypoechoIclocalanesthetIcfluIdcollectIonIsoftenseenaroundthehyperechoIcnerve
wIthInthesheathcompartmentdurIngInjectIon.
Comments
WIththenecessItyofusIngacurvedarrayprobeInmanycases,theneedletIpas
vIewedbyDDPneedlIngwIllbeevenmoredIffIculttoIdentIfythanwhenusInghIgher
resolutIonlInearprobes.0espItethIs,thIsapproachIsusedoftenbecauseIndwellIng
cathetersarecommonlyplacedInthesubglutealarea.twIllbeImportanttouseNSIn
addItIontoUSguIdedtechnIquetoconfIrmtheneedleandlocalanesthetIcplacement.
4. AnterIorScIatIcNerve8lock.ThIsblockIsmostsuItableforthosepatIentswhocannotbe
posItIonedlaterally.TheblockIsIndIcatedforsurgerybelowtheknee,wIththeonly
sensorydefIcIencybeIngthemedIalstrIpofskInsupplIedbythesaphenousnerve.The
anterIorblockIsperformedonashortportIonofthescIatIcnerveclosetothelesser
trochanterofthefemur.ThepatIentIsposItIonedsupIne,wIththelegtobeblocked
externallyrotatedslIghtly.
Landmarks:AlIneIsdrawnconnectIngtheanterIorsuperIorIlIacspInewIththepubIc
tubercle(InguInallIgament).AsecondlIne,paralleltothefIrst,Isdrawnacrossthe
thIghfromthegreatertrochanter.ThenerveIsusuallylocatedattheIntersectIonon
thelowerlIne,wIthalInedrawndownwardfromapoIntatthemedIalthIrdofthe
upperlIne.AlternatIvely,thenerveIslocatedlateraltothefemoralarterypulseat
theleveloftheInguInalcrease.
NeedlIng:A22gauge,12to15cmInsulatedneedlewIllberequIredforthIsdeep
block.TheneedleIsInsertedperpendIculartotheskInandadvanceduntIlcontact
wIththefemuroccurs;theneedleIsthenwIthdrawnslIghtly,angulatedslIghtlymedIal
andcephalad,andIntroduced5cmfurther.
P.996
NervelocalIzatIon:|otorresponsesoftheanklejoIntorfootaresought.
njectIon:TwentytoJ0mLoflocalanesthetIcIsInjectedaftercarefulaspIratIonand
admInIstratIonofatestdose.
Figure 38-36.UltrasoundguIdedscIatIcblockfromananterIorapproach.The
clinical pictureandupper imageshowprobeposItIonIngandashortaxIsvIewof
thenervethatmaybeused.UsIngalongItudInallyplacedprobetocapturethelong
axIsofthenerve(lower image)maybebenefIcIalIfthetransversevIewIsdIffIcult
tocapturebecauseofbonyshadowIngfromthelessertrochanter.
ScannIng:tIsmostcommontouseacurved,lowerfrequency2to5|Hzprobefor
scannIngthescIatIcnerveIntheproxImalthIgh(FIg.J8J6).Placetheprobeoverthe
proxImalthIghapproxImately8cmdIstaltothefemoralcrease.Atransverselyplaced
probeIscommonlyused,althoughthenervemaybebestvIsualIzedbyplacIngthe
probeaxIslongItudInallyalongthecourseofthenerve,ascapturIngalongItudInalaxIs
ofthenervemayImproveItsIdentIfIcatIon.|ovIngInamedIaltolateraldIrectIon
maybehelpfultocaptureanImageofthenerve.
Appearance:ntransverseaxIs,thescIatIcnerveoftenappearsovalorround,
predomInantlyhyperechoIc,medIalandposterIortothelessertrochanter,anddeepto
theadductormagusmuscle.fusIng0oppler,thefemoralneurovascularstructuresare
seensuperfIcIallybelowthehyperechoIcfascIaltIssueandlateraltothescIatIcnerve
InthIsprojectIonwhenthelegIsexternallyrotated.AlongItudInalvIewcapturesa
broad,lInear,andhyperechoIccableoffIbersandmayalloweasIerIdentIfIcatIonof
thenerve.
157
NeedlIng:WhenusIngaprobeposItIonedIntransverseaxIstothenerve,anP
approachIncludesadvancIngtheneedleInamedIaltolateralandanterIorto
posterIordIrectIon,whIleanDDPapproachInvolvesInsertIngtheneedlealongthe
mIdlIneoftheprobeatalocatIon2toJcmInferIorandperpendIculartotheprobe.f
theprobeIsplacedlongItudInally,theneedledIrectIonforDDPalIgnmentwIllbe
sImIlartothatforthePasprevIouslydescrIbed.WIthPalIgnment,theneedleshould
beplacedafewcentImeterscaudadtotheprobetoImproveneedlevIsIbIlItyby
reducIngtheangleofInsertIon.tIshIghlyrecommendedtousecombInedUSandNS
guIdanceforthIsprocedure.
LocalanesthetIcspread:AftercarefulaspIratIonandInjectIonofasmallamountof
05WtovIsualIzetheprobableanesthetIcspread,InjectthelocalanesthetIcwhIle
ensurIngthatItspreadscIrcumferentIallyaroundthenerve.
Comments
AlthoughdeposItIngthelocalanesthetIcaroundthenerveIsdesIrable,ItIstechnIcally
challengIngtoreposItIontheneedleonbothsIdesofthenervebecauseofItsdepth
wIthInthemusclelayers.
SImIlartootherscIatIcnerveblocks,IfotherblocksarebeIngcombInedwIththIs
block,thelocalanesthetIcmayneedtobedIlutedtoreducetherIskoftoxIcIty.
ComplIcatIonsarerare,butIncludeIntravascularInjectIon(e.g.,femoralartery),
InfectIonIntheInjectIonarea,hematomaformatIon,nerveInjury.andpotentIalCNS
toxIcIty.
5. PosterIorPoplItealScIatIc8lock.ThescIatIcnervecanbeblockedbelowthehIpatthe
lateralmIdfemoralorlateralpoplIteallocatIonsInaddItIontotheposterIorpoplIteal
locatIon,
158,159
butwhenusIngUSguIdancetheposterIorapproachallowstheneedleto
beplacedcloselytotheprobeandthusmayImproveneedletrackIngandvIsIbIlIty.
Furthermore,theposterIorpoplItealapproachIsmostamenabletoInsertIngIndwellIng
catheters.ThepatIentIsposItIonedlaterallyorpronewIththeoperatIvelegslIghtly
flexed.deally,theanklesshouldbeposItIonedbeyondtheendofthetablesothat
motorresponsestoNScanbereadIlyobserved.ThelandmarksbecomemorevIsIble
whenthekneeIsflexedagaInstresIstance.
Figure 38-37.UltrasoundguIdedpoplItealnerveblock.TheprobeIsInItIallyplaced
atthepoplItealcrease(lower image)andsubsequentlyIsusedtoscanproxImallyto
capturethescIatIcnervejustproxImaltoItsbIfurcatIon(I.e.,theIdealblocksIte)
approxImately6to10cmabovethecrease(upper image).
Landmarks:ThepuncturesIteIsoftenlocatedatthetIpofatrIangleformedbythe
poplItealcreaseatthebase,thebIcepsfemorIstendonlaterally,andthe
semImembranosus
P.997
tendonmedIally(thIstendongenerallylIesmedIaltothetendonofthesemItendInosus
atthIslocatIon).AlternatIvely,drawInglInes8cmlongInthecephaladdIrectIon,from
theInsertIonsIteofthemedIalandlateraltendons(above),thepuncturepoIntIsat
themIdpoIntofalIneattachIngthetwo(almostparallel)lInes.tmaybebestto
InserttheneedleatapproxImately10cmabovethepoplItealfossaInordertoensure
thescIatIcnerveIsblockedbeforeItsbIfurcatIon.
NeedlIng:0ependIngonthepatIent,a5to10cmInsulated22gaugeneedlecanbe
InsertedusInganangle45degreescephaladtotheskIn.AfanwIsesearchIsconducted
perpendIculartothIslIneuntIlthenerveIscontacted.fthefemurIscontactedbythe
needle,thedepthIsnoted.ThenerveshouldlIemIdwaybetweentheskInandthe
femur.
NervelocalIzatIon:NSIsusedtolocalIzethenervebyelIcItIngmotorresponsesatthe
ankleorfoot.TheaImshouldbetolocalIzethescIatIcnervebeforeItsbIfurcatIon
IntotIbIalandcommonperonealnervecomponents.fonlyankleInversIonand/or
plantarflexIon(tIbIalnerve)oreversIonand/ordorsIflexIon(commonperoneal)Is
seen,ItwouldbeapproprIatetoadjusttheneedleInsertIonsIteafewcentImeters
cephaladtoobtaIncompleteankleandfootmovements.DtherwIse,InjectIngafter
obtaInIngasoletIbIalnerveresponsehasbeenshowntoprovIdesImIlarsuccessto
thatafterbothtIbIalandcommonperonealresponses(wIthtwoInjectIons).
160
|aIntaInIngamotorresponsewIthcurrents0.5mAwIllhelpensurethenerveneedle
dIstanceIsapproprIateforsuccessfulblock.
161
njectIon:TwentytoJ0mLoflocalanesthetIcshouldbedeposItedatthefInalneedle
locatIon.
Procedure Using Ultrasound Guidance
ScannIng:AlInear,hIgherfrequency10to15|HzprobeIscommonlyusedforscannIng
thescIatIcnervetransverselyInthepoplItealfossa(FIg.J8J7).AtechnIquethatuses
adIstaltoproxImalscancaneffectIvelylocatethescIatIcnerveIntheposterIor
poplItealfossaatalocatIonwhereIthasyettobIfurcate(FIg.J8J7).AtthepoplIteal
crease,thetransverseprobecapturesthetIbIalandcommonperonealnerves,wIth
theprIorbeIngadjacentandlateraltothepoplItealvessels(0opplerIsveryvaluable
here).0urIngaproxImalscan,thetIbIalandcommonperonealnervesapproacheach
otherandfInallyjoIntoformthescIatIcnerve.
Appearance:AtthelevelofthepoplItealcrease,thetIbIalandcommonperoneal
nerveslIesuperfIcIalandlateraltothepoplItealvessels(commonperonealnerveIs
themostlateral);bothnervesappearroundtoovalandhyperechoIccomparedwIth
thesurroundIngmusculature.ThehyperechoIcborderofthefemur(condyles)maybe
apparent.0urIngtheproxImalscan,thetIbIalnervemovesawayfromthevesselsand
approachesthecommonperonealnerve.|orecephaladIntheposterIorthIgh,the
bIcepsfemorIsmusclelIessuperfIcIaltothejoInIngnervesandappearsasalarger,
ovalshapedstructurewIthlessInternalpunctuateareas(hypoechoIcspots)thanthe
nerves.ThescIatIcnerveappearsasalarge,roundtoflatovalhyperechoIcstructure.
P.998
Figure 38-38.UltrasoundguIdedposterIortIbIalnerveblockattheankleusInga
smallfootprIntlInearprobe.ThenerveIscapturedadjacenttotheposterIortIbIal
artery,prIortoItsdIvIsIonIntothemedIalandlateralplantarnerves.
NeedlIng:AnDDPapproachwIllbecommonlyperformed,especIallyIfplacIng
IndwellIngcatheters.TheprobeIsposItIoneddIrectlyabovethescIatIcnerveator
slIghtlycephaladtoItsbIfurcatIonpoIntandsothatthenerveIsplacedInthecenter
oftheImage.TheneedleshouldbeInsertedatthecaudalsurfaceofprobe,wIththe
needletIpcontactIngtheskInapproxImatelyJto4cmcaudaltotheprobesurface.
LocalanesthetIcspread:ThecorrectresponsetoproperInjectIonIsanexpansIonof
hypoechoIcfluIdcompletelyaroundthehyperechoIcnervestructure,producInga
donutsIgn;twoseparateInjectIons(medIalandlateral)mayberequIredfor
completecIrcumferentIalspread.
Comments
TheUSprobemayberotated90degreestoshowthescIatIcnerveInlongaxIs.ThIsIs
helpfultodIfferentIatethescIatIcnervefromothernonneuralstructures.
0urIngneedleInsertIonusInganDDPapproach,ItmaybehelpfultouseIncremental
needleangulatIons:theneedlemaybebesttrackedwIthInthetIssueIfanInItIal
shallowangleIsusedtoclearlyIdentIfytheneedletIpasahyperechoIcdot,whIchcan
befollowedwIthsubsequentsteeperneedleangulatIons(seethedescrIptIonofthe
walkdowntechnIqueunderPractIcalApproachesforUltrasoundCuIdance).
J4
Ankle Block
AllfIvenervesofthefootcanbeblockedattheleveloftheankle.ThesuperfIcIalnerves
(sural,superfIcIalperoneal,andsaphenousnerves)canbeblockedbysImpleInfIltratIon
technIques.USguIdancecanbeusefulforblockIngtheposterIortIbIalanddeepperoneal
(fIbular)nervesastheIrlocatIonscanbeeasIlyIdentIfIednexttorelIablelandmarks(I.e.,
bonesandvessels)thatareclearlyvIsIble.
1. PosterIorTIbIalNerve
Procedure Using Landmark Technique
Landmarks:TheposterIortIbIalnerveIsthemajornervetothesoleofthefoot.tcan
beapproachedwIththepatIenteItherIntheproneposItIonorlyIngsupInewIththe
hIpandkneeflexedsothatthefootrestsonthebed.ThemedIalmalleolusIs
IdentIfIed,alongwIththepulsatIonoftheposterIortIbIalarterybehIndIt.Thenerve
IslocatedposterIortotheartery.
NeedlIng:AneedleIsIntroducedthroughtheskInjustbehIndtheposterIortIbIalartery
anddIrected45degreesanterIorly,seekIngaparesthesIaInthesoleofthefoot.
AlthoughnottypIcal,IfNSIsused,twItchesofthefIrst(medIalplantarbranch)and
fIfth(lateralplantarbranch)toeswIllbesought.
njectIon:FIvemIllIlItersofalocalanesthetIcproducesanesthesIaIfaparesthesIaIs
IdentIfIed.fnot,afanshapedInjectIonof10mLcanbeperformedInthetrIangle
formedbytheartery,theAchIllestendon,andthetIbIaItself.
ScannIng:AlInear(hockeystIck)10|HzprobewIthasmallfootprIntIsposItIonedIn
transverse(short)axIstothenervejustposterIorandInferIortothemedIalmalleolus
(FIg.J8J8).AlternatIvely,thenervecanbeIdentIfIedJto5cmabovethemalleolus.
Color0opplerIshelpfultolocalIzethenerveattheselocatIonsasthenervelIes
posterIoranddeeptotheposterIortIbIalarteryatbothlocatIons.Thenerveshouldbe
localIzedbeforeItbranchesIntothemedIalandlateralplantarnerves.
Appearance:mmedIatelyanterIortothearterylIesthehypoechoIccIrcularposterIor
tIbIalveIn;thIsmaybecompressedandnotapparentonthescreen.PosterIortothe
artery,thenerveappearsslIghtlymorehyperechoIcthanthesurroundIngtIssuesand
lookslIkeacondensedhoneycombappearIngstructure.
NeedlIng:AJ.5to5cmneedleIsInsertedusIngeItheranDDPapproachwIththe
needlecaudaloranPapproachwIththeneedleanterIortothetransversely
posItIonedprobe.
2. Suralnerve.ThepatIentIsplacedeItherIntheproneposItIonorsupInewIththehIpand
kneeflexedsothatthefootrestsonthebed.TheposterIorlylocatedsuralnervecanbe
blockedbyInjectIononthelateralsIde.ThesubcutaneousInjectIonofarIdgeof
anesthesIabehIndthelateralmalleolus,fIllIngthegroovebetweenItandthecalcaneus,
producesanesthesIaofthesuralnerve.ThIswIllrequIreanother5mLoflocal
anesthetIc.
J. 0eepPeronealNerve.
Procedure Using Landmark Technique
Landmarks:ThIsIsthemajornervetothedorsumofthefootandlIesInthedeep
planeoftheanterIortIbIalartery.ThepatIentIsposItIonedsupIne,generallywIththe
leg
P.999
extended.PulsatIonofthearteryIssoughtattheleveloftheskIncreaseonthe
anterIormIdlInesurfaceoftheankle.fthearteryIsnotpalpable,thetendonofthe
extensorhallucIslonguscanbeIdentIfIed(thenervelIesImmedIatelylateraltothIs)
byaskIngthepatIenttoextendthebIgtoe.
NeedlIngandInjectIon:fthearterypulsecanbefelt,5mLoflocalanesthetIcIs
InjectedjustlateraltothIs.fthearteryIsnotpalpable,thetendonoftheextensor
hallucIslonguscanbeIdentIfIedbyaskIngthepatIenttoextendthebIgtoe.fusIng
NS,toeextensIonIssoughtforthIsnerve.njectIoncanbemadeIntothedeepplanes
belowthefascIausIngeItheroneoftheselandmarks.
Figure 38-39.UltrasoundguIdeddeepperonealnerveblockattheanterIorankle.t
Ishelpfultousecolor0opplertolocalIzetheanterIortIbIalarterylyIngImmedIately
medIalandadjacenttothenerve.
ScannIng:AsmallfootprIntlInear(hockeystIck)10|HzprobeIsplacedIntransverse
(short)axIstothenerveattheanterIorsurfaceoftheanklejoInt(FIg.J8J9).
AlternatIvely,thenervecanalsobefoundJto5cmabovetheanklejoInt.However,
thenerveItselfcanbedIffIculttoseeandonlythearterycanbeconsIstentlylocated.
Color0opplercanbeusedatbothlocatIonstoIllumInatetheanterIortIbIalartery
lyIngmedIaltothenerve.
Appearance:fseen,thenerveappearsasasmallclusterofhyperechoIcfascIcular
appearIngfIbersImmedIatelylateraltotheartery,wIthbothadjacenttothewell
demarcateddIstalendofthetIbIa.
NeedlIng:AnDDPapproachwIllbemostsuItablehereasthetendonslIeoneIthersIde
ofthenerve.AJ.5to5cmneedleIsInsertedDDPandcaudaltothetransversely
posItIonedsmallfootprIntprobe.
LocalanesthetIcspread:njectIonof4to5mLoflocalanesthetIcsolutIonlateralto
thenervewIllhelpavoIdtheanterIortIbIalartery.AspIratIonIsImportanttoperform
prIortoInjectIon.
4. Saphenousnerve.ThepatIentIsplacedsupInewIththelegextended.Thesaphenous
nerveIsanesthetIzedbyInfIltratIng5mLoflocalanesthetIcaroundthesaphenousveIn
atthelevelwherethIsveInpassesanterIortothemedIalmalleolus.AwallofanesthesIa
betweentheskInandtheboneItselfsuffIcestoblockthenerve.SeeSeparate8locksof
theTermInalNervesoftheLumbarPlexusforblockadeofthIsnervemoreproxImallyIn
thethIgh.
5. SuperfIcIalperonealbranches.FInally,asubcutaneousrIdgeofanesthetIcsolutIonIslaId
alongtheskIncreasebetweentheanterIortIbIalarteryandthelateralmalleolus.ThIs
subcutaneousrIdgeoverlIestheprevIoussubfascIalInjectIonforthedeepperoneal
nerve.Another5to10mLoflocalanesthetIcmayberequIredtocoverthIsarea.
6. Comments.
AnesthesIaofthefootusuallyensueswIthIn15mInutesafterperformanceofthesefIve
InjectIons.
ComplIcatIonsofthIsblockarerare,althoughneuropathycanbeproduced.Care
shouldbetakennottopInanyofthedeepnervesagaInsttheboneatthetImeof
InjectIon,andIntraneuralInjectIonshouldbeavoIded.EpInephrIneshouldnotbe
addedtolocalanesthetIcsusedforthIsblockInordertoavoIdcompromIsIngthedIstal
cIrculatIon.
USImagIngforthedeepnervesmayhelpavoIdbonecontactandavoIdthemultIple
InjectIonsoftheInfIltratIontechnIque.
Acknowledgments
Theauthorsthank0r.|IchaelF.|ulroy,authorofthePerIpheralNerve8lockchapterIn
thefIfthedItIonofthIstextbook,forprovIdInganInvaluabletemplatefromwhIchthIs
chapterwasfashIoned.|anyofthesImplIfIedanatomIcdrawIngsforthIschapterwere
producedbyandusedwIthpermIssIonfrom|s.CarolChan.|ostfIgureswereadapted
fromoneoftheauthor's(8.T.)textbooks,entItledAtlasofUltrasoundandNerve
StImulatIonCuIdedFegIonalAnesthesIa.
J4
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Stock, M. Christine
TableofContentsSectIon7AnesthesIaforSurgIcalSubspecIaltIesChapterJ9AnesthesIaforNeurosurgery
ChapterJ9
Anesthesia for Neurosurgery
M. Sean Kincaid
Arthur M. Lam
Key Points
1. Anatomically, blood flow to the normal brain is supplied by the two
carotid arteries and vertebral arteries. Collateral circulation is
provided via the Circle of Willis.
2. Physiologically, blood flow to the brain is tightly regulated. The
homeostatic mechanisms include flow-metabolism coupling, pressure
autoregulation, and CO
2
reactivity.
3. These homeostatic mechanisms are affected by diseases as well as
anesthetic drugs and techniques.
4. Multiple monitoring modalities are available to monitor brain function,
perfusion, and oxygenation/metabolism. These include
electroencephalogram, somatosensory evoked potentials, motor
evoked potentials, electromyogram, intracranial pressure,
transcranial Doppler ultrasonography, brain tissue oxygenation, and
jugular venous oximetry. Although most are applicable for monitoring
in the neurointensive care unit, many are useful in the operating
room to increase patient safety and improve outcome.
5. Definitive cerebral protective therapy remains elusive, but many
techniques have been investigated and some are frequently used in
the operating room on theoretical grounds. These include the use of
hypothermia, tight control of blood glucose, and maintenance of
adequate perfusion. Anemia threshold for blood transfusion remains
controversial.
6. Anesthetic management of the patient with neurologic disease
mandates a thorough preoperative assessment as there are often
multisystem manifestations.
7. Anesthetic techniques may influence brain relaxation conditions. In
general intravenous agents cause more cerebral vasoconstriction
than inhalation agents. There are no outcome studies demonstrating
the superiority of any particular anesthetic agent. The use of
intraoperative monitoring of evoked potentials makes an impact on
the choice of anesthetic technique.
8. Movement of water into the brain is primarily determined by the
osmotic gradient, which in turn is determined by serum osmolarity.
Outcome studies do not provide guidance regarding the choice of
crystalloids versus colloids. In patients with brain trauma the use of
albumin for resuscitation is associated with increased mortality.
9. Common neurosurgical procedures requiring special understanding
and expertise include tumor excision, transphenoidal or transcranial
removal of pituitary lesions, extirpation of arteriovenous
malformation, repair or clipping of aneurysms, carotid
endarterectomy, craniotomy for traumatic brain lesions including
epidural and subdural hematomas.
P.1006
Goals
ThegoalofthIschapterIstoprovIdetheanesthesIologIstwIththerequIsIteknowledge
basewIthwhIchtoapproachtheanesthetIcmanagementofpatIentswIthdIseaseofthe
centralnervoussystem(CNS),IncludIngthebraInandthespIne.AfteranovervIewof
neuroanatomyandneurophysIology,thefocusofthechapterIsonanesthesIafor
neurosurgIcalproceduresandspInesurgery,buttheInformatIonshouldalsoberelevantto
thepatIentwIthneurologIcdIseasewhoIsundergoIngnonneurosurgIcalprocedures.
Neuroanatomy
AbasIcknowledgeofneuroanatomyIsessentIalforallanesthesIologIsts,partIcularlythose
carIngforpatIentswIthdIseaseoftheCNS.AlthoughthebraInandspInalcord,whIchmake
uptheCNS,arefragIleorgans,thebonystructuresthatsurroundthemprovIdeprotectIon.
YetbyvIrtueoftheIrprotectIvenature,thesestructuresarenondIstensIble.The
IntracranIalvolumeIsfIxed,therebyprovIdInglIttleroomforanythIngotherthanthe
braIn,cerebrospInalfluId(CSF),andbloodcontaInedInthecerebralvasculature.Eventhe
spaceInthespInalcolumn,althoughnotasrestrIctIveasthecranIum,IsquIcklyexhausted
byanexpandInghematomaorabscess.tIsInthecontextoftherestrIctIvenatureofthe
spaceInwhIchtheCNSIshousedthatallInterventIonsmustbeconsIdered.
ThebloodsupplytothebraInIsalsounIque.ThecarotIdarteryIntheneckbIfurcatesInto
theexternalandInternalcarotIdarterIes,sendIngtheInternalbranchthroughthebaseof
theskull,perfusIngtheeyevIatheophthalmIcartery,andultImatelybIfurcatIngIntothe
anterIorandmIddlecerebralarterIes.ThesevesselsdefInetheanterIorcerebral
cIrculatIon.TheposterIorcIrculatIonresultsfromthevertebralarterIes,whIchascendIn
theposterIoraspectoftheneckthroughforamInaInthecervIcalvertebralbodIesbefore
exItIng,coursIngaroundthebraInstem,andjoInIngthecontralateralvesseltoformthe
basIlarartery.ThebasIlararteryascendsalongthebraInstembeforedIvIdIngIntothe
posterIorcerebralarterIes.TheanterIorandposterIorcIrculatIonsanastomosethroughthe
posterIorcommunIcatIngarterIestoprovIdecollateralflow;collateralcIrculatIoncanalso
occurthroughtheanterIorcommunIcatIngarteryconnectIngthebIlateralanterIorcerebral
arterIes.ThIssystemofcollateralIzatIon,namedthecircle of Willis(FIg.J91),was
descrIbedbyThomasWIllIs(16211675)wIththerecognItIonofItspurposethatthere
maybeamanIfoldway,andthatmorecertaIn,forthebloodabouttogoIntodIvers
FegIonsofthe8raIn.
ThespInalcolumnIsthebonystructuremadeupofthe7cervIcal,12thoracIc,5lumbar
vertebrae,aswellasthesacrum.ThespInalcordexItstheskullthroughtheforamen
magnumandentersthecanalformedbythevertebralbodIes.ntheadult,thecord
typIcallyendsattheloweraspectofthefIrstlumbarvertebralbody.
8loodsupplytotheentIrecordIsprovIdedbyseveralsources.TheanterIorspInalartery,
whIcharIsesfromthevertebralarterIes,supplIestheanterIortwothIrdsofthespInalcord.
ThIsvesselrunsthelengthofthecord,receIvIngcontrIbutIonfromradIculararterIesvIa
Intercostalvessels.ThearteryofAdamkIewIczIsthemostImportantradIcularvessel,
typIcallyjoInIngtheanterIorspInalarteryInthelowerthoracIcregIonandprovIdIngblood
tothethoracolumbarcord.TheposterIorthIrdofthecordIssupplIedbytwoposterIor
spInalarterIes,whIcharIsefromthevertebralarterIesandalsoreceIvecontrIbutIonfrom
radIculararterIes(FIg.J92).
Figure 39-1.CIrcleofWIllIs,andotherbloodsupplytobraInandspInalcord.
Neurophysiology
CerebralmetabolIcrateIsdIrectlyrelatedtothenumberandfrequencyofneuron
depolarIzatIons.Therefore,anyactIvItyorstImulatIonraIsesthemetabolIcrate.Cerebral
bloodflow(C8F)IstIghtlycoupledtometabolIsm,onaregIonalaswellonagloballevel.
Asanexample,althoughvIsualstImulatIonmayraIsebloodflowtotheoccIpItalcortex,
mIldhyperthermIa,whIchraIsesglobalcerebralmetabolIcrate,Increasesflowtothe
entIrebraIn.
TheCSFoccupIesthesubarachnoIdspace,provIdIngaprotectIvelayeroffluIdbetweenthe
braInandthetIssuethatsurroundsIt.CSFIsproducedbythechoroIdplexusInthe
ventrIcles.CSFproducedInthelateralventrIclestravelsIntothethIrdventrIclevIathe
InterventrIcularforamIna.tsubsequentlytransItsthroughthecerebralaqueductIntothe
fourthventrIcle,andthenIntothespacearoundthebraInvIatheforamInaofLuschkaand
|agendIe.tbathesboththespInalcordandthebraIn.AbsorptIonIntotheduralvenous
sInusesoccursthroughthearachnoIdgranulatIons.AlthoughCSFvolumeIsapproxImately
150mL,morethanJtImesthIsamountIsproducedIna24hourperIod.ThIscontInuous
flowofCSFfromsourcetosInkallowsIttopartIcIpateInmanyfunctIonsInaddItIonto
cushIonIngthebraIn.tmaIntaInsamIlIeuInwhIchthebraIncanfunctIonbyregulatIngpH
andelectrolytes,carryIngawaywasteproducts,anddelIverIngnutrIents.
1,2
ntracranIalpressure(CP)IslowexceptInpathologIcstates.The|onroeKellIedoctrIne
statesthatInthesettIngofanondIstensIblecranIalvault,thevolumeofblood,CSF,and
braIntIssuemustbeInequIlIbrIum.AnIncreaseInoneofthesethreeelements,
P.1007
ortheaddItIonofaspaceoccupyInglesIon,canbeaccommodatedInItIallythrough
dIsplacementofCSFIntothethecalsac,butonlytoasmallextent.FurtherIncrease,as
wIthsIgnIfIcantcerebraledemaoraccumulatIonofanextraduralhematoma,wIllquIckly
leadtoamarkedIncreaseInIntracranIalpressureduetothelowIntracranIalcomplIance
(FIg.J9J).
Figure 39-2.8loodsupplytothespInalcord.8oththesIngleanterIorspInalarteryand
thepaIredposterIorspInalarteryarIsefromthevertebralarterIes.TheradIcular
arterIesandpartIcularlythearteryofAdamkIewIczareImportantcontrIbutors.The
anterIorspInalarterysupplIestheanterIortwothIrdsofthespInalcord,wIththe
posterIorspInalarterysupplyIngtherest.vert.,vertebral;art.,artery;ant.,anterIor.
AsmentIonedearlIer,bloodflowtothebraInIstIghtlycoupledtocerebralmetabolIsm.As
such,manyfactorsaffectC8FbecauseoftheIreffectonmetabolIsm.StImulatIon,arousal,
nocIceptIon,andmIldhyperthermIaelevatemetabolIsmandflow,whIlesedatIvehypnotIc
agentsandhypothermIadecreasebothmetabolIsmandflow.Anumberofotherfactors
governC8FdIrectlywIthoutchangIngmetabolIsm.ApotentdetermInantofC8FIsarterIal
CD
2
tensIon(Paco
2
).WIthInphysIologIcrange,C8FhasanapproxImatelylInearrelatIonshIp
wIthPaco
2
.C8FchangesbyapproxImatelyJofbaselIneforeach1mmHgchangeInPaco
2
(FIg.J94).AsC8Fchanges,sodoescerebralbloodvolume(C87),whIchIswhy
hyperventIlatIoncanbeusedforshortperIodsoftImetorelaxthebraInordecreaseCP.
ThIseffectIsthoughttobeshortlIved,however.CSFpHnormalIzesovertIme,andvessel
calIberreturnstobaselIne.TheexactduratIonofhypocapnIcvasoconstrIctIonIsuncertaIn;
aperIodofmInutestohourshasbeenfoundIndIfferentpatIentpopulatIons.
J
8ecausethe
decreaseInC8FoccurswIthoutachangeIncerebralmetabolIcrate,therIskofIschemIaIs
atheoretIcalconcern.ThesIgnIfIcanceofthIsconcernIsuncertaIn,however.Wehaveno
evIdenceofharmofmoderatehyperventIlatIontothenormalbraInundergeneral
anesthesIa.EarlyhyperventIlatIonIntraumatIcbraInInjury(T8)IsassocIatedwIthpoor
outcome,andtheconsequenceofhyperventIlatIonInT8aftertheInItIal24hoursIsof
uncertaInconsequence
4,5,6
(seeChapterJ6).
Figure 39-3.ntracranIalcomplIance(elastance)curve.ThebraInhasmInImal
compensatorycapacIty,andanyIncreaseInmassfromhematomaorbraInswellIng
wIllresultInanInordInateIncreaseInIntracranIalpressure.
ncontrasttoCD
2
,D
2
haslIttleeffectonC8Fexceptatabnormallylowlevels(FIg.J95).
WhenPao
2
fallsbelow50mmHg,C8FbegInstoIncreasesharply.AteleologIcalexplanatIon
forthIsphenomenonIsthatC8FneedstoIncreaseonlywhenD
2
contentofthebloodbegIns
todecreasesIgnIfIcantly.
C8FremaInsapproxImatelyconstantdespItemodestswIngsInarterIalbloodpressure.The
mechanIsmbywhIchC8FIsmaIntaIned,orIgInallydescrIbedbyLassen,
7
Iscalled
autoregulation
P.1008
ofC8F,orattImes,pressureautoregulatIonofC8F.AscerebralperfusIonpressure(CPP),
defInedasthedIfferenceofmeanarterIalpressure(|AP)andCP,changes,
cerebrovascularresIstanceadjuststomaIntaInstableflow.TheresIstanceIsvarIedatthe
arterIolarlevel.TherangeofCPPoverwhIchautoregulatIonIsmaIntaInedIstermedthe
autoregulatory plateau.AlthoughthIsrangeIsfrequentlyquotedasa|APrangeof60to
150mmHg,thereIssIgnIfIcantvarIabIlItybetweenIndIvIduals,andthesenumbersareonly
approxImate.Atthelowendoftheplateau,cerebrovascularresIstanceIsatamInImum,
andanyfurtherdecreaseInCPPwIllcompromIseC8F.AtthehIghendoftheplateau,
cerebrovascularresIstanceIsatamaxImum,andanyfurtherIncreaseInCPPwIllresultIn
hyperemIa(FIg.J96).7arIousmechanIsmshavebeenproposedtoaccountfor
autoregulatIon,IncludIngmyogenIc,neurogenIc,andlocalmetabolIcmedIators.However,
theexactmechanIsmremaInsundefIned.
Figure 39-4.CerebrovascularresponsetochangeInPaco
2
partIalpressure.The
changeIslInearbetweenPaco
2
of25and65mmHg.
Figure 39-5.CerebrovascularresponsetochangeInPao
2
partIalpressure.The
responseofcerebralbloodflowtochangeInPao
2
IsflatuntIlPao
2
fallsbelow50mm
Hg.
ThereIsInteractIonbetweenCD
2
reactIvItyandpressureautoregulatIon,althoughthe
molecularmechanIsmIslIkelydIfferentforthesetwohomeostatIcprocesses.Whenblood
pressureIslow,CD
2
reactIvItyIsreduced.ncontrast,underhypercapnIccondItIons,
autoregulatorycapacItyIslostbecauseoftheconcurrentvasodIlatIon.
Figure 39-6.CerebralautoregulatIon.tIsgenerallyacceptedthatcerebralbloodflow
IsmaIntaInedconstantbetween60and160mmHg.However,theseareaverage
values,andthereIsconsIderablevarIatIonInboththelowerandtheupperlImItof
cerebralautoregulatIonamongnormalIndIvIduals.
DtherfactorsaffectC8Faswell.AnemIaIncreasesC8F,whIchhasbeendemonstratedIn
postoperatIvecardIacpatIents,forexample.
8
WhetherthesechangesplayaroleInthe
perIoperatIveneurologIcchangescommontocardIacsurgerypatIentsIsuncertaIn.
Anesthetic Influences
AnesthetIcagentshavevarIableInfluenceonC8FandmetabolIsm,CD
2
reactIvIty,and
autoregulatIon.nhalatIonanesthetIcstendtocausevasodIlatIonInadoserelatedmanner,
butdonotperseuncoupleflowandmetabolIsm.ThusthevasodIlatoryInfluenceIs
opposedbymetabolIsmmedIateddecreaseInflow.TheresultanteffectIsthatdurInglow
dosesofInhalatIonanesthesIa,C8FIseItherunchangedorslIghtlyIncreased.Sevoflurane
hasbeenshowntoactuallyresultInadecreaseInC8FInposItronemIssIontomography
studIes.HIgherdosesresultIndomInanceofthevasodIlatoryeffectandanIncreaseInC8F.
ntravenousagentsIncludIngthIopentalandpropofolcausevasoconstrIctIoncoupledwIth
reductIonInmetabolIsm.KetamIne,ontheotherhand,IncreasesflowandmetabolIsm.
CD
2
reactIvItyIsarobustmechanIsmandIspreservedunderallanesthetIccondItIons.
CerebralautoregulatIon,ontheotherhand,IsabolIshedbyInhalatIonagentsInadose
relatedmannerbutpreserveddurIngpropofolanesthesIa.
Pathophysiology
ThehomeostatIcmechanIsmsthatensureprotectIonofthebraInandspInalcord,removal
ofwaste,anddelIveryofadequateoxygenandsubstratetothetIssuecanbeInterrupted
throughamultItudeofmechanIsms.TraumatIcInsultsmayresultIncontusIonwIth
subsequentedemaformatIon,dIrectInjuryfromdepressedskullfracturesorspIne
fractures,dIffuseInjurytoneuronsfromrapIddeceleratIon,anddIsruptIonofthe
vasculature,resultIngInIschemIaorhemorrhage.AlloftheseInsultsmayultImately
compromIseCNSperfusIon.
|asslesIons,suchastumors,maycompressadjacentstructures,raIseCP,andobstruct
normalflowofCSF.HemorrhagemaybespontaneousortraumatIc.0ependIngonIts
locatIon,theymaycausemasseffect,ImpaIrCSFcIrculatIon,or,Inthecaseof
subarachnoIdblood,breakdownofthebloodmayleadtofurtherIschemIcInjurybycausIng
cerebralvasospasm.
HydrocephalusIscausedbyanImbalancebetweenCSFproductIonandremoval.t
frequentlyresultsInelevatIonofCP.HydrocephalusIscommonlydIvIdedIntotwo
categorIes:communIcatInghydrocephalusandobstructIvehydrocephalus.TheformerIs
characterIzedbyafaIluretoabsorbCSF,typIcallybecauseofdysfunctIonalarachnoId
granulatIons.ThelattermaybecausedbyanydIrectobstructIonorextrInsIccompressIon
ofapassagewaythroughwhIchCSFmustpass,suchasthecerebralaqueduct.ThIs
obstructIon,forexample,mayresultfromclotwIthInthespaceorfromtumoradjacentto
It.0ependIngonthecIrcumstances,hydrocephaluscanhaveasubtleordramatIc
presentatIon.Forexample,acutehydrocephalusfollowInganIntraventrIcularhemorrhage
mayresultInrapIdlyprogressIveobtundatIonthatImprovesdramatIcallywIthexternal
ventrIculardraInage.ncontrast,normalpressurehydrocephalusmayevolveoveryears,
resultIngInbarelyperceptIblechangesIncognItIonandgaIt.
P.1009
Monitoring
AnesthesIaforneurosurgeryandspInesurgeryrequIresthestandardAmerIcanSocIetyof
AnesthesIologIstsmonItorIngforphysIologIcparameters.TherIskImposedtotheCNSby
thesesurgIcalprocedureswarrantsmoreextensIvemonItorIng,however.Formany
procedures,adequateoxygenatIon,ventIlatIon,andsystemIcbloodpressuredonotensure
thewellbeIngofthebraInandspInalcord.nstead,theIntegrItyoftheCNSneedstobe
evaluatedIntraoperatIvelywIthmonItorsthatspecIfIcallydetectCNSfunctIon,perfusIon,
ormetabolIsm.AttImes,themonItorIngmodalItIescanbecombInedtoprovIdegreater
InformatIonregardIngthewellbeIngoftheCNS.
Central Nervous System Function
Electroencephalogram
Theelectroencephalogram(EEC)IsthequIntessentIalcerebralfunctIonmonItor.The
depolarIzatIonofcortIcalneuronsprovIdesapatternofelectrIcalactIvItythatcanbe
measuredonthescalp.TypIcallytheactIvItyIsmeasuredbetweentwopoIntsonthescalp
(bIpolar),asthereIsnoelectrIcallyneutralplacefromwhIchtoreferencethesIgnal.Dther
sourcesofelectrIcalactIvIty,suchasthatfromtheheartandmuscles,mustbefIltered
fromthesIgnal,otherwIsetheywouldoverwhelmthesmallvoltagesgeneratedbythe
cortIcalactIvIty.CommonmoderejectIon,thatIs,rejectIonofsIgnalcommontoboth
electrodes,allowsInterferencefromcardIacandmuscleactIvItytobemInImIzed.
SeveralstandardIzedsystemsofelectrodeplacementhavebeendevelopedtofacIlItate
relIableandconsIstentEECmonItorIng,themostcommonofwhIchIsthenternatIonal10
20System.nbrIef,artIfIcIalmerIdIansaregeneratedonthescalprunnIngfronttoback
andsIdetosIde,wherethe1020referstothepercentageofthedIstanceacrossthescalp,
eItherfromtragustotragusornasIontoInIon,thatdefInesthatmerIdIan(FIg.J97).
ElectrodescanbeplacedattheIntersectIonofeachmerIdIan.EachsuchIntersectIonor
poIntIsgIvenanameeItheracombInatIonoflettersandanumber,ortwoletters,where
thefInalletterIsZ.ThelettersareFforfrontal,Cforcentral,PforparIetal,Tfor
temporal,DforoccIpItal,AforaurIcular,andFpforfrontalpole.Aletterfollowedbyan
oddnumberIsapoIntonthelefthemIsphere,whIlealetterfollowedbyanevennumberIs
apoIntontherIghthemIsphere.Twoletters,wIththesecondletteraZ,IndIcateapoInt
alongmIdlIne.
Figure 39-7.TheInternatIonal1020systemforelectroencephalogramelectrode
montage.Theoddnumbersdenotetheleft(L)hemIspherewhereastheevennumbers
representtherIght(F)hemIsphere.SeetextfordetaIls.
Table 39-1 Electroencephalogram Frequencies
WAVE
RANGE
(Hz)
DESCRIPTION
0elta 0J
Lowfrequency,hIghamplItude;presentIndeepcoma,
encephalopathy,anddeepanesthesIa
Theta 47
NotpromInentInadults,althoughmaybeseenIn
encephalopathy
Alpha 812
PromInentIntheposterIorregIondurIngrelaxatIonwItheyes
closed
8eta 12
HIghfrequency,lowamplItude;thedomInantfrequencydurIng
arousal
AlthoughsophIstIcatedEECmonItorIngforepIlepsyevaluatIonmayrequIrerecordIngof
multIplechannels,provIdIngInformatIonontheactIvItybetweennumerouspoInts,theEEC
monItorIngperformeddurInganesthesIafrequentlyusesabroadmontagewIthfewer
channels(twoorfour)toevaluatehemIspherIcactIvIty.DncethesIgnalIsrecorded,Itcan
beevaluatedInseveralways.7IewIngrawEECmaybeapproprIateattImes,butsubtle
changesaredIffIculttodetect,partIcularlyfortheInfrequentuser.However,theEECcan
beprocessedtoyIeldreadIlyInterpretableInformatIon.AcommonmethoduseIsfrequency
domaInanalysIs.UsIngFourIeranalysIs,theapparentrandomactIvItyofrawEECcanbe
brokendownIntoaserIesofwavefrequencIes,thesummatIonofwhIchgIvestheoverall
EECpattern.TherangeoffrequencIesseenInEECIsdescrIbedInTableJ91.Thepower
(amplItudesquared)ateachfrequencycanthenbeplottedasaspectralarray,whereby
theeffectofvarIousInfluencessuchasanesthetIcagentsorIschemIcInsultcanbe
detectedbyhowtheymodIfythespectralanalysIs.AcommonparametertoIncludeIn
analysIsofEECIsthespectraledgefrequency,whIchIsthefrequencybelowwhIch95of
thepowerresIdes.
AprogressIvereductIonInC8FwIllproducearelIablepatternchangeInEEC,consIstIngof
alossofhIghfrequencyactIvIty,alossofpower,andtheeventualprogressIontoEEC
sIlence.ThemonItorIsthereforeusefulwhensurgIcalproceduresjeopardIzetheperfusIon
ofthebraIn,suchascrossclampofthecarotIdarterydurIngcarotIdendarterectomy
(CEA).EECIspartIcularlyusefulInthIssettIngbecausethespectralanalysIsontheatrIsk
sIdecanbecomparedInrealtImewIththeunaffectedsIde,thusfacIlItatIngdetectIonof
IschemIabytheresultantasymmetryofthespectraledgefrequency.
ThechangesIntheEECspectrumseenwIthIschemIacanoccurasaresultofother
Influences,however.ntravenousanesthetIcagentssuchaspropofolandthIopental,as
wellasInhaledagentssuchasIsoflurane,wIllcauseasImIlardecreaseInthespectraledge
frequency,wItheventualprogressIontoadrugInducedIsoelectrIcEECInadoserelated
manner.0urIngcertaInsurgIcalprocedures,suchasextracranIaltoIntracranIalbypass
procedures,maxImalsuppressIonofcerebralmetabolIcrateIsdesIrabletoprotectthe
braIndurInganIschemIcInsult.UndersuchcIrcumstances,theanesthetIcagentcanbe
tItratedagaInsttheEECuntIlthedesIredeffectIsachIeved.TypIcally,Insteadofan
IsoelectrIcEEC,thegoalIsastatecalledburst suppression.nthIsstate,perIodsof
IsoelectrIcEECarepunctuatedbyburstsofEECactIvIty.WhenburstsuppressIonIsthe
goal,asuppressIonratIocanbecalculatedasthepercentageofanepochInwhIchthe
patIent'sEECIsIsoelectrIc.ThesuppressIonratIoallowsonetoachIevenearcomplete
suppressIon(90)ofEECactIvIty,whIleremaInIngcertaInthatregularEECactIvItywIll
return
P.1010
InashortwhIlewIthcessatIonofadmInIstratIonofthedrug.ncontrast,whencomplete
IsoelectrIcEECIsachIeved,tImetoarousalbecomesunpredIctable.DthersettIngsInwhIch
EECmonItorIngandburstsuppressIonmaybeusefularelIstedInTableJ92.
Table 39-2 Indications for Electroencephalogram Monitoring
0urInganesthesIa
1. CarotIdendarterectomy
2. CardIopulmonarybypassprocedures
J. Cerebrovascularsurgery
1. AneurysmsurgeryInvolvIngtemporaryclIppIng
2. 7ascularbypassprocedures
4. WhenburstsuppressIonIsdesIredforcerebral
protectIon
ntheIntensIvecare
unIt
1. 8arbIturatecomaforpatIentswIthtraumatIcbraIn
Injury
2. WhensubclInIcalseIzuresaresuspected
Evoked Potential Monitoring
AlthoughEECIsacerebralfunctIonmonItorthatdetectsspontaneousactIvIty,evoked
potentIalmodalItIesdetectsIgnalsthataretheresultofspecIfIcstImulIapplIedtothe
patIent.TheseIncludesomatosensoryevokedpotentIal(SSEP),braInstemaudItoryevoked
potentIal(8AEP),vIsualevokedpotentIal(7EP),andmotorevokedpotentIal(|EP).
Somatosensory Evoked Potential
SSEPIsasIgnalthatIsdetectableonEECandthatIsgeneratedInatImelockedfashIonIn
responsetoaspecIfIcapplIedsensoryInput,typIcallyacutaneouselectrIcalstImulatIon
(I.e.,ofaperIpheralsensorynerve,butalsoofacranIalnervewIthasensorypathway).As
aresult,anIntactneuralpathwayfromtheperIpherytothecerebralsensorycortexIs
essentIalforasIgnaltobegenerated.ThIsmonItorIngmodalItyhasapplIcatIonInany
surgIcalprocedurethatmayjeopardIzethIspathway.SpecIfIcally,spInesurgeryInwhIch
thedorsalcolumnofthespInalcordmaybeplacedatrIskIsapartIcularlyapproprIate
applIcatIon,butItmayalsobeuseddurIngotherproceduressuchascranIotomyand
carotIdsurgerywhereanypartofthepathwaymaybesubjectedtoIschemIaorsurgIcal
retractIon.
8ecauseofthepresenceofspontaneousEECactIvIty,asIngleperIpheralstImulus,whIch
generatescortIcalactIvItyofrelatIvelylowamplItude,wouldnotbedetectableamIdstthe
backgroundnoIse.SummatIonfollowedbysIgnalaveragIngofrepetItIvestImulIIs
thereforenecessaryInordertoextractmeanIngfulsIgnals.
StImulatIonIstypIcallydoneIntheregIonsofthemedIannerve,ulnarnerve,andposterIor
tIbIalnervetogeneratepredIctableandrelIablesIgnals.ntheory,however,anysensory
nervecouldbeusedtogenerateSSEP.TheSSEPIsdescrIbedbyItspolarIty(thedIrectIon
ofthewavedeflectIon)andItslatency(thetImerequIredforasIgnaltobedetectedafter
thestImulushasbeenapplIed),andIsquantIfIedbyboththeamplItudeofthatsIgnaland
Itslatency.Forexample,N20IstheSSEPgeneratedvIastImulatIonofthemedIannerve
thatIsexpectedtohavealatencyofapproxImately20msandanegatIvedIsplacement
(FIg.J98).
0IsruptIonoftheneuralpathwayatanypoIntwIllresultIncompletelossofSSEP.|ore
commonly,IschemIa,notmechanIcaldIsruptIon,IstheIntraoperatIveInsult.Asaresultof
IschemIa,theamplItudeofthesIgnaldecreasesandthelatencyIncreases.A50decrease
InsIgnalamplItudeIsgenerallyacceptedasclInIcallysIgnIfIcant,asIsa10IncreaseIn
latency.
Figure 39-8.FepresentatIvetracIngsofmultIplemodalItIesofsensoryevoked
potentIal.8AEP,braInstemaudItoryevokedpotentIal;n,nerve;SSEP,somatosensory
evokedpotentIal;7EP,vIsualevokedpotentIal.
Brainstem Auditory Evoked Potential
8AEPIsaspecIalIzedtypeofsensoryevokedpotentIal.nsteadofanelectrIcalstImulus
applIedtoasomatosensorynerve,astandardIzedsound(clIck)IsapplIedtotheeIghth
cranIalnervevIatheaudItoryapparatus.ArecognIzedserIesofpeaksaregeneratedwIth
thIstechnIque,wherethelatencyofeachpeakhassIgnIfIcancewIthrespecttothe
IntegrItyofvarIouspartsoftheaudItorypathway.AlthoughthIsmonItorIngmodalItyIs
specIfIctocranIalnerve7,andIspartIcularlyusefulInacoustIcneuromasurgery,Itmay
beuseddurInganysurgIcalprocedurearoundthebraInstemtoInferItsIntegrIty,although
suchuseIsassocIatedwIthbothlowsensItIvItyandspecIfIcIty.
Visual Evoked Potential
7EPsIgnalsaregeneratedvIalIghtstImulatIonoftheretIna.TypIcally,gogglesthatemIt
LE0lIghtsareworn.AlthoughthIsmodalItyIspartIcularlyappealIngtomonItorthe
IntegrItyoftheoptIcnerveInsettIngsInwhIchvIsuallossIsaconcern,suchasInprone
spInesurgery,thesIgnalsarenotrobust.TheyaredIffIculttorecordInaconsIstentfashIon
durInganesthesIa.FesearchIsongoIngwIthrespecttoItsIntraoperatIveuse,partIcularly
wIthregardtoItsInterpretatIon.
P.1011
Motor Evoked Potential
|EPmonItorIngIsdIfferentfromtheotherevokedpotentIalmodalItIesdescrIbedthusfar.
WhereasSSEP,8AEP,and7EPprovIdeInformatIonaboutascendIngsensoryneural
pathways(I.e.,fromtheperIpherytothecerebralcortex),|EPevaluatesdescendIng
motorpathways(I.e.,fromthecerebralcortex,pasttheneuromuscularjunctIon,to
perIpheralmusclegroups).ThIsdIfferenceallows|EPtocomplementSSEP,partIcularlyIn
thesettIngofspInesurgery,InwhIchthetwomodalItIesprovIdeInformatIonaboutthe
IntegrItyofanatomIcallydIfferentareasofthespInalcord.WIth|EP,thestImulusIs
applIedInatranscranIalfashIonoverthemotorcortex.ThedeflectIon,essentIallyan
electromyographIcsIgnal,IsthendetectedbyelectrodesembeddedInthemusclebelly.
AlthoughtheoretIcallythestImuluscanbedelIveredwItheItheramagnetIcorelectrIcal
source,transcranIalmagnetIcstImulatIonIsoblIteratedunderanesthesIa.ThetranscranIal
electrIcalsIgnalIsusuallydelIveredasarapIdtraInoffourormorestImulI,thevoltageof
whIchIsadjustedtoachIeveadequatesIgnalsInboththeupperandlowerextremItIes.The
|EPIstypIcallydetectedatthethenaremInenceandtheabductorhallucIsmuscle.
TranscranIalelectrIcal|EPIsofsubstantIallygreatermagnItudecomparedwIthSSEP,and
sIgnalaveragIngwIthrepetItIvestImulIIsthereforenotrequIred.However,ItIsvery
sensItIvetoanesthetIcagents,partIcularlytheInhalatIonanesthetIcs.tsamplItudecanbe
augmentedbyIncreasIngthetranscranIalvoltage,orthenumberofstImulIInthetraIn.
ThestImuluscancausepatIentmovement,so|EPsIgnalsaretypIcallyobtaIned
IntermIttentlyatpoIntsdurIngthesurgerywhenslIghtpatIentmovementsarenot
problematIc.AbIteblockIsmandatorytopreventInjurytothetonguedurIngtranscranIal
stImulatIon.
WIth|EP,latencyofthesIgnalIssomewhatunrelIable,andnottypIcallyusedtomake
clInIcaldecIsIons.0ecIsIonmakIngIsbasedonamplItudealone,wherea50decreaseIs
consIderedsIgnIfIcant(FIg.J99).Although|EPcanbeuseddurInganyspIneorIntracranIal
surgIcalprocedure,ItIsbecomIngIncreasInglyuseddurIngcervIcalspInesurgery.
|EPsIgnalsaremuchmoresensItIvetovolatIleanesthesIathanSSEP.AlthoughthereIs
someevIdencethat|EPsIgnalsareadequatedurIngdesfluraneanesthesIa,moreresearch
ontheeffIcacyofthIstechnIqueIsrequIred,andtotalIntravenousanesthesIaIsthe
preferredtechnIquewhen|EPmonItorIngIsrequIred.
9
SomecentersusepartIal
neuromuscularblockade,butmostcentersavoIdmusclerelaxantsaltogetherwIth|EPIn
ordertoavoIdcompromIseofthesIgnal.
10
Figure 39-9.FepresentatIvetracIngofmotorevokedpotentIal(|EP)recordedfrom
thethenarmusclesInresponsetotranscranIalelectrIcalstImulatIon.
Spontaneous Electromyography
Spontaneouselectromyography(E|C)IsdIfferentfromotherevokedpotentIalsInthata
sIgnalIsnotIntentIonallygeneratedthroughstImulatIonatsomepoIntInaknownneural
pathway.nstead,ItIsacontInuousrecordIngofE|CactIvItyInthemuscleofregIons
InnervatedbynerverootsaroundwhIchsurgeonsareworkIng.tspurposeIstodetect
InjurytothosenerverootsbythesurgIcalprocedure.mpIngementonanerverootbyan
InstrumentwIllcauseImmedIatemotoractIvItythatIseasIlydetectable,whIchmayallow
thesurgeontomodIfyhIsorhertechnIque.AlthoughspontaneousE|CIsarobustsIgnal
thatIstolerantofvarIousanesthetIctechnIques,musclerelaxantmustbeavoIded.
SpontaneousE|CIsfrequentlyuseddurIngcervIcalandlumbarspInesurgerywherethe
brachIalplexusandlumbosacralplexusareencountered.
Cranial Nerve Monitoring
SurgeryIntheposterIorcranIalfossaandadjacenttothebraInstemplacesthesurgeonIn
closeproxImItytocranIalnerves.AlthoughcranIalnerve7canbemonItoredwIth8AEP
asdIscussedearlIer,severalothercranIalnervescanbemonItoredaswell.Cenerally,only
theIntegrItyofnerveswIthmotorcomponentscanbedetected,eItherthrough
spontaneousE|CorthroughE|CevokedbylocalelectrIcalstImulatIon.TheseInclude
cranIalnerves7,7,X,X,andX.
Influence of Anesthetic Technique
AsmentIonedprevIously,anesthetIcagentscanhaveprofoundInfluenceontheamplItude
andlatencyofevokedpotentIals.ForInstance,thequalItyofsIgnalsobtaInedwIthSSEP
monItorIngdependsontheanesthetIcagentsused.SIgnalsareobtaInableundervolatIle
anesthesIa,buttheanesthetIcIstypIcallykeptatsub|AC(mInImumalveolar
concentratIon)dosestoavoIddegradatIonInqualIty(IncreaseInlatencyanddecreaseIn
amplItude),asamplItudeofSSEPsIgnalsaredepressedbyvolatIleagentsInadoserelated
manner;theyarerecordabledurInglowdoseandoblIteratedwIthhIghdoses.Potent
volatIleanesthetIcsshouldnotbecombInedwIthnItrousoxIde,asthIstechnIquewIll
furthercompromIsequalIty.ThesIgnalsareunaffectedbyopIoIds,andopIoIdInfusIonsare
frequentlyusedtofacIlItatelowdosevolatIleanesthesIa.SIgnalqualItyIsalsoexcellent
underIntravenousanesthesIawIthpropofol.
TosummarIzetheInfluenceofanesthetIcagentsonevokedpotentIalmonItorIng,general
statementscanbemade.
1. nhalatIonagentsIncludIngnItrousoxIdegenerallyhavemoredepressanteffectson
evokedpotentIalmonItorIngthanIntravenousagents.
2. CortIcalevokedpotentIalswIthlonglatencyInvolvIngmultIplesynapsesareexquIsItely
sensItIvetoInfluenceofanesthetIcwhIleshortlatencybraInstemandspInalcomponents
areresIstanttoanesthetIcInfluence.Thus,8AEPcanberecordedunderanyanesthetIc
technIquewhereas7EPandSSEPareverysensItIve.
J. |onItorIngof|EPandcranIalnerveE|CIngeneralprecludetheuseofmuscle
relaxants,althoughuseofashortactIngneuromuscularblockIngagentforthepurposeof
trachealIntubatIonIsnotcontraIndIcatedasItseffectusuallywearsoffbefore
monItorIngandsurgerybegIns.
4. |EPIsexquIsItelysensItIvetothedepressanteffectsofInhalatIonanesthetIcsIncludIng
nItrousoxIde.AlthoughItcanberecordedwIthlowdoseagents,thesIgnalsareso
severelyattenuatedthatthIspractIceIsgenerallynotadvIsable.TotalIntravenous
anesthesIawIthoutnItrousoxIdeIstheIdealanesthetIctechnIqueformonItorIngof|EP.
P.1012
6. DpIoIdsandbenzodIazepIneshaveneglIgIbleeffectsonrecordIngofevokedpotentIals.
Figure 39-10.TranscranIal0opplertracIngwIthreleaseofcrossclampdurIng
carotIdendarterectomy.TheresultanthyperemIaIsaccompanIedwIthevIdenceof
aIrembolI(vertIcalstreaksonthetracIng).|CA,mIddlecerebralartery;CA,
InternalcarotIdartery.
7. PropofolandthIopentalattenuatetheamplItudeofvIrtuallyallmodalItIesofevoked
potentIalbutdonotoblIteratethem.SSEPand|EPcanbemonItoredevendurIngburst
suppressIonInducedbytheseagents.8AEPcanberecordedwIthanyanesthetIc
technIque.
8. 0urIngcrucIaleventsInwhIchpartofthecentralneuralpathwayIsspecIfIcallyplacedat
rIskbysurgIcalmanIpulatIon,asInplacementofatemporaryclIpdurInganeurysm
surgery,changeInanesthetIcdepthshouldbemInImIzedtoavoIdmIsInterpretatIonof
thechangesInevokedpotentIalrecorded.
9. KetamIneandetomIdatehavebeenreportedtoenhancethequalItyofsIgnalsInpatIents
wIthweakbaselInesIgnals,althoughtheclInIcalsIgnIfIcanceandInterpretatIonof
sIgnalsobtaInedunderthesecIrcumstancesremaInunclear.
Cerebral Perfusion
AlthoughadequateC8FdoesnotguaranteethewellbeIngoftheCNS,ItIsonefactorthat
IsessentIaltoItsIntegrIty.|easurIngC8FIsthereforeanattractIvemethodofmonItorIng
theCNS.CurrentlyavaIlabletechnIquesforquantItatIvemeasurementofC8Farenot
practIcalasanIntraoperatIvemonItor,othermethodsforlookIngatrelatIvechangesIn
C8FdolendthemselvestouseIntheoperatIngroom.TranscranIal0opplerultrasonography
(TC0)andlaser0opplerflowmetryareexamples.Furthermore,asadequateC8Fdepends
onanapproprIateCPP,measurIngIntracranIalpressuremaybeusefulIncertaInpatIentsto
ensurecondItIonsareadequateforsuffIcIentC8F.FInally,numerousothermodalItIesthat
evaluateC8FandthatmaynotbepractIcalIntheoperatIngroomareusedcommonlyIn
theperIoperatIvesettIng.
Laser Doppler Flowmetry
Laser0opplerflowmetryIsatechnIquethatmeasurescortIcalbloodflowInasmallregIon
ofthebraInadjacenttotheplacementofthedevIce.AlthoughItIsusefulfordetectIng
relatIvechangesInC8F,ItsutIlItyIslImItedbyseveralfactors.FIrst,ItrequIresaburrhole
forplacement,whIchpreventsItsuseInmostpatIents.Second,ItmeasuresflowInonlya
smallregIonofthebraIn;ItcouldmIsshypoperfusIonInanyareaofthebraInnotdIrectly
monItored.8ecauseoftheselImItatIons,laser0opplerflowmetryhasfoundonlylImIted
applIcatIons.
Transcranial Doppler Ultrasonography
TC0IsanonInvasIvemonItorforevaluatIngrelatIvechangesInflowthroughthelarge
basalarterIesofthebraIn(I.e.,thecIrcleofWIllIs).TC0doesnotmeasureflowdIrectly,
andthereforecannotprovIdeInformatIonregardIngabsoluteC8F.TC0measuresflow
velocIty(FIg.J910),whIchIsdIrectlyproportIonaltoflowIfthedIametersoftheselarge
vesselsareconstant.ExceptInwellknowncIrcumstancessuchascerebralvasospasm
followInganeurysmalsubarachnoIdhemorrhage,thesevesselsarethoughttobe
conductancevessels,wheredIametersofthebasalarterIesarestable.
11
Pressure
autoregulatIonandCD
2
reactIvItyofC8FoccurvIachangesInarterIolardIameterdIstalto
theselargevessels.
AlthoughthevesselsthatcanbeevaluatedwIthTC0IncludethemIddlecerebralartery,
InternalcarotIdartery,anterIorcerebralartery,posterIorcerebralartery,ophthalmIc
artery,vertebralartery,andbasIlarartery,notallofthesevesselscanbemonItored
contInuouslydurIngsurgIcalprocedures.|anyofthesevesselscanonlybeevaluatedwIth
ahandheldTC0probe,whIchIsusefulforprovIdIngabrIefsnapshotofflowvelocItyIn
thatvesse

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Editors: Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael K.

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