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PositivePressureVentilation:Whatisthe
RealCost?
N.SoniP.Williams
BrJAnaesth.2008101(4):446457.

AbstractandIntroduction
Abstract

Positivepressureventilationisaradicaldeparturefromthephysiologyofbreathingspontaneously.The
immediatephysiologicalconsequencesofpositivepressureventilationsuchashaemodynamicchanges
arerecognized,studied,andunderstood.Thereareothersignificantphysiologicalinteractionswhichare
lessobvious,moreinsidious,andmayonlyproducecomplicationsifventilationisprolonged.The
interactionofpositivepressurewithairwayresistanceandalveolarcomplianceaffectsdistributionofgas
flowwithinthelung.Theresultisawiderangeofventilationefficacythroughoutdifferentareasofthe
lung,butthepressuredifferentialsbetweenalveolusandinterstitiumalsoinfluencecapillaryperfusion.
Thehydrostaticforcesacrossthecapillariesassociatedwiththeeffectsofraisedvenouspressures
compoundthesechangesresultingininterstitialfluidsequestration.Thisisincreasedbyimpaired
lymphaticdrainagewhichissecondarytoraisedintrathoracicpressurebutalsoinfluencedbyraised
centralvenouspressure.VentilationandPEEPpromulgatefurtherphysiologicalderangement.Intheory,
avoidingthesephysiologicaldisturbancesinarestedlungmaybebetterforthelungandotherorgans.
Analternativetopositivepressureventilationmightbetoinvestigateoxygensupplementationofa
physiologicallyneutralandrestedlung.Abandoningheroicventilationwouldbeamassivedeparturefrom
currentpracticebutmightbeamorerationaleapproachtofuturepractice.
Introduction

PositivepressureventilationduringtheCopenhagenpolioepidemicwasthekeytothereductionin
mortalityfrom87%to40%.Itwasachievedusingmedicalstudentsnotsophisticatedventilators,with
minimalunderstandingofthephysiologyofgasexchange,andwithnorealmeansofmonitoringeither
oxygenationorcarbondioxide.Itrapidlybecameobviousthatitsusecouldbeextrapolatedtothe
managementofrespiratoryfailure.[72,73,144]InthefirsteditionofVentilationoftheLungs,Mushin
commentsthat'positivepressureventilationisaconsiderabledeviationfromthenormalphysiological
mechanismofrespiration'.Implicitinthisstatementisthenotionthattherewillbeapathophysiological
pricetopayfordisturbingthenormalphysiologyofbreathing.Theimmediateinteractions,suchas
haemodynamicchanges,arewelldelineated,butitisincreasinglyclearthatnotallthecomplicationsare
eitherobviousorimmediate.TheARDSnetstudyexposedpreviouslyconcealedmortalitysuggestingthe
insidiousandlateimpactofshearforcesandotherinflammatoryreactionssecondarytomechanical
ventilation.[1]
Thedrivingforceofventilatorytechniquesintheintensivecareunit(ICU)istoachieveoxygenation
whichinseverelunginjurymaybebothdifficultandprolonged.
Thisreviewrevisitsthephysiologicalcostinvolvedinachievingoxygenationusingpositivepressure
ventilationinthecriticallyill,anddiscussessomeofthepossibleinteractions().
SomeAreasofPotentialPhysiologicalInteractionwithPositivePressureVentilation

Positivepressureeffectsonintrathoracicpressures

Pressureanddistributionofairflowintothealveoli
Pressure,stretch,andthelung
Surfactantfunctions
Positivepressureandcardiacoutput
Pulmonarycapillarybloodflow
Positivepressureandthelymphatics
Positivepressureandorgansystemfunction

OxygenationandVentilation
EachICUhasrulesastowhatconstitutesacceptableoxygenationandthisvarieswiththepatientand
circumstances.[16]Therearemanyexamplesofpeoplefunctioningreasonablywithfarloweroxygenation
indicesthanwouldbeacceptableinanICU.Theserangefromhighaltituderesidentsandmountaineers
topatientslivingwithchronicairwaysdisease.[98]IntheICU,monitoringofoxygenationstillfocuseson
inspiredoxygenconcentrationandarterialbloodgasestoindicateadequacy,whereasinotherareasof
practice,emphasishasmovedtosurrogatesoftissuehypoxiasuchasScVO2andlactate(Figure1).
Withcirculation,tissueandcelltransport,andmitochondrialfunctioninterposedbetweenlungandcell,
thearterialvaluesofoxygenationmaynotbetheidealmonitoringparameters.

Monitoringoxygenation.Basedonarterialvalueswhichcorrelatepoorlywithadequacyoftissue
oxygenation.
Inthecriticallyill,severalobservationsregardingoxygenationcanbemade.
i.Evenwithrelativelylowarterialsaturations,theremaybeadequatetissueoxygenation.

ii.Whentissueoxygenationisinjeopardy,itisveryoftenduetoproblemsnotrelateddirectlytothe
lungs.

iii.SaturationandPaO2belowtheacceptablenormalrangecorrelatepoorlywithtissueoxygenation.

iv.Whenpatientsaredifficulttooxygenate,toleranceoflowervaluesdevelopsrapidly,provided
therearenomarkersoftissuehypoxia.

v.Itisoftenstatedthat'fewpatientswithlunginjurydieofhypoxaemia'.Clearly,somedobutoften
deathisduetoacquiredcomplications.
Marginsofsafetyforoxygenationareessential,butdifficultyariseswhenitisnecessarytouse
aggressiveventilationtoachievemarginsthatmaybefarinexcessofactualrequirement.Ifthisis
associatedwithlatecomplications,thenmethodsofassessingadequacyofoxygenationmayneedtobe
reconsidered.

Breathing,Ventilation,andIntrathoracicPressures
Ininspiration,smallnegativeintrapleural,interstitial,andalveolarpressuresaregeneratedallowingthe
lungtoinflate.Onexpiration,intrapleuralpressurereturnstowardsatmospheric,butremainsnegative,
whereasinterstitialandalveolarpressuresreturntowardsatmosphericorslightlypositivepressure.
Positivepressureventilationreversesthiscyclewithhighintrathoracicpressuresoninspirationwhichare
transmitted,tothealveoliandtheinterstitialtissues,followingthepathofleastresistancetoinflatethe
alveoli.Theintrapulmonaryandinterstitialpressuresremainpositivethroughoutinspirationbutwillreturn
towardsatmosphericpressureonexpiration,unlessPEEPisaddedwhenthepressuresremainpositive
throughout.

Ventilation,AlveolarVentilation,andRecruitment
Duringspontaneousbreathing,thenegativepressuregradientgeneratesairdistributionwhichislocally
influencedbythestateoftheairways,alveoli,andinterstitium.Surfactantmodifiestheeffectsof
Laplace'slawattheselowpressuressothatsmallalveoliarebothrelativelyeasytoinflateandhaveless
tendencytocollapseonexpiration.Despitetheseeffects,thereisregionalvariationingasvolume
distributioneveninvolunteersbreathingnormally.[89]Thesamefactorsinfluenceflowwithpositive
pressureventilation,buttheforcesactingaredifferent.Inthetrachealtube,asinglepressureapplied
overaspecifictimeproducesawaveformwhichforcesgasthroughtheairways.Thestateofthe
airways,inparticulartheirresistance,andthealveolarcompliancedeterminetheeffectofthatpressure
indifferentregionsofthelung.Thesefactorscombinedcanbeconsideredastheindividual'time
constants'ofthelungregionsorofindividualalveoli.Indamagedlung,therangeofdifferenttime
constantsbetweenregionswillincreaseevenifthesurfactantwasnormal.Positivepressurewill
preferentiallyaeratehighcomplianceareasattheexpenseoflowercomplianceareas,whereas
collapsedalveolimayrequirehighsustainedpressuretoforcethemopen,butthismaybeineffective.It
isadailyobservationintheoperatingtheatrethatreinflationofacollapsedbutpreviouslynormallung
requiressustainedhighpositivepressureanditisagradualandfarfromuniformprocess(Figure2).

Alveolarinflation.(A)Representsthebeginningofinspiration.PressurePactsonaconsolidated
alveolus,anormalalveolusandadistendedalveolus.(B)Endinspiration.PressurePproducesabroad
spectrumofeffects.
Recruitmentistheopeningandmaintainingopenpotentiallyunderventilatedareas.Thefundamental
conceptbehindrecruitmentistousethephysicsofinflationjudiciously,toincreasethenumberofalveoli
andhencealveolarsurfaceareainvolvedingasexchange.Thecentraltenetisthatthiswillimprove
oxygenation.Awiderangeofstrategiesaimedto'recruit'alveolihavebeenadvocated,buttheproblem
withanyofthesetechniquesisthatthevariationintimeconstantsbetweenalveoliandlungregions
precludesasinglepressureorwaveformbeingsuitableforalllungregions.
CTscanningandelectricalimpedancetomography(EIT)haverevolutionizedtheabilityto'see'what
actuallyhappenstolunginflationwithpositivepressureventilation.UsingEIT,theinferredpressure
volumecurveclearlyshowsalowerandupperinflectionpoint(increased/reducedconductivity).The
lowerinflectionpointisthoughttorepresentrecruitmentwhereastheupperinflectionpointrepresents
overdistension,althoughthisiscontentious(Figure3).Physiologically,thismethodologyhasclearly
shownnotonlyregionalvariationinbothrecruitmentandoverdistensionbutthatpathologyinthelung
increasesthediversityofthesechanges.[34]EITindicatesahugeregionalvariationinbothrecruitment
andoverinflation,ininjuredlungs,bothwithinandbetweenlungs.[18,5860,133]Italsodemonstratesthat
wholelunginflectionpointsdonotrepresentindividualareas.

Pressurevolumecurveandtheeffectsonalveoli.
CThasalsobeenusedtoassessrecruitment.InARDS,arecruitmenttechniqueusinganinitial
sustainedhighpressurewithsubsequentPEEPatvariouslevelstomaintainrecruitmentonlyachieved
anestimatedmeanrecruitmentof13%,andshowedthatalargepartofthelungwasnotrecruitable.
[48,65]ItdidindicatethathighlevelsofPEEP,15mmHg,aremoreeffectivethanlowerlevels,5mmHg,
bothinmaintainingalveolarpatencyandimprovingoxygenation.PEEPisalsoeffectiveinpreventing
collapseandderecruitment.[43,87,130]Allthesetechniquesresultinsustainedincreaseinintrathoracic
pressure.
Afurtherconsiderationisthatpressureiseffectivelydistributedacrosscompliantlungbutdampenedby
poorlycompliantareas.Paradoxically,thetechniquesusedtoopenclosedairways,probablyresultsin
increasedgasdistributionnottotheabnormalareasbutrathertothefunctionalareasoverinflatingthem
andpotentiallyimpairingtheirfunction.[17,127]Theresultofrecruitmentisthereforeunpredictable.
Insummary,thephysicsofthelunginflatedbyasinglepressurewaveformwillresultinunpredictable
gasdistributionduetovariableregionalcompliance.Therewillbeoverdistensionofnormalalveoli,and
althoughtherewillbesomerecruitment,itmaybeverylimited,especiallyinareasofcollapseor
consolidation.ThecombinationofhighinspiratorypressuresandhighlevelsofPEEPwillresultin
sustainedpressuresthroughouttherespiratorycycle.
Recruitmentintheshorttermwithrelativelynormallungsworkswellbutindamagedlungs,and
particularlyovertime,recruitmenttechniquesmayexacerbateproblemswhileapparentlyimproving
oxygenationindices.

VentilationPressureandStretch
ThereductioninmortalityhighlightedbytheARDSnetstudywasassociatedwithlowerpeakpressure
ventilation,butitalsoappearsthattheshearforcesthatoccurparticularlyininitiatinginflationmaycause
injury.[1,20,24,36,49,85,121,122,124,149]

injury.[1,20,24,36,49,85,121,122,124,149]
Stressandshearforcesexertedduringthecyclicopeningandclosingofalveoliresultinincreased
cytokineproductionandwhitecellsequestration,asdoesoverdistensionofalveoli.[19,20]Theseeffects
areseenoverarangeofventilatorypatternsanditmaypredisposetoinjuryandinfection.[78,128,143]
Repetitiveidenticalventilationexertsdifferentandmoredamagingshearforcesthanvariableventilation
wherebothvolumeanddurationarevaried.[13,95]Theseinflammatoryeffectsoriginatinginthelungmay
causesecondaryinflammatoryproblemsinotherorgans.[35,38,68,84,92]
Inrecruitment,manoeuvrestheloweringofthepeakpressureisimportantwhereastheuseofhigher
PEEPmaintainsalveolarpatencyandreducestheshearforces.Theneteffectishighpressure
throughouttheventilatorycycle.

VentilationandSurfactant
SurfactantsmodifythesurfacetensionandhencethelawofLaplace.Thedenserthemolecules,the
lowerthesurfacetensionwhichenablessmallalveoli,withdensesurfactant,toremainopenbutalso
facilitatesinflationduringinspiration.Inlargeralveoliduringinflation,thedensityofsurfactantdecreases
asthesurfaceareaincreasesandtheinfluenceonthesurfacetensiondecreases,sothatthesurface
tensionincreases.Thisishighlyefficientinspontaneousbreathingatlowpressuresasitfacilitates
effectivegasdistributionthroughoutthelung.Withpositivepressureventilation,airisforcedintothelung
underpressureandtheresultantpressurewaveformmaygeneratewaveformationinthesurfactant
layersalteringtheuniformityofspread.Thisisknowninsurfactanttechnology,butthereislittleorno
informationrelatingtosurfactantwavebehaviourinthelung.Afundamentaldifferenceinthe
performanceofsurfactantbetweenspontaneousandpositivepressureventilationmaybedueto
distortionofsurfactantspread.Thisisunlikelytobeuniformacrossthelungduetowidevariationin
pressureandthereforeofflow.
Positivepressurealsoinfluencestheproductionandfunctionofsurfactant.Inlunginjury,typeII
pneumocytesarereducedinnumberandsurfactantproductionisreduced.[99]Functionisalteredbythe
mixofcholesterolandproteinwhichthenaffectstheabilityofthesurfactanttoformsurfacestructures.
[83,99,137]Thisisexacerbatedbyinflammationwhichreleasesproteinandothermaterialsthatmixwith
thesurfactant,mediatorsthatdirectlyaffectsurfactant,membranepermeabilitychangesthatallowfluid
dilutionofsurfactant,andpolymerizingfibrinthatadsorbsthesesurfaceactivecompounds,effectively
removingthem.[115,116,126,129,131,138]Infectionisimplicated,withevidencethatbothpseudomonasand
pneumocystispneumoniasaltersurfactantfunction,althoughitisuncertainwhetheritisduetothe
diseaseortheventilation.Itislikelyotherinfectionsdolikewise.[40,113,136]Medicalinterventionsuchas
lavageeffectivelyremovessurfactantimpairingregionalandwholelungcompliance.[29]Surfactant
dysfunctionchangescomplianceandexaggeratesheterogeneouslunginflationnecessitatingventilation
patternswhichmaycausefurtherdamage.[11,30,69,123]
Surfactanthasaroleintheimmunedefencesofthelung.Thelungprovidesmorethan50m2ofcontact
acrossafinemembraneandisthereforeapotentialsiteforinvasion.Notonlydoessurfactantinfluence
inflammatoryresponse,butithasasubstantialroleinmucosalimmunityandatleasttwosurfactants
haveactivityascollectins(moleculesthatbindtoforeignparticlessuchasbacteria,fungi,andviral
particlesandassistintheirphagocytosis).[21,50,53,54,67]
Inconclusion,bothpositivepressureandlunginjuryaltertheproductionandfunctionofsurfactant.
Changesinsurfacetensionandlossofimmunocompetencebothpredisposetolunginjuryandinfection.
Aviciouscycleensueswherethediseaseandthesupportivetreatmentmaybesynergisticinproducing

deleteriouseffectsandwillmakepositivepressureventilationbothmoredifficultandmoreproneto
causefurtherinjury.

EffectontheCardiovascularSystem
Theeffectsofpositivepressureventilationonthecardiovascularsystemarewellknown.Innormal
breathing,thenegativepressurephaseofinspirationassistsvenousreturn,alleviatespressureonthe
pulmonarycapillaries,andencouragesflow.Withpositivepressureventilation,theintrathoracicpressure
increasesduringinspirationcausingadecreaseinvenousreturn,rightventricularoutput,andpulmonary
bloodflow.Paradoxically,theremaybeareductioninrightventricularimpedance,butwhetherthis
offsetsthedecreaseinvenousreturnisunknown.[90]ThereissomeevidencetoshowthatasPEEP
increases,rightventricularoutflowtendstodecrease,reducingreturntotheleftventricle.[91,134]This
effectmaybepartiallyoffsetbytheincreasedintrathoracicextrathoracicgradientassistingleftventricular
output.Thismaybebeneficialincardiacfailurebutisnotusuallyrelevantinothercircumstanceswhere
raisedintrathoracicpressurereducesoutput.[102]
Onexpiration,theintrathoracicpressurereturnstowardszerosothatvenousreturnwillincrease.If
PEEPisapplied,positiveintrathoracicpressurecontinuestoinhibitvenousreturnthroughexpiration.The
reducedcollapsibilityoftheinferiorvenacavaoftenseenwithventilationandPEEPisaclearindicatorof
adegreeofvenousstasis.[91]Fluidadministrationimprovesvenousreturnandcardiacoutputbutatthe
costofincreasedcentralvenouspressures(CVP)andhenceincreasedendcapillarypressuresinthe
lungsandotherorgans.
Positivepressureventilationisassociatedwithsaltandwaterretention.Whileclassicallythisisdueto
increasedsecretionofantidiuretichormonemediatedthroughthereducedatrialdistensionseenwith
positivepressureventilation,morerecentlyatrialnatriureticpeptidehasbeenimplicated.[4,42,66]
Correctionofthisbyintravascularfluidadministrationresultsinfurtherfluidretention.[5,7,139]

ThePulmonaryCapillaryandBloodFlow
Themeancapillarypressureisusually710mmHg,avaluederivedfromthegradientbetweenthe
pulmonaryarterypressureandthevenousoutflowpressureinthepulmonaryvein.Intrathoracicpressure
willactuniformlyacrossthecapillaryandshouldnotdirectlyinfluencegradient,unlessthecapillaryis
physicallycompressedbytheraisedinterstitialpressurealongitscourse.
Duringnormalbreathing,thepressuresintheinterstitiumandthealveoliaresmallrelativetothecapillary
perfusionpressure.Thislowpressuresystemenablesthehydrostaticandoncoticpressurestofacilitate
fluidandsubstratemovementbetweencompartmentsbutalsoensuresunimpededbloodflow.
Furthermore,thepressureswithinthelunggenerallyarelowerthancapillarypressureinallphasesand
donotinfluencecapillaryflow.Theexceptionsbeingareashigherthantheatriumwherethepressure
gradientsarelower,andinthedependentareaswhere,theoretically,lungtissueweightmaypresson
capillaries.Theseeffectsaresmallandtransient.Indisease,thiscanbedifferent.Patientswithchronic
obstructivepulmonarydiseasewithhyperinflationhaveahighintrathoracicpressureonexpirationwhich
compressestheinterstitiumandthecapillaries,thusincreasingcapillaryresistanceandmodifyingblood
flow.[88]Oninspiration,astheintrathoracicpressuresdecrease,flowcanrecover.
Positivepressureventilationinacriticallyillpatient,evenwithpeakinspiratorypressureslimitedto30
mmHg,producesinterstitialpressuresconsiderablyinexcessofcapillarypressureandwilltendto
compressthecapillaryandimpedeflow.Inexpiration,PEEPof15mmHgmaystillexceedcapillary
pressureandpreventsrecoveryofnormalflow.[97]Compensatorymechanismswillalsobemodified.

Hypoxicvasoconstriction,whichisprecapillaryandwhichishighlyeffectiveindivertingbloodflowduring
spontaneousbreathingatlowpressures,maybeoffsetbythemagnitudeoftheexternalpressuresbeing
applied.[140]Thecapillarypressureitselfincreasesminimallywithprecapillaryvasoconstriction,probably
intheorderof1mmHghence,thecapillarywillremainsusceptibletoexternalpressure.[23,120]Athigh
altitude,someindividualsrespondtohypoxiabyamoregeneralized,albeitstillregionallyheterogeneous,
increaseinpulmonaryarterypressurewhichinfluencesflow,presumablydivertingittoappropriateareas.
[32,64]Duringpositivepressureventilation,compliantinflatablelungregionsreadilytransmitpressureand
intheseareasthepressurewillimpedecapillaryflowwhereasnoncompliantdamagedorinfectedlung
willdampenpressuretransmissionandmayhavebetterperfusion.Compensatorydiversionisunlikelyto
overwhelmtheeffectsofthismagnitude.Perfusionventilationmismatchisinevitable.
Thehighvenouspressures,secondarytopositivepressureventilation,willalsoadverselyaffectthe
pressuregradientsaffectingStarling'sforcesandencouragingfluidflux,leadingtointerstitialfluid
retention.
Inthecriticallyill,increasingpulmonaryarterypressures,highinflationpressures,andpersistentlyhigh
venouspressuresprobablydamagetheintegrityofthecapillaryendothelium.'Capillarystressfailure'or
disruptionofthecapillaryisseeninextremeexerciseinracehorsesandisprobablyalsoseeninhumans
withhighpulmonaryarterypressures,highalveolarpressure,andinaltitudehypoxia.[64,132,143]
Capillaryperfusionpressureisofcentralimportancetolungfunction.Theconsequencesofpersistently
raisedintrathoracicpressurearealteredflowbycompressionofthecapillary,modifiedStarling'sforces,
andraisedendcapillarypressures.Compensatorymechanismsareunlikelytobeeffectiveandmay
aggravateventilationperfusionmismatch.

Lymphatics
Thelymphaticssubserveatleasttwofunctions,drainageanddefence.Thelunghasamassivesurface
areacontinuouslyexposedtoalargevolumeofpoorlyfilteredair.Fluidisdrainedfromtheinterstitiumby
thereticuloendothelialsystemthatremovesextraneousmaterialbeforeitreachesthecirculation.
Thelunglymphaticsconsistofthin,singlecell,conduitswithintheinterstitiumwithvalvestoassist
unidirectionalflow.Duringinspiration,thenegativepressureinthelungistransmittedtotheinterstitium
andtothelymphaticsandagradientallowsfluidtodrainintothelymphatics.Thisishighlyefficientand
lymphflowcanincreaseconsiderablyifneeded.[9,41,51,52,76]Asthelymphaticsfill,pressureincreases
andelasticityincreasesforwardflowaidedbymuscleactivityinthelimbsorbyventilatorymovement.[2]
Towardsthehilum,smallerchannelscoalesceintolargeronesandtheyendinthethoracicductorlarge
lymphaticswhichdrainintocentralveins.[112]
Thepressureintheperipherallymphaticsreachesamaximumaround4mmHg,atwhichflowis
maximalbutifthepressurecontinuestoincreasethewallsoverstretchandleak.Thispressureofaround
4mmHgisadequatetoprovideahydrostaticgradientbetweenthelymphaticsandthecentralveins
whichhaveverylowpressuresduringtheinspiration.Thecollectingductsareslightlymorerobustand
containsmoothmuscle.Thishelpsthelymphaticscompensateforsomeoutflowresistance,buttheyare
stilleasilycompressed.Flowwillberelativelyeasilyimpededbothbyexternalpressureonthelymphatic
wallsorbyoutflowresistance.
Positivepressureventilationwillpushfluidfromalveolustowardstheinterstitiumandpotentiallytowards
andintothelymphatics.Thepositivepressureontheinterstitiummaycompresssomeperipheral
lymphaticspotentiallyaidingflow,butitmayalsocompressthesethinwalledvesselsimpedingflow.
[93,100]AsecondeffectisthathighCVPsassociatedwithventilationwillformasignificanthydrostatic
barriertoflow,giventhatthelymphaticpressureisusuallyinsinglefigures.[15,70,71,125]Lymphflowis

barriertoflow,giventhatthelymphaticpressureisusuallyinsinglefigures.[15,70,71,125]Lymphflowis
againimpeded.[147]
Duringexpiration,lowerintrathoracicpressureanddecreasingCVPsmayallowresumptionofflow,but
theuseofPEEP,especiallyhighPEEP,mayobviatethisrecovery[112](Figure4).Positivepressure
ventilationincreaseslungwaterasdoesPEEP.[3,12,44,45,55,57,74,86,135]PEEPhelpsremovefluidfrom
alveoli,butthereductioninthoracicductdrainageresultsinfluidretentionintheinterstitium.
[45,55,70,82,86]

Airwaypressureandthelymphatics.Peakflowatapressureof4mmHg.Airwaypressureof15mmHg
orhighercompressesthinwalledcollapsiblelymphatics.Thelymphaticsdrainintothecentralveins
characterizedbythesuperiorvenacava(SVC).IftheSVCpressureishigh,12mmHginthisexample,
drainagewillbeimpeded.Hencebothairwaypressuresandvenouspressureswillpotentiallyimpede
drainage.
Inthedeliberatelyinjuredlung,PEEPincreaseslymphproductionbutimpairslymphflow.[55,93,111,135]
Measuringflowinthethoracicductusingafistulashowsthatbothpositivepressureventilationand
PEEPthenincreaseflowbut,asthefistulabypassesthehydrostaticbarrierofthecentralveins,this
mightbeexpected.Anaesthetized,ventilatedanimalsonPEEPwithhighatrialpressureshadless
pulmonaryoedemaandreducedformationofpleuraleffusioniftheyhadthoracicductdrainage.[3,55]A
similarmechanismwasinferredinventilatedpatientswithpancreatitiswherethoracicductdrainagewas
associatedwithanimprovementinlungfunction.[37]Theinformationavailableislimited,butatpresent
thereisnoclearexplanationofhowaverylowpressuresystemcandraineffectivelyifthereishighCVP.
[148]Theneteffectofimpaireddrainageovertimewouldbefluidaccumulationinthelungandpleural
spacesandpotentiallyincreasedsusceptibilitytolunginfection.[28]
Inthelung,thereisnodirectevidencelinkingimpairedlymphaticdrainagetoinfectionriskbutelsewhere,
suchaswithchroniclymphoedemathereisbothfluidsequestrationandpredispositiontoinfection.
[28,79,108,117,147]

Circumstantialassociationsincludetheobservationthatinthecriticallyillnosocomiallunginfection
usuallystartssomedaysaftercommencingventilationeveninotherwisefitindividualsandthattime
intervaliscommensuratewiththeeffectsoflymphaticobstruction.Afterlungtransplant,theinfectionrate
inthefirstfewdaysishighandantibodyresponsesareminimal.[142]Inthesepatients,lymphatic

inthefirstfewdaysishighandantibodyresponsesareminimal.[142]Inthesepatients,lymphatic
drainagereestablishesitselfasearlyasthesecondweek.[107]Thereisalsoanadverserelationship
betweenaCVP>7mmHgandoutcomeinventilatedlungtransplantpatients.[101]
Ventilationimpairslymphaticdrainageandchroniclymphaticobstructionpredisposestoinfectioninother
situations,butthereislimitedevidenceforthesestatements.[2,9,28]

OrganSystemsandPositivePressureVentilation
Theobviousimmediateeffectsofpositivepressureventilationonotherorgansrelatetoadecreasein
cardiacoutput(Figure5).Thepredominanteffectsonthekidneyareadecreaseinglomerularfiltration
rateanddiversionofintrarenalbloodflowbothduetoreducedcardiacoutputandbothreadilycorrected
eitherbyfluidadministrationorbychangingtoaspontaneousmodeofventilation.[5,47,103,139]

Flowdiagramillustratingthephysiologicalinteractionsofpositivepressureventilation.(A)leadsto(B)
leadsto(C)
SomeoftheeffectsofPEEPonthehepatosplanchniccirculationcanbereversedbyfluid
administration,implyingaprimaryroleforcardiacoutput.However,thisdoesnotapplytoreducedportal
bloodfloworincreasedhepaticbloodvolumebothofwhicharesecondarytovenouscongestion,northe
reducedhepatosplanchniclymphaticdrainage.[6,14,39,46,80,104,114,141,146]Hepaticmetabolicfunctionis
impairedbyPEEPof10mmHginsepsisbutislesssignificantaftercardiacsurgery.[61,114]PEEPhas
beenshowntoincreasetranscapillaryfluidfluxperipherally,therebyincreasinginterstitialfluid,anditalso
influencesmicrocirculatoryflow.[10,57,77,96]
ThesustainedincreasesinCVPsecondarytopositivepressureventilationleadtovenouscongestion,
increasedendcapillarypressureandalteredfluiddynamicswithinorganswithpotentiallydeleterious
effects.[14,94,106,118,119]Italsoaffectslymphaticfunction.Inthekidney,venouscongestioncompresses
lymphaticcollectingductsimpedingdrainageandasimilarmechanismispostulatedforbothmesenteric
andperitonealdrainage.[74][75][105]Raisedintraabdominalpressureimpairslymphaticdrainageand
affectsorganfunction.[81]Highthoracicductpressureincreasesinterstitialfluidinbothliverandkidneys
andhasmeasurableeffectsonrenalfunction.[110]Thismayprovidelinkagetotheincreasingevidence
thatexcessfluiditselfmaydelayrecoveryinareasasdiverseaslowergastrointestinalsurgery,freeflap
surgery,andventilationofacutelunginjury,althoughthisiscontentious.[22,56,62,63,109,145]
Theevidencefortheeffectsofvenousandlymphaticcongestionimpairingorganfunctionisasyet
rudimentary,butthephysicsishardtodismiss.

Conclusions
VentilationwithPEEPisaproven,effectivemodalityinbothanaesthesiaandICU,despitetheimmense
physiologicalderangementitcauses.Thetruecostsincurredcannotbeassesseduntilthese
physiologicalderangementsarerecognizedandevaluated.Theredistributionofalveolarventilationand
theassociatedalteredcapillaryperfusion,thefunctionalchangesinsurfactant,thetranscapillaryfluid
shifts,theimpairedlymphaticdrainage,andimpededvenousreturnallcontributetowet,harderto
ventilatelungs.Thisnecessitatesmoreaggressiveventilation,whileimpededlymphaticdrainage
predisposestostasisandinfection.Correctionoftheimmediateproblemofreducedcardiacoutputby
fluidadministrationincreasescentralandsystemicvenouspressuresfurther.Therecentlyrecognized
complicationsofventilationhavebeenattributedtobarotraumaandinflammation,buttheother
physiologicalmechanismsoutlinedheremayhavebeenignored.Prolongedventilationisassociatedwith
lunginjury,infection,andmultiorgansystemdysfunctionandifthesemay,eveninpart,beattributableto
thephysiologicalderangementsdescribed,thentherealcostofventilation,oroxygenation,isandhas
alwaysbeenhigherthanwasrealized.(SeeFigure5)
Thereareotherreasonswhyventilationshouldbereassessed.Genuinedevelopmentsinpositive
pressureventilationareconstrainedbyphysics.Thesimplefactthatonlyonepressureandonetime
relatedwaveformcanbedeliveredatthetrachealtubeprecludesthepotentialforgenuinetechnological
advance.Isventilationasamodalityatanevolutionarydeadend?Aretherepotentialalternatives?It
wouldseemlogicalinsevereillnesstoavoidphysiologicalderangementandtorestthelung.Tankor
cuirassescouldusethethoraxtogenerateanegativeinspiratorypressure,andmaintainnearnormal
gradientsthatarefundamentaltoalveolar,capillary,andlymphaticfunctionwhileminimizing
haemodynamicdisturbance.Insevereillness,oxygensupplementationwouldinevitablyberequiredto
meettissuerequirements.Fundamentaltothiswouldbeanewapproachtodefiningtissueoxygen
requirementsdivorcedfromthecurrentapproachbasedonmeasurementofarterialcontent.Doesthe
technologytosupplementoxygenexist?Thesametechnologicalprinciplesthatrevolutionizedcritical
caredialysisfrom'hightech'tobedsidehaemofiltrationshouldallowthedevelopmentofbedside
extracorporealoxygenationusingtheheartasthepump.Lungassistdevicesalreadyexist,butarein
theirinfancy.[8,31,33,150,151]
Willmaintenanceof'normal'ventilatorypatternsassistrecovery?Theevidencefromnoninvasive
ventilationandtheoccasionalstudyusinganironlungprovidescircumstantialencouragement.[2527]
Therearemanyunansweredquestions,butforfutureprogresstherearethreepreliminarystepstobe
taken:
i.recognitionofthefullrangeofphysiologicalderangementanditspotentialconsequences

ii.acceptingthephysicalandphysiologicalconstraintsinthefurtherevolutionofpositivepressure
ventilation

iii.acknowledgmentthatwhilepositivepressureventilation,atechnologynowmorethan50yrold,
servesanimmenselyusefulfunction,itmaybetimetoconsideralternativesinthecriticallyill.
Whatistherealcostofventilation?Wewillnotknowuntilweevaluatetheroleofphysiological
derangementonlatecomplications.Itislikelythecostishigh.
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BrJAnaesth.2008101(4):446457.2008OxfordUniversityPress
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