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AnaestheticManagementofthePatientWithAcute
IschaemicStroke
Z.H.Anastasian
BrJAnaesth.2014113(S2):ii9ii16.

AbstractandIntroduction
Abstract

Anaestheticmanagementoftheacutestrokepatientdemandsconsiderationofthepenumbraasthecentralfocus.
Recentstudieshaveshownthatpatientswhoreceivegeneralanaesthesiaforendovasculartherapyforacute
ischaemicstrokehaveworseoutcomesthanthosewhoreceivelocalanaesthesia.Althoughbaselineconditionofthe
patientsinthesestudiesdiffered,weshouldheedthewarningsevidentintheresults.'Timeisbrain':therapyshould
bequicklyprovided.Arterialpressureshouldbemonitoredcarefullyuponinduction,avoidingadrasticreduction,and
allowingforareductioninarterialpressureuponrecanalization.Keepingthesefactorsinmind,anaesthetictechnique
(general,monitoredanaesthesiacare,orlocal)mustbeselectedconsideringtheindividualpatient'srisksand
benefits.Unfortunately,therearenoprovenneuroprotectivestrategiestodateforuseinacuteischaemicstroke.

Introduction

Acutestrokeisthesecondleadingcauseofdeathworldwideandtheleadingcauseoflongtermdisability. [1]
Ischaemicstrokeisresponsiblefor87%ofstrokes. [2]Inacuteischaemicstrokes,anembolus,thrombus,orstenosis
candecreasebrainperfusion.Thegoalofearlytherapyforacuteischaemicstrokeistorestoreperfusion.I.V.
thrombolysiswithrecombinanttissueplasminogenactivator(rtPA)istheonlyprovenmedicaltherapyshownto
improvepatientoutcomesinacuteischaemicstroke,withbetteroutcomesachievedwithearlieradministration. [3,4]
Patientswhopresentwithin4.5hofstrokesymptomonsetandhavenocontraindicationstotherapyshouldbe
treatedwithi.v.rtPA. [5]However,only38.5%ofallstrokepatientsaretreatedwithi.v.rtPA. [6]Inaddition,treatment
withi.v.rtPAisunsuccessfulinachievingrecanalizationinoverhalfofpatientswithlargearteryocclusions. [7]
Patientswhoarenoteligiblefori.v.rtPAduetodelayedtimetopresentation,contraindicationstoi.v.rtPAtherapy
(recentsurgeryorcoagulopathy),orfailedi.v.rtPAcanbeconsideredforendovasculartherapy.Althoughrecentdata
fromrandomizedclinicaltrialssuggestthatendovasculartherapywasnotsuperiortoi.v.rtPA, [8,9]studiesshowintra
arterialthrombolysisormechanicalclotremovingdevicestobeefficaciousforrecanalizationandrestorationof
cerebralbloodflow. [1012]

Thisarticlereviewsthecurrentbodyofliteratureontheanaestheticmanagementoftheacuteischaemicstroke
patient,withafocusontherecentliteraturecomparingoutcomesafterendovasculartherapyperformedwithgeneral
comparedwithlocalanaesthesia,theimportanceofavoidingatimedelayintreatment,therecentliteratureinvolving
haemodynamicmanagementoftheacutestrokepatient,andpotentiallyneuroprotectivestrategies.

AnaestheticTechniqueandOutcomes
Therehasrecentlybeenanincreasedinterestinevaluatingtherelationshipbetweentypeofanaesthesiaapatient
receivesduringendovasculartherapyforstrokeandoutcomes.Generalanaesthesiacanofferthebenefitsof
immobility,paincontrol,andairwayprotection.Themajordisadvantagesofgeneralanaesthesiainclude
haemodynamicchangeswithintubation,thepossibilityofdelayingtimetorecanalization,pulmonaryaspiration,and
therequirementforadditionalworkforce.Localanaesthesiaorsedation(includingmonitoredanaesthesiacare)can
maintainsmootherhaemodynamicsduetothedecreasedadministrationofpharmacologicalvasodilators,andallow
intraproceduralclinicalneurologicalevaluation.Buttheseapproacheshavethedisadvantagesofthelackofairway
protection,continuedpatientmovement,uncontrolledpainandagitation,andaprolongedproceduretime.Whilethe
choiceofanaesthetictechniquecanbeindividualizedbasedontheneedsofeachpatient,theanaesthesiologist
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monitorsandprovidesairwaysupporttoassureproperoxygenation,haemodynamicsupporttoassureproper
perfusionofthepenumbra,andpotentiallyimmobilityintheconfusedandagitatedpatienttoprovidebetterworking
conditionsforrevascularization().

Table1.Generalanaesthesiaorlocalanaesthesiaforendovasculartherapyafteracuteischaemicstroke

Generalanaesthesia Localanaesthesia

Pros Pros

Immobility Smootherhaemodynamics

Paincontrol Intraproceduralneurologicalevaluation

Airwayprotection

Cons Cons

Haemodynamicchanges Lackofairwayprotection

Additionalworkforce Patientmovementpossible

Potentialoftimedelaybeforestartofprocedure Uncontrolledpainandagitation

Prolongedproceduretime

In2010,threestudies [1315]andmultipleeditorials [1618]werepublished,evaluatingoutcomesandanaesthetic

technique.Jumaaandcolleaguesperformedaretrospective,singlecentrestudyof126patientsundergoing
endovascularproceduresforacuteischaemicstroke.Theyreportedthatintubatedpatientshadlongerintensivecare
unitstays,increasedinhospitalmortality,worseclinicaloutcome,andlargerfinalinfarctvolumesize.However,the
clinicalconditionsoftheintubatedpatientsdifferedfromthosenotintubatedbeforeendovasculartherapyinhaving
significantlyhigherbaselineNationalInstitutesofHealthStrokeScale(NIHSS)scores. [13]Nicholsandcolleagues
reviewedtheanaestheticmanagementof75patientsintheInterventionalManagementofStroke(IMS)IItrialwith
anteriorcirculationstrokewhounderwentangiographywithorwithoutintraarterialtreatment.Theycategorizedthe
anaestheticmanagementintofourlevels(nosedation,mildsedation,heavysedation,andpharmacologicalparalysis).
Theyfoundthatthegroupofpatientswhoreceivednosedationhadrelativelygoodoutcome(modifiedRankinscoreof
02),lowerdeathrates,andhigherreperfusionrates.Patientswhoreceivedmoresedationalsohadhigherbaseline
NIHSSscores. [14]AbouCheblandcolleaguesperformedalarge(980patients)retrospectivemulticentre(12centres)
study,whichfoundthatgeneralanaesthesiaduringanendovascularprocedureforanteriorcirculationischaemic
strokewasanindependentpredictorforpooroutcome.Similarly,patientswhoreceivedageneralanaesthetichad
higherbaselineNIHSSscoresandweremorelikelytohavecarotidterminusocclusions. [15]

Morerecently,studieshaveincludedarterialpressuremeasurementsinevaluatingtherelationshipbetweengeneral
anaesthesiaandpooroutcomesafterendovasculartherapyforacuteischaemicstroke.Davisandcolleagues
performedaretrospectivesinglecentrestudyof96patientsundergoingendovasculartherapyforacuteischaemic
strokeandalsofoundanassociationbetweengeneralanaesthesiaandpooroutcomes(15%probabilityofgood
outcomescomparedwith60%inthelocalanaesthesiagroup).Patientswhounderwentgeneralanaesthesiahad
higherbaselineNIHSSscoresthanthosegivenlocalanaesthesia.However,theinvestigatorsalsofoundan
associationofgoodoutcomeswithsystolicarterialpressure(SAP)>140mmHg.Therewasacorrelationbetween
lowarterialpressure(definedastheminimumpressurerecorded)andgeneralanaesthesia. [19]AbouChebland
colleaguesreviewedtheNorthAmericanSOLITAIREStentRetrieverAcuteStroke(NASA)Registrytocomparethe
outcomesofpatientsreceivinggeneralanaesthesiawiththosereceivingsedation. [20]Theyincludeddatafrom281
patientsfrom18sitesthatdescribedanaesthesiatype,andgroupedpatientsintogeneralanaesthesia(iftheywere
intubated)orlocalanaesthesia(iftheywerenotintubated,regardlessofwhetherornottheyreceivedsedation).
PatientswhoreceivedgeneralanaesthesiahadhigherbaselineNIHSSscoreandlowerbaselinearterialpressures.In
amultivariateanalysis,hypertension,NIHSSscore,unsuccessfulrevascularization,nonutilizationofballoonguide
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catheter,andgeneralanaesthesiawereassociatedwithmortality.Therelationshipbetweengeneralanaesthesiaand
worseoutcomespersistedwhentheyexcludedpatientswhoarrivedintubated(andwereintubatedemergently)and
thosewhohadposteriorcirculationstrokes. [20]Morerecently,Raiandcolleaguespublishedanabstractthatshowed
thatalthoughgeneralanaesthesiawasassociatedwithhigherpatientmortality,itwasnotanindependentpredictorof
outcomewhenbaselineNIHSSscore,age,andrecanalizationweretakenintoaccount.Inaddition,theinterval
betweenarrivalandgroinpuncturewashigherinpatientswithgeneralanaesthesia.Theyalsofoundahigher
differenceinpreandpostSAPwasassociatedwithaworseoutcomeinpatientswithgeneralanaesthesia[21]().

Table2.Studiesongeneralcomparedwithregionalanaesthesiaforendovasculartherapyforacutestroke.ICH,
intracranialhaemorrhage

Anaesthetic
Study Patients Outcomes Limitations
management

Retrospective,
singlecentre, IntubatedpatientshadlongerICU
Intubatedpatients
Jumaaand 126patients Intubatedornot stays,increasedinhospital
13 hadhigherbaseline
colleagues withacute intubated mortality,worseclinicaloutcome,
NIHSSscores
ischaemic largerfinalinfarctsize
stroke

Retrospective, Patientswithmore
75patients Nosedation,mild Lowersedationwasassociated sedationhadhigher
enrolledin sedation,heavy withgoodoutcome(modified baselineNIHSS
Nicholsand
IMSIItrial sedation, Rankinscoreof02),lower scoresandhadless
colleagues14
withanterior pharmacological mortalityandhighersuccessful successful
circulation paralysis reperfusionrates angiography
stroke reperfusionrates

Patientswithgeneral
Independentpredictorsofpoor
anaesthesiahad
outcomeandmortality:age,
AbouChebl Retrospective, higherbaseline
Generalanaesthesiaor NIHSS,generalanaesthesia,
and multicentre, NIHSSscoresand
conscioussedation recanalization,ICH,carotid
colleagues15 980patients weremorelikelyto
terminusocclusion.Predictorsof
havecarotidterminus
pooroutcome:nostentplaced
occlusions

Patientswithgeneral
Generalanaesthesiaor Independentpredictorsforgood anaesthesiahad
localanaesthesia(local outcomesare:localanaesthesia, higherbaseline
Retrospective, anaesthesiaincludes lowbaselinestrokescores,and NIHSSscores
Davisand
singlecentre, lightsedationwith systolicpressure>140mmHg.
colleagues19
96patients midazolamandfentanyl, Goodoutcomeswere
ifneeded,providedby Generalanaesthesiaiscorrelated associatedhigh
thestrokeneurologist) withlowarterialpressures higherarterial
pressures

Patientswho
Generalanaesthesia Independentpredictorsofmortality: receivedgeneral
Retrospective,
AbouChebl (intubated)orlocal hypertension,NIHSS,unsuccessful anaesthesiahad
multicentre
and anaesthesia(not revascularization,nonutilizationof higherbaseline
(18sites),
colleagues20 intubated,butunknown balloonguidecatheter,andgeneral NIHSSandlower
281patients
ifsedated) anaesthesia baselinearterial

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pressures

Patientswho
Generalanaesthesiaisnotan
receivedgeneral
Generalanaesthesiaor independentfactorwhenNIHSS,
anaesthesiahad
Raiand Retrospective, nongeneralanaesthesia ageandrecanalizationare
higherbaseline
colleagues singlecentre, (bothmonitored included.Arrivaltopuncturetimeis
NIHSS.Arrivalto
(abstract)21 190patients anaesthesiacareand longerwithgeneralanaesthesia
timetopuncturetime
local) andarterialpressurevariationsare
waslongerwith
largerwithgeneralanaesthesia
generalanaesthesia

Unfortunately,todate,therearenorandomizedcontrolledclinicaltrialsandnoprospectivelycollecteddataspecific
toanaestheticmanagementofendovasculartreatmentofacuteischaemicstroke.Studiesthathavebeenpublished
includepatientswhohavedifferentbaselinecharacteristics.Inaddition,inmoststudies,thetypesofanaesthesia
oftenareclassifiedas'generalanaesthesia'or'intubated'vs'localanaesthesia'or'notintubated'.Thisbinary
stratificationexcludeshaemodynamicmanagement,depthofsedation,andthepresenceofanaesthesiologist.

Thetopicandstudyresultsareimportantandmoredataarenecessary:theinductionofgeneralanaesthesiaineach
individualpatienthasindividualrisksandbenefits,andasMolinaandSelim[16]summarizedcanbecomeachoiceof
generalanaesthesia,'sailingquietlyinthedarkness',orlocalanaesthesia,sailing'fastunderadaylightstorm'.

Theresultsofthesestudiesandthedifferencesbetweenthegroupsthatreceivedgeneralanaesthesia,sedation,or
localanaesthesiasuggestseveralhypothesesastowhypatientswhohavegeneralanaesthesiahaveworse
outcomes.First,patientswhohavegeneralanaesthesiaineverystudyare'sicker'atbaselinebyNIHSSscores.
Evenaftercorrectingforthis'sicker'patientstatus,selectionbiasisinherentinanyretrospectivestudy.Inaddition,
patientswhoreceivedgeneralanaesthesiahad,incertaincentres,longertimefromarrivaltogroinpuncture. [21]
Finally,patientswhoreceivedgeneralanaesthesiahadlowerarterialpressuresrecorded,includingbaseline[20]and
lowestrecorded, [19]andhadgreaterarterialpressurefluctuations. [21]

TimeIsBrain
AsurveyofmembersoftheSocietyforVascularandInterventionalNeurology(SVIN)foundthatinterventional
surgeonsfeltthemostimportantlimitationofgeneralanaesthesiaandthemainreasonfornotpreferringitforall
caseswastimedelay. [22]Timedelaytotherapyisindeedamajorconcernintherapyforthepatientwithacute
ischaemicstroke.Thetargetoftherapyinacuteischaemicstrokeistheischaemicpenumbra,whichisthe
threatenedbutsalvageabletissuesurroundingtheinfarctcore.Theischaemicpenumbraisshortlived,lastingonlyfor
afewhoursinhumanpatients. [23]Thetypicalischaemicstrokepatientloses1.9millionneuronesforeachminute
theyareuntreated.Comparedwiththenormalrateofneuronelossinbrainageing,theischaemicbrainages3.6yr
eachhourwithouttreatment. [24]Recanalizationofoccludedarteriesisanecessary,butnotsufficient,conditionfor
achievinggoodclinicaloutcomeswithendovasculartherapy.Iftheentiretissueatriskhasalreadyprogressedto
irreversibleinfarction,reperfusionwillbefutile,andcanevencauseharmbyincreasingtheriskofhaemorrhagic
transformation.

Althoughinductionofgeneralanaesthesiaandtheinvolvementofananaesthesiacareteamcouldconceivablydelay
endovasculartreatmentofacuteischaemicstroke,moststudiesshownodifferenceintimefrompatientarrivalto
treatmentforpatientsreceivinggeneralanaesthesiaorlocalanaesthesia. [14,15,19,20]Asingleinstitutionalstudydid
findasignificantlylongerarrivaltogroinpuncturetimeinpatientswhoreceivedgeneralanaesthesia. [21]Incontrast,
interventionalproceduretimehasbeennotedtobelessforpatientswhoreceivegeneralanaesthesia. [13]Although
thisistrueinreportedstudies,therecanbesubstantialvariabilitybetweeninstitutions.Itiscriticaltorememberthe
racetosavethepenumbraandavoiddelayoftherapy.

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HaemodynamicManagement
Morethan60%ofpatientswhopresentwithischaemicstrokehaveelevatedarterialpressures. [25,26]Theelevated
systemicarterialpressuresaredue,inpart,tobaselinehypertension.Inadditiontobaselinehypertension,there
existsasuperimposedearlyhypertensiveresponsetobrainischaemia.Potentialmechanismsbehindthisresponse
includetheCushingresponsetoamasseffectofoedema, [27]autoregulationresponseinahypertensivepatient, [28]
andneuroendocrineresponsetophysiologicalstress. [29]Withinthefirst24hafterstroke,arterialpressuredeclines
byabout25%inmostpatients. [30]Presentationwithhighsystemicarterialpressureatthetimeonischaemicstroke
isassociatedwithpooroutcome. [31]Inaddition,presentationwithlowsystemicarterialpressureatthetimeof
ischaemicstrokeisalsoassociatedwithpooroutcome.DatafromtheInternationalStrokeTrialsuggestthatthe
relationshipbetweenarterialpressureatthetimeofacuteischaemicstrokeandoutcomesisaUshapedcurve,with
bothlowarterialpressureandhigharterialpressureincreasingdeathanddependency,withthelowestriskofdeathor
dependencyatasystolicarterialpressureof150mmHg. [32]

Optimalmanagementoftheacuteischaemicstrokepatientwithhypertensionisunclear.Loweringarterialpressure
shouldreducecerebraloedemaanddecreaseprobabilityofhaemorrhagictransformationoftheinfarct.However,
loweringarterialpressuremightpotentiallydecreasecollateralflowinthepenumbralarea,especiallyinthesettingof
ischaemiaandimpairedautoregulation. [25]Animaldatashowthathypertensioninduceduponcerebralartery
occlusionimproveslocalcerebralbloodflow[33]anddecreasesinfarctvolume. [34]Inananimalmodelofchronic
hypertension,maintainingarterialpressureresultedinanimalswithincreasedregionalbloodflow,decreasedoedema,
decreasedstrokevolume,andimprovedneurologicalscores. [35]Inhumans,arterialpressureelevationduringcarotid
occlusionduringacarotidendartectomyhasbeenshowntoimprovepostoperativecognitivefunction. [36]ACochrane
metaanalysisthrough2008identified12randomizedtrialsthatincluded1153patientswithstroke,andconcluded
therewasinsufficientevidencetoevaluatetheeffectofalteringarterialpressureonpatientoutcomes. [37]

Threelarge,prospectivetrialsfocusedonarterialpressuremanagementinthetimeintervalafterstroke.The
COSSACStrialrandomized763patientswhopresentedwithin48hofstroke(only5%haemorrhagic)toeither
continuetheirchronicprestrokeantihypertensivetherapyortotemporarilydiscontinueantihypertensivemedications
forthefirst2weeksafterstroke.Therewasnodifferenceat2weeksintherateofdeathordependency.Thestudy
wasstoppedbeforetargetrecruitmentduetoslowrecruitmentandlackoffunding,andthereforethestudywas
potentiallyunderpowered. [38]TheSCASTtrialrandomized2029patientswithin30hofstroke(~85%ischaemic,15%
haemorrhagic)andaSAP>140mmHgtoreceiveanangiotensinreceptorblocker(ARB)orplacebofor7days.
Additionalantihypertensivemedicationswerereceivedbymorethanonequarterofenrolledpatients.Thestudy
showedthattherewasnoindicationthatARBtherapywasbeneficialtotheendpointsdeath,myocardialinfarction,or
recurrentstrokeata6monthtimepoint.Infact,therewasahigherriskofpoorfunctionaloutcomeinpatientswho
receivedanARB. [39]TheCATIStrialrandomized4071patientswhopresentedwithin48hofischaemicstrokeand
hadelevatedSAP.Twothousandandthirtyeightpatientsassignedtotheinterventiongroupreceivedantihypertensive
therapytodecreaseSAPby1025%withinthefirst24hafterrandomization,andachievedarterialpressure<140/90
mmHgwithin7days,maintainingthisduringhospitalization.Twothousandandthirtythreewereassignedtothe
controlgroupthathadallantihypertensivemedicationdiscontinued.Patientswhoreceivedthrombolysiswere
excluded.Therewasnosignificantdifferenceindeathormajordisabilityat14daysordischarge,orincomposite
deathandmajordisabilityat3monthsposttreatment.Subgroupanalysisshowedthattimetotreatmentdidaffect
theprimaryoutcome,withpatientswhowereenrolledmorethan24hafterstrokehavingsignificantlybetteroutcomes
inthetreatmentarm.Thesedatafavourtheuseofloweringarterialpressureafter24h,whentheimpactofarterial
pressureonthepenumbraisdecreased.Limitationsofthestudyincludeanopenlabelinterventionthatcanintroduce
raterbias,exclusionofcervicocerebraldisease,anethnicallyChinesepopulation,andamediantimeto
randomizationof15h. [40]

Recently,theEfficacyofNitricOxidetrial(ENOS)finishedrecruitmentof4011patientswithanewonsetmotor
deficit,SAPbetween140and220mmHg,andpresentingwithin48hofonsetofsymptoms.Patientswere
randomizedtotreatmentwithtransdermalglyceryltrinitrate(GTN)(5mgfor1hdaily)for7daysornoGTN.Patients
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withahistoryofpriorantihypertensivetreatmentwererandomizedindependentlyintocontinuingtheirtreatmentor
stoppingit.Theprimaryoutcomemeasurewascombineddeathanddependency.Secondaryoutcomemeasures
werearterialpressureover7daysoftreatment,death/impairment,recurrence,qualityoflife,andcognition.Results
werepresentedatthe23rdEuropeanStrokeConference.Therewasnosignificantchangeinprimaryoutcomefor
patientswhocontinuedorstoppedtheirantihypertensivemedication.However,somesecondaryoutcomeswere
betterinpatientswhostoppedtakingtheirantihypertensivemedicationfortheweekafterthestroke.Inaddition,there
appearedtobeabenefitinpatientswhoweretreatedwithGTNintheveryearly(<6h)timeframe. [41,42]

TheENCHANTEDtrialisanongoinginterventional,international,randomizedtrialstartedin2012designedtoenrol
3300patientspresentingwithacuteischaemicstrokeconfirmedbyimagingwithin4.5hofonsetofsymptoms,and
withSAP<185mmHg.Patientswillberandomizedtotwoarms:alowdose(0.6mgkg1])rtPAcomparedwith
standarddose(0.9mgkg1)rtPAarm,andanintensive(targetsystolicpressure140150mmHg)lowering
comparedwithstandardguideline(targetsystolicpressure180mmHg)arterialpressuremanagementarm.The
primaryoutcomewillbemeasuredintermsofcombineddeathanddisability90daysafterdischarge.Thesecondary
outcomemeasureswillbeoccurrenceofsecondaryintracerebralhaemorrhagewithin36hofadministrationofrtPA,
deathanddisabilityasseparatemeasuresattheendof90days,neurologicaldeterioration,qualityoflife,and
admissiontoresidentialcare[43]().

Table3.Haemodynamicmanagementtrialsinacutestroke

Study Patients Methods Outcomes

Analysisofdata
frompatientsinthe
AUshapedrelationshipwasfoundbetweenbaseline
17398patientsfrom randomized
LeonardiBee arterialpressureandbothearlydeathandlatedeath
theinternationalstroke internationalstroke
and ordependency:bothhigharterialpressureandlow
trialwithischaemic trialdesignedto
colleagues32 arterialpressurewereindependentprognosticfactors
stroke evaluateaspirinand
forpooroutcome
heparinusein
acutestroke

Randomizedto:

Continueprestroke
antihypertensive
COSSACS medicationsfor2 Primaryoutcome:nodifferenceat2weeksinrateof
763patientswithin48
Robinsonand weeks deathordependency.Studystoppedearlydueto
hofstroke
colleagues38 slowrecruitmentandlackoffunding
Stopprestroke
antihypertensive
medicationsfor2
weeks

Randomizedto:
Primaryoutcome:ARBtherapynotbeneficialto
2029patientswithin30
SCAST ReceiveARBfor7 compositevascularendpoint
hofstrokewith
Sandsetand days
systolicarterial
colleagues39 Secondaryoutcome:Higherriskofpoorfunctional
pressure>140mmHg
Receiveplacebofor outcomeinpatientswhoreceivedARB
7days

Randomizedto:

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Decreasearterial Primaryoutcome:nosignificantdifferenceindeath
pressureby10 andmajordisabilityat14daysordischarge,orin
4071patientswithin48 25%within24h, compositedeathandmajordisabilityat3months
CATISHe hofischaemicstroke achievearterial posttreatment
and andhadelevated pressure<140/90
colleagues40 systolicarterial within7days,and Subgroupanalysis:timetotreatmentdidaffectthe
pressure maintainingitduring primaryoutcome,withpatientswhowereenrolled
hospitalization morethan24hafterstrokehavingsignificantlybetter
outcomesinthetreatmentarm
Discontinue
antihypertensives

Randomizedto:

Treatmentwith
Primaryoutcome:deathanddependency:no
transdermalGTNfor
significantchangeforpatientswhocontinuedvs
7days
stoppedtheirantihypertensivemedication.Secondary
4011patientswitha
outcomes:arterialpressureover7daysoftreatment,
newonsetmotor NoGTN
death/impairment,recurrence,qualityoflife,and
ENOS deficit,systolicarterial
cognitionbetterinpatientswhostoppedtakingtheir
(recently pressurebetween140 Patientswitha
antihypertensivemedicationfortheweekofthe
completed) and220mmHgand historyofprior
stroke
presentingwithin48h antihypertensive
ofonsetofsymptoms treatmentwere
Subgroupanalysis:potentialbenefitinpatientswho
randomized
weretreatedwithGTNintheveryearly(<6h)time
independentlyinto
frame
continuingtheir
treatmentor
stoppingit

Patientswillbe
randomizedintwo
arms:

Lowdose(0.6mg
kg1)rtPAarm

3300patients Standarddose(0.9 Primaryoutcome:deathanddisability90daysafter

presentingwithacute
ischaemicstroke
ENCHANTED confirmedbyimaging,
(ongoing) within4.5hofonsetof
symptoms,andwith
systolicarterial
pressure<185mmHg
mgkg1)rtPAarm discharge.
Intensive(target Secondaryoutcome:secondaryintracerebral
systolicarterial haemorrhagewithin36hofadministrationofrtPA,
pressure140150 deathanddisabilityasseparatemeasuresattheend
mmHg)lowering of90days,neurologicaldeterioration,qualityoflife,
arm andadmissiontoresidentialcare

Standardguideline
(targetsystolic
arterialpressure
180mmHg)
managementarm

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Thequestionofhowarterialpressureshouldbemanagedinearlyischaemicstroke,especiallywhenthereisstill
substantialpenumbral,tissueatriskremainsunansweredbythecurrentbodyofliterature.Apotentialstrategyfor
managementsupportedbycurrentliteratureistoavoidloweringarterialpressuredramaticallyduringthefirst12h
afterstrokeonset,whencollateralcirculationcompromiseisstillaconcern.Thistimeperiodlikelyincludesthe
periodinwhichanendovascularproceduremightbeattempted.TheSocietyforNeuroscienceinAnesthesiaand
CriticalCare(SNACC)hasrecommendedthatsystolicarterialpressureshouldbemaintained>140mmHg(fluids
andvasopressors)and<180mmHg(withorwithouti.v.rtPA),anddiastolicarterialpressure<105mmHg(classIIa,
levelofevidenceB).Aftersuccessfulrecanalization,arterialpressuretargetsshouldbeadjustedtoavoidpotential
haemorrhagicconversion. [44]

FutureDirections:NeuroprotectiveStrategies
Aconsiderableamountofresearchhasbeeninvestedintothedevelopmentofpotentialneuroprotectiveagents:
ideallyonethatwouldbeadministeredinthefieldimmediatelyafterstroketogetmaximumpenetrationinto
ischaemictissueandthepenumbra.Multipleneuroprotectivetreatmentshavebeenidentifiedthatshowgreatpromise
inanimalmodelsofstroke.Unfortunately,nearlyallhavefailedtoprovideprotectioninhumantrials.Inastudyof178
acutestroketrialsperformedinthe20thcentury,49involvedpromisingneuroprotectiveagentsthatemergedfrom
preclinicalstrokestudiesandenteredhumantesting.Onehundredandfourteenclinicaltrialswereperformedwith
morethan21000patients.Everyagenttestedfailed. [45]

Anaestheticagents,includingthiopental,isoflurane,sevoflurane,andxenon,havealsobeeninvestigatedfortheir
neuroprotectiveeffects. [46]Whileanimaldata[47,48]andhumandataforcardiopulmonarybypass [49]haveshown
promise,andstudiesareongoingtoevaluatethepossibilityofneuroprotection, [50]thereisnohumanevidenceforthe
neuroprotectiveeffectsofanaesthesiainfocalischaemia. [46]

Magnesiumhasshownpromiseforneuroprotectionduringcarotidendartectomy [51]andcardiacbypasssurgery. [52]

ThepotentialuseofmagnesiuminacutestrokeisbeinginvestigatedintherecentlycompletedFASTMAGPhase3
trial.Thegoalofthetrialwastoenrolpatientsatanearlytimeperiodtoadministermagnesiumwhileitcouldhavean
effectonthepenumbra.Patientswereenrolledinthefieldwithin2hofonsetofsymptoms,receiveda4gbolusof
magnesiumsulphatei.v.over15min,followedbya16gmaintenanceinfusioninhospitalover24h. [53]

Hypothermiahasbeenshowntobeneuroprotectiveinexperimentalandfocalhypoxicbraininjurymodels. [54]
Hypothermiadecreasescerebralmetabolism,suppressesglutamaterelease,reducesneuroinflammatoryresponse,
disruptsapoptoticpathways,reducesfreeradicalgeneration,andminimizesoedemaformation. [55]Mildtomoderate
hypothermiaisassociatedwithimprovedneurologicaloutcomeamongpatientswithcardiacarrest,whichresultedin
hypothermiabecomingthefirstneuroprotectivestrategytoberecommendedbytheAmericanHeartAssociationin
comatosepatientsaftercardiacarrest. [56,57]Inaddition,hypothermiahasbeenshowntoreducemortalitywithout
increasingmajordisabilityintermandlatepretermnewbornswithhypoxicischaemicencephalopathy.In2010,the
InternationalLiaisonCommitteeonResuscitationrecommendedtherapeutichypothermiabeofferedtotermornear
terminfantswithmoderatetosevereencephalopathy. [58,59]However,intheinvestigationofmildhypothermiainthe
settingofpotentialfocalischaemia,theIHASTtrial,amulticentreclinicaltrial,foundthatmildhypothermia
administeredduringsurgeryfortreatmentofarupturedintracranialaneurysmdidnotimproveoutcomeafter
neurosurgicalaneurysmclipping. [60]

Pilotclinicaltrialstodatehavebeendesignedtoestablishthesafetyandfeasibilityofvariouscoolingtechniquesin
strokepatients.Nostudyhashadsufficientsamplesizetoprovideresults. [61,62]Twoongoingclinicaltrialsare
assessingtheefficacyoftherapeutichypothermiainacuteischaemicstroke.TheIntravascularCoolinginthe
TreatmentofStroke(ICTuS)2/3studywasdesignedtocomparethesafetyandclinicalbenefitofendovascular
hypothermiaandthrombolysiscomparedwiththrombolysisalone.Theprojectedenrolmentis1600patientsin
multiplecentrespresentingwithin3hofstrokewhoareeligibletoreceivertPA. [63]TheEuroHYP1trialistargetedto
enrol1500patientspresentingwithin6hofstrokesymptomsandwillrandomizethemtohypothermiaandbest

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medicaltreatmentorbestmedicaltreatmentalone. [64]

Withoutconclusiveevidencethathypothermiaisbeneficialinacuteischaemicstrokeinadults,current
recommendationsaretomaintainnormothermiaandtotreatpatientswithantipyreticsiffebrile. [44]

Conclusions
Inapatientwithacuteischaemicstroke,timeisoftheessencetosavethevulnerablepenumbra.Withthecurrent
evidence,thedecisionbetweengeneralanaesthesia,monitoredanaesthesiacare,orlocalanaesthesiafor
endovascularproceduresshouldbemadewiththeindividualrisksandbenefitsofeachpatientconsidered.Arterial
pressureshouldbemonitoredcarefullyuponinductionofanaesthesiaandinductionshouldbeexpedienttoallowfor
timelyendovascularinterventionifpossible.Targetarterialpressuresshouldbesystolicreadingsof140180mmHg
withareductioninpressureuponrecanalization.Unfortunately,therearenoprovenneuroprotectivestrategiestodate
forischaemicstroke.

Sidebar
Editor'sKeyPoints

Anaestheticmanagementforendovasculartreatmentofacuteischaemicstrokehasbeenshowntoaffect
outcome.

Generalanaesthesiacanresultinworseoutcomescomparedwithlocalanaesthesia,althoughtechniquemust
betailoredtopatientspecificvariables.

Timetoreperfusionandarterialpressurearecriticalinmaximizingsurvivaloftheischaemicpenumbra.

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Copyright2007TheBoardofManagementandTrusteesoftheBritishJournalofAnaesthesia.PublishedbyOxford
UniversityPress.Allrightsreserved.

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