spontaneous是什么意思ntaneous在线翻译读音

ISSN:1524-4628

CopyrightSSN:

StrokeispublishedbytheAmericanHeartAssociation.7272GreenvilleAvenue,Dallas,TX72514

DOI:10.1161/STR.0b013e3181ec611b

publishedonlineJul22,2010;Stroke

CardiovascularNursing

andonbehalfoftheAmericanHeartAssociationStrokeCouncilandCouncilon

Macdonald,,ll,MagdySelim,o

ick,Connolly,Jr,erg,,R.

stern,Hemphill,III,CraigAnderson,KyraBecker,Joseph

Association/AmericanStrokeAssociation

GuidelineforHealthcareProfessionalsFromtheAmericanHeart

GuidelinesfortheManagementofSpontaneousIntracerebralHemorrhage.A

locatedontheWorldWideWebat:

Theonlineversionofthisarticle,alongwithupdatedinformationandservices,is

/reprints

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byonJuly30,nloadedfrom

GuidelinesfortheManagementofSpontaneous

IntracerebralHemorrhage

AGuidelineforHealthcareProfessionalsFromtheAmericanHeart

Association/AmericanStrokeAssociation

TheAmericanAcademyofNeurologyaffirmsthevalueofthisguidelineasaneducational

toolforneurologists.

TheAmericanAssociationofNeurologicalSurgeonsandtheCongressofNeurological

Surgeonshavereviewedthisdocumentandaffirmitseducationalcontent.

stern,MD,FAHA,FAAN,Chair;

HemphillIII,MD,MAS,FAAN,Vice-Chair;CraigAnderson,MBBS,PhD,FRACP;

KyraBecker,MD;ick,MD,FAHA;Connolly,Jr,MD,FAHA;

erg,MD,PhD,FAHA,FAAN;,MD;cdonald,MD,PhD;

,MD,FAHA;ll,RN,PhD,FAHA,FAAN;

MagdySelim,MD,PhD,FAHA;o,MD;onbehalfoftheAmericanHeartAssociation

StrokeCouncilandCouncilonCardiovascularNursing

Pur重阳节的古诗10首小学二年级 pose—Theaimofthisguidelineistopresentcurrentandcomprehensiverecommendationsforthediagnosisand

treatmentofacutespontaneousintracerebralhemorrhage.

Methods—resynthesizedwiththeuseofevidencetables.

WritingcommittericanHeart

AssociationStrokeCouncil’sLease

reviewofthedraftguidelinewasperformedby6expertpeerreviewersandbythemembersoftheStrokeCouncil

Scientifictendedth罪臣之妻斐妩 atthisguideline

befullyupdatedin3years’time.

Results—Evidence-basedguidelinesarepre

focuswassubdividedintodiagnosis,hemostasis,bloodpressuremanagement,inpatientandnursingmanagement,

preventingmedicalcomorbidities,surgicaltreatment,outcomeprediction,rehabilitation,preventionofrecurrence,and

futureconsiderations.

Conclusions—Intracerebralhemorrhageisaseriousmedicalconditionforwhichoutcomecanbeimpactedbyearly,

delinesofferaframeworkforgoal-directedtreatmentofthepatientwithintracerebral

hemorrhage.(Stroke.2010;41:00-00.)

KeyWords:AHAScientificStatementsⅢintracerebralhemorrhageⅢtreatmentⅢdiagnosis

ⅢintracranialpressureⅢhydrocephalusⅢsurgery

TheAmericanHeartAssociationmakeseveryefforttoavoidanyactualorpotentialconflictsofinterestthatmayariseasaresultofanoutside

relationshiporapersonal,professional,ically,allmembersofthewritinggrouparerequired

tocompleteandsubmitaDisclosureQuestionnaireshowingallsuchrelationshipsthatmightbeperceivedasrealorpotentialconflictsofinterest.

ThisstatementwasapprovedbytheAmericanHeartAssociationScienceAdvisoryandCoordinatingCommitteeonMay19,fthe

statementisavailableat/?identifier3003999byselectingeitherthe“topiclist”linkorthe“chronological

list”link(-0044).Topurchaseadditionalreprints,@.

TheAmericanHeartAssociationrequeststhatthisdocumentbecitedasfollows:MorgensternLB,HemphillJC3rd,AndersonC,BeckerK,Broderick

JP,ConnollyESJr,GreenbergSM,HuangJN,MacdonaldRL,MessSR,MitchellPH,SelimM,TamargoRJ;onbehalfoftheAmericanHeart

inesforthemanagementofspontaneousintracerebralhemorrhage:aguideline

forhealthcareprofessionalsfromtheAmericanHeartAssociation/.2010;41:●●●–●●●.

ExpertpeerreonAHAstatementsandguidelinesdevelopment,

visit/?identifier3023366.

Permissions:Multiplecopies,modification,alteration,enhancement,and/ordistributionofthisdocumentarenotpermittedwithouttheexpress

ctionsforobtainingpermissionarelocatedat/?

identifierothe“PermissionRequestForm”appearsontherightsideofthepage.

2010AmericanHeartAssociation,Inc.

Strokeisavailableat:10.1161/STR.0b013e3181ec611b

1

byonJuly30,nloadedfrom

Spontaneous,nontraumaticintracerebralhemorrhage(ICH)

isasignificantcauseofmorbidityandmortalitythroughout

ghmuchhasbeenmadeofthelackofa

specifictargetedtherapy,muchlessiswrittenaboutthesuccess

andgoalsofaggressivemedicalandsurgicalcareforthis

population-basedstudiessuggestthatmost

patientspresentwithsmallICHsthatarereadilysurvivablewith

goodmedicalcare.1Thissuggeststhatexcellentmedicalcare

likelyhasapotent,directimpactonICHmorbidityandmortality

now,,as

discussedlater,theoverallaggressivenessofICHcareisdirectly

relatedtomortalityfromthisdisease.2Oneofthepurposesof

thisguideline,therefore,istoremindcliniciansoftheimpor-

tanceoftheircareindeterminingICHoutcomeandtoprovide

anevidence-basedframeworkforthatcare.

Inordertomakethisreviewbriefandreadilyusefulto

practicingclinicians,thereaderisreferredelsewhereforthe

detailsofICHepidemiology.1,3,4Similarly,therearemany

ongoingclinicalstudiesthroughouttheworldrelatedtothis

derisencouragedtoconsiderreferring

patientstotheseimportantefforts,whichcanbefoundat

/trials/.Wewillnotdiscusson-

goingstudiesbecausewecannotcoverthemall;thefocusof

y,a

recentguidelineonpediatricstrokewaspublished5that

obviatestheneedtorepeattheissuesofpediatricICHhere.

ThelastICHGuidelineswerepublishedin2007,6andthis

,

differencesfromformerrecommendationsarespecifiedinthe

tinggroupmetbyphonetodetermine

ncludedemergencydiagnosis

andassessmentofICHanditscauses;hemostasis,blood

pressure(BP);intracranialpressure(ICP)/fever/glucose/

seizures/hydrocephalus;iron;ICPmonitors/tissueoxygenation;

clotremoval;intraventricularhemorrhage(IVH);withdrawalof

technologicalsupport;preventionofrecurrentICH;nursing

care;rehab/recovery;bcategory

wasledbyanauthorwith1or2additionalauthorsmaking

DLINEsearchesweredoneofall

English-languagearticlesregardingrelevanthumandisease

ofsummariesandrecommendationswere

rence

nswere

ultingdraftwassentto

tswereincor-

poratedbytheViceChairandChair,andtheentirecommittee

stothedocument

weremadebytheChairandViceChairinresponsetopeer

review,andthedocumentwasagainsenttotheentirewriting

endations

followtheAmericanHeartAssociationStrokeCouncil’s

methodsofclassifyingthelevelofcertaintyofthetreatment

effectandtheclassofevidence(Tables1and2).AllClassI

recommendationsarelistedinTable3.

EmergencyDiagnosisandAssessmentofICH

andItsCauses

iagnosisandattentive

managementofpatientswithICHiscrucialbecauseearly

deteriorationiscommoninthefirstfewhoursafterICH

an20%ofpatientswillexperienceadecrease

intheGlasgowComaScale(GCS)scoreof2points

betweentheprehospitalemergencymedicalservicesassess-

mentandtheinitialevaluationintheemergencydepartment

(ED).7Amongthosepatientswithprehospitalneurological

decline,theGCSscoredecreasesbyanaverageof6points

andthemortalityrateis75%.Further,withinthefirsthour

ofpresentationtoahospital,15%ofpatientsdemonstratea

decreaseintheGCSscoreof2points.8Theriskforearly

neurologicaldeteriorationandthehighrateofpoorlong-term

outcomesunderscorestheneedforaggressiveearly

management.

PrehospitalManagement

Theprimaryobjectiveintheprehospitalsettingistoprovide

ventilatoryandcardiovascularsupportandtotransportthepatientto

theclosestfacilitypreparedtocareforpatientswithacutestroke

(seeEDManagementsectionthatfollows).Secondaryprioritiesfor

emergencymedicalservicesprovidersincludeobtainingafocused

historyregardingthetimingofsymptomonset(orthetimethe

patientwaslastnormal)andinformationaboutmedicalhistory,

medication,y,emergencymedicalservices

providersshouldprovideadvancenoticetotheEDoftheimpending

arrivalofapotentialstrokepatientsothatcriticalpathwayscanbe

enoticeby

emergencymedicalserviceshasbeendemonstratedtosignificantly

shortentimetocomputedtomography(CT)scanningintheED.9

EDManagement

ItisoftheutmostimportancethateveryEDbepreparedto

treatpatientswithICHorhaveaplanforrapidtransfertoa

cialresourcesnecessarytoman-

agepatientswithICHincludeneurology,neuroradiology,

neurosurgery,andcriticalcarefacilitiesincludingadequately

D,appropriateconsul-

tativeservicesshouldbecontactedasquicklyaspossibleand

theclinicalevaluationshouldbeperformedefficiently,with

4describes

theintegralcomponentsofthehistory,physicalexamination,

anddiagnosticstudiesthatshouldbeobtainedintheED.

ForpatientswithICH,emergencymanagementmayin-

cludeneurosurgicalinterventionsforhematomaevacuation,

externalventriculardrainageorinvasivemonitoringand

treatmentofICP,BPmanagement,intubation,andreversalof

ghmanycentershavecriticalpathways

developedforthetreatmentofacuteischemicstroke,few

haveprotocolsforthemanagementofICH.18Suchpathways

mayallowformoreefficient,standardized,andintegrated

managementofcriticallyillpatientswithICH.

Neuroimaging

Theabruptonsetoffocalneurologicalsymptomsispresumedto

r,itis

impossibletoknowwhethersymptomsareduetoischemiaor

ng,

systolicBP220mmHg,severeheadache,comaordecreased

levelofconsciousness,andprogressionoverminutesorhoursall

suggestICH,althoughnoneofthesefindingsarespecific;

2StrokeSeptember2010

byonJuly30,nloadedfrom

neuroimagingisthusmandatory.19CTandmagneticresonance

imaging(MRI)

verysensitiveforidentifyingacutehemorrhageandisconsid-

eredthegoldstandard;gradi《春》原声朗读 entechoandT2*susceptibility-

weightedMRIareassensitiveasCTfordetectionofacuteblood

andaremoresensitiveforidentificationofpriorhemorrhage.20,21

Time,cost,proximitytotheED,patienttolerance,clinicalstatus,

andMRIavailabilitymay,however,precludeemergentMRIin

asizeableproportionofcases.22

ThehighrateofearlyneurologicaldeteriorationafterICHis

inpartrelatedtoactivebleedingthatmayproceedforhoursafter

liertimefromsymptomonsettofirst

neuroimage,themorelikelysubsequentneuroimageswill

demonstratehematomaexpansion.15,23,24Amongpatients

undergoingheadCTwithin3hoursofICHonset,28%to

38%havehematomaexpansionofgreaterthanonethirdon

follow-upCT.8,25Hematomaexpansionispredictiveof

clinicaldeteriorationandincreasedmorbidityandmortali-

ty.8,10,15,25Assuch,identifyingpatientsatriskforhematoma

ographyand

contrast-enhancedCTmayidentifypatientsathighriskof

ICHexpansionbasedonthepresenceofcontrastextravasa-

tionwithinthehematoma.26–30MRI/angiogram/venogram

andCTangiogram/venogramarereasonablysensitiveat

identifyingsecondarycausesofhemorrhage,includingarte-

riovenousmalformations,tumors,moyamoya,andcerebral

veinthrombosis.31–33Acatheterangiogrammaybeconsid-

eredifclinicalsuspicionishighornoninvasivestudiesare

alsuspicion

ofasecondarycauseofICHmayincludeaprodromeof

headache,neurological,-

logicalsuspicionsofsecondarycausesofICHshouldbe

ngClassificationofRecommendationsandLevelofEvidence

*Dataavailablefromclinicaltrialsorregistriesabouttheusefulness/efficacyindifferentsubpopulations,suchassex,age,historyofdiabetes,historyofprior

myocardialinfarction,historyofheartfailure,mendationwithLevelofEvidenceBorCdoesnotimplythattherecommendationisweak.

Manyimportantclinicalquestoughrandomizedtrialsarenotavailable,theremay

beaveryclearclinicalconsensusthataparticulartestortherapyisusefuloreffective.

†In2003,theACCF/AHATaskForceonPracticeGuidelinesdeline

recommendationshavebeenwritteninfullsentencesthatexpressacompletethought,suchthatarecommendation,evenifseparatedandpresentedapartfrom

therestofthedocument(includingheadingsabovesetsofrecommendations),pedthatthiswill

increasereaders’comprehensionoftheguidelinesandwillallowqueriesattheindividualrecommendationlevel.

MorgensternetalIntracerebralHemorrhageGuideline3

byonJuly30,nloadedfrom

invokedbythepresenceofsubarachnoidhemorrhage,un-

usual(noncircular)hematomashape,thepresenceofedema

outofproportiontotheearlytimeanICHisfirstimaged,an

unusuallocationforhemorrhage,andthepresenceofother

CT

venogramshouldbeperformedifhemorrhagelocation,rela-

tiveedemavolume,orabnormalsignalinthecerebralsinuses

onroutineneuroimagingsuggestcerebralveinthrombosis.

Insummary,ICHisamedicalemergency,characterizedbyhigh

morbidityandmortality,whichshouldbepromptlydiagnosedand

maexpansionandearlydeteriora-

tionarecommonwithinthefirstfewhoursafteronset.

Recommendations

euroimagingwithCTorMRIisrecommended

todistinguishischemicstrokefromICH(ClassI;Level

ofEvidence:A).(Unchangedfromthepreviousguideline)

ographyandcontrast-enhancedCTmaybe

consideredtohelpidentifypatientsatriskforhema-

tomaexpansion(ClassIIb;LevelofEvidence:B),and

CTangiography,CTvenography,contrast-enhanced

CT,contrast-enhancedMRI,magneticresonancean-

giography,andmagneticresonancevenographycanbe

usefultoevaluateforunderlyingstructurallesions,

includingvascularmalformationsandtumorswhen

thereisclinicalorradiologicalsuspicion(ClassIIa;

LevelofEvidence:B).(Newrecommendation)

MedicalTreatmentforICH

Hemostasis/Antiplatelets/DeepVein

ThrombosisProphylaxis

UnderlyinghemostaticabnormalitiescancontributetoICH.

Patientsatriskincludethoseonoralanticoagulants(OACs),

thosewithacquiredorcongenitalcoagulationfactordeficien-

cies,andthosewithqualitativeorquantitativeplateletabnormal-

tsundergoingtreatmentwithOACsconstitute12%

to14%ofpatientswithICH,34,35andwithincreaseduseof

warfarin,theproportionappearstobeincreasing.36Recognition

ofanunderlyingcoagulopathythusprovidesanopportunityto

ientswitha

coagulationfactordeficiencyandthrombocytopenia,replace-

mentoftheappropriatefactororplateletsisindicated.

ForpatientsbeingtreatedwithOACswhohavelife-threatening

bleeding,suchasintracranialhemorrhage,thegeneralrecommen-

dationistocorrecttheinternationalnormalizedratio(INR)as

rapidlyaspossible.37,38InfusionsofvitaminKandfresh-frozen

plasma(FFP)havehistoricallybeenrecommended,butmore

recently,prothrombincomplexconcentrates(PCCs)andrecom-

binantfactorVIIa(rFVIIa)haveemergedaspotentialtherapies.

VitaminKremainsanadjuncttomorerapidlyactinginitial

therapyforlife-threateningOAC-associatedhemorrhagebe-

causeevenwhengivenintravenously,itrequireshourstocorrect

theINR.39–41TheefficacyofFFPislimitedbyriskofallergic

andinfectioustransfusionreactions,processingtime,andthe

hoodofINRcorrectionat

24hourswaslinkedtotimetoFFPadministrationin1study,

although17%ofpatientsstilldidnothaveanINR1.4atthis

time,suggestingthatFFPadministeredinthismannermaybe

insufficientforrapidcorrectionofcoagulopathy.42

PCCsareplasma-derivedfactorconcentratesprimarily

ePCCsalsocontain

factorsII,VII,andXinadditiontoIX,theyareincreasingly

vetheadvan-

tagesofrapidreconstitutionandadministration,havinghigh

concentrationsofcoagulationfactorsinsmallvolumes,and

different

PCCpreparationsdifferinrelativeamountsoffactors(with

VIIthemostlikelytobelow),severalstudieshaveshown

thatPCCscanrapidlynormalizeINR(withinminutes)in

patientstakingOACs(reviewedin43–45).Nonrandomized

retrospectivereviewsandasmallcase-controlstudyhave

shownmorerapidcorrectionofINRwithvitaminKandPCC

thanvitaminKandFFP,buthavenotrevealedadifferencein

clinicaloutcome.46–48Onerandomizedtrialcomparedtheuse

ofaPCC(Konyne)tosupplementFFPversusFFPalonein

patientswithOAC-relatedICH,findingthatthosewho

receivedPCChadsignificantlyshortertimetoINRcorrection

ghtherewasno

differenceinoutcome,thosewhoreceivedFFPalsohadmore

adverseevents,primarilyattributabletofluidoverload.49

AlthoughPCCsmaytheoreticallyincreasetheriskofthrom-

boticcomplications,thisriskappearsrelativelylow.43De-

tionofClassesandLevelsofEvidenceUsedin

AmericanHeartAssociationStrokeCouncilRecommendations

ClassIConditionsforwhichthereisevidencefor

and/orgeneralagreementthatthe

procedureortreatmentisusefuland

effective

ClassIIConditionsforwhichthereisconflicting

evidenceand/oradivergenceof

opinionabouttheusefulness/efficacy

ofaprocedureortreatment

ClassIIaTheweightofevidenceoropinionisin

favoroftheprocedureortreatment

ClassIIbUsefulness/efficacyislesswell

establishedbyevidenceoropinion

ClassIIIConditionsforwhichthereisevidence

and/orgeneralagreementthatthe

procedureortreatmentisnot

useful/effectiveandinsomecases

maybeharmful

Therapeuticrecommendations

LevelofEvidenceADataderivedfrommultiplerandomized

clinicaltrialsormeta-analyses

LevelofEvidenceBDataderivedfromasinglerandomized

trialornonrandomizedstudies

LevelofEvidenceCConsensusopinionofexperts,case

studies,orstandardofcare

Diagnosticrecommendations

LevelofEvidenceADataderivedfrommultipleprospective

cohortstudiesusingareference

standardappliedbyamasked

evaluator

LevelofEvidenceBDataderivedfromasinglegradeAstudy,

oroneormorecase-controlstudies,or

studiesusingareferencestandard

appliedbyanunmaskedevaluator

LevelofEvidenceCConsensusopinionofexperts

4StrokeSeptember2010

byonJuly30,nloadedfrom

spitethelackoflarge,well-controlled,randomizedtrials,

PCCsarebeingincreasinglyrecommendedasanoptionin

guidelinespromulgatedforwarfarinreversalinthesetting

ofOAC-associatedlife-threateningorintracranialhemor-

rhages.37,38,50–52Table5providesalistofseveralproducts

forfactorreplacementinwarfarinreversalthatarecommer-

ciallyavailableintheUnitedStatesatthepresenttime.

rFVIIa,licensedtotreathemophiliapatientswithhightiter

inhibitorsorcongenitalfactorVIIdeficiency,hasgarnered

attentionasapotentialtreatmentforspontaneousandOAC-

ghrFVIIacanrapidlynormalizeINR

inthesettingofOAC-associatedICH,53–57itdoesnot

replenishallofthevitaminK–dependentfactorsandthere-

foremaynotrestorethrombingenerationaswellasPCCs.58

Inlightofthelimiteddata,arecentAmericanSocietyof

Hematologyevidence-basedreviewrecommendedagainst

routineuseofrFVIIaforwarfarinreversal.59

rFVIIahasalsobeentestedinpatientswithnon-OACICH.

Aphase2randomizedtrialshowedthattreatmentwith

rFVIIawithin4hoursafterICHonsetlimitedhematoma

growthandimprovedclinicaloutcomesrelativetoplacebo,

thoughwithincreasedfrequencyofthromboembolicevents

(7%versus2%).60Asubsequentphase3studycomparing

placebowith20␮g/kgand80␮g/kgofrFVIIafailedtoshow

differencesinclinicaloutcome,despiteconfirmingtheability

ofbothdosestodiminishhematomaenlargement.61Although

overallseriousthromboembolicadverseeventsweresimilar,

thehigherrFVIIa(80␮g/kg)grouphadsignificantlymore

horsnoted

imbalancesinthetreatmentgroups,particularlythegreater

numberofpatientswithIVHinthehigher-doserFVIIa

group.60ItremainstobedeterminedwhetherrFVIIawill

benefitaparticularsubsetofpatientswithICH,butcurrently

itsbenefitsinICHpatients,whetherornottheyareunder-

goingtreatmentwithOACs,remainunproven.

Studiesoftheeffectofpriorantiplateletagentuseor

plateletdysfunctiononICHhematomagrowthandoutcome

edantiplateletagentuse

wasnotassociatedwithhematomaexpansionorclinical

outcomeintheplacebogroupofanICHneuroprotective

study.62However,othershavesuggestedthatplateletdys-

functionasmeasuredbyplateletfunctionassaysmaybe

associatedwithhematomaexpansionandclinicalout-

come.63,64Theutilityandsafetyofplatelettransfusionor

Recommendations

RecommendationsClass/LevelofEvidence

EmergencydiagnosisandassessmentofICHand

itscauses

RapidneuroimagingwithCTorMRIisrecommendedtodistinguish

ischemicstrokefromICH.(Unchangedfromtheprevious

guideline)

ClassI,LevelA

MedicaltreatmentforICHPatientswithaseverecoagulationfactordeficiencyorsevere

thrombocytopeniashouldreceiveappropriatefactorreplacement

therapyorplatelets,respectively.(Newrecommendation)

ClassI,LevelC

Hemostasis/antiplatelets/DVTprophylaxisPatientswithICHwhoseINRiselevatedduetoOACshouldhave

theirwarfarinwithheld,receivetherapytoreplacevitamin

K–dependentfactorsandcorrecttheINR,andreceive

intravenousvitaminK.(Revisedfromthepreviousguideline)

ClassI,LevelC

PatientswithICHshouldhaveintermittentpneumaticcompression

forpreventionofvenousthromboembolisminadditiontoelastic

stockings.(Unchangedfromthepreviousguideline)

ClassI,LevelB

Inpatientmanagementandpreventionof

secondarybraininjury

GeneralmonitoringInitialmonitoringandmanagementofICHpatientsshouldtake

placeinanintensivecareunit,preferablyonewithphysician

andnursingneuroscienceintensivecareexpertise.(Unchanged

fromthepreviousguideline)

ClassI,LevelB

ManagementofglucoseGlucoseshouldbemonitoredandnormoglycemiaisrecommendedClassI,LevelC

SeizuresandantiepilepticdrugsPatientswithclinicalseizuresshouldbetreatedwithantiepileptic

drugs.(Revisedfrompreviousguideline)

Patientswithachangeinmentalstatuswhoarefoundtohave

electrographicseizuresonEEGshouldbetreatedwith

antiepilepticdrugs

ClassI,LevelA

ClassI,LevelC

Procedures/surgery—clotremovalPatientswithcerebellarhemorrhagewhoaredeteriorating

neurologicallyorwhohavebrainstemcompressionand/or

hydrocephalusfromventricularobstructionshouldundergo

surgicalremovalofthehemorrhageassoonaspossible.

(Revisedfromthepreviousguideline)

ClassI,LevelB

PreventionofrecurrentICHAftertheacuteICH,absentmedicalcontraindications,BPshould

bewellcontrolled,particularlyforpatientswithICHlocation

typicalofhypertensivevasculopathy.(Newrecommendation)

ClassI,LevelA

CTindicatescomputedtomography;MRI,magneticresonanceimaging;DVT,deepveinthrombosis;INR,internationalnormalizedratio;OAC,oralanticoagulants;

andEEG,electroencephalogram.

MorgensternetalIntracerebralHemorrhageGuideline5

byonJuly30,nloadedfrom

otheragentsinpatientswithanormalplateletcount,butuse

ofantiplateletagentsorplateletdysfunction,isnotknown.

PatientswithICHhaveahighriskofthromboembolic

disease.65WomenandAfricanAmericansappeartobeatgreater

risk.65–67Intermittentpneumaticcompressioncombinedwith

elasticstockingshasbeenshownbyarandomizedtrialtobe

superiortoelasticstockingsaloneinreducingoccurrenceof

asymptomaticdeepveinthrombosisafterICH(4.7%versus

15.9%).68Graduatedcompressionstockingsaloneareineffec-

tiveinpreventingdeepveinthrombosis.69Lessclear,however,is

smallrandomizedstudiesfoundnodifferenceindeepveinthrom-

bosisincidence,andnoincreaseinbleeding,inpatientsgivenlow-

dosesubcutaneousheparininitiatedatday4oratday10after

ICH.70,71Anuncontrolledstudyoftreatmentinitiatedonday2

foundareductioninthromboembolicdiseasewithoutincreased

rebleeding.70

Recommendations

tswithaseverecoagulationfactordeficiencyor

severethrombocytopeniashouldreceiveappropriatefac-

torreplacementtherapyorplatelets,respectively(ClassI;

LevelofEvidence:C).(Newrecommendation)

tswithICHwhoseINRiselevatedduetoOACs

shouldhavetheirwarfarinwithheld,receivetherapyto

replacevitaminK–dependentfactorsandcorrectthe

INR,andreceiveintravenousvitaminK(ClassI;Level

ofEvidence:C).PCCshavenotshownimproved

outcomecomparedwithFFPbutmayhavefewer

complicationscomparedwithFFPandarereasonable

toconsiderasanalternativetoFFP(ClassIIa;Levelof

Evidence:B).rFVIIadoesnotreplaceallclotting

factors,andalthoughtheINRmaybelowered,clotting

maynotberestoredinvivo;therefore,rFVIIaisnot

routinelyrecommendedasasoleagentforOACre-

versalinICH(ClassIII;LevelofEvidence:C).(Revised

fromthepreviousguideline).

ghrFVIIacanlimittheextentofhematoma

expansioninnoncoagulopathicICHpatients,there

alComponentsoftheHistory,Physical

Examination,andWork-UpofthePatientWithICHintheED

Comments

History

Timeofsymptomonset(or

timethepatientwaslast

normal)

Initialsymptomsand

progressionofsymptoms

VascularriskfactorsHypertension,diabetes,

hypercholesterolemia,andsmoking

MedicationsAnticoagulants,antiplateletagents,

decongestants,antihypertensive

medications,stimulants(includingdiet

pills),sympathomimetics

RecenttraumaorsurgeryCarotidendarterectomyorcarotidstenting

inparticular,asICHmayberelatedto

hyperperfusionaftersuchprocedures

DementiaAssociatedwithamyloidangiopathy

AlcoholorillicitdruguseCocaineandothersympathomimetic

drugsareassociatedwithICH,

stimulants

Seizures

LiverdiseaseMaybeassociatedwithcoagulopathy

Cancerandhematologic

disorders

Maybeassociatedwithcoagulopathy

Physicalexamination

VitalsignsFeverisassociatedwithearlyneurologic

deterioration10

Higherinitialbloodpressureisassociated

withearlyneurologicdeteriorationand

increasedmortality11

Ageneralphysical

examinationfocusingon

thehead,heart,lungs,

abdomen,andextremities

Athoroughbuttime-urgent

neurologicexamination

Astructuredexaminationsuchasthe

NationalInstitutesofHealthStroke

Scalecanbecompletedinminutesand

providesaquantificationthatallows

easycommunicationoftheseverityof

scoreissimilarlywellknownand

easilycomputed,andtheinitialGCS

scoreisastrongpredictoroflong-term

outcome.12,13Thesecanbe

supplementedasneeded

Serumandurinetests

Completebloodcount,

electrolytes,bloodurea

nitrogenandcreatinine,

andglucose

Highercreatinineisassociatedwith

serum

glucoseisassociatedwithhematoma

expansionandworseoutcome

(althoughtherearenodatatosuggest

thatnormalizationimproves

outcome)11,14

ProthrombintimeorINR

andanactivatedpartial

thromboplastintime

Warfarin-relatedhemorrhagesare

associatedwithanincreased

hematomavolume,greaterriskof

expansion,andincreasedmorbidityand

mortality15–17

(Continued)

ued

Comments

Toxicologyscreeninyoung

ormiddle-agedpatientsto

detectcocaineandother

sympathomimeticdrugsof

abuse

Cocaineandothersympathomimetic

drugsareassociatedwithICH

Urinalysisandurineculture

andapregnancytestina

womanofchildbearingage

Otherroutinetests

ECGToassessforactivecoronaryischemiaor

priorcardiacinjurythatmayindicate

poorcardiacfunctionandtoobtaina

baselineintheeventof

cardiopulmonaryissuesduring

hospitalization

Chestradiograph

NeuroimagingAsdescribedinthetext

GCSindicatesGlasgowComaScale;ECG,electrocardiogram.

6StrokeSeptember2010

byonJuly30,nloadedfrom

isanincreaseinthromboembolicriskwithrFVIIa

andnoclearclinicalbenefitinunselectedpatients.

ThusrFVIIaisnotrecommendedinunselected

patients.(ClassIII;LevelofEvidence:A).(New

recommendation)Furtherresearchtodetermine

whetheranyselectedgroupofpatientsmaybenefit

fromthistherapyisneededbeforeanyrecommenda-

tionforitsusecanbemade.

fulnessofplatelettransfusionsinICHpa-

tientswithahistoryofantiplateletuseisunclearand

isconsideredinvestigational(ClassIIb;Levelof

Evidence:B).(Newrecommendation)

tsCommerciallyAvailableintheUnitedStatesforCoagulationFactorReplacement

ProductFactor(s)

Dose(ConsultationWithaHematologist

IsRecommendedforSpecificDosing)Uses

Fresh-frozenplasmaI(fibrinogen),II,V,VII,IX,X,XI,

XIII,antithrombin

10–15mL/kgwithidealrecovery

wouldraisefactorlevels15%–20%

OACreversal

Consumptivecoagulopathy

Hepaticdysfunction

CryoprecipitateI,VIII,XIII,vWF1–2U/10kgHypo/a-fibrinogenemia

Lackoffactor-specificproductsfor

factorVIIIdeficiencyorvWD

FactorXIIIdeficiency

Prothrombincomplex

concentrates

II,IX,X(smallamountsofVII)AssayedinfactorIXactivityFactorIXdeficiency(hemophiliaB)

BebulinVH(Baxter),Profilnine

SD(Grifols)

BothBebulinandProfilnineare

3-factorPCCsthathave

approximately1/10ththefactorVII

activityrelativetofactorIXactivity.

TheamountsoffactorIIandX

relativetoIXisvariable,butfor

BebulinXIIIXandforProfilnine

IIXIX

DosingforfactorIXdeficiency—

1U/kgraisesactivityby1%

DosingforOACreversalhasnotbeen

wellestablished

OACreversal(notFDA-approved)

NovoSevenRT(NovoNordisk)RecombinantactivatedVIIHigherriskofthromboembolic

complicationswithhigherdoses

ForhemophiliaAorBpatientswith

inhibitors,90␮g/kgevery2h

ForfactorVII–deficientpatients,15–30

␮g/kgevery4–6h

FactorVIIIorIXdeficiencywithinhibitors

tofactorVIIIorIX

CongenitalfactorVIIdeficiency

NotrecommendedforspontaneousICH

orOACreversal

FactorVIIIconcentrates

Plasma-derived

Alphanate(Grifols)*†

Humate-P(CSL-Behring)*†

Koate-DVI(Bayer)*

Wilate(Octapharma)*†

Immunoaffinitypurified

Hemofil-M(Baxter)

Monarc-M(Baxter)

Monoclate-P(CSL-Behring)

Recombinant

Advate(Baxter)

HelixateFS(CSL-Behring)

KogenateFS(Bayer)

Recombinate(Baxter)

Xyntha(Wyeth)

VIIIEachfactorVIIIunit/kgraisesthe

serumfactorVIIIlevelby2%

(typically,a50-U/kgdoseisusedto

raisethefactorVIIIlevelto100%)

FactorVIIIdeficiency(hemophiliaA)

WilateisnotindicatedforhemophiliaA.

FactorIXconcentrates

Plasma-derived

AlphaNineSD(Grifols)

Mononine(Baxter)

Recombinant

BeneFix(Wyeth)

IXEachFactorIXunit/kgraisesthe

serumlevelby1%(typically,a

100-U/kgdoseisusedtoraisethe

levelto100%)

FactorIXdeficiency(hemophiliaB)

OneunitofBeneFixraisestheserum

levelby0.83%,so120U/kgraises

theactivityto100%.

vWDindicatesvonWillebranddisease;FDA,USFoodandDrugAdministration;andPCCs,prothrombincomplexconcentrates.

*AlsocontainsvonWillebrandfactor.

†IndicatedforvonWillebranddisease(dosebyristocetincofactorunits;ratiooffVIIItoristocetincofactorunitvariesbyproduct).

MorgensternetalIntracerebralHemorrhageGuideline7

byonJuly30,nloadedfrom

tswithICHshouldhaveintermittentpneu-

maticcompressionforpreventionofvenousthrom-

boembolisminadditiontoelasticstockings(ClassI;

LevelofEvidence:B).(Unchangedfromtheprevious

guideline)

ocumentationofcessationofbleeding,low-

dosesubcutaneouslow-molecular-weightheparinor

unfractionatedheparinmaybeconsideredforpre-

ventionofvenousthromboembolisminpatientswith

lackofmobilityafter1to4daysfromonset(Class

IIb;LevelofEvidence:B).(Revisedfromtheprevious

guideline)

BloodPressure

BloodPressureandOutcomeinICH

Bloodpressure(BP)isfrequently,andoftenmarkedly,

elevatedinpatientswithacuteICH;theseelevationsinBP

aregreaterthanthatseeninpatientswithischemicstroke.72,73

AlthoughBPgenerallyfallsspontaneouslywithinseveral

daysafterICH,highBPpersistsinasubstantialproportionof

patients.72,73Potentialpathophysiologicmechanismsinclude

stressactivationoftheneuroendocrinesystem(sympathetic

nervoussystem,renin-angiotensinaxis,orglucocorticoidsys-

tem)ensiontheoreti-

callycouldcontributetohydrostaticexpansionofthehematoma,

peri-hematomaedema,andrebleeding,allofwhichmaycon-

tributetoadverseoutcomesinICH,althoughaclearassociation

betweenhypertensionwithinthefirstfewhoursafterICHand

theriskofhematomaexpansion(oreventualhematomavolume)

hasnotbeenclearlydemonstrated.25,74

Asystematicreview75andarecentlargemultisitestudyin

China73showthatameasurementofsystolicBPabove140to

150mmHgwithin12hoursofICHisassociatedwithmore

thandoubletheriskofsubsequentdeathordependency.

Comparedwithischemicstroke,whereconsistentU-or

J-shapedassociationsbetweenBPlevelsandpooroutcome

havebeenshown,76only1studyofICHhasshownapoor

outcomeatverylowsystolicBPlevels(140mmHg).77For

bothischemicstrokeandpossiblyICH,alikelyexplanation

forsuchassociationisreversecausation,wherebyverylow

BPlevelsoccurdisproportionatelyinmoreseverecases,so

thatalthoughlowBPlevelsmaybeassociatedwithahigh

casefatality,itmaynotinitselfbecausal.

EffectsofBP-LoweringTreatments

Thestrongobservationaldatacitedpreviouslyandsophisti-

catedneuroimagingstudiesthatfailtoidentifyanischemic

penumbrainICH78formedthebasisfortheINTensiveBlood

PressureReductioninAcuteCerebralHemorrhageTrial

(INTERACT)pilotstudy,publishedin2008.79INTERACT

wasanopen-label,randomized,controlledtrialundertakenin

404mainlyChinesepatientswhocouldbeassessed,treated,

andmonitoredwithin6hoursoftheonsetofICH;203were

randomizedtoatreatmentwithlocallyavailableintravenous

BP-loweringagentstotargetalowsystolicBPgoalof

140mmHgwithin1hourandmaintainedforatleastthenext

24hours,and201wererandomizedtoamoremodestsystolic

BPtargetof180mmHg,asrecommendedinanearlierAHA

guideline.80Thestudyshowedatrendtowardlowerrelative

andabsolutegrowthinhematomavolumesfrombaselineto

24hoursintheintensivetreatmentgroupcomparedwiththe

tion,therewasnoexcessofneurolog-

icaldeteriorationorotheradverseeventsrelatedtointensive

BPlowering,norwerethereanydifferencesacrossseveral

measuresofclinicaloutcome,includingdisabilityandquality

oflifebetweengroups,althoughthetrialwasnotpoweredto

dyprovidesanimportantproof

ofconceptforearlyBPloweringinpatientswithICH,butthe

-

otherstudy,theAntihypertensiveTreatmentinAcuteCere-

bralHemorrhage(ATACH)trial,81alsoconfirmsthefeasi-

bilityandsafetyofearlyrapidBPloweringinICH.82This

studyuseda4-tier,doseescalationofintravenous

nicardipine-basedBPloweringin80patientswithICH.

Thus,advanceshavebeenmadeinourknowledgeofthe

mechanismsofICHandthesafetyofearlyBPloweringsince

thepublicationofthe2007AmericanHeartAssociationICH

CTandATACHnowrepresentthebest

availableevidencetohelpguidedecisionsaboutBPlowering

ghthesestudieshaveshownthatintensiveBP

loweringisclinicallyfeasibleandpotentiallysafe,theBP

pressuretarget,durationoftherapy,andwhethersuchtreat-

mentimprovesclinicaloutcomesremainunclear.

Recommendations

ngoingclinicaltrialsofBPinterventionfor

ICHarecompleted,physiciansmustmanageBPon

thebasisofthepresentincompleteefficacyevidence.

CurrentsuggestedrecommendationsfortargetBP

invarioussituationsarelistedinTable6andmaybe

considered(ClassIIb;LevelofEvidence:C).(Un-

changedfromthepreviousguideline)

entspresentingwithasystolicBPof150to

220mmHg,acuteloweringofsystolicBPto

140mmHgisprobablysafe(ClassIIa;Levelof

Evidence:B).(Newrecommendation)

InpatientManagementandPreventionof

SecondaryBrainInjury

GeneralMonitoring

PatientswithICHarefrequentlymedicallyandneurologi-

callyunstable,particularlywithinthefirstfewdaysafter

tedRecommendedGuidelinesforTreating

ElevatedBPinSpontaneousICH

s200mmHgorMAPis150mmHg,thenconsider

aggressivereductionofBPwithcontinuousintravenousinfusion,with

frequentBPmonitoringevery5min.

s180mmHgorMAPis130mmHgandthereisthe

possibilityofelevatedICP,thenconsidermonitoringICPandreducingBP

usingintermittentorcontinuousintravenousmedicationswhile

maintainingacerebralperfusionpressure60mmHg.

s180mmHgorMAPis130mmHgandthereisnot

evidenceofelevatedICP,thenconsideramodestreductionofBP(eg,

MAPof110mmHgortargetBPof160/90mmHg)usingintermittentor

continuousintravenousmedicationstocontrolBPandclinically

reexaminethepatientevery15min.

icatessystolicblood

pressure盎然是什么意思 ;MAP,meanarterialpressure.

8StrokeSeptember2010

byonJuly30,nloadedfrom

ICHpatientsinadedicatedneuroscience

intensivecareunitisassociatedwithalowermortalityrate.83

Frequentvitalsignchecks,neurologicalassessments,and

continuouscardiopulmonarymonitoringincludingacycled

automatedBPcuff,electrocardiographictelemetry,andO

2

uousintra-arterial

BPmonitoringshouldbeconsideredinpatientsreceiving

intravenousvasoactivemedications.

NursingCare

ThespecificnursingcarerequiredforICHpatientsin

intensivecareunitsmayinclude(1)surveillanceandmoni-

toringofICP,cerebralperfusionpressureandhemodynamic

function;(2)titrationandimplementationofprotocolsfor

managementofICP,BP,mechanicalventilation,fever,and

serumglucose;and(3)preventionofcomplicationsofim-

mobilitythroughpositioning,airwaymaintenance,andmo-

sensusdoc-

umentfromtheBrainAttackCoalitiononcomprehensive

strokecentersdelineatestheseasspecificareasofmonitoring

andcomplicationpreventioninwhichnursesshouldbe

cumentalsorecommendsthatnursesbe

trainedindetailedassessmentofneurologicalfunctionin-

cludingstandardizedscalessuchastheNationalInstitutesof

HealthStrokeScale,GCS,andtheGlasgowOutcomeScale.

InaCanadianstudyof49hospitalsthatincludedICH

patients,ahigherproportionofregisterednursesandbetter

nurse–physiciancommunicationswereindependentlyassoci-

atedwithlower30-daymortalityevenafteradjustingfor

diseaseseverity,comorbidities,andhospitalcharacteristics.84

Recommendation

lmonitoringandmanagementofICHpatients

shouldtakeplaceinanintensivecareunitwith

physicianandnursingneuroscienceintensivecare

expertise(ClassI;LevelofEvidence:B).(Unchanged

fromthepreviousguideline)

ManagementofGlucose

Highbloodglucoseonadmissionpredictsanincreasedriskof

mortalityandpooroutcomeinpatientswithandwithoutdiabetes

andICH.85–87Arandomizedtrialshowingimprovedoutcomes

withtightglucosecontrol(range80to110mg/dL)usinginsulin

infusionsinmainlysurgicalcriticalcarepatients88hasincreased

r,morerecentstudieshave

demonstratedincreasedincidenceofsystemicandcerebral

hypoglycemiceventsandpossiblyevenincreasedriskofmor-

talityinpatientstreatedwiththisregimen.89–92Atpresentthe

optimalmanagementofhyperglycemiainICHandthetarget

ycemiashouldbeavoided.

TemperatureManagement

Feverworsensoutcomeinexperimentalmodelsofbraininju-

ry.93,94Theincidenceoffeverafterbasalganglionicandlobar

ICHishigh,ents

survivingthefirst72hoursafterhospitaladmission,theduration

offeverisrelatedtooutcomeandappearstobeanindependent

prognosticfactorinthesepatients.95Thesedataprovidea

rationaleforaggressivetreatmenttomaintainnormothermiain

patientswithICH;however,therearenodatalinkingfever

rly,therapeuticcoolinghasnot

beensystematicallyinvestigatedinICHpatients.

SeizuresandAntiepilepticDrugs

Theincidenceofclinicalseizureswithinthefirst2weeksafter

ICHhasbeenreportedtorangefrom2.7%to17%,withthe

majorityoccurringatornearonset.96–100Studiesofcontinuous

electroencephalography(EEG)havereportedelectrographicsei-

zuresin28%to31%ofselectcohortsofICHpatients,despite

mosthavingreceivedprophylacticanticonvulsants.101,102Ina

large,single-centerstudy,prophylacticantiepilepticdrugsdid

significantlyreducethenumberofclinicalseizuresafterlobar

ICH.98However,inprospectiveandpopulation-based

studies,clinicalseizureshavenotbeenassociatedwith

worsenedneurologicaloutcomeormortality.97,103,104The

clinicalimpactofsubclinicalseizuresdetectedonEEGisalso

tanalysisfromtheplaceboarmofanICH

neuroprotectantstudyfoundthatpatientswhoreceivedanti-

epilepticdrugs(primarilyphenytoin)withoutadocumented

seizureweresignificantlymorelikelytobedeadordisabled

at90days,afteradjustingforotherestablishedpredictorsof

ICHoutcome.105Anotherrecentsingle-centerobservational

studyhadsimilarfindings,specificallyforphenytoin.106Thus

onlyclinicalseizuresorelectrographicseizuresinpatients

withachangeinmentalstatusshouldbetreatedwith

uousEEGmonitoringshouldbe

consideredinICHpatientswithdepressedmentalstatusout

lityof

prophylacticanticonvulsantmedicationremainsuncertain.

Recommendations

ManagementofGlucose

eshouldbemonitoredandnormoglycemiais

recommended(ClassI:LevelofEvidence:C).(New

recommendation)

SeizuresandAntiepilepticDrugs

alseizuresshouldbetreatedwithantiepileptic

drugs(ClassI;LevelofEvidence:A).(Revisedfrom

thepreviousguideline)ContinuousEEGmonitoring

isprobablyindicatedinICHpatientswithdepressed

mentalstatusoutofproportiontothedegreeof

braininjury(ClassIIa;LevelofEvidence:B).Pa-

tientswithachangeinmentalstatuswhoarefound

tohaveelectrographicseizuresonEEGshouldbe

treatedwithantiepilepticdrugs(ClassI;Levelof

Evidence:C).Prophylacticanticonvulsantmedica-

tionshouldnotbeused(ClassIII;LevelofEvidence:

B).(Newrecommendation)

Iron

Systemictreatmentwiththeironchelatordeferoxamine

amelioratesICH-inducedchangesinmarkersofDNAdam-

age,attenuatesbrainedema,andimprovesfunctionalrecov-

eryinratmodelsofICH.107–111Afewstudieshaveexamined

theroleofironinICHpatientsandreportedthathighserum

ferritinlevelsareassociatedwithpooroutcomeafterICH112

andcorrelatewiththeperihematomaedemavolume.113,114

Limitingiron-mediatedtoxicityisapromisingtherapeutic

schelatingiron,deferoxamineexhibits

otherneuroprotectiveproperties.115Itinducestranscriptionof

MorgensternetalIntracerebralHemorrhageGuideline9

byonJuly30,nloadedfrom

hemeoxygenase-1andinhibitshemoglobin-mediatedglutamate

excitotoxicityandhypoxiainduciblefactorprolylhydroxy-

lases.116–119Furtherstudiesinthisareaarewarranted,butno

currenttherapeuticrecommendationcanbemadeatpresent.

Procedures/Surgery

ICPMonitoringandTreatment

ICPmonitoringisoftenperformedinpatientswithICH.

However,onlyverylimitedpublisheddataexistregardingthe

frequencyofelevatedICPanditsmanagementinpatients

withICH.120,121Thereisevidencefordifferentialpressure

gradientsinatleastsomecasessothatICPmaybeelevated

inandaroundthehematomabutnotdistantfromit.122

BecausetheusualcausesofelevatedICParehydrocephalus

fromIVHormasseffectfromthehematoma(orsurrounding

edema),patientswithsmallhematomasandlimitedIVH

usuallywillnotrequiretreatmenttolowerICP.

ICPismeasuredusingdevicesinsertedintothebrain

parenchyma,ptictechnology

icularcatheter

(VC)insertedintothelateralventricleallowsfordrainageof

cerebrospinalfluid,whichcanhelpreduceICPinpatients

chymalcatheterICPdeviceis

insertedintothebrainparenchymaandallowsformonitoring

ofICP,enceof

publishedstudiesshowingthatmanagementofelevatedICP

impactsonICHoutcomemakesthedecisionwhetherto

ssociatedwith

ICPmonitorinsertionanduseincludeinfectionandintracra-

ral,theriskofhemorrhageor

infectionisthoughttobehigherwithVCthanwithparen-

chymalcatheters,althoughdataontheseratesarenotderived

frompatientswithICH,butratherprincipallyfromthosewith

traumaticbraininjuryoraneurysmalsubarachnoidhemor-

1997seriesof108intraparenchymaldevices,the

rateofinfectionwas2.9%andtherateofintracranial

hemorrhagewas2.1%(15.3%inpatientswithcoagulopa-

thies).123Adirectcomparisonofthecomplicationsassociated

witheachtypeofmonitoringdevicewasreportedina1993to

1997seriesof536intracerebralmonitoringdevices(274VCs,

229intraparenchymalparenchymalcatheters,and33othertypes

ofdevices)inwhichtheoverallrateofinfectionwas4%andthe

overallrateofintracranialhemorrhagewas3%.124Before

insertionofamonitoringdevice,thepatient’scoagulationstatus

seofantiplateletagentsmayjustify

platelettransfusionbeforetheprocedure,andtheuseofwarfarin

decisiontouseaVCoraparenchymalcatheterdeviceshouldbe

basedonthespecificneedtodraincerebrospinalfluidinpatients

withhydrocephalusortrappedventricleandthebalanceof

monitoringriskswiththeunknownutilityofICPmanagementin

patientswithICH.

ICPtreatmentshouldbedirectedattheunderlyingcause,

especiallyifduetohydrocephalusormasseffectfromthe

eoflimiteddataregardingICPinICH,

managementprinciplesforelevatedICPareborrowedfrom

ranialpressuretreatment

icatescerebralperfu-

sionpressure;CSF,cerebrospinalfluid.

AdaptedfromBrainTraumaFoundation

HeadInjuryGuidelines.126Copyright

2000,BrainTraumaFoundation.

10StrokeSeptember2010

byonJuly30,nloadedfrom

traumaticbraininjuryguidelines,whichemphasizemaintaining

acerebralperfusionpressureof50to70mmHg,dependingon

thestatusofcerebralautoregulation125,126(seeFigure).ICH

patientswithaGCSscoreof8,thosewithclinicalevidenceof

transtentorialherniation,orthosewithsignificantIVHorhydro-

cephalusmaybeconsideredforICPmonitoringandtreatment.

Numerousstudieshaveassessedventricularsizeandeffects

ofenlargementonICHoutcome.127–130Among902patients

withfollow-updatarandomizedintotheinternationalSurgical

TrialofIntracerebralHemorrhage(STICH)trialofearlyhema-

tomaevacuation,377hadIVHand208ofthesehadhydroceph-

alus(23%ofallpatients,55%ofthosewithIVH).131Hydro-

cephaluspredictedpooroutcomeinthisstudy,aswellasother

previousstudies.127Thus,hydrocephalusisanimportantcause

ofICH-relatedmorbidityandmortality,1andtreatmentshould

beconsideredinpatientswithdecreasedlevelofconsciousness.

Smallcaseserieshavedescribedtheuseofbraintissue

oxygenandcerebralmicrodialysismonitoringinpatients

withICH.132,133Becauseofthesmallnumbersofpatientsand

limiteddata,norecommendationcanbemaderegardingthe

useofthesetechnologiesatthistime.

Recommendations

tswithaGCSscoreof<8,thosewithclinical

evidenceoftranstentorialherniation,orthosewith

significantIVHorhydrocephalusmightbeconsid-

ral

perfusionpressureof50to70mmHgmaybe

reasonabletomaintaindependingonthestatusof

cerebralautoregulation(ClassIIb;LevelofEvi-

dence:C).(Newrecommendation)

culardrainageastreatmentforhydrocepha-

lusisreasonableinpatientswithdecreasedlevelof

consciousness(ClassIIa;LevelofEvidence:B).(New

recommendation)

IntraventricularHemorrhage

IVHoccursin45%ofpatientswithspontaneousICH.134IVH

canbeprimary(confinedtotheventricles)orsecondary

(originatingasanextensionofanICH).MostIVHsare

secondaryandarerelatedtohypertensivehemorrhagesin-

volvingthebasalgangliaandthethalamus.134,135

AlthoughinsertingaVCshouldtheoreticallyaidindrainage

ofbloodandcerebrospinalfluidfromtheventricles,VCuse

alonemaybeineffectivebecauseofdifficultymaintaining

catheterpatencyandtheslowremovalofintraventricular

blood.136Thustherehasbeenrecentinterestintheuseof

thrombolyticagentsasadjunctstoVCuseinthesettingofIVH.

Animalstudiesandclinicalseriesreportedthatintraventricu-

laradministrationoffibrinolyticagents,includingurokinase,

streptokinase,andrecombinanttissue-typeplasminogenactiva-

tor,inIVHmayreducemorbidityandmortalitybyaccelerating

bloodclearanceandclotlysis.137–142RecentlytheClotLysis:

EvaluatingAcceleratedResolutionofIVH(CLEAR-IVH)Trial

prospectivelyevaluatedthesafetyofopen-labeldosesofintra-

ventricularrecombinanttissue-typeplasminogenactivatorin52

maticbleedingoccurredin4%andbacte-

rialventriculitisin2%,andthe30-daymortalityratewas

17%.143Theefficacyofthistreatmentrequiresconfirmation

beforeitsusecanberecommendedoutsideofaclinicaltrial.

SomereportssuggestalternativeproceduresforIVHsuch

asendoscopicsurgicalevacuationandventriculostomy,144–146

ventriculoperitonealshunting,147orlumbardrainageforhy-

drocephalus.148Fewdataexisttosupportthesestrategies.

Recommendation

ghintraventricularadministrationofrecom-

binanttissue-typeplasminogenactivatorinIVH

appearstohaveafairlylowcomplicationrate,

efficacyandsafetyofthistreatmentisuncertainand

isconsideredinvestigational(ClassIIb;Levelof

Evidence:B).(Newrecommendation)

ClotRemoval

SurgicalTreatmentofICH

Thedecisionaboutwhetherandwhentosurgicallyremove

hophysiologyofbrain

injurysurroundingthehematomaisduetothemechanical

effectsofthegrowingmassofbloodaswellasthesubsequent

surgerytolimitthemechanicalcompressionofbrainandthe

toxiceffectsofbloodmaylimitinjury,butthesurgicalrisks

addition,operativeremovalofhemorrhagebycraniotomyin

allbutthemostsuperficialhemorrhagesinvolvescutting

helimitationsofICHsurgical

trialsisthatyoungandmiddle-agedpatientsatriskofherniation

fromlargeICHswereunlikelytoberandomizedfortreatment.

Recommendationsforthesepatientsareuncertain.

CraniotomybyLocationofICH

Mostbutnotall149oftherandomizedtrialsofsurgeryforICH

excludedpatientswithcerebellarICH,whichcomprises10%to

15%usversionsoftheseguidelines6cited

nonrandomizedstudiesshowingthatpatientswithcerebellar

ICHlargerthan3cmindiameterorthosewithbrainstem

compressionorhydrocephalushadgoodoutcomeswithsurgery

toremovethehematoma,whereassimilarpatientsmanaged

medicallydidpoorly.150–155Ifthehemorrhageis3cmin

diameterandthereisnobrainstemcompressionorhydroceph-

alus,reasonableoutcomesmaybeachievedwithoutsurgery.

Eventhoughrandomizedtrialsofcerebellarhematomaevacua-

tionhavenotbeenundertaken,thedifferencesinoutcomeinthe

earlierstudiesaresuchthatclinicalequipoisedoesnotexistfor

rmore,theuseofaVCaloneinsteadofimmediate

cerebellarhematomaevacuationisgenerallyconsideredinsuffi-

cientandisnotrecommended,especiallyinpatientswith

compressedcisterns.155

TheSTICHtrialfoundthatpatientswithhematomasextend-

ingtowithin1cmofthecorticalsurfacehadatrendtoward

morefavorableoutcomewithsurgerywithin96hours,although

thisfindingdidnotreachstatisticalsignificance(oddsratio,

0.69;95%confidenceinterval,0.47to1.01).156Patientswith

lobarhemorrhagesandaGCSscoreof9to12alsohadatrend

ethebenefitofsurgeryfor

patientswithsuperficialICHwasnotstatisticallysignificant

afteradjustingformultipletesting,theauthorsrecommended

additionalclinicaltrialstoconfirmthisbenefit.157

MorgensternetalIntracerebralHemorrhageGuideline11

byonJuly30,nloadedfrom

Bycontrast,patientsintheSTICHstudywithanICH1

cmfromthecorticalsurfaceorwithaGCSscoreof8

tendedtodoworsewithsurgicalremovalascomparedwith

rstudyrandomized108patients

withsupratentorialsubcorticalorputaminalICH30mLin

volumetocraniotomyormedicalmanagementwithin8hoursof

onset.158Goodoutcome(goodrecoveryormoderatedisability

ontheGlasgowOutcomeScaleat1year)wassignificantly

betterinthosetreatedwithsurgery,buttherewasnodifference

andomizedtrialshavehadtoofew

patientstodetermineoutcomesinsubgroupsbylocation,ran-

domizedonlypatientswithdeepICH,ordidnotreportthese

results.159–161Enthusiasmforsurgicalevacuationofthalamic

andpontineICHhasbeenlimited.154,162,163

MinimallyInvasiveSurgicalRemovalofICH

Iftheindicationsforsurgicalevacuationofintracerebral

hematomasarecontroversial,themeansbywhichtoachieve

lgroups

havedevelopedminimallyinvasiveclotremovaltechniques.

Thesetechniquestendtomakeuseofstereotacticguidance

combinedwitheitherthrombolytic-enhancedorendoscopic-

ndomizedtrialsofthrombolytic-

enhancedaspirationforsubcorticalICH149,161,164and

endoscopic-enhancedaspiration165–167withorwithoutste-

reotaxishavereportedincreasedclotremovalandde-

creasedmortalityinthosesubjectstreatedsurgically

within12to72hours,butimprovedfunctionaloutcome

hasnotbeenconsistentlydemonstrated.

TimingofSurgery

Onekeyissuehasbeenthelackofconsensusonthetimeframe

alstudieshavereported

awidevariabilityinthetimingofsurgery,rangingfromwithin

4hoursupto96hoursfromtheonsetofsymptomstotimeof

operation.156,158,161,168Suchtimevarianceamongthestudieshas

madedirectcomparisonandanalysisoftheimpactofsurgical

spectiveJapaneseseriesofsurgical

removalof100putaminalICHswithin7hoursofonset(60

within3hours)reportedbetterthanexpectedoutcomes.169

However,subsequentrandomizedtrialsthattreatedsubjects

within12hoursofonsetreportedmixedresults.158,161,168An

increasedriskofrebleedingwasnotedinthesmalltrialof

subjectsrandomizedwithin4hoursofonset.170

Trialsthatrandomizedpatientswithin24hours,17148

hours,159,16572hours,149,160and96hours156havealsodemon-

stratednoclearbenefitforsurgeryascomparedwithinitial

medicalmanagementexceptforimprovedoutcomeinthe

subgroupofpatientsintheSTICHtrialwithsuperficialICHand

decreasedmortalityinthosepatientswithsubcorticalhemor-

rhagestreatedwithminimallyinvasivemethodswithin12to72

hours,asnotedabove.

Recommendations

tpatientswithICH,theusefulnessofsur-

geryisuncertain(ClassIIb;LevelofEvidence:C).

(Newrecommendation)Specificexceptionstothis

recommendationfollow

tswithcerebellarhemorrhagewhoaredeteriorat-

ingneurologicallyorwhohavebrainstemcompression

and/orhydrocephalusfromventricularobstruction

shouldundergosurgicalremovalofthehemorrhageas

soonaspossible(ClassI;LevelofEvidence:B).(Revised

fromthepreviousguideline)Initialtreatmentofthese

patientswithventriculardrainagealoneratherthan

surgicalevacuationisnotrecommended(ClassIII;Level

ofEvidence:C).(Newrecommendation)

ientspresentingwithlobarclots>30mLand

within1cmofthesurface,evacuationofsupraten-

torialICHbystandardcraniotomymightbeconsid-

ered(ClassIIb;LevelofEvidence:B).(Revisedfrom

thepreviousguideline)

ectivenessofminimallyinvasiveclotevacua-

tionutilizingeitherstereotacticorendoscopicaspi-

rationwithorwithoutthrombolyticusageisuncer-

tainandisconsideredinvestigational(ClassIIb;

LevelofEvidence:B).(Newrecommendation)

ghtheoreticallyattractive,noclearevidenceat

presentindicatesthatultra-earlyremovalofsupraten-

torialICHimprovesfunctionaloutcomeormortality

rlycraniotomymaybeharmfuldueto

increasedriskofrecurrentbleeding(ClassIII;Levelof

Evidence:B).(Revisedfromthepreviousguideline)

OutcomePredictionandWithdrawalof

TechnologicalSupport

Manyobservationalandepidemiologicalstudieshaveidentifieda

widerangeoffactorsthatarepredictiveofoutcomeafteracuteICH.

Fromthesestudiesnumerousoutcomepredictionmodelshavebeen

esfoundin

mostofthesepredictionmodelsincludeindividualpatientcharac-

teristicssuchasthescoreontheGCSorNationalInstitutesof

HealthStrokeScale,age,hematomavolumeandlo辫的拼音 cation,andthe

presenceandamountofIVH.12,172–180Nooutcomeprediction

modelforICH,however,hasconsideredtheimpactofcare

limitationssuchasdonotresuscitate(DNR)ordersorwithdrawalof

technologicalsupport.

MostpatientsthatdiefromICHdosoduringtheinitialacute

hospitalization,andthesedeathsusuallyoccurinthesettingof

withdrawalofsupportduetopresumedpoorprognosis.181,182

Severalstudies,however,havenowidentifiedwithdrawalof

medicalsupportandotherearlycarelimitations,suchasDNR

orderswithinthefirstdayofhospitalization,asindependent

outcomepredictors.2,183,184Itislikelythatcurrentoutcome

predictionmodelsaswellasmoreinformalmethodsofearly

prognosticationafterICHarebiasedbythefailuretoaccountfor

nhasbeenraisedthatdecisionsby

physicianstolimitcareearlyafterICHareresultinginself-

fulfillingpropheciesofpooroutcomeduetoinaccuratelypessi-

misticprognosticationandfailuretoprovideinitialaggressive

therapyinseverelyillICHpatientswhononethelessstillhave

thepossibilityoffavorableoutcome.

AlthoughaDNRorderbydefinitionmeansthatnoattempt

atresuscitationshouldbemadeintheeventthatacardiopul-

monaryarrestoccurs,inpracticaluse,whenadministered

earlyafterICH,itisaproxyforoveralllackofaggres-

sivenessofcare.2Thisimpliesthattheoverallaggressive-

nessofICHcareatahospitalmaybecriticallyimportant

indeterminingpatients’outcome,irrespectiveofspecific

individualcharacteristics.2,83,185

12StrokeSeptember2010

byonJuly30,nloadedfrom

AlthoughprognosticationearlyafterICHmaybedesired

byphysicians,patients,andfamilies,itiscurrentlybasedon

hisuncertaintyandthepotentialfor

self-fulfillingpropheciesofpooroutcome,greatcaution

shouldbeundertakeninattemptingpreciseprognostication

earlyafterICH,especiallyifthepurposeistoconsider

withdrawalofsupportorDNRorders.186Thus,aggressive

guideline-concordanttherapyisrecommendedforallICH

patientswhodonothaveadvanceddirectivesspecifyingthat

mitationssuchasDNR

ordersorwithdrawalofsupportshouldnotberecommended

bytreatingphysiciansduringthefirstfewdaysafterICH.

Recommendation

sivefullcareearlyafterICHonsetand

postponementofnewDNRordersuntilatleastthe

secondfulldayofhospitalizationisprobablyrecom-

mended(ClassIIa;LevelofEvidence:B).Patients

withpreexistingDNRordersarenotincludedinthis

tmethodsofprognostica-

tioninindividualpatientsearlyafterICHarelikely

biasedbyfailuretoaccountfortheinfluenceof

-

tientswhoaregivenDNRstatusatanypointshould

receiveallotherappropriatemedicalandsurgical

interventionsunlessotherwiseexplicitlyindicated.

(Revisedfromthepreviousguideline)

PreventionofRecurrentICH

Population-basedstudiesofsurvivorsofafirsthemorrhagic

strokehaveidentifiedratesofrecurrentICHof2.1%to3.7%

perpatient-year,187,188substantiallyhigherthantheseindivid-

uals’rateofsubsequentischemicstroke.

ThemostconsistentlyidentifiedriskfactorforrecurrentICH

islobarlocationoftheinitialICH.187,189Thisfindinglikely

representstheassociationofcerebralamyloidangiopathywith

lobarlocationandincreasedrecurrence.190,191Hemorrhagein

locationscharacteristicofhypertensivevasculopathy,suchas

basalganglia,thalamus,orbrainstem,192alsorecur,butless

actorslinkedtoICHrecurrenceinsome

studiesincludeolderage,188post-ICHanticoagulation,188previ-

oushemorrhagebeforethepresentingICH,191carriershipofthe

apolipoproteinE␧2or␧4alleles,191,193andgreaternumberof

microbleedsonT2*-weightedgradient-echoMRI.194

Hypertensionisthemostimportantcurrentlymodifiablerisk

factorforpreventionofICHrecurrence.195,196Theimportanceof

BPcontrolwassupportedbydatafromthePerindoprilProtec-

tionAgainstRecurrentStrokeStudy(PROGRESS)showingthat

subjectswithcerebrovasculardiseaserandomizedtoperindopril

plusoptionalindapamidehadsignificantlylowerriskoffirst

ICH(adjustedhazardratio,0.44;95%confidenceinterval,0.28

to0.69)andasimilar,thoughstatisticallyinsignificant,reduction

inrecurrentICH(adjustedhazardratio,0.37;95%confidence

interval,0.10to1.38).193Notably,thisreductionappearedto

gh

specificdataontheoptimalBPforreducingICHrecurrenceare

notavailable,areasonabletargetisaBP140/90(or130/80

inthepresenceofdiabetesorchronickidneydisease)as

suggestedbythemostrecentreportfromtheJointNational

CommitteeonPrevention,Detection,Evaluation,andTreatment

ofHighBloodPressure.197

OralanticoagulationisassociatedwithworseICHout-

come198,199andincreasedriskofrecurrence,188raisingthe

questionofwhetherthebenefitsofanticoagulationforprevent-

hypothetical69-year-oldmanwithnonvalvularatrialfibrillation

andpriorlobarICH,Markovmodelingpredictedthatlong-term

anticoagulationwouldshortenquality-adjustedsurvivalbecause

ofthehighriskofrecurrenceafterlobarICH.200Theresultsfor

anticoagulationafterdeephemisphericICHwerelessclear-cut

andvarieddependingonassumptionsaboutriskoffuture

ectsofantiplateletagentson

ICHrecurrenceandseverityappeartobesubstantiallysmaller

thanforanticoagulation,16,62,189,201suggestingthatantiplatelet

treatmentmaybeasaferalternativetoanticoagulationafterICH.

Recently,theACTIVEA(AtrialFibrillationClopidogrelTrial

withIrbesartanforPreventionofVascularEvents–Aspirin)

studyreportedonarandomized,double-blindstudyofthesafety

andefficacyofaddingclopidogrel75mgdailytoaspirin75to

100mgdailyinpatientswithhigh-riskatrialfibrillationanda

ghpreviousICHwaslisted

asoneofthemanyreasonsforstudyentry,theauthorsdidnotreport

theproportionofsubjectswithpreviousICH,andthereforethe

studyresultsmaynotdirectlyapplytothosewithpreviousICH.

Subjectswhoreceivedclopidogreladdedtoaspirinhada0.8%per

yearabsoluteriskreductionofmajorvasculareventsatthecostof

0.7%peryearincreaseinmajorbleedingevents.202

TherecentStrokePreventionwithAggressiveReductionsin

CholesterolLevels(SPARCL)studyfoundincreasedriskof

subsequentICH(unadjustedhazardratio,1.68;95%confidence

interval,1.09to2.59)amongsubjectswithpriorstrokerandom-

izedtohigh-doseatorvastatin.203Itremainsunclearwhetherthis

effectoutweighsthebenefitsofstatintreatmentinreducingische-

ntalcohol

use(definedintheGreaterCincinnati/NorthernKentuckystudyas

2drinksperday)hasbeenlinkedtoincreasedICHrisk204andis

ehaviors,suchas

physicalexertion,sexualactivity,orstress,havenotbeenlinkedto

ICH,205thoughlittlesystematicdatahavebeenreported.

Recommendations

ationswherestratifyingapatient’sriskof

recurrentICHmayaffectothermanagementdeci-

sions,itisreasonabletoconsiderthefollowingrisk

factorsforrecurrence:lobarlocationoftheinitial

ICH,olderage,ongoinganticoagulation,presenceof

theapolipoproteinE␧2or␧4alleles,andgreater

numberofmicrobleedsonMRI(ClassIIa;Levelof

Evidence:B).(Newrecommendation)

heacuteICHperiod,absentmedicalcontra-

indications,BPshouldbewellcontrolled,particu-

larlyforpatientswithICHlocationtypicalofhyper-

tensivevasculopathy(ClassI;LevelofEvidence:A).

(Newrecommendation)

heacuteICHperiod,agoaltargetofanormal

BPof<140/90(<130/80ifdiabetesorchronic

kidneydisease)isreasonable(ClassIIa;Levelof

Evidence:B).(Newrecommendation)

MorgensternetalIntracerebralHemorrhageGuideline13

byonJuly30,nloadedfrom

nceoflong-termanticoagulationastreatment

fornonvalvularatrialfibrillationisprobablyrecom-

mendedafterspontaneouslobarICHbecauseofthe

relativelyhighriskofrecurrence(ClassIIa;Levelof

Evidence:B).AnticoagulationafternonlobarICH

andantiplatelettherapyafterallICHmightbe

considered,particularlywhentherearedefinitein-

dicationsfortheseagents(ClassIIb;LevelofEvi-

dence:B).(Unchangedfromthepreviousguideline)

nceofheavyalcoholusecanbebeneficial

(ClassIIa;LevelofEvidence:B).Thereisinsufficient

datatorecommendrestrictionsonuseofstatin

agentsorphysicalorsexualactivity(ClassIIb;Level

ofEvidence:C).(Newrecommendation)

RehabilitationandRecovery

Knowledgeofdifferencesinthenaturalhistoryofrecovery

patternsandprognosisforresidualdisabilityandfunctioning

betweenICHandischemicstrokeiscomplicatedbythe

disproportionatelylowerrateofICHcomparedwithischemic

strokeandthelumpingofsubarachnoidhemorrhageandICH

realsoproblemsassociated

withtheinsensitivityofmanyoftheoutcomemeasuresusedin

rehabilitationtoallowdetectionofclinicallymeaningfuldiffer-

,thereissomeevidencethat

patientswithICHmakeslightlygreaterandfastergainsin

recovery206–208comparedwithpatientswithischemicstroke.

Ingeneral,recoveryismorerapidinthefirstfewweeksbut

maycontinueformanymonthsafterICH,208,209withapproxi-

matelyhalfofallsurvivorsremainingdependentonothersfor

activitiesofdailyliving.176However,patientsvaryintheirspeed

anddegreeofrecovery,andthereisnohardruleregardingwhen

ion,mood,motivation,andsocial

supportallinfluencerecovery,anditisdifficulttoseparate

eprognosticscore

utilizingage,ICHvolumeandlocation,levelofconsciousnessat

admission,andpre-ICHcognitiveimpairmenthasbeenshown

topredictindependenceat90days.176GiventhatICHisoften

locatedinlobarregionsandcomplicatedbyintraventricular

extension,somepatientswithspecificcognitivedeficitsor

delayedrecoverythatisdisproportionatetothesizeofthelesion

mayrequirespecializedtherapyinrehabilitation.

Theprovisionofstrokerehabilitationserviceshasreceived

thisrepresentsa

needtotailorservicestoensureoptimalrecoveryforpatientsand

strongevidenceforthebenefitsofwell-organized,multidisci-

plinaryinpatient(strokeunit)careintermsofimprovedsurvival,

recovery,andreturninghomecomparedwithconventional

nondedicatedstrokewards,210effortshavebeenmadetoextend

thisservicemodelofcoordinatedcareintothecommunity.

Specifically,earlysupportedhospitaldischargeandhome-based

rehabilitationprogramshavebeenshowntobecost-effective,210

whereashome-basedtherapyinstablepatientshasbeenshown

toproducecomparableoutcomestoconventionaloutpatient

rehabilitation.211Thesuccessoftheseprogramsdependson

r,thelikelyconfigura-

tionofstrokerehabilitationservicesinanyregionwilldependon

rtionof

rehabilitationshouldincludeeducationforthepatientand

caregiverregardingsecondarystrokepreventionandmeansto

litationprogramsshould

considerlifestylechanges,depression,andcaregiverburdenas

importantissuestoworkonwiththepatientandcaregivers.

Recommendations

hepotentiallyseriousnatureandcomplexpat-

ternofevolvingdisability,itisreasonablethatall

patientswithICHhaveaccesstomultidisciplinary

rehabilitation(ClassIIa;LevelofEvidence:B).Where

possible,rehabilitationcanbebeneficialwhenbegunas

earlyaspossibleandcontinuedinthecommunityas

partofawell-coordinated(seamless)programofac-

celeratedhospitaldischargeandhome-basedresettle-

menttopromoteongoingrecovery(ClassIIa;Levelof

Evidence:B).(Newrecommendation)

FutureConsiderations

ThefutureofICHtreatmentcentersonaclusteroftargets.

ity-basedprojectsto

reduceBPthroughhealthylifestylesandmedicationadher-

encearelikelytobequitesuccessfulinreducingICH

incidence.212Animalstudiesaimedatpreventingcerebral

amyloidangiopathyshowearlypromise.213,214

OnceanICHhasoccurred,effortstomobilizecommunitiesto

facilitateprompttreatmentaresimilartoeffortsaimedatacute

ischemicstroketreatment.215Advancedimagingcurrentlymay

identifypatientswithongoingbleedingandprovidesatargetfor

improvedpatientselectionfortestingofhemostaticagents.28

Hemostaticagents’efficacymustbeclearlyweighedagainst

potentialarterialandvenousthromboticrisk.

BPcontroltheoreticallymayreducehematomagrowth

and/tudiessuggestthata

randomizedcontrolledBP-loweringstudyisfeasible.79,81

Safetyandefficacyremaintobeshowninlargerstudies.

Thereisactiveresearchoninterferingwithoxidativeinjury

-chelatingagentssuchasdeferoxaminearebeing

studiedinearly-phasetrials.107,115Pathwaysthatcenteraround

hypoxia-induciblefactorsandprolylhydroxylasesofferother

potentialtargetsforinterventioncenteredaroundoxidative

stress.216Theroleofmicrogliaandmacrophagesinhematoma

resolutionisgettingmoreattention.217Autophagymaybeacellular

processthatcouldbealteredtopreventICH-relatedcelldeath.218

Thereareprobablymanyfactorsthatcontributetoinjuryafter

ICH,includingmasseffect,toxicityrelatedtoblood,and

gly,asimplesolution

,however,surgeryhasnotproved

ortsutilizing

minimallyinvasivesurgicaltechniquesthatmayremoveblood’s

toxicandpressureeffectswhileavoidingthedamagecausedby

moreinvasiveprocedures,aswellasnewtreatmentstodissolveand

drainintraventricularblood,arecurrentlybeingstudied.143,164

PrioritiesforICHresearchhavebeenpublishedandreviewed

extensively.13Anaggressive,collaborativeapproachtoboth

basicandclinicalresearchinthisfieldislikelytopromotethe

eantime,itisclearthatourabilityto

prognosticateaboutICHislimited,184andthataggressivecare

now,andhopeforthefuture,arebothclearlyindicated.

14StrokeSeptember2010

byonJuly30,nloadedfrom

Disclosures

WritingGroupDisclosures

WritingGroup

MemberEmploymentResearchGrant

OtherResearch

Support

Speakers’

Bureau/Honoraria

Expert

Witness

Ownership

Interest

Consultant/Advisory

BoardOther

LewisB.

Morgenstern

Universityof

Michigan

NIH(R01NS057127)

Consultant—Safetyand

Tolerabilityof

DeferoxamineinAcute

CerebralHemorrhage

(genericstudydrug)*;

NINDS(U01NS052510)

Co-I(Deferoxamine

therapyfor

intracerebral

hemorrhage—animal

translationalgrant

examininggeneric

deferoxamineinICH)†;

NIH(R01NS38916)

PI—BrainAttack

SurveillanceinCorpus

Christi(observational

studyofstrokeina

biethniccommunity)†

NoneNoneNoneNoneNoneMedicaladjudication

boardmember

Wyeth*

CraigAndersonGeorgeInstitute,

Sydney,

Australia

TheAustralianNational

Health&Medical

ResearchCouncil

(employer);Senior

PrincipalResearch

Fellowship(632918);

ProgramGrant

(571281);ProjectGrant

(INTERACT2

study—512402)†;

NINDS(IMSIIITrial1

V01NSO52220-02;

subawardSRS#19449

SAP-G100121-

1005817)†;FIA

(RO1NS39512R-01-NS

36695)†

NoneBoehringer-Ingelheim*;

Servier*;

Sanofi-Aventis*

NoneNoneBoehringer-Ingelheim*None

KyraBeckerUniversityof

Washington

NoneNoneNoneNoneNoneNoneNone

JosephP.

Broderick

Universityof

Cincinnati

NINDSR-01NS36695

(Geneticand

EnvironmentalRisk

FactorsforHemorrhagic

Stroke—Co-

Investigator)†;

NIH/NINDS(P50

SPOTRIAS

NS44283—PIofPPG)†

Novo

Nordisk-

supplies-

FactorVIIafor

NINDS-funded

STOP-ITtrial*

NoneNoneNoneNoneNone

Connolly,Jr

Columbia

University

NoneNoneNoneNoneNoneNoneNone

StevenM.

Greenberg

Massachusetts

GeneralHospital

NIH(R01NS057127,

Consultant)—Safety

andTolerabilityof

DeferoxamineinAcute

CerebralHemorrhage

(genericstudydrug)†

NoneNoneNoneNoneNoneNone

HemphillIII

Universityof

CaliforniaatSan

Francisco

NIH/NINDS;U10

NS058931(PI)†;

(SF-NET:SanFrancisco

Neurological

EmergenciesTrials

Network—national

networkforphaseIII

clinicaltrials—no

currentICHtrials);Novo

Nordisk(PI)†

NoneNoneNoneNoneNovoNordisk*None

(Continued)

MorgensternetalIntracerebralHemorrhageGuideline15

byonJuly30,nloadedfrom

WritingGroupDisclosuresContinued

WritingGroup

MemberEmploymentResearchGrant

OtherResearch

Support

Speakers’

Bureau/Honoraria

Expert

Witness

Ownership

Interest

Consultant/Advisory

BoardOther

JamesN.

Huang

Universityof

CaliforniaatSan

Francisco

NoneProspective

AdvateITI

Registry(PAIR)

Studysponsored

byBaxter(Local

PI—UCSF)*

NoneNoneNoneNoneNone

Macdonald

Universityof

Toronto

PhysiciansServices,

tionGrant

forstudyof

subarachnoid

hemorrhage†

NoneNoneNoneEdge

Therapeutics*

Actelion

Pharmaceuticals(study

ofsubarachnoid

hemorrhage)*

None

StevenR.

Mess

Universityof

Pennsylvania

NoneNoneBoehringer-Ingelheim*NoneNoneNoneNone

PamelaH.

Mitchell

Universityof

Washington

NoneNoneNoneNoneNoneNoneNone

MagdySelimBethIsraelNIH(R01

NS057127)—Safety

andTolerabilityof

DeferoxamineinAcute

CerebralHemorrhage

(genericstudydrug)†

NoneNoneNoneNoneNoneNone

RafaelJ.

Tamargo

JohnsHopkins

University

NoneNoneNoneNoneNoneNoneNone

Thistablerepresentstherelationshipsofwritinggroupmembersthatmaybeperceivedasactualorreasonablyperceivedconflictsofinterestasreportedonthe

DisclosureQuestionnaire,ionshipisconsideredtobe“significant”if(a)theperson

receives$10000ormoreduringany12-monthperiod,or5%ormoreoftheperson’sgrossincome;or(b)thepersonowns5%ormoreofthevotingstockorshare

oftheentity,orowns$ionshipisconsideredtobe“modest”ifitislessthan“significant”underthe

precedingdefinition.

*Modest.

†Significant.

ReviewerDisclosures

ReviewerEmploymentResearchGrant

Other

Research

Support

Speakers’

Bureau/Honoraria

Expert

Witness

Ownership

Interest

Consultant/Advisory

BoardOther

TamilynBakasIndianaUniversity

PurdueUniversity

Indianapolis

NoneNoneNoneNoneNoneNoneNone

JohnColeUniversityof

Maryland

NoneNoneNoneNoneNoneNoneNone

Matthew

Flaherty

Universityof

Cincinnati

AcademicHealth

Center

NoneNoneNoneNoneNoneNoneNone

KarenC.

Johnston

Universityof

Virginia

NIH-NINDSR01NS050192-

GRASPtrial†

NoneMultiplegrandrounds,

nationaltalkson

stroke*

NoneNoneDiffussionPharmaceuticals,

Inc.*;Remedy

Pharmaceuticals,Inc.*

AANasassociate

editorofneurology

throughJuly

2009†

Christina

Stewart-Amidei

Universityof

CentralFlorida

NoneNoneNoneNoneNoneNoneNone

GregZipfelWashington

University

NoneNoneNoneNoneNoneNoneNone

ThistablerepresentstherelationshipsofreviewersthatmaybeperceivedasactualorreasonablyperceivedconflictsofinterestasreportedontheDisclosure

Questionnaire,ionshipisconsideredtobe“significant”if(a)thepersonreceives$10000ormore

duringany12-monthperiod,or5%ormoreoftheperson’sgrossincome;or(b)thepersonowns5%ormoreofthevotingstockorshareoftheentity,orowns

$ionshipisconsideredtobe“modest”ifitislessthan“significant”undertheprecedingdefinition.

*Modest.

†Significant.

16StrokeSeptember2010

byonJuly30,nloadedfrom

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