Christopher S. Ogilvy, Aman B. Patel, B. Gregory Thompson and Paul Vespa Jacques Dion ...

28 Pages·2012·2.03 MB·English

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage : A Guideline
for Healthcare Professionals From the American Heart Association/American Stroke
Association
E. Sander Connolly, Jr, Alejandro A. Rabinstein, J. Ricardo Carhuapoma, Colin P. Derdeyn,
Jacques Dion, Randall T. Higashida, Brian L. Hoh, Catherine J. Kirkness, Andrew M. Naidech,
Christopher S. Ogilvy, Aman B. Patel, B. Gregory Thompson and Paul Vespa
Stroke. 2012;43:1711-1737; originally published online May 3, 2012;
doi: 10.1161/STR.0b013e3182587839
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2012 American Heart Association, Inc. All rights reserved.
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AHA/ASA Guideline
Guidelines for the Management of Aneurysmal
Subarachnoid Hemorrhage
A Guideline for Healthcare Professionals From the American Heart
Association/American Stroke Association
The American Academy of Neurology affirms the value of this statement as an educational tool
for neurologists.
Endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons;
and by the Society of NeuroInterventional Surgery
E. Sander Connolly, Jr, MD, FAHA, Chair; Alejandro A. Rabinstein, MD, Vice Chair;
J. Ricardo Carhuapoma, MD, FAHA; Colin P. Derdeyn, MD, FAHA; Jacques Dion, MD, FRCPC;
Randall T. Higashida, MD, FAHA; Brian L. Hoh, MD, FAHA; Catherine J. Kirkness, PhD, RN;
Andrew M. Naidech, MD, MSPH; Christopher S. Ogilvy, MD; Aman B. Patel, MD;
B. Gregory Thompson, MD; Paul Vespa, MD, FAAN; on behalf of the American Heart Association
Stroke Council, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular
Nursing, Council on Cardiovascular Surgery and Anesthesia, and Council on Clinical Cardiology
Purpose—The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and
treatment of aneurysmal subarachnoid hemorrhage (aSAH).
Methods—A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were
synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived
recommendations.TheAmericanHeartAssociationStrokeCouncil’sLevelsofEvidencegradingalgorithmwasusedtograde
eachrecommendation.Theguidelinedraftwasreviewedby7expertpeerreviewersandbythemembersoftheStrokeCouncil
LeadershipandManuscriptOversightCommittees.Itisintendedthatthisguidelinebefullyupdatedevery3years.
Results—Evidence-basedguidelinesarepresentedforthecareofpatientspresentingwithaSAH.Thefocusoftheguideline
wassubdividedintoincidence,riskfactors,prevention,naturalhistoryandoutcome,diagnosis,preventionofrebleeding,
surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair,
managementofvasospasmanddelayedcerebralischemia,managementofhydrocephalus,managementofseizures,and
management of medical complications.
Conclusions—aSAHisaseriousmedicalconditioninwhichoutcomecanbedramaticallyimpactedbyearly,aggressive,expert
care.Theguidelinesofferaframeworkforgoal-directedtreatmentofthepatientwithaSAH. (Stroke.2012;43:1711-1737.)
Key Words: AHA Scientific Statements (cid:1) aneurysm (cid:1) delayed cerebral ischemia (cid:1) diagnosis (cid:1) subarachnoid
hemorrhage (cid:1) treatment (cid:1) vasospasm
The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside
relationshiporapersonal,professional,orbusinessinterestofamemberofthewritingpanel.Specifically,allmembersofthewritinggrouparerequired
tocompleteandsubmitaDisclosureQuestionnaireshowingallsuchrelationshipsthatmightbeperceivedasrealorpotentialconflictsofinterest.
TheAmericanHeartAssociationrequeststhatthisdocumentbecitedasfollows:ConnollyESJr,RabinsteinAA,CarhuapomaJR,DerdeynCP,Dion
J,HigashidaRT,HohBL,KirknessCJ,NaidechAM,OgilvyCS,PatelAB,ThompsonBG,VespaP;onbehalfoftheAmericanHeartAssociationStroke
Council,CouncilonCardiovascularRadiologyandIntervention,CouncilonCardiovascularNursing,CouncilonCardiovascularSurgeryandAnesthesia,
andCouncilonClinicalCardiology.Guidelinesforthemanagementofaneurysmalsubarachnoidhemorrhage:aguidelineforhealthcareprofessionals
fromtheAmericanHeartAssociation/AmericanStrokeAssociation.Stroke.2012;43:1711–1737.
ExpertpeerreviewofAHAScientificStatementsisconductedbytheAHAOfficeofScienceOperations.FormoreonAHAstatementsandguidelines
development,visithttp://my.americanheart.org/statementsandselectthe“PoliciesandDevelopment”link.
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express
permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/
Copyright-Permission-Guidelines_UCM_300404_Article.jsp.Alinktothe“CopyrightPermissionsRequestForm”appearsontherightsideofthepage.
ThisstatementwasapprovedbytheAmericanHeartAssociationScienceAdvisoryandCoordinatingCommitteeonJanuary30,2012.Acopyofthe
documentisavailableathttp://my.americanheart.org/statementsbyselectingeitherthe“ByTopic”linkorthe“ByPublicationDate”link.Topurchase
additionalreprints,[email protected].
©2012AmericanHeartAssociation,Inc.
Strokeisavailableathttp://stroke.ahajournals.org DOI:10.1161/STR.0b013e3182587839
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1712 Stroke June 2012
Torespondtothegrowingcallformoreevidenced-based ence call was held to discuss controversial issues. Sections
medicine, the American Heart Association (AHA) com- were revised and merged by the writing group chair. The
missions guidelines on various clinical topics and endeavors resulting draft was sent to the entire writing group for
to keep them as current as possible. The prior aneurysmal comment.Commentswereincorporatedintothedraftbythe
subarachnoid hemorrhage (aSAH) guidelines, sponsored by writing group chair and vice chair, and the entire writing
theAHAStrokeCouncil,werepreviouslyissuedin19941and groupwasaskedtoapprovethefinaldraft.Thechairandvice
2009.2 The 2009 guidelines covered literature through No- chair revised the document in response to peer review, and
vember 1, 2006.2 The present guidelines primarily cover the document was again sent to the entire writing group for
literature published between November 1, 2006, and May 1, additional suggestions and approval.
2010,butthewritinggrouphasstrivedtoplacethesedatain The recommendations follow the AHA Stroke Council’s
the greater context of the prior publications and recommen- methodsofclassifyingthelevelofcertaintyofthetreatment
dations. In cases in which new data covered in this review effectandtheclassofevidence(Tables1and2).AllClassI
have resulted in a change in a prior recommendation, this is recommendations are listed in Table 3. All new or revised
explicitly noted. recommendations are listed in Table 4.
aSAH is a significant cause of morbidity and mortality
throughouttheworld.AlthoughtheincidenceofaSAHvaries Incidence and Prevalence of aSAH
widely among populations, perhaps because of genetic dif-
Considerable variation in the annual incidence of aSAH
ferences, competing burden of disease, and issues of case
exists in different regions of the world. A World Health
ascertainment, at the very least, a quarter of patients with
Organization study found a 10-fold variation in the age-
aSAH die, and roughly half of survivors are left with some
adjusted annual incidence in countries in Europe and Asia,
persistent neurological deficit. That said, case-fatality rates
from2.0casesper100000populationinChinato22.5cases
appear to be falling, and increasing data suggest that early
per100000inFinland.3Alatersystematicreviewsupported
aneurysm repair, together with aggressive management of
a high incidence of aSAH in Finland and Japan, a low
complications such as hydrocephalus and delayed cerebral
incidenceinSouthandCentralAmerica,andanintermediate
ischemia(DCI),isleadingtoimprovedfunctionaloutcomes.
incidenceof9.1per100000populationinotherregions.4In
These improvements underscore the need to continually
amorerecentsystematicreviewofpopulation-basedstudies,
reassess which interventions provide the greatest benefit to
theincidenceofaSAHrangedfrom2to16per100000.5In
patients.
that review, the pooled age-adjusted incidence rate of aSAH
Although large, multicenter, randomized trial data con-
in low- to middle-income countries was found to be almost
firming effectiveness are usually lacking for many of the
doublethatofhigh-incomecountries.5Althoughsomereports
interventions discussed, the writing group did its best to
havesuggestedtheincidenceofaSAHintheUnitedStatesto
summarize the strength of the existing data and make prac-
be 9.7 per 100000,6 the 2003 Nationwide Inpatient Sample
tical recommendations that clinicians will find useful in the
providedanannualestimateof14.5dischargesforaSAHper
day-to-day management of aSAH. This review does not
100000 adults.7 Because death resulting from aSAH often
discuss the multitude of ongoing studies. Many of these can
occurs before hospital admission (an estimated 12% to 15%
be found at http://www.strokecenter.org/trials/. The mecha-
ofcases),8,9thetrueincidenceofaSAHmightbeevenhigher.
nismofreviewingtheliterature,compilingandanalyzingthe
Although a number of population-based studies have indi-
data,anddeterminingthefinalrecommendationstobemade
cated that the incidence of aSAH has remained relatively
is identical to the 2009 version of this guideline.2
stable over the past 4 decades,5,10–16 a recent review that
The members of the writing group were selected by the
adjusted for age and sex suggested a slight decrease in
AHAtorepresentthebreadthofhealthcareprofessionalswho
incidence between 1950 and 2005 for regions other than
must manage these patients. Experts in each field were
screened for important conflicts of interest and then met by Japan, South and Central America, and Finland.4 These data
are consistent with studies that show that the incidence of
telephone to determine subcategories to evaluate. These
aSAHincreaseswithage,withatypicalaverageageofonset
subcategories included incidence, risk factors, prevention,
natural history and outcome, diagnosis, prevention of re- inadults(cid:1)50yearsofage.3,7,17,18aSAHisrelativelyuncom-
bleeding, surgical and endovascular repair of ruptured aneu- mon in children; incidence rates increase as children get
rysms,systemsofcare,anestheticmanagementduringrepair, older, with incidence ranging from 0.18 to 2.0 per
management of vasospasm and DCI, management of hydro- 100000.4,19 The majority of studies also indicate a higher
cephalus,managementofseizures,andmanagementofmed- incidence of aSAH in women than in men.7,11–13,20–22 Most
icalcomplications.Together,thesecategorieswerethoughtto recent pooled figures report the incidence in women to be
encompass all of the major areas of disease management, 1.24(95%confidenceinterval,1.09–1.42)timeshigherthan
including prevention, diagnosis, and treatment. Each subcat- in men.4 This is lower than a previous estimate of 1.6 (95%
egory was led by 1 author, with 1 or 2 additional coauthors confidence interval, 1.1–2.3) for the years 1960 to 1994.23
who made contributions. Full MEDLINE searches were Evidenceofasex-ageeffectonaSAHincidencehasemerged
conducted independently by each author and coauthor of all from pooled study data, with a higher incidence reported in
English-language papers on treatment of relevant human younger men (25–45 years of age), women between 55 and
disease. Drafts of summaries and recommendations were 85 years of age, and men (cid:1)85 years of age.4 Differences in
circulatedtotheentirewritinggroupforfeedback.Aconfer- incidence of aSAH by race and ethnicity appear to exist.
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Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1713
Table1. ApplyingClassificationofRecommendationandLevelofEvidence
ArecommendationwithLevelofEvidenceBorCdoesnotimplythattherecommendationisweak.Manyimportantclinicalquestionsaddressedintheguidelines
donotlendthemselvestoclinicaltrials.Althoughrandomizedtrialsareunavailable,theremaybeaveryclearclinicalconsensusthataparticulartestortherapyis
usefuloreffective.
*Dataavailablefromclinicaltrialsorregistriesabouttheusefulness/efficacyindifferentsubpopulations,suchassex,age,historyofdiabetes,historyofprior
myocardialinfarction,historyofheartfailure,andprioraspirinuse.
†Forcomparativeeffectivenessrecommendations(ClassIandIIa;LevelofEvidenceAandBonly),studiesthatsupporttheuseofcomparatorverbsshouldinvolve
directcomparisonsofthetreatmentsorstrategiesbeingevaluated.
BlacksandHispanicshaveahigherincidenceofaSAHthan familial aneurysms (at least 1 first-degree family member
white Americans.6,24,25 with an intracranial aneurysm, and especially if (cid:1)2 first-
degreerelativesareaffected)andfamilyhistoryofaSAH,26,27
Risk Factors for and Prevention of aSAH and certain genetic syndromes, such as autosomal dominant
BehavioralriskfactorsforaSAHincludehypertension,smok- polycystic kidney disease and type IV Ehlers-Danlos syn-
ing, alcohol abuse, and the use of sympathomimetic drugs drome.28,29 Novel findings reported since publication of the
(eg, cocaine). In addition to female sex (above), the risk of previous version of these guidelines include the following:
aSAHisincreasedbythepresenceofanunrupturedcerebral (1) Aneurysms in the anterior circulation appear to be more
aneurysm (particularly those that are symptomatic, larger in prone to rupture in patients (cid:2)55 years of age, whereas
size,andlocatedeitherontheposteriorcommunicatingartery posterior communicating aneurysms ruptured more fre-
or the vertebrobasilar system), a history of previous aSAH quently in men, and basilar artery aneurysm rupture is
(withorwithoutaresidualuntreatedaneurysm),ahistoryof associatedwithlackofuseofalcohol.30(2)Thesizeatwhich
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1714 Stroke June 2012
Table2. DefinitionofClassesandLevelsofEvidenceUsedin Itispossiblethatdietincreasestheriskofstrokeingeneral
AHAStrokeCouncilRecommendations and aSAH in particular. In an epidemiological study of
Finnish smokers who were monitored for (cid:1)13 years, in-
ClassI Conditionsforwhichthereisevidencefor
and/orgeneralagreementthatthe creased consumption of yogurt (but not all dairy products)
procedureortreatmentisusefuland was associated with a higher risk of aSAH.41 Greater vege-
effective. table consumption is associated with a lower risk of stroke
ClassII Conditionsforwhichthereisconflicting andaSAH.42Highercoffeeandteaconsumption43andhigher
evidenceand/oradivergenceofopinion
magnesiumconsumption44wereassociatedwithreducedrisk
abouttheusefulness/efficacyofa
of stroke overall but did not change the risk of aSAH.
procedureortreatment.
Predicting the growth of an individual intracranial aneu-
ClassIIa Theweightofevidenceoropinionisin
rysm and its potential for rupture in a given patient remains
favoroftheprocedureortreatment.
problematic. When followed up on magnetic resonance im-
ClassIIb Usefulness/efficacyislesswellestablished
byevidenceoropinion. aging,largeraneurysms((cid:1)8mmindiameter)tendedtogrow
ClassIII Conditionsforwhichthereisevidence more over time,45 which implies a higher risk of rupture.
and/orgeneralagreementthatthe Several characteristics of aneurysm morphology (such as a
procedureortreatmentisnot bottleneckshape46andtheratioofsizeofaneurysmtoparent
useful/effectiveandinsomecasesmay vessel47,48)havebeenassociatedwithrupturestatus,buthow
beharmful.
thesemightbeappliedtoindividualpatientstopredictfuture
Therapeuticrecommendations
aneurysmal rupture is still unclear.33 Variability within each
LevelofEvidenceA Dataderivedfrommultiplerandomized patient is unpredictable at this time, but such intraindividual
clinicaltrialsormeta-analyses
variability markedly changes the risk of aneurysm detection
LevelofEvidenceB Dataderivedfromasinglerandomized
andruptureandmayattenuatethebenefitsofroutinescreen-
trialornonrandomizedstudies
ing in high-risk patients.49
LevelofEvidenceC Consensusopinionofexperts,case
Given such uncertainties, younger age, longer life expec-
studies,orstandardofcare
tancy, and higher rate of rupture all make treatment of
Diagnosticrecommendations
unruptured aneurysms more likely to be cost-effective and
LevelofEvidenceA Dataderivedfrommultipleprospective
reduce morbidity and mortality.50 Two large observational
cohortstudiesusingareference
studies of familial aneurysms suggest that screening these
standardappliedbyamaskedevaluator
patients may also be cost-effective in preventing aSAH and
LevelofEvidenceB DataderivedfromasinglegradeAstudy,
or(cid:1)1case-controlstudies,orstudies improvingqualityoflife.26,27Smallerstudieshavesuggested
usingareferencestandardappliedby thatscreeningofthosewith1first-degreerelativewithaSAH
anunmaskedevaluator may be justified as well, but it is far less clear whether
LevelofEvidenceC Consensusopinionofexperts patients who underwent treatment for a previous aSAH
require ongoing screening.51,52 In the Cerebral Aneurysm
aneurysms rupture appears to be smaller in those patients ReruptureAfterTreatment(CARAT)study,recurrentaSAH
with the combination of hypertension and smoking than in waspredictedbyincompleteobliterationoftheaneurysmand
thosewitheitherriskfactoralone.31(3)Significantlifeevents occurredamedianof3daysaftertreatmentbutrarelyafter1
suchasfinancialorlegalproblemswithinthepastmonthmay year.53Repeatednoninvasivescreeningatlatertimesmaynot
increase the risk of aSAH.32 (4) Aneurysm size (cid:1)7 mm has becost-effective,increaselifeexpectancy,orimprovequality
been shown to be a risk factor for rupture.33 (5) There does of life in unselected patients.54 Patients with adequately
not appear to be an increased risk of aSAH in pregnancy, obliteratedaneurysmsafteraSAHhavealowriskofrecurrent
delivery, and puerperium.34,35 aSAH for at least 5 years,55,56 although some coiled aneu-
Inflammation appears to play an important role in the
rysms require retreatment.57
pathogenesis and growth of intracranial aneurysms.36 Prom-
inent mediators include the nuclear factor (cid:2)-light-chain en-
hancerofactivatedBcells(NF-(cid:2)B),37tumornecrosisfactor, Risk Factors for and Prevention of aSAH:
macrophages, and reactive oxygen species. Although there Recommendations
are no controlled studies in humans, 3-hydroxy-3-
methylglutarylcoenzymeAreductaseinhibitors(statin”)38 1. Treatment of high blood pressure with antihyper-
andcalciumchannelblockersmayretardaneurysmforma- tensivemedicationisrecommendedtopreventische-
tion through the inhibition of NF-(cid:2)B and other pathways. mic stroke, intracerebral hemorrhage, and cardiac,
Among the risk factors for aSAH, clearly attributable and renal, and other end-organ injury (Class I; Level of
modifiable risks are very low body mass index, smoking, Evidence A).
and high alcohol consumption.31,39,40 Yet, despite marked 2. Hypertensionshouldbetreated,andsuchtreatment
improvements in the treatment of hypertension and hyper- may reduce the risk of aSAH (Class I; Level of
lipidemia and the decrease in rates of smoking over time, Evidence B).
the incidence of aSAH has not changed appreciably in 30 3. Tobaccouseandalcoholmisuseshouldbeavoidedto
years.16 reducetheriskofaSAH(ClassI;LevelofEvidenceB).
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Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1715
Table3. ClassIRecommendations
LevelofEvidence Recommendation
A 1. Treatmentofhighbloodpressurewithantihypertensivemedicationisrecommendedtopreventischemicstroke,intracerebral
hemorrhage,andcardiac,renal,andotherend-organinjury.
A 2. OralnimodipineshouldbeadministeredtoallpatientswithaSAH.(Itshouldbenotedthatthisagenthasbeenshownto
improveneurologicaloutcomesbutnotcerebralvasospasm.Thevalueofothercalciumantagonists,whetheradministered
orallyorintravenously,remainsuncertain.)
B 1. Hypertensionshouldbetreated,andsuchtreatmentmayreducetheriskofaSAH
B 2. TobaccouseandalcoholmisuseshouldbeavoidedtoreducetheriskofaSAH.
B* 3. Afteranyaneurysmrepair,immediatecerebrovascularimagingisgenerallyrecommendedtoidentifyremnantsorrecurrence
oftheaneurysmthatmayrequiretreatment.
B 4. TheinitialclinicalseverityofaSAHshouldbedeterminedrapidlybyuseofsimplevalidatedscales(eg,HuntandHess,World
FederationofNeurologicalSurgeons),becauseitisthemostusefulindicatorofoutcomeafteraSAH.
B 5. Theriskofearlyaneurysmrebleedingishighandisassociatedwithverypooroutcomes.Therefore,urgentevaluationand
treatmentofpatientswithsuspectedaSAHisrecommended.
B 6. aSAHisamedicalemergencythatisfrequentlymisdiagnosed.AhighlevelofsuspicionforaSAHshouldexistinpatients
withacuteonsetofsevereheadache.
B 7. AcutediagnosticworkupshouldincludenoncontrastheadCT,which,ifnondiagnostic,shouldbefollowedbylumbar
puncture.
B* 8. DSAwith3-dimensionalrotationalangiographyisindicatedfordetectionofaneurysminpatientswithaSAH(exceptwhen
theaneurysmwaspreviouslydiagnosedbyanoninvasiveangiogram)andforplanningtreatment(todeterminewhetheran
aneurysmisamenabletocoilingortoexpeditemicrosurgery).
B* 9. BetweenthetimeofaSAHsymptomonsetandaneurysmobliteration,bloodpressureshouldbecontrolledwithatitratable
agenttobalancetheriskofstroke,hypertension-relatedrebleeding,andmaintenanceofcerebralperfusionpressure.
B 10. Surgicalclippingorendovascularcoilingoftherupturedaneurysmshouldbeperformedasearlyasfeasibleinthemajority
ofpatientstoreducetherateofrebleedingafteraSAH.
B 11. Completeobliterationoftheaneurysmisrecommendedwheneverpossible.
B† 12. Forpatientswithrupturedaneurysmsjudgedtobetechnicallyamenabletobothendovascularcoilingandneurosurgical
clipping,endovascularcoilingshouldbeconsidered.
B* 13. Intheabsenceofacompellingcontraindication,patientswhoundergocoilingorclippingofarupturedaneurysm
shouldhavedelayedfollow-upvascularimaging(timingandmodalitytobeindividualized),andstrongconsideration
shouldbegiventoretreatment,eitherbyrepeatcoilingormicrosurgicalclipping,ifthereisaclinicallysignificant
(eg,growing)remnant.
B† 14. Low-volumehospitals(eg,(cid:2)10aSAHcasesperyear)shouldconsiderearlytransferofpatientswithaSAHtohigh-volume
centers(eg,(cid:1)35aSAHcasesperyear)withexperiencedcerebrovascularsurgeons,endovascularspecialists,and
multidisciplinaryneuro-intensivecareservices.
B† 15. MaintenanceofeuvolemiaandnormalcirculatingbloodvolumeisrecommendedtopreventDCI.
B† 16. InductionofhypertensionisrecommendedforpatientswithDCIunlessbloodpressureiselevatedatbaselineorcardiac
statusprecludesit.
B† 17. aSAH-associatedacutesymptomatichydrocephalusshouldbemanagedbycerebrospinalfluiddiversion(EVDorlumbar
drainage,dependingontheclinicalscenario).
B* 18. Heparin-inducedthrombocytopeniaanddeepvenousthrombosis,althoughinfrequent,arenotuncommonoccurrencesafter
aSAH.Earlyidentificationandtargetedtreatmentarerecommended,butfurtherresearchisneededtoidentifytheideal
screeningparadigms.
C† 1. Determinationofaneurysmtreatment,asjudgedbybothexperiencedcerebrovascularsurgeonsandendovascularspecialists,
shouldbeamultidisciplinarydecisionbasedoncharacteristicsofthepatientandtheaneurysm.
C† 2. aSAH-associatedchronicsymptomatichydrocephalusshouldbetreatedwithpermanentcerebrospinalfluiddiversion.
aSAHindicatesaneurysmalsubarachnoidhemorrhage;CT,computedtomography;DSA,digitalsubtractionangiography;DCI,delayedcerebralischemia;andEVD,
externalventriculardrainage.
*Anewrecommendation.
†Achangeineitherlevelofevidenceorstrengthoftherecommendationfrompreviousguidelines.
4. Inadditiontothesizeandlocationoftheaneurysm 5. Consumptionofadietrichinvegetablesmaylower
and the patient’s age and health status, it might be the risk of aSAH (Class IIb; Level of Evidence B).
reasonable to consider morphological and hemody- (New recommendation)
namiccharacteristicsoftheaneurysmwhendiscuss- 6. It may be reasonable to offer noninvasive screening
ingtheriskofaneurysmrupture(ClassIIb;Levelof to patients with familial (at least 1 first-degree
Evidence B). (New recommendation) relative)aSAHand/orahistoryofaSAHtoevaluate
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1716 Stroke June 2012
Table4. NeworRevisedRecommendations
Classof
Newor Recommendation/
Revised Recommendation LevelofEvidence
New 1. Inadditiontothesizeandlocationoftheaneurysmandthepatient’sageandhealthstatus,itmightbereasonable ClassIIb,LevelB
toconsidermorphologicalandhemodynamiccharacteristicsoftheaneurysmwhendiscussingtheriskofaneurysm
rupture.
New 2. ConsumptionofadietrichinvegetablesmaylowertheriskofaSAH. ClassIIb,LevelB
New 3. Afteranyaneurysmrepair,immediatecerebrovascularimagingisgenerallyrecommendedtoidentifyremnantsor ClassI,LevelB
recurrenceoftheaneurysmthatmayrequiretreatment.
New 4. Afterdischarge,itisreasonabletoreferpatientswithaSAHforacomprehensiveevaluation,includingcognitive, ClassIIa,LevelB
behavioral,andpsychosocialassessments.
New 5. CTAmaybeconsideredintheworkupofaSAH.IfananeurysmisdetectedbyCTA,thisstudymayhelpguidethe ClassIIb,LevelC
decisionforthetypeofaneurysmrepair,butifCTAisinconclusive,DSAisstillrecommended(exceptpossiblyin
theinstanceofclassicperimesencephalicSAH).
New 6. Magneticresonanceimaging(fluid-attenuatedinversionrecovery,protondensity,diffusion-weightedimaging,and ClassIIb,LevelC
gradientechosequences)maybereasonableforthediagnosisofSAHinpatientswithanondiagnosticCT
scan,althoughanegativeresultdoesnotobviatetheneedforcerebrospinalfluidanalysis.
New 7. DSAwith3-dimensionalrotationalangiographyisindicatedfordetectionofaneurysminpatientswithaSAH(except ClassI,LevelB
whentheaneurysmwaspreviouslydiagnosedbyanoninvasiveangiogram)andforplanningtreatment(to
determinewhetherananeurysmisamenabletocoilingortoexpeditemicrosurgery).
New 8. BetweenthetimeofaSAHsymptomonsetandaneurysmobliteration,bloodpressureshouldbecontrolledwitha ClassI,LevelB
titratableagenttobalancetheriskofstroke,hypertension-relatedrebleeding,andmaintenanceofcerebral
perfusionpressure.
New 9. Themagnitudeofbloodpressurecontroltoreducetheriskofrebleedinghasnotbeenestablished,butadecrease ClassIIa,LevelC
insystolicbloodpressureto(cid:2)160mmHgisreasonable.
New 10. Intheabsenceofacompellingcontraindication,patientswhoundergocoilingorclippingofarupturedaneurysm ClassI,LevelB
shouldhavedelayedfollow-upvascularimaging(timingandmodalitytobeindividualized),andstrongconsideration
shouldbegiventoretreatment,eitherbyrepeatcoilingormicrosurgicalclipping,ifthereisaclinicallysignificant
(eg,growing)remnant.
New 11. Microsurgicalclippingmayreceiveincreasedconsiderationinpatientspresentingwithlarge((cid:1)50mL) ClassIIb,LevelC
intraparenchymalhematomasandmiddlecerebralarteryaneurysms.Endovascularcoilingmayreceiveincreased
considerationintheelderly((cid:1)70yofage),inthosepresentingwithpoor-gradeWFNSclassification(IV/V)aSAH,
andinthosewithaneurysmsofthebasilarapex.
New 12. Stentingofarupturedaneurysmisassociatedwithincreasedmorbidityandmortality. ClassIII,LevelC
New 13. Annualmonitoringofcomplicationratesforsurgicalandinterventionalproceduresisreasonable. ClassIIa,LevelC
New 14. Ahospitalcredentialingprocesstoensurethatpropertrainingstandardshavebeenmetbyindividualphysicians ClassIIa,LevelC
treatingbrainaneurysmsisreasonable.
New 15. Prophylactichypervolemiaorballoonangioplastybeforethedevelopmentofangiographicspasmisnot ClassIII,LevelB
recommended.
New 16. TranscranialDopplerisreasonabletomonitorforthedevelopmentofarterialvasospasm. ClassIIa,LevelB
New 17. PerfusionimagingwithCTormagneticresonancecanbeusefultoidentifyregionsofpotentialbrainischemia. ClassIIa,LevelB
New 18. WeaningEVDover(cid:1)24hoursdoesnotappeartobeeffectiveinreducingtheneedforventricularshunting. ClassIII,LevelB
New 19. Routinefenestrationofthelaminaterminalisisnotusefulforreducingtherateofshunt-dependenthydrocephalus ClassIII,LevelB
andthereforeshouldnotberoutinelyperformed.
New 20. Aggressivecontroloffevertoatargetofnormothermiabyuseofstandardoradvancedtemperaturemodulating ClassIIa,LevelB
systemsisreasonableintheacutephaseofaSAH.
New 21. TheuseofpackedredbloodcelltransfusiontotreatanemiamightbereasonableinpatientswithaSAHwhoare ClassIIb,LevelB
atriskofcerebralischemia.Theoptimalhemoglobingoalisstilltobedetermined.
New 22. Heparin-inducedthrombocytopeniaanddeepvenousthrombosisarerelativelyfrequentcomplicationsafteraSAH. ClassI,LevelB
Earlyidentificationandtargetedtreatmentarerecommended,butfurtherresearchisneededtoidentifytheideal
screeningparadigms.
Revised 1. Forpatientswithanunavoidabledelayinobliterationofaneurysm,asignificantriskofrebleeding,andno ClassIIa,LevelB
compellingmedicalcontraindications,short-term((cid:2)72hours)therapywithtranexamicacidoraminocaproicacidis
reasonabletoreducetheriskofearlyaneurysmrebleeding.
Revised 2. Determinationofaneurysmtreatment,asjudgedbybothexperiencedcerebrovascularsurgeonsandendovascular ClassI,LevelC
specialists,shouldbeamultidisciplinarydecisionbasedoncharacteristicsofthepatientandtheaneurysm.
(Continued)
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Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1717
Table4. Continued
Classof
Newor Recommendation/
Revised Recommendation LevelofEvidence
Revised 3. Forpatientswithrupturedaneurysmsjudgedtobetechnicallyamenabletobothendovascularcoilingand ClassI,LevelB
neurosurgicalclipping,endovascularcoilingshouldbeconsidered.
Revised 4. Low-volumehospitals(eg,(cid:2)10aSAHcasesperyear)shouldconsiderearlytransferofpatientswithaSAHto ClassI,LevelB
high-volumecenters(eg,(cid:1)35aSAHcasesperyear)withexperiencedcerebrovascularsurgeons,endovascular
specialists,andmultidisciplinaryneuro-intensivecareservices.
Revised 5. MaintenanceofeuvolemiaandnormalcirculatingbloodvolumeisrecommendedtopreventDCI. ClassI,LevelB
Revised 6. InductionofhypertensionisrecommendedforpatientswithDCIunlessbloodpressureiselevatedatbaselineor ClassI,LevelB
cardiacstatusprecludesit.
Revised 7. Cerebralangioplastyand/orselectiveintra-arterialvasodilatortherapyisreasonableinpatientswithsymptomatic ClassIIa,LevelB
cerebralvasospasm,particularlythosewhoarenotrapidlyrespondingtohypertensivetherapy.
Revised 8. aSAH-associatedacutesymptomatichydrocephalusshouldbemanagedbycerebrospinalfluiddiversion(EVDor ClassI,LevelB
lumbardrainage,dependingontheclinicalscenario).
Revised 9. aSAH-associatedchronicsymptomatichydrocephalusshouldbetreatedwithpermanentcerebrospinalfluid ClassI,LevelC
diversion.
aSAHindicatesaneurysmalsubarachnoidhemorrhage;CTA,computedtomographyangiography;DSA,digitalsubtractionangiography;CT,computedtomography;
DSA,digitalsubtractionangiography;EVD,externalventriculardrainage;DCI,delayedcerebralischemia;andWFNS,WorldFederationofNeurologicalSurgeons.
fordenovoaneurysmsorlateregrowthofatreated mortality in blacks, American Indians/Alaskan Natives, and
aneurysm, but the risks and benefits of this screen- Asians/Pacific Islanders than in whites.63
ing require further study (Class IIb; Level of Evi- Available population-based studies offer much less infor-
dence B). mation about the functional outcome of survivors. Rates of
7. After any aneurysm repair, immediate cerebrovas-
persistent dependence of between 8% and 20% have been
cular imaging is generally recommended to identify
reportedwhenthemodifiedRankinScaleisused.59Although
remnants or recurrence of the aneurysm that may
not population based, trial data show a similar picture, with
require treatment (Class I; Level of Evidence B).
12%ofpatientsintheInternationalSubarachnoidAneurysm
(New recommendation)
Trial (ISAT) showing significant lifestyle restrictions (mod-
ifiedRankinScale3)and6.5%beingfunctionallydependent
(modified Rankin Scale score of 4–5) 1 year after aSAH.
Natural History and Outcome of aSAH
Furthermore,scalesthatarerelativelyinsensitivetocognitive
Although the case fatality of aSAH remains high world-
impairment, behavioral changes, social readjustment, and
wide,5 mortality rates from aSAH appear to have declined
energy level may substantially underestimate the effect of
in industrialized nations over the past 25 years.9,11,15,58,59
aSAHonthefunctionandqualityoflifeofsurvivingpatients.
OnestudyintheUnitedStatesreportedadecreaseof(cid:3)1%
Multiple studies using diverse designs have consistently
peryearfrom1979to1994.60Othershaveshownthatcase
demonstrated that intellectual impairment is very prevalent
fatalityratesdecreasedfrom57%inthemid-1970sto42%
after aSAH. Although cognitive function tends to improve
in the mid-1980s,11 whereas rates from the mid-1980s to
over the first year,64 global cognitive impairment is still
2002 are reported to be anywhere from 26% to present in (cid:3)20% of aSAH patients and is associated with
36%.6,12,13,18,20,61,62 Mortality rates vary widely across poorer functional recovery and lower quality of life.65 Cog-
published epidemiological studies, ranging from 8% to
nitive deficits and functional decline are often compounded
67%.59 Regional variations become apparent when num- by mood disorders (anxiety, depression), fatigue, and sleep
bers from different studies are compared. The median disturbances.66 Therefore, scales assessing well-being and
mortality rate in epidemiological studies from the United quality of life can be particularly useful in the integral
States has been 32% versus 43% to 44% in Europe and assessment of patients with aSAH, even among those who
27% in Japan.59 These numbers are based on studies that regain functional independence.67,68 Behavioral and psycho-
didnotalwaysfullyaccountforcasesofprehospitaldeath. social difficulties, as well as poor physical and mental
This is an important consideration because the observed endurance, are some of the most commonly encountered
decrease in case fatality is related to improvements in factorsaccountingfortheinabilityofotherwiseindependent
survival among hospitalized patients with aSAH. patients to return to their previous occupations.66,68
ThemeanageofpatientspresentingwithaSAHisincreas- Much remains to be learned about the causes of cognitive
ing, which has been noted to have a negative impact on and functional deficits after aSAH and the best methods to
survivalrates.59Sexandracialvariationsinsurvivalmayalso assess intellectual outcome and functional recovery in these
playaroleinthevariablerates,withsomestudiessuggesting patients.Theseverityofclinicalpresentationisthestrongest
higher mortality in women than in men9,11,60 and higher prognostic indicator in aSAH. Initial clinical severity can be
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1718 Stroke June 2012
reliablycategorizedbyuseofsimplevalidatedscales,suchas sciousnessin53%,andnuchalrigidityin35%.88Asmanyas
the Hunt and Hess and World Federation of Neurological 12% of patients die before receiving medical attention.
Surgeons scales.69,70 Aneurysm rebleeding is another major Despite the classic presentation of aSAH, individual find-
predictor of poor outcome, as discussed in a later section. ings occur inconsistently, and because the type of headache
Otherfactorspredictiveofpoorprognosisincludeolderage, from aSAH is sufficiently variable, misdiagnosis or delayed
preexisting severe medical illness, global cerebral edema on diagnosis is common. Before 1985, misdiagnosis of aSAH
computed tomography (CT) scan, intraventricular and intra- occurred in as many as 64% of cases, with more recent data
cerebralhemorrhage,symptomaticvasospasm,delayedcere- suggesting a misdiagnosis rate of (cid:3)12%.89,90 Misdiagnosis
bralinfarction(especiallyifmultiple),hyperglycemia,fever, wasassociatedwithanearly4-foldhigherlikelihoodofdeath
anemia,andothersystemiccomplicationssuchaspneumonia or disability at 1 year in patients with minimal or no
and sepsis.71–77 Certain aneurysm factors, such as size, neurological deficit at the initial visit.89 The most common
location,andcomplexconfiguration,mayincreasetheriskof diagnostic error is failure to obtain a noncontrast head CT
periprocedural complications and affect overall prognosis.78 scan.89,91–93 In a small subset of patients, a high degree of
Treatmentinhigh-volumecenterswithavailabilityofneuro- suspicion based on clinical presentation will lead to the
surgical and endovascular services may be associated with correct diagnosis despite normal head CT and cerebrospinal
fluidtestresults,asshowninarecentstudyinwhich1.4%of
better outcomes.79–81
patients were diagnosed with aSAH only after vascular
Natural History and Outcome of aSAH: imaging techniques were used.94
Patients may report symptoms consistent with a minor
Recommendations
hemorrhage before a major rupture, which has been called a
1. The initial clinical severity of aSAH should be deter- sentinel bleed or warning leak.83,84 The majority of these
mined rapidly by use of simple validated scales (eg, minor hemorrhages occur within 2 to 8 weeks before overt
Hunt and Hess, World Federation of Neurological aSAH. The headache associated with a warning leak is
Surgeons), because it is the most useful indicator of usuallymilderthanthatassociatedwithamajorrupture,but
outcomeafteraSAH(ClassI;LevelofEvidenceB). it may last a few days.95,96 Nausea and vomiting may occur,
2. The risk of early aneurysm rebleeding is high, and but meningismus is uncommon after a sentinel hemorrhage.
rebleeding is associated with very poor outcomes. Among 1752 patients with aneurysm rupture from 3 series,
Therefore, urgent evaluation and treatment of pa- 340 (19.4%; range, 15%–37%) had a history of a sudden
tients with suspected aSAH is recommended (Class
severeheadachebeforetheeventthatledtoadmission.82,95,97
I; Level of Evidence B).
The importance of recognizing a warning leak cannot be
3. After discharge, it is reasonable to refer patients
overemphasized. Headache is a common presenting chief
with aSAH for a comprehensive evaluation, in-
complaintintheemergencydepartment,andaSAHaccounts
cluding cognitive, behavioral, and psychosocial
for only 1% of all headaches evaluated in the emergency
assessments(ClassIIa;LevelofEvidenceB).(New
recommendation) department.92 Therefore, a high index of suspicion is war-
ranted, because diagnosis of the warning leak or sentinel
hemorrhagebeforeacatastrophicrupturemaybelifesaving.93
Clinical Manifestations and Diagnosis
Seizuresmayoccurinupto20%ofpatientsafteraSAH,most
of aSAH
commonlyinthefirst24hoursandmorecommonlyinaSAH
The clinical presentation of aSAH is one of the most
associated with intracerebral hemorrhage, hypertension, and
distinctive in medicine. The hallmark of aSAH in a patient
middle cerebral and anterior communicating artery
who is awake is the complaint “the worst headache of my
aneurysms.98,99
life,” which is described by (cid:3)80% of patients who can give
NoncontrastheadCTremainsthecornerstoneofdiagnosis
ahistory.82Thisheadacheischaracterizedasbeingextremely of aSAH; since publication of the previous version of these
sudden and immediately reaching maximal intensity (thun-
guidelines,1,2therehavebeenonlyminorchangesinimaging
derclap headache). A warning or sentinel headache that
technology for this condition. The sensitivity of CT in the
precedes the aSAH-associated ictus is also reported by 10% first 3 days after aSAH remains very high (close to 100%),
to 43% of patients.83,84 This sentinel headache increases the after which it decreases moderately during the next few
odds of early rebleeding 10-fold.85 Most intracranial aneu- days.2,100After5to7days,therateofnegativeCTincreases
rysms remain asymptomatic until they rupture. aSAH can sharply, and lumbar puncture is often required to show
occur during physical exertion or stress.86 Nevertheless, in a xanthochromia. However, advances in magnetic resonance
review of 513 patients with aSAH, the highest incidence of imaging of the brain, particularly the use of fluid-attenuated
rupture occurred while patients were engaged in their daily inversionrecovery,protondensity,diffusion-weightedimag-
routines,intheabsenceofstrenuousphysicalactivity.87The ing, and gradient echo sequences,101–103 can often allow the
onsetofheadachemaybeassociatedwith(cid:1)1additionalsigns diagnosis of aSAH to be made when a head CT scan is
andsymptoms,includingnauseaand/orvomiting,stiffneck, negative and there is clinical suspicion of aSAH, possibly
photophobia, brief loss of consciousness, or focal neurolog- avoidingtheneedforlumbarpuncture.Theroleofmagnetic
ical deficits (including cranial nerve palsies). In a retrospec- resonanceimaginginperimesencephalicaSAHiscontrover-
tive study of 109 patients with proven aSAH, headache was sial.104 Indications for magnetic resonance angiography in
present in 74%, nausea or vomiting in 77%, loss of con- aSAH are still few because of limitations with routine
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Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1719
availability,logistics(includingdifficultyinscanningacutely coiling was achieved in 92.6%. The authors concluded that
illpatients),predispositiontomotionartifact,patientcompli- CTAwitha64-slicescannerisanaccuratetoolfordetecting
ance,longerstudytime,andcost.Aneurysms(cid:2)3mminsize andcharacterizinganeurysmsinacuteaSAHandthatCTAis
continue to be unreliably demonstrated on computed tomo- useful in deciding whether to coil or clip an aneurysm.115
graphic angiography (CTA),105,106 and this generates contin- Partial volume averaging phenomena may artificially widen
ued controversy in the case of CTA-negative aSAH.107 In the aneurysmal neck and may lead to the erroneous conclu-
casesofperimesencephalicsubarachnoidhemorrhage(SAH), sion that an aneurysm cannot be treated by endovascular
someauthorsclaimthatanegativeCTAresultissufficientto coiling. This controversy is likely caused by the different
rule out aneurysmal hemorrhage and that cerebral angiogra- technological specifications (16- versus 64-detector rows),
phy is not required, but this is controversial. In 1 study, the slicethickness,anddataprocessingalgorithmsofvariousCT
overallinterobserverandintraobserveragreementfornonan- systems, which have different spatial resolutions. Three-
eurysmalperimesencephalichemorrhagewasgood,butthere dimensional cerebral angiography is more sensitive for de-
was still a level of disagreement among observers, which tectinganeurysmsthan2-dimensionalangiography.121,122The
suggests that clinicians should be cautious when deciding combination of 3- and 2-dimensional cerebral angiography
whethertopursuefollow-upimaging.108Inanotherstudy,109 usually provides the best morphological depiction of aneu-
a negative CTA result reliably excluded aneurysms when rysm anatomy with high spatial resolution, and it is, of
head CT showed the classic perimesencephalic SAH pattern course,alwaysusedinpreparationforendovasculartherapy.
or no blood. Digital subtraction angiography (DSA) was Flat-panel volumetric CT is a relatively recent develop-
indicatediftherewasadiffuseaneurysmalpatternofaSAH, ment that allows the generation of CT-like images from a
and repeat delayed DSA was required if the initial DSA rotational 3-dimensional spin of the x-ray gantry in the
findingswerenegative,whichledtothedetectionofasmall angiographyroom.Forthemoment,ithasnosubstantialrole
aneurysm in 14% of cases. When the blood is located in the in the initial diagnosis of aSAH because its spatial and
sulci, CTA should be scrutinized for vasculitis, and DSA is contrast resolutions are not high enough123; however, this
recommended for confirmation.109 Others have shown that technology can be used intraprocedurally during emboliza-
CTA may not reveal small aneurysms and that 2- and tions to rule out hydrocephalus.124 Recently, radiation dose
3-dimensional cerebral angiography should be performed, hasemergedasanimportantandworrisomeconsiderationfor
especially when the hemorrhage is accompanied by loss of patients with SAH.125,126 The combination of noncontrast
consciousness.110 In cases of diffuse aSAH pattern, most headCTforthediagnosisofaSAH,confirmationofventric-
agree that negative CTA should be followed by 2- and ulostomy placement, investigation of neurological changes,
3-dimensional cerebral angiography. In older patients with CTA for aneurysmal diagnosis, CTA and CT perfusion for
degenerative vascular diseases, CTA can replace catheter recognitionofvasospasm,andcathetercerebralangiography
cerebral angiography in most cases if the image quality is foraneurysmembolizationandthenforendovasculartherapy
excellent and analysis is performed carefully.111 Overlying of vasospasm can result in substantial radiation doses to the
bone can be problematic with CTA, especially at the skull head, with possible risk of radiation injury, such as scalp
base. A new technique, CTA-MMBE (multisection CTA erythema and alopecia. Although some or all of these radio-
combined with matched mask bone elimination), is accurate logical examinations are often necessary, efforts need to be
indetectingintracranialaneurysmsinanyprojectionwithout made to reduce the amount of radiation exposure in patients
superimposedbone.112CTA-MMBEhaslimitedsensitivityin with aSAH whenever possible.
detecting very small aneurysms. The data suggest that DSA
Clinical Manifestations and Diagnosis of aSAH:
and 3-dimensional rotational angiography can be limited to
Recommendations
the vessel harboring the ruptured aneurysm before endovas-
cular treatment after detection of a ruptured aneurysm with
1. aSAH is a medical emergency that is frequently
CTA. Another new technique, dual-energy CTA, has diag-
misdiagnosed. A high level of suspicion for aSAH
nostic image quality at a lower radiation dose than digital
should exist in patients with acute onset of severe
subtractionCTAandhighdiagnosticaccuracycomparedwith
headache (Class I; Level of Evidence B).
3-dimensional DSA (but not 2-dimensional DSA) in the 2. Acutediagnosticworkupshouldincludenoncontrast
detection of intracranial aneurysms.113 headCT,which,ifnondiagnostic,shouldbefollowed
Cerebral angiography is still widely used in the investiga- by lumbar puncture (Class I; Level of Evidence B).
tion of aSAH and the characterization of ruptured cerebral 3. CTA may be considered in the workup of aSAH. If
aneurysms. Although CTA is sometimes considered suffi- an aneurysm is detected by CTA, this study may
cient on its own when an aneurysm will be treated with helpguidethedecisionfortypeofaneurysmrepair,
butifCTAisinconclusive,DSAisstillrecommended
surgical clipping,114 substantial controversy remains about
(exceptpossiblyintheinstanceofclassicperimesen-
theabilityofCTAtodeterminewhetherornotananeurysm
cephalic aSAH) (Class IIb; Level of Evidence C).
is amenable to endovascular therapy.115–120 In 1 series,115
(New recommendation)
95.7%ofpatientswithaSAHwerereferredfortreatmenton
4. Magneticresonanceimaging(fluid-attenuatedinver-
the basis of CTA. In 4.4% of patients, CTA did not provide sion recovery, proton density, diffusion-weighted
enoughinformationtodeterminethebesttreatment,andthose imaging, and gradient echo sequences) may be rea-
patients required DSA; 61.4% of patients were referred to sonableforthediagnosisofaSAHinpatientswitha
endovascular treatment on the basis of CTA; and successful nondiagnostic CT scan, although a negative result
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