SAH Guideline Evidence-Based Guidelines for the Management of Aneurysmal Subarachnoid ...

75 Pages·2012·0.82 MB·English

Neurol Med Chir (Tokyo) 52, 355¿429, 2012
SAH Guideline
Evidence-Based Guidelines for the Management of
Aneurysmal Subarachnoid Hemorrhage
English Edition
Committee for Guidelines for Management of
Aneurysmal Subarachnoid Hemorrhage,
Japanese Society on Surgery for Cerebral Stroke
Foreword July, 2011
Akira TERAMOTO, MD, PhD
On behalf of the Japan Neurosurgical Society, I am President, the Japan Neurosurgical Society
proud to welcome the publication of this English Dean, Graduate School of Medicine,
edition of ``Evidence-Based Guidelines for the Nippon Medical School
Management of Aneurysmal Subarachnoid Hemor-
rhage''by our colleagues of the Japanese Society on
Surgery for Cerebral Stroke.
The treatment of aneurysmal subarachnoid Foreword
hemorrhage, i.e. the rupture of cerebral aneurysm,
has been a major concern for neurosurgeons in our On behalf of the Japan Stroke Society, I am pleased
country over the past several decades. Many to extend my warmest congratulations to our col-
pioneers have enthusiastically worked to improve leagues of the Japanese Society on Surgery for
the surgery of cerebral aneurysms, to develop high CerebralStrokeforpublishingtheEnglisheditionof
quality aneurysm clips, and to establish the optimal ``Evidence-Based Guidelinesforthe Managementof
timingforsurgeryofrupturedaneurysm.TheJapan Aneurysmal Subarachnoid Hemorrhage.'' Together
Neurosurgical Society has trained many neurosur- with our society, we are fighting against stroke in
geons capable of operating for cerebral aneurysm Japan.
who now work in neurosurgical institutions, large ThefirsteditionofthissetofGuidelineswaspub-
or small, throughout the country. lished in 2003 in Japanese as one of the pioneering
The original edition of this set of Guidelines was guidelines in Japan, developed according to the
published in 2003, aiming to standardize the process of evidence-based medicine (EBM). This
management of aneurysmsby avoiding unfavorably event had profound reverberations on the medical
biased strategies while respecting reasonable deci- society and has been a model for developing guide-
sions of individual neurosurgeons. The Guidelines lines in many other fields.
were revised in 2008 following the rapid develop- The Guidelineswere revised in 2008byincluding
ment of endovascular technique. The present set of some new evidences mainly from the field of en-
GuidelinesistheEnglishversionofthisrevisededi- dovascular treatment. The Guidelines contributed
tion.ItisgratifyingtointroducethisEnglishversion greatly to standardize the strategy and improve the
of the Guidelines, a commendable achievement to qualityofmanagementofsubarachnoidhemorrhage
record the enthusiasm of Japanese neurosurgeons, in our country. The present set of Guidelines is the
handed down from our pioneers. English version of this revised edition. I hope that
On publication of this English edition of the this set of Guidelines will become a valuable refer-
Guidelines, we hope that the Guidelines will be use- ence in the management of aneurysmal subara-
ful to many colleagues in different countries with chnoid hemorrhage not only in Japan but also in
different medicosocial backgrounds. We also wel- many other countries as well.
comevaluablefeedbackfrommanyinternationalex- Finally, I would like to express my deepest grati-
perts. tude to the chairman, Prof. Toshiki Yoshimine, and
the committee members, who volunteered their
335555
335566 Evidence-Based Guidelines for the Management of Aneurysmal SAH
strenuousefforts,time,and expertise ineditingand Japan.'' The access of patients to medical care is
translating this set of Guidelines. rather easy in Japan throughout the country. Every
patientisbasicallytreatedwithstandardprocedures
July, 2011 approved by the public insurance. There is often a
Akira OGAWA, MD, PhD rough consensus in the management among neu-
President, the Japan Stroke Society rosurgeons. The strategies described in this set of
President, Iwate Medical University Guidelines are, we suppose, not largely different
from the typical procedures in Japan.4)
In medical practice, however, the best strategy of
choice in an individual patient is determined by a
Preface to the English Edition numberofscientificandnon-scientificfactors.This
set of Guidelines may not globally be applicable to
The first edition of ``Evidence-Based Guidelines for every patient. Each patient may be managed by the
the Management of Aneurysmal Subarachnoid decision of the physician in charge based on per-
Hemorrhage''waspublishedin2003bytheJapanese sonal experience and knowledge. It is our pleasure
Society on Surgery for Cerebral Stroke, sponsored to present this set of Guidelines to be an additional
by the Ministry of Health, Labour and Welfare of source of information. Valuable comments and ad-
Japan.1) According to the process of evidence-based vice about this set of Guidelines from colleagues
medicine(EBM),theGuidelineswereeditedbycriti- worldwide would be highly appreciated.
cal review of the medical information published in
Japanandoverseasfrom1990to2000,collectedbya April, 2011
systemic search of MEDLINE, Cochrane Library, Toshiki YOSHIMINE, MD, PhD
and Japan MedicalAbstracts Society(Ichushi).This Chairman,
set of Guidelines has been widely adapted as a fun- Committee for Guidelines for Management of
damental reference in medical as well as non-medi- Aneurysmal Subarachnoid Hemorrhage,
cal fields in Japan soon after publication, and was Japanese Society on Surgery for Cerebral Stroke
also translated into Korean.2) The revised edition
waspublishedin2008toincludenewinformationof Nobuo HASHIMOTO, MD, PhD
therapeutic and diagnostic measures. The present President,
set of Guidelines is the English translation of this Japanese Society on Surgery for
revised edition. Cerebral Stroke
In a recent meta-analysis on population-based
case fatality following subarachnoid hemorrhage,
the case fatality in Japan was significantly lower
From the Preface to the Revised
than in Europe, the USA, Australia, and New
Zealand.3) The authors stated that these differences Japanese Edition
might be attributable to the methodological differ-
encesbetweenthestudiesortothedifferencesinthe The first edition of ``Evidence-Based Guidelines for
managementofpatients.Theyalsostatedthat``With the Management of Aneurysmal Subarachnoid
regardtothemanagement,thestrategyofadmitting Hemorrhage'' was published in Japanese by the
patients early and the early occlusion of aneurysm Japanese Society on Surgery for Cerebral Stroke in
might, in part, explain the low case fatality rates in 2003. Prepared with systematic review of Japanese
and international literature, it was one of the first
1) Health Sciences Research Grants for Research on setsofhealthcareguidelinesinJapaneditedaccord-
HealthTechnologyAssessment,2000,andforDevelop- ing to the process of evidence-based medicine
mentandPromotionof21stCentury-typeMedicalCare, (EBM). Soon after publication, the Guidelines have
2001,from the MinistryofHealth,Labour andWelfare beenwidelyconsultedinbothmedicalandnon-med-
of Japan.
ical areas. Many important developments have,
2) Korean translation by Seo Dae-Hee and Park Sung-
Choon(KwandongUniversity)waspublishedbyKoonja
Publishing Inc., Seoul, in 2007. 4) ThissetofGuidelinesisapprovedforpublicationbythe
3) Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij Japan Neurosurgical Society.
NK, Rinkel GJ: Changes in case fatality of aneurysmal
subarachnoidhaemorrhageovertime,accordingtoage, ＊Special thanks are due to Khoo Hui Ming, MD, Osaka,
sex, and region: a meta-analysis. Lancet Neurol 8: Japan,forherirreplaceableassistanceintranslatingthis
635–642,2009. work.
Neurol Med Chir (Tokyo) 52, June, 2012
Evidence-Based Guidelines for the Management of Aneurysmal SAH 335577
however,occurredduringthesubsequentfewyears, Medicine)
particularly in the field of endovascular treatment. Takeshi KAWASE (Professor emeritus, Department
We have also received some critical questions and of Neurosurgery, Keio University Graduate
valuablecommentsfromourreaders.Therefore,the School of Medicine)
Committee was formed to revise the Guidelines. Takaaki KIRINO (Dean, Faculty of Medicine and
Mostoftherevisionsaretoincorporateupdatesof Graduate School of Medicine,the University of
advances in endovascular treatment and torespond Tokyo)
to the questions and comments from readers: Shigeaki KOBAYASHI (Professor, Department of
1) Contents and expressions in the revised edition Neurosurgery, Shinshu University School of
were modified and corrected to resolve the ques- Medicine)
tions and to adopt the comments from clinicians IzumiNAGATA(Director,DepartmentofNeurosur-
and legal experts. gery, National Cardiovascular Center)
2) Statements on drugs and treatments, not yet offi- Hideaki NUKUI (Professor, Department of Neu-
cially approved in Japan, but supported by some rosurgery, Yamanashi University Graduate
internationalevidence,wereaddedinthisedition School of Medicine)
in answer to feedback from readers overseas. AkiraOGAWA(Professor,DepartmentofNeurosur-
3) Expressions of ``levelofevidence''and ``grade of gery, Iwate Medical University)
recommendation'' were revised by applying the TakashiOHMOTO(Professor,Departmentofneuro-
scheme adopted from the ``Japanese Guidelines logical Surgery, Okayama University Graduate
for the Management of Stroke, 2004,''5) which School of Medicine)
were published after the publication of the first Isamu SAITO (Director, Fuji Brain Institute and
edition,jointlywiththeJapanStrokeSocietyand Hospital)
other academic organizations. Mamoru TANEDA (Professor, Department of Neu-
The executive summary is outlined in the ``Com- rosurgery, Kinki University Faculty of Medi-
mentary on the revised edition.'' cine)
Every sentence constituting the Guidelines is Hirotsugu UESHIMA (Professor, Department of
based on serious and earnest discussions by the Health Science, Shiga University of Medical
Committeemembers.Iwishtothankallmembersof Science)
the Committee without whom this revision would Kazuo YAMADA (Professor, Department of Neu-
not have been possible, for their commitment in rosurgery, Nagoya City University Graduate
preparing this edition. School of Medicine)
TakenoriYAMAGUCHI(PresidentEmeritus,Nation-
Toshiki YOSHIMINE, MD, PhD al Cardiovascular Center, Department of Medi-
Chairman, cine, Cerebrovascular Division)
Committee for Guidelines for the Management of Akira YAMAURA (Professor, Department of Neu-
Aneurysmal Subarachnoid Hemorrhage rosurgery,ChibaUniversityGraduateSchoolof
Japanese Society on Surgery for Cerebral Stroke Medicine)
Takashi YOSHIMOTO (Director, Tohoku University
Graduate School of Medicine; Department of
Neurosurgery)
Contributor:
COMMITTEE MEMBERS Kazuo HASHI (Professor emeritus, Department of
Neurosurgery, Sapporo Medical University)
〈First Japanese Edition〉
Chief Researcher: 〈Second Japanese Edition〉
ToshikiYOSHIMINE(Professor,DepartmentofNeu- Chairman:
rosurgery,OsakaUniversityGraduateSchoolof Toshiki YOSHIMINE (Osaka University Graduate
Medicine) School of Medicine)
Sub-researchers: Members:
NobuoHASHIMOTO(Professor,DepartmentofNeu- Isao DATE (Okayama University Graduate School
rosurgery,KyotoUniversityGraduateSchoolof of Medicine)
Nobuo HASHIMOTO (National Cardiovascular Cen-
5) TheJointCommitteeonGuidelinesfortheManagement ter)
of Stroke: Japanese Guidelines for the Management of Kazuhiro HONGO (Shinshu University School of
Stroke (2004).Tokyo, KyowaKikaku Ltd.,2004. Medicine)
Neurol Med Chir (Tokyo) 52, June, 2012
335588 Evidence-Based Guidelines for the Management of Aneurysmal SAH
Kiyohiro HOUKIN (Hokkaido University Graduate of Medicine)
School of Medicine) Kazuhide FURUYA (Teikyo University Graduate
TakeshiKAWASE(KeioUniversityGraduateSchool School of Medicine)
of Medicine) Kenichi HATTORI (Nagoya University Graduate
Takamasa KAYAMA (Yamagata University Faculty School of Medicine)
of Medicine) KojiIIHARA(NationalCerebralandCardiovascular
Hiroyuki KINOUCHI (Yamanashi Graduate School Center)
of Medicine) Takashi INOUE (Iwate Medical University)
Takaaki KIRINO (International Medical Center of YukinariKAKIZAWA(ShinshuUniversitySchoolof
Japan) Medicine)
Eiji KOHMURA (Kobe University Graduate School Hiroshi KASHIMURA (Iwate Medical University)
of Medicine) Kazuo KATAOKA (Nara Hospital, Kinki University
Susumu MIYAMOTO (Kyoto University Graduate Faculty of Medicine)
School of Medicine) Naoki KITAGAWA (Nagasaki University Graduate
Izumi NAGATA (Nagasaki University Graduate School of Medicine)
School of Medicine) Eiichi KOBAYASHI (Chiba University Graduate
Akira OGAWA (Iwate Medical University) School of Medicine)
Naokatsu SAEKI (Chiba University Graduate ReiKONDO(YamagataUniversityFacultyofMedi-
School of Medicine) cine)
Isamu SAITO (Fuji Brain Institute and Hospital) Hiroki KURITA (Kyorin University Faculty of
NobuhitoSAITO(theUniversityofTokyoGraduate Medicine)
School of Medicine) MitsuhitoMASE(NagoyaCityUniversityGraduate
NobuyukiSAKAI(KobeCityMedicalCenterGener- School of Medicine)
al Hospital) Shigeru MIYACHI (Nagoya University Graduate
Hirotoshi SANO (Fujita Health University) School of Medicine)
Tomio SASAKI (Kyushu University Graduate Akio MORITA (NTT Medical Center Tokyo)
School of Medicine) Shinji NAGATA (National Hospital Organization
Yoshiaki SHIOKAWA (Kyorin University Graduate Kyushu Medical Center)
School of Medicine) Tadashi NONAKA (Sapporo Medical University)
Akira TAKAHASHI (Tohoku University Graduate Kazuhiko NOZAKI (Kyoto University Graduate
School of Medicine) School of Medicine)
Waro TAKI (Mie University) Sho OKAMOTO (Nagoya University Graduate
Mamoru TANEDA (Kinki University Faculty of School of Medicine)
Medicine) Tomonori OKAMURA (National Cardiovascular
Teiji TOMINAGA (Tohoku University Graduate Center)
School of Medicine) Shigeki ONO (Okayama University Graduate
Hirotsugu UESHIMA (Shiga University of Medical School of Medicine)
Science) Satoshi ONOZUKA (Keio University Graduate
KazuoYAMADA (Nagoya City University Graduate School of Medicine)
School of Medicine) Ryoichi OTSUBO (National Cardiovascular Center)
Takenori YAMAGUCHI (National Cardiovascular HiroshiSAKAIDA(MieUniversityGraduateSchool
Center) of Medicine)
Akira YAMAURA (Chiba University Graduate Masao SUGITA (Yamanashi University Graduate
School of Medicine) School of Medicine)
Jun YOSHIDA (Japan Labour Health and Welfare Yasushi TAKAGI (Kyoto University Graduate
Organization Chubu Rosai Hospital) School of Medicine)
Secretariat Members: AtsushiUMEMURA(NagoyaCityUniversityGradu-
Toshiyuki FUJINAKA (Osaka University Graduate ate School of Medicine)
School of Medicine) Contributor:
Hajime NAKAMURA (Osaka University Graduate HiroakiSHIMIZU(KohnanHospital;Secretariatfor
School of Medicine) the Japanese Society on Surgery for Cerebral
Working Group Members: Stroke)
Masayuki EZURA (Sendai Medical Center)
Miki FUJIMURA (Sendai Medical Center) (In alphabetical order of family name)
Atsushi FUJITA (Kobe University Graduate School
Neurol Med Chir (Tokyo) 52, June, 2012
Evidence-Based Guidelines for the Management of Aneurysmal SAH 335599
GUIDELINES
Introduction
Methodology for Preparation
Accordingtothepopulationstatisticsof1998bythe of the Guidelines
MinistryofHealth,LabourandWelfare,themortali-
ty from subarachnoid hemorrhage (SAH)is 11.8per 〈First Japanese edition〉
100,000 population, accounting for about 1/10 of all InanefforttodeveloptheGuidelinesbasedonthe
deaths from stroke. About half of the deaths from concept of evidence-based medicine, we conducted
stroke in the younger population are attributable to a systematic literature review on the Japanese and
SAH.SAHoccursatahighincidenceduringtheso- international published data in this field, between
cially active period of life (youth to middle-age),
often resulting in severe disability or death. In the
management of SAH, appropriate judgment is re-
Table 1 Methods used for preparation of the first
quired on many aspects, including diagnosis, edition
pathophysiological evaluation, method and timing
of aneurysm treatment, and management of in- 1) Research questions were selected from fields related to the
managementofpatientswithsubarachnoidhemorrhage.
tracranialas well as systemic complications in both
2) Foreachresearchquestion,medicalpaperspublishedinJapan
acute and the chronic stages. These judgments im- andoverseasbetween1990and2001werecollectedthrougha
search of MEDLINE, Cochrane Library, and Japana Centra
pact greatly on the outcome of the patients.
RevuoMedicina.Atotalof15,830paperswerecollected.
Given the severity of the disease and the number 3) From the collected medical papers, 1,101 presenting high-
of patients affected, the Healthcare Technology qualityevidence wereselectedaccordingtotheprinciplesof
evidence-based medicine and their abstract forms were pre-
Evaluation and Promotion Committee of the Minis- pared.
try of Health, Labour and Welfare of Japan ranked 4) Evidencetableswerepreparedfromthedatabasecomposedof
theabstractforms.
SAH as one of the top 10 high priority diseases,
5) On the basis of the evidence tables, a set of management
whichurgentlyneedhighqualityguidelinesforclin- guidelineswaspreparedbasedonageneralassessmentofthe
ical practice (March, 1999). Subsequently, the first quality of evidence, magnitude of the benefits arising from
each healthcare procedure, magnitude of the burden on the
edition of the Guidelines was published in 2003 by individuals and the society, and so on. The grade of recom-
theJapaneseSocietyonSurgeryforCerebralStroke, mendationwasspecifiedforeachhealthcareprocedure.
supported by the Ministry of Health, Labour and
Welfare of Japan.
Afterthepublicationofthefirstedition,however, Table 2 Methods used for preparation of the first
the techniques in the diagnosis and treatment of edition
SAH have advanced rapidly, particularly in en-
1) Usingasimilarproceduretothatusedforthepreparationof
dovascular treatment. We also have received valua- the first edition, medical papers on each research question
pertaining to subarachnoid hemorrhage published in Japan
blecommentsfromourcolleagues.Thisrevisededi-
andoverseasbetween2001and2004werecollectedthrougha
tion was prepared to update the information and search of MEDLINE, Cochrane Library, and Japana Centra
RevuoMedicina.Atotalof5,799paperswerecollected.
recommendations,aswellastorespond tothe feed-
2) Allofthese5,799paperswerereviewedandpaperswithlow
back from readers in various fields. evidence level were excluded. Finally, 342 papers were
adopted.Paperspertainingtocasestudieswereadoptedifthey
involved a large number of cases or addressed important
Objectives of the Guidelines
researchquestions.Inaddition,drugsandtreatmentmethods
notyetapprovedinJapanwerealsoinvestigated.
3) The342papersmentionedaboveweregroupedby field,and
Management of aneurysmal SAH involves high lev-
theirabstractformswereprepared.Somepaperspertainedto
elsofexpertiseandhasbeenperformedprimarilyby twoormorefields.Finally,483abstractformswereprepared.
neurosurgeons. However, the cooperation of other The main text of the revised Guidelines was drafted on the
basisoftheseabstractforms,primarilybycommitteemembers
specialties, including critical care, neurology, radi- responsible for the individual fields. The draft was then
ology,intensivecare,anesthesiology,andrehabilita- reviewed by all committee members to produce the revised
Guidelines.Finally,77paperswereaddedtothereferences.
tionisalsorequired.ThissetofGuidelinesisaimed 4) ``Evidence level'' and ``grades of recommendation'' were
not only at providing guidance to neurosurgeons, modifiedintoonesidenticaltothoseadoptedinthe``Japanese
GuidelinesfortheManagementofStroke.''Thiswaspublished
but also at supporting healthcare professionals of
bytheJointCommitteeonGuidelinesfortheManagementof
other specialties to understand the management of StrokecomposedofmembersoftheJapanStrokeSociety,the
JapanNeurosurgicalSociety(theJapaneseSocietyonSurgery
this condition, with the goal of facilitating effective
for Cerebral Stroke), the Societas Neurologica Japonica, and
cooperation and improving the outcome of patients theJapaneseAssociationofRehabilitationMedicine(Tables4
and5).
with SAH.
Neurol Med Chir (Tokyo) 52, June, 2012
336600 Evidence-Based Guidelines for the Management of Aneurysmal SAH
Table 3 Summary of collected articles
Firstedition Addedduringrevision Secondedition
Totalnumberofpapers Numberofaddedpapers: Totalnumberofpapers
collected:15,830 5,799 collected:21,629
(1990–2001) (2001–2004) (1990–2004)
Numberof Numberof Numberof Numberof Numberof Numberof
abstract evidence abstract evidence abstract evidence
forms tables forms tables forms tables
I. Epidemiology 123 28 67 11 190 39
II. Diagnosis 268 67 121 4 389 71
III. Treatment
1. Managementintheacutestage
1–1. Initialtreatment 64 15 78 6 142 21
1–2. Treatmentofcerebralaneurysm
1–2–1. Selectionoftreatmentmeasures 36 20 49 6 85 26
1–2–2. Surgicaltreatment 181 29 32 9 213 38
1–2–3. Endovasculartreatment 80 54 49 22 129 76
1–2–4. Conservativetreatment 27 11 8 2 35 13
1–3. Treatmentofcerebralvasospasm 144 24 67 13 211 37
2. Managementaftertheacutestage 185 27 12 4 197 31
Total 1108 275 483 77 1591 352
(7papers (141papers (148papers
overlapped) overlapped) overlapped)
1990 and 2001. Only studies with high level of evi- Table 4 Classification of evidence levels
dence were selected and summarized in an abstract
form. The Guidelines, intended to summarize the Levelof Typeofevidence
evidence
best available evidence for treatment of patients
withaneurysmalSAH,waspreparedbasedonthese Ia Meta-analysis (with homogeneity) of randomized
controltrials
selected studies (Table 1). A grade of recommenda- Ib Atleastonerandomizedcontroltrial
tionisattachedtoeachrecommendationofmanage- IIa At least one well designed, controlled study but
ment. withoutrandomization
IIb Atleastonewelldesigned,quasi-experimentalstudy
III Atleastonewelldesigned,non-experimentaldescrip-
〈Revised Japanese edition〉 tive study (ex. comparative studies, correlation
studies,casestudies)
This second edition of the Guidelines revisits the
IV Expertcommitteereports,opinionsand/orexperience
recommendations based on Japanese and interna- ofrespectedauthorities
tional updated evidence, published between 2001
and2004,andwasdevelopedinaccordancewiththe
methodologyofthe first edition(Table 2).The num-
Table 5 Classification of recommendation grades
bers of abstract forms and evidence tables prepared
duringthedevelopmentofboththefirstandthesec- Gradesof Typeofrecommendation
recommendation
ond edition were summarized based on research
question (Table 3). A Strongly recommended (based on strong
evidence)
B Recommended(basedonmoderateevidence)
Grades of Recommendation
C1 Deserving consideration (based on weak
evidence)
For each healthcare measure listed in this set of C2 Neutral(nosupportiveordenyingevidence)
D Notrecommended(nosupportiveevidence)
Guidelines,thegradeofrecommendationwasspeci-
fied as follows.
First,thelevelofevidenceforeacharticlewasrat-
ed on the basis of its research design (Table 4). The were classified into five levels (four in the first edi-
grades of recommendation were formulated based tion) and are indicated in parentheses (Table 5).
onprimarilythelevelofevidence;nevertheless,fur- Furthermore, for epidemiology and diagnosis, in-
therassessmentofotherfactorsbeyondthescopeof stead of ``grades of recommendation,'' ``strength of
evidencewasalsoconsidered.Intherevisededition evidence'' was indicated based on the aforemen-
of the Guidelines, the grades of recommendation tioned basis.
Neurol Med Chir (Tokyo) 52, June, 2012
Evidence-Based Guidelines for the Management of Aneurysmal SAH 336611
Points of Revision ble or even better than digital subtraction an-
giography (DSA) in providing information for de-
In this revision, we conducted a systematic litera- veloping surgical strategies.
ture review on the Japanese and international pub-
lished data in this field, between 1990 and 2001, 〈Treatment〉
based on 5,799 articles yielded from a search of Managementintheacutestage:Thereweresome
MEDLINE, Cochrane Library, and Japan Medical new reports on the effect of antifibrinolytic therapy
Abstracts Society (Ichushi). After excluding articles in preventing rebleeding. As described in the first
with low levels of evidence, 342 articles were edition, the use of antifibrinolytic agents does not
retrieved. Case studies, chosen on the basis of sam- improve the overall outcome of SAH, because the
plesizeorrelevanceoftheparticularstudiestocriti- reduction in the incidence of rebleeding is offset by
cal research questions, were included. In addition, an increasedrate ofcerebralischemia.Therefore,it
this revised edition also included studies on drugs is not recommended in the routine practice. Never-
and treatments not yet approved in Japan. Finally, theless, some investigators have reported its useful-
the342paperswereaddedtothe1,101papersadopt- ness in preventing rebleeding during patient trans-
edforthefirstedition,toproducetherevisededition fer. Therefore, the decision regarding the use of an-
of the Guidelines. tifibrinolytic therapy should be customized to the
The essential points in this revision are outlined situation in a given case.
below. In regard to the most severe SAH cases, the first
edition stated that ``In principle, preventive meas-
〈Epidemiology〉 uresforrebleedingarenotindicatedinthesecases.''
No major modifications were made in the section However, evidence demonstrating that ``favorable
on epidemiology, although 11 additional papers outcomesareattainable withsurgeryeveninsevere
wereadopted.Thenewcontentsinclude:1)reported casesifperformedwithin6hoursaftertheinitialic-
higher mortality of SAH in women than in men, in- tus,sincetheriskofrebleedinginthesecasesisobvi-
dependent of race; 2) multiple reports on family ouslyhigherthanthosewithmildhemorrhage''was
historyasariskfactorforSAH;and3)reportonpsy- foundinthestudiesadditionallyadoptedduringthe
chophysiological tension as a risk factor for SAH. revision, and therefore this statement was included
Ananalysisofthelong-termresultsshowedthatthe in the second edition of the Guidelines.
mortalityofpatientswithSAHishigherthanthatof Numerous reports, including the International
the generalpopulation,evenafterappropriate treat- Subarachnoid Aneurysm Trial, have been newly
mentoftherupturedcerebralaneurysm,attributable published inthe field ofendovascularmanagement.
to cerebrovascular or cardiovascular disease. Therehasbeengrowingacceptancethattheefficacy
of this approach is comparable to that of surgical
〈Diagnosis〉 treatment, despite the issues of long-term incidence
The validity of cerebral angiography as the initial ofrebleeding(22ofthe77papersadoptedduringthe
test for localization of the ruptured aneurysm has revision pertained to endovascular treatment).
been discussed. The first edition stated that ``Given Therefore,astatementwasaddedtothesecondedi-
the high incidence and poor outcome of re-rupture, tion to suggest that endovascular treatment should
angiographywithin6hoursisavoidedinsomefacil- be considered as a preventive measure for rebleed-
ities.'' However, some readers did not agree with ing, not only in high risk cases for surgery, but
thisstatementbecauseofinadequatesupportingevi- wheneverendovasculartreatmentistechnicallypos-
dence. After a thorough discussion, the Committee sible.Thesectiononendovascularmanagementwas
decided to state only the available evidence in the substantiallyrevised,asaresultofrapidevolutionof
second edition, i.e. ``The incidence of rupture asso- newer evidence in this field.
ciated with cerebral angiography performed within Monitoring of cerebral blood flow and oxygen
6 hours of initial ictus is reported to be 4.8%.'' saturationduringtemporaryocclusionoftheparent
The first edition stated that ``Three-dimensional vessel,aswellassupportivemeasureswithneuroen-
computed tomographyangiography(3D-CTA)isun- doscopy or intraoperative cerebral angiography,
suitable for detecting aneurysms less than 3–4mm have been reported useful for preventing complica-
in diameter.'' However, with marked improvement tions. In addition, the usefulness of combined treat-
in the detection capability of this modality, this ment such as a combination of endovascular treat-
statement was revised and ``less than 3–4mm'' has ment and bypass surgery has also been reported.
beenchangedto``lessthan2mm''inthesecondedi- Concerningcerebralvasospasm,investigationson
tion. Moreover, 3D-CTA is reported to be compara- drugs and treatment methods not yet approved in
Neurol Med Chir (Tokyo) 52, June, 2012
336622 Evidence-Based Guidelines for the Management of Aneurysmal SAH
Japan were also included in this revision. There is icpatientsneedtobeindividualizedbasedonthe
no consensusavailable onthe usefulnessofnimodi- assessment of the attending physician.
pine(acalciumchannelantagonistnotyetapproved 2) As stated above, the Guidelines are not intended
in Japan), as well as other calcium channel an- for either the standardization of management of
tagonists; therefore, only the fact was added in the SAHortheevaluationofindividualmanagement
second edition. No other drug of this category has ofSAH.Therefore,thecontentsoftheGuidelines
been shown to be effective to date. shouldnot be quoted forevaluationofindividual
The effectiveness of the intra-arterial infusion of management,orusedinmedicalmalpracticeliti-
fasudil hydrochloride (a drug often used in Japan) gation.Cautionshouldbetakenintheimplemen-
for cerebral vasospasm is well-documented. There- tation of the Guidelines, since subjects related to
fore, the current status of the off-label use of this drugs/treatment not yet approved in Japan, off-
druginJapan,aswellasothers,wasincludedinthis labeluse ofdrugs/treatment and etc.,are also co-
revisededition.Fasudilhydrochloridewasprevious- vered.
ly termed ``myosin phosphatase activation inhibi- 3) SAH is a sudden and devastating event and is
tor.'' Based on the recent findings, the term ``Rho characterized by diverse pathophysiological fea-
kinase inhibitor'' was indicated in the second edi- tures. There are still many unresolved problems
tion. andpoorlyevidencedclinicalquestionsrelatedto
Managementaftertheacutestage:Inthesection its management. Therefore, the Guidelines may
of the chronic stage pathophysiology, in addition to also contain some incomplete or inaccurate
hydrocephalus,whichwasdescribedinthefirstedi- statements/descriptions. Due to rapid evolution
tion, epilepsy associated with SAH and Terson's of newer treatment modalities, as well as other
syndromewerealsodescribedinthesecondedition. practicalandethicalconsiderations,theevidence
Since recurrenthemorrhage ismorelikelyaftercoil providedinthisGuidelinesisnotalwaysthemost
embolization,comparedtosurgicalclipping,theim- updated or the best available.
portance of outpatient follow-up of the former was 4) During this revision, the level of evidence and
emphasized in the second edition. grade of recommendation were decided by ap-
plying the scheme adopted from the ``Japanese
Using the Guidelines GuidelinesfortheManagementofStroke,''which
was published by the Joint Committee on Guide-
1) The Guidelines are intended to recommend the lines for the Management of Stroke composed of
best available evidence for the management of members of the Japan Stroke Society, the Japan
SAH, so should not be used as a comprehensive Neurosurgical Society (the Japanese Society on
clinicalmanagementmanualforthetreatmentof SurgeryforCerebralStroke),theJapaneseSociety
individualpatients.Since the pathophysiologyof ofNeurology,andtheJapaneseAssociationofRe-
SAHvariesamongpatients,treatmentsforspecif- habilitation Medicine.
I. EPIDEMIOLOGY
1. Incidence and risk factors tributed to SAH had increased as of the late 1980s
1–1. Incidence compared with the 1950s.30) The age-adjusted mor-
The age-adjusted annualincidence of SAH varied tality tended to remain unchanged for men but in-
10-fold between different countries,13) from 1.04 creasedbytwofoldamongwomen,probablyreflect-
cases per 100,000 population/year in the Middle ingrecentchangesinthelifestylesofwomenduring
East27) to approximately 20per 100,000/year in Fin- recent years.30) Therefore, a closer follow up on the
land13) and Japan.12,18,25,28) The sex difference varied trends in age-adjusted mortality is necessary (Grade
between studies; some studies reported no sex B).
difference,13)whileothershavereportedahigherin-
cidence among women. In Japan, the incidence 1–2. Risk factors
tends to be higher in women (male:female ratio 1: Smoking, hypertension, and heavy alcohol use
2).12) Based on data from the national mortality (over 150g alcohol/week) are known to be indepen-
statisticsoftheUS,themortalityofSAHwashigher dent risk factors for SAH,2,5,17,20,22,33,38,39) with rela-
in women than in men, independent of race.3) In tive risks of 1.9, 2.8, and 4.7, respectively. Thus,
Japan, the proportion of cerebrovascular disease at- heavy alcohol use is the most critical risk factor for
Neurol Med Chir (Tokyo) 52, June, 2012
Evidence-Based Guidelines for the Management of Aneurysmal SAH 336633
SAH. Heart disease, diabetes mellitus, serum 2. Natural history and outcome of SAH, and
cholesterol level, hematocrit, or history of non- determinants of poor outcome
steroidalanti-inflammatorydrugadministrationare 2–1. Outcome
not associated with the incidence of SAH.4,36,38) Data from overseas suggest that approximately
Obesity,as indicated bybodymass index,showsan 40% of SAH patients have poor outcome, and ap-
inversecorrelationwith the incidence ofSAH.This proximately 20% of persons with SAH do not
alsoappliesto smokers and hypertensives;i.e.there receive prompt medical attention from neurosur-
is an increased risk in lean patients with hyperten- geons.7) Therefore, improvement of the social
sion and lean smokers.19) The odds ratio was 10.5 healthcare system is indispensable (Grade B). The
(95% confidence interval 1.9–56.4) for individuals overall mortality rate for aneurysmal SAH varies
who were both hypertensive (odds ratio 8.3, 95% among studies (10–67%).26,33,39) The fatality rate is
confidence interval 4.6–16.7) and smokers (odds ra- significantlyhighinpatientswithmassiveSAHwith
tio4.0,95%confidenceinterval2.0–8.6).6)Thus,con- massive intraventricular hematoma or large in-
trol ofhypertension and cessation ofsmokingin in- tracerebral hematoma.34) Vitreous hemorrhage,
dividuals with these risk factors are desirable to found in 17.2% of patients with SAH, is correlated
reducetheriskofSAH(GradeA).Inaddition,infec- withtheseverityofthedisease9)(GradeB).TheGlas-
tionwithintheprevious4weekswasfoundtobean gow Coma Scale (GCS) score on admission is found
independent risk factor for SAH.21) to be well correlated with the outcome10) (Grade B).
There are several studies on the influence of tem- An analysis of the long-term results showed that
poral, meteorological, and psychophysiological fac- manypatientswithSAHdiedevenafterappropriate
torsonthe incidenceofSAH.Thereappearstobea treatment of the ruptured cerebral aneurysm, at-
somewhat higher incidence of SAH onset between tributable to cerebrovascular or cardiovascular dis-
6:00am and noon as reported in one study,8) ease31) (Grade C1).
whereas another study has reported two-peak tem-
poral distribution of SAH onset; i.e. 8:00am–10:00 2–2. Determinants of poor outcome
am and 6:00pm–8:00pm.11) For meteorological fac- Recurrent hemorrhage and cerebral vasospasm
tors, studies have provided variable results. Some are the most important causes of poor outcomes.15)
studies suggest a higher incidence of SAH in the Particularly, recurrent hemorrhage significantly
winter and spring, in the southern hemisphere.8) In worsenedtheoutcome,32)anditspreventionisthere-
the northern hemisphere, there is a study demon- fore very important in the management of this dis-
strating a trend towards a two-peak seasonal distri- ease.Two-thirdsofpatientswithpooroutcomehave
bution (i.e. early spring and autumn),16) however, severe initial hemorrhage or recurrent hemor-
this was not found in another study.21) On the other rhage23) (Grade B). Other known factors which in-
hand, results on the correlation between psy- fluencetheoutcomeincludeage,presenceofhyper-
chophysiological tension and the incidence of SAH tension, history of angiopathy, history of atherosc-
are variable1,16) (Grade C1). lerotic diseases,37) alcohol consumption,14) etc. The
Family history was found to be a risk factor for rate of medical comorbidities (especially pulmo-
SAHinseveralstudies.20,29)Theriskofharboringan nary complications) is as high as 40% within 7
aneurysm was 4% in individual having affected days after the onset of SAH. These medical comor-
close relatives (first-degree relatives)24) (Grade A). bidities are highly dangerous, with fatality rates
Family history should be taken during the manage- comparable to that associated with initial hemor-
ment of patients with suspected signs of ruptured rhage, recurrent hemorrhage, or cerebral vaso-
aneurysm. spasm.35) Preventive measures for these comorbid-
ities are therefore important (Grade B).
II. DIAGNOSIS
1. Clinical manifestations 〈Typical symptoms〉
1–1. Early diagnosis ``Suddensevereheadache''thathasneverbeenex-
Delayed diagnosis will result in poor outcome in perienced before, is the most characteristic com-
aneurysmal SAH. Early and accurate diagnosis, as plaintinSAH.Itshouldbenotedthatnuchalrigidity
well as treatment by specialists, is therefore essen- is sometimes absent in the early stage.
tial13,24,36,37,39,57) (Grade A).
Neurol Med Chir (Tokyo) 52, June, 2012
336644 Evidence-Based Guidelines for the Management of Aneurysmal SAH
〈Warning signs〉 DSA, a technique increasingly used36) (Grade A).
Some patients may report symptoms consistent Although the localization of the ruptured aneurysm
with minor hemorrhage/warning leak before major is sometimes possible with CT finding, evaluation
rupture. Misdiagnosis is associated with a higher with cerebral angiography including all of the in-
likelihood of poor outcome in comparison with an tracranial vessels is recommended because of the
accurate diagnosis at the initial visit. The impor- possibility of coexisting unruptured aneurysms47)
tanceofrecognizinga warningleakcannotbeover- (Grade A). Care should be taken not to overlook the
emphasized5,14,17) (Grade A). The most common characteristic signs of dissecting aneurysm (e.g.,
warning sign is headache. If headache is accompa- pearlandstringsign,doublelumen),whichareusu-
nied by symptoms such as nausea and/or vomiting, ally found in the vertebral artery.26)
brieflossofconsciousness,anddizziness,ahighin- The reported neurological morbidity of cerebral
dexofsuspicionofSAHiswarranted.Amongstroke angiography in patients with SAH is approximately
patientswithsuddenheadache,thereisahighlikeli- 1.8%.10) The incidence of rerupture during cerebral
hood of SAH if nuchal rigidity or seizure, without angiography performed within 6 hours of the onset
otherfocalneurologicaldeficits,ispresent54)(Grade of SAH is reported to be 4.8%,48) and poor outcome
B). Oculomotor palsy, due to direct compression of in these patients has been reported.32,69)
the aneurysm on the oculomotor nerve, might be
another warning sign for SAH.55) 〈Re-examination〉
Onlyapproximately60%to80%ofinitialcerebral
2. Diagnosis of SAH angiograms performed for SAH reveal a source of
2–1. Cranial computed tomography (CT) scan bleeding.11) Re-examination (e.g. repeat angiogra-
ThecornerstoneofSAHdiagnosisisthedetection phy)isindispensable ifthe sourceofbleedingisnot
of a high density area in the subarachnoid space indicated in the first evaluation12,22,53) (Grade A).
with cranial CT without contrast medium. The sen- Repeat angiography will disclose a previously un-
sitivity of CT for SAH is 92% at 24 hours after the recognized aneurysm in an additional 1% to 12.5%
onset,29)andtheprobabilityofdetectinghemorrhage of cases.7,11,36,56,60) However, in a special variant of
declinesovertime(GradeA).Intheinterpretationof SAHcharacterizedbymildbleedinglocalizedinthe
theCT,itshouldbenotedthatintracerebralhemato- perimesencephalic area, ruptured aneurysm is usu-
ma may be documented as the main finding,58) or ally not the source of bleeding. Therefore, an
ventricular dilation (especially dilation of the in- aneurysm is very unlikely to be identified in this
ferior horn) as the only finding of ruptured variant despite repeat angiography (perimesen-
aneurysm18,25) (Grade B). cephalic nonaneurysmal SAH).28,45) These patients
are reported to have favorable outcome8,70) and
2–2. Lumbar puncture repeat angiography is not necessary15,44) (Grade B).
LumbarpunctureisunnecessaryifSAHisinitial-
ly diagnosed by CT. However, diagnostic lumbar 3–2. 3D-CTA
puncture is highly recommended if the initial CT In recent years, the use of 3D-CTA has increased
scan is negative despite the presence of warning in the detection of cerebral aneurysms, with a diag-
signs, or if SAH is clinically strongly suspected nostic rate of over 80–90%. Although the detection
despite the delay between onset and presenta- rate for small (under 2mm in diameter) aneurysms
tion62,68) (Grade A). may be low,27,67) it is a highly useful modalityforas-
sessing the 3D orientation of vessels around the
2–3. Magnetic resonance imaging (MRI) aneurysm1,2,9,20,27,33,42,63,64,71) (Grade B). Recently, it
In comparison with CT, the diagnostic rate of has been reported that 3D-CTA is comparable to
MRIforSAH,especiallyintheacutestage,islower. DSAinthedetectionofcerebralaneurysm,andthat
However, evolvement of MRI techniques (gradient it is even better in providing information for de-
echo T2* or fluid attenuated inversion recovery) veloping surgical strategies. In addition, 3D-CTA is
may improve the diagnosis of SAH,38) especially in rapidandlessinvasive,andthusisconsideredtobe
the subacute and chronic stages40) (Grade B). a useful diagnostic modality for cerebral aneu-
rysm.35,50,65)
3. Diagnosis of cerebral aneurysm
3–1. Cerebral angiography 3–3. Magnetic resonance angiography (MRA)
Once SAH is diagnosed, an immediate investiga- and transcranial ultrasonography
tion for an intracranial aneurysm must be under- MRA can detect an aneurysm Æ5mm in di-
taken with conventional cerebral angiography or ameter.19,34,46) Because of the comparable sensitivity
Neurol Med Chir (Tokyo) 52, June, 2012