Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage : A Guideline   for Healthcare Professionals From the ...
AHA/ASA Guideline                 Guidelines for the Management of Aneurysmal                          Subarachnoid Hemorr...
1712      Stroke       June 2012T    o respond to the growing call for more evidenced-based     medicine, the American Hea...
Connolly et al             Management of Aneurysmal Subarachnoid Hemorrhage                                           1713...
1714           Stroke    June 2012Table 2. Definition of Classes and Levels of Evidence Used in                   It is po...
Connolly et al            Management of Aneurysmal Subarachnoid Hemorrhage                                       1715Table...
1716       Stroke        June 2012Table 4.   New or Revised Recommendations                                               ...
Connolly et al             Management of Aneurysmal Subarachnoid Hemorrhage                                   1717Table 4....
1718      Stroke       June 2012reliably categorized by use of simple validated scales, such as     sciousness in 53%, and...
Connolly et al        Management of Aneurysmal Subarachnoid Hemorrhage                   1719availability, logistics (incl...
1720      Stroke       June 2012     does not obviate the need for cerebrospinal fluid              Medical Measures to Pr...
Connolly et al          Management of Aneurysmal Subarachnoid Hemorrhage                     1721reporting no coils deploy...
1722       Stroke       June 2012     (World Federation of Neurological Surgeons classi-                  One recent effor...
Connolly et al        Management of Aneurysmal Subarachnoid Hemorrhage                        1723gery,172–181 but none ha...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
Guidelines for the managment of aneurysmal subarachnoide hemorrhage  a guideline for healthcare professionals from the Ame...
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Guidelines for the managment of aneurysmal subarachnoide hemorrhage a guideline for healthcare professionals from the American Heart Association/American Stroke Association 2012

  1. 1. 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. Print ISSN: 0039-2499. Online ISSN: 1524-4628The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/43/6/1711 Data Supplement (unedited) at: http://stroke.ahajournals.org/content/suppl/2012/05/02/STR.0b013e3182587839.DC1.html Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/ Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  2. 2. AHA/ASA Guideline Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage A Guideline for Healthcare Professionals From the American Heart Association/American Stroke AssociationThe 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 CardiologyPurpose—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. The American Heart Association Stroke Council’s Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years.Results—Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications.Conclusions—aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH. (Stroke. 2012;43:1711-1737.)Key Words: AHA Scientific Statements Ⅲ aneurysm Ⅲ delayed cerebral ischemia Ⅲ diagnosis Ⅲ subarachnoid hemorrhage Ⅲ treatment Ⅲ 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 outsiderelationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are requiredto complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. The American Heart Association requests that this document be cited as follows: Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, DionJ, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P; on behalf of the American Heart Association StrokeCouncil, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Nursing, Council on Cardiovascular Surgery and Anesthesia,and Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionalsfrom the American Heart Association/American Stroke Association. Stroke. 2012;43:1711–1737. Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelinesdevelopment, visit http://my.americanheart.org/statements and select the “Policies and Development” link. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the expresspermission 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. A link to the “Copyright Permissions Request Form” appears on the right side of the page. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 30, 2012. A copy of thedocument is available at http://my.americanheart.org/statements by selecting either the “By Topic” link or the “By Publication Date” link. To purchaseadditional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. © 2012 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STR.0b013e3182587839 Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013 1711
  3. 3. 1712 Stroke June 2012T o respond to the growing call for more evidenced-based medicine, the American Heart Association (AHA) com-missions guidelines on various clinical topics and endeavors ence call was held to discuss controversial issues. Sections were revised and merged by the writing group chair. The resulting draft was sent to the entire writing group forto keep them as current as possible. The prior aneurysmal comment. Comments were incorporated into the draft by thesubarachnoid hemorrhage (aSAH) guidelines, sponsored by writing group chair and vice chair, and the entire writingthe AHA Stroke Council, were previously issued in 19941 and group was asked to approve the final draft. The chair and vice2009.2 The 2009 guidelines covered literature through No- chair revised the document in response to peer review, andvember 1, 2006.2 The present guidelines primarily cover the document was again sent to the entire writing group forliterature published between November 1, 2006, and May 1, additional suggestions and approval.2010, but the writing group has strived to place these data in The recommendations follow the AHA Stroke Council’sthe greater context of the prior publications and recommen- methods of classifying the level of certainty of the treatmentdations. In cases in which new data covered in this review effect and the class of evidence (Tables 1 and 2). All Class Ihave resulted in a change in a prior recommendation, this is recommendations are listed in Table 3. All new or revisedexplicitly noted. recommendations are listed in Table 4. aSAH is a significant cause of morbidity and mortalitythroughout the world. Although the incidence of aSAH varies Incidence and Prevalence of aSAHwidely among populations, perhaps because of genetic dif- Considerable variation in the annual incidence of aSAHferences, competing burden of disease, and issues of case exists in different regions of the world. A World Healthascertainment, 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 from 2.0 cases per 100 000 population in China to 22.5 casesappear to be falling, and increasing data suggest that early per 100 000 in Finland.3 A later systematic review supportedaneurysm repair, together with aggressive management of a high incidence of aSAH in Finland and Japan, a lowcomplications such as hydrocephalus and delayed cerebral incidence in South and Central America, and an intermediateischemia (DCI), is leading to improved functional outcomes. incidence of 9.1 per 100 000 population in other regions.4 InThese improvements underscore the need to continually a more recent systematic review of population-based studies,reassess which interventions provide the greatest benefit to the incidence of aSAH ranged from 2 to 16 per 100 000.5 Inpatients. 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 almostfirming effectiveness are usually lacking for many of the double that of high-income countries.5 Although some reportsinterventions discussed, the writing group did its best to have suggested the incidence of aSAH in the United States tosummarize the strength of the existing data and make prac- be 9.7 per 100 000,6 the 2003 Nationwide Inpatient Sampletical recommendations that clinicians will find useful in the provided an annual estimate of 14.5 discharges for aSAH perday-to-day management of aSAH. This review does not 100 000 adults.7 Because death resulting from aSAH oftendiscuss 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-nism of reviewing the literature, compiling and analyzing the of cases),8,9 the true incidence of aSAH might be even higher.data, and determining the final recommendations to be made Although a number of population-based studies have indi-is identical to the 2009 version of this guideline.2 cated that the incidence of aSAH has remained relatively The members of the writing group were selected by the stable over the past 4 decades,5,10 –16 a recent review thatAHA to represent the breadth of healthcare professionals who adjusted for age and sex suggested a slight decrease inmust manage these patients. Experts in each field were incidence between 1950 and 2005 for regions other thanscreened for important conflicts of interest and then met by Japan, South and Central America, and Finland.4 These datatelephone to determine subcategories to evaluate. These are consistent with studies that show that the incidence ofsubcategories included incidence, risk factors, prevention, aSAH increases with age, with a typical average age of onsetnatural history and outcome, diagnosis, prevention of re- in adults Ն50 years of age.3,7,17,18 aSAH is relatively uncom-bleeding, surgical and endovascular repair of ruptured aneu- mon in children; incidence rates increase as children getrysms, systems of care, anesthetic management during repair, older, with incidence ranging from 0.18 to 2.0 permanagement of vasospasm and DCI, management of hydro- 100 000.4,19 The majority of studies also indicate a highercephalus, management of seizures, and management of med- incidence of aSAH in women than in men.7,11–13,20 –22 Mostical complications. Together, these categories were thought to recent pooled figures report the incidence in women to beencompass all of the major areas of disease management, 1.24 (95% confidence interval, 1.09 –1.42) times higher thanincluding 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 1994.23who made contributions. Full MEDLINE searches were Evidence of a sex-age effect on aSAH incidence has emergedconducted independently by each author and coauthor of all from pooled study data, with a higher incidence reported inEnglish-language papers on treatment of relevant human younger men (25– 45 years of age), women between 55 anddisease. Drafts of summaries and recommendations were 85 years of age, and men Ͼ85 years of age.4 Differences incirculated to the entire writing group for feedback. A confer- incidence of aSAH by race and ethnicity appear to exist. Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  4. 4. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1713Table 1. Applying Classification of Recommendation and Level of Evidence A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelinesdo not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy isuseful or effective. *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of priormyocardial infarction, history of heart failure, and prior aspirin use. †For comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involvedirect comparisons of the treatments or strategies being evaluated.Blacks and Hispanics have a higher incidence of aSAH than familial aneurysms (at least 1 first-degree family memberwhite Americans.6,24,25 with an intracranial aneurysm, and especially if Ն2 first- degree relatives are affected) and family history of aSAH,26,27 Risk Factors for and Prevention of aSAH and certain genetic syndromes, such as autosomal dominantBehavioral risk factors for aSAH include hypertension, 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:aSAH is increased by the presence of an unruptured cerebral (1) Aneurysms in the anterior circulation appear to be moreaneurysm (particularly those that are symptomatic, larger in prone to rupture in patients Ͻ55 years of age, whereassize, and located either on the posterior communicating artery posterior communicating aneurysms ruptured more fre-or the vertebrobasilar system), a history of previous aSAH quently in men, and basilar artery aneurysm rupture is(with or without a residual untreated aneurysm), a history of associated with lack of use of alcohol.30 (2) The size at which Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  5. 5. 1714 Stroke June 2012Table 2. Definition of Classes and Levels of Evidence Used in It is possible that diet increases the risk of stroke in generalAHA Stroke Council Recommendations and aSAH in particular. In an epidemiological study ofClass I Conditions for which there is evidence for Finnish smokers who were monitored for Ͼ13 years, in- and/or general agreement that the creased consumption of yogurt (but not all dairy products) procedure or treatment is useful and was associated with a higher risk of aSAH.41 Greater vege- effective. table consumption is associated with a lower risk of strokeClass II Conditions for which there is conflicting and aSAH.42 Higher coffee and tea consumption43 and higher evidence and/or a divergence of opinion magnesium consumption44 were associated with reduced risk about the usefulness/efficacy of a procedure or treatment. of stroke overall but did not change the risk of aSAH. Class IIa The weight of evidence or opinion is in Predicting the growth of an individual intracranial aneu- favor of the procedure or treatment. rysm and its potential for rupture in a given patient remains Class IIb Usefulness/efficacy is less well established problematic. When followed up on magnetic resonance im- by evidence or opinion. aging, larger aneurysms (Ն8 mm in diameter) tended to growClass III Conditions for which there is evidence more over time,45 which implies a higher risk of rupture. and/or general agreement that the Several characteristics of aneurysm morphology (such as a procedure or treatment is not bottleneck shape46 and the ratio of size of aneurysm to parent useful/effective and in some cases may vessel47,48) have been associated with rupture status, but how be harmful. these might be applied to individual patients to predict futureTherapeutic recommendations aneurysmal rupture is still unclear.33 Variability within each Level of Evidence A Data derived from multiple randomized patient is unpredictable at this time, but such intraindividual clinical trials or meta-analyses variability markedly changes the risk of aneurysm detection Level of Evidence B Data derived from a single randomized and rupture and may attenuate the benefits of routine screen- trial or nonrandomized studies ing in high-risk patients.49 Level of Evidence C Consensus opinion of experts, case Given such uncertainties, younger age, longer life expec- studies, or standard of care tancy, and higher rate of rupture all make treatment ofDiagnostic recommendations unruptured aneurysms more likely to be cost-effective and Level of Evidence A Data derived from multiple prospective cohort studies using a reference reduce morbidity and mortality.50 Two large observational standard applied by a masked evaluator studies of familial aneurysms suggest that screening these Level of Evidence B Data derived from a single grade A study, patients may also be cost-effective in preventing aSAH and or Ն1 case-control studies, or studies improving quality of life.26,27 Smaller studies have suggested using a reference standard applied by that screening of those with 1 first-degree relative with aSAH an unmasked evaluator may be justified as well, but it is far less clear whether Level of Evidence C Consensus opinion of experts patients who underwent treatment for a previous aSAH require ongoing screening.51,52 In the Cerebral Aneurysmaneurysms rupture appears to be smaller in those patients Rerupture After Treatment (CARAT) study, recurrent aSAHwith the combination of hypertension and smoking than in was predicted by incomplete obliteration of the aneurysm andthose with either risk factor alone.31 (3) Significant life events occurred a median of 3 days after treatment but rarely after 1such as financial or legal problems within the past month may year.53 Repeated noninvasive screening at later times may notincrease the risk of aSAH.32 (4) Aneurysm size Ͼ7 mm has be cost-effective, increase life expectancy, or improve qualitybeen shown to be a risk factor for rupture.33 (5) There does of life in unselected patients.54 Patients with adequatelynot appear to be an increased risk of aSAH in pregnancy, obliterated aneurysms after aSAH have a low risk of recurrentdelivery, 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.57pathogenesis and growth of intracranial aneurysms.36 Prom-inent mediators include the nuclear factor ␬-light-chain en-hancer of activated B cells (NF-␬B),37 tumor necrosis factor, Risk Factors for and Prevention of aSAH:macrophages, and reactive oxygen species. Although there Recommendationsare no controlled studies in humans, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin”)38 1. Treatment of high blood pressure with antihyper-and calcium channel blockers may retard aneurysm forma- tensive medication is recommended to prevent ische-tion through the inhibition of NF-␬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 ofmodifiable risks are very low body mass index, smoking, Evidence A).and high alcohol consumption.31,39,40 Yet, despite marked 2. Hypertension should be treated, and such treatmentimprovements in the treatment of hypertension and hyper- may reduce the risk of aSAH (Class I; Level oflipidemia and the decrease in rates of smoking over time, Evidence B).the incidence of aSAH has not changed appreciably in 30 3. Tobacco use and alcohol misuse should be avoided toyears.16 reduce the risk of aSAH (Class I; Level of Evidence B). Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  6. 6. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1715Table 3. Class I RecommendationsLevel of Evidence RecommendationA 1. Treatment of high blood pressure with antihypertensive medication is recommended to prevent ischemic stroke, intracerebral hemorrhage, and cardiac, renal, and other end-organ injury.A 2. Oral nimodipine should be administered to all patients with aSAH. (It should be noted that this agent has been shown to improve neurological outcomes but not cerebral vasospasm. The value of other calcium antagonists, whether administered orally or intravenously, remains uncertain.)B 1. Hypertension should be treated, and such treatment may reduce the risk of aSAHB 2. Tobacco use and alcohol misuse should be avoided to reduce the risk of aSAH.B* 3. After any aneurysm repair, immediate cerebrovascular imaging is generally recommended to identify remnants or recurrence of the aneurysm that may require treatment.B 4. The initial clinical severity of aSAH should be determined rapidly by use of simple validated scales (eg, Hunt and Hess, World Federation of Neurological Surgeons), because it is the most useful indicator of outcome after aSAH.B 5. The risk of early aneurysm rebleeding is high and is associated with very poor outcomes. Therefore, urgent evaluation and treatment of patients with suspected aSAH is recommended.B 6. aSAH is a medical emergency that is frequently misdiagnosed. A high level of suspicion for aSAH should exist in patients with acute onset of severe headache.B 7. Acute diagnostic workup should include noncontrast head CT, which, if nondiagnostic, should be followed by lumbar puncture.B* 8. DSA with 3-dimensional rotational angiography is indicated for detection of aneurysm in patients with aSAH (except when the aneurysm was previously diagnosed by a noninvasive angiogram) and for planning treatment (to determine whether an aneurysm is amenable to coiling or to expedite microsurgery).B* 9. Between the time of aSAH symptom onset and aneurysm obliteration, blood pressure should be controlled with a titratable agent to balance the risk of stroke, hypertension-related rebleeding, and maintenance of cerebral perfusion pressure.B 10. Surgical clipping or endovascular coiling of the ruptured aneurysm should be performed as early as feasible in the majority of patients to reduce the rate of rebleeding after aSAH.B 11. Complete obliteration of the aneurysm is recommended whenever possible.B† 12. For patients with ruptured aneurysms judged to be technically amenable to both endovascular coiling and neurosurgical clipping, endovascular coiling should be considered.B* 13. In the absence of a compelling contraindication, patients who undergo coiling or clipping of a ruptured aneurysm should have delayed follow-up vascular imaging (timing and modality to be individualized), and strong consideration should be given to retreatment, either by repeat coiling or microsurgical clipping, if there is a clinically significant (eg, growing) remnant.B† 14. Low-volume hospitals (eg, Ͻ10 aSAH cases per year) should consider early transfer of patients with aSAH to high-volume centers (eg, Ͼ35 aSAH cases per year) with experienced cerebrovascular surgeons, endovascular specialists, and multidisciplinary neuro-intensive care services.B† 15. Maintenance of euvolemia and normal circulating blood volume is recommended to prevent DCI.B† 16. Induction of hypertension is recommended for patients with DCI unless blood pressure is elevated at baseline or cardiac status precludes it.B† 17. aSAH-associated acute symptomatic hydrocephalus should be managed by cerebrospinal fluid diversion (EVD or lumbar drainage, depending on the clinical scenario).B* 18. Heparin-induced thrombocytopenia and deep venous thrombosis, although infrequent, are not uncommon occurrences after aSAH. Early identification and targeted treatment are recommended, but further research is needed to identify the ideal screening paradigms.C† 1. Determination of aneurysm treatment, as judged by both experienced cerebrovascular surgeons and endovascular specialists, should be a multidisciplinary decision based on characteristics of the patient and the aneurysm.C† 2. aSAH-associated chronic symptomatic hydrocephalus should be treated with permanent cerebrospinal fluid diversion. aSAH indicates aneurysmal subarachnoid hemorrhage; CT, computed tomography; DSA, digital subtraction angiography; DCI, delayed cerebral ischemia; and EVD,external ventricular drainage. *A new recommendation. †A change in either level of evidence or strength of the recommendation from previous guidelines. 4. In addition to the size and location of the aneurysm 5. Consumption of a diet rich in vegetables may lower 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) namic characteristics of the aneurysm when discuss- 6. It may be reasonable to offer noninvasive screening ing the risk of aneurysm rupture (Class IIb; Level of to patients with familial (at least 1 first-degree Evidence B). (New recommendation) relative) aSAH and/or a history of aSAH to evaluate Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  7. 7. 1716 Stroke June 2012Table 4. New or Revised Recommendations Class ofNew or Recommendation/Revised Recommendation Level of EvidenceNew 1. In addition to the size and location of the aneurysm and the patient’s age and health status, it might be reasonable Class IIb, Level B to consider morphological and hemodynamic characteristics of the aneurysm when discussing the risk of aneurysm rupture.New 2. Consumption of a diet rich in vegetables may lower the risk of aSAH. Class IIb, Level BNew 3. After any aneurysm repair, immediate cerebrovascular imaging is generally recommended to identify remnants or Class I, Level B recurrence of the aneurysm that may require treatment.New 4. After discharge, it is reasonable to refer patients with aSAH for a comprehensive evaluation, including cognitive, Class IIa, Level B behavioral, and psychosocial assessments.New 5. CTA may be considered in the workup of aSAH. If an aneurysm is detected by CTA, this study may help guide the Class IIb, Level C decision for the type of aneurysm repair, but if CTA is inconclusive, DSA is still recommended (except possibly in the instance of classic perimesencephalic SAH).New 6. Magnetic resonance imaging (fluid-attenuated inversion recovery, proton density, diffusion-weighted imaging, and Class IIb, Level C gradient echo sequences) may be reasonable for the diagnosis of SAH in patients with a nondiagnostic CT scan, although a negative result does not obviate the need for cerebrospinal fluid analysis.New 7. DSA with 3-dimensional rotational angiography is indicated for detection of aneurysm in patients with aSAH (except Class I, Level B when the aneurysm was previously diagnosed by a noninvasive angiogram) and for planning treatment (to determine whether an aneurysm is amenable to coiling or to expedite microsurgery).New 8. Between the time of aSAH symptom onset and aneurysm obliteration, blood pressure should be controlled with a Class I, Level B titratable agent to balance the risk of stroke, hypertension-related rebleeding, and maintenance of cerebral perfusion pressure.New 9. The magnitude of blood pressure control to reduce the risk of rebleeding has not been established, but a decrease Class IIa, Level C in systolic blood pressure to Ͻ160 mm Hg is reasonable.New 10. In the absence of a compelling contraindication, patients who undergo coiling or clipping of a ruptured aneurysm Class I, Level B should have delayed follow-up vascular imaging (timing and modality to be individualized), and strong consideration should be given to retreatment, either by repeat coiling or microsurgical clipping, if there is a clinically significant (eg, growing) remnant.New 11. Microsurgical clipping may receive increased consideration in patients presenting with large (Ͼ50 mL) Class IIb, Level C intraparenchymal hematomas and middle cerebral artery aneurysms. Endovascular coiling may receive increased consideration in the elderly (Ͼ70 y of age), in those presenting with poor-grade WFNS classification (IV/V) aSAH, and in those with aneurysms of the basilar apex.New 12. Stenting of a ruptured aneurysm is associated with increased morbidity and mortality. Class III, Level CNew 13. Annual monitoring of complication rates for surgical and interventional procedures is reasonable. Class IIa, Level CNew 14. A hospital credentialing process to ensure that proper training standards have been met by individual physicians Class IIa, Level C treating brain aneurysms is reasonable.New 15. Prophylactic hypervolemia or balloon angioplasty before the development of angiographic spasm is not Class III, Level B recommended.New 16. Transcranial Doppler is reasonable to monitor for the development of arterial vasospasm. Class IIa, Level BNew 17. Perfusion imaging with CT or magnetic resonance can be useful to identify regions of potential brain ischemia. Class IIa, Level BNew 18. Weaning EVD over Ͼ24 hours does not appear to be effective in reducing the need for ventricular shunting. Class III, Level BNew 19. Routine fenestration of the lamina terminalis is not useful for reducing the rate of shunt-dependent hydrocephalus Class III, Level B and therefore should not be routinely performed.New 20. Aggressive control of fever to a target of normothermia by use of standard or advanced temperature modulating Class IIa, Level B systems is reasonable in the acute phase of aSAH.New 21. The use of packed red blood cell transfusion to treat anemia might be reasonable in patients with aSAH who are Class IIb, Level B at risk of cerebral ischemia. The optimal hemoglobin goal is still to be determined.New 22. Heparin-induced thrombocytopenia and deep venous thrombosis are relatively frequent complications after aSAH. Class I, Level B Early identification and targeted treatment are recommended, but further research is needed to identify the ideal screening paradigms.Revised 1. For patients with an unavoidable delay in obliteration of aneurysm, a significant risk of rebleeding, and no Class IIa, Level B compelling medical contraindications, short-term (Ͻ72 hours) therapy with tranexamic acid or aminocaproic acid is reasonable to reduce the risk of early aneurysm rebleeding.Revised 2. Determination of aneurysm treatment, as judged by both experienced cerebrovascular surgeons and endovascular Class I, Level C specialists, should be a multidisciplinary decision based on characteristics of the patient and the aneurysm. (Continued) Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  8. 8. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1717Table 4. Continued Class ofNew or Recommendation/Revised Recommendation Level of EvidenceRevised 3. For patients with ruptured aneurysms judged to be technically amenable to both endovascular coiling and Class I, Level B neurosurgical clipping, endovascular coiling should be considered.Revised 4. Low-volume hospitals (eg, Ͻ10 aSAH cases per year) should consider early transfer of patients with aSAH to Class I, Level B high-volume centers (eg, Ͼ35 aSAH cases per year) with experienced cerebrovascular surgeons, endovascular specialists, and multidisciplinary neuro-intensive care services.Revised 5. Maintenance of euvolemia and normal circulating blood volume is recommended to prevent DCI. Class I, Level BRevised 6. Induction of hypertension is recommended for patients with DCI unless blood pressure is elevated at baseline or Class I, Level B cardiac status precludes it.Revised 7. Cerebral angioplasty and/or selective intra-arterial vasodilator therapy is reasonable in patients with symptomatic Class IIa, Level B cerebral vasospasm, particularly those who are not rapidly responding to hypertensive therapy.Revised 8. aSAH-associated acute symptomatic hydrocephalus should be managed by cerebrospinal fluid diversion (EVD or Class I, Level B lumbar drainage, depending on the clinical scenario).Revised 9. aSAH-associated chronic symptomatic hydrocephalus should be treated with permanent cerebrospinal fluid Class I, Level C diversion. aSAH indicates aneurysmal subarachnoid hemorrhage; CTA, computed tomography angiography; DSA, digital subtraction angiography; CT, computed tomography;DSA, digital subtraction angiography; EVD, external ventricular drainage; DCI, delayed cerebral ischemia; and WFNS, World Federation of Neurological Surgeons. for de novo aneurysms or late regrowth of a treated 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 reported when the modified Rankin Scale is used.59 Although 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% of patients in the International Subarachnoid Aneurysm (New recommendation) Trial (ISAT) showing significant lifestyle restrictions (mod- ified Rankin Scale 3) and 6.5% being functionally dependent (modified Rankin Scale score of 4 –5) 1 year after aSAH. Natural History and Outcome of aSAH Furthermore, scales that are relatively insensitive to cognitiveAlthough the case fatality of aSAH remains high world- impairment, behavioral changes, social readjustment, andwide,5 mortality rates from aSAH appear to have declined energy level may substantially underestimate the effect ofin industrialized nations over the past 25 years.9,11,15,58,59 aSAH on the function and quality of life of surviving patients.One study in the United States reported a decrease of Ϸ1% Multiple studies using diverse designs have consistentlyper year from 1979 to 1994.60 Others have shown that case demonstrated that intellectual impairment is very prevalentfatality rates decreased from 57% in the mid-1970s to 42% after aSAH. Although cognitive function tends to improvein the mid-1980s,11 whereas rates from the mid-1980s to over the first year,64 global cognitive impairment is still2002 are reported to be anywhere from 26% to present in Ϸ20% of aSAH patients and is associated with36%.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 compounded67%.59 Regional variations become apparent when num- by mood disorders (anxiety, depression), fatigue, and sleepbers from different studies are compared. The median disturbances.66 Therefore, scales assessing well-being andmortality rate in epidemiological studies from the United quality of life can be particularly useful in the integralStates has been 32% versus 43% to 44% in Europe and assessment of patients with aSAH, even among those who27% in Japan.59 These numbers are based on studies that regain functional independence.67,68 Behavioral and psycho-did not always fully account for cases of prehospital death. social difficulties, as well as poor physical and mentalThis is an important consideration because the observed endurance, are some of the most commonly encountereddecrease in case fatality is related to improvements in factors accounting for the inability of otherwise independentsurvival among hospitalized patients with aSAH. patients to return to their previous occupations.66,68 The mean age of patients presenting with aSAH is increas- Much remains to be learned about the causes of cognitiveing, which has been noted to have a negative impact on and functional deficits after aSAH and the best methods tosurvival rates.59 Sex and racial variations in survival may also assess intellectual outcome and functional recovery in theseplay a role in the variable rates, with some studies suggesting patients. The severity of clinical presentation is the strongesthigher mortality in women than in men9,11,60 and higher prognostic indicator in aSAH. Initial clinical severity can be Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  9. 9. 1718 Stroke June 2012reliably categorized by use of simple validated scales, such as sciousness in 53%, and nuchal rigidity in 35%.88 As many asthe 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 headacheOther factors predictive of poor prognosis include older age, from aSAH is sufficiently variable, misdiagnosis or delayedpreexisting severe medical illness, global cerebral edema on diagnosis is common. Before 1985, misdiagnosis of aSAHcomputed tomography (CT) scan, intraventricular and intra- occurred in as many as 64% of cases, with more recent datacerebral hemorrhage, symptomatic vasospasm, delayed cere- suggesting a misdiagnosis rate of Ϸ12%.89,90 Misdiagnosisbral infarction (especially if multiple), hyperglycemia, fever, was associated with a nearly 4-fold higher likelihood of deathanemia, and other systemic complications such as pneumonia or disability at 1 year in patients with minimal or noand sepsis.71–77 Certain aneurysm factors, such as size, neurological deficit at the initial visit.89 The most commonlocation, and complex configuration, may increase the risk of diagnostic error is failure to obtain a noncontrast head CTperiprocedural complications and affect overall prognosis.78 scan.89,91–93 In a small subset of patients, a high degree ofTreatment in high-volume centers with availability of neuro- suspicion based on clinical presentation will lead to thesurgical and endovascular services may be associated with correct diagnosis despite normal head CT and cerebrospinalbetter outcomes.79 – 81 fluid test results, as shown in a recent study in which 1.4% of patients were diagnosed with aSAH only after vascularNatural History and Outcome of aSAH: imaging techniques were used.94Recommendations Patients may report symptoms consistent with a minor 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 usually milder than that associated with a major rupture, but outcome after aSAH (Class I; Level of Evidence B). 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 severe headache before the event that led to admission.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- complaint in the emergency department, and aSAH accounts cluding cognitive, behavioral, and psychosocial assessments (Class IIa; Level of Evidence B). (New for only 1% of all headaches evaluated in the emergency recommendation) department.92 Therefore, a high index of suspicion is war- ranted, because diagnosis of the warning leak or sentinel hemorrhage before a catastrophic rupture may be lifesaving.93 Clinical Manifestations and Diagnosis Seizures may occur in up to 20% of patients after aSAH, most of aSAH commonly in the first 24 hours and more commonly in aSAHThe clinical presentation of aSAH is one of the most associated with intracerebral hemorrhage, hypertension, anddistinctive in medicine. The hallmark of aSAH in a patient middle cerebral and anterior communicating arterywho is awake is the complaint “the worst headache of my aneurysms.98,99life,” which is described by Ϸ80% of patients who can give Noncontrast head CT remains the cornerstone of diagnosisa history.82 This headache is characterized as being extremely of aSAH; since publication of the previous version of thesesudden and immediately reaching maximal intensity (thun- guidelines,1,2 there have been only minor changes in imagingderclap headache). A warning or sentinel headache that technology for this condition. The sensitivity of CT in theprecedes 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 fewodds of early rebleeding 10-fold.85 Most intracranial aneu- days.2,100 After 5 to 7 days, the rate of negative CT increasesrysms remain asymptomatic until they rupture. aSAH can sharply, and lumbar puncture is often required to showoccur during physical exertion or stress.86 Nevertheless, in a xanthochromia. However, advances in magnetic resonancereview of 513 patients with aSAH, the highest incidence of imaging of the brain, particularly the use of fluid-attenuatedrupture occurred while patients were engaged in their daily inversion recovery, proton density, diffusion-weighted imag-routines, in the absence of strenuous physical activity.87 The ing, and gradient echo sequences,101–103 can often allow theonset of headache may be associated with Ն1 additional signs diagnosis of aSAH to be made when a head CT scan isand symptoms, including nausea and/or vomiting, stiff neck, negative and there is clinical suspicion of aSAH, possiblyphotophobia, brief loss of consciousness, or focal neurolog- avoiding the need for lumbar puncture. The role of magneticical deficits (including cranial nerve palsies). In a retrospec- resonance imaging in perimesencephalic aSAH is controver-tive study of 109 patients with proven aSAH, headache was sial.104 Indications for magnetic resonance angiography inpresent in 74%, nausea or vomiting in 77%, loss of con- aSAH are still few because of limitations with routine Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  10. 10. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1719availability, logistics (including difficulty in scanning acutely coiling was achieved in 92.6%. The authors concluded thatill patients), predisposition to motion artifact, patient compli- CTA with a 64-slice scanner is an accurate tool for detectingance, longer study time, and cost. Aneurysms Ͻ3 mm in size and characterizing aneurysms in acute aSAH and that CTA iscontinue to be unreliably demonstrated on computed tomo- useful in deciding whether to coil or clip an aneurysm.115graphic angiography (CTA),105,106 and this generates contin- Partial volume averaging phenomena may artificially widenued controversy in the case of CTA-negative aSAH.107 In the aneurysmal neck and may lead to the erroneous conclu-cases of perimesencephalic subarachnoid hemorrhage (SAH), sion that an aneurysm cannot be treated by endovascularsome authors claim that a negative CTA result is sufficient to coiling. This controversy is likely caused by the differentrule 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 slice thickness, and data processing algorithms of various CToverall interobserver and intraobserver agreement for nonan- systems, which have different spatial resolutions. Three-eurysmal perimesencephalic hemorrhage was good, but there dimensional cerebral angiography is more sensitive for de-was still a level of disagreement among observers, which tecting aneurysms than 2-dimensional angiography.121,122 Thesuggests that clinicians should be cautious when deciding combination of 3- and 2-dimensional cerebral angiographywhether to pursue follow-up imaging.108 In another study,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, ofhead CT showed the classic perimesencephalic SAH pattern course, always used in preparation for endovascular therapy.or no blood. Digital subtraction angiography (DSA) was Flat-panel volumetric CT is a relatively recent develop-indicated if there was a diffuse aneurysmal pattern of aSAH, ment that allows the generation of CT-like images from aand repeat delayed DSA was required if the initial DSA rotational 3-dimensional spin of the x-ray gantry in thefindings were negative, which led to the detection of a small angiography room. For the moment, it has no substantial roleaneurysm in 14% of cases. When the blood is located in the in the initial diagnosis of aSAH because its spatial andsulci, CTA should be scrutinized for vasculitis, and DSA is contrast resolutions are not high enough123; however, thisrecommended 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 dose3-dimensional cerebral angiography should be performed, has emerged as an important and worrisome consideration forespecially when the hemorrhage is accompanied by loss of patients with SAH.125,126 The combination of noncontrastconsciousness.110 In cases of diffuse aSAH pattern, most head CT for the diagnosis of aSAH, confirmation of ventric-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 fordegenerative vascular diseases, CTA can replace catheter recognition of vasospasm, and catheter cerebral angiographycerebral angiography in most cases if the image quality is for aneurysm embolization and then for endovascular therapyexcellent and analysis is performed carefully.111 Overlying of vasospasm can result in substantial radiation doses to thebone can be problematic with CTA, especially at the skull head, with possible risk of radiation injury, such as scalpbase. 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 bein detecting intracranial aneurysms in any projection without made to reduce the amount of radiation exposure in patientssuperimposed bone.112 CTA-MMBE has limited sensitivity in with aSAH whenever possible.detecting very small aneurysms. The data suggest that DSAand 3-dimensional rotational angiography can be limited to Clinical Manifestations and Diagnosis of aSAH:the vessel harboring the ruptured aneurysm before endovas- Recommendationscular treatment after detection of a ruptured aneurysm withCTA. Another new technique, dual-energy CTA, has diag- 1. aSAH is a medical emergency that is frequently misdiagnosed. A high level of suspicion for aSAHnostic image quality at a lower radiation dose than digital should exist in patients with acute onset of severesubtraction CTA and high diagnostic accuracy compared with headache (Class I; Level of Evidence B).3-dimensional DSA (but not 2-dimensional DSA) in the 2. Acute diagnostic workup should include noncontrastdetection of intracranial aneurysms.113 head CT, which, if nondiagnostic, should be followed 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. Ifaneurysms. Although CTA is sometimes considered suffi- an aneurysm is detected by CTA, this study maycient on its own when an aneurysm will be treated with help guide the decision for type of aneurysm repair,surgical clipping,114 substantial controversy remains about but if CTA is inconclusive, DSA is still recommendedthe ability of CTA to determine whether or not an aneurysm (except possibly in the instance of classic perimesen- cephalic aSAH) (Class IIb; Level of Evidence C).is amenable to endovascular therapy.115–120 In 1 series,115 (New recommendation)95.7% of patients with aSAH were referred for treatment on 4. Magnetic resonance imaging (fluid-attenuated inver-the basis of CTA. In 4.4% of patients, CTA did not provide sion recovery, proton density, diffusion-weightedenough information to determine the best treatment, and those imaging, and gradient echo sequences) may be rea-patients required DSA; 61.4% of patients were referred to sonable for the diagnosis of aSAH in patients with aendovascular treatment on the basis of CTA; and successful nondiagnostic CT scan, although a negative result Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  11. 11. 1720 Stroke June 2012 does not obviate the need for cerebrospinal fluid Medical Measures to Prevent Rebleeding After analysis (Class IIb; Level of Evidence C). (New aSAH: Recommendations recommendation) 5. DSA with 3-dimensional rotational angiography is 1. Between the time of aSAH symptom onset and indicated for detection of aneurysm in patients aneurysm obliteration, blood pressure should be with aSAH (except when the aneurysm was previ- controlled with a titratable agent to balance the risk ously diagnosed by a noninvasive angiogram) and of stroke, hypertension-related rebleeding, and for planning treatment (to determine whether an maintenance of cerebral perfusion pressure (Class I; aneurysm is amenable to coiling or to expedite Level of Evidence B). (New recommendation) microsurgery) (Class I; Level of Evidence B). (New 2. The magnitude of blood pressure control to reduce recommendation) the risk of rebleeding has not been established, but a decrease in systolic blood pressure to <160 mm Hg Medical Measures to Prevent Rebleeding is reasonable (Class IIa; Level of Evidence C). (New After aSAH recommendation)Aneurysm rebleeding is associated with very high mortality 3. For patients with an unavoidable delay in oblitera-and poor prognosis for functional recovery in survivors. The tion of aneurysm, a significant risk of rebleeding,risk of rebleeding is maximal in the first 2 to 12 hours, with and no compelling medical contraindications, short- term (<72 hours) therapy with tranexamic acid orreported rates of occurrence between 4% and 13.6% within aminocaproic acid is reasonable to reduce the risk ofthe first 24 hours.127–130 In fact, more than one third of early aneurysm rebleeding (Class IIa; Level of Evi-rebleeds occur within 3 hours and nearly half within 6 hours dence B). (Revised recommendation from previousof symptom onset,131 and early rebleeding is associated with guidelines)worse outcome than later rebleeding.132 Factors associatedwith aneurysm rebleeding include longer time to aneurysm Surgical and Endovascular Methods fortreatment, worse neurological status on admission, initial loss Treatment of Ruptured Cerebral Aneurysmsof consciousness, previous sentinel headaches (severe head- Microsurgical clip obliteration of intracranial aneurysms wasaches lasting Ͼ1 hour that do not lead to the diagnosis of the primary modality of treatment before 1991, when Gug-aSAH), larger aneurysm size, and possibly systolic blood lielmi first described occlusion of an aneurysm by an endo-pressure Ͼ160 mm Hg.87,129,130 Genetic factors, although vascular approach with electrolytically detachable coils.139related to the occurrence of intracranial aneurysms, do not With advancements in both microsurgical and endovascularappear to be related to an increased incidence of rebleed- approaches, algorithms to determine the proper patient pop-ing.133 Early treatment of the ruptured aneurysm can reduce ulation and aneurysmal characteristics for each treatment arethe risk of rebleeding.71 Among patients who present in a continually undergoing refinement. The only multicenterdelayed manner and during the vasospasm window, delayed randomized trial comparing microsurgical and endovascularobliteration of aneurysm is associated with a higher risk of repair, ISAT, randomized 2143 of 9559 screened patientsrebleeding than early obliteration of aneurysm.134 with aSAH across 42 neurosurgical centers.140 For a patient to There is general agreement that acute hypertension should be considered eligible for the trial, neurosurgeons and inter-be controlled after aSAH and until aneurysm obliteration, but ventionalists had to agree that the aneurysm was comparablyparameters for blood pressure control have not been defined. suitable for treatment with either modality. Primary outcomesA variety of titratable medications are available. Nicardipine included death or dependent living, and secondary outcomesmay give smoother blood pressure control than labetalol135 included risk of seizures and risk of rebleeding. Initial 1-yearand sodium nitroprusside,136 although data showing different outcomes revealed a reduction in death and disability fromclinical outcomes are lacking. Although lowering cerebral 31% in the microsurgery arm to 24% in the endovascular armperfusion pressure may lead to cerebral ischemia, a cohort (relative risk reduction, 24%).141 This difference was mainlystudy of neurologically critically ill patients did not find an driven by a decrease in the rate of disability among survivorsassociation between use of nicardipine and reduced brain 16% in the endovascular arm and 22% in the craniotomy arm)oxygen tension.137 Clevidipine, a very short-acting calcium and was likely attributable at least in part to the greaterchannel blocker, is another option for acute control of incidence of technical complications in the clipping (19%)hypertension, but data for aSAH are lacking at this time. versus the coiling (8%) arms and the longer time needed to Antifibrinolytic therapy has been shown to reduce the secure the aneurysm.142,143 The risk of epilepsy and signifi-incidence of aneurysm rebleeding when there is a delay in cant cognitive decline was also reduced in the endovascularaneurysm obliteration. One referral center instituted a policy group, but the incidence of late rebleeding (2.9% afterof short-term use of aminocaproic acid to prevent rebleeding endovascular repair versus 0.9% after open surgery) wasduring patient transfer. Such use led to a decreased incidence higher in the endovascular arm, and only 58% of coiledin rebleeding without increasing the risk of DCI, but 3-month aneurysms were completely obliterated compared with 81%clinical outcomes were not affected.138 There was an in- of clipped aneurysms.140 A large retrospective analysis foundcreased risk of deep venous thrombosis but not pulmonary that the rate of incomplete occlusion and subsequent aneu-embolism. Neither aminocaproic acid nor tranexamic acid is rysm recurrence depended critically on neck diameter andapproved by the US Food and Drug Administration for dome size.139 It can also be difficult to achieve completeprevention of aneurysm rebleeding. obliteration in very small aneurysms (Ͻ3 mm), with 1 study Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  12. 12. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1721reporting no coils deployed in 5% of cases, residual dome posterior circulation aneurysms. One study that comparedfilling or a neck remnant in 30%, and a higher procedural clipping versus coiling of basilar apex aneurysm (44 patientscomplication rate than in larger aneurysms.144 in each treatment arm) found a poor outcome rate of 11% in Although the complete obliteration rate can be increased the endovascular treatment group versus 30% in the surgicalby the addition of a high-porosity stent, this has been group. In that study, the main difference was the rate ofassociated with an increased risk of complications, especially ischemia and hemorrhage during the surgical intervention.in patients with SAH, in large part because of the need for The rates of recurrent hemorrhage and delayed ischemia wereperiprocedural dual-antiplatelet therapy to prevent arterial actually similar in both groups.159thromboembolism.145 Whether low-porosity flow-diverting Incomplete aneurysm occlusion and recurrent aneurysmstents with or without coils represent a better option for many filling from progressive coil compaction are particularlyor most of those presenting with SAH from saccular aneu- difficult challenges encountered with endovascular treatmentrysms remains to be studied, but these stents make more of basilar artery aneurysms. In a study of 41 posteriorconceptual sense for use in the patient with a dissecting circulation aneurysms, 35 (85%) had complete or near-aneurysm, in whom vessel sacrifice is not an option and complete immediate angiographic occlusion. The follow-upmicrosurgical solutions carry higher risk. time frame for this study was 17 months, and of the 29 Another approach to increasing complete obliteration rates patients for whom follow-up was obtained, those with com-involves the deployment of biologically active rather than pletely occluded aneurysms did not reveal any compaction. Inpure platinum coils.146 Although uncontrolled studies suggest the remaining patients who had near-complete occlusion,a potential reduction in the risk of recurrence, these data are 47% had experienced recanalization, with 1 patient experi-preliminary and have yet to be confirmed in prospective encing a rehemorrhage.160 On the basis of these findings,controlled trials.147,148 Thus, although the short-term efficacy closer follow-up with sequential DSA is needed in patientsof endovascular coil obliteration is well established compared who undergo coiling of posterior circulation aneurysms,with microsurgical approaches, close long-term surveillance particularly those who do not exhibit complete occlusion oncontinues to be warranted, because durability remains a immediate follow-up angiography.significant concern.149 Given this delicate balance between safety and durability, Surgical and Endovascular Methods of Treatmentthere have been multiple efforts to identify subgroups of of Ruptured Cerebral Aneurysms:patients who might be best treated with endovascular or Recommendationsmicrosurgical techniques. Although the quality of the data ismodest, most agree that with current endovascular technol- 1. Surgical clipping or endovascular coiling of the rup-ogy, middle cerebral artery aneurysms can be difficult to treat tured aneurysm should be performed as early aswith coil embolization, and in this location, surgical treatment feasible in the majority of patients to reduce the rate of rebleeding after aSAH (Class I; Level of Evidence B).has tended to yield more favorable results.146,150 –152 Although 2. Complete obliteration of the aneurysm is recom-some have suggested that older patients are ideal candidates mended whenever possible (Class I; Level of Evi-for coiling rather than clipping, data on this population are dence B).sparse and at times conflicting.141,153,154 Although patients 3. Determination of aneurysm treatment, as judged bypresenting with an intraparenchymal hematoma Ͼ50 mL both experienced cerebrovascular surgeons and en-have a higher incidence of unfavorable outcome, hematoma dovascular specialists, should be a multidisciplinaryevacuation within Ͻ3.5 hours has been shown to improve decision based on characteristics of the patient andoutcome in this subgroup and argues in favor of microsurgery the aneurysm (Class I; Level of Evidence C). (Revisedfor most patients with large parenchymal clots.155 By con- recommendation from previous guidelines)trast, patients presenting during the vasospasm period, espe- 4. For patients with ruptured aneurysms judged to be technically amenable to both endovascular coilingcially those with confirmed vasospasm, may be better treated and neurosurgical clipping, endovascular coilingwith endovascular techniques, depending on the anatomy of should be considered (Class I; Level of Evidence B).the aneurysm and its relationship to the spasm.150 Patients (Revised recommendation from previous guidelines)presenting with poor clinical grade appear to benefit more from 5. In the absence of a compelling contraindication,endovascular coiling, especially if they are also elderly, because patients who undergo coiling or clipping of a rup-advanced age renders long-term durability less important.156 tured aneurysm should have delayed follow-up vas-Still, it is critical that patients with poor clinical grade be treated cular imaging (timing and modality to be individu-in centers where both modalities are available.157 alized), and strong consideration should be given to Endovascular treatment of posterior circulation aneurysms retreatment, either by repeat coiling or microsurgi-has been gaining widespread acceptance based on several cal clipping, if there is a clinically significant (eg,observational studies. A meta-analysis revealed that the growing) remnant (Class I; Level of Evidence B). (New recommendation)mortality from coiling of a basilar bifurcation aneurysm was 6. Microsurgical clipping may receive increased con-0.9%, and the risk of permanent complications was 5.4%.158 sideration in patients presenting with large (>50More recently, with regard to treatment of posterior circula- mL) intraparenchymal hematomas and middle cere-tion aneurysms, the mortality and morbidity in 112 ruptured bral artery aneurysms. Endovascular coiling mayaneurysms was 3.7% and 9.4%, respectively.159 These data receive increased consideration in the elderly (Ͼ70have led to an increasing tendency toward coiling ruptured years of age), in those presenting with poor-grade Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  13. 13. 1722 Stroke June 2012 (World Federation of Neurological Surgeons classi- One recent effort to increase the uniformity of care is the fication IV/V) aSAH, and in those with aneurysms of development of an Accreditation Council on Graduate Med- the basilar apex (Class IIb; Level of Evidence C). ical Education–approved fellowship training program for (New recommendation) endovascular surgical neuroradiology.166 Another effort is 7. Stenting of a ruptured aneurysm is associated with legislation or regulation in Ͼ10 states that defines elements increased morbidity and mortality, and should only of comprehensive stroke centers and their role in networks be considered when less risky options have been excluded (Class III; Level of Evidence C). (New and stroke systems of care. The Brain Attack Coalition paper recommendation) that proposed the establishment of these centers included management of aSAH in its scope.167 From the endovascularHospital Characteristics and Systems of Care perspective, this expertise includes the ability to treat patientsIn a US study of 31 476 nontraumatic cases of aSAH from with intracranial aneurysms, SAH-induced vasospasm, brain2003, definitive aneurysm repair was delivered in fewer than arteriovenous malformations, and ischemic stroke. Otherone third of cases. That said, the adjusted odds of definitive important required elements of these centers are vascularrepair were significantly higher in urban teaching hospitals neurosurgical expertise, dedicated intensive care units, andthan in urban nonteaching hospitals (odds ratio, 1.62) or rural 24/7 access to advanced neuroimaging. The rationale forhospitals (odds ratio, 3.08).7 In another study from 1993 to comprehensive stroke centers is based on the success of2003, teaching status and larger hospital size were associated similar models for trauma.with higher charges and longer stay but also with betteroutcomes (PϽ0.05) and lower mortality rates (PϽ0.05), Hospital Characteristics and Systems of Care:especially in patients who underwent aneurysm clipping Recommendations(PϽ0.01). Endovascular treatment, which was more oftenused in the elderly, was also associated with significantly 1. Low-volume hospitals (eg, <10 aSAH cases perhigher mortality rates in smaller hospitals (PϽ0.001) and year) should consider early transfer of patients withsteadily increasing morbidity rates (45%). Large academic aSAH to high-volume centers (eg, >35 aSAH cases per year) with experienced cerebrovascular sur-centers were associated with better results, particularly for geons, endovascular specialists, and multidisci-surgical clip placement.161 Prior studies have also indi- plinary neuro-intensive care services (Class I; Levelcated that 82% of US hospitals admitted Ͻ19 patients with of Evidence B). (Revised recommendation from previ-aSAH annually, and the 30-day mortality rate was signif- ous guidelines)icantly higher in hospitals that admitted Ͻ10 patients with 2. Annual monitoring of complication rates for surgicalaSAH versus Ͼ35 patients with aSAH (39% versus 27%; and interventional procedures is reasonable (Classodds ratio, 1.4).80 IIa; Level of Evidence C). (New recommendation) Two factors associated with better outcomes were greater 3. A hospital credentialing process to ensure thatuse of endovascular services and a higher percentage of proper training standards have been met by indi-patients transferred from other hospitals.79 – 81 Institutions that vidual physicians treating brain aneurysms isused endovascular coil embolization more frequently had reasonable (Class IIa; Level of Evidence C). (New recommendation)lower in-hospital mortality rates, a 9% reduction in risk forevery 10% of cases treated. In addition, there was a 16%reduction in risk of in-hospital death at institutions that used Anesthetic Management During Surgical andinterventional therapies such as balloon angioplasty to treat Endovascular Treatmentarterial vasospasm.2,81,162 Therefore, hospital treatment vol- The general goals of anesthetic management involve hemo-umes and availability of both endovascular and neurological dynamic control to minimize the risk of aneurysm reruptureintensive care services at hospitals are important determinants and strategies to protect the brain against ischemic injury.of improved outcomes in aSAH.163 In addition, a cost-utility Although induced hypotension has been used in the past toanalysis estimated that transferring a patient with aSAH from prevent aneurysm rupture, data suggest that there could bea low- to a high-volume hospital would result in a gain of 1.6 potential harm, with an increased risk of early and delayedquality-adjusted life-years at a cost of $10 548.162,163 neurological deficits.168,169 A retrospective study suggests Although 1 study suggested that care was uniformly that a decrease in mean arterial pressure of Ͼ50% is associ-delivered within an institution when weekend and weekday ated with poor outcome; however, after adjustment for age,admissions were compared,164 others have shown that inten- this association was no longer statistically significant.170 Insive care specialists followed evidence-based recommenda- patients undergoing cerebral aneurysm surgery, intraopera-tions very inconsistently, and these variations in practice did tive hyperglycemia has been associated with long-term de-not depend on the quality of the supporting data.165 Signifi- cline in cognition and gross neurological function.171 Thesecant practice differences were noted between respondents associations are seen at levels of hyperglycemia commonlyfrom North America and Europe and between those working encountered in practice, with increased risk of alterations inin high- and low-volume centers. Thus, the study demon- cognition with glucose concentrations Ͼ129 mg/dL andstrated that the practices of intensive care unit physicians neurological deficits with glucose concentrations Ͼ152 mg/treating aSAH are heterogenous and often at variance with dL.171 Numerous pharmacological agents have been used toavailable evidence.165 promote cerebral protection during cerebral aneurysm sur- Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013
  14. 14. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1723gery,172–181 but none have been clearly shown to improve undergone anticoagulation require rapid reversal with prota-outcome. mine if intraprocedural aneurysm rupture occurs. With the Systemic hypothermia has been used in several clinical increasing use of intravascular stents, the administration ofsettings, including head injury, ischemic stroke, and circula- antiplatelet agents (aspirin, clopidogrel, and glycoproteintory arrest, to protect the brain against ischemic injury.182–188 IIb/IIIa receptor antagonists) during these procedures hasUse of hypothermia during craniotomy for the treatment of become more common. In case of intraprocedural rupture,ruptured cerebral aneurysm was evaluated in a multicenter rapid reversal of antiplatelet activity can be attempted byrandomized, controlled trial. The study showed that hypother- platelet transfusion.mia was relatively safe but was not associated with abeneficial effect in mortality or neurological outcome among Anesthetic Management During Surgical andpatients with good-grade aSAH.189 In addition, intraoperative Endovascular Treatment: Recommendationshypothermia had no beneficial effect on neuropsychologicalfunction after SAH.190 Of note, the power of these 2 studies 1. Minimization of the degree and duration of intraop-was not sufficient to detect more modest benefits from erative hypotension during aneurysm surgery ishypothermia, and there were some trends in favor of hypo- probably indicated (Class IIa; Level of Evidence B).thermia for secondary end points. 2. There are insufficient data on pharmacological strate- Temporary clipping is frequently used to improve surgical gies and induced hypertension during temporary ves- sel occlusion to make specific recommendations, butconditions and prevent intraoperative rupture during the there are instances when their use may be consideredsurgical dissection of aneurysms. In a retrospective study, reasonable (Class IIb; Level of Evidence C).outcome was not affected by temporary vascular occlusion.191 3. Induced hypothermia during aneurysm surgery is notInduced hypertension can be considered when the duration of routinely recommended but may be a reasonable op-temporary clipping is expected to be Ͼ120 seconds, but the tion in selected cases (Class III; Level of Evidence B).value of this strategy has not been well studied in aneurysm 4. Prevention of intraoperative hyperglycemia duringsurgery. In selected patients with giant aneurysms, deep aneurysm surgery is probably indicated (Class IIa;hypothermia with circulatory arrest under cardiopulmonary Level of Evidence B).extracorporeal circulation has been shown to be a feasible 5. The use of general anesthesia during endovascularand possibly useful technique, but outcome data are treatment of ruptured cerebral aneurysms can belacking.192–196 Transient cardiac pause induced by adenosine beneficial in selected patients (Class IIa; Level ofhas been used to control bleeding from intraoperative aneu- Evidence C).rysm rupture or to decompress large aneurysms and facilitateaneurysm clip application197,198; however, controlled studies Management of Cerebral Vasospasm and DCIare needed to validate this intervention. After aSAH There is little information in the literature about anesthetic Narrowing (vasospasm) of the angiographically visible cere-management of patients undergoing endovascular treatment bral arteries after aSAH is common, occurring most fre-of ruptured cerebral aneurysms.199 –201 Generally, the anes- quently 7 to 10 days after aneurysm rupture and resolvingthetic principles that apply to open surgical treatment of spontaneously after 21 days. The cascade of events culminat-ruptured cerebral aneurysms also apply to endovascular ing in arterial narrowing is initiated when oxyhemoglobintreatment. The choice of anesthetic technique varies depend- comes in contact with the abluminal side of the vessel.205 Theing on the institution, with the most common techniques pathways leading to arterial narrowing have been the focus ofbeing conscious sedation and general anesthesia.202–204 There extensive basic research, but no effective preventive therapyhave been no studies comparing these 2 techniques. One of has been developed to date. Part of the reason for this lack ofthe main goals of the anesthetic technique is keeping the success likely stems from the fact that vasospasm occurs atpatient motionless to optimize the quality of the images used multiple levels in the arterial and arteriolar circulation. Largeto perform the endovascular procedure; hence, general anes- artery narrowing seen in angiographically visible vessels onlythesia with endotracheal intubation is often preferred for results in ischemic neurological symptoms in 50% of cases,these procedures. and although there is a correlation between the severity of Intraprocedural aneurysm rupture during endovascular large artery spasm and symptomatic ischemia, there are patientstreatment presents a major challenge unlike that encountered with severe large artery spasm who never become symptomaticwith open craniotomy. There may be a sudden and massive and others with quite modest spasm who not only developrise in blood pressure with or without bradycardia attributable symptoms but go on to develop infarction.206 Probably manyto an elevation in intracranial pressure. Hyperventilation and factors contribute to the development of ischemia and infarction,osmotic diuresis may be required to control the intracranial including but not limited to distal microcirculatory failure, poorhypertension. Aggressive treatment of surges in blood pres- collateral anatomy, and genetic or physiological variations insure may induce ischemia; therefore, antihypertensive ther- cellular ischemic tolerance.207,208apy should be reserved for patients with extreme elevations in DCI, especially that associated with arterial vasospasm,blood pressure. remains a major cause of death and disability in patients with Endovascular procedures differ from open procedures in aSAH. The management of aSAH-induced vasospasm isthat anticoagulation with heparin is frequently administered complex. Many significant advances in the understanding ofduring the embolization of aneurysms. Patients who have aSAH-induced vasospasm and DCI have been made since Downloaded from http://stroke.ahajournals.org/ by guest on March 10, 2013

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