Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 2. Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* James C. Fang University of Utah Cardiovascular Division  Boston Scientific None None None None None and Barry A. Franklin William Beaumont Hospital Director, Cardiac Rehabilitation and Exercise Laboratories None None None None None None None Christopher B. Granger Duke Clinical Research Institute Director, Cardiac Care Unit; Professor of Medicine None None None  Medtronic Foundation  Merck None None and Harlan M. Krumholz Yale University School of Medicine Professor of Epidemiology and Public Health None None None  Johnson & Johnson  Medtronic None None and Jane A. Linderbaum Mayo Clinic Assistant Professor of Medicine None None None None None None None David A. Morrow Harvard Medical School Professor of Medicine  Abbott  Merck None None  Abbott  GlaxoSmithKline  Johnson & Johnson  Merck None None and L. Kristin Newby Duke University Medical Center, Division of Cardiology Professor of Medicine  Philips None None  Merck None None and Joseph P. Ornato Department of Emergency Medicine Virginia Commonwealth University Professor and Chairman None None None None None None None Narith Ou Mayo Clinic Pharmacotherapy Coordinator, Cardiology None None None None None None None Martha J. Radford NYU Langone Medical Center Chief Quality Officer; NYU School of Medicine Professor of Medicine (Cardiology) None None None None None None None Jacqueline E. Tamis-Holland Mount Sinai Saint Luke s Hospital and The Icahn School of Medicine Program Director, Interventional Cardiology Fellowship Program None None None None None None None 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1013 Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.


Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* James C. Fang University of Utah Cardiovascular Division  Boston Scientific None None None None None and Barry A. Franklin William Beaumont Hospital Director, Cardiac Rehabilitation and Exercise Laboratories None None None None None None None Christopher B. Granger Duke Clinical Research Institute Director, Cardiac Care Unit; Professor of Medicine None None None  Medtronic Foundation  Merck None None and Harlan M. Krumholz Yale University School of Medicine Professor of Epidemiology and Public Health None None None  Johnson & Johnson  Medtronic None None and Jane A. Linderbaum Mayo Clinic Assistant Professor of Medicine None None None None None None None David A. Morrow Harvard Medical School Professor of Medicine  Abbott  Merck None None  Abbott  GlaxoSmithKline  Johnson & Johnson  Merck None None and L. Kristin Newby Duke University Medical Center, Division of Cardiology Professor of Medicine  Philips None None  Merck None None and Joseph P. Ornato Department of Emergency Medicine Virginia Commonwealth University Professor and Chairman None None None None None None None Narith Ou Mayo Clinic Pharmacotherapy Coordinator, Cardiology None None None None None None None Martha J. Radford NYU Langone Medical Center Chief Quality Officer; NYU School of Medicine Professor of Medicine (Cardiology) None None None None None None None Jacqueline E. Tamis-Holland Mount Sinai Saint Luke s Hospital and The Icahn School of Medicine Program Director, Interventional Cardiology Fellowship Program None None None None None None None 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1013 Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 2.


Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 2. Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* Carl L. Tommaso Skokie Hospital Director of Catheterization Laboratory; NorthShore University HealthSystems Partner None None None None None None None Cynthia M. Tracy George Washington University Medical Center Associate Director, Division of Cardiology None None None None None None None Y. Joseph Woo Stanford University Professor and Chair, Cardiothoracic Surgery None None None None None None None David X. Zhao Wake Forest Baptist Health Professor of Medicine, Heart and Vascular Center of Excellence Director None None None  St. Jude Medical  Medtronic None None and This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document. These relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the writing committee during the document development process. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of of the voting stock or share of the business entity, or ownership of of the fair market value of the business entity; or if funds received by the person from the business entity exceed of the person s gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted.


Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) the person or a member of the person s household has a reasonable potential for financial, professional, or other personal gain or loss as a result of the issues/con- tent addressed in the document. *Writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply. Dr. Deborah D. Ascheim accepted a position at Capricor Therapeutics in August after the writing effort was completed. According to policy, she recused herself from the final voting process. Significant relationship. No financial benefit. ACC indicates American College of Cardiology; AHA, American Heart Association; NYU, New York University; UCSF, University of California San Francisco; and UT, University of Texas. 1014 Levine et al. Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3.


Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3. Reviewer Relationships With Industry and Other Entities ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Interven- tion for Patients With ST-Elevation Myocardial Infarction (Combined Peer Reviewers From PCI and STEMI Guidelines) Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Elliott M. Antman Official Reviewer AHA Harvard Medical School Professor of Medicine, Associate Dean for Clinical and Translational Research None None None None None None Deepak L. Bhatt Official Reviewer AHA Harvard Medical School Professor; Interventional Cardiovascular Programs Executive Director None None None  Bristol- Myers Squibb*  Ischemix*  Medtronic*  St. Jude Medical  Regado Biosciences None Christopher P. Cannon Official Reviewer AHA Harvard Medical School Professor of Medicine; Brigham and Women s Hospital Senior Investigator, TIMI Study Group, Cardiovascular Division  Bristol-Myers Squibb  Merck  Regeneron/ Sanofi-aventis* None None  Merck* None None Joaquin E. Cigarroa Official Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Oregon Health & Science University Clinical Professor of Medicine None None None None None None George Dangas Official Reviewer ACC Board of Trustees Icahn School of Medicine Professor of Cardiology and Vascular Surgery; Mount Sinai Medical Center Director, Cardiovascular Innovation  Abbott  Biosensors  Boston Scientific  Johnson & Johnson*  Merck  Osprey Medical*  Regado Biosciences None None None  Abbott  Medtronic  Osprey None Charles J. Davidson Official Reviewer SCAI Northwestern University Feinberg School of Medicine Professor of Medicine, Director of Cardiac Catheterization Lab None None None  Baxter International None None 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1015 Catheterization and Cardiovascular Interventions DOI 10.1002/ccd.


Reviewer Relationships With Industry and Other Entities ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Interven- tion for Patients With ST-Elevation Myocardial Infarction (Combined Peer Reviewers From PCI and STEMI Guidelines) Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Elliott M. Antman Official Reviewer AHA Harvard Medical School Professor of Medicine, Associate Dean for Clinical and Translational Research None None None None None None Deepak L. Bhatt Official Reviewer AHA Harvard Medical School Professor; Interventional Cardiovascular Programs Executive Director None None None  Bristol- Myers Squibb*  Ischemix*  Medtronic*  St. Jude Medical  Regado Biosciences None Christopher P. Cannon Official Reviewer AHA Harvard Medical School Professor of Medicine; Brigham and Women s Hospital Senior Investigator, TIMI Study Group, Cardiovascular Division  Bristol-Myers Squibb  Merck  Regeneron/ Sanofi-aventis* None None  Merck* None None Joaquin E. Cigarroa Official Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Oregon Health & Science University Clinical Professor of Medicine None None None None None None George Dangas Official Reviewer ACC Board of Trustees Icahn School of Medicine Professor of Cardiology and Vascular Surgery; Mount Sinai Medical Center Director, Cardiovascular Innovation  Abbott  Biosensors  Boston Scientific  Johnson & Johnson*  Merck  Osprey Medical*  Regado Biosciences None None None  Abbott  Medtronic  Osprey None Charles J. Davidson Official Reviewer SCAI Northwestern University Feinberg School of Medicine Professor of Medicine, Director of Cardiac Catheterization Lab None None None  Baxter International None None 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1015 Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3.


Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Kirk N. Garratt Official Reviewer SCAI Hofstra University Medical School Associate Chair of Quality and Research; Professor of Medicine  Abbott  Boston Scientific  The Medicines Company  Daiichi- Sankyo/Eli Lilly  AstraZeneca None  LifeCuff Technologies  Global Delivery Systems None  Boston Scientific None Steven L. Goldberg Official Reviewer SCAI University of Washington Medical Center Cath Lab Director  Terumo None None None None None G. B. John Mancini Official Reviewer ACC Board of Governors Vancouver Hospital Research Pavilion Professor of Medicine  Merck  Sanofi- aventis/ Regeneron None None None None None Jonathan M. Tobis Official Reviewer SCAI University of California Los Angeles Professor of Medicine and Cardiology  St. Jude Medical None None None None None Jeffrey L. Anderson Content Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Intermountain Medical Center Associate Chief of Cardiology None None None None None None Thomas M. Bashore Content Reviewer Duke University Professor of Medicine None None None None None None James A. Burke Content Reviewer ACC Interventional Scientific Council Lehigh Valley Heart Specialists Associate Chief, Division of Cardiology None None None None None None Jeffrey J. Cavendish Content Reviewer ACC Prevention of Cardiovascular Disease Committee Kaiser Permanente Cardiology Interventional Cardiologist None None None None  Abbott None Gregory J. Dehmer Content Reviewer ACC Appropriate Use Criteria Texas A&M College of Medicine Professor of Medicine; Scott & White Healthcare None None None None None None 1016 Levine et al. Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3.


Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness John S. Douglas, Jr. Content Reviewer Emory University Hospital Professor of Medicine None None None  Abbott  Medtronic None None John P. Erwin III Content Reviewer ACC/AHA Task Force on Performance Measures Texas A&M College of Medicine Associate Professor; Scott & White Healthcare Vice Chair of the Department of Medicine None None None None None None T. Bruce Ferguson Content Reviewer ACC Surgeons Scientific Council East Carolina Institute Brody School of Medicine Professor of Surgery and Physiology None None None None None None Anthony Gershlick Content Reviewer University Hospitals of Leicester, Department of Cardiology  Abbott  Boston Scientific  Cordis  Medtronic  Abbott None None None None Jonathan L. Halperin Content Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Mt.


Content Reviewer Emory University Hospital Professor of Medicine None None None  Abbott  Medtronic None None John P. Erwin III Content Reviewer ACC/AHA Task Force on Performance Measures Texas A&M College of Medicine Associate Professor; Scott & White Healthcare Vice Chair of the Department of Medicine None None None None None None T. Bruce Ferguson Content Reviewer ACC Surgeons Scientific Council East Carolina Institute Brody School of Medicine Professor of Surgery and Physiology None None None None None None Anthony Gershlick Content Reviewer University Hospitals of Leicester, Department of Cardiology  Abbott  Boston Scientific  Cordis  Medtronic  Abbott None None None None Jonathan L. Halperin Content Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Mt. Sinai Medical Professor of Medicine  Bayer Healthcare  Boston Scientific  Johnson & Johnson  Medtronic None None None None None Howard C. Herrmann Content Reviewer University of Pennsylvania Perelman School of Medicine Professor of Medicine, Director of Interventional Cardiology Program  Seimens Medical  St. Jude Medical None None  Abbott*  Medtronic  Siemens Medical*  St. Jude Medical None None Morton J. Kern Content Reviewer University of California Irvine Professor of Medicine, Associate Chief of the Division of Cardiology  Acist Medical  Merit Medical*  St. Jude Medical* None None None None Fred M. Kosumoto Content Reviewer Mayo Clinic Director, Pacing and Electrophysiology Service None None None None None None David J. Maron Content Reviewer Stanford University School of Medicine Professor of Medicine and Emergency Medicine None None None None None None 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1017 Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3.


Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Douglass A. Morrison Content Reviewer University of Arizona Professor of Medicine; Southern Arizona VA Health Care System Cardiac Catheterization Laboratories, Director None None None None None None Manesh R. Patel Content Reviewer ACC Appropriate Use Criteria Duke University Medical Center Associate Professor of Medicine  Bayer Healthcare*  Janssen Pharmaceuticals* None None  Johnson & Johnson* None None M. Eugene Sherman Content Reviewer ACC Board of Governors Aurora Denver Cardiology None None None None  Bristol-Myers Squibb*  Hospira* None Daniel I. Simon Content Reviewer University Hospitals Case Medical Center Professor of Cardiovascular Research  Cordis/Johnson & Johnson*  Janssen Pharmaceuticals/ Johnson & Johnson  Medtronic Vascular  Merck  Abbott None None None None Richard W. Snyder Content Reviewer ACC Board of Governors HeartPlace None None None None None None William A. Tansey III Content Reviewer Summit Medical Group Cardiologist None None None None None None David D. Waters Content Reviewer San Francisco General Hospital Chief, Division of Cardiology None None None None  Merck None Patrick L. Whitlow Content Reviewer Cleveland Clinic Foundation Director, Interventional Cardiology None None None  Abbott  Medtronic* David O. Williams Content Reviewer Harvard Medical School Professor of Medicine; Brigham and Women s Hospital None None None None None None 1018 Levine et al. Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3.


Published on behalf of The Society for governed by the applicable Creative Commons License APPENDIX 3. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Clyde W. Yancy Content Reviewer ACC/AHA Task Force on Practice Guidelines Northwestern University Feinberg School of Medicine Vice Dean for Diversity and Inclusion, Chief of Medicine-Cardiology, Professor None None None None None None Yerem Yeghiazarians Content Reviewer University of California San Francisco Associate Professor None None None None None None This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review and determined to be relevant to this document. It does not neces- sarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of of the voting stock or share of the business entity, or ownership of of the fair market value of the business entity; or if funds received by the person from the business entity exceed of the person s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding definition. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Names are listed in alphabetical order within each category of review.


Names are listed in alphabetical order within each category of review. According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) the person or a member of the person s household has a reasonable potential for financial, professional, or other personal gain or loss as a result of the issues/con- tent addressed in the document. *Significant relationship. No financial benefit. ACC indicates American College of Cardiology; AHA, American Heart Association; HF, heart failure; SCAI, Society for Cardiovascular Angiography and Interventions; STEMI, ST-elevation myocardial infarction; PCI, percutaneous coronary interventions; TIMI, Thrombolysis In Myocardial Infarction; and VA, Veterans Affairs. 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1019 Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for governed by the applicable Creative Commons License


AHA/ASA Guideline Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and by the Society of NeuroInterventional Surgery E. Sander Connolly, Jr, MD, FAHA, Chair; Alejandro A. Rabinstein, MD, Vice Chair; J. Ricardo Carhuapoma, MD, FAHA; Colin P. Derdeyn, MD, FAHA; Jacques Dion, MD, FRCPC; Randall T. Higashida, MD, FAHA; Brian L. Hoh, MD, FAHA; Catherine J. Kirkness, PhD, RN; Andrew M. Naidech, MD, MSPH; Christopher S. Ogilvy, MD; Aman B. Patel, MD; B. Gregory Thompson, MD; Paul Vespa, MD, FAAN; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Nursing, Council on Cardiovascular Surgery and Anesthesia, and Council on Clinical Cardiology Purpose The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. 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.


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 aneurysm delayed cerebral ischemia diagnosis subarachnoid hemorrhage treatment vasospasm The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to 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, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Nursing, Council on Cardiovascular Surgery and Anesthesia, and Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from 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.


Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, 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 express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/ Copyright-Permission-Guidelines_UCM_300404_Article.jsp. 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 the document is available at http://my.americanheart.org/statements by selecting either the By Topic link or the By Publication Date link. To purchase additional 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 To respond to the growing call for more evidenced-based medicine, the American Heart Association (AHA) com- missions guidelines on various clinical topics and endeavors to keep them as current as possible. The prior aneurysmal subarachnoid hemorrhage (aSAH) guidelines, sponsored by the AHA Stroke Council, were previously issued in 19941 and 2009.2 The 2009 guidelines covered literature through No- vember 1, 2006.2 The present guidelines primarily cover literature published between November 1, 2006, and May 1, 2010, but the writing group has strived to place these data in the greater context of the prior publications and recommen- dations. In cases in which new data covered in this review have resulted in a change in a prior recommendation, this is explicitly noted. aSAH is a significant cause of morbidity and mortality throughout the world.


aSAH is a significant cause of morbidity and mortality throughout the world. Although the incidence of aSAH varies widely among populations, perhaps because of genetic dif- ferences, competing burden of disease, and issues of case ascertainment, at the very least, a quarter of patients with aSAH die, and roughly half of survivors are left with some persistent neurological deficit. That said, case-fatality rates appear to be falling, and increasing data suggest that early aneurysm repair, together with aggressive management of complications such as hydrocephalus and delayed cerebral ischemia (DCI), is leading to improved functional outcomes. These improvements underscore the need to continually reassess which interventions provide the greatest benefit to patients. Although large, multicenter, randomized trial data con- firming effectiveness are usually lacking for many of the interventions discussed, the writing group did its best to summarize the strength of the existing data and make prac- tical recommendations that clinicians will find useful in the day-to-day management of aSAH. This review does not discuss the multitude of ongoing studies. Many of these can be found at http://www.strokecenter.org/trials/. The mecha- nism of reviewing the literature, compiling and analyzing the data, and determining the final recommendations to be made is identical to the 2009 version of this guideline.2 The members of the writing group were selected by the AHA to represent the breadth of healthcare professionals who must manage these patients. Experts in each field were screened for important conflicts of interest and then met by telephone to determine subcategories to evaluate. These subcategories included incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of re- bleeding, surgical and endovascular repair of ruptured aneu- rysms, systems of care, anesthetic management during repair, management of vasospasm and DCI, management of hydro- cephalus, management of seizures, and management of med- ical complications.


These subcategories included incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of re- bleeding, surgical and endovascular repair of ruptured aneu- rysms, systems of care, anesthetic management during repair, management of vasospasm and DCI, management of hydro- cephalus, management of seizures, and management of med- ical complications. Together, these categories were thought to encompass all of the major areas of disease management, including prevention, diagnosis, and treatment. Each subcat- egory was led by 1 author, with 1 or 2 additional coauthors who made contributions. Full MEDLINE searches were conducted independently by each author and coauthor of all English-language papers on treatment of relevant human disease. Drafts of summaries and recommendations were circulated to the entire writing group for feedback. A confer- 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 for comment. Comments were incorporated into the draft by the writing group chair and vice chair, and the entire writing group was asked to approve the final draft. The chair and vice chair revised the document in response to peer review, and the document was again sent to the entire writing group for additional suggestions and approval. The recommendations follow the AHA Stroke Council s methods of classifying the level of certainty of the treatment effect and the class of evidence (Tables 1 and 2). All Class I recommendations are listed in Table 3. All new or revised recommendations are listed in Table 4. Incidence and Prevalence of aSAH Considerable variation in the annual incidence of aSAH exists in different regions of the world.


Incidence and Prevalence of aSAH Considerable variation in the annual incidence of aSAH exists in different regions of the world. A World Health Organization study found a 10-fold variation in the age- adjusted annual incidence in countries in Europe and Asia, from 2.0 cases per 100 000 population in China to 22.5 cases per 100 000 in Finland.3 A later systematic review supported a high incidence of aSAH in Finland and Japan, a low incidence in South and Central America, and an intermediate incidence of 9.1 per 100 000 population in other regions.4 In a more recent systematic review of population-based studies, the incidence of aSAH ranged from 2 to 16 per 100 000.5 In that review, the pooled age-adjusted incidence rate of aSAH in low- to middle-income countries was found to be almost double that of high-income countries.5 Although some reports have suggested the incidence of aSAH in the United States to be 9.7 per 100 000,6 the 2003 Nationwide Inpatient Sample provided an annual estimate of 14.5 discharges for aSAH per 100 000 adults.7 Because death resulting from aSAH often occurs before hospital admission (an estimated 12% to 15% of cases),8,9 the true incidence of aSAH might be even higher.


A World Health Organization study found a 10-fold variation in the age- adjusted annual incidence in countries in Europe and Asia, from 2.0 cases per 100 000 population in China to 22.5 cases per 100 000 in Finland.3 A later systematic review supported a high incidence of aSAH in Finland and Japan, a low incidence in South and Central America, and an intermediate incidence of 9.1 per 100 000 population in other regions.4 In a more recent systematic review of population-based studies, the incidence of aSAH ranged from 2 to 16 per 100 000.5 In that review, the pooled age-adjusted incidence rate of aSAH in low- to middle-income countries was found to be almost double that of high-income countries.5 Although some reports have suggested the incidence of aSAH in the United States to be 9.7 per 100 000,6 the 2003 Nationwide Inpatient Sample provided an annual estimate of 14.5 discharges for aSAH per 100 000 adults.7 Because death resulting from aSAH often occurs before hospital admission (an estimated 12% to 15% of cases),8,9 the true incidence of aSAH might be even higher. Although a number of population-based studies have indi- cated that the incidence of aSAH has remained relatively stable over the past 4 decades,5,10 16 a recent review that adjusted for age and sex suggested a slight decrease in incidence between 1950 and 2005 for regions other than Japan, South and Central America, and Finland.4 These data are consistent with studies that show that the incidence of aSAH increases with age, with a typical average age of onset in adults 50 years of age.3,7,17,18 aSAH is relatively uncom- mon in children; incidence rates increase as children get older, with incidence ranging from 0.18 to 2.0 per 100 000.4,19 The majority of studies also indicate a higher incidence of aSAH in women than in men.7,11 13,20 22 Most recent pooled figures report the incidence in women to be 1.24 (95% confidence interval, 1.09 1.42) times higher than in men.4 This is lower than a previous estimate of 1.6 (95% confidence interval, 1.1 2.3) for the years 1960 to 1994.23 Evidence of a sex-age effect on aSAH incidence has emerged from pooled study data, with a higher incidence reported in younger men (25 45 years of age), women between 55 and 85 years of age, and men 85 years of age.4 Differences in incidence of aSAH by race and ethnicity appear to exist.


Although a number of population-based studies have indi- cated that the incidence of aSAH has remained relatively stable over the past 4 decades,5,10 16 a recent review that adjusted for age and sex suggested a slight decrease in incidence between 1950 and 2005 for regions other than Japan, South and Central America, and Finland.4 These data are consistent with studies that show that the incidence of aSAH increases with age, with a typical average age of onset in adults 50 years of age.3,7,17,18 aSAH is relatively uncom- mon in children; incidence rates increase as children get older, with incidence ranging from 0.18 to 2.0 per 100 000.4,19 The majority of studies also indicate a higher incidence of aSAH in women than in men.7,11 13,20 22 Most recent pooled figures report the incidence in women to be 1.24 (95% confidence interval, 1.09 1.42) times higher than in men.4 This is lower than a previous estimate of 1.6 (95% confidence interval, 1.1 2.3) for the years 1960 to 1994.23 Evidence of a sex-age effect on aSAH incidence has emerged from pooled study data, with a higher incidence reported in younger men (25 45 years of age), women between 55 and 85 years of age, and men 85 years of age.4 Differences in incidence of aSAH by race and ethnicity appear to exist. Blacks and Hispanics have a higher incidence of aSAH than Risk Factors for and Prevention of aSAH Behavioral risk factors for aSAH include hypertension, smok- ing, alcohol abuse, and the use of sympathomimetic drugs (eg, cocaine).


Blacks and Hispanics have a higher incidence of aSAH than Risk Factors for and Prevention of aSAH Behavioral risk factors for aSAH include hypertension, smok- ing, alcohol abuse, and the use of sympathomimetic drugs (eg, cocaine). In addition to female sex (above), the risk of aSAH is increased by the presence of an unruptured cerebral aneurysm (particularly those that are symptomatic, larger in size, and located either on the posterior communicating artery or the vertebrobasilar system), a history of previous aSAH (with or without a residual untreated aneurysm), a history of familial aneurysms (at least 1 first-degree family member with an intracranial aneurysm, and especially if 2 first- degree relatives are affected) and family history of aSAH,26,27 and certain genetic syndromes, such as autosomal dominant polycystic kidney disease and type IV Ehlers-Danlos syn- drome.28,29 Novel findings reported since publication of the previous version of these guidelines include the following: (1) Aneurysms in the anterior circulation appear to be more prone to rupture in patients 55 years of age, whereas posterior communicating aneurysms ruptured more fre- quently in men, and basilar artery aneurysm rupture is associated with lack of use of alcohol.30 (2) The size at which Table 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 guidelines do 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 is useful 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 prior myocardial infarction, history of heart failure, and prior aspirin use.


*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial 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 involve direct comparisons of the treatments or strategies being evaluated. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1713 aneurysms rupture appears to be smaller in those patients with the combination of hypertension and smoking than in those with either risk factor alone.31 (3) Significant life events such as financial or legal problems within the past month may increase the risk of aSAH.32 (4) Aneurysm size 7 mm has been shown to be a risk factor for rupture.33 (5) There does not appear to be an increased risk of aSAH in pregnancy, delivery, and puerperium.34,35 Inflammation appears to play an important role in the pathogenesis 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, macrophages, and reactive oxygen species. Although there are no controlled studies in humans, 3-hydroxy-3- methylglutaryl coenzyme A reductase inhibitors (statin )38 and calcium channel blockers may retard aneurysm forma- tion through the inhibition of NF- B and other pathways. Among the risk factors for aSAH, clearly attributable and modifiable risks are very low body mass index, smoking, and high alcohol consumption.31,39,40 Yet, despite marked improvements in the treatment of hypertension and hyper- lipidemia and the decrease in rates of smoking over time, the incidence of aSAH has not changed appreciably in 30 It is possible that diet increases the risk of stroke in general and aSAH in particular.


Among the risk factors for aSAH, clearly attributable and modifiable risks are very low body mass index, smoking, and high alcohol consumption.31,39,40 Yet, despite marked improvements in the treatment of hypertension and hyper- lipidemia and the decrease in rates of smoking over time, the incidence of aSAH has not changed appreciably in 30 It is possible that diet increases the risk of stroke in general and aSAH in particular. In an epidemiological study of Finnish smokers who were monitored for 13 years, in- creased consumption of yogurt (but not all dairy products) was associated with a higher risk of aSAH.41 Greater vege- table consumption is associated with a lower risk of stroke and aSAH.42 Higher coffee and tea consumption43 and higher magnesium consumption44 were associated with reduced risk of stroke overall but did not change the risk of aSAH. Predicting the growth of an individual intracranial aneu- rysm and its potential for rupture in a given patient remains problematic. When followed up on magnetic resonance im- aging, larger aneurysms ( 8 mm in diameter) tended to grow more over time,45 which implies a higher risk of rupture.


When followed up on magnetic resonance im- aging, larger aneurysms ( 8 mm in diameter) tended to grow more over time,45 which implies a higher risk of rupture. Several characteristics of aneurysm morphology (such as a bottleneck shape46 and the ratio of size of aneurysm to parent vessel47,48) have been associated with rupture status, but how these might be applied to individual patients to predict future aneurysmal rupture is still unclear.33 Variability within each patient is unpredictable at this time, but such intraindividual variability markedly changes the risk of aneurysm detection and rupture and may attenuate the benefits of routine screen- ing in high-risk patients.49 Given such uncertainties, younger age, longer life expec- tancy, and higher rate of rupture all make treatment of unruptured aneurysms more likely to be cost-effective and reduce morbidity and mortality.50 Two large observational studies of familial aneurysms suggest that screening these patients may also be cost-effective in preventing aSAH and improving quality of life.26,27 Smaller studies have suggested that screening of those with 1 first-degree relative with aSAH may be justified as well, but it is far less clear whether patients who underwent treatment for a previous aSAH require ongoing screening.51,52 In the Cerebral Aneurysm Rerupture After Treatment (CARAT) study, recurrent aSAH was predicted by incomplete obliteration of the aneurysm and occurred a median of 3 days after treatment but rarely after 1 year.53 Repeated noninvasive screening at later times may not be cost-effective, increase life expectancy, or improve quality of life in unselected patients.54 Patients with adequately obliterated aneurysms after aSAH have a low risk of recurrent aSAH for at least 5 years,55,56 although some coiled aneu- rysms require retreatment.57 Risk Factors for and Prevention of aSAH: Recommendations 1.


Several characteristics of aneurysm morphology (such as a bottleneck shape46 and the ratio of size of aneurysm to parent vessel47,48) have been associated with rupture status, but how these might be applied to individual patients to predict future aneurysmal rupture is still unclear.33 Variability within each patient is unpredictable at this time, but such intraindividual variability markedly changes the risk of aneurysm detection and rupture and may attenuate the benefits of routine screen- ing in high-risk patients.49 Given such uncertainties, younger age, longer life expec- tancy, and higher rate of rupture all make treatment of unruptured aneurysms more likely to be cost-effective and reduce morbidity and mortality.50 Two large observational studies of familial aneurysms suggest that screening these patients may also be cost-effective in preventing aSAH and improving quality of life.26,27 Smaller studies have suggested that screening of those with 1 first-degree relative with aSAH may be justified as well, but it is far less clear whether patients who underwent treatment for a previous aSAH require ongoing screening.51,52 In the Cerebral Aneurysm Rerupture After Treatment (CARAT) study, recurrent aSAH was predicted by incomplete obliteration of the aneurysm and occurred a median of 3 days after treatment but rarely after 1 year.53 Repeated noninvasive screening at later times may not be cost-effective, increase life expectancy, or improve quality of life in unselected patients.54 Patients with adequately obliterated aneurysms after aSAH have a low risk of recurrent aSAH for at least 5 years,55,56 although some coiled aneu- rysms require retreatment.57 Risk Factors for and Prevention of aSAH: Recommendations 1. Treatment of high blood pressure with antihyper- tensive medication is recommended to prevent ische- mic stroke, intracerebral hemorrhage, and cardiac, renal, and other end-organ injury (Class I; Level of Evidence A). 2.


Treatment of high blood pressure with antihyper- tensive medication is recommended to prevent ische- mic stroke, intracerebral hemorrhage, and cardiac, renal, and other end-organ injury (Class I; Level of Evidence A). 2. Hypertension should be treated, and such treatment may reduce the risk of aSAH (Class I; Level of Evidence B). 3. Tobacco use and alcohol misuse should be avoided to reduce the risk of aSAH (Class I; Level of Evidence B). Table 2. Definition of Classes and Levels of Evidence Used in AHA Stroke Council Recommendations Class I Conditions for which there is evidence for and/or general agreement that the procedure or treatment is useful and effective. Class II Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment. Class IIa The weight of evidence or opinion is in favor of the procedure or treatment. Class IIb Usefulness/efficacy is less well established by evidence or opinion. Class III Conditions for which there is evidence and/or general agreement that the procedure or treatment is not useful/effective and in some cases may be harmful. Therapeutic recommendations Level of Evidence A Data derived from multiple randomized clinical trials or meta-analyses Level of Evidence B Data derived from a single randomized trial or nonrandomized studies Level of Evidence C Consensus opinion of experts, case studies, or standard of care Diagnostic recommendations Level of Evidence A Data derived from multiple prospective cohort studies using a reference standard applied by a masked evaluator Level of Evidence B Data derived from a single grade A study, or 1 case-control studies, or studies using a reference standard applied by an unmasked evaluator Level of Evidence C Consensus opinion of experts 4.


Therapeutic recommendations Level of Evidence A Data derived from multiple randomized clinical trials or meta-analyses Level of Evidence B Data derived from a single randomized trial or nonrandomized studies Level of Evidence C Consensus opinion of experts, case studies, or standard of care Diagnostic recommendations Level of Evidence A Data derived from multiple prospective cohort studies using a reference standard applied by a masked evaluator Level of Evidence B Data derived from a single grade A study, or 1 case-control studies, or studies using a reference standard applied by an unmasked evaluator Level of Evidence C Consensus opinion of experts 4. In addition to the size and location of the aneurysm and the patient s age and health status, it might be reasonable to consider morphological and hemody- namic characteristics of the aneurysm when discuss- ing the risk of aneurysm rupture (Class IIb; Level of Evidence B). (New recommendation) 5. Consumption of a diet rich in vegetables may lower the risk of aSAH (Class IIb; Level of Evidence B). (New recommendation) 6. It may be reasonable to offer noninvasive screening to patients with familial (at least 1 first-degree relative) aSAH and/or a history of aSAH to evaluate Table 3. Class I Recommendations Level of Evidence Recommendation A 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 aSAH B 2.


Hypertension should be treated, and such treatment may reduce the risk of aSAH B 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.


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, 10 aSAH cases per year) should consider early transfer of patients with aSAH to high-volume centers (eg, 35 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.


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. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1715 Table 4. New or Revised Recommendations New or Revised Recommendation Class of Recommendation/ Level of Evidence New 1. In addition to the size and location of the aneurysm and the patient s age and health status, it might be reasonable to consider morphological and hemodynamic characteristics of the aneurysm when discussing the risk of aneurysm rupture. Class IIb, Level B New 2. Consumption of a diet rich in vegetables may lower the risk of aSAH. Class IIb, Level B New 3. After any aneurysm repair, immediate cerebrovascular imaging is generally recommended to identify remnants or recurrence of the aneurysm that may require treatment. Class I, Level B New 4. After discharge, it is reasonable to refer patients with aSAH for a comprehensive evaluation, including cognitive, behavioral, and psychosocial assessments. Class IIa, Level B New 5. CTA may be considered in the workup of aSAH. If an aneurysm is detected by CTA, this study may help guide the 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). Class IIb, Level C New 6. Magnetic resonance imaging (fluid-attenuated inversion recovery, proton density, diffusion-weighted imaging, and 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. Class IIb, Level C New 7.


Magnetic resonance imaging (fluid-attenuated inversion recovery, proton density, diffusion-weighted imaging, and 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. Class IIb, Level C New 7. 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). Class I, Level B New 8. 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. Class I, Level B New 9. The magnitude of blood pressure control to reduce the risk of rebleeding has not been established, but a decrease in systolic blood pressure to 160 mm Hg is reasonable. Class IIa, Level C New 10. 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. Class I, Level B New 11. Microsurgical clipping may receive increased consideration in patients presenting with large ( 50 mL) intraparenchymal hematomas and middle cerebral artery aneurysms. Endovascular coiling may receive increased consideration in the elderly ( 70 y of age), in those presenting with poor-grade WFNS classification (IV/V) aSAH, and in those with aneurysms of the basilar apex. Class IIb, Level C New 12.


Endovascular coiling may receive increased consideration in the elderly ( 70 y of age), in those presenting with poor-grade WFNS classification (IV/V) aSAH, and in those with aneurysms of the basilar apex. Class IIb, Level C New 12. Stenting of a ruptured aneurysm is associated with increased morbidity and mortality. Class III, Level C New 13. Annual monitoring of complication rates for surgical and interventional procedures is reasonable. Class IIa, Level C New 14. A hospital credentialing process to ensure that proper training standards have been met by individual physicians treating brain aneurysms is reasonable. Class IIa, Level C New 15. Prophylactic hypervolemia or balloon angioplasty before the development of angiographic spasm is not recommended. Class III, Level B New 16. Transcranial Doppler is reasonable to monitor for the development of arterial vasospasm. Class IIa, Level B New 17. Perfusion imaging with CT or magnetic resonance can be useful to identify regions of potential brain ischemia. Class IIa, Level B New 18. Weaning EVD over 24 hours does not appear to be effective in reducing the need for ventricular shunting. Class III, Level B New 19. Routine fenestration of the lamina terminalis is not useful for reducing the rate of shunt-dependent hydrocephalus and therefore should not be routinely performed. Class III, Level B New 20. Aggressive control of fever to a target of normothermia by use of standard or advanced temperature modulating systems is reasonable in the acute phase of aSAH. Class IIa, Level B New 21. The use of packed red blood cell transfusion to treat anemia might be reasonable in patients with aSAH who are at risk of cerebral ischemia. The optimal hemoglobin goal is still to be determined. Class IIb, Level B New 22. Heparin-induced thrombocytopenia and deep venous thrombosis are relatively frequent complications after aSAH.


Heparin-induced thrombocytopenia and deep venous thrombosis are relatively frequent complications after aSAH. Early identification and targeted treatment are recommended, but further research is needed to identify the ideal screening paradigms. Class I, Level B Revised 1. For patients with an unavoidable delay in obliteration of aneurysm, a significant risk of rebleeding, and no compelling medical contraindications, short-term ( 72 hours) therapy with tranexamic acid or aminocaproic acid is reasonable to reduce the risk of early aneurysm rebleeding. Class IIa, Level B Revised 2. 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. Class I, Level C (Continued) for de novo aneurysms or late regrowth of a treated aneurysm, but the risks and benefits of this screen- ing require further study (Class IIb; Level of Evi- dence B). 7. After any aneurysm repair, immediate cerebrovas- cular imaging is generally recommended to identify remnants or recurrence of the aneurysm that may require treatment (Class I; Level of Evidence B). (New recommendation) Natural History and Outcome of aSAH Although the case fatality of aSAH remains high world- wide,5 mortality rates from aSAH appear to have declined in industrialized nations over the past 25 years.9,11,15,58,59 One study in the United States reported a decrease of 1% per year from 1979 to 1994.60 Others have shown that case fatality rates decreased from 57% in the mid-1970s to 42% in the mid-1980s,11 whereas rates from the mid-1980s to 2002 are reported to be anywhere from 26% to 36%.6,12,13,18,20,61,62 Mortality rates vary widely across published epidemiological studies, ranging from 8% to 67%.59 Regional variations become apparent when num- bers from different studies are compared.


(New recommendation) Natural History and Outcome of aSAH Although the case fatality of aSAH remains high world- wide,5 mortality rates from aSAH appear to have declined in industrialized nations over the past 25 years.9,11,15,58,59 One study in the United States reported a decrease of 1% per year from 1979 to 1994.60 Others have shown that case fatality rates decreased from 57% in the mid-1970s to 42% in the mid-1980s,11 whereas rates from the mid-1980s to 2002 are reported to be anywhere from 26% to 36%.6,12,13,18,20,61,62 Mortality rates vary widely across published epidemiological studies, ranging from 8% to 67%.59 Regional variations become apparent when num- bers from different studies are compared. The median mortality rate in epidemiological studies from the United States has been 32% versus 43% to 44% in Europe and 27% in Japan.59 These numbers are based on studies that did not always fully account for cases of prehospital death. This is an important consideration because the observed decrease in case fatality is related to improvements in survival among hospitalized patients with aSAH. The mean age of patients presenting with aSAH is increas- ing, which has been noted to have a negative impact on survival rates.59 Sex and racial variations in survival may also play a role in the variable rates, with some studies suggesting higher mortality in women than in men9,11,60 and higher mortality in blacks, American Indians/Alaskan Natives, and Asians/Pacific Islanders than in whites.63 Available population-based studies offer much less infor- mation about the functional outcome of survivors.


The mean age of patients presenting with aSAH is increas- ing, which has been noted to have a negative impact on survival rates.59 Sex and racial variations in survival may also play a role in the variable rates, with some studies suggesting higher mortality in women than in men9,11,60 and higher mortality in blacks, American Indians/Alaskan Natives, and Asians/Pacific Islanders than in whites.63 Available population-based studies offer much less infor- mation about the functional outcome of survivors. Rates of persistent dependence of between 8% and 20% have been reported when the modified Rankin Scale is used.59 Although not population based, trial data show a similar picture, with 12% of patients in the International Subarachnoid Aneurysm 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. Furthermore, scales that are relatively insensitive to cognitive impairment, behavioral changes, social readjustment, and energy level may substantially underestimate the effect of aSAH on the function and quality of life of surviving patients. Multiple studies using diverse designs have consistently demonstrated that intellectual impairment is very prevalent after aSAH.


Multiple studies using diverse designs have consistently demonstrated that intellectual impairment is very prevalent after aSAH. Although cognitive function tends to improve over the first year,64 global cognitive impairment is still present in 20% of aSAH patients and is associated with poorer functional recovery and lower quality of life.65 Cog- nitive deficits and functional decline are often compounded by mood disorders (anxiety, depression), fatigue, and sleep disturbances.66 Therefore, scales assessing well-being and quality of life can be particularly useful in the integral assessment of patients with aSAH, even among those who regain functional independence.67,68 Behavioral and psycho- social difficulties, as well as poor physical and mental endurance, are some of the most commonly encountered factors accounting for the inability of otherwise independent patients to return to their previous occupations.66,68 Much remains to be learned about the causes of cognitive and functional deficits after aSAH and the best methods to assess intellectual outcome and functional recovery in these patients. The severity of clinical presentation is the strongest prognostic indicator in aSAH. Initial clinical severity can be Table 4. Continued New or Revised Recommendation Class of Recommendation/ Level of Evidence Revised 3. For patients with ruptured aneurysms judged to be technically amenable to both endovascular coiling and neurosurgical clipping, endovascular coiling should be considered. Class I, Level B Revised 4. Low-volume hospitals (eg, 10 aSAH cases per year) should consider early transfer of patients with aSAH to high-volume centers (eg, 35 aSAH cases per year) with experienced cerebrovascular surgeons, endovascular specialists, and multidisciplinary neuro-intensive care services. Class I, Level B Revised 5. Maintenance of euvolemia and normal circulating blood volume is recommended to prevent DCI. Class I, Level B Revised 6. Induction of hypertension is recommended for patients with DCI unless blood pressure is elevated at baseline or cardiac status precludes it.


Induction of hypertension is recommended for patients with DCI unless blood pressure is elevated at baseline or cardiac status precludes it. Class I, Level B Revised 7. Cerebral angioplasty and/or selective intra-arterial vasodilator therapy is reasonable in patients with symptomatic cerebral vasospasm, particularly those who are not rapidly responding to hypertensive therapy. Class IIa, Level B Revised 8. aSAH-associated acute symptomatic hydrocephalus should be managed by cerebrospinal fluid diversion (EVD or lumbar drainage, depending on the clinical scenario). Class I, Level B Revised 9. aSAH-associated chronic symptomatic hydrocephalus should be treated with permanent cerebrospinal fluid diversion. Class I, Level C 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. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1717 reliably categorized by use of simple validated scales, such as the Hunt and Hess and World Federation of Neurological Surgeons scales.69,70 Aneurysm rebleeding is another major predictor of poor outcome, as discussed in a later section. Other factors predictive of poor prognosis include older age, preexisting severe medical illness, global cerebral edema on computed tomography (CT) scan, intraventricular and intra- cerebral hemorrhage, symptomatic vasospasm, delayed cere- bral infarction (especially if multiple), hyperglycemia, fever, anemia, and other systemic complications such as pneumonia and sepsis.71 77 Certain aneurysm factors, such as size, location, and complex configuration, may increase the risk of periprocedural complications and affect overall prognosis.78 Treatment in high-volume centers with availability of neuro- surgical and endovascular services may be associated with Natural History and Outcome of aSAH: Recommendations 1.


Other factors predictive of poor prognosis include older age, preexisting severe medical illness, global cerebral edema on computed tomography (CT) scan, intraventricular and intra- cerebral hemorrhage, symptomatic vasospasm, delayed cere- bral infarction (especially if multiple), hyperglycemia, fever, anemia, and other systemic complications such as pneumonia and sepsis.71 77 Certain aneurysm factors, such as size, location, and complex configuration, may increase the risk of periprocedural complications and affect overall prognosis.78 Treatment in high-volume centers with availability of neuro- surgical and endovascular services may be associated with Natural History and Outcome of aSAH: Recommendations 1. The initial clinical severity of aSAH should be deter- mined 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 (Class I; Level of Evidence B). 2. The risk of early aneurysm rebleeding is high, and rebleeding is associated with very poor outcomes. Therefore, urgent evaluation and treatment of pa- tients with suspected aSAH is recommended (Class I; Level of Evidence B). 3. After discharge, it is reasonable to refer patients with aSAH for a comprehensive evaluation, in- cluding cognitive, behavioral, and psychosocial assessments (Class IIa; Level of Evidence B). (New recommendation) Clinical Manifestations and Diagnosis of aSAH The clinical presentation of aSAH is one of the most distinctive in medicine. The hallmark of aSAH in a patient who is awake is the complaint the worst headache of my life, which is described by 80% of patients who can give a history.82 This headache is characterized as being extremely sudden and immediately reaching maximal intensity (thun- derclap headache).


The hallmark of aSAH in a patient who is awake is the complaint the worst headache of my life, which is described by 80% of patients who can give a history.82 This headache is characterized as being extremely sudden and immediately reaching maximal intensity (thun- derclap headache). A warning or sentinel headache that precedes the aSAH-associated ictus is also reported by 10% to 43% of patients.83,84 This sentinel headache increases the odds of early rebleeding 10-fold.85 Most intracranial aneu- rysms remain asymptomatic until they rupture. aSAH can occur during physical exertion or stress.86 Nevertheless, in a review of 513 patients with aSAH, the highest incidence of rupture occurred while patients were engaged in their daily routines, in the absence of strenuous physical activity.87 The onset of headache may be associated with 1 additional signs and symptoms, including nausea and/or vomiting, stiff neck, photophobia, brief loss of consciousness, or focal neurolog- ical deficits (including cranial nerve palsies). In a retrospec- tive study of 109 patients with proven aSAH, headache was present in 74%, nausea or vomiting in 77%, loss of con- sciousness in 53%, and nuchal rigidity in 35%.88 As many as 12% of patients die before receiving medical attention. Despite the classic presentation of aSAH, individual find- ings occur inconsistently, and because the type of headache from aSAH is sufficiently variable, misdiagnosis or delayed diagnosis is common.


Despite the classic presentation of aSAH, individual find- ings occur inconsistently, and because the type of headache from aSAH is sufficiently variable, misdiagnosis or delayed diagnosis is common. Before 1985, misdiagnosis of aSAH occurred in as many as 64% of cases, with more recent data suggesting a misdiagnosis rate of 12%.89,90 Misdiagnosis was associated with a nearly 4-fold higher likelihood of death or disability at 1 year in patients with minimal or no neurological deficit at the initial visit.89 The most common diagnostic error is failure to obtain a noncontrast head CT scan.89,91 93 In a small subset of patients, a high degree of suspicion based on clinical presentation will lead to the correct diagnosis despite normal head CT and cerebrospinal fluid test results, as shown in a recent study in which 1.4% of patients were diagnosed with aSAH only after vascular imaging techniques were used.94 Patients may report symptoms consistent with a minor hemorrhage before a major rupture, which has been called a sentinel bleed or warning leak.83,84 The majority of these minor hemorrhages occur within 2 to 8 weeks before overt aSAH. The headache associated with a warning leak is usually milder than that associated with a major rupture, but it may last a few days.95,96 Nausea and vomiting may occur, but meningismus is uncommon after a sentinel hemorrhage. Among 1752 patients with aneurysm rupture from 3 series, 340 (19.4%; range, 15% 37%) had a history of a sudden severe headache before the event that led to admission.82,95,97 The importance of recognizing a warning leak cannot be overemphasized.


Among 1752 patients with aneurysm rupture from 3 series, 340 (19.4%; range, 15% 37%) had a history of a sudden severe headache before the event that led to admission.82,95,97 The importance of recognizing a warning leak cannot be overemphasized. Headache is a common presenting chief complaint in the emergency department, and aSAH accounts for only 1% of all headaches evaluated in the emergency 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 Seizures may occur in up to 20% of patients after aSAH, most commonly in the first 24 hours and more commonly in aSAH associated with intracerebral hemorrhage, hypertension, and middle cerebral and anterior communicating artery Noncontrast head CT remains the cornerstone of diagnosis of aSAH; since publication of the previous version of these guidelines,1,2 there have been only minor changes in imaging technology for this condition. The sensitivity of CT in the first 3 days after aSAH remains very high (close to 100%), after which it decreases moderately during the next few days.2,100 After 5 to 7 days, the rate of negative CT increases sharply, and lumbar puncture is often required to show xanthochromia. However, advances in magnetic resonance imaging of the brain, particularly the use of fluid-attenuated inversion recovery, proton density, diffusion-weighted imag- ing, and gradient echo sequences,101 103 can often allow the diagnosis of aSAH to be made when a head CT scan is negative and there is clinical suspicion of aSAH, possibly avoiding the need for lumbar puncture.


However, advances in magnetic resonance imaging of the brain, particularly the use of fluid-attenuated inversion recovery, proton density, diffusion-weighted imag- ing, and gradient echo sequences,101 103 can often allow the diagnosis of aSAH to be made when a head CT scan is negative and there is clinical suspicion of aSAH, possibly avoiding the need for lumbar puncture. The role of magnetic resonance imaging in perimesencephalic aSAH is controver- sial.104 Indications for magnetic resonance angiography in aSAH are still few because of limitations with routine availability, logistics (including difficulty in scanning acutely ill patients), predisposition to motion artifact, patient compli- ance, longer study time, and cost. Aneurysms 3 mm in size continue to be unreliably demonstrated on computed tomo- graphic angiography (CTA),105,106 and this generates contin- ued controversy in the case of CTA-negative aSAH.107 In cases of perimesencephalic subarachnoid hemorrhage (SAH), some authors claim that a negative CTA result is sufficient to rule out aneurysmal hemorrhage and that cerebral angiogra- phy is not required, but this is controversial. In 1 study, the overall interobserver and intraobserver agreement for nonan- eurysmal perimesencephalic hemorrhage was good, but there was still a level of disagreement among observers, which suggests that clinicians should be cautious when deciding whether to pursue follow-up imaging.108 In another study,109 a negative CTA result reliably excluded aneurysms when head CT showed the classic perimesencephalic SAH pattern or no blood. Digital subtraction angiography (DSA) was indicated if there was a diffuse aneurysmal pattern of aSAH, and repeat delayed DSA was required if the initial DSA findings were negative, which led to the detection of a small aneurysm in 14% of cases.


Digital subtraction angiography (DSA) was indicated if there was a diffuse aneurysmal pattern of aSAH, and repeat delayed DSA was required if the initial DSA findings were negative, which led to the detection of a small aneurysm in 14% of cases. When the blood is located in the sulci, CTA should be scrutinized for vasculitis, and DSA is recommended for confirmation.109 Others have shown that CTA may not reveal small aneurysms and that 2- and 3-dimensional cerebral angiography should be performed, especially when the hemorrhage is accompanied by loss of consciousness.110 In cases of diffuse aSAH pattern, most agree that negative CTA should be followed by 2- and 3-dimensional cerebral angiography. In older patients with degenerative vascular diseases, CTA can replace catheter cerebral angiography in most cases if the image quality is excellent and analysis is performed carefully.111 Overlying bone can be problematic with CTA, especially at the skull base. A new technique, CTA-MMBE (multisection CTA combined with matched mask bone elimination), is accurate in detecting intracranial aneurysms in any projection without superimposed bone.112 CTA-MMBE has limited sensitivity in detecting very small aneurysms. The data suggest that DSA and 3-dimensional rotational angiography can be limited to the vessel harboring the ruptured aneurysm before endovas- cular treatment after detection of a ruptured aneurysm with CTA. Another new technique, dual-energy CTA, has diag- nostic image quality at a lower radiation dose than digital subtraction CTA and high diagnostic accuracy compared with 3-dimensional DSA (but not 2-dimensional DSA) in the detection of intracranial aneurysms.113 Cerebral angiography is still widely used in the investiga- tion of aSAH and the characterization of ruptured cerebral aneurysms.


Another new technique, dual-energy CTA, has diag- nostic image quality at a lower radiation dose than digital subtraction CTA and high diagnostic accuracy compared with 3-dimensional DSA (but not 2-dimensional DSA) in the detection of intracranial aneurysms.113 Cerebral angiography is still widely used in the investiga- tion of aSAH and the characterization of ruptured cerebral aneurysms. Although CTA is sometimes considered suffi- cient on its own when an aneurysm will be treated with surgical clipping,114 substantial controversy remains about the ability of CTA to determine whether or not an aneurysm is amenable to endovascular therapy.115 120 In 1 series,115 95.7% of patients with aSAH were referred for treatment on the basis of CTA. In 4.4% of patients, CTA did not provide enough information to determine the best treatment, and those patients required DSA; 61.4% of patients were referred to endovascular treatment on the basis of CTA; and successful coiling was achieved in 92.6%. The authors concluded that CTA with a 64-slice scanner is an accurate tool for detecting and characterizing aneurysms in acute aSAH and that CTA is useful in deciding whether to coil or clip an aneurysm.115 Partial volume averaging phenomena may artificially widen the aneurysmal neck and may lead to the erroneous conclu- sion that an aneurysm cannot be treated by endovascular coiling. This controversy is likely caused by the different technological specifications (16- versus 64-detector rows), slice thickness, and data processing algorithms of various CT systems, which have different spatial resolutions. Three- dimensional cerebral angiography is more sensitive for de- tecting aneurysms than 2-dimensional angiography.121,122 The combination of 3- and 2-dimensional cerebral angiography usually provides the best morphological depiction of aneu- rysm anatomy with high spatial resolution, and it is, of course, always used in preparation for endovascular therapy.


Three- dimensional cerebral angiography is more sensitive for de- tecting aneurysms than 2-dimensional angiography.121,122 The combination of 3- and 2-dimensional cerebral angiography usually provides the best morphological depiction of aneu- rysm anatomy with high spatial resolution, and it is, of course, always used in preparation for endovascular therapy. Flat-panel volumetric CT is a relatively recent develop- ment that allows the generation of CT-like images from a rotational 3-dimensional spin of the x-ray gantry in the angiography room. For the moment, it has no substantial role in the initial diagnosis of aSAH because its spatial and contrast resolutions are not high enough123; however, this technology can be used intraprocedurally during emboliza- tions to rule out hydrocephalus.124 Recently, radiation dose has emerged as an important and worrisome consideration for patients with SAH.125,126 The combination of noncontrast head CT for the diagnosis of aSAH, confirmation of ventric- ulostomy placement, investigation of neurological changes, CTA for aneurysmal diagnosis, CTA and CT perfusion for recognition of vasospasm, and catheter cerebral angiography for aneurysm embolization and then for endovascular therapy of vasospasm can result in substantial radiation doses to the head, with possible risk of radiation injury, such as scalp erythema and alopecia. Although some or all of these radio- logical examinations are often necessary, efforts need to be made to reduce the amount of radiation exposure in patients with aSAH whenever possible. Clinical Manifestations and Diagnosis of aSAH: Recommendations 1. 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 (Class I; Level of Evidence B). 2. Acute diagnostic workup should include noncontrast head CT, which, if nondiagnostic, should be followed by lumbar puncture (Class I; Level of Evidence B). 3.


Acute diagnostic workup should include noncontrast head CT, which, if nondiagnostic, should be followed by lumbar puncture (Class I; Level of Evidence B). 3. CTA may be considered in the workup of aSAH. If an aneurysm is detected by CTA, this study may help guide the decision for type of aneurysm repair, but if CTA is inconclusive, DSA is still recommended (except possibly in the instance of classic perimesen- cephalic aSAH) (Class IIb; Level of Evidence C). (New recommendation) 4. Magnetic resonance imaging (fluid-attenuated inver- sion recovery, proton density, diffusion-weighted imaging, and gradient echo sequences) may be rea- sonable for the diagnosis of aSAH in patients with a nondiagnostic CT scan, although a negative result Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1719 does not obviate the need for cerebrospinal fluid analysis (Class IIb; Level of Evidence C). (New recommendation) 5. DSA with 3-dimensional rotational angiography is indicated for detection of aneurysm in patients with aSAH (except when the aneurysm was previ- ously diagnosed by a noninvasive angiogram) and for planning treatment (to determine whether an aneurysm is amenable to coiling or to expedite microsurgery) (Class I; Level of Evidence B). (New recommendation) Medical Measures to Prevent Rebleeding After aSAH Aneurysm rebleeding is associated with very high mortality and poor prognosis for functional recovery in survivors.


(New recommendation) Medical Measures to Prevent Rebleeding After aSAH Aneurysm rebleeding is associated with very high mortality and poor prognosis for functional recovery in survivors. The risk of rebleeding is maximal in the first 2 to 12 hours, with reported rates of occurrence between 4% and 13.6% within the first 24 hours.127 130 In fact, more than one third of rebleeds occur within 3 hours and nearly half within 6 hours of symptom onset,131 and early rebleeding is associated with worse outcome than later rebleeding.132 Factors associated with aneurysm rebleeding include longer time to aneurysm treatment, worse neurological status on admission, initial loss of consciousness, previous sentinel headaches (severe head- aches lasting 1 hour that do not lead to the diagnosis of aSAH), larger aneurysm size, and possibly systolic blood pressure 160 mm Hg.87,129,130 Genetic factors, although related to the occurrence of intracranial aneurysms, do not appear to be related to an increased incidence of rebleed- ing.133 Early treatment of the ruptured aneurysm can reduce the risk of rebleeding.71 Among patients who present in a delayed manner and during the vasospasm window, delayed obliteration of aneurysm is associated with a higher risk of rebleeding than early obliteration of aneurysm.134 There is general agreement that acute hypertension should be controlled after aSAH and until aneurysm obliteration, but parameters for blood pressure control have not been defined. A variety of titratable medications are available. Nicardipine may give smoother blood pressure control than labetalol135 and sodium nitroprusside,136 although data showing different clinical outcomes are lacking.


Nicardipine may give smoother blood pressure control than labetalol135 and sodium nitroprusside,136 although data showing different clinical outcomes are lacking. Although lowering cerebral perfusion pressure may lead to cerebral ischemia, a cohort study of neurologically critically ill patients did not find an association between use of nicardipine and reduced brain oxygen tension.137 Clevidipine, a very short-acting calcium channel blocker, is another option for acute control of hypertension, but data for aSAH are lacking at this time. Antifibrinolytic therapy has been shown to reduce the incidence of aneurysm rebleeding when there is a delay in aneurysm obliteration. One referral center instituted a policy of short-term use of aminocaproic acid to prevent rebleeding during patient transfer. Such use led to a decreased incidence in rebleeding without increasing the risk of DCI, but 3-month clinical outcomes were not affected.138 There was an in- creased risk of deep venous thrombosis but not pulmonary embolism. Neither aminocaproic acid nor tranexamic acid is approved by the US Food and Drug Administration for prevention of aneurysm rebleeding. Medical Measures to Prevent Rebleeding After aSAH: Recommendations 1. 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 (Class I; Level of Evidence B). (New recommendation) 2. The magnitude of blood pressure control to reduce the risk of rebleeding has not been established, but a decrease in systolic blood pressure to <160 mm Hg is reasonable (Class IIa; Level of Evidence C). (New recommendation) 3.


The magnitude of blood pressure control to reduce the risk of rebleeding has not been established, but a decrease in systolic blood pressure to <160 mm Hg is reasonable (Class IIa; Level of Evidence C). (New recommendation) 3. For patients with an unavoidable delay in oblitera- tion of aneurysm, a significant risk of rebleeding, and no compelling medical contraindications, short- term (<72 hours) therapy with tranexamic acid or aminocaproic acid is reasonable to reduce the risk of early aneurysm rebleeding (Class IIa; Level of Evi- dence B). (Revised recommendation from previous guidelines) Surgical and Endovascular Methods for Treatment of Ruptured Cerebral Aneurysms Microsurgical clip obliteration of intracranial aneurysms was the primary modality of treatment before 1991, when Gug- lielmi first described occlusion of an aneurysm by an endo- vascular approach with electrolytically detachable coils.139 With advancements in both microsurgical and endovascular approaches, algorithms to determine the proper patient pop- ulation and aneurysmal characteristics for each treatment are continually undergoing refinement. The only multicenter randomized trial comparing microsurgical and endovascular repair, ISAT, randomized 2143 of 9559 screened patients with aSAH across 42 neurosurgical centers.140 For a patient to be considered eligible for the trial, neurosurgeons and inter- ventionalists had to agree that the aneurysm was comparably suitable for treatment with either modality. Primary outcomes included death or dependent living, and secondary outcomes included risk of seizures and risk of rebleeding.


Primary outcomes included death or dependent living, and secondary outcomes included risk of seizures and risk of rebleeding. Initial 1-year outcomes revealed a reduction in death and disability from 31% in the microsurgery arm to 24% in the endovascular arm (relative risk reduction, 24%).141 This difference was mainly driven by a decrease in the rate of disability among survivors 16% in the endovascular arm and 22% in the craniotomy arm) and was likely attributable at least in part to the greater incidence of technical complications in the clipping (19%) versus the coiling (8%) arms and the longer time needed to secure the aneurysm.142,143 The risk of epilepsy and signifi- cant cognitive decline was also reduced in the endovascular group, but the incidence of late rebleeding (2.9% after endovascular repair versus 0.9% after open surgery) was higher in the endovascular arm, and only 58% of coiled aneurysms were completely obliterated compared with 81% of clipped aneurysms.140 A large retrospective analysis found that the rate of incomplete occlusion and subsequent aneu- rysm recurrence depended critically on neck diameter and dome size.139 It can also be difficult to achieve complete obliteration in very small aneurysms ( 3 mm), with 1 study reporting no coils deployed in 5% of cases, residual dome filling or a neck remnant in 30%, and a higher procedural complication rate than in larger aneurysms.144 Although the complete obliteration rate can be increased by the addition of a high-porosity stent, this has been associated with an increased risk of complications, especially in patients with SAH, in large part because of the need for periprocedural dual-antiplatelet therapy to prevent arterial thromboembolism.145 Whether low-porosity flow-diverting stents with or without coils represent a better option for many or most of those presenting with SAH from saccular aneu- rysms remains to be studied, but these stents make more conceptual sense for use in the patient with a dissecting aneurysm, in whom vessel sacrifice is not an option and microsurgical solutions carry higher risk.


Another approach to increasing complete obliteration rates involves the deployment of biologically active rather than pure platinum coils.146 Although uncontrolled studies suggest a potential reduction in the risk of recurrence, these data are preliminary and have yet to be confirmed in prospective controlled trials.147,148 Thus, although the short-term efficacy of endovascular coil obliteration is well established compared with microsurgical approaches, close long-term surveillance continues to be warranted, because durability remains a Given this delicate balance between safety and durability, there have been multiple efforts to identify subgroups of patients who might be best treated with endovascular or microsurgical techniques.


Although the quality of the data is modest, most agree that with current endovascular technol- ogy, middle cerebral artery aneurysms can be difficult to treat with coil embolization, and in this location, surgical treatment has tended to yield more favorable results.146,150 152 Although some have suggested that older patients are ideal candidates for coiling rather than clipping, data on this population are sparse and at times conflicting.141,153,154 Although patients presenting with an intraparenchymal hematoma 50 mL have a higher incidence of unfavorable outcome, hematoma evacuation within 3.5 hours has been shown to improve outcome in this subgroup and argues in favor of microsurgery for most patients with large parenchymal clots.155 By con- trast, patients presenting during the vasospasm period, espe- cially those with confirmed vasospasm, may be better treated with endovascular techniques, depending on the anatomy of the aneurysm and its relationship to the spasm.150 Patients presenting with poor clinical grade appear to benefit more from endovascular coiling, especially if they are also elderly, because advanced age renders long-term durability less important.156 Still, it is critical that patients with poor clinical grade be treated in centers where both modalities are available.157 Endovascular treatment of posterior circulation aneurysms has been gaining widespread acceptance based on several observational studies. A meta-analysis revealed that the mortality from coiling of a basilar bifurcation aneurysm was 0.9%, and the risk of permanent complications was 5.4%.158 More recently, with regard to treatment of posterior circula- tion aneurysms, the mortality and morbidity in 112 ruptured aneurysms was 3.7% and 9.4%, respectively.159 These data have led to an increasing tendency toward coiling ruptured posterior circulation aneurysms.


A meta-analysis revealed that the mortality from coiling of a basilar bifurcation aneurysm was 0.9%, and the risk of permanent complications was 5.4%.158 More recently, with regard to treatment of posterior circula- tion aneurysms, the mortality and morbidity in 112 ruptured aneurysms was 3.7% and 9.4%, respectively.159 These data have led to an increasing tendency toward coiling ruptured posterior circulation aneurysms. One study that compared clipping versus coiling of basilar apex aneurysm (44 patients in each treatment arm) found a poor outcome rate of 11% in the endovascular treatment group versus 30% in the surgical group. In that study, the main difference was the rate of ischemia and hemorrhage during the surgical intervention. The rates of recurrent hemorrhage and delayed ischemia were actually similar in both groups.159 Incomplete aneurysm occlusion and recurrent aneurysm filling from progressive coil compaction are particularly difficult challenges encountered with endovascular treatment of basilar artery aneurysms. In a study of 41 posterior circulation aneurysms, 35 (85%) had complete or near- complete immediate angiographic occlusion. The follow-up time frame for this study was 17 months, and of the 29 patients for whom follow-up was obtained, those with com- pletely occluded aneurysms did not reveal any compaction. In the remaining patients who had near-complete occlusion, 47% had experienced recanalization, with 1 patient experi- encing a rehemorrhage.160 On the basis of these findings, closer follow-up with sequential DSA is needed in patients who undergo coiling of posterior circulation aneurysms, particularly those who do not exhibit complete occlusion on immediate follow-up angiography. Surgical and Endovascular Methods of Treatment of Ruptured Cerebral Aneurysms: Recommendations 1. Surgical clipping or endovascular coiling of the rup- tured aneurysm should be performed as early as feasible in the majority of patients to reduce the rate of rebleeding after aSAH (Class I; Level of Evidence B).


Surgical clipping or endovascular coiling of the rup- tured aneurysm should be performed as early as feasible in the majority of patients to reduce the rate of rebleeding after aSAH (Class I; Level of Evidence B). 2. Complete obliteration of the aneurysm is recom- mended whenever possible (Class I; Level of Evi- dence B). 3. Determination of aneurysm treatment, as judged by both experienced cerebrovascular surgeons and en- dovascular specialists, should be a multidisciplinary decision based on characteristics of the patient and the aneurysm (Class I; Level of Evidence C). (Revised recommendation from previous guidelines) 4. For patients with ruptured aneurysms judged to be technically amenable to both endovascular coiling and neurosurgical clipping, endovascular coiling should be considered (Class I; Level of Evidence B). (Revised recommendation from previous guidelines) 5. In the absence of a compelling contraindication, patients who undergo coiling or clipping of a rup- tured aneurysm should have delayed follow-up vas- cular imaging (timing and modality to be individu- alized), and strong consideration should be given to retreatment, either by repeat coiling or microsurgi- cal clipping, if there is a clinically significant (eg, growing) remnant (Class I; Level of Evidence B). (New recommendation) 6. Microsurgical clipping may receive increased con- sideration in patients presenting with large (>50 mL) intraparenchymal hematomas and middle cere- bral artery aneurysms. Endovascular coiling may receive increased consideration in the elderly ( 70 years of age), in those presenting with poor-grade Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1721 (World Federation of Neurological Surgeons classi- fication IV/V) aSAH, and in those with aneurysms of the basilar apex (Class IIb; Level of Evidence C). (New recommendation) 7.


Endovascular coiling may receive increased consideration in the elderly ( 70 years of age), in those presenting with poor-grade Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1721 (World Federation of Neurological Surgeons classi- fication IV/V) aSAH, and in those with aneurysms of the basilar apex (Class IIb; Level of Evidence C). (New recommendation) 7. Stenting of a ruptured aneurysm is associated with increased morbidity and mortality, and should only be considered when less risky options have been excluded (Class III; Level of Evidence C). (New recommendation) Hospital Characteristics and Systems of Care In a US study of 31 476 nontraumatic cases of aSAH from 2003, definitive aneurysm repair was delivered in fewer than one third of cases. That said, the adjusted odds of definitive repair were significantly higher in urban teaching hospitals than in urban nonteaching hospitals (odds ratio, 1.62) or rural hospitals (odds ratio, 3.08).7 In another study from 1993 to 2003, teaching status and larger hospital size were associated with higher charges and longer stay but also with better outcomes (P 0.05) and lower mortality rates (P 0.05), especially in patients who underwent aneurysm clipping (P 0.01). Endovascular treatment, which was more often used in the elderly, was also associated with significantly higher mortality rates in smaller hospitals (P 0.001) and steadily increasing morbidity rates (45%).