(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. 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. 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). 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. 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%). Large academic centers were associated with better results, particularly for surgical clip placement.161 Prior studies have also indi- cated that 82% of US hospitals admitted 19 patients with aSAH annually, and the 30-day mortality rate was signif- icantly higher in hospitals that admitted 10 patients with aSAH versus 35 patients with aSAH (39% versus 27%; odds ratio, 1.4).80 Two factors associated with better outcomes were greater use of endovascular services and a higher percentage of patients transferred from other hospitals.79 81 Institutions that used endovascular coil embolization more frequently had lower in-hospital mortality rates, a 9% reduction in risk for every 10% of cases treated. In addition, there was a 16% reduction in risk of in-hospital death at institutions that used interventional therapies such as balloon angioplasty to treat arterial vasospasm.2,81,162 Therefore, hospital treatment vol- umes and availability of both endovascular and neurological intensive care services at hospitals are important determinants of improved outcomes in aSAH.163 In addition, a cost-utility analysis estimated that transferring a patient with aSAH from a low- to a high-volume hospital would result in a gain of 1.6 quality-adjusted life-years at a cost of $10 548.162,163 Although 1 study suggested that care was uniformly delivered within an institution when weekend and weekday admissions were compared,164 others have shown that inten- sive care specialists followed evidence-based recommenda- tions very inconsistently, and these variations in practice did not depend on the quality of the supporting data.165 Signifi- cant practice differences were noted between respondents from North America and Europe and between those working in high- and low-volume centers. Thus, the study demon- strated that the practices of intensive care unit physicians treating aSAH are heterogenous and often at variance with One recent effort to increase the uniformity of care is the development of an Accreditation Council on Graduate Med- ical Education approved fellowship training program for endovascular surgical neuroradiology.166 Another effort is legislation or regulation in 10 states that defines elements of comprehensive stroke centers and their role in networks and stroke systems of care. The Brain Attack Coalition paper that proposed the establishment of these centers included management of aSAH in its scope.167 From the endovascular perspective, this expertise includes the ability to treat patients with intracranial aneurysms, SAH-induced vasospasm, brain arteriovenous malformations, and ischemic stroke. Other important required elements of these centers are vascular neurosurgical expertise, dedicated intensive care units, and 24/7 access to advanced neuroimaging. The rationale for comprehensive stroke centers is based on the success of similar models for trauma. Hospital Characteristics and Systems of Care: Recommendations 1. 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 sur- geons, endovascular specialists, and multidisci- plinary neuro-intensive care services (Class I; Level of Evidence B). (Revised recommendation from previ- ous guidelines) 2. Annual monitoring of complication rates for surgical and interventional procedures is reasonable (Class IIa; Level of Evidence C). (New recommendation) 3. A hospital credentialing process to ensure that proper training standards have been met by indi- vidual physicians treating brain aneurysms is reasonable (Class IIa; Level of Evidence C). (New recommendation) Anesthetic Management During Surgical and Endovascular Treatment The general goals of anesthetic management involve hemo- dynamic control to minimize the risk of aneurysm rerupture and strategies to protect the brain against ischemic injury. Although induced hypotension has been used in the past to prevent aneurysm rupture, data suggest that there could be potential harm, with an increased risk of early and delayed neurological deficits.168,169 A retrospective study suggests that a decrease in mean arterial pressure of 50% is associ- ated with poor outcome; however, after adjustment for age, this association was no longer statistically significant.170 In patients undergoing cerebral aneurysm surgery, intraopera- tive hyperglycemia has been associated with long-term de- cline in cognition and gross neurological function.171 These associations are seen at levels of hyperglycemia commonly encountered in practice, with increased risk of alterations in cognition with glucose concentrations 129 mg/dL and neurological deficits with glucose concentrations 152 mg/ dL.171 Numerous pharmacological agents have been used to promote cerebral protection during cerebral aneurysm sur- gery,172 181 but none have been clearly shown to improve outcome. Systemic hypothermia has been used in several clinical settings, including head injury, ischemic stroke, and circula- tory arrest, to protect the brain against ischemic injury.182 188 Use of hypothermia during craniotomy for the treatment of ruptured cerebral aneurysm was evaluated in a multicenter randomized, controlled trial. The study showed that hypother- mia was relatively safe but was not associated with a beneficial effect in mortality or neurological outcome among patients with good-grade aSAH.189 In addition, intraoperative hypothermia had no beneficial effect on neuropsychological function after SAH.190 Of note, the power of these 2 studies was not sufficient to detect more modest benefits from hypothermia, and there were some trends in favor of hypo- thermia for secondary end points. Temporary clipping is frequently used to improve surgical conditions and prevent intraoperative rupture during the surgical dissection of aneurysms. In a retrospective study, outcome was not affected by temporary vascular occlusion.191 Induced hypertension can be considered when the duration of temporary clipping is expected to be 120 seconds, but the value of this strategy has not been well studied in aneurysm surgery. In selected patients with giant aneurysms, deep hypothermia with circulatory arrest under cardiopulmonary extracorporeal circulation has been shown to be a feasible and possibly useful technique, but outcome data are lacking.192 196 Transient cardiac pause induced by adenosine has been used to control bleeding from intraoperative aneu- rysm rupture or to decompress large aneurysms and facilitate aneurysm clip application197,198; however, controlled studies are needed to validate this intervention. There is little information in the literature about anesthetic management of patients undergoing endovascular treatment of ruptured cerebral aneurysms.199 201 Generally, the anes- thetic principles that apply to open surgical treatment of ruptured cerebral aneurysms also apply to endovascular treatment. The choice of anesthetic technique varies depend- ing on the institution, with the most common techniques being conscious sedation and general anesthesia.202 204 There have been no studies comparing these 2 techniques. One of the main goals of the anesthetic technique is keeping the patient motionless to optimize the quality of the images used to perform the endovascular procedure; hence, general anes- thesia with endotracheal intubation is often preferred for these procedures. Intraprocedural aneurysm rupture during endovascular treatment presents a major challenge unlike that encountered with open craniotomy. There may be a sudden and massive rise in blood pressure with or without bradycardia attributable to an elevation in intracranial pressure. Hyperventilation and osmotic diuresis may be required to control the intracranial hypertension. Aggressive treatment of surges in blood pres- sure may induce ischemia; therefore, antihypertensive ther- apy should be reserved for patients with extreme elevations in blood pressure. Endovascular procedures differ from open procedures in that anticoagulation with heparin is frequently administered during the embolization of aneurysms. Patients who have undergone anticoagulation require rapid reversal with prota- mine if intraprocedural aneurysm rupture occurs. With the increasing use of intravascular stents, the administration of antiplatelet agents (aspirin, clopidogrel, and glycoprotein IIb/IIIa receptor antagonists) during these procedures has become more common. In case of intraprocedural rupture, rapid reversal of antiplatelet activity can be attempted by platelet transfusion. Anesthetic Management During Surgical and Endovascular Treatment: Recommendations 1. Minimization of the degree and duration of intraop- erative hypotension during aneurysm surgery is probably indicated (Class IIa; Level of Evidence B). 2. There are insufficient data on pharmacological strate- gies and induced hypertension during temporary ves- sel occlusion to make specific recommendations, but there are instances when their use may be considered reasonable (Class IIb; Level of Evidence C). 3. Induced hypothermia during aneurysm surgery is not routinely recommended but may be a reasonable op- tion in selected cases (Class III; Level of Evidence B). 4. Prevention of intraoperative hyperglycemia during aneurysm surgery is probably indicated (Class IIa; Level of Evidence B). 5. The use of general anesthesia during endovascular treatment of ruptured cerebral aneurysms can be beneficial in selected patients (Class IIa; Level of Evidence C). Management of Cerebral Vasospasm and DCI After aSAH Narrowing (vasospasm) of the angiographically visible cere- bral arteries after aSAH is common, occurring most fre- quently 7 to 10 days after aneurysm rupture and resolving spontaneously after 21 days. The cascade of events culminat- ing in arterial narrowing is initiated when oxyhemoglobin comes in contact with the abluminal side of the vessel.205 The pathways leading to arterial narrowing have been the focus of extensive basic research, but no effective preventive therapy has been developed to date. Part of the reason for this lack of success likely stems from the fact that vasospasm occurs at multiple levels in the arterial and arteriolar circulation. Large artery narrowing seen in angiographically visible vessels only results in ischemic neurological symptoms in 50% of cases, and although there is a correlation between the severity of large artery spasm and symptomatic ischemia, there are patients with severe large artery spasm who never become symptomatic and others with quite modest spasm who not only develop symptoms but go on to develop infarction.206 Probably many factors contribute to the development of ischemia and infarction, including but not limited to distal microcirculatory failure, poor collateral anatomy, and genetic or physiological variations in cellular ischemic tolerance.207,208 DCI, especially that associated with arterial vasospasm, remains a major cause of death and disability in patients with aSAH. The management of aSAH-induced vasospasm is complex. Many significant advances in the understanding of aSAH-induced vasospasm and DCI have been made since Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1723 publication of the previous version of these guidelines, which focused on prevention with oral nimodipine and maintenance of euvolemia, as well as treatment with triple-H therapy (hemodynamic augmentation therapy) and/or endovascular therapy with vasodilators and angioplasty balloons. First, the case for nimodipine is even stronger, with a recent compre- hensive meta-analysis confirming improved neurological out- comes by preventing processes other than large-vessel nar- rowing.209,210 Although there have been sparse new important data on the lack of benefit for prophylactic hypervolemia compared with maintenance of euvolemia, new data show that both prophylactic angioplasty of the basal cerebral arteries and antiplatelet prophylaxis are ineffective in reduc- ing morbidity.211 213 Similarly, the only supportive data for the use of lumbar drainage come from a single case-control although there is ongoing investigation on the value of this intervention to reduce arterial spasm and DCI.214 The data are a bit better for intrathecal thrombolytic infusions, with a recent meta-analysis of 5 randomized, controlled trials suggesting a benefit despite some method- ological weaknesses.215,216 There are also emerging data for several novel methods to reduce the incidence and ischemic consequences of aSAH-induced vasospasm. These new ap- proaches are based on robust experimental data that indicate a critical role for endothelial dysfunction, particularly at the Several recent clinical trials have investigated the utility of statins, endothelin-1 antagonists, and magnesium sulfate.218 Statin agents have been studied in several small, single-center randomized trials with variable results. Although a recent meta-analysis reported no evidence for clinical benefit,219 a larger phase 3 trial (SimvasTatin in Aneurysmal Subarach- noid Hemorrhage [STASH]) is in progress. Clazosentan, an endothelin-1 receptor antagonist, had been shown to be associated with a dose-dependent reduction in the incidence of angiographic vasospasm in a phase IIb trial (Clazosentan to Overcome Neurological iSChemia and Infarct OccUrring after Subarachnoid hemorrhage [CONSCIOUS-1]).220 A ben- efit for clinical outcomes was not initially apparent but then was judged present when a stricter definition of vasospasm- related stroke was used. However, a subsequent trial (CONSCIOUS-2) that tested the drug in patients treated with aneurysm clipping found no improvement in clinical outcome in the clazosentan group.221 A similar study in patients treated with coiling (CONSCIOUS-3) was then stopped before com- pletion. Magnesium sulfate has been studied in several pilot trials. Although there is some suggestion of reduction in delayed ischemic deficits associated with magnesium infusion, a benefit has not been conclusively shown in a meta-analysis.222 A phase 3 trial (Intravenous Magnesium sulfate for Aneurysmal Subarachnoid Hemorrhage [IMASH]) did not support any clin- ical benefit from magnesium infusion over placebo in aSAH.223 A larger randomized trial is under way. With regard to the diagnosis of DCI, which can often be problematic, it is increasingly clear that although serial neurological examinations are important, they are of limited sensitivity in patients with poor clinical grade. Therefore, the diagnostic approach needs to be tailored to the clinical situation. Various diagnostic tools are commonly used to identify (1) arterial narrowing and/or (2) perfusion abnormal- ities or reduced brain oxygenation. These different tools have advantages and disadvantages. Although comparative studies of diagnostic accuracy for large arterial narrowing have been performed for some modalities, no randomized trials have compared the impact of the use of different diagnostic methods on patient outcomes. That said, there are emerging data that perfusion imaging, demonstrating regions of hypo- perfusion, may be more accurate for identification of DCI than anatomic imaging of arterial narrowing or changes in blood flow velocity by transcranial Doppler, for which the data are best for the middle cerebral artery territory.224 226 Perfusion CT is a promising technology, although repeat measurements are limited by the risks of dye load and When DCI is diagnosed, the initial treatment is the induc- tion of hemodynamic augmentation to improve cerebral perfusion. No randomized trials of this intervention have been performed, but the rapid improvement of many patients with this therapy and their worsening when it is stopped prema- turely are convincing proof of efficacy. The exact mechanism of benefit is unclear. In some patients, increased mean arterial pressures may increase cerebral blood flow in the setting of autoregulatory dysfunction. In others, there may be some direct transluminal pressure effect that leads to arterial dilation.227 Traditionally, hemodynamic augmentation has consisted of he- modilution (a common occurrence in this population), hypervol- emia, and hypertensive therapy. Accumulating literature has shifted the focus from this triple-H therapy to the maintenance of euvolemia and induced hypertension.228 One novel method of hemodynamic augmentation under investigation is an aortic balloon device, approved under a humanitarian device exemption.229 Endovascular intervention is often used in patients who do not improve with hemody- namic augmentation and those with sudden focal neurological deficits and focal lesions on angiography referable to their symptoms.230 Interventions generally consist of balloon an- gioplasty for accessible lesions and vasodilator infusion for more distal vessels. Many different vasodilators are in use. In general, these are calcium channel blockers, but nitric oxide donors have been used in small series as well.231 Papaverine is used less frequently because it can produce neurotoxic- ity.232 The primary limitation of vasodilator therapy is the short duration of benefit. As with hemodynamic augmenta- tion, there have been no randomized trials of these interven- tions, but large case series have demonstrated angiographic and clinical improvement.233 Management of Cerebral Vasospasm and DCI After aSAH: Recommendations 1. Oral nimodipine should be administered to all patients with aSAH (Class I; Level of Evidence A). (It should be noted that this agent has been shown to improve neuro- logical outcomes but not cerebral vasospasm. The value of other calcium antagonists, whether administered orally or intravenously, remains uncertain.) 2. Maintenance of euvolemia and normal circulating blood volume is recommended to prevent DCI (Class I; Level of Evidence B). (Revised recommendation from previous guidelines) 3. Prophylactic hypervolemia or balloon angioplasty before the development of angiographic spasm is not recommended (Class III; Level of Evidence B). (New recommendation) 4. Transcranial Doppler is reasonable to monitor for the development of arterial vasospasm (Class IIa; Level of Evidence B). (New recommendation) 5. Perfusion imaging with CT or magnetic resonance can be useful to identify regions of potential brain ischemia (Class IIa; Level of Evidence B). (New recommendation) 6. Induction of hypertension is recommended for pa- tients with DCI unless blood pressure is elevated at baseline or cardiac status precludes it (Class I; Level of Evidence B). (Revised recommendation from previ- ous guidelines) 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 of Evidence B). (Revised recommendation from previous guidelines) Management of Hydrocephalus Associated With aSAH Acute hydrocephalus occurs in 15% to 87% of patients with aSAH.234 240 Chronic shunt-dependent hydrocephalus, on the other hand, occurs in 8.9% to 48% of patients with aSAH.234 238,240 244 There is only 1 randomized, controlled trial pertaining to the management of hydrocephalus associ- ated with aSAH245 and 2 meta-analyses236,243; the rest of the literature consists of nonrandomized case-control, case series, or case reports. Acute hydrocephalus associated with aSAH is usually managed by external ventricular drainage (EVD) or lumbar drainage. EVD for patients with aSAH-associated hydrocephalus is generally associated with neurological im- provement.246 249 The risk of aneurysm rebleeding with EVD has been studied in 3 retrospective case series, 1 of which found a higher risk of rebleeding with EVD,250 whereas the other 2 studies found no increased risk.239,251 Lumbar drainage for the treatment of aSAH-associated hydrocephalus has been reported to be safe (no increase in the risk of rebleeding), but it has only been examined in retro- spective series,214,252 255 1 of which specifically evaluated intraoperative lumbar drainage for brain relaxation.256 The theoretical risk of tissue shift after placement of a lumbar drain in patients with severe intracranial hypertension should be considered when deciding what method of cerebrospinal fluid diversion to use, particularly in patients with associated intraparenchymal hematomas. When obstructive hydroceph- alus is suspected, an EVD should be preferred. Preliminary data have suggested that lumbar drainage is associated with reduced incidence of vasospasm.214,255 Serial lumbar punc- tures to manage acute aSAH-associated hydrocephalus have been described as safe, but this strategy has only been assessed in small retrospective series.239,257 Chronic hydrocephalus associated with aSAH is usually treated with ventricular shunt placement. Only a proportion of patients with aSAH-associated acute hydrocephalus develop shunt-dependent chronic hydrocephalus. The method of deter- mining which patients require ventricular shunt placement was studied in a single-center, prospective, randomized, controlled trial in which 41 patients were randomized to rapid weaning of EVD (wean period 24 hours) and 40 patients were randomized to gradual EVD weaning (wean period 96 hours).245 There was no difference in the rate of shunt placement (63.4% rapid versus 62.5% gradual), but the gradual wean group had 2.8 more days in the intensive care unit (P 0.0002) and 2.4 more days in the A number of retrospective series have attempted to identify factors predictive of aSAH-associated shunt-dependent nonrandomized studies236,258 261 with 1718 pooled patients (1336 who underwent clipping, 382 who underwent coiling) found a lower risk of shunt dependency in the clipping group (relative risk, 0.74; 95% confidence interval, 0.58 0.94) than in the coiling group (P 0.01); however, only 1 of the 5 studies showed an independent significant difference.258 Three other nonrandomized series not included in the meta- analysis showed no significant difference between clipping and coiling in shunt-dependent chronic hydrocepha- lus.237,244,262 Fenestration of the lamina terminalis has been suggested to reduce the incidence of shunt-dependent chronic hydrocephalus, yet a meta-analysis243 of 11 nonrandomized studies234,260,263 271 pooled 1973 patients (975 who had un- dergone fenestration and 998 who had not) and found no significant difference in shunt-dependent hydrocephalus be- tween patients who had undergone fenestration of the lamina terminalis and those who had not (10% in the fenestrated cohort versus 14% in the nonfenestrated cohort; P 0.09). A nonrandomized study not included in the meta-analysis com- pared 95 patients who underwent aneurysm clipping, cisternal blood evacuation, and lamina terminalis fenestration with 28 comparable, non blood-cleansed, endovascular therapy treated patients and found that shunt-dependent hydrocepha- lus occurred in 17% of surgical patients versus 33% of patients treated with endovascular therapy (statistical signif- icance not reported).237 Management of Hydrocephalus Associated With aSAH: Recommendations 1. aSAH-associated acute symptomatic hydrocephalus should be managed by cerebrospinal fluid diversion (EVD or lumbar drainage, depending on the clinical scenario) (Class I; Level of Evidence B). (Revised recommendation from previous guidelines) 2. aSAH-associated chronic symptomatic hydrocepha- lus should be treated with permanent cerebrospinal fluid diversion (Class I; Level of Evidence C). (Re- vised recommendation from previous guidelines) 3. Weaning EVD over >24 hours does not appear to be effective in reducing the need for ventricular shunt- ing (Class III; Level of Evidence B). (New recommendation) 4. Routine fenestration of the lamina terminalis is not useful for reducing the rate of shunt-dependent hydrocephalus and therefore should not be routinely Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1725 performed. (Class III; Level of Evidence B). (New recommendation) Management of Seizures Associated With aSAH The incidence, future implications, and management of sei- zures associated with aSAH are controversial. At present, no randomized, controlled trials are available to guide decisions on prophylaxis or treatment of seizures.2,272 A relatively high percentage of aSAH patients (as many as 26%) experience seizure-like episodes,99,272,273 but it remains unclear whether these episodes are verifiably epileptic in origin.99,274 More recent retrospective reviews suggest a lower seizure inci- dence of 6% to 18%,275 278 and 2 of these studies276,278 found that the majority of such patients reported onset of seizure occurring before medical evaluation. Delayed seizures occurred in 3% to 7% of patients.276,278 Retrospective studies have identified several risk factors for the development of early seizures associated with aSAH, including aneurysm in the middle cerebral artery,279 thickness of aSAH clot,276 associated neurological grade,276 and history of hypertension.98 The mode of treatment for patients with ruptured aneu- rysms also appears to influence the subsequent development of seizures. One study of patients treated by endovascular means reported no periprocedural seizures and a delayed seizure rate of 3%.284 Moreover, extended follow-up of patients enrolled in the ISAT demonstrated a significantly lower incidence of seizures in patients treated with endovas- cular coiling.140 The association between seizures and func- tional outcome remains unclear. Some studies have reported no impact on outcome,276,278 whereas others found seizures to be independently associated with worse outcome.275 Two recent large, retrospective, single-institution studies of pa- tients with aSAH found that nonconvulsive status epilepticus is a very strong predictor of a poor outcome.285,286 Although high-quality evidence for routine anticonvulsant use in aSAH is lacking, short-term prophylactic antiepileptic therapy is still commonly used in patients with aSAH,274,276,278 based on the argument that seizures in acutely ill patients with aSAH could lead to additional injury or rebleeding from an unse- cured aneurysm. Evidence from a few relatively small non- randomized studies of craniotomy patients supports this position,281,282,287 but the efficacy of routine use of anticon- vulsants in patients with aSAH managed with microsurgical techniques remains unproven.288 290 Any purported benefit of routine anticonvulsant use in aSAH must be tempered by a consideration of the potential risks of such use. In 1 large single-institution study in which anticonvulsants were used routinely, adverse drug effects were seen in 23% of patients.276 Another single-center retro- spective study found that the use of prophylactic phenytoin was independently associated with a worse cognitive out- come at 3 months after aSAH.291 Data pooled from trials of the impact of other therapies also suggest a worse outcome in those treated with anticonvulsants, but use of anticonvulsants was also associated with vasospasm, DCI, and fever, which suggests that there may have been bias in who was treated with antiepileptic drugs.292 Although retrospective studies have not demonstrated a benefit for use of prophylactic anticonvulsants after aSAH,273,288 the studies were small and hampered by limitations (eg, anticonvulsant levels were not Management of Seizures Associated With aSAH: Recommendations 1. The use of prophylactic anticonvulsants may be considered in the immediate posthemorrhagic pe- riod (Class IIb; Level of Evidence B). 2. The routine long-term use of anticonvulsants is not recommended (Class III; Level of Evidence B) but may be considered for patients with known risk factors for delayed seizure disorder, such as prior seizure, intracerebral hematoma, intractable hyper- tension, infarction, or aneurysm at the middle cere- bral artery (Class IIb; Level of Evidence B). Management of Medical Complications Associated With aSAH Both hypernatremia and hyponatremia are frequently ob- served in the acute phase after aSAH.293,294 The reported incidence of hyponatremia in this disease ranges from 10% to 30%. Hyponatremia has been chronologically associated with the onset of sonographic and clinical vasospasm.295,296 Hy- ponatremia can develop from different mechanisms after aSAH. The syndrome cerebral salt wasting is produced by excessive secretion of natriuretic peptides and causes hypo- natremia from excessive natriuresis, which may also provoke volume contraction.297 The diagnosis of cerebral salt wasting is more common in patients with poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocepha- lus, and it may be an independent risk factor for poor outcome.298 300 Uncontrolled studies using crystalloid or colloid agents suggest that aggressive volume resuscitation can ameliorate the effect of cerebral salt wasting on the risk of cerebral ischemia after aSAH.301,302 One retrospective study has suggested that 3% saline solution is effective in correcting hyponatremia in this setting.303 In addition, use of hypertonic saline solution appears to increase regional cere- bral blood flow, brain tissue oxygen, and pH in patients with Two randomized, controlled trials have been performed to evaluate fludrocortisones to correct hyponatremia and fluid balance. One trial found that it helped to correct the negative sodium balance, and the other reported a reduced need for fluids and improved sodium levels using this mineralocorti- coid.305,306 A similar randomized, placebo-controlled trial showed reduced natriuresis and a lower rate of hyponatremia in aSAH patients treated with hydrocortisone.307 The value of albumin as an efficient volume expander during the vasospasm phase in aSAH has been suggested in uncontrolled studies, but there is no clear evidence of its superiority over crystalloids in patients with aSAH.308 Fever is the most common medical complication in aSAH.309 The presence of fever of noninfectious (central) origin has been associated with severity of injury, amount of hemorrhage, and development of vasospasm, and it may represent a marker of a systemic inflammatory state triggered by blood and its byproducts.310 312 Analysis of data from a prospectively collected registry of aSAH indicated that fever was independently associated with worse cognitive outcome in survivors of aSAH.313,314 Improved functional outcome with effective control of fever has been reported.315 Both animal studies and human case series have demonstrated an association between elevated blood glucose concentration and poor outcome after ischemic brain injury.316 323 The mecha- nisms explaining such an association in human beings are unclear. Data obtained from consecutive patients with aSAH using historical controls to compare aggressive versus stan- dard management of hyperglycemia suggest that effective glucose control after aSAH can significantly reduce the risk of poor outcome in these patients.324 Nevertheless, even serum glucose levels within the normal range may be asso- ciated with brain energy metabolic crisis and lactate-pyruvate ratio elevation in patients with poor-grade aSAH.325 Anemia is common after aSAH and may compromise brain oxygen delivery.326 Transfusion of red blood cells in anemic patients with aSAH results in a significant rise in cerebral oxygen delivery and a reduction in oxygen extraction ratio.327 Data obtained from prospective registries of patients with aSAH suggest that higher hemoglobin values are associated with improved outcomes after aSAH.328,329 Nevertheless, thresholds for blood transfusion have been dictated in a nonsystematic manner and have therefore varied widely. Furthermore, red blood cell transfusions, as used in daily practice, have been associated with worse outcomes in aSAH in some series.330,331 Recently, a prospective randomized trial has shown the safety and feasibility of keeping a higher hemoglobin goal in patients with aSAH who are at high risk of vasospasm.332 The optimal hemoglobin goal after aSAH is not yet known, however. Two additional medical complications are heparin-induced thrombocytopenia333 335 and deep venous thrombosis. With regard to the former, the incidence, based on 3 single-center series, is likely 5% and does not appear to be related to the use of heparin for deep venous thrombosis prophylaxis, but rather to the number of angiographic procedures performed. Patients with heparin-induced thrombocytopenia type II appear to have higher rates of thrombotic complications and symptom- atic vasospasm/DCI, more deaths, and significantly less favor- able outcomes. It is currently unclear whether there is a practical means of preventing heparin-induced thrombocytopenia, given the need for heparin in many angiographic procedures, but it is clearly important to recognize this complication to avoid further heparin exposure and to use instead a nonheparin alternative under the guidance of a hematologist.336 By comparison, deep venous thrombosis has long been recognized as a relatively frequent occurrence after aSAH, especially in patients immobi- lized because of poor mental status.337,338 Nevertheless, in examining cohorts in which routine prophylaxis (subcutaneous heparinoids and external pneumatic compression sleeves) was used, recent data suggest that although screening protocols may identify additional cases of asymptomatic thrombosis, there is no significant difference in the incidence of pulmonary embolism between those screened and those not screened. Management of Medical Complications Associated With aSAH: Recommendations 1. Administration of large volumes of hypotonic fluids and intravascular volume contraction is not recom- mended after aSAH (Class III; Level of Evidence B). 2. Monitoring volume status in certain patients with recent aSAH by some combination of central venous pressure, pulmonary wedge pressure, and fluid bal- ance is reasonable, as is treatment of volume con- traction with crystalloid or colloid fluids (Class IIa; Level of Evidence B). 3. Aggressive control of fever to a target of normothermia by use of standard or advanced temperature modulat- ing systems is reasonable in the acute phase of aSAH (Class IIa; Level of Evidence B). (New recommendation) 4. Careful glucose management with strict avoidance of hypoglycemia may be considered as part of the general critical care management of patients with aSAH (Class IIb; Level of Evidence B). 5. 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 of Evidence B). (New recommendation) 6. The use of fludrocortisone acetate and hypertonic saline solution is reasonable for preventing and cor- recting hyponatremia (Class IIa; Level of Evidence B). 7. Heparin-induced thrombocytopenia and deep ve- nous thrombosis are relatively frequent complica- tions after aSAH. Early identification and targeted treatment are recommended, but further research is needed to identify the ideal screening paradigms (Class I; Level of Evidence B). (New recommendation) Summary and Conclusions The management of aSAH is a complex undertaking, and the current state of knowledge is in rapid evolution. This update, which is based on a mere 42 months of publications, identified 22 new recommendations (Table 4), 5 of which were Class I recommendations. There were also 9 changes in prior recommendations. In total, there are now 22 Class I recommendations (Table 3). Although these data show that frequent revision of these guidelines is clearly needed, the data presented here only begin to scratch the surface of the burgeon- ing knowledge in this fast-developing field. Those faced with managing these patients will thus do well to use these guidelines as merely the starting point for doing everything possible to improve the outcomes of patients with aSAH. Connolly et al Management of Aneurysmal Subarachnoid Hemorrhage 1727 Disclosures Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other E. Sander Connolly, Jr. Columbia University None None None None None None None Alejandro A. Rabinstein Mayo Clinic None None None None None None None J. Ricardo Carhuapoma Johns Hopkins Hospital None None None None None None None Colin P. Derdeyn Washington University School of Medicine (St. Louis) NIH None None Witness for plaintiff* Nfocus* None None Jacques Dion Emory University Hospital None None None None NeuroVasx*; Nfocus Neuromedical*; Sequent Medical* MicroVention/ Terumo* None Randall T. Higashida University of California at San Francisco Medical Center None None None None None None None Brian L. Hoh University of Florida Brain Aneurysm Foundation ; Micrus Endovascular*; NIH ; Thomas H. Maren Foundation None None None None Actelion Pharmaceuticals*; Codman Neurovascular* None Catherine J. Kirkness University of Washington NIH* None None None None None None Andrew M. Naidech Northwestern University/FDA Astellas Pharma*; Gaymar, Inc* None None None None Journal Watch Neurology* None Christopher S. Ogilvy Massachusetts General Hospital Actelion Pharmaceuticals ; NIH None None None None Mizuho America, Inc* None Aman B. Patel Mount Sinai Medical Center None None None None None Cordis/Codman Neurovascular*; Penumbra* None B. Gregory Thompson University of Michigan None None None None None None None Paul Vespa University of California at Los Angeles NIH None None None InTouch Health* EDGE Therapeutics* None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all writing group members are required to complete and submit. A relationship is considered to be significant if (1) the person receives $10 000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. References 1. 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Claude Hemphill University of California, San Francisco None None None Raphaelson law firm* None None None Stephan Mayer Columbia University None None None None None Edge Therapeutics*; Actelion Pharmaceuticals None Gene Sung University of Southern California None None None None None None None This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be significant if (1) the person receives $10 000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. 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