Andrew M. Naidech

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

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 Councils Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years. Results— Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications. Conclusions— aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH.

Phenytoin Exposure Is Associated With Functional and Cognitive Disability After Subarachnoid Hemorrhage

Background and Purpose— Phenytoin (PHT) is routinely used for seizure prophylaxis after subarachnoid hemorrhage (SAH), but may adversely affect neurologic and cognitive recovery. Methods— We studied 527 SAH patients and calculated a “PHT burden” for each by multiplying the average serum level of PHT by the time in days between the first and last measurements, up to a maximum of 14 days from ictus. Functional outcome at 14 days and 3 months was measured with the modified Rankin scale, with poor functional outcome defined as dependence or worse (modified Rankin Scale ≥4). We assessed cognitive outcomes at 14 days and 3 months with the telephone interview for cognitive status. Results— PHT burden was associated with poor functional outcome at 14 days (OR, 1.5 per quartile; 95% CI, 1.3 to 1.8; P<0.001), although not at 3 months (P=0.09); the effect remained (OR, 1.6 per quartile; 95% CI, 1.2 to 2.1; P<0.001) after correction for admission Glasgow Coma Scale, fever, stroke, age, National Institutes of Health Stroke Scale ≥10, hydrocephalus, clinical vasospasm, and aneurysm rebleeding. Seizure in hospital (OR, 4.1; 95% CI, 1.5 to 11.1; P=0.002) was associated with functional disability in a univariate model only. Higher quartiles of PHT burden were associated with worse telephone interview for cognitive status scores at hospital discharge (P<0.001) and at 3 months (P=0.003). Conclusions— Among patients treated with PHT, burden of exposure to PHT predicts poor neurologic and cognitive outcome after SAH.

Reduced Platelet Activity Is Associated With Early Clot Growth and Worse 3-Month Outcome After Intracerebral Hemorrhage

Background and Purpose— Antiplatelet medication use and reduced platelet activity may be associated with mortality after intracerebral hemorrhage (ICH). We tested the hypothesis that reduced platelet activity is associated with early ICH clot growth and worse outcomes. Methods— We prospectively identified patients with spontaneous ICH, measured platelet activity (VerifyNow-ASA, Accumetrics) on admission, and recorded antiplatelet medication use. ICH volume was calculated using computerized volumetric analysis. Data were analyzed with nonparametric statistics and repeated measures ANOVA as appropriate. Patients were prospectively followed for functional outcomes. Data are presented as mean±SD or median [Q1 to Q3]. Results— Reduced platelet activity (≤550 aspirin reaction units [ARU]) was associated with increased ICH volume growth (P<0.05) for patients with the diagnostic CT within 12 hours. In the subset of patients not known to take aspirin, 24% had reduced platelet activity. Sixteen (24%) patients received a platelet transfusion 21.2±11.4 hours after symptom onset with an increase in platelet activity (448 [414-479] to 586 [530-639] ARU, P=0.001), but without impact on outcomes. Reduced platelet activity was associated with worse modified Rankin Scores at 3 months (P=0.02). Conclusions— Reduced platelet activity was associated with early ICH volume growth and worse functional outcome. Because platelet activity can be increased with platelet transfusion, increasing platelet activity is a potential method to reduce ICH volume growth and improve functional outcomes.

Higher hemoglobin is associated with improved outcome after subarachnoid hemorrhage

Objective:There are few data regarding anemia and transfusion after subarachnoid hemorrhage (SAH). We addressed the hypothesis that higher hemoglobin (HGB) levels are associated with less death and disability after SAH. Design:Prospective registry with automated data retrieval. Patients:Six hundred eleven patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. Setting:Neurologic intensive care unit. Interventions:Patients were treated according to standard management protocols. Measurements and Main Results:We electronically retrieved all HGB readings during the acute hospital stay for 611 consecutively admitted SAH patients. Outcomes were measured with the modified Rankin Scale at 14 days or discharge, and at 3 months. Patients who were independent (modified Rankin Scale, 0–3) at discharge or 14 days had higher mean (11.7 ± 1.5 vs. 10.9 ± 1.2, p < .001) and nadir (9.9 ± 2.1 vs. 8.6 ± 1.8, p < .001) HGB, and had higher HGB values every day in the hospital. There were similar results when patients were stratified by mortality. Higher HGB was associated with reduced risk of poor outcome (modified Rankin Scale, 4–6) at 14 days/discharge and 3 months after correcting for Hunt and Hess grade, age, history of diabetes, and cerebral infarction. Length of stay and HGB interacted such that lower HGB has a more pronounced effect with length of stay > 14 days. Conclusions:Higher HGB values are associated with improved outcomes after SAH at 14 days/discharge and 3 months. In contrast to general critical care patients, SAH patients may benefit from higher HGB. Determination of the optimal goal HGB after SAH will require separate prospective research.

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants’ collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Anticonvulsant Use and Outcomes After Intracerebral Hemorrhage

Background and Purpose— There are few data on the effectiveness and side effects of antiepileptic drug therapy after intracerebral hemorrhage. We tested the hypothesis that antiepileptic drug use is associated with more complications and worse outcome after intracerebral hemorrhage. Methods— We prospectively enrolled 98 patients with intracerebral hemorrhage and recorded antiepileptic drug use as either prophylactic or therapeutic along with clinical characteristics. Antiepileptic drug administration and free phenytoin serum levels were retrieved from the electronic medical records. Patients with depressed mental status underwent continuous electroencephalographic monitoring. Outcomes were measured with the National Institutes of Health Stroke Scale and modified Rankin Scale at 14 days or discharge and the modified Rankin Scale at 28 days and 3 months. We constructed logistic regression models for poor outcome at 3 months with a forward conditional model. Results— Seven (7%) patients had a clinical seizure, 5 on the day of intracerebral hemorrhage. Phenytoin was associated with more fever (P=0.03), worse National Institutes of Health Stroke Scale at 14 days (23 [9 to 42] versus 11 [4 to 23], P=0.003), and worse modified Rankin Scale at 14 days, 28 days, and 3 months. In a forward conditional logistic regression model, phenytoin prophylaxis was associated with an increased risk of poor outcome (OR, 9.8; 1.4 to 68.6; P=0.02), entering after admission National Institutes of Health Stroke Scale and age. Excluding patients with a seizure did not change the results. Levetiracetam was not associated with demographics, seizures, complications, or outcomes. Conclusions— Phenytoin was associated with more fever and worse outcomes after intracerebral hemorrhage.

Higher hemoglobin is associated with less cerebral infarction, poor outcome, and death after subarachnoid hemorrhage.

OBJECTIVE:Higher-goal hemoglobin (hgb) and more packed red blood cell transfusions lead to worse outcomes in general critical care patients. There are few data on hgb, transfusion, and outcomes after aneurysmal subarachnoid hemorrhage (SAH). METHODS:We reviewed the daily hgb levels of 103 patients with aneurysmal SAH. Cerebral infarction was diagnosed by computed tomographic scan. We corrected for Hunt and Hess grade, age, and angiographic vasospasm in multivariate models. RESULTS:Of 103 patients, the mean age was 55.3 ± 14.5 years, 63% were women, and 29% were Hunt and Hess Grades 4 and 5; hgb values steadily declined from 12.6 ± 1.7 g/dl the day of SAH to 10.4 ± 1.2 g/dl by Day 14. Patients who died had lower hgb than survivors on Days 0, 1, 2, 4, 6, 10, 11, and 12 (P ≤ 0.05). Higher mean hgb was associated with reduced odds of poor outcome (odds ratio, 0.57 per g/dl; 95% confidence interval [CI], 0.38–0.87; P = 0.008) after correcting for Hunt and Hess grade, age, and vasospasm; results for hgb on Days 0 and 1 were similar. Higher Day 0 (odds ratio, 0.7 per g/dl; 95% CI, 0.5–0.99; P = 0.05) and mean hgb (odds ratio, 0.57 per g/dl; 95% CI, 0.38–0.87; P = 0.009) predicted a lower risk of cerebral infarction independent of vasospasm. There were no associations between hgb and other prognostic variables. CONCLUSION:We found that SAH patients with higher initial and mean hgb values had improved outcomes. Higher hgb in SAH patients may be beneficial. The efficacy and safety of blood transfusions to increase hgb in patients with SAH may warrant further study.

Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

Objectives: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. Methods: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. Results: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). Conclusions: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.

PRIOR ANTIPLATELET USE DOES NOT AFFECT HEMORRHAGE GROWTH OR OUTCOME AFTER ICH 2

Objective: To examine whether antiplatelet medication use at onset of intracerebral hemorrhage (ICH) is associated with hemorrhage growth and outcome after spontaneous ICH using a large, prospectively collected database from a recent clinical trial. Methods: The Cerebral Hemorrhage and NXY-059 Treatment trial was a randomized, placebo-controlled trial of NXY-059 after spontaneous ICH. We analyzed patients in the placebo arm, and correlated antiplatelet medication use at the time of ICH with initial ICH volumes, ICH growth in the first 72 hours, and modified Rankin Score at 90 days. Patients on oral anticoagulation were excluded. Results: There were 282 patients included in this analysis, including 70 (24.8%) who were taking antiplatelet medications at ICH onset. Use of antiplatelet medications at ICH onset had no association with the volume of ICH at presentation, growth of ICH at 72 hours, initial edema volume, or edema growth. In multivariable analysis, there was no association of use of antiplatelet medications with any hemorrhage expansion (relative risk [RR] 0.85 [upper limit of confidence interval (UCI) 1.03], p = 0.16), hemorrhage expansion greater than 33% (RR 0.77 [UCI 1.18], p = 0.32), or clinical outcome at 90 days (odds ratio 0.67, 95% confidence interval 0.39–1.14, p = 0.14). Conclusions: Use of antiplatelet medications at intracerebral hemorrhage (ICH) onset is not associated with increased hemorrhage volumes, hemorrhage expansion, or clinical outcome at 90 days. These findings suggest that attempts to reverse antiplatelet medications after ICH may not be warranted.

Cardiac Arrhythmias after Subarachnoid Hemorrhage: Risk Factors and Impact on Outcome

Objective: Serious cardiac arrhythmias have been described in approximately 5% of patients after subarachnoid hemorrhage (SAH). The aim of this study was to identify the frequency, risk factors and clinical impact of cardiac arrhythmia after SAH. Methods: We prospectively studied 580 spontaneous SAH patients and identified risk factors and complications associated with the development of clinically significant arrhythmia. Multiple logistic regression analysis was used to calculate adjusted odds ratios for the effect of arrhythmia on hospital complications and 3-month outcome, as measured by the modified Rankin Scale, after controlling for age, neurological grade, APACHE-2 physiologic subscore, brain herniation and aneurysm size. Results: Arrhythmia occurred in 4.3% (n = 25) of patients. Atrial fibrillation and flutter were the most common arrhythmias, occurring in 76% (n = 19) of these patients. Admission predictors of cardiac arrhythmia included older age, history of arrhythmia and abnormal admission electrocardiogram (all p < 0.05). After adjusting for length of stay, hospital complications associated with arrhythmia included myocardial ischemia, hyperglycemia, and herniation (all p < 0.05). Arrhythmia was associated with an excess ICU stay of 5 days (p = 0.002). After adjusting for other predictors of outcome, arrhythmia was associated with an increased risk of death (adjusted OR 8.0, 95% confidence interval 1.9–34.0, p = 0.005), and death or severe disability (adjusted OR 6.9, 95% confidence interval 1.5–32.0, p = 0.014). Conclusions: Clinically important arrhythmias, most often atrial fibrillation or flutter, occurred in 4% of SAH patients. Arrhythmias are associated with an increased risk of cardiovascular comorbidity, prolonged hospital stay and poor outcome or death after SAH, after adjusting for other predictors of poor outcome.