Anemia and Transfusion After Subarachnoid Hemorrhage

Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) may be affected by a number of factors, including cerebral blood flow and oxygen delivery. Anemia affects about half of patients with SAH and is associated with worse outcome. Anemia also may contribute to the development of or exacerbate delayed cerebral ischemia. This review was designed to examine the prevalence and impact of anemia in patients with SAH and to evaluate the effects of transfusion. A literature search was made to identify original research on anemia and transfusion in SAH patients. A total of 27 articles were identified that addressed the effects of red blood cell transfusion (RBCT) on brain physiology, anemia in SAH, and clinical management with RBCT or erythropoietin. Most studies provided retrospectively analyzed data of very low-quality according to the GRADE criteria. While RBCT can have beneficial effects on brain physiology, RBCT may be associated with medical complications, infection, vasospasm, and poor outcome after SAH. The effects may vary with disease severity or the presence of vasospasm, but it remains unclear whether RBCTs are a marker of disease severity or a cause of worse outcome. Erythropoietin data are limited. The literature review further suggests that the results of the Transfusion Requirements in Critical Care Trial and subsequent observational studies on RBCT in general critical care do not apply to SAH patients and that randomized trials to address the role of RBCT in SAH are required.     

Rebleeding After Aneurysmal Subarachnoid Hemorrhage

Rebleeding after initial aneurysmal subarachnoid hemorrhage (SAH) can have substantial impact on overall patient outcome. While older studies have suggested rebleeding occurs in about 4% of patients during the first day after initial aneurysmal bleed, these studies may have failed to capture very early rebleeds and, consequently, underestimated the impact of rebleeding. An electronic literature search was performed to identify English-language articles published or available for review from February 1975 through October 2010. A total of 43 articles (40 original research and 3 review articles) focused on rebleeding after initial aneurysmal SAH in humans were selected for review. Although most studies supported an incidence of rebleeding ≤4%, studies investigating ultra-early rebleeding reported bleeding within the first 24 h following aneurysmal SAH in as many as 9–17% of patients, with most cases occurring within 6 h of initial hemorrhage. Overall, studies investigating antifibrinolytic therapy to reduce rebleeding have failed to clearly demonstrate overall therapeutic benefit. Short-course antifibrinolytic therapy may have a role prior to initial aneurysm repair, although insufficient data are currently available.     

Magnesium Sulfate Administration in Subarachnoid Hemorrhage

Magnesium offers theoretic vascular and neuroprotective benefits for patients with subarachnoid hemorrhage. An electronic literature search was conducted to identify original research studies describing intravenous magnesium treatment in patients with SAH published in English between January 1990 and October 2010. Seventeen articles were identified and reviewed, including one phase III randomized-controlled clinical trial and six phase II randomized-controlled trials. Study quality was low for most of the included studies, with the phase III trial considered to be of moderate quality. Due to inconsistently reported benefits and the occurrence of side effects, phase II data suggested that intravenous magnesium for SAH provided either no overall net benefit or uncertain trade-offs. Benefit was likewise not supported in the single phase III clinical trial.     

Clinical Differences Between Angiographically Negative, Diffuse Subarachnoid Hemorrhage and Perimesencephalic Subarachnoid Hemorrhage

Objective  To identify prognostic factors for vasospasm, hydrocephalus, and clinical outcomes in patients with angiographically negative, non-traumatic, diffuse subarachnoid hemorrhage (d-SAH). Methods  Retrospective review of patients who experienced angiographically negative SAH at our institution over the past 6 years was undertaken. The patients were stratified based on grade at presentation, severity, and pattern of SAH on initial non-enhanced, computed tomography (CT) of the head into perimesencephalic and diffuse subtypes. The patients were further differentiated based on the development of vasospasm, hydrocephalus and required treatments, and clinical outcomes. Patients were excluded if a causative lesion was discovered subsequently. Results  Ninety-four patients with angiographically negative SAH were identified. A total of 31 patients were considered to have the perimesencephalic (p-SAH) subtype, while 63 patients fit criteria for the diffuse (d-SAH) subtype. Compared to the p-SAH subtype, those patients with d-SAH subtype had significantly higher risk for complications related to SAH with an increased incidence of hydrocephalus (50.8% vs. 9.6%), requirement for external ventricular drainage (41% vs. 9.6%), and for the hydrocephalus requiring eventual permanent cerebrospinal fluid diversion (20.6% vs. 0%). Patients with d-SAH were also at an increased risk for symptomatic vasospasm (28.6% vs. 9.6%). Ultimately, only 76% of d-SAH patients achieved complete recovery and independent living, compared to 96.7% of p-SAH patients. Conclusion  The angiographically negative d-SAH pattern is associated with worse presentations and outcome. These patients are at increased risk for vasospasm and hydrocephalus requiring aggressive treatment and should therefore be cared for with a higher level of surveillance.     

Fever Burden in Patients With Subarachnoid Hemorrhage and the Increased Use of Antibiotics

Background: Fever occurs in the majority of subarachnoid hemorrhage (SAH) patients. Nearly 50% of SAH patients have noninfectious fevers. Data are lacking describing the effects of fever burden in the SAH patient population. Methods: This was a single-center, retrospective observational cohort study in patients more or equal to 18 years of age with a diagnosis of nontraumatic SAH admitted to an ICU between January 1, 2010 and September 1, 2015. Exclusion criteria were SAH secondary to trauma or admission for more than 48 hours. Temperature measurements, demographic data, and other pertinent information were collected from Day 0 to Day 13. Daily fever burden was calculated for each patient by calculating an area under the curve. Results: A total of 194 subjects were included. The mean study period maximum temperature (Tmax) for all 194 patients was 40.8 ± 0.83°C. The mean overall fever burden for all 194 patients was 89.2 ± 99.59°C h more than 37°C. The overall fever burden peaked on day 5 and declined thereafter. Fever burden, Tmax, and length of stay in the hospital were all significantly associated with receipt of antibiotics. Only Tmax was associated with poor outcome. The 31 patients who had fever but no identified cause of infection received 1000 doses of antibiotics or 32.25 doses per patient. Conclusion: Fever is common in SAH patients and is associated with antibiotic use, infection, vasospasm, and poor outcome. Some SAH patients may receive antibiotics unnecessarily for noninfectious fever. Clinicians should consider using site-specific parameters related to infection rather than systemic symptoms such as fever to evaluate infection in SAH patients.     

Cervical Schwannoma Presenting with Acute Intracranial Subarachnoid Hemorrhage

A subarachnoid hemorrhage (SAH) associated with negative finding on four-vessel angiography is seen in 5 to 30% of patients with intracranial SAH. A previously silent lesion in the spinal canal may be responsible for the angiographically negative finding for cause of intracranial SAH. We report a case of upper cervical (C1-2) intradural schwannoma presenting with acute intracranial SAH. Repeated cerebral angiographic studies were negative, but cervical magnetic resonance imaging study and tissue pathology revealed a intradural-extramedullary schwannoma in C1-2 level. This case illustrates the importance of a high index of clinical suspicion for spinal disease in angiographically negative intracranial SAH patients.     

Cardiovascular Predictors of Long-Term Outcomes After Non-Traumatic Subarachnoid Hemorrhage

Background and Purpose

Cardiac injury is common after subarachnoid hemorrhage (SAH) and is associated with adverse early outcomes, but long-term effects are unknown. The first aim of this study was to compare the long-term rates of death, stroke, and cardiac events in SAH survivors versus a matched population without SAH. The second aim was to quantify the effects of cardiac injury on the outcome rates.

Methods

This was a retrospective cohort study of patients with and without non-traumatic SAH. For aim #1, the predictor variable was SAH and the outcome variables were all-cause and cerebrovascular mortality, stroke, cardiac mortality, acute coronary syndrome (ACS), and heart failure (HF) admission. A multivariable Cox proportional hazards analysis was performed. For aim #2, the predictor variables were cardiac injury (elevated serum cardiac enzymes or a diagnosis code for ACS) and dysfunction (pulmonary edema on X-Ray or a diagnosis code for HF).

Results

Compared with 4,695 members without SAH, the 910 SAH patients had higher rates of all-cause mortality (hazard ratio [HR 2.6], 95% confidence intervals [CI] 2.0?C3.4), cerebrovascular mortality (HR 30.6, CI 13.5?C69.4), and stroke (HR 10.2, CI 7.5?C13.8). Compared with the non-SAH group, the SAH patients with cardiac injury had increased rates of all-cause mortality (HR 5.3, CI 3.0?C9.3), cardiac mortality (HR 7.3, CI 1.7?C31.6), and heart failure (HR 4.3, CI 1.53?C11.88).

Conclusions

SAH survivors have increased long-term mortality and stroke rates compared with a matched non-SAH population. SAH-induced cardiac injury is associated with an increased risk of death and heart failure hospitalization.     

Intracerebral Monitoring of Silent Infarcts After Subarachnoid Hemorrhage

Background

Silent infarction is common in poor-grade subarachnoid hemorrhage (SAH) patients and associated with poor outcome. Invasive neuromonitoring devices may detect changes in cerebral metabolism and oxygenation.

Methods

From a consecutive series of 32 poor-grade SAH patients we identified all CT-scans obtained during multimodal neuromonitoring and analyzed microdialysis parameters and brain tissue oxygen tension (PbtO2) preceding CT-scanning.

Results

Eighteen percent of the reviewed head-CTs (12/67) revealed new infarcts. Of the eight infarcts in the vascular territory of the neuromonitoring, seven were clinically silent. Neuromonitoring changes preceding radiological evidence of infarction included lactate-pyruvate-ratio elevation and brain glucose decreases when compared to those with distant or no ischemia (P ≤ 0.03, respectively). PbtO2 was lower, but this did not reach statistical significance.

Conclusions

These data suggest that there may be distinct changes in brain metabolism and oxygenation associated with the development of silent infarction within the monitored vascular territory in poor-grade SAH patients. Larger prospective studies are needed to determine whether treatment triggered by neuromonitoring data has an impact on outcome.     

蛛网膜下腔出血患者并发下肢深静脉血栓的危险因素分析

目的 分析蛛网膜下腔出血(subarachnoid hemorrhage,SAH)患者并发下肢深静脉血栓(deep venous thrombosis,DVT)的危险因素,为DVT的预防和治疗提供临床指导.方法 连续收集2017年5-12月于首都医科大学附属北京天坛医院神经内科收治的SAH患者的临床资料,根据患者住院期...     

The Potential Role of Neuromodulation in Subarachnoid Hemorrhage

ObjectivesAneurysmal subarachnoid hemorrhage (SAH) continues to be a difficult cerebrovascular disease with limited pharmacologic treatment options. Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are leading causes of morbidity and mortality after SAH. Despite the advances in the understanding of its pathophysiology and tremendous efforts to date, nimodipine is currently the sole Food and Drug Administration–approved treatment for patients with SAH, with benefits that are marginal at best. The neuromodulation therapies are promising, especially those that target CV and DCI to improve functional outcomes. The aim of this review is therefore to summarize the available evidence for each type of neuromodulation for CV and DCI, with a special focus on its pathophysiological mechanisms, in addition to their clinical utility and drawbacks, which we hope will lead to future translational therapy options after SAH.Materials and MethodsWe conducted a comprehensive review of preclinical and clinical studies demonstrating the use of neuromodulation for SAH. The literature search was performed using PubMed, Embase, and ClinicalTrials.gov. A total of 21 articles published from 1992 to 2021 and eight clinical trials were chosen.ResultsThe studies reviewed provide a compelling demonstration that neuromodulation is a potentially useful strategy to target multiple mechanisms of DCI and thus to potentially improve functional outcomes from SAH. There are several types of neuromodulation that have been tested to treat CV and DCI, including the trigeminal/vagus/facial nerve stimulation, sphenopalatine ganglion and spinal cord stimulation, transcranial direct electrical stimulation, transcutaneous electrical neurostimulation, and electroacupuncture. Most of them are in the preclinical or early phases of clinical application; however, they show promising results.ConclusionsDCI has a complex pathogenesis, making the unique anatomical distribution and pleiotropic capabilities of various types of neuromodulation a promising field of study. We may be at the cusp of a breakthrough in the use of these techniques for the treatment of this stubbornly difficult disease.     

Metaanalysis of Tirilazad Mesylate in Patients with Aneurysmal Subarachnoid Hemorrhage

Background  Tirilazad is a non-glucocorticoid, 21-aminosteriod that inhibits lipid peroxidation. It had neuroprotective effects in experimental ischemic stroke and reduced angiographic vasospasm after experimental subarachnoid hemorrhage (SAH). Five randomized clinical trials of tirilazad were conducted in patients with SAH. We performed a meta-analysis of these trials to assess the effect of tirilazad on unfavorable outcome, symptomatic vasospasm, and cerebral infarction after SAH. Methods  Data from 3,797 patients were analyzed and modeled using random effect and Mantel-Haenszel meta-analyses and multivariable logistic regression to determine the effect of tirilazad on clinical outcome, symptomatic vasospasm, and cerebral infarction. Clinical outcome was assessed 3 months after SAH using the Glasgow outcome scale, and symptomatic vasospasm was defined by clinical criteria with laboratory and radiological exclusion of other causes of neurological deterioration. Results  The five trials were randomized, double-blind, and placebo-controlled. Tirilazad did not significantly decrease unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89–1.20) or cerebral infarction (OR 1.04, 95% CI 0.89–1.22). There was a significant reduction in symptomatic vasospasm in patients treated with tirilazad (OR 0.80, 95% CI 0.69–0.93). There was no heterogeneity across the five trials. Conclusion  Tirilazad had no effect on clinical outcome but did decrease symptomatic vasospasm in five trials of aneurysmal SAH. The dissociation between clinical outcome and symptomatic vasospasm deserves further investigation.     

Subarachnoid Hemorrhage: Clinical Presentation and Neuropsychological Outcome

Subarachnoid hemorrhage (SAH) following ruptured intracranial aneurysm affects 28,000 people each year in the United States. Despite advances in surgical treatment and a significant reduction in mortality over the past two decades, SAH remains a devastating disease. Although most survivors are free of physical handicap, a large percentage suffer from significant long-term cognitive and emotional disturbances. These may include deficits in memory, executive function, attention and concentration, psychomotor speed, language, anxiety, and depression. The severity of these deficits is attested to by the fact that over 50% of patients employed full time before SAH do not return to the same level of work. This article presents a review of the clinical presentation of SAH and the significant areas of neurological and cognitive dysfunction that occur after the hemorrhage.     

Monitoring with the Somanetics INVOS 5100C After Aneurysmal Subarachnoid Hemorrhage

Introduction  Vasospasm is a major cause of morbidity after subarachnoid hemorrhage (SAH), and current screening techniques (angiography, transcranial Doppler [TCD], and clinical examination) have serious limitations. Brain oximetry is a promising noninvasive tool to detect reduced brain oxygenation from vasospasm. Methods  Consecutive SAH patients at high risk for vasospasm were monitored with the INVOS (Somanetics, IL, USA) 5100C cerebral oximeter. We prospectively collected oximeter readings (rO2) with concurrent values for vital signs, intracerebral pressure (ICP), arterial blood gas measurement, and hemoglobin (HGB). Data were prospectively collected every 12 h and at clinical events (angiography, transfusion, etc.). We prospectively recorded clinical history, clinical events, radiology results, and outcomes. Results  Six patients were measured 123 times. rO2 values were correlated with the contralateral side, HGB, blood pressure, and PaO2, but not with ICP or perfusion pressure. There were no measured effects of angiography or transfusion. Patterns relating rO2 readings to clinical, angiographic, or TCD evidence of vasospasm were unclear, and there were no associations with the outcome (cerebral infarction, NIH Stroke Scale, or modified Rankin Scale). Conclusion  INVOS rO2 readings are associated with other factors that relate to cerebral oxygen delivery but seem to be of limited use as a screening tool for vasospasm or cerebral infarction after SAH.     

Common Data Elements for Unruptured Intracranial Aneurysms and Subarachnoid Hemorrhage Clinical Research: A National Institute for Neurological Disorders and Stroke and National Library of Medicine Project

Objectives

The goal for this project was to develop a comprehensive set of common data elements (CDEs), data definitions, case report forms and guidelines for use in unruptured intracranial aneurysm (UIA) and subarachnoid hemorrhage (SAH) clinical research, as part of a new joint effort between the National Institute of Neurological Disorders and Stroke (NINDS) and the National Library of Medicine of the US National Institutes of Health. These UIA and SAH CDEs will join several other neurological disease-specific CDEs that have already been developed and are available for use by research investigators.

Methods

A Working Group (WG) divided into eight sub-groups and a Steering Committee comprised of international UIA and SAH experts reviewed existing NINDS CDEs and instruments, created new elements when needed and provided recommendations for UIA and SAH clinical research. The recommendations were compiled, internally reviewed by the entire UIA and SAH WG and posted online for 6 weeks for external public comments. The UIA and SAH WG and the NINDS CDE team reviewed the final version before posting the SAH Version 1.0 CDE recommendations.

Results

The NINDS UIA and SAH CDEs and supporting documents are publicly available on the NINDS CDE (https://www.commondataelements.ninds.nih.gov/#page=Default) and NIH Repository (https://cde.nlm.nih.gov/home) websites. The recommendations are organized into domains including Participant Characteristics and Outcomes and Endpoints.

Conclusion

Dissemination and widespread use of CDEs can facilitate UIA and SAH clinical research and clinical trial design, data sharing, and analyses of observational retrospective and prospective data. It is vital to maintain an international and multidisciplinary collaboration to ensure that these CDEs are implemented and updated when new information becomes available.

     

蛛网膜下腔出血病理生理机制研究进展

蛛网膜下腔出血（subarachnoid hemorrhage，SAH）是临床上常见的脑血管病急危重症，具有 高致死率和高致残率的特点。尽管药物和血管内治疗不断进步，SAH患者功能预后的改善仍是目前面 临的一大难题。现研究已表明SAH脑血管痉挛，氧化应激反应，炎症反应，血脑屏障破坏与脑水肿， 细胞凋亡、焦亡与坏死，细胞自噬，皮质传播抑制和微血栓形成等病理变化过程是影响患者临床转 归的潜在机制。本文就SAH病理生理机制进行综述，以期为SAH临床预防、治疗和药物研发提供参考 依据。     

动脉瘤性蛛网膜下腔出血后慢性脑积水

目的探讨动脉瘤性蛛网膜下腔出血后(aSAH)慢性脑积水的发生率及其易患因素。方法回顾性研究2003年1月至2005年9月我科aSAH病例221例,采用单因素及多因素统计方法分析与慢性脑积水发生的相关影响因素。结果慢性脑积水的发生率为12.7%(28/221)。经单因素分析显示,患者年龄、Hunt-Hess级别、Fisher级别、前交通动脉瘤、aSAH次数以及脑室内出血具有统计学意义;多因素logistic回归分析显示,Fisher级别、脑室内出血、aSAH次数、前交通动脉瘤具有统计学意义。结论慢性脑积水为aSAH后一较常见并发症,影响其发生的高危因素包括Fisher级别、脑室内出血、aSAH次数、前交通动脉瘤。对具上述危险因素的aSAH患者应注意跟踪随访,及时诊治。     

MRI Detection of Cerebral Infarction in Subarachnoid Hemorrhage

Objective

To investigate magnetic resonance imaging (MRI) detection of cerebral infarction (CI) in patients presenting with subarachnoid hemorrhage (SAH).

Background

CI is a well-known complication of SAH that is typically detected on computed tomography (CT). MRI has improved sensitivity for acute CI over CT, particularly with multiple, small, or asymptomatic lesions.

Methods

With IRB approval, 400 consecutive SAH patients admitted to our institution from August 2006 to March 2011 were retrospectively reviewed. Traumatic SAH and secondary SAH were excluded. Data were collected on demographics, cause of SAH, Hunt Hess and World Federation of Neurosurgical Societies grades, and neuroimaging results. MRIs were categorized by CI pattern as single cortical (SC), single deep (SD), multiple cortical (MC), multiple deep (MD), and multiple cortical and deep (MCD).

Results

Among 123 (30.8 %) SAH patients who underwent MRIs during their hospitalization, 64 (52 %) demonstrated acute CI. The mean time from hospital admission to MRI was 5.7 days (range 0–29 days). Among the 64 patients with MRI infarcts, MRI CI pattern was as follows: MC in 20 (31 %), MCD in 18 (28 %), SC in 16 (25 %), SD in 3 (5 %), MD in 2 (3 %), and 5 (8 %) did not have images available for review. Most infarcts detected on MRI (39/64 or 61 %) were not visible on CT.

Conclusions

The use of MRI increases the detection of CI in SAH. Unlike CT studies, MRI-detected CI in SAH tends to involve multiple vascular territories. Studies that rely on CT may underestimate the burden of CI after SAH.

     

Summary of Evidence on Immediate Statins Therapy Following Aneurysmal Subarachnoid Hemorrhage

Statins were shown to have neuroprotective effects, with reduced vasospasm and delayed ischemic deficits in statin-treated patients after aneurysmal subarachnoid hemorrhage in two small, randomized, controlled clinical trials published in 2005. This review consolidated data from available published studies evaluating statin treatment for subarachnoid hemorrhage. A literature search was conducted to identify original research studies published through October 2010 testing immediate treatment with a statin in statin-na?ve patients following aneurysmal SAH. Six randomized controlled clinical trials and four observational studies were identified. Despite inconsistent results among studies, a meta-analysis of randomized controlled data showed a significant reduction in delayed ischemic deficits with statins. Effect on vasospasm was more difficult to determine, due to differences in definitions used among studies. Interpretations from observational studies were limited by the use of relatively small sample sizes, historical controls, and treatment variability.     

动脉瘤性蛛网膜下腔出血急诊手术治疗分析

目的探讨动脉瘤性蛛网膜下腔出血的诊断、急诊手术治疗以及脑血管痉挛的防治措施。方法回顾性分析33例动脉瘤性蛛网膜下腔出血患者的临床资料。结果术前12例行DSA检查,检出动脉瘤16枚;27例行CTA检查,检出动脉瘤30枚;其中有6例先后行CTA、DSA检查,两者完全符合。全部病例均在早期行显微手术治疗,无术中死亡病例,术后16例恢复良好,9例有轻度神经功能障碍,3例重度神经功能障碍,植物生存1例,死亡4例。结论动脉瘤性蛛网膜下腔出血急诊CTA检查明确病因更具优势;早期手术、预防脑血管痉挛能有效改善患者的预后。