The Burden of the Systemic Inflammatory Response Predicts Vasospasm and Outcome after Subarachnoid Hemorrhage

Introduction  Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce the systemic inflammatory response syndrome (SIRS). This may promote both extra-cerebral organ dysfunction and delayed cerebral ischemia, contributing to worse outcome. We ascertained the frequency and predictors of SIRS after spontaneous SAH, and determined whether degree of early systemic inflammation predicted the occurrence of vasospasm and clinical outcome. Methods  Retrospective analysis of prospectively collected data on 276 consecutive patients admitted to a neurosciences intensive care unit with acute, non-traumatic SAH between 2002 and 2005. A daily SIRS score was derived by summing the number of variables meeting standard criteria (HR >90, RR >20, Temperature >38°C, or <36°C, WBC count <4,000 or >12,000). SIRS was considered present if two or more criteria were met, while SIRS burden over the first four days was calculated by averaging daily scores. Regression modeling was used to determine the relationship among SIRS burden (after controlling for confounders including infection, surgery, and corticosteroid use), symptomatic vasospasm, and outcome, determined by hospital disposition. Results  SIRS was present in over half the patients on admission and developed in 85% within the first four days. Factors associated with SIRS included poor clinical grade, thick cisternal blood, larger aneurysm size, higher admission blood pressure, and surgery for aneurysm clipping. Higher SIRS burden was independently associated with death or discharge to nursing home (OR 2.20/point, 95% CI 1.27–3.81). All of those developing clinical vasospasm had evidence of SIRS, with greater SIRS burden predicting increased risk for delayed ischemic neurological deficits (OR 1.77/point, 95% CI 1.12–2.80). Conclusions  Systemic inflammatory activation is common after SAH even in the absence of infection; it is more frequent in those with more severe hemorrhage and in those who undergo surgical clipping. Higher burden of SIRS in the initial four days independently predicts symptomatic vasospasm and is associated with worse outcome. Financial support: Supported by NIH-N535906 (MND).     

Lower incidence of cerebral infarction correlates with improved functional outcome after aneurysmal subarachnoid hemorrhage

Despite an undisputed association between vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH), there is debate if this association implies causality. It has been suggested that cerebral infarction is a better outcome measure than vasospasm in clinical trials and observational studies. To further investigate the relationship between infarction and outcome, we performed a systematic review and meta-analysis of all randomized, double-blind, placebo-controlled trials that studied the efficacy of pharmaceutical preventive strategies in SAH patients, and had both cerebral infarction and clinical outcome as outcome events. Effect sizes were expressed in (pooled) risk ratio (RR) estimates with corresponding 95% confidence intervals (CIs). Sensitivity analyses were performed for studies with a low risk of bias and for those who reported outcome at 3 months after SAH. Twenty-four studies including 8,552 patients were included. Pharmaceutical treatments decreased the incidence of both cerebral infarction (RR: 0.83; 95% CI: 0.74 to 0.93) and of poor functional outcome (RR: 0.92; 95% CI: 0.86 to 0.98). The sensitivity analyses did not change the results essentially. These data suggest that the previously observed association between cerebral infarction and functional outcome implies causality, and that cerebral infarction is a better outcome measure than vasospasm in clinical trials and observational studies.     

Interobserver agreement and predictive value for outcome of two rating scales for the amount of extravasated blood after aneurysmal subarachnoid haemorrhage

Background In patients with SAH the amount of extravasated blood on the initial CT scan is related with delayed cerebral ischemia and clinical outcome. We investigated the interobserver variation of the Hijdra and Fisher scales for the amount of extravasated blood and the predictive values of these scales for delayed cerebral ischemia and outcome. Methods For 132 patients admitted within 48 hours after SAH three observers assessed the amount of blood on the initial CT scan by means of the Hijdra and Fisher scale. We analyzed interobserver agreement with kappa statistics and used multivariate logistic regression for the association with delayed cerebral ischemia and clinical outcome. Results The interobserver agreement of all three pairs of observers was good for the Hijdra scale (kappas for total sum scores ranging from 0.67 to 0.75) and mild to moderate for the Fisher scale (kappas ranging from 0.37 to 0.55). For the Hijdra scale the risk of DCI was higher for intermediate (OR 4.2; 95% CI 1.1–16.3) and large (OR 3.6; 95% CI 0.8–16.4) amounts of blood with small amount as reference. Fisher grade III (OR 1.0; 95% CI 0.2–5.2) and IV (OR 0.3; 95% CI 0.02–4.0) were not related with DCI. For the Hijdra scale and clinical outcome we found an increasing risk for poor outcome with intermediate (OR 3.9; 95% CI 1.0–15.9) and large (OR 10.7; 95% CI 2.3–50.1) amounts of blood. Such a relation was not found for Fisher grade III (OR 1.2; 95% CI 0.2–7.0) and IV (OR 0.2; 95% CI 0.01–3.4). Conclusions For the Hijdra scale we found a distinct better interobserver agreement than for the Fisher score. Moreover, the Hijdra scale was an independent prognosticator for DCI and clinical outcome, which was not the case for the Fisher score. Received in revised form: 9 February 2006     

The Effect of Locally Administered Fibrinolytic Drugs Following Aneurysmal Subarachnoid Hemorrhage : A Meta-Analysis with Eight Randomized Controlled Studies

ObjectiveRapid dissolution of blood clots reduces vasospasm and hydrocephalus after subarachnoid hemorrhage (SAH), and locally administered fibrinolytic drugs (LAFDs) could facilitate the dissolution. However, the efficacy of LAFDs remains controversial. The aim of this meta-analysis was to determine the efficacy of LAFDs for vasospasm and hydrocephalus and in clinical outcomes. MethodsFrom PubMed, EMBASE, and Cochrane database, data were extracted by two authors. Meta-analysis was performed using a random effect model. Inclusion criteria were patients who had LAFDs with urokinase-type or recombinant tissue-plasminogen activator after SAH in comparison with medically untreated patients with fibrinolytic drugs. We only included randomized controlled trials (RCTs) in this analysis. The outcomes of interest were vasospasm, hydrocephalus, mortality, and 90-day unfavorable functional outcome. ResultsData from eight RCTs with 550 patients were included. Pooled-analysis revealed that the LAFDs were significantly associated with lower rates of vasospasm (LAFDs group vs. control group, 26.5% vs. 39.2%; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32–0.73); hydrocephalus (LAFDs group vs. control group, 26.0% vs. 31.6%; OR, 0.54; 95% CI, 0.32–0.91); and mortality (LAFDs group vs. control group, 10.5% vs. 15.7%; OR, 0.58; 95% CI, 0.34–0.99). The proportion of 90-day unfavorable outcomes was lower in the LAFDs group (LAFDs group vs. control group, 32.7% vs. 43.5%; OR, 0.55; 95% CI, 0.37–0.80). ConclusionThis meta-analysis with eight RCTs indicated that LAFDs were significantly associated with lower rates of vasospasm and hydrocephalus after SAH. Thus, LAFDs could consequently reduce mortality and improve clinical outcome after SAH.     

Effect of cilostazol in patients with aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis

Previous studies with small sample size have shown that cilostazol can reduce the risk of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether cilostazol is effective in patients with aneurysmal SAH. Studies investigating the effect of cilostazol in patients with aneurysmal SAH were identified using Embase.com without language or publication-type restrictions. We used the random-effect model to combine data. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. Two randomized controlled trials and two quasi-randomized controlled trials with a total of 340 patients were included. The incidence of symptomatic vasospasm (RR = 0.47; 95% CI, 0.31–0.72; p < 0.001), severe vasospasm (RR = 0.48; 95% CI, 0.28–0.82; p = 0.007), vasospasm-related new cerebral infarctions (RR = 0.38; 95% CI, 0.22–0.67; p = 0.001), and poor outcome (RR = 0.57; 95% CI, 0.37–0.88; p = 0.011) were significantly lower in the cilostazol group. The numbers needed to treat for these outcomes were 6.4, 6.3, 5.7, and 5.4, respectively. Mortality rate differences between the two groups were insignificant. No statistical heterogeneity was found for all outcomes. These results show that cilostazol can decrease the incidence of symptomatic vasospasm, severe vasospasm, vasospasm-related new cerebral infarctions, and poor outcome in patients with aneurysmal SAH.     

High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients

ObjectiveThe goal of this study was to assess the effect of high-dose simvastatin on cerebral vasospasm and its clinical outcome after aneurysmal subarachnoid hemorrhage (SAH) in Korean patients.MethodsThis study was designed as a prospective observational cohort study. Its subjects were aneurysmal SAH patients who had undergone aneurysm clipping or coiling. They were assigned to 1 of 3 groups : the 20 mg, 40 mg, and 80 mg simvastatin groups. The primary end-point was the occurrence of symptomatic vasospasm. The clinical outcome was assessed with the modified Rankin Scale (mRS) score after 1 month and 3 months. The risk factors of the development of vasospasm were assessed by logistic regression analysis.ResultsNinety nine patients with aneurysmal SAH were treated and screened. They were sequentially assigned to the 20 mg (n=22), 40 mg (n=34), and 80 mg (n=31) simvastatin groups. Symptomatic vasospasm occurred in 36.4% of the 20 mg group, 8.8% of the 40 mg group, and 3.2% of the 80 mg group (p=0.003). The multiple logistic regression analysis showed that poor Hunt-Hess grades (OR=5.4 and 95% CI=1.09-26.62) and high-dose (80 mg) simvastatin (OR=0.09 and 95% CI=0.1-0.85) were independent factors of symptomatic vasospasm. The clinical outcomes did not show a significant difference among the three groups.ConclusionThis study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients.     

Effect of pharmaceutical treatment on vasospasm,delayed cerebral ischemia,and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

As it is often assumed that delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is caused by vasospasm, clinical trials often focus on prevention of vasospasm with the aim to improve clinical outcome. However, the role of vasospasm in the pathogenesis of DCI and clinical outcome is possibly smaller than previously assumed. We performed a systematic review and meta-analysis on all randomized, double-blind, placebo-controlled trials that studied the effect of pharmaceutical preventive strategies on vasospasm, DCI, and clinical outcome in SAH patients to further investigate the relationship between vasospasm and clinical outcome. Effect sizes were expressed in pooled risk ratio (RR) estimates with corresponding 95% confidence intervals (CI). A total of 14 studies randomizing 4,235 patients were included. Despite a reduction of vasospasm (RR 0.80 (95% CI 0.70 to 0.92)), no statistically significant effect on poor outcome was observed (RR 0.93 (95% CI 0.85 to 1.03)). The variety of DCI definitions did not justify pooling the DCI data. We conclude that pharmaceutical treatments have significantly decreased the incidence of vasospasm, but not of poor clinical outcome. This dissociation between vasospasm and clinical outcome could result from methodological problems, sample size, insensitivity of clinical outcome measures, or from mechanisms other than vasospasm that also contribute to poor outcome.     

Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage: a systematic review and meta-analysis

In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.     

Acute physiological derangement is associated with early radiographic cerebral infarction after subarachnoid haemorrhage

Background

Cerebral infarction after aneurysmal subarachnoid haemorrhage (SAH) is presumed to be due to cerebral vasospasm, defined as arterial lumen narrowing from days 3 to 14.

Methods

We reviewed the computed tomography scans of 103 patients with aneurysmal SAH for radiographic cerebral infarction and controlled for other predictors of outcome. A blinded neuroradiologist reviewed the angiograms. Cerebral infarction from vasospasm was judged to be unlikely if it was visible on computed tomography within 2 calendar days of SAH or if angiography showed no vasospasm in a referable vessel, or both.

Results

Cerebral infarction occurred in 29 (28%) of 103 patients with SAH. 18 patients had cerebral infarction that was unlikely to be due to vasospasm because it was visible on computed tomography by day 2 (6 (33%)) or because angiography showed no vasospasm in a referable artery (7 (39%)), or both (5 (28%)). In a multivariate model, cerebral infarction was significantly related to World Federation of Neurologic Surgeons grade (odds ratio (OR) 1.5/grade, 95% confidence interval (CI) 1.1 to 2.01, p = 0.006) and SAH‐Physiologic Derangement Score (PDS) >2 (OR 3.7, 95% CI 1.4 to 9.8, p = 0.01) on admission. Global cerebral oedema (OR 4.3, 95% CI 1.5 to 12.5, p = 0.007) predicted cerebral infarction. Patients with cerebral infarction detectable by day 2 had a higher SAH‐PDS than patients with later cerebral infarction (p = 0.025).

Conclusions

: Many cerebral infarctions after SAH are unlikely to be caused by vasospasm because they occur too soon after SAH or because angiography shows no vasospasm in a referable artery, or both. Physiological derangement and cerebral oedema may be worthwhile targets for intervention to decrease the occurrence and clinical impact of cerebral infarction after SAH.Subarachnoid haemorrhage (SAH) is a common and serious disorder, affecting approximately 11 in every 100 000 people.¹ Cerebral infarction after SAH is a well‐described complication and is strongly associated with a poor outcome.² Strategies to improve outcome after SAH usually focus on preventing or treating vasospasm.Nimodipine reduces the risk of cerebral infarction after SAH due to vasospasm³; yet, cerebral infarction still occurs and remains a major predictor of poor outcome in multivariate models.⁴ Vasospasm is traditionally defined as arterial narrowing 3–14 days after SAH.⁵ Cerebral infarction after SAH is generally assumed to be due to vasospasm, but causality is difficult to prove in critically ill patients. Radiographic cerebral infarction allows different observers to independently review studies at leisure, but may not be symptomatic. Acute cerebral infarction may be due to the acute effects of haemorrhage and the spike in intracranial pressure, but there are few objectively defined risk factors. We sought to identify patients with cerebral infarction associated with SAH in whom the cerebral infarction was unlikely to be due to vasospasm and to describe novel risk factors for targeted intervention.     

Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The role of type of treatment on cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage (SAH) has not been studied. Through multivariate analysis we determined the independent prognostic factors of the occurrence of symptomatic vasospasm following aneurysmal SAH in a study cohort of 244 patients undergoing either surgical or endovascular treatment. The prognostic factors of sequelae after aneurysmal SAH were studied as well. METHODS: Symptomatic vasospasm was defined as the association of deterioration in a patient's neurological condition between 3 and 14 days after SAH with no other explanation and an increase in mean transcranial Doppler velocities of >120 cm/s. The prognostic factors were registered on admission and during the intensive care stay. RESULTS: Symptomatic vasospasm occurred in 22.2% surgical patients compared with 17.2% endovascular treatment patients (P=0.37). Multivariate analysis revealed that the probability of occurrence of symptomatic vasospasm decreased with age >50 years (relative risk [RR], 0.47 [0.25 to 0.88]) and severe World Federation of Neurological Surgeons (WFNS) grade measured on admission (RR, 0.43 [0.20 to 0.90]) and increased with hyperglycemia occurring during the intensive care stay (RR, 1.94 [1.04 to 3.63]). No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment. Symptomatic vasospasm (OR, 4.73 [CI, 1. 77 to 12.6]) as well as WFNS grade of >2 (OR, 8.95 [3.46 to 23.2]), treatment complications (OR, 8.39 [3.16 to 22.3]), and secondary brain insults were associated with an increased risk of 6-month sequelae. CONCLUSIONS: Age <50 years, good neurological grade, and hyperglycemia were all associated with an increased risk of cerebral vasospasm whereas treatment was not. This provides a basis for future clinical prospective randomized trials comparing both treatments.     

Relationship Between Hemoglobin Concentrations and Outcomes Across Subgroups of Patients with Aneurysmal Subarachnoid Hemorrhage

Objective  Anemia predicts poor outcome following aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that this association would be stronger among patients with more severe SAH, since these patients are likely to be more vulnerable to secondary brain injury in the form of reduced cerebral oxygen delivery. Methods  Daily nadir hemoglobin (Hb) concentrations over 2 weeks following SAH were retrieved in 245 consecutive patients, and compared between those with a favorable versus unfavorable outcome. The analysis was repeated with patients dichotomized as follows: WFNS score 4–5 vs. 1–3; modified Fisher score (MFS) 4 vs. 0–3; and vasospasm present vs. absent. Mixed effect models and multivariable analysis using the generalized estimating equation were employed to assess correlated data with repeated measures. Results  Patients with an unfavorable outcome consistently had lower Hb concentrations, especially between days 6–11 following SAH (P ranging from <0.001 to 0.009), as well as a greater fall in Hb over time (β = −0.07, P < 0.001). This was true regardless of WFNS score, MFS, or the presence or absence of vasospasm. However, the effect was somewhat more pronounced among patients with higher WFNS and modified Fisher scores. Conclusion  Lower Hb levels are associated with worse outcomes regardless of SAH severity or the development of vasospasm. This finding may imply that a lower Hb concentration is largely a marker for a greater degree of systemic illness, rather than necessarily causing direct harm. However, the association is somewhat stronger among patients with more severe SAH. Thus, if there is a benefit for maintaining higher Hb levels with transfusions or erythropoietin, it may be more pronounced among these patients. Supported in part by the Louise Nerancy endowment of The University of Virginia.     

Predictors and outcome of acute symptomatic cerebral infarctions following aneurysmal subarachnoid hemorrhage

The leading cause of unfavorable outcomes following aneurysmal subarachnoid hemorrhage (SAH) is cerebral infarction. In this 3-year retrospective study, we have retrospectively evaluated 172 hospitalized patients with aneurysmal SAH, and compared those who developed a complicated cerebral infarction with those who did not. In this study, acute symptomatic cerebral infarctions accounted for 22.6% (39/172) of all episodes. Significant statistical analysis between the two patient groups included age at onset, hypertension as the underlying disease, presence of symptomatic vasospasm, mean hospitalization days and Glasgow Outcome Score at the time of discharge. After a minimum 1.5-year follow-up period, the median (interquantile range) Barthel index score was 75 (6–85) for those patients who had cerebral infarctions, and 80 (0–90) for those who had no cerebral infarctions. Multiple logistic regression analysis demonstrated that the presence of symptomatic vasospasm was independently associated with the presence of acute symptomatic cerebral infarctions. The presence of symptomatic vasospasm implies the danger of acute symptomatic cerebral events after aneurysmal SAH. Although our study demonstrates a worse short-term outcome and longer duration of hospitalization in this special group of patients, the functional outcome for patients with cerebral infarction was not inferior to those patients without cerebral infarction after a follow-up of at least 1.5-years.     

Calcium Homeostasis During Magnesium Treatment in Aneurysmal Subarachnoid Hemorrhage

Objective  Magnesium treatment in patients with subarachnoid hemorrhage (SAH) can result in hypocalcemia; this hypocalcemia increases the risk of delayed cerebral ischemia (DCI) and poor outcome. We assessed whether low serum levels of total calcium in patients with SAH treated with magnesium is mediated by parathyroid hormone (PTH) or calcitriol, and whether increased PTH or low serum levels of ionized calcium are associated with an increased risk of DCI and poor outcome. Patients and Methods  We studied 167 patients included in a randomized, placebo controlled trial on magnesium in SAH. Mean serum magnesium during treatment was related to mean serum levels of ionized calcium, PTH and calcitriol with linear regression. Hypocalcemia (Ca²⁺) and high serum PTH were related to the occurrence of DCI by means of the Cox proportional hazards model and to poor outcome by logistic regression. Results  Serum magnesium was inversely related to ionized calcium (B = −0.1; 95% CI −0.12 to −0.06), but not to PTH or calcitriol. Neither hypocalcemia nor high serum PTH was related to DCI. Hypocalcemia did not increased the risk for poor outcome (OR 1.2; 95% CI 0.6–2.3). In the subgroup of patients with known PTH (n = 67), high serum PTH increased the risk for poor outcome (OR 5.4; 1.6–18.9). Conclusions  Magnesium treatment in patients with SAH leads to hypocalcemia without effect on outcome. PTH is related to poor outcome, but this is independent of magnesium therapy.     

Occurrence and impact of delayed cerebral ischemia after coiling and after clipping in the International Subarachnoid Aneurysm Trial (ISAT)

Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). We studied differences in incidence and impact of DCI as defined clinically after coiling and after clipping in the International Subarachnoid Aneurysm Trial. We calculated odds ratios (OR) for DCI for clipping versus coiling with logistic regression analysis. With coiled patients without DCI as the reference group, we calculated ORs for poor outcome at 2 months and 1 year for coiled patients with DCI and for clipped patients without, and with DCI. With these ORs, we calculated relative excess risk due to Interaction (RERI). Clipping increased the risk of DCI compared to coiling in the 2,143 patients OR 1.24, 95% confidence interval (95% CI 1.01–1.51). Coiled patients with DCI, clipped patients without DCI, and clipped patients with DCI all had higher risks of poor outcome than coiled patients without DCI. Clipping and DCI showed no interaction for poor outcome at 2 months: RERI 0.12 (95% CI −1.16 to 1.40) or 1 year: RERI −0.48 (95% CI −1.69 to 0.74). Only for patients treated within 4 days, coiling and DCI was associated with a poorer outcome at 1 year than clipping and DCI (RERI −2.02, 95% CI −3.97 to −0.08). DCI was more common after clipping than after coiling in SAH patients in ISAT. Impact of DCI on poor outcome did not differ between clipped and coiled patients, except for patients treated within 4 days, in whom DCI resulted more often in poor outcome after coiling than after clipping.     

Impact of aneurysm morphology on aneurysmal subarachnoid hemorrhage severity,cerebral infarction and functional outcome

ObjectiveAneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity. The objective was to evaluate, whether specific morphological aneurysm characteristics could serve as predictive values for aSAH severity, disease-related complications and clinical outcome.MethodsA total of 453 aSAH patients (mean age: 54.9 ± 13.8 years, mean aneurysm size: 7.5 ± 3.6 mm) treated at a single center were retrospectively included. A morphometric analysis was performed based on angiographic image sets, determining aneurysm location, aneurysm size, neck width, aneurysm size ratios, aneurysm morphology and vessel size. The following outcome measures were defined: World Federation of Neurosurgical Societies (WFNS) grade 4 and 5, Fisher grade 4, vasospasm, cerebral infarction and unfavorable functional outcome.ResultsRegarding morphology parameters, aneurysm neck width was an independent predictor for Fisher 4 hemorrhage (OR: 1.1, 95%CI: 1.0–1.3, p = 0.048), while dome width (OR: 0.92, 95%CI: 0.86–0.97, p = 0.005) and internal carotid artery location (OR: 2.1, 95%CI: 1.1–4.2, p = 0.028) predicted vasospasm. None of the analyzed morphological characteristics prognosticated functional outcome. Patient age (OR: 0.95, 95%CI: 0.93–0.96, p < 0.001), WFNS score (OR: 4.8, 95%CI: 2.9–8.0, p < 0.001), Fisher score (OR: 2.3, 95%CI: 1.4–3.7, p < 0.001) and cerebral infarction (OR: 4.5, 95%CI: 2.7–7.8, p < 0.001) were independently associated with unfavorable outcome.ConclusionsThe findings indicate a correlation between aneurysm morphology, Fisher grade and vasospasm. Further studies will be required to reveal an independent association of aneurysm morphology with cerebral infarction and functional outcome.     

Massive intraventricular haemorrhage from aneurysmal rupture: patient proportions and eligibility for intraventricular fibrinolysis

Massive intraventricular haemorrhage (IVH) complicating aneurysmal subarachnoid haemorrhage (SAH) is associated with a poor prognosis. Small observational studies suggest favourable results from fibrinolysis of the intraventricular blood. We performed an observational study on IVH in a large series of patients with SAH to assess the proportion of patients that may benefit from fibrinolytic treatment. From our prospective database we retrieved patients with aneurysmal SAH admitted between January 2000 and January 2005. We calculated the proportion of patients with massive IVH and the proportion of patients that are eligible for fibrinolysis on basis of clinical and CT-scan characteristics and assessed neurological outcome in a treatment strategy without fibrinolysis. Poor neurological condition was defined as World Federation of Neurological Surgeons scale 4 and 5, poor outcome as death or dependence 3 months after SAH. Of the 573 patients admitted with aneurysmal SAH, 59 (10%; 95% confidence interval CI 8–13%) had massive IVH, of which 55 were in poor clinical condition. For these 55 patients, the case-fatality rate was 78% (95% CI 66–88%) and the proportion with poor outcome 91% (95% CI 81–97%). Of the 55 patients, 31 (56%, and 5% of all patients SAH within the study period) fulfilled our eligibility criteria and were considered suitable for intraventricular fibrinolysis. At 3 months, 30 of these 31 eligible patients (97%; 95% CI 85–100%) had a poor outcome. Massive IVH occurs in 10% of patients with aneurysmal SAH. Half of these patients may benefit from intraventricular fibrinolysis. Without fibrinolysis outcome is almost invariably poor in these patients.     

西洛他唑用于动脉瘤性蛛网膜下腔出血患者疗效的meta分析

目的本研究旨在评价西洛他唑用于动脉瘤性蛛网膜下腔出血患者的临床疗效,为其应用提供依据。方法计算机检索西洛他唑用于动脉瘤性蛛网膜下腔出血的对照研究,时间截止2013年1月。由2位研究者独立评价纳人研究的质量、提取数据,统计分析采用RevMan5．2．3软件进行。结果纳入3个研究,共259例患者。Meta分析结果显示：西洛他唑降低症状性脑血管痉挛（RR=0．46;95％CI=0．30～0．71;P=0．0005）、血管造影脑血管痉挛（RR=0．60;95％CI=0．44～0．81;P=0．0008）、血管痉挛性脑梗死（RR=0．38;95％CI：0．22～0．67;P=0．0008）发生率,但不改善短期临床预后（RR=1．28;95％CI=0．98～1．66;P=0．07）。结论西洛他唑可预防动脉瘤性蛛网膜下腔出血后脑血管痉挛、血管痉挛性脑梗死,对患者预后影响还需大样本多中心临床研究进一步证实。     

Cerebral inflammatory response and predictors of admission clinical grade after aneurysmal subarachnoid hemorrhage

Poor admission clinical grade is the most important determinant of outcome after aneurysmal subarachnoid hemorrhage (aSAH); however, little attention has been focused on independent predictors of poor admission clinical grade. We hypothesized that the cerebral inflammatory response initiated at the time of aneurysm rupture contributes to ultra-early brain injury and poor admission clinical grade. We sought to identify factors known to contribute to cerebral inflammation as well as markers of cerebral dysfunction that were associated with poor admission clinical grade. Between 1997 and 2008, 850 consecutive SAH patients were enrolled in our prospective database. Demographic data, physiological parameters, and location and volume of blood were recorded. After univariate analysis, significant variables were entered into a logistic regression model to identify significant associations with poor admission clinical grade (Hunt–Hess grade 4–5). Independent predictors of poor admission grade included a SAH sum score >15/30 (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.5–3.6), an intraventricular hemorrhage sum score >1/12 (OR 3.1, 95% CI 2.1–4.8), aneurysm size >10 mm (OR 1.7, 95% CI 1.1–2.6), body temperature ?38.3 °C (OR 2.5, 95% CI 1.1–5.4), and hyperglycemia >200 mg/dL (OR 2.7, 95% CI 1.6–4.5). In a large, consecutive series of prospectively enrolled patients with SAH, the inflammatory response at the time of aneurysm rupture, as reflected by the volume and location of the hemoglobin burden, hyperthermia, and perturbed glucose metabolism, independently predicts poor admission Hunt–Hess grade. Strategies for mitigating the inflammatory response to aneurysmal rupture in the hyper-acute setting may improve the admission clinical grade, which may in turn improve outcomes.     

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.     

Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome

OBJECTIVE: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. BACKGROUND: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may be both caused by, and potentiate, VSP-mediated brain injury. METHODS: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt-Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 degrees C for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 degrees C). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. RESULTS: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was related to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). CONCLUSION: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection.