国际蛛网膜下腔出血动脉瘤试验:栓塞与夹闭后迟发性脑缺血的发生与影响(英文)

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.     

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.     

Magnesium and aspirin treatment in patients with subarachnoid haemorrhage

Objective   Aneurysm treatment with endovascular coiling is associated with a better outcome than neurosurgical clipping in patients with subarachnoid haemorrhage (SAH). The better outcome after coiling may decrease the risk reduction from other treatments in these patients, and thus may increase sample sizes for current or future neuroprotective trials. The influence of the method of aneurysm treatment was studied in our randomised MASH trial, which assessed in a factorial design the efficacy of magnesium and aspirin in preventing delayed cerebral ischaemia (DCI) and poor outcome. Methods   Between November 2000 and January 2004 315 patients were enrolled in the trial; 55 of them had no aneurysm treatment and were excluded for the current analysis, 176 underwent neurosurgical and 84 endovascular treatment. The effect of treatment on the risk of DCI was assessed by means of Cox proportional hazards modelling and that of poor outcome by means of logistic regression analysis. Results   The hazard ratio of DCI with aspirin was 1.4 (95 % CI 0.3 – 1.7) after coiling and 1.9 (0.8 – 4.4) after clipping, and with magnesium 0.4 (0.1 – 1.2) after coiling and 0.8 (0.4 – 1.7) after clipping. The odds ratio of poor outcome with aspirin was 0.7 (0.2 – 2.9) after coiling and 0.8 (0.3 – 2.3) after clipping, and with magnesium 0.3 (0.1 – 1.0) after coiling and 0.8 (0.4 – 1.6) after clipping. Conclusion   This post hoc analysis does not suggest that medical treatments are less effective after endovascular than after neurosurgical treatment in patients with SAH, and thus do not support a need for adjusting sample size calculations in future trials. Magnesium and Acetylsalicylic acid in Subarachnoid Haemorrhage (MASH) Study Group: W. M. van den Bergh,A. Algra, S. M. Dorhout Mees,J. van Gijn,G. J. E. Rinkel,Dept. of Neurology,University Medical Centre Utrecht,Utrecht, The Netherlands Ale Algra,Julius Centre for Health Sciences and Primary Care,University Medical Centre Utrecht,Utrecht, The Netherlands Fop van Kooten,Dept. of Neurology,Erasmus Medical Centre,Rotterdam, The Netherlands Clemens M.F. Dirven,Dept. of Neurology,VU University Medical Centre,Amsterdam, The Netherlands Marinus Vermeulen,Dept. of Neurology,Academic Medical CentreUniversity of Amsterdam,Amsterdam, The Netherlands W. M. van den Bergh, MD, PhD ✉, Dept. of Intensive Care, Room Q04.460,University Medical Centre Utrecht,P.O. Box 85500,3508 GA, Utrecht, The Netherlands,Tel.: +31-30/2508350,Fax: +31-30/2522782,E-Mail: w.m.vandenbergh@umcutrecht.nl     

Endovascular coiling versus neurosurgical clipping in patients with a ruptured basilar tip aneurysm

OBJECTIVES: To compare endovascular coiling with neurosurgical clipping of ruptured basilar bifurcation aneurysms. METHODS: Patient and aneurysm characteristics, procedural complications, and clinical and anatomical results were compared retrospectively in 44 coiled patients and 44 patients treated by clipping. The odds ratios for poor outcome (Glasgow outcome scale 1, 2, 3) adjusted for age, clinical condition, and aneurysm size were assessed by logistic regression analysis. RESULTS: In the endovascular group, five patients (11%) had a poor outcome v 13 (30%) in the surgical group; the adjusted odds ratio for poor outcome after coiling v clipping was 0.28 (95% confidence interval, 0.08 to 0.99). Procedural complications were more common in the surgical group. Optimal or suboptimal occlusion of the aneurysm immediately after coiling was achieved in 41 patients (93%). Clipping was successful in 40 patients (91%). CONCLUSIONS: The results suggest that embolisation with coils is the preferred treatment for patients with ruptured basilar bifurcation aneurysms.     

Clipping or coiling of ruptured cerebral aneurysms and shunt-dependent hydrocephalus

Background  Hydrocephalus may develop either early in the course of aneurysmal subarachnoid hemorrhage (SAH) or after the first 2 weeks. Because the amount of SAH is a predictor of hydrocephalus, the two available aneurysmal treatments, clipping or coiling, may lead to differences in the need for cerebrospinal fluid (CSF) diversion, as only surgery permits clot removal. Methods  Hospital and University Hospitals Consortium (UHC) databases were used to retrieve data on all patients admitted to our hospital with aneurysmal SAH during the last 4 years. The incidence of permanent ventricular shunt (VS) according to treatment modality used was evaluated. Results  One hundred eighty-eight patients were admitted with aneurysmal SAH. Coiling was performed on 48 (26%) and clipping on 135 (73.8%) patients. Fifty-six (31%) patients required CSF diversion. External ventricular drain was placed in 30 (22.2%) clipped and 13 (27.1%) coiled patients (p=0.5), and VS in 6 patients of the two treatment groups (4.4 versus 12.5%, respectively; p=0.08). Patients requiring VS had longer UHC-expected hospital length of stay (LOS), as well as observed ICU and hospital LOS, compared to patients with temporary or no CSF diversion (24±14 versus 15±8, 20.5±9 versus 11±7, and 30±13 versus 16±11 days, respectively; p≤0.01). In a logistic regression model, VS was independently associated with rebleeding, external ventricular drain placement, coiling, and UHC-expected LOS (odds ratios, 95% confidence interval 12.1, 2.3–62.6, 6.9, 1.6–30, 6.25, 1.3–29, and 1.1, 1.02–1.14, respectively). Conclusions  One-third of patients admitted with aneurysmal SAH require temporary or permanent CSF diversion. Permanent shunting was found to be associated with coiling in our patient population.     

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     

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.     

Fluid Balance and Blood Volume Measurement after Aneurysmal Subarachnoid Hemorrhage

Background  Patients with aneurysmal subarachnoid hemorrhage (SAH) are at risk for circulatory volume depletion, which is a risk factor for delayed cerebral ischemia (DCI). In a prospective observational study we assessed the effectiveness of fluid administration based on regular evaluation of the fluid balance in maintaining normovolemia. Methods  A total of 50 patients with aneurysmal SAH were included and were treated according to a standard protocol aimed at maintaining normovolemia. Fluid intake was adjusted on the basis of the fluid balance, which was calculated at 6-h intervals. Circulating blood volume (CBV) was measured by means of pulse dye densitometry (PDD) on alternating days during the first 2 weeks after SAH. Results  Of the 265 CBV measurements, 138 (52%) were in the normovolemic range of 60–80 ml/kg; 76 (29%) indicated hypovolemia with CBV < 60 ml/kg; and 51 (19%) indicated hypervolemia with CBV > 80 ml/kg. There was no association between CBV and daily fluid balance (regression coefficient β = −0.32; 95% CI: −1.81 to 1.17) or between CBV and a cumulative fluid balance, adjusted for insensible loss through perspiration and respiration (β = 0.20; 95% CI: −0.31 to 0.72). Conclusion  Calculations of fluid balance do not provide adequate information on actual CBV after SAH, as measured by PDD. This raises doubt whether fluid management guided by fluid balances is effective in maintaining normovolemia.     

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.     

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).     

脑动脉瘤夹闭术与栓塞术:竞争还是互补?

目的探讨颅内动脉瘤开颅夹闭术和介入栓塞术两种治疗方式的相互关系。方法回顾总结动脉瘤夹闭术和栓塞术互补性治疗的6例病例，其中3例先行手术治疗，3例先行介入治疗。3例手术治疗的患者其中1例出现后交通动脉瘤复发，1例前交通动脉瘤术后前交通动脉上发现新的动脉瘤，均行动脉瘤栓塞术补充治疗，1例双侧后交通动脉瘤左侧手术夹闭1年后行右侧后交通动脉瘤颅内支架血管内介入治疗。3例先介入治疗的患者中1例发生栓塞物堵塞载瘤动脉瘤导致大面积脑梗塞，1例发生栓塞物移位，1例发生再出血，均采取开颅手术予以补充治疗，夹闭动脉瘤并取出了栓塞物。结果所有补充治疗均未造成新的病残，其中5例恢复满意，1例恢复良好。结论颅内动脉瘤夹闭术和栓塞术之间既是竞争的关系同时也是互补的关系，两种手术方式都有需要发展的余地同时也有相互结合的必要。     

Acute systematic inflammatory response syndrome and serum biomarkers predict outcomes after subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce systematic inflammatory response syndrome (SIRS). Serum inflammatory biomarkers and SIRS can predict a poor outcome. The relationship between surgical stress and inflammatory response is well known but described in few reports in the neurosurgical population. We aimed to ascertain whether postoperative SIRS and initial serum biomarkers were associated with outcomes and evaluate whether the postoperative SIRS score differed between those with clipping and coil embolization. We evaluated 87 patients hospitalized within 24 h from onset of nontraumatic SAH. Serum biomarkers, such as levels of C-reactive protein (CRP), white blood cells (WBC), and D-dimer, as well as stress index (SI: blood sugar/K ratio) were obtained at admission. SIRS scores 3 days after admission were derived by adding the number of variables meeting the standard criteria (heart rate [HR] >90, respiratory rate [RR] >20, temperature >38 °C or <36 °C, and WBC count <4000 or >12,000). Clinical variables were compared according to whether they were associated with poor outcomes. Coil embolization was performed in 30 patients and clipping in 57. WBC, SI, D-dimer levels, and SIRS scores were significantly higher in patients with poor-grade SAH and were associated with poor outcomes. SIRS scores were significantly higher with clipping than with coil embolization among patients with good-grade SAH without intracerebral hemorrhage. Acute SIRS and serum biomarkers predict outcomes after SAH. Moreover, our study suggests the influence of surgical invasion via clipping on SIRS after SAH.     

Impact of Systemic Inflammatory Response Syndrome on Vasospasm,Cerebral Infarction,and Outcome After Subarachnoid Hemorrhage: Exploratory Analysis of CONSCIOUS-1 Database

Background  

Systemic inflammatory response syndrome (SIRS) may develop after aneurysmal subarachnoid hemorrhage (SAH). We investigated factors associated with SIRS after SAH, whether SIRS was associated with complications of SAH such as vasospasm, cerebral infarction, and clinical outcome, and whether SIRS could contribute to a difference in outcome between patients treated by endovascular coiling or neurosurgical clipping of the ruptured aneurysm.     

Which treatment modality is more injurious to the brain in patients with subarachnoid hemorrhage? Degree of brain damage assessed by serum s100 protein after aneurysm clipping or coiling

Background: Serum S100 protein has been known to reflect the severity of brain damage. The purpose of this study was to compare the degree of brain damage based on the serum S100 protein level between aneurysm clipping and coiling groups and to evaluate the prognostic value of S100 protein in patients with subarachnoid hemorrhage (SAH). Methods: Serum S100 protein was measured by Elecsys S100 immunoassay at admission, and at 6 and 24 h, and days 3 and 5 postoperatively for 100 consecutive SAH patients (clipping group: 56, coiling group: 44) and for 74 healthy controls. Hunt-Hess grade (HHG), Fisher grade (FG), the presence of intraventricular (IVH) or intracerebral hemorrhage (ICH), and outcome at discharge were evaluated. The time course of serum S100 was compared between the groups. The prognostic value of S100 protein was evaluated by logistic regression analysis. Results: The median S100 level in SAH patients on admission was significantly higher than in healthy controls (0.081 vs. 0.05 μg/l, p < 0.0001) and it was also higher as HHG and FG increased (p < 0.0001). Logistic regression analysis revealed that only the S100 value at admission was an independent prognostic factor for poor outcomes after adjusting for age, sex, HHG, presence of IVH or ICH, and treatment modality (OR: 100.5, 95% CI: 1.65-6,053.61). The baseline S100 value of 0.168 predicted poor outcomes with a sensitivity of 75% and a specificity of 83%. The time course of the median S100 level peaked at 6 h and then decreased serially in both clipping and coiling groups. However, the degree of S100 elevation was marked in the clipping group, especially at 6 h postoperatively (0.177 vs. 0.116 μg/l, p = 0.022), suggesting more severe brain damage in the clipping group. In the coiling group, the S100 value was significantly higher in patients who showed high signal intensity lesions in diffusion-weighted images, suggesting ischemic brain damage. Furthermore, even in patients who were categorized as good clinical grade at admission and as good outcome at discharge, the median S100 values at 6 and 24 h postoperatively were significantly higher in the clipping group than in the coiling group (p < 0.05). Conclusion: The initial S100 protein value is an independent prognostic factor for poor outcomes in SAH patients. Based on the S100 protein level, aneurysm clipping seems to provoke more brain damage than aneurysm coiling. Endovascular coiling should be considered the first therapeutic option for aneurysmal SAH patients.     

Relation of Serum TNF-α and TNF-α Genotype with Delayed Cerebral Ischemia and Outcome in Subarachnoid Hemorrhage

Introduction  

The pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) remains obscure. The authors assessed the relationship of tumor necrosis factor alpha (TNF-α) and TNF-α gene polymorphisms with occurrence of DCI and poor outcome at 3 months.     

Achieved serum magnesium concentrations and occurrence of delayed cerebral ischaemia and poor outcome in aneurysmal subarachnoid haemorrhage

Background

Magnesium therapy probably reduces the frequency of delayed cerebral ischaemia (DCI) in subarachnoid haemorrhage (SAH) but uncertainty remains about the optimal serum magnesium concentration. We assessed the relationship between serum magnesium concentrations achieved with magnesium sulphate therapy 64 mmol/day and the occurrence of DCI and poor outcome in patients with SAH.

Methods

Differences in magnesium concentrations between patients with and without DCI and with and without poor outcome were calculated. Quartiles of last serum magnesium concentrations before the onset of DCI, or before the median day of DCI in patients without DCI, were related to the occurrence of DCI and poor outcome at 3 months using logistic regression.

Results

Compared with the lowest quartile of serum magnesium concentration (1.10–1.28 mmol/l), the risk of DCI was decreased in each of the higher three quartiles (adjusted odds ratio (OR) in each quartile 0.2; lower 95% CI 0.0 to 0.1; upper limit 0.8 to 0.9). The OR for poor outcome was 1.8 (95% CI 0.5 to 6.9) in the second quartile, 1.0 (95% CI 0.2 to 4.5) in the third quartile and 4.9 (95% CI 1.2 to 19.7) in the highest quartile.

Discussion

Magnesium sulphate 64 mmol/day results in a stable risk reduction of DCI over a broad range of achieved serum magnesium concentrations, and strict titration of the dosage therefore does not seem necessary. However, concentrations ⩽1.28 mmol/l could decrease the effect on DCI while concentrations ⩾1.62 might have a negative effect on clinical outcome.Aneurysmal subarachnoid haemorrhage (SAH) has a poor prognosis: half of patients die and one out of every five survivors remains dependent.¹ In patients who survive the initial hours after the haemorrhage and undergo early aneurysm treatment, delayed cerebral ischaemia (DCI) is the most important cause of poor outcome. DCI occurs in approximately one‐third of patients and develops mostly between the fourth and tenth day after SAH.^2,3Magnesium is a neuroprotective agent with a well established clinical profile, and is commonly used in obstetric medicine.^4,5 Hypomagnesaemia occurs in more than half of patients with SAH and is related to the occurrence of DCI.⁶ Recently, we conducted a randomised, placebo controlled phase II trial with magnesium sulphate in patients with SAH.⁷ Magnesium therapy reduced the occurrence of DCI by 34% (95% CI −14 to 62) and of poor outcome by 23% (95% CI −9 to 46). In this trial, magnesium sulphate was given in a standard dose of 64 mmol/day. With this dosage, 85% of patients had serum magnesium levels between 1.0 and 2.0 mmol/l.⁸ Whether there is an optimal serum magnesium concentration within this range is unclear.In this study, we assessed whether there is a relationship between achieved serum magnesium levels and the occurrence of DCI and poor outcome in patients with aneurysmal SAH treated with continuous magnesium sulphate infusion at a fixed dose.     

Direct costs of surgical clipping and endovascular coiling of unruptured intracranial aneurysms

BACKGROUND: Unruptured intracranial aneurysms can be preventively treated by surgical clipping or endovascular coiling. We determined in detail the costs of these treatments. METHODS: We included patients who were treated for an unruptured aneurysm between 1997 and 2003. Patients coiled in this period were matched with clipped patients according to the year of treatment, age and gender. Considering clipping and coiling, we compared all pre-admission costs of diagnostic procedures, all costs of treatment, and costs during follow-up including standard angiographic control examinations at 6 and 18 months after coiling. Costs were calculated as the product of the used resources and the costs of these resources. RESULTS: The mean price for clipping was EUR 8,865.42 and that for coiling EUR 10,370.29. The difference was mainly determined by the higher material costs of coiling (EUR 5,300) compared with clipping (EUR 690). Costs of clipping were mainly determined by the need for intensive care facilities (1.2 days after clipping and 0 days after coiling) and the length of hospital stay (10.5 days after clipping and 3.4 days after coiling). After bootstrapping the data, costs of coiling were on average EUR 1,553 (95% confidence interval: EUR 1,539-1,569) higher than those of clipping. CONCLUSIONS: For unruptured intracranial aneurysms, direct in-hospital costs of coiling are on average higher than those of clipping, mostly because of the more expensive coils.     

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.     

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.     

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.