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Cerebrovascular Diseases (Basel,... 2022Delayed cerebral ischemia is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Cilostazol, a selective inhibitor of... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Delayed cerebral ischemia is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Cilostazol, a selective inhibitor of phosphodiesterase 3, was reported to reduce cerebral vasospasm and improve outcomes. We aimed to conduct an updated systematic review and meta-analysis of the efficacy and safety of cilostazol in aSAH.
METHODS
We systematically searched PubMed, Embase, MEDLINE, and the Cochrane Library for articles published in English with the latest publishing time in August 2020. Articles reporting favorable outcome as the primary outcome and reporting severe angiographic vasospasm (aVS), symptomatic vasospasm (sVS), new cerebral infarction, or mortality as the secondary outcome were included in this review. Furthermore, we examined whether clinical outcomes were associated with the dosage of cilostazol (300 mg/day vs. 100-200 mg/day).
RESULTS
Data from 405 patients in 4 randomized controlled trials (RCTs) and 461 patients in 4 observational studies (OSs) were included. In RCT studies, cilostazol was associated with significant favorable outcomes at discharge or 1 month (risk ratio [RR] 1.41, 95% confidence interval [CI] 1.01-1.97, p = 0.04) or 3 or 6 months (RR 1.16, 95% CI 1.05-1.28, p = 0.002). However, in OSs, no significant difference was indicated in favorable outcomes at discharge or 1 month (RR 1.22, 95% CI 0.94-1.60, p = 0.14) nor 3 or 6 months (RR 1.29, 95% CI 0.92-1.81, p = 0.14). The analyses found that cilostazol significantly reduced the incidences of severe aVS (RCT: RR 0.64, 95% CI 0.41-1.01, p = 0.05; OS: RR 0.61, 95% CI 0.43-0.88, p = 0.007), sVS (RCT: RR 0.46, 95% CI 0.31-0.70, p = 0.0002; OS: RR 0.38, 95% CI 0.21-0.68, p = 0.001), and new cerebral infarction (RCT: RR 0.40, 95% CI 0.24-0.67, p = 0.0005; OS: RR 0.38, 95% CI 0.23-0.64, p = 0.0002). However, no significant difference in mortality (RCT: RR 0.86, 95% CI 0.23-3.21, p = 0.82; OS: RR 0.16, 95% CI 0.02-1.24, p = 0.08) was found. In 3 OSs which reported different doses of cilostazol (300 mg/day vs. 100-200 mg/day) for aSAH, the 300-mg/day cilostazol groups showed decreased delayed cerebral infarction (RR 0.27, 95% CI 0.09-0.81, p = 0.02) but no significant difference in shunt-dependent hydrocephalus (RR 0.92, 95% CI 0.33-2.60, p = 0.88) or functional outcomes (RR 1.14, 95% CI 0.74-1.75, p = 0.56) compared with the 100-200 mg/day cilostazol groups.
CONCLUSIONS
The meta-analyses suggest the credible efficacy and safety of cilostazol in treating aSAH. Furthermore, 300-mg/day cilostazol treatment appeared to be more effective than 100-200 mg/day treatment.
Topics: Cerebral Infarction; Cilostazol; Humans; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial
PubMed: 35288494
DOI: 10.1159/000518731 -
Journal of Neurosciences in Rural... 2023This study reviews the effect of albumin-induced volume expansion therapy on symptomatic vasospasm and clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH). (Review)
Review
OBJECTIVES
This study reviews the effect of albumin-induced volume expansion therapy on symptomatic vasospasm and clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH).
MATERIALS AND METHODS
Computer searches carried out from the Scopus, Medline, Embase, Web of Science, the Cochrane Library, and Internet documents; hand searching of medical journals; and review of reference lists. Randomized controlled trials (RCT) and observational studies (OSs) comparing albumin therapy in combination or alone with crystalloid therapy for the treatment of cerebral vasospasm in aSAH were included in the study. Risk-of-bias assessment was conducted using ROB2.0 and ROBINS-I tools for RCTs and Oss, respectively.
RESULTS
Out of a total of 1078 searches, one RCT (published in two articles) and one observational (retrospective) study were included for final analysis. In RCT, albumin was used for volume expansion therapy with a baseline crystalloid regime and comparison made between hypervolemic and normovolemic groups and it showed no beneficial effects on symptomatic vasospasm and clinical outcomes based on the Glasgow outcome scale. Furthermore, the use of albumin showed a tendency for sodium retention with lowering of glomerular filtration rate, limiting the amount of total fluid required for targeted central venous pressure values, and thereby avoiding fluid overload manifestations. The retrospective study results between albumin versus non-albumin groups (crystalloids only) supported improved outcomes in the former group with lower in-hospital mortality. Cardiorespiratory complications were equivocal in RCT and increased in non-albumin group in the retrospective study. Risk-of-bias assessment analyses revealed "some concerns" in RCT and "serious" limitation in OS due to its retrospective design.
CONCLUSION
Albumin-induced volume expansion therapy for cerebral vasospasm does not have substantiative evidence to improve cerebral vasospasm and clinical outcomes in aSAH. Studies with well-designed RCTs are required to compare the use of albumin for volume expansion therapy versus standard fluid management using crystalloids to mitigate the scarcity of published data.
PubMed: 38059246
DOI: 10.25259/JNRP_372_2023 -
Neurosurgical Review Oct 2021Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the... (Review)
Review
Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the management of aSAH in pregnancy. We identified all available literature and compiled management decisions as well as reported outcomes through a systematic literature review without meta-analysis to provide recommendations for management of aSAH during pregnancy. We included a total of 23 articles containing 54 cases of pregnancy-related aSAH in our review. From these reports and other literature, we evaluated information on aSAH pathophysiology, diagnosis, and management with respect to pregnancy. Early transfer to an appropriate facility with neurocritical care, a high-risk obstetric service, and a neurosurgery team available is crucial for the management of aSAH in pregnancy. Intensive monitoring and a multidisciplinary approach remain fundamental to ensure maternal and fetal health.
Topics: Female; Humans; Neurosurgical Procedures; Pregnancy; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 33409763
DOI: 10.1007/s10143-020-01457-2 -
Journal of Cerebral Blood Flow and... Apr 2010Despite extensive effort to elucidate the cellular and molecular bases for delayed cerebral injury after aneurysmal subarachnoid hemorrhage (aSAH), the pathophysiology... (Review)
Review
Despite extensive effort to elucidate the cellular and molecular bases for delayed cerebral injury after aneurysmal subarachnoid hemorrhage (aSAH), the pathophysiology of these events remains poorly understood. Recently, much work has focused on evaluating the genetic underpinnings of various diseases in an effort to delineate the contribution of specific molecular pathways as well as to uncover novel mechanisms. The majority of subarachnoid hemorrhage genetic research has focused on gene expression and linkage studies of these markers as they relate to the development of intracranial aneurysms and their subsequent rupture. Far less work has centered on the genetic determinants of cerebral vasospasm, the predisposition to delayed cerebral injury, and the determinants of ensuing functional outcome after aSAH. The suspected genes are diverse and encompass multiple functional systems including fibrinolysis, inflammation, vascular reactivity, and neuronal repair. To this end, we present a systematic review of 21 studies suggesting a genetic basis for clinical outcome after aSAH, with a special emphasis on the pathogenesis of cerebral vasospasm and delayed cerebral ischemia. In addition, we highlight potential pitfalls in the interpretation of genetic association studies, and call for uniformity of design of larger multicenter studies in the future.
Topics: Brain; Brain Ischemia; Genetic Association Studies; Humans; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial
PubMed: 20068580
DOI: 10.1038/jcbfm.2009.278 -
World Neurosurgery Feb 2022Surgical management of aneurysmal subarachnoid hemorrhage (SAH) often involves red blood cell (RBC) transfusion, which increases the risk of postoperative complications.... (Review)
Review
OBJECTIVE
Surgical management of aneurysmal subarachnoid hemorrhage (SAH) often involves red blood cell (RBC) transfusion, which increases the risk of postoperative complications. RBC transfusion guidelines report on chronically critically ill patients and may not apply to patients with SAH. Our study aims to synthesize the evidence to recommend RBC transfusion thresholds among adult patients with SAH undergoing surgery.
METHODS
A systematic review was conducted using PubMed, Google Scholar, and Web of Science electronic databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to critically assess primary articles discussing RBC transfusion thresholds and describe complications secondary to RBC transfusion in adult patients with SAH in the perioperative period.
RESULTS
Sixteen articles meeting our search strategy were reviewed. Patients with SAH who received blood transfusion were older, female, had World Federation of Neurosurgical Societies grade IV-V and modified Fisher grade 3-4 scores, and presented with more comorbidities such as hypertension, diabetes, and cardiovascular and pulmonary diseases. In addition, transfusion was associated with multiple postoperative complications, including higher rates of vasospasms, surgical site infections, cardiovascular and respiratory complications, increased postoperative length of stay, and 30-day mortality. Analysis of transfused patients showed that a higher hemoglobin (>10 g/dL) goal after SAH was safe and that patients may benefit from a higher whole hospital stay hemoglobin nadir, as shown by a reduction in risk of cerebral vasospasm and improvement in clinical outcomes (level B class II).
CONCLUSIONS
Among patients with SAH, the benefits of reducing cerebral ischemia and anemia are shown to outweigh the risks of transfusion-related complications.
Topics: Adult; Anemia; Erythrocyte Transfusion; Female; Hemoglobins; Humans; Subarachnoid Hemorrhage; Transfusion Reaction; Vasospasm, Intracranial
PubMed: 34890850
DOI: 10.1016/j.wneu.2021.12.007 -
Frontiers in Neurology 2023The use of magnesium sulfate for treating aneurysmal subarachnoid hemorrhage (aSAH) has shown inconsistent results across studies. To assess the impact of magnesium...
INTRODUCTION
The use of magnesium sulfate for treating aneurysmal subarachnoid hemorrhage (aSAH) has shown inconsistent results across studies. To assess the impact of magnesium sulfate on outcomes after aSAH, we conducted a systematic review and meta-analysis of relevant randomized controlled trials.
METHODS
PubMed, Embase, and the Cochrane Library were searched for relevant literature on magnesium sulfate for aSAH from database inception to March 20, 2023. The primary outcome was cerebral vasospasm (CV), and secondary outcomes included delayed cerebral ischemia (DCI), secondary cerebral infarction, rebleeding, neurological dysfunction, and mortality.
RESULTS
Of the 558 identified studies, 16 comprising 3,503 patients were eligible and included in the analysis. Compared with control groups (saline or standard treatment), significant differences were reported in outcomes of CV [odds ratio (OR) = 0.61, = 0.04, 95% confidence interval (CI) (0.37-0.99)], DCI [OR = 0.57, = 0.01, 95% CI (0.37-0.88)], secondary cerebral infarction [OR = 0.49, = 0.01, 95% CI (0.27-0.87)] and neurological dysfunction [OR = 0.55, = 0.04, 95% CI (0.32-0.96)] after magnesium sulfate administration, with no significant differences detected in mortality [OR = 0.92, = 0.47, 95% CI (0.73-1.15)] and rebleeding [OR = 0.68, = 0.55, 95% CI (0.19-2.40)] between the two groups.
CONCLUSION
The superiority of magnesium sulfate over standard treatments for CV, DCI, secondary cerebral infarction, and neurological dysfunction in patients with aSAH was demonstrated. Further randomized trials are warranted to validate these findings with increased sample sizes.
PubMed: 38020616
DOI: 10.3389/fneur.2023.1249369 -
Neurocritical Care Jun 2023Cilostazol, a phosphodiesterase III inhibitor, appears to be a promising agent for preventing cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cilostazol, a phosphodiesterase III inhibitor, appears to be a promising agent for preventing cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Here, the authors perform a systematic review and meta-analysis to quantitatively assess the effects of cilostazol on brain structural and functional outcomes in animal models of cerebral ischemia and subarachnoid hemorrhage-induced cerebral vasospasm.
METHODS
By using the PRISMA guidelines, a search of the PubMed, Scopus, and Web of Science was conducted to identify relevant studies. Study quality of each included study for both systematic reviews were scored by using an adapted 15-item checklist from the Collaborative Approach to Meta-Analysis of Animal Data from Experimental Studies. We calculated a standardized mean difference as effect size for each comparison. For each outcome, comparisons were combined by using random-effects modeling to account for heterogeneity, with a restricted maximum likelihood estimate of between-study variance.
RESULTS
A total of 22 (median [Q1, Q3] quality score of 7 [5, 8]) and 6 (median [Q1, Q3] quality score of 6 [6, 6]) studies were identified for cerebral ischemia and subarachnoid hemorrhage-induced cerebral vasospasm, respectively. Cilostazol significantly reduced the infarct volume in cerebral ischemia models with a pooled standardized mean difference estimate of - 0.88 (95% confidence interval [CI] [- 1.07 to - 0.70], p < 0.0001). Cilostazol significantly reduced neurofunctional deficits in cerebral ischemia models with a pooled standardized mean difference estimate of - 0.66 (95% CI [- 1.06 to - 0.28], p < 0.0001). Cilostazol significantly improved the basilar artery diameter in subarachnoid hemorrhage-induced cerebral vasospasm with a pooled standardized mean difference estimate of 2.30 (95% CI [0.94 to 3.67], p = 0.001). Cilostazol also significantly improved the basilar artery cross-section area with a pooled standardized mean estimate of 1.88 (95% CI [0.33 to 3.43], p < 0.05). Overall, there was between-study heterogeneity and asymmetry in the funnel plot observed in all comparisons.
CONCLUSIONS
Published animal data support the overall efficacy of cilostazol in reducing infarct volume and neurofunctional deficits in cerebral ischemia models and cerebral vasospasm in subarachnoid hemorrhage models.
Topics: Animals; Cilostazol; Subarachnoid Hemorrhage; Vasospasm, Intracranial; Likelihood Functions; Cerebral Infarction; Brain Ischemia; Models, Animal
PubMed: 36450971
DOI: 10.1007/s12028-022-01637-6 -
Acta Neurochirurgica. Supplement 2013Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to... (Meta-Analysis)
Meta-Analysis Review
Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of -translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates, and humans. Animal studies were generally of poor methodologic quality, and there was evidence of publication bias. Fresh blood injection to simulate SAH (vs. clot placement) and evaluation of vasospasm more than 3 days after SAH were independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans, and that injection of fresh blood and evaluation of vasospasm more than 3 days after SAH may be preferable for preclinical models.
Topics: Animals; Cerebral Angiography; Disease Models, Animal; Humans; PubMed; Subarachnoid Hemorrhage; Vasoconstriction; Vasodilator Agents; Vasospasm, Intracranial
PubMed: 22890676
DOI: 10.1007/978-3-7091-1192-5_44 -
Neurosurgical Focus Sep 2006Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are... (Comparative Study)
Comparative Study Review
Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness. The purpose of this work was to perform a systematic review of the literature on the treatment of cerebral vasospasm. A literature search for randomized controlled trials of therapies used for prevention or treatment of cerebral vasospasm and/or delayed cerebral ischemia was conducted, and 41 articles meeting the review criteria were found. Study characteristics and primary results of these articles are reviewed. Key indicators of quality were poor when averaged across all studies, but have improved greatly over time. The only proven therapy for vasospasm is nimodipine. Tirilazad is not effective, and studies of hemodynamic maneuvers, magnesium, statin medications, endothelin antagonists, steroid drugs, anticoagulant/antiplatelet agents, and intrathecal fibrinolytic drugs have yielded inconclusive results. The following conclusions were made: nimodipine is indicated after SAH and tirilazad is not effective. More study of hemodynamic maneuvers, the effectiveness of other calcium channel antagonists such as nicardipine delivered by other routes (for example intrathecally), magnesium, statin drugs, endothelin antagonists, and intrathecal fibrinolytic therapy is warranted. There is less enthusiasm for the study of steroid drugs and anticoagulant/antiplatelet agents because they entail more risks and investigations so far have shown little evidence of efficacy. The study of rescue therapy such as balloon angioplasty and intraarterial vasodilating agents will be difficult. The quality of clinical trials should be improved.
Topics: Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; MEDLINE; Magnesium; Peptides, Cyclic; Randomized Controlled Trials as Topic; Review Literature as Topic; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 17029347
DOI: 10.3171/foc.2006.21.3.8 -
Journal of Neurology Jun 2020Delayed cerebral ischemia seriously affects the prognosis of patients surviving the initial aneurysmal subarachnoid hemorrhage. Application of cilostazol was reported to...
BACKGROUND
Delayed cerebral ischemia seriously affects the prognosis of patients surviving the initial aneurysmal subarachnoid hemorrhage. Application of cilostazol was reported to ameliorate vasospasm and improve outcomes in series and clinical trials. But the effectiveness and feasibility of cilostazol on aneurysmal subarachnoid hemorrhage remained controversial. We performed a systematic review to clarify this issue.
METHODS
PubMed, Ovid and Cochrane library database were systematically searched up to May 2018 for eligible publications in English. Quality assessment was conducted for included studies. Meta-analysis was conducted to evaluate the overall effect on events of interest. Subgroup analyses and sensitivity analyses were used to check whether the results were robust. Publication bias was evaluated with the funnel plot.
RESULTS
Pooled analyses found cilostazol significantly reduced incidences of severe angiographic vasospasm (p = 0.0001), symptomatic vasospasm (p < 0.00001), new cerebral infarction (p < 0.00001) and the poor outcome (p < 0.0001). Subgroup and sensitivity analyses achieved consistent results. There was no statistical difference between cilostazol and the control group in reducing mortality (p = 0.07). But sensitivity analysis changed the result after excluding one study. Under the prescribed dosage, complication was few and non-lethal.
CONCLUSIONS
Cilostazol was effective and safe to reduce incidences of severe angiographic vasospasm, symptomatic vasospasm, new cerebral infarction and poor outcome in patients after aneurysmal subarachnoid hemorrhage. However, its effect on mortality and the interactive effect with nimodipine warranted further research.
Topics: Brain Ischemia; Cardiovascular Agents; Cerebral Infarction; Cilostazol; Humans; Intracranial Aneurysm; Outcome Assessment, Health Care; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 30739182
DOI: 10.1007/s00415-019-09198-z