Faculty Opinions recommendation of Effect of nicardipine prolonged-release implants on cerebral vasospasm and clinical outcome after severe aneurysmal subarachnoid hemorrhage: a prospective, randomized, double-blind phase IIa study.

Background: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. Methods: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. Results: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. Conclusions: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

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Abstract TMP105: Endovascular Treatment of Severe and Refractory Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage Improves Outcome: A Systematic Review and Meta-analysis of Different Treatment Options Evaluated Since 2006 for Cerebral Vasospasm

Stroke ◽

10.1161/str.47.suppl_1.tmp105 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Gregoire Boulouis ◽

Marc-Antoine Labeyrie ◽

Jean Raymond ◽

Christine Rodriguez-Regent ◽

Anne-Claire Lukaszewicz ◽

...

Keyword(s):

Systematic Review ◽

Subarachnoid Hemorrhage ◽

Clinical Outcome ◽

Endovascular Treatment ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Meta Analysis ◽

Route Of Administration ◽

Unfavorable Outcome ◽

Q Value

Introduction: To report clinical outcome of aneurysmal subarachnoid hemorrhage (aSAH) patients exposed to cerebral vasospasm (CVS) targeted treatments in a systematic review and meta-analysis and compare the efficacy of endovascular and non-endovascular treatments in severe / refractory vasospasm patients. Methods: The literature was searched using PubMed, EMBASE, and The Cochrane Library database. Eligibility criteria were (1) Rated clinical outcome; (2) at least 10 patients; (3) aSAH; (4) study published in English or French (January 2006 - October 2014); and (5) methodological quality score > 10, according to STROBE criteria. Endpoint included unfavorable outcome rate, defined as mRS 3-6, GOS 1-3 or GOSE 1-4 at latest follow-up. Analyses included stratification per route of administration (oral, i.v., intra-arterial or cisternoventricular) and per study inclusion criteria (severe, CVS, refractory CVS or high risk for CVS). Univariate and multivariate subgroup analyses were performed to identify interventions associated with a better outcome. Results: Sixty-two studies, including 26 randomized controlled trials, were included (8976 patients). Overall 2490 patients had unfavorable outcome including death (random-effect weighted average: 33.7%, 99%CI, 28.1-39.7%; Q-value: 806.0, I 2 =92.7%). Clinical outcome was significantly better in severe or refractory patients for whom, on top of best medical treatment, endovascular intervention was performed (RR=0.76, IC95% [0.66-0.89], p <0.00001) whereas other route of administration didn’t show significant differences. RR of unfavorable outcome was significantly lower, vs control groups, in patients treated with Cilostazol (RR=0.46 (IC99% [0.25-0.85], P = 0.001, Q value 1.5, I 2 = 0). Conclusion: In case of CVS following aSAH, endovascular treatment in severe / refractory vasospasm patients. including intra-arterial injection of pharmacological agents or balloon angioplasty, improves outcome as compared to other route of administration.

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Noninfectious Fever in Aneurysmal Subarachnoid Hemorrhage: Association with Cerebral Vasospasm and Clinical Outcome

World Neurosurgery ◽

10.1016/j.wneu.2018.10.203 ◽

2019 ◽

Vol 122 ◽

pp. e1014-e1019 ◽

Cited By ~ 1

Author(s):

Pui Man Rosalind Lai ◽

Alfred Pokmeng See ◽

Michael A. Silva ◽

William B. Gormley ◽

Kai U. Frerichs ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Clinical Outcome ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage

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Abstract T P352: Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage - A Randomized Placebo-Controlled Trial to Assess Safety, Tolerability and Feasibility

Stroke ◽

10.1161/str.45.suppl_1.tp352 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Susanne Muehlschlegel ◽

Raphael Carandang ◽

Wiley Hall ◽

Kini Nisha ◽

Saef Izzy ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Liver Toxicity ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Statistical Significance ◽

Delayed Cerebral Ischemia ◽

Double Blind ◽

Outcome Differences ◽

Infusion Period

Introduction: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) after aneurysmal subarachnoid hemorrhage (aSAH) in humans. We evaluated safety/tolerability and feasibility of intravenous dantrolene (IV-D) after aSAH. Methods: In this single-center, randomized, double-blind, placebo-controlled trial, 31 patients with acute aSAH were randomized to IV-D 1.25 mg IV every 6 hours x 7 days (n=16) or placebo (n=15). Primary endpoint was incidence of hyponatremia (sNa ≤ 134 mmol/L) and liver toxicity (% patients with ALT, AST and AlkPhos >5x upper limit of normal). Secondary safety endpoints included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored by clinical, transcranial Doppler (TCD) or angiographic cVSP occurrence, delayed cerebral ischemia (DCI) and 3-month modified-Rankin-Scale, Glasgow Outcome Scale and Barthel Index. Statistical analysis was performed using non-parametric tests, generalized estimating equations and mixed models. Results: Between IV-D vs. placebo, no differences were observed in the primary outcome (hyponatremia: 44% vs. 67% [p=0.29]; liver toxicity 6% vs. 0% [p=1.0]). Numerically more AEs and SAEs were seen in the IV-D group, but did not reach statistical significance (16 vs. 5 AEs, of which 5 vs. 2 were severe; RR 2.2; 95% CI 0.7-6.7; p=0.16). Three IV-D vs. two placebo patients reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain edema requiring osmotherapy. No differences in angiographic, TCD, clinical cVSP, DCI, or 3-month functional outcomes were seen. Quantitative angiogram analysis revealed a trend towards increased vessel diameters in the IV-D group after the 7-day infusion-period (p=0.05). Conclusion: In this small trial, IV-Dantrolene after aSAH was feasible, tolerable and safe, but was underpowered to show efficacy or outcome differences.

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Long-acting statin for aneurysmal subarachnoid hemorrhage: A randomized, double-blind, placebo-controlled trial

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x17724682 ◽

2017 ◽

Vol 38 (7) ◽

pp. 1190-1198 ◽

Cited By ~ 8

Author(s):

Masato Naraoka ◽

Naoya Matsuda ◽

Norihito Shimamura ◽

Kenichiro Asano ◽

Kenichi Akasaka ◽

...

Keyword(s):

Placebo Group ◽

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Delayed Cerebral Ischemia ◽

Pleiotropic Effects ◽

Neurological Deficits ◽

Double Blind ◽

Long Acting

Statins have pleiotropic effects that are considered beneficial in preventing cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). Many studies using statins have been performed but failed to show remarkable effects. We hypothesized that a long-acting statin would be more effective, due to a longer half-life and stronger pleiotropic effects. Patients with aSAH were randomly assigned to a pitavastatin group (4 mg daily; n = 54) and a placebo group ( n = 54) after repair of a ruptured aneurysm. The primary efficacy end point was vasospasm-related delayed ischemic neurological deficits (DIND), and the secondary end points were cerebral vasospasm evaluated by digital subtraction angiography (DSA), vasospasm-related new cerebral infarctions, and outcome at three months. Severe cerebral vasospasms on DSA were statistically fewer in the pitavastatin group than in the placebo group (14.8% vs. 33.3%; odds ratio, 0.32; 95% confidence interval, 0.11–0.87, p = 0.042); however, the occurrence of DIND and new infarctions and outcome showed no statistically significant differences between the groups. The present study is the first to prove the definite, statin-induced amelioration of cerebral vasospasm on DSA. However, administration of any type of statin at the acute phase of aSAH is not recommended.

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Clazosentan (AXV-034343), a Selective Endothelin A Receptor Antagonist, in the Prevention of Cerebral Vasospasm Following Severe Aneurysmal Subarachnoid Hemorrhage: Results of a Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase IIa Study

Yearbook of Anesthesiology and Pain Management ◽

10.1016/s1073-5437(08)70353-x ◽

2006 ◽

Vol 2006 ◽

pp. 86-90

Author(s):

S. Black

Keyword(s):

Subarachnoid Hemorrhage ◽

Receptor Antagonist ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Double Blind ◽

Double Blind Placebo ◽

Multicenter Phase ◽

Endothelin A Receptor ◽

Endothelin A

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Correlation between plasma total nitric oxide levels and cerebral vasospasm and clinical outcome in patients with aneurysmal subarachnoid hemorrhage in Indian population

Journal of Neurosciences in Rural Practice ◽

10.4103/0976-3147.145196 ◽

2014 ◽

Vol 05 (S 01) ◽

pp. S022-S027 ◽

Cited By ~ 2

Author(s):

Shruthi Shimoga Ramesh ◽

Aripirala Prasanthi ◽

Dhananjaya Ishwar Bhat ◽

Bhagavatula Indira Devi ◽

Rita Cristopher ◽

...

Keyword(s):

Nitric Oxide ◽

Subarachnoid Hemorrhage ◽

Clinical Outcome ◽

Cerebral Vasospasm ◽

Indian Population ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Tertiary Hospital ◽

Poor Grade ◽

Nitric Oxide Level ◽

Neuro Imaging

ABSTRACT Context: Cerebral vasospasm remains a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Reduced bioavailability of nitric oxide has been associated with the development of cerebral vasospasm after aSAH. Such data is not available in Indian population. Aims: The objective of the study was to measure the plasma total nitric oxide (nitrite and nitrate-NO x ) level in aSAH patients and healthy controls treated at a tertiary hospital in India and to investigate a possible association between plasma total nitric oxide level and cerebral vasospasm and clinical outcome following treatment in patients with aSAH. Settings and Design: A case-control study of aSAH patients was conducted. Plasma total NO x levels were estimated in aSAH patients with and without vasospasm and compared the results with NO x levels in healthy individuals. Materials and Methods: aSAH in patients was diagnosed on the basis of clinical and neuro-imaging findings. Plasma total NO x levels in different subject groups were determined by Griess assay. Results: Plasma total NO x level was found to be significantly decreased in patients with aSAH when compared to controls. Plasma total NO x level in the poor-grade SAH group was lower than that in the good-grade SAH group. Plasma total NO x level further reduced in patients with angiographic (P < 0.05) and clinical vasospasm. Conclusions: Reduced plasma NO x level is seen in aSAH patients as compared to normal individuals. In aSAH patients reduced levels are associated with increased incidence of cerebral vasospasm and poor outcome. Plasma total NO x level could be used as a candidate biomarker for predicting vasospasm and outcome for this pathology.

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