The Effect of Glibenclamide in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Introduction: Preclinical and clinical studies have demonstrated the neuroprotective effects of glibenclamide and the reduction of cerebral edema following intracranial hemorrhage and ischemic stroke. The mechanism is by blocking the sulfonylurea receptor 1 transient receptor potential melastatin 4 (SUR1-TRPM4) channel, which is overexpressed during cerebral ischemia and subarachnoid hemorrhage (SAH). Several studies have reported the use of glibenclamide in cases of aneurysmal SAH (aSAH), but there are some controversies.

Methods: We systematically searched PubMed, Scopus, Cochrane, and Web of Science for randomized controlled trials (RCTs) evaluating the addition of glibenclamide to the treatment of patients with aSAH. We estimated outcomes for all-cause mortality, functional outcomes measured by the modified Rankin Scale (mRs), delayed cerebral ischemia (DCI), hydrocephalus, and hypoglycemia. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for binary outcomes and the mean difference (MD) for continuous outcomes.

Results: We included 3 RCTs with 235 patients, of whom 123 (52.3%) received glibenclamide. Mean follow-up ranged from 90 to 180 days. In the pooled analysis, DCI was significantly lower in patients treated with glibenclamide (22.7%) compared with those who did not receive glibenclamide (36%) (RR 0.65; 95% CI 0.44-0.96; p=0.03). All-cause mortality (RR 0.96; 95% CI 0.55-1.77; p=0.90), mRs at 3 months (MD 0.00; 95% CI -0.75-0.75; p=1.00), mRs at 6 months (MD -0.34; 95% CI -1.62-0. 94; p=0.60), incidence of hydrocephalus (RR 1.42; 95% CI 0.92-2.20; p=0.11) and hypoglycemia (RR 3.24; 95% CI 0.80-13.11; p=0.10) were not significantly different between groups.

Conclusion : Our meta-analysis indicates that glibenclamide use in patients with aSAH is linked to a lower incidence of DCI. However, no significant differences were observed in the other outcomes between the two groups. Additional randomized controlled trials are needed to confirm these findings, as the current sample size is limited.