Does duration of nimodipine therapy impact outcome in aneurysmal subarachnoid hemorrhage: systematic review and meta-analysis.

Abstract

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurosurgical emergency with high morbidity and mortality risks. Vasospasm, a severe subacute complication, may be mitigated by nimodipine, a calcium channel blocker. The optimal duration of nimodipine therapy remains uncertain. We sought to evaluate the optimal duration of nimodipine therapy in relation to overall morbidity in aSAH patients through a systematic review and meta-analysis. A PRISMA-compliant systematic review searched MEDLINE, EMBASE, and Cochrane Library (1/1975-9/2024). Included studies reported nimodipine protocols and standardized outcomes. Data extracted included demographics, nimodipine dosing, duration, and outcomes. The primary outcome was overall morbidity, assessed via extended Glasgow Outcome Scale (eGOS), Glasgow Outcome Scale (GOS), or modified Rankin Scale (mRS). The secondary outcome was neuroimaging-validated delayed cerebral ischemia (DCI) incidence. Random-effects meta-analyses were performed. Fourteen studies (19 cohorts) included 759 standard-of-care (SOC, 21-day nimodipine) and 781 dose duration reduction (DDR, < 21 days) patients. SOC had a pooled favorable outcome proportion of 0.52 [95% CI: 0.34-0.70], versus 0.74 [95% CI: 0.64-0.83] for DDR (p = 0.03). Subgroup analyses showed significant differences by outcome scale (p < 0.01) and administration route (p = 0.01), with oral DDR linked to better outcomes (p = 0.02). Heterogeneity was significant (I² = 95%, p < 0.01). DCI incidence was 0.39 [95% CI: 0.20-0.57] in SOC and 0.31 [95% CI: 0.18-0.44] in DDR (p = 0.50). DDR nimodipine protocols do not increase aSAH morbidity or DCI incidence compared to SOC and may improve outcomes. These findings support individualized treatment durations, especially for patients with adverse effects, though heterogeneity necessitates cautious interpretation.