milrinone infusion reduces delayed cerebral ischemia risk in aneurysmal subarachnoid hemorrhage

Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life‐threatening neurological condition can be complicated by delayed cerebral ischemia (DCI), a leading cause of secondary brain injury. Milrinone, a phosphodiesterase‐3 inhibitor with vasodilatory and anti‐inflammatory properties, has been proposed as a potential therapeutic agent to mitigate DCI, yet its clinical utility remains uncertain. This systematic review and metaanalysis aimed to evaluate the efficacy and safety of intravenous milrinone in patients with aSAH. Methods We systematically searched PubMed, Embase, and Cochrane Library databases from inception through June 1, 2025. Eligible studies included randomized and observational trials comparing outcomes between patients treated with and without milrinone infusion following aSAH. Primary outcomes included incidence of DCI, good functional outcome (modified Rankin Scale score 0‐2), and mortality. Cardiovascular adverse events were also assessed. Data were pooled using a random‐effects model, and heterogeneity was evaluated using the I 2 statistic. Results Seven studies comprising 859 patients were included in the meta‐analysis. Milrinone infusion was associated with a significantly lower risk of DCI compared to controls (OR 0.47, 95% CI 0.24‐0.93; p < 0.03; I 2 = 41%). However, no significant differences were found in good functional outcome (OR 1.09, 95% CI 0.62‐1.90; p = 0.77) or mortality (OR 0.97, 95% CI 0.51‐1.85; p = 0.93). Cardiovascular adverse events occurred more frequently in the milrinone group (OR 1.72, 95% CI 0.97‐3.02; p = 0.06), but the difference did not reach statistical significance. Conclusions Milrinone administration in patients with aSAH is associated with a lower incidence of delayed cerebral ischemia, without a significant increase in cardiovascular adverse events. However, this did not translate into improved functional outcomes or reduced mortality. Further large‐scale randomized controlled trials are warranted to clarify