Efficacy and safety of intranasal and buccal midazolam versus intravenous, intramuscular, and rectal benzodiazepines for the termination of acute seizures in children: a systematic review and meta-analysis.
Seizure · 2026-10-24 · Meta-analysis
Abstract
Background Intranasal and buccal midazolam offer practical alternatives to conventional benzodiazepine administration routes; however, their comparative efficacy and safety remain incompletely defined. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of transmucosal midazolam versus other benzodiazepine therapies for acute seizure termination in children. Methods PubMed, Scopus, Web of Science, and Embase were searched from inception to January 15, 2026. Randomized controlled trials comparing intranasal or buccal midazolam with intravenous, intramuscular, rectal, or oral benzodiazepines in pediatric patients with acute seizures were included. Random-effects meta-analyses were performed using risk ratios (RRs) and standardized mean differences (SMDs). Results Twenty-three randomized controlled trials involving 2238 pediatric patients were included. Transmucosal midazolam achieved seizure cessation within 10 min at rates comparable to active comparators (13 studies; n = 1368; RR 1.04, 95% CI 0.99-1.09) and within 5 min (7 studies; n = 552; RR 1.05, 95% CI 0.92-1.19). Compared with rectal diazepam, transmucosal midazolam significantly improved seizure cessation within 10 min (6 studies; n = 904; RR 1.18, 95% CI 1.02-1.37), while efficacy was similar to intravenous diazepam and intravenous lorazepam. Transmucosal midazolam reduced seizure recurrence within 60 min (7 studies; n = 791; RR 0.62, 95% CI 0.43-0.91), was administered significantly faster (7 studies; n = 546; SMD -1.94, 95% CI -3.16 to -0.72), and shortened overall time to seizure cessation (6 studies; n = 379; SMD -0.91, 95% CI -1.64 to -0.18). Treatment failure, respiratory depression, and hypoxia did not differ significantly between groups. Conclusions Intranasal and buccal midazolam provide efficacy comparable to conventional benzodiazepine therapies while offering faster treatment delivery and shorter overall time to seizure control, with no increase in major adverse events. These findings support transmucosal midazolam as an effective and safe first-line rescue therapy for pediatric acute seizures.
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Tags
Intranasal administration · Sedatives & anxiolytics · Midazolam · Children · Diazepam · Other benzodiazepines & Z-drugs
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