Intranasal Versus Intramuscular Midazolam in Pediatric Seizure Control: A Systematic Review and Meta-Analysis

Rapid termination of pediatric seizures is a critical determinant of neurological outcomes. Benzodiazepines are the established first-line therapy, yet intravenous (IV) access is frequently unavailable at initial presentation, necessitating reliance on non-IV routes. However, the optimal non-IV route remains controversial. We aimed to perform a meta-analysis comparing intranasal (IN) and intramuscular (IM) midazolam administration to determine which route is associated with more rapid and reliable seizure control in pediatric patients.

We searched PubMed, Embase, and Cochrane Library for studies comparing IN and IM midazolam in pediatric patients with seizures. Pooled risk ratios (RR) and mean differences (MD) were calculated using a random-effects model, with heterogeneity quantified using the I² statistic. Subgroup analyses were performed by administration setting and benzodiazepine dose. The prospective protocol was registered with PROSPERO (CRD420251237948).

Five studies comprising 3,933 pediatric patients requiring pharmacological intervention for seizures were included, of whom 97.9% were managed in the prehospital setting. IM midazolam was associated with a lower likelihood of requiring rescue therapy overall (RR 1.29; 95% CI 1.15-1.45; p = 0.004; I² = 5%) and in the out-of-hospital setting (RR 1.30; 95% CI 1.11-1.51; p = 0.01; I² = 0%). The association persisted when the analysis was restricted to studies using the recommended 0.2 mg/kg dose (RR 1.26; 95% CI 1.10-1.43; p = 0.01; I² = 6%). IM midazolam was also associated with a shorter time to seizure termination (MD 23.60 s; 95% CI 2.31-44.89; p = 0.03; I² = 0%).

Among pediatric patients with acute seizures managed in settings where IV access is not established, particularly the prehospital environment, IM midazolam was associated with more rapid seizure termination and lower rescue therapy use than IN midazolam and represents a reasonable first-line option in these settings.