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

Rapid termination of pediatric seizures is a critical determinant of neurological outcomes, particularly in status epilepticus, where prolonged seizure activity increases the risk of pharmacoresistance and neurologic injury. Benzodiazepines are the established first-line therapy;however, intravenous access is frequently unavailable at initial presentation, necessitating reliance on non-intravenous routes. The optimal non-intravenous route remains uncertain. We therefore performed a meta-analysis to compare the effectiveness and speed of seizure termination between intranasal (IN) and intramuscular (IM) midazolam in pediatric patients.

We searched PubMed/MEDLINE, Embase, and Cochrane Central for studies comparing intranasal and intramuscular midazolam in pediatric patients with seizures. Primary outcomes included the need for rescue therapy and time to seizure termination. Risk ratios and mean differences were pooled using random-effects models with inverse-variance weighting and restricted maximum likelihood estimation. Heterogeneity was assessed using Cochran Q and I². Statistical analyses were performed using Review Manager 9.17.0 (Cochrane Collaboration).

Five studies comprising 3,933 pediatric patients requiring pharmacologic intervention for seizures were included;1,654 (42.1%) received IN midazolam. IN midazolam was associated with a higher 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 = 9%). This association persisted when 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%). IN midazolam was also associated with a longer time to seizure termination (MD 23.6 seconds;95% CI 2.3–43.9;p = 0.03;I² = 0%).

Among pediatric patients with acute seizures, IM midazolam was more effective and faster at achieving seizure termination than IN midazolam. This is critical given the narrow therapeutic window imposed by seizure-induced pharmacoresistance and the emerging “time is brain” framework in seizure management. Therefore, IM midazolam appears to be a reasonable first-line non-intravenous option for pediatric seizure management in emergency settings when intravenous access is not readily available.