The Effectiveness of Intranasal Midazolam for the Treatment of Prehospital Pediatric Seizures: A Non-inferiority Study

Background: Intranasal (IN) midazolam allows for rapid, painless treatment of pediatric seizures in the prehospital setting and may be a preferred administration route if determined to be non-inferior to intravenous (IV) or intramuscular (IM) routes. We sought to evaluate the effectiveness of IN midazolam for terminating prehospital pediatric seizures compared to midazolam administered by alternate routes. Methods: We performed a retrospective, non-inferiority analysis using data from a regional Emergency Medical Services (EMS) database. We included pediatric patients ≤ 14 years treated with midazolam (0.1 mg/kg) by EMS for non-traumatic seizures. The primary outcome was the proportion of patients requiring redosing of midazolam after initial treatment with IN midazolam compared to those that received IV or IM midazolam. We established a priori a risk difference of 6.5% as the non-inferiority margin. Results: We evaluated outcomes from 2,034 patients (median age 6 years [interquartile range 3 - 10 years], 55% male). Initial administration routes were 461 (23%) IN, 547 (27%) IM, 1024 (50%) IV, and 2 (0.1%) intraosseous (IO). Midazolam redosing occurred in 116 patients (25%) who received IN midazolam versus 222 patients (14%) treated initially with midazolam via alternate routes (risk difference 11% [95%CI 7 - 15%]). The age-adjusted odds ratio for redosing midazolam after intranasal administration compared to alternate route administration was 2.0 (95% CI 1.6 - 2.6). Conclusion: Prehospital treatment of pediatric seizure with intranasal midazolam was associated with increased frequency of redosing compared to midazolam administered by other routes, suggesting that 0.1 mg/kg is a subtherapeutic dose for intranasal midazolam administration.