A systematic review of efficacy and safety of intramuscular midazolam versus midazolam by other routes or other non-intravenous benzodiazepines in children with convulsive status epilepticus

BackgroundConvulsive status epilepticus (CSE) is the most common neurological emergency in children. Without prompt, safe and effective intervention, CSE can cause adverse neurological sequelae or death. There is increasing use of intramuscular midazolam for the treatment of childhood CSE. The aim of this systematic review is to investigate the efficacy and safety of intramuscular midazolam versus midazolam by other routes or other non-intravenous benzodiazepines in childhood CSE. MethodsMEDLINE, PubMed, Embase, Cochrane CENTRAL and Google Scholar were searched from 01/01/1980 to 29/08/2025. The primary outcome of interest was cessation of seizures within 5-10 minutes of treatment. Secondary outcomes included time to seizure cessation and incidence of respiratory depression/hypotension. ResultsFive studies were identified comparing intramuscular midazolam with buccal midazolam, intranasal midazolam or rectal diazepam. In single studies, there was no difference between intramuscular midazolam and intranasal midazolam or rectal diazepam in achieving seizure cessation, but intramuscular midazolam was associated with shorter time to seizure cessation. Meta-analysis was only possible comparing intramuscular midazolam with buccal midazolam. Intramuscular midazolam was superior to buccal midazolam for time to seizure cessation (p<0.00001). While there were no inter-group differences in other outcomes, point estimates favoured intramuscular midazolam. Few cases of respiratory depression or hypotension were reported with no inter-group differences. No studies involved treatment by paramedics, sample sizes were modest, and none were in Western high-income countries. Quality of evidence was low or very low. DiscussionThere is insufficient clinical trial evidence for safety and efficacy of intramuscular midazolam compared to midazolam by other routes or other non-intravenous benzodiazepines for childhood CSE. Key pointsO_LIOut-of-hospital treatment is usually needed to achieve prompt seizure cessation in convulsive status epilepticus. C_LIO_LILimited data indicate that intramuscular midazolam achieves faster seizure cessation than buccal midazolam. C_LI