Intranasal Versus Intramuscular Midazolam in Pediatric Seizure Control: A Systematic Review and Meta-Analysis
Mohnkern et al. · Prehospital Emergency Care · 2026
Systematic review & meta-analysis · 5 studies · n = 3 933
Paediatrics · Seizures · Pharmacology
Written by: Pat Leighton
Paediatric seizures are frequently encountered, and the quicker we can administer medication to abort them, the greater chance of success in terminating the seizure. There is the added advantage of preventing the long-term neurological damage that prolonged seizure activity can cause. In the absence of IV access, intramuscular (IM) midazolam looked faster and more reliable than intranasal (IN), but there was confounding of the data in these studies.
This systematic review evaluated five studies (two randomised control trials, three observational) including 3 933 children, mostly managed out-of-hospital. IN and IM midazolam were compared for seizure control. IM was linked to less need for rescue therapy (additional medication doses) and about 24 seconds faster seizure termination overall. Whether this time difference translates into clinically meaningful neurological benefit remains uncertain.
All three observational studies were judged to have high risk of bias with participant selection and missing data, and one randomised control trial only had 16 participants, limiting the generalisability of these findings. The concentration of midazolam used for IN administration was inconsistently reported across included studies, with only one study explicitly reporting the use of the concentrated 5mg/mL preparation.
Safety profile data for midazolam via either route, such as respiratory depression, hypotension, and bradycardia were evaluated but lacked sufficient data to include in this meta-analysis.
children across 5 studies
managed out-of-hospital
higher rescue therapy risk with IN
faster seizure termination with IM
Paediatric seizures are distressing for health care providers and caregivers alike. Benzodiazepines are recommended as first line treatment to abort seizures, with the IV route preferred due to rapid onset of action. However, in prehospital and other resource-limited settings where IV access is frequently unavailable, non-IV routes are increasingly relied upon to minimize treatment delays.
This paper doesn’t offer a good reason to choose either route preferentially. It’s worth bearing in mind that multiple options exist for administration (intravenous, intraosseous, intramuscular, intranasal, buccal and rectal), and the best route is probably the one for which you have the correct equipment and medication concentration, that offers the quickest treatment with the appropriate dose.
If your service already uses intranasal drugs with proper atomiser technique, the authors recommend using the concentration of 5mg/mL of midazolam for the best absorption, at a dose of 0.2mg/kg.
