IM Versus Buccal Midazolam for Pediatric Seizures: A Randomized Double-Blinded Trial

Date reviewed 1/14/21

Seizures are among the most common pediatric presenting emergencies, accounting for 1% of all emergency department visits. Benzodiazepines are recommended internationally as first-line treatment for seizure episodes lasting longer than 5min. When IV access is not available, the available routes/medications include rectal diazepam (perceived psychological disadvantage), IN midazolam (requires specialized atomizer), buccal midazolam and IM midazolam. The efficacy of IM vs buccal midazolam has not previously been compared. 

To compare the efficacy and safety of IM with buccal midazolam as first-line treatment for active seizures in children brought to the emergency department. 

Double-blind, double-dummy (buccal 0.3mg/kg and IM 0.35mg/kg) RCT of patients with seizures lasting >5min. Primary outcome was seizure termination at 5min. Secondary outcomes included proportion of patients needing additional anti-seizure medication in each group, duration of seizure activity, proportion of patients with cessation of seizures within 10min of study drug administration, proportion of patients who continued with active seizures >30min after arrival, recurrence of seizure activity within 1hr, length of hospital stay, proportion of patients requiring PICU admission and reported side effects frequency for each treatment group.  

46% of buccal midazolam and 61% of IM midazolam had seizure cessation within 5min (significant higher termination rate in buccal group). However, mean duration of seizure activity was not statistically different (15.9minn in the IM group and 17.8min in the buccal group) and the hazard ratio for cessation of seizures after study medication administration was 1.13 (95% CI 0.08 – 1.24) for I midazolam and 0.89 (95% CI 0/63 – 1.24) for buccal midazolam, both with a CI crossing 1 and thus not statistically significant  

Strengths: randomized, double-blind, double dummy control trial with deferred informed consent 

Limitations: 13 patients excluded AFTER randomization (10% of the sample, slightly unbalanced)  


Efficacy and safety of IM midazolam as first-line treatment for pediatric seizures compares favorably to that of buccal midazolam (authors conclusion), likely equivalent based on trial limitations  

Alansari K, Barkat M, Mohamed AH, Al Jawala SA, Othman SA. Intramuscular Versus Buccal Midazolam for Pediatric Seizures: A Randomized Double-Blinded Trial. Pediatr Neurol. 2020;109:28-34. doi:10.1016/j.pediatrneurol.2020.03.011