BackgroundBenzodiazepines are the recommended first line of treatment of acute seizures. We wished to compare the efficacy, side effects and satisfaction after midazolam administration by the buccal, intranasal, or intramuscular route in the treatment of acute seizures in children both at homes and Emergency room (ER). MethodsA prospective, randomized, controlled trial was performed in children aged 1 months to 17 years with acute seizures lasting longer than 5 minutes. The primary endpoint was seizure cessation within 10 minutes of drug administration and no seizure recurrence within 30 minutes. ResultsIn home group, 67 patients received midazolam via buccal route, 60 via intranasal, and 69 via intramuscular route while in ER group, 37 patients received buccal midazolam, 34 received intranasal and 34 received intramuscular midazolam. The primary endpoint was achieved in 94.2% and 85.3% after intramuscular midazolam in home and ER groups respectively. On the other hand, intranasal midazolam was successful to stop seizures in 93.3% in home group and 88.2% in ER group. The buccal route was effective in 91% in home group and 78.4% in ER group. There were no significant differences in efficacy between all groups, (P=0.763 and P=0.509) among home and ER groups respectively. There were no significant cardio-respiratory events in all groups. ConclusionsIntramuscular, intranasal, and buccal doses of midazolam resolved most seizures in pre-hospital and emergency settings. Our results indicate that there is no statistically significant difference detected between different routes of administration of midazolam. Intranasal route showed highest satisfaction rate among caregivers.