Objective:

This systematic review and meta-analysis aimed to compare the efficacy and safety of midazolam versus diazepam for the management of pediatric status epilepticus, with a specific focus on the impact of the administration route.

Background:

Status epilepticus is a life-threatening neurological emergency in children. Benzodiazepines are the first-line treatment, but the optimal choice between the commonly used midazolam and diazepam remains debated, particularly regarding the advantages of different administration routes in acute settings.

Design/Methods:

We systematically searched four major databases for randomized controlled trials (RCTs) up to November 2024. Nine RCTs involving 1,135 children were included. Meta-analysis was performed using RevMan, with Trial Sequential Analysis (TSA) to control for random errors and the GRADE framework to assess the certainty of evidence.

Results:

Midazolam demonstrated a statistically significant higher therapeutic success rate (RR=1.13, p=0.01) and a lower treatment failure rate (RR=0.74, p=0.02) compared to diazepam. This superiority was particularly pronounced for buccal midazolam over rectal diazepam. Time to seizure cessation was shorter for midazolam via non-IV routes, though IV diazepam was faster than non-IV midazolam. Midazolam was also associated with a lower risk of seizure relapse. No significant differences were found in major adverse events like respiratory depression or intubation. TSA confirmed the conclusiveness of the efficacy findings.

Conclusions:

Midazolam is more effective than diazepam for terminating pediatric status epilepticus, especially when administered via the buccal route. Its favorable efficacy profile supports its use as a preferred first-line benzodiazepine, particularly in pre-hospital or resource-limited settings where intravenous access is unavailable. The safety profile between the two drugs appears comparable.