Effectiveness and safety of midazolam versus lorazepam for pediatric status epilepticus: A systematic review and meta-analysis

Introduction

Status epilepticus is a life‐threatening pediatric emergency with high morbidity and mortality, where rapid benzodiazepine administration is critical. However, the optimal agent and route of administration remain subjects of ongoing evaluation, with direct head-to-head comparison between lorazepam and midazolam remaining limited.

Methods

An aggregate-level meta-analysis was conducted on randomized controlled trials (RCTs) comparing the efficacy of midazolam against lorazepam in managing pediatric status epilepticus. Primary outcomes included treatment success and failure rates, time to seizure cessation from drug administration, and safety outcomes (respiratory depression and need for intubation). Secondary outcomes included seizure recurrence, need for rescue medications, and two time intervals: from hospital arrival to drug administration, and from hospital arrival to seizure cessation. Pooled standardized mean difference (SMD) and risk ratios (RRs) were analyzed using a random-effects model. Risk of bias was assessed by the Cochrane risk-of-bias tool.

Results

Four RCTs were included in the analysis, encompassing a total of 326 patients. The two interventions were comparable in terms of seizure termination success (RR = 0.98, 95 % CI [0.92, 1.04], p = 0.45) and failure (RR = 0.91, 95 % CI [0.44, 1.89], p = 0.81). The mean time of seizure cessation following drug administration was similar for both medications (SMD = 0.01, 95 % CI [-0.27, 0.28], p = 0.95), although the intranasal midazolam subgroup exhibited a shorter duration (SMD = -0.02 [-0.38, 0.34], p = 0.90). A qualitative synthesis indicated that intranasal midazolam was associated with a shorter administration time and more rapid seizure control upon hospital arrival. Safety profiles were comparable.

Conclusion

In this meta-analysis, midazolam, irrespective of the route of administration, is shown to be non-inferior to lorazepam in the management of pediatric status epilepticus. Preliminary evidence indicates that intranasal midazolam may provide more rapid and practical administration, making it more favorable in certain clinical contexts. Further multicenter trials are needed to confirm these findings.