Early Midazolam Infusion in Pediatric Status Epilepticus: Defining an Early Therapeutic Window for Seizure Control

Status epilepticus (SE) is a neurological emergency with high morbidity and mortality in childhood, where rapid and effective intervention is essential to prevent neuronal injury. Experimental studies suggest that time-dependent loss of GABAergic responsiveness creates an early therapeutic window during which benzodiazepines are most effective for acute seizure suppression.

This retrospective study analyzed 63 pediatric patients (mean age 46.5 ± 4.9 months) with first-episode SE treated between 2008 and 2022. Patients were categorized according to the timing of continuous midazolam infusion as early (≤15 min from seizure onset) or late (>15 min). Primary outcome was time to seizure control; secondary outcomes included infusion duration and epilepsy development during two-year follow-up.

Early infusion significantly shortened time to seizure control (21.8 ± 1.5 min vs. 29.3 ± 2.8 min, p = 0.029) and reduced infusion duration (18.4 ± 2.5 h vs. 32.7 ± 7.5 h, p = 0.049) compared with later initiation. Epilepsy developed in 74.6% of patients over two years, with no significant difference between early and late infusion groups (p = 0.079).

Initiating continuous midazolam infusion within 15 min of seizure onset defines a clinically relevant early therapeutic window for pediatric SE. While infusion timing did not significantly alter long-term epileptogenesis, early initiation was associated with improved acute seizure control and shorter treatment duration, underscoring the importance of time-sensitive intervention in pediatric neuroemergencies.