Efficacy and safety of levetiracetam intravenous infusion combined with midazolam continuous pump infusion for stepwise emergency treatment of convulsive status epilepticus in children: a retrospective cohort study.

OBJECTIVES

To evaluate the efficacy and safety of intravenous levetiracetam (LEV) combined with continuous midazolam (MDZ) infusion versus MDZ monotherapy as second-line treatment for pediatric convulsive status epilepticus (CSE).

METHODS

This retrospective cohort study included 159 pediatric patients with generalized convulsive status epilepticus (GCSE) treated between June 2017 and December 2025. Patients received either LEV+MDZ (n=86) or MDZ alone (n=73). Outcomes included seizure cessation at 20 and 40 minutes, 24-hour seizure control, requirement for third-line antiseizure medication, adverse events, change in Status Epilepticus Severity Score (STESS), lengths of pediatric intensive care unit (PICU), and Pediatric Cerebral Performance Category (PCPC) score at discharge.

RESULTS

Compared to MDZ monotherapy, the combination group showed significantly greater reduction in STESS at 24 hours (1.94 ± 0.46 vs. 2.67 ± 0.53, P < 0.001) and a lower requirement for third-line medication (11.63% vs. 24.66%, P=0.032). Midazolam cumulative dose at 1 hour was lower with combination therapy (0.28 ± 0.10 vs. 0.32 ± 0.11 mg/kg, P=0.013). Incidence of adverse events was similar between groups (16.28% vs. 21.92%, P=0.365). Furthermore, the combination group had shorter PICU stay (2.73 ± 1.28 vs. 3.42 ± 1.56 days, P=0.003), shorter total hospitalization (6.52 ± 2.01 vs. 7.85 ± 2.27 days, P < 0.001), and better PCPC scores at discharge (1.89 ± 0.71 vs. 2.32 ± 0.82, P < 0.001).

CONCLUSIONS

Early administration of LEV combined with MDZ was associated with reduced seizure severity, decreased need for rescue therapy, lower benzodiazepine exposure, shorter hospitalization, and improved short-term neurological outcome without increasing adverse events in pediatric patients with CSE.