Combined Ketamine and Midazolam Versus Midazolam Alone for Initial Treatment of Pediatric Generalized Convulsive Status Epilepticus (Ket-Mid Study): A Randomized Controlled Trial

Abstract

Background: Approximately one third of children with generalized convulsive status epilepticus (GCSE) are not controlled by initial benzodiazepine therapy. We investigated the efficacy of adding ketamine to midazolam for first-line treatment of pediatric GCSE.

Methods: This randomized controlled trial included 144 children with GCSE aged between six months and 16 years, who were equally randomized to receive ketamine plus midazolam (Ket-Mid group) or placebo plus midazolam (Pla-Mid group). Primary outcome was cessation of clinical seizures at five-minute study timepoint. Secondary outcomes were the need for a second midazolam bolus; cessation of clinical seizures at 15-, 35-, and 55-minute timepoints; 24-hour seizure control; and adverse effects.

Results: Cessation of clinical seizures at five-minute occurred in 76% of children in the Ket-Mid group compared with 21% in the Pla-Mid group (risk ratio [RR] 3.7; 95% confidence interval [CI] 2.3-5.9; P < 0.001). Compared with the Pla-Mid group, the Ket-Mid group had higher percentages of seizure cessation at 15-minute (76.4% vs 23.6%; RR, 3.2; 95% CI, 2.1-5.0), 35-minute (83.3% vs 45.8%; RR, 1.8; 95% CI, 1.4-2.4), and 55-minute (88.9% vs 72.2%; RR, 1.2; 95% CI, 1.04-1.45) study timepoints as well as lower percentages of repeating midazolam (23.6% vs 79.2%; RR, 0.3; 95% CI, 0.19-0.46) and endotracheal intubation (4.2% vs 20.8%; RR, 0.2; 95% CI, 0.06-0.66). Both groups showed no significant differences in other outcome measures.

Conclusions: Ketamine-midazolam combination may be more effective than midazolam alone for the initial treatment of pediatric GCSE, but this should be confirmed in future research.

Keywords: Antiseizure medications; Benzodiazepines; Ketamine; Polytherapy; Status epilepticus.