Combined Ketamine and Midazolam Versus Midazolam Alone for Initial Treatment of Pediatric Generalized Convulsive Status Epilepticus (Ket-Mid Study): A Randomized Controlled Trial.
Amr A Othman, Abdelrahim A Sadek, Esraa A Ahmed, Elsayed Abdelkreem
Pediatric neurology June 1, 2025 Peer reviewed DOI: 10.1016/j.pediatrneurol.2025.03.011 via PubMed
Summary
When treating severe seizures in children, combining two medications proves significantly more effective than traditional single-drug approaches. A groundbreaking advance shows that pairing ketamine with benzodiazepines stops dangerous status epilepticus in 76% of cases within 5 minutes, compared to just 21% with standard treatment. This polytherapy approach reduces the need for breathing tubes and additional antiseizure medications, offering a safer, faster way to help young patients.
Abstract
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. 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. 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. 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.