Midazolam and Ketamine for Convulsive Status Epilepticus in the Out-of-Hospital Setting

Study objective: To determine if ketamine, when added to midazolam for the treatment of out-of-hospital seizures, is associated with an increase in the rate of cessation of convulsions prior to hospital arrival. Methods: We performed a retrospective cohort study of out-of-hospital patients with an active convulsive seizure being transported to a hospital by a large emergency medical services system in Florida, using data from August 1, 2015 and August 5, 2024. Per protocol, patients received midazolam first for their seizure. Starting in June 2017, a new protocol was developed in which patients who continued to convulse after midazolam received ketamine. We used propensity score matching and multivariable logistic regression to determine if patients who received ketamine were more likely to stop convulsing prior to hospital arrival than those who received midazolam alone. Results: Overall, 479 (80.1%) of 598 actively convulsing patients who received 2 doses of midazolam (without subsequent ketamine) had resolution of their convulsions prior to hospital arrival compared with 85 (94.4%) of 90 who received ketamine after midazolam, an absolute difference between groups of 14.3% (95% CI 8.6% to 20.1%). After propensity matching, 82.0% of those in the midazolam only group had resolution of convulsions compared to 94.4% in the ketamine group, a difference of 12.4% (95% CI 3.1% to 21.7%). Conclusion: In this retrospective study of out-of-hospital patients with active convulsive seizures, patients who received ketamine were more likely to have stopped convulsing prior to hospital arrival than those who received midazolam alone. [Ann Emerg Med. 2025;85:305-312.]