Tony Zitek, MD*; Kenneth A. Scheppke, MD; Peter Antevy, MD; Charles Coyle, EMT-P; Sebastian Garay, EMT-P; Eric Scheppke, DO;
David A. Farcy, MD
📌 Key Points
Ketamine for Seizure Control: After two midazolam doses, ketamine increased seizure cessation rates significantly in the prehospital setting.
Not Yet Standard of Care: Ketamine remains investigational—it wasn’t directly compared to traditional second-line antiepileptics
No Increase in Harm: Ketamine use was not associated with higher rates of intubation or cardiac arrest, supporting its safety in this context.
EMS-Friendly & Practical: Ketamine is already familiar practical option to EMS providers and was effective when administered via IV or IO.
Study Limitations Limit Change: This retrospective, non-randomized design and variable midazolam dosing mean caution is warranted before changing protocols.
ABSTRACT 
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
