Effectiveness of Ketamine As a Rescue Drug for Patients Experiencing Benzodiazepine-Resistant Status Epilepticus in the Prehospital Setting

Abstract

Objectives: Accumulating basic science data, early clinical findings and various feasibility considerations have provided rationales for administering ketamine as a proposed rescue medication for midazolam-resistant status epilepticus (SE) in the logistically challenging prehospital environment. This report details the multiyear experience of paramedics managing midazolam-resistant SE following the introduction of a ketamine-rescue protocol.

Design: A 7-year, population-based, observational study was conducted to evaluate outcomes of patients treated with IV, intraosseous, intramuscular, or intranasal ketamine for SE despite sufficient midazolam dosings. Tracked outcomes included: 1) rapid/sustained termination of clinical seizures in adults while under paramedics' care; 2) corresponding evaluations in children/adolescents; 3) any concerning observations regarding need for assisted ventilation, intubation, or other active interventions post-ketamine; and 4) any identifiable associations between outcomes and circumstances, demographics, or medical history.

Setting: Emergency response 9-1-1 system serving a large, diverse U.S. county (jurisdictional population, 961,000/1,769 sq miles).

Patients: Those receiving ketamine from paramedics for persistent seizures.

Interventions: Adults and adolescents: 100 mg ketamine IV/intraosseous/intramuscular/intranasal; children: 1 mg/kg intramuscular/intranasal.

Measurements and main results: Among 81 total cases, 57 involved adults (18-86 yr old) receiving the SE-midazolam + ketamine protocol. Ketamine rapidly terminated convulsions in 56 (98.2%) without recurrence during prehospital and hospital arrival phases. For approved reasons, paramedics administered ketamine directly (no midazolam) in eight adults and one child, terminating convulsions in every case. Among 15 childhood/adolescent cases treated per protocol, ketamine rapidly terminated SE activity in 11, but only mitigated it in four, including two retrospectively judged to involve nonseizure activity and two involving intranasal administration. Among all 81 ketamine-treated cases, there were no identifiable clinically significant complications attributable to ketamine, particularly the need for any additional active interventions.

Conclusions: Ketamine appeared to be consistently effective in treating adults with ongoing out-of-hospital seizures that were resistant to sufficient dosings of midazolam. Similar results were observed in children/adolescents.