Pre-hospital midazolam for benzodiazepine-treated seizures before and after the Rapid Anticonvulsant Medication Prior to Arrival Trial: A national observational cohort study

Background: Implementation of evidence-based treatment for pre-hospital status epilepticus can improve outcomes. We hypothesized that publication of a pivotal pre-hospital clinical trial (RAMPART), demonstrating superiority of intramuscular midazolam over intravenous lorazepam, altered the national utilization rates of midazolam for pre-hospital benzodiazepine-treated seizures, while upholding its safety and efficacy outside the trial setting. Methods and findings: This is a retrospective, observational cohort study of pre-hospital patient encounters throughout the United States in the National Emergency Medicine Services Information System database, from January 2010 through December 2014. We compared the rates and odds of midazolam use as first-line treatment among all adult and pediatric benzodiazepine-treated seizures before and after RAMPART publication (February 2012). Secondary analyses were conducted for rates of airway interventions and rescue therapy, as proxies for safety and efficacy of seizure termination. 156,539 benzodiazepine-treated seizures were identified. Midazolam use increased from 26.1% in January 2010 to 61.7% in December 2014 (difference +35.6%, 95% CI, 32.7%-38.4%). The annual rate of midazolam adoption increased significantly from 5.9% per year to 8.9% per year after the publication of RAMPART (difference +3.0% per year; 95%CI, 1.6%-4.5% per year; adjusted OR 1.24; 95%CI, 1.17–1.32). Overall frequency of rescue therapy and airway interventions changed little after the publication of RAMPART. Conclusions: These data are consistent with effective, ongoing, but incomplete clinical translation of the RAMPART results. The effects of the trial, however, cannot be isolated. The study was limited by broad inclusion of all benzodiazepine-treated seizures as well as a lack of information on route of drug of administration. The safety and effectiveness of midazolam for benzodiazepine-treated seizures in prehospital clinical practice appear consistent with trial data, which should encourage continuing increases in utilization.