Prehospital Flumazenil: Five-Year Review of Use, Indications, Outcomes, and Adverse Events in Suspected Benzodiazepine Overdose.

INTRODUCTION

Historically, flumazenil was employed as both a diagnostic aid in unresponsive patients and as an antidote for suspected benzodiazepine overdose in both emergency departments and out-of-hospital settings. However, its prehospital application has been historically constrained by long-standing concerns regarding adverse events, leading many emergency medical service (EMS) systems to restrict or avoid its use. The use of flumazenil in the prehospital setting remains underreported in the literature, despite its inclusion in the treatment protocols of various EMS agencies. We conducted a descriptive analysis of the use of flumazenil by EMS in the out-of-hospital setting across the state of Kansas over a five-year period. We characterize the frequency, indications, patient outcomes, and associated adverse events of flumazenil administration, thereby contributing to a better understanding of its role, safety, and clinical relevance in prehospital care.

METHODS

We performed a retrospective observational cohort design to evaluate the use of flumazenil by EMS clinicians in the state of Kansas from January 2015-August 2020. Patient care reports documenting prehospital administration of flumazenil were obtained from the Kansas Board of EMS. Data extracted included demographics, indications, initial and subsequent Glasgow Coma Scale (GCS) scores when available, clinical response, and the occurrence of adverse events. Our primary outcome measure was GCS improvement following administration, with secondary outcome measures including patterns and outcomes with flumazenil use in the prehospital setting, clinical response, and occurrence of adverse side effects.

RESULTS

A total of 80 cases involving EMS administration of flumazenil were identified with 69 cases meeting inclusion criteria. No seizures or adverse events were associated with flumazenil use (0/69; 95% CI, 0-4.3%), even in administrations with possible contraindications. Of the 69 cases analyzed, 24 cases documented suspected benzodiazepine overdose, all of which documented neurologic improvement (24/24; 95% CI, 87.5-100%), with 17 receiving flumazenil alone and 7 with naloxone coadministration.

CONCLUSION

In this small sample, no adverse events were noted with flumazenil administration in the prehospital setting. Flumazenil administration was commonly associated with documented improvement in GCS in suspected benzodiazepine overdose. These findings suggest that exclusion in EMS protocols based solely on concern for adverse events in the prehospital setting can be reconsidered. Further research is needed to better define its safety, efficacy, and clinical utility in this setting.