Low risk of adverse events associated with flumazenil administration: a retrospective poison center analysis of acutely poisoned patients.

Abstract

Introduction: Benzodiazepine overdose can lead rarely to life-threatening central nervous system and respiratory depression. Flumazenil is a benzodiazepine antagonist. However, reported adverse effects, including seizures and cardiac dysrhythmias, has led some experts to recommend its use only in select populations. Recent studies, however, report low rates of adverse effects. Our objective was to determine the updated incidence of response and adverse effects following flumazenil with or without naloxone.

Methods: We performed a retrospective review of cases involving flumazenil administration reported to a state poison center between January 1, 2012 and December 31, 2022. The primary outcome was the incidence of adverse effects secondary to flumazenil. Secondary outcomes were associated risk factors, including pro-convulsant co-exposure. We characterized outcomes in cases of naloxone co-administration. The difference in age between groups was compared using the t-test and categorical data was analyzed using Fisher's Exact test. A 2 × 2 table was constructed and 95% confidence intervals for seizures.

Results: Two-hundred eighty-six cases involved flumazenil administration. Dosing information was available for 115/286 (40.2%). Chronic benzodiazepine or non-benzodiazepine sedative-hypnotic use was reported in 161/286 (56.3%). Adverse effects occurred in 23/115 patients (20%) with reported dosing information, the most common being agitation in 16/115 (13.9%). Seizures occurred in three patients (2.6%), all of whom had pro-convulsant co-exposure (P = 0.0128). Most patients with adverse events were chronic benzodiazepine users, 15/161 (9.3%). Naloxone co-administration occurred in 140/286 patients (49.0%) and 64/140 patients (45.7%) who received naloxone had improved mentation. Two deaths (0.7%), not attributable to flumazenil, were reported.

Discussion: Low rates of adverse drug events occurred after flumazenil administration. The occurrence of seizures, regardless of pro-convulsant exposure, was low. Chronic benzodiazepine use was not associated with seizures. This may support the utility of flumazenil in precluding costly diagnostic evaluation and invasive therapeutic interventions.

Conclusion: This study suggests a low rate of adverse events following flumazenil administration in patients with suspected benzodiazepine overdose with or without naloxone.