Flumazenil use in acute poisoning: improved composite clinical outcomes in a propensity-matched retrospective cohort study.

INTRODUCTION: Despite being an effective benzodiazepine antagonist, flumazenil is not routinely used in patients with overdose due to the potential risk of major adverse events. Although recent studies have reported a low rate of major adverse events, the benefit of its utility on clinical outcomes remains unclear. This study aims to determine the effect of flumazenil treatment on the clinical outcomes of comatose patients with acute benzodiazepine or nonbenzodiazepine hypnotics poisoning.

METHODS: This was a retrospective observational study on consecutive adult patients reported to the Hong Kong Poison Control Centre from 1 July 2008 to 31 December 2024 for benzodiazepine or nonbenzodiazepine hypnotics overdose with Glasgow Coma Scale eight or less. Patients treated with flumazenil, the intervention, were matched with patients in the control group by propensity score matching. The Finkelstein-Schoenfeld method with matched pairs approach was used to compare the primary outcome, a hierarchical composite endpoint consisting of in-hospital death, intensive care unit admission, and length of hospital stay. Secondary outcomes included mechanical ventilation and pneumonia within two days.

RESULTS: A total of 599 patients were included for propensity score matching, and 98 patients in the intervention group and 501 patients in the control group were matched in a 1:1 ratio. Two patients in the intervention group and one patient in the control group died during the in-patient episode of care; the deaths in the intervention group were not attributed to flumazenil. The hierarchical composite endpoint (in-hospital death, then ICU admission, then length of hospital stay) in the interventional group was significantly improved, with a win ratio of 1.68 (95% CI 1.17-2.41). The ICU admission rate (42.9% vs 69.4%, P <0.001) and the proportion of patients who received mechanical ventilation (35.7% versus 65.3%, P <0.001) was significantly lower in the intervention group. No difference was found in the death, length of stay and occurrence of rapid-onset pneumonia.

DISCUSSION: These results indicate the improvement of primary outcome in the intervention group was predominantly attributed to the reduction in ICU admission and mechanical ventilation. The effect size of flumazenil treatment could be partially offset by the adoption of non-invasive airway management strategy.

CONCLUSION: Among comatose patients with acute benzodiazepine or nonbenzodiazepine hypnotics poisoning, flumazenil treatment was associated with reduction in ICU admission and mechanical ventilation; as well as a better outcome for the composite endpoint of in-hospital death, ICU admission rate, and length of hospital stay.