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The use of flumazenil in the management of acute drug poisoning — a review

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Abstract

The popularity and widespread availability of benzodiazepines (BZD) has led to their frequent abuse in intentional drug poisoning. Although mortality from pure BZD overdose is usually small, in elderly, debilitated patients, or when BZD are combined with other CNS depressant drugs, morbidity increases significantly and outcome may be fatal. Drug overdose is therefore a medical emergency necessitating close obervation and support of vital functions. Recently, the specific BZD antagonist flumazenil (Anexate®) has become clinically available and much experience in its usefulness has accumulated. The present review summarizes a total of 30 studies and reports published to date, involving approximately 760 intoxicated patients. Flumazenil was evaluated both in prehospital use as well as in emergency rooms or in intensive care units. The age of patients ranged from 4–90 years and doses of flumazenil varied between 0.3–10 mg, approximately 1 mg being the most frequently used. All patients intoxicated with only BZD returned to full consciousness within minutes after the injection of flumazenil. When a mixture of BZD and other CNS depressants was abused, a range of effects was observed. This varied from no change to a return to full orientation, depending on the contribution of the BZD to the state of unconsciousness. Re-sedation occurred in about 65% of flumazenil treated patients, usually within 0.5–3 h after the first dose, the shorter interval being associated with mixed-drug poisoning. Repeated doses of the antagonist (0.2–2 mg), sometimes followed by continuous infusion (0.1–0.5 mg/h), were effective in maintaining patients fully oriented. Of 78 intubated patients 27% could be extubated safely while in 14 instances intubation was avoided following arousal with flumazenil. General and local tolerance to flumazenil were excellent. No significant hemodynamic changes were observed. Side effects (anxiety, agitation, etc.) occured in one third of the patients and were mild and self-limited. Seven (out of the 760) patients developed convulsions, attributable to either rapid injection of a high dose of the drug or to combination of BZD and cyclic antidepressants. The efficacy and safety of flumazenil in reversing coma due to BZD intoxication has been confirmed in this large number of studies. It is recommended that flumazenil be given by slow titration and that patients remain under close observation to guard against re-sedation.

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Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care, Tel-Aviv-Elias Sourasky Medical Center Ichilov Hospital, 6 Weizman Street, 64239, Tel-Aviv, Israel

    A. Weinbroum, P. Halpern & E. Geller MD

  2. Sackler Faculty of Medicine, Tel-Aviv University Ichilov Hospital, 6 Weizman Street, 64239, Tel-Aviv, Israel

    A. Weinbroum, P. Halpern & E. Geller MD

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  1. A. Weinbroum
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  2. P. Halpern
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  3. E. Geller MD
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Weinbroum, A., Halpern, P. & Geller, E. The use of flumazenil in the management of acute drug poisoning — a review. Intensive Care Med 17 (Suppl 1), S32–S38 (1991). https://doi.org/10.1007/BF01731152

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