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Flumazenil

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Critical Care Toxicology

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Abstract

Flumazenil (Romazicon®) (US brand names are given here as examples. These may be the same or different in other countries.) is a specific benzodiazepine receptor antagonist that has generated debate regarding its clinical indications since its initial release in the USA in 1991. A major argument against the use of flumazenil in the management of benzodiazepine intoxication is the relatively high safety index (i.e., toxic-to-therapeutic dose ratio) of benzodiazepines, even in cases of overdose. In addition, the anticonvulsant effects of benzodiazepines may be advantageous in individuals simultaneously poisoned with proconvulsant substances, such as tricyclic antidepressants. Another significant concern regarding the clinical use of flumazenil in the emergent management of poisoning is the possibility of precipitating acute withdrawal in individuals with pharmacodynamic tolerance to benzodiazepine receptor agonists. Withdrawal from benzodiazepines is associated with a spectrum of effects, which can include epileptic seizures [1]. These safety concerns have prevented flumazenil from gaining widespread clinical acceptance as a component of the initial pharmacologic management of coma.

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Authors and Affiliations

  1. Department of Emergency Medicine, University of California, San Diego Health Sciences, La Jolla, CA, USA

    Allyson Kreshak

  2. Sharp-Rees-Stealy Medical Group, San Diego, CA, USA

    Stephen Munday

Authors
  1. Allyson Kreshak
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  2. Stephen Munday
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Correspondence to Allyson Kreshak or Stephen Munday .

Editor information

Editors and Affiliations

  1. Department of Medicine, Division of Clinical Pharmacology and Toxicology, University of Colorado, School of Medicine, Aurora, Colorado, USA

    Jeffrey Brent

  2. FDA, Office of New Drugs/Immediate Office, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA

    Keith Burkhart

  3. Clinical Toxicology, St Thomas’ Hospital, Silver Spring, Maryland, USA

    Paul Dargan

  4. Toxicology Associates, University of Colorado, School of Medicine, Denver, Colorado, USA

    Benjamin Hatten

  5. Medical Toxicological Intensive Care Unit, Lariboisiere Hospital, Paris-Diderot University, Paris, France

    Bruno Megarbane

  6. Toxicology Associates, University of Colorado, School of Medicine, Denver, Colorado, USA

    Robert Palmer

  7. Toxinology Department, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia

    Julian White

Grading System for Levels of Evidence Supporting Recommendations in Critical Care Toxicology, 2nd Edition

  1. I

    Evidence obtained from at least one properly randomized controlled trial.

  2. II-1

    Evidence obtained from well-designed controlled trials without randomization.

  3. II-2

    Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.

  4. II-3

    Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.

  5. III

    Opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.

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Kreshak, A., Munday, S. (2017). Flumazenil. In: Brent, J., et al. Critical Care Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-17900-1_152

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