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Correspondence|Articles in Press

Experience with lower dose flumazenil at an academic medical center

Published:February 04, 2021DOI:https://doi.org/10.1016/j.ajem.2021.02.002
Experience with lower dose flumazenil at an academic medical center
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      Benzodiazepines (BZDs) are frequently used in self-poisonings [
      • Ngo A.S.
      • Anthony C.R.
      • Samuel M.
      • Wong E.
      • Ponampalam R.
      Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department?.
      Resuscitation. 2007; 74: 27-37
      ]. Flumazenil effects for BZD reversal are dose-dependent and higher doses are often used to achieve desired outcomes. However, higher doses are associated with increased risk of seizures, cardiac dysrhythmias, and other adverse drug effects (ADEs) [
      • Penninga E.I.
      • Graudal N.
      • Ladekarl M.B.
      • Jürgens G.
      Adverse events associated with flumazenil treatment for the management of suspected benzodiazepine intoxication--a systematic review with meta-analyses of randomised trials.
      Basic Clin Pharmacol Toxicol. 2016; 118: 37-44
      ,
      • Seger D.L.
      Flumazenil--treatment or toxin.
      J Toxicol Clin Toxicol. 2004; 42: 209-216
      ]. Multidrug intoxications involving tricyclic antidepressants (TCAs), stimulants, ethanol, anticonvulsants, propoxyphene, barbiturates, and other anxiolytics increase the frequency of significant ADEs from flumazenil [
      • Ngo A.S.
      • Anthony C.R.
      • Samuel M.
      • Wong E.
      • Ponampalam R.
      Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department?.
      Resuscitation. 2007; 74: 27-37
      ,
      • Penninga E.I.
      • Graudal N.
      • Ladekarl M.B.
      • Jürgens G.
      Adverse events associated with flumazenil treatment for the management of suspected benzodiazepine intoxication--a systematic review with meta-analyses of randomised trials.
      Basic Clin Pharmacol Toxicol. 2016; 118: 37-44
      ,
      • Seger D.L.
      Flumazenil--treatment or toxin.
      J Toxicol Clin Toxicol. 2004; 42: 209-216
      ,
      • Winkler E.
      • Almog S.
      • Kriger D.
      • Tirosh M.S.
      • Halkin H.
      • Ezra D.
      Use of flumazenil in the diagnosis and treatment of patients with coma of unknown etiology.
      Crit Care Med. 1993; 21: 538-542
      ,
      • Marraffa J.M.
      • Cohen V.
      • Howland M.A.
      Antidotes for toxicological emergencies: a practical review.
      Am J Health Syst Pharm. 2012; 69: 199-212
      ,
      • Gueye P.N.
      • Hoffman J.R.
      • Taboulet P.
      • Vicaut E.
      • Baud F.J.
      Empiric use of flumazenil in comatose patients: limited applicability of criteria to define low risk.
      Ann Emerg Med. 1996; 27: 730-735
      ]. In BZD overdose patients without evidence of underlying stimulation (e.g., neuromuscular excitation, tachycardia, hypertension) we often administer flumazenil 0.05–0.1 mg IV every 2–3 min to response. Patients receiving flumazenil for reversal of therapeutic BZD use are typically administered 0.2 mg [
      • Flumazenil. Lexi-Drugs. Lexicomp
      Wolters Kluwer Health, Inc. Hudson, OH.
      http://online.lexi.com
      Date: 2020
      ]. Characterization of efficacy and safety of flumazenil in different populations and doses is necessary.
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      References

        • Ngo A.S.
        • Anthony C.R.
        • Samuel M.
        • Wong E.
        • Ponampalam R.
        Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department?.
        Resuscitation. 2007; 74: 27-37
        View in Article
        • Penninga E.I.
        • Graudal N.
        • Ladekarl M.B.
        • Jürgens G.
        Adverse events associated with flumazenil treatment for the management of suspected benzodiazepine intoxication--a systematic review with meta-analyses of randomised trials.
        Basic Clin Pharmacol Toxicol. 2016; 118: 37-44
        View in Article
        • Seger D.L.
        Flumazenil--treatment or toxin.
        J Toxicol Clin Toxicol. 2004; 42: 209-216
        View in Article
        • Winkler E.
        • Almog S.
        • Kriger D.
        • Tirosh M.S.
        • Halkin H.
        • Ezra D.
        Use of flumazenil in the diagnosis and treatment of patients with coma of unknown etiology.
        Crit Care Med. 1993; 21: 538-542
        View in Article
        • Marraffa J.M.
        • Cohen V.
        • Howland M.A.
        Antidotes for toxicological emergencies: a practical review.
        Am J Health Syst Pharm. 2012; 69: 199-212
        View in Article
        • Gueye P.N.
        • Hoffman J.R.
        • Taboulet P.
        • Vicaut E.
        • Baud F.J.
        Empiric use of flumazenil in comatose patients: limited applicability of criteria to define low risk.
        Ann Emerg Med. 1996; 27: 730-735
        View in Article
        • Flumazenil. Lexi-Drugs. Lexicomp
        Wolters Kluwer Health, Inc. Hudson, OH.
        (Available at:)
        http://online.lexi.com
        Date: 2020
        View in Article
        • Weinbroum A.A.
        • Flaishon R.
        • Sorkine P.
        • et al.
        A risk-benefit assessment of flumazenil in the management of benzodiazepine overdose.
        Drug Saf. 1997; 17: 181-196
        View in Article
        • Nguyen T.T.
        • Troendle M.
        • Cumpston K.
        • et al.
        Lack of adverse effects from flumazenil administration: an ED observational study.
        Am J Emerg Med. 2015; 33: 1677-1679
        View in Article

      Article Info

      Publication History

      Published online: February 04, 2021
      Accepted: February 2, 2021
      Received in revised form: February 2, 2021
      Received: December 10, 2020

      Publication stage

      In Press Journal Pre-Proof

      Identification

      DOI: https://doi.org/10.1016/j.ajem.2021.02.002

      Copyright

      © 2021 Elsevier Inc. All rights reserved.

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