UMEM Educational Pearls

Category: Toxicology

Title: Is Flumazenil Making a Comeback? (Hint: no)

Keywords: flumazenil, benzodiazepine, overdose (PubMed Search)

Posted: 8/7/2015 by Bryan Hayes, PharmD (Emailed: 8/13/2015) (Updated: 8/13/2015)
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Flumazenil is generally avoided in most adult patients with suspected benzodiazepine overdose due to resedation, seizures/withdrawal, inconsistent reversal of respiratory depression, and the potential for proconvulsant coingestants.

Three relatively recent poison center studies have attempted to demonstrate the safety of flumazenil in this setting. [1-3] In the first study there were 904 adult patients with 13 reported seizures and 1 death. [1] A second study specific to pediatric patients reported 83 patients with no seizures and no deaths. [2] A third study found 80 patients with 1 seizure and 0 deaths. [3]

On the surface, it may appear that flumazenil is safe to give. But, retrospective poison center studies from voluntary reporting cannot be used to prove a drug's safety. The true denominator is unknown. In the pediatric study, we wouldn't expect children to experience withdrawal since they aren't on chronic benzodiazepine therapy. [2] So, it's no surprise there weren't any seizures or deaths.

A recent systematic review and meta-analysis of randomized trials summed it up perfectly: "Flumazenil should not be used routinely, and the harms and benefits should be considered carefully in every patient." [4] Cases in which to consider flumazenil are pediatric patients and reversal of procedural sedation if needed.


  1. Kreshak AA, et al. A poison center's ten-year experience with flumazenil administration to acutely poisoned patients. J Emerg Med 2012;43(4):677-82. [PMID 22766408]
  2. Kreshak AA, et al. Flumazenil administration in poisoned pediatric patients. Pediatr Emerg Care 2012;28(5):448-50. [PMID 22531190]
  3. Veiraiah A, et al. Flumazenil use in benzodiazepine overdose in the UK: a retrospective survey of NPIS data. Emerg Med J 2012;29(7):565-9. [PMID 21785147]
  4. Penninga EL, et al. 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 2015 Jun 19. Epub ahead of print. [PMID 26096314]

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