Is ED use of flumazenil safe?

September 3, 2015, 10:24 pm


Lack of adverse effects from flumazenil administration: an ED observational study. Nguyen TT et al. Am J Emerg Med 2015 Jul 21 [Epub ahead of print]


The use of the antidote flumazenil in patients with suspected benzodiazepine poisoning is controversial. The major concern is for inducing seizures in a patient who has a proconvulsant medication on board, is tolerant to benzodiazepines, or has an underlying seizure disorder.

The goal of this single-hospital retrospective observational study was to “assess adverse events and clinical outcomes of flumazenil administration in known and suspected BZD [benzodiazepine] overdose . . .” The authors identified records of 23 eligible adult patients with adequate data recorded. Eight patients had ingested a proconvulsant drug (4 cocaine, 1 bupropion, 1 diphenhydramine, 1 MDMA.) The authors claim that 60% of these patients “experienced some type of mental status improvement.” (One should certainly hope so, since the only alternative would be death or persistent neurological dysfunction. Unfortunately, the paper does not indicate when this improvement took place in relation to administration of flumazenil, or exactly what criteria the chart reviewers used to establish improvement.)

The authors discuss some of the limitations of this study: the retrospective design, the lack of laboratory confirmation of BZD exposure, the subjective nature of both documentation and abstraction regarding evidence of improved mental status. This only scratches the surface. For example, the study involved a total of 23 patients over 7 years — that’s a whopping average of a little over 3 patients per year. Since the incidence of seizures in patients given flumazenil is certainly low, it does not require advanced statistical analysis to realize that the study is way underpowered to determine the incidence of adverse events.

But the numbers are even worse. In over half of these patients, the overdoses were iatrogenic. It is, I think, generally accepted that reversing an iatrogenic BZD overdose with flumazenil may be warranted. The controversy involves administering the antidote to the undifferentiated patient with mental status depression and uncertain history. It seems that at most 11 of the patients in this study may have fit that bill.

Related posts:

Flumazenil-induced seizures

Is use of flumazenil in poisoned pediatric patients safe?

The problem with observational studies



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