UMEM Educational Pearls

Title: Adverse events (AE) associated with flumazenil for the management of suspected benzodiazepine intoxication

Keywords: flumazenil, benzodiazepine overdose, adverse events (PubMed Search)

Posted: 1/13/2022 by Hong Kim, MD, MPH
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Flumazenil is a reversal agent for benzodiazepine overdose. Adverse events including seizure, agitation and cardiac arrhythmias have been reported but the frequency of adverse events is unknown.

AE and serious AEs were defined as:

AE:

Aggressive behavior, agitation, screaming, restlessness
Nausea/vomiting, abdominal cramps
Sweating, shivering, chills, hot flashes
Headache, dizziness
Anxiety, distress, depressed mood, abnormal crying
Tremors

Serious AE (SAE):

Seizures
Supraventricular arrhythmia
Multiple ventricular beats
Tachycardia
Sudden fall in systolic BP

A systematic review/meta-analyses of 13 randomized controlled trials showed

AEs more common in flumazenil group vs. placebo (risk ratio: 2.85; 95% CI: 2.11-3.84)
SAEs more common in flumazenil group vs. placebo (risk ratio: 3.81; 95% CI: 1.28-11.39)

Most common AEs

Aggressive behavior, agitation, screaming: 26.2% (n=33/126)
Nausea/vomiting, abdominal cramps: 20.6% (n=26/126)
Anxiety, distress, depressed mood: 15.7% (n=19/126)

Most common SAEs

Supraventricular arrhythmia: 30% (n=4/12)
Seizure: 25% (n=3/12)
Tachycardia: 25% (n=3/12)

Conclusion

Administration of flumazenil to patients with known or suspected benzodiazepine overdose is associated with increased risk of AEs

References

PENNINGA E ET AL.Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication--A Systematic Review with Meta-Analyses of Randomized Trials. Basic Clin Pharmacol Toxicol. 2016

DOI: 10.1111/bcpt.12434