Flumazenil

General information

Flumazenil is used as a benzodiazepine antagonist in the treatment of poisoning or the reversal of benzodiazepine effects in anesthesia [ , ] or in neonates [ ]. Guidelines for its use have been summarized [ ]. The problems in its use are those of dose adjustment, the risks of panic anxiety, seizures, or other signs of excessively rapid benzodiazepine withdrawal, and pharmacokinetic problems due to the short half-life of flumazenil (about 1 hour) compared with the longer half-lives of most benzodiazepines [ ]. Its use is also commonly associated with vomiting and headache, and rarely with psychosis or sudden cardiac death [ ], especially in mixed overdoses. Flumazenil was not effective in reversing the amnesic effects of midazolam [ ], but it may be useful in hepatic coma, regardless of cause [ ]. In patients with a history of seizures or chronic benzodiazepine dependence, or after mixed drug overdose, flumazenil can trigger convulsions, which are occasionally fatal. It is not generally helpful to measure benzodiazepine plasma concentrations, but they can assist in the diagnosis of overdose and thus guide the use of antagonists [ ].

Midazolam can cause paradoxical reactions, including increased agitation and poor cooperation [ , ]. Often other drugs are required to continue the procedure successfully. Reversal of these reactions by flumazenil has been reported. In 58 patients undergoing surgery under spinal or epidural anesthesia, flumazenil 0.1 mg over 10 seconds abolished the agitation without reversing sedation (total dose range 0.1–0.5 mg) [ ]. In 30 patients who had been given midazolam, flumazenil 0.15–0.5 mg resulted in cessation of the agitation without reversal of sedation [ ]. Adverse reactions to flumazenil were not reported in these studies.

The usefulness and relative safety of midazolam in children have been reviewed [ ]. Myoclonic-like movements associated with midazolam in three full-term newborns were reversed by flumazenil [ ]. However, care must be taken when considering the use of flumazenil for reversal of midazolam-induced agitation, as no controlled trials have been published.

Organs and systems