Flumazenil. A reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist

Abstract

Flumazenil is a specific benzodiazepine antagonist which is indicated when the central effects of a benzodiazepine need to be attenuated or terminated. Following intravenous administration of up to 1 mg, flumazenil effectively reverses sedation and improves psychomotor performance following administration of short and longer acting benzodiazepines used for sedation, or general anaesthesia supplemented with benzodiazepines. The duration of action is short at generally 30 to 60 minutes and supplemental doses of flumazenil may be needed to maintain the desired level of consciousness in some patients. After poisoning with high dosages of benzodiazepines alone or combined with other drugs, the initial single dose of flumazenil will require supplementing with repeated low intravenous doses or an infusion to maintain wakefulness. In such patients, flumazenil also facilitates differential diagnosis and reduces the necessity for interventions. Flumazenil thus enhances recovery and allows more rapid discharge of patients sedated with benzodiazepines for diagnostic procedures and facilitates management of patients during the initial recovery period following general anaesthesia supplemented with benzodiazepines, but does not preclude normal monitoring during the recovery period. Flumazenil is clearly very useful in treating drug poisoning when benzodiazepines are a major component. By virtue of its specific benzodiazepine antagonist effects, flumazenil provides an innovative and well tolerated approach in clinical situations requiring rapid reversal of benzodiazepine-induced central nervous system depressant effects.