In anaesthesia and in the intensive care unit, benzodiazepines have proven safe 
and effective agents for the induction and maintenance of sedation for a variety 
of therapeutic goals. However, in these contexts, or in benzodiazepine overdose, 
it is often desirable to be able to terminate or interrupt sedation without 
waiting for the effect of the benzodiazepine to become dissipated by normal 
metabolism and excretion. Flumazenil, a 1,4-imidazobenzodiazepine, is a highly 
effective, specific benzodiazepine antagonist which is indicated for use when 
the effect of a benzodiazepine must be attenuated or terminated at short notice. 
It acts by displacing other benzodiazepines from the receptor site by 
competitive inhibition. The onset of effect after intravenous administration 
occurs within 1 to 3 minutes. The optimal dosage is determined for each patient 
by a dose titration procedure and lies in the range 0.2 to 1.0mg in 
anaesthesiology, and 0.1 to 2.0mg in intensive care use. Despite its short 
elimination half-life of around 1 hour, after general anaesthesia or conscious 
to moderate sedation for short procedures, a single dose of flumazenil is 
usually sufficient to attain and maintain the desired level of consciousness. 
After intoxication with high benzodiazepine doses, the duration of effect of a 
single dose of flumazenil is not expected to exceed 1 hour. In such cases, the 
period of wakefulness can be prolonged as necessary by repeated low intravenous 
doses of flumazenil or by infusion (0.1 mg/hour). Flumazenil is well tolerated 
both systemically and locally. The only adverse events seen with greater 
frequency after flumazenil compared with placebo were nausea and/or vomiting 
after general anaesthesia, although the incidence of actual vomiting was not 
significantly different between the 2 groups. Since these effects were virtually 
absent in studies of intensive care patients and after sedation for short 
procedures, and were not seen in tolerability studies in healthy volunteers 
receiving intravenous bolus doses of up to 100mg, there may be a link between 
these symptoms and the other agents used in general anaesthesia, some of which 
have well-known emetic properties. Thus, flumazenil provides a safe and 
effective means of attenuating or reversing the CNS-depressant effects of 
benzodiazepines whenever indicated, e.g. following benzodiazepine-induced 
general anaesthesia, conscious sedation, or after benzodiazepine overdose, 
either alone or in combination with other agents.(ABSTRACT TRUNCATED AT 400 
WORDS)