Uses
The relatively few uses for a benzodiazepine antagonist ( Table
10-10
) include the diagnostic and therapeutic reversal of the effects of
benzodiazepine receptor agonists.[437]
For diagnostic
use in suspected benzodiazepine overdose, flumazenil may be given in incremental
intravenous doses of 0.2 to 0.5 mg up to 3 mg. If no change in CNS sedation is noted,
it is unlikely that the CNS depression is based solely on benzodiazepine overdose.
More commonly in anesthesia, flumazenil is used to reverse the sedation of a patient
who remains depressed after the administration of a benzodiazepine for conscious
sedation
*The
dose required to reverse each benzodiazepine (BZD) depends on the residual amount
of BZD and the particular BZD (i.e., higher doses are required for more potent BZDs)
(see text).
†The
degree of reversal should be titrated by repeating the 0.2-mg increment every 1 to
2 minutes until the desired level of reversal is achieved.
or for general anesthesia. Flumazenil reliably reverses the sedation, respiratory
depression, and amnesia induced by benzodiazepines. However, there is now evidence
of differential reversal effects on the different agonist actions. Thus, flumazenil
tends to reverse the hypnotic and respiratory effects more than the amnesic effects
of the agonist benzodiazepines.[434]
[438]
[439]
Dosage guidelines are presented in Table
10-10
, but it must be emphasized that large-scale dosing studies have not
yet been completed. The dose varies with the particular benzodiazepine being reversed,
and the duration of reversal is dependent on the kinetics of both the agonist and
flumazenil. Surveillance is recommended if a long-lasting benzodiazepine is reversed
with a single administration of flumazenil because of its relatively short-lived
effect. Flumazenil may be administered by continuous infusion to prevent resedation
with longer-lasting benzodiazepine receptor agonists. It is postulated that the
availability of flumazenil will extend the usefulness of benzodiazepine agonists,
although it will not necessarily alter the safety of this class of drugs.
