FLUMAZENIL
Flumazenil (Romazicon), an
imidazobenzodiaze-pine, is a specific and competitive antagonist of
ben-zodiazepines at benzodiazepine receptors.
Flumazenil is useful in the reversal of
benzo-diazepine sedation and the treatment of benzodiazepine overdose. Although
it promptly (onset <1 min) reverses the hypnotic effects of
benzodiaz-epines, amnesia has proved to be less reliably pre-vented. Some
evidence of respiratory depression may linger despite an alert and awake
appearance. Specifically, tidal volume and minute ventilation return to normal,
but the slope of the carbon diox-ide response curve remains depressed. Effects
in elderly patients appear to be particularly difficult to reverse fully, and
these patients are more prone to resedation.
Rapid administration of flumazenil may
cause anxi-ety reactions in previously sedated patients and symptoms of
withdrawal in those on long-term benzodiazepine therapy. Flumazenil reversal
has been associated with increases in intracranial pres-sure in patients with
head injuries and abnormal intracranial compliance. Flumazenil may induce
seizure activity if benzodiazepines have been given as anticonvulsants or in
conjunction with an over-dose of tricyclic antidepressants. Flumazenil
rever-sal following a midazolam–ketamine anesthetic technique may increase the
incidence of emergence dysphoria and hallucinations. Nausea and vomit-ing are
not uncommon following administration of flumazenil. The reversal effect of
flumazenil is based on its strong antagonist affinity for benzodiazepine receptors.
Flumazenil does not affect the minimum alveolar concentration of inhalation
anesthetics.
Gradual titration of flumazenil is
usually accom-plished by intravenous administration of 0.2 mg/ min until
reaching the desired degree of reversal. The usual total dose is 0.6–1.0 mg.
Because of flu-mazenil’s rapid hepatic clearance, repeat doses may be required
after 1–2 h to avoid resedation and pre-mature recovery room or outpatient
discharge. A continuous infusion (0.5 mg/h) may be helpful in the case of an
overdose of a longer-acting benzodi-azepine. Liver failure prolongs the
clearance of flu-mazenil and benzodiazepines.
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