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Chapter: Clinical Anesthesiology: Clinical Pharmacology: Adjuncts to Anesthesia

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Flumazenil

Flumazenil (Romazicon), an imidazobenzodiaze-pine, is a specific and competitive antagonist of ben-zodiazepines at benzodiazepine receptors.

FLUMAZENIL

Mechanism of Action

Flumazenil (Romazicon), an imidazobenzodiaze-pine, is a specific and competitive antagonist of ben-zodiazepines at benzodiazepine receptors.

Clinical Uses

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.

Side Eects & Drug Interactions

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.

Dosage

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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