Flumazenil

#completed #carded

Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

Presentations

• Flumazenil 0.5 mg/5 mL ampoules.

Toxicological Indications

• Benzodiazepine overdose:
  • Accidental paediatric ingestion with airway or breathing compromise.
  • Deliberate self-poisoning with airway or breathing compromise when intubation is not feasible (rare).
  • Note: Isolated benzodiazepine overdose rarely necessitates intervention.
• Diagnostic use: To confirm benzodiazepine intoxication if it avoids invasive/expensive diagnostics.
• Reversal of procedural sedation: Used to reverse benzodiazepine-induced sedation.

Contraindications

• Known seizure disorder.
• Suspected co-ingestion of pro-convulsant drugs.
• Known or suspected benzodiazepine dependence.
• ECG QRS prolongation (may indicate tricyclic antidepressant co-ingestion).

Mechanism of Action

• Structurally similar to midazolam; acts as a competitive antagonist at CNS benzodiazepine receptor sites.
• Inhibits benzodiazepine activity at the GABA–benzodiazepine complex, reversing CNS effects.

Pharmacokinetics

• Volume of distribution: 1 L/kg.
• Rapid hepatic metabolism to inactive metabolites.
• Elimination half-life: 40–80 minutes.
• Pharmacokinetics unchanged after benzodiazepine overdose.

Administration

General

• Administer only in settings with seizure management capability.

Dosing

• Initial dose: 0.1–0.2 mg IV; repeat every minute until sedation reversal occurs.
• Maximum dose: 2 mg.
• Re-sedation: Anticipated at ~90 minutes; repeat doses or infusion may be needed.
• Paediatric dose: 0.01–0.02 mg/kg IV, repeated every minute as necessary.
• Observe for re-sedation several hours post-administration.

Adverse Drug Reactions

Benzodiazepine Withdrawal Syndrome

• Symptoms: Agitation, tachycardia, seizures.
• Management:
  • Mild withdrawal: Typically self-limiting.
  • Severe withdrawal: Treat with titrated benzodiazepine doses.

Seizures

• Most common in benzodiazepine-dependent patients, co-ingestion of pro-convulsants, or pre-existing seizure disorders.
• Management:
  • Withhold further flumazenil.
  • Treat recurrent/prolonged seizures with titrated benzodiazepines.

Specific Considerations

• Pregnancy: Safety not established; administer if clinically necessary.
• Paediatric use: Safe, especially as dependence is unlikely.

Handy Tip

• Flumazenil may be critical in settings lacking definitive airway control capabilities.

Pitfalls

• Unnecessary use in mild benzodiazepine poisoning.
• Use despite contraindications (e.g., seizure risk).
• Failure to monitor for re-sedation.

Controversy

• Role in managing undifferentiated overdose patients.