Naloxone

#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.

Toxicological Indications

• Reversal of CNS and respiratory depression due to opioid intoxication.
• Empirical treatment for coma suspected to be opioid-related.

Contraindications

• Avoid in opioid-dependent individuals unless:
  • Respiratory rate <8 or significant hypoxia.
  • CNS depression (GCS <12).

Mechanism of Action

• Competitive opioid antagonist at mu, kappa, and delta receptors.
• Reverses sedation, respiratory depression, and hypoxia caused by opioids.

Pharmacokinetics

• Poor oral bioavailability due to extensive first-pass metabolism.
• Rapid distribution and action after IV or IM administration.
• Liver metabolism; elimination half-life: 60–90 minutes.
• Effect duration: 20–90 minutes (varies with dose and agonist kinetics).

Administration

• Monitor respiratory rate, GCS, and oxygen saturation. Prepare for full resuscitation if necessary.
• Initial dose:
  • 100 micrograms IV or 400 micrograms IM/SC if no IV access.
  • Larger doses are safe in non-opioid-dependent patients.
• Repeat 100 micrograms IV every 30–60 seconds until spontaneous respiration is restored.
• Doses >400 micrograms rarely needed for heroin overdose but may be necessary for partial opioid agonists.
• For prolonged opioid effects (e.g., methadone, controlled-release opioids):
  • Naloxone infusion: Start at 2/3 of initial effective dose/hour.
  • Example: Dilute 2 mg naloxone in 100 mL saline, infuse at 5 mL/hour (100 microgram/hour).
• Monitor for withdrawal symptoms; adjust infusion rate based on clinical response.

Therapeutic Endpoints

• In non-opioid-dependent patients: Restore normal mental status.
• In opioid-dependent patients: Maintain adequate airway, respiratory rate, and rousability (GCS 13–14) without full reversal.

Observation Period

• Monitor for re-sedation for at least 2 hours after the last naloxone dose.

Adverse Drug Reactions

• Non-opioid-dependent patients: Minimal adverse effects, even at high doses.
• Opioid-tolerant patients: Dose-dependent withdrawal syndrome (agitation, aggression).
  • Management: Cease naloxone and provide physical/chemical control if necessary. Avoid long-acting sedation as withdrawal is short (<90 minutes).

Specific Considerations

• Pregnancy: Use if clinically indicated. Be cautious of maternal and fetal withdrawal.
• Paediatrics: Safe for suspected opioid intoxication. Use 400-microgram IV bolus for diagnosis.

Handy Tips

• Avoid complete reversal in opioid-dependent patients to prevent withdrawal, which complicates assessment and management.
• Use IV administration for precise dose titration.
• Plan for ongoing naloxone administration in methadone, oxycodone, or controlled-release morphine overdoses.
• Monitor for both re-sedation and withdrawal during naloxone infusion.

Pitfalls

• Acute withdrawal syndrome in opioid-dependent patients.
• Failure to detect re-sedation after initial response.
• Insufficient dose for partial agonist overdoses.

Controversies

• Intranasal/nebulised naloxone: Potentially useful but not validated.
• Other intoxications: No proven benefit for clonidine, alcohol, benzodiazepines, or sodium valproate.