Pralidoxime

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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

• Organophosphate (OP) poisoning.
• Carbamate poisoning (use in severe cases or if poisoning agent is uncertain).
• Nerve agent poisoning.

Contraindications

• Hypersensitivity.

Mechanism of Action

• Reactivates acetylcholinesterase inhibited by OP or carbamates, provided irreversible binding ("ageing") has not occurred.
• Rapidly reverses nicotinic and muscarinic effects of OP poisoning.
• Often used synergistically with atropine (effective at muscarinic but not nicotinic receptors).
• Muscle strength improvement observed within 10–40 minutes post-administration.

Pharmacokinetics

• Volume of distribution: 0.8 L/kg.
• Over 80% excreted unchanged by kidneys; elimination half-life: 75 minutes.
• Poisoning increases volumes of distribution and half-lives.
• IV infusion (500 mg/hour) reaches target levels (>4 μg/mL) within 15 minutes and maintains them.

Administration

• Critical care environment with full resuscitation facilities.
• Initial dose: 2 g pralidoxime in 100 mL normal saline IV over 15 minutes.
• Infusion: 500 mg/hour (6 g in 500 mL normal saline at 42 mL/hour).
  • Higher rates considered if response is poor.
• Discontinue infusion after 24 hours if the patient is clinically stable, in daylight hours, and under close observation for 24 hours.
• Recommence infusion if OP poisoning symptoms recur.
• Perform rapid red cell anticholinesterase activity assays if available before stopping infusion; repeat after 4–6 hours.

Adverse Drug Reactions

• Mild or minimal effects: Nausea, headache, dizziness, drowsiness, blurred vision, hyperventilation.
• Rapid administration effects: Tachycardia, laryngospasm, muscle rigidity, hypertension, transient neuromuscular blockade.

Specific Considerations

• Pregnancy: Safety not established; use if clinically indicated.
• Paediatrics: Initial dose: 25–50 mg/kg IV; infusion: 10–20 mg/kg/hour.

Handy Tips

• Administration beyond 24 hours is generally ineffective but may be trialed.
• Effectiveness may vary across different OP compounds.

Pitfalls

• Insufficient dose administration.
• Inadequate treatment duration.
• Delayed initiation of therapy.

Controversies

• Clinical benefit of pralidoxime in OP poisoning is debated.
  • Red cell acetylcholinesterase reactivation is established but survival improvement and reduced intubation rates are not.
• Variability in OP responses suggests current dosing may not be optimal.
• Role in carbamate poisoning remains unclear.