What is the treatment for organophosphate poisoning?

Treatment of Organophosphate Poisoning

Immediately administer high-dose atropine (1-2 mg IV for adults, doubled every 5 minutes until full atropinization), pralidoxime (1-2 g IV over 15-30 minutes), and benzodiazepines for seizures, while ensuring proper decontamination and airway protection. 1, 2

Immediate Decontamination and Personal Safety

• Healthcare providers must wear proper personal protective equipment (PPE) to prevent secondary contamination. 1
• Remove all contaminated clothing immediately and perform copious irrigation with soap and water (or sodium bicarbonate/alcohol) for dermal exposure. 1, 2
• Decontamination is critical as continuing absorption from skin or gastrointestinal tract can cause fatal relapses even after initial improvement. 2

Airway Management

• Secure the airway early with endotracheal intubation for life-threatening poisoning, as observational data suggests better outcomes with early intubation. 1
• Avoid succinylcholine and mivacurium (cholinesterase-metabolized neuromuscular blockers) as they cause prolonged paralysis in organophosphate poisoning. 1, 2

Atropine Administration (First-Line Antidote)

• Administer atropine immediately after correcting hypoxemia, as atropine given during significant hypoxia can trigger ventricular fibrillation. 2
• Initial adult dose: 1-2 mg IV (0.02-0.1 mg/kg for children), doubled every 5 minutes until full atropinization is achieved. 1, 2
• Full atropinization endpoints: cessation of bronchorrhea, bronchospasm, and bradycardia. 1, 2
• Continue doubling doses until secretions are inhibited or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching). 2
• Maintain atropinization for at least 48-72 hours via continuous infusion, as symptoms can recur with ongoing absorption. 1, 2
• High-dose atropine therapy is essential—case reports document successful treatment requiring up to 11.6 grams over 12 days. 3

Pralidoxime (2-PAM) Administration

• Administer pralidoxime early (Class 2a recommendation, Level A evidence) at 1-2 g IV over 15-30 minutes for adults, preferably as an infusion in 100 mL normal saline. 1, 2
• If pulmonary edema is present, give slowly over at least 5 minutes as a 50 mg/mL solution. 2
• Maintenance dosing: 400-600 mg/hour continuous infusion for adults (10-20 mg/kg/hour for children) to maintain therapeutic plasma levels above 4 µg/mL. 1, 2
• Pralidoxime is most effective when given early, before "aging" of the phosphorylated enzyme occurs (typically within 36 hours of exposure). 1, 2
• Continuous infusion maintains therapeutic levels longer than intermittent boluses (257.5 vs. 118 minutes above 4 µg/mL). 2
• Do not withhold pralidoxime when the class of poison (organophosphate vs. carbamate) is unknown. 1
• Combination therapy with atropine and pralidoxime significantly improves survival compared to atropine alone. 4, 5

Seizure and Agitation Management

• Administer benzodiazepines (diazepam or midazolam) for seizures and agitation. 1
• Benzodiazepines may also facilitate mechanical ventilation when needed. 1

Medications to Avoid

• Avoid morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers in organophosphate poisoning. 2
• Avoid succinylcholine and mivacurium (cholinesterase-dependent neuromuscular blockers). 1, 2

Monitoring and Duration of Care

• Monitor all patients for at least 48-72 hours, as delayed muscle weakness can occur up to 4 days after acute exposure. 1, 2
• Titrate pralidoxime dosing based on recurrence of symptoms—additional doses may be needed every 3-8 hours or 10-12 hours if muscle weakness persists. 2
• Watch for complications including myonecrosis, rhabdomyolysis, and renal damage from calcium overload in skeletal muscle. 1
• Monitor for depressed blood cholinesterase activity and maintain atropinization until enzyme activity reverses. 2

Critical Pitfalls to Avoid

• Underdosing atropine is the most common error—aggressive, high-dose atropine is required and should not be limited by conventional dosing concerns. 3
• Failure to recognize ongoing absorption from the gastrointestinal tract can lead to fatal relapses after initial improvement. 2
• Administering atropine before correcting hypoxemia risks ventricular fibrillation. 2
• Delaying pralidoxime beyond 36 hours significantly reduces efficacy due to enzyme "aging." 2
• Hospitals must maintain sufficient stocks of atropine and pralidoxime, as individual patients may require gram quantities. 3

Special Considerations

• Organophosphates cause permanent inactivation of acetylcholinesterase through covalent bonding ("aging"), while carbamates spontaneously dissociate—however, treatment should not be delayed to differentiate between the two. 1
• Male gender, age >50 years, and certain treatment patterns are independently associated with higher mortality. 5
• Continuous pralidoxime infusion maintains therapeutic levels more effectively than intermittent dosing, with plasma levels of 11-17 µg/mL achieved at infusion rates of 400-600 mg/hour. 2