What is the treatment for organophosphorus poisoning?

Treatment of Organophosphorus Poisoning

Immediate Life-Saving Interventions

Atropine should be administered immediately at 1-2 mg IV for adults (0.02 mg/kg for children, minimum 0.1 mg, maximum single dose 0.5 mg) for severe poisoning manifestations such as bronchospasm, bronchorrhea, seizures, or significant bradycardia, with doses doubled every 5 minutes until full atropinization is achieved. 1

Critical First Steps (Within Minutes)

• Personal protective equipment must be worn by all healthcare providers to prevent secondary contamination 1, 2

• Immediate dermal decontamination through removal of all contaminated clothing and copious irrigation with soap and water (or sodium bicarbonate/alcohol) is essential for external exposure 1, 3

• Secure airway, breathing, and circulation as the absolute first priority, with early endotracheal intubation recommended for life-threatening organophosphate poisoning 1, 2

• Atropine must be given only after hypoxemia is improved, as atropine should not be administered in the presence of significant hypoxia due to risk of ventricular fibrillation 3

Atropinization Protocol

• Initial adult dose: 2-4 mg IV (some guidelines recommend 1-2 mg, but FDA labeling supports 2-4 mg) 3

• Pediatric dose: 0.02 mg/kg IV/IO (minimum 0.1 mg, maximum single dose 0.5 mg), but higher doses than standard pediatric resuscitation are often required 1

• Double the dose every 5 minutes until bronchorrhea, bronchospasm, and bradycardia resolve 1, 3

• Therapeutic endpoints include: dry lungs, adequate oxygenation, dry skin and mucous membranes, mydriasis, and inhibition of secretions 1, 3

• Maintain atropinization for at least 48-72 hours until depressed blood cholinesterase activity is reversed 1, 3

Critical Pitfall: Atropine-Induced Tachycardia

• Tachycardia is NOT a contraindication to continued atropine administration - it is an expected pharmacologic effect and the therapeutic endpoint is control of life-threatening muscarinic symptoms, not heart rate 1

• The tachycardia may actually result from nicotinic receptor overstimulation from the organophosphate itself, not the atropine 1

• In children, tachycardia is even less concerning and atropine should never be stopped based on tachycardia alone 1

Oxime Therapy (Pralidoxime)

Pralidoxime should be administered early (Class 2a recommendation, Level A evidence) to reactivate acetylcholinesterase before "aging" of the phosphorylated enzyme occurs, and should not be withheld when the class of poison is unknown. 1

Pralidoxime Dosing

• Initial adult dose: 1-2 g IV administered slowly, preferably by infusion over 30 minutes 1, 3

• Maintenance therapy: 400-600 mg/hour continuous infusion for adults 1

• Pediatric dose: 10-20 mg/kg/hour continuous infusion 1

• Treatment is most effective if initiated immediately and generally little is accomplished if given more than 36 hours after termination of exposure 3

Mechanism and Timing

• Pralidoxime reactivates acetylcholinesterase by competing with the bond between organophosphates and the enzyme, restoring normal enzyme activity 1

• Must be given early before "aging" occurs - organophosphates form a permanent covalent bond with acetylcholinesterase over time 1

• Pralidoxime reverses nicotinic effects (muscle weakness, fasciculations) that atropine cannot address 1

Important Considerations

• Pralidoxime alone is insufficient - atropine must always be administered concurrently as pralidoxime does not manage respiratory depression 1

• Despite some studies questioning efficacy, the American Heart Association maintains a Class 2a recommendation for pralidoxime use 1

• Continuous infusion maintains therapeutic plasma levels (>4 µg/mL) longer than intermittent bolus dosing 3

Airway Management

• Early endotracheal intubation is recommended for life-threatening organophosphate poisoning, with observational data suggesting better outcomes 1

• Avoid succinylcholine and mivacurium - these neuromuscular blockers are metabolized by cholinesterase and can cause prolonged paralysis 1, 3

• Patients should be considered to have a "full stomach" requiring rapid sequence induction with appropriate precautions 2

Seizure and Agitation Management

• Benzodiazepines (diazepam or midazolam) should be administered to treat seizures and agitation 1, 2, 3

• Benzodiazepines are essential for seizure control and to facilitate mechanical ventilation if needed 1

Monitoring and Ongoing Care

Duration of Observation

• Patients must be monitored for at least 48-72 hours after exposure 1, 3

• Continuing absorption from the lower bowel after ingestion constitutes new exposure and fatal relapses have been reported after initial improvement 3

• Additional doses of pralidoxime may be needed every 3-8 hours if signs of poisoning recur - the patient should be "titrated" with pralidoxime as long as symptoms persist 3

Delayed Complications

• Monitor for delayed muscle weakness (intermediate syndrome) which can occur as late as 4 days after acute exposure, even after initial improvement 1, 2

• Watch for myonecrosis, rhabdomyolysis, and renal damage due to calcium overload in skeletal muscle 1

Continuous Monitoring

• Continuous cardiac monitoring for dysrhythmias 1

• Serial respiratory assessments to auscultate for bronchorrhea resolution 1

• Monitor for signs of adequate atropinization versus atropine toxicity (delirium, hyperthermia, muscle twitching) 3

Medications to Avoid

• Do NOT use: morphine, theophylline, aminophylline, reserpine, or phenothiazine-type tranquilizers in organophosphate poisoning 3

• Avoid succinylcholine and mivacurium due to prolonged paralysis risk 1, 3

Supportive Care

• Correction of metabolic abnormalities 3

• Judicious fluid administration for potential hypovolemia 2

• External cooling measures if hyperthermia develops 4

• Bladder catheterization for urinary retention 4

Gastric Decontamination

• Gastric lavage should only be undertaken once the patient is stable and airway is protected 5

• Activated charcoal may be considered if recent oral ingestion and airway is secured 4

Emerging Therapies

While atropine, pralidoxime, and benzodiazepines remain the cornerstone of treatment 1, several adjunctive therapies show promise but require larger phase III trials to establish efficacy, including magnesium sulfate, sodium bicarbonate alkalinization, and bioscavengers 6, 7. However, these should not delay or replace standard therapy with the established three-drug regimen.