What is the treatment for organophosphate (OP) poisoning with chlorpyrifos?

Treatment of Chlorpyrifos (Organophosphate) Poisoning

Immediate treatment of chlorpyrifos poisoning requires aggressive supportive care with atropine as first-line therapy, followed by pralidoxime (2-PAM), while recognizing that treatment must be initiated within 36 hours of exposure for optimal effectiveness. 1

Immediate Management Algorithm

1. Decontamination and Supportive Care (First Priority)

• Remove all contaminated clothing immediately and wash hair and skin thoroughly with sodium bicarbonate or alcohol to prevent continued dermal absorption 1
• Establish airway management, respiratory support, and cardiovascular stabilization before administering antidotes, as these are critical in severe organophosphate poisoning 1
• Correct metabolic abnormalities and provide seizure control as needed 1

2. Atropine Administration (Second Priority)

Critical timing consideration: Atropine should NOT be given in the presence of significant hypoxia due to risk of atropine-induced ventricular fibrillation 1

• Once hypoxemia is corrected, administer atropine 2-4 mg IV in adults 1
• Repeat atropine every 5-10 minutes until full atropinization is achieved (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching) 1
• Maintain some degree of atropinization for at least 48 hours until depressed blood cholinesterase activity reverses 1

3. Pralidoxime (2-PAM) Administration (Third Priority)

Timing is critical: Pralidoxime is most effective if initiated immediately after poisoning and generally accomplishes little if given more than 36 hours after termination of exposure 1

Adult dosing:

• Initial dose: 1000-2000 mg IV, preferably as infusion in 100 mL normal saline over 15-30 minutes 1
• If infusion not practical or pulmonary edema present, give slowly over at least 5 minutes as 50 mg/mL solution 1
• Second dose of 1000-2000 mg may be given after 1 hour if muscle weakness persists 1
• Additional doses every 10-12 hours if muscle weakness continues 1

Alternative continuous infusion approach:

• Loading dose of 4 mg/kg over 15 minutes, followed by 3.2 mg/kg/hr continuous infusion maintains therapeutic levels (>4 µg/mL) longer than intermittent dosing 1
• Case reports support 400-600 mg/hr continuous infusion rates 1

Critical Monitoring Requirements

Observation Period

• Keep patient under observation for at least 48-72 hours due to risk of fatal relapses 1
• With ingested poison, continuing absorption from lower bowel constitutes new exposure—additional pralidoxime doses may be needed every 3-8 hours 1
• "Titrate" the patient with pralidoxime as long as signs of poisoning recur 1

Clinical Manifestations to Monitor

Mild symptoms: 1

• Miosis (constricted pupils) 2
• Excessive salivation, lacrimation, bronchorrhea 2
• Blurred vision, chest tightness
• Tremors and muscular twitching
• Nausea and vomiting

Severe symptoms: 1

• Severe respiratory difficulty or secretions
• Severe muscular twitching and weakness
• Convulsions
• Unconsciousness
• Involuntary urination and defecation

Medications to AVOID

Do not use the following in organophosphate poisoning: 1

• Morphine
• Theophylline or aminophylline
• Reserpine
• Phenothiazine-type tranquilizers
• Succinylcholine (use with extreme caution only—causes prolonged paralysis with anticholinesterase drugs) 1

Pathophysiology Considerations

• Chlorpyrifos causes irreversible acetylcholinesterase inhibition leading to acetylcholine accumulation and cholinergic syndrome 3, 4, 2
• The toxicity extends beyond simple cholinesterase inhibition to include neuroinflammation and disruption of multiple neurotransmitter systems 3, 4
• Acetylcholinesterase inhibition levels are uninformative regarding neurodevelopmental effects—toxic effects occur at concentrations too low to inhibit cholinesterase 5, 3

Delayed Complications

Be aware of delayed neurological sequelae:

• Chlorpyrifos can cause delayed myelopathy and pure motor neuropathy appearing 6-8 weeks after initial recovery from cholinergic crisis 3
• This results in permanent paralysis at sites of dermal exposure, particularly affecting hands and feet with atrophy and loss of function 3

Common Pitfalls

• Failing to maintain atropinization for full 48 hours leads to relapse 1
• Delaying pralidoxime beyond 36 hours renders it largely ineffective 1
• Giving atropine before correcting hypoxia risks fatal ventricular fibrillation 1
• Underestimating continuing absorption from ingested poison—requires repeated pralidoxime dosing 1
• Premature discharge before 48-72 hour observation period misses fatal relapses 1