What is the treatment for organophosphorus poisoning?

Treatment of Organophosphorus Poisoning

Immediate Life-Saving Interventions

Atropine is the immediate first-line treatment and should be administered as soon as possible after hypoxemia is improved, starting with 1-2 mg IV for adults (0.02 mg/kg for children, minimum 0.1 mg, maximum single dose 0.5 mg), doubling the dose every 5 minutes until bronchorrhea, bronchospasm, and bradycardia resolve. 1, 2

Critical Initial Steps (First 5 Minutes)

• Ensure personal protective equipment (PPE) before approaching the patient to prevent caregiver contamination 1

• Immediate dermal decontamination by removing all contaminated clothing and copious irrigation with soap and water (or sodium bicarbonate/alcohol) for external exposure 1, 2

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

  • Avoid succinylcholine and mivacurium (neuromuscular blockers metabolized by cholinesterase) as they cause prolonged paralysis 1, 2

• Correct hypoxemia first before giving atropine, as atropine should not be given in the presence of significant hypoxia due to risk of ventricular fibrillation 2

Atropine Dosing Algorithm

Adult Dosing

• Initial dose: 1-2 mg IV (some sources recommend 2-4 mg for severe cases) 1, 2
• Double the dose every 5 minutes until secretions are inhibited (full atropinization) 1, 2
• Do not stop for tachycardia - atropine-induced tachycardia is an expected pharmacologic effect and NOT a contraindication to continued administration 1
• Maintenance atropinization can be achieved by continuous infusion for at least 48-72 hours 1, 2

Pediatric Dosing

• Initial dose: 0.02 mg/kg IV/IO (minimum 0.1 mg, maximum single dose 0.5 mg) 1
• Higher doses than standard pediatric resuscitation are required - standard doses are insufficient 1
• Tachycardia is even less of a concern in children than adults 1

Endpoints of Atropinization

• Dry lungs and adequate oxygenation 1
• Dry skin and mucous membranes 1
• Mydriasis (dilated pupils) 1
• Heart rate is NOT an endpoint - continue despite tachycardia 1

Common Atropine Pitfalls

• Fever is an expected adverse effect with high-dose atropine therapy and does not indicate treatment failure - never withhold or prematurely discontinue atropine due to fever 1
• Undertreating is more dangerous than overtreating - the risk of inadequate atropinization leading to respiratory failure and death far exceeds the risk of atropine toxicity 1
• Maintain some degree of atropinization for at least 48 hours until depressed blood cholinesterase activity is reversed 2

Pralidoxime (2-PAM) Administration

Pralidoxime should be administered early (Class 2a recommendation, Level A evidence) and is most effective before "aging" of the phosphorylated enzyme occurs. 1, 2

Dosing Regimen

• Adult loading dose: 1-2 g IV administered slowly over 5-30 minutes, preferably by infusion 1, 2
• Maintenance therapy: 400-600 mg/hour continuous infusion (or 1 g/hour for 48 hours in moderately severe cases) 1, 3
• Pediatric dosing: 10-20 mg/kg/hour 1

Evidence for High-Dose Continuous Infusion

• A high-dose regimen (1 g/hour continuous infusion for 48 hours after 2 g loading dose) reduces atropine requirements (median 6 mg vs 30 mg in first 24 hours), intubation rates (64% vs 88%), and ventilator days (5 vs 10 days) compared to intermittent bolus dosing 3
• Continuous infusion maintains therapeutic plasma levels (>4 µg/mL) longer than intermittent bolus therapy (257.5 minutes vs 118 minutes) 2

Critical Pralidoxime Considerations

• Always administer atropine concurrently - pralidoxime alone is insufficient to manage respiratory depression 1
• Do not withhold when the class of poison is unknown (organophosphate vs carbamate) 1
• Little is accomplished if given >36 hours after exposure termination, but continue dosing if ongoing absorption from GI tract 2
• Repeat doses every 3-8 hours if signs of poisoning recur, effectively "titrating" the patient 2

Adjunctive Therapies

Benzodiazepines

• Administer for seizures and agitation - diazepam or midazolam are first-line 1
• Also useful to facilitate mechanical ventilation 1

Decontamination

• Gastric lavage or induced vomiting if recent oral ingestion 4
• Consider continuing absorption from lower bowel - fatal relapses have been reported after initial improvement 2

Supportive Care

• Continuous cardiac monitoring for dysrhythmias 1
• Mechanical ventilation with PEEP as needed 5
• IV fluids for volume resuscitation 1
• Monitor for at least 48-72 hours even after apparent recovery 1, 2

Delayed Complications to Monitor

• Intermediate syndrome - delayed muscle weakness occurring up to 4 days after acute exposure 1
• Myonecrosis, rhabdomyolysis, and renal damage from calcium overload in skeletal muscle 1
• Aspiration pneumonia from bronchorrhea 1

Drugs to Avoid

• Morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers should be avoided 2
• Succinylcholine and mivacurium cause prolonged paralysis 1, 2

Treatment Sequence Based on Severity

For severe poisoning (unconsciousness, severe respiratory distress, convulsions):

1. PPE and decontamination
2. Secure airway (early intubation)
3. Correct hypoxemia
4. Atropine 2-4 mg IV, double every 5 minutes
5. Pralidoxime 2 g loading dose, then 1 g/hour infusion
6. Benzodiazepines for seizures

For moderate poisoning (fasciculations, miosis, bronchorrhea without respiratory failure):

1. Decontamination
2. Atropine 1-2 mg IV, titrate to effect
3. Pralidoxime 1-2 g loading dose, then 400-600 mg/hour
4. Close monitoring for deterioration

Contact poison control (1-800-222-1222 in US) for expert guidance on specific case management. 6