What is the recommended management of organophosphate (OP) poisoning?

Organophosphate Poisoning Treatment

Immediately administer atropine 1-2 mg IV for adults (0.02 mg/kg for children, minimum 0.1 mg, maximum 0.5 mg per dose), doubling the dose every 5 minutes until full atropinization is achieved, while simultaneously giving pralidoxime 1-2 g IV loading dose followed by continuous infusion, along with benzodiazepines for seizures and early intubation for life-threatening cases. 1, 2

Initial Resuscitation and Decontamination

• Ensure all healthcare workers wear personal protective equipment (PPE) before patient contact to prevent secondary contamination—documented cases show providers requiring atropine, pralidoxime, and intubation after exposure to contaminated gastric contents. 1

• Remove all contaminated clothing and perform copious irrigation with soap and water immediately for any dermal exposure. 1, 3

• Secure airway, breathing, and circulation first—early endotracheal intubation is recommended for life-threatening poisoning with bronchorrhea, bronchospasm, or altered mental status. 1, 2

• Avoid succinylcholine and mivacurium for intubation—these neuromuscular blockers are metabolized by cholinesterase and are absolutely contraindicated in organophosphate poisoning. 1, 3, 4

Atropine Dosing Protocol

Initial Bolus Dosing

• Start with 1-2 mg IV for adults (0.02 mg/kg for children, minimum 0.1 mg, maximum 0.5 mg per dose) immediately upon recognition of severe poisoning. 1, 2

• Double the dose every 5 minutes until full atropinization is achieved—this is not a fixed-dose schedule but an aggressive escalation protocol. 1, 2

Atropinization Endpoints

• Clear chest on auscultation (resolution of bronchorrhea) 1, 2
• Heart rate >80 beats/min 1, 2
• Systolic blood pressure >80 mm Hg 1, 2
• Dry skin and mucous membranes 1, 2
• Mydriasis 1, 2

Expected Atropine Requirements

• Typical cumulative dose is 10-20 mg within the first 2-3 hours; some patients require up to 50 mg in the first 24 hours. 1

• Once atropinization is achieved, maintain with continuous infusion at 10-20% of the total loading dose per hour, not exceeding 2 mg/hour in adults. 1

Critical Atropine Management Principles

• Never stop or reduce atropine due to tachycardia—atropine-induced tachycardia is an expected pharmacologic effect and is NOT a contraindication to continued administration. 1, 2

• The tachycardia may originate from nicotinic receptor overstimulation by the organophosphate itself, not from atropine. 1, 2

• The risk of undertreating organophosphate poisoning far exceeds the risk of atropine-induced tachycardia—inadequate atropinization leads to respiratory failure and death. 1, 2

• Do not withhold atropine due to fever—repeated atropine administration produces central nervous system effects including fever, but this does not indicate treatment failure. 1

Pralidoxime (2-PAM) Administration

Dosing and Timing

• Give pralidoxime 1-2 g IV loading dose for adults (25-50 mg/kg for children) over 15-30 minutes, followed by continuous infusion of 400-600 mg/hour for adults (10-20 mg/kg/hour for children). 1, 4

• Administer pralidoxime as early as possible—ideally within minutes to hours after exposure, before the organophosphate-acetylcholinesterase complex "ages" and becomes irreversible. 1

• The therapeutic window varies by agent: for nerve agents like soman, aging occurs within minutes; for agricultural organophosphates like dimethoate, a window of up to 24 hours exists, but efficacy drops by roughly 50% after 6 hours. 1

Mechanism and Rationale

• Pralidoxime reactivates acetylcholinesterase by competing with the covalent bond between organophosphate and enzyme, restoring normal neuromuscular transmission at nicotinic receptors. 1

• Atropine alone is insufficient—it addresses muscarinic effects but has minimal impact on nicotinic-mediated muscle paralysis and respiratory failure; only oximes reverse these life-threatening nicotinic effects. 1

• The American Heart Association gives pralidoxime a Class 2a recommendation with Level A evidence, meaning "it is reasonable to use" with high-quality evidence supporting efficacy. 1

Safety Considerations

• Pralidoxime may cause transient hypotension, reduced cardiac output, dizziness, blurred vision, diplopia, headache, nausea, tachycardia, and muscle rigidity, especially when administered rapidly as a bolus. 1

• Mild, transient hepatic enzyme elevations have been observed with higher doses, but these are generally not clinically significant and do not require dose modification. 1

Benzodiazepine Therapy

• Administer diazepam 0.2 mg/kg IV or midazolam 0.05-0.1 mg/kg IV in fractionated doses for seizures or agitation. 1, 2, 3

• Benzodiazepines are essential for seizure control and to facilitate mechanical ventilation in severe cases. 1

Gastric Decontamination

• Perform gastric lavage with nasogastric tube only with full PPE—healthcare workers handling gastric contents without PPE have developed severe secondary poisoning requiring atropine, pralidoxime, and intubation. 1

• Consider activated charcoal and induced diarrhea for ingested organophosphates to prevent continued absorption from the gastrointestinal tract. 5

• When the poison has been ingested, additional doses of pralidoxime may be needed every 3-8 hours due to continuing absorption from the lower bowel—fatal relapses have been reported after initial improvement. 4

Monitoring and Supportive Care

• Maintain close observation for at least 48-72 hours—delayed complications and relapses can occur, especially with ingested organophosphates due to continued absorption from the GI tract. 1, 2, 4

• Monitor for rhabdomyolysis: check creatine kinase and potassium levels, as severe myonecrosis can result from excessive acetylcholine accumulation causing calcium flux into skeletal muscle. 1

• If urine turns reddish (from myoglobin, not hemoglobin), treat rhabdomyolysis with adequate hydration, forced diuresis, and urine alkalinization. 1

• Watch for aspiration pneumonia from bronchorrhea. 3

• Continuous cardiac monitoring to detect dysrhythmias, but do not use heart rate to limit atropine dosing. 1, 2

Carbamate vs. Organophosphate Poisoning

• Organophosphates form a covalent bond with acetylcholinesterase causing permanent inactivation ("aging"), while carbamates spontaneously dissociate from the enzyme. 1

• Do not withhold pralidoxime when the class of poison is unknown—organophosphate and carbamate poisoning are clinically indistinguishable, and organophosphates require early oxime therapy. 1, 3

• The role of pralidoxime in carbamate poisoning is less clear, but the American Heart Association recommends not withholding it when uncertainty exists. 1

Common Pitfalls to Avoid

• Never delay atropine administration—it is the immediate life-saving intervention with Class 1, Level A evidence. 2, 3

• Never underdose atropine—organophosphate poisoning requires much higher doses than typical bradycardia treatment (10-20 mg vs. 0.5-1 mg). 1, 2

• Never stop atropine escalation due to tachycardia—the therapeutic endpoint is control of bronchorrhea, bronchospasm, and adequate blood pressure, not heart rate normalization. 1, 2

• Never give atropine in the presence of significant hypoxia—correct hypoxemia first due to the risk of atropine-induced ventricular fibrillation. 4

• Never delay pralidoxime while considering hemodialysis—organophosphates are highly lipophilic and rapidly distribute into tissues, making them poor candidates for extracorporeal removal. 1

• Never use succinylcholine or mivacurium for intubation—these are metabolized by cholinesterase and are contraindicated. 1, 3, 4

• Never allow healthcare workers to handle gastric contents without PPE—organophosphates in emesis and gastric aspirate can cause severe secondary poisoning. 1

Pediatric Considerations

• Children require relatively higher atropine doses compared to standard pediatric resuscitation doses—the standard 0.02 mg/kg may be insufficient and should be escalated aggressively. 1

• In children, tachycardia is even less of a concern than in adults—atropine should not be stopped in the presence of tachycardia in pediatric organophosphate poisoning. 1

• For a 13 kg child, initial atropine dose is 0.26 mg IV (0.02 mg/kg), then double every 5 minutes until full atropinization, with expected total requirements of 10-20 mg in the first 2-3 hours for severe poisoning. 1