What are the WHO guidelines for managing suspected organophosphate poisoning?

Management of Organophosphate Poisoning

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 performing urgent decontamination with appropriate personal protective equipment. 1, 2

Critical Initial Actions

Personal Protection and Decontamination

• Healthcare workers must wear full personal protective equipment before patient contact, as secondary exposure from contaminated clothing, skin, and gastric contents has caused severe poisoning requiring atropine, pralidoxime, and intubation in exposed staff 2
• Immediately remove all contaminated clothing and perform copious irrigation with soap and water for any external exposure 1, 2
• Never allow staff to handle gastric contents or perform gastric lavage without PPE—documented cases show healthcare workers developing severe cholinergic crisis requiring 24 hours of mechanical ventilation from secondary exposure 2

Airway Management

• Perform early endotracheal intubation for life-threatening poisoning, particularly when bronchorrhea, bronchospasm, altered mental status, or respiratory muscle weakness threatens airway protection 1, 2, 3
• Absolutely avoid succinylcholine and mivacurium for intubation—these neuromuscular blockers are metabolized by cholinesterase and are contraindicated in organophosphate poisoning 1, 2, 3

Atropine Therapy Protocol

Initial Dosing and Escalation

• Adults: 1-2 mg IV immediately; Children: 0.02 mg/kg IV (minimum 0.1 mg, maximum 0.5 mg per single dose) 1, 2, 3
• Double the dose every 5 minutes until full atropinization is achieved—this is not a fixed-dose schedule but an aggressive escalation protocol 2, 3
• Typical cumulative requirements are 10-20 mg in the first 2-3 hours, with severe cases requiring up to 50 mg in the first 24 hours 2

Atropinization Endpoints

• Clear chest on auscultation (resolution of bronchorrhea) 2, 3
• Heart rate >80 beats/min 2, 3
• Systolic blood pressure >80 mmHg 2, 3
• Dry skin and mucous membranes 2, 3
• Mydriasis 2, 3

Maintenance Therapy

• Once atropinization is achieved, continue atropine as continuous infusion at 10-20% of the total loading dose per hour, not exceeding 2 mg/hour in adults 2

Critical Management Principle for Tachycardia

• Atropine-induced tachycardia is an expected pharmacologic effect and is NOT a contraindication to continued atropine administration 2, 3
• The tachycardia may originate from nicotinic receptor overstimulation by the organophosphate itself, not from atropine 2, 3
• Never withhold or reduce atropine due to tachycardia—the risk of undertreating organophosphate poisoning (leading to respiratory failure and death) far exceeds the risk of atropine-induced tachycardia 2, 3
• The therapeutic endpoint is control of life-threatening muscarinic symptoms (bronchorrhea, bronchospasm, adequate blood pressure), not heart rate normalization 2, 3

Pralidoxime (Oxime) Therapy

Dosing Protocol

• Adults: 1-2 g IV loading dose administered slowly over 15-30 minutes, followed by continuous infusion of 400-600 mg/hour 1, 2
• Children: 25-50 mg/kg IV loading dose over 15-30 minutes, followed by continuous infusion of 10-20 mg/kg/hour 2
• 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, 2

Timing Considerations

• Administer pralidoxime as early as possible—ideally within minutes to hours after exposure, before the organophosphate-acetylcholinesterase complex "ages" and becomes irreversible 2
• For nerve agents like soman, aging occurs within minutes; for agricultural organophosphates (e.g., dimethoate), a therapeutic window of up to 24 hours exists, but efficacy drops by approximately 50% after 6 hours 2
• Do not withhold oximes when the class of poison (organophosphate versus carbamate) is unknown—organophosphate and carbamate poisoning are clinically indistinguishable, and organophosphate poisoning requires early oxime therapy 1, 2, 4

Mechanism and Rationale

• Pralidoxime reactivates acetylcholinesterase by competing with the covalent bond between organophosphate molecules and the enzyme, thereby restoring normal neuromuscular transmission 2
• Atropine does not reverse nicotinic effects (muscle weakness, paralysis, respiratory failure)—only oximes can reverse these life-threatening nicotinic manifestations 2, 3
• Pralidoxime must always be given concurrently with atropine, as pralidoxime alone is insufficient to manage respiratory depression 1, 2

Seizure Management

• Administer benzodiazepines for seizures and agitation—diazepam is first-line, or midazolam as alternative 1, 2, 3
• Adults: Diazepam 5-10 mg IV or midazolam 2-5 mg IV in fractionated doses 2
• Children: Diazepam 0.2 mg/kg IV or midazolam 0.05-0.1 mg/kg IV in fractionated doses 2

Monitoring and Complications

Duration of Observation

• Monitor closely for at least 48-72 hours, as delayed complications and relapses can occur, especially with ingested organophosphates due to continued absorption from the gastrointestinal tract 2, 3

Specific Complications to Monitor

• Intermediate syndrome: Delayed muscle weakness occurring 24-96 hours after acute exposure, manifesting as respiratory muscle weakness, proximal limb weakness, and cranial nerve palsies 2, 5
• Aspiration pneumonia: From bronchorrhea and altered mental status 2, 4, 5
• Rhabdomyolysis: Severe myonecrosis from excessive acetylcholine causing calcium flux into skeletal muscle, leading to myocyte death—monitor creatine kinase and potassium levels 2
• Myoglobinuric renal failure: Reddish urine from myoglobin (not hemoglobin) requires adequate hydration, forced diuresis, and urine alkalinization 2
• Atropine-induced fever and hallucinations: Expected adverse effects with high-dose atropine therapy that do not indicate treatment failure—never withhold atropine due to fever 2

Monitoring Parameters

• Continuous cardiac monitoring for dysrhythmias (not to limit atropine dosing) 2, 3
• Serial respiratory assessments every 5-10 minutes during escalation phase 3
• Creatine kinase and potassium for rhabdomyolysis detection 2
• Watch for increasing respiratory rate (e.g., from 22 to 38 breaths/min) as an important sign of impending respiratory distress requiring immediate intubation 5

Common Pitfalls to Avoid

• Never delay atropine administration—it is the immediate life-saving intervention with Class 1, Level A evidence 1, 3, 4
• Never underdose atropine—organophosphate poisoning requires much higher doses than typical bradycardia treatment (10-20 mg in first 2-3 hours versus 0.5-1 mg for bradycardia) 2, 3
• Never stop atropine escalation due to tachycardia—this is an expected effect and inadequate atropinization leads to death 2, 3
• Never delay intubation in patients with intermediate syndrome—three deaths occurred in one series due to delayed recognition of respiratory distress 5
• Never use succinylcholine or mivacurium for intubation—these are absolutely contraindicated 1, 2, 3, 4
• Never withhold pralidoxime when poison class is unknown—give it empirically as organophosphate and carbamate poisoning are clinically indistinguishable 1, 2, 4

Special Considerations for Carbamate Poisoning

• The management algorithm is identical to organophosphate poisoning: atropine, benzodiazepines, decontamination, and supportive care 4
• The role of pralidoxime in carbamate poisoning is less clear (carbamates spontaneously dissociate from acetylcholinesterase), but pralidoxime should not be withheld when the poison class is unknown 1, 2, 4
• Carbamates do not cause "aging" of the acetylcholinesterase enzyme, unlike organophosphates 1, 4