What is the treatment for a patient with organophosphorus poisoning?

Treatment of Organophosphorus Poisoning

Immediate administration of high-dose atropine is the cornerstone of treatment, starting with 1-2 mg IV in adults (0.02 mg/kg in children, minimum 0.1 mg), doubling the dose every 5 minutes until full atropinization is achieved, combined with pralidoxime, benzodiazepines for seizures, and early intubation for severe cases. 1, 2

Immediate Decontamination and Safety

• Healthcare providers must wear personal protective equipment (PPE) before patient contact to prevent secondary exposure—documented cases exist of 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 dermal exposure 1
• Secure airway, breathing, and circulation as the foundation of management 1

Atropine: First-Line Life-Saving Therapy (Class 1, Level A Evidence)

Initial Dosing

• Adults: 1-2 mg IV immediately upon recognition of severe poisoning (bronchospasm, bronchorrhea, seizures, or significant bradycardia) 1, 2, 3
• Children: 0.02 mg/kg IV/IO (minimum 0.1 mg, maximum single dose 0.5 mg)—note that standard pediatric resuscitation doses are insufficient and higher doses are required 1, 2
• This initial adult dose is substantially higher than the 0.5-1.0 mg used for bradycardia from other causes 2

Dose Escalation Protocol

• Double the dose every 5 minutes until atropinization endpoints are reached—this doubling strategy is critical and differs from fixed-dose repetition 2, 3
• Continue escalation regardless of heart rate—tachycardia is NOT a contraindication to continued atropine administration 2, 3
• Patients may require cumulative doses of 10-20 mg in the first 2-3 hours, with some requiring up to 50 mg in 24 hours 2
• The highest documented dose in clinical practice was 100 mg IV on admission and 100 mg/h/day during follow-up, totaling 11.6 g over 12 days 4

Endpoints of Atropinization (All Must Be Achieved)

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

Maintenance Therapy

• Administer 10-20% of the total loading dose per hour, up to 2 mg/h in adults 2
• Continuous infusion is preferred over intermittent boluses 2
• Maintain some degree of atropinization for at least 48 hours until depressed blood cholinesterase activity is reversed 5
• Repeated doses must be readministered as clinically necessary—restoration of normal enzyme activity may take up to 6 weeks in untreated patients 2

Critical Management Principles for Atropine

• The therapeutic endpoint is control of muscarinic symptoms (bronchorrhea, bronchospasm), NOT heart rate normalization 3
• Tachycardia may originate from nicotinic receptor overstimulation by the organophosphate itself, not from atropine 1, 3
• The risk of undertreating organophosphate poisoning far exceeds the risk of atropine-induced tachycardia—inadequate atropinization leads to respiratory failure and death 3
• Atropine-induced fever is an expected adverse effect with high-dose therapy and does not indicate treatment failure—never withhold or prematurely discontinue atropine due to fever 1

Pralidoxime (2-PAM): Essential Oxime Therapy (Class 2a, Level A Evidence)

Rationale and Timing

• Pralidoxime reactivates acetylcholinesterase by competing with the bond between organophosphates and the enzyme, restoring normal enzyme activity 1
• Most effective when administered early, before "aging" of the phosphorylated enzyme occurs (generally within 36 hours of exposure) 1, 5
• Reverses nicotinic effects (muscle weakness, fasciculations, potentially some tachycardia) that atropine cannot address 1, 3
• Should not be withheld when the class of poison (organophosphate vs. carbamate) is unknown 1

Dosing Regimen

• Adults: 1-2 g IV administered slowly over 15-30 minutes as initial loading dose 1, 3, 5
• If pulmonary edema is present, give slowly over not less than 5 minutes as a 50 mg/mL solution 5
• Maintenance infusion: 400-600 mg/hour for adults or 10-20 mg/kg/hour for children 1, 3
• A second dose of 1-2 g may be indicated after about one hour if muscle weakness has not been relieved 5
• Additional doses may be given every 10-12 hours if muscle weakness persists 5

Special Considerations

• Always administer atropine concurrently—pralidoxime alone is insufficient to manage respiratory depression 1
• For ingested organophosphates, additional doses may be needed every 3-8 hours due to continuing absorption from the GI tract, and fatal relapses have been reported after initial improvement 5
• The patient should be "titrated" with pralidoxime as long as signs of poisoning recur 5

Evidence Controversy

• Despite clear red cell acetylcholinesterase reactivation in clinical studies, one large randomized controlled trial (235 patients) found no survival benefit with pralidoxime (mortality 24.8% vs. 15.8% placebo, though not statistically significant) 6
• However, the American Heart Association maintains a Class 2a recommendation based on the biological rationale and other supporting evidence 1
• The failure to demonstrate benefit may relate to dosing regimens, timing of administration, or specific organophosphate compounds involved 6

Airway Management

• Early endotracheal intubation is recommended for life-threatening organophosphate poisoning—observational data suggest better outcomes with early intubation 1, 3
• Mechanical ventilation with positive end-expiratory pressure (PEEP) should be used as indicated 7
• Avoid succinylcholine and mivacurium for intubation—these neuromuscular blockers are metabolized by cholinesterase and are contraindicated 1, 3, 5

Seizure and Agitation Management

• Administer benzodiazepines (diazepam first-line or midazolam) to treat seizures and agitation 1, 3
• Benzodiazepines may also facilitate mechanical ventilation 1

Monitoring and Duration of 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, 3, 5
• Continuous cardiac monitoring to detect dysrhythmias (not to limit atropine dosing) 3
• Serial respiratory assessments every 5-10 minutes during escalation phase 3
• Monitor for delayed muscle weakness (intermediate syndrome), which can occur as late as 4 days after acute exposure 1
• Monitor creatine kinase and potassium levels for rhabdomyolysis detection 1

Complications to Anticipate

Musculoskeletal Complications

• Severe myonecrosis can result from excessive acetylcholine accumulation causing calcium flux into skeletal muscle, leading to myocyte death 1
• Rhabdomyolysis with subsequent myoglobinuria can cause renal damage 1
• Treatment for rhabdomyolysis includes adequate hydration, forced diuresis, and urine alkalinization when urine turns reddish from myoglobin (not hemoglobin) 1

Atropine-Related Adverse Effects

• Central nervous system effects including hallucinations and fever with repeated administration 1
• Fever may have multiple etiologies beyond atropine, including nicotinic effects causing muscle fasciculations and aspiration pneumonia from bronchorrhea 1

Medications to Avoid

• Morphine, theophylline, aminophylline, reserpine, and phenothiazine-type tranquilizers should be avoided 5
• Succinylcholine should be used with caution due to prolonged paralysis when given with anticholinesterase activity 5

Gastric Decontamination Considerations

• Never allow healthcare workers to handle gastric contents without PPE—organophosphates in emesis and gastric aspirate can cause severe secondary poisoning requiring atropine, pralidoxime, and even intubation 1
• Personal protective equipment is mandatory when performing gastric lavage 1

Role of Hemodialysis

• No established role for hemodialysis in organophosphate poisoning 1
• Organophosphates are highly lipophilic compounds that rapidly distribute into tissues and bind covalently to acetylcholinesterase, making them poor candidates for extracorporeal removal 1
• Delaying antidote administration while considering hemodialysis can be harmful—time-critical interventions like atropine and pralidoxime must be given immediately 1