What is the management of organophosphate (OP) poisoning?

Management of Organophosphate Poisoning

Immediately administer atropine 1-2 mg IV (0.02 mg/kg in children), doubling the dose every 5 minutes until bronchorrhea, bronchospasm, and bradycardia resolve, while simultaneously giving pralidoxime 1-2 g IV (loading dose) followed by continuous infusion of 400-600 mg/hour, and perform early endotracheal intubation for life-threatening poisoning. 1, 2, 3

Immediate Decontamination and Safety

• Remove all contaminated clothing and perform copious irrigation with soap and water immediately to prevent further absorption and protect healthcare workers from secondary exposure. 1, 2
• Healthcare workers must wear personal protective equipment (PPE) when handling patients or gastric contents, as documented cases exist of providers requiring atropine, pralidoxime, and intubation after secondary exposure. 2
• Avoid gastric lavage unless absolutely necessary due to high risk of secondary exposure to staff from contaminated gastric contents. 2

Atropine Therapy: The Primary Life-Saving Intervention

Atropine is a Class 1 recommendation with Level A evidence and must be given immediately for severe manifestations. 1, 2

Dosing Algorithm

• Adults: Start with 1-2 mg IV, doubling every 5 minutes until full atropinization is achieved. 1, 2, 3
• Children: 0.02 mg/kg IV/IO initially (minimum 0.1 mg, maximum single dose 0.5 mg), but higher doses than standard pediatric resuscitation are required for organophosphate poisoning. 2
• Do not stop atropine due to tachycardia - this is an expected pharmacologic effect and NOT a contraindication to continued administration. 2
• Do not withhold atropine due to fever - atropine-induced fever is expected with high-dose therapy, and the risk of undertreating organophosphate poisoning far exceeds the risk of fever. 2

Endpoints of Atropinization

• Dry lungs (resolution of bronchorrhea on auscultation) 2
• Adequate oxygenation 2
• Dry skin and mucous membranes 2
• Mydriasis 2
• Systolic blood pressure >80 mmHg 4
• Pulse >80 beats/min 4

Maintenance Therapy

• Continue atropine infusion to maintain atropinization for at least 48-72 hours until depressed cholinesterase activity reverses. 1, 3
• Atropine does NOT reverse nicotinic effects (muscle weakness, paralysis) or prevent intermediate syndrome - it only blocks muscarinic overstimulation. 1, 5

Pralidoxime (Oxime) Therapy

Pralidoxime carries a Class 2a recommendation with Level A evidence and should be administered early before "aging" occurs. 1, 2, 3

Dosing Protocol

• Loading dose: 1-2 g IV administered slowly over 15-30 minutes, preferably as infusion in 100 mL normal saline. 1, 2, 3
• If pulmonary edema present: Give slowly over at least 5 minutes as 50 mg/mL solution (e.g., 1000 mg in 20 mL water). 3
• Maintenance: 400-600 mg/hour continuous infusion for adults (10-20 mg/kg/hour for children). 2, 3
• Second dose: 1000-2000 mg may be given after 1 hour if muscle weakness persists. 3
• Additional doses: Every 10-12 hours if muscle weakness continues. 3

Critical Timing

• Most effective when given early before organophosphate-acetylcholinesterase bond "ages" (becomes permanent). 2, 6
• Do not withhold oximes when the class of poison is unknown (organophosphate vs. carbamate). 2
• Little benefit if given more than 36 hours after exposure termination. 3

Mechanism and Limitations

• Pralidoxime reactivates acetylcholinesterase enzyme, reversing nicotinic effects including respiratory and skeletal muscle weakness. 1, 2
• Pralidoxime alone is insufficient - always administer concurrently with atropine. 2
• Does NOT prevent intermediate syndrome despite adequate dosing and continuous infusion. 5

Airway Management

Early endotracheal intubation is recommended for life-threatening organophosphate poisoning, with observational data suggesting better outcomes. 1, 2

Neuromuscular Blocker Selection

• AVOID succinylcholine and mivacurium - these are metabolized by cholinesterase and will have prolonged effects. 1, 5, 2, 3
• Consider rocuronium at doses slightly above normal due to mild vagolytic effect and lack of cholinesterase-dependent metabolism. 5

Seizure and Agitation Management

• Administer benzodiazepines (diazepam or midazolam) for seizures and agitation. 1, 2
• Benzodiazepines are essential for preventing and treating CNS effects of organophosphate poisoning. 1

Monitoring and Observation Period

All patients must be observed in intensive care for at least 48-96 hours, regardless of initial clinical improvement. 5, 3

Why Extended Monitoring is Critical

• Intermediate syndrome (IMS) can develop 24-96 hours after initial cholinergic crisis, even after apparent resolution of symptoms. 5
• Continuing absorption from lower bowel after ingestion constitutes new exposure, and fatal relapses have been reported. 3
• IMS presents with weakness of proximal limb muscles, neck flexors, and respiratory muscles, potentially progressing to complete respiratory failure. 5

Monitoring Parameters

• Continuous cardiac monitoring for dysrhythmias 2
• Serial respiratory assessments for bronchorrhea resolution 2
• Creatine kinase and potassium levels for rhabdomyolysis detection 5, 7
• Methemoglobin level if sudden hemoglobin drop or cyanosis resistant to oxygen therapy occurs 7
• Repetitive nerve stimulation (RNS) testing provides objective early detection of IMS before clinical signs appear 5

Management of Intermediate Syndrome

The primary treatment for IMS is supportive respiratory care with mechanical ventilation - neither atropine nor pralidoxime effectively prevents or reverses this complication once it develops. 5

• Early intubation and mechanical ventilation is the life-saving intervention, as respiratory failure is the primary cause of mortality. 5
• Continue atropine and pralidoxime during IMS phase to manage residual cholinergic effects, but recognize these will not reverse neuromuscular weakness. 5
• Monitor for complications including aspiration pneumonia, sepsis, rhabdomyolysis, and renal failure. 5

Management of Complications

Rhabdomyolysis

• Results from excessive acetylcholine causing calcium flux into skeletal muscle, leading to myocyte death. 5, 7
• Reddish urine is from myoglobin (muscle breakdown), not hemoglobin - crucial distinction. 5, 7
• Treatment: Adequate hydration, forced diuresis, and urine alkalinization. 5, 7

Methemoglobinemia

• Check if chocolate-brown blood or oxygen saturation discrepancy between pulse oximetry and arterial blood gas. 7
• If methemoglobin >20%: Administer methylene blue 1-2 mg/kg IV over 3-5 minutes (Class 1 recommendation, Level B-NR evidence). 7
• Do NOT give methylene blue if G6PD deficiency present - consider exchange transfusion instead. 7

Hemolysis

• Organophosphates can induce direct hemolytic effects through oxidative stress, ROS generation, and calcium overload. 7
• Supportive care with blood transfusion if hemoglobin continues to drop or patient is symptomatic. 7

Medications to AVOID

• Morphine 3
• Theophylline and aminophylline 3
• Reserpine 3
• Phenothiazine-type tranquilizers 3
• Succinylcholine and mivacurium (prolonged paralysis) 1, 5, 2, 3

Clinical Pitfalls to Avoid

• Never delay antidote administration - atropine and pralidoxime must be given immediately, not after considering other interventions. 2
• Never stop atropine for tachycardia or fever - these are expected effects and stopping risks fatal undertreatment. 2
• Never discharge before 48-72 hours observation - intermediate syndrome can develop after apparent recovery. 5, 3
• Never use standard pediatric atropine doses - children require relatively higher doses for organophosphate poisoning. 2
• Never handle gastric contents without PPE - secondary exposure can cause severe poisoning in healthcare workers. 2