What is the treatment for organophosphorus poisoning?

Treatment of Organophosphorus Poisoning

Immediate atropine administration, pralidoxime, benzodiazepines for seizures, aggressive decontamination, and early intubation form the cornerstone of organophosphate poisoning management, with atropine doses escalated rapidly by doubling every 5 minutes until full atropinization is achieved. 1

Initial Stabilization and Decontamination

Personal Protection and Decontamination

• Healthcare providers must wear appropriate personal protective equipment (PPE) to prevent secondary contamination before approaching the patient 1
• Remove all contaminated clothing immediately and perform copious irrigation with soap and water (or sodium bicarbonate/alcohol) for dermal exposures 1, 2
• Secure airway, breathing, and circulation as the first priority 1

Early Airway Management

• Perform early endotracheal intubation for life-threatening organophosphate poisoning, as observational data suggests better outcomes with early intubation 1
• Avoid succinylcholine and mivacurium for intubation, as these neuromuscular blockers are metabolized by cholinesterase and will have prolonged effects 1, 2
• Use alternative neuromuscular blocking agents if paralysis is required 1

Atropine Therapy (First-Line Treatment)

Initial Dosing

• Administer atropine immediately at 1-2 mg IV for adults (0.02 mg/kg for children, with higher doses of 0.02-0.1 mg/kg acceptable in severe poisoning) 1, 2
• In severe cases with bronchospasm, bronchorrhea, seizures, or significant bradycardia, start with 2-4 mg IV in adults 2
• Do not delay atropine for hypoxemia correction in severe cases, though ideally improve oxygenation first to reduce risk of atropine-induced ventricular fibrillation 2

Dose Escalation Algorithm

• Double the atropine dose every 5 minutes until bronchorrhea, bronchospasm, and bradycardia resolve 1, 2
• Continue escalation until full atropinization is achieved, defined by: dry lungs, adequate oxygenation, dry skin and mucous membranes, and mydriasis 1
• Do not stop atropine administration due to tachycardia—this is an expected pharmacologic effect and NOT a contraindication to continued therapy 1
• Patients may require extraordinarily high doses: case reports document up to 100 mg IV bolus and 100 mg/hour infusions, with total doses reaching 11.6 grams over 12 days 3

Maintenance Therapy

• Maintain some degree of atropinization for at least 48-72 hours and until depressed blood cholinesterase activity reverses 1, 2
• Consider atropine infusion for maintenance after initial bolus dosing achieves atropinization 1
• Continue monitoring for recurrent symptoms, as fatal relapses have been reported after initial improvement, particularly with ingested organophosphates due to continued GI absorption 2

Pediatric Considerations

• Children require 0.02 mg/kg IV/IO initially, with a minimum dose of 0.1 mg and maximum single dose of 0.5 mg 4
• Higher doses may be used with organophosphate poisoning in children—the standard pediatric resuscitation doses are insufficient 4, 1
• Tachycardia is even less concerning in children than adults and should not prompt discontinuation 1

Pralidoxime (Oxime) Therapy

Indications and Timing

• Pralidoxime receives a Class 2a recommendation with Level A evidence from the American Heart Association and should be administered early to reactivate acetylcholinesterase enzyme 1
• Administer pralidoxime after atropine effects become apparent, as pralidoxime alone is insufficient to manage respiratory depression 1, 2
• Do not withhold oximes when the class of poison (organophosphate vs. carbamate) is unknown 1
• Pralidoxime is most effective when given early, before "aging" of the phosphorylated enzyme occurs (generally within 36 hours of exposure) 1, 2

Adult Dosing

• Initial dose: 1-2 grams IV administered slowly over 15-30 minutes, preferably as an infusion in 100 mL normal saline 1, 2
• If infusion is not practical or pulmonary edema is present, give slowly over at least 5 minutes as a 50 mg/mL solution 2
• Maintenance therapy: 400-600 mg/hour continuous infusion for adults 1
• A second dose of 1-2 grams may be given after one hour if muscle weakness persists 2
• Additional doses may be given every 10-12 hours if muscle weakness continues 2

Pediatric Dosing

• Initial dose: 20-50 mg/kg IV (maximum 2 grams) 1
• Maintenance: 10-20 mg/kg/hour continuous infusion 1

Duration and Monitoring

• "Titrate" the patient with pralidoxime as long as signs of poisoning recur, particularly with ingested organophosphates 2
• Pralidoxime has a short half-life (74-77 minutes), and repeated doses are necessary unless continuous infusion is used 2
• Therapeutic plasma levels are maintained above 4 µg/mL with continuous infusion regimens 2

Benzodiazepine Therapy

Indications

• Administer benzodiazepines (diazepam or midazolam) to treat seizures and agitation in organophosphate poisoning 1
• Benzodiazepines are essential adjunctive therapy alongside atropine and pralidoxime 1

Dosing

• Use standard seizure dosing protocols for diazepam or midazolam 1
• Continue as needed for ongoing seizure activity or severe agitation 1

Supportive Care and Monitoring

Respiratory Support

• Provide mechanical ventilation with positive end-expiratory pressure (PEEP) as indicated for respiratory failure 5
• Correct hypoxemia aggressively with supplemental oxygen 2

Metabolic Support

• Administer IV fluids for hydration and circulatory support 2
• Correct metabolic abnormalities as they arise 2

Observation Period

• Monitor all patients for at least 48-72 hours, as delayed complications can occur 1, 2
• Watch for delayed muscle weakness (intermediate syndrome), which can develop up to 4 days after acute exposure 1
• Monitor for complications including myonecrosis, rhabdomyolysis, and renal damage 1

Critical Medications to Avoid

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

Common Pitfalls and Caveats

Underdosing Atropine

• The most common error is insufficient atropine dosing—aggressive atropinization with very high doses is often necessary 3, 6
• Modern recommendations emphasize rapid dose escalation by doubling every 5 minutes, a significant change from older, slower protocols 6

Premature Discontinuation

• Do not stop therapy prematurely—continue atropine and pralidoxime as long as cholinergic symptoms persist 2, 7
• Fatal relapses occur when treatment is discontinued too early, especially with ingested organophosphates 2

Misinterpreting Tachycardia

• Tachycardia during atropinization may result from nicotinic effects of the organophosphate itself, not atropine toxicity 1
• Continue atropine despite tachycardia—the therapeutic endpoint is control of muscarinic symptoms (secretions, bronchospasm), not heart rate 1

Delayed Pralidoxime Administration

• Pralidoxime effectiveness decreases after enzyme "aging" occurs, making early administration critical 1, 2
• Generally little benefit occurs if pralidoxime is given more than 36 hours after exposure termination 2