What is the treatment for organophosphate (OP) poisoning?

Treatment of Organophosphate Poisoning

Immediately administer atropine 1-2 mg IV for adults (0.02 mg/kg for children, minimum 0.1 mg), doubling the dose every 5 minutes until full atropinization is achieved, while simultaneously giving pralidoxime 1-2 g IV over 15-30 minutes, along with early intubation for severe cases and benzodiazepines for seizures. 1, 2

Critical First Steps: The ABC Approach

Personal Protection and Decontamination

• Healthcare providers must wear appropriate personal protective equipment before patient contact to prevent secondary contamination. 1
• Remove all contaminated clothing immediately and perform copious irrigation with soap and water (or sodium bicarbonate/alcohol) for any dermal exposure. 1, 2
• Perform gastric lavage and administer activated charcoal via nasogastric tube if ingestion occurred, recognizing that continuing absorption from the lower bowel can cause fatal relapses even after initial improvement. 2, 3

Airway Management

• Perform early endotracheal intubation for life-threatening poisoning, particularly when bronchorrhea, bronchospasm, altered mental status, or respiratory failure threatens airway protection. 1
• Avoid succinylcholine and mivacurium for intubation—these neuromuscular blockers are metabolized by cholinesterase and are contraindicated in organophosphate poisoning. 1, 2
• Use alternative agents like rocuronium or vecuronium for rapid sequence intubation if needed. 1

Pharmacologic Treatment Algorithm

Atropine: The Immediate Life-Saving Intervention

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

Dosing Protocol:

• Adults: Start with 1-2 mg IV (FDA label recommends 2-4 mg), doubling every 5 minutes until full atropinization. 1, 2
• Children: 0.02 mg/kg IV/IO initially (minimum 0.1 mg, maximum single dose 0.5 mg), but recognize that children require relatively higher doses than standard pediatric resuscitation doses. 1
• Critical timing: Atropine should be given as soon as possible after hypoxemia is improved, but never give atropine in the presence of significant hypoxia due to risk of atropine-induced ventricular fibrillation. 2

Endpoints of Atropinization:

• Clear chest on auscultation (dry lungs, no bronchorrhea) 1
• Heart rate >80/min 1
• Systolic blood pressure >80 mm Hg 1
• Dry skin and mucous membranes 1
• Mydriasis (pupil dilation) 1

Maintenance Therapy:

• Maintain atropinization with continuous infusion for at least 48 hours and until depressed blood cholinesterase activity is reversed. 1, 2
• Some degree of atropinization should be maintained throughout the critical period. 2

Managing Atropine-Related Concerns

Common Pitfall: Providers often hesitate to continue atropine when tachycardia or fever develops—this is dangerous.

• Atropine-induced tachycardia is NOT a contraindication to continued administration. 1
• The tachycardia may actually be from nicotinic receptor overstimulation from the organophosphate itself, not the atropine. 1
• Never withhold or prematurely discontinue atropine due to fever—inadequate atropinization leads to respiratory failure and death. 1
• Fever is an expected adverse effect with high-dose atropine therapy and does not indicate treatment failure. 1
• Continue escalating atropine doses based on muscarinic symptoms (bronchorrhea, bronchospasm, bradycardia), not heart rate. 1

Pralidoxime (2-PAM): Essential Oxime Therapy

Pralidoxime carries a Class 2a recommendation with Level A evidence and should be administered early to reactivate acetylcholinesterase. 1

Dosing Protocol:

• Adults: 1-2 g IV administered slowly over 15-30 minutes, preferably by infusion in 100 mL normal saline. 1, 2
• If pulmonary edema is present, give slowly over at least 5 minutes as a 50 mg/mL solution. 2
• Maintenance: 400-600 mg/hour continuous infusion for adults or 10-20 mg/kg/hour for children. 1
• A second dose of 1-2 g may be indicated after one hour if muscle weakness persists. 2
• Additional doses may be given every 10-12 hours if muscle weakness continues. 2

Critical Timing Considerations:

• Pralidoxime is most effective when administered early, before "aging" of the phosphorylated enzyme occurs (typically within 24-36 hours). 1, 2
• Generally, little is accomplished if pralidoxime is given more than 36 hours after termination of exposure. 2
• However, when the poison has been ingested, continuing absorption from the lower bowel constitutes new exposure—additional doses may be needed every 3-8 hours. 2
• In effect, "titrate" the patient with pralidoxime as long as signs of poisoning recur. 2

Mechanism and Rationale:

• Pralidoxime reactivates acetylcholinesterase by competing with the bond between organophosphates and the enzyme, restoring normal enzyme activity. 1
• Pralidoxime reverses nicotinic effects (muscle weakness, fasciculations) that atropine cannot address. 1
• The minimum therapeutic plasma concentration is 4 µg/mL, reached in about 16 minutes after a 600 mg injection. 2
• Pralidoxime has a short half-life (74-77 minutes), and concentrations fall below therapeutic levels in about 1.5 hours after a 1000 mg dose. 2

Important Caveat:

• Do not withhold pralidoxime when the class of poison (organophosphate vs. carbamate) is unknown—organophosphate poisoning is clinically indistinguishable from carbamate poisoning initially. 1
• While pralidoxime's role in carbamate poisoning is less clear, the risk of withholding it in true organophosphate poisoning far exceeds any theoretical risk. 1

Controversy Note: Some studies have questioned pralidoxime's efficacy, and one retrospective study found no mortality difference between patients who did and did not receive it. 3 However, the American Heart Association still recommends its use based on the strength of mechanistic evidence and the potential for benefit when given early. 1

Benzodiazepines: Seizure and Agitation Control

• Administer benzodiazepines (diazepam first-line or midazolam) to treat seizures and agitation. 1
• Benzodiazepines also facilitate mechanical ventilation when needed. 1
• Seizures are a life-threatening manifestation requiring immediate treatment. 1

Drugs to Avoid

Critical contraindications that worsen outcomes:

• Morphine 2
• Theophylline and aminophylline 2
• Reserpine 2
• Phenothiazine-type tranquilizers 2
• Succinylcholine (prolonged paralysis reported) 2

Monitoring and Complications

Observation Period

• Keep all patients under close observation for at least 48-72 hours, even if initially stable. 1, 2
• Fatal relapses have been reported after initial improvement due to continuing absorption. 2

Intermediate Syndrome

• Monitor for delayed muscle weakness developing 24-96 hours after acute exposure, even as the initial cholinergic crisis resolves. 1
• Intermediate syndrome was observed in 19.1% of patients in one series. 3
• Three patients with intermediate syndrome died due to delayed intubation when respiratory rate increased from 22 to 38 breaths/min—this is an important sign of respiratory distress requiring immediate action. 3
• Early recognition and intubation is life-saving. 3

Respiratory Complications

• Respiratory failure is the most troublesome complication, occurring in up to 74% of patients. 3
• Causes include aspiration of gastric content, excessive secretions, aspiration pneumonia, and septicemia complicating acute respiratory distress syndrome. 3
• The mortality rate for patients requiring mechanical ventilation was 50% vs. 21.6% for those not mechanically ventilated in one series, highlighting the severity of respiratory involvement. 3

Other Complications to Monitor

• Aspiration pneumonia 3
• Urinary tract infections 3
• Convulsions 1, 3
• Septic shock 3
• Rhabdomyolysis and renal damage (less common than with carbamates) 1
• Cardiac arrhythmias 4
• Acute pancreatitis (rare) 4
• Hepatic dysfunction (rare) 4
• Delayed polyneuropathy 5, 6

Clinical Recognition: Symptoms by Severity

Mild Symptoms:

• Blurred vision and sore eyes 2
• Teary eyes and runny nose 2
• Increased salivation/sudden drooling 2
• Chest tightness or difficulty breathing 2
• Tremors or muscular twitching 2
• Nausea and vomiting 2
• Involuntary respiratory secretions 2

Severe Symptoms:

• Strange or confused behavior 2
• Severe difficulty breathing or respiratory secretions 2
• Severe muscular twitching and general weakness 2
• Involuntary urination and defecation 2
• Convulsions 2
• Unconsciousness 2

Physical Examination Findings:

• Miosis (most frequent) 3
• Change in mental status 3
• Hypersalivation 3
• Fasciculations 3

Pediatric Note: In infants and young children, teary eyes, runny nose, and salivation are sometimes observed in healthy children and are less reliable. Infants may become drowsy or unconscious with muscle floppiness rather than twitching. 2

Supportive Care Essentials

• Establish IV access and administer fluids for volume resuscitation. 1
• Provide supplemental oxygen and support ventilation as needed. 1
• Perform continuous cardiac monitoring for dysrhythmias. 1
• Correct metabolic abnormalities. 2
• Contact Poison Control (1-800-222-1222 in the US) for expert guidance on specific case management. 1

Key Pitfalls to Avoid

1. Delaying atropine administration—it is the immediate life-saving intervention and must not be delayed. 1
2. Underdosing atropine—organophosphate poisoning requires much higher doses than typical bradycardia treatment. 1
3. Stopping atropine due to tachycardia or fever—these are expected effects and not contraindications. 1
4. Withholding pralidoxime when poison class is unknown—give it empirically. 1
5. Using succinylcholine or mivacurium for intubation—these are contraindicated. 1
6. Delaying intubation in respiratory distress—early intubation is life-saving, especially when respiratory rate increases dramatically. 3
7. Giving atropine in the presence of significant hypoxia—correct hypoxemia first to avoid ventricular fibrillation. 2
8. Inadequate observation period—monitor for at least 48-72 hours for delayed complications. 1, 2