Atropine and Pralidoxime Dosing for Organophosphate Poisoning
Immediately administer atropine 1–2 mg IV bolus for adults (0.02 mg/kg for children, minimum 0.1 mg, maximum 0.5 mg per dose), then double the dose every 5 minutes until full atropinization is achieved—defined as clear lungs, dry skin, heart rate >80 bpm, systolic BP >80 mmHg, and mydriasis—regardless of tachycardia. 1, 2, 3
Initial Atropine Dosing and Escalation Protocol
The initial adult dose of 1–2 mg is substantially higher than the 0.5–1.0 mg used for bradycardia from other causes, reflecting the aggressive treatment required in organophosphate poisoning. 3
Dose-Doubling Algorithm
- Start with 1–2 mg IV for adults (0.02 mg/kg for children) 1, 2, 3
- Double the dose every 5 minutes (not fixed-dose repetition) until all atropinization endpoints are met 1, 3
- Typical cumulative requirements: 10–20 mg within the first 2–3 hours, with some patients needing up to 50 mg in 24 hours 1, 2, 3
- Never stop escalation due to tachycardia—tachycardia may result from nicotinic receptor overstimulation by the organophosphate itself, not atropine 1
Atropinization Endpoints (All Must Be Achieved)
- Clear chest on auscultation (resolution of bronchorrhea) 1, 3
- Heart rate >80 bpm 1, 3
- Systolic blood pressure >80 mmHg 1, 3
- Dry skin and mucous membranes 1, 3
- Mydriasis (pupil dilation) 1, 3
Maintenance Infusion After Atropinization
Once atropinization is achieved, transition to a continuous infusion at 10–20% of the total loading dose per hour (maximum 2 mg/hour in adults). 2, 3 Continuous infusion is preferred over intermittent boluses to maintain stable therapeutic levels. 3
Pralidoxime (Oxime) Therapy
Administer pralidoxime concurrently with atropine—never delay oxime therapy, even when the specific class of poison is unknown. 2
Loading Dose
- Adults: 1–2 g IV over 15–30 minutes 1, 2
- Children: 20–50 mg/kg (maximum 2 g) IV over 15–30 minutes 2
- The slow infusion over 15–30 minutes is critical to avoid transient hypotension, autonomic instability, and other adverse effects 2
Maintenance Infusion (Start Immediately After Loading)
- Adults: 400–600 mg/hour continuous IV infusion 1, 2
- Children: 10–20 mg/kg/hour continuous IV infusion 1, 2
- Rationale for continuous infusion: Intermittent bolus dosing allows plasma levels to fall below therapeutic thresholds within 1.5–2 hours, leaving patients unprotected during prolonged absorption of lipophilic organophosphates 2, 4
Timing Is Critical
Pralidoxime must be given early—within minutes to hours—before the organophosphate-acetylcholinesterase bond "ages" and becomes irreversible. 2 For nerve agents like soman, aging occurs within minutes; for agricultural organophosphates, a therapeutic window of up to 24 hours exists, but efficacy drops by roughly 50% after 6 hours. 2
Duration of Therapy
Continue pralidoxime for 48–72 hours or longer, as organophosphates may be absorbed slowly from the GI tract or redistributed from lipid stores. 2
Mandatory Concurrent Therapies
Benzodiazepines for Seizures and Agitation
Early Airway Management
Early endotracheal intubation is recommended for life-threatening organophosphate poisoning. 1, 2
Avoid succinylcholine and mivacurium—these neuromuscular blockers are metabolized by cholinesterase and are absolutely contraindicated in organophosphate poisoning. 1, 2
Critical Pitfalls to Avoid
Undertreating Atropine
The risk of undertreating organophosphate poisoning far exceeds the risk of atropine-induced tachycardia—inadequate atropinization leads to respiratory failure and death. 1 The therapeutic endpoint is control of bronchorrhea, bronchospasm, and adequate blood pressure, not heart rate normalization. 1
Delaying Pralidoxime
Do not delay pralidoxime while awaiting laboratory confirmation—enzyme "aging" renders the antidote ineffective. 2 Treatment should start immediately based on clinical suspicion. 2
Using Intermittent Pralidoxime Boluses
Intermittent bolus dosing is inadequate—plasma levels drop below therapeutic thresholds within 1.5–2 hours. 2, 4 A 2015 randomized study demonstrated that continuous micropump infusion of atropine and pralidoxime resulted in faster atropinization, faster acetylcholinesterase recovery, lower atropine requirements, and lower mortality compared to intermittent boluses. 5
Omitting Concurrent Atropine
Pralidoxime alone is insufficient—atropine must always be administered concurrently because pralidoxime reverses only nicotinic effects (muscle weakness, paralysis), while atropine controls muscarinic toxicity (bronchorrhea, bronchospasm, bradycardia). 1, 2
Rapid IV Push of Pralidoxime
Rapid IV push causes hypotension, tachycardia, and autonomic instability—infusion must be given over 15–30 minutes. 2
Monitoring and Duration
- Continuous cardiac monitoring to detect dysrhythmias, not to limit atropine dosing 1
- Serial respiratory assessments every 5–10 minutes during escalation phase 1
- Maintain close observation for at least 48–72 hours, as delayed complications and relapses can occur, especially with ingested organophosphates due to continued GI absorption 1, 2
- Monitor for delayed muscle weakness (intermediate syndrome), which can occur up to 4 days after acute exposure 2
- Watch for rhabdomyolysis: monitor creatine kinase and potassium; treat with hydration, forced diuresis, and urine alkalinization if myoglobinuria develops 2
Decontamination and Safety
- Use personal protective equipment (PPE) when handling contaminated patients or gastric contents—documented cases of healthcare workers requiring atropine, pralidoxime, and intubation after secondary exposure 2
- Remove all contaminated clothing immediately and irrigate skin thoroughly with soap and water 2
- Avoid gastric lavage or activated charcoal unless specifically directed by poison control—these measures pose significant secondary exposure risk to healthcare workers without proven benefit 2
Evidence Quality
The American Heart Association assigns atropine a Class 1 recommendation with Level A evidence (definitive benefit, highest quality data) for severe organophosphate poisoning. 2, 3
Pralidoxime receives a Class 2a recommendation with Level A evidence (reasonable to use, supported by high-quality data), despite one randomized trial failing to show mortality benefit—the recommendation persists due to clear biochemical reactivation of acetylcholinesterase and reversal of nicotinic effects. 2
A 2014 systematic review found that current recommendations have greatly increased the speed of atropinization compared to older protocols, with 13 of 24 current regimens able to reach mean and high atropine doses within 30 minutes, and 15 of 24 now including dose-doubling strategies. 6