What is the recommended per‑kilogram dosing regimen of pralidoxime (2‑PAM) for adult and pediatric organophosphate poisoning?

Pralidoxime Dosing for Organophosphate Poisoning

For adults, administer pralidoxime 1–2 g IV as a loading dose over 15–30 minutes, followed by a continuous infusion of 400–600 mg/hour; for children, give 20–50 mg/kg IV loading dose (maximum 2 g) followed by 10–20 mg/kg/hour continuous infusion. 1

Adult Dosing Protocol

• Loading dose: Administer 1–2 g IV slowly over 15–30 minutes as the initial bolus 1, 2
• Maintenance infusion: Continue with 400–600 mg/hour as a continuous IV infusion to maintain therapeutic plasma concentrations above 13.8 mg/L 1, 2, 3
• Duration: Maintain the infusion as long as circulating poison is expected, which may require therapy for up to 10 days in severe cases 4

The continuous infusion regimen is superior to intermittent bolus dosing because it maintains therapeutic levels (>4 µg/mL) for approximately 257 minutes versus only 118 minutes with short infusion alone 5. Pharmacokinetic data demonstrate that after a single 1 g bolus, pralidoxime concentrations fall below therapeutic levels within 1.5–2 hours, necessitating continuous infusion 3, 6.

Pediatric Dosing Protocol

• Loading dose: Administer 20–50 mg/kg IV (maximum 2 g) over 15–30 minutes 1, 2
• Maintenance infusion: Continue with 10–20 mg/kg/hour as a continuous IV infusion 1, 2, 7
• Severe poisoning consideration: Use the higher end of the loading dose range (50 mg/kg) in more severely poisoned patients, as volume of distribution is significantly higher in this population 7

Pediatric pharmacokinetics are highly variable, with steady-state concentrations averaging 22.2 mg/L (range 6.9–47.4 mg/L) and elimination half-life of 2.4–5.3 hours 3, 7. The volume of distribution ranges from 1.7 to 13.8 L/kg and is significantly higher in more severely poisoned children 7.

Critical Timing Considerations

• Administer early: Pralidoxime must be given as soon as possible, ideally within minutes to hours after exposure, before the organophosphate-acetylcholinesterase complex undergoes "aging" and becomes irreversible 2
• Agent-specific windows: For nerve agents like soman, aging occurs within minutes; for agricultural organophosphates (e.g., dimethoate), a therapeutic window of up to 24 hours exists, but efficacy drops by approximately 50% after 6 hours 2
• Never delay for diagnostic certainty: Oximes should not be withheld when the class of poison (organophosphate versus carbamate) is unknown 1, 2

Mandatory Concurrent Therapies

• Atropine is essential: Always administer atropine concurrently, starting with 1–2 mg IV for adults (0.02 mg/kg for children, minimum 0.1 mg, maximum 0.5 mg per dose), doubling every 5 minutes until bronchorrhea, bronchospasm, and bradycardia resolve 1, 2, 8
• Atropine maintenance: Once atropinization is achieved, continue as a continuous infusion at 10–20% of the total loading dose per hour, not exceeding 2 mg/hour in adults 2, 8
• Benzodiazepines for seizures: Administer diazepam 0.2 mg/kg or midazolam 0.05–0.1 mg/kg IV for seizures or agitation 1, 2, 8

Pralidoxime reverses nicotinic effects (muscle weakness, respiratory failure) that atropine cannot address, while atropine manages muscarinic symptoms (bronchorrhea, bronchospasm, bradycardia) 2, 4.

Target Plasma Concentrations

• Pralidoxime chloride: Maintain plasma concentrations around 80 µmol/L (13.8 mg/L pralidoxime chloride) to antagonize the toxic effects of most frequently used organophosphates 4
• Dismiss the "4 mg/L concept": The traditional 4 mg/L threshold is inappropriate; higher concentrations (13.8 mg/L) are required for effective reactivation of acetylcholinesterase with common agricultural organophosphates 4

Common Pitfalls to Avoid

• Do not use intermittent bolus dosing: The traditional regimen of 1 g every 8–12 hours results in subtherapeutic levels for most of the dosing interval 6
• Avoid rapid IV push: Rapid administration causes transient hypotension, reduced cardiac output, dizziness, blurred vision, and tachycardia 2, 5
• Do not stop prematurely: Continue pralidoxime infusion for the entire duration that circulating poison is expected, which may be 3–10 days depending on the agent and exposure route 4, 9
• Avoid succinylcholine and mivacurium: These neuromuscular blockers are metabolized by cholinesterase and are contraindicated in organophosphate poisoning 1, 2

Evidence Quality and Guideline Strength

The American Heart Association gives pralidoxime a Class 2a recommendation with Level A evidence, meaning "it is reasonable to use" with high-quality evidence supporting its efficacy 1, 2. The continuous infusion regimen is supported by pharmacokinetic studies in both healthy volunteers and poisoned patients, demonstrating superior maintenance of therapeutic levels compared to intermittent dosing 3, 5, 7.

Human case series demonstrate that continuous pralidoxime infusion (500–600 mg/hour) maintains blood levels of 11.6–17.26 µg/mL with an elimination half-life of approximately 4 hours 3. In pediatric patients, continuous infusion after a loading dose resulted in complete clinical recovery in all patients, with only one requiring additional atropine for recurrent muscarinic symptoms 7.

Monitoring Parameters

• Clinical endpoints: Monitor for reversal of muscle weakness, improved respiratory effort, and resolution of fasciculations 2
• Atropinization status: Assess for clear lungs, dry skin and mucous membranes, heart rate >80 bpm, systolic BP >80 mmHg, and mydriasis 2, 8
• Duration of therapy: Continue monitoring for at least 48–72 hours, as delayed muscle weakness can occur up to 4 days after acute exposure 2
• Renal function: Pralidoxime is rapidly excreted by renal tubular secretion; renal clearance is 7.2 mL/min/kg in healthy volunteers and 3.6 mL/min/kg in poisoned patients 3