Pralidoxime Dosing for Organophosphate Poisoning
For acute organophosphate poisoning, administer pralidoxime as a loading dose of 1–2 g IV over 15–30 minutes in adults (25–50 mg/kg, maximum 2 g, in children), followed immediately by a continuous infusion of 400–600 mg/hour in adults (10–20 mg/kg/hour in children) to maintain therapeutic plasma concentrations above 4 µg/mL throughout the poisoning period. 1
Adult Dosing Protocol
Loading dose: Give 1–2 g pralidoxime IV over 15–30 minutes; the slow infusion is critical to avoid transient hypotension and autonomic instability that occur with rapid bolus administration. 1
Maintenance infusion: Immediately after the loading dose, start a continuous infusion of 400–600 mg/hour (approximately 8–10 mg/kg/hour) to sustain plasma levels above the therapeutic threshold of 4 µg/mL. 1, 2
Duration: Continue pralidoxime for at least 48–72 hours or longer as clinically indicated, because organophosphates may be absorbed slowly from the gastrointestinal tract or redistributed from lipid stores. 1
Pediatric Dosing Protocol
Loading dose: Administer 25–50 mg/kg IV (maximum 2 g) over 15–30 minutes; use the higher end of the range (50 mg/kg) for more severely poisoned patients due to their larger volume of distribution. 1, 3
Maintenance infusion: Follow with a continuous infusion of 10–20 mg/kg/hour. Pharmacokinetic studies in poisoned children show wide variability in clearance (0.88 ± 0.55 L/h/kg) and volume of distribution (1.7–13.8 L/kg), with more severely poisoned patients often requiring higher doses. 1, 3
Critical Timing Considerations
Do not delay pralidoxime while awaiting toxin confirmation. The organophosphate–acetylcholinesterase bond undergoes irreversible "aging" within minutes to hours, after which oxime therapy becomes ineffective; for nerve agents such as soman, aging occurs within minutes. 1
Start pralidoxime immediately based on clinical suspicion of organophosphate poisoning—the American Heart Association advises that oximes should not be withheld even when the specific class of cholinesterase inhibitor is unknown. 1
Why Continuous Infusion Is Superior to Intermittent Bolus Dosing
Intermittent bolus dosing fails to maintain therapeutic levels. Pharmacokinetic simulations show that after a 1 g IV bolus, pralidoxime concentrations fall below the therapeutic threshold of 4 µg/mL within 1.5–2 hours, leaving patients unprotected during prolonged absorption of lipophilic organophosphates. 1, 2, 4
Continuous infusion maintains therapeutic concentrations. In healthy volunteers, a loading dose followed by continuous infusion maintained plasma levels above 4 µg/mL for 257.5 ± 50.5 minutes versus only 118.0 ± 52.1 minutes with short intermittent infusion. 2
High-dose continuous infusion reduces morbidity and mortality. A randomized controlled trial of 200 patients with moderately severe organophosphate poisoning found that a 2 g loading dose followed by 1 g/hour continuous infusion for 48 hours (versus 1 g every 4 hours) reduced atropine requirements (median 6 mg vs 30 mg in first 24 hours, p<0.0001), decreased intubation rates (64% vs 88%, p=0.0001), and shortened ventilator days (median 5 vs 10 days, p<0.0001). 5
Mandatory Concurrent Therapies
Atropine (Must Always Be Given with Pralidoxime)
Atropine controls muscarinic toxicity; pralidoxime reverses nicotinic effects. Pralidoxime alone is insufficient to manage respiratory depression, bronchorrhea, and bronchospasm. 1
Adult dosing: 1–2 mg IV initially, doubling the dose every 5 minutes until bronchorrhea, bronchospasm, and bradycardia resolve. Typical cumulative requirements are 10–20 mg in the first 2–3 hours; some patients may need up to 50 mg in 24 hours. 1, 6
Pediatric dosing: 0.02 mg/kg IV (minimum 0.1 mg, maximum 0.5 mg per dose), doubling every 5 minutes until full atropinization is achieved. 1, 6
Maintenance: After achieving atropinization, continue atropine as a continuous infusion at 10–20% of the total loading dose per hour, not exceeding 2 mg/hour in adults. 6
Benzodiazepines for Seizures and Agitation
- Administer diazepam 0.2 mg/kg IV or midazolam 0.05–0.1 mg/kg IV to control seizures or severe agitation. 1
Airway Management
Early endotracheal intubation is recommended for life-threatening organophosphate poisoning. 1
Avoid succinylcholine and mivacurium for intubation—these neuromuscular blockers are metabolized by cholinesterase and are absolutely contraindicated in organophosphate poisoning. 1
Route of Administration and Reconstitution
Intravenous or intra-osseous access is required. Intramuscular injection cannot achieve the rapid therapeutic plasma concentrations needed in acute poisoning. 1
Reconstitute and dilute pralidoxime with sterile water for injection or normal saline (0.9% sodium chloride). 1
Evidence Quality and Guideline Strength
The American Heart Association assigns pralidoxime a Class 2a recommendation with Level A evidence, indicating that its use is reasonable and supported by high-quality data. 1
Although one randomized trial failed to show a mortality benefit with low-dose intermittent pralidoxime (1 g bolus followed by 1 g every 4 hours), the recommendation remains strong due to clear biochemical reactivation of acetylcholinesterase and reversal of nicotinic effects. 1, 7
The most recent high-quality trial (2006) demonstrated that high-dose continuous infusion (1 g/hour for 48 hours after a 2 g loading dose) significantly reduces morbidity and mortality in moderately severe organophosphate poisoning. 5
Target Plasma Concentrations
Maintain pralidoxime plasma concentrations above 4 µg/mL throughout the poisoning period; this is the minimum therapeutic level suggested by animal studies. 2, 8
For the most frequently used organophosphates, target pralidoxime plasma concentrations of approximately 80 µmol/L (13.8 mg/L pralidoxime chloride) may be needed to effectively antagonize toxic effects, which is well above the traditional 4 mg/L threshold. 8
The 4 mg/L concept should be considered a minimum threshold, not an optimal target, as in vitro studies with human erythrocyte acetylcholinesterase reveal marked differences in oxime potency depending on the specific organophosphate compound. 8
Common Pitfalls to Avoid
Delaying pralidoxime while awaiting laboratory confirmation allows enzyme aging and renders the antidote ineffective; treatment must start immediately based on clinical suspicion. 1
Using intermittent bolus dosing instead of continuous infusion leads to subtherapeutic plasma levels within 1.5–2 hours, leaving patients unprotected. 1, 2, 4
Omitting concurrent atropine results in uncontrolled muscarinic toxicity; atropine administration is mandatory and must be given alongside pralidoxime. 1
Rapid IV push administration causes hypotension, tachycardia, and autonomic instability; the loading dose must be infused over 15–30 minutes. 1
Stopping pralidoxime too early (before 48–72 hours) may allow recurrent toxicity from continued absorption or redistribution of lipophilic organophosphates. 1
Monitoring During Therapy
Continuous cardiac monitoring to detect dysrhythmias (not to limit atropine dosing). 9
Serial respiratory assessments every 5–10 minutes during the escalation phase to evaluate resolution of bronchorrhea. 9
Close observation for at least 48–72 hours as delayed complications and relapses can occur, especially with ingested organophosphates due to continued gastrointestinal absorption. 9
Adverse Effects of Pralidoxime
Common adverse effects include transient hypotension, reduced cardiac output, autonomic ganglion blockade (especially with rapid administration), dizziness, blurred vision, diplopia, headache, nausea, tachycardia, and muscle rigidity. 1
Mild, transient hepatic enzyme elevations have been observed with higher pralidoxime doses but are generally not clinically significant and do not necessitate dose modification. 1