What is the recommended dose and administration of pralidoxime (2-PAM) for organophosphate poisoning?

From the Guidelines

The recommended dose of pralidoxime (2-PAM) for organophosphate poisoning is 1-2 grams administered intravenously, with a maintenance infusion of 400-600 mg/hour for adults and 10-20 mg/kg/hour for children. This dosing regimen is based on the most recent guidelines from the American Heart Association, as outlined in the 2023 focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning 1.

Key Considerations for Administration

• The initial dose should be administered as soon as possible after exposure, ideally within 24-48 hours.
• Treatment may need to be continued for several days depending on the severity of poisoning and clinical response.
• Pralidoxime should always be administered after ensuring adequate airway protection and following atropine administration to control muscarinic symptoms.
• For children, the loading dose is 20-50 mg/kg, which is crucial for effective treatment in pediatric cases.
• The medication works by reactivating acetylcholinesterase that has been inhibited by organophosphates, thereby restoring normal neurotransmission at synapses.

Monitoring and Side Effects

• Pralidoxime administration should be accompanied by close monitoring for potential side effects including tachycardia, hypertension, laryngospasm, and neuromuscular weakness at high doses.
• It is essential to be aware of these potential side effects to provide timely and appropriate management, as highlighted in the guidelines 1.

Clinical Context

• The treatment of organophosphate poisoning involves a comprehensive approach that includes decontamination, atropine, benzodiazepines, and oximes, with pralidoxime playing a critical role in reactivating acetylcholinesterase.
• Understanding the pathophysiology of organophosphate and carbamate poisoning, as discussed in the guidelines 1, is crucial for effective management and underscores the importance of timely and appropriate dosing of pralidoxime.

From the FDA Drug Label

In one study of healthy adult volunteers and patients self-poisoned with organophosphate compounds, a single intramuscular injection of 1000 mg of pralidoxime chloride resulted in mean peak plasma levels of 7.5 ± 1.7 µg/mL and 9.9 ± 2. 4 µg/mL, respectively. Some evidence suggests that a loading dose followed by continuous intravenous infusion of pralidoxime chloride may maintain therapeutic levels longer than short intermittent infusion therapy In a cross-over study of seven healthy adults (18 – 50 years) a short intravenous infusion dose of 16 mg/kg over 30 minutes was compared to an intravenous loading dose of 4 mg/kg over 15 minutes, followed by 3.2 mg/kg/hr for 3. 75 hours (for a total dose of 16 mg/kg). Use of continuous intravenous infusion in adult patients with organophosphate poisoning has been described in several case reports, with and without loading doses. Infusion rates ranged from 400 – 600 mg/hr.

The recommended dose of pralidoxime (2-PAM) for organophosphate poisoning is:

• A loading dose of 1000 mg given intravenously
• Followed by a continuous infusion of 400-600 mg/hr The administration of pralidoxime can be via intravenous or intramuscular injection 2.

From the Research

Dose of Pralidoxime (2-PAM)

The recommended dose of pralidoxime (2-PAM) for organophosphate poisoning varies depending on the study.

• A study from 1987 3 suggests that a serum concentration of 4 micrograms/ml may be a minimal level to protect against the toxic effects of organophosphates, and that continuous iv infusion (0.5 g/h) maintains pralidoxime levels greater than 4 micrograms/ml throughout the length of infusion.
• A study from 1996 4 compared a single bolus dose of 1 gm with a continuous infusion of 12 gm over 4 days, and found that the low dose group had a lower prevalence of intermediate syndrome and ventilatory requirement.
• A study from 2001 5 used a continuous iv infusion of 2-PAM in dose of 7.5 mg/ kg body weight/h (maximum 500 mg/h) after an initial bolus dose of 2 g, and found that this regimen improved the outcome in patients with severe organophosphate poisoning.
• A study from 1998 6 recommended a loading dose of 25-50 mg/kg followed by a continuous infusion of 10-20 mg/kg/h in children with organophosphate poisoning.
• A study from 2006 7 compared a constant pralidoxime infusion with repeated bolus injections, and found that the high-dose regimen reduced morbidity and mortality in moderately severe cases of acute organophosphorus-pesticide poisoning.

Administration of Pralidoxime (2-PAM)

The administration of pralidoxime (2-PAM) can be either as a bolus dose or as a continuous infusion.

• A study from 1987 3 suggests that continuous iv infusion may be the preferred method of administration in patients with acute organophosphate poisoning.
• A study from 2006 7 found that a constant infusion of 1 g/h for 48 h after a 2 g loading dose reduced morbidity and mortality in moderately severe cases of acute organophosphorus-pesticide poisoning.
• Other studies 4, 5, 6 also used continuous infusion or bolus doses, and found that these regimens were effective in treating organophosphate poisoning.