What is the administration protocol for Pralidoxime (PAM) in organophosphate (OP) poisoning?

From the Guidelines

In organophosphate (OP) poisoning, pralidoxime (PAM) should be administered promptly alongside atropine, with a recommended initial dose of 1-2 g, followed by a maintenance infusion of 400-600 mg/h (adults) or 10-20 mg/kg/h (pediatric) 1. The administration of PAM is crucial in the management of OP poisoning, as it reactivates acetylcholinesterase that has been inhibited by the organophosphate compound.

• The dose of PAM should be titrated to achieve control of critical signs and symptoms, and it is often necessary to administer large doses to overcome competitive inhibition of molecular targets.
• PAM is most effective when combined with atropine, which blocks the muscarinic effects of acetylcholine excess, and the use of PAM is reasonable for organophosphate poisoning 1. Some key considerations in the administration of PAM include:
• The need for early administration, ideally within 24-48 hours of exposure, before "aging" of the enzyme-OP complex occurs.
• The importance of adequate respiratory support, decontamination, and monitoring for complications alongside PAM administration.
• The potential need for dosage adjustments in patients with renal impairment, and the continuation of treatment until respiratory secretions diminish and the patient shows clinical improvement. It is essential to consult a medical or clinical toxicologist, regional poison center, or topic-specific reference for detailed dosing and administration instructions, as the ideal dose of PAM is not known and is often controversial 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Organophosphate Poisoning Treatment should include general supportive care, atropinization, and decontamination, in addition to the use of PROTOPAM Chloride. Administration of PROTOPAM Chloride should be carried out slowly and, preferably, by infusion If intravenous administration is not feasible, intramuscular or subcutaneous injection should be used.

Administration of PAM in OP poisoning:

• PAM (PROTOPAM Chloride) should be administered slowly, preferably by infusion.
• If intravenous administration is not feasible, intramuscular or subcutaneous injection can be used.
• Treatment is most effective if initiated immediately after poisoning.
• The patient should be “titrated” with PROTOPAM Chloride as long as signs of poisoning recur, with additional doses given every three to eight hours if necessary 2.

From the Research

Administration of PAM in OP Poisoning

• The administration of Pralidoxime (PAM) in organophosphate (OP) poisoning is a topic of discussion among medical professionals, with some studies suggesting its efficacy and others questioning its benefits 3, 4, 5.
• According to a study published in 2007, treatment with intravenous atropine and pralidoxime was started as soon as possible in patients with OP poisoning, and the mortality rate was 18% in patients who were treated with pralidoxim and 21% in patients without pralidoxim 3.
• Another study published in 2014 discussed the importance of high-dose atropine therapy and early intervention, as well as novel treatment approaches, including hemofiltration treatments and lipid solutions, in the management of OP poisoning 4.
• A study published in 2001 found that continuous pralidoxime (2-PAM) infusion along with aggressive atropinisation improved the outcome in patients with severe OP poisoning who required assisted ventilation 5.
• However, a systematic review and meta-analysis published in 2020 found that pralidoxime was not shown to be beneficial in patients with acute OP poisoning, and may even cause harm 6.

Dosage and Administration

• The dosage and administration of PAM in OP poisoning vary depending on the severity of the poisoning and the patient's response to treatment.
• A study published in 2001 used a continuous iv infusion of 2-PAM in a dose of 7.5 mg/kg body weight/h (maximum 500 mg/h) after an initial bolus dose of 2 g 5.
• Another study published in 2014 used a total dose of 11.6 g/12 days of atropine, with a highest dose of 100 mg intravenously on admission and 100 mg/h/day during follow-up 4.

Clinical Considerations

• The diagnosis of OP poisoning is based essentially on a clinical assessment, followed by laboratory examinations 7.
• Early recognition of OP poisoning is crucial to institute appropriate management, including the administration of PAM and atropine, as well as supportive care such as mechanical ventilation if necessary 3, 4, 5, 7.