What is the treatment for Monocrotophos (Organophosphate) 36% Solution (SL - Soluble Liquid) poisoning?

From the Guidelines

Treatment for monocrotophos 36% SL poisoning requires immediate administration of atropine, starting with 1-5mg IV (adults) or 0.01-0.05mg/kg (children), repeated every 5-10 minutes until signs of atropinization appear, as recommended by the 2023 American Heart Association guidelines 1. The management of monocrotophos poisoning involves several key steps to mitigate the effects of organophosphate toxicity.

• Decontamination is crucial and involves removing contaminated clothing and washing the skin thoroughly with soap and water, as emphasized in the guidelines 1.
• Gastric lavage may be considered if the patient presents within 1-2 hours of ingestion, followed by activated charcoal administration (1g/kg).
• The primary antidote, atropine, is administered to block parasympathetic overstimulation, with dosing as mentioned, and repeated as necessary until atropinization is achieved, as supported by observational data 1.
• Oximes like pralidoxime (2-PAM) may be used, with a recommended dose of 1-2g IV initially, followed by 500mg every 6 hours or as continuous infusion at 500mg/hour for 24-48 hours, although the benefit is considered reasonable and not definitive 1.
• Supportive care is essential and includes oxygen therapy, ventilatory support if needed, correction of electrolyte imbalances, and management of seizures with benzodiazepines, such as diazepam or midazolam, which have demonstrated efficacy in patients 1.
• Continuous cardiac monitoring is critical due to the risk of arrhythmias. Monocrotophos, being an organophosphate insecticide, inhibits acetylcholinesterase, leading to accumulation of acetylcholine and overstimulation of cholinergic receptors, resulting in the characteristic symptoms of cholinergic crisis that require these specific interventions, as described in the guidelines 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. Treatment is most effective if initiated immediately after poisoning. 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. Generally, little is accomplished if PROTOPAM Chloride is given more than 36 hours after termination of exposure to the poison When the poison has been ingested, it is particularly important to take into account the likelihood of continuing absorption from the lower bowel since this constitutes new exposure and fatal relapses have been reported after initial improvement. In such cases, additional doses of PROTOPAM Chloride may be needed every three to eight hours In effect, the patient should be “titrated” with PROTOPAM Chloride as long as signs of poisoning recur. As in all cases of organophosphate poisoning, care should be taken to keep the patient under observation for at least 48 to 72 hours. If dermal exposure has occurred, clothing should be removed and the hair and skin washed thoroughly with sodium bicarbonate or alcohol as soon as possible Supportive care, including airway management, respiratory and cardiovascular support, correction of metabolic abnormalities, and seizure control, may be necessary in cases of severe organophosphate poisoning. Atropine should be given as soon as possible after hypoxemia is improved Atropine should not be given in the presence of significant hypoxia due to the risk of atropine-induced ventricular fibrillation. In adults, atropine may be given intravenously in doses of 2 to 4 mg. This should be repeated at 5- to 10-minute intervals until full atropinization (secretions are inhibited) or signs of atropine toxicity appear (delirium, hyperthermia, muscle twitching) Some degree of atropinization should be maintained for at least 48 hours, and until any depressed blood cholinesterase activity is reversed.

The treatment for Monocrotophos 36% SL poisoning includes:

• General supportive care
• Atropinization: atropine should be given as soon as possible after hypoxemia is improved, in doses of 2 to 4 mg, repeated at 5- to 10-minute intervals until full atropinization or signs of atropine toxicity appear
• Decontamination: if dermal exposure has occurred, clothing should be removed and the hair and skin washed thoroughly with sodium bicarbonate or alcohol as soon as possible
• Pralidoxime (PROTOPAM Chloride): administration should be carried out slowly and preferably by infusion, with additional doses needed every three to eight hours if signs of poisoning recur 2. Key points:
• Treatment is most effective if initiated immediately after poisoning
• The patient should be kept under observation for at least 48 to 72 hours
• Some degree of atropinization should be maintained for at least 48 hours, and until any depressed blood cholinesterase activity is reversed 2.

From the Research

Monocrotophos 36% SL Poisoning Treatment

• The treatment for monocrotophos poisoning involves aggressive atropinisation and continuous pralidoxime (2-PAM) infusion, as seen in a study of patients with severe organophosphate poisoning 3.
• Atropine is administered as an intravenous bolus of 5 mg at onset, followed by 2.5 mg every 5-10 minutes until atropinisation is achieved, and then maintained through intermittent bolus doses or continuous infusion 3.
• Pralidoxime is given as a continuous intravenous infusion of 7.5 mg/kg body weight/h (maximum 500 mg/h) after an initial bolus dose of 2 g 3.
• The use of atropine and pralidoxime has been shown to improve outcomes in patients with organophosphate poisoning, including those with respiratory failure 4.
• Monocrotophos is a highly toxic organophosphate insecticide that inhibits cholinesterase activity, and its poisoning can be controlled with therapeutic doses of atropine, preferably in combination with an oxime 5.
• The toxicity of monocrotophos can be reduced through various degradation processes, including microbial degradation, and efforts have been made to summarize and present the role of different microbial populations in its degradation and mineralization 6.
• Recent studies have also explored the use of succinate prodrugs in combination with atropine and pralidoxime to protect cerebral mitochondrial function in a rodent model of acute organophosphate poisoning 7.

Treatment Outcomes

• The mortality rate for patients with organophosphate poisoning treated with pralidoxime has been reported to be around 18%, compared to 21% for those without pralidoxime 4.
• The duration of intensive care stay for patients with organophosphate poisoning has been reported to be around 7.1 +/- 2 days 4.
• The use of atropine and pralidoxime has been shown to improve outcomes in patients with severe organophosphate poisoning, with 14 out of 16 patients successfully extubated in one study 3.

Mechanism of Action

• Monocrotophos inhibits the activity of the acetylcholine esterase enzyme, affecting neurotransmission between neurons 5, 6.
• The inhibition of acetylcholinesterase leads to impairment of the central- and peripheral nervous system, and mitochondrial dysfunction may contribute to the overall toxicity of organophosphates 7.