Respiratory arrest caused by accidental rapid pralidoxime infusion

To the Editor:

Pralidoxime chloride (PAM) is a cholinesterase-reactivating compound which is generally used as an antidote together with atropine in organophosphorus (OPP) insecticide poisoning. Adverse effects are typically minimal and transient even in high-dose PAM regimens.¹ Rapid infusion of PAM can be associated with short periods of dizziness, blurred vision, or elevation of diastolic pressure.^2,3 PAM infusion at a rate of 200 mg/min for 2 min resulted in cardiac arrest in a previous case.⁴ Here, we report a case of respiratory arrest following accidental rapid infusion of high-dose PAM.

A 41-year-old previously healthy man was brought to our emergency department (ED) 1.5 h after ingestion of approximately 250 ml of diethoxy organophosphate pesticide (34% diazinon emulsion). On arrival, he was alert and had no cholinergic symptoms. Gastric lavage and charcoal instillation were performed. Despite the absence of cholinergic symptoms, PAM therapy was started according to our institute's policy that PAM infusion should be commenced and maintained at least 1–2 days in all OPP-poisoned patients due to the risk of delayed cholinergic manifestations and the general safety of PAM. Continuous infusion of PAM was started at a rate of 21 ml per hour using an infusion pump (12 g of PAM diluted with 500 ml of 5% dextrose) after a 2-g intravenous infusion of PAM diluted with 150 ml of 0.9% saline over 30 min as a loading dose. His vital signs were closely monitored. Laboratory results received after the incident showed that the initial serum pseudocholinesterase level was 688 U/L (reference range: 3,400–14,200 U/L) and returned to the normal range (3,767 U/L) on the second hospital day. He was stable until the third hospital day (approximately 36 h after admission) and was prepared for discharge. At this time, the ED nurse removed the infusion pump while the roller clamp of the intravenous tube was fully open. Consequently, approximately 150–200 ml of the remaining PAM solution (approximately 4–5 g of PAM) was rapidly infused over 10–20 min. He complained of blurred vision, rigidity of the extremities, and of being unable to open his eyes. Although the patient was not fully cooperative, neurologic examination showed lateral gaze palsy at this time. His blood pressure increased to 190/110 mmHg and tachycardia (116 bpm) was observed. Respiratory arrest and rigidity of whole extremities developed. He was intubated and received mechanical ventilation with sedation. The results of a portable electroencephalography were normal. One day after the beginning of ventilator support, he became alert and extubation was performed. The remainder of his course was uneventful, and on hospital day 5 he was discharged.

In an animal study, high-dose PAM caused an anti-cholinesterase effect and induced fasciculation and neuromuscular block.^5,6 The antagonism of PAM on the neuromuscular action of non-depolarizing agents and its synergism with depolarizing agents can be explained by its anti-cholinesterase effect.⁷ In a study using anesthetized cats, high-dose PAM was injected repeatedly, initially increasing respiratory volume without altering respiratory rate and then inducing bradypnea and apnea.⁷ This study also showed that PAM can reach the brain at high doses and induce excitatory central effects and desynchronization of discharge, followed by central depression. We assume that the respiratory arrest which developed in our patient was a result of neuromuscular block and depression of the respiratory center due to rapid infusion of high-dose PAM.

PAM is a relatively safe antidote when used according to protocol. However, physicians treating patients with OPP poisoning should be aware that the infusion rate of PAM must be handled with caution, and that rapid infusion of high-dose PAM can lead to neuromuscular effects and respiratory depression. The incident has led to a change in treatment protocol in our unit in that routine use of PAM is now restricted and rate and amount of PAM infusion are closely monitored. Respiratory arrest caused by PAM infusion can be managed by adequate supportive care, including sedation and mechanical ventilation.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.