Intermediate Syndrome After Chlorpyrifos and Cypermethrin Poisoning

Dear Editor,

Acute organophosphate (OP) poisoning is a significant cause of morbidity and mortality in developing countries including India. It is action on the enzyme acetylcholinesterase (AChE) is of most clinical significance. These compounds bind to the esteratic site on the AChE molecule phosphorylating the enzyme, leading to inhibition of its normal action. Studies have shown that a phenomenon of enzyme ageing occurs which involves cleavage of a radicle from the inhibited enzyme, making it resistant to rephosphorylation. The net result is the accumulation of excess acetylcholine (ACh) at the cholinergic nerve endings all over the body resulting in the characteristic clinical manifestations. Following inhibition, recovery of this enzyme occurs at a rate of about 1% per day. ¹

Case Study

A 43-year-old alcoholic and depressed person drank a bottle of Hamla 550 (probably about 60 mL) containing Chlorpyrifos and Cypermethrin on 17/6/2023. He was hospitalized in Baramati, Pune and treated with gastric lavage, intravenous atropine, pralidoxime (PAM), intubated, mechanical ventilation, supportive treatment, and extubated on 23/6/23. After three to four days, he developed respiratory weakness and was unable to lift his head. On the eighth day, his vital capacity fell, facial muscles were weak, as was shoulder abduction and hip flexion. The distal muscles were normal. He had normal reflexes and no sensory deficit. ² He was referred to private hospital in Pune. Serum cholinesterase levels measured 1722.8 U/L on 26/6/23. After clinically corelating symptoms to intermediate syndrome (IMS), treatment with atropine and PAM was restarted. Neurophysiological studies were carried out on 14th day. Results from motor and sensory nerve conduction studies on the median nerve on 14th day were normal. His muscle strength slowly improved and by 15th day he was neurologically normal. He recovered completely after three weeks. It shows that downregulation of acetylcholine receptors (AChRs) could explain the IMS and neurophysiological findings. These receptors have a half-life of 10 days.

Discussion

The IMS is comprised of characteristic symptoms and signs occurring after apparent recovery from the acute cholinergic syndrome. As the syndrome occurs after the acute cholinergic syndrome but before OP-induced delayed polyneuropathy, the syndrome is called “Intermediate Syndrome” (IMS). ² The IMS occurs in approximately 20% of patients following oral ingestion of OP pesticides, with no clear association between the type of OP compound involved and the development of the syndrome.

With appropriate therapy, complete recovery occurs 5–18 days later. The treatment of IMS is mainly supportive; early aggressive decontamination, appropriate antidote therapy, and prompt institution of ventilatory support should be helpful in ameliorating the magnitude and/or the incidence of IMS. Although IMS is well recognized as a disorder of neuromuscular junctions, its exact etiology, incidence, and risk factors are not clearly defined because existing studies are mostly the small-scale case series and do not employ a consistent and rigorous definition of IMS. ³ The prognosis of IMS is likely to be favorable if respiratory failure can be promptly recognized and treated accordingly.