Oxidative damage in intermediate syndrome of acute organophosphorous poisoning.

BACKGROUND & OBJECTIVES The main cause of morbidity due to organophosphate poisoning is intermediate syndrome (Type II paralysis) that can occur 48-72 h after poisoning. Mechanisms that underlie the intermediate syndrome are not known. This study investigates the role of oxidative damage to muscles as a possible mechanism underlying the development of the intermediate syndrome. METHODS Nineteen patients with acute organophosphate poisoning were evaluated from admission to discharge from intensive care for the severity of poisoning and the development and duration of the intermediate syndrome. Blood cholinesterases and parameters of oxidative stress were studied daily and their temporal profiles analysed according to the severity of poisoning and the development and duration of the intermediate syndrome. RESULTS Fifteen patients had severe poisoning and 16 developed intermediate syndrome. There was a positive association between the severity of poisoning and the occurrence of intermediate syndrome. There was no association between the organophosphate ingested and the development of intermediate syndrome. Erythrocyte membrane acetylcholinesterase and serum butyrylcholinesterase levels at admission and over the course of poisoning were significantly (P < 0.001) reduced in patients compared to controls. There were significantly (P < 0.05) higher levels of lipid peroxidation, conjugated dienes and protein thiols in erythrocyte membranes of patients who developed the intermediate syndrome compared to healthy controls, in patients who developed intermediate syndrome compared to those who did not and in patients with long compared to short duration intermediate syndrome. INTERPRETATION & CONCLUSION In acute organophosphate poisoning, severe and prolonged acetylcholinesterase inhibition is associated with oxidative stress, detected in erythrocyte membranes, that occurs early in the course of poisoning and may contribute to the development and severity of intermediate syndrome.