Paraquat poisoning in Sri Lanka

Abstract

Self poisoning is a major medical problem in Asia. Patients are treated at rural, ill equipped hospitals which are under staffed- both in terms of numbers and training. Paraquat, a popular herbicide that has become an integral part of agriculture has been the most lethal pesticide in Sri Lanka and many other parts of Asia due to its very high case fatality (>70%). Paraquat self poisoning posed many challenges to both physicians and researchers. The natural history had been described only in one small case series reported in the West. The mechanism of toxicity of paraquat poisoning and treatment methods available had not been comprehensively reviewed to prioritise and design new antidote trials. The best way to estimate prognosis was unclear as prior studies did not directly compare the various markers of prognosis and many tests proposed were not widely available. The most widely used treatment for paraquat poisoning is immunosuppression with cyclophosphamide, dexamethasone and methylprednisolone. This treatment had however not been shown to work in an adequately powered RCT. This thesis presents a comprehensive review of the literature on paraquat poisoning and data from a cohort of 605 patients. The natural history and evolution of paraquat self poisoning is described and dozens of clinical and biochemical markers of prognosis were evaluated to create a simple decision support tool to aid determination of prognosis. A double blind randomized controlled clinical trial demonstrated that immunosuppression was ineffective in reducing mortality. A phase I/II trial with intravenous salicylate highlighted that this is a promising new treatment that requires further evaluation in larger trials. Show more