Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Acute Human Lethal Toxicity of Agricultural Pesticides: A Prospective Cohort Study

In a prospective cohort study of patients presenting with pesticide self-poisoning, Andrew Dawson and colleagues investigate the relative human toxicity of agricultural pesticides and contrast it with WHO toxicity classifications, which are based on toxicity in rats

Suicides by pesticide ingestion in Pakistan and the impact of pesticide regulation

Introduction: Suicide is a major public health problem in Pakistan, accounting to approximately 19,331 deaths every year. Many are due to consumption of acutely toxic pesticides; however, there is a lack of national suicide data, limiting knowledge and potential for intervention. In this paper, we aimed to review the literature on pesticide self-poisoning in Pakistan to identify the most problematic pesticides in relation to national pesticide regulations. Methods: Information on the currently registered and banned pesticides was obtained from Ministry of National Food Security and Research while data on pesticide import and use was extracted from FAOSTAT. We searched the following sources for articles and research papers on poisoning in Pakistan: Cumulative Index to Nursing and Allied Health (CINAHL), Google Scholar, Applied Social Sciences Index and Abstracts (ASSIA), Excerpta Medica (EMBASE), National Library of Medicine\u27s MEDLINE (PUBMED), PS102YCHINFO and Pakmedinet.com using the search terms \u27self-poisoning\u27, \u27deliberate self-harm\u27, \u27suicide\u27, \u27methods and means of suicide\u27, \u27organophosphate\u27, \u27wheat pill\u27, \u27aluminium phosphide\u27, \u27acute poisoning\u27, OR \u27pesticides\u27, AND \u27Pakistan\u27. Results: As of May 2021, 382 pesticide active ingredients (substances) were registered in Pakistan, of which five were WHO hazard class Ia (extremely hazardous) and 17 WHO hazard class Ib (highly hazardous). Twenty-six pesticides, four formulations, and seven non-registered pesticides had been banned, of which two were WHO class Ia and five Ib. We identified 106 hospital-level studies of poisoning conducted in Pakistan, of which 23 did not mention self-poisoning cases and one reported no suicidal poisoning cases. We found no community or forensic medicine studies. Of 52,323 poisoning cases identified in these papers, 24,546 [47%] were due to pesticides. The most commonly identified pesticide classes were organophosphorus (OP) insecticides (13,816 cases, 56%) and the fumigant aluminium phosphide (3 g 56% tablets, often termed \u27wheat pills\u27; 686 cases, 2.7%). Few studies identified the particular pesticides involved or the resulting case fatality. Conclusion: We found pesticide poisoning to be a major cause of poisoning in Pakistan, with OP insecticides and the fumigant aluminium phosphide the main pesticides identified. Withdrawal of Class I pesticides (as proposed to occur nationally in 2022) and high concentration aluminium phosphide tablets should rapidly reduce suicidal deaths by reducing the case fatality for low-intention poisoning cases. National cause of death data and forensic toxicology laboratory data identifying the pesticides responsible for deaths will be important to assess impacts of the proposed national ba