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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. 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. 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.

The case-fatality for intentional self-poisoning in the rural developing world is 10–50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment. We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander ( Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054. Mortality did not differ between the groups. 97 (6·3%) of 1531 participants in the multiple-dose group died, compared with 105 (6·8%) of 1554 in the no charcoal group (adjusted odds ratio 0·96, 95% CI 0·70–1·33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early. We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed.

Background Deliberate self-poisoning with agricultural pesticides is the commonest means of suicide in rural Asia. It is mostly impulsive and facilitated by easy access to pesticides. The aim of this large observational study was to investigate the immediate source of pesticides used for self-harm to help inform suicide prevention strategies such as reducing domestic access to pesticides. Methods The study was conducted in a district hospital serving an agricultural region of Sri Lanka. Patients who had self-poisoned with pesticides and were admitted to the adult medical wards were interviewed by study doctors following initial resuscitation to identify the source of pesticides they have ingested. Results Of the 669 patients included in the analysis, 425 (63.5%) were male; the median age was 26 (IQR 20-36). In 511 (76%) cases, the pesticides had been stored either inside or immediately outside the house; among this group only eight patients obtained pesticides that were kept in a locked container. Ten percent (n = 67) of the patients used pesticides stored in the field while 14% (n = 91) purchased pesticides from shops within a few hours of the episode. The most common reasons for choosing the particular pesticide for self-harm were its easy accessibility (n = 311, 46%) or its popularity as a suicide agent in their village (n = 290, 43%). Conclusion Three quarters of people who ingested pesticides in acts of self-harm used products that were available within the home or in close proximity; relatively few patients purchased the pesticide for the act. The study highlights the importance of reducing the accessibility of toxic pesticides in the domestic environment.

Background Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. At present symptomatic oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to gastric decontamination and atropine administration. The only proven effective antidote is digoxin antibodies but these are not available for routine use because of the high cost. The main objective of this study is to investigate the effectiveness of a new and inexpensive antidote for patients with life threatening arrhythmias due oleander poisoning. Method/design We set up a randomised double blind clinical trial to assess the effectiveness of Fructose 1, 6 diphosphate (FDP) in acute yellow oleander poisoning patients admitted to the adult medical wards of a tertiary hospital in Sri Lanka. Patients will be initially resuscitated following the national guidelines and eligible patients will be randomised to receive either FDP or an equal amount of normal saline. The primary outcome measure for this study is the sustained reversion to sinus rhythm with a heart rate greater than 50/min within 2 hours of completion of FDP/placebo bolus. Secondary outcomes include death, reversal of hyperkalaemia on the 6, 12, 18 and 24 hour samples and maintenance of sinus rhythm on the holter monitor. Analysis will be on intention-to-treat. Discussion This trial will provide information on the effectiveness of FDP in yellow oleander poisoning. If FDP is effective in cardiac glycoside toxicity, it would provide substantial benefit to the patients in rural Asia. The drug is inexpensive and thus could be made available at primary care hospitals if proven to be effective. Trial Registration Current Controlled trial ISRCTN71018309

There have been many animal studies on the effects of organophosphorus pesticide (OP) poisoning on thermoregulation with inconsistent results. There have been no prospective human studies. Our aim was to document the changes in body temperature with OP poisoning. A prospective study was conducted in a rural hospital in Polonnaruwa, Sri Lanka. We collected data on sequential patients with OP poisoning and analyzed 12 patients selected from 53 presentations who had overt signs and symptoms of OP poisoning and who had not received atropine prior to arrival. All patients subsequently received specific management with atropine and/or pralidoxime and general supportive care. Tympanic temperature, ambient temperature, heart rate, and clinical examination and interventions were recorded prospectively throughout their hospitalization. Initial hypothermia as low as 32°C was observed in untreated patients. Tympanic temperature increased over time from an early hypothermia (<35°C in 6/12 patients) to later fever (7/12 patients >38°C at some later point). While some of the late high temperatures occurred in the setting of marked tachycardia, it was also apparent that in some cases fever was not accompanied by tachycardia, making excessive atropine or severe infection an unlikely explanation for all the fevers. In humans, OP poisoning causes an initial hypothermia, and this is followed by a period of normal to high body temperature. Atropine and respiratory complications may contribute to fever but do not account for all cases.

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. Trial Registration Controlled-trials.com ISRCTN55264358 Please see later in the article for Editors' Summary

Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. At present symptomatic oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to gastric decontamination and atropine administration. The only proven effective antidote is digoxin antibodies but these are not available for routine use because of the high cost. The main objective of this study is to investigate the effectiveness of a new and inexpensive antidote for patients with life threatening arrhythmias due oleander poisoning. We set up a randomised double blind clinical trial to assess the effectiveness of Fructose 1, 6 diphosphate (FDP) in acute yellow oleander poisoning patients admitted to the adult medical wards of a tertiary hospital in Sri Lanka. Patients will be initially resuscitated following the national guidelines and eligible patients will be randomised to receive either FDP or an equal amount of normal saline. The primary outcome measure for this study is the sustained reversion to sinus rhythm with a heart rate greater than 50/min within 2 hours of completion of FDP/placebo bolus. Secondary outcomes include death, reversal of hyperkalaemia on the 6, 12, 18 and 24 hour samples and maintenance of sinus rhythm on the holter monitor. Analysis will be on intention-to-treat. This trial will provide information on the effectiveness of FDP in yellow oleander poisoning. If FDP is effective in cardiac glycoside toxicity, it would provide substantial benefit to the patients in rural Asia. The drug is inexpensive and thus could be made available at primary care hospitals if proven to be effective.