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

Prediction of outcome after paraquat poisoning by measurement of the plasma paraquat concentration

Background: Paraquat is a herbicide with a good occupational safety record, but a high mortality after intentional ingestion that has proved refractory to treatment. For nearly three decades paraquat concentration–time data have been used to predict the outcome following ingestion. However, none of the published methods has been independently or prospectively validated. We aimed to use prospectively collected data to test the published predictive methods and to determine if any is superior

Poisoning with the S-Alkyl organophosphorus insecticides profenofos and prothiofos

Background: Many organophosphorus (OP) insecticides have either two O-methyl or two O-ethyl groups attached to the phosphorus atom. This chemical structure affects their responsiveness to oxime-induced acetylcholinesterase (AChE) reactivation after poisoning. However, several OP insecticides are atypical and do not have these structures

Pattern of pesticide storage before pesticide self-poisoning in rural Sri Lanka

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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%).</p> <p>Conclusion</p> <p>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.</p

Evaluation of acceptability and use of lockable storage devices for pesticides in Sri Lanka that might assist in prevention of self-poisoning

<p>Abstract</p> <p>Background</p> <p>Self-poisoning with pesticides is a major reason for high suicide rates in rural areas of many developing countries. Safer storage of pesticides may be one means of prevention. We have conducted a study to assess the acceptability and use of lockable boxes for storing pesticides in rural Sri Lanka.</p> <p>Methods</p> <p>Four hundred lockable metal storage boxes were given to farming households, 100 in each of four villages. Assessment interviews were conducted by Sumithrayo (NGO) field workers immediately after boxes were supplied (T1), 11 – 14 weeks later (T2), 30 weeks later (T3), and 18 months later (T4). Data on suicide and self-harm were collected from local police and hospitals.</p> <p>Results</p> <p>At T1 only 1.8% (7/396) of households reported locking up pesticides, 72.5% (279/385) easy access to pesticides for adults and 50.4% (195/387) easy access for children. At T3 most informants in households using pesticides reported using the box all (82.3%, 298/362) or most of the time (7.2%, 26/362). Informants usually reported always locking the box (92.8%, 336/362) and most boxes were locked on inspection (93.6%, 339/362). By T4 there was some reduction in reporting that the box was kept locked all of the time (75.2%, 267/355) and the box being locked on inspection (73.8%, 262/355). Easy child access to the key was reported in relatively few households (10.7% at T4), although interviewers judged that this was possible in rather more (20.6%). Most informants regarded the box as useful (100% at T3 and 99.4% at T4), with convenience for storage, security, avoiding wastage, and protection of children being major factors. A message on the box about how to deal with bad feelings and the importance of safer storage was well received. The locks had been broken or the key lost in a few households.</p> <p>Conclusion</p> <p>Introduction of lockable boxes for storing pesticides to farming households in Sri Lanka appeared to be acceptable. Most households used the boxes responsibly, although there was some decline in the proper usage over time. A large-scale trial of lockable storage devices in farming households in rural areas as a means of prevention of suicide and accidental poisoning is now indicated.</p

The Importance of Poisoning vs. Road Traffic Injuries as a Cause of Death in Rural Sri Lanka

Road traffic crashes are considered by the WHO to be the most important global cause of death from injury. However, this may not be true for large areas of rural Asia where road vehicles are uncommon. The issue is important, since emphasising the importance of road traffic crashes risks switching resources to urban areas, away from already underfunded rural regions. In this study, we compared the importance of road traffic crashes with other forms of injury in a poor rural region of South Asia.We collected data on all deaths from injury in the North Central Province of Sri Lanka (NCP; population 1,105,198 at 2001 census) over 18 months using coronial, hospital, and police data. We calculated the incidence of death from all forms of intentional and unintentional injury in the province. The annual incidence of death from injury in the province was high: 84.2 per 100,000 population. Half of the deaths were from self-harm (41.3/100,000). Poisoning (35.7/100,000)-in particular, pesticide self-poisoning (23.7/100,000)-was the most common cause of death, being 3.9-fold more common than road traffic crashes (9.1/100,000).In poor rural regions of South Asia, fatal self-harm and pesticide self-poisoning in particular are significantly more important than road traffic injuries as a cause of death. It is possible that the data used by the WHO to calculate global injury estimates are biased towards urban areas with better data collection but little pesticide poisoning. More studies are required to inform a debate about the importance of different forms of injury and how avoidable deaths from any cause can be prevented. In the meantime, marked improvements in the effectiveness of therapy for pesticide poisoning, safer storage, reduced pesticide use, or reductions in pesticide toxicity are required urgently to reduce the number of deaths from self-poisoning in rural Asia

Hypothermia and Fever After Organophosphorus Poisoning in Humans—A Prospective Case Series

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

Personal and professional challenges in the management of deliberate self-poisoning patients in rural Sri Lanka: a qualitative study of rural hospital doctors' experiences and perceptions

Background. Deliberate self-poisoning is a major public heath issue in developing countries. In rural Sri Lanka deliberate self-poisoning is one of the leading causes of hospital death. The majority of patients with poisoning present to rural hospitals for initial treatment that are staffed by non-specialist and often relatively junior doctors. The treatment of self-poisoning patients poses numerous clinical challenges and further difficulties are experienced if patients are uncooperative and aggressive, intoxicated with alcohol or suffering mental illness. Previous research in developed countries has examined self-poisoning patients and their treatment but little is know about self-poisoning patient care in the context of rural health provision in developing countries. This study provides the first focused exploration of the experiences and perceptions of primary care rural hospital doctors in Sri Lanka toward the treatment of self-poisoning patients. Methods. Semi-structured in-depth interviews were conducted with fifteen doctors from rural hospitals in the North Central Province, Sri Lanka. All interviews were recorded and transcribed and subject to thematic analysis. Results. Participating doctors did perceive that treating self-poisoning patients in a primary care rural hospital as potentially confidence-building. However, resource issues such as the lack of medication, equipment and staffing were seen as important challenges to treating self-poisoning patients. Other challenges identified included disparity with community and other staff members regarding expectations of care, a sense of professional isolation and a lack of continuing education programs. Conclusion. Addressing professional isolation through educational and trainee programs for doctors and reducing the variance in expectations between professional groups and the community has the potential to improve delivery of care for self-poisoning patients