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

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

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

Pitching to the Home Shopping Network: An Exercise in Opportunity Assessment and Personal Selling

The purpose of this exercise is to help students of entrepreneurship understand opportunity assessment and the personal selling process. After watching a short video about the challenges and opportunities of launching a product on the Home Shopping Network (video is optional), students are asked to identify a unique product that could be successfully sold on the Home Shopping Network (HSN). Students are then required to pitch their product to the class demonstrating how their product suits HSN’s requirements, meets customer needs, and can be personally sold effectively to the network’s audience. By participating in this exercise students will experience the opportunity assessment process, aspects of marketing strategies, and the importance of personal selling

Pitching to the Home Shopping Network: An Exercise in Opportunity Assessment and Personal Selling

The purpose of this exercise is to help students of entrepreneurship understand opportunity assessment and the personal selling process. After watching a short video about the challenges and opportunities of launching a product on the Home Shopping Network (video is optional), students are asked to identify a unique product that could be successfully sold on the Home Shopping Network (HSN). Students are then required to pitch their product to the class demonstrating how their product suits HSN’s requirements, meets customer needs, and can be personally sold effectively to the network’s audience. By participating in this exercise students will experience the opportunity assessment process, aspects of marketing strategies, and the importance of personal selling

Relationship between alcohol co-ingestion and outcome in profenofos self-poisoning - A prospective case series

<div><p>Introduction</p><p>The importance of alcohol co-ingestion for outcome in organophosphorus (OP) insecticide self-poisoning has only been studied for the relatively hydrophilic dimethyl insecticide, dimethoate. We aimed to assess the effect of alcohol in acute poisoning with the lipophilic S-alkyl OP insecticide, profenofos.</p><p>Methodology</p><p>Demographic and clinical data, including an alcohol history, were prospectively collected from all cases of acute poisoning with agricultural profenofos EC50 presenting to two Sri Lankan hospitals over seven years.</p><p>Results</p><p>Of 1859 patients with acute OP insecticide self-poisoning, 243 (13.1%) reported ingestion of profenofos (male 182/243, 74.9%). Alcohol co-ingestion was reported by 64/243 (26.3%). All patients reporting alcohol co-ingestion were male (64/64 [100%] vs 118/179 [65.9%] not reporting alcohol ingestion, p<0.001). More patients reporting alcohol co-ingestion died (10/64 [15.6%] vs 10/179 [5.6%]; p = 0.013) and required intubation (13/64 [20.3%] vs 16/179 [8.9%], p = 0.016) compared to those who did not co-ingest alcohol. Using multi-logistic regression, controlling for the estimated dose ingested, age (OR 11.1 [2.5 to 48.9] for age > 35 years vs ≤35 years) and alcohol co-ingestion (OR 3.1 [1.2 to 7.9]) were independently associated with increased risk of death. Increased risk of intubation was independently associated with age (OR 3.2 [1.6 to 6.6] for age > 35 years vs ≤35 years) and alcohol co-ingestion (OR 3.2 [1.6 to 6.4]).</p><p>Conclusion</p><p>A history of alcohol co-ingestion, as well as older age, is independently associated with worse outcome in patients’ self-poisoned with profenofos.</p></div

Community uptake of safe storage boxes to reduce self-poisoning from pesticides in rural Sri Lanka

BACKGROUND: Acute poisoning by agricultural pesticides is a well established global public health problem. Keeping pesticides under safe storage is now promoted as a potential way to reduce the number of severe poisoning cases. However, there have been no published studies documenting the feasibility of such an approach. Therefore, the objective of the study presented here was to determine community perceptions and use of in-house safe storage boxes for pesticides in rural Sri Lanka. METHODS: Boxes with a lock, to be used for the in-house safe storage of pesticides, were distributed to 200 randomly selected farming households in two agricultural communities. A baseline survey determined pesticide storage practices and household characteristics prior to distribution. The selected households were encouraged to make use of the box at community meetings and during a single visit to each household one month after distribution. No further encouragement was offered. A follow-up survey assessed storage practices seven months into the project. RESULTS: Following the distribution of the boxes the community identified a number of benefits including the protection of pesticide containers against exposure from the rain and sun and a reduced risk of theft. Data were analysed for 172 households that reported agricultural use of pesticides at follow-up. Of these, 141 (82%) kept pesticides in the house under lock against 3 (2%) at baseline. As expected, the distribution of boxes significantly reduced the number of households storing pesticides in the field, from 79 (46%) at baseline to 4 (2%) at follow-up. There was a significant increase in the number of households keeping pesticides safe from children between baseline (64%) and seven months after the distribution of boxes (89%). The same was true for adults although less pronounced with 51% at baseline and 66% at follow-up. CONCLUSION: The farming community appreciated the storage boxes and made storage of pesticides safer, especially for children. It seems that additional, intensive promotion is needed to ensure that pesticide boxes are locked. The introduction of in-house safe storage boxes resulted in a shift of storage into the farmer's home and away from the field and this may increase the domestic risk of impulsive self-poisoning episodes. This increased risk needs attention in future safe storage promotion projects

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