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1.  Management of acute paracetamol poisoning in a tertiary care hospital 
The Ceylon medical journal  2008;53(3):89-92.
Objectives
To compare the management of acute paracetamol poisoning with the best evidence available, and to determine the effect of plasma paracetamol level estimation on the management.
Design
Descriptive study with an intervention.
Setting
Medical wards of the National Hospital of Sri Lanka, Colombo.
Patients
Patients admitted with a history of acute paracetamol poisoning.
Intervention
Measurement of plasma paracetamol.
Methods
Data were obtained from the patients, medical staff and medical records. Plasma paracetamol was estimated between 4-24 hours of paracetamol ingestion. The current management practices were compared with the best evidence on acute paracetamol poisoning management.
Results
157 patients were included. The mean ingested dose of paracetamol was 333 mg/kg body weight. Majority of the patients (84%) were transfers. Induced emesis and activated charcoal were given to 91% of patients. N-acetylcysteine was given to 66, methionine to 55, and both to 2. A clinically important delay in the administration of antidotes was noted; 68% of patients received antidotes after 8 hours of the acute ingestion. Only 31 (26%) had paracetamol levels above the Rumack-Matthew normogram. 74 patients received an antidote despite having a plasma paracetamol level below the toxic level according to the normogram.
Interpretation
Management of acute paracetamol poisoning could be improved by following best available evidence and adapting cheaper methods for plasma paracetamol estimation.
PMCID: PMC3145136  PMID: 18982801
acute paracetamol poisoning; N-acetylcysteine; methionine
2.  Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial 
PLoS Medicine  2009;6(6):e1000104.
In a randomized controlled trial of individuals who had taken organophosphorus insecticides, Michael Eddleston and colleagues find that there is no evidence that the addition of the antidote pralidoxime offers benefit over atropine and supportive care.
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
Editors' Summary
Background
Each year, about 200,000 people worldwide die from poisoning with organophosphorous insecticides, toxic chemicals that are widely used in agriculture, particularly in developing countries. Organophosphates disrupt communication between the brain and the body in both insects and people. The brain controls the body by sending electrical impulses along nerve cells (neurons) to the body's muscle cells. At the end of the neurons, these impulses are converted into chemical messages (neurotransmitters), which cross the gap between neurons and muscle cells (the neuromuscular junction) and bind to proteins (receptors) on the muscle cells that pass on the brain's message. One important neurotransmitter is acetylcholine. This is used at neuromuscular junctions, in the part of the nervous system that controls breathing and other automatic vital functions, and in parts of the central nervous system. Normally, the enzyme acetylcholinesterase quickly breaks down acetylcholine after it has delivered its message, but organophosphates inhibit acetylcholinesterase and, as a result, disrupt the transmission of nerve impulses at nerve endings. Symptoms of organophosphate poisoning include excessive sweating, diarrhea, muscle weakness, and breathing problems. Most deaths from organophosphate poisoning are caused by respiratory failure.
Why Was This Study Done?
Treatment for organophosphorous insecticide poisoning includes resuscitation and assistance with breathing (intubation) if necessary and the rapid administration of atropine. This antidote binds to “muscarinic” acetylcholine receptors and blocks the effects of acetylcholine at this type of receptor. Atropine can only reverse some of the effects of organophosphate poisoning, however, because it does not block the activity of acetylcholine at its other receptors. Consequently, the World Health Organization (WHO) recommends that a second type of antidote called an oxime acetylcholinesterase reactivator be given after atropine. But, although the beneficial effects of atropine are clear, controversy surrounds the role of oximes in treating organophosphate poisoning. There is even some evidence that the oxime pralidoxime can be harmful. In this study, the researchers try to resolve this controversy by studying the effects of pralidoxime treatment on patients poisoned by organophosphorous insecticides in Sri Lanka in a randomized controlled trial (a study in which groups of patients are randomly chosen to receive different treatments).
What Did the Researchers Do and Find?
The researchers enrolled 235 adults who had been admitted to two Sri Lankan district hospitals with organophosphorous insecticide self-poisoning (in Sri Lanka, more than 70% of fatal suicide attempts are the result of pesticide poisoning). The patients, all of whom had been given atropine, were randomized to receive either the WHO recommended regimen of pralidoxime or saline. The researchers determined how much and which pesticide each patient had been exposed to, measured the levels of pralidoxime and acetylcholinesterase activity in the patients' blood, and monitored the patients' progress during their hospital stay. Overall, 48 patients died—30 of the 121 patients who received pralidoxime and 18 of the 114 control patients. After adjusting for the baseline characteristics of the two treatment groups and for intubation at baseline, pralidoxime treatment increased the patients' risk of dying by two-thirds, although this increased risk of death was not statistically significant. In other words, this result does not prove that pralidoxime treatment was bad for the patients in this trial. However, in further analyses that adjusted for the ingestion of different insecticides, the baseline levels of insecticides in patients' blood, and other prespecified variables, pralidoxime treatment always increased the patients' risk of death.
What Do These Findings Mean?
These findings provide no evidence that the WHO recommended regimen of pralidoxime improves survival after organophosphorous pesticide poisoning even though other results from the trial show that the treatment reactivated acetylcholinesterase. Indeed, although limited by the small number of patients enrolled into this study (the trial recruited fewer patients than expected because results from another trial had a deleterious effect on recruitment), these findings actually suggest that pralidoxime treatment may be harmful at least in self-poisoned patients. This suspicion now needs be confirmed in trials that more fully assess the risks/benefits of oximes and that explore the effects of different dosing regimens and/or different oximes.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000104.
The US Environmental Protection Agency provides information about all aspects of insecticides (in English and Spanish)
Toxtown, an interactive site from the US National Library of Medicine provides information on exposure to pesticides and other environmental health concerns (in English and Spanish)
The US National Pesticide Information Center provides objective, science-based information about pesticides (in English and Spanish)
MedlinePlus also provides links to information on pesticides (in English and Spanish)
For more on Poisoning Prevention and Management see WHO's International Programme on Chemical Safety (IPCS)
WikiTox, a clinical toxicology teaching resource project, has detailed information on organophosphates
doi:10.1371/journal.pmed.1000104
PMCID: PMC2696321  PMID: 19564902
3.  A quick inexpensive laboratory method in acute paracetamol poisoning could improve risk assessment, management and resource utilization 
Indian Journal of Pharmacology  2012;44(4):463-468.
Objectives:
Acute paracetamol poisoning is an emerging problem in Sri Lanka. Management guidelines recommend ingested dose and serum paracetamol concentrations to assess the risk. Our aim was to determine the usefulness of the patient's history of an ingested dose of >150 mg/kg and paracetamol concentration obtained by a simple colorimetric method to assess risk in patients with acute paracetamol poisoning.
Materials and Methods:
Serum paracetamol concentrations were determined in 100 patients with a history of paracetamol overdose using High Performance Liquid Chromatography (HPLC); (reference method). The results were compared to those obtained with a colorimetric method. The utility of risk assessment by reported dose ingested and colorimetric analysis were compared.
Results:
The area under the receiver operating characteristic curve for the history of ingested dose was 0.578 and there was no dose cut-off providing useful risk categorization. Both analytical methods had less than 5% intra- and inter-batch variation and were accurate on spiked samples. The time from blood collection to result was six times faster and ten times cheaper for colorimetry (30 minutes, US$2) than for HPLC (180 minutes, US$20). The correlation coefficient between the paracetamol levels by the two methods was 0.85. The agreement on clinical risk categorization on the standard nomogram was also good (Kappa = 0.62, sensitivity 81%, specificity 89%).
Conclusions:
History of dose ingested alone greatly over-estimated the number of patients who need antidotes and it was a poor predictor of risk. Paracetamol concentrations by colorimetry are rapid and inexpensive. The use of these would greatly improve the assessment of risk and greatly reduce unnecessary expenditure on antidotes.
doi:10.4103/0253-7613.99305
PMCID: PMC3469948  PMID: 23087506
Acute poisoning; paracetamol concentration; risk assessment
4.  Paracetamol (acetaminophen) poisoning 
BMJ Clinical Evidence  2007;2007:2101.
Introduction
Mortality from paracetamol overdose is now about 0.4%, although severe liver damage occurs without treatment in at least half of people with blood paracetamol levels above the UK standard treatment line. In adults, ingestion of less than 125 mg/kg is unlikely to lead to hepatotoxicity; even higher doses may be tolerated by children without causing liver damage.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute paracetamol poisoning? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: activated charcoal (single or multiple dose), gastric lavage, ipecacuanha, liver transplant, methionine, N-acetylcysteine.
Key Points
Paracetamol (acetaminophen) is a common means of self-poisoning in Europe and North America, often taken as an impulsive act of self-harm in young people. Mortality from paracetamol overdose is now about 0.4%, although without treatment, severe liver damage occurs in at least half of people with blood paracetamol levels above the UK standard treatment line.In adults, ingestion of less than 125 mg/kg is unlikely to lead to hepatotoxicity; even higher doses may be tolerated by children without causing liver damage.
Standard treatment of paracetamol overdose is acetylcysteine, which based on animal studies and clinical experience, is widely believed to reduce liver damage and mortality, although few studies have been done. Adverse effects from acetylcysteine include rash, urticaria, vomiting, and anaphylaxis which can, rarely, be fatal.We don't know what the optimal dose, route, and duration of acetylcysteine treatment should be. However, liver damage is less likely to occur if treatment is started within 8 to 10 hours of ingestion.
It is possible that methionine reduces the risk of liver damage and mortality after paracetamol poisoning compared with supportive care, but we don't know for sure.
We don't know whether activated charcoal, gastric lavage, or ipecacuanha reduce the risks of liver damage after paracetamol poisoning. The rapid absorption of paracetamol suggests that a beneficial effect from treatments that reduce gastric absorption is unlikely in many cases.
Liver transplantation may increase survival rates in people with fulminant liver failure after paracetamol poisoning compared with waiting list controls, but long-term outcomes are unknown.
PMCID: PMC2943815  PMID: 19450343
5.  Fructose-1, 6-diphosphate (FDP) as a novel antidote for yellow oleander-induced cardiac toxicity: A randomized controlled double blind study 
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
doi:10.1186/1471-227X-10-15
PMCID: PMC2912827  PMID: 20587052
6.  Exchange transfusion can be life-saving in severe propanil poisoning: a case report 
BMC Research Notes  2014;7:700.
Background
Propanil is an important cause of herbicide poisoning in Sri Lanka, accounting for about 2% of all cases of self-poisoning. The outcome is extremely poor when the poisoning is severe and current medical care is of limited efficacy. Death usually occurs due to the severe and prolonged methaemoglobinaemia. We describe a case of severe Propanil poisoning, successfully treated by exchange transfusion at a tertiary care hospital in Sri Lanka.
Case presentation
A 17-year old Sri Lankan male (body weight – 42 kg), presented to a local hospital 1 hour after self-ingestion of nearly 500 ml (4.3 g/kg) of liquid Propanil (concentration – 360 g/l). On admission he had dizziness and peripheral cyanosis. He was given intravenous methylene blue (1 mg/kg) within one hour of admission, which was repeated subsequently due to minimal response. The next day morning, (18 hours after poisoning) the patient was transferred to the National Hospital of Sri Lanka (NHSL) for further management. On admission to NHSL, he was drowsy and confused, had a shallow respiratory effort and marked central and peripheral cyanosis. Respiratory rate was 20/min, with a pulse-oximetry of 77% on room air. The arterial blood gas analysis was as follows; pH–7.24, HCO3−–12 mmol/l, pCO2–28 mmHg, pO2–239 mmHg and O2 saturation–100%. Exchange transfusion was commenced within two hours of admission to NHSL. A dramatic improvement in oxygen saturation was observed immediately afterwards, with the saturation in pulse-oximetry rising to >95%. The level of consciousness and respiratory effort also improved. He was discharged subsequently 8 days after the initial poisoning.
Conclusion
Propanil has potential to produce severe life threatening clinical manifestations, despite categorization as a herbicide with low toxicity. In cases of severe poisoning, exchange transfusion may be life saving. Since methylene blue, intensive care and exchange transfusion facilities are also not readily available in local hospitals, which frequently encounter cases of severe Propanil poisoning, early transfer of patients to tertiary care hospitals should be considered. Exchange transfusion may be helpful even in late stages in patients with severe poisoning.
doi:10.1186/1756-0500-7-700
PMCID: PMC4195897  PMID: 25292188
Propanil; Poisoning; Exchange transfusion; Sri Lanka
7.  Cost-effectiveness analyses of self-harm strategies aimed at reducing the mortality of pesticide self-poisonings in Sri Lanka: a study protocol 
BMJ Open  2015;5(2):e007333.
Introduction
An estimated 803 900 people worldwide died as a result of self-harm in 2012. The deliberate ingestion of pesticides has been identified as the method most frequently used to commit fatal self-harm globally. In Sri Lanka, it is estimated that up to 60% of all suicides are committed using this method. The aim of the present study is to assess the cost-effectiveness of an ongoing safe storage intervention currently taking place in a rural Sri Lankan district and to model the cost-effectiveness of implementing the safe storage intervention as well as four potential interventions (legislative, medical management, follow-up contact and mobile phone contact) on a national level.
Methods and analysis
Study design for all the strategies is a cost-effectiveness analysis. A governmental perspective is adopted. The time horizon for tracking the associated costs and health outcomes of the safe storage intervention on district level runs over 3 years. The time horizon is extended to 5 years when modelling a full national roll-out of the respective interventions. The discounting of costs and health outcomes are undertaken at the recommended real rate of 3%. Threshold analyses of the modelled strategies are employed to assess the strategies potential for cost-effectiveness, running scenarios with health outcome improvements ranging from 1% to 100%. Sensitivity analyses are also performed. The main outcome measures of the safe storage intervention are incremental cost-effectiveness ratios.
Ethics and dissemination
Ethical approval was granted for the safe storage project from the University of Peradeniya, Sri Lanka, in March of 2008. An amendment for the present study was granted from Rajarata University of Sri Lanka in November of 2013. Findings will be disseminated to public and private stakeholders in local and national government in Sri Lanka as well as the wider academic audience through peer-reviewed publications and international conferences.
Trial registration number
The safe storage cluster trial is registered with the Clinical Trials, ref: NCT1146496 (http://clinicaltrialsfeeds.org/clinical-trials/show/NCT1146496).
doi:10.1136/bmjopen-2014-007333
PMCID: PMC4346671  PMID: 25724984
HEALTH ECONOMICS; PUBLIC HEALTH
8.  Interrupted Time-Series Analysis of Regulations to Reduce Paracetamol (Acetaminophen) Poisoning 
PLoS Medicine  2007;4(4):e105.
Background
Paracetamol (acetaminophen) poisoning is the leading cause of acute liver failure in Great Britain and the United States. Successful interventions to reduced harm from paracetamol poisoning are needed. To achieve this, the government of the United Kingdom introduced legislation in 1998 limiting the pack size of paracetamol sold in shops. Several studies have reported recent decreases in fatal poisonings involving paracetamol. We use interrupted time-series analysis to evaluate whether the recent fall in the number of paracetamol deaths is different to trends in fatal poisoning involving aspirin, paracetamol compounds, antidepressants, or nondrug poisoning suicide.
Methods and Findings
We calculated directly age-standardised mortality rates for paracetamol poisoning in England and Wales from 1993 to 2004. We used an ordinary least-squares regression model divided into pre- and postintervention segments at 1999. The model included a term for autocorrelation within the time series. We tested for changes in the level and slope between the pre- and postintervention segments. To assess whether observed changes in the time series were unique to paracetamol, we compared against poisoning deaths involving compound paracetamol (not covered by the regulations), aspirin, antidepressants, and nonpoisoning suicide deaths. We did this comparison by calculating a ratio of each comparison series with paracetamol and applying a segmented regression model to the ratios. No change in the ratio level or slope indicated no difference compared to the control series. There were about 2,200 deaths involving paracetamol. The age-standardised mortality rate rose from 8.1 per million in 1993 to 8.8 per million in 1997, subsequently falling to about 5.3 per million in 2004. After the regulations were introduced, deaths dropped by 2.69 per million (p = 0.003). Trends in the age-standardised mortality rate for paracetamol compounds, aspirin, and antidepressants were broadly similar to paracetamol, increasing until 1997 and then declining. Nondrug poisoning suicide also declined during the study period, but was highest in 1993. The segmented regression models showed that the age-standardised mortality rate for compound paracetamol dropped less after the regulations (p = 0.012) but declined more rapidly afterward (p = 0.031). However, age-standardised rates for aspirin and antidepressants fell in a similar way to paracetamol after the regulations. Nondrug poisoning suicide declined at a similar rate to paracetamol after the regulations were introduced.
Conclusions
Introduction of regulations to limit availability of paracetamol coincided with a decrease in paracetamol-poisoning mortality. However, fatal poisoning involving aspirin, antidepressants, and to a lesser degree, paracetamol compounds, also showed similar trends. This raises the question whether the decline in paracetamol deaths was due to the regulations or was part of a wider trend in decreasing drug-poisoning mortality. We found little evidence to support the hypothesis that the 1998 regulations limiting pack size resulted in a greater reduction in poisoning deaths involving paracetamol than occurred for other drugs or nondrug poisoning suicide.
Analysis of mortality rates for paracetamol poisoning in England and Wales does not support the view that regulations limiting pack size have been responsible for a reduction in deaths.
Editors' Summary
Background.
Paracetamol—known as acetaminophen in the United States—is a cheap and effective painkiller. It is widely used to relieve minor aches and pains as well as fevers and headaches. Recommended doses of paracetamol are considered safe in humans, but overdoses are toxic and can cause liver failure and death. Because this drug is very easy to get hold of, there are many overdoses each year, either accidental or deliberate. In the UK, paracetamol poisoning is the most common cause of acute liver failure. Toward the end of 1998, new laws were introduced in the UK to try to reduce the number of paracetamol overdoses. These laws said that pharmacies could not sell packs of paracetamol containing more than 32 tablets and other shops could not sell packs with more than 16 tablets. One of the reasons behind the introduction of this law was that many suicides are not preplanned and, therefore, if it was harder for people to get hold of or keep large quantities of tablets, they might be less likely to attempt suicide or accidentally overdose.
Why Was This Study Done?
Following the introduction of these new laws, the number of deaths caused by paracetamol overdose in the UK dropped. However, it is possible that the drop in deaths came about for a variety of different reasons and not just as a result of the new laws on paracetamol pack size. For example, the suicide rate might have been falling anyway due to other changes in society and the fall in death rate from paracetamol might just have been part of that trend. It is important to find out whether the legal changes that were introduced to address a public health problem did in fact bring about a change for the better. This knowledge would also be relevant to other countries that are considering similar changes.
What Did the Researchers Do and Find?
The researchers used data from the Office of National Statistics, which holds information on drug poisoning deaths in England and Wales. These data were then broken down by the type of drug that was mentioned on the death certificate. The researchers compared death rates involving the following drugs: paracetamol; paracetamol-containing compounds (which were not subject to the new pack size laws); aspirin; antidepressant drugs; and then finally non-drug poisoning suicides. The reason for comparing death rates involving paracetamol against death rates involving other drugs, or non-drug suicide, was that this method would allow the researchers to see if the drop in paracetamol deaths followed overall trends in the poisoning or suicide rates or not. If the paracetamol death rate dropped following introduction of the new laws but the rates of other types of poisoning or suicide did not, then there would be a link between the new laws and a fall in paracetamol suicides. The researchers compared these death data within specific time periods before the end of 1998 (when the new laws on paracetamol pack size were introduced) and after.
Overall, there were nearly 2,200 deaths involving paracetamol between 1993 and 2004. The number of deaths per year involving paracetamol dropped substantially when comparing the periods of time before the end of 1998 and after it. However, the number of deaths per year involving any drug, and the non-drug suicides, also fell during this period of time. When comparing the trends for paracetamol deaths with other poisoning or suicide deaths, the researchers did not find any statistical evidence that the fall in paracetamol deaths was any different to the overall trend in poisoning or suicide death rates.
What Do These Findings Mean?
Although the paracetamol death rate fell immediately following the new laws on pack size, this study suggests the link might just be coincidence. The researchers could not find any data supporting the idea that the new laws caused a drop in paracetamol deaths. However, this was an observational study, not a true experimental one: the researchers here were clearly not able to set up equivalent “experimental” and “control” groups for comparison. It is very difficult to prove or disprove conclusively that new laws such as this are, or are not, effective.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040105
Information is available from Medline Plus about suicide
Wikipedia has an entry on paracetamol (note that Wikipedia is an internet encyclopedia anyone can edit)
Information about regulation of drugs in the UK is available from the Medicines and Healthcare Regulatory Agency
The Office for National Statistics provides key economic and social data about the UK, and is involved in many other important projects
doi:10.1371/journal.pmed.0040105
PMCID: PMC1845154  PMID: 17407385
9.  Improvement in Survival after Paraquat Ingestion Following Introduction of a New Formulation in Sri Lanka 
PLoS Medicine  2008;5(2):e49.
Background
Pesticide ingestion is a common method of self-harm in the rural developing world. In an attempt to reduce the high case fatality seen with the herbicide paraquat, a novel formulation (INTEON) has been developed containing an increased emetic concentration, a purgative, and an alginate that forms a gel under the acid conditions of the stomach, potentially slowing the absorption of paraquat and giving the emetic more time to be effective. We compared the outcome of paraquat self-poisoning with the standard formulation against the new INTEON formulation following its introduction into Sri Lanka.
Methods and Findings
Clinical data were prospectively collected on 586 patients with paraquat ingestion presenting to nine large hospitals across Sri Lanka with survival to 3 mo as the primary outcome. The identity of the formulation ingested after October 2004 was confirmed by assay of blood or urine samples for a marker compound present in INTEON. The proportion of known survivors increased from 76/297 with the standard formulation to 103/289 with INTEON ingestion, and estimated 3-mo survival improved from 27.1% to 36.7% (difference 9.5%; 95% confidence interval [CI] 2.0%–17.1%; p = 0.002, log rank test). Cox proportional hazards regression analyses showed an approximately 2-fold reduction in toxicity for INTEON compared to standard formulation. A higher proportion of patients ingesting INTEON vomited within 15 min (38% with the original formulation to 55% with INTEON, p < 0.001). Median survival time increased from 2.3 d (95% CI 1.2–3.4 d) with the standard formulation to 6.9 d (95% CI 3.3–10.7 d) with INTEON ingestion (p = 0.002, log rank test); however, in patients who did not survive there was a comparatively smaller increase in median time to death from 0.9 d (interquartile range [IQR] 0.5–3.4) to 1.5 d (IQR 0.5–5.5); p = 0.02.
Conclusions
The survey has shown that INTEON technology significantly reduces the mortality of patients following paraquat ingestion and increases survival time, most likely by reducing absorption.
Martin Wilks and colleagues compared the outcome of paraquat self-poisoning with the standard formulation against a new formulation following its introduction into Sri Lanka.
Editors' Summary
Background.
Paraquat is a non-selective herbicide used in many countries on a variety of crops including potatoes, rice, maize, tea, cotton, and bananas. It is fast-acting, rainfast, and facilitates “no-till” farming, but it has attracted controversy because of the potential for misuse, particularly in developing countries. Better training of workers has been shown to reduce the number of accidents, and additions to the liquid formulation have contributed to a reduction in cases where paraquat was drunk by mistake—blue color and a stench agent made it less attractive to drink, and an emetic to induce vomiting aimed to reduce the time it is retained in the body.
Why Was This Study Done?
Despite the changes made to the formulation, paraquat is still taken deliberately as a poison by agricultural workers in parts of the developing world. Although other pesticides cause more deaths overall, paraquat poisoning is more frequently fatal than other common pesticides. Syngenta, a commercial producer of paraquat, has developed a new paraquat formulation designed to reduce its toxicity. Syngenta introduced the new formulation in Sri Lanka, a country well known for its high level of suicides with pesticides, in 2004. This new formulation includes three components designed to reduce paraquat absorption from the stomach and intestines: a gelling agent to thicken the formulation in the acidic environment of the stomach and slow its passage into the small intestine; an increase in the amount of emetic to induce more vomiting more quickly; and a purgative to speed its exit from the small intestine, the main site of its absorption. The researchers wished to know whether the new formulation could contribute to improved survival in instances where paraquat had been ingested.
What Did the Researchers Do and Find?
The researchers gathered information on the time and circumstances of when paraquat was taken, the amount that was taken, the times, and details of any vomiting, treatment, and outcomes for cases of attempted suicide by paraquat poisoning at nine large hospitals in agricultural regions of Sri Lanka from December 2003 to January 2006. In total, 774 patients were tracked in this time. Syngenta introduced the new formulation in Sri Lanka on 1 October 2004. The researchers gathered information on the formulation involved in subsequent cases, by either interview or analysis of samples. After excluding some unusual or less certain cases, they analyzed data on 586 patients, of whom 297 had deliberately taken the standard formulation and 289 the new formulation.
Although the new formulation was still toxic, the data showed an increase in the proportion of cases surviving for at least three months—from 27% (standard formulation) to 37% (new formulation), an effect that was unlikely to be due to chance. More patients vomited within 15 minutes of taking the new formulation of paraquat. Patients who died generally survived longer if they had taken the new rather than the standard formulation. The researchers estimated that the new formulation is just over half as toxic as the standard formulation, meaning that a patient was likely to suffer the same level of ill effects after taking twice as much of the new formulation compared to the standard formulation.
What Do these Findings Mean?
This study was designed, funded, and led by Syngenta, the manufacturer of the standard and new formulations of paraquat but the study team included a number of independent Sri Lankan and international scientists. As the researchers observed the effects of the introduction of the new formulation across the entire country at the same time, they could not completely rule out other possible reasons for the differences in outcomes for those who had taken the two formulations, such as differences in treatment.
Despite this inherent drawback, the researchers estimate that during the study the new formulation saved about 30 lives. They conclude that the the new formulation does reduce the amount of paraquat absorbed by the body, although the study does not answer the question whether this was due to the gelling agent, the increased emetic in the new formulation or a combination of factors. The researchers suggest that the new formulation, by keeping patients alive longer, may allow doctors more time to treat patients. As no effective treatment exists at present, this benefit relies on a treatment being developed in the future.
The researchers note that the most important factor in predicting the outcome when paraquat has been taken deliberately is the dose. As a result, they suggest that the new formulation can only be one part of a wider strategy to reduce deaths by deliberate self-poisoning using paraquat. They suggest that such an integrated approach might include generic measures to reduce incidents of self-harm, reduced access to paraquat, reduced formulation strength, and improvements in treatment.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050049.
The US Environmental Protection Agency has published its Reregistration Eligibility Decision for paraquat
The Department of Health and Human Services of the US Centers for Disease Control and Prevention provides a fact sheet on how to handle paraquat and suspected cases of exposure
The World Health Organisation has recently finished consulting on a draft Poisons Information Monograph for paraquat
The International Programme on Chemical Safety (IPCS) has published a review of paraquat in its Environmental Health Criteria Series
MedlinePlus provides links to information on health effects of paraquat
doi:10.1371/journal.pmed.0050049
PMCID: PMC2253611  PMID: 18303942
10.  Acute Human Lethal Toxicity of Agricultural Pesticides: A Prospective Cohort Study 
PLoS Medicine  2010;7(10):e1000357.
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.
Background
Agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000–370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy.
Methods and Findings
We examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides—from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications.
Conclusion
The human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Suicide is a preventable global public health problem. About 1 million people die each year from suicide and many more harm themselves but survive. Although many people who commit suicide have a mental illness, stressful events (economic hardship or relationship difficulties, for example) can sometimes make life seem too painful to bear. Suicide attempts are frequently impulsive and use methods that are conveniently accessible. Strategies to reduce suicide rates include better treatment of mental illness and programs that help people at high risk of suicide deal with stress. Suicide rates can also be reduced by limiting access to common suicide methods. The single most important means of suicide worldwide is agricultural pesticide poisoning. Every year, between 250,000 and 370,000 people die from deliberate ingestion of pesticides (chemicals that kill animal pests or unwanted plants). Most of these suicides occur in rural areas of the developing world where high levels of pesticide use in agriculture combined with pesticide storage at home facilitate this particular method of suicide.
Why Was This Study Done?
To help reduce suicides through the ingestion of agricultural pesticides, the Food and Agriculture Organization of the United Nations recommends the withdrawal of the most toxic pesticides—World Health Organization (WHO) class I pesticides—from agricultural use. This strategy has proven successful in Sri Lanka where a ban on class I pesticides in 1995 and on the class II pesticide endosulfan in 1998 has reduced pesticide deaths by 50% over the past 20 years without decreasing agricultural output. Further reductions in suicides from pesticide ingestion could be achieved if regulatory restrictions on the sale and distribution of the most toxic class II pesticides were imposed. But such restrictions must balance agricultural needs against the impact of pesticides on public health. Unfortunately, the current WHO pesticide classification is based on toxicity in rats. Because rats handle pesticides differently from people, there is no guarantee that a pesticide with low toxicity in rodents is safe in people. Here, the researchers try to determine the relative human toxicity of agricultural pesticides in a prospective cohort study (a study in which people who share a characteristic—in this case, deliberate pesticide ingestion—are enrolled and followed to see how they fare).
What Did the Researchers Do and Find?
The researchers examined the case fatality (the proportion of patients dying after hospital admission) of different agricultural pesticides among patients who presented with pesticide self-poisoning at two Sri Lankan referral hospitals. Between April 2002 and November 2008, 9,302 people were admitted to the hospitals after swallowing a single pesticide. The researchers identified the pesticide ingested in 7,461 cases by asking the patient what he/she had taken or by identifying the container brought in by the patient or relatives. 10% of the patients died but there was a large variation in case fatality between pesticides. The herbicide paraquat was the most lethal pesticide, killing 42% of patients; several other pesticides killed no one. Compounds in the same chemical class and/or the same WHO toxicity class sometimes had very different toxicities. For example, dimethoate and malathione, both class II organophosphate insecticides, had case fatalities of 20.6% and 1.9%, respectively. Similarly, pesticides used for similar agricultural purposes sometimes had very different case fatalities.
What Do These Findings Mean?
These findings provide a toxicity ranking for pesticides that deviates markedly from the WHO toxicity classification based on rat toxicity. Although the findings are based on a study undertaken at just two Sri Lankan hospitals, they are likely to be generalizable to other hospitals and to other parts of rural Asia. However, because the study only included patients who were admitted to hospital after ingesting pesticides, the actual case fatalities for some pesticides may be somewhat different. Nevertheless, these findings have several important public health implications. For example, they suggest that the decision taken in January 2008 to withdraw paraquat, dimethoate, and fenthion from the Sri Lankan market should reduce deaths from pesticide poisoning in Sri Lanka by a further 33%–65% (equivalent to about 1,000 fewer suicides per year). More generally, they suggest that basing the regulation of pesticides on human toxicity has the potential to prevent hundreds and thousands of intentional and accidental deaths globally without compromising agricultural needs.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000357.
This study is further discussed in a PLoS Medicine Perspective by Matt Miller and Kavi Bhalla
The World Health Organization provides information on the global burden of suicide and on suicide prevention (in several languages) and on its classification of pesticides
The US Environmental Protection Agency provides information about all aspects of pesticides (in English and Spanish)
Toxtown, an interactive site from the US National Library of Science, provides information on environmental health concerns including exposure to pesticides (in English and Spanish)
The nonprofit organization Pesticide Action Network UK provides information about all aspects of pesticides
The US National Pesticide Information Center provides objective, science-based information about pesticides (in several languages)
The Food and Agriculture Organization of the United Nations leads international efforts to reduce hunger; as part of this effort, it has introduced pesticide policy reforms (in several languages)
MedlinePlus provides links to further resources about suicide and about pesticides (in English and Spanish)
doi:10.1371/journal.pmed.1000357
PMCID: PMC2964340  PMID: 21048990
11.  A MODIFIED LOW COST COLOURIMETRIC METHOD FOR PARACETAMOL (ACETAMINOPHEN) MEASUREMENT IN PLASMA 
Background
Despite a significant increase in the number of patients with paracetamol poisoning in the developing world, plasma paracetamol assays are not widely available. The purpose of this study was to assess a low cost modified colorimetric paracetamol assay that has the potential to be performed in small laboratories with restricted resources.
Methods
The paracetamol assay used in this study was based on the Glynn and Kendal colorimetric method with a few modifications in order to decrease the production of nitrous gas and thereby reduce infrastructure costs. Preliminary validation studies were performed using spiked aqueous samples with known concentrations of paracetamol. Subsequently, the results from the colorimetric method for 114 stored clinical samples from patients with paracetamol poisoning were compared with those from the current gold-standard high-performance liquid chromatography (HPLC) method. A prospective survey, assessing the clinical use of the paracetamol assay, was performed on all patients with paracetamol poisoning attending the Peradeniya General Hospital, Sri Lanka over a ten-month period.
Results
The recovery study showed an excellent correlation (r2 >0.998) for paracetamol concentrations from 25- 400 mg/l. The final yellow colour was stable for at least 10 minutes at room temperature. There was also excellent correlation with the HPLC method (r2=0.9758). In the clinical cohort study, use of the antidote N-acetylcysteine was avoided in over a third of patients who had a plasma paracetamol concentration measured. The cost of consumables used per assay was $0.50 (US).
Conclusions
This colorimetric paracetamol assay is reliable and accurate and can be performed rapidly, easily and economically. Use of this assay in resource poor clinical settings has the potential to have a significant clinical and economic impact on the management of paracetamol poisoning.
doi:10.3109/15563650903443137
PMCID: PMC3145116  PMID: 20095813
Paracetamol; Acetaminophen; paracetamol concentration; hepatotoxicity; overdose
12.  Effect of a Brief Outreach Educational Intervention on the Translation of Acute Poisoning Treatment Guidelines to Practice in Rural Sri Lankan Hospitals: A Cluster Randomized Controlled Trial 
PLoS ONE  2013;8(8):e71787.
Background
In developing countries, including Sri Lanka, a high proportion of acute poisoning and other medical emergencies are initially treated in rural peripheral hospitals. Patients are then usually transferred to referral hospitals for further treatment. Guidelines are often used to promote better patient care in these emergencies. We conducted a cluster randomized controlled trial (ISRCTN73983810) which aimed to assess the effect of a brief educational outreach (‘academic detailing’) intervention to promote the utilization of treatment guidelines for acute poisoning.
Methods and Findings
This cluster RCT was conducted in the North Central Province of Sri Lanka. All peripheral hospitals in the province were randomized to either intervention or control. All hospitals received a copy of the guidelines. The intervention hospitals received a brief out-reach academic detailing workshop which explained poisoning treatment guidelines and guideline promotional items designed to be used in daily care. Data were collected on all patients admitted due to poisoning for 12 months post-intervention in all study hospitals. Information collected included type of poison exposure, initial investigations, treatments and hospital outcome. Patients transferred from peripheral hospitals to referral hospitals had their clinical outcomes recorded. There were 23 intervention and 23 control hospitals. There were no significant differences in the patient characteristics, such as age, gender and the poisons ingested. The intervention hospitals showed a significant improvement in administration of activated charcoal [OR 2.95 (95% CI 1.28–6.80)]. There was no difference between hospitals in use of other decontamination methods.
Conclusion
This study shows that an educational intervention consisting of brief out-reach academic detailing was effective in changing treatment behavior in rural Sri Lankan hospitals. The intervention was only effective for treatments with direct clinician involvement, such as administering activated charcoal. It was not successful for treatments usually administered by non-professional staff such as forced emesis for poisoning.
Trial Registration
Controlled-Trials.com ISRCTN73983810 ISRCTN73983810
doi:10.1371/journal.pone.0071787
PMCID: PMC3747188  PMID: 23990989
13.  Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. 
British Medical Journal  1979;2(6198):1097-1100.
One hundred cases of severe paracetamol poisoning were treated with intravenous N-acetylcysteine (acetyl-cysteine). There was virtually complete protection against liver damage in 40 patients treated within eight hours after ingestion (mean maximum serum alanine transaminase activity 27 IU/1). Only one out of 62 patients treated within 10 hours developed severe liver damage compared with 33 out of 57 patients (58%) studied retrospectively who received supportive treatment alone. Early treatment and acetylcysteine also prevented renal impairment and death. The critical ingestion-treatment interval for complete protection against severe liver damage was eight hours. Efficacy diminished progressively thereafter, and treatment after 15 hours was completely ineffective. Intravenous acetylcysteine was more effective than cysteamine and methionine and noticeably free of adverse effects. It is the treatment of choice for paracetamol poisoning.
PMCID: PMC1597048  PMID: 519312
14.  Scottish and Newcastle Antiemetic Pre-treatment for paracetamol poisoning study (SNAP) 
Background
Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. The intravenous (IV) N-acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively unchanged. This involves 3 different infusion regimens (dose and time) lasting over 20 hours. The same weight-related dose of NAC is used irrespective of paracetamol dose. Complications include frequent nausea and vomiting, anaphylactoid reactions and dosing errors. We designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard NAC and a modified, shorter, regimen.
Methods/Design
We designed a double-blind trial using a 2 × 2 factorial design involving four parallel groups. Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was stratified on: paracetamol dose, perceived risk factors, and time to presentation. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions and end of treatment liver function documented. Where clinically necessary further doses of NAC were administered as per standard UK protocols at the end of the first antidote course.
Discussion
This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first attempt to formally examine new methods of administering IV NAC in paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new NAC regimen. In addition as anaphylactoid response appears related to plasma concentrations of both NAC and paracetamol anaphylactoid reactions should be less likely. This study is not powered to assess the relative efficacy of the two NAC regimens, however it will give useful information to power future studies. As the first formal randomised clinical trial in this patient group in over 30 years this study will also provide information to support further studies in patients in paracetamol overdose, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk.
Trial registration
EudraCT number 2009-017800-10, ClinicalTrials.gov IdentifierNCT01050270
doi:10.1186/2050-6511-14-20
PMCID: PMC3626543  PMID: 23556549
Paracetamol; Acetylcysteine; Overdose; Antidotes; Hepatotoxicity
15.  Characteristics of non-fatal self-poisoning in Sri Lanka: a systematic review 
BMC Public Health  2013;13:331.
Background
The rate of non-fatal self-poisoning in Sri Lanka has increased in recent years, with associated morbidity and economic cost to the country. This review examines the published literature for the characteristics and factors associated with non-fatal self-poisoning in Sri Lanka.
Methods
Electronic searches were conducted in Psychinfo, Proquest, Medline and Cochrane databases from inception to October 2011.
Results
26 publications (representing 23 studies) were eligible to be included in the review. A majority of studies reported non-fatal self-poisoning to be more common among males, with a peak age range of 10–30 years. Pesticide ingestion was the most commonly used method of non-fatal self-poisoning. However three studies conducted within the last ten years, in urban areas of the country, reported non-fatal self-poisoning by medicinal overdose to be more common, and also reported non-fatal self-poisoning to be more common among females. Interpersonal conflict was the most commonly reported short-term stressor associated with self-poisoning. Alcohol misuse was reported among males who self-poisoned, and data regarding other psychiatric morbidity was limited.
Conclusions
The findings indicate that pesticide ingestion is the commonest method of non-fatal self-poisoning in Sri Lanka, and it is more common among young males, similar to other Asian countries. However there appears to be an emerging pattern of increasing medicinal overdoses, paralleled by a gender shift towards increased female non-fatal self-poisoning in urban areas.
Many non-fatal self-poisoning attempts appear to occur in the context of acute interpersonal stress, with short premeditation, and associated with alcohol misuse in males. Similar to other Asian countries, strategies to reduce non-fatal self-poisoning in Sri Lanka require integrated intervention programs with several key aspects, including culturally appropriate interventions to develop interpersonal skills in young people, community based programs to reduce alcohol misuse, and screening for and specific management of those at high risk of repetition following an attempt of self-poisoning.
doi:10.1186/1471-2458-13-331
PMCID: PMC3637511  PMID: 23575389
16.  Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial 
PLoS Medicine  2011;8(5):e1000435.
In a factorial randomized trial conducted in Sri Lanka, de Silva and colleagues evaluate the safety and efficacy of pretreatments intended to reduce the risk of serious reactions to antivenom following snakebite.
Background
Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial.
Methods and Findings
In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline.
Conclusions
Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized.
Trial registration
www.ClinicalTrials.gov NCT00270777
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Of the 3,000 or so snake species in the world, about 600 are venomous. Venomous snakes, which are particularly common in equatorial and tropical regions, immobilize their prey by injecting modified saliva (venom) into their prey's tissues through their fangs—specialized hollow teeth. Snakes also use their venoms for self-defense and will bite people who threaten, startle, or provoke them. A bite from a highly venomous snake such as a pit viper or cobra can cause widespread bleeding, muscle paralysis, irreversible kidney damage, and tissue destruction (necrosis) around the bite site. All these effects of snakebite are potentially fatal; necrosis can also result in amputation and permanent disability. It is hard to get accurate estimates of the number of people affected by snakebite, but there may be about 2 million envenomings (injections of venom) and 100,000 deaths every year, many of them in rural areas of South Asia, Southeast Asia, and sub-Saharan Africa.
Why Was This Study Done?
The best treatment for snakebite is to give antivenom (a mixture of antibodies that neutralize the venom) as soon as possible. Unfortunately, in countries where snakebites are common (for example, Sri Lanka), antivenoms are often of dubious quality, and acute allergic reactions to them frequently occur. Although some of these reactions are mild (for example, rashes), in up to 40% of cases, anaphylaxis—a potentially fatal, whole-body allergic reaction—develops. The major symptoms of anaphylaxis—a sudden drop in blood pressure and breathing difficulties caused by swelling of the airways—can be treated with adrenaline. Injections of antihistamines (for example, promethazine) and hydrocortisone can also help. In an effort to prevent anaphylaxis, these drugs are also widely given before antivenom, but there is little evidence that such “prophylactic” treatment is effective or safe. In this randomized double-blind controlled trial (RCT), the researchers test whether low-dose adrenaline, promethazine, and/or hydrocortisone can prevent acute adverse reactions to antivenom. In an RCT, the effects of various interventions are compared to a placebo (dummy) in groups of randomly chosen patients; neither the patients nor the people caring for them know who is receiving which treatment until the trial is completed.
What Did the Researchers Do and Find?
The researchers randomized 1,007 patients who had been admitted to secondary referral hospitals in Sri Lanka after snakebite to receive low-dose adrenaline, promethazine, hydrocortisone, or placebo alone and in all possible combinations immediately before treatment with antivenom. The patients were monitored for at least 96 hours for adverse reactions to the antivenom; patients who reacted badly were given adrenaline, promethazine, and hydrocortisone as “rescue medication.” Three-quarters of the patients had acute reactions—mostly moderate or severe—to the antivenom. Most of the acute reactions occurred within an hour of receiving the antivenom, and nearly half of all the patients were given rescue medication during the first hour. Compared with placebo, pretreatment with adrenaline reduced severe reactions to the antivenom by 43% at one hour and by 38% over 48 hours. By contrast, neither hydrocortisone nor promethazine given alone reduced the rate of adverse reactions to the antivenom. Moreover, adding hydrocortisone negated the beneficial effect of adrenaline.
What Do These Findings Mean?
These findings show that pretreatment with low-dose adrenaline is safe and reduces the risk of acute severe reactions to snake antivenom, particularly during the first hour after infusion. They do not provide support for pretreatment with promethazine or hydrocortisone, however. Indeed, the findings suggest that the addition of hydrocortisone could negate the benefits of adrenaline, although this finding needs to be treated with caution because of the design of the trial, as does the observed increased risk of death associated with pretreatment with hydrocortisone. More generally, the high rate of acute adverse reactions to antivenom in this trial highlights the importance of improving the quality of antivenoms available in Sri Lanka and other parts of South Asia. The researchers note that the recent World Health Organization guidelines on production, control, and regulation of antivenom should help in this regard but stress that, for now, it is imperative that physicians carefully monitor patients who have been given antivenom and provide prompt treatment of acute reactions when they occur.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000435.
The MedlinePlus Encyclopedia has pages on snakebite and on anaphylaxis (in English and Spanish)
The UK National Health Service Choices website also has pages on snakebite and on anaphylaxis
The World Health Organization has information on snakebite and on snake antivenoms (in several languages); its Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins are also available
The Global Snakebite Initiative has information on snakebite
A PLoS Medicine Research Article by Anuradhani Kasturiratne and colleagues provides data on the global burden of snakebite
A PLoS Medicine Neglected Diseases Article by José María Gutiérrez and colleagues discusses the neglected problem of snakebite envenoming
doi:10.1371/journal.pmed.1000435
PMCID: PMC3091849  PMID: 21572992
17.  The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka 
PLoS Medicine  2008;5(7):e147.
Background
Intermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulation (RNS) predictors of IMS that would assist in patient management and clinical research.
Methods and Findings
Seventy-eight consenting symptomatic patients with organophosphate poisoning were assessed prospectively with daily physical examination and RNS. RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. The study was conducted as a prospective observational cohort study in the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients using a priori clinical diagnostic criteria, and five of them developed respiratory failure. All ten patients showed progressive RNS changes correlating with the severity of IMS. A decrement-increment was observed at intermediate and high frequencies preceding the onset of clinical signs of IMS. As the patient developed clinical signs of IMS, decrement-increment was progressively noted at low and intermediate frequencies and a combination of decrement-increment and repetitive fade or severe decrement was noted at high frequencies. Severe decrement preceded respiratory failure in four patients. Thirty patients developed forme fruste IMS with less severe weakness not progressing to respiratory failure whose RNS was characterized by decrement-increment or a combination of decrement-increment and repetitive fade but never severe decrements.
Conclusions
Characteristic changes in RNS, preceding the development of IMS, help to identify a subgroup of patients at high risk of developing respiratory failure. The forme fruste IMS with the characteristic early changes on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and precede the diagnosis and complications of IMS. Thus they may be useful in clinical management and research.
Jayawardane and colleagues evaluate a cohort of 78 patients with organophosphate poisoning from Sri Lanka, and identify changes in repetitive nerve stimulation that precede, and may help predict, the onset of intermediate syndrome.
Editors' Summary
Background.
Each year, many thousands of deaths around the world are caused by pesticide poisoning. Often, the pesticide involved is an organophosphate. These highly toxic compounds, which are widely used in agriculture, particularly in developing countries, disrupt the transmission of messages from the brain to the body in insect pests and in people. The brain controls body movements by sending electrical impulses along nerve cells (neurons). At the end of the neurons, these impulses are converted into chemical messengers (neurotransmitters), which cross the gap between neurons and muscle cells (the neuromuscular junction) and bind to proteins on the surface of the muscle cells to pass on the brain's message. One important neurotransmitter is acetylcholine. This is used in the part of the nervous system that controls breathing and other automatic vital functions, at neuromuscular junctions, and in parts of the central nervous system. Normally, acetylcholine is quickly broken down after it has delivered its message, but organophosphates disrupt this process and, consequently, affect nerve transmission to muscles. Organophosphate poisoning causes three syndromes. The cholinergic syndrome, which can be fatal, happens soon after organophosphates are swallowed, inhaled, or absorbed through the skin. The intermediate syndrome (IMS), which results in muscle weakness in the limbs, neck, and throat, develops in some patients 24–96 hours after poisoning. Finally, long-term nerve damage sometimes develops 2–3 weeks after poisoning.
Why Was This Study Done?
Although IMS is a major contributor to the illness caused by organophosphate poisoning and can result in respiratory (breathing) failure and death, the functional changes that are associated with IMS (its pathophysiology) are poorly understood. With a better understanding of these changes, it might be possible to find ways to prevent or treat IMS or to predict which patients with IMS are likely to develop respiratory failure. In this study, the researchers make a set of measurements of nerve transmission in a large group of organophosphate-poisoned patients in Sri Lanka to discover more about the pathophysiology of IMS.
What Did the Researchers Do and Find?
Seventy-eight patients with organophosphate poisoning were assessed several times a day for clinical signs of IMS. In addition, nerve transmission was measured daily in the patients using an electrophysiological technique called repetitive nerve stimulation (RNS). For this, a series of small electrical shocks was applied to the certain nerves in the arm and the responses in the muscles that these nerves control were recorded. In the ten study participants who developed IMS, the researchers observed several characteristic changes in their muscle responses to RNS, some of which were seen before the clinical signs of IMS. Other changes in muscle responses to RNS correlated with the development of clear IMS. Most importantly, in the four patients with IMS who developed respiratory failure, an RNS response pattern called severe decrement (a reduced response to the first electrical shock and then no response to the subsequent shocks) was seen before respiratory failure. Finally, there were other characteristic changes in muscle responses to RNS in 30 patients with muscle weakness not severe enough for a diagnosis of IMS (incomplete or “forme fruste” IMS).
What Do These Findings Mean?
These findings indicate that changes in nerve transmission that can be objectively monitored using RNS evolve during the development of IMS. In other words, IMS is a “spectrum” disorder in which the weakness and neuromuscular junction problems caused by organophosphate poisoning gradually progress over time through a series of electrophysiological changes that will sometimes resolve quickly and only in the most severe cases will result in respiratory failure. These findings need to be validated in further studies, particularly since most of the patients in this study had been exposed to a single organophosphate (chlorpyrifos). However, they suggest that the RNS tests might be useful in the clinical management of patients with organophosphate poisoning, particularly since such tests could provide an early warning of impending respiratory failure.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050147.
This study is further discussed in a PLoS Medicine Perspective by Cynthia Aaron
The US Environmental Protection Agency provides information about all aspects of pesticides (in English and Spanish)
Toxtown, an interactive site from the US National Library of Science, provides information on environmental health concerns including exposure to pesticides (in English and Spanish)
The US National Pesticide Information Center provides objective, science-based information about pesticides
MedlinePlus also provides links to information on pesticides (in English and Spanish)
The International Programme on Chemical Safety has information on poisoning prevention and management; its INTOX databank has a description of the cholinergic syndrome
WikiTox is a clinical toxicology resource
doi:10.1371/journal.pmed.0050147
PMCID: PMC2459203  PMID: 18630983
18.  Effect of the UK’s revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment 
Aims
In September 2012 the UK’s Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l−1’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning.
Methods
Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose.
Results
There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million).
Conclusions
The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning.
doi:10.1111/bcp.12362
PMCID: PMC4243911  PMID: 24666324
acetylcysteine; adverse effects; paracetamol; poisoning; regulation
19.  Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment 
Aims
In September 2012 the UK's Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l−1’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning.
Methods
Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose.
Results
There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million).
Conclusions
The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning.
doi:10.1111/bcp.12362
PMCID: PMC4243911  PMID: 24666324
acetylcysteine; adverse effects; paracetamol; poisoning; regulation
20.  Study protocol: a randomised controlled trial of multiple and single dose activated charcoal for acute self-poisoning 
Background
The case fatality for intentional self-poisoning in rural Asia is 10–30 times higher than in the West, mostly due to the use of highly toxic poisons. Activated charcoal is a widely available intervention that may – if given early – bind to poisons in the stomach and prevent their absorption. Current guidelines recommend giving a single dose of charcoal (SDAC) if patients arrive within an hour of ingestion. Multiple doses (MDAC) may increase poison elimination at a later time by interrupting any enterohepatic or enterovascular circulations. The effectiveness of SDAC or MDAC is unknown. Since most patients present to hospital after one hour, we considered MDAC to have a higher likelihood of clinical benefit and set up a study to compare MDAC with no charcoal. A third arm of SDAC was added to help determine whether any benefit noted from MDAC resulted from the first dose or all doses.
Methods/design
We set up a randomised controlled trial assessing the effectiveness of superactivated charcoal in unselected adult self-poisoning patients admitted to the adult medical wards of three Sri Lankan secondary hospitals. Patients were randomised to standard treatment or standard treatment plus either a single 50 g dose of superactivated charcoal dissolved in 300 ml of water or six doses every four hours. All patients with a history of poison ingestion were approached concerning the study and written informed consent taken from each patient, or their relative (for unconscious patients or those <16 yrs), recruited to the study. The exclusion criteria were: age under 14 yrs; prior treatment with activated charcoal during this poisoning episode; pregnancy; ingestion of a corrosive or hydrocarbon; requirement for oral medication; inability of the medical staff to intubate the patient with a Glasgow Coma Score <13; presentation >72 hrs post-ingestion, and previous recruitment. The primary outcome was in-hospital mortality; secondary outcomes included the occurrence of serious complications (need for intubation, time requiring assisted ventilation, fits, cardiac dysrhythmias). Analysis will be on an intention-to-treat basis; the effects of reported time to treatment after poisoning and status on admission will also be assessed.
Discussion
This trial will provide important information on the effectiveness of both single and multiple dose activated charcoal in the forms of poisoning commonly seen in rural Asia. If charcoal is found to be effective, it should be possible to make it widely available across rural Asia in an affordable formulation.
Trial registration
Current Controlled Trials ISRCTN02920054
doi:10.1186/1471-227X-7-2
PMCID: PMC1885817  PMID: 17498281
21.  Peripheral Burning Sensation: A Novel Clinical Marker of Poor Prognosis and Higher Plasma Paraquat Levels in Paraquat Poisoning 
Introduction
Self poisoning with paraquat has a case fatality ratio (CFR) over 65% in Sri Lanka. Plasma paraquat concentration is the best prognostic indicator for patient outcome but is not readily available. Alternative surrogate clinical markers could be useful in management and determining prognosis.
Anecdotal reports by medical and research staff suggested that patients who complained of burning sensation of the body had a poor prognosis and a prospective study was initiated.
Methods
This was a prospective observational study in 3 hospitals in Sri Lanka. We collected demographic data, presence or absence of burning sensation and major outcome and determined plasma paraquat concentration within 24 hours post ingestion.
Results
There were 179 patients with deliberate self ingestion of paraquat over 30 months.
Burning sensation was reported in 84 patients (48%) which initiated at a median of 1 day (range 1-3 days) post ingestion. Of the patients who had burning, 61 died (case fatality rate72.62%; 95% CI 62-81). Of the 91 patients who had no peripheral burning, 23 died (CFR 25.27%, 95% CI 18.15-35.9).figure 1.
Presence of peripheral burning sensation was associated with a significantly higher risk of death (Odds Ratio: 7.8, 95% CI: 3.9-15, p <0.0001). Patients who complained of peripheral burning died at a median of 36 hours (IQR 30.5-88) following ingestion while those who had no peripheral burning died at a median of 50.5 hours (IQR 16.75-80). The difference was not significant (p>0.05). Median admission plasma paraquat concentration in patients with peripheral burning (2.67 μg/mL, 95% CI 0.84-14.2) was significantly higher than in the patients with no peripheral burning (0.022 μg/mL, 95% CI 0.005-0.78; p<0.001).
Peripheral burning has a sensitivity of 0.72 (95% CI: 0.6-8) and specificity of 0.74 (95% CI: 0.64-.08) and a positive predictive value of 0.73 (95% CI: 0.6-.8).
Discussion
It is possible that this symptom may help discriminate between patients who have poor chance of survival and those who may potentially benefit from interventions. The mechanism is not clear but could include either a direct concentration related effect or be a marker of oxidative stress.
Conclusion
Presence of burning sensation is associated with high plasma paraquat concentrations and is strongly predictive of death.
doi:10.3109/15563651003641794
PMCID: PMC3145098  PMID: 20507246
22.  Clinical outcomes and kinetics of propanil following acute self-poisoning: a prospective case series 
Background
Propanil is an important cause of death from acute pesticide poisoning, of which methaemoglobinaemia is an important manifestation. However, there is limited information about the clinical toxicity and kinetics. The objective of this study is to describe the clinical outcomes and kinetics of propanil following acute intentional self-poisoning.
Methods
431 patients with a history of propanil poisoning were admitted from 2002 until 2007 in a large, multi-centre prospective cohort study in rural hospitals in Sri Lanka. 40 of these patients ingested propanil with at least one other poison and were not considered further. The remaining 391 patients were classified using a simple grading system on the basis of clinical outcomes; methaemoglobinaemia could not be quantified due to limited resources. Blood samples were obtained on admission and a subset of patients provided multiple samples for kinetic analysis of propanil and the metabolite 3,4-dichloroaniline (DCA).
Results
There were 42 deaths (median time to death 1.5 days) giving a case fatality of 10.7%. Death occurred despite treatment in the context of cyanosis, sedation, hypotension and severe lactic acidosis consistent with methaemoglobinaemia. Treatment consisted primarily of methylene blue (1 mg/kg for one or two doses), exchange transfusion and supportive care when methaemoglobinaemia was diagnosed clinically. Admission plasma concentrations of propanil and DCA reflected the clinical outcome. The elimination half-life of propanil was 3.2 hours (95% confidence interval 2.6 to 4.1 hours) and the concentration of DCA was generally higher, more persistent and more variable than propanil.
Conclusion
Propanil is the most lethal herbicide in Sri Lanka after paraquat. Methylene blue was largely prescribed in low doses and administered as intermittent boluses which are expected to be suboptimal given the kinetics of methylene blue, propanil and the DCA metabolite. But in the absence of controlled studies the efficacy of these and other treatments is poorly defined. More research is required into the optimal management of acute propanil poisoning.
doi:10.1186/1472-6904-9-3
PMCID: PMC2656468  PMID: 19220887
23.  A comparison of non-fatal self-poisoning among males and females, in Sri Lanka 
BMC Psychiatry  2014;14:221.
Background
In the recent past Sri Lanka has had a high rate of attempted suicide by pesticide ingestion, among both males and females. Recent evidence suggests that these trends in self-poisoning may be changing, with increasing medicinal overdoses and changing gender ratios. In the past, attempted suicide in Sri Lanka has been described as impulsive acts, but research regarding aspects such as suicidal intent is limited, and there has been no comparison between genders. The objective of this study was to describe gender differences in non-fatal self-poisoning in Sri Lanka with respect to substances ingested, triggers, stressors, suicidal intent and psychiatric morbidity.
Methods
Persons admitted to Teaching Hospital Peradeniya, Sri Lanka, for medical management of non-fatal self-poisoning over a consecutive 14-month period were eligible for the study. Participants were interviewed within one week of admission, with regard to demographic details, poison type ingested, triggers, psychiatric morbidity and suicidal intent. 949 participants were included in the study, of whom 44.2% were males, with a median age of 22 years.
Results
Males were significantly more likely to ingest agrochemicals, whereas females were more likely to overdose on pharmaceutical drugs. Interpersonal conflict was a common trigger associated with non-fatal self-poisoning for both males and females. Alcohol use disorders and high suicidal intent were significantly more likely in males. There was no difference in rates of depression between the genders. Multiple regression for both genders separately showed that the presence of depression and higher levels of hopelessness was the strongest predictor of suicidal intent, for both genders.
Conclusions
Patterns of non-fatal self-poisoning in Sri Lanka appear to be changing to resemble Western patterns, with females having a greater rate of self-poisoning and more medicinal overdoses than males. Alcohol use disorder is a gender specific risk factor associated with non-fatal self-poisoning among males, indicating a need for specific intervention. However there are also many common risk factors that are common to both genders, particularly associations with interpersonal conflict as an acute trigger, and psychiatric morbidity such as depression and hopelessness being related to increased suicidal intent.
doi:10.1186/s12888-014-0221-z
PMCID: PMC4149235  PMID: 25103532
24.  Changing epidemiologic patterns of deliberate self poisoning in a rural district of Sri Lanka 
BMC Public Health  2012;12:593.
Background
Acute poisoning is a major public health issue in many parts of the world. The epidemiology and the mortality rate is higher in low and middle income countries, including Sri Lanka. The aim of this study was to provide details about the epidemiology of acute poisoning in a rural Sri Lankan district and to identify the changing patterns and epidemiology of poisoning.
Methods
A prospective study was conducted from September 2008 to January 2010 in all hospitals with inpatient facilities in Anuradhapura district of North Central Province of Sri Lanka. Acute poisoning data was extracted from patient charts. Selected data were compared to the data collected from a 2005 study in 28 hospitals.
Results
There were 3813 poisoned patients admitted to the hospitals in the Anuradhapura district over 17 months. The annual population incidence was 447 poisoning cases per 100,000 population. The total number of male and female patients was approximately similar, but the age distribution differed by gender. There was a very high incidence of poisoning in females aged 15–19, with an estimated cumulative incidence of 6% over these five years. Although, pesticides are still the most common type of poison, medicinal drug poisonings are now 21% of the total and have increased 1.6 fold since 2005.
Conclusions
Acute poisoning remains a major public health problem in rural Sri Lanka and pesticide poisoning remains the most important poison. However, cases of medicinal drug poisoning have recently dramatically increased. Youth in these rural communities remain very vulnerable to acute poisoning and the problem is so common that school-based primary prevention programs may be worthwhile.
Lalith Senarathna, Shaluka F Jayamanna, Patrick J Kelly, Nick A Buckley,michael J Dibley, Andrew H Dawson. These authors contributed equally to this work.
doi:10.1186/1471-2458-12-593
PMCID: PMC3458971  PMID: 22852867
25.  Do Targeted Bans of Insecticides to Prevent Deaths from Self-Poisoning Result in Reduced Agricultural Output? 
Environmental Health Perspectives  2008;116(4):492-495.
Background
The pesticides monocrotophos, methamidophos, and endosulfan were a very common cause of severe poisoning in Sri Lanka during the 1980s and early 1990s, before they were banned in 1995 and 1998. Now, the most commonly used insecticides are the less toxic World Health Organization Class II organophosphorus pesticides and carbamates. These bans were followed by a large reduction in both fatal poisonings and suicide in Sri Lanka.
Objective
We aimed to see if these bans adversely affected agricultural production or costs.
Methods
We used data from the World Resources Institute to compare the yields of the main crop groups in Sri Lanka with those from surrounding South Asian countries for 1980–2005. We also examined data from the Sri Lankan Department of Census and Statistics to examine the yields of 13 specific vegetable crops and rice for 1990–2003, along with the costs of rice production.
Results
We found no drop in productivity in the years after the main bans were instituted (1995, 1998). We observed substantial annual fluctuation in estimated yields in all data sources, but these did not coincide with the bans and were no larger than the fluctuations in other countries. Also, there was no sudden change in costs of rice production coinciding with bans.
Conclusions
Countries aiming to apply restrictions to reduce deaths from pesticide poisoning should evaluate agricultural needs and develop a plan that encourages substitution of less toxic pesticides. If farmers have an affordable alternative for pest control for each crop, there is no obvious adverse effect on agricultural output.
doi:10.1289/ehp.11029
PMCID: PMC2291009  PMID: 18414632
food production; pesticide poisoning; pesticide regulation; public health policy; suicide prevention

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