Nicholas A. Buckley

Management of acute organophosphorus pesticide poisoning

Summary Organophosphorus pesticide self-poisoning is an important clinical problem in rural regions of the developing world, and kills an estimated 200 000 people every year. Unintentional poisoning kills far fewer people but is a problem in places where highly toxic organophosphorus pesticides are available. Medical management is difficult, with case fatality generally more than 15%. We describe the limited evidence that can guide therapy and the factors that should be considered when designing further clinical studies. 50 years after first use, we still do not know how the core treatments—atropine, oximes, and diazepam—should best be given. Important constraints in the collection of useful data have included the late recognition of great variability in activity and action of the individual pesticides, and the care needed cholinesterase assays for results to be comparable between studies. However, consensus suggests that early resuscitation with atropine, oxygen, respiratory support, and fluids is needed to improve oxygen delivery to tissues. The role of oximes is not completely clear; they might benefit only patients poisoned by specific pesticides or patients with moderate poisoning. Small studies suggest benefit from new treatments such as magnesium sulphate, but much larger trials are needed. Gastric lavage could have a role but should only be undertaken once the patient is stable. Randomised controlled trials are underway in rural Asia to assess the effectiveness of these therapies. However, some organophosphorus pesticides might prove very difficult to treat with current therapies, such that bans on particular pesticides could be the only method to substantially reduce the case fatality after poisoning. Improved medical management of organophosphorus poisoning should result in a reduction in worldwide deaths from suicide.

Pesticide poisoning in the developing world—a minimum pesticides list

In parts of the developing world, pesticide poisoning causes more deaths than infectious diseases. Use of pesticides is poorly regulated and often dangerous; their easy availability also makes them a popular method of self-harm. In 1985, the UN Food and Agriculture Organisation (FAO) produced a voluntary code of conduct for the pesticide industry in an attempt to limit the harmful effects of pesticides. Unfortunately, a lack of adequate government resources in the developing world makes this code ineffective, and thousands of deaths continue today. WHO has recommended that access to highly toxic pesticides be restricted--where this has been done, suicide rates have fallen. Since an Essential Drugs List was established in 1977, use of a few essential drugs has rationalised drug use in many regions. An analogous Minimum Pesticides List would identify a restricted number of less dangerous pesticides to do specific tasks within an integrated pest management system. Use of safer pesticides should result in fewer deaths, just as the change from barbiturates to benzodiazepines has reduced the number of deaths from pharmaceutical self-poisoning.

Web 2.0, social networks and the future of market research

Market Research is often accused of failing to provide the insights sought by our clients, and in an increasingly complex society we are challenged to embrace a different model of thinking with different principles at its centre. We believe that a Web 2.0 research platform and a social network approach offers marketing research new tools to meet the challenges of the future. The paper identifies a number of trends that may well provide fertile ground for marketing researchers to develop new approaches. The open source movement will not only affect the way that we think but the very methodologies that we use. The emergence of Web 2.0 offers us an array of collaborative tools with which to develop new research approaches to explore the rapidly changing social and media environment. At the same, the rapid growth of online social networks has fuelled the already rich research literature on the importance of studying humankind in ‘tribes’ or ‘groups’. We argue that the combination of social computing tools and an understanding of social networks will allow us to build new types of research communities, in which respondents interact not only with the researchers but with the clients and most fertilely with each other. Moreover as we examine these types of networks we will become increasingly better able to handle multiple sources of data, and be as comfortable with these new forms of user generated content as we are with the traditional data collection tools of the last fifty years. We believe that these social software tools and trends provide the blueprint for researchers to build new types of ‘participatory panels’ or ‘research communities’ and we describe our experiences in developing such a community.

Medical management of paraquat ingestion

Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to inherent toxicity and lack of effective treatments. We conducted a systematic search for human studies that report toxicokinetics, mechanisms, clinical features, prognosis and treatment. Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12-24 h. Clinical features are largely due to intracellular effects. Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF-κB, mitochondrial damage and apoptosis in many organs. Kinetics of distribution into these target tissues can be described by a two-compartment model. Paraquat is actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis. Paraquat also causes renal and liver injury. Plasma paraquat concentrations, urine and plasma dithionite tests and clinical features provide a good guide to prognosis. Activated charcoal and Fullers earth are routinely given to minimize further absorption. Gastric lavage should not be performed. Elimination methods such as haemodialysis and haemoperfusion are unlikely to change the clinical course. Immunosuppression with dexamethasone, cyclophosphamide and methylprednisolone is widely practised, but evidence for efficacy is very weak. Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti-inflammatory and NF-κB inhibitory actions. However, there are no published human trials. The case fatality is very high in all centres despite large variations in treatment.

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

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

Cardiovascular adverse effects of antipsychotic drugs.

Minor cardiovascular adverse effects from antipsychotic drugs are extremely common. They include effects such as postural hypotension and tachycardia due to anticholinergic or α1-adrenoceptor blockade, and may occur in the majority of patients at therapeutic dosages. There are a number of pharmacological effects that are of uncertain clinical significance, such as blockade of calmodulin, sodium and calcium channels and α2-adrenoceptors in the central nervous system. The most serious consequences of treatment, arrhythmias and sudden death, are probably uncommon and are most likely to be caused primarily by blockade of cardiac potassium channels such as HERG. Incomplete evidence suggests that arrhythmias and sudden death are a particular problem with certain drugs (thioridazine and droperidol), high risk populations (elderly, pre-existing cardiovascular disease, inherited disorders of cardiac ion channels or of antipsychotic drug metabolism) or people taking interacting drugs (such as drugs that prolong the QT interval, e.g. tricyclic antidepressants, drugs that inhibit antipsychotic drug metabolism, or diuretics). Clozapine may be unique in also causing death from myocarditis and cardiomyopathy. Much further research is required to more clearly identify high risk drugs and the populations that are at risk of sudden death, as well as the mechanisms involved and the extent of the risk.

Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial

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

Cardiotoxicity More Common in Thioridazine Overdose than with Other Neuroleptics

On the basis of case reports and small non-comparative series it has been suggested that thioridazine has greater cardiotoxicity in overdose. Limited evidence also suggests an increased association with sudden death in therapeutic doses. The aim of our study is to examine the clinical and electrocardiographic features associated with neuroleptic poisoning and compare thioridazine with other neuroleptics. Consecutive adult patients with neuroleptic poisoning presenting to metropolitan hospitals in Newcastle between 1987 and 1993 were studied. The main outcome measures examined were ECG changes (QRS, QT and QTc intervals), arrhythmias, seizures, degree of sedation, heart rate and blood pressure. Two-hundred ninety-nine patients had ingested thioridazine (104), chlorpromazine (69), trifluoperazine (36), pericyazine (35), haloperidol (33), prochlorperazine (18), fluphenazine (8), or other neuroleptics (7). Sixteen patients had ingested more than one neuroleptic and were excluded from comparative analysis. Thioridazine was more likely to cause tachycardia (odds ratio 1.7, 95% CI 1.1-2.9, p = 0.03), a prolonged QT interval (odds ratio 5.2, 95% CI 1.6-17.1, p = 0.006), prolonged QTc > 450 ms1/2 (odds ratio 4.7, 95% CI 2.7-7.9, p = 0.001), a widened QRS (> 100 ms) (odds ratio 3.1, 95% CI 1.5-6.3, p = 0.001) and arrhythmias (odds ratio infinity, 95% CI 2.4- infinity, p = 0.004). There were no significant differences in the odds of coma (odds ratio 0.5 (0.2-1.5)), hypotension (odds ratio 0.9 (0.4-1.9)) or seizures (odds ratio 3.9 (0.3-43.5)). Adjustment for age, sex, dose ingested and co-ingestion of tricyclic antidepressants or lithium had no major effect on the odds ratios observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Early management after self-poisoning with an organophosphorus or carbamate pesticide - a treatment protocol for junior doctors

Severe organophosphorus or carbamate pesticide poisoning is an important clinical problem in many countries of the world. Unfortunately, little clinical research has been performed and little evidence exists with which to determine best therapy. A cohort study of acute pesticide poisoned patients was established in Sri Lanka during 2002; so far, more than 2000 pesticide poisoned patients have been treated. A protocol for the early management of severely ill, unconscious organophosphorus/carbamate-poisoned patients was developed for use by newly qualified doctors. It concentrates on the early stabilisation of patients and the individualised administration of atropine. We present it here as a guide for junior doctors in rural parts of the developing world who see the majority of such patients and as a working model around which to base research to improve patient outcome. Improved management of pesticide poisoning will result in a reduced number of suicides globally.

Pesticide poisoning in south India : opportunities for prevention and improved medical management

Objective  Warangal district in Andhra Pradesh, southern India, records >1000 pesticide poisoning cases each year and hundreds of deaths. We aimed to describe their frequency and distribution, and to assess quality of management and subsequent outcomes from pesticide poisoning in one large hospital in the district.