Lalith Senarathna

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.

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.

Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial.

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.

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

Background: Paraquat is a herbicide with a good occupational safety record, but a high mortality after intentional ingestion that has proved refractory to treatment. For nearly three decades paraquat concentration–time data have been used to predict the outcome following ingestion. However, none of the published methods has been independently or prospectively validated. We aimed to use prospectively collected data to test the published predictive methods and to determine if any is superior. Methods: Plasma paraquat concentrations were measured on admission for 451 patients in 10 hospitals in Sri Lanka as part of large prospective cohort study. All deaths in hospital were recorded; patients surviving to hospital discharge were followed up after 3 months to detect delayed deaths. Five prediction methods that are based on paraquat concentration–time data were then evaluated in all eligible patients. Results: All methods showed comparable performance within their range of application. For example, between 4- and 24-h prediction of prognosis was most variable between Sawada and Proudfoot methods but these differences were relatively small [specificity 0.96 (95% CI: 0.90–0.99) vs. 0.89 (0.82–0.95); sensitivity 0.57 vs. 0.79, positive and negative likelihood ratios 14.8 vs. 7.40 and 0.44 vs. 0.23 and positive predictive values 0.96 vs. 0.92, respectively]. Conclusions: All five published methods were better at predicting death than survival. These predictions may also serve as tools to identify patients who need treatment and for some assessment to be made of new treatments that are trialled without a control group.

Speed of Initial Atropinisation in Significant Organophosphorus Pesticide Poisoning—A Systematic Comparison of Recommended Regimens

Objective: Early deaths from organophosphorus (OP) pesticide self‐poisoning result from respiratory failure and cardiovascular collapse. Therapy requires the urgent use of atropine to reverse cholinergic excess, thereby improving respiratory function, heart rate, and blood pressure. We aimed to assess variation in textbook recommendations for early atropinisation and to see whether this variation affected time to stabilisation using model data from 22 severely poisoned patients seen in a Sri Lankan clinical trial. Methods: We extracted prospectively recorded data on atropine requirements for 22 OP poisoned patients who required intubation but survived to discharge. We did a systematic search for textbook recommendations for initial atropinisation regimens. These regimens were then applied to data from the Sri Lankan patients. Results: The patients required a mean of 23.4 mg (standard deviation 22.0, range 1–75 mg) atropine to clear the lungs, raise the pulse above 80 bpm, and restore systolic blood pressure to more than 80 mmHg. Textbook recommendations varied markedly—atropinisation of an average patient, requiring the mean dose of 23.4 mg, would have taken 8 to 1380 mins; atropinisation of a very ill patient, requiring 75 mg, would have taken 25 to 4440 mins. Atropinisation was attained most rapidly with a regimen of increasing bolus doses after failure to respond to the previous bolus. Conclusions: There is great variation in recommendations for atropinisation, with some regimens taking hours and even days to stabilise a patient. The guidelines are very flexible—possibly appropriate for experienced emergency physicians or clinical toxicologists, but completely inappropriate for the inexperienced junior doctors who see most cases worldwide. We recommend that a consensus guideline be developed by appropriate organisations to bring order to this important part of OP therapy, while acknowledging the paucity of data to drive the guidelines.

Acute Human Self-Poisoning with the N-Phenylpyrazole Insecticide Fipronil –A GABAA-Gated Chloride Channel Blocker

Objective: Fipronil, a broad spectrum N‐phenylpyrazole insecticide that inhibits GABAA‐gated chloride channels, has been in use since the mid‐1990s. A high affinity for insect compared to mammalian GABA receptors results in lower animal toxicity than other insecticides blocking this channel. To date, only two accidental cases of fipronil poisoning in humans have been published. Case Series: We report seven patients with fipronil self‐poisoning seen prospectively in Sri Lanka together with pharmacokinetics for four patients. Non‐sustained generalized tonic‐clonic seizures were seen in two patients (peak measured plasma fipronil concentrations 1600 and 3744 µg/L); both were managed with diazepam without complications. A patient with a peak measured plasma concentration of 1040 µg/L was asymptomatic throughout his stay. Plasma concentration was still high at discharge 3–4 days post‐ingestion when the patients were well. Retrospective review of > 1000 pesticide poisoning deaths since 1995 found only one death from fipronil‐based products. In contrast to the good outcome of the above cases, this patient required intubation and ventilation and had continuous fits despite therapy with barbiturates and benzodiazepines. Conclusions: Our experience with prospectively observed patients suggests that fipronil poisoning is characterized by vomiting, agitation, and seizures, and normally has a favorable outcome. Management should concentrate on supportive care and early treatment of seizures. However, further experience is needed to determine whether increased susceptibility to fipronil or larger doses can produce status epilepticus.

Patterns of hospital transfer for self-poisoned patients in rural Sri Lanka: implications for estimating the incidence of self-poisoning in the developing world

OBJECTIVES Most data on self-poisoning in rural Asia have come from secondary hospitals. We aimed to: assess how transfers from primary to secondary hospitals affected estimates of case-fatality ratio (CFR); determine whether there was referral bias according to gender or poison; and estimate the annual incidence of all self-poisoning, and of fatal self-poisoning, in a rural developing-world setting. METHODS Self-poisoning patients admitted to Anuradhapura General Hospital, Sri Lanka, were reviewed on admission from 1 July to 31 December 2002. We audited medical notes of self-poisoning patients admitted to 17 of the 34 surrounding peripheral hospitals for the same period. FINDINGS A total of 742 patients were admitted with self-poisoning to the secondary hospital; 81 died (CFR 10.9%). 483 patients were admitted to 17 surrounding peripheral hospitals. Six patients (1.2%) died in peripheral hospitals, 249 were discharged home, and 228 were transferred to the secondary hospital. There was no effect of gender or age on likelihood of transfer; however, patients who had ingested oleander or paraquat were more likely to be transferred than were patients who had taken organophosphorus pesticides or other poisons. Estimated annual incidences of self-poisoning and fatal self-poisoning were 363 and 27 per 100,000 population, respectively, with an overall CFR of 7.4% (95% confidence interval 6.0-9.0). CONCLUSION Fifty per cent of patients admitted to peripheral hospitals were discharged home, showing that CFRs based on secondary hospital data are inflated. However, while incidence of self-poisoning is similar to that in England, fatal self-poisoning is three times more common in Sri Lanka than fatal self-harm by all methods in England. Population based data are essential for making international comparisons of case fatality and incidence, and for assessing public health interventions.

Deaths due to absence of an affordable antitoxin for plant poisoning

There is a severe shortage of affordable antivenoms and antitoxins in the developing world. An anti-digoxin antitoxin for oleander poisoning was introduced in Sri Lanka in July, 2001, but because of its cost, stocks ran out in July, 2002. We looked at the effect of its introduction and withdrawal on case fatality, and determined its cost-effectiveness. The antitoxin strikingly reduced the case fatality; its absence resulted in a three-fold rise in deaths. At the present price of US2650 dollars per course, every life saved cost 10209 dollars and every life year cost 248 dollars. Reduction of the antitoxins price to 400 dollars would reduce costs to 1137 dollars per life gained; a further reduction to 103 dollars would save money for every life gained. Treatments for poisoning and envenoming should be included in the present campaign to increase availability of affordable treatments in the developing world.

Cost to government health-care services of treating acute self-poisonings in a rural district in Sri Lanka

OBJECTIVE To estimate the direct financial costs to the Sri Lanka Ministry of Health of treating patients after self-poisoning, particularly from pesticides, in a single district. METHODS Data on staff, drug, laboratory and other inputs for each patient admitted for self-poisoning were prospectively collected over a one-month period from one general hospital (2005) and five peripheral hospitals (2006) in the Anuradhapura district. Data on transfers to secondary- and tertiary-level facilities were obtained for a 6-month period from 30 peripheral hospitals. The cost of the inputs in United States dollars (US

Changing epidemiologic patterns of deliberate self poisoning in a rural district of Sri Lanka

), using 2005 figures, was derived from hospital accounts. FINDINGS The average total cost of treating a self-poisoned patient at the general hospital was US