Lalith Senarathna

Publications of Lalith Senarathna

• Toxicokinetics, including saturable protein binding, of 4-chloro-2-methyl phenoxyacetic acid (MCPA) in patients with acute poisoning.

  Authors: Darren M Roberts, Andrew H Dawson, Lalith Senarathna, Fahim Mohamed, Ron Cheng, Geoffrey Eaglesham, Nick A Buckley

  Toxicology letters. 01/2011; 201(3):270-6.

  Human data on protein binding and dose-dependent changes in toxicokinetics for MCPA are very limited. 128 blood samples were obtained in 49 patients with acute MCPA poisoning and total and unboundHuman data on protein binding and dose-dependent changes in toxicokinetics for MCPA are very limited. 128 blood samples were obtained in 49 patients with acute MCPA poisoning and total and unbound concentrations of MCPA were determined. The Scatchard plot was biphasic suggesting protein binding to two sites. The free MCPA concentration increased when the total concentration exceeded 239mg/L (95% confidence interval 198-274mg/L). Nonlinear regression using a two-site binding hyperbola model estimated saturation of the high affinity binding site at 115mg/L (95%CI 0-304). Further analyses using global fitting of serial data and adjusting for the concentration of albumin predicted similar concentrations for saturable binding (184mg/L and 167mg/L, respectively) without narrowing the 95%CI. In 25 patients, the plasma concentration-time curves for both bound and unbound MCPA were approximately log-linear which may suggest first order elimination, although sampling was infrequent so zero order elimination cannot be excluded. Using a cut-off concentration of 200mg/L, the half-life of MCPA at higher concentrations was 25.5h (95%CI 15.0-83.0h; n=16 patients) compared to 16.8h (95%CI 13.6-22.2h; n=10 patients) at lower concentrations. MCPA is subject to saturable protein binding but the influence on half-life appears marginal.

• Acute human lethal toxicity of agricultural pesticides: a prospective cohort study.

  Authors: Andrew H Dawson, Michael Eddleston, Lalith Senarathna, Fahim Mohamed, Indika Gawarammana, Steven J Bowe, Gamini Manuweera, Nicholas A Buckley

  PLoS medicine. 01/2010; 7(10):e1000357.

  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 theagricultural 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. 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. 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.

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

  Authors: Michael Eddleston, Peter Eyer, Franz Worek, Edmund Juszczak, Nicola Alder, Fahim Mohamed, Lalith Senarathna, Ariyasena Hittarage, Shifa Azher, K Jeganathan, Shaluka Jayamanne, Ludwig von Meyer, Andrew H Dawson, Mohamed Hussain Rezvi Sheriff, Nick A Buckley

  PLoS medicine. 07/2009; 6(6):e1000104.

  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 recommendsBACKGROUND: 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.

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

  Authors: Kanchana Wickramasinghe, Paul Steele, Andrew Dawson, Dinusha Dharmaratne, Asha Gunawardena, Lalith Senarathna, Dhammika de Siva, Kusal Wijayaweera, Michael Eddleston, Flemming Konradsen

  Bulletin of the World Health Organization. 04/2009; 87(3):180-5.

  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 onOBJECTIVE: 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$), using 2005 figures, was derived from hospital accounts. FINDINGS: The average total cost of treating a self-poisoned patient at the general hospital was US$ 31.83, with ward staff input and drugs being the highest expenditure category and only US$ 0.19 of this sum related to capital and maintenance costs. The average total cost of treatment was highest for self-poisoning with pesticides (US$ 49.12). The patients placed in the intensive care unit, who comprised 5% of the total, took up 75% of the overall treatment cost for all self-poisoned patients at the general hospital. The average total cost of treating self-poisoned patients at peripheral hospitals was US$ 3.33. The average patient cost per transfer was US$ 14.03. In 2006, the total cost of treating self-poisoned patients in the Anuradhapura district amounted to US$ 76 599, of which US$ 53 834 were comprised of pesticide self-poisonings. Based on the total treatment cost per self-poisoned patient estimated in this study, the cost of treating self-poisoned patients in all of Sri Lanka in 2004 was estimated at US$ 866 304. CONCLUSION: The cost of treating pesticide self-poisonings may be reduced by promoting the use of less toxic pesticides and possibly by improving case management in primary care hospitals. Additional research is needed to assess if increasing infrastructure and staff at peripheral hospitals could reduce the overall cost to the government, optimize case management and reduce pressure on secondary services.

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

  Authors: Michael Eddleston, Edmund Juszczak, Nick A Buckley, Lalith Senarathna, Fahim Mohamed, Wasantha Dissanayake, Ariyasena Hittarage, Shifa Azher, K Jeganathan, Shaluka Jayamanne, MH Rezvi Sheriff, David A Warrell

  Lancet. 03/2008; 371(9612):579-87.

  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 toxicBACKGROUND: 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.

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

  Authors: Lalith Senarathna, Jon Adams, Dhammika de Silva, Nick A Buckley, Andrew H Dawson

  BMC public health. 02/2008; 8:373.

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

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

  Authors: Lalith Senarathna, Jon Adams, De Silva Dhammika, Nick Buckley, Andrew Dawson

  BMC Public Health. 01/2008;

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

• Compliance for single and multiple dose regimens of superactivated charcoal: a prospective study of patients in a clinical trial.

  Authors: Fahim Mohamed, M Roshini Sooriyarachchi, Lalith Senarathna, Shifa Azhar, M H Rezvi Sheriff, Nick A Buckley, Michael Eddleston

  Clinical toxicology (Philadelphia, Pa.). 02/2007; 45(2):132-5.

  BACKGROUND: Although activated charcoal is widely used for the treatment of self-poisoning, its effectiveness is unknown. An important consideration is patient compliance since poor compliance willBACKGROUND: Although activated charcoal is widely used for the treatment of self-poisoning, its effectiveness is unknown. An important consideration is patient compliance since poor compliance will limit effectiveness. We aimed to describe compliance in a randomized controlled trial (RCT) performed in Sri Lanka, presuming that this would set the upper limits for compliance in routine clinical use. METHOD: 1,103 patients randomized to single or multiple (six doses q4h) 50 g doses of superactivated charcoal were prospectively observed. Charcoal was given by study doctors who recorded the amount ingested and the amount of persuasion required for the patients to drink the charcoal. RESULTS: 559 patients were randomized to receive one dose and 544 to receive six doses. Data was available for 1,071 (97%) patients. Eighty-eight were unable to complete their course; 98 required a NG tube, leaving 885 patients that received the first dose by mouth. The mean estimated amount of the prescribed dose of charcoal taken orally as a single or first dose was 83% (95% C.I. 82-84%). For patients receiving multiple doses, this amount fell over the next five doses to 66% (63-69%). While only 3.2% of patients refused the first dose, 12.3% refused the sixth. Relatively less persuasion was required for patients ingesting the first or single dose; 38% of patients required intense persuasion by the sixth dose. CONCLUSION: Compliance for a single dose of superactivated charcoal among trial patients was good. However, even in the ideal circumstances of a RCT, compliance decreased thereafter for patients taking more than one dose.

• Study protocol: a randomised controlled trial of multiple and single dose activated charcoal for acute self-poisoning.

  Authors: Michael Eddleston, Edmund Juszczak, Nick A Buckley, Lalith Senarathna, Fahim Mohammed, Stuart Allen, Wasantha Dissanayake, Ariyasena Hittarage, Shifa Azher, K Jeganathan, Shaluka Jayamanne, M H Rezvi Sheriff, David A Warrell

  BMC emergency medicine. 01/2007; 7:2.

  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 widelyBACKGROUND: 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.

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

  Authors: Michael Eddleston, K Sudarshan, M Senthilkumaran, K Reginald, Lakshman Karalliedde, Lalith Senarathna, Dhammika de Silva, M H Rezvi Sheriff, Nick A Buckley, David Gunnell

  Bulletin of the World Health Organization. 05/2006; 84(4):276-82.

  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-fatalityOBJECTIVES: 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.

• Intentional self-poisoning with the chlorophenoxy herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA).

  Authors: Darren M Roberts, Ruwan Seneviratne, Fahim Mohammed, Renu Patel, Lalith Senarathna, Ariyasena Hittarage, Nick A Buckley, Andrew H Dawson, Michael Eddleston

  Annals of emergency medicine. 10/2005; 46(3):275-84.

  STUDY OBJECTIVE: Data on poisoning with MCPA (4-chloro-2-methyl-phenoxyacetic acid) are limited to 6 case reports. Our objective is to describe outcomes from intentional self-poisoning with MCPA in aSTUDY OBJECTIVE: Data on poisoning with MCPA (4-chloro-2-methyl-phenoxyacetic acid) are limited to 6 case reports. Our objective is to describe outcomes from intentional self-poisoning with MCPA in a prospective case series of 181 patients presenting to hospitals in Sri Lanka. METHODS: Patient information was collected by on-site study physicians as part of an ongoing prospective cohort study of poisoned patients. Medical history, clinical details, and blood samples were obtained prospectively. RESULTS: Overall clinical toxicity was minimal in 85% of patients, including mild gastrointestinal symptoms in 44% of patients. More severe clinical signs of chlorophenoxy poisoning reported previously, such as rhabdomyolysis, renal dysfunction, and coma, also occurred but were uncommon. Eight patients died (4.4%). Most deaths occurred suddenly from cardiorespiratory arrest within 48 hours of poisoning; the pathophysiological mechanism of death was not apparent. The correlation between admission plasma MCPA concentration and clinical markers of severity of toxicity (physical signs, symptoms, and increased creatine kinase level) was poor. CONCLUSION: Intentional self-poisoning with MCPA generally causes mild toxicity, but cardiorespiratory arrest and death may occur. All patients should receive routine resuscitation and supportive care. It seems reasonable to correct acidosis and maintain an adequate urine output, but there is insufficient evidence to support other specific interventions. Our data do not support a clinical role for measurement of plasma MCPA in the acute management of poisoning, and insufficient data were available to fully examine the utility of measured electrolytes and creatine kinase levels.

• Speed of initial atropinisation in significant organophosphorus pesticide poisoning--a systematic comparison of recommended regimens.

  Authors: Michael Eddleston, Nick A Buckley, Helaina Checketts, Lalith Senarathna, Fahim Mohamed, M H Rezvi Sheriff, Andrew Dawson

  Journal of toxicology. Clinical toxicology. 02/2004; 42(6):865-75.

  OBJECTIVE: Early deaths from organophosphorus (OP) pesticide self-poisoning result from respiratory failure and cardiovascular collapse. Therapy requires the urgent use of atropine to reverseOBJECTIVE: 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.

  Authors: Fahim Mohamed, Lalith Senarathna, Adrian Percy, Manel Abeyewardene, Geoffrey Eaglesham, Ron Cheng, Shifa Azher, Ariyasena Hittarage, Wasantha Dissanayake, M H Rezvi Sheriff, Willie Davies, Nick A Buckley, Michael Eddleston

  Journal of toxicology. Clinical toxicology. 01/2004; 42(7):955-63.

  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 mammalianOBJECTIVE: 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 microg/L); both were managed with diazepam without complications. A patient with a peak measured plasma concentration of 1040 microg/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.

• Deaths due to absence of an affordable antitoxin for plant poisoning.

  Authors: Michael Eddleston, Lalith Senarathna, Fahim Mohamed, Nick Buckley, Edmund Juszczak, M H Rezvi Sheriff, Ariaranee Ariaratnam, Senaka Rajapakse, David Warrell, K Rajakanthan

  Lancet. 10/2003; 362(9389):1041-4.

  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 ofThere 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 antitoxin's 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.

• Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study.

  Authors: Michael Eddleston, Peter Eyer, Franz Worek, Fahim Mohamed, Lalith Senarathna, Ludwig von Meyer, Edmund Juszczak, Ariyasena Hittarage, Shifa Azhar, Wasantha Dissanayake, M H Rezvi Sheriff, Ladislaus Szinicz, Andrew H Dawson, Nick A Buckley

  Lancet. 366(9495):1452-9.

  BACKGROUND: Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals.BACKGROUND: Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals. We aimed to determine whether the three most common organophosphorus insecticides used for self-poisoning in Sri Lanka differ in the clinical features and severity of poisoning they cause. METHODS: We prospectively studied 802 patients with chlorpyrifos, dimethoate, or fenthion self-poisoning admitted to three hospitals. Blood cholinesterase activity and insecticide concentration were measured to determine the compound and the patients' response to insecticide and therapy. We recorded clinical outcomes for each patient. FINDINGS: Compared with chlorpyrifos (35 of 439, 8.0%), the proportion dying was significantly higher with dimethoate (61 of 264, 23.1%, odds ratio [OR] 3.5, 95% CI 2.2-5.4) or fenthion (16 of 99, 16.2%, OR 2.2, 1.2-4.2), as was the proportion requiring endotracheal intubation (66 of 439 for chlorpyrifos, 15.0%; 93 of 264 for dimethoate, 35.2%, OR 3.1, 2.1-4.4; 31 of 99 for fenthion, 31.3%, 2.6, 1.6-4.2). Dimethoate-poisoned patients died sooner than those ingesting other pesticides and often from hypotensive shock. Fenthion poisoning initially caused few symptoms but many patients subsequently required intubation. Acetylcholinesterase inhibited by fenthion or dimethoate responded poorly to pralidoxime treatment compared with chlorpyrifos-inhibited acetylcholinesterase. INTERPRETATION: Organophosphorus insecticide poisoning is not a single entity, with substantial variability in clinical course, response to oximes, and outcome. Animal toxicity does not predict human toxicity since, although chlorpyrifos is generally the most toxic in rats, it is least toxic in people. Each organophosphorus insecticide should be considered as an individual poison and, consequently, patients might benefit from management protocols developed for particular organophosphorus insecticides.