Lakshman Karalliedde

Publications of Lakshman Karalliedde

• The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka.

  Authors: Pradeepa Jayawardane, Andrew H Dawson, Vajira Weerasinghe, Lakshman Karalliedde, Nicholas A Buckley, Nimal Senanayake

  PLoS medicine. 07/2008; 5(7):e147.

  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 stimulationIntermediate 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. 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. 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.

• The hazards of gastric lavage for intentional self-poisoning in a resource poor location.

  Authors: Michael Eddleston, Sapumal Haggalla, K Reginald, K Sudarshan, M Senthilkumaran, Lakshman Karalliedde, Ariaranee Ariaratnam, M H Rezvi Sheriff, David A Warrell, Nick A Buckley

  Clinical toxicology (Philadelphia, Pa.). 02/2007; 45(2):136-43.

  OBJECTIVE: The 10-20% case fatality found with self-poisoning in the developing world differs markedly from the 0.5% found in the West. This may explain in part why the recent movement away from theOBJECTIVE: The 10-20% case fatality found with self-poisoning in the developing world differs markedly from the 0.5% found in the West. This may explain in part why the recent movement away from the use of gastric lavage in the West has not been followed in the developing world. After noting probable harm from gastric lavage in Sri Lanka, we performed an observational study to determine how lavage is routinely performed and the frequency of complications. CASE SERIES: Fourteen consecutive gastric lavages were observed in four hospitals. Lavage was given to patients unable or unwilling to undergo forced emesis, regardless of whether they gave consent or the time elapsed since ingestion. It was also given to patients who had taken non-lethal ingestions. The airway was rarely protected in patients with reduced consciousness, large volumes of fluid were given for each cycle (200 to more than 1000 ml), and monitoring was not used. Serious complications likely to be due to the lavage were observed, including cardiac arrest and probable aspiration of fluid. Health care workers perceived lavage as being highly effective and often life-saving; there was peer and relative pressure to perform lavage in self-poisoned patients. CONCLUSIONS: Gastric lavage as performed for highly toxic poisons in a resource-poor location is hazardous. In the absence of evidence for patient benefit from lavage, (and in agreement with some local guidelines), we believe that lavage should be considered for few patients - in those who have recently taken a potentially fatal dose of a poison, and who either give their verbal consent for the procedure or are sedated and intubated. Ideally, a randomized controlled trial should be performed to determine the balance of risks and benefits of safely performed gastric lavage in this patient population.

• 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.

• Organophosphate-induced intermediate syndrome: aetiology and relationships with myopathy.

  Authors: Lakshman Karalliedde, David Baker, Timothy C Marrs

  Toxicological reviews. 02/2006; 25(1):1-14.

  The intermediate syndrome (IMS) following organophosphorus (OP) insecticide poisoning was first described in the mid-1980s. The syndrome described comprised characteristic symptoms and signsThe intermediate syndrome (IMS) following organophosphorus (OP) insecticide poisoning was first described in the mid-1980s. The syndrome described comprised characteristic symptoms and signs occurring after apparent recovery from the acute cholinergic syndrome. As the syndrome occurred after the acute cholinergic syndrome but before organophosphate-induced delayed polyneuropathy, the syndrome was called 'intermediate syndrome'. The IMS occurs in approximately 20% of patients following oral exposure to OP pesticides, with no clear association between the particular OP pesticide involved and the development of the syndrome. It usually becomes established 2-4 days after exposure when the symptoms and signs of the acute cholinergic syndrome (e.g. muscle fasciculations, muscarinic signs) are no longer obvious. The characteristic features of the IMS are weakness of the muscles of respiration (diaphragm, intercostal muscles and accessory muscles including neck muscles) and of proximal limb muscles. Accompanying features often include weakness of muscles innervated by some cranial nerves. It is now emerging that the degree and extent of muscle weakness may vary following the onset of the IMS. Thus, some patients may only have weakness of neck muscles whilst others may have weakness of neck muscles and proximal limb muscles. These patients may not require ventilatory care but close observation and monitoring of respiratory function is mandatory.Management is essentially that of rapidly developing respiratory distress and respiratory failure. Delays in instituting ventilatory care will result in death. Initiation of ventilatory care and maintenance of ventilatory care often requires minimal doses of non-depolarising muscle relaxants. The use of depolarising muscle relaxants such as suxamethonium is contraindicated in OP poisoning. The duration of ventilatory care required by patients may differ considerably and it is usual for patients to need ventilatory support for 7-15 days and even up to 21 days. Weaning from ventilatory care is best carried out in stages, with provision of continuous positive airway pressure prior to complete weaning. Continuous and close monitoring of respiratory function (arterial oxygen saturation, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood) and acid-base status are an absolute necessity. Prophylactic antibiotics are usually not required unless there has been evidence of aspiration of material into the lungs. Close monitoring of fluid and electrolyte balance is mandatory in view of the profuse offensive diarrhoea that most patients develop. Maintenance of nutrition, physiotherapy, prevention of bed sores and other routine measures to minimise discomfort during ventilatory care are necessary. Recovery from the intermediate syndrome is normally complete and without any sequelae.The usefulness of oximes during the IMS remains uncertain. In animal experiments, very early administration of oximes has prevented the occurrence of myopathy. There are reports from developed countries where administration of oximes at recommended doses and within 2 hours of ingestion of OP insecticide did not prevent the onset of the IMS. Controlled randomised clinical studies are necessary to evaluate the efficacy of oximes in combating the IMS.Electrophysiological studies following OP poisoning have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). Of these, the decrementing response is the most frequent finding during the IMS, whilst repetitive firing is observed during the acute cholinergic syndrome. The distribution of the weakness in human cases of the IMS, in general, parallels the distribution of the myopathy observed in a number of studies in experimental animals. This has led to speculation that myopathy is involved in the causation of the IMS. However, while myopathy and the IMS have a common origin in acetylcholine accumulation, they are not causally related to one another.

• Case report does not report sufficient data to support a diagnosis of fatal organophosphorus poisoning.

  Authors: Michael Eddleston, Tissa Wijeratne, Lakshman Karalliedde, Mike Hurrell, Andrew H Dawson

  Clinical toxicology (Philadelphia, Pa.). 02/2005; 43(7):887-8.

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

  Authors: Michael Eddleston, Andrew Dawson, Lakshman Karalliedde, Wasantha Dissanayake, Ariyasena Hittarage, Shifa Azher, Nick A Buckley

  Critical care (London, England). 01/2005; 8(6):R391-7.

  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 littleSevere 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.

• Where is the evidence for treatments used in pesticide poisoning? Is clinical toxicology fiddling while the developing world burns?

  Authors: Nicholas A Buckley, Lakshman Karalliedde, Andrew Dawson, Nimal Senanayake, Michael Eddleston

  Journal of toxicology. Clinical toxicology. 02/2004; 42(1):113-6.

• Pesticide poisoning in the developing world--a minimum pesticides list.

  Authors: Michael Eddleston, Lakshman Karalliedde, Nick Buckley, Ravindra Fernando, Gerard Hutchinson, Geoff Isbister, Flemming Konradsen, Douglas Murray, Juan Carlos Piola, Nimal Senanayake, Rezvi Sheriff, Surjit Singh, S B Siwach, Lidwien Smit

  Lancet. 11/2002; 360(9340):1163-7.

  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 aIn 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.