Browsing by Author "Hittarage, A."

Now showing 1 - 6 of 6

Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease
(Oxford University Press, 2007) Wanigasuriya, K. P.; Peiris-John, R. J.; Wickremasinghe, R.; Hittarage, A.
This study was conducted to determine the aetiology of chronic renal failure (CRF) in the North Central Province of Sri Lanka. Patients (n=183) with CRF of unknown aetiology were compared with controls (n=200) who had no evidence of chronic renal dysfunction. Exposure to possible risk factors were determined by an interviewer-administered questionnaire. Being a farmer (P<0.001), using pesticides (P<0.001), drinking well water (P<0.001), a family history of renal dysfunction (P=0.001), use of ayurvedic treatment (P<0.001) and a history of snake bite (P<0.001) were risk factors for CRF of unknown aetiology. Using logistic regression analysis, a family history of chronic renal disease, taking ayurvedic treatment and history of snake bite were found to be significant predictors for CRF of unknown aetiology. There is evidence to support an environmental aetiology to CRF in Sri Lanka.
Exposure to acetylcholinesterase-inhibiting pesticides and chronic renal failure
(Sri Lanka Medical Association, 2006) Peiris-John, R.J.; Wanigasuriya, J.K.; Wickremasinghe, A.R.; Dissanayake, W.P.; Hittarage, A.
No Abstract Available.
Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial
(Public Library of Science, 2011) de Silva, H.A.; Pathmeswaran, A.; Ranasinha, C.D.; Jayamanne, S.; Samarakoon, S.B.; Hittarage, A.; Kalupahana, R.; Ratnatilaka, G.A.; Uluwatthage, W.; Aronson, J.K.; Armitage, J.M.; Lalloo, D.G.; de Silva, H.J.
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.
Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial
(Lancet Publishing Group, 2008) Eddleston, M.; Juszczak, E.; Buckley, N.A.; Senarathna, L.; Mohamed, F.; Dissanayake, W.; Hittarage, A.; Azher, S.; Jeganathan, K.; Jayamanne, S.; Sheriff, M.R.; Warrell, D.A.; Ox-Col Poisoning Study collaborators
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-dosegroup 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. Comment in : Is this the epitaph for multiple-dose activated charcoal? [Lancet. 2008]
Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial
(Public Library of Science, 2009) Eddleston, M.; Eyer, P.; Worek, F.; Juszczak, E.; Alder, N.; Mohamed, F.; Senarathna, L.; Hittarage, A.; Azher, S.; Jeganathan, K.; Jayamanne, S.; von Meyer, L.; Dawson, A.H.; Sheriff, M.H.; Buckley, N.A.
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 receivepralidoxime (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.
Study protocol: a randomised controlled trial of multiple and single dose activated charcoal for acute self-poisoning
(London : BioMed Central, 2007) Eddleston, M.; Juszczak, E.; Buckley, N.A.; Senarathna, L.; Mohammed, F.; Allen, S.; Dissanayake, W.; Hittarage, A.; Azher, S.; Jeganathan, K.; Jayamanne, S.; Sheriff, M.H.; Warrell, D.A.; Ox-Col Poisoning Study collaborators
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 charcoalduring 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.