Browsing by Author "Ratnatilaka, G.A."
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Item Low-dose adrenaline, promethazine and hydrocortisone, (alone and in combination) in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double blind, placebo-controlled trial(Sri Lanka Medical Association, 2011) de Silva, H.A.; Pathmeswaran, A.; Ranasinha, C.D.; Jayamanne, S.; Samarakoon, S.B.; Hittharage, A.; Kalupahana, R.; Ratnatilaka, G.A.; Uluwatthage, W.; Aronson, J.K.; Armitage, J.M.; Lalloo, D.G.; de Silva, H.J.INTRODUCTION AND OBJECTIVES: 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 have assessed whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka. METHODS: We randomized 1007 patients, using a 2x2x2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 mi of a 1:1000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), a!one 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 hours. The pre-specified primary endpoints were the effects of the interventions on the incidence of severe reactions over 48 hours. Results: 752 (75%) patients had acute reactions to antivenom; 9% mild, 48% moderate, 43% severe; 89% of the reactions occurred within one hour and 40% of all patients were given rescue medication during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% at one hour (95%CI 25-67) and by 38% (26-49) over 48 hours; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. CONCLUSIONS: Pre-treatment with tow-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.Item 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.Item Multiple-dose activated charcoal for treatment of yellow oleander poisoning : a single-blind randomized placebo controlled trial(Lancet Publishing Group, 2003) de Silva, H.A.; Fonseka, M.M.D.; Pathmeswaran, A.; Alahakoon, D.G.S.; Ratnatilaka, G.A.; Gunatilake, S.B.; Ranasinha, C.D.; Lalloo, D.G.; Aronson, J.K.; de Silva, H.J.BACKGROUND: Deliberate self-poisoning with yellow oleander seeds is common in Sri Lanka and is associated with severe cardiac toxicity and a mortality rate of about 10%. Specialised treatment with antidigoxin Fab fragments and temporary cardiac pacing is expensive and not widely available. Multiple-dose activated charcoal binds cardiac glycosides in the gut lumen and promotes their elimination. We aimed to assess the efficacy of multiple-dose activated charcoal in the treatment of patients with yellow-oleander poisoning. METHODS: On admission, participants received one dose of activated charcoal and were then randomly assigned either 50 g of activated charcoal every 6 h for 3 days or sterile water as placebo. A standard treatment protocol was used in all patients. We monitored cardiac rhythm and did 12-lead electocardiographs as needed. Death was the primary endpoint, and secondary endpoints were life-threatening cardiac arrhythmias, dose of atropine used, need for cardiac pacing, admission to intensive care, and number of days in hospital. Analysis was by intention to treat. FINDINGS: 201 patients received multiple-dose activated charcoal and 200 placebo. There were fewer deaths in the treatment group (five [2.5%] vs 16 [8%]; percentage difference 5.5%; 95% CI 0.6-10.3; p=0.025), and we noted difference in favour of the treatment group for all secondary endpoints, apart from number of days in hospital. The drug was safe and well tolerated. INTERPRETATION: Multiple-dose activated charcoal is effective in reducing deaths and life-threatening cardiac arrhythmias after yellow oleander poisoning and should be considered in all patients. Use of activated charcoal could reduce the cost of treatment.