Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial

作者：H. Asita de Silva, H. Asita de Silva, A. Pathmeswaran, Channa D Ranasinha, Shaluka Jayamanne, Senarath B. Samarakoon, Ariyasena Hittharage, Ranjith Kalupahana, G.A. Ratnatilaka, Wimalasiri Uluwatthage, Jeffrey K Aronson, Jane Armitage, David G. Lalloo, Hithanadura Janaka de Silva, Hithanadura Janaka de Silva · 发表于：PLoS Medicine · 年份：2011 · DOI：10.1371/journal.pmed.1000435 · 被引用次数：186 · 研究领域：Venomous Animal Envenomation and Studies、Healthcare and Venom Research、Entomological Studies and Ecology

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...