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

Abstract

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.