A Randomised Controlled Trial of Two Infusion Rates to Decrease Reactions to Antivenom

Geoffrey K Isbister,Fahim Mohamed,Seyed Shahmy,Harendra Karunathilake,Chandana Abeysinghe,Ariaranee Ariaratnam,Vasee Moorthy

doi:10.1371/journal.pone.0038739

Abstract

BackgroundSnake envenoming is a major clinical problem in Sri Lanka, with an estimated 40,000 bites annually. Antivenom is only available from India and there is a high rate of systemic hypersensitivity reactions. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions.Methods and FindingsThis was a randomized comparison trial of two infusion rates of antivenom for treatment of non-pregnant adult patients (>14 y) with snake envenoming in Sri Lanka. Snake identification was by patient or hospital examination of dead snakes when available and confirmed by enzyme-immunoassay for Russell’s viper envenoming. Patients were blindly allocated in a 11 randomisation schedule to receive antivenom either as a 20 minute infusion (rapid) or a two hour infusion (slow). The primary outcome was the proportion with severe systemic hypersensitivity reactions (grade 3 by Brown grading system) within 4 hours of commencement of antivenom. Secondary outcomes included the proportion with mild/moderate hypersensitivity reactions and repeat antivenom doses. Of 1004 patients with suspected snakebites, 247 patients received antivenom. 49 patients were excluded or not recruited leaving 104 patients allocated to the rapid antivenom infusion and 94 to the slow antivenom infusion. The median actual duration of antivenom infusion in the rapid group was 20 min (Interquartile range[IQR]:20–25 min) versus 120 min (IQR:75–120 min) in the slow group. There was no difference in severe systemic hypersensitivity reactions between those given rapid and slow infusions (32% vs. 35%; difference 3%; 95%CI:−10% to +17%;p = 0.65). The frequency of mild/moderate reactions was also similar. Similar numbers of patients in each arm received further doses of antivenom (30/104 vs. 23/94).ConclusionsA slower infusion rate would not reduce the rate of severe systemic hypersensitivity reactions from current high rates. More effort should be put into developing better quality antivenoms.Trial Registration www.slctr.lk SLCTR/2007/005

Highlights

Snake envenoming is an important public health problem in tropical and subtropical countries in Africa, Asia, Oceania and Latin America
A slower infusion rate would not reduce the rate of severe systemic hypersensitivity reactions from current high rates
More effort should be put into developing better quality antivenoms

Summary

Introduction

Snake envenoming is an important public health problem in tropical and subtropical countries in Africa, Asia, Oceania and Latin America. [1] Most of the estimated burden of snakebite is from South and Southeast Asia, Sub-Saharan Africa, and Central and South America This means that large amounts of antivenom are administered in the treatment of snake envenoming in some of these countries where antivenom is available. [2] Antivenom reactions appear to be non-IgE mediated (‘‘anaphylactoid’’) but otherwise resemble type I ‘‘immediate hypersensitivity’’ reactions This has been a particular problem in Sri Lanka where snake envenoming is common, large amounts of Indian polyvalent antivenom are used and severe systemic hypersensitivity reactions or anaphylaxis have been reported in up to 50% of cases in some studies. This study aimed to investigate whether the rate of infusion of antivenom reduced the frequency of severe systemic hypersensitivity reactions

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Conclusion