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

Background: Snake 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 findings: This 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). Conclusions: 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

Consort diagram showing all patient recruitments, exclusions and outcomes in each of the arms of the study. *

<p>Exclusion criteria were age <14 years, pregnancy, clinician excluded, premedication given, prior administration of antivenom, were missed or did not consent to the study.</p

Comparison of patients with and without antivenom reactions, subdividing into severe and mild/moderate reactions. Proportions are reported with 95% confidence intervals.

1<p>Venom concentration for Russell’s viper patients only.</p

The hazards of gastric lavage for intentional self-poisoning in a resource poor location

Objective. The 10-20% case fatality found with self-poisoning in the developing world differs markedly from the 0.5% found in the West. This may explain in part why the recent movement away from the use of gastric lavage in the West has not been followe

Deaths due to absence of an affordable antitoxin for plant poisoning

There is a severe shortage of affordable antivenoms and antitoxins in the developing world. An anti-digoxin antitoxin for oleander poisoning was introduced in Sri Lanka in July, 2001, but because of its cost, stocks ran out in July, 2002. We looked at the effect of its introduction and withdrawal on case fatality, and determined its cost-effectiveness. The antitoxin strikingly reduced the case fatality; its absence resulted in a three-fold rise in deaths. At the present price of US$2650 per course, every life saved cost$10 209 and every life year cost $248. Reduction of the antitoxin's price to$400 would reduce costs to $1137 per life gained; a further reduction to$103 would save money for every life gained. Treatments for poisoning and envenoming should be included in the present campaign to increase availability of affordable treatments in the developing world

The time of onset of the reaction after antivenom comparing the rapid and slow infusion groups.

<p>(The whiskers are the minimum and maximum, the box the interquartile range, and the median line across the box).</p

Demographic features, snake type and clinical effects for patients randomised to the rapid infusion arm and the slow infusion arm.

<p>Demographic features, snake type and clinical effects for patients randomised to the rapid infusion arm and the slow infusion arm.</p

Secondary outcomes for patients randomised to the rapid infusion arm and the slow infusion arm.

<p>Secondary outcomes for patients randomised to the rapid infusion arm and the slow infusion arm.</p