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

Abstract

In a factorial randomized trial conducted in Sri Lanka, de Silva and colleagues evaluate the safety and efficacy of pretreatments intended to reduce the risk of serious reactions to antivenom following snakebite.

Dealing with adverse reactions to snake antivenom

“…With adrenaline, the balance of benefit over harm when given prophylactically varies with the baseline risk of developing the adverse reactions. Prophylactic use of subcutaneous adrenaline appears safe, as no serious adverse events were reported by de Silva et al [3] or in previous studies [14,15]. Adverse reaction rates have been known to vary between different brands of antivenom due to different manufacturers' procedural differences and between different batches of the same brand of antivenom due to production process variability.…”

“…However, the study was small (105 patients) and could not firmly establish the safety of adrenaline. Recently, de Silva et al [3], in a study of 1007 patients who received antivenoms currently being used in Sri Lanka, reports that using low-dose subcutaneous adrenaline (0.25 ml, 1:1000 solution) for prophylaxis is both effective and safe, and recommends its use especially in countries where adverse reactions to antivenoms are frequent. Adrenaline reduced the rate of severe adverse reactions compared with placebo by 43% at 1 hour (OR 0.57, 95% CI 0.43-0.75) and by 38% over 48 hours (OR 0.62, 0.51-0.74).…”

“…Importantly, all of these drugs used for prophylaxis have potential adverse effects, particularly hydrocortisone and adrenaline. The study by de Silva et al [3], showed a significantly higher number of deaths among those who received hydrocortisone compared to no hydrocortisone (ten [2%] versus three [0.6%]; OR 3.3, 95% CI 1.28-8.52) [3]. With adrenaline, the balance of benefit over harm when given prophylactically varies with the baseline risk of developing the adverse reactions.…”

“…Most doctors serving in countries with a high snakebite burden dread the experience of having to rescue patients from potentially life threatening complications of envenomation and, in addition, having to treat antivenom-induced adverse reactions; these can occur in up to 75% of patients (severe in 40%) who receive antivenom in some countries [3]. The medical implications for use of antivenoms associated with such a high rate of adverse reactions are not without consequence: the early use of antivenom is frequently discouraged at some rural hospitals allowing time for serious complications of systemic envenoming to develop and become well established.…”

Anti-snake venom induced reactions among children with snake envenomation

“…14 17 However steroids have been used post ASV to prevent serum sickness in Australia. 18 Studies by williams et al had shown adrenaline to be effective.…”