Antivenoms for local effects of snake envenoming

Abstract

Snake envenoming is a significant public health issue that disproportionately affects the poorest communities in the tropical regions. There is a spectrum of local effects following snakebite, including pain, swelling, bluish discolouration, haemorrhagic blistering, local tissue necrosis and gangrene at the bite site. In severe local envenomings, significant tissue loss and impaired function can occur and may result in permanent disability in snakebite survivors. Although the mainstay of hospital treatment for snake envenoming is antivenom, its effectiveness for local effects remains contentious.  The preclinical efficacy of antivenoms against the local effects of envenoming is examined with a range of in-vivo and in-vitro tests. Most of these tests are only capable of examining the ability of the antivenom to prevent, rather than reverse, the local effect. A limitation of the above tests is that they do not consider venom pharmacokinetics or the time course of irreversible effects in envenomed humans. Therefore, more clinically relevant experimental models of antivenom efficacy are required. We searched MEDLINE for studies on the local effects of snakebite. The current clinical literature on the effectiveness of antivenom for local effects appears to be limited. We identified only two randomised trials that compared antivenom with placebo and six randomised trials that tested the effectiveness of one antivenom or one dosage regimen of an antivenom compared to another antivenom or different dosage of antivenom for preventing or reversing the local effects. All these studies were on viperine envenomings. In addition, several studies without a control/comparative group have commented on antivenom effectiveness, although they invariably have significant bias. The existing studies had contrasting conclusions, including no effect of antivenom, antivenom halting the progression of local effects, early antivenom preventing the occurrence of severe local effects including necrosis, early antivenom leading to faster functional improvement, antivenom accelerating the resolution of local effects, or no conclusion. Future research needs to focus on well-designed studies investigating whether the early administration of antivenom will prevent severe local effects.