Snakebite, recently declared a neglected tropical disease and global health priority by the World Health Organization (WHO), results in an estimated 2.5 million envenomations, 138,000 deaths and over 500,000 cases of permanent disability worldwide every year.1–10 Snake, spider, and scorpion envenomations are a common environmental and occupational hazard for military forces worldwide.11–46 The consequences of an envenomation range from mild local effects to permanent disability or death, and the outcome is largely determined by the time to antivenom treatment and the level of training of the medical providers involved. Clinical outcomes and survival of the snakebite patient require administering antivenom quickly and immediate care by trained medics or medical professionals. Antivenom and appropriate early care are critical to saving lives and preventing long-term complications like amputations, blindness, or loss of limb function.
Venomous snakebites can induce a range of clinical syndromes, largely categorized by the primary type of toxin in the venom. Cytotoxic venoms, found in snakes like spitting cobras, copperheads, and puff adders cause severe localized tissue damage. This manifests as painful progressive swelling that starts at the bite site and can spread rapidly, leading to complications such as blistering, tissue death (necrosis), and compartment syndrome, a condition where swelling cuts off blood circulation. Hemotoxic venoms, on the other hand, disrupt the body's ability to clot blood, leading to bleeding from various sites, including the gums, nose, and the bite wound itself. Snakes such as Russell's vipers, saw-scaled vipers, and boomslangs possess hemotoxic venom, which can cause coagulopathy, a condition of abnormal blood clotting, and in severe instances, disseminated intravascular coagulation (DIC).
Neurotoxic venoms primarily affect the nervous system, causing progressive weakness and paralysis. Symptoms of neurotoxic envenomation include drooping eyelids (ptosis), blurred vision, difficulty breathing, and can advance to paralysis of the respiratory muscles, which can be fatal. Cobras, kraits, and mambas are well-known for their neurotoxic venom. Systemic instability is a broader category of effects that can result from various types of snake venoms and their systemic impacts. This can include a mix of syndromes (eg HEMO + CYTO), such as painful progressive swelling combined with bleeding, as seen in bites from many vipers including rattlesnakes, gaboon vipers, the Fer-de-lance, and others. It can also manifest as life-threatening systemic complications like dangerously low blood pressure (hypotension), shock, acute kidney injury, and acute respiratory distress syndrome (ARDS), which can be triggered by fluid loss from cytotoxic effects, widespread bleeding from hemotoxic effects, or direct shock-inducing venom components.