Snakebite Treatment & Management

The overall envenomation severity is determined by local and systemic findings and can be classified as follows:

• Dry bites: These occur when there is no venom deposition, and therefore there are no signs or symptoms beyond a puncture wound. It is estimated that less than 10% of pit viper bites and 30-50% or coral snake bites are dry.
• Minimal envenomations: These are characterized by local findings such as bruising, tenderness immediately adjacent to the bite site, and an absence of laboratory abnormalities and systemic findings.
• Mild envenomations: These also lack laboratory abnormalities and systemic findings, but the local damage extends several centimeters from the bite site, all the way to a major joint (eg, ankle, wrist).
• Moderate envenomations: These may be associated with non–life-threatening signs and symptoms (eg, vomiting, hematotoxicity without bleeding) and/or local damage that extends beyond two joints.
• Severe envenomations: These result in extensive local damage (eg, beyond two joints) and/or significant systemic toxicity (eg, hypotension, airway swelling, muscle paralysis).

Snakebite severity score

Many hospitals rely on the snakebite severity score (SSS) to make treatment decisions. This research tool considers the local findings as well as the following five body systems that may be impacted by an envenomation:

• Gastrointestinal system
• Pulmonary system
• Cardiovascular system
• Central nervous system
• Local wound
• Hematologic system

Scores range from 0 (normal) to a maximum score of 23. Typically, antivenom is withheld for scores less than 5. However, the SSS frequently results in undertreatment. An envenomation causing swelling and ecchymosis beyond an entire extremity, but without systemic effects or laboratory abnormalities, would produce a score of 4 and would not be treated with antivenom, even though this would be considered a severe envenomation by more accepted standards.

Important to note: The SSS was not intended to guide patient care and has not been validated for clinical decision making. Its use should be restricted to research. ^[42]

The general approach to snakebite management is as follows:

• Recognize and correct any immediately life-threatening conditions
• Provide analgesia
• Assess for local and systemic toxicity
• Minimize local tissue damage
• Prevent or correct any systemic toxicity (eg, hypotension, weakness)
• Prevent or correct hematologic toxicity
• Improve limb function
• Minimize harm from unnecessary and potentially dangerous interventions

Treatment includes both nonpharmacologic and pharmacologic interventions.

The first priority in prehospital care is scene safety. It is essential to prevent creating additional victims. There is no need to capture or transport the snake to the hospital. Even a recently killed snake can envenomate because bite reflexes may persist for several hours. Severe envenomation and death have resulted from bites from decapitated snakes. ^{[18, 19]} It is reasonable to obtain a photograph of the snake, but only if it can be done so safely and does not delay transport. Identifying the species of snake can be helpful if it expedites treatment, facilitates antivenom selection where relevant, or enables experts to tailor therapy.

The most important prehospital interventions are establishing a patent airway, ensuring adequate oxygenation and ventilation, and maintaining euvolemia.

Analgesia should be provided. Opioids are preferred. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended because of their potential hematologic effects, which could compound with venom-induced coagulopathies.

Proper positioning of the affected extremity in the prehospital setting is controversial. Previously, experts recommended keeping the extremity below heart level to minimize the spread of the venom. However, this could exacerbate local swelling, which is almost always present in crotalid envenomation. Elevating the extremity above heart level can reduce the swelling, and patients often report significant pain relief with elevation. Some people fear that elevation can accelerate systemic absorption of the venom, but there is no evidence demonstrating this occurs. In areas where bites are unlikely to cause significant systemic toxicity, elevation is recommended. If systemic illness is a major concern, it is reasonable to keep the affected extremity at heart level. Once the patient arrives in the hospital, however, elevation is recommended for all pit viper envenomations. ^[42] Coral snake envenomations do not result in tissue damage. Place the affected extremity in whatever position the patient finds most comfortable.

Unstable patients should generally be taken to the closest hospital. Stable patients should be brought to the closest appropriate hospital, that is, one that carries antivenom and has one or more staff physicians with expertise in managing snake envenomations.

Most of the interventions that had once been proposed to treat snakebites in the prehospital environment have failed to show benefit, and many have proven to be harmful. Tourniquets were once recommended, but the harm of compromising arterial blood supply is much greater than any benefit in limiting the spread of venom. Methods of obstructing lymphatic flow (eg, constriction bands, pressure immobilization) were also once touted because they may limit systemic absorption of venom. However, they also expose the local tissue to venom for a longer duration and increase the local hydrostatic pressure that contributes to tissue injury. ^[43] The American College of Medical Toxicology issued a position statement condemning these interventions whenever tissue damage is expected. ^[44] Pressure immobilization may be considered in envenomations from exclusively neurotoxic snakes (eg, Eastern coral snakes. ^[45]

Electrical therapy has been proposed to treat snakebites as well as other envenomations, but there is no evidence that it neutralizes venom. ^[46] Furthermore, there is ample evidence of harm, including burns, hypopigmentation, and death. ^[47]

Prolonged cryotherapy also does not appear to offer any benefit and may be harmful to tissue. Animal studies have indicated that local cooling may increase tissue injury without improving mortality. ^{[48, 49]} Anecdotally, some snakebite victims report relief following cold application. It is reasonable to consider using icepacks briefly (eg, 5 min on for every 15-20 min), but prolonged application is discouraged.

Surgical intervention such as excising the affected tissue and “cutting and sucking”, in which an incision is made and then someone uses his or her mouth to “suck” out the venom, confers no benefit and potentially worsens outcomes by causing a bigger wound and introducing mouth flora into the tissue. ^[50]

The prehospital intervention for which there still seems to be much popularity, despite evidence that it is harmful, is venom extraction. Various commercially available suction devices promise to remove venom if applied shortly after the envenomation. However, the amount of venom they can remove is negligible. In an animal study using radioactive-labeled mock venom, these devices removed 0.04-2% of the envenomation load. ^[51] In a different animal study, tissue damage was increased following application of the negative-pressure device. ^[52] An editorial summarizing the use of extraction devices concluded that the risks of harm greatly outweigh any benefits and their use should be abandoned. ^[53]

Once the patient has arrived at the hospital, definitively manage any life-threatening airway, breathing, and circulatory issues. Airway patency may be compromised in severe envenomations or in the rare case of anaphylaxis in response to snake venom. Epinephrine should be administered to anyone with anaphylaxis, and intubation should be performed if patients do not respond. Intubation is also necessary for patients who have impaired ventilation secondary to respiratory muscle weakness. Intravenous fluid resuscitation may be needed to restore euvolemia in patients with significant hypovolemia secondary to gastrointestinal losses and/or third-spacing. Excessive fluid administration should be avoided because it can theoretically exacerbate tissue swelling.

Analgesia is an essential component to snakebite management. Intravenous opioids are preferred initially. NSAIDs are discouraged because of the potential hematologic effects.

There is consensus that the crotalid-envenomated limb should be elevated once the patient has arrived at the hospital. This prevents the venom from accumulating in the extremity and reduces the hydrostatic pressures that can exacerbate tissue swelling. The authors recommend using plaster to prevent the extremity from bending, but it is important to splint loosely; there should be no constriction and no obstruction to lymphatic flow.

Coral snake envenomations are not associated with tissue injury, and patients should be allowed to maintain a position of comfort.

Pictured below is proper elevation of an affected extremity. Notice that this is loosely applied so there is no obstruction to lymphatic flow.

Laboratory tests should be obtained, and the affected extremity should be monitored for progression of swelling and tenderness. Evaluation of neuromuscular strength is recommended for envenomations from suspected neurotoxic snakes.

Physicians who are inexperienced with snakebites sometimes delay treatment until the exact species has been identified. This is unnecessary. Crotalid envenomation is generally a clinical diagnosis, and any pit viper can cause a combination of local damage, hematologic laboratory abnormalities, and systemic toxicity. It has also been demonstrated that many physicians cannot adequately distinguish one crotalid species from another. ^[54] It is easy to distinguish a crotalid envenomation from a coral snake envenomation, which is characterized by varying degrees of motor and sensory abnormalities but not by local tissue injury.

The specific treatment for crotalid envenomations is antivenom, and each patient should be assessed individually to determine if antivenom is indicated. As of March 2020, there are there two US Food and Drug Administration (FDA)–approved products. Crotalidae Polyvalent Immune Fab Ovine (CroFab®, FabAV) was first studied in 1993 and has been commercially available since 2000. ^[55] It is approved by the FDA for the treatment of all North American crotalid envenomation, so it can be used even when the species has not been determined. It is made by immunizing different flocks of sheep with the venom of one of four crotalid species: Western diamondback rattlesnake (Crotalus atrox), Eastern diamondback rattlesnake (Crotalus adamanteus), Mojave rattlesnake (C scutulatus), and cottonmouth (A piscivorus). The antibodies collected from the sheep are then treated with papain to liberate the individual Fab fragments of the immunoglobulin molecule. It has proven to terminate both local and systemic venom effects, resulting in faster and more complete recovery from envenomation when compared with placebo. ^{[56, 57]}

Crotalidae Immune F(ab’)₂ Equine (Anavip®) was first used in Mexico in 1994 and became available in the United States in October, 2018. ^[58] It is approved by the FDA for the treatment of North American rattlesnake bites but not envenomations from copperheads or cottonmouths. It is made by immunizing horses with venoms from the Terciopelo (Bothrops asper) and the South American rattlesnake (Crotalus durissus). The antibodies are then treated with pepsin to create a F(ab)₂ fragment without the F_c portion of the immunoglobulin that is typically responsible for adverse reactions to antivenom.

Indications for antivenom use include progression of local tissue findings and/or evidence of systemic toxicity (eg, hematotoxicity, airway swelling, cardiovascular collapse). The precise definition of hematologic toxicity is unclear, but many providers use prothrombin time greater than >15 seconds, platelet count less than 150 x 10³/µL, or fibrinogen level less than 220 mg/dL, or a significant change from baseline, as indications to treat. It should be emphasized that the SSS should not be used to determine the need for treatment. Reliance on this scale can result in significant undertreatment.

If the swelling and tenderness are more than minimal and have extended beyond a major joint (eg, wrist, ankle), antivenom is warranted. ^[42] If there is significant local tissue injury (eg, necrosis), antivenom is also indicated, even if the swelling has not progressed across a joint. A randomized clinical trial studying the effects of FabAV on copperhead bites demonstrated that even mild bites recovered better when treated with antivenom. ^[59] Specifically, patients had improved limb function at 7, 10, and 14 days post envenomation compared with the placebo group, and 75% of treated patients had full recovery of limb use by day 31, whereas the control group did reach this milestone until 57 days. Treatment was especially beneficial in patients who were treated within 5.5 hours of envenomation. ^[60] Additionally, people who were treated with antivenom required opioids for a much shorter duration. ^[61]

The decision to use one over the other will likely be based on several variables, including availability, cost, and safety concerns, such as prior sensitization to equine- or ovine-derived products.

Epinephrine is useful in patients with anaphylaxis, and diphenhydramine can help with mild urticaria and pruritus, but neither is a substitute for antivenom.

Coral snakes are elapids, not crotalids, and neither FabAV or F(ab)₂AV is indicated for coral snake envenomations. There is only one FDA-approved antivenom for native coral snake envenomations. ^[62] The North American Coral Snake Antivenom (NACSAV) (Micrurus fulvius) (Equine Origin) was first developed in the 1960s. Production was halted in 2010. However, some lots of antivenom are still in circulation, and as of late 2019, production has resumed. Most hospitals will not keep NACSAV in stock, and it may be necessary to contact poison control to locate the antivenom or a suitable alternative.

There are several foreign antivenoms that have demonstrated efficacy against native coral snake venom. ^{[63, 64, 65]} Coralmyn®, manufactured by Bioclon, has proven to be effective in the treatment of Eastern coral snake (M fulvius) envenomations. Another antivenom, produced by Costa Rica’s Instituto Clodomiro Picado, has also been used successfully in the treatment of US coral snake envenomations.

Neostigmine is a peripherally acting cholinesterase inhibitor that can increase synaptic concentrations of acetylcholine, allowing the neurotransmitter to compete with the toxins, preventing paralysis. Several case reports have suggested a modest temporizing benefit in envenomations from coral snake and other elapids. ^{[66, 67]} There are few adverse effects from neostigmine at therapeutic doses, so it is reasonable to administer it following Eastern coral snake (M fulvius) envenomations in which the likelihood of objective neurotoxicity is high.

Patients with suspected dry bites should be monitored for at least 8 hours, and laboratory tests should be rechecked prior to discharge. Snakebites are dynamic, and bites that appear insignificant at first can evolve into severe envenomations. Minimal envenomations that do not require antivenom initially should be observed for a minimum of 12-24 hours to see if there is any progression of the local effects and/or the development of any systemic or hematologic toxicity.

Patients should be admitted to the hospital or an observation unit if there is any evidence of envenomation, whether or not antivenom has been administered. The decision to admit to a general medical ward versus the ICU depends on the severity of the envenomation, the availability of resources, and specific hospital protocols. The authors recommend that the initial dose of antivenom should be administered in a monitored setting (eg, emergency department, ICU).

Most snake envenomations do not require prolonged hospitalization. Unless the patient requires a prolonged course of antivenom, develops end-organ damage, or requires parenteral narcotics, most snakebite victims can be discharged within 24-36 hours. During the hospitalization, it is advisable to have a physical therapist consult on patients with lower extremity bites to assist them with crutches training. Consultation with an occupational therapist and/or a hand specialist may be indicated for bites to the hand.

Patients may be discharged home once the following criteria are satisfied:

• The antivenom course has been completed
• Pain can be controlled with oral medication
• Vital signs have stabilized
• The patient can tolerate a regular diet
• Any hematologic laboratory abnormalities have normalized
• All of the appropriate consultations have been completed

Patients with a crotalid envenomation should be instructed to keep the affected extremity elevated as much as possible. The authors also recommend no weight-bearing for at least 1 week and until it is no longer painful. Snakebite victims should follow up 3-4 days post discharge with a snakebite expert, if possible, or their primary care provider for reassessment and, if indicated, repeat bloodwork. Patients should be instructed to avoid NSAIDs if there is any risk of hematologic toxicity. Surgery should also be avoided for the first 2 weeks post envenomation.

Although surgeons are often involved in the management of snake envenomation in the United States, it is essential to recognize that snakebites are a medical, not surgical, condition. Excision of the bite site was once recommended, but it is now understood that this is a disfiguring procedure that does not confer any survival benefit.

Compartment syndrome is an exceptionally uncommon complication from crotalid envenomation, and prophylactic fasciotomies are no longer recommended. Animal studies prove that morbidity and mortality are increased following prophylactic fasciotomy when compared with antivenom therapy. ^{[68, 69, 70]} In a review of 99 publications evaluating the efficacy of fasciotomy in animals and humans, the author could not identify any situation in which surgical intervention was beneficial. ^[71] An expert panel consisting of trauma surgeons and medical toxicologists also concluded that prophylactic fasciotomy was not beneficial and was possibly harmful. ^[50] The same authors concluded that even in the exceptionally rare case of confirmed compartment syndrome, the initial treatment should be additional doses of antivenom, not fasciotomy. The rationale, supported by animal studies, is that elevated compartment pressure represents a severe envenomation but is not the cause of the morbidity. Rather, it is the venom that is causing the damage, and neutralizing the venom is the definitive treatment. ^[72] Fasciotomy should only be considered in those patients with persistently elevated compartment pressures despite adequate antivenom therapy.

Delayed surgical intervention following envenomation is indicated when there is full-thickness necrosis requiring amputation. Premature surgery must be avoided, however, because many patients with superficial necrosis recover fully if managed with conservative wound care.

Coral snake envenomations are not characterized by tissue injury and do not require surgical intervention.

Consulting your local or regional snakebite expert early in the hospital course is recommended. Medical toxicologists are often the physicians with the most knowledge and experience managing envenomations, but some institutions have experts from other specialties. Help is also available by calling the regional poison center at 1-800-222-1222.

Antivenom-associated complications are rare but may include immediate (anaphylaxis, type I) and delayed (serum sickness, type III) hypersensitivity reactions. Anaphylaxis is an event mediated by IgE, involving degranulation of mast cells that can result in laryngospasm, vasodilatation, and leaky capillaries. Death is common without pharmacological intervention. Serum sickness occurs 1-2 weeks after administering antivenom. Precipitation of antigen-IgG complexes in the skin, joints, and kidneys is responsible for the arthralgias, urticaria, and glomerulonephritis (rarely).

In a meta-analysis of 11 studies, Schaeffer et al reported an 8% incidence of acute adverse reactions following FabAV use. ^[73] Data from the North American Snakebite Registry indicated that only 2.3% of adults and 2.7% of children who received FabAV had acute adverse reactions, including rash (0.9%), hypotension (0.9%), and bronchospasm (0.9%). ^[74] Finally, in a study of 1,340 patients treated with FabAV in Arizona, the incidence of acute adverse reactions was 1.4%. ^[75] None was serious enough to require discontinuation. Serum sickness was reported in 13% of patients in the meta-analysis. Serum sickness from FabAV was not observed in the other studies.

There are no studies that specifically measure the incidence of adverse reactions following F(ab’)₂AV use. The package insert cites an incidence of 76%, including pruritus (43%) and rash (12%). In a randomized clinical trial comparing F(ab’)₂AV to FabAV, the incidences of pruritus and rash were 42.5% and 12.5%, respectively, in the F(ab’)₂AV group. ^[76]

There is an unfounded fear of administering antivenom to patients who have previously received it. Most people who have been treated with FabAV more than once have no adverse reaction to the second and subsequent exposures. In one exceptional case, a man who received FabAV at least 19 times had two episodes of mild acute hypersensitivity but tolerated the antivenom the other 17 times without incident. ^[77]

Also see Complications in Presentation.

While in the hospital and for approximately 1 week after discharge, the patient should not bear weight with the affected extremity.

Prevention is key; people who live in snake-endemic areas should wear appropriate footwear and avoid placing their hands and feet where they cannot see.