Bites, Snake

Erica M. Lash, M.D.
Neha P. Raukar, M.D., M.S.

Basic Information

Definition

Injury resulting from a snake biting a human.

ICD-10CM CODES
T63.0	Toxic effect of snake venom
T63.001A	Toxic effect of unspecified snake venom, accidental (unintentional), initial encounter

Epidemiology & Demographics

The CDC reports between 7000 and 9000 venomous snakebites annually in the United States, with <1% resulting in death. The highest incidence is reported in southern states, peaking during the warmer months of April through November. Worldwide, farm workers have the highest incidence of snakebites, whereas in the U.S., most snakebites result from intentional provocation of wild snakes or in the setting of handling captive snakes. Intentional interactions tend to result in bites to the upper extremities, whereas accidental encounters usually result in bites to the legs and feet. White men ages 25 to 34 are at the highest risk of envenomation. Alcohol use and drug intoxication are implicated in many snakebites. The risk of death is highest in children, the elderly, and in those with delayed presentation to care.
Exotic, nonnative pets also account for 1% to 2% of snake envenomations.

In the U.S., at least one species of poisonous snake (Fig. 1) has been identified in every state, with the exception of Alaska, Hawaii, and Maine. Table 1 summarizes medically important snake families.

FIG.1

Comparison of pit vipers and nonvenomous snakes.

Rattle in D *(top)* applies to rattlesnakes only.

A to D, From Sullivan JB, et al.: North American venomous reptile bites. In Auerbach PS, [ed]: *Wilderness medicine: management of wilderness and environmental emergencies,* ed 3, p. 684, St Louis, 1995, Mosby.

TABLE1 Medically Important Snake FamiliesFrom Kliegman RM, et al.: Nelson textbook of pediatrics, ed 19, Philadelphia, 2011, Saunders.

Family	Venomous?	Location	Examples	Toxin Effects/Other Comments
Colubridae	Some species	Most parts of the world	Garter snakes (Thamnophis spp.), king snakes and milk snakes (Lampropeltis spp.)	Largest family of snakes; most are considered harmless to humans; a few species are dangerously toxic (e.g., African boomslang [Dispholidus typus])
Boidae	None	Most parts of the world	Boa sp., Python sp.	Constrictors; unsupervised children should not be allowed access to large constrictors
Viperidae
Subfamily Crotalinae (pit vipers)	All	Americas, Asia	Rattlesnakes (Crotalus spp.), cottonmouths and copperheads (Agkistrodon spp.), Lancehead pit vipers (Bothrops spp.)	Heat-sensing “pit” between each eye and nostril
Subfamily Viperinae (true vipers)	All	Europe, Africa, Middle East, Asia	Puff adder (Bitis arietans), Gaboon viper (Bitis gabonica)	No heat-sensing pits
Elapidae	All	Americas, Africa, Middle East, Asia	Cobras (Naja spp.), mambas (Dendroaspis spp.), kraits (Bungarus spp.), coral snakes (Micrurus spp.), and the venomous snakes of Australia	Highly variable venom effects—some largely neurotoxic, others causing severe local tissue damage
Hydrophiidae	All	Warm waters of the Pacific Ocean, Indian Ocean, and Oceania (none in the Atlantic Ocean)	Sea snakes including the pelagic sea snake (Pelamis platurus)	Neurotoxins and myotoxins; rarely bite humans unless provoked

The Crotalinae subfamily (Viperidae family), commonly referred to as crotalids or pit vipers, includes rattlesnakes, copperheads, and cottonmouths (water moccasins). Crotalids are responsible for the vast majority of snake envenomations in the U.S. They are characterized by a prominent, diamond-shaped head, a heat-sensing pit between the eye and nostril, long retractable fangs, and, in the case of rattlesnakes, the telltale rattler. Crotalid bites are typically very painful.
The Elapidae family includes mambas, cobras, and coral snakes. Coral snakes are the only member of the Elapidae family found in the U.S. Coral snakes are much less common than crotalids, are innately less aggressive, and represent only 1% to 2% of venomous snakebites in the U.S. Elapids have smaller heads and shorter fangs, and they are identified by vibrant bands of yellow, red, and black. The popular saying “Red on yellow, kill a fellow; red on black, venom lack” is used to distinguish between venomous and nonvenomous snakes in the U.S. Caution should be used when applying this axiom internationally, as some coral snakes within South America display red-on-black coloring and are in fact venomous. Elapid bites cause less local tissue destruction and are typically less painful. However, because elapids must “chew” in order to inject venom, victims may report difficulty dislodging the snake after the bite.
The degree of envenomation correlates to the size of the snake, with envenomation from larger snakes producing significantly worse local and systemic symptoms than bites from smaller animals.

Physical Findings & Clinical Presentation

The effects of envenomation vary by the type of snake but may include local tissue injury, coagulopathy, neurotoxicity, and cardiovascular instability, as well as renal failure. Crotalids typically cause severe local effects as well as hematologic symptoms including primary consumptive coagulopathies and less commonly cause neurologic complications. The exception is the Mojave rattlesnake bite, in which case local tissue destruction following envenomation is minimal, but severe neurologic symptoms can occur up to 12 hours after the bite. This is similar to elapid bites, which cause less localized tissue damage but have more severe and often delayed neurotoxic manifestations.

Crotalinae (Pit Vipers)

Local signs and symptoms:
1. Intense pain within 5 minutes
2. Localized edema within 30 minutes
3. Erythema, ecchymosis, and serous/hemorrhagic bullae can develop over hours (Fig. 2)
  
  FIG.2
  
  Southern Pacific rattlesnake (Crotalus helleri) bite wounds.
  
  Courtesy Sean Bush, M.D.
4. Compartment syndrome may rarely develop around the site of the bite from significant amounts of soft tissue swelling and subcutaneous tissue fluid accumulation.
5. If edema or erythema does not occur within 8 hours of a confirmed crotalid snakebite, it is assumed envenomation did not occur (“dry bite”). Roughly 25% of crotalid bites are “dry bites.”
Systemic manifestations:
1. Nonspecific: nausea, vomiting, diarrhea, lightheadedness, weakness, diaphoresis, chills
2. Coagulopathy: epistaxis, bleeding from gums, internal hemorrhage
3. Neurotoxicity: perioral paresthesias, metallic taste, tingling of fingers or toes (especially with rattlesnake bites), localized/generalized fasciculations, mental status change
4. Nephrotoxicity: secondary to rhabdomyolysis
5. Increased vascular permeability: severe hypotension, tachycardia, respiratory distress

Elapidae (Coral Snakes)

Local signs and symptoms:
1. Absent or minimal local effects, such as mild pain, swelling, or paresthesias at site of bite.
Systemic Manifestations:
1. May be delayed for up to 12 hours.
2. Nonspecific: Nausea, vomiting, abdominal pain, dizziness
3. Neurotoxic: Cranial neuropathies typically appear first, including ptosis, ophthalmoplegia, dysphagia, drooling, and mydriasis with absent or prolonged pupillary light reflex. Descending paralysis and respiratory failure (due to diaphragmatic weakness) can be delayed many hours.

Diagnosis

Differential Diagnosis

Bite: nonvenomous snakebite, “dry bite,” scorpion bite, insect bite, cellulitis, laceration, puncture wound, necrotizing fasciitis
Descending paralysis: myasthenia gravis, botulism, shellfish poisoning
Rhabdomyolysis: crush injury, prolonged immobilization, marked exercise, hyperthermia, metabolic myopathies, drugs or toxins, infections, electrolyte disorders
Coagulopathy: sepsis, multiple trauma, obstetrical complications, malignancy

Workup

Stabilize and resuscitate unstable patients.
Initial evaluation of the bite (see the following):
1. Complete physical and neurologic examination
2. Obtain past medical history, including any history of allergic reaction to horse serum, sheep serum, or papaya in those previously treated for snakebite.
Labs and imaging (see the following)

Determine need for antivenom (see the following and Table 2)

TABLE2 Indications for Snake Antivenom AdministrationFrom Kliegman RM, et al.: Nelson textbook of pediatrics, ed 19, Philadelphia, 2011, Saunders.

Evidence of Systemic Toxicity:
Hemodynamic or respiratory instability	Hypotension, respiratory distress
Hemotoxicity	Clinically significant bleeding or abnormal coagulation studies
Neurotoxicity	Any evidence of toxicity: usually beginning with cranial nerve abnormalities and progressing to descending paralysis including the diaphragm
Evidence of local toxicity	Progressive soft tissue swelling

Call Poison Control Hotline: 1-800-222-1222
Call local zoo when treating patients with envenomations from exotic pets or nonnative snakes
Serially reassess, including serial neurologic exams, all cases of suspected envenomation for 8 hours, longer if clinical status deteriorates

Laboratory Tests

CBC with peripheral smear, electrolytes, BUN, creatinine, PT, INR, PTT, fibrinogen, d-dimer, creatine kinase, liver function tests (LFTs), sedimentation rate (ESR), arterial blood gas (ABG), type and crossmatch, urinalysis, and electrocardiogram (ECG).
Repeat labs every 4 to 6 hours to monitor trend.

Imaging Studies

Consider chest x-ray in cases of severe envenomation or in patients over 40 years old with underlying cardiopulmonary disease to rule out pulmonary edema
Plain films of bite site for retained fangs (poor sensitivity). Bedside ultrasound is another option to rule out a retained foreign body in the setting of a snakebite (negative predictive value of 96%).
Computed tomography (CT) of head if concern for intracranial hemorrhage or if any cognitive/neurologic deficit is appreciated on exam
CT abdomen or focused assessment with sonography in trauma (FAST) if concern for intraabdominal bleeding exists or if patient complains of abdominal pain or distention

Treatment

Acute General Rx

In the Field

There is no field first aid that will significantly treat the envenomation; therefore, the most important intervention is to transport the patient quickly to the nearest medical facility.
Remove any constricting items including rings, watches, jewelry, or tight clothing.
The affected part should be kept at the level of the heart. Keep the joint in a functional position to minimize disability should the limb or joint become severely swollen or immobile.
Do not apply a tourniquet, incise wound, apply mechanical or oral suction, attempt electrotherapy, or apply ice. These interventions have not been shown to provide any benefit and have the potential to cause further harm, including tissue damage, infection, and caregiver envenomation.
In general, do not apply a pressure dressing. Since most bites are from crotalids, a pressure dressing can exacerbate local tissue destruction and necrosis. However, if the bite is known to be from a coral snake, applying a pressure dressing can prevent the spread of neurotoxin. A properly applied pressure bandage should produce a pressure of 40 to 70 mm Hg and 55 to 70 mm Hg in the upper and lower extremity, respectively.
Avoid alcohol, stimulants (caffeine), or agents that can suppress mental status.
Do not pick up a dead snake, as the strike reflexes remain intact and can still envenomate.
When possible, a picture can be taken from a safe distance for later classification of the snake.

In the Hospital

Assess airway, breathing, and circulation and intervene as needed. Patients with neurotoxic envenomation from elapids or Mojave rattlesnakes can develop respiratory failure (from diaphragmatic paralysis) and may require intubation. Be cautious and repeat the examination as neurotoxic symptoms may be delayed for many hours.
Place on monitor, obtain vital signs, place 2 large-bore IVs and give crystalloid.
Unstable patients should be given antivenom immediately. Administration should not be delayed for wound care of bite.
If patient is stable, obtain a history, including the time of bite and description of snake.
Inspect bite site for fang marks and local tissue injury. Clean bite site and remove any retained fangs. Bite may appear like two distinct puncture wounds or small scratches.
Mark leading edge of erythema and edema, and obtain circumferential measurements every 15 minutes to assess for progression.
Obtain initial labs and repeat every 4 to 6 hours.
Determine need for antivenom and begin preparation. It can take up to 1 hour to reconstitute antivenom, so this process should be started as early as possible.
Contact Poison Control at 1-800-222-1222, which will connect you to your local poison control center. They will provide guidance for treatment and use of antivenom, and also track snakebite incidence.
Immunize against tetanus if no booster within the past 5 years. If never immunized, give immunoglobulin as well as toxoid.
Prophylactic antibiotics are not recommended. Antibiotics should be given only if purulence or other signs of infection progress. When indicated, broad-spectrum antibiotics should be used to cover gram-negative bacteria (i.e., ampicillin-sulbactam or quinolone derivatives).
Aggressive pain control with opioids. Avoid NSAIDs, as they increase risk of bleeding, platelet dysfunction, and nephrotoxicity.

Antivenom Treatment

Crotalid (Rattlesnake, Copperhead, Cottonmouth) Envenomations

CroFab (Crotalinae polyvalent ovine immune Fab), made from sheep serum, is the antivenom commercially available in the U.S. for crotalid envenomations.
Indications for antivenom administration include swelling, pain, and/or ecchymosis extending beyond area immediately adjacent to bite, any progression of local symptoms (≥2 cm of erythema spread), any systemic symptoms, any development of coagulation lab abnormalities, or abnormal bleeding.
Patients with crotalid envenomation who have minimal or nonprogressive symptoms should not be given CroFab and instead should be monitored for 8 to 12 hours.
Dosing:
1. For moderate symptoms, reconstitute 4 to 6 vials of antivenom. Each vial should be mixed in 25 ml of normal saline. The 4 to 6 reconstituted vials should then be mixed in 250 ml normal saline and infused over 60 minutes. Infuse the first 25 ml slowly over the first 10 minutes to monitor for allergic reaction.
2. For patients with shock or serious active bleeding, give an initial dose of 8 to 12 vials.
3. If no improvement after first round (defined as progression of local symptoms, persistent systemic symptoms, derangement of laboratory values, or continued bleeding), repeat the initial dose of antivenom.
4. Between 4 and 18 vials of antivenom may be necessary to control initial symptoms.
After initial control of symptom progression, give maintenance dose of 2 vials every 6 hours for 3 doses to prevent recurrent toxicity.
Hematologic labs (fibrinogen, platelet levels, and coagulation studies) should be repeated within an hour of antivenom administration.
The manufacturer of CroFab maintains a 24/7 hotline: 877-377-3784.
A new Crotalinae antivenom, Anavip, was approved by the FDA in May 2015, with anticipated availability in October 2018. Anavip is an equine antivenom that has venom specific F(ab’)₂ fragments of immunoglobulin G (IgG), as opposed to two separate Fab fragments, increasing the half-life in the blood and leading to greater binding and therefore greater elimination of the venom. Because of the longer half-life, dosing with Anavip also eliminates the need for repeat outpatient antivenom dosing, as is required with CroFab. There is a low risk of adverse reactions and serum sickness because, similar to CroFab, these antivenoms lack the Fc component of the IgG.

Elapid (Coral Snake) Envenomations

In the U.S., production of coral snake antivenom was discontinued in 2003, and only one lot of antivenom still exists. The antivenom’s expiration date was extended to January 31, 2018. The use of expired antivenom may be considered in a patient with life-threatening symptoms but should only be administered in conjunction with Poison Control and/or a medical toxicologist. If coral snake antivenom is not available, providers may consider contacting their local zoo to determine whether a provisional antivenom is available. Small-animal studies support the use of Mexican Coral Snake, Australian Tiger Snake, or anticoral antivenom for neutralization of North American coral snake venom. Many zoos caring for wild snake species stock these specific antivenoms. It is important to note that the effectiveness of these particular antivenoms in human snakebites by the North American coral snake has not been studied. If considering administering alternate antivenom, the provider should contact Poison Control to help orchestrate acquisition.
A potent, safe, sheep-based antivenom for elapid bites exists and is being used internationally but is not yet approved in the U.S. The University of Arizona is currently sponsoring a clinical trial evaluating the use of a new F(ab’)2 antivenom in management of coral snakebites in the U.S. The results of this study have not yet been published.
In the U.S., only symptomatic patients with confirmed coral snake bites should receive antivenom. The initial dose is 3 to 5 vials given by slow intravenous push, although a higher dose may be necessary in children or in envenomations from large coral snakes.
There is a high risk of allergic reaction with horse serum-based elapid antivenom so epinephrine, diphenhydramine, IV corticosteroids, and albuterol should be readily available prior to giving antivenom.

Nonnative or Exotic Snake Envenomations

Contact the Poison Control Center or your local zoo, as zoos with exotic snakes are required to maintain a supply of snake-specific antivenom on their premises.

Disposition

All patients who are given antivenom must be admitted and monitored in an ICU for further observation and supportive care. Patients should be observed for a minimum of 18 to 24 hours after initial control of symptom progression, and they are safe for discharge when symptom progression has resolved and laboratory values have normalized.
Victims of crotalid envenomations with minimal to no toxicity and normal serial lab values should be observed for 8 to 12 hours.
Children, the elderly, those with significant comorbidities, and patients who sustain bites to the legs, face, or neck may require observation for 24 hours.
Suspected Mojave rattlesnake bites should be observed 12 to 24 hours as their venom predominantly causes neurotoxicity and symptoms may be delayed (similar to elapids).
Asymptomatic patients with coral snakebites should be observed for 12 to 24 hours because neurotoxicity may be delayed.

Follow-up

All patients who receive antivenom should have repeat labs at 2 to 3 days and 5 to 7 days after the last administered antivenom dose to evaluate for delayed hematologic complications or serum sickness.
Return for worsening, nondependent swelling, abnormal bleeding, or signs of serum sickness, which include fatigue, rash, or arthralgias.
Patients should adhere to bleeding precautions (no contact sports, dental extractions, elective surgery, etc.) for 2 weeks.

Referral

Refer to a medical facility with an ICU for administration of antivenom. The approach to snakebites should be multidisciplinary and should include medical toxicology or other physician snakebite specialists, as well as hematology or nephrology if needed. All snakebites should be reported to Poison Control and the local health department for surveillance.

Pearls & Considerations

Other Considerations

Frequent assessment and clinical judgment is essential in the treatment of snakebites, as patients do not have a uniform response to envenomation and treatment.
Dosage of antivenom is based on typical envenomation rather than age or weight, so the dose is the same for children and adults.
Antivenom is most effective when given within 4 hours of the bite and least effective if delayed beyond 12 hours. Systemic symptoms (coagulopathy, CNS effects, etc.) respond better to treatment than do local symptoms (erythema/edema, bullae, etc.).
Antivenom is not contraindicated in pregnancy. There have been no adverse reactions to mother or to fetus reported secondary to antivenom treatment. The potential coagulopathy associated with envenomation may place the fetus at higher risk for placental abruption, so prompt treatment with antivenom is prudent. Pregnant victims of snakebites who are treated with antivenom have a significantly lower rate of miscarriage when compared with those who did not receive antivenom.
Although local wound effects can be severe, wound management should not take precedence over antivenom administration. Some studies suggest that even in the case of compartment syndrome, antivenom may be more effective than fasciotomy, although both may be necessary.

Complications

Hypersensitivity reactions and serum sickness can occur following any antivenom administration. These reactions are much more common with equine-derived antivenom than with ovine-derived antivenom. CroFab derived from sheep serum should be used preferentially over equine serum if available, given the decreased risk for adverse reaction. Elapid antivenom is derived from horse serum, so the risk for allergic reaction and anaphylaxis remains high.
Anaphylaxis can occur within 30 minutes and should be treated by immediately stopping the infusion and managing the symptoms. Give epinephrine, diphenhydramine, and hydrocortisone as needed. If the anaphylaxis is well-controlled and the envenomation is severe, the infusion can then be resumed.
In patients with a known hypersensitivity to antivenom, prophylactic epinephrine has been found to reduce the rate of adverse effects.
Delayed or recurrent hematologic complications are common and can manifest up to 2 weeks post treatment. Most bleeding is self-limited but can rarely be severe, necessitating close follow-up and occasionally repeat doses of antivenom.
Serum sickness occurs 7 to 14 days after antivenom administration and is characterized by fever, rash, arthralgias, and lymphadenopathy. It can be treated with prednisone 60 mg PO daily, tapered over 7 to 10 days.

Ferri – Bites, Snake