Venomous Animal Injuries

Foundations

Of the 3000 species of snakes, approximately 800 are venomous. All venomous snakes belong to four of the 14 families of snakes—Viperidae, Elapidae, Colubridae, and Atractaspididae. Snakes are found throughout most of the earth’s surface, including fresh and saltwater. The major exceptions are the Arctic and Antarctic zones, New Zealand, Malagasy, and many small islands. With recent trends in climate change, many of these geographic regions are in a state of flux and have altered snake biodiversity. The activity and native distribution of snakes are restricted to a fairly narrow range given they are poikilotherms; however, nonnative snakes, including venomous snakes, are popular pets worldwide and often transported out of their natural habitat illegally. All snakes are carnivorous, and their venom apparatus evolved for the purpose of obtaining food.

Approximately 5000 to 10,000 snakebites are reported to US poison centers every year. The incidence of reported venomous snakebites in the United States is greatest in the southern states, especially in Arizona and Texas. Within the United States, the vast majority of snakebites result from native pit vipers, although snakebites from coral snakes and nonnative species are also represented.

Snakebites are often classified by the inflicting species, the age and gender of the victim, the location of the wound, and whether it followed intentional or unintentional contact with the snake. Men are more likely than women to have snakebites as a result of intentional contact, and snakebites following intentional contact are more likely to affect an upper extremity. Overall, the majority of reported venomous snakebites in the United States result from unintentional contact with snakes and affect a lower extremity.

In addition to native venomous snakes, imported venomous snakes are a problem throughout the United States and worldwide. In the past, only zoos, research centers, and herpetologists kept exotic venomous snakes. Today, private owners have easy access to a wide variety of exotic pets including venomous snakes through a 15 billion USD global industry in exotic animal trade. Emergency providers may lack experience treating exotic snakebites, and, depending on the species, may lack access to antivenoms crucial for patient management. In the United States, laws designed to limit exotic pet ownership have proven difficult to enforce. Approximately 30–50 snakebites from exotic venomous species are reported to US poison centers annually. Worldwide, venomous snakebites are an increasing public health threat with more than 150,000 estimated deaths annually, most occurring in tropical regions of Africa, the Middle East, Southeast Asia, and South America.

Classification and Characteristics

The four venomous families of snakes are the Colubridae, Elapidae, Viperidae, and Atractaspididae ( Table 53.1 ). The Colubridae, although representing 70% of all species of snakes, have very few venomous members dangerous to humans; these include the boomslang and bird snake. They are rear-fanged snakes, and although many possess venom, they generally do not envenomate humans. The Elapidae are more common and include deadly cobras, kraits, mambas, and coral snakes. The Hydrophiidae are sea snakes and a subfamily of the Elapidae. The yellow-bellied sea snake, Hydrophis platurus , has been found off the coast of southern California, western Mexico, Japan, and the Korean peninsula, but bites from this snake are uncommon. The Viperidae, or true vipers, are represented by the Russell viper, puff adder, Gaboon viper, saw-scaled viper, and European viper. The Crotalidae, or pit vipers, are sometimes considered a separate family or subfamily (Crotalinae) of the Viperidae. Among the pit vipers are the most common American venomous snakes, such as rattlesnakes, water moccasins, copperheads, the bushmaster, cantil, and the fer-de-lance. The Atractaspididae are the mole vipers, which have side-positioned fangs; they rarely envenomate humans and are found only in Africa and the Middle East.

Pit vipers, the most prevalent venomous snakes in the United States, are native to every state except Maine, Alaska, and Hawaii. They are classified into three main groups: true rattlesnakes (genus Crotalus ), copperheads and water moccasins (genus Agkistrodon ), and pygmy or Massasauga rattlesnakes (genus Sistrurus ). Pit vipers account for nearly all venomous snakebites in the United States.

The other major group of venomous snakes in the United States are the coral snakes. The eastern coral snake (Micrurus fulvius) is found in North Carolina, South Carolina, Florida, Louisiana, Mississippi, Georgia, and Texas. Envenomation from the eastern coral snake can be deadly. The Texas coral snake (Micrurus tener) and the western or Arizona coral snake (Micruroides euryxanthus) are found in the western United States and generally considered less dangerous than the eastern variety.

Anatomy and Identification

There are two key principles for identifying venomous snakes: only experts should handle live snakes, and even dead snakes can envenomate careless handlers.

It is not difficult to differentiate between pit vipers and harmless snakes found in the United States ( Fig. 53.1 ). Pit vipers, as their name implies, have a characteristic pit midway between the eye and the nostril on both sides of the head. This pit is a heat-sensitive organ that enables the snake to locate warm-blooded prey. Pit vipers may be identified through other methods, but this characteristic is very consistent. The triangular shape of the head, the presence of an elliptical pupil, the tail structure, and the presence of fangs are useful characteristics but are inconsistent. The arrangement of subcaudal plates may be used for Crotalinae if the head has been damaged or is unavailable. An individual specimen may not fit the classic description, depending on the age of the snake, the time of the year, and the condition of the tail and mouthparts. Neither color nor skin pattern is a reliable method of identifying pit vipers.

Coral snakes can be readily identified by their color pattern. At first glance, they resemble one of several varieties of king snake found in the southern United States. The coral snake can be differentiated from the king snake by two characteristics: The nose of the coral snake is black, and the red and yellow bands are adjacent on the coral snake but separated by a black band on the king snake ( Fig. 53.2 ). The popular rhyme is as follows:

Red on yellow, kill a fellow.

Red on black, venom lack.

This rhyme can be used only in the United States because there is significant color variation in coral snakes from other regions of the world.

Size is not an important factor in identifying venomous reptiles. Venomous snakes range in length from several inches to several feet. Although a 6-foot eastern diamondback rattlesnake is much more dangerous than a 10-inch copperhead, all venomous snakes are able to envenomate from birth and should be treated as though they are dangerous.

Exotic or international snakes that are not pit vipers are not as easily identified. If possible, rather than capturing and transporting an unidentified snake, a safe-distanced digital picture can be taken and electronically sent to an expert for positive identification. Local zoos, herpetologists, poison control centers, and universities often have resources to assist in identification of unknown snakes.

Other Reptiles

Only two venomous lizards are found in the world, both in the southwestern United States and Mexico. They are the Gila monster (Heloderma suspectum) and the Mexican beaded lizard (Heloderma horridum). Fortunately, both of these lizards are nonaggressive and rarely encountered. Bites usually result from handling the animals in captivity and victims are usually male. The Gila monster and the Mexican beaded lizard are easily identifiable. Both have thick bodies, beaded scales, and either white and black or pink and black coloration ( Fig. 53.3 ).

Pathophysiology and Toxins

The two main factors influencing the pathophysiology of any venomous animal injury are the toxic properties of the venom and the victim’s response to these toxins. In the past, snake venoms were classified as either neurotoxic or hematotoxic, depending on the observed response of the victim to the various venoms. Modern toxicologic investigation has shown that this classification is inadequate because most snake venoms contain compounds that have many toxic properties. However, it is true that the venom of a particular species of snake may cause a systemic clinical response that is predominantly neurotoxic or hematotoxic.

Between different species, the components of snake venom are variable. Between individual snakes of the same species, there is also considerable variability of venom components depending on factors such as age, geographic location, and diet. The toxic components of snake venom include a mixture of small molecules and peptides. Peptides and proteins, which account for most of the toxic manifestations, make up to 90% to 95% of the venom. Common peptide/protein families include phospholipases A2, three-finger toxins, metalloproteases, and serine proteases. Phospholipases A2 are a major component of elapid and viper venom. The phospholipases A2 are a diverse group of enzymes whose activity is responsible for a wide variety of clinical effects, including neurotoxicity through inhibition of acetylcholine release from axon terminals as well as tissue damage through calcium dependent lipid hydrolysis. Metalloproteases are also major components of elapid and viper venom and have an important role in causing hemorrhage as well as local tissue damage. The major component of elapid venom are the three-finger toxins. The three-finger toxin family is extensive, with a wide variety of targets and resulting clinical effects including neurotoxicity and cardiotoxicity. Although there are many other protein families in snake venoms, the shared components of venoms across species have important medical implications regarding cross-neutralization by specific antivenoms and the possibility of a universal antivenom.

Heloderma venom is perhaps most famous for its use in drug design. The identification of exedins in Heloderma venom led to the development of exanatide, a GLP-1 receptor agonist used in the treatment of diabetes. Exendins in venom functional similarly to stimulate glucose-dependent insulin release. Other components of Heloderma venom include phospholipases A2, helofensin, kallikrein, helofensin, and cysteine-rich secretory protein.

Venom Delivery

The mechanism for delivering venom is fairly standard among snakes. It consists of two venom glands, hollow or grooved fangs, and ducts connecting the glands to the fangs. The glands, which evolved from salivary glands, are located on each side of the head above the maxillae and behind the eyes. Each gland has an individual muscle and a separate nerve supply that allow the snake to vary the amount of venom injected. The venom duct leads from the anterior portion of the gland along the maxilla to the fangs. Pit vipers have fangs that are large anterior maxillary teeth. These teeth are hollow and rotate outward from a resting position to a striking position. The coral snake has fixed, hollow maxillary teeth that are much smaller than those of pit vipers. The fangs in most snakes are shed and replaced regularly, and it is not unusual to see a snake with double fangs on one or both sides of its mouth.

The snake can control the amount of venom injected. In biting a human, a prey much too large to swallow, the snake may inject little or no venom (a “dry” bite), especially if injured or surprised. It is estimated that up to one-third of potentially venomous bites to humans are actually “dry” bites. However, the snake may inject more than 90% of the contents of the gland for the same reasons.

Heloderma have venom glands located in the lower jaw that deliver venom through ducts into grooved lower teeth. Heloderma are known for prolonged, “chewing” bites.

Clinical Features

The signs and symptoms of a venomous snakebite vary considerably and depend on many factors. Clinical signs can include local tissue damage, myolysis, kidney injury, coagulopathy, cardiotoxicity, and neurotoxicity. Up to 50% of venomous snakebites result in little or no envenomation. A person with comorbidities including impaired cardiovascular, renal, or pulmonary function is less able to cope with even a moderately severe envenomation. The victim’s autopharmacologic response to the envenomation must also be taken into account. An immunoglobulin E (IgE)-mediated anaphylactic-type reaction may develop in victims of a previous snakebite when reexposed to the venom or in individuals sensitized to snake proteins through frequent handling. Because of these multiple variables, the individual clinical response is the best judge of the severity of a venomous snakebite. Factors that influence the effects of a snakebite are the age, health, and size of the snake; the relative toxicity of the venom; the condition of the fangs; whether the snake has recently fed or is injured; the size, age, and medical problems of the victim; and the anatomic location of the bite. In the Americas, clinical features including time to presentation of greater than 6 hours, age 12 years of younger, bites from adult snakes, presence of ptosis, and evidence of coagulopathy on initial labs are associated with more severe envenomations.

Elapidae and Hydrophiidae venoms have predominantly systemic effects, whereas Colubridae, Viperidae, and Crotalinae venoms have significant local effects. There are many exceptions to this general division. For example, the venom of the Mojave rattlesnake (Crotalus scutulatus) may show minimal local effects and significant systemic neurotoxic effects, whereas the venom of the Indian cobra (Naja naja) may cause extensive local tissue destruction.

Gila monster and beaded lizard bites are generally associated with pain, edema, and weakness. Hypotension is common with severe bites. There are no reported deaths from Heloderma bites, although myocardial infarctions have been reported.

Crotalids (Pit Vipers)

The most consistent symptom associated with pit viper bites is immediate burning pain in the area of the bite. Swelling typically develops minutes after envenomation and may progress for several hours to days; however, onset may be delayed. Ecchymosis, petechiae, blebs, and bullae may develop early at the site of envenomation ( Fig. 53.4 ). The cytotoxic effects of envenomation including pain and paresthesias may suggest a developing compartment syndrome; however, a true compartment syndrome is rare in North American snakebites, even in the setting of severe edema, because most bites are subcutaneous in nature and not intramuscular. Systemic effects are generally less common but can include weakness, nausea, fever, vomiting, sweating, numbness and tingling around the mouth, metallic taste in the mouth, muscle fasciculations, and hypotension.

Hematotoxicity is especially common after North American rattlesnake envenomation. Laboratory abnormalities can include thrombocytopenia, hypofibrinogenemia, increased prothrombin time, and increased partial thromboplastin time. These laboratory abnormalities do not always correspond to clinical bleeding; however, the risk of bleeding increases with the presence of both thrombocytopenia and coagulopathy. Hypofibrinogenemia can occur for up to 2 weeks after treatment with Crotalidae polyvalent immune Fab (CroFab).

Neurotoxicity can be seen with several species of North American pit vipers including the Mojave rattlesnake (C. scutulatus) and Timber rattlesnake (Crotalus horridus ). There is significant geographic variation in Mojave rattlesnake venom; however, envenomation by snakes with venom type A (phospholipase A2 [PLA2] dependent neurotoxin [PLA2]-dependent neurotoxin) can result in cranial nerve dysfunction, skeletal muscle weakness, paralysis, and respiratory failure. Type A venom does not have significant hematotoxic effects, whereas type B venom contains a large component of fibrinogenolytic metalloproteinases responsible for hematotoxicity. Although most Mojave rattlesnakes carry one phenotype or the other, there are small populations of Mojave rattlesnakes with both type A and type B venom phenotypes. Similarly, the Timber rattlesnake has a largely neurotoxic type A venom and a proteolytic and hemorrhagic type B venom. There are small populations of Timber rattlesnakes with both type A and type B venom phenotypes.

Coral Snakes

Signs and symptoms can vary considerably with bites of coral snakes. Coral snakes are not aggressive, and a significant number of bites are “dry bites” that do not result in envenomation. Unlike many crotalid bites, envenomation by coral snakes typically causes minimal local pain and swelling. The neurotoxic effects of the eastern coral snake are often delayed for several hours but can progress rapidly after onset. Neurologic symptoms can include ptosis, vertigo, paresthesias, fasciculations, slurred speech, drowsiness, dysphagia, restlessness, increased salivation, nausea, and proximal muscle weakness. Although rare, the usual cause of death after coral snake envenomation is respiratory failure.

Infection

Although snakebite envenomation has been stressed here, any bite or puncture wound carries a risk for secondary bacterial contamination. There are significant geographic differences in rates of secondary infection, causative microorganisms, and standard use of prophylactic antibiotics following snakebites. In the United States, the rate of secondary infection after rattlesnake bite is less than 1%. The majority of bacteria isolated from these infections were human skin flora and not rattlesnake oral flora. This is in stark contrast to victims of viper bites in Costa Rica, where more than 20% of patients developed secondary infection, and isolated organisms were commonly snake oral flora. Secondary infections may include osteomyelitis, cellulitis, or gas gangrene, and these infections may occur with or without associated envenomation. In the United States, routine prophylactic antibiotics are not recommended; however, it is reasonable to offer patients with deep puncture wounds from any mechanism antibiotic prophylaxis if they are at high risk for secondary infection. Risk factors may include immunodeficiency, delay to care, and heavily contaminated wounds. Antibiotics for infected wounds should include gram-negative coverage for snake oral flora and coverage for human skin flora.

Differential Diagnoses

The differential diagnosis of venomous snakebites includes dry bites, bites from nonpoisonous snakes, spider and tick bites, scorpion and hymenoptera stings, dermatologic disorders such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, and methicillin-resistant Staphylococcus aureus (MRSA) infections.

Diagnostic Testing

Diagnosis of snakebite relies largely on clinical history and examination. Diagnostic testing following pit viper envenomation should include complete blood count, prothrombin time, partial thromboplastin time, and fibrinogen levels at presentation and repeated in 4 to 6 hours. Patients with evidence of systemic illness following snakebite should also have renal function, electrolytes, and electrocardiogram (ECG) assessed. Depending on clinical presentation, a creatinine kinase and urinalysis may also be indicated. Detection of venom in blood or urine by enzyme-linked immunosorbent assay is possible, although the results of these assays are too delayed to have any clinical impact in the ED. There are no standard laboratory or imaging diagnostics recommended in suspected Heloderma envenomation.

Patient History

Specific historical information includes time elapsed since the bite, the number of bites, whether first aid was administered and what type, location of the bite, and symptoms (e.g., pain, numbness, nausea, tingling around the mouth, metallic taste in the mouth, muscle cramps, dyspnea, and dizziness). A brief medical history includes the last tetanus immunization, medications, and cardiovascular, hematologic, renal, and respiratory problems. An allergy history with emphasis on symptoms after exposure to horse or sheep products, previous injection of horse or sheep serum, and a history of asthma, hay fever, urticaria, or allergy to wool, papain, chymopapain, papaya, or pineapple should be obtained if antivenom treatment is being considered.

Patient Examination

The bite area is examined for signs of fang marks, scratches, or bleeding and local signs of envenomation (e.g., extremity edema, petechiae, ecchymosis, and bullae). The area distal to the bite is checked for pulses. A general physical examination is performed, with emphasis on the cardiorespiratory system and the neurologic examination, especially if a Mojave rattlesnake, coral snake, or exotic snake is suspected. The leading edge of local injury should be noted and marked. If the bite involves an extremity, the circumference of the extremity at the site of the bite and approximately 5 inches proximal to the bite should be measured and recorded.

Initial Medical Care

Initial medical management of snakebites should address the patient’s airway, breathing, and circulation status. Snakebite victims with or without initial clinical evidence of envenomation should have an intravenous line with normal saline placed in an unaffected extremity as onset of systemic symptoms can be delayed but precipitous.

Following crotalid envenomation, the affected limb should be immobilized and elevated to prevent dependent edema. The leading edge of injury should be serially assessed. Intravenous opioids can be given for analgesia. Tetanus prophylaxis should be administered if the patient is not current on their immunization status. Labs including complete blood count, fibrinogen, and prothrombin time are obtained during initial evaluation. The emergency clinician should then determine if there is any evidence of envenomation by local signs (swelling, ecchymosis, blebs), laboratory abnormalities, or systemic signs (hypotension, neurotoxicity, abnormal bleeding). Bedside ultrasonography can be used by trained providers in conjunction with their physical exam to assess for underlying injury and edema. If signs of envenomation are present, the need for antivenom is then assessed.

Pit Viper Envenomation Classification

Crotalid envenomation may be classified according to severity into five grades, from grade 0 (no sign of envenomation) to grade IV (very severe envenomation) ( Table 53.2 ). Patient management, including the use of antivenom, can be correlated and guided with the grade of envenomation.

Antivenom

Any victim of a pit viper snakebite with moderate or severe envenomation is a candidate for antivenom. CroFab was approved by the US Food and Drug Administration (FDA) for treatment of North American pit viper envenomations. CroFab is derived from Fab fragments of immunoglobins from sheep immunized with one of four species of pit vipers in the United States: the western diamondback rattlesnake (Crotalus atrox) , eastern diamondback rattlesnake (Crotalus adamanteus), Mojave rattlesnake (C. scutulatus), and the cottonmouth (Agkistrodon piscivorus). In 2015, the FDA approved Anavip, an F(ab′)2 immunoglobulin derived from horses immunized against the fer-de-lance (Bothrops asper) and tropical rattlesnake (Crotalus durissus). Anavip has a similar safety profile compared with CroFab and a longer half-life that results in lower rates of recurrent or late onset coagulopathy. Anavip has a lower cost per vial than CroFab; however, it is unclear how many vials of Avavip will be needed for treatment of severe envenomation. Given the low rates of severe coagulopathies with copperhead envenomation, the efficacy of Anavip in treatment of copperhead envenomation is still yet to be determined. Avavip became commercially available in 2019.

A polyvalent, horse serum–derived antivenom was previously manufactured by Wyeth Laboratories for treatment of North American pit viper envenomation. Vials of this antivenom may still be found in zoos and hospitals, although most have been replaced with the ovine-derived Fab antivenom (CroFab).

The treatment of snakebites is expected to evolve as researchers discover new ways to create antivenoms. Currently, the process of creating antivenoms is highly labor intensive and antivenoms remain unavailable in many parts of the world with the most pressing need. Recently, researchers have discovered a method to culture snake venom glands from snake stem cells. These cultured gland cells are functional and can secrete active toxins. This breakthrough may allow for the creation of large banks of venoms for further study and also eliminate the need to “milk” venomous snakes for their venom. New research on the Indian cobra genome and transcriptome also raises the possibility of creating synthetic venom and, ultimately, a synthetic humanized recombinant antivenom. At least one National Institutes of Health (NIH)-funded phase I trial is underway investigating monoclonal human-derived IgG as a potential source of a broad-spectrum, low immunogenicity antivenom (Project #1R43AI147898-01).

Dosage and Precautions

The CroFab package insert recommends an initial dose of four to six vials of CroFab intravenously (IV) as soon as possible after a rattlesnake or Crotalid bite in patients with systemic signs of envenomation or evidence of a coagulation abnormality ( Table 53.3 ). Based on the severity of envenomation, the initial dose may be increased to a maximum dose of 12 vials. The patient should be observed for the next 1 hour to determine if initial control (defined as lack of progression in local signs of the leading wound edge, resolution in systemic symptoms, and normalization or near normalization of coagulation studies) has been achieved. If initial control is not achieved, an additional four to six vials can be administered repeatedly as needed. Once control is established, an additional two vials of CroFab are administered every 6 hours for 18 hours as maintenance. Given the high cost of antivenom, some experts will administer the maintenance vials on an as-needed basis only. This strategy can reduce intensive care unit (ICU) length of stay and the amount of antivenom administered without worsening patient outcomes; however, success rates rely on frequent bedside reevaluation by a clinician who is experienced in treating snake envenomation.

The Anavip package insert recommends an initial dose of 10 vials given intravenously over 60 minutes as soon as possible after a rattlesnake or Crotalid bite in patients with signs of envenomation (see Table 53.3 ). A complete blood count, prothrombin time, partial thromboplastin time, serum fibrinogen, and chemistries should be obtained prior to the first dose. A repeat dose of 10 vials can be given as needed to establish initial control. Currently, there is no maximum known dose. Once initial control has been achieved, at least 18 hours of monitoring is recommended for observation of recurrence of symptoms. Initial control is demonstrated by lack of progression or improvement in local signs, resolution in systemic signs, and normalization (or near normalization) of coagulation studies. Return of symptoms can be treated with an additional four vials of Anavip IV.

Both CroFab and Anavip can cause severe allergic reactions. Patients who are allergic to papin, chymopapain, papaya extract, or bromelain (pineapple) may develop a hypersensitivity reaction to CroFab. Patient with allergies to sheep or horse proteins can develop anaphylactic reactions. Any evidence of hypersensitivity including wheezing, urticaria, and hypotension should be managed by immediate cessation of antivenom infusion and treatment with epinephrine, corticosteroids, and diphenhydramine as needed. Patients who are treated with a course of antivenom can become sensitized to it and should be cautiously monitored if the patient has a subsequent envenomation that requires antivenom.

The following are general guidelines to maximize patient care when antivenom is used:

• 1.

  Because anaphylaxis may occur whenever antivenom is administered, appropriate therapeutic agents (e.g., oxygen supply, airway support, epinephrine, diphenhydramine, corticosteroids, and other pressor agents such as norepinephrine) must be ready for immediate use. Any patient requiring antivenom should have two intravenous lines inserted. If an allergic reaction occurs, the line with the antivenom can be clamped and the other line used for resuscitation.

• 2.

  The pediatric antivenom dose is the same as the adult dose. A bitten child usually receives more venom in proportion to body weight and thus requires more antivenom to neutralize it. The smaller the body of the patient, the larger the relative initial dose that may be required. However, the total fluid requirements of children are lower, so the antivenom can be given in a more concentrated solution.

• 3.

  Pregnancy is not a contraindication to antivenom therapy.

• 4.

  Administration of antivenom at or around the site of the bite is not recommended.

• 5.

  The need for subsequent doses to achieve initial control is based on the patient’s clinical response. The patient is monitored closely after the initial dose, and local and systemic symptoms, as well as laboratory findings, are determinants of the need for further antivenom. Additional injections of antivenom are administered every 1 or 2 hours if symptoms progress. Most hospital pharmacies do not stock large amounts of antivenom, and the pharmacy should be notified to obtain additional antivenom from surrounding hospitals or the regional poison control center for treating a severe bite.

• 6.

  Even with a history or signs of allergy, patients with severe envenomation are treated with a dilute form of antivenom and epinephrine to maximize antivenom administration but minimize allergic symptoms.

• 7.

  Consultation with an expert medical toxicologist or herpetologist should be obtained in cases of severe or complicated envenomation including allergic reactions to antivenom. Poison centers (1-800-222-1222) are an excellent resource for expert advice.

Coral and Exotic Snakes

Any patient bitten by an eastern coral snake is at risk for neurotoxicity that may not become evident for many hours. As a result, these patients require hospital admission, preferably to an ICU where they can be monitored closely for 24 hours for respiratory depression. Historically, it was recommended that all snakebite victims of the eastern coral snake (M. fulvius) be treated with antivenom even before any symptoms developed. North American coral snake antivenin (NACSA), a horse-derived IgG antibody, is currently in diminishing supply. Clinicians can still obtain the antivenom but might delay administration until the first signs of neurologic or respiratory compromise are observed. A local expert or certified poison center (1-800-222-1222) can help providers to determine the use of NACSA and aid in procuring it.

The stores of NACSA will eventually be depleted. Options for the future treatment of North American coral snake envenomation include prolonged supportive and respiratory care, the creation of a new antivenom, or relying on the cross-reactivity of a preexisting antivenom raised against another elapid species. Coralmyn antivenom is a polyclonal (Fab)2 fragment produced in Mexico that is obtained from horses inoculated with venom from the Black-banded coral snake (Micrurus nigrocinctus nigrocinctus). Effective neutralization of both M. fulvius and M. tener venoms by Coralmyn antivenom has been demonstrated in a murine model. A murine model of M. fulvius envenomation was also successfully treated with an Australian tiger snake (Notechis scutatus) antivenom. The commercially available Australian polyvalent snake antivenom has effectively neutralized M. fulvius venom in another murine model.

The challenges with managing bites of exotic or international snakes are threefold: Positive identification of the specimen is often difficult, even for experts; specific antivenom is not always readily available; and even if the antivenom is available, the instructions for reconstitution and dosage may not be described in English. Many zoos maintain a supply of antivenom for their exotic venomous snakes, and this may be the best source of antivenom for an exotic species. Some collectors keep appropriate antivenom on hand for the species that they collect. The Antivenom Index at the Arizona Poison Center (602-626-6016) can assist in identifying sources of exotic antivenom or in obtaining more pit viper antivenom. As with coral snakes, many patients do not show any early signs after envenomation by exotic neurotoxic snakes, so prolonged and intensive monitoring may be warranted.

Although exotic snake species are a source of concern in the United States, envenomation by these species in their native countries is a much more significant problem. The WHO estimates that up to 2 million people in Asia and 580,000 people in Africa are envenomated by snakes yearly. Many of these snakebite victims lack timely access to an appropriate antivenom. In 2017, the WHO placed snakebites on the list of “Neglected Tropical Diseases.”

Wound Care

The snakebite wound should be cleaned and examined for foreign bodies (e.g., retained fangs or teeth), the area immobilized, and proper analgesia administered. Elevation at or above heart level may relieve some of the pain. Local excision of the bitten area is not recommended. As with any puncture wound, one should ensure that tetanus immunization is current. The use of prophylactic antibiotics is previously discussed and not routinely administered with North America snakebites. Wounds should be cleansed daily with soap and water and a sterile dressing should be placed over any open wounds.

Surgical consultation may be required for management of necrotic wounds or in cases of true compartment syndrome refractory to adequate doses of antivenom. Superficial débridement of bullae allows for assessment of underlying tissue. Once necrotic tissue is identified, multiple surgeries may be needed for complete débridement of the nonviable tissue. In rattlesnake bites to the upper extremity, predictors of the development of necrosis include ecchymosis, initial cyanosis, and chronic alcohol use. In the same study, cocaine use was associated with the need for surgical intervention. Skin grafts are occasionally necessary after bites by pit vipers that produce large necrotic areas. Fasciotomy is rarely indicated unless compartment pressures are elevated greater than 30 mm Hg and signs of true compartment syndrome are present, which is uncommon because most snakebites involve subcutaneous layers and not deep into the musculature. Adequate doses of antivenom to lower intracompartmental pressures should be done prior to any consideration of fasciotomy in North American crotalid envenomation. Although not widely available in rural or remote settings, hyperbaric oxygen therapy is a potential adjunct to surgical management of severe snakebite wounds.

Serum Sickness

Serum sickness can occur after administration of any animal protein derivative. The onset of serum sickness is typically 5 to 14 days after antivenom administration. Symptoms include fever, arthralgias, skin rash, and lymphadenopathy. Symptoms can be treated with oral antihistamines, nonsteroidal antiinflammatory drugs (NSAIDs), and corticosteroid taper. There is no role for prophylactic corticosteroids in the prevention of serum sickness.

Heloderma Envenomation

Gila monster and Mexican beaded lizard bites are treated similarly to pit viper bites with regards to first aid. No definitive medical treatment exists. Antivenom is currently not available. Local wound care, tetanus prophylaxis, use of antibiotics and analgesics, and supportive care are the extent of ED treatment for these types of envenomation.