Chapter 212: Reptile Bites

An estimated 1.5 to 3 million bites and possibly greater than 100,000 deaths occur each year in the world from venomous snakes.¹ The American Association of Poison Control Centers reports an average of 6000 bites each year, approximately 2000 of them by venomous snakes. Because of underreporting, the true number of snakebites is possibly as high as 45,000 per year in the United States, with 7000 to 8000 by venomous snakes.² The major venomous snakes of the world can be divided into three groups: Viperidae (vipers and pit vipers), Elapidae (includes Hydrophiinae, or sea snakes; see chapter 213, titled "Marine Trauma and Envenomation"), and the diverse group of non–front-fanged colubrid snakes (former family Colubridae, now split into several families).

In the United States, most snakebites occur in the warm summer months, when snakes and victims are most active. In the past, it was estimated that mortality from venomous snakebite approached 25%. Because of the availability of antivenom and advances in emergency and critical care, mortality rates today are <0.5%; approximately five deaths occur per year.³

Except for bites by imported species, North American venomous snakebites involve the pit vipers (Crotalinae subfamily of Viperidae) or coral snakes (Elapidae family). The crotaline snakes are represented by the rattlesnakes (Crotalus species), pygmy rattlesnakes, and massasauga (Sistrurus species), as well as the copperheads and water moccasins (Agkistrodon species). Venomous snakebites from imported exotic species are infrequent but may occur in zoo personnel as well as in amateur herpetologists. A regional poison control center can provide information on snake identification, expected toxicity, and location of antivenom.

The crotaline snakes are called pit vipers because of bilateral depressions or pits located midway between and below the level of the eye and the nostril (Figure 212-1). The pit is a heat receptor that guides strikes at warm-blooded prey or predators. Crotaline snakes are also distinguished by the presence of two fangs that fold against the roof of the mouth, in contrast to the coral snakes, which have shorter, fixed, erect fangs. Within the pit viper group, the rattle distinguishes the rattlesnake from other crotaline snakes. The mistaken belief that rattlesnakes always rattle before striking has persisted for centuries. In truth, many strikes occur without a warning rattle.

Crotaline venom is a complex enzyme mixture that causes local tissue injury, systemic vascular damage, hemolysis, fibrinolysis, and neuromuscular dysfunction, resulting in a combination of local and systemic effects. Crotaline venom quickly alters blood vessel permeability; this leads to loss of plasma and blood into the surrounding tissue, which causes hypovolemia. Crotaline venom activates and consumes fibrinogen and platelets, causing a coagulopathy. In some species, specific venom fractions block neuromuscular transmission, which leads to cranial nerve weakness (e.g., ptosis), respiratory failure, and altered sensorium.

Up to 25% of crotaline snakebites are dry bites: venom effects do not develop. The manifestations of crotaline envenomation involve a complex interaction of the venom and the victim. The species and size of the snake, the age and size of the victim, the time elapsed since the bite, and characteristics of the bite or bites (location, depth, and number; the amount of venom injected) all affect the clinical evolution. The severity of envenomation following a crotaline bite is therefore variable. An initially minimal bite may evolve into a more serious bite and require large amounts of antivenom.

The cardinal manifestations of crotaline envenomation are the presence of one or more fang marks, localized pain, and progressive edema extending from the bite site.² Other early symptoms and signs are nausea and vomiting, weakness, oral numbness or tingling of the tongue and mouth, dizziness, and muscle fasciculation. Systemic effects include tachypnea, tachycardia, hypotension, and altered level of consciousness. In general, local swelling at the bite site becomes apparent within 15 to 30 minutes, but in some cases, swelling may not start for several hours. In severe cases, edema can involve an entire limb within an hour. In less severe cases, edema may progress over 1 to 2 days. Edema near an airway or in a muscle compartment may threaten life or limb without causing systemic effects. Rapid onset of angioedema may occur.

Progressive ecchymosis may also develop because of leakage of blood into subcutaneous tissue. Ecchymoses may appear within minutes or hours, and hemorrhagic blebs may be seen within several hours. Hemoconcentration often develops as a result of fluid extravasation into subcutaneous tissue, followed by a decrease in hemoglobin level over several days as intravascular volume is restored.

The diagnosis of snakebite is based on the presence of fang marks and a history consistent with exposure to a snake (e.g., walking through a field). Snake envenomation involves the presence of a snakebite plus evidence of tissue injury. Clinically, the injury may be manifest in three ways: local injury (swelling, pain, ecchymosis), hematologic abnormality (thrombocytopenia, elevated prothrombin time, hypofibrinogenemia), or systemic effects (e.g., oral swelling or paresthesias, metallic or rubbery taste in the mouth, hypotension, tachycardia). Abnormalities in any one of these areas indicate that venom effect is developing. The absence of any of these manifestations for a period of 8 to 12 hours following the bite indicates a dry bite.

FIRST AID

First aid measures should never substitute for definitive medical care or delay the administration of antivenom (Table 212-1). Take all patients bitten by a pit viper to a healthcare facility. Avoid dangerous first aid treatments such as suction and incision. Do not use Snake Bite Kit and similar products because they contain cups that produce little suction and seal poorly on digits. The blade in the kit, or any method of incision, can injure digital nerves, arteries, and tendons. The Sawyer Extractor (Sawyer Products, Inc., Safety Harbor, FL) suction pump is said to remove venom without incision, but safety and efficacy of the product are questioned.⁴ Electric shock treatment of the bite site is dangerous and ineffective and can cause electrical injuries. Ice water immersion worsens the venom injury.

Do not use tourniquets because they obstruct arterial flow and cause ischemia. Constriction bands may be useful, especially when immediate medical care is not available. A constriction band is an elastic bandage or Penrose drain, thick rope, or piece of clothing wrapped circumferentially above the bite, applied with enough tension to restrict superficial venous and lymphatic flow while maintaining distal pulses and capillary filling. Apply the band snugly but loose enough to avoid arterial compromise. A constriction band can delay venom absorption without causing increased swelling.⁵

PREHOSPITAL MANAGEMENT

In the prehospital phase, immobilize the limb, establish IV access in another limb, administer oxygen, and transport the victim to a medical facility. Do not remove tourniquets or constricting bands until antivenom is available.

Institute advanced life support measures as indicated. If the patient is hypotensive, rapidly administer IV isotonic fluids. Continue to immobilize the limb in a neutral position during transport to reduce further venom absorption. Consult with a physician or poison control center familiar with the management of snake envenomation for most cases.

ED MANAGEMENT

Antivenom is the mainstay of therapy for venomous snakebites^2,6 (Table 212-2). Antivenom is composed of heterologous antibodies derived from the serum of animals immunized with the appropriate snake venoms. The antibodies bind and neutralize the venom molecules.

Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) is used in the United States; equine-derived products (Antivenom [Crotalidae] Polyvalent; see below) are no longer available. FabAV is produced by immunizing herds of sheep with one of four crotaline snake venoms: eastern diamondback (Crotalus adamanteus), western diamondback (Crotalus atrox), Mojave (Crotalus scutulatus), or cottonmouth (Agkistrodon piscivorus). The immune serum is harvested from each group and then digested with papain to produce antibody fragments (Fab and Fc). The more immunogenic Fc portion of the antibody is eliminated during purification. The four individual monospecific Fab preparations are combined to form the final antivenom product.

Treat all patients with bites who develop progressive signs and symptoms with antivenom promptly. Progression is defined as worsening of local injury (e.g., pain, ecchymosis, or swelling), abnormal results on laboratory tests (e.g., worsening platelet count, prolonged coagulation times, or decreased fibrinogen level), or systemic manifestations (e.g., unstable vital signs or abnormal mental status) (Table 212-3).

Administer FabAV IV as a large "initial control" dose followed by three smaller maintenance doses (Figure 212-2). Initial control is cessation of progression of three clinical evaluation parameters: local effects, systemic effects, and hematologic abnormalities. The initial dose is four to six vials, which may be repeated to establish initial control of the envenomation. After initial control has been established, two-vial maintenance doses are recommended (Figure 212-2). After reconstitution, dilute each dose of FabAV in 250 mL of crystalloid and infuse over 1 hour. The total volume, but not the number of vials, may be reduced in small children.⁷ If IV access is unavailable, consider intraosseous administration.

Do not inject antivenom directly into a digit, or IM, because venom-induced hypovolemia may retard absorption of antivenom. Hospital pharmacies in those regions of the United States where venomous snakes are prevalent should maintain adequate stocks of antivenom. Unfortunately, many hospitals stock insufficient amounts of antivenom, even in endemic areas.⁸

The package insert is useful as a guide for antivenom preparation. Give antivenom in a critical care facility such as an ED or intensive care unit, under direct physician supervision, and with resuscitative drugs and equipment immediately available (including epinephrine). The incidence of acute reactions to FabAV is <10%.⁹ If an acute allergic reaction occurs, stop the infusion immediately and administer antihistamines (both histamine-1 and histamine-2 receptor blockers). Epinephrine should be readily available and administered for anaphylaxis.

Continue to observe for progression of edema and systemic signs of envenomation during and after antivenom infusion. Measure limb circumference at several sites above and below the bite, and outline the advancing border of edema with a pen every 30 minutes. These measures serve as an index of the progression as well as a guide for antivenom administration. Repeat laboratory determinations every 4 hours or after each course of antivenom therapy, whichever is more frequent. Additional doses of FabAV may be warranted if the patient's condition worsens. FabAV has been formally tested only in the treatment of rattlesnake bites. Initial case reports support its efficacy in treatment of copperhead snakebites.¹⁰

The value of aggressive supportive care cannot be overemphasized. Administer isotonic fluid resuscitation followed by vasopressor agents for hypotension. Antivenom is the best treatment for hematologic abnormalities, but if active bleeding occurs, blood component replacement may be necessary. Compartment syndrome is another complication of snakebite: increased compartment pressure may occur when venom is injected or spreads into a compartment. This is often manifested by severe pain, localized to a compartment and usually resistant to opiate analgesia. Table 212-4 presents the suggested treatment of compartment syndrome.¹¹ The use of fasciotomy is controversial, and there is no firm evidence supporting its use.

Clean the bite wound and determine the need for tetanus immunization. Obtain wound specimens for culture and administer antibiotics if signs of infection are present. Although antibiotic prophylaxis is recommended by some authors, the data available do not support its use.¹² Steroids are not effective and could be harmful. Steroids should be reserved for the treatment of allergic reactions or serum sickness.

Serum sickness develops in about 5% of patients after FabAV treatment. The symptoms are fever, rash, and arthralgias. Start oral prednisone, 1 milligram/kg/d, and taper over 1 to 2 weeks.

It cannot be overemphasized that one can easily be deceived by a bite that initially appears innocuous. Unremarkable physical examination and laboratory test results at presentation do not reliably exclude significant envenomation. Observe patients for at least 6 to 8 hours in the ED before determining disposition.

Discharge patients with dry bites who have been observed for 6 to 8 hours with instructions to return if pain, swelling, or bleeding develop. Admit patients with severe or life-threatening bites and patients receiving antivenom to an intensive care unit; the general ward is appropriate for patients with mild or moderate envenomations who have completed or do not require further antivenom therapy.

Patients are ready for discharge from the hospital when swelling begins to resolve, coagulopathy has been reversed, and the patient is ambulatory. Physical therapy for the bitten part (particularly the hand) is recommended after swelling has lessened and coagulopathy has resolved. Outpatient follow-up is necessary to monitor for infection and serum sickness, and as with all antivenoms, the patient should be advised of the symptoms of serum sickness prior to discharge and advised to report if such symptoms develop.

U.S. CORAL SNAKEBITES

U.S. coral snakes include the eastern coral snake (Micrurus fulvius fulvius), the Texas coral snake (Micrurus fulvius tenere), and the Arizona (Sonoran) coral snake (Micruroides euryxanthus). The eastern coral snake is found primarily in the southeastern United States. The Texas and Arizona coral snakes are found primarily in the states that bear their names. Coral snakes account for 20 to 25 bites a year.

All coral snakes are brightly colored with black, red, and yellow rings. The red and yellow rings touch in coral snakes, but they are separated by black rings in nonvenomous snakes, which led to the well-known rhyme, "Red on yellow, kill a fellow; red on black, venom lack." This rule is not always true outside of the United States.

Coral snake venom is primarily composed of neurotoxic components that do not cause marked local injury (Table 212-2). Admit potential victims of coral snakebite to the hospital for observation, because venom effects may develop hours after a bite and are not easily reversed. Administer three to five vials of Antivenin (Micrurus fulvius) to patients who have definitely been bitten, because it may not be possible to prevent further effects or reverse effects once they develop.¹³ Additional doses of coral snake antivenom are reserved for cases in which symptoms or signs of coral snake envenomation appear. Because respiratory failure may result from clinical effects of the neurotoxin, baseline and serial measurement of pulmonary function parameters (such as inspiratory pressure and vital capacity), in addition to intensive care observation, may be useful. Prolonged ventilatory support may be required in severe cases. Observe the patient closely for signs of respiratory muscle weakness and hypoventilation. Bites by the Sonoran coral snake are mild, and antivenom is not usually needed.

Elapids are found throughout the world in warm climates. Elapids occur in Australia, New Guinea, Asia, Africa, and the Americas. All sea snakes are elapids (subfamily Hydrophiinae). Medically significant groups include some venomous snakes of Australia (tiger snakes [Notechis], brown snakes [Pseudonaja], taipans [Oxyuranus], death adders [Acanthophis], "black" snakes [Pseudechis], copperheads [Austrelaps], rough scaled snake [Tropidechis carinatus], broad headed snakes [Hoplocephalus]), cobras (Naja), mambas (Dendroaspis), kraits (Bungarus), coral snakes (Micrurus), and a variety of less common genera/species.¹⁴

Elapid bites produce systemic effects, particularly neurologic effects: tremor, salivation, dysarthria, diplopia, bulbar paralysis with ptosis, fixed and constricted pupils, dysphagia, dyspnea, and seizure.¹⁴ Some groups like the cobra species also produce pain and local injury and necrosis, which may be more clinically prominent than systemic effects.¹⁴ The immediate cause of death is usually paralysis of respiratory muscles. Signs and symptoms may be delayed up to 12 or more hours.

The Elapidae possess nonretractile small- to medium-sized paired fangs that have grooved, often enclosed venom channels rather than hollow venom ducts.¹⁴ It is thought that the Elapidae exert voluntary control over the injection of venom, hence the frequent occurrence of a dry bite.

The venom of the Australian elapids contains several important components.^14,15 Neurotoxins (tiger snake, taipan, and death adder) act at the neuromuscular junction and cause descending symmetric flaccid paralysis. Signs usually develop within 2 to 12 hours after the bite and may include ptosis, partial ophthalmoplegia (diplopia), dysarthria, loss of facial expression, and loss of airway control, as well as respiratory paralysis in severe cases. The procoagulant toxins (brown snake, tiger snake, taipan) act as prothrombin converters, leading to a venom-induced consumptive coagulopathy with fibrinogen depletion and variable thrombocytopenia. Intracranial hemorrhage is a recognized complication.

The brown snake can cause rapid collapse and death.^15,16 Renal impairment or failure may also result from snakebite. The mechanisms are poorly understood and may include hypotension, myoglobinuria, coagulopathy, and direct renal toxicity.^14,15 Myolysins (tiger snake, taipan, mulga snake) are structurally related to the neurotoxins but instead produce rhabdomyolysis, which may result in muscle pain, weakness, myoglobinuria, renal failure, and hyperkalemia.^14,15 Rarely, a venom-induced thrombotic microangiopathy may complicate brown and tiger envenomation.^16-18 Local tissue destruction is uncommon with the bite of any Australian species, although mild to moderate ecchymosis and swelling may occur.¹⁵

The severity of elapid envenomation cannot be estimated by the clinical appearance of the bite site or initial symptoms.^14,15,16,17 Even with severe envenomation patients may initially feel well and manifest few clinical features. Initial symptoms include nausea, vomiting, headache, abdominal pain, diplopia, dysphonia, progressive muscle weakness, discolored urine, and seizures.¹⁵ Young children may not provide a history of snakebite, so a high index of suspicion for elapid snakebite is needed if a child develops symptoms of toxicity in a region populated with elapids.¹⁵

The diagnosis requires correlation of history, clinical features of envenomation, and laboratory investigations. Laboratory tests often determine if the patient requires antivenom treatment.^14,15,16,17 Key tests include prothrombin time, INR, activated PTT, D-dimer, fibrinogen, fibrin degradation products, hemoglobin, platelet count, electrolytes, renal function test, and creatine kinase and should be performed prior to removal of first aid, 1 hour after removal of first aid, and at 6 hours and 12 hours after bite (earlier if abnormalities or clinical symptoms/signs develop).^15,19 Look for evidence of procoagulant coagulopathy (prolonged prothrombin time and activated PTT, high INR, raised D-dimer/fibrin degradation products, low fibrinogen), anticoagulant coagulopathy (abnormal prothrombin time, activated PTT, and INR, but normal fibrinogen, D-dimer/fibrin degradation products), platelet effects, rhabdomyolysis (grossly elevated creatine kinase, myoglobinuria), renal damage (abnormal renal function tests, reduced urine output), hyponatremia, and hemolytic-uremic syndrome–like syndrome (thrombocytopenia, anemia, intravascular hemolysis).¹⁵ A Snake Venom Detection Kit (bioCSL, Parkville, Victoria, Australia) is available to identify snake venom identified at the bite site or in the urine, correlated to venom immunotype (which corresponds to "monovalent" antivenom type), for use exclusively with Australian and New Guinea snakes.¹⁵ Positive Snake Venom Detection Kit identification of venom at the bite site or in the urine assists in selecting a "monovalent" antivenom, but does not represent an indication for antivenom therapy without other evidence of systemic venom effects.¹⁵ World Health Organization guidelines on treating snakebite in Asia and Africa are a useful resource on diagnosis and treatment for these regions and are available online.^20,21

FIRST AID

In Australia and New Guinea, pressure bandaging and immobilization of the involved limb is used. The principle is to contain the venom locally and prevent venom transport by lymphatic vessels. Wrap an elastic bandage firmly over the bite site and then extend it to cover the entire limb (bandage pressure similar to that used for sprains: firm, but not tourniquet tight).¹⁵ Splint the limb to prevent movement, an essential part of the method. Examination of lymphatic flow rates with simulated venom has demonstrated that, even if the upper or lower limb is appropriately bandaged and immobilized, walking will hasten systemic envenoming.²² Use of tourniquets is contraindicated. In the rare circumstance that a bite is inflicted on the trunk, apply firm pressure to the affected area without restricting breathing.

Outside of Australia and New Guinea, the choice of first aid is more nuanced. If the bite is from an elapid that may cause local tissue damage or is from an unidentified snake, then pressure bandaging and immobilization may increase local tissue injury.¹⁴ Omit the pressure bandage but splint the bitten part.

ED MANAGEMENT

Any history suggestive of snakebite should prompt appropriate first aid and transport to a medical facility with appropriate medical expertise, laboratory facilities, and antivenom supplies. Maintain pressure bandage immobilization (or immobilization only) until envenomation is excluded or until the patient can receive antivenom.¹⁵ If the patient's condition deteriorates immediately after removal of first aid measures, reapply and give antivenom. Once antivenom is infusing, remove the pressure bandage so that antivenom can reach the envenomed area. There is no evidence that venom is inactivated by being trapped at the bite site.¹⁵

Antivenom should be given only in cases in which there is clear clinical or laboratory evidence of systemic envenomation. Clinical indications for immediate antivenom therapy include evidence of neurotoxic effects (ptosis, cranial nerve involvement, progressive muscle weakness, or diaphragmatic involvement), coagulopathy, rhabdomyolysis, renal failure, cardiac collapse, significant local tissue injury, or vomiting unresponsive to antiemetics.^14,15 In the absence of clinical or laboratory evidence of systemic envenomation, remove the first aid measures and observe the patient for at least 12 hours, longer for some species.^15,19 Repeat laboratory tests 1 hour after removing the first aid measures and at intervals thereafter dictated by the patient's condition.

For Australian elapid snakebites, there is only one producer (CSL Ltd, Melbourne, Australia), producing five "monovalent" antivenoms corresponding to the five venom immunotypes, a polyvalent antivenom that covers all of the five venom immunotypes, plus a sea snake antivenom that is effective for all sea snake species globally.^14,15 The initial dose of antivenom is controversial, but simply following the product instructions is prudent. Similarly, the initial dose of antivenom for non-Australian snakes should be based on manufacturer recommendations. For patients presenting with severe envenomation, higher initial doses may be warranted. Always administer antivenom IV. If IV access is unavailable, consider intraosseous administration. IM administration is strongly discouraged due to slow absorption and potential complications of anticoagulation. Dilute antivenom about 1:10 in normal saline (lower dilution in small children or cardiac-compromised adults), then commence the infusion slowly, looking for evidence of adverse reaction (rash, wheeze, hypotension, angioedema); gradually increase the rate to give the entire dose over 20 to 30 minutes (longer if high volume antivenom).^14,15 Give the same dose to children as adults. Skin testing before antivenom administration is not recommended,^14,15 and equipment for treatment of anaphylaxis should be at the bedside. Hypersensitivity is an uncommon complication of antivenom therapy in Australia.^23-25 Elsewhere, antivenoms may have high rates of adverse reactions. A 5-day course of prednisolone may be prescribed to reduce the incidence of serum sickness, but clear evidence of efficacy is lacking.¹⁵

Antivenom cannot reverse some venom effects, such as established presynaptic neurotoxic paralysis, renal failure, and rhabdomyolysis. It is therefore important to give antivenom as soon as indicated. If this is not possible, support respiration and renal function as clinically required. Advanced flaccid paralysis usually requires protection of airway and respiratory support for periods of days to months.

When indicated, give monovalent or polyvalent antivenom immediately in sufficient doses to improve coagulation values. Pregnancy is not a contraindication to antivenom therapy.

Gila monsters are slow-moving lizards that inhabit the desert in the southwestern United States. They possess venom as potent as rattlesnake venom but lack the apparatus to inject it effectively. Instead of fangs, they have short, grooved teeth down which their venom flows. Therefore, envenomation requires a prolonged bite. Gila monsters bite tenaciously and may be difficult to remove from the bitten extremity, so fractures and deep injury are possible.

There are few if any documented deaths from Gila monster bite. Most bites result in local pain and swelling only, which worsens over several hours and then subsides over several more hours. Dislodged teeth often contaminate the wound. Occasionally, a more severe syndrome of systemic toxicity develops, including weakness, light-headedness, paresthesia, and diaphoresis. Severe hypertension may occur, which also resolves over several hours.

First aid involves removal of the reptile from the bite site without sustaining another bite. This may require force. It helps to place the animal on a solid surface, because it often loosens its grip when it is no longer suspended in midair. Once the animal is removed, standard local wound care is sufficient, with care taken to remove any teeth in the wound. Radiographs should be considered if bony injury is possible. Update tetanus immunization status and give antibiotics if infection develops.