Venomous Animal Injuries

Perspective

Venomous animals account for considerable morbidity and mortality worldwide. Snakes alone are estimated to inflict 2.5 million venomous bites annually, with approximately 125,000 deaths. The actual numbers may be much larger. Southeast Asia, India, Brazil, and areas of Africa lead the world in snakebite mortality.¹ It is impossible to estimate the worldwide morbidity and mortality resulting from other venomous animals such as bees, wasps, ants, and spiders.

Approximately 45,000 snakebites occur annually in the United States; 7000 to 8000 are inflicted by venomous snakes, and 5 to 10 result in death. Insects are responsible for 52% of deaths, snakes for 30%, and spiders for 13%. Specifically, bees are responsible for the most fatalities, followed by rattlesnakes, wasps, and spiders. Historically, most of the recorded deaths from spider bites were caused by the black widow, although the brown recluse spider has been implicated in an increasing number of deaths.

The American Association of Poison Control Centers began collecting data in 1983 on deaths caused by venomous animals. Their 25-year experience shows a significant number of exposures by bite or sting but relatively few deaths (Table 62-1).² Although these data include most of the United States, there is no requirement that hospitals, emergency departments, coroners, or public health agencies report deaths or exposures to regional drug and poison information centers. This decline in deaths may be caused by an actual decrease in mortality or may be a result of inadequate reporting. Meaningful morbidity data, such as the number of amputations, hospitalizations, and disabilities, do not exist. The number of exposures and deaths from exotic snakes seems to be increasing, possibly because of interest in collecting so-called “hot” or venomous varieties such as cobras, mambas, and vipers. The morbidity from marine animal injuries is increasing in proportion to the number of people exposed to the ocean and the number of private collectors, but the mortality has not increased dramatically. An increase in outdoor recreational activities, such as camping, scuba diving, and wilderness trekking, puts more people in proximity to venomous animals and increases the risk of envenomation. Most exposures occur from April to October, when animals are most active and potential victims are outdoors and involved in activities that might increase their risk for envenomation. Of course, many spider bites and exotic animal envenomations that occur indoors can take place at any time. Most deaths seem to occur in very young, elderly, or inappropriately treated patients.

Table 62-1

Venomous Animal Injuries and Deaths, 1983-2009

Data compiled from Watson WA, Litovitz TL, et al: American Association of Poison Control Centers data. Am J Emerg Med 2:1984–2005; Lai et al: Clin Toxicol 44, 2006; and Bronstein et al: Clin Toxicol 45, 2007, Clin Toxicol 46, 2008, Clin Toxicol 47, 2009, Clin Toxicol 48, 2010.

Venom Delivery

Animals that have developed specific venom glands and venom delivery systems can be found in every class, including birds.³ The toxin and toxic apparatus vary from class to class. For example, the rattlesnake has modified salivary glands and maxillary teeth and uses this system primarily to obtain food. The bee has a modified ovipositor that is used mainly for defense. Poisonous and venomous animals are not the same and should be differentiated. Animals can be considered poisonous because of various toxins distributed in their tissues. For example, certain shellfish, toads, and barracuda have been known to cause death after ingestion. However, only animals with specific glands for producing venom connected to an apparatus for delivering that venom to another animal can be considered venomous.

Venomous Reptiles

Snakes

Of the 3000 species of snakes, approximately 10 to 15% are venomous. Of the 14 families of snakes, four contain venomous species. Snakes are distributed throughout most of the earth’s surface, including fresh and salt water. The major exceptions are the Arctic and Antarctic zones, New Zealand, Malagasy, and many small islands. Most snakebites occur in tropical and subtropical climates, especially in agricultural settings where the inhabitants go barefoot. Sea snakes are found only in the Pacific and Indian Oceans. Snakes are poikilotherms, which accounts for their distribution and activity. Their inability to raise their body temperature above ambient levels restricts their activity to a fairly narrow temperature range, approximately 25 to 35° C. All snakes are carnivorous, and their venom apparatus evolved for the purpose of obtaining food.

Epidemiology

The incidence of reported venomous snakebites in the United States is greatest in the South. States having the highest death rates are North Carolina, Arkansas, Texas, and Georgia. Of all snakebites, 97% occur on the extremities, with two thirds on the upper extremities and one third on the lower extremities. This reversal of historical distribution may reflect bites being provoked rather than accidental. Bites that occur accidentally are considered “legitimate,” whereas bites that occur during attempts to handle or disturb a snake are considered “illegitimate.” Men are bitten nine times more frequently than women.⁴

Imported venomous snakes have recently been an increasing problem throughout the United States. In the past, only zoos, research centers, and herpetologists kept exotic venomous snakes. Today, however, hundreds of people are raising deadly venomous snakes without the necessary precautions, such as specialized cages, safe handling techniques, and rapid access to specific antivenin. They place not only themselves, but also their families and the general public, in danger.

Classification and Characteristics

The four venomous families of snakes are the Colubridae, Elapidae, Viperidae, and Atractaspididae. 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 the cobras, kraits, mambas, and coral snakes. The Hydrophiidae are sea snakes and a subfamily of the Elapidae. The Viperidae, or true vipers, are represented by Russell’s viper, the puff adder, the Gaboon viper, the saw-scaled viper, and the European viper. The Crotalidae, or pit vipers, are sometimes considered a separate family and sometimes a subfamily (Crotalinae) of the Viperidae. Among the pit vipers are the most common American venomous snakes, such as rattlesnakes, water moccasins, copperheads, the bushmaster, and the fer-de-lance. Several species of Asian pit vipers are responsible for bites in Okinawa and bites by imported snakes in the United States. 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 98% of all venomous snakebites in the United States.⁵

The Colubridae and Hydrophiidae have few venomous encounters with humans and are responsible for even fewer injuries. Some colubrid species found in the United States that were previously thought to be harmless may indeed be venomous. Examples are the lyre snake, the hognose snake, and the wandering garter snake. No deaths have been reported, but the problem has generated much interest among herpetologists and toxicologists. The yellow-bellied sea snake (Pelamis platurus; subfamily Hydrophiidae) has been found off the coast of southern California and western Mexico, but bites by this snake are rare.

The other major group of venomous snakes in the United States is the coral snakes. The eastern coral snake (Micrurus fulvius) is found in North Carolina, South Carolina, Florida, Louisiana, Mississippi, Georgia, and Texas. There are two subspecies that have similar clinical presentations and will be discussed together. The western or Sonoran (Micruroides euryxanthus) coral snake is native to Arizona and New Mexico. Although both species are generally quite shy unless handled, the eastern coral snake is considered deadly. There are no records of fatalities caused by the western species.

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. The popular rhyme is as follows:

Red next to yellow, kill a fellow.

Red next to black, venom lack.

This rhyme can be used only in the United States; Brazilian coral snakes have red next to black bands, and some coral snakes have no red bands.

Identification

There are two key principles for identifying venomous snakes: Only experts should handle live snakes, and even dead snakes can envenomate careless handlers.⁶ It is not difficult to differentiate between pit vipers and harmless snakes found in the United States (Fig. 62-1). 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 100% 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 (Fig. 62-2).

Figure 62-1 Identification of venomous and nonvenomous North American snakes.

Figure 62-2 Western diamondback rattlesnake (Crotalus atrox).

Size is not an important factor in identifying various 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 snakes that are not pit vipers are not as easily identified. If possible, they should be safely transported to an expert for positive identification. Local zoos, herpetology groups, and colleges often have individuals who can identify unknown snakes.

Pit Vipers

The most consistent symptom associated with pit viper bites is immediate burning pain in the area of the bite, whereas pain may be minimal with bites of Elapidae and other exotic snakes. With pit vipers, the severity of pain is probably related to the amount of venom injected or the degree of swelling. Edema surrounding the bite that gradually spreads proximally is a common finding. This edema is usually subcutaneous, begins early, and may involve the entire extremity. Compartment syndrome has been described; however, it is unusual even with severe edema. It has been reported more frequently in models involving intracompartmental venom injection.10–12 Most fangs do not penetrate into the fascial compartments, although muscle destruction may result from direct toxicity. Mortality is less frequent with distal bites to the toe and finger and is greatly increased with intravenous bites. An intravenous bite from any venomous snake is likely to be fatal. Petechiae, ecchymosis, and serous or hemorrhagic bullae are other local signs. Necrosis of skin and subcutaneous tissue is noted later and may result from inadequate doses of antivenin. Many systemic symptoms, such as weakness, nausea, fever, vomiting, sweating, numbness and tingling around the mouth, metallic taste in the mouth, muscle fasciculations, and hypotension, often occur after pit viper envenomation.

Death from pit viper bites is associated with disruption of the coagulation mechanism and increased capillary membrane permeability. Ultimately, these two processes lead to massive pulmonary edema, shock, and death. Heart and kidney damage occur secondary to these mechanisms. Specific toxins in certain species may act directly on specific organs, such as the heart or skeletal muscle. An allergic type of reaction may add to this process through release of histamine and bradykinin.¹³

Coral Snakes

Signs and symptoms can vary considerably with bites of coral snakes, Mojave rattlesnakes, and many exotic snakes, especially cobras and Australian elapids. Little pain and swelling may occur. Many of these species’ venoms contain compounds that block neuromuscular transmission at acetylcholine receptor sites and have direct inhibitory effects on cardiac and skeletal muscle. Ptosis is common and often the first outward sign of envenomation. Other signs and symptoms include vertigo, paresthesias, fasciculations, slurred speech, drowsiness, dysphagia, restlessness, increased salivation, nausea, and proximal muscle weakness. The usual cause of death is respiratory failure.¹⁴

Gila Monster

Gila monster bites are generally associated with pain, edema, and weakness. Hypotension is common with severe bites. Envenomation involves secretion of the venom from glands along the lower jaws. The venom is introduced into the victim through grooved teeth and a chewing mechanism. There are no reported deaths from Gila monster bites.

Infection

Although snakebite envenomation has been stressed here, any bite or puncture wound carries a risk for bacterial contamination. Gram-negative organisms predominate when snake venom and mouthparts are cultured. Although several studies have shown that prophylactic antibiotics are not indicated for snakebite, tetanus, osteomyelitis, cellulitis, or gas gangrene may occur in cases of snakebite with or without envenomation. This is especially true when a large amount of local tissue destruction has occurred, treatment has been delayed, or inappropriate first aid was attempted.

Management

Out-of-Hospital Care

All snakebites are considered an emergency, and any victim should be medically evaluated. The initial 6- to 8-hour period after a snakebite is critical. During this time, medical therapy can help prevent the morbidity associated with severe envenomation. Effective out-of-hospital care can be important.¹⁶

Out-of-hospital care is relatively simple if guided by four basic concepts. First, the estimated time until arrival at a medical facility, as well as the skill of the on-scene assistants, must be considered when first aid is instituted. Separate the victim from the snake if possible to prevent further bites. A stick, pole, or other object longer than the snake can be used to move the snake away from the victim or, if necessary, to kill the snake by striking it behind the head. Rapid transportation to a medical facility is the best first aid for a snakebite. Any constricting jewelry or clothing should be removed from an extremity to prevent a tourniquet effect proximal to the swelling.

Second, spread of the venom should be slowed if possible; several methods are known. The patient’s excitement and physical activity, movement of the bitten area, alcohol consumption, and greater depth of the bite may increase the spread of venom. Except for the last factor, these issues can be addressed by calming the victim, immobilizing the bitten area with a sling or splint, and not giving anything by mouth. A method of first aid for venomous snakebites that was developed in Australia—the immobilization and compression technique (also called the Commonwealth Serum Laboratory technique)—slows uptake of Elapidae venom and mock venom in humans. The bitten extremity is either wrapped in an elastic bandage or placed in an air splint. In another technique from Australia called the Monash method, a thick pad and bandage are placed over the bite wound and extremity. Both these techniques have similar postulated mechanisms of action: The lymphatic vessels and superficial veins are collapsed, and the proximal spread of venom is slowed.¹⁷ Although this method is successful as first-aid therapy for Elapidae bites, its use for pit vipers has not been demonstrated. If less than 30 minutes has elapsed since the bite, a constricting band applied tightly enough to impede superficial venous and lymph flow, but not arterial blood flow, may be used. The band is applied loosely enough to admit a finger between the band and the skin after application. It is used with caution to prevent the development of a tourniquet effect under swollen tissue, which may cause more destruction than the snakebite.¹⁸ Incision of bite wounds has no proven efficacy and poses potential danger to underlying structures and therefore is not recommended. The use of ice is not helpful in slowing the spread of venom, but an ice bag wrapped in a towel and applied to the bite area helps relieve pain. Ice water immersion and packing of the extremity in ice are dangerous and only contribute to tissue destruction. The use of suction devices has not been shown to be beneficial.¹⁹

Third, when feasible, the snake should be identified or brought to the treating facility with the victim, though this should not delay transport of the patient to definitive medical care. Identification of the snake must be done safely—usually only by someone expert in handling snakes. A photo may be useful in identifying the snake if a close-up of the head and tail are included. Dead snakes can be placed in a hard container, such as a bucket or ice chest. Care should be taken to not touch the head of the snake because envenomation can occur even after death.

Fourth, additional medical interventions, if available, should be initiated, including cardiac monitoring, intravenous fluids, and analgesics.

Emergency Department Care

Many snakes do not envenomate the victim when they bite, which has provided false support for the historical use of whiskey, clam juice, or split chickens in the treatment of snakebite. The only proven therapy is antivenin. Emergency department care of a snakebite focuses on supportive care and rapid treatment with the appropriate antivenin. Rapid decision-making is required to determine the optimal type, amount, and route of administration of the antivenin. By the time the emergency physician examines a snakebite victim, the venom may have already caused much damage, both locally and systemically. In this case, the emergency physician must be prepared to support the victim’s cardiovascular and respiratory systems.

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 antivenin treatment is being considered.

Patient Examination.: The bite area is examined for signs of fang marks or scratches and local envenomation (e.g., 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. 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. These data aid in objectively estimating both spread of the venom and the effect of antivenin (Fig. 62-3).

Figure 62-3 Northern copperhead (Agkistrodon contortrix mokasen) bite on right hand with normal left hand for comparison.

Initial Medical Care.: If the bite occurred less than 30 minutes before arrival in the emergency department, first-aid measures can be instituted, including a constricting band until antivenin, can be obtained. Snakebite victims with clinical evidence of envenomation should have an intravenous line with normal saline placed in an unaffected extremity. An electrocardiogram, complete blood count, urinalysis, protime, and levels of fibrinogen, fibrin split products, electrolytes, blood urea nitrogen, and creatinine are recommended; blood should be typed and crossmatched for 4 units of packed red blood cells.

The patient’s vital signs are monitored closely. Snakebite victims may be hypotensive because of third-space losses and hemorrhage. In an edematous extremity, the distal pulse may have to be examined with a Doppler instrument. If a compartment syndrome is suspected, insert a pressure monitor and obtain surgical consultation. If signs and symptoms of compartment syndrome are present, pressure greater than 30 mm Hg may necessitate fasciotomy, although there is evidence that administration of antivenin may lower compartment pressures.12,13

Once stabilization is initiated, the severity of the bite must be determined and a decision made regarding whether to administer antivenin. The more distal the bite on the extremity, the less toxicity associated with the bite.²⁰ Intravenous bites may be rapidly fatal. Bites occurring on the trunk, neck, and face have increased risk because of rapid transit of the venom.

Antivenin.: The emergency physician must determine the type of antivenin to administer, how much, and over what period. If the bite is from a pit viper, the problem is not too difficult. Bites from copperheads usually cause a moderate amount of edema but generally do not require antivenin, although it may be indicated in selected cases.²¹ Envenomation may be classified according to severity into five grades, from grade 0 (no sign of envenomation) to grade IV (very severe envenomation). The amount of antivenin to be given is correlated with the grade of envenomation:

• Grade 0 (minimal). There is no evidence of envenomation, but snakebite is suspected. A fang wound may be present. Pain is minimal, with less than 1 inch of surrounding edema and erythema. No systemic manifestations are present during the first 12 hours after the bite. No laboratory changes occur.

• Grade I (minimal). There is minimal envenomation, and snakebite is suspected. A fang wound is usually present. Pain is moderate or throbbing and localized to the fang wound, surrounded by 1 to 5 inches of edema and erythema. No evidence of systemic involvement is present after 12 hours of observation. No laboratory changes occur.

• Grade II (moderate). There is moderate envenomation, more severe and widely distributed pain, edema spreading toward the trunk, and petechiae and ecchymoses limited to the area of edema. Nausea, vomiting, and a mild elevation in temperature are usually present.

• Grade III (severe). The envenomation is severe. The case may initially resemble a grade I or II envenomation, but the course is rapidly progressive. Within 12 hours, edema spreads up the extremity and may involve part of the trunk. Petechiae and ecchymoses may be generalized. Systemic manifestations may include tachycardia and hypotension. Laboratory abnormalities may include an elevated white blood cell count, creatine phosphokinase, prothrombin time, and partial thromboplastin time, as well as elevated fibrin degradation products and D-dimer. Decreased platelets and fibrinogen are common. Hematuria, myoglobinuria, increased bleeding time, and renal or hepatic abnormalities may also occur.

• Grade IV (very severe). The envenomation is very severe and is seen most frequently after the bite of a large rattlesnake. It is characterized by sudden pain, rapidly progressive swelling that may reach and involve the trunk within a few hours, ecchymoses, bleb formation, and necrosis. Systemic manifestations, often commencing within 15 minutes of the bite, usually include weakness, nausea, vomiting, vertigo, and numbness or tingling of the lips or face. Muscle fasciculations, painful muscular cramping, pallor, sweating, cold and clammy skin, rapid and weak pulse, incontinence, convulsions, and coma may also be observed. An intravenous bite may result in cardiopulmonary arrest soon after the bite.

Dart and colleagues have advocated slightly different grading systems and higher doses of antivenin: Grades 0 and I correspond to minimal envenomation, grade II represents moderate envenomation, and grades III and IV correspond to severe envenomation.22,23 Either system can be used interchangeably.

Onset of symptoms after a pit viper bite may be delayed and may involve a variety of neurologic symptoms, including weakness, ptosis, stupor, bulbar paralysis, and other cranial nerve dysfunction, as well as nausea, abdominal pain, and headache.

Administration of Antivenin.: Any victim of a venomous snakebite with moderate or severe envenomation is a candidate for antivenin. The choice of antivenin depends on the species of snake, and the antivenin may be horse serum- or sheep-derived Fab fragments. Wyeth Laboratories, producer of the polyvalent horse serum–derived antivenin for Western Hemisphere pit vipers, no longer manufactures that antivenin. Many zoos and hospitals still maintain vials of this antivenin until it can be replaced with the ovine-derived Fab antivenin (FabAV). This antivenin is derived from four species of U.S. pit vipers and has not been clinically studied with regard to bites from Mexican, Central American, or South American pit vipers.23,24 There is a reported case of a patient bitten by a South American rattlesnake who was successfully treated with FabAV.²⁵

Most antivenin for exotic snakes and the eastern coral snake is derived from horse serum. A recent polyvalent Fab(2) antivenin derived form horse serum and produced in Mexico has been shown to be effective against both North and South American crotalid species.²⁶ Skin testing was commonly performed before administration of horse serum–derived antivenin, but it is not medically indicated because of the inaccuracy of the test. Moreover, testing with normal horse serum may precipitate an allergic reaction, and even a positive test result may not preclude treatment if a patient has sustained severe envenomation. The incidence of allergic reactions with Fab antivenins has been much less than previously seen with whole IgG. The incidence of allergic reactions was 17% for early reactions and 12% for late reactions in postmarketing analysis. This was thought to be a result of incomplete purification of one lot contaminated by Fc fragments. Most of these reactions were minor and did not require stopping the infusion of the antivenin. The true incidence is unknown.^27–30

Dosage and Precautions.: Current treatment of pit viper envenomation in the United States is to use a FabAV polyvalent antivenin rather than the horse serum product.³¹ This is designed to limit the allergic reactions associated with horse serum antivenin by use of antigen-binding fragments (Fabs) of sheep (ovine) immunized against four species of venomous snake found in the United States. CroFab has been shown to be as effective as the Wyeth antivenin, with fewer allergic reactions. Because of more rapid clearance of smaller Fab fragments by the kidney, however, a repeat-dose regimen must be used to prevent the recurrence of coagulopathy. The duration of action of the venom may be longer than the therapeutic effect of the antivenin. Initial studies have shown promise for a new affinity-purified, mixed monospecific ovine Fab antivenin that has been tested with favorable results in humans after minimal to moderate crotalid envenomation.²³ Its efficacy in pit vipers from South America or Asia has not been proved. Purification of antivenin by separation of active fractions may lead to safer administration of horse serum–derived antivenin. An algorithm has been developed that can aid in decision-making after a crotalid bite (Table 62-2 and Fig. 62-4).³¹ In the next decade, snakebite management will probably change radically throughout the world. Phytotherapy (botanical therapy) and other nonantivenin drug therapies for snakebite have shown promise in experimental animal studies, and some centers have successfully treated snakebite with medical support only. Hyperbaric oxygen therapy has also been used as an adjunct to antivenin in the treatment of venomous snakebite; however, there is insufficient evidence to recommend its use.³²

Table 62-2

Antivenin Dosage for Pit Viper Envenomation *