Chapter 54 Bites by Venomous Reptiles in Canada, the United States, and Mexico

Robert L. Norris, Jr., Sean P. Bush, Jennifer Cohen Smith

For online-only figures, please go to www.expertconsult.com

The medical impact of venomous reptiles in the “New World” is relatively low when compared with that in the Eastern Hemisphere. Recent estimates suggest approximately 300,000 snakebites per year in North America and Latin America, with approximately 4000 deaths, compared with more than 2 million bites per year in the Eastern Hemisphere, with approximately 80,000 deaths.⁸³ Although these estimates are inexact, given major barriers to data gathering in developing regions of the world, they paint a picture of snakebite at a “macro” level in the New World as an annoyance, but as a major health issue on the other side of the planet. However, the bites of rattlesnakes or Gila monsters that occur in North America are very significant to the individual victims and to those called on to render care in the field and hospital. This chapter reviews venomous reptiles of major medical importance in Canada, the United States, and Mexico, detailing clinical effects and proper approach to management of their bites. A general discussion of antivenom therapy is included. Venomous snakes are discussed first, followed by venomous lizards.

Venomous Snakes

Scope of the Problem

The oft-quoted number of venomous snakebites in the United States is 7000 to 8000 per year. This estimate stems from work originally done in the late 1960s by Dr. Henry Parrish ¹⁶⁴ and expanded on by Dr. Findley Russell.¹⁷⁶ Parrish estimated deaths due to snakebite in the United States to be about 15 per year.¹⁶⁴ No rigorous, systematic review has ever been done in the United States to determine a precise incidence of venomous snakebite, but compared with much of the developing world, the problem is relatively uncommon. A review of bites by native U.S. venomous snakes reported to the American Association of Poison Control Centers (AAPCC) from 2001 through 2005 revealed 23,676 cases (average 4735 per year) with 14 total deaths (just under 3 per year).¹⁹⁰ Given that some unknown percentage of snakebites go unreported to poison control centers, these numbers are an underestimate but give an idea of the scope of the problem in the United States. The incidence of snakebite in Canada is much lower than in the United States because of fewer snake species and numbers in colder climates. In Mexico, snakebite has greater medical importance because Mexico has more venomous snake species than any other nation in the New World.³⁴ An estimated 3000 snakebites, with as many as 150 deaths, occur in Mexico each year.^74,¹⁹²

Table 54-1 lists the species of dangerous venomous reptiles found in Canada, the United States, and Mexico.³⁵ All of the medically important North American venomous snakes are in the families Viperidae (subfamily Crotalinae, the pit vipers) and Elapidae (subfamily Elapinae [the coral snakes] and subfamily Hydrophiinae [the sea snakes]).

TABLE 54-1 Venomous Reptiles of Canada, the United States, and Mexico

Being poikilothermic, snakes rely on environmental heat energy to support locomotion, feeding, digestion, and reproduction. Thus the number of species decreases as the distance from the equator increases. Pit vipers are widely dispersed throughout most of the New World south of southern Canada (i.e., south of 55° north latitude).¹⁴⁸ North American pit vipers include the rattlesnakes (genera Crotalus and Sistrurus); copperheads, cottonmouth water moccasins, and cantils (genus Agkistrodon); and numerous species unique to Latin America (genera Atropoides [jumping pit vipers], Bothriechis [palm-pit vipers], Bothrops [lancehead pit vipers], Cerrophidion [montane pit vipers], Ophryacus [Mexican pit vipers], and Porthidium [hognose pit vipers]). There are three pit viper species (all rattlesnakes) found in Canada, 18 in the United States, and approximately 50 in Mexico.³⁵

Rattlesnakes are the most widespread pit vipers, found throughout much of North America (Figures 54-1 to 54-10). At least one species is found in each of the 48 contiguous states except Maine. Copperheads (Agkistrodon contortrix) are found in the central and southeastern United States and westward into the Big Bend region of Texas (Figure 54-11). Cottonmouth water moccasins (Agkistrodon piscivorus) are found in the southeast from Virginia to Florida and extend westward into central Texas (Figure 54-12). In Mexico, copperhead and cottonmouth snakes are replaced by the cantils, Agkistrodon bilineatus (Figure 54-13) and Agkistrodon taylori.

FIGURE 54-1 Eastern diamondback rattlesnake (Crotalus adamanteus) is the largest pit viper of the United States and can attain lengths of 2 m (6.5 feet).

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

FIGURE 54-2 Western diamondback rattlesnake (Crotalus atrox) causes many serious bites in the U.S. Southwest.

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

FIGURE 54-3 Mohave rattlesnake (Crotalus scutulatus) has two geographic populations in terms of venom composition, one with predominantly neurotoxic effects and one with more local sequelae.

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

FIGURE 54-4 Timber rattlesnake (Crotalus horridus) is a large, dangerous snake of the eastern United States.

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

FIGURE 54-5 Canebrake rattlesnake (Crotalus horridus), a form of the timber rattlesnake found in Florida, Georgia, and South Carolina, possesses a more neurotoxic and myotoxic venom than does its more northern variant.

(Courtesy Michael Cardwell and Medtoxin Venom Labs.)

FIGURE 54-6 Prairie rattlesnake (Crotalus viridis viridis) is a widely distributed species of the western United States.

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

FIGURE 54-7 Northern Pacific rattlesnake (Crotalus oreganus oreganus, formerly C. viridis oreganus) is a moderate-sized but very toxic snake of the Pacific Northwest.

(Courtesy Joel Levis, MD.)

FIGURE 54-8 Southern Pacific rattlesnake (Crotalus oreganus helleri, formerly C. viridis helleri) replaces C. oreganus oreganus in southern California and northwestern Mexico.

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

FIGURE 54-9 Tropical rattlesnake (Crotalus simus, formerly C. durissus durissus) is a large, dangerous species found in southern Mexico.

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

FIGURE 54-10 Western pygmy rattlesnake (Sistrurus miliarius streckeri) is one of the smaller rattlesnake species of North America.

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

FIGURE 54-11 Southern copperhead (Agkistrodon contortrix contortrix) has markings that make it almost invisible when lying in leaf litter.

(Courtesy Michael Cardwell and Medtoxin Venom Labs.)

FIGURE 54-12 Cottonmouth water moccasin (Agkistrodon piscivorus) exhibiting its threat display. This snake is found most often around standing water sources in the southeastern United States.

(Courtesy Sherman Minton, MD.)

FIGURE 54-13 Cantil (Agkistrodon bilineatus) is a close relative of the copperheads (A. contortrix) and cottonmouths (A. piscivorus) of the United States. This pit viper is found in Mexico and Central America.

(Courtesy Michael Cardwell and William W. Lamar.)

In terms of elapids, coral snakes (akin to cobras [Naja sp.]), mambas (Dendroaspis sp.), and kraits (Bungarus sp.) of the Eastern Hemisphere are the only land-dwelling members of this family in North America, with two genera (Micrurus and Micruroides) on the continent (Figures 54-14 to 54-16). There are no coral snakes indigenous to Canada and only three species in the United States, but 16 species are found in Mexico. In the United States, these colorful reptiles are found in Arizona (Sonoran coral snake, Micruroides euryxanthus), the southeastern United States (eastern coral snake, Micrurus fulvius), and Texas (Texas coral snake, Micrurus tener [formerly M. fulvius tenere]). Mexican coral snakes include Micruroides euryxanthus and 15 Micrurus species.³⁵ One species of sea snake (Pelamis platurus) reaches the southwestern coast of North America, occasionally visiting the coast of southern California. Sea snakes are discussed in Chapters 55 and 81.

FIGURE 54-14 Eastern coral snake (Micrurus fulvius) has a highly potent venom but is secretive, and bites are uncommon.

(Courtesy Michael Cardwell, Extreme Wildlife Photography and Medtoxin Venom Labs.)

FIGURE 54-15 Texas coral snake (Micrurus tener, formerly M. fulvius tenere), which although dangerous, tends to cause less severe envenomation than does Micrurus fulvius.

(Courtesy Michael Cardwell and the Gladys Porter Zoo.)

FIGURE 54-16 Sonoran coral snake (Micruroides euryxanthus) is also known as the Arizona coral snake. No documented fatality has followed a bite by this species.

(Courtesy Michael Cardwell and Jude McNally.)

The largest and most cosmopolitan snake family, Colubridae, consists largely of species that are completely harmless. However, there are occasional reports, particularly in tropical regions of the world, of human envenomations and even deaths caused by a handful of colubrid species (see Chapter 55). These species possess secretory glands (Duvernoy’s glands) and enlarged maxillary teeth (sometimes grooved) in the rear of their mouths (opisthoglyphous). Secretions from these glands are variable, depending on the species, with a number including proteolytic enzymes and phospholipases.⁹⁸ The venoms may help to immobilize, kill, and digest prey and, when injected into humans, may cause envenomation—generally limited to pain, soft tissue swelling, bruising, and blister formation. Such local consequences have been reported in the United States after bites by the western hognose snake (Heterodon nasicus)²¹⁴ and the wandering garter snake (Thamnophis elegans vagrans).⁷⁵ Effective envenomation generally requires that these snakes maintain a bite for several minutes in order to get sufficient venom into the tissues via their posterior teeth. These bites in the United States do well with conservative treatment alone, but it is important that they be differentiated from bites by pit vipers that may require antivenom therapy. A careful description of the involved snake should be obtained.

Throughout North America, pit vipers are responsible for approximately 98% of venomous snakebites.¹⁹⁰ Coral snakes tend to be secretive in nature and possess a less efficient venom delivery mechanism compared with pit vipers (see Anatomy, later). Coral snake bites are infrequent, even in regions where the snakes are relatively common. The 2008 report of the AAPCC Toxic Exposure Surveillance System recorded 99 coral snake bites in the United States that year.¹⁵

Anatomy

Pit Vipers

Pit vipers of North America come in a wide range of sizes. Smaller rattlesnakes include the sidewinders (Crotalus cerastes), ridge-nosed rattlesnakes (Crotalus willardi), and pygmy rattlesnakes (Sistrurus miliarius), whose adult lengths are routinely less than 65 cm (25.6 inches).¹¹⁴ At the other extreme, the eastern diamondback rattlesnake (Crotalus adamanteus) can exceed 2 m (6.5 feet).¹¹⁴

The term pit viper comes from the presence of paired, thermal receptor organs (pits) present on the forward portion of the snakes’ heads (Figure 54-17). Also known as foveal organs, these structures assist with prey location, aiming strikes (Figure 54-18), and metering venom dose through a neurologic feedback loop with the elaborate crotaline venom delivery apparatus²²¹ (Figure 54-19). Encased in the muscularis compressor glandulae, bilateral venom glands are located at the sides of the head behind the eyes. These glands, which produce and store venom, are connected through ducts to more anterior accessory glands, whose secretions serve to potentiate the venom.¹⁷⁸ From here, the venom moves forward through other ducts into the venom sheaths located adjacent to the proximal portion of the hollow, needle-like fangs with which the snake pierces its victim in a stabbing motion. These fangs, found on the anterior surfaces of the maxillary bones, are large (up to 20 mm [0.79 inches] in big rattlesnakes¹¹⁴) and highly mobile. At rest, the snake folds the fangs against the roof of its mouth. For a strike, the fangs are brought into an upright position, perpendicular to the maxillae. The snake has voluntary control over its fangs and can open its mouth without raising the fangs or can raise each fang individually at will. The fangs are relatively brittle and fracture or become dull with time and use. Replacement fangs, at varying stages of development behind the functional set, move forward on the maxillary bone when needed (Figure 54-20). Pit vipers can strike at speeds of up to 2.4 m (8 feet) per second and reach distances of approximately one-half their body length.²²¹ Table 54-2 lists venom yields for various North American pit vipers.

FIGURE 54-17 Pit viper’s head. Note the elliptical pupil and the heat-sensing pit for which these reptiles are named. Viewed from above, the head has a distinctly triangular shape. Many nonvenomous snakes also possess triangular heads, and this is not a reliable means of differentiation.

(Courtesy Marlin Sawyer, 1994.)

FIGURE 54-18 Paired heat-sensing pits of the pit vipers used to help the snake locate its prey, direct its strike, and probably determine the volume of venom to be expended.

(Courtesy Marlin Sawyer, 1994.)

FIGURE 54-19 Venom delivery apparatus of a pit viper. Venom is produced in large venom glands just posterior to the eyes and is passed through a duct system into the hollow, anterior fangs when the snake bites.

(Courtesy Marlin Sawyer, 1994.)

FIGURE 54-20 Rattlesnake skull. Replacement fangs are behind the primary, functional fangs. The smaller teeth of the palatine, pterygoid, and mandibular bones are used for gripping food.

(Courtesy Michael Cardwell/Extreme Wildlife Photography.)

TABLE 54-2 Venom Yields of Some Medically Important Snakes of North America

Species	Maximum Venom Yield (mg Dry Weight)	Reference
Crotalus adamanteus	848	*
Crotalus atrox	1145	*
Crotalus cerastes	63	*
Crotalus durissus	514 (average)	*
Crotalus horridus	229	*
Crotalus molossus	540	*
Crotalus oreganus helleri (formerly C. viridis helleri)	390	*
Crotalus oreganos (formerly C. viridis oreganus)	289	*
Crotalus scutulatus	141	*
Crotalus viridis	162	*
Sistrurus catenatus	33	†
Sistrurus miliarius	18 (average)	*
Agkistrodon contortrix	45	‡
Agkistrodon piscivorus	150	‡
Micruroides euryxanthus	6	§
Micrurus fulvius	38	§
Micrurus nigrocinctus	20	§

* From Klauber LM: Rattlesnakes: Their habits, life histories, and influence on mankind, ed 2, Berkeley, Calif, 1997, University of California Press.

† From Glenn JL, Straight RC: The rattlesnakes and their venom yield and lethal toxicity. In Tu AT, editor: Rattlesnake venoms: Their actions and treatment. New York, 1982, Marcel Dekker, pp 3-119.

‡ From Parrish HM: Poisonous snakebites in the United States, New York, 1980, Vantage Press.

§ From Roze JA: Coral snakes of the Americas: Biology, identification, and venoms, Melbourne, Fla, 1996, Krieger.

The fastest pit viper can crawl at a maximum speed of approximately 4.8 km (3 miles) per hour, which approximates an average adult walking pace.²²¹ Crotaline snakes do not chase people. Accounts suggesting otherwise can be explained by snakes’ poor eyesight; when threatened, they may unwittingly retreat in the direction of people.

The characteristic forked tongue of the snake is an olfactory tool and possesses none of the offensive “stinging” function ascribed to it in folklore. The snake extends its tongue to detect chemical odors in its environment. The tongue is then retracted and its tips placed into the paired Jacobson’s organs, lined with olfactory epithelium, in the roof of its mouth. This sensory system is highly sensitive, allowing the snake to identify potential mates, locate prey, and track down an intended food item that has been bitten by the snake and released to die.

Pit vipers have elliptical, or “catlike,” pupils (see Figure 54-17), whereas most North American harmless snakes have round pupils. A few, essentially harmless, rear-fanged colubrids in the United States, such as the night snake (Hypsiglena torquata) and lyre snake (Trimorphodon biscutatus) (Figure 54-21), also possess elliptical pupils but lack facial pits. Although these opisthoglyphous species possess Duvernoy’s glands (see earlier discussion), they are innocuous creatures. They are reluctant to bite humans, and their salivary toxins are likely to cause few signs or symptoms, other than slight swelling, bruising, and pain, in the event of a bite. The two small species of boas in North America, the rosy boa (Lichanura trivirgata) and the rubber boa (Charina bottae), also possess elliptical pupils, but their body form (more cigar-shaped and lacking the broad, triangular head of a pit viper) and skin patterns are very different from those of any crotaline.

FIGURE 54-21 Although most members of the largely harmless Colubridae snake family have round pupils, some, like this lyre snake (Trimorphodon biscutatus), a mildly venomous, rear-fanged colubrid of the southwestern United States, have elliptical pupils similar to those of pit vipers.

(Courtesy Robert L. Norris, Jr., MD.)

The caudal rattle of the rattlesnake is composed of loosely interlocked plates of keratin that emit a buzzing sound when the snake rapidly vibrates its tail. This characteristic sound serves as a warning to a perceived threat. A new segment is added to the rattle each time the snake sheds its skin, which can occur from one to several times each year, depending on its age, health, and feeding success. Newborn rattlesnakes have a single button present at birth (Figure 54-22). Not until after their first shed do they possess a true rattle that can create a sound. Rattles are commonly broken off during the snake’s life, so the number cannot be used reliably to determine age. Although rattlesnakes are generally quick to sound a warning when threatened, it is a misconception that they will always do so before striking.

FIGURE 54-22 Newborn western diamondback rattlesnake (Crotalus atrox). Note the single “button” of its “rattle.”

(Courtesy Michael Cardwell, Extreme Wildlife Photography.)

Another helpful anatomic feature of pit vipers in the United States is the scale pattern on the underside of the tail—the subcaudal scales. The junction of a dead snake’s body and its tail can be easily ascertained by viewing its ventral side. At this location is a large scale (sometimes divided) known as the anal plate. Just distal to this in U.S. pit vipers is a sequence of single scales that entirely cross the ventral surface. In nonvenomous snakes and in coral snakes (as well as some Latin American pit vipers), the subcaudal scales are paired (i.e., each covers approximately half the width of the tail) (Figures 54-23 and 54-24). This feature becomes clinically useful when a U.S. snakebite victim brings in the body of a decapitated snake for identification and when the skin pattern is unfamiliar to the physician.

FIGURE 54-23 Subcaudal scale patterns of U.S. snakes. In the United States, pit vipers have a single row of scales on the ventral side of the tail, just distal to the anal plate. Most harmless colubrid snakes have double rows of subcaudal scales, as do coral snakes and some species of Latin American pit vipers.

(Courtesy Marlin Sawyer, 1994.)

FIGURE 54-24 Comparison of the subcaudal scale pattern of a rattlesnake on the left with a harmless rat snake on the right.

(Courtesy Robert L. Norris, Jr., MD.)

Coral Snakes

Coral snakes are identified primarily by color pattern. U.S. coral snakes are banded in a red-yellow-black-yellow-red pattern (Figure 54-25), and the bands completely encircle the snake’s body. The contiguity of the red and yellow bands distinguishes U.S. coral snakes from a number of harmless mimics (e.g., several kingsnakes and milksnakes, genus Lampropeltis), which generally have red and yellow bands separated by black bands. This can best be remembered by recalling the phrase “red on yellow, kill a fellow; red on black, venom lack” or by considering that the red and yellow lights on a traffic signal are the warning lights. Contiguous red and yellow bands can be used to reliably identify coral snakes only in North America, north of Mexico City. Farther south, bicolor (red and black) coral snake species may be found, and there are many harmless mimics that closely resemble these venomous serpents.¹⁵⁰ One harmless U.S. colubrid, the shovel-nosed snake (Chionactis species), has contiguous red and yellow bands, but the bands do not completely encircle its body and the snake is completely inoffensive. In exceptionally rare cases, coral snakes can be all black (melanistic) or albino.¹⁴³

FIGURE 54-25 Comparison of the Texas coral snake (Micrurus tener) with the harmless Mexican milk snake (Lampropeltis triangulum annulata). Coral snake (bottom) has contiguous red and yellow bands, whereas red and yellow bands of the milk snake are separated by black.

(Courtesy Charles Alfaro.)

The coral snake venom apparatus is much less complex than that of pit vipers. The paired venom glands connect through ducts to slightly enlarged, hollow fangs that are fixed in an upright position in the forward portion of the maxillae (Figure 54-26). For the coral snake to inflict a potentially serious bite, it must chew on the victim to inject a sufficient volume of venom through its relatively small fangs. These animals are not capable of striking out with the stabbing motion of a pit viper. In the vast majority of coral snake bite cases, the victim was handling the creature when bitten; in some cases, this occurred when the victim misidentified the snake as a harmless kingsnake.¹⁶⁷

FIGURE 54-26 Coral snake’s skull. Note the slightly enlarged anterior maxillary fang that is fixed in its upright position.

(Courtesy Marlin Sawyer, 1994.)

Venoms

Pit Vipers

Snake venoms are extraordinarily variable and complex chemical cocktails of approximately 100 distinct molecular moieties. Some of the better characterized and more interesting of these include the phospholipase A₂ neurotoxins, metalloproteinases, and thrombin-like enzymes.^53,¹⁰⁹ Phospholipase A₂ neurotoxins are among the most toxic of pit viper venom components and can increase lethality of the venom 10- to almost 100-fold.⁶⁹ The first of these, crotoxin, was isolated in 1938 from the South American rattlesnake (Crotalus durissus terrificus).¹ Phospholipase A₂ neurotoxins noncompetitively bind to presynaptic calcium channels, inhibiting acetylcholine release and thereby blocking neurotransmission at the neuromuscular junction, inactivating the muscle. This can cause paralysis of the muscles of respiration, for example, and lead to respiratory difficulty. Additionally, phospholipase A₂ damages muscle cell membranes, allowing calcium influx and release of creatine and creatine kinase (CK), which can progress to diffuse myonecrosis and rhabdomyolysis.¹¹⁰ Metalloproteinases, the enzymes that cause much of the locally destructive effects of pit viper envenomation, activate tumor necrosis factor alpha and stimulate endogenous human metalloproteinases, intensifying inflammation. Certain metalloproteinases, the hemorrhagins, cause leakage of red blood cells out of the vasculature, leading to ecchymosis (characteristic of more severe pit viper bites) and fluid shifts.^82,²¹⁷ High venom toxicity is generally associated with phospholipase A₂ neurotoxins, which are typically (but not always) inversely related in proportionate concentrations to the tissue-damaging metalloproteinases.¹³⁷ Thrombin-like enzymes cause consumptive coagulopathy but do not directly activate coagulation factors or form a complex with antithrombin III (and so are not affected by heparin). Disintegrins bind to proteins on blood platelets, blocking their combination with fibrinogen necessary to form clots.³¹ Bradykinins cause hypotension, vomiting, and pain. Hyaluronidase decreases the viscosity of connective tissues, allowing venom to spread. Lysolecithin, a by-product of the enzymatic action of phospholipase A₂, damages mast cell membranes and results in histamine release.⁴²

Pit viper venom has both offensive (i.e., food gathering) and defensive functions. In predatory strikes, venom immobilizes prey, facilitates its retrieval by altering its scent, and accelerates digestion.^41,^88,⁹⁵ Defensive strikes are meant to deter predators and tormentors. The amount of venom injected differs from bite to bite. Factors such as prey size and species, duration of fang contact, and time elapsed since last meal influence the amount of venom released.^88,⁹⁵ Rattlesnakes have been shown to inject significantly more venom into large mice than into small mice.⁸⁸ The mass of venom expended differs between predatory and defensive bites. In comparison studies, venom expenditure by North American pit vipers appears to be greater in defensive bites than in predatory bites.⁹⁵ In one comparison, the northern Pacific rattlesnake (Crotalus oreganus [formerly C. viridis oreganus]) expended almost four times more venom when biting a hand model (defensive) than when biting a mouse (predatory).^88,⁹⁵ The most important factor influencing potential venom delivery is the size of the snake.⁹⁵ A direct relationship in both predatory and defensive bites has been demonstrated between snake length and mass of venom expended.^85,⁹⁵

A popular belief is that juvenile rattlesnakes are more dangerous than are adult snakes because their venom is more toxic and they are unable to control the volume released. The venom of some juvenile rattlesnakes may be slightly more toxic, but larger rattlesnakes are capable of delivering much greater amounts of venom in a bite. Juvenile prairie rattlesnakes (Crotalus viridis [formerly C. viridis viridis]) have been shown in one small study to possess venom that is 2 to 3 times more toxic than that of adults.⁶² Large adult snakes, however, deliver an average of 17 times (range, approximately 10 times to greater than 100 times) more venom than do juveniles.⁸⁵ The ability to control venom expenditure has been demonstrated in juvenile rattlesnakes. In a series of first exposures to different-sized prey, “naive” juvenile rattlesnakes injected similar quantities of venom into all size classes. However, in the second series of exposures, “experienced” snakes injected significantly more venom into larger prey.⁸⁶ The clinical relevance of this is uncertain. In many species, venom composition appears to change as the snake ages. Phospholipase A₂ activity decreases with age, probably accounting for some decrease in toxicity. Proteolytic activity increases with age, possibly to aid digestion of larger prey eaten by older, larger snakes.⁸⁵ Coagulopathic effects can be different between juvenile and adult western diamondback rattlesnakes (Crotalus atrox), partly because of the greater amounts of thrombin-like enzymes in younger snakes.¹⁷²

Clinical studies showing that envenomations by large rattlesnakes are generally more severe than are envenomations by smaller ones corroborate and complement these findings in the laboratory and the field.^87,¹⁰⁵ Juvenile pit vipers can, however, deliver a very serious, even life-threatening, envenomation.

Venom characteristics vary with geographic origin of the snake.⁷¹ For example, certain populations of the Mohave rattlesnake (less correctly spelled “Mojave”) (Crotalus scutulatus) cause human neurotoxicity with severe envenomation while causing minimal local tissue destruction and no hemorrhagic effects.^46,¹⁰⁶ Neurotoxic findings may include respiratory difficulty, generalized weakness, and cranial nerve palsies.⁴⁶ The venoms of these snakes possess a presynaptic neurotoxin, originally designated “Mojave toxin”⁶ (and this spelling persists), and are classified as venom A populations. Venom B populations lack Mojave toxin and are less toxic. Bites by venom B snakes result in consequences more typical of most rattlesnake envenomations: soft tissue swelling, necrosis, and coagulopathy. Venom A populations are found in California, western Arizona, Nevada, Utah, New Mexico, and Texas. Venom B populations are found in eastern parts of Arizona. A zone of intergradation between venom A and venom B populations occurs along a line between Phoenix and Tucson.^89,²¹⁹ Envenomations manifesting both venom A and venom B effects (i.e., neurotoxicity plus coagulopathy and swelling) have been observed in inland southern California. Toxins with structures and physiologic effects similar to those of Mojave toxin have been isolated from venoms of other species of rattlesnakes, including southern Pacific rattlesnakes (Crotalus oreganus helleri [formerly C. viridis helleri ]), prairie rattlesnakes (C. viridis [formerly C. viridis viridis ]), midget faded rattlesnakes (C. concolor [formerly C. viridis concolor ]), tropical rattlesnakes (C. durissus), timber rattlesnakes (Crotalus horridus), and tiger rattlesnakes (Crotalus tigris).^64,^70,^72,^94,²¹⁵ Geographic differences occur in the venoms of other snakes as well. Timber rattlesnakes (sometimes referred to as canebrake rattlesnakes) (C. horridus) from Florida, Georgia, and South Carolina possess more “canebrake toxin,” a neurotoxic and myotoxic component, than do specimens from Alabama, Mississippi, Tennessee, and North Carolina.⁷² Differences in concentration of this toxin correlate with varying clinical effects seen after bites by this species from different geographic regions.³⁹

Neurotoxicity has been clinically associated with severe myotoxicity in many cases.^28,^39,^50,¹⁰⁶ Severe rhabdomyolysis and myoglobinuric renal failure have been reported after Mohave rattlesnake envenomation and are thought to be related to Mojave toxin.¹⁰⁶ The association between neurotoxicity and myotoxicity has been confirmed in laboratory animals.⁷ C. horridus specimens possessing significant amounts of the neurotoxin, canebrake toxin, produce a rise in serum CK levels as a biochemical signature of significant envenomation. The rise in CK level appears to parallel severity of envenomation by these snakes.³⁹ Autopsy findings have demonstrated that myonecrosis in this setting is systemic and not limited to the bite site.^39,¹¹² Concomitant rises in MB fractions of CK can occur in the absence of any clinical evidence of cardiac damage. In one such case, troponin-T level was normal despite abnormal total CK and CK-MB levels.³⁹ Lesser CK elevations (usually less than 500 units/L) may be seen with other rattlesnake bites, such as that of the eastern diamondback (C. adamanteus). In these cases, the elevations appear to more closely parallel local effects.³⁹

Mojave toxin is thought to inhibit acetylcholine release at the presynaptic terminal of the neuromuscular junction.⁴⁶ Myokymia, or muscle fasciculations, may be considered by some to be a manifestation of neurotoxicity. This phenomenon, however, occurs through a different mechanism than does Mojave toxin–induced neurotoxicity. Myokymia is believed to be caused by interaction of certain venom components with calcium or calcium-binding sites on the nerve membrane.⁴⁶ Myokymia has been reported to occur after envenomation by certain species of rattlesnakes, most notably the southern Pacific rattlesnake, C. oreganus helleri (formerly C. viridis helleri).^14,²¹¹

The variability of southern Pacific rattlesnake venom, for example, has clinical implications. It has been suggested that envenomation by specimens possessing Mojave toxin responds well to treatment with the current U.S. pit viper antivenom, CroFab Crotalidae Polyvalent Immune Fab (Ovine) likely because the antivenom was developed using C. scutulatus venom A, which contains Mojave toxin. In contrast, certain clinical manifestations, such as myokymia, are much less responsive to CroFab, possibly because of non-neutralized or partially neutralized components in southern Pacific rattlesnake venom. These envenomations often require more antivenom than do those by Mojave toxin–possessing specimens. Novel venom components, such as hellerase or yet-to-be characterized small, basic, neurotoxic peptides, may explain this phenomenon.¹⁸³

Many modern medicines are derived from reptile venoms. These are being investigated and used for treatment of heart disease, stroke, cancer, diabetes, hypertension, pain, and other conditions. Some of the most promising of these venom-derived pharmaceuticals come from the disintegrins.³¹

Coral Snakes

Coral snake venoms are less complex than are pit viper venoms and have received less research attention. Micrurus and Micruroides venoms have minimal proteolytic activity but contain the spreading enzyme hyaluronidase and some phospholipase A₂.¹⁸² The primary lethal component is a low-molecular-weight, postsynaptic neurotoxin that blocks acetylcholine binding sites at the neuromuscular junction.^40,²⁰⁴ In addition, the venom contains at least one myotoxic component that may clinically produce a rise in serum CK level.⁸¹

What coral snake venom lacks in complexity, it makes up in potency. Among U.S. snakes, Micrurus and Micruroides venom potency, as determined by median lethal dose (LD₅₀) values in mice, is surpassed only by that of the Mohave rattlesnake (C. scutulatus).¹⁷⁸ It is indeed fortunate that these reptiles are shy and inoffensive and possess a less effective venom delivery device than do pit vipers.

Clinical Presentation

Pit Vipers

The clinical presentation of pit viper envenomation is quite variable and depends on the circumstances of the bite. Important factors include the species, size, and health of the snake, age and health of the victim, circumstances that led to the bite, number of bites and their anatomic locations, and quality of the care rendered to the victim, both in the field and hospital. Although statistics vary, most bites occur to the lower extremities.¹⁶⁴ The next most common anatomic site is an upper extremity, often bitten while the victim is intentionally interacting with the snake (e.g., tormenting the animal, trying to catch it, or handling a captive specimen). Less often, bites occur to the head, neck, or trunk. Most bites occur around dawn or dusk and during warmer months, when snakes and people are more active outdoors.¹⁶⁴ A young, intoxicated male bitten on the hand while intentionally interacting with a snake is a common clinical profile in the United States.

About 75% to 80% of pit viper bites result in envenomation. Approximately one in every four to five bites is “dry,” meaning no venom has been injected.^165,¹⁷⁸ The precise mechanisms behind “dry bites” are unclear. The snake may elect to save its venom for its next meal rather than waste it on a large human. Alternatively, the feedback mechanism may “short-circuit” between the heat-sensing pit organs and the venom delivery apparatus, so that when faced with a huge, heat-radiating mass (a human), the system fails and no venom is expelled. Other possible causes of dry bites include glancing blows that fail to penetrate the skin and an exhausted venom supply. Approximately 35% of bites result in mild envenomations, 25% moderate, and 10% to 15% severe.¹⁶⁵

The clinical findings found in crotaline envenomation can be divided into local and systemic signs and symptoms (Table 54-3). After most pit viper bites, severe burning pain at the site begins within minutes. Soft tissue swelling then progresses outward to a variable distance from the bite site. Over hours, a bitten extremity can swell all the way to the trunk. Bites to the face or neck may result in rapid, severe swelling that can compromise the airway.¹⁷³ Blood may persistently ooze from fang marks, marking the presence of anticoagulant substances in the venom. Ecchymosis is common, both locally and at more remote sites, as the vasculature becomes leaky and red blood cells (RBCs) escape into soft tissues (Figure 54-27). Over a period of hours to days, the patient may develop hemorrhagic or serum-filled vesicles and bullae at the bite site and more proximally, especially if there is a delay in obtaining care (Figure 54-28). Fang marks are usually evident as small puncture wounds, but the precise bite pattern can be misleading.¹⁵³ Most nonvenomous snakebites result in multiple rows of tiny puncture wounds (from the maxillary, palatine, pterygoid, and mandibular teeth) that usually cease bleeding quickly. Pit vipers also possess palatine, pterygoid, and mandibular teeth, which can result in more than the classic paired puncture marks from the maxillary fangs. Also, a snake may make contact with only a single fang. For this reason, associated signs and symptoms should carry more significance than the bite pattern in determining whether a bite was inflicted by a pit viper or another snake. Some rattlesnake bites result in little or no local pain or swelling despite serious envenomation. For example, serious bites by specimens of Mohave rattlesnakes (C. scutulatus) coming from regions where their venom contains substantial quantities of Mojave toxin (venom-A, see earlier discussion) may result in little if any local findings such as pain, swelling, or ecchymosis. Such a presentation could result in early underestimation of the severity of envenomation by the treating physician.²²¹

TABLE 54-3 Signs and Symptoms Following Rattlesnake Bites

Sign or Symptom	Frequency*
Fang marks	100/100
Swelling and edema	74/100
Pain	65/100
Ecchymosis	51/100
Vesiculations	40/100
Change in pulse rate	60/100
Weakness	72/100
Sweating and/or chill	64/100
Numbness or tingling of tongue and mouth or scalp or feet	63/100
Faintness or dizziness	57/100
Nausea, vomiting, or both	48/100
Blood pressure changes	46/100
Change in body temperature	31/100
Swelling regional lymph nodes	40/100
Fasciculations	41/100
Increased blood clotting time	39/100
Spherical red blood cells	18/100
Tingling or numbness of affected part	42/100
Necrosis	27/100
Respiratory rate changes	40/100
Decreased hemoglobin	37/100
Abnormal electrocardiogram	26/100
Cyanosis	16/100
Hematemesis, hematuria, or melena	15/100
Glycosuria	20/100
Proteinuria	16/100
Unconsciousness	12/100
Thirst	34/100
Increased salivation	20/100
Swollen eyelids	2/100
Retinal hemorrhage	2/100
Blurring of vision	12/100
Convulsions	1/100
Muscle contractions	6/100
Increased blood platelets	4/25
Decreased blood platelets	42/100

* Number of times symptom or sign is reported as observed per total number of patients.

From Russell FE: Snake venom poisoning, New York, 1983, Scholium International, p 281, with permission.

FIGURE 54-27 Rattlesnake envenomation can lead to varying degrees of ecchymosis over time. A, Mottled rock rattlesnake (Crotalus lepidus lepidus) bite in a young man at 24 hours. Note the exudation of red cells into the soft tissues remote from the bite site. The man was bitten on his left thumb. B, Northern Pacific rattlesnake (Crotalus oreganus oreganus) bite to the left pretibial region resulted in extensive ecchymosis of the right lower extremity and extended into his flank (seen here one week after the bite).

(Courtesy Robert L. Norris, Jr., MD.)

FIGURE 54-28 Hemorrhagic bleb at the site of a western diamondback rattlesnake (Crotalus atrox) bite at 24 hours.

(Courtesy Robert L. Norris, Jr., MD.)

Systemic findings after pit viper bites are extremely variable; any organ system can be affected. Nausea with or without vomiting is common and may occur early in serious bites. The victim may complain of an overall sense of weakness. An odd sense of taste, such as a rubbery, minty, or metallic taste, may be present.¹⁷⁸ The victim may complain of numbness of the mouth or tongue. Vital signs may be abnormal, with respiratory and heart rates increased. The victim may experience respiratory distress as a result of neurotoxic components of the venom, especially after bites by venom A–producing Mohave rattlesnakes (C. scutulatus).¹⁷⁸ Another important cause of respiratory distress is pulmonary edema from pulmonary artery congestion and translocation of intravascular fluid into alveoli. This can be compounded by myocardial depressant factors in some venoms.¹⁷⁸ The victim’s blood pressure may be elevated; however, hypotension, which may progress to frank shock, is more common in severe cases. In the first several hours, hypotension is usually caused by blood pooling in the pulmonary and splanchnic beds. Later, as swelling progresses and fluid exudes into soft tissues, intravascular volume can become significantly depleted. A rare cause of early shock is nonallergic (and possibly allergic) anaphylaxis to the venom itself (see Allergy to Reptile Venom, later).^18,^29,^56,¹⁵⁸

Musculoskeletal and neurologic abnormalities may be present. As mentioned previously, some rattlesnake venoms possess one or more components that can cause local or systemic myokymia as a sign of significant envenomation. These repetitive, fine muscle contractions may persist for many hours and are variably responsive to antivenom administration.^138,²⁰⁶

Myokymia involving the shoulders, chest wall or torso has been associated with respiratory insufficiency and the need for endotracheal intubation.²⁰⁶ Other findings of neurologic dysfunction can include paresthesias, numbness, and frank motor weakness, especially after bites by some Mohave rattlesnakes (C. scutulatus) and eastern diamondback rattlesnakes (C. adamanteus).

Although uncommon, hemorrhage can occur at multiple anatomic locations because of the complex procoagulant, anticoagulant, and metalloproteinase components of some venoms.¹⁷⁸ Bleeding can occur in the gingival membranes, renal system (microscopic or frank hematuria), gastrointestinal tract (occultly heme-positive stool, frank blood per rectum, or hematemesis), pulmonary tree (hemoptysis) or central nervous system.

Laboratory evaluation of a victim of pit viper bite may reveal significant abnormalities. The white blood cell count may be elevated, reflecting neutrophilic leukocytosis. Hematocrit may be elevated from hemoconcentration or may be depressed secondary to bleeding or hemolysis. Platelet count can drop precipitously as a result of consumptive coagulopathy, sequestration at the bite site, or direct venom effects.²¹⁶ Serum chemistries may be abnormal. Blood glucose level may be elevated. Muscle damage can result in elevated serum potassium and CK levels. Renal dysfunction may result from hypotension, myoglobin and hemoglobin deposition, and direct venom effects.⁴³ Hepatic dysfunction with elevations of serum transaminases may be seen.¹⁴² Coagulation studies may reveal significant abnormalities. Prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) can be elevated. Fibrinogen levels may be depressed, along with elevation of fibrin degradation products and D-dimer levels.⁹ In resource-constrained environments, a 20-minute whole blood clotting test can be used to diagnose coagulopathy. A few milliliters of blood are drawn and placed in a clean, new, dry, glass test tube and allowed to sit, undisturbed, for 20 minutes. After this time, the tube is tipped once to 45 degrees. If the blood is still liquid, coagulopathy is present.²⁰⁷ Major abnormalities may be seen in serum coagulation studies in the absence of any clinically significant bleeding (i.e., no evidence of bleeding or nothing more serious than gingival oozing or microscopic hematuria).¹⁹ This is particularly relevant for determining when to use blood products in treating these victims (see Hospital Care, later). Recurrent coagulopathic parameters (e.g., thrombocytopenia and/or hypofibrinogenemia) may persist or recur for as long as 2 weeks after envenomation, particularly after rattlesnake bites (see Indications for Antivenom, later).^8,^46,⁴⁸

Urinalysis should be performed to identify hematuria. Proteinuria and glycosuria may be seen.¹⁸¹ Each time the victim voids, the urine should be evaluated with bedside testing strips for the presence of blood.

If envenomation is severe or if the victim has significant underlying medical problems (e.g., cardiovascular or respiratory disease), an electrocardiogram (ECG), arterial blood gases (ABGs), and chest radiograph should be obtained. The ECG may reveal evidence of myocardial ischemia. ABGs give important information regarding adequacy of tissue perfusion and respiratory status, but caution should be used in performing arterial puncture in the setting of potential coagulopathy. Pulmonary vascular congestion or frank pulmonary edema may be confirmed radiographically.

Coral Snakes

Given their less efficient venom delivery system, coral snakes effectively envenom their victims only about 40% of the time.¹⁷⁸ Following envenomation, the effects are predominantly neurotoxic. In the United States, bites by the eastern coral snake (Micrurus fulvius) tend to be more severe than those by Texas coral snakes (Micrurus tener), and both are significantly more severe than those of the Sonoran coral snake (Micruroides euryxanthus).^152,^175,¹⁸⁵ The victim may have variable, early, and transient pain of the bitten extremity.¹⁷⁷ Local swelling is uncommon. Fang marks may be difficult to see and should be carefully sought.¹⁵⁵ Systemic signs and symptoms may be delayed as long as 13 hours after significant bites and can then progress rapidly.¹¹³ The earliest findings may be nausea and vomiting, followed by headache, abdominal pain, diaphoresis, and pallor.⁵⁷ Victims may complain of paresthesias or numbness. They may have altered mental status, such as drowsiness or euphoria.¹⁴³ The victim may develop cranial nerve dysfunction (e.g., ptosis, difficulty speaking, difficulty swallowing), followed by peripheral motor nerve dysfunction.¹⁴³ In severe cases, respiratory insufficiency and aspiration are significant risks.¹¹³ Cardiovascular insufficiency may also be seen.¹⁸¹ Unlike with many crotaline envenomations, coagulopathy is not a feature of coral snake envenomation.

Laboratory studies are of little value in evaluation of a victim of coral snake bite. Occasionally, a rise in serum CK and myoglobinuria occur, reflecting myotoxicity.¹¹³ ABGs may be useful in evaluating the victim’s respiratory status if endotracheal intubation is considered or performed. A chest radiograph is indicated in the setting of apparent cardiac dysfunction or after endotracheal intubation.

Management

Prehospital Care

Pit Vipers

The factors that most reduce venomous snakebite-related injury and mortality in the United States are rapid transport, antivenom therapy, and intensive care.²¹ All victims should be transported to the hospital as expeditiously and safely as possible, preferably through activating the emergency 911 system (where available). Increasing the area of coverage for cellular phone services provides snakebite victims with easier access to ambulance or helicopter rescue (Figure 54-29, online).

FIGURE 54-29 A, The fastest and safest way out of a deep wilderness setting may entail helicopter evacuation, where available. B, Specialized techniques, such as hoisting, may be required to rescue a snakebite victim out of a tenuous situation.

(A courtesy Jeff Grange; B courtesy Carlos Quezada.)

Attempts to kill the snake are not recommended because of the risk for additional bites to the victim or rescuer and because precious time can be wasted. All emergency personnel should be able to distinguish native venomous from nonvenomous snakes. However, if rescuers are uncertain about whether a particular snake is venomous, photographs may be taken of the snake from a safe distance (at least 2 m [6.5 feet] away) using a digital camera. These images may help facilitate clinical decisions. Although helpful in identifying the species of snake,^23,²⁵ transporting it (alive or dead) is discouraged because of inherent dangers. On scene, snakes should be moved or contained only if absolutely necessary (i.e., for safety). A snake hook or long shovel may be helpful to move a snake into a large, empty trash canister where it can be recovered by a professional, such as an animal control agent. Serious morbidity and even death have been reported after envenomation by decapitated rattlesnake heads.^39,^112,¹⁹⁸ A recently killed snake or severed snake head can maintain a bite reflex for at least 90 minutes after its death. Emergency personnel and hospital care providers should exercise extreme caution in handling any specimen accompanying the victim, even if it appears dead.

Recommendations for first aid and prehospital treatment of pit viper envenomation have historically been based on speculation and anecdotal experience, although better evidence is accumulating in the literature. In one large retrospective series, first aid treatment had no relationship to ultimate envenomation severity.²²⁰ Some first aid measures recommended in the past have caused more injury than have the bites, and delays in care have been shown to increase morbidity and mortality.^56,⁹⁰ It is inappropriate to use any technique that could potentially injure the patient or delay travel to the nearest facility where antivenom is available. General support of the airway, breathing, and circulation should be provided, depending on the capabilities at hand. Oxygen, cardiac monitoring, and intravenous (IV) fluids should be used in the field when available. Although it may be necessary for the victim to hike out from the scene of the incident, exertion should be minimized as much as possible. Alternative methods (e.g., stretcher, helicopter, boat) of extracting the victim from a wilderness setting can be used when available and when conditions such as weather and terrain allow. Jewelry and tight-fitting clothing are removed from the involved extremity in anticipation of swelling. The border of advancing edema is marked with a pen every 15 minutes so that emergency personnel can estimate the severity of envenomation by following the rate of progression. These measures suffice as adequate prehospital care for the vast majority of pit viper bites in the United States. To be avoided are measures such as incision, suction, tourniquets, electric shock, ice, alcohol, and folk therapies.

Incising the bite site is contraindicated. This creates additional injury and has never been shown to be effective. Because viperid fangs are curved, incisions may miss the track along which venom is actually injected. Incisions made by laypersons can cause serious injury to underlying blood vessels, nerves, or tendons. Because of venom-induced coagulopathy, bleeding from such incisions can be severe.⁸⁹ Furthermore, the lack of sterile conditions in the field increases the risk for infection.

Although use of the Sawyer Extractor Pump to apply mechanical suction was recommended for a number of years, at least three studies using different methodologies independently found that the Extractor does not work for venomous snakebite and can make things worse.^2,^26,^27,²² Mouth suction is contraindicated for the additional concern of potentially contaminating the wound with oral flora.

Venom sequestration techniques, such as application of a lymphatic or superficial venous constriction band or pressure immobilization, may inhibit the systemic spread of venom.^20,¹⁹⁹ It is not clear, however, whether such measures improve outcome after pit viper envenomation. Some argue that restricting the spread of potentially necrotizing venom to local tissues may intensify injury.⁹² Because local sequelae are the predominant complications after pit viper envenomation (see Morbidity and Mortality, later), and because permanent systemic injury and death are rare, especially in North America, any attempt to strictly limit venom to the bite site is ill advised.⁵⁶ Tourniquets have worsened injury when used for snakebite and are contraindicated.⁸⁹

Pressure immobilization (P-I) has been used effectively in Australia for field management of elapid snakebites (see Chapter 55).²⁰⁰ This technique involves immediately wrapping the entire bitten extremity with an elastic wrap or crepe bandage as tightly as would be done for a sprain, and then splinting and immobilizing the extremity (Figure 54-30). P-I resulted in significantly longer survival, but higher intracompartmental pressures after artificial, intramuscular western diamondback rattlesnake (C. atrox) envenomation in a pig model.²⁴ In a separate small pig study using C. atrox venom, P-I again prolonged survival without evidence of worsening local tissue sequelae.¹⁴⁷ Additional conclusive research is necessary to definitively assess the risk–benefit ratio of using P-I in bites by snakes with necrotizing venoms. Furthermore, studies have shown that lay people as well as physicians have difficulty properly applying the bandage, generally underestimating the necessary tightness for effective application.^36,¹⁵⁶ Further complicating the clinical use of P-I is the fact that the victim must be carried out of the field following application of pressure immobilization, because walking stimulates muscular pumping of venom into the systemic circulation and negates any benefit, even in upper extremity bites.¹⁰² For these reasons, P-I is not routinely recommended at this time for use in pit viper bites. Certain scenarios may, however, warrant consideration of its use. Although it is difficult to predict snakebite severity at the time of the bite, certain factors may suggest an increased likelihood of a more severe envenomation: large snake size, particularly dangerous snake species, small patient size, prolonged fang contact, previous venomous snakebites (treated or not) or exposures to snakes, and delays to medical care and antivenom administration.¹⁰⁵ Individuals who consider using P-I must thoroughly familiarize themselves with the technique and must assess risks, benefits, and alternatives on a case-by-case basis. If P-I is applied after a snakebite, however, the wrap should not be removed until a source of definitive care is reached. Loosening the wrap may result in release of a venom bolus into the systemic circulation. Antivenom must be immediately available to treat such an event, and medications and equipment available to treat an immediate hypersensitivity reaction (see Allergy to Reptile Venom, later).