Snake Bite: Pit Vipers Michael E. Peterson, DVM, MS Pit vipers are the largest group of venomous snakes in the United States and are involved in an estimated 150,000 bites annually of dogs and cats. The severity of any pit viper bite is related to the volume and toxicity of the venom injected as well as the location of the bite, which may influence the rate of venom uptake. The toxicity of rattlesnake venom varies widely. It is possible for pit vipers’ venom to be strictly neurotoxic with virtually no local signs of envenomation. Venom consists of 90% water and has a minimum of 10 enzymes and 3 to 12 nonenzymatic proteins and peptides in any individual snake. The onset of clinical signs after envenomation may be delayed for several hours. The presence of fang marks does not indicate that envenomation has occurred, only that a bite has taken place. Systemic clinical manifestations encompass a wide variety of problems including pain, weakness, dizziness, nausea, severe hypotension, and thrombocytopenia. The victim’s clotting abnormalities largely depend upon the species of snake involved. Venom induced thrombocytopenia occurs in approximately 30% of envenomations. Many first aid measures have been advocated for pit viper bite victims, none has been shown to prevent morbidity or mortality. Current recommendations for first aid in the field are to keep the victim calm, keep the bite site below heart level if possible, and transport the victim to a veterinary medical facility for primary medical intervention. The patient should be hospitalized and monitored closely for a minimum of 8 hours for the onset of signs of envenomation. The only proven specific therapy against pit viper envenomation is the administration of antivenin. The dosage of antivenin needed is calculated relative to the amount of venom injected, the body mass of the victim, and the bite site. The average dosage in dogs and cats is 1 to 2 vials of antivenin. Clin Tech Small Anim Pract 21:174-182 © 2006 Elsevier Inc. All rights reserved. KEYWORDS rattlesnake, copperhead, water moccasin, pit viper, envenomation, snake bite, antivenin wo families of poisonous snakes, the Elapidae and Cro- scales distal to the anal plate, and triangular shaped heads Ttalidae, indigenous to the United States. The Crotalids (Fig. 1).Crotalus and Sistrurus genera (the rattlesnakes) have are represented by the pit vipers. Every state except Maine, special keratin rattles on the ends of their tails, with the Alaska, and Hawaii is home to at least one species of venom- exception of one subspecies (C. catalinensis). Agkistrodon spe- ous snake. cies (the copperheads and water moccasins) are found Pit vipers are the largest group of venomous snakes in the throughout the eastern and central United States. Copper- United States and are involved in an estimated 150,000 bites heads are responsible for the majority of venomous snake annually of dogs and1 Approximatelycats. 99% of all venom-bites in North America because of their habit of living next to ous snake bites in the United States are inflicted by pit vipers. human habitation. Water moccasins can be pugnacious and In North America members of the family Crotalidae belong to have a greater tendency to deliver venom when they bite. three genera: the rattlesnakes (Crotalus and Sistrurus spp.) Rattlesnakes (Crotalus spp., Sistrurus spp.) are found and the copperheads and cottonmouth water moccasins throughout the continental United States and account for the (Agkistrodon spp.). majority of snake bite fatalities. Clinicians should become Pit vipers can be identified by their characteristic retract- familiar with their regional indigenous poisonous snake spe- able front fangs, bilateral heat sensing “pits” between the cies. nostrils and eyes, elliptical pupils, a single row of subcaudal Ninety percent of venomous snake bites occur during the months of April through October. Two-thirds of the bites are inflicted by snakes less than 20 inches in length. These snakes Reid Veterinary Hospital, Albany, OR. can strike approximately one-half of their body length at a Address reprint requests to Michael E. Peterson, DVM, MS, Reid Veterinary Hospital, 933 SW Queen Avenue, Albany, OR 97321. E-mail: speed of 8 feet per second. The heat-sensing pit located be- [email protected] tween the eye and the nostril can differentiate a temperature 174 1096-2867/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.ctsap.2006.10.008 Snake bite: Pit vipers 175 Table 2 Examples of Enzymes From Pit Viper Venoms Arginine ester hydrolase Phosphodiesterase Proteolytic enzymes Acetylcholinesterase Thrombinlike enzyme RNAse Collagenase DNAse Hyaluronidase 5’-Nucleotidase Phospholipase A2 NAD-nucleotidase Phospholipase B Lactate dehydrogenase Phosphomonoesterase L-amino acid oxidase liver a controlled amount of venom into the victim, and agonal bites deliver the entire venom load and are therefore the most dangerous. Toxic Dose The severity of any pit viper bite is related to the volume and toxicity of the venom injected as well as to the location of the bite, which may influence the rate of venom uptake. Gener- ally, the toxicity of pit viper venoms ranges in descending order from the rattlesnakes to the water moccasins and then to the copperheads (Table 1). The toxicity of rattlesnake venom varies widely. Nine species and 12 subspecies of rat- Figure 1 Pit viper skull retractable front fangs. Note secondary and tlesnakes have populations with venoms containing proteins tertiary fangs. Courtesy of the Arizona Desert Museum, Tucson, AZ. that are immunologically similar to mojave toxin, a potent (Color version of figure is available online.) neurotoxin. It is possible for pit viper venom to be strictly neurotoxic with virtually no local signs of envenomation. Examples of these venom types can be found in certain sub- gradient of 0.003°C at a distance of 14 inches. Rattlesnakes populations of rattlesnakes: Mojave rattlesnakes (C. scutula- do not always rattle before striking. A decapitated snake head tus), canebrake rattlesnakes (C. horridus atricaudatus), and can bite reflexively for up to an hour after decapitation. tiger rattlesnakesC. ( tigris).3-5 The venom is not more toxic in the summer months; how- ever, snakes show increased aggression and venom yield with environmental warming and increased photoperiod (as in the Toxicokinetics spring and summer).2 The maximum venom yields occur It may take weeks for all venom fractions to be cleared by the during the hottest months of summer. body. Because of the complexity of the venom, the victim’s Pit vipers control the amount of venom they inject depend- metabolic response to the venom components varies with the ing on the snake’s perception of the situation. Initial defen- species of snake, the volume of venom injected, and the sive strikes are often nonenvenomating. Offensive bites de- species of the bite recipient. Table 1 Venom Yields of North American Snakes Mechanism of Toxicity Dry Weight LD50 IV The primary purpose of the venom is not to kill but rather to Snake Species (mg venom) (mice) immobilize the prey and predigest its tissues. The venom is Eastern diamondback 200-850 1.68 derived from modified salivary glands. Pit viper venoms are a (Crotalus complex combination of enzymatic and nonenzymatic pro- adamanteus) teins (Table 2). Venom consists of 90% water and has a Western 175-800 2.18 minimum of 10 enzymes and 3 to 12 nonenzymatic proteins diamondback and peptides in any individual snake. The nonenzymatic (Crotalus atrox) Mojave rattlesnake 75-150 0.23 components, called the “killing fraction,” have a median le- (Crotalus thal dose (LD50) over 50 times smaller than that of the crude scutulatus) venom. Eastern coral 2-20 0.28 Over 60 purified polypeptides have been identified in cro- (Micrurus fulvius) talid venoms. Approximately 50 enzymatic crotalid venom Copperhead 40-75 10.92 fractions have been characterized. Proteolytic-trypsin like en- (Agkistrodon zymes, which are catalyzed by metals (eg, calcium, magne- contortrix) sium, zinc), are common constituents of pit viper venom and Cottonmouth 90-170 4.19 cause marked tissue destruction. Arginine ester hydrolase is a (Agkistrodon bradykinin-releasing agent that may adversely affect clotting piscivorus) activity. Thrombin like enzymes also can mediate increased 176 M.E. Peterson Table 3 Common Signs of Envenomation Table 4 Variables Affecting the Severity of Envenomation Pain Sloughing tissue Victim Snake Swelling Shock Body mass Species Ecchymosis Puncture(s) Bite location Size Weakness Nausea Time to medical facility Age of snake Type of first aid applied Motivation for bite Concurrent medications Time since last venom use clotting activity. The eastern diamondback rattlesnake (C. (nonsteroidal anti-inflammatory Time of year adamanteus) venom enzyme protease H induces systemic drugs, etc.) hemorrhage.6 Five proteolytic toxins from western -diamond back rattlesnake (C. atrox) venom induce hemorrhage by cleaving laminin and the basement membrane 7,8at band A. Crotavirin, found in prairie rattlesnake (C. viridis viridis) also be present and is responsible for hydrolyzing lysophos- venom, is a potent platelet aggregation inhibitor and prevents phatides. The phosphodiesterases, such as diester phospho- platelet-collagen interaction by binding to collagen fibers. hydrolase, breaks free the 5-mononucleotide, thereby attack- Interference with the platelet-collagen interaction has the net ing DNA and RNA and derivatives of arabinose. effect of blocking collagen-mediated platelet functions such L-amino acid oxidase catalyzes oxidation of L-alpha-amino as adhesion, release reaction, thromboxane formation, and and alpha-hydroxy acids. This is the most active of the aggregation.9 The predominant mechanism of afibrinogene- known amino acid oxidases and has been found in all pit mia seen in a patient after western diamondback rattlesnake viper venoms studied; it is responsible for the yellow color of (C. atrox) envenomation is a reflection of fibrinogenolysis the venom. NAD-nucleotidase is found in Agkistrodon but not and not a primary consumptive coagulopathy.