STANDARDS of CARE. There are two groups of venomous snakes in North EMERGENCY AND CRITICAL CARE MEDICINE CROTALID ENVENOMATIONS

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1 Peer Reviewed SEPTEMBER 2007 VOL 9.8 STANDARDS of CARE EMERGENCY AND CRITICAL CARE MEDICINE FROM THE PUBLISHER OF COMPENDIUM CROTALID ENVENOMATIONS Karen E. Seibold, DVM, DACVECC Animal Urgent Care and Specialty Group Escondido, California There are two groups of venomous snakes in North America, the Elapidae and the Viperidae. Crotalids are a genus of the Viperidae family. The Elapidae include the eastern and western coral snakes and are almost exclusively found in the southern states. The venom of the Elapidae is primarily neurotoxic. Elapidae envenomations generally result in minimal localized signs because of the need for these snakes to chew their prey for envenomation. Clinical signs that occur after envenomation include generalized weakness, which may progress to quadriplegia. Envenomation from these snakes is much less likely because the coral snake must chew its prey for envenomation. The Viperidae are the pit vipers and include rattlesnakes (genus Crotalus), cotton mouth water moccasins (Agkistrodon piscivorous), and copperheads (genus Agkistrodon). The venom of these snakes is hemotoxic and neurotoxic. Members of this group are found in all of the contiguous 48 states. This group accounts for the majority of envenomations that are encountered in veterinary patients. The majority of veterinary patients with these envenomations are dogs, but envenomations can also occur in cats. The severity of crotalid envenomation varies based on several criteria, including the time of year the bite occurs; location of the bite; age, species, and temperament of the envenomating snake at the time of the bite (warning strike vs. protective strike); age of the animal; preexisting health problems of the animal; and the time between envenomation and veterinary care. Pit vipers control the amount of venom they inject during a bite, so there is wide variation in bite severity. Crotalid venom is composed of a variety of proteolytic enzymes and peptides, including hyaluronidase, collagenase, and phospholipase A 2 and B. The venom varies in character depending on the time of the year, whether the snake has had a recent meal, and whether a defensive or offensive strike has occurred. Proteolytic enzymes can cause acute localized pain, swelling, erythema, ecchymosis, and tissue necrosis near the site of envenomation. Shock, fever, cardiac arrhythmias, disorientation, weakness, and petechiation remote to the site can also occur. Coagulopathies are often associated with crotalid envenomations. The Mojave rattlesnake contains a component in its venom that appears to have a curare-like effect that leads to paresis or paralysis. Death is caused by ventilatory failure. Venoms from other rattlesnakes have proteins that are immunologically similar to the Mojave rattlesnake neurotoxin. The Southern Pacific rattlesnake is believed to be a cross between western diamondback and Mojave green rattlesnakes, and it has produced some of the most toxic venom encountered in veterinary patients. DIAGNOSTIC CRITERIA Historical Information Being in a region known to harbor venomous snakes. Owners often witness the bite, see the snake, or hear the rattlesnake. Gender Predisposition None. Age Predisposition None. Breed Predisposition There is no breed predisposition, although small-breed dogs such as Parson Russell terriers (formerly known as Also in this issue: 5 Pulmonary Hypertension in Dogs 1

2 Jack Russell terriers) often present with multiple bites because of continued attacks on the snake. Owner Observations Progressive swelling of the muzzle or limb (Figure 1), which is very painful. Blood drops may be seen at the puncture sites. Dogs may have long strands of drool or bruising evident near the puncture wounds. Animals with Mojave rattlesnake envenomation may only have weakness and neurologic deficits. Physical Examination Findings Acute swelling associated with the envenomation site is generally asymmetric and painful and may reveal bruising near the puncture wounds. In animals with thick or long hair coats, puncture wounds can be difficult to identify. The wounds should be examined with care in case a fang has broken off and is protruding from the wound (a rare occurrence). Pain-related tachycardia. Dried blood spots. Tenacious drool. Ecchymosis or petechia. Lethargy or depression. Tachypnea. Weakness. Laboratory Findings Prothrombin time (PT) or activated partial thromboplastin time (aptt) may be elevated or become elevated. $ Echinocytes are present in 70% to 90% of crotalid envenomations. $ Elevated packed cell volume (PCV) and increased total protein. $ Elevated lactate levels. $ The chemistry panel may reveal elevations in liver and renal enzymes, which can progress to hypoalbuminemia if vasculitis and severe swelling are present. $ Complete blood count (CBC) and chemistry panels on presentation may be normal. Results of these tests may become abnormal over the course of therapy depending on the severity of the envenomation. $ Other Diagnostic Findings D-dimer tests may become positive in the face of disseminated intravascular coagulation (DIC). $$ Summary of Diagnostic Criteria History of being in environment that is known to harbor venomous snakes. Acute, painful, progressive swelling in the area of envenomation. KEY TO COSTS $ indicates relative costs of any diagnostic and treatment regimens listed. $ costs less than $250 $$ costs between $250 and $500 $$$ costs between $500 and $1,000 $$$$ costs more than $1,000 SEPTEMBER 2007 VOL 9.8 STANDARDS of CARE EMERGENCY AND CRITICAL CARE MEDICINE Editorial Mission: To provide busy practitioners with concise, peer-reviewed recommendations on current treatment standards drawn from published veterinary medical literature. This publication acknowledges that standards may vary according to individual experience and practices or regional differences. The publisher is not responsible for author errors. Compendium s Standards of Care: Emergency and Critical Care Medicine is published 11 times yearly (January/February is a combined issue) by Veterinary Learning Systems, 780 Township Line Road, Yardley, PA The annual subscription rate is $83. For subscription information, call , fax , soc.vls@medimedia.com, or visit Copyright 2007, Veterinary Learning Systems. Editor-in-Chief Douglass K. Macintire, DVM, MS, DACVIM, DACVECC macindk@vetmed.auburn.edu Group Publisher Ray Lender rlender@vetlearn.com Editorial, Design, and Production Maureen McKinney, Editorial Director Danielle Shaw, Editor Michelle Taylor, Senior Art Director Bethany L. Wakeley, Studio Manager Whitney Etter, Editorial Assistant Editorial Review Board Mark Bohling, DVM University of Tennessee Harry W. Boothe, DVM, DACVS Auburn University Derek Burney, DVM, PhD, DACVIM Houston, TX Joan R. Coates, DVM, MS, DACVIM University of Missouri Curtis Dewey, DVM, DACVIM, DACVS Plainview, NY Nishi Dhupa, DVM, DACVECC Cornell University D. Michael Tillson, DVM, MS, DACVS Auburn University 2 S E P T E M B E R V O L U M E 9. 8

3 Presence of dried blood spots consistent with fang punctures. Ecchymotic hemorrhages or progressive bruising. Echinocyte positive. Elevated PT or aptt. Progressive weakness, paresis, or quadriparesis. Diagnostic Differentials Anaphylactic reactions to bee or wasp stings: Stingrelated swelling is usually not painful and is often bilateral with hives. Systemic signs of vomiting, diarrhea, and collapse are not indicative of rattlesnake envenomation. Infection, cellulitis: History of illness generally for 24 to 48 hours associated with some kind of wound. This can occur secondary to envenomation that is not treated, which leads to infection. Hematoma. TREATMENT RECOMMENDATIONS Treatments recommendations vary with the severity of the envenomation. In some cases, the envenomation may be very mild and not require hospitalization or treatment. The following recommendations are for animals that have received a severe envenomation and require hospitalization and monitoring. Initial Treatment If the animal is in shock, it should be stabilized with IV fluids, oxygen, and analgesia. $$ Pain medications with or without sedatives should be administered if needed (butorphanol mg/kg SC, IM, or IV or hydromorphone mg/kg SC, IM, or IV). For very agitated dogs, acepromazine at mg/kg SC or IM may be given for sedation. Dosing should be repeated as needed. $ Dexamethasone sodium phosphate mg/kg IV single dose only should be given if the animal is presented within the first 2 hours after envenomation. Administration of corticosteroids is controversial for the treatment of inflammation associated with the local reaction of venom. If antivenin is going to be administered, then pretreatment with corticosteroids may suppress systemic reactions to the antivenin or delayed serum sickness. Repeated doses are not indicated. $ Diphenhydramine 2 4 mg/kg IM may suppress systemic reactions to antivenin and aid in calming the animal. $ Broad-spectrum antibiotics: Cefazolin 22 mg/kg IV tid or ampicillin 22 mg/kg IV tid until oral adminis- FIGURE 1 STANDARDS of CARE: EMERGENCY AND CRITICAL CARE MEDICINE Beagle puppy with severe swelling of the face and muzzle caused by envenomation. tration can be accomplished. (Ampicillin has a better anaerobic spectrum.) $ Crotalidae polyvalent antivenin should be given to animals with progressive signs of increased bruising, prolongation of clotting parameters, increasing pain, weakness, or paresis. Ten to 50 ml (one to five vials) of the rehydrated antivenin is administered IV. Repeat dosing is based on the clinical and laboratory parameters of the patient. In rare cases, additional doses may be indicated. Cats and smaller dogs often require multiple dose administration. Animals that have previously received antivenin must be treated very cautiously because secondary anaphylactic reactions are more common in them. Skin testing before administration may provide some indication of the potential reaction to antivenin administration. $$$$ Fresh-frozen plasma: Severe envenomations may result in marked vasculitis or disruption of the coagulation cascade, necessitating the administration of plasma. $$$ Hetastarch may be administered in animals with severe vasculitis that results in decreasing oncotic pressure and hypotension. $ Rarely, a dog is presented with an envenomation of the tongue or neck; these animals are at risk for upper airway obstruction and may require emergency tracheostomy. $$$ Tetanus toxoid, if available, is recommended because Clostridium tetani has been cultured from the mouths of some rattlesnake species. $ If an animal requires antivenin therapy and cannot tolerate or does not respond to equine polyvalent antivenin, then Crotalidae polyvalent immune Fab (CroFab), an ovine polyvalent antivenin, may be considered. CroFab antivenin is currently the 3

4 4 antivenin of choice in humans. Unpublished data in dogs suggest that a single vial of CroFab antivenin is equivalent to five vials of the equine-based polyvalent antivenin and has a lower risk of reaction and serum sickness. Although it has been reported in dogs, serum sickness is rarely encountered in veterinary patients. The author s experience with this product in dogs is promising, but given the tremendous cost ($1,000/vial), it is unlikely to ever become a recommended treatment in veterinary patients. $$$$ Supportive Treatment The bite area should be cleaned well. Shaving the area and marking the edge of the bruising provides a means to follow the progression of the bruising and swelling during the course of therapy. Nutritional support should be provided, especially in animals that have severe vasculitis resulting in hypoalbuminemia. Envenomations that occur on the limbs often result in profound swelling and oozing from the limb. These areas can lose vascular supply, resulting in death and necrosis of the surrounding tissue. Appropriately managing these wounds is important to reduce infection. Skin flap repair is warranted in wounds that result in large defects. Patient Monitoring PT or partial thromboplastin time (PTT) after the initial treatment and then again in 8 to 12 hours. Often there is an initial improvement, but a prolongation of PT or PTT is an indication for repeated administration of antivenin. CBC and platelet counts. Chemistry panels if the patient is not responding. Repeat physical examinations and examinations of mucous membrane color and capillary refill time. Urine production. Electrocardiography monitoring for arrhythmias. ON THE NEWS FRONT Rattlesnake Vaccine, Red Rocks Biologics (Woodland, CA): Crotalus atrox toxoid is produced from inactivated C. atrox (western diamondback rattlesnake) venom combined with an aluminum hydroxide adjuvant and thimerosal as a preservative. There have not been any peer-reviewed data, publications, or independent research on the vaccine s efficacy or potential for adverse effects. Red Rocks Biologics has provided the only information about the product. Further investigation of this vaccine is warranted before routine administration. S E P T E M B E R V O L U M E 9. 8 Home Management All patients should be treated with antibiotics Observing for listlessness, low-grade fever, and joint pain for several weeks after envenomation is important because these may be early signs of serum sickness. The CBC and general health profiles should be rechecked 7 to 10 days after envenomation to evaluate for any residual renal or hepatic changes. Milestones/Recovery Time Frames Dogs that are willing to eat within the first 12 hours after envenomation and treatment generally have a good prognosis. Reduction in the pain associated with the envenomation generally coincides with antivenin administration. Continued severe pain is an indication that additional antivenin is required. Reduction in the progression of bruising is expected when adequate antivenin administration has been administered. Swelling associated with crotalid envenomation may take 5 to 10 days to resolve. Treatment Contraindications Surgical placement of drains into the areas of edema associated with the vasculitis that occurs after recent envenomation is not indicated and may lead to introduction of deleterious bacteria into already compromised tissue. Nonsteroidal antiinflammatory drugs. Dimethyl sulfoxide. Any form of suction of the venom from the wound via kits provided for human use or by mouth. PROGNOSIS Favorable Criteria Reduction in pain, swelling, and bruising associated with the envenomation site. Normal CBC and clotting parameters 8 to 12 hours after therapy. Normal appetite after treatment. Unfavorable Criteria Prolongation of PT or PTT after repeated doses of antivenin. Azotemia. Hemoglobinuria. Progressive weakness to quadriplegia. Development of labored breathing, hypotension, bloody diarrhea, or oliguria. (continues on page 12)

5 CROTALID ENVENOMATIONS (continued from page 4) Development of DIC. Cardiac arrest. RECOMMENDED READING Berdoulay P, Schaer M: Case report: Serum sickness in a dog associated with antivenin therapy for snake bite caused by Crotalus adamanteus. JVECC 15:206, Fogel JE: Pit viper envenomation in dogs. Stand Care 6(8):1 5, Ford RB, Mazzaferro EM: Handbook of Veterinary Procedures and Emergency Treatment, ed 8. St Louis, Saunders Elsevier, 2006, pp Hackett TB, Wingfield WE, Mazzaferro EM, et al: Clinical findings associated with prairie rattlesnake bites in dogs: 100 cases ( ) JAVMA 220(11): , Macintire DK: Miscellaneous emergencies, in Manual of Small Animal Emergency and Critical Care Medicine. Philadelphia, Lippincott Williams and Wilkins, 2005, pp Najman L, Seshardi R: Rattlesnake envenomations. Compend Contin Educ Vet 2007, pp Willey JR, Schaer M: Eastern diamondback rattlesnake (C. adamanteus) envenomation of dogs: 31 cases ( ). JAAHA 41:22 33, Woods P: Snakebite (envenomations), in Mathews KA (ed): Veterinary Emergency and Critical Care Manual. Guelph, Ontario, Canada, Lifelearn, 2006, pp