Visit us at www.vetlearn.com SEPTEMBER 2004 VOL 6.8 STANDARDS of CARE EMERGENCY AND CRITICAL CARE MEDICINE FROM THE PUBLISHER OF COMPENDIUM PIT VIPER ENVENOMATION IN DOGS Jonathan E. Fogle, DVM Resident, Internal Medicine Clinician Investigator Program Small Animal Internal Medicine College of Veterinary Medicine North Carolina State University Venomous snakes inhabit every region of the contiguous United States. Clinicians should be knowledgeable about the venomous snakes in their geographic region; such knowledge can assist in the diagnosis and treatment of snakebites in most veterinary patients. Geographic distribution of species, relative venom potency among species (Table 1), patient size, and location of bite(s) are important factors in selecting the most appropriate and cost-effective diagnostic and therapeutic regimens. A significant percentage of bites can be dry bites in which little or no venom is injected. Treatment ranges from minimal therapeutic intervention for mild envenomation to intensive critical care management for severe envenomation. For example, a large, healthy Labrador retriever bitten by a copperhead in a single site generally experiences mild to moderate swelling that typically resolves in 24 to 48 hours with minimal or no veterinary intervention. Conversely, a miniature dachshund suffering from rattlesnake envenomation may experience life-threatening cardiovascular collapse, even with aggressive therapeutic intervention. Two families of venomous snakes inhabit the United States: (1) pit vipers (so named for the heatsensing organ on their head; see box on page 3; also known as crotalids), which include copperheads, cottonmouths (also called water moccasins), and many species of rattlesnakes, and (2) elapids, which include coral snakes, cobras, mambas, and kraits. Of the elapids, only the coral snake (Micrurus fulvius fulvius and Micrurus fulvius tenere) is found in the United States. Although their venom is highly neurotoxic, coral snakes are generally docile. Envenomation of veterinary patients by coral snakes is extremely rare and is not discussed in this article. DIAGNOSTIC CRITERIA Historical Information Gender Predisposition: None. Age Predisposition: Dogs of any age can be affected. Geriatric patients with concurrent disease may be more difficult to manage. Breed Predisposition: Any breed can be affected, although hunting breeds are more at risk because their chances of encountering a snake are higher. Owner Observations Acute onset of swelling. The forelimbs, face, and muzzle are the most common sites of envenomation. Geographic Ranges of Selected Pit Vipers Clinicians should know which snakes are found in their geographic region. Copperheads (Agkistrodon contortrix) are found from southwestern Massachusetts west to Nebraska and south from central Texas to the Florida panhandle. Cottonmouths or water moccasins (Agkistrodon piscivorus) are found in wetlands from southeast Vir- Inside this issue: Peer-Reviewed Articles on 1 Pit Viper Envenomation in Dogs 6 Intestinal Intussusception 11 Instructions to Authors Questions? Comments? Email soc.vls@medimedia.com, fax 800-556-3288, or post on the Feedback page at www.vetlearn.com. 1
ginia to the Florida Keys, west to central Texas and Oklahoma, and north through central Missouri and southern Illinois. Eastern diamondback rattlesnakes (Crotalus adamanteus) are found from the coastal plains of southeastern North Carolina south to the Florida Keys and west along the Gulf Coast to extreme southeastern Louisiana. Timber rattlesnakes (Crotalus horridus) are found from southwestern Maine to the Florida panhandle, west to central Texas, and north to southwestern Minnesota. Western diamondback rattlesnakes (Crotalus atrox) are found from southeastern California east to central Arkansas. Western rattlesnakes or prairie rattlesnakes (Crotalus viridis) are found from western Iowa to Washington State south through California and western Texas. Other rattlesnakes of the genus Crotalus include the Mojave, sidewinder, tiger, rock, black-tailed, twin-spotted, speckled, red diamond, and ridgenosed rattlers; they are found in very discreet, localized regions throughout the western and southwestern United States. Readers are advised to consult a good reptile guide for more information. Rattlesnakes of the genus Sistrurus include massasaugas and pygmy rattlers. Pygmy rattlers are found in the southern quarter of the United States, south and east of Oklahoma and Arkansas. Massasaugas can be found in the southwestern United States north and east through New York State. Massasaugas are generally not found in the more extreme southeast portions of the country. Physical Examination Findings Swelling and pain at the envenomation site. Puncture wounds may not always be evident but often ooze blood. Tachycardia, pale mucous membranes, and prolonged capillary refill time. Laryngeal or pharyngeal edema resulting in dyspnea can occur with bites to the face, muzzle, or neck. Laboratory Findings Thrombocytopenia: Platelet count below 150,000/µl is a significant finding in an envenomated patient. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin clotting time (TT), and fibrin degradation products (FDPs) or D-dimers should all be evaluated every 6 to 8 hours for evidence of disseminated intravascular coagulation (DIC). Echinocytosis observed on peripheral blood smears may indicate envenomation. A wet mount prepared by mixing a drop of blood with a drop of saline can be examined for echinocytosis. Staining with Diff-Quik type stains can sometimes cause erythrocyte artifact similar to echinocytosis; thus, comparison of stained and unstained preparations is recommended. The degree of echinocytosis correlates somewhat with the severity of envenomation. KEY TO COSTS $ indicates relative costs of any diagnostic and treatment regimens listed. $ costs under $250 $$ costs between $250 and $500 $$$ costs between $500 and $1,000 $$$$ costs over $1,000 SEPTEMBER 2004 VOL 6.8 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 19067. The annual subscription rate is $69. For subscription information, call 800-426-9119, fax 800-556-3288, email soc.vls@medimedia.com, or visit www.vetlearn.com. Copyright 2004, Veterinary Learning Systems. Editor-in-Chief Douglass K. Macintire, DVM, MS, DACVIM, DACVECC Editorial, Design and Production Lilliane Anstee, Vice President, Editorial and Design Maureen McKinney, Editorial Director Cheryl Hobbs, Senior Editor Michelle Taylor, Senior Art Director Bethany L. Wakeley, Studio Manager Chris Reilly, Editorial Assistant Editorial Review Board Shane Bateman, DVM, DVSc, DACVECC The Ohio State University Jamie Bella, DVM, DACVS Auburn University Derek Burney, DVM, PhD, DACVIM Houston, TX Curtis Dewey, DVM, DACVIM, DACVS Plainview, NY Nishi Dhupa, DVM, DACVECC Cornell University Karen Inzana, DVM, PhD, DACVIM Virginia Maryland Regional College of Veterinary Medicine Fred Anthony Mann, DVM, MS, DACVS, DACVECC Missouri State University 2 S E P T E M B E R 2 0 0 4 V O L U M E 6. 8
TABLE 1 Relative Venom Toxicities of Selected Pit Viper Species a Snake Species Median Lethal Dose (mg/kg -1 ) in Mice Rattlesnakes (Crotalus) Mojave (C. scutulatus scutulatus) 0.23 Eastern diamondback (C. adamanteus) 1.68 Western diamondback (C. atrox) 2.18 Timber (C. horridus) 2.69 Pygmy rattlesnakes (Sistrurus) Pygmy (S. miliaris) 2.85 Massassauga (S. catentatus) 2.91 Other pit vipers (Agkistrodon) Cottonmouth (A. piscivorus) 4.19 Copperhead (A. contortrix) 10.92 a Adapted from Senter D, Carson T: Pit viper envenomation in dogs: Pathophysiology and treatment. Iowa Univ Vet 61(1): 21 26, 1999. Selected Anatomic Characteristics of Pit Vipers Double row of scales caudal to the anus Elliptic pupils Retractable fangs to inject venom Triangular-shaped head Heat sensing pits rostral to the eye and dorsal to the nostril Other Diagnostic Findings Blood pressure should be evaluated initially for evidence of hypotension and circulatory collapse. Because pit viper venom can contain cardiotoxins (Table 2), electrocardiographic monitoring is indicated for at least the first 24 hours. Summary of Diagnostic Criteria Identification of the snake species is very important. Rattlesnakes (especially the eastern diamondback) have very potent venom. Do not attempt to handle a live or dead snake. Recently killed snakes can still inject venom via postmortem muscle contractions. The presence of swelling is usually a hallmark of pit viper envenomation. The swelling should be measured periodically with a sewing tape measure or marked with a permanent marker to monitor progression. The only exception is Mojave rattlesnake envenomation, which may induce minimal swelling, but its venom contains a deadly neurotoxin. Hypotension results from a combination of factors. The primary etiology is massive release of fluid and protein from the vascular space into the extracellu- lar space following envenomation. Cardiotoxins can also reduce the pumping efficiency of the heart. Coagulation abnormalities often occur and can range from relatively benign defibrination syndromes to DIC and accompanying circulatory collapse. Diagnostic Differentials Other types of trauma. Wasp and bee stings. Anaphylactic or allergic reactions. TREATMENT RECOMMENDATIONS Initial Treatment Initially, one to five vials (10 ml/vial) of crotalid antivenin (Fort Dodge Animal Health) should be administered intravenously (refer to manufacturer s instructions for delivery guidelines). Antivenin administration is acceptable for any serious envenomation and in patients exhibiting thrombocytopenia, DIC, or circulatory collapse. There is no maximal dose of antivenin; the need for further doses should be evaluated every 2 to 4 hours. Serum sickness or other anaphylactic-type reactions reported in humans are rarely observed in dogs following antivenin administration. $$ $$$ Crystalloid fluid administration is indicated to maintain circulatory volume and adequate systemic pressure, as well as to ensure adequate renal blood flow and diuresis. $ Dexamethasone sodium phosphate (0.5 1 mg/kg; up to three does as needed) may be administered to patients not given antivenin. The major component of crotalid venom is phospholipase A 2. Steroids are potent inhibitors of phospholipase A 2 and can inhibit deleterious effects resulting from its actions. $ CHECKPOINTS The main constituent of crotalid venom is phospholipase A 2. Corticosteroids are potent phospholipase inhibitors, but some practitioners debate their utility in treatment. Fasciotomy for the treatment of compartment syndrome following envenomation is advocated by some veterinarians. Some practitioners with many years of experience in treating snakebites advocate the use of topical dimethyl sulfoxide. All reports to date are anecdotal, and no benefit has been demonstrated in controlled studies. STANDARDS of CARE: EMERGENCY AND CRITICAL CARE MEDICINE 3
TABLE 2 Venom Components and Actions of Selected Pit Vipers Component Action Phospholipase A 2 Elaboration of arachidonic acid from cell membranes. Formation of prostaglandins that promote vasodilation and thromboxanes that promote platelet aggregation. Echinocyte formation by erythrocytes. Hyaluronidase Digestion of connective tissue allows venom to spread along tissue planes. Kininogenase Formation of bradykinins and subsequent vasodilation Crotalase (eastern Defibrination syndrome diamondback) Crotalocytin Platelet activation with subsequent (timber rattler) thrombocytopenia Cardiotoxin Induction of arrhythmias and poor contractility Butorphanol (0.1 0.2 mg/kg IV q4h) may be administered once the patient is stable. Opioid analgesics at dosages that have minimal respiratory and cardiac inhibitory effects are preferred. Human patients report resolution of pain with antivenin administration alone. $ A patent airway should be maintained as needed. Supportive Treatment Diuresis: Snake venom toxins are highly destructive to blood vessels and basement membranes and can cause acute renal failure. $ Broad-spectrum antibiotics (ampicillin sulbactam or cefazolin [22 mg/kg IV q8h]): Used to combat infection at wound sites, especially from Clostridium spp. $ If adequate doses of antivenin are administered, supportive care with crystalloid fluids, antibiotics, and pain control is generally all that is needed. Fresh-frozen plasma (10 ml/kg IV over 4 6 hours) may be indicated in patients with abnormalities of PT or PTT and/or evidence of DIC if coagulation abnormalities are not controlled by antivenin administration alone. $$ Other Treatment Considerations Copperhead and cottonmouth envenomations rarely require antivenin treatment in dogs weighing more than 15 to 20 kg unless multiple bites are inflicted. Patients with lower body weights may require more antivenin than larger patients. Corticosteroids can be used if antivenin is unavailable or cost-prohibitive. ON THE NEWS FRONT Pure defibrination syndrome can result from eastern diamondback envenomation (C. adamanteus). The causative factor is a venom component called crotalase. Human patients with pure defibrination syndrome have very low concentrations of fibrinogen and increased concentrations of FDPs. Platelet counts, antithrombin III activity, and D-dimer concentration are usually normal. These patients generally do not experience uncontrolled hemorrhage. Human antivenin may be available for treatment of veterinary patients but is much more expensive than the veterinary product. Corticosteroids are contraindicated if antivenin is administered. Antivenin can be effective more than 24 hours after envenomation but is most effective when administered early. Patient Monitoring Blood pressure and heart rate should be closely monitored for the first 24 hours following envenomation. Normal blood pressure and heart rate are positive prognostic indicators. A high heart rate with normal or increased blood pressure may indicate that analgesia is inadequate. Hypotension, tachycardia, and coagulation abnormalities indicate the need for further doses of antivenin and more aggressive cardiovascular support. Progressive swelling, especially laryngeal or pharyngeal edema, indicates the need for antivenin. Coagulation parameters (platelet counts, PT, PTT, TT, and FDPs or D-dimers) should be monitored every 6 to 8 hours in patients showing evidence of coagulation abnormalities or other signs consistent with severe envenomation. Although serum sickness is not commonly observed in dogs administered antivenin, epinephrine is the treatment of choice if it does occur. Home Management Massive sloughing of skin may occur in the days to weeks after envenomation. Clients need to be counseled about wound care before their pet is sent home. Large areas of necrotic skin can slough, and the wound needs to be kept clean and dry. 4 S E P T E M B E R 2 0 0 4 V O L U M E 6. 8
Treatment Highlights Crotalid antivenin (Fort Dodge Animal Health), 1 5 vials (10 ml/vial) IV (follow manufacturer s instruction for delivery), should be administered initially. Crystalloid fluid administration is indicated to maintain circulatory volume and adequate systemic pressure, as well as to ensure adequate renal blood flow and diuresis. In those patients not given antivenin, one to three doses dexamethasone sodium phosphate (0.5 1 mg/kg as needed) should be administered. Butorphanol (0.1 0.2 mg/kg IV q4h) should be administered once the patient is stable. Ampicillin sulbactam or cefazolin (22 mg/kg IV q8h) is used to treat wound infections. Administration of fresh-frozen plasma (10 ml/kg IV over 4 6 hours) is indicated for patients with abnormalities of PT or PTT and/or evidence of DIC if coagulation abnormalities are not controlled by antivenin administration alone. Oral antibiotics should be administered until skin wounds have healed adequately. Milestones/Recovery Time Frames The most severe effects are generally seen within the first 12 to 24 hours following envenomation. Wounds that have severe sloughing may require surgical treatment, such as skin flaps or periodic debridement. Treatment Contraindications Diphenhydramine has no therapeutic benefit for envenomation and may unnecessarily sedate the patient. Intramuscular administration of antivenin is wasteful. With intravenous administration, venom is bound both systemically and at the envenomation site. Cryotherapy (ice packs) intensifies tissue damage. Incisions, sucking the wound, and fasciotomy exacerbate tissue damage. Topical dimethyl sulfoxide has not been proven to be beneficial. NSAIDs may exacerbate coagulation abnormalities and should not be used for analgesia. PROGNOSIS Favorable Criteria A bright attitude, alertness, and mobility indicate a patient with a favorable prognosis. Cessation of swelling indicates a favorable response to treatment and/or the lessening of venom effects. Normotensive patients with minimal coagulation abnormalities have a favorable prognosis. Dogs of large body size generally experience less severe signs. Unfavorable Criteria Progressive decline in blood pressure despite aggressive antivenin and crystalloid therapy is a poor prognostic indicator. Bites causing progressive swelling and closure of the airway may be more difficult to manage. Patients of small body size, patients with rapid systemic venom absorption (bites to the eye, tongue, or superficial veins), and geriatric patients generally have a less favorable outcome. Eastern diamondback rattlesnakes have extremely potent venom, and their bite can cause rapid cardiovascular decline despite aggressive treatment. Mojave rattlesnakes (found in Arizona, southern California, Nevada, and New Mexico) have a neurotoxin that may cause rapid death from respiratory failure. RECOMMENDED READING Behler JL, King FW: National Audubon Society Field Guide to Reptiles and Amphibians. New York, Alfred A. Knopf, 1979. and evaluation of treatments Part I. Compend Contin Educ Pract Vet 17(7):889 896, 1995. and evaluation of treatments Part II. Compend Contin Educ Pract Vet 17(8):1035 1040, 1995. and evaluation of treatments Part III. Compend Contin Educ Pract Vet 17(11):1385 1393, 1995. Senter D, Carson T: Pit viper envenomation in dogs: Pathophysiology and treatment. Iowa Univ Vet 61(1): 21 26, 1999. STANDARDS of CARE: EMERGENCY AND CRITICAL CARE MEDICINE 5