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Pit viper envenomation in a military working dog.

During routine training in a wooded area on Marine Corps Air Station Cherry Point, North Carolina, on December 5, 2011, military working dog (MWD) Dingo M063 was bitten by a pit viper on the left front limb. The MWD handlers rushed the dog to the Cherry Point Veterinary Treatment Facility (VTF) for initial stabilization. The dog had profound swelling and bruising of the affected limb, along with puncture wounds consistent with a potentially fatal venomous snake bite. The patient was assessed and initial stabilization performed at the Cherry Point VTF. Based upon consultation and Dingo's clinical condition, administration of antivenin was selected as the course of treatment. After initial efforts to obtain the antivenin locally were unsuccessful, the decision was made to evacuate Dingo to the Norfolk (Virginia) Naval Station VTF for antivenin administration and continued intensive care and monitoring.

When a snake bite occurs, occasionally the dog handler, or owner in the case of a pet, sees the offending snake. Often the snake is never seen or identified. The attending veterinarian must use the clinical presentation, patient history, and knowledge of the local fauna to determine the appropriate treatment protocol. Occasionally the dog may vocalize, which is followed by lameness, swelling, bruising, and sometimes bleeding from the bite wounds. Many venomous bites are due to accidental contact with the snake. There are 37 species of snakes located throughout North Carolina; of those only 6 are venomous, (1) and only 5 of the 6 could inflict a venomous bite consistent with that suffered by Dingo. The 5 snakes all belong to the family Viperidae, subfamily Crotalinae. (2) Specifically, they are the Copperhead (Agkistrodon contortrix), Canebrake rattlesnake (Crotalus horridus atricaudatus), Eastern Diamondback rattlesnake (Crotalus adamanteus), Pigmy rattlesnake (Sistrurus miliarius), and Cottonmouth or Water Moccasin (Agkistrodon piscivorus). (1)

When the snake bite occurred, the area veterinary clinical medicine officer was consulted to provide guidance on the immediate treatment of the bite and aid in development of the most appropriate treatment plan. This input facilitated prompt decision-making, resulting in evacuation of the MWD. The local kennel master at Cherry Point reported the incident to his chain of command, and helped coordinate with Marine Transport Squadron One to arrange emergency medical evacuation from Cherry Point to the Norfolk Naval Station. Dingo M063 was transported to Norfolk in a Marine Corps HH-46D Sea Knight search and rescue helicopter. The MWD did well during transport and arrived at Norfolk in stable, albeit critical, condition. The antivenin, CroFab (BTG International Ltd, London), was provided by the Naval Medical Center, Portsmouth, Virginia. The MWD was treated with antivenin and received supportive care overnight. Dingo M063 improved significantly after antivenin administration and made a full recovery with return to duty one week later.

CLINICAL VIGNETTE

At time of initial presentation, the handlers did not report any vocalization or decrease in effort while working, but noticed profound swelling of the left front leg after clearing the edge of a wooded area. Dingo M063 was bright, alert, responsive, and panting heavily upon presentation. He had a barely perceptible lameness in the left front limb, despite marked swelling in the area of the distal elbow. Abnormal physical exam findings included an elevated temperature at 106.4[degrees]F (99.5[degrees]F -102[degrees]F), tachycardia at 140 beats per minute (bpm) (80 bpm-100 bpm) with strong synchronous pulses, and a small spot of fresh blood on the left dorsal antebrachium. He also had moderate to severe firm swelling extending from the left mid-antebrachium to the region of the elbow. The area of the swelling was gently palpated to rule out trauma and/or fracture, and then the skin overlying the swelling was shaved (Figure 1). Two small puncture wounds (Figure 2) and severe bruising were noted on the left dorsal antebrachium. Based on the history, presentation, and initial findings, it was determined the MWD had been struck by a venomous pit viper.

A cephalic intravenous catheter was placed, and the MWD was given 2 quarter shock doses of intravenous crystalloid fluids (1,500 mL lactated ringers), followed by a maintenance fluid rate. The area of the puncture wounds was scrubbed with an antiseptic solution. As shown in Figure 1, the margin of the bruising was marked with permanent ink to allow monitoring for progression of the swelling. The blood pressure was normal, and an electrocardiogram (ECG) showed a normal sinus rhythm. A complete blood count and serum biochemistry profile were performed. A mild decrease in platelet count was noted (125,000/ul, reference interval 200,000/ul to 400,000/ul), and all other values were normal. An intravenous dose of buphrenorphine (0.0075 mg/kg, 0.0034 mg/lb) was given to relieve discomfort associated with the bite. The patient's temperature dropped to 99.1[degrees]F within 35 minutes after presentation, and the pulse and respiratory rate normalized. The mucous membranes were pink, but tacky. The MWD was quiet, alert, and responsive, but clearly uncomfortable.

The MWD was evacuated to the Norfolk Naval Station VTF by helicopter, and arrived in stable condition. The swelling and bruising showed significant progression since presentation, and a second bite wound was noted on the mid-caudal aspect of the antebrachium (Figure 3). Activated partial thromboplastin time, and prothrombin time were normal upon arrival at the Norfolk VTF. After Dingo M063 was reassessed, one vial of intravenous Crotalidae Polyvalent Immune Fab (CroFab) was administered. Marked improvement in the swelling and bruising (Figure 4) was noted within one hour of beginning administration of the antivenin. The majority of the swelling resolved over the next 24 to 48 hours. The MWD was bright and alert the next morning, and using the limb with minimal signs of discomfort. He was transported back to Cherry Point 72 hours later (Figure 5), and was returned to work within one week. He went on to make a full recovery, with no lasting effects of the envenomation.

CURRENT TREATMENT FOR PIT VIPER ENVENOMATION

Background

The name pit viper is derived from the presence of a heat sensing pit organ located on the head. (3) Pit viper envonomation occurs throughout the United States, with the majority of bites occurring between the months of April and October. (4) However, the seasonal occurrence can vary significantly depending on location and weather patterns, as was the case with Dingo M063. Approximately 25% of pit viper bites are known as "dry bites," meaning no venom was injected. (3-5) As expected, dry bites result in a much less severe presentation. In the absence of the snake itself, or accurate owner/handler identification of the snake, the clinician must use the history and physical examination to rule out other causes for the given presentation, such as trauma, other animal bites, wounds, or bites from venomous insects.

The severity of the bite can vary considerably between patients. Factors such as size and age of the victim, species of snake, size and age of the snake, amount of venom injected, location of bite, number of bites, and depth of envenomation can all play a role in the severity of clinical signs in the patient. (5,6) General location of the bite may vary between patients, but bites to the head and neck can be particularly serious if swelling causes obstruction of airflow. Studies have found the majority of dog envenomations occur in the head and neck. (7)

The venom itself is 90% water (6) combined with a very stable and complex mix of proteins such as phospholipase, hyaluronidase, collagenase, and proteases. (3) These compounds cause various local and systemic effects on the victim, including local tissue destruction, and endothelial damage. Endothelial damage results in extravasation of fluid and red blood cells, followed by edema, swelling, and potentially reduced circulating blood volume leading to hypotension, hypovolemia, and shock. (4) Pooling of blood within the shock organ (liver and spleen in dogs) also contributes to hypotension and shock. (6) The venom proteins also have a variety of toxic effects on other cells throughout the body, including blood cells, myocardium, skeletal muscle, soft tissues, and cells of the respiratory and nervous systems. (5) Venom characteristics vary significantly across snake species, with some causing more severe and varied damage compared to others. (6) Some pit vipers, such as the Mojave rattlesnake and several others, possess a neurotoxin containing venom which results in ascending flaccid paralysis. These snakes can possess only a neurotoxic venom, which would cause neurologic dysfunction in the absence of the other clinical signs, or a combination of neurotoxic and hematoxic venom. (8)

The complex venom composition can also have various effects on the coagulation system. The venom proteins have pro- and anticoagulant properties, and can cause fibrin degradation, direct damage to blood vessel walls, and impaired platelet function. (3) These changes can result in an anticoagulant condition similar to disseminated intravascular coagulation. (3) Therefore, monitoring clotting times, (prothrombin time (PT), activated partial thromboplastin time (APTT)), and platelet levels is an important component of patient evaluation and monitoring.

Initial Evaluation

A thorough evaluation and physical examination should be performed when a pit viper envenomation is suspected. Signs observed are related to the toxic effects of the venom as previously discussed, and vary in onset. Most commonly, the first clinical signs appear 30 to 60 minutes after the bite, (4) but may take up to 24 hours to develop in some cases. (5) Due to the wide-ranging effects of venom throughout the body, a varying array of both local and systemic clinical signs can be observed. These clinical signs include hypotension, tachycardia, tachypnea, swelling and bruising in the area of the bite, bleeding/oozing puncture wound, pain, weakness, nausea, diarrhea, mental depression, and potentially neurologic deficits. (9) A snake bite severity score is a useful tool for determining severity of the bite, and for monitoring progression. This can allow the clinician to make a more impartial patient assessment. (10)

A complete blood count, serum biochemistry profile, and coagulation parameters (PT, APTT, and fibrinogen if available) should be checked as soon as possible after presentation. Thrombocytopenia and coagulation abnormalities are common with pit viper envenomation, and echinocytosis is commonly seen on blood film examination. (9) Other diagnostic tests should include ECG, urinalysis, and blood pressure. (5) Repeat tests should be conducted as necessary, based on the patient's clinical condition and response to treatment.

Treatment

Significant variation in treatment protocols for pit viper envenomation exists in both human (11) and veterinary medicine. (5) Evidenced-based support in veterinary medicine for therapies commonly used in the past, such as glucocorticoids and antihistamines, is not available and therefore these therapies are controversial. They are often reserved for treatment of antivenin hypersensitivity reactions, as opposed to the envenomation itself. Emergency treatments such as tourniquets, incision and suction, and cryotherapy are not recommended in human (11) or veterinary medicine (6) due to lack of efficacy. Immobilization and timely transport to the nearest veterinary treatment facility is the most appropriate emergency treatment. (4,5) The fundamentals of treatment are fluid therapy, pain management, wound management, and antivenin therapy when appropriate and practical.

The area around the envenomation site is clipped and scrubbed to allow visualization of the degree of bruising and swelling; the area is scrubbed with an antiseptic to prevent further infection. It is useful to mark the area of swelling and bruising with a marker every 15 minutes, and to measure the circumference of the limb. This will help determine severity and progression, and aid in determining the need for antivenin administration. (3,4)

Crystalloid fluid therapy is administered to correct hypovolemia and treat shock. It is generally administered in one-quarter shock doses, followed by a maintenance rate. Assessment of response to therapy and need for additional boluses is generally done using clinical parameters such as mucous membrane color, capillary refill time, blood pressure, and urine output. (3)

Administration of antibiotics is left to the discretion of the clinician, but is generally not recommended for prophylactic treatment, (5) but rather if there are signs of an actual infection. (3,11) Venom can travel in the lymphatics, resulting in a lymphadenopathy which may be mistaken for secondary infection. (9) The human literature only advocates the use of antimicrobials where there is evidence of wound infection, and then the choice should be based on culture and sensitivity. (4) There are recommendations in the veterinary literature suggesting broad-spectrum antibiotics are appropriate due to the degree of tissue damage that occurs, and because of the population of bacteria found in the mouth of snakes. (6,9)

Opioids are a good analgesic choice for snakebite envenomation. It is important to avoid high doses of potent opioids in the acute treatment phase to prevent masking of the patient's neurologic status. Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally not recommended due to risk of associated side effects such as gastrointestinal ulceration and nephropathy in a compromised patient. The use of NSAIDS can also increase the risk of bleeding due to impaired platelet aggregation in a coagulopathic patient. (5)

One of the primary therapies for pit viper envenomation is administration of antivenin. Historically, not all studies have supported the use of antivenin in every type of pit viper envenomation (9,12) and others have found a higher survival rate in dogs administered antivenin as compared with those that did not receive it. (7) These converging findings from studies of different pit viper species highlights the significant variation in venom composition among species, which influences the severity of the bite. Indications for use include rapidly advancing local swelling and tissue damage, severe and ongoing coagulation abnormalities, neurologic signs, and cardiovascular compromise. (13) In general, its use in veterinary medicine is determined by affordability, availability, (5) severity of envenomation, and the clinician's education and experience in treating snake envenomations. It is ideally administered within 4 hours of the bite, but may be effective up to 24 hours after envenomation. (3) Antivenin administration is known to slow the progression of swelling and resolve venom-associated coagulopathies, (5) and is the only proven specific therapy to treat pit viper envenomation. (6)

There are currently 2 antivenin products available in the United States, Antivenin (Crotalidae) Polyvalent (ACP) (Boehringer Ingelheim Vetmedica, St Joseph, MO) and CroFab. The ACP product has been around much longer, contains whole IgG, and is an equine-derived product. The CroFab product is ovine-derived. The individual molecules in CroFab are much smaller because the antigenic [F.sub.c] portion of the antibody is eliminated, and the product contains much less constituent total protein than the ACP product. (4) CroFab is more potent than ACP (5.2 times), (14) but it is also more expensive. A recent study found that the CroFab antivenin was effective in treating rattlesnake envenomation in dogs. (14) The smaller sized Fab molecules are also eliminated much faster, and therefore could result in excretion prior to neutralization of all venom and recurrence of clinical signs, which would necessitate re-dosing. This has been observed in humans. (14) CroFab antivenin was available at the Naval Medical Center, Portsmouth, and was used to treat Dingo M063.

The newer ovine-derived product carries a lower risk of reaction following administration. (3,8) The occurrence of adverse reactions following administration is less common with CroFab (14.3%) than with ACP (23% to 56%) in human medicine. (4) The above mentioned study using CroFab in dogs showed a 5.2% incidence rate of adverse reactions. (14) Hypersensitivity reactions can occur, resulting in anaphylaxis (type 1), anaphylactoid reactions (complement mediated), or delayed serum sickness (type 3), and are treated with a combination of diphenhydramine and epinephrine. (5) Anaphylactoid reactions are most common, (6) but delayed serum sickness has been reported following ACP administration. (15) Antivenin dosing in dogs is based on clinical signs and coagulation parameters, (3) and can therefore vary significantly between patients. A snake bite severity score can also aid in guiding antivenin dosing. (14)

Even with antivenin administration, significant tissue damage can occur. Due to the toxic and complex nature of the venom, the damage can occur quickly depending on the location of the bite and amount of venom injected. Once tissue necrosis has occurred, antivenin administration will not reverse the damage, only prevent further damage. (3,5) If tissue sloughing occurs, long term wound management becomes necessary.

PREVENTION

There is a veterinary-approved rattlesnake vaccine available (Red Rock Biologics, Woodland, CA) which was developed to provide protection against envenomation by a Western Diamondback Rattlesnake. However, there are no peer-reviewed canine studies available to document its efficacy. The 2011 American Animal Hospital Association Canine Vaccination Guidelines do not make a specific recommendation for or against the vaccine due to lack of available data regarding its efficacy. (16) As a practical matter, prevention of the actual bite would be very challenging in most dogs because of their curious disposition and the nature of pit vipers.

CONCLUSION

In certain parts of the United States, pit viper envenomation can occur throughout the year, particularly during mild winters when envenomation is unexpected. It is useful for veterinary practitioners to be aware of the local fauna, and which animals or insects commonly cause illness/injury to dogs. This can be challenging for Veterinary Corps officers who are frequently assigned to duty sites in areas with which they are unfamiliar, but should be a priority if they are caring for military working dogs. It is also important to know the availability of antivenin in the local area. Cornerstones of treatment include pain management, intravenous fluid administration, antivenin administration, and wound management as needed. Prompt decision making, use of available resources, and appropriate treatment of clinical signs can result in a very positive outcome in these cases.

REFERENCES

(1.) North Carolina Venomous Snakes. North Carolina State University Cooperative Extension web site. Available at: http://www.ces.ncsu.edu/gaston/ Pests/reptiles/venomousnake.htm. Accessed June 3, 2012.

(2.) Castoe T, Parkinson C. Bayesian mixed models and the phylogeny of pit vipers (Viperidae: Serpentes). Mol Phylogenet Evol. 2006;39:91-110.

(3.) Najman L, Seshadri R. Rattlesnake envenomation. Compend Cont Educ Vet. 2007;29(3):166-177.

(4.) Gold B, Barish R, Dart R. North American snake envenomation: diagnosis, treatment, and management. Emerg Med Clin North Am. 2004;22:423-443

(5.) Armentano R, Schaer M. Overview and controversies in the medical management of pit viper envenomation in the dog. J Vet Emerg Crit Care. 2011;21(5):461-470.

(6.) Peterson M. Snake bite: pit vipers. Clin Tech Small Anim Pract. 2006;21:174-182.

(7.) Willey J, Schaer M. Eastern diamondback rattlesnake (Crotalus adamanteus) envenomation of dogs: 31 cases (1982-2002). J Am Anim Hosp Assoc. 2005;41:22-33.

(8.) Hoggan S, Carr A, Sausman K. Mojave toxin-type ascending flaccid paralysis after an envenomation by a southern pacific rattlesnake in a dog. J Vet Emerg Crit Care. 2011;21(5):558-564.

(9.) Gilliam L, Brunker J. North American snake envenomation in the dog and cat. Vet Clin North Am Small Anim Pract. 2011;41:1239-1259.

(10.) Peterson M. Snake envenomation. In: Silverstein DC, Hopper K. Small Animal Critical Care Medicine. St. Louis: Saunders Elsevier; 2009:399.

(11.) Lavonas EJ, Ruha AM, Banner W, et al. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med. 2011;11(2):1-15.

(12.) Hackett TB, Wingfield WE, Mazzaferro EM, Benedetti JS. Clinical findings associated with prairie rattlesnake bites in dogs: 100 cases (1989-1998). J Am Vet Med Assoc. 2002;220(11):1675-1680.

(13.) McCown JL, Cooke KL, Hanel RM, Jones GL,

Hill RC. Effect of antivenin dose on outcome from crotalid envenomation: 218 dogs (1988-2006). J Vet Emerg Crit Care. 2009;19(6):603-610.

(14.) Peterson ME, Matz M, Seibold K, Plunkett S, Johnson S, Fitzgerald K. A randomized multicenter trial of Crotalidae polyvalent immune F(ab) antivenom for the treatment of rattlesnake envenomation in dogs. J Vet Emerg Crit Care. 2011;21(4):335-345.

(15.) Berdoulay P, Schaer M, Starr J. Serum sickness in a dog associated with antivenin therapy for snake bite caused by Crotalus adamanteus. J Vet Emerg Crit Care. 2005;15(3):206-212.

(16.) Welborn LV, DeVries JG, Ford R, et al. 2011 AAHA Canine Vaccination Guidelines. American Animal Hospital Association website. Available at: https:// www.aahanet.org/PublicDocuments/CanineVac cineGuidelines.pdf. Accessed September 18, 2012.

CPT Curtis R. Cline, VC, USA

MAJ Michelle E. Goodnight, VC, USA

CPT Cline is the Officer-in-Charge, Cherry Point Veterinary Treatment Facility, Marine Corps Air Station, Cherry Point, North Carolina.

MAJ Goodnight is the Chief of Clinical Services, Fort Bragg Veterinary Center, Fort Bragg, North Carolina. She is also the Veterinary Clinical Specialist, US Army Public Health Command District, Fort Eustis, Virginia.
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Author:Cline, Curtis R.; Goodnight, Michelle E.
Publication:U.S. Army Medical Department Journal
Article Type:Clinical report
Geographic Code:1USA
Date:Jan 1, 2013
Words:3433
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