Y. Bruchim
Snakebites are a common problem in human and veterinary medicine. Vipers are member of the family Viperidae, a group of snakes found all over the world, except in Madagascar and Australia.
The viper family includes 223 species of venomous snakes that are divided into 2 main subfamilies: pit vipers (subfamily Crotalinae), true vipers (subfamily Viperinae). Vipers are characterized by a pair of long, hollow, venom-injecting fangs. They feed on small animals and hunt by striking and envenomating their prey. Pit vipers are the largest group of venomous snakes with 151 species and are responsible for ∼150,000 envenomations of dogs and cats in the United States annually.1 The other major subfamily, the true vipers, includes 66 species and is also known as pitless vipers. They are distinguished by their lack of the heat-sensing pit organs that characterize the pit vipers. Among them, Vipera berus is found from Western Europe and Great Britain to the Far East.2 Vipera palaestinae (VP) is the most common venomous snake in the Middle East. It is responsible for most envenomations in humans and domestic animals in Israel.3 The snake is endemic to Israel, can be found in all country parts except the desert, and has adapted to life in agricultural and suburban areas. Envenomations were reported in people, dogs, cats, horses and a ram.3,4
The viper’s venom contains about 30 components, 16 of which were identified, with the most important ones being proteases, hemorrhagins (metalloproteinases), amino acid esterases, phospholipase A2, phospholipase B and neurotoxins.5 The hemorrhagins’ activity leads to endothelial cell damage, causing high vascular permeability, bleeding and fluid extravasations into inflamed tissues. Phospholipase A2 is considered the most important component in many snake venoms. It has both procoagulant and anticoagulant activities as reflected by inhibition of the prothrombinase, inhibition and activation of platelet aggregation, and activation of Factor V and plasminogen.5 The amount of venom injected in a single bite increases with increased ambient temperatures and may reach as much as one gram (dry weight); nevertheless, bites may contain no venom at all.6
Most of canine Vp envenomations in Israel occur between May and October and between 14:00–22:00, and parallel the viper’s seasonal and diurnal activity. This pattern, however, may also result from increased seasonal and diurnal dog activity.4
The onset of clinical signs following envenomation may be delayed for several hours. This phenomenon is highlighted by the fact that 40% of all severe envenomations in humans are graded as mild to non-clinical signs upon admission. In addition, 20% of the bites were dry envenomations (venom free) with an additional 25% classified as mild envenomations.1 The severity of the envenomation is influenced by species and victim factors such as the bite location, victim body mass, post-bite excitability, the species and snake size, its age and motivation and the degree of venom regeneration since last bite.1
Risk factors (RF) for mortality in dogs included envenomation during the first summer months and low body weight (<15 kg), envenomations in the limbs and identification of the snake’s bite as well as shock and bleeding tendencies.3,4 In a recent study describing envenomation of 18 cats in Israel, variables associated with mortality included lower body weight, lower body temperature and haematocrit at arrival and 12–24 hours later, and lower total plasma proteins 12–24 hours post-presentation.
Most canine VP envenomations are in the head and neck area (80%) and less frequently in the limbs (20%).3,4 In a study on dogs with Vp envenomation, skin marks consistent of snakebite were identified in only 51% of the dogs.4 The most common local signs in canine snakebite include swelling, edema and hematoma which are attributed mostly to venom hemorrhaging activity. Acute lameness with pain may appear when limb envenomations occur.3 Reported systemic signs include anaphylactic, hemorrhagic or neurogenic shock, tachypnea, tachycardia, local lymphadenomegaly and cardiac arrhythmias.3 To date, no specific cardiotoxin has been identified in the viper’s venom, although myocardial necrosis as a rare complication was reported in dogs and horses following VP envenomation.7 Cardiac injury in VP-envenomed dogs was reflected by increased serum cardiac troponin T and I (biomarkers of myocardial damage).8,9 In the study, serum cardiac troponins concentrations were increased in 65% of the dogs envenomed by Vp. Dogs with increased cardiac troponin were found to have a significantly higher occurrence of arrhythmias (58% vs. 19%).8
The most common hematological findings in Viper envenomation include hemoconcentration, leucocytosis and thrombocytopenia and nucleated red blood cells in the peripheral circulation. Drastic drop of total solids in the first 24 h after envenomation is very common, as well as mild elongation of prothrombin (PT) and activated partial thromboplastin (aPTT) times and decrease in antithrombin activity. The most common biochemical abnormalities observed include increased activities of muscle enzymes: lactate dehydrogenase, creatine kinase and aspartate aminotransferase. Additional abnormalities included hypertriglyceridaemia, mild hyperglycaemia, hyperbilirubinaemia, hyperglobulinaemia and hypocholesterolaemia.4
Reported complications of Viper envenomation in dogs include bacterial infections (clostridial or other), local necrosis, upper respiratory airway obstruction due to laryngeal edema, acute renal failure, coagulation disorders namely venom-induced consumptive coagulopathy (VICC) and death.3 For dogs with Vp envenomation, the reported mortality rate in the literature is relatively low (3.7–6%).3,4
Venom-induced hemostatic abnormalities, potentially culminating in venom-induced consumptive coagulopathy (VICC), include thrombin inhibition and activation, increased fibrinolysis, hypofibrinogenemia, release of kinins, endothelial damage, and platelet aggregation, destruction and dysfunction. Viper-envenomed dogs commonly develop VICC, its frequency increasing over time during hospitalization. Although VICC is similar to DIC in many ways, it differs from the former by a rapid onset and resolution, different mechanism of initiation and it is not usually resulting in end-organ effects.
Cats are considered more resistant to snakebites than other animals.9 However, several studies published in the last decade have shown that mortality rate in cats varied between 6–22%. Although bleedings are not so common in cats, haemostatic abnormalities were reported in all cats, expressed by elongated aPTT in 100% and PT in 93% of the cats. Several RF were identified, including lower rectal temperature (p=0.02, 35.9°C vs. 38.0°C), lower haematocrit (29 vs. 44%, p<0.001) upon admission and lower haematocrit 24 h post-admission (22 vs. 33%, p=0.001). In our emergency department we see 2–6 cases of cat’s snakebites a year, as compared to 30–40 cases of dogs with snakebite. The discrepancy between dogs and cats for the limited cases might be the caution and the ability of cats to cope with snakes, cats are not referred to medical treatment since they do not show clinical signs nor are outdoor cats. Based on our limited experience, the diagnosis of cats with snake bites is not as obvious as in dogs. As the time lag from the snakebite to admission in cats is usually longer than in dogs, the most common clinical signs are local swelling with severe hematoma, which might develop over the 24–48 h post-snakebite, depression and shock. Hematological findings are hemoconcentration, thrombocytopenia, hypoproteinemia, hemolysis and consequent anemia, and the appearance of peripheral nucleated red blood cells. Disseminated intravascular coagulation also is a common complication in cats with snakebites with dramatic elongation of the PT and aPTT but relatively slight clinical signs that are characteristic to DIC in other species.
The clinical outcome following envenomation, however, is highly variable, partly depending on its anatomical location and the amount of venom delivered. Accordingly, clinical signs may remain local in up to 49% of human cases, limited to pain, hemorrhage, edema and regional lymphadenopathy, while in other cases in humans and dogs, systemic clinical signs may ensue, including shock, cardiac arrhythmias and bleeding. The reported mortality rate in humans is low, ranging from 0.5% to 2%, whereas in dogs it may reach 15%. Different VP-specific antivenin treatment protocols, the result of lower availability and financial constraints in veterinary medicine, may partly account for the discrepancy. Retrospective studies of VP envenomations in humans, unlike studies in dogs, espouse the use of specific antivenin to improve outcome, although robust evidence is lacking.
Different treatment regimes are used for VP envenomation in different (human or veterinary) institutions. These include antibiotics, antihistamines, steroids and specific antivenin.10 Dosing and timing are controversial, and may vary in different medical institutions. The Hebrew University Veterinary Treating Hospital (HUVTH) treatment protocol includes:
1. Fluid therapy
• Crystalloids: 10–20 mL/kg as a bolus.
• Colloids/fresh frozen plasma when DIC is suspected or when total solids (TS) are low (below 4 g/dL), as needed.
2. Antimicrobial therapy (ampicillin 25 mg/kg q8h for 5 days) to prevent clostridial or other infection that may have been transferred by the snake’s teeth.
3. Antihistamine - Diphenhydramine (2 mg/kg q8h for 24 h), only after hypersensitivity skin test for the antivenom has been completed.
4. Steroids - The use of glucocorticosteroids in snakebites has always been controversial. They are used in cases of shock and severe edema, particularly when in the larynx area, as they may minimize and/or prevent further endothelial damage. However, steroids may slow and diminish antivenom activity and increase the risk for bacterial infection. Some clinicians believe that the use of steroids is contraindicated in snakebites.10 In a retrospective study of 327 dogs with snakebite it has been shown that glucocorticoid therapy was significantly associated with mortality (p=0.002).4 Therefore, the use of steroids in HUVTH is limited to cases in which laryngeal edema is severe and may prevent tracheostomy.
5. Antivenin - it has been shown that treatment with low specific antivenin dose (10 mL) did not decrease mortality rate in dogs.4 However, in humans, the mortality is reported to decrease sharply from 6–10% to 0.5–2% since the introduction of the specific antivenin.12 Our recommendations, based on the findings in human medicine and our clinical experience, are that antivenin is to be administered to effect in cases of:
a. Clinical signs of shock.
b. Severe swelling at the site of the bite.
c. Abnormal coagulation parameters, including thrombocytopenia.
d. Owner’s financial abilities (10 mL cost in Israel approximately $250).
6. Monitoring for 24 h. This includes complete blood count (CBC), creatinine (q12h), PT and aPTT (q12h), PCV/TS (q12h), ECG (q2h), and blood pressure.
In conclusion, as was demonstrated by VP, a member of the viper family, viper snakebite has relatively low mortality rate both in humans and in dogs. Further investigation of snakebites in cats is needed. Risk factors for mortality include the first months of the summer, low patient body weight, limb envenomation, systemic clinical signs and coagulation disorders. Treatment with steroid is controversial and should be further investigated, while antivenin should be considered in cases in which one of the risk factors to death is present and not as a fixed dose but rather to effect.
References
1. Peterson ME. Snake envenomation. In: Proceedings of the International Veterinary Emergency and Critical Care Symposium, May 2007, New Orleans.
2. Kangström LE. Snake bites (Vipera berus) in dogs and cats. Svensk Veterinärtidning. 1989;41:38–46.
3. Segev G, Shipov A, Klement E, et al. Vipera palaestinae envenomation in 327 dogs: a retrospective cohort study and analysis of risk factors for mortality. Toxicon. 2004;43:691–699.
4. Lenchner I, Aroch I, Kelmer E, Segev G, Bruchim Y. A retrospective evaluation of Vipera palaestinae envenomation in 18 cats (2006–2011). J Vet Emerg Crit Care. 2014;24:437–443.
5. Shiloah J, Klibansky C, de Vries A, et al. Phospholipase B activity of a purified phospholipase A from Vipera palestinae venom. J Lipid Res. 1973;14:267–278.
6. Allon N, Kochva E. The quantities of venom injected into prey of different size by Vipera palaestinae in a single bite. J Exp Zool. 1974;188:71-75.
7. Leisner S, Aroch I, Perl S, et al. Acute myocardial necrosis associated with Vipera xanthina palestinae bite in a dog. Isr J Vet Med. 1999;54:81–85.
8. Segev G, Ohad DG, Shipov A, et al. Cardiac arrhythmias and serum cardiac troponins in Vipera palaestinae envenomation in dogs. J Vet Intern Med. 2008;22(1):106–13.
9. Langhorn R, Persson F, Ablad B, et al. Myocardial injury in dogs with snake envenomation and its relation to systemic inflammation. J Vet Emerg Crit Care. 2014;24:174–181.
10. Mazaki-Tovi M, Lavy E. Suspected Vipera palestinae envenomation in three cats. Vet Hum Toxicol. 1999;41:145–148.
11. Ben Abraham R, Winkler E, Eshel G, Barzilay Z, Paret G. Snakebite poisoning in children - a call for unified clinical guidelines. Eur J Emerg Med. 2001;8:189–192.
12. Garland T. Recognition and treatment for snakebites. In: Proceedings of the 18th Annual American College of Veterinary Internal Medicine, Seattle, USA. 2000:48–49.
13. Efrati P, Reif L. Viper bites. Fam Phys. 1977;7:94–104 (in Hebrew).