Lyndi L. Gilliam, DVM, DACVIM
The purpose of this lecture will be to discuss rattlesnake envenomation in the horse. There are 26 species of rattlesnakes in the United States.1 Texas is home to at least 10 of those rattlesnake species.2
Snake venom is an extremely complex mixture of enzymes, proteins and peptides that cause a variety of clinical signs. Clinical problems that a clinician will face when confronted with a snakebite victim can be divided into five categories: tissue damage, coagulopathy, thrombocytopenia, cardiovascular toxicity, and neurotoxicity.
Tissue damage around the bite site is the most common and easily noticed complication. The cause of this damage is multifactorial and not completely understood. Venom contains many different enzymes and each enzyme is responsible for breaking down specific components of the tissue to allow the venom to penetrate further into the body. Venom metalloproteinases (VMPs) are important in tissue necrosis caused by a snake bite. If antivenin is administered within 20 minutes of envenomation it may block VMPs, however once this cycle is started antivenin will have little effect on tissue necrosis.3
Myotoxin-a is another venom component responsible for tissue necrosis secondary to a snake bite. It causes an increase in intracellular Ca which ultimately leads to muscle cell necrosis. The commercially available antivenin lacks antibodies to myotoxin-a, therefore administration of antivenin will not block this effect of the venom.3
The exact point at which snake venom interrupts the coagulation process varies from species to species and even among members of the same species. The first mechanism is that of defibrination. Many of the snake venoms contain fibrinolysins which destroy both fibrinogen and fibrin and thus prevent effective clot formation. With defibrination platelet counts are generally normal and clinical bleeding is uncommon. Defibrination may be benign and self limiting, however, it allows for the presence of fibrin degradation products (FDPs) which themselves act as anticoagulants.3 Defibrination is commonly misdiagnosed as DIC because of clinically observed failure to clot and increase in FDPs. It is important to note that defibrination can not be inhibited by heparin because the thrombin-like enzymes of venom are not affected by antithrombin III as true thrombin is.3
Some venoms contain a Thrombin-like enzyme. This enzyme differs from the animal's thrombin because it cleaves only fibrinopeptide A from fibrinogen, thus resulting in an imperfect fibrin clot.3 This thrombin like enzyme also does not activate factor XIII (fibrin stabilizing factor). A deficiency in activated Factor XIII results in a weak and unstable clot. The combined activities of these enzymes result in a decreased fibrinogen, a lack of intravascular clotting, elevated fibrin degradation products, and secondary prolonged clotting profiles.3
Venoms can also inhibit the activation of clotting proteins by action of phospholipase A2(PLA2). Venom PLA2 forms complexes with phospholipids, making the phospholipids unavailable for use in the clotting cascade inhibiting the activation of factor X and thus the cascade.3
The most common clinical presentation of these coagulopathies is persistent bleeding at the site of the bite.
Thrombocytopenia commonly follows rattlesnake envenomation but rarely reflects DIC. The mechanisms for venom-induced thrombocytopenia are not completely understood but many explanations have been offered and will be discussed. It is unsure whether the affect of the venom is on platelet number, platelet function or both.
The effect of rattlesnake venom on the circulatory system is complex in and of itself.
Envenomation can result in the production of bradykinin which can cause an immediate fall in arterial resistance and a decrease in systemic arterial blood pressure.3 Blood pressure is typically rapidly restored by the body's homeostatic mechanisms. If venom levels are persistent, increased stimulation of the sympathetic nervous system will cause normal or increased systemic resistance in the face of decreased cardiac output. Prostaglandins E2 and I2 are released and decrease systemic arterial pressure by causing vasodilation, which will further contribute to hypotension.3
The bradykinins and prostaglandins also increase permeability to albumin and induce pooling of the blood in the vasculature.3 The end result is hypoproteinemia and hypotension. Progressive hypotension decreases coronary perfusion and compounds decreased cardiac output.
PLA2 activity of the venom also causes a release of prostaglandins. The concentrations of prostaglandins may raise high enough to cause severe congestion in the lungs and increase vascular permeability and hemorrhage.3
Western diamondback rattlesnake venom has been shown to disrupt the basal lamina and collagen of the capillaries. The endothelial membrane becomes thin and develops gaps that allow red blood cells to leak through the membrane and results in the clinical sign of petechiae. Red blood cells may also move through the intercellular junctions which will appear as ecchymosis.3
A lethal factor in crotalus venom causes lysis of plasma membranes and a resulting microangiopathic vascular permeability which allows plasma proteins and red blood cells to leak into surrounding tissues. This leakage leads to hemoconcentration, lactic acidosis, and hypovolemic shock which could eventually lead to pulmonary edema and hemorrhage. These severe clinical manifestations are not often noted in the horse. They are most pronounced in cats, and are often delayed in dogs.
There are no documented direct cardiotoxic effects of venom that produces progressive, irreversible cardiac damage, but cardiac collapse secondary to myocardial ischemia may occur. The cardiotoxic effect of rattlesnake venom in the horse is my primary area of research interest. Research in our laboratory has shown cardiotoxic effects of rattlesnake venom in the horse. There are also documented cases of cardiac abnormalities secondary to rattlesnake envenomation in the horse.4
We will touch only briefly on this aspect of snake venoms since most of the more commonly encountered rattlesnakes do not posses this toxin. Most of the neurotoxins have an effect on the peripheral nervous system resulting in respiratory paralysis, general weakness and flaccid paralysis.
Perhaps the area of most interest to most of us is the treatment of rattlesnake bites. The first rule of thumb in treatment is to immobilize the animal as much as possible. If the horse is on a trail ride and a trailer can be taken to the horse rather than walk the horse back to the trailer, this is ideal. Any movement may allow the venom to spread systemically more rapidly. It is very important in animals that are bitten on the head that an airway be established. In horses this can easily be accomplished by the owner by placing a piece of hose a short distance up the horse's nostril to maintain patency of the nare.
A few older treatment regimens include ice, tourniquets, and suction. Ice is contraindicated because cold will cause vasoconstriction leading to ischemia of tissue that is already deficient in blood flow causing further tissue necrosis. Tourniquets are still controversial.5
Laboratory analysis may aid in the diagnosis (generally not a problem) of a snake bite as well as help you to assess the severity. Abnormalities that may be present are hypofibrinogenemia, thrombocytopenia, a prolonged prothrombin time, and increased FDPs.
Echinocytosis can be caused by rattlesnake venom in humans, dogs, cats and horses.6 A peripheral blood smear should be examined for the presence of echinocytes to aid in diagnosis, if necessary, and to determine severity of envenomation. The severity of the echinocytosis may be associated with the dose of venom.7 Heparin or citrate samples must be used to look for the presence of echinocytes as they will not be found in an EDTA sample.7
Fluids are beneficial in treating the shock of the animal. Fluid losses are often less severe in large animals, however, crystalloid therapy can be used to improve tissue perfusion.
Antivenin is very beneficial but is often cost prohibitive. The standard antivenin is made from horse serum therefore there is a risk when using it in horses. Major indications for antivenin are rapid progression of swelling, significant coagulopathy, defibrination or thrombocytopenia, neuromuscular toxicity, and/or shock. Factors determining antivenin dosing will be discussed.
Analgesics are definitely indicated in these patients. The wound area is generally extremely painful to the touch. Extreme lameness can occur in affected limbs.
Multiple analgesic protocols will be discussed. Nonsteroidal anti-inflammatory drugs are a mainstay of analgesic and anti-inflammatory therapy in these patients as long as perfusion and hydration are maintained.
The incidence of infection following snake bite in humans is low and, in fact, venom has been shown to have some antibacterial properties.8
Veterinary medicine is a different scenario simply due to the challenge of keeping the wound clean. It is my opinion that the use of prophylactic antibiotics in our patients is appropriate. Tetanus prophylaxis is definitely indicated in horses.
Steroids are controversial in the treatment of snake bites. At least one study performed in mice showed that steroids had no beneficial effect and actually had detrimental effects in the treatment of snake bites.9 Dogs have shown an increased survival when treated with steroids, however they did not have an effect on the amount of swelling or tissue necrosis.10 The anti-inflammatory effects of steroids may make them very valuable in the initial therapy of the snake bite victim. They also may be important in treating myocardial inflammation and preventing or decreasing myocardial scarring.
Secondary complications are not uncommon in snake bite victims. Our research in horses indicates that cardiac dysfunction may be a long term complication of rattlesnake envenomation as well. Close examination of this system is indicated for at least one year after a bite occurs.
Vaccines to prevent the toxic effects of rattlesnake venom are being investigated and could certainly be beneficial in endemic areas.
It is important to know the snakes indigenous to your area and their specific toxicities. Rattlesnake envenomation is a very complex clinical scenario and treatment centers around antivenin and supportive care. It is important to make clients aware that immediate recovery does not rule out long term complications.
1. Parrish HM. Poisonous Snakebites in the United States. New York, Vantage Press, Inc., 1980.
3. Tu AT (ed). Rattlesnake Venoms: Their Actions and Treatment. New York, Marcel Dekker, 1982.
4. Dickinson CE, Traub-Dargatz JL. Rattlesnake venom poisoning in horses: 32 cases (1973-1993). JAVMA 208(11): 1866-1871.
5. PE McKinney, Out-of-hospital and interhospital management of crotaline snakebite. Ann Emerg Med 37 (2001), pp. 168-174.
6. Brown DE, Meyer DJ, et al. Echinocytosis Associated with Rattlesnake Envenomation in Dogs. Veterinary Pathology 31: 654-657, 1994.
7. Walton RM, Brown DE, et al. Mechanism of Echinocytosis Induced by Crotalus atrox Venom. Veterinary Pathology 34: 442-449, 1997.
8. Burch JM, Agarwal R, et al. The Treatment of Crotalid Envenomation without Antivenin. The Journal of Trauma 28(1): 35-43, 1988.
9. Cunningham ER, Sabback MS, et al. Snakebite: Role of Corticosteroids as immediate therapy in an animal model. The American Surgeion 45(12): 757-759, 1979.
10. Mansfield PD. The Management of Snake Venom Poisoning in Dogs. The Compendium on Continuing Education 6(11): 988-994, 1984.