By: Crystal Connor, DVM
The common venomous snake encountered in our area is the Prairie rattlesnake, part of the pit viper family of venomous snakes.
The venom of the Prairie rattlesnake contains proteins that have enzymatic properties resulting in varied deleterious effects on the body ranging from severe tissue necrosis to coagulopathy, thrombocytopenia, and even cardiovascular shock.
Diagnosis is often made by a combination of historical and physical exam findings in addition to laboratory changes.
Current treatment recommendations include aggressive pain management, IV fluids, antibiotics and antivenin therapy. Treatment with glucocorticoid and antihistamines still remain controversial.
Prognosis is often favorable if the injury is recognized early and appropriate aggressive medical therapy is initiated with in 2-4 hours of the bite.
The season is upon us, that of snakebites. More specifically, rattlesnake bites resulting in envenomation of our canine (and on rare occasion feline) patients. In our hospital setting we see on average 20 snake bites a season, almost all of those being to the canine patient. These visits can occur as early as April and will generally continue through the end of September. Patients can present with varying symptoms and most often present with signs of envenomation requiring treatment.
North American venomous snakes can be divided into two families: Crotalidae and Elapidae. The Crotalidae family is sometimes referred to as pit vipers. In the front range/northeastern Colorado, the common venomous snake encountered is the Prairie rattlesnake (C. viridis viridis), subspecies of the Western diamondback rattlesnake (C. viridis).
Crotalidae venom consists of 90% water, numerous enzymes, and peptides. These proteins vary in specific components resulting in the wide-ranging effects of envenomation. Components such as hyaluronidase and collagenase aid in spreading venom through interstitial spaces, which results in tissue injury. Phospholipases cause cytotoxic effects that lead to both endothelial cell damage and inflammation, in addition to having some anticoagulant effects. Cardiovascular effects are often the result of increased vascular permeability and consequential third spacing of fluid. This can result in hypotension and cardiovascular shock. The pathophysiology for the coagulopathy seen secondary to envenomation extends past the scope of this article; however, it is important to note that it is the result of multiple mechanisms. The various proteins and enzymes present in the venom can be categorized as fibrinolytics, fibrinogen-clotting enzymes, procoagulants, anticoagulants, proteins affecting platelet function, and proteins affecting vessel wall. All of which can affect the coagulation cascade in various ways. Another important note is that snakebite coagulopathy differs from other forms of coagulopathy making standard treatments such as plasma transfusions ineffective. Thrombocytopenia as a result of envenomation is not entirely understood but thought to be secondary to damage to platelet membranes, platelet aggregation or secondary to consumption at the sites of envemonation and associated inflammation.
Diagnosis is generally based on history and corresponding physical exam findings. Most dogs are bitten on the face/muzzle, neck, or extremity. The typical patient presents with rapid onset of swelling that is extremely painful. They are generally tachycardic, exhibiting some weakness, and can be hyperthermic. Small puncture wounds in the center of or located in the region of the swelling are most often found in addition to ecchymosis. If the patient was bitten around the muzzle it is also not uncommon to have mild to moderate ptyalism present. In more cases of severe envenomation you can also see collapse, hypovolemic shock, respiratory distress, vomiting, diarrhea, and even ventricular arrhythmias. In dry bites, there is little to no true envenomation. These patients will have less swelling and pain, and generally lack systemic symptoms.
Laboratory changes that are commonly seen include echinocytosis and thrombocytopenia. When a patient presents to our hospital and concerns arise of a rattlesnake bite we immediately obtain a blood sample for a blood smear to look for echinocytes and to obtain a platelet estimate. This often gives us an immediate answer. In the study done by Hackett, et al 92% of bitten dogs were found to have echinocytosis. Thrombocytopenia was found in 88% of the dogs in this study. Prolongation of PT/PTT is a common finding due to the coagulopathic effects of the venom. Full blood work should be obtain because it is not uncommon to see other changes such as hemoconcentration or even mild anemia, hypoalbuminemia, leukocytosis, azotemia, elevated CK, and elevated liver enzymes.
When appropriate treatment is provided mortality rates are very low with rattlesnake envenomation. With that in mind, treatment should be aimed at decreasing the morbidity associated with envenomation. Essential aspects of treatment include: IV fluid therapy, administration of pain medications, prophylactic antibiotic therapy, and if appropriate antivenin administration. The area associated with the bite wound should be clipped and cleaned to help prevent secondary bacterial infection. This will allow for close monitoring of the swelling and for developing ecchymosis and tissue necrosis. Patients often present in some degree of hypovolemic shock making IV fluids an important aspect of stabilization therapy. Additionally fluid therapy helps support the patient through ongoing fluid losses, such as vomiting and diarrhea, as well as third spacing, which may occur as a result of increased vascular permeability. Due to the severe pain associated with the bite, opioid therapy is strongly recommended. In our hospital setting patients are often given an initial injection of Hydromorphone (0.05-0.2mg/kg) for immediate pain control and then once admitted to hospital started on a Fentanyl CRI 2-5 mcg/kg/hr. When patients are discharged from the hospital we will prescribe Tramadol 2-4 mg/kg PO TID (up to QID if warranted) for 5-7 days.
According to the 2011 JVECC clinical practical review by Armentano and Schaer, “ NSAIDs are not recommended for pit viper envenomation because of their ability to impair platelet aggregation, which can worsen the bleeding associated with the venom-induced coagulopathy. The impaired visceral perfusion that commonly occurs in many snakebite victims might promote the onset of NSAID-associated nephropathy and gastrointestinal ulceration, which can be a catastrophic complication in a patient that is already critically ill.”
The bacteria that have been found in snakes’ mouths include: gram-negative rods (Enterobacter, Pseudomonas, Salmonella, Aerobacter, Proteus), gram-positive cocci, and Clostridium. The interesting point to make is prophylactic antibiotic therapy is not a common standard of practice in human medicine due to multiple studies showing low incidence of secondary wound infection either with or with out antibiotic use. Research is lacking in veterinary medicine and many feel based on anecdotal evidence that antimicrobial use is warranted. Broad-spectrum coverage with anaerobic coverage is important.
Antivenin is strongly recommended for patients who are exhibiting moderate to severe tissue injury, or in those that are found to have thrombocytopenia and/ or elevated clotting times. Additionally, if the patient is exhibiting systemic signs, such as hypotension or cardiac arrhythmias, antivenin should be administered. The current recommendation is to administer antivenin with in 4 hours of the incident, for the benefits start to decrease when treatment is delayed. With that said, the positive effects of antivenin can still be seen for up to 24 hours (or more) after envenomation.
Antivenin works by binding to the venom itself, subsequently neutralizing it, reversing some clinical manifestations of envenomation, and preventing further progression. Currently there are two approved antivenin products available in the United States: Antivenin (Crotalidae) Polyvalent (ACP; Fort Dodge Animal Health), and Crotalidae polyvalent immune Fab (ovine; CroFab, FabAV, Protherics, Nashville, TN). ACP is the antivenin we carry here at AMVS/AECC. This consists of a whole IgG and horse serum albumin and can neutralize venom from all North Central and South American crotalids. There are also 2 foreign products that are effective against North American pit viper venoms but they are not currently available with in the U.S. The availability of both products requires a special importer's permit acquired from the USDA and the approval from the state veterinarian. The ACP label recommends 1–5 vials to be administered IV to dogs depending on the severity of symptoms, lapse of time after the bite, size of snake, and size of patient, with additional doses given every 2 hours as required. Human patients often receive upwards of 20 vials during treatment for envenomation; the average human patient receives 12 vials.
When administering a vial of antivenin to a patient here at AMVS/AECC they are monitored closely for any signs of allergic reaction, similar to those patients receiving blood products. The contents of one vial is reconstituted (taking special effort not to shake the vial!) in 100-250mL of 0.9% NaCl and the rate of administration is based on patient size but the goal is to administer the vial within 30-60 minutes. Repeated administration occurs for persistent, worsening local swelling, and/or coagulopathy.
Treatment with corticosteroids and antihistamines still remains controversial. Although once considered standard of care, these therapies have fallen out of favor as current studies have failed to document any benefits in treatment of snakebites. Literature can be found that debates both sides, with reasonable arguments for the pros and cons of each. At AMVC/AECC these therapies are not part of our standard of care.
As mentioned previously, when appropriate treatment is provided mortality rates are reportedly very low with rattlesnake envenomation and prognosis is often favorable if the injury is recognized early and appropriate aggressive medical therapy is initiated with in 2-4 hours of the bite. The first 12-24 hours is the critical time period for aggressive treatment. In most cases, patients are discharged within 48-72 hours.