Copperhead (Agkistrodon contortrix) Envenomation of Dogs: 52 Cases (2004–2011)
Copperhead envenomation is common within the US, and no studies exist describing the clinical course of copperhead envenomation in dogs. Almost all treatment decisions regarding those bites are extrapolated from retrospective studies evaluating the clinical course of rattlesnake bites. Because copperheads and rattlesnakes produce venom with different potency, assumptions that treatment of the different envenomations should be similar may be incorrect. The purpose of this retrospective study was to evaluate the clinical course of copperhead envenomation in dogs and administered treatments. Medical records of 52 dogs treated for copperhead envenomation were reviewed, and owners were contacted regarding outcome. The most common clinical signs associated with copperhead envenomation included swelling, pain, and ecchymosis. Clinicopathological abnormalities (e.g., thrombocytopenia, elevated clotting times, leukocytosis) were mild, and red blood cell morphology changes and coagulopathies were rare. Most dogs were treated with antimicrobials, analgesics, and fluid therapy. No dogs in this study required the use of antivenin and all survived to discharge. This study found that the clinical course after copperhead envenomation is generally limited to local rather than systemic illness. Copperhead envenomation in dogs is largely self-limiting and responsive to supportive care with hospitalization for monitoring.
It has come to the authors' attention that ecchinocytes were noted as “poikilocytosis” in the medical records of dogs included in this study. Blood films from 32 study dogs were available for review, 28 of 32 dogs (87.5%) had ecchinocytes present at the time of presentation for copperhead envenomation. It is important to note that similar to dogs with rattlesnake envenomation, the majority of dogs with copperhead envenomation also exhibit ecchinocytosis.
Introduction
In the US, there are >120 species of snakes, 20 of which are venomous.1 It has been estimated that as many as 150,000 dogs and cats are bitten by one of those venomous species each year.2 The venomous snakes are divided into two families, the Elapidae (coral snakes) and Crotalidae or pit vipers (rattlesnakes, moccasins, and copperheads). Pit viper envenomation is a common hazard for dogs, especially in the southern US. The clinical course of pit viper envenomation can range from local effects, such as bite site swelling and tissue necrosis, to more serious effects, including coagulopathies, hypotension, myocardial damage, and death.3,4 Reported mortality rates range from 1 to 30%.4,5 Pain at the bite site is immediate and usually followed quickly by swelling.6 Onset of the more serious clinical signs may be delayed for hours.1,6
Clinical signs related to snakebites stem from trauma from the bite itself as well as venom contents. Venom from snakes in the family Crotalidae contains mostly water, along with additional enzymes and peptides, varying by snake genera.7 The Crotalidae are divided into three genera, Crotalus (rattlesnakes), Sistrurus (pygmy rattlesnakes), and Agkistrodon (copperheads and moccasins), each with different venom characteristics. Based on lethal dose 50% calculations, rattlesnake venom is the most potent, followed by moccasin and copperhead venom.1,2,8 There are several retrospective studies evaluating the clinical course of, and treatments associated with, rattlesnake envenomation in dogs.3,4 However, no similar studies exist evaluating copperhead envenomation in dogs.
The copperhead (Agkistrodon contortrix) is found in North America from as far north as New York, west to Oklahoma, and as far south as Mexico. Copperheads can be identified by a pale tan base color overlaid with a series of dark brown, hourglass-shaped crossbands. They are most frequently found in deciduous forests, hibernating during the winter in rocky outcroppings. In 2009, copperhead bites to humans comprised 40% of all venomous snakebite calls to American Poison Control Centers, more than any other venomous snake in the US.9 Despite the prevalence of copperhead snakebites in the US, the lack of information describing the clinical course of envenomation in dogs forces clinicians to extrapolate treatment decisions based on the small amount of evidence from human literature, studies on rattlesnake envenomation in dogs, and anecdotal evidence. Because little information is available to prognosticate what animals will develop more serious signs, hospitalization for supportive care, continued monitoring, and repeated laboratory work are often recommended.2,8
In North Carolina, up to 90% of snakebites to humans are from copperhead snakes, and that state has the highest incidence of copperhead bites per capita in the nation.10,11 Wake County, North Carolina, the region from which the cases for this study were selected, is home to primarily one venomous snake: the copperhead.11 Given the limited population of venomous snakes in Wake County, it is an ideal location for performing a retrospective study describing the clinical course of copperhead envenomation in dogs and treatment measures.
Materials and Methods
Case Selection
The electronic discharge database of the North Carolina State University Veterinary Teaching Hospital from 2004 to 2011 was searched for medical records containing the terms, “snakebite,” “snake bite,” “envenomation,” “copperhead,” “copper head,” “Crotalid,” and “Agkistrodon.” Criteria for inclusion included dogs residing in Wake County that presented within 12 hr of a suspected copperhead bite and that had not previously been presented for medical treatment at another facility. Dogs were categorized as “confirmed” if the owners either saw the copperhead bite the dog or found the dog with fang marks and a snake nearby. “Suspected” cases were categorized as those in which an animal had at least one fang mark, clinical signs consistent with snakebite, and a history compatible with the possibility of snakebite. A total of 52 cases met the inclusion criteria.
Medical Records Review
For each dog, the signalment, presenting complaint, date of presentation, vital parameters (temperature, pulse, and respiration), weight, and clinical signs as described by the attending clinician were recorded. A pain scoring system raging from 0 to 4 (0, no pain; 4, intractable pain) was used to assess discomfort in some patients and recorded when available. Clinicopathological test results were recorded when performed (packed cell volume, total solids, blood glucose, complete blood count, serum biochemical analysis, coagulation panel). Treatments administered in hospital, including pain control, antibiotics, sedation, and fluid therapy, were recorded. Additionally, medications and treatments prescribed to be given at home were also recorded. Outcome was recorded for each patient, as well as the bill total for the visit and total hospitalization time. Efforts were made to assess whether the patients either improved or worsened during their hospitalization time given the information provided by the record. Owners were contacted by either phone or e-mail as part of the study and were asked about their dog’s improvement at home after discharge, if the dog required follow-up medical care at another facility, and if the dog developed evidence of bite site necrosis.
Results
Case Information
During the study period, 52 dogs met the inclusion criteria. Twenty of 52 dogs (38%) had confirmed bites and 32 of 52 dogs (62%) had suspected bites. Dogs ranged in age from 6 mo to 15 yr, with a median age of 6 yr. Median body weight was 24.1 kg, ranging from 5 to 55 kg. Twenty-seven breeds were represented, with the most common being Labrador retrievers (n = 9), mixed-breed dogs (n = 7), golden retrievers (n = 4), dachshunds (n = 3), and Jack Russell terriers (n = 3). Castrated male dogs were most frequently presented (46%), followed by spayed females (36%), males (12%), and females (6%). Bites were reported between April and October, with 94% (49 of 52) occurring between May and September. The exact time to presentation from suspected envenomation, rather than an estimate, was recorded for 32 of 52 dogs, with a median time of 60.5 min (range, 17–360 min).
Clinical Findings
The most common presenting complaint was snakebite in 42 of 52 dogs (81%), followed by facial swelling in 3 of 52 dogs (6%) and lameness in 2 of 52 dogs (4%). Thirty-four of 52 dogs (65%) were bitten in the face, followed by a forelimb in 10 of 52 dogs (19%), and a hind limb in 6 of 52 dogs (12%). One dog was bitten in two locations (face and forelimb) and another was bitten on the thorax. All 52 dogs (100%) had swelling at the bite site. Other common local effects of envenomation included bleeding at the bite site in 14 of 52 dogs (27%), bruising/ecchymosis in 14 of 52 dogs (27%), petechiation at the bite site in 2 of 52 dogs (4%), and erythema at the bite site in 5 of 52 dogs (10%). Five of 52 dogs (10%) had the lymph nodes draining the bite site enlarged on palpation. Forty-nine of 52 dogs (94%) had evidence of only one bite (≤2 puncture wounds), while the remaining 3 dogs (6%) had evidence of more >1 bite (>2 puncture wounds). Of the dogs that had an exact number of puncture wounds recorded (n = 50), 5 of 50 dogs (10%) had no visible puncture wounds despite the owners seeing a snake strike their dogs and clinical signs consistent with a snakebite. Thirteen of 50 dogs (26%) had one puncture wound, 31 of 50 dogs (62%) had two puncture wounds (constituting one bite), and 1 of 50 dogs (2%) had four puncture wounds reported.
On presentation, 49 dogs had vital signs (temperature, pulse, and respiration) recorded. Thirteen of 49 dogs (27%) were hyperthermic (>39.2°C), and 3 of 49 dogs (6%) were hypothermic (<37.7°C). Twenty-six of 49 dogs (53%) were tachycardic (>120 beats/min). One of 49 dogs (2%) was bradycardic (30 beats/min). A pain scoring system assessed discomfort in 35 dogs on admission. Of the dogs assigned a pain score, 2 of 35 dogs (6%) were given a 0, 4 of 35 dogs (11%) were given a 1, 15 of 35 dogs (43%) were given a 2, 11 of 35 dogs (31%) were given a 3, and 3 of 35 dogs (9%) were given a 4. Of the dogs assessed to be the most painful, two of the three were bitten on the face, and the final dog was bitten on the thorax. There were no discernible differences in clinically assessed vital parameters between dogs with confirmed snakebites versus those with suspected snakebites.
Laboratory Findings
Results of initial complete blood count, reported in 38 dogs, included thrombocytopenia in 9 of 38 dogs (24%) with a median platelet count of 229,000 platelets/μL (range 122,000–546,000; reference range, 190,000–468,000/μL), leukocytosis in 10 of 38 dogs (26%) with a median leukocyte count of 9.4 × 103/μL (range, 3.6–23.7 × 103/μL; reference range, 4.39–11.6 × 103/μL), mature neutrophilia in 9 of 38 dogs (24%), with a median neutrophil count of 7.8 × 103/μL (range, 1.6–18.2 × 103/μL; reference range, 2.841–9.112 × 103/μL), decreased plasma protein in 7 of 38 dogs (18%), with a median plasma protein of 6.6 g/dL (range, 4.5–7.8 g/dL; reference range, 6.1–7.5 g/dL), nucleated red blood cells observed in 8 of 38 dogs (21%), and elevated packed cell volume in 2 of 38 dogs (5%), with a median packed cell volume of 51.5% (range, 26–64%; reference range, 39–58%). Only 1 of 38 dogs was listed as having echinocytes present. On serum biochemical evaluation, 4 of 29 dogs (14%) had elevated total Ca values with a median value of 10.4 mg/dL (range, 9.6–12.7 mg/dL). Five of 29 dogs (17%) were mildly hypokalemic. Mean serum potassium concentration was 4.6 mEq/L (range, 3.7–5.7 mEq/L; reference range, 4.0–5.3 mEq/L) as shown in Table 1.
*Median and range values for all dogs assessed in the study.
ORR, out of the reference range; —, value was not calculated/reported.
Twenty-eight dogs had prothrombin and activated partial thromboplastin times evaluated on presentation. Only 1 of 28 dogs (3.5%) had a mild elevation in activated partial thromboplastin (106 sec; reference range, 72–102 sec). None of the patients tested had elevated prothrombin values.
Antibiotics
Thirty-five of 52 dogs received antimicrobials while hospitalized. Thirty-one of 35 dogs (88%) received a combination penicillin β-lactamase inhibitor, either ampicillin Na/sulbactam Na in 25 of 35 dogs (20–26.5 mg/kg IV q 8 hr) or amoxicillin trihydrate/clavulanate potassium in 6 of 35 dogs (12.3–17.86 mg/kg per os [PO] q 12 hr). Two of 35 dogs (6%) received cephalosporins (22 mg/kg cefazolin IV q 8 hr), and 2 of 35 dogs (6%) received fluoroquinolones (10 mg/kg ciprofloxacin IV q 24 hr). Forty-eight of 52 dogs were sent home with antimicrobial therapy. Forty of 48 dogs (83%) received amoxicillin trihydrate/clavulanate potassium (8.1–28.2 mg/kg PO q 12 hr), 6 of 48 dogs (13%) received cephalexin (13.4–26.3 mg/kg PO q 12 hr), and 2 of 48 dogs (4%) received ciprofloxacin (20 mg/kg PO q 24 hr).
Glucocorticoids
Nine of 52 dogs received a single IV dose of dexamethasone as part of their treatment. Seven of those dogs were bitten on the face. The average dose was 0.5 mg/kg, ranging from 0.1 to 2.0 mg/kg. No dogs were sent home with glucocorticoids.
Pain Control
While hospitalized, 48 of 52 dogs (92%) received at least one analgesic. Twenty of 48 dogs (42%) received intermittent IV hydromorphone boluses (0.05–0.1 mg/kg IV), 18 of 48 dogs (38%) received fentanyl as an IV continuous rate infusion (2–6 μg/kg/min IV), 9 of 48 dogs (19%) received buprenorphine (0.01–0.02 mg/kg IV q 6–12 hr), 4 of 48 dogs (8%) received tramadol (2.8–4.1 mg/kg PO q 8–12 hr), and 2 of 48 dogs (4%) received carprofen (2.2–4 mg/kg PO q 12–24 hr). Forty-nine of 52 dogs (94%) were prescribed at least one analgesic at discharge. Forty-one of 49 dogs (84%) received tramadol (1.3–5.7 mg/kg PO q 8–12 hr), 10 of 49 dogs (20%) received carprofen (1.6–3.6 mg/kg PO q 12 –24 hr), 5 of 49 dogs (10%) had fentanyl transdermal patches placed, 5 of 49 dogs (10%) received meloxicam (0.08–0.1 mg/kg PO q 24 hr), and 1 of 49 dogs (2%) received buprenorphine (0.01 mg/kg PO q 8–12 hr).
Other Treatments
No dogs received antivenin, and no dogs required blood products. Eleven of 52 dogs (21%) received diphenhydramine (1–2.2 mg/kg intramuscularly q 1–8 hr). Three of 52 dogs (6%) received famotidine (0.4–0.5 mg/kg IV q 12 hr). Thirty-three of 52 dogs (63%) received IV fluids. Of those 26 dogs (79%) received maintenance rates (1.5–4 mL/kg/hr) of IV fluids while hospitalized. Six of 52 dogs (11%) were judged to be hypovolemic and received either a fluid bolus and maintenance rates of IV fluids or maintenance and replacement rates of IV fluids.
Outcome
All dogs survived to discharge. The median hospitalization time was 14.8 hr (range, 63 min to 48.9 hr). The median cost was $539.50 (range, $119.40–1283.50). Owner follow-up through response to phone or e-mail survey was available for 27 of 52 dogs (52%). Tissue necrosis at the bite site was reported by 3 of 27 owners (11%). Of those, only one required follow-up care at another veterinary facility and resolved with antibiotic treatment without the need for surgical debridement. Self-limiting infection at the bite site was reported by 1 of 27 owners (4%) that did not require either follow-up treatment at an additional veterinary facility or changes in treatment protocol.
Discussion
In the veterinary literature, there is a lack of data describing the clinicopathological characteristics of copperhead envenomation in dogs. Almost all treatment decisions regarding those bites have been extrapolated from a few retrospective studies evaluating the clinical course of rattlesnake bites.3,4 Because copperheads and rattlesnakes produce venom with different potency, assumptions that the treatment of the different envenomations should be similar may be incorrect.
Similar to previous studies evaluating snakebites in dogs, in this retrospective study, most copperhead bites occurred between May and September.3,4 That was likely due to both the hibernation patterns of copperheads (that retreat to rocky dens from October through March) and seasonal changes resulting in more humans and animals being outside (thus having an increased chance of interaction with a copperhead). As seen in dogs with rattlesnake envenomation, the most common clinical signs were swelling, puncture wounds, and bleeding or ecchymosis, with most of the bites occurring on the head or neck.3–5 Despite swelling in the head and neck area, no dogs struck by copperheads had upper airway obstruction described in the medical record. However, of the nine dogs that were given single doses of corticosteroids in hospital, seven had bites to the face. In this study, five dogs had regional lymph node enlargement. That finding was unique to this study, but was not surprising given that venom travels via lymphatics.8 In humans with copperhead envenomation, the most common clinical signs are pain and swelling.10 While pain is difficult to subjectively quantify in dogs, most dogs that had a pain score recorded in the medical record were listed as being at least minimally painful (a score of ≥1) and the majority of dogs were given analgesics while hospitalized.
A retrospective study looking at 31 dogs bitten by Eastern diamondback rattlesnakes found 42% developed cardiac arrhythmias, while another retrospective study of 100 dogs bitten by prairie rattlesnakes found that those dogs were often hypovolemic and required IV fluid resuscitation.3,4 In contrast, the majority of dogs in this study did not require fluid therapy beyond maintenance and none had reported cardiac arrhythmias other than sinus tachycardia based on auscultation at admission.
Three studies of rattlesnake envenomation in dogs have reported varying degrees of thrombocytopenia (88%, 81%, and 35%, respectively) and coagulation abnormalities requiring blood product administration in (4%, 12%, and 35%, respectively).3–5 While almost one-quarter of dogs bitten by copperheads that had platelet numbers assessed were thrombocytopenic, elevation in prothrombin time or partial thromboplastin time was a rare finding and none of the patients required blood product administration. That observation was unexpected because copperhead venom contains fibrolase, a known anticoagulant.12,13 There are other components of venom that differ between rattlesnakes and copperheads, such as crotalocytin (a serine protease in timber rattlesnake venom that causes platelet aggregation in vitro) and crovidisin in prairie rattlesnake venom (that prevents platelets from interacting with collagen, resulting in bleeding).8 A lack of those components in copperhead venom, and other differences in venom fraction composition, may explain the differences between copperheads and other snakebites in terms of clinically assessable bleeding and coagulation abnormalities.12,13
Echinocytosis has frequently been associated with snake envenomation in dogs and in one study of prairie rattlesnake envenomation echinocytosis was seen in 92% of dogs evaluated.2,4,8,14 Only one dog with copperhead envenomation had echinocytosis noted on blood smear evaluation. There are several possible explanations for this difference. First, evaluation of echinocyte formation in humans showed that a venom concentration of 200 ng/mL was necessary to cause echinocytosis using various snake venoms.15 It is possible that lower volumes of venom are delivered from copperheads compared with rattlesnake studies. Alternatively, phospholipase A2, the phospholipase shown to induce echinocytosis, could be present in decreased concentrations in copperhead venom as compared with rattlesnake venom.16
Fourteen percent of dogs were hypercalcemic on presentation; however, none had ionized Ca evaluated. The hypercalcemia is likely due in part to hemoconcentration as all dogs also had elevated albumin concentrations. In humans, creatine kinase is used as a marker of envenomation severity and it is hypothesized that increased Ca may be due to rhabdomyolysis in association with local envenomation effects.14 All dogs with creatinine kinase measurements had values within the normal range in this study.
Ten percent of dogs were mildly hypokalemic on presentation. None were azotemic and none of the hypokalemic dogs were hyponatremic. It has been hypothesized that hypokalemia in snake envenomations is a result of cation depletion during red blood cell membrane transformation and formation of echinocytes.16 In this study, the single dog with echinocytes did have a low serum potassium concentration. The hypokalemia reported in the remainder of the dogs may be secondary to a shift of potassium from the extracellular fluid to the intracellular fluid as a consequence of catecholamine release.17,18
The most commonly recommended treatments for dogs bitten by rattlesnakes include volume expansion, analgesia, antivenin administration, and antibiotic therapy.3,5 No dogs bitten by copperheads required the use of antivenin. In humans with copperhead envenomation, clinical management most frequently involves analgesia and antibiotics. In rare cases, antivenin, blood products, and surgical wound management are needed.10 One study of management of copperhead snakebites in humans recommended withholding antivenin based on the belief and experience that copperhead envenomation in humans is largely a self-limiting event.19
Few dogs received glucocorticoids as part of their treatment. Glucocorticoid use in snakebites is controversial. More recent studies have largely shown either no harm or benefit to the use of steroids in envenomation in dogs.3,5 However, previous studies have shown mixed results, with some showing potential deleterious effects of steroids when given to envenomated rodents and showing a possible protective effect against death due to envenomation.20,21 Concerns are also raised about impairment of tissue healing after steroid administration, although that seems unlikely after one anti-inflammatory dose of corticosteroids in hospital.
Antibiotic usage for snake envenomation is controversial in both humans and dogs. Studies of microbiology of both snakebites and snake oral cavities have shown a mixed population of bacteria, likely reflecting those found in the feces of ingested prey.22 One study has also shown venom to have antibacterial properties, although only against aerobic isolates.23 Despite studies on copperhead bites in humans questioning the necessity of antibiotic therapy for snake envenomation, studies of dogs bitten by snakes document the use of empirical antibiotic therapy.5,19 Both the flora within snakes’ mouths and on dogs’ skin may factor into antibiotic choices for clinicians. No dog bitten by a copperhead was re-presented to the study authors’ emergency facility for snakebite-associated abscess formation. During follow-up questioning, one owner reported an infection at the bite site, but not severe enough to cause re-presentation to another facility after discharge. There are no known prospective studies in dogs evaluating the use of antimicrobials in snakebites or evaluating snakebite wounds for infection. Antibiotics were administered to the majority of the dogs in this study.
Median duration of hospitalization in dogs was 14.8 hr, and dogs presented (on average) 1 hr after envenomation, meaning most dogs were observed at least 16 hr postenvenomation. However, that time period was almost 10 hr shorter than the duration of hospitalization in humans admitted for copperhead envenomation.10 The difference in hospitalization may be related to the time of maximal swelling. In humans, maximal swelling is thought to occur 36 hr postenvenomation.19 In the patients included in this study, in which changes in swelling and inflammation were documented (n = 6), a median time of 6.9 hr from presentation to improved swelling was noted. This difference in time to maximal swelling between dogs and humans may possibly be due to either skin perfusion differences causing faster accumulation of inflammatory cytokines at the bite site in dogs or because the small number of dogs with swelling timelines recorded do not accurately reflect the typical course of envenomation.24
All dogs survived to discharge. That finding was in contrast to rattlesnake envenomation, in which mortality rates ranged from 1 to 19%.3,4 Copperhead venom is significantly less potent than that of either moccasins or rattlesnakes.1 It is therefore not surprising that the course of copperhead envenomation in dogs appears largely self-limiting and minor. One study of Eastern diamondback rattlesnake envenomation found that smaller dogs had a worse prognosis.3 That finding was not reflected in copperhead envenomation in dogs because all dogs survived to discharge with minimal intervention beyond supportive care. Based on the lack of severe clinicopathological, hemodynamic, or local effects observed in the dogs in this study, it is reasonable to conclude that similar to humans, copperhead bites in dogs are largely self-limiting injuries requiring minimal veterinary interventions beyond analgesia and monitoring.
The limitations of this study are similar to those inherent in all retrospective studies. Information is limited to that which was recorded in the medical record at the time of hospitalization. Comparing outcomes is difficult without standardized treatment. Additionally, although the study was designed to avoid inclusion of snakes other than copperheads, there is the chance that dogs were bitten by snakes other than copperheads because counties surrounding Wake County contain moccasins and rattlesnakes. Follow-up information was limited. Additionally, it is known that up to 25% of snakebites are “dry,” containing no venom, and bites that do inflict venomation can contain various amounts of venom.25 This varying amount of venom makes it difficult to compare one case to another in terms of severity of signs and outcome. Finally, the patient population was drawn from a number of years, with changing clinicians and treatment recommendations.
Future prospective studies evaluating the time to peak clinical signs could help guide hospitalization and treatment decisions. Additionally, the use of antibiotics, not just in copperhead envenomations but other snake envenomations as well, should be evaluated. Prospective studies with additional follow-up could better reveal the extent of local tissue damage after discharge from the hospital and assist in decisions regarding the need for antibiotic therapy.
Conclusion
Clinical signs associated with copperhead envenomation in dogs most commonly included swelling, pain, and ecchymosis. Clinicopathological abnormalities such as thrombocytopenia, elevated clotting times, and leukocytosis, were mild and required no further treatment. Most dogs were treated with antimicrobials, analgesics, and fluid therapy. No dogs bitten by copperheads in this study required the use of antivenin and all survived to discharge. There were rare instances of necrosis at the bite site. Copperhead envenomation in dogs in this study appears to be self-limiting and responsive to supportive care.
Contributor Notes
