Pit Viper Envenomation in Two Pregnant Bitches
ABSTRACT
Snake envenomation is relatively common in small animals, particularly in endemic areas. Effects and outcomes of envenomation during pregnancy are poorly described in humans and more so in veterinary patients. Two young pregnant female dogs presented to a university teaching hospital with a history of acute soft tissue swelling and bleeding. History, physical examination findings, and diagnostics were consistent with envenomation by crotalid snakes. Medical management of one of the dogs included administration of antivenin. Both dogs survived envenomation with minimal complications and went on to whelp without complications, and all fetuses survived. This is the first description of the management of pit viper envenomation in pregnant dogs.
Introduction
Pit vipers belong to the family Crotalidae, one of two families of venomous snakes indigenous to the United States. Pit viper envenomation is the most common snake envenomation of small animals reported in the United States, with an estimated 150,000 cases reported annually in dogs and cats.1 Pit vipers can control the amount of venom injected; therefore, not all snakebites result in envenomation. When envenomation does occur, it is capable of causing soft tissue necrosis around and proximal to the bite, in addition to dysfunction in multiple organ systems, most notably the cardiovascular, hematologic, respiratory, and nervous systems. The mainstays of treatment include the administration of antivenom, fluid therapy, analgesia, and serial monitoring of clinical signs.1–4 In humans, a standardized snakebite severity score (SSS) has been validated to evaluate the progression of envenomation.5 Though not validated for use in dogs, the human SSS has been adapted for use in veterinary patients (Table 1).3,6
In humans, snake envenomation by the family Viperidae (pit viper and pit-less vipers) during pregnancy is uncommonly reported but has been associated with decreased survivability of both the fetus and the mother.7 Previous literature reviews in humans have published an overall fetal death rate of up to 43% and a maternal fatality rate of up to 10%.7–10 Poor fetal outcomes have been reported more commonly in cases of envenomation early in the gestational period.10 Studies performed in animals suggest teratogenic effects of the venom in early gestation, as well as the ability of the venom to induce premature uterine contractions.11,12 Information on outcomes of pit viper envenomation during pregnancy in veterinary patients does not exist. This is the first report describing the management of pit viper envenomation in two pregnant bitches. With medical management, each dog went on to whelp without complications and all fetuses survived.
Case Reports
Case 1
A 2 yr 10 mo old, 30 kg intact female boxer dog was presented to a university teaching hospital 1 hr after the owner noticed a bleeding wound on the dorsal surface of her left front paw. The wound was found after she was outdoors in a fenced-in yard. She had been bred by live cover 4 wk prior and suspected to be pregnant at presentation. Within 15 min of the owner noticing the wound, the dog became acutely lethargic, and swelling of the affected limb was noted. On initial evaluation, the pertinent findings included panting with clear lung sounds, tachycardia (200 beats/min), and two actively bleeding puncture wounds on the dorsal aspect of her left front paw with mild to moderate swelling extending to her mid-antebrachium. The mammary glands were noticeably enlarged. The dog was assigned a pain score of one out of four per the Colorado Pain Scoring Scalea. Based on the typical history and presenting clinical signs, pit viper envenomation was suspected.
A venous Stat Profileb, packed cell volume (PCV), total solids (TS), blood smear, and an activated clotting time (ACT) were performed. The PCV was mildly decreased (35%; reference interval [RI]: 37–55%), and TS were normal (54.0 g/L; RI: 54.0–71.0). The serum was mildly hemolytic, and the ACT was normal (80 sec; RI: <120 sec). Although the blood pH was normal (7.399, RI: 7.335–7.446), a mild metabolic acidosis (HCO3− 16.3 mmol/L; RI: 18–27) and hyperlactatemia (3.0 mmol/L; RI: 0.4–1.5) with incomplete respiratory compensation (pCO2 26 mm Hg; RI: 35-40) were present. The calculated base excess was −8.7 mEq/L (RI: −2 to +2). In addition, mild electrolyte abnormalities included hyponatremia (143.4 mmol/L; RI: 146–151), hypokalemia (3.85 mmol/L; RI: 3.98–4.41), and hypomagnesemia (0.45 mmol/L; RI: 0.51–0.65). The remainder of the Stat Profileb values were normal (hematocrit 47% [RI: 40–52], hemoglobin mmol/L 15.3 [RI: 14–26], chloride 114 mmol/L [RI: 108.5–116], ionized calcium 1.24 mmol/L [RI: 1.18–1.35], glucose 110 mmol/L [RI: 87–111], creatinine 0.7 mg/dL [RI: 0.8–1.5], blood urea nitrogen 12 mg/dL [RI: 10–30]). The blood smear showed 1+ echinocytes and 10–12 platelets per high-power field, equating to an estimated 150,000–180,000 total platelet count per microliter.
Given the presence of tachycardia and a mildly swollen bite site, the dog was assigned an SSS of two and admitted to the intensive care unit for supportive care and serial monitoring (Table 2). IV fluid therapy was initiated using lactated Ringer’s solutionc (LRS) at 40 mL/kg/day, and 3.3 mg/kg tramadold was administered orally q 8 hr for analgesia. One hour after presentation, the dog’s heart rate decreased to 170 beats/min and there was no progression of the limb swelling. Two hours after presentation, her heart rate normalized and her SSS was reduced to one.
On day 2 (12 hr after presentation), repeat blood test results were normal (PCV and TS 41% [RI: 37–55%] and 64 g/L [RI: 54.0–71.0], respectively, with clear serum). The ACT remained normal (76 sec [RI: <120 sec]). The swelling around the wound was subjectively static from the night prior. Fetal heart rates were normal (>180 beats/min) on a brief ultrasound examination. The dog was discharged 16 hr after her initial presentation with instructions to return for serial fetal heart rate monitoring. On days 39 and 48 after live cover, the physical examination parameters and fetal heart rates remained normal (>180 beats/min). Abdominal radiographs performed on day 48 of gestation showed eight fetuses.
On day 63 of gestation, the dog whelped nine puppies via vaginal delivery at home, with no reported complications. Per the owner, no apparent congenital defects were present, and all puppies survived to at least 1 yr of age, when they were lost to follow-up.
Case 2
A 1 yr old, 34 kg intact female golden retriever dog was presented to a university teaching hospital for a previously bleeding and moderately swollen wound on the rostral aspect of the right upper lip. The wound had been found after the dog had been outside unsupervised for 2 hr. She arrived at the hospital ∼3.5 hr later. The dog had been bred via live cover 19 days prior but had not been confirmed to be pregnant at the time of presentation. On initial evaluation, the dog was panting with mildly increased respiratory effort and normal airway sounds on auscultation. The dog had a normal temperature, heart rate, capillary refill time, and pulse rate/quality. Two puncture wounds were present on the upper lip with associated swelling extending along the ventral mandible. No active bleeding was evident around the puncture wounds; however, ptyalism with blood-tinged saliva was visible. The dog had minor sensitivity at the bite site; a pain score of one out of foura was assigned. The remainder of the physical examination was unremarkable. A diagnosis of pit viper envenomation was suspected.
A PCV, ACT, and indirect systolic blood pressure measurement were measured. The PCV was normal (50% with clear serum color; [RI: 37–55%]); TS was unable to be obtained because of an error in sample handling). The ACT was normal at 74 sec (RI: <120 sec), and the blood pressure was 165 mm Hg (RI: 120–160 mm Hg). She was assigned an SSS of two based on local wound appearance and mild hypertension.
The dog was admitted to the intensive care unit overnight for supportive care and serial monitoring (Table 2). One hour after presentation, the dog’s respiratory effort remained mildly increased. Treatment with one vial of F(ab)2 polyvalent crotalidae antivenine was initiated as a continuous rate infusion. The antivenom was reconstituted in 100 mL of 0.9% salinef and delivered via a syringe pump at 25 mL/hr for a total of 4 hr. Six hours after presentation (following completion of the antivenom infusion), IV fluid therapy was initiated using LRS at 50 mL/kg/day. Eight hours after presentation, the dog remained clinically stable with a normal heart rate and rhythm, pulse quality, respiratory rate and effort, and capillary refill time. The dog’s SSS was reduced to one. The following morning (14 hr after presentation), the dog’s facial swelling had progressed from the right rostral maxillary lip to an accumulated swelling on the ventral neck. An open wound caused by focal bite site necrosis was noted on the right side of the face. The dog’s appetite was normal and IV fluid therapy was discontinued. Antibiotic therapy with 15 mg/kg amoxicillin/clavulanic acidg by mouth q 12 hr was initiated. The dog remained comfortable without administration of analgesic therapy, and her SSS remained at one for the remainder of her hospitalization. She was discharged 26 hr after her initial presentation with a 2 wk course of amoxicillin/clavulanic acidg. Follow-up conversations with the owner confirmed that the swelling had resolved within 2 wk of the envenomation.
Twenty days later, the dog re-presented to the same university teaching hospital for evaluation of facial swelling that was identified after the dog had been playing outside for 1 hr. She was known to be 38 days pregnant at the time of presentation. On initial evaluation, the dog was panting, but all other vital signs were within normal limits. Puncture wounds were identified on the left ventral aspect of the muzzle with moderate bilateral asymmetrical submandibular swelling that was more pronounced on the left side; a pain score of one out of foura was given. The dog was otherwise normal. Pit viper envenomation was suspected again.
Laboratory test results included a PCV of 37% (RI: 37–55%) and normal TS at 62 g/L (RI: 54.0–71.0) with clear serum. The ACT was normal (68 sec [RI: <120 sec]). She was assigned an SSS of one based on the appearance of the wound and the absence of systemic abnormalities.
The dog was admitted to the intensive care unit overnight for supportive care and serial monitoring (Table 2). Treatment consisting of one vial of Fab2 polyvalent crotalidae antivenin was initiated immediately as a continuous rate infusion over a 4 hr period. Three hours after initiation of antivenom therapy (3 hr after presentation), the dog was noted to develop a mild increase in respiratory effort while other physical parameters remained stable. Immediately following completion of the antivenom infusion, IV fluid therapy using LRSc at 50 mL/kg/day was started. Eight hours after presentation, her SSS increased to two given the presence of the persistent mild increase in respiratory effort in the absence of cyanosis or abnormalities on lung auscultation. The SSS increased to four 16 hr after presentation after the dog vomited a small amount of brown food and liquid, which was suspected to represent additional effects of the envenomation. The following morning (20 hr after presentation), the dog’s facial swelling had worsened, but she remained comfortable; the SSS was reduced to two given the resolution of the gastrointestinal signs and dyspnea but progression in local wound appearance. Fluid therapy was discontinued after 14 hr when the IV catheter was found to be nonfunctional. Repeat blood test results included a PCV of 33% (RI: 37–55%) and TS of 54 g/L (RI: 54.0–71.0) with clear serum. The ACT remained normal at 83 sec (RI: <120 sec). She was discharged 20 hr after presentation for at-home monitoring.
On day 63 of gestation, the dog whelped 13 puppies via vaginal delivery at home, with no reported complications. Per the owner, no apparent congenital defects were present, and all puppies survived to at least 1 yr of age, when they were lost to follow-up.
For both cases, informed owner consent was obtained, and the dogs were clinically managed according to contemporary standards of care.
Discussion
Pit viper envenomation during pregnancy is rarely reported in humans and is more common in developing countries. Like dogs, pit viper envenomation in humans can result in multisystemic effects and significant local tissue damage. Envenomation in pregnant humans can also result in adverse effects on the fetus, including placental abruption (abruptio placentae), early labor, maternal hemorrhage and subsequent fetal anemia, and potentially fetal malformations.13 Snake venom is capable of inducing uterine contractions and has direct toxic effects on portions of the placenta.9,14 Some literature in humans suggests that poor fetal outcome is more common when envenomation occurs earlier in pregnancy, but there are reports documenting fetal loss at all stages of pregnancy and in the neonatal period.7,9,10 However, literature providing concrete guidance on management of pit viper envenomation during pregnancy in humans is scarce.
The decision to administer antivenom has traditionally been based on the severity of presentation and progression of clinical signs. The SSS system is based on scoring the severity of clinical signs in six categories—five body systems (pulmonary, cardiovascular, coagulation, nervous, and gastrointestinal) and the appearance of the local wound. The SSS has been validated for use in humans and is considered an important tool in serial evaluation of envenomation patients as it allows for standardization in clinician assessments.5 The SSS has not been validated in veterinary medicine but has been adapted from the human version and found useful for assessing animals.6 Scoring animals is challenging as the frequent measurement of all components of the SSS would require increased cost to the pet owner, and animals cannot provide verbal descriptive responses. The SSS is a helpful aid in serial monitoring of envenomation victims, but it should not be used as the sole factor in guiding antivenin administration.
Antivenom administration is considered fundamental in treatment of pit viper envenomation as it is used to neutralize the circulating venom with the goals of limiting the progression of neuropathies, alleviating pain, and reversing coagulopathy.2,15,16 Although a human publication reports less opioid use when antivenom is used to treat copperhead envenomation, the role of antivenom as an analgesic in veterinary medicine warrants further investigation. The main concern with antivenom administration is the potential for allergic reactions, particularly in those animals that do not need it, such as those with dry bites. Allergic reactions to antivenin can manifest as anaphylactoid (not mediated by immunoglobulin [Ig] E) reactions, anaphylaxis (IgE mediated), and delayed serum sickness. Both anaphylactoid reactions and anaphylaxis are complement-mediated and potentially lethal; often, both terms are used interchangeably to describe type 1 hypersensitivity. Serum sickness is a type 3 hypersensitivity reaction characterized by fever, gastrointestinal signs, lymphadenopathy, and vasculitis; it is an uncommon complication in veterinary patients but is still a concern in those animals requiring large doses of antivenom, particularly of the IgG type.8,15,17
The safety of IgG and F(ab)2 types of antivenin therapy in pregnant dogs and cats is unknown. Case series in humans have demonstrated a highly variable rate of fetal death (3.4–61%) and malformations in pregnant women who were envenomated and treated with antivenom.7,9,10 However, there is no direct causal relationship between poor fetal outcome and antivenom administration in humans. The occurrence of poor fetal outcome in those cases reported may reflect a worse clinical condition of the mother, which necessitated antivenom therapy. Other theories include the potential for direct embryotoxicity of the venom or teratogenic effects of the mercury preservative in some antivenin products.7,8,13 It is unclear how much, if any, antivenom crosses the placenta (especially considering humans with hemochorial and dogs with endotheliochorial placentae). Drugs larger than 1 kDa have been shown to poorly cross the placenta in humans.13 The F(ab)2 antivenome, as administered to the second dog in this series, has a molecular weight of approximately 100 kDa. As a F(ab) dimer, this product has a smaller molecular size than the antivenom crotalid polyvalenth product, which has also been approved for veterinary use. Such information was weighed in the decision to administer antivenom to the second dog, as it was considered unlikely that either of the available antivenom products approved for use in veterinary patients would cross the placenta to a significant degree. As with all envenomation patients, the potential for allergic reactions to antivenom remains, although no studies have demonstrated an increased frequency of hypersensitivity reactions in pregnant women.7 One study found a lower risk of hypersensitivity reactions in pregnant women administered antivenom compared with the general population.8 Whether there is an increased risk of hypersensitivity reactions in pregnant dogs administered antivenom remains unknown. Despite two infusions of antivenom during a single gestational period, no long-term negative effects of antivenom on the bitch or the fetuses were identified in the second case. However, the development of vomiting and diarrhea in the absence of documented hypotension after the second vial of antivenom and the development of a mildly increased respiratory effort after the first vial of antivenom administered to the second dog may have represented a minor allergic reaction or progression of the envenomation. The choice to administer an additional vial of antivenom to the second dog was a clinical decision due to perceived progression based on the mildly increased respiratory effort and concern for fetal injury due to the venom. In retrospect, this could have been a minor reaction to the antivenom, and the severity of signs in this dog was mild; thus, the additional dose may not have been warranted. In humans, pregnancy is not considered a contraindication to antivenom administration.12 Additional studies on the safety and efficacy of antivenom therapy during pregnancy in veterinary patients are warranted.
Conclusion
This is the first case report describing pit viper envenomation in pregnant bitches. This report suggests that positive outcomes are possible after envenomation and the use of antivenom during pregnancy in dogs. However, prospective studies are needed to provide additional guidance on managing these cases and outcomes.
Contributor Notes
