Introduction
India harbors approximately 472 species of amphibians [1] and 610 species of reptiles [2]. Among the amphibians, toads are abundantly found in rural and urban areas of the Odisha state where serve as prey for predator snakes and have poisonous compounds (buffo toxins) in their skin. The buffo toxin serves as a chemical defensive strategy against the predators [3]. Marine toads belonging to the family Bufonidae, in the order Anura, are among the poisonous toads found in India. Among the animal species, dogs are most likely to be the victims because of their inquisitive nature and attracted by the sluggish movement of the toad. Dogs are poisoned by mouthing, chewing, or swallowing the toads, particularly while playing or roaming around the lakes, rivers, and oceans [4]. Sialorrhea and hyperemic mucus membrane develop quickly after oral exposure to the toad toxins followed by vomiting, nystagmus, mydriasis, cardiac arrhythmia, and status epilepticus in the moderate to severe cases [5,6].
Among the reptiles found in India, there are more than 270 species of serpents including about 60 venomous species. Russell’s viper (Daboia russelii) is one of the highly venomous snakes, and its envenomation causes aberrations in the blood coagulation mechanism and renal failure. Horses and dogs are more common victims of snakebites, compared to other animal species such as cattle, sheep, and goats [7]. The most common sites for snakebites in dogs are the head, face, and limbs because of the playing and attacking behavior of dogs. In contrast to snakebite cases in humans, very few cases in animals are witnessed by the pet owner, leaving the diagnosis to be made based on clinical findings, such as the presence of fang marks, edema at the site of the bite, signs of systemic coagulopathy, hemolysis, cardiac arrhythmia, and, sometimes, neurological disorders [8]. The present study describes the medical management of an unusual case of concurrent marine toad toxicity along with envenomation by Russell’s viper snake in a German shepherd dog.
Case History
A German shepherd dog aged 6 years was presented to the Veterinary Clinical Complex, Bhubaneswar, from the coastal area of Odisha, Konark subdivision of Puri district, with a complaint of frothy salivation, vomiting, dullness, depression, recumbence, and bloody urination. Anamnesis revealed roaming of the dog around a river bank near the house in the morning time and fighting with a viper snake while the snake was predating a toad, 5 hours before reporting at the hospital. As per the pet owner’s statement, the snake and toad were Russell’s viper and marine toad, respectively.
Clinical observations
Physical examination revealed a cyanotic swollen area on the left forepaw, ulcers on the tongue epithelium (Fig. 1), brick red discoloration of mucus membrane oral cavity and conjunctiva (Fig. 2), and ptyalism. There was a subnormal temperature (37.6ºC), increased respiration rate (46 breaths/minute), and tachycardia (heart rate 234 bpm).
Figure 1.
Ulcerative lesions on the tongue mucosa.
A peripheral blood sample was collected with and without anticoagulant for complete blood cell count and serum biochemistry profile, respectively. Hematological examinations revealed increased hemoglobin and packed cell volume (PCV), leucocytosis, and neutrophilia. Serum biochemistry showed elevated alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), serum creatinine and serum potassium concentration (Table 1). Five milliliters of fresh whole blood was also collected in a test tube and left undisturbed to determine the blood clotting time and was found unclotted even after 90 minutes of the collection, which indicated a clotting disturbance. Electrocardiogram (ECG) (CARDIART 8108 VIEW, BPL Limited, Palakkad678007, India) and thoracic radiographs were performed for cardiac and thoracic evaluation, respectively. ECG revealed ventricular tachycardia with an indistinct T wave (Fig. 3A). However, no significant abnormalities were observed in the morphology of lungs and heart in thoracic radiography (Fig. 4). Coupled with history from an educated pet owner, ulcerative lesions on the tongue and ventricular tachycardia in an ECG indicated exposure to the toad toxin. On the other hand, fang marks on the paw (13 mm apart), extended blood clotting time, and alterations in hemato-biochemical parameters strongly suggested snake envenomation [9]. Therefore, the case was diagnosed as an envenomation by a viper snakebite along with marine toad toxicities from the clinical investigation as well as the owner’s observation.
Figure 2.
Brick-red color of the mucous membrane of the conjunctiva.
Table 1.
Hemato-biochemical findings of the dog before and after treatment.
| Parameters | Pre-treatment | Post-treatment | Reference range | |
|---|---|---|---|---|
| Third day | Seventh day | |||
| Clotting time (minute) | >90 | 5 | 3 | 3–5 |
| Hemoglobin (g/dl) | 20.8 | 14.6 | 13.4 | 12–18 |
| Red blood cells (106/µl) | 8.73 | 6.2 | 5.6 | 5–7.9 |
| PCV (%) | 58 | 44 | 39 | 35–57 |
| MCV (fl) | 75 | 78 | 77 | 66–77 |
| MCH (pg) | 17 | 21 | 23 | 21–26.2 |
| MCHC (g/dl) | 32.4 | 31.4 | 32 | 32–36 |
| TLC (/µl) | 22,000 | 18,000 | 6,400 | 6,000–17,000 |
| Relative neutrophil count (%) | 82 | 74 | 64 | 60–77 |
| Relative lymphocyte count (%) | 9 | 20 | 28 | 12–30 |
| Relative monocyte count (%) | 9 | 4 | 5 | 2–10 |
| Relative eosinophil count (%) | 0 | 2 | 3 | 2–10 |
| Relative basophil count (%) | 0 | 0 | 0 | 0–1 |
| Absolute neutrophil count (/µl) | 18,040 | 13,320 | 4,096 | 3,000–11,500 |
| Absolute lymphocyte count (/µl) | 1,980 | 3,600 | 1,792 | 1,000–4,800 |
| Absolute monocyte count (/µl) | 1,980 | 720 | 320 | 150–1,350 |
| Absolute eosinophil count (/µl) | 0 | 360 | 192 | 100–1,250 |
| Absolute basophil count (/µl) | 0 | 0 | 0 | 0–200 |
| ALT (U/l) | 144 | 86 | 36 | 10–110 |
| AST (U/l) | 95 | 61 | 34 | 15–30 |
| ALP (U/l) | 168 | 32 | 28 | 3–60 |
| Creatinine (mg/dl) | 2.2 | 1.8 | 1.4 | 0.5–1.7 |
| BUN (mg/dl) | 35 | 26 | 15 | 8–28 |
| Total protein (g/dl) | 5.1 | 5.2 | 5.5 | 5.4–7.5 |
| Albumin (g/dl) | 2.3 | 2.4 | 2.3 | 2.3–3.1 |
| Globulin (g/dl) | 2.8 | 2.8 | 3.2 | 2.4–4.4 |
| Potassium (mEq/l) | 8.2 | 4.8 | 4.4 | 3.9–5.1 |
| Sodium (mEq/l) | 143 | 136 | 139 | 142–152 |
| Chloride (mEq/l) | 112 | 126 | 125 | 110–124 |
| Calcium (mg/dl) | 12 | 11 | 11.2 | 9.1–11.7 |
Bold values indicate <0.05.
Treatment and follow-up
The oral cavity of the dog was lavaged with normal saline immediately after reporting. The animal was admitted and treated with 10 ml of polyvalent snake antivenom (Bharat Serums and Vaccines Ltd., India) along with 500 ml of 5% dextrose normal saline intravenously, 1 ml of tetanus toxoid (Serum Institute of India Pvt. Ltd., India) intramuscularly, dexamethasone [at] 1 mg/kg IM q24h for 2 days (Dexona, Zydus Cadila, India), and chlorpheniramine maleate [at] 0.5 mg/kg IM q24h for 2 days (Avili® VET, MSD Animal Health, India). Furthermore, propranolol [at] 0.02 mg/kg (Properol, Samarth Life Sciences Pvt. Ltd., India) was administered intravenously once to alleviate cardiac arrhythmia. Besides, Enrofloxacin [at] 5 mg/kg IM q24h was used for 5 days (Enrocin, Intervet Pvt. Ltd., India) to prevent secondary bacterial infection. Besides, ondansetron [at] 1 mg/kg IM q12h for 3 days (Sun Pharma Laboratories Ltd., India) to check vomiting and hemocoagulase (1 ml IM q24h for 3 days; Botropase, Juggat Pharma, India) to check hemorrhage were also administered. Glycerine-based oral gel preparation containing choline salicylate and benzalkonium chloride solution (Oraflora Gel; McW Healthcare Pvt Ltd, India) was applied over the tongue thrice a day for 10 days for healing of the oral ulcer. The antibiotic therapy was continued for 5 days along with intravenous polyionic isotonic crystalloid fluid (Lactated Ringer’s solution) and 5% dextrose solution.
Figure 3.
(A) ECG picture before treatment, indicating ventricular tachycardia, decreased R-R interval (6 mm); heart rate of 250 beats per minute (bpm). (B) ECG picture showing R-R interval (11 mm); heart rate of136 bpm [Red arrow on lead II showing R-R interval (normal=10–18 mm) on the 2nd day following treatment (paper speed-25 mm/second, each large square measure 5 mm)].
Figure 4.
Thoracic radiograph of heart and lungs showing no radiographic abnormalities. Vertebral heart score=9.5 (normal=8.7–10.5).
ECG report was normal with regular cardiac rhythms along with all distinct ECG waves on the second day of treatment (Fig. 3B). Vomiting and bloody urination subsided within 2 days of treatment and on the 3rd day blood clotting time was normal (Table 1). However, the animal refused to take food orally for the first 4–5 days, which might be due to oral ulcers and the dog slowly started taking a very small amount of liquid food after the 5th day. On the 7th day, hemato-biochemical parameters were estimated again where all the parameters were within the reference range (Table 1), and the animal was discharged. The owner was contacted telephonically after 3 weeks, who reported the dog normal with respect to all the regular activities with a playful nature.
Discussion
Snakebites have been incriminated for a significant degree of morbidity and mortality worldwide, particularly in low-resource countries. There are over 600 species of identified venomous snakes worldwide, with the majority belonging to the Viperidae and Elapidae families. Common names among the Viperidae family include vipers, pit vipers, and adders [10]. The evidence of snakebites in dogs is most commonly found in the head, neck, and limbs. In the current study, the fang marks were identified on the left forepaw. The enzyme “hyaluronidase” in viper venom cleaves the glycoside bonds in the hyaluronic acid present in the extracellular connective tissue matrix and acts as a spreading factor, thus facilitating the penetration of other toxins [11]. The toxin “hemorrhages” in snake venom causes damage to endothelial cells and increases vascular permeability, which, in addition to the action of hyaluronidase, may cause cyanotic swelling at the site of the bite, as evidenced in the present case [12]. The enzyme “phospholipase-A2” in snake venom contains both pro- and anticoagulant activities as reflected by inhibition of the prothrombinase, inhibition, and activation of platelet aggregation, which is responsible for coagulation defects [12]. This might be the reason for the elevation of clotting time in the present case. Bloody urination observed in this study might be due to the hemotoxic effect of snake venom mainly hemorrhages that cause spontaneous bleeding [13].
Symptoms like ptyalism and hyperemic mucous membrane found in the case were consistent with other reports [14,15] and are attributed to the local irritant effects of the orally exposed toad toxins such as bufadienolide, catecholamines, and indole alkylamines [16]. These toxins in the parotid glands of toads are drained out through the tiny orifices of their skin [17]. However, ptyalism and vomiting are attributed to envenomation by viper snakes [12].
The common cardiac arrhythmias found in marine toad intoxication include sinus bradycardia, sinus tachycardia, first- and second-degree AV block, ventricular tachycardia, and ventricular fibrillation [3]. However, in the current study, only ventricular tachycardia was evidenced by decreased R-R interval in ECG (Fig. 3A) which corroborated with other studies [14,18]. Such alterations might be due to the increase in intracellular calcium concentration in cardiac muscle due to the inhibition of the Na+-K+-ATPase pump by the compound bufadienolide present in the toad toxin.
Alterations in the hematological parameters like leukocytosis, neutrophilia, and monocytosis observed in this case might be due to acute inflammation at the site of bite and ulceration [19]. Hemoconcentration is a common finding following a viper snakebite that results from splenic contraction and fluid loss to the third space due to hemorrhagins present in snake venom [20]. An elevated level of the ALT, AST, ALP, serum creatinine, and BUN in this study might be due to the hepatotoxic and nephrotoxic effect of either toad toxins [6] and/or snake venom [11]. Hyperkalemia, the most common electrolyte alteration found in marine toad intoxication, recorded in this case, could be the result of the trans-cellular shifting of potassium out of the cell due to inhibition of Na+-K+ATPase pump by bufadienolides present in toad toxins [6].
Oral lavage is an important decontamination method adopted in this study, which played a vital role in removing the toad’s secretions as soon as possible, thus limiting the continued absorption of toxins through the oral mucosa [3]. Although the therapeutic efficacy of digoxin-specific antigen-binding fragments (Fab) has proven to be beneficial in reversing the cardiac arrhythmias evidenced in toad intoxication, the higher cost and non-availability rendered its use unfeasible in veterinary medicine [6]. Propranolol, a β-adrenergic receptor antagonist, has been recommended in toad intoxication by several authors [15,18] due to its outstanding response in reversing ventricular arrhythmias. The use of atropine to control hyper-salivation in toad intoxication is controversial and was not recommended as it reduces the elimination of poison through saliva [21]. The use of centrally acting anti-emetic drugs like ondansetron is recommended to inhibit the action of serotonin-derived indole alkylamine compounds present in toad toxins [3]. Dexamethasone was administered to prevent shock and, also, for its anti-inflammatory properties. Acute kidney injury caused due to the nephrotoxic effect of snake venom and/or toad toxin was managed by fluid therapy as it was for a transient period, and serum creatinine and BUN were normal by day 3rd post-treatment. Similarly, no hepatoprotectants were used as the cause of hepatic injury was removed by neutralizing the venom with snake antivenom. Furthermore, serum ALT, AST, and ALP became normal by the 3rd day post-treatment.
Antivenom administration is the only specific therapy for serpent envenomation that binds and neutralizes the effect of toxins present in snake venom and prevents further damage. In India, horses are hyperimmunized against the venom of four common venomous snakes the “Big Four” (Cobra, Krait, Russell’s viper, and Saw scaled viper) to produce polyvalent snake antivenom [9] that was used in this case. Antihistamines and corticosteroids were used to surmount the anaphylactic reactions of the lyophilized polyvalent snake antivenom. The dog was also administered with tetanus toxoid to ensure protection from spores of Clostridium tetani that could have come into the biting site from contaminated fangs of the snake [9].
Conclusion
Propranolol administration provided an excellent therapeutic result in restoring the cardiac rhythm in case of marine toad poisoning and polyvalent snake anti-venom was found to be efficacious against viper snake venom. Such toxicities can be fatal and should be considered critical, where early diagnosis and adoption of an appropriate therapeutic regimen contribute to the uneventful recovery of the patient. Client education, especially in the areas where these species commonly inhabit, is essential for early recognition and correct identification of the venomous creatures that simplify the management of toxicity.
Conflict of interest
No conflict of interest declared by the authors.
