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RPCV (2015) 110 (593-594) 116-119

Toad poisoning in dogs from SW Spain: too many cases in a few days!

Envenenamento por sapos en cães do Sudeste de Espanha: muitos casos em poucos días!

Emilio Hernández-Rebollo1,2, Francisco Javier Duque-Carrasco2, Concepción Zaragoza-Bayle2, Marcos Pérez-López1*

1Toxicology and 2Internal Medicine Units. Fac of Veterinary Medicine (University of Extremadura). Avda de la Universidad s/n. 10003 Cáceres (Spain).

Resumo: Os sapos usam a secreção de veneno como um meca-nismo de defesa contra predadores como aves de rapina e répteis. Embora os animais domesticados também estão em risco de ser envenenados com veneno de sapo, o número de relatórios a dis-cutir a toxicidade do veneno de sapo em cães é limitado. Neste relatório, os sintomas, as estratégias de tratamento e a evolu-ção clínica de três cães que foram envenenados com veneno de sapo são descritos. Os pacientes apresentaram sintomas associa-dos com problemas gastrointestinais, neurológicos e cardíacos. Tanto a gravidade dos sintomas e o tempo de recuperação variou entre os cães. Os nossos dados indicam que o envenenamento de cães com veneno de sapo deve ser considerado uma emergência médica. Além disso, a monitorização intensa dos pacientes é im-portante para a recuperação completa.

Palavras-chave: sapo, veneno, toxinologia.

Summary: Toads use venom secretion as a defense mechanism against predators such as birds of prey and reptiles. Although do-mesticated animals are also at risk of being poisoned with toad venom, the number of reports discussing the toxicity of toad ve-nom in dogs is limited. In this report, the symptoms, treatment strategies and clinical outcome of three dogs that were poisoned with toad venom are described. The patients displayed symp-toms associated with gastrointestinal, neurological and cardiac problems. Both the severity of the symptoms and the recovery time varied between the dogs. Our data indicates that poisoning of dogs with toad venom should be considered a medical emer-gency. In addition, intense monitoring of the patients is impor-tant for complete recovery.

Keywords: toad, venom, dog, toxinology.

Introduction

Multiple toad species, including six members of the Bufonidae family, can be found in Spain. One of these members, Bufo bufo, also known as the common toad, is widely distributed throughout the European continent, Northern Africa and the western part of North-Asia. Although toads lack a venom inoculation system, these animals are considered poisonous. Their skin granular

glands, also known as parotid glands, can produce and se-crete venom of variable toxicity. These parotid glands are not salivary glands, but large aggregations that can empty on the skin’s surface through small orifices (Eubig, 2001). Venom secretion through the skin is an effective defense mechanism against predators (Hardy et al., 2014).

Although the composition of toad venom varies among species (Chen and Kovaríková, 1967), two main groups of chemical compounds, including bioge-nic amines and steroid derivatives, can be detected in venom from all species (Zelnik, 1965). Biogenic com-pounds include both the agonists of the sympathetic autonomic nervous system adrenalin and noradrenalin and the hallucinogens bufotenine, dihydrobufotenine and bufotionin (Zelnik, 1965; Barbosa et al., 2009). In addition to its hallucinogenic effect, bufotenine is known to induce vomiting, diarrhea, depression, tre-mors, seizures, hyperthermia and hypersensitivity to sensory stimuli (Foss, 2011). The main steroid deri-vative in toad venom is the bufogenin-derived bufo-toxin. Bufotoxin exhibits digitalis-related activity and inhibits the sodium-potassium pump in cardiac muscle cells, resulting in gastrointestinal, cardiac and neurolo-gical problems (Camplesi, 2006; Barbosa et al., 2009).

Poisoning of dogs often occurs when the toad is cap-tured with the dog’s mouth, resulting in contact betwe-en the animal’s oral mucosa and the toad’s toxic secre-tions. Since the toxins are rapidly absorbed by the mu-cous membranes of the digestive system, the effects of the venom are manifested within minutes (MacDonald, 1990). For dogs, exposure to 1 mg/kg venom is suffi-cient to induce clinical symptoms of intoxication. The severity of the clinical effects can vary between ca-ses. In mild and moderate cases, signs of oral mucous membrane irritation, sialorrhea, vomiting, depression, ataxia, abnormal cardiac rhythm and neurological disturbances can be observed. In severe cases, unres-ponsive pupils, seizures, pulmonary edema, cyanosis and death may also occur (Knowles, 1968; Otani et al., 1969; Palumbo and Perry, 1983; McFarland, 1999; Barbosa et al., 2009). Due to the variety of the symp-

*Correspondence: marcospl@unex.esTel: +34 927257106; Fax: +34 927257110

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toms that may occur, the veterinary practitioner must be cautious in predicting the clinical outcome of the poisoned animal. Since some poisoned animals die wi-thin 15 minutes of symptom onset, poisoning with toad venom should always be considered a medical emer-gency (Godoy et al., 2005).

Although a few clinical cases have been described, the number of reports discussing amphibian-induced veterinary toxicity remains limited (Moyano Salgado et al., 2009). Described cases not only include pets, but also wildlife, such as marsupials, birds of prey and reptiles from different geographical areas (Wilson et al., 2011).

In this case report, we have described the clinical symptoms, treatment procedures and clinical outcomes of three dogs that were affected by toad venom. All tho-se cases took place during a very short period of time, thus constituting an unexpected toxicological outbreak.

Presentation of clinical cases.

Clinical cases 1 and 2

At the end of September 2013, the veterinary toxico-logy service in Cáceres was contacted by the owner of a 5-year-old male French bulldog. The dog displayed the following symptoms: intense salivation, vomiting, and a low level of apathy and stupor. The owner indica-ted that the dog had licked a small toad in a field. Since the owner lived in a small village, he was instructed to go to a veterinary clinic in his area and to keep in con-tact. Two hours later, a colleague from the local veteri-nary clinic called to inform the toxicology service that he had examined the patient. Although the patient was conscious, he started to develop multiple abnormalities in cardiac rhythm, including tachycardia and arrhyth-mias of ventricular origin. The toxicology service did not receive any information on the treatment strategy and clinical outcome.

Two days later, another veterinary practitioner pho-ned the toxicology service. He had just examined a 2-year-old Rottweiler with suspicion of toad poi-soning. The patient was fully alert, but drowsy and weak. In addition, ptyalism and vomiting were profu-se. Furthermore, a slight hyperthermia was observed. Electrocardiography revealed arrhythmias of ventricu-lar origin and tachycardia. To eliminate venom from the body, the mouth was lavaged with water. Additional therapy included intravenous fluid therapy (NaCl 0.9%), oxygen treatment (2 L/min) and subcutaneous administration of metoclopramide (0.4 mg/kg, every 8 hours). To reduce the arrhythmias, the dog was treated with a mixture of oral propranolol (0.5 mg/kg) and IV lidocaine (2.0 mg/kg). The dog responded well to this treatment strategy. After six days, the dog was released from the clinic and continued treatment at home. At that moment, the communication with the toxicology service was ended.

Clinical case 3

In October 2013, a 10-year-old male Epagneul Breton was admitted to the Veterinary Clinical Hospital of Caceres (University of Extremadura). The dog’s symptoms, including congestion of oral mucosa, sli-ght dehydration and hypersalivation, indicated contact with an irritative substance. In addition, some foam was observed on the mouth. Although his body tem-perature was slightly low (37.5ºC), both tachycardia and tachypnea were observed (200 beats/min and 40 breaths/min, respectively). In contrast, respiratory and cutaneous explorations revealed no aberrations. During anamnesis, the owner stated that the patient had vomited twice. Subsequent examination of the digestive system revealed abdominal pain. Locomotory examination re-vealed moderate ataxia and muscle rigidity, both evo-luting to muscle weakness and prostration within minu-tes. In addition, the dog initially walked in circles and was somewhat confuse due to neurological problems. Electrocardiography revealed the occurrence of ventri-cular extrasystoles (figure 1). Furthermore, a number of laboratory tests (biochemistry and blood) were per-formed (table I). The patient exhibited elevated levels of urea and hypoalbuminemia. Since toad venom does not directly affect the kidneys (Simão, 2007), these symptoms could have been due to dehydration instead of renal failure (Barbosa et al., 2009). The levels of po-tassium and chlorine were slightly enhanced. However, reduced levels have also been reported in other studies. Finally, while a modest reduction in the number of red blood cells and hemoglobin was observed, the numbers of both white blood cells and platelets were markedly increased.

Table 1 - Biochemistry and blood analysis.

parameter value Normal range

Urea 63.3 mg/dl 10-58

Creatinine 0.6 mg/dl 0.5-1.6

Calcium 10.3 mg/dl 9.2-11.6

Phosphorous 4.9 mg/dl 2.0-6.7

Sodium 151.4 mEq/l 147-154

Potassium 5.36 mEq/l 3.9-5.2

Chlorine 120.4 104-117

Total proteins 6.6 g/dl 5.5-7.2

Albumin 2.7 g/dl 2.8-4.0

Red blood cells 5.12 * 106 /µl 5.32-7.75 *106

White blood cells 21.2 *103 /µl 4.36-14.8 *103

Hemoglobin 11.6 g/dl 13.5-19.5

Hematocrit 39.7 % 39.4-56.2

Medium Corpuscular Volume

77.5 65.7-75.7

Medium Corpuscular Hemoglobin

29.2 32-36

Platelets 573 *103 /µl 194-419 *103

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Since digestive lavage is recommended for all ex-posures, the treatment started with a single dose of activated charcoal (Eubig, 2001). However, due to the rapid absorption of the venom by the mucous mem-brane, treatment with activated charcoal is only effec-tive immediately after toxin ingestion (Barbosa et al., 2009).

Although an initial shock dose of fluids is highly recommended for dogs displaying moderate to severe symptoms of poisoning, fluids were not administered in this case. The arrhythmias were treated with IV li-docaine (antiarrhythmic, 2.0 mg/kg). In addition, to reduce motion sickness and vomiting, the dog was treated with ranitidine (gastric protector, Zantac®) and SC Maropitant (Cerenia®). Since some poiso-ned dogs develop perivascular edema in the brain, IV Methylprednisolone (Urbason®, anti-inflammatory 15 mg/kg) (Peneyra and Masanga, 1966) was admi-nistered. Since treatment and supportive care were initiated shortly after exposure to toad toxins, a fa-vorable outcome was expected. Indeed, the cardiac rhythm had normalized after two days of treatment (figure 2). In addition, laboratory tests revealed that, after five days of treatment, the number of blood cells were within the normal range. Furthermore, all cli-nical symptoms had disappeared, indicating that the dog had recovered completely.

Figure 1 - Rhythm strip recorded from a dog affected by toad en-venomation (case 3). The continuous lead II electrocardiogram (25 mm/s, 10 mm/mV) reveals ventricular tachycardia (VT) and ventricular premature complex (VPC).

Figure 2 - An ECG tracing (lead II) obtained from a poisoned dog (case 3) after treatment with lidocaine bolus at 2 mg/kg/IV. Please note that there is a sinus rhythm. Paper speed = 25 mm/s; 10 mm/mV.

Discussion

Poisonous amphibians include frogs, salamanders and toads. To date, only toads have been associated with toxicosis in domestic animals (Gwaltney-Brant et al., 2007). Toad poisoning may cause local and/or systemic toxicity (Pantanowitz et al., 1998). Although poisoning is usually caused by mouthing or ingestion of the amphibian, it can also occur when secretions are brought into contact with skin, mucosa or conjunctiva. In addition, venom may directly enter the circulation

when cuts or abrasions are present (Lutz, 1971). It is therefore important to eliminate non-absorbed venom from the patient´s body by extensive rinsing of the mouth and affected areas with tap water (Hardy et al., 2014).

Envenomation effects range from local irritation to systemic symptoms (gastrointestinal, cardiac and neurological) that eventually result in death (Sakate and Lucas de Oliveira, 2001; Barbosa et al., 2009). Some of the digestive symptoms, including vomi-ting and sialorrhea, help eliminate venom from the body. Although vomiting induction may be beneficial in some cases, it is contraindicated when patients are prostrated (e.g., dog of case 3). To stop nausea and persistent vomiting due to gastric irritation, an-tiemetic therapy can be used (as observed in dog 3) (Barbosa et al., 2009). The use of atropine, to redu-ce salivation and lung secretion, is not recommended since it reduces the elimination of poison through sa-liva. However, a low dose may be used to treat severe bradycardia (Eubig, 2001).

For the treatment of arrhythmias, monitoring is es-sential. Although Lidocaine can effectively suppress ventricular arrhythmias, it has no effect on supraven-tricular arrhythmias. In addition, animals that deve-lop negative ventricular deflections cannot be treated with Lidocaine (Sakate and Lucas de Oliveira, 2001). In some cases, treatment with Lidocaine alone is not sufficient. In these cases either combination therapy or the use of an alternative compound, such as pro-pranolol, is necessary.

In general, toad poisoning causes inflammation, which is usually associated with leukocytosis (as ob-served in case 3) and neutrophilia. Antibiotic therapy can be employed to reduce the risk of septic compli-cations in animals that display clinical signs of seve-re intoxication (Barbosa et al., 2009). Hyperkalemia can be treated with glucose, insulin or bicarbonate. The administration of calcium is not required in ca-ses of toad poisoning (Roder, 2004). Digoxin-specific antigen-binding fragments have been administered to people who developed clinical symptoms upon expo-sure to Bufo toxins. However, the use of this product in veterinary practice may be cost-prohibitive (Eubig, 2001). Finally, the lifespan of poisoned dogs can be increased by anesthetizing the animals with pento-barbital sodium. However, a low mortality rate has been reported for dogs affected by toad poisoning. In America and Australia, for example, the survival rate appears to be over 90% (Hardy et al., 2014).

The treatment strategy and clinical outcome depend on the severity of the symptoms, the duration of the exposure, and the amount and toxicity of the venom (Barbosa et al., 2009). In addition, the size of the affected animal is important for the clinical outcome. Smaller dogs are, in general, hospitalized for longer periods and are more likely to die from the symptoms (Sonne et al., 2008).

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