A previously healthy 3-year-old 8-lb (3.6-kg) intact male Yorkshire terrier was found seizing and hypersalivating in the owner’s backyard next to a partially consumed toad.
Upon arriving at the clinic, the dog was hypersalivating, hypermetric, disoriented, and moderately tachycardic (200 bpm).
Shortly after the examination, the dog had a short seizure episode and vomited parts of the toad, including aspects of the head. The dog’s owner also gave the clinic the remnants of the consumed toad and a live specimen from the same area. Based on comparison of the cranial morphology, the toad was identified as a cane toad (Bufo marinus).
From the toad identification and consistent clinical signs, Bufo species toad intoxication was diagnosed, and treatment was initiated.
An intravenous catheter was placed, and the dog was started on intravenous fluids (Normosol R [Hospira]; 60 mg/kg/day). An antiemetic was administered (maropitant, 2 mg/kg subcutaneously), followed by activated charcoal (2 g/kg orally). Shortly after receiving the charcoal, the dog started seizing but responded quickly to a single injection of diazepam (0.5 mg/kg intravenously). The diazepam also sedated the dog slightly, and his heart rate decreased from 200 to 160 bpm. A baseline complete blood count (CBC) showed a mild leukocytosis (17.6 x 103/µl; normal = 6 to 16 x 103/µl) and mild elevation in serum alanine aminotransferase (ALT) activity (258 U/L; normal = 10 to 100 U/L).
Thirty minutes after administration of diazepam, the dog redeveloped sustained tachycardia (200 bpm), which was responsive to 0.03 mg/kg of propranolol given intravenously. Three hours after presentation, the dog developed a short period of chewing gum-like seizures, which resolved before diazepam was administered. Shortly after this episode, sustained tachycardia (210 bpm) returned with multiple episodes of ventricular premature contractions (VPCs) identified on continuous electrocardiogram (ECG). The dog was given a slow intravenous injection of lidocaine (3 mg/kg) and then a continuous rate infusion (CRI) of lidocaine at 30 µg/kg/min. The CRI was continued for two hours, after which no further VPCs were seen, so the dog was slowly weaned off the CRI lidocaine over an hour.
Over the next eight hours, the dog continued to recover with no further cardiac abnormalities noted on ECG and no clinical central nervous system (CNS) effects seen. A mild diarrhea was noted when the dog passed additional sections of the toad, but it resolved without treatment. The dog was discharged without any clinical signs to the owners 16 hours after presentation. Blood work evaluation 48 hours after the exposure showed complete resolution of the leukocytosis and elevated ALT activity.
Bufo marinus, also known as the giant toad, marine toad, or cane toad, is a large nocturnal toad found mostly in Florida, Hawaii, and a small section of southern Texas. Extensions of these traditional geographical boundaries have been recently noted as a result of environmental change.1 It’s the most commonly reported source of bufotoxin exposure cases in dogs in North America.1
Other members of the Bufo genus of toads are found throughout the world, with toxic species found in every U.S. state and Canadian province. Toads are most active in the spring and summer, with most clinical cases reported between June and September.1,2
Clinical signs are most commonly seen after an animal mouths or consumes an adult toad. Additional cases have been reported after ingestions of dried Bufo species toads, toad eggs, or tadpoles as well as aphrodisiac supplements (e.g. Love Stone, ch’an su, Rock Hard) made from the toads.1 Direct or referred ocular contact has also been shown to be sufficient to induce clinical signs.1 Anecdotal reports also exist of dogs developing gastrointestinal (GI) upset and cardiac arrhythmias after consuming water from bowls where Bufo species had been seen sitting for prolonged periods.1
Toxic properties and effects
Contact with a member of the Bufo species exposes a person or animal to a wide range of toxins. The most common causes of clinical signs are the cardioactive substances called bufogenins and bufotoxins. These substances function similar to digoxin, via inhibition of the function of the cardiac sodium-potassium-ATPase pump, resulting in potentially fatal cardiac arrhythmias.1 These toxins have some enterohepatic recirculation, potentially prolonging the clinical effects of the toxins.1
Venom may also contain varying mixtures of bufotenines, which are indolealkylamines with differing degrees of oxytocic, pressor, and hallucinogenic properties. These toxins are contained in small amounts in the skin and more heavily concentrated in the parotid glands found on the head, with some species having additional toxin glands on their hindlimbs (e.g. Incilius alvarius [formerly Bufo alvarius]). Additionally, some venom is known to contain active catecholamines (epinephrine, norepinephrine), though rapid GI degradation likely limits the clinical effect.1
While LD50 values do exist for the individual bufotoxins and some bufogenins in some animals, these values provide little clinical or treatment guidance since the clinical syndrome that occurs after Bufo species exposure is the result of the combination of various toxins, rather than one single toxin.
GI signs (hypersalivation, retching, vomiting) after exposure are often seen immediately or within 30 minutes. The more severe cardiac signs have occurred in as short as 15 minutes after exposure, though delayed signs up to four hours have been reported.1,2
The most commonly reported cardiac abnormality in dogs is tachycardia, with heart rate at times exceeding 260 bpm. More serious cardiac aberrations reported include VPCs, junctional escape beats, and atrioventricular block (first and second degree). Frequently, these arrthymias are profound enough to cause hypotension, resulting in acute collapse or prolonged recumbency.2,3 In people, bradycardia is the most commonly seen cardiac disturbance. This difference in people could be attributable to a more consistently seen hyperkalemia contributing to the decreased heart rate.1,4
Additional signs commonly reported in animals include tremors, seizures, dypsnea, tachypnea, disorientation, and ataxia. These signs were consistently reported within the first hour of exposure to the toad.2 Hyperkalemia is a consistent hematologic abnormality found in people, though not consistently reported in animals.1,2,4 No other hematologic abnormalities are consistently reported in people or animals.
Diagnosis is based on history of exposure (toads in yard, history of interaction with toads, or evidence of toad tissue in vomitus), with rapid onset of GI signs (vomiting, hypersalivation), CNS effects (shaking, trembling, seizures), and, potentially, cardiac signs (ECG changes, collapse, pale mucous membranes). Differential diagnoses include exposure to organophosphates, grayanotoxin-containing plants (Rhododendron, Kalmia, Pieris species), digoxin-containing plants (Oleander, Digitalis, Convallaria species), beta-blockers, and methylxanthines.
The goals of therapy are early decontamination, control of GI signs, and monitoring and stabilization of CNS and cardiac signs.
1) Decontamination. Because of the rapid onset of signs, emesis should only be employed in patients exhibiting no or mild clinical signs known to have consumed aspects of the toad. Emesis can be induced with either hydrogen peroxide (2.2 ml/kg orally, can be repeated once) or apomorphine (0.03 mg/kg intravenously).
Animals that have simply mouthed the toad receive no benefit from the induction of emesis. For such cases, immediately rinse the mouth with a copious amount of water. Activated charcoal (2 to 4 g/kg) has been shown to bind other cardiac glycosides and is likely effective with bufotoxins as well. Administration of activated charcoal is contraindicated in an animal showing central nervous signs or significant vomiting. A second dose (six to eight hours after the initial dose) may be warranted in cases with persistent clinical signs where immunoglobulin fragments (ovine digoxin immune Fab [Digibind—Smithkline Beecham]) is not available. Gastric lavage is also a potential option, especially when large pieces or amounts of the toad have been consumed or seizure activity necessitates the use of anesthesia.
2) Control of GI signs. For control of additional GI signs, antiemetics (maropitant 1 mg/kg subcutaneously once a day) are indicated. Atropine should not be used for hypersalivation unless additional cardiac indications (bradycardia) also exist as it may aggravate tachyarrhythmias later in the clinical course. Seizure activity can be controlled with either diazepam (0.5 to 1 mg/kg intravenously), pentobarbital (3 to 15 mg/kg intravenously), propofol (3 to 6 mg/kg intravenously), or gas anesthesia. Tremors can also be controlled with methocarbamol (55 to 220 mg/kg intravenously to effect).
Fluid therapy is warranted to prevent dehydration from GI signs, support cardiovascular functions, and increase the elimination of the venom. As with digoxin toxicity, noncalcium-containing fluids (e.g. Plasma-Lyte A [Baxter], Normosol R [Hospira]) are recommended.
3) Control of CNS and cardiac signs. Potential heart rate and rhythm abnormalities produced by toad toxins are varied and can change significantly over the course of the treatment period. Therefore, it’s recommended that, if available, constant ECG monitoring should be used in severely affected animals.
Multiple drug therapies are available for the various cardiac arrhythmias that can present with exposure to toad toxins. Phenytoin (10 mg/kg slowly intravenously; not recommended in cats) or lidocaine (2 to 4 mg/kg slowly intravenously, followed by CRI of 25 to 100 µg/kg/min) are effective for ventricular arrhythmias, whereas propranolol (0.02 to 0.06 mg/kg intravenously) or esmolol (0.5 mg/kg slowly intravenously, followed by 50 to 200 µg/kg intravenously CRI) are preferred for supraventricular tachyarrhythmias. Atropine (0.02 to 0.04 mg/kg intravenously or intramuscularly) remains the drug of choice for bradycardia, provided that hyperkalemia is not present.
For persistent cardiac abnormalities or profound hyperkalemia, the use of ovine digoxin immune Fab should be considered. This agent directly binds digoxin and other cardioactive sterols, thereby inactivating them.5,6 In people, the amount administered is based on serum digoxin concentrations, which may not be readily available to veterinary practitioners. Because of this, administration of one to two vials intravenously has been recommended as an initial treatment, with additional vials administered as dictated by clinical signs. Administered ovine digoxin immune Fab that does not bind digoxin is not expected to be detrimental.
Serum digoxin or digitoxin immunoassays (polyclonal) can be used to confirm the presence of cardiac glycosides in suspected cases, though they cannot confirm a toad as the source of the toxin1 in animals without a witnessed exposure to a toad or in the cases of supplement exposures. High-performance liquid chromatography can be used to determine the presence of toad toxins in water, food, supplements, or tissues, but the time delay for results renders it ineffective in guiding emergency management.
Baseline complete blood count and serum chemistry profiles should be performed to identify any underlying pathologies that may complicate treatment (hepatic disease). With cases involving profound cardiac signs, especially prolonged hypotension, renal values should be monitored for two to three days after the resolution of signs to determine if secondary renal injury develops.
Although hyperkalemia is infrequently seen in animals, serial serum potassium concentrations (every two to four hours) should be obtained for the first 12 hours of monitoring.
Conclusion and clinical relevance
The territory inhabited by poisonous Bufo species is expanding rapidly, as is the use and distribution of products containing extracts of these species. This increases the chances of clinical cases developing in areas where this form of toxicosis has not previously been considered as a differential diagnosis.
The multiple components of toad venom can cause a multifocal life-threatening clinical condition rapidly. So a swift diagnosis, combined with aggressive initial decontamination, is necessary to prevent extended clinical signs or fatalities.
1. POISINDEX editorial staff: Toad toxins. POISINDEX System [intranet database]. Micromedex, Englewood, Colorado, 2012.
2. AnTox Database, Urbana, Illinois: ASPCA Animal Poison Control Center, 2013.
3. Eubig PA. Bufo species toxicosis: big toad, big problem. Vet Med 2001;96(8):594-599.
4. Gowda RM, Cohen RA, Khan IA. Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications. Heart 2003;89(4):e14.
5. Brubacher JR, Lachmanen D, Ravikumar PR, et al. Efficacy of digoxin specific Fab fragments (Digibind) in the treatment of toad venom poisoning. Toxicon 1999;37(6):931-943.
6. Morgan R. Digoxin immune Fab. In: Small animal drug handbook. 5th ed. St. Louis: Saunders Elsevier;2008;67.
The ASPCA Animal Poison Control Center (APCC) is a 24-hour animal emergency consultation service that provides treatment and diagnostic recommendations to animal owners and veterinarians regarding animal poisoning cases 24 hours a day, 7 days a week, 365 days a year. Since 1978, the veterinary staff at the APCC has experience of handling more than 2 million animal poisoning cases involving pesticides, herbicides, plants, human and animal drugs, heavy metals, and many other potentially hazardous chemicals. A $65 consultation fee may apply. This includes follow-up consultations for the duration of the case. If you think your animal may have ingested a potentially poisonous substance, call (888) 426-4435. Additional information can be found online at www.aspca.org/apcc.