Cane Toad (Rhinella marina) Toxicity in Dogs and Cats

Philip R Judge BVSc MVS PG Cert Vet Stud MACVSc (Vet Emergency and Critical Care; Medicine of Dogs)

Introduction:

Cane toads (Bufo marinus – recently re-classified as Rhinella marina) are an invasive species of toad in Australia and many tropical regions worldwide, that are native to Central and South America. 

Their presence as introduced, or invasive species is a concern for both native wildlife, as well as domesticated pets – who may become envenomed during interactions.  Cane toad toxicity is particularly common in dogs, as they are more likely to antagonise and mouth or bite the toads.

This short review outlines the composition of the cane toad toxin, how the components of the toxin produce clinical symptoms of cane toad poisoning, and the emergency treatment of toxicity in both dogs and cats.

The Toxins

When threatened, cane toads secrete a potent milky venom containing over 70 biologically active compounds. The most clinically significant toxins include:

1. Bufogenins (bufadienolides) are cardiotoxic, owing to their mechanism of action on the ATPase enzyme in cardiac tissue
   1. Are structurally similar to cardiac glycosides, and have a similar effect to digitalis
   2. Inhibit sodium-potassium ATPase enzyme in cardiac myocytes and neurological tissue, producing cardiac arrhythmias
   3. Cardiac arrhythmias such as ventricular tachycardia, which can progress to ventricular fibrillation are the most common clinical effect
   4. Bufadienolides also affect voltage-gated sodium, potassium, and calcium channels, further destabilizing excitable membranes, and can produce CNS stimulation in addition to cardiac arrhythmias
2. Bufotenine is a psychedelic tryptamine compound that binds to the 5HT2 receptor (serotonin), producing the following symptoms
   1. Agitation and restlessness
   2. Twitching muscle
   3. Dilated pupils
   4. Hypertension
   5. Muscle rigidity
   6. Respiratory distress
   7. Cardiac arrhythmias
3. Bufotoxins – are a family of toxic compounds, and are chemically related to the bufadienolides and substituted tryptamines – but are less potent.  Bufotoxins can cause a range of effective including
   1. Tachycardia
   2. Arrhythmias
   3. Cardiac arrest
   4. Vomiting and diarrhoea
   5. Seizures and tremors
4. Indole alkylamines – are 5HT (serotonin) analogues that produce hallucinogenic symptoms, and symptoms of serotonin stimulation, including seizures, ataxia, tremors, hyperactivity, and bronchoconstriction.
5. Catecholamines are found in secretions of R marina, and contain adrenaline, noradrenaline and dopamine. Mucosal absorption of adrenaline can contribute to arrhythmias, especially in the presence of other arrhythmogenic compounds contained within the toad secretions

These toxins are rapidly absorbed through mucous membranes – particularly the oral cavity – but they may also enter circulation through open wounds.

Clinical Presentation

Exposure most commonly occurs when a curious animal bites or mouths a toad. The first signs can be dramatic and develop within seconds to minutes.

Initial symptoms are usually related to the irritant effects of toad toxins in the oral cavity or skin and eyes and include pawing at the mouth, facial rubbing and irritation, and excessive salivation)

Secondarily, effects related to the systemic effects of the various toxins contained in the toad venom, with clinical signs seen related to toxin effects on cardiovascular system, nervous system, and respiratory system. The following table outlines the most common symptoms observed:

Incidence of Physical Examination Findings

• Neuropathy (seizures, ataxia, nystagmus, coma) – 55% 
• Brick-red mucous membranes – 50% 
• Hyper-salivation- 40% 
• Anxiety, shaking – 25% 
• Collapsed, recumbent – 20% 
• Vomiting – 10% 
• Mydriasis/Anisocoria- 5%

Differential Diagnoses

Because signs may overlap with other intoxications, it is important to differentiate cane toad toxicity from common toxicants producing similar clinical signs, including (but not limited to):

• Organophosphate poisoning
• Metaldehyde ingestion
• Pyrethrin/pyrethroid toxicity
• Oleander poisoning
• Heat stroke
• Compost/organic mater ingestion 

How to treat toad poisoning with Bufo marinus

First Aid

Owners should be instructed to thoroughly clean the mouth with a damp cloth for 10 minutes prior to transporting in order to minimize amount of toxin absorbed and time of contact with the mucosa, since the toxins are very rapidly absorbed. All surfaces of the mouth that are accessible should be cleaned, including the lips, inside of the lips, gums around teeth, tongue etc. by thorough and repeated wiping. As the cloth dries, owners should be instructed to re-moisten the cloth with water and repeat the oral cleaning for at least 10 minutes – provided the patient tolerates this without the potential to traumatise the owner by biting etc.

In-Hospital Treatment

On admission to the veterinary clinic, treatment is usually directed at the following: 

• Commence oxygen therapy
• Perform a full physical examination
  • Respiratory Evaluation
    • Examine the oral cavity. Suction or remove excess oral secretions to reduce aspiration risk.
    • Auscultate the chest to assess lung sounds
    • Perform lung ultrasound or TFAST to assess for the presence of pulmonary oedema
    • Pulse oximetry
    • Blood gas analysis 
  • Cardiovascular Assessment
    • Obtain heart rate
    • ECG analysis
    • Systolic arterial blood pressure
  • Neurological Assessment
    • Obtain small animal coma score to facilitate serial neurological assessments
• Begin in-hospital treatment
  • Prevent Absorption
    • Wash mucous membranes liberally; use cloth as saliva is very tenacious and sticks to the oral mucosa 
    • Induce emesis if toad was observed to be ingested (contraindicated if CNS signs) 
    • In patients with reduced gag and swallow responses, anaesthesia, endotracheal intubation and oral +/- gastric decontamination (if toad observed to have been ingested) should be performed 
  • Respiratory Support
    • Provide supplemental oxygen at all times during the initial resuscitation process 
    • Aspiration of saliva and toad secretions is common, especially during nervous system excitation, and during lavage of the oral cavity and pharynx. Suction of the oral, pharyngeal and laryngeal cavities is recommended to remove excess secretions.
    • Terbutaline 0.01 mg/kg IV is a potent bronchodilator, and can be helpful in reducing bronchoconstriction 
    • Morphine 0.1 – 0.5 mg/kg has been used for management of pulmonary oedema, in combination with furosemide at 2-4 mg/kg IV q 4-6 hours.
    • Hypertension may be managed with acepromazine 0.01-0.1 mg/kg IV or hydralazine at 0.5 mg/kg PO once. 
    • Ventilation assistance may be required in patients that remain dyspnoeic despite therapy

• Cardiovascular
  • Patients exhibiting clinical symptoms of shock may benefit from boluses of isotonic crystalloid fluid, such as lactated Ringer’s solution at 7 ml/kg (cat) or 10 ml/kg (dog) given intravenously over 10 minutes, and repeated for up to 30 minutes (3 boluses), followed by reduction to maintenance rates.
  • Anti-arrhythmic therapy is dependent on the type of heart rhythm that is present in the patient. An ECG tracing should be obtained at the earliest opportunity. 
  • In general, the following guidelines should be used when treating arrhythmias
    • Tachyarrhythmias
      • Supraventricular:
        • Propranolol 0.5-2.0 mg/kg IV, then 0.02-0.06 mg/kg/min CRI OR 
        • Esmolol 0.05-0.1 mg/kg slow IV q 5 minutes, or 50-200 micrograms/kg/min
      • Ventricular:
        • Lignocaine 2 mg/kg IV then CRI of 50-100 micrograms/kg/min titrated upwards to effect
    • Bradyarrhythmias
      • Atropine 0.01-0.05 mg/kg slow IV to effect
• Neurological
  • Convulsions
    • Administer diazepam (0.25 – 0.5 mg/kg) OR midazolam (0.25-0.5 mg/kg) IV to effect and repeat as necessary. Midazolam continuous infusion may be required in some patients with sustained convulsions 
    • Propofol boluses of 2-6 mg/kg or CRI 0.1 – 0.4 mg/kg/min with or without benzodiazepine infusion.
  • Elevated intra-cranial pressure
    • Mannitol (0.5 – 1.0 g/kg) slow IV over 20 minutes may be administered in patients that have had numerous seizures and have a worsening neurological status despite oxygen, and appropriate airway, respiration and cardiovascular system management 
• Supportive care
  • Antiemetic therapy, including metoclopramide and/or maropitant citrate, and/or ondansetron should be considered to reduce nausea experienced by some patients, secondary to irritation of the gastrointestinal tract, chemoreceptor trigger zone and vomiting centre by the toad toxins
  • Electrolyte analysis should be performed and abnormalities corrected as appropriate – particularly in those patients with sustained cardiac arrhythmias or neurological dysfunction
  • Control hyperthermia with active cooling to a rectal body temperature of 39.5 degrees Celsius

Complications

Complications are rare in appropriately managed patients, but can include

• refractory convulsions 
• refractory arrhythmias
• aspiration pneumonitis, pulmonary oedema, bronchoconstriction 
• hyperthermia, hypothermia 
• death (uncommon)

Outcomes and Summary

The risk of mortality in Rhinella marina toxicity is low (<5% in dogs, 1% in cats). However, morbidity can be high, especially in dogs, where up to 50-60% of cases may require in-hospital management – compared to only 6% of cats requiring hospitalisation.

Cane toad toxicity in both dogs and cats is a true emergency requiring prompt recognition and therapy to minimise morbidity and risk of mortality.

Despite the dramatic clinical presentation, mortality risk remains low with appropriate medical therapy.

Further Learning for Veterinary Professionals

This blog supports the upcoming Management of Envenomations in Dogs and Cats course from Vet Education, starting in September.

The course enables participants to improve recognition, diagnosis and treatment outcomes for animal venom and toxin exposures in small animals.

References:

1. Leong OS, Padula AM, Webster RA, Maldonado R. A retrospective study of cane toad (Rhinella marina) toxicity in 190 domestic cats in Southeastern Queensland: Clinical presentations, treatments, and outcomes. Australian Veterinary Journal. 2023 Jun;101(6):219-24.
2. Reeves MP. A retrospective report of 90 dogs with suspected cane toad (Bufo marinus) toxicity. Australian Veterinary Journal. 2004 Oct;82(10):608-11.
3. Camplesi AC, Simao NM, Sakate M, Sobreira MF, Bersano PR, Freitas SH, Moya-Araujo CF. Clinical and laboratory evaluation of dogs experimentally intoxicated with toad venom.
4. Roberts BK, Aronsohn MG, Moses BL, Burk RL, Toll J, Weeren FR. Bufo marinus intoxication in dogs: 94 cases (1997–1998). Journal of the American Veterinary Medical Association. 2000 Jun 15;216(12):1941-4.
5. Camplesi AC, Sakate M, Simao NM, Marucio R, Mota FC, Moya-Araujo CF. Clinical and electrocardiographic evaluation during experimental toad poisoning in dogs. Journal of venomous animals and toxins including tropical diseases. 2010; 16:342-54.
6. Johnnides S, Green T, Eubig P. Toad intoxication in the dog by Rhinella marina: The clinical syndrome and current treatment recommendations. Journal of the American Animal Hospital Association. 2016 Jul 1;52(4):205-11.