You are presented with a four-year-old male German shepherd dog weighing 40kg at your emergency veterinary clinic.

The dog’s owner has recently experienced several incidents involving intruders on his property and suspected malicious poisoning. His dog is not confined, but ranged over a park.

The owner remembers finding a heap of dyed blue pellets near the park gateway that morning. The dog vomited prior to consultation, and the owner reports excessive salivation, panting and starting seizures.

Question

What is the toxic dose, and mechanism of toxicity, of metaldehyde?

Answer

High oral toxicity. The oral median lethal dose in dogs is 100mg/kg to 300mg/kg, and in cats is 200mg/kg.

Dogs may be attracted to the snail and slug metaldehyde baits (molluscicide). These baits are highly palatable, and formulated in dyed blue or green pellets with bran and molasses, making it extremely attractive and resulting in consumption of large quantities by dogs.

Metaldehyde toxicosis is one of the most common toxicoses in dogs. It is also used as solid fuel (meta fuel) for camp stoves, marketed as white tablets. Dogs can ingest the abandoned tablets similar to lumps of sugar. The majority of toxicities are accidental, but malicious poisoning can occur sometimes.

Metaldehyde is partially hydrolysed in the stomach by gastric acidity to acetaldehyde, which readily crosses the blood-brain barrier.

This neurotoxicant decreases the levels in the brain of several neurotransmitters:

• γ-aminobutyric acid (GABA) – inhibitory neurotransmitter
• noradrenalin (NA) and serotonin (hydroxytryptamine; 5-HT) – excitatory neurotransmitters

The reduced concentrations of GABA cause a disinhibition of neuronal excitability, which causes seizure activity.

Decreases in NA and 5-HT concentrations may contribute to seizure activity because of a lowering of the seizure threshold. Increases in the activity of monoamine oxidase – causing the breakdown of NA and 5-HT – may be also responsible for the decreased concentrations of these neurotransmitters.

Question

What are the clinical features of metaldehyde poisoning in dogs?

Answer

The following appear usually within 30 minutes to 1 to 3 hours after ingestion:

• anxiety
• restlessness
• tachycardia
• nystagmus
• mydriasis
• muscle tremors
• continuous seizures
• ataxia
• hyperpnoea (respiratory compensation of metabolic acidosis)
• hypersalivation
• vomiting (formaldehyde-like odour may be noted in the vomitus)
• diarrhoea
• hyperthermia (may reach 42.2°C)
• death (respiratory failure)

Transient blindness has also been reported. Dogs are not as hyperaesthetic by external stimuli as with strychnine toxicosis. If the animal survives, acute liver failure can occur within two or three days after exposure.

Seizures can cause rhabdomyolysis (increase creatine kinase serum levels; normal values in dogs: 46U/L to 467U/L). The released myoglobin caused by muscle damage can result in acute renal failure. Toxicological diagnosis is based on analysis of bait, vomitus, plasma, and urine by gas chromatography coupled with mass spectrometry.

Question

How should metaldehyde poisoning in dogs be managed?

Answer

Metaldehyde poisoning is a medical emergency, with no antidote. Delayed treatment may result in death within hours of exposure.

Supportive therapy

Controlling seizures

An IV catheter should be placed. To control seizures, diazepam (0.5mg/kg to 2mg/kg IV bolus) should be administered and repeated if necessary within 20 minutes (serum half-life in dogs is 2.5 hours to 3.2 hours) up to three times in a 24-hour period, or 1mg/kg to 2mg/kg rectally.

This is contraindicated in patients with severe liver disease, however. Alternatively, administer lorazepam (long-acting benzodiazepine 0.2mg/kg IV bolus, because of its high affinity for benzodiazepine receptors in the CNS), or midazolam 0.2mg/kg to 0.4mg/kg IV may be repeated once.

Barbiturates are not recommended because they compete with acetaldehyde metabolism. Ketamine is contraindicated (seizure-like effects have been reported). Valproic acid is not recommended (serum half-life in dogs is 1.5 hours to 2 hours). In cases of refractory seizures, administer propofol (3mg/kg to 6mg/kg IV initial bolus), followed by 0.1mg/kg/min to 0.6mg/kg/min constant rate infusion.

Alternatively, 2% to 2.5% concentrations of isoflurane alone with oxygen can be used. For maintenance, use 1.5% to 1.8% concentrations of isoflurane in oxygen. Attention to airway, breathing and circulation are paramount. Intubate affected animals and provide artificial respiration with O2 during convulsions.

Detoxification therapy

Emesis should be induced only if the patient is asymptomatic. Administer apomorphine 0.03mg/kg IV, 0.04mg/kg IM or 0.025mg tablet crushed and dissolved in physiological saline. Instil in the conjunctival sac and rinse with water after emesis has occurred. Alternatively, use xylazine (1.1 mg/kg SC or IM).

To prevent further absorption of metaldehyde from the intestinal tract, use activated charcoal (AC; 1g/kg to 4g/kg) mixed with water to make a 20% slurry (1g/5ml water) via a nasogastric tube as soon as possible post-ingestion, and after the airway is secured. AC admitted orally is contraindicated in convulsing or comatose animals. Maintain the patient on IV-balanced crystalloid fluids, such as lactated Ringer’s solution 40ml/kg/hour to 90ml/kg/hour.

Correction of metabolic acidosis (normal values in dogs: pH less than 7.33; standardised base excess less than −4mmol/L) by sodium bicarbonate 8.4% solution: 1ml/Lb to 2.5ml/Lb bodyweight constant rate infusion depending on the severity of the acidosis, over a four-hour period.

Correction of hypoglycaemia (dextrose 5%: 40mg/kg IV every 24 hours; monitor blood glucose). Correction of hyperthermia by external cooling every two to four hours (ice baths should be avoided as they may create hypothermia). Should be stopped when rectal temperature reaches 39.4°C.

Monitoring of liver function is recommended (normal enzyme levels in dogs: serum alanine aminotransferase: 10U/L to 130U/L; alkaline phosphatase: 24U/L to 147U/L and gamma-glutamyl transferase: 0U/L to 25U/L). Diuretics are not recommended (urinary elimination of metaldehyde is less than 1% of the dose). IV lipid emulsion therapy is contraindicated because metaldehyde is not lipid soluble (log P values of 0.12).

The patient should be observed for a minimum of three days. Educate clients to keep pets away from metaldehyde bait products (they may remain effective for as long as 15 days). A bitter-tasting agent – denatonium benzoate – has been added to discourage pets from ingesting it.