Canine bromethalin toxicosis

You are presented with a five-year-old male Labrador retriever weighing 40kg at your emergency veterinary hospital.

The dog’s owner found him with an open box of green pellets hanging out of his mouth – the label of which listed the active ingredient as bromethalin 0.01%. The owner has noted subnormal behaviour, including hyperaesthesia, rigidity and intermittent tremors.

Question

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

Answer

High oral toxicity. The oral median lethal dose in dogs is 1.8 mg/kg. Dogs younger than one year of age may be more sensitive.

Bromethalin and its metabolite (desmethyl bromethalin) cross the blood-brain barrier. Both uncouple oxidative phosphorylation in brain mitochondria, causing depletion of adenosine triphosphate (ATP).

Decreased ATP production disrupts the sodium-potassium pump. Sodium and fluid accumulate with the myelin sheaths, leading to cerebral oedema and increased cerebrospinal fluid pressure.

Question

What are the main clinical features of bromethalin poisoning in dogs?

Answer

Clinical signs can be divided into two syndromes – acute and chronic – depending on the dose ingested:

• Acute syndrome (larger exposure dosages) occurs within 4 to 36 hours post-ingestion. Symptoms include hyperexcitability, severe muscle tremors, seizures, hyperthermia and death (respiratory failure).
• Chronic syndrome (lower exposure dosages) occurs up to seven days post-ingestion. Symptoms include depression, ataxia, hindlimb paralysis and lateral recumbency.

Question

How should bromethalin poisoning in dogs be managed?

Answer

Bromethalin poisoning is a medical emergency, with is no antidote.

Supportive therapy

Controlling seizures

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).

If seizures persist or recur, administer phenobarbital (2mg/kg to 5mg/kg IV bolus). This can be repeated at 20-minute intervals, up to two times. Do not use in patients with significant liver disease, though.

In case 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 and breathing is paramount.

Intubate affected animals and provide artificial respiration with O2 during convulsions.

Relieve cerebral oedema

To relieve cerebral oedema, use osmotic diuretics, such as mannitol 20% 500mg/kg to 1,500mg/kg via an IV catheter over 20 to 30 minutes. This may be repeated every 6 to 8 hours, but has limited efficacy.

Corticosteroids are also an option, such as dexamethasone 2mg/kg IV initially, repeated in 6 to 8 hours with 1mg/kg. Again, this has limited efficacy.

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 (1.1mg/kg SC or IM).

To prevent further absorption of bromethalin 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. This may be repeated at 8-hour intervals for 3 days (reduce enterohepatic recirculation of bromethalin and its metabolite).

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.

Because bromethalin and desmethyl bromethalin are highly lipid soluble (log P values of 6.70 and 4.26, respectively), consider lipid emulsion therapy – an initial IV lipid emulsion (ILE) 20% 1.5ml/kg IV bolus over one minute, followed by a continuous rate infusion of 0.25ml/kg/min for the next 30 to 60 minutes.

In non-responsive patients, an additional intermittent bolus can be given IV slowly, up to 7ml/kg. If clinical signs do not improve after 24 hours, discontinue ILE. ILE 20% preparations are isotonic and can be given by a peripheral vein or in a central catheter using aseptic techniques.

The patient should be observed for a minimum of four days (long elimination half-life of bromethalin).