Bromethalin Poisoning in Animals

Bromethalin is a neurotoxin that may cause cerebral edema, and after enforcement of the EPA's risk mitigation measures began, it quickly became the most common rodenticide exposure in companion animals.

Bromethalin was developed in the mid-1970s in response to warfarin-resistant rodents and, at the time, was touted as having almost 90% efficacy in rodent control. Available in many formulations, including blocks, soft baits, pellets, worms, and seed, bromethalin can vary in concentration from 0.01% to 0.025% (0.1–0.25 mg/g). 

Typically, nontarget species are exposed by unintended direct ingestion of the bait product; in rare cases, however, exposure results from malicious intent. Relay toxicosis after ingestion of prey or carrion has not been documented in research settings; however, it is theoretically possible, particularly in cats, and has been anecdotally reported in very rare cases.

Bromethalin is a nonanticoagulant rodenticide that is intended to lead to death in target species after ingestion of a single dose. The LD₅₀ may vary in the literature; however, toxic doses are widely accepted at one-tenth of the lowest reported LD₅₀ in companion animal species. Cats tend to be exquisitely sensitive, with an LD₅₀ of 0.4–0.71 mg/kg; dogs are moderately sensitive, with an LD₅₀ of 2.38–5.6 mg/kg; and guinea pigs are uniquely resistant, with an LD₅₀ that exceeds 1,000 mg/kg.

Bromethalin is rapidly absorbed, reaching peak plasma concentrations in rats within 4 hours. It must be bioactivated to its active compound, desmethylbromethalin, which then uncouples oxidative phosphorylation in the mitochondria of cells in the CNS. The uncoupling of oxidative phosphorylation results in the disruption of sodium-potassium pumps, loss of osmotic control, long nerve demyelination with intramyelinic fluid accumulation, and subsequent cerebral edema and spinal cord edema.

Clinically, cerebral edema and neurological dysfunction manifest in a dose-dependent manner. Published LD₅₀ in dogs may range from 2.38 to 4.7 mg/kg. Ingested doses equivalent to or higher than the average LD₅₀ (approximately 3.54 mg/kg) may cause a convulsant syndrome in dogs within 4–36 hours.

Clinical signs may include hyperexcitability, muscle tremors, grand mal seizures, hindlimb hyperreflexia, CNS depression, hyperthermia, and death.

Ingested toxic doses lower than the average LD₅₀ (approximately 3.54 mg/kg) may result in a paralytic (subacute or chronic) syndrome in some dogs, typically within 1–5 days after exposure. Cats typically develop the paralytic syndrome irrespective of the dose of bromethalin.

A presumptive diagnosis of bromethalin toxicosis is based on a known or suspected history of exposure to the bait, followed by the development of neurological signs within 1–7 days after exposure. Diagnosis can be confirmed by the detection of bromethalin or its major metabolite in the liver, kidney, brain, or fat; however, this analysis is available in only a limited number of veterinary diagnostic laboratories and is rarely performed, unless at the time of necropsy.

If the patient has a history of exposure, bromethalin toxicosis should be considered when clinical signs include moderate to acute onset of weakness, hindlimb paralysis, tremors, and seizures.

Differential diagnoses include illicit or pharmaceutical drug exposure (marijuana/THC, benzodiazepines, opiates, sleep aids, or antidepressants), ethanol or ethylene glycol ingestion, neurotoxic mushroom ingestion, cyanobacteria (blue-green algae) exposure, mycotoxin ingestion, envenomation, tickborne disease, primary musculoskeletal disease or intervertebral disk problems, and spinal cord or CNS trauma.

1. Decontamination in nonclinically affected patients:

• Induction of emesis, if ingestion occurred within 4 hours, using the following:

  • In dogs: apomorphine, ropinirole, or hydrogen peroxide

  • In cats: dexmedetomidine, hydromorphone, or xylazine

• Administration of activated charcoal in multiple doses, if the quantity consumed is of concern for poisoning in the patient (because bromethalin undergoes enterohepatic circulation):

  • Activated charcoal (1–2 g/kg, PO as aqueous slurry) with a cathartic (eg, sorbitol) followed by activated charcoal without a cathartic every 8 hours for up to two additional doses. Ensure that the patient is at low risk of aspiration, receives IV fluid therapy for a minimum of 4–6 hours after the last dose, maintains normal and stable serum sodium concentrations as checked before each dose, and is passing stool.

1. Decontamination in clinically affected patients:

   • Gastric lavage, if the product remains in the stomach in large quantities (consider abdominal radiographs to evaluate). Return may be poor.

   • Enema, if the product is noted in stool

1. Diagnostic tests:

   • Minimum baseline database of PCV, TP concentration, and electrolyte panel. If CNS signs develop during administration of activated charcoal, confirm normal serum sodium concentrations.

   • Monitor blood glucose and lactate concentration if intractable seizures.

   • Monitor blood gas analysis parameters if obtunded or comatose.

1. Treatment in clinically affected patients:

   • Mannitol: 0.25–2 g/kg, IV, over 20–30 minutes. Crystalloids should be discontinued for the duration of administration and restarted 30 minutes after administration is completed. Repeat every 4–8 hours in the well-hydrated patient, if needed.

   • Methocarbamol as needed for tremors: 55–220 mg/kg, IV, to effect; or as CRI at 10 mg/kg/h

   • Anticonvulsants as needed for seizures

   • The use of corticosteroids is controversial and unlikely to be helpful in bromethalin-induced cerebral edema.

   • The use of intralipid treatment is also controversial, with some concern that its use early in the exposure may actually encourage systemic bromethalin absorption from bait product in the gut. Intralipid treatment does not mitigate cerebral edema directly, and it may interfere with other treatments and efforts. Intralipid use should be considered on a case-by-case basis; it is typically reserved for patients that are not responding well to first-line treatments.

In large-ingestion exposures, early and aggressive decontamination should be emphasized to decrease the risk of extensive neurological changes. If clinical signs develop, recovery can be prolonged. 

The half-life of bromethalin has not been established in dogs and cats; however, it may be similar to that in rats (approximately 6 days). Therefore, affected patients may have clinical signs that persist for weeks, rarely in mild form with some amount of permanency.