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 to have almost 90% efficacy in rodent control. Available in many formulations, including blocks, pellets, worms, and seed, bromethalin may 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 toxicity after ingestion of prey or carrion has not been documented in research settings, but it is theoretically possible 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 median lethal dose (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 the 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 intramyelin fluid accumulation, and subsequent cerebral edema and spinal cord edema.
Clinically, cerebral edema and neurologic dysfunction manifest in a dose-dependent manner. Published median lethal dose (LD50) values in dogs may range from 2.38-4.7 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. Signs may include hyperexcitability, muscle tremors, grand mal seizures, hind limb hyperreflexia, CNS depression, hyperthermia, and death. Ingested 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 of 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 neurologic 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 by necropsy. Given a history of exposure, bromethalin toxicosis should be considered when clinical signs include moderate to acute onset of weakness, hind limb paralysis, tremors, and seizures.
Differential diagnoses include illicit or nonillicit drug exposure (marijuana/THC, benzodiazepines, opiates, sleep aids, or antidepressants), ethanol or ethylene glycol ingestion, neurotoxic mushroom ingestion, blue-green algae exposure, mycotoxin ingestion, envenomation, tickborne disease, primary musculoskeletal disease or intervertebral disk problems, and spinal cord or CNS trauma.
Decontamination in non-clinically affected patients:
Induction of emesis, if ingestion occurred within 4 hours, using the following:
In dogs: apomorphine 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 g/kg, PO as aqueous slurry) with a cathartic 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.
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
Minimum baseline PCV/TP, electrolyte panel, blood glucose concentration
Treatment in clinically affected patients:
Mannitol: 0.25–0.5 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 a continuous rate infusion (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 bromethalin absorption from bait product in the gut into the body. Intralipid treatment does not mitigate cerebral edema directly, and it may interfere with other treatments and efforts. The use of intralipids 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 neurologic 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 of rats: ~6 days. Therefore, affected patients may have clinical signs that persist for weeks, rarely in mild form with some amount of permanency.