Bromethalin Toxicity

Bromethalin: The Lesser Known Rodenticide
Megan Kaplan, DVM, DACVECC

One of the most common toxicities we see in our busy ER is inadvertent ingestion of rodenticide. While most people are aware of the anticoagulant rodenticides, such as warfarin, there are others that work in different ways, such as bromethalin and cholecalciferol. These other forms are becoming more popular, given recent FDA changes that have made the anticoagulant rodenticides less readily available.

One such alternative form that is significant and should be known by all veterinary practitioners is bromethalin. Some of the trade names for rodenticides containing this toxin include CyKill®, Fastrac®, Tomcat® and Assault®.

Bromethalin targets the central nervous system (CNS) via the uncoupling of oxydative phosphorylation thereby reducing production of ATP and causing cerebral edema and impaired sodium/potassium pump function. In affected animals, this leads to clinical signs such as muscle tremors, ataxia, seizures, paresis/paralysis, hyperthermia and sometimes coma and death. In addition, anisocoria, nystagmus, and alteration in pupillary light reflex can be noted on physical exam. If severe CNS effects develop, then in some cases respiratory depression can occur, leading to cardiopulmonary arrest. In some cases of chronic lower-dose ingestion, there can be a delay of onset of neurologic symptoms from days to 2 weeks.

Rodenticide bait usually contains concentrations of 0.01% or 0.025% bromethalin. The LD 50 dose in dogs and cats are 2.4-3.7mg/kg and 0.54mg/kg respectively. However, the minimum lethal dose has been reported to be 1mg/kg in dogs and as low as 0.25mg/kg in cats. Once ingested, there is rapid absorption of this toxin in the GI tract with peak concentrations in the plasma by 4-6 hours after ingestion. Bromethalin is metabolized in the liver and excreted in bile with enterohepatic recirculation occurring, causing slow clearance from the body.

Diagnosis can be based on history of exposure or witnessed ingestion of rodenticide containing bromethalin. If not known, but suspected, it is important to question owners about the color of feces, because the baits have a green and/or blue dye base that will be seen in stools. Definitive diagnosis for unknown ingestion can be made from gas chromatography of formalin fixed liver and/or brain samples or chemical confirmation on fresh frozen fat, liver, kidney or brain tissue.

Inducing emesis via apomorphine or hydrogen peroxide is recommended if the ingestion was no longer than 2 hours before presentation and the patient is mentally appropriate to handle oral therapy. Further decontamination with activated charcoal (0.5-1mg/kg PO q4-8hrs) is recommended at repeat dosing for 2-3 days given the long elimination half-life and enterohepatic circulation.

Unfortunately, there is no antidote for bromethalin, making it a much more dangerous rodenticide than the anticoagulants. At this time, the recommended treatment for such intoxications relies on supportive care and symptomatic treatment. Patients with neurologic signs should be admitted for IV fluids if not able to eat/drink, anti-emetic medications to try and prevent aspiration, and basic nursing care (turning sides, application of eye lube, bladder and defecation care/monitoring). It is important to frequently monitor vitals, including blood pressure and blood glucose. If signs include seizure activity, then diazepam (up to 1mg/kg) can be given IV, and phenobarbitol can be considered with refractory seizures. If neuromuscular tremors are noted, then methocarbamol (40mg/kg IV bolus vs. CRI not to exceed 330mg/kg/day) can be used to limit tremors to ensure patient is still functional and not overly sedated. For those patients with severe neurologic signs, respiratory status (SPO2 and PCO2) should be monitored frequently, and if signs of hypoxia and/or hypercapnea are present, mechanical ventilation must be provided to prevent respiratory failure. In patients who have signs of cerebral edema (anisocoria, hypertension with bradycardia, mental stupor), mannitol should be given at 500-1000mg/kg via an IV catheter with filter needle over 20-30 minutes. Finally, for patients in the hospital for more than 2-3 days, nutritional support should be instituted with temporary and/or long-term feeding tubes for patients unable to eat.

In addition to the above symptomatic treatment and supportive care, new evidence suggests the use of intravenous lipid emulsions (ILE) in bromethalin acute toxicosis may be helpful. This therapy is given via the use of 20% intravenous lipid emulsions at a bolus dose of 1.5ml/kg over 2-3 minutes vs. a CRI of 0.25ml/kg/min for 30-60 minutes. Up to three doses can be given, provided that the patient’s serum pre-administration is clear. If the serum is already indicative of high lipids (cloudy/white), then repeat doses should be avoided. It is thought that the ILE provides a lipid sink for the bromethalin to bind to, therefore making it inactive, but the true mechanism is not fully known.

For those pets with mild poisonings, it is possible that the body can recover and clinical symptoms resolve, but usually this takes 1-2 weeks, and in some cases neurologic signs can persist up to 2 months. Once signs resolve, the patient is usually normal thereafter without chronic neurologic deficits. In severely affected animals in acute toxicity, the prognosis is guarded given the extreme neurologic signs and possible need for ongoing mechanical ventilation due to respiratory depression and long-term hospital care of a paralyzed patient.

Overall, bromethalin is often underestimated as far as the damage/effects it can have in our veterinary patients. In cats and small patients, the effects are more likely to be fatal. But even in large patients, the effects can have a high morbidity/mortality. Therefore, early recognition and decontamination of this toxin is imperative for a favorable outcome. With new evidence to support that ILE therapy helps to speed up the metabolism/elimination of bromethalin, it should be strongly considered in patients exposed to toxic doses of bromethalin.