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Bromethalin Ingestion

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Bromethalin Ingestion PEEER REVR IEWEWED PRACTICAL TOXICOLOGY The Decontamination Dilemma: Bromethalin Ingestion Renee Tourdot, DVM, ASPCA Animal Poison Control Center shutterstock.com/Ysbrand Cosijn Bromethalin-based rodenticide bait exposures have become increasingly common since the Welcome to Practical Toxicology, brought to you in 1 partnership between Today’s Veterinary Practice and product became available in 1985. In 2015, the ASPCA Animal Poison Control Center (APCC) the American Society for the Prevention of (www.aspcapro.org/poison). This column provides practical clinical information about diagnosing and Cruelty to Animals Animal Poison Control treating pets that have been exposed to potentially Center received 2791 calls regarding exposures harmful substances. to bromethalin-based rodenticides.2 The APCC: • Provides 24-hour diagnostic and treatment Exposures to this toxin present a unique challenge recommendations by specially trained veterinary to clinicians. Once signs of convulsant syndrome—a toxicologists neurologic syndrome caused by bromethalin • Protects and improves animal lives through toxicology toxicosis—have developed, prognosis for recovery is education, consulting services, and case data review poor.3,4 Therefore, most clinicians seem aware that • Developed and maintains AnTox, an animal toxicology database system that identifies and characterizes prompt and aggressive decontamination measures toxic effects of substances in animals must be taken. However, if decontamination • Works closely with human poison control centers to is too aggressive, iatrogenic hypernatremia can provide animal poisoning information develop, and clinical hypernatremia can be just as • Offers extensive veterinary life-threatening as a large bromethalin exposure. toxicology consulting to organizations in industry, government, and agriculture. To further complicate matters, clinical signs of hypernatremia can appear similar to the neurologic If treating a patient that 5 requires emergency care for signs caused by bromethalin. If clinicians are not poisoning, call the APCC at aware of, or monitoring for, a significant rise in 888-426-4435. the patient’s serum sodium level, hypernatremia may be mistaken for bromethalin toxicosis, JANUARY/FEBRUARY 2017 TVPJOURNAL.COM 95 PEER REVIEWED resulting in incorrect treatment being instituted, Based on patient history, it can be determined which can worsen the patient’s prognosis. that Dusty was exposed to up to 6.75 ounces of the rodenticide (12−5.25 = 6.75 blocks). This This article provides guidance on how to treat is the worst-case scenario: the largest amount patients with bromethalin exposure, while of bait that Dusty may have ingested is the taking these challenges into consideration. missing portion of the block he was discovered carrying plus the missing blocks from the box. CONSIDER THIS CASE: EVALUATION To calculate the dosage ingested, the concentration Dusty, a 6-year-old, 21-kg male castrated hound of bromethalin in the bait needs to be determined. mix, is presented to an emergency hospital. • It is important to verify the rodenticide History product, active ingredient, and concentration. This information should be taken directly Shortly before presentation, Dusty’s owner found from the packaging whenever possible. him carrying part of a rodenticide bait block and • While most bromethalin-based rodenticides have subsequently discovered a box of bait blocks on a concentration of 0.01%, some commercial the basement floor. The owner believes the box products have higher concentrations. of bait blocks was stored in the basement when • A bromethalin concentration of 0.01% equals she purchased the home 5 years ago, and she 0.1 mg of bromethalin in each gram of bait. knows the box was not on the floor yesterday evening—the last time the owner was in the Using a concentration of 0.01%, the potential basement. There are no other pets in the home. dosage ingested by Dusty can then be calculated: 1. There are 28.4 grams in 1 ounce; therefore, Dusty Learn More may have ingested up to 192 grams of bait. The Animal Poison Control Center (APCC) provides 24-hour diagnostic and treatment 6.75 oz × 28.4 g/oz = 192 g recommendations by specially trained veterinary toxicologists. If treating a patient that requires emergency care for poisoning, 2. If each gram of bait has 0.1 mg of call the APCC at 888-426-4435. bromethalin, Dusty may have ingested up to 19 mg of bromethalin. 0.1 mg/g × 192 g = 19.2 mg Rodenticide Evaluation 3. Finally, when 19 mg bromethalin is Evaluation of the box label suggests that it once converted to mg/kg, Dusty may have held 12 rodenticide bait blocks, each weighing 1 ingested up to 0.9 mg/kg of bromethalin. ounce. The box now contains 5 blocks plus the portion of the block the owner recovered from 19 mg / 21 kg = 0.9 mg/kg the dog’s mouth, which appears to be no larger than one quarter of a block. The label on the box What does this mean? Is this a concerning says the active ingredient is 0.01% bromethalin. exposure and, if so, how concerning? How aggressive does decontamination need to be? Calculating Rodenticide Dosage To answer these questions, the kinetics and After evaluating patient history and the toxicity of bromethalin need to be discussed. rodenticide itself, the dosage of bromethalin ingested needs to be calculated. 96 APCC PRACTICAL TOXICOLOGY PEER REVIEWED BROMETHALIN TOXICITY Cats demonstrate a similar clinical course to dogs, but are much more sensitive Mechanism of Action & Kinetics to bromethalin. The LD50 in cats is 0.54 mg/kg.4 Cats may also demonstrate ileus Bromethalin’s metabolite, desmethyl bromethalin, and resultant abdominal distention.1,5 is primarily responsible for the uncoupling of oxidative phosphorylation in neuronal Range of Dosages mitochondria.4 This results in a depletion of adenosine triphosphate from the cell, causing The dosages cited for dogs and cats are impairment of the sodium potassium pump. medians, and any individual patient may be more sensitive to the effects of bromethalin. When pump function is poor, sodium and fluid accumulate within the myelin sheaths. This The APCC has recorded hindlimb weakness edema accounts for the neurologic signs seen occurring, although rarely, at dosages as low as with bromethalin ingestion. Because the edema 0.15 mg/kg in dogs, and tremors, depression, is within the myelin, this may also explain why anorexia, and death occurring at dosages as low traditional medical management of central as 0.95 mg/kg, even though the experimental nervous system edema, such as administration of minimum lethal dose is reported to be 2.5 mg/kg.1,2 diuretics and mannitol, has limited success.3 In cats, signs have occurred at dosages Bromethalin is excreted primarily through the less than 0.24 mg/kg,2 and depression, bile, and it is suspected to undergo enterohepatic ataxia, paresis, and death have occurred recycling because experimental studies have at dosages as low as 0.45 mg/kg.3 shown that multiple doses of activated charcoal are more effective at preventing the neurologic It also appears that dogs younger than 1 year syndrome rather than a single dose.4 of age may be more susceptible to the effects of bromethalin, which may be due to the Clinical Presentation immature blood–brain barrier in juveniles. The clinical presentation of bromethalin MANAGEMENT OF toxicosis is dose dependent. BROMETHALIN EXPOSURES At lower exposure dosages (below the 50% Based on the kinetics and toxicity of bromethalin, lethal dose [LD50] of 3.65 mg/kg for dogs), clinicians must take a conservative approach a paralytic syndrome can develop, typically when deciding at what dosage to begin within 24 to 86 hours after exposure. This decontamination efforts and how aggressively to syndrome can cause hindlimb paresis and decontaminate. In addition, the time that has ataxia, and patients may recover from these elapsed between exposure and decontamination signs over a period of weeks to months. must be taken into account (Table, page 98). The signs of paralytic syndrome may progress, with ADMINISTRATION OF development of absent deep pain sensation, upper ACTIVATED CHARCOAL motor neuron bladder paralysis, central nervous system depression, tremors, hyperesthesia, seizures, Prior to decontamination with activated charcoal, and death.1,4 This convulsant syndrome is usually, consider administering an antiemetic. This may but not always, associated with larger exposures to help reduce the risk for aspiration secondary bromethalin (above the LD50), and signs typically to vomiting, as well as treat any nausea, which develop within 4 to 36 hours after ingestion.1,6,7 may encourage the patient to drink water. JANUARY/FEBRUARY 2017 TVPJOURNAL.COM 97 PEER REVIEWED The first dose of activated charcoal should be the largest dose (1 to 2 g/kg)2 and, ideally, contain Decontamination Measures: Not Recommended a cathartic agent, such as sorbitol, unless the patient already has diarrhea. Subsequent doses Alternative decontamination measures have been should be half the original dose, with no cathartic proposed and tried, yet no published evidence included. If there is no evidence of charcoal in supports a recommendation for their clinical use at this time. The following measures are not recommended as the rectum within 8 hours after the first dose, the standard of care for bromethalin exposures. consider administering a warm water enema.6 Intralipid Emulsion Bromethalin is very lipophilic; therefore, in theory, The potential for activated charcoal to cause intralipid emulsion therapy has the potential to reduce potentially lethal hypernatremia should not bromethalin concentrations in the body.9 If this therapy is to benefit the patient at all, it would likely be underestimated. The mechanism for this be within the first several hours after an exposure effect is not definitively understood but is because bromethalin is rapidly absorbed (peak plasma thought to result from the osmotic effect of concentrations occur in 4 hours in rats).1,4 Reversal of the neurologic syndrome by intralipid emulsion is the activated charcoal pulling water into the unlikely once the neurons are damaged.
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