In today's VETgirl online veterinary CE video, we review a case of ivermectin toxicosis in a dog that responded well to treatment with intravenous lipid emulsion (e.g., ILE). This 11-month-old, male neutered, Pit Bull mixed breed dog presented for tremors, lethargy, and decreased appetite. This dog was started on ivermectin for treatment for demodectic mange two weeks prior. Initially, a lower dose of ivermectin was used for the first week of treatment; this was gradually increased to a higher dose (e.g., 0.7 mg/kg or 700 mcg/kg once daily) the second week. During the first week of ivermectin treatment, the owner noticed mild tremoring, which would resolve after playing. During the second week of ivermectin treatment, the dog gradually became more lethargic, inappetent, and started tremoring much more significantly.
On presentation, this dog was stable but had a slightly dull mentation. He was weakly ambulatory, ataxic, and had both mydriasis and generalized tremors. Based on his history of previous treatment with ivermectin, toxicosis was immediately suspected.
Certain breeds, such as collies, sheepdogs, border collies, Australian shepherds, and other herding breeds are more susceptible to ivermectin toxicity due to the MDR1-allele mutation, known as the ATP-binding cassette polymorphism. This dog, being a mixed breed, could have had such a mutation. That said, in normal healthy dogs, we typically don't see signs of ivermectin toxicosis until 2.5 mg/kg (where we can see mydriasis). At higher doses (e.g., 5 mg/kg), we can see signs of ataxia, tremoring and seizuring. Note that in normal healthy dogs, the LD50 is reported to be as high as 80 mg/kg (in healthy Beagles). In MDR-allele mutation dogs, the LD50 is reported to be as low as 0.12 mg/kg!
What we don't know is if this dog had the MDR1-allele mutation, as the owner declined testing. Turns out, upon confirmation of the administered dose in this dog, the owner stated that it was giving it with a poorly labeled squeeze bottle (e.g., something like "a little squeeze once daily"). So, who knows what dose this dog was truly receiving. (Appropriate client communication here, folks!).
Due to the severity of clinical signs in this dog, the extra-label use of intravenous lipid emulsion (ILE) was recommended. ILE can be used as an "antidote" for fat-soluble toxicants (e.g., such as ivermectin, baclofen, cholecalciferol, bromethalin, lidocaine, etc.). ILE is thought to work by creating a "lipid sink." Most fat-soluble drugs have a wide volume of distribution (e.g., it goes into their tissue quickly, resulting in clinical signs acutely). By creating a lipid sink, it helps trap the fat-soluble toxicant out of the tissue into this lipid compartment within the blood, thereby reducing the severity of clinical signs.
This patient was given a 1.5 mL/kg bolus of ILE (over 3 min), followed by a CRI of 0.5 mL/kg/min for 30 minutes (This dose is extrapolated from human dosing and published in Fernandez et al along with numerous other veterinary sources). Afterwards, the patient was started on a balanced crystalloid at 75 mL/hr and administered maropitant (to help prevent secondary aspiration in his sedated state). Within 30 minutes of administration of ILE, the patient was more alert when walking. Within 2 hours, however, clinical signs of ivermectin toxicosis returned. Another 1.5 mL/kg bolus of 20% ILE was given and the signs regressed. This patient was then maintained on a 0.5 mL/kg/hr CRI for 24 hours. In this dog, whenever the ILE was discontinued, the clinical signs seemed to return; therefore, leviteracetam (e.g., Keppra) was started, which seemed to help control his tremors even after the ILE was discontinued.
So, what can we take from this VETgirl video? First, make sure to confirm how much ivermectin a patient is being administered. Second, consider having a bag of ILE on hand in your hospital for lipophilic toxicities! Thankfully, this patient responded well to treatment and survived his ivermectin toxicosis. When in doubt, contact the ASPCA Animal Poison Control Center if you need life-saving veterinary medical advice!