Using Lipid Emulsion to Treat Lipophilic Toxicities

Lipophilic (fat-loving) intoxication cases have always been challenging to treat in the veterinary hospital. It was first reported in 1998 by Weinberg and colleagues that pretreatment with a lipid emulsion, typically used as a parenteral nutritional supplement, could reverse or improve the clinical signs seen in rats following a bupivacaine overdose.

The mechanism of action of lipid emulsions in these cases is not well understood. There are multiple hypotheses, including acting as a “lipid sink” where the toxin is sequestered within the intravascular space, enhancing mitochondrial function through increased fatty acids, and providing substrate for cardiomyocytes to enhance function.

Over the past 2 decades, lipid emulsions have been used in practice to treat these severe toxicities, although use of lipid emulsions is far from common in most practices. In a study from a private, specialty hospital in the United States, 10 toxicity cases treated with intravenous lipid emulsion (ILE) therapy were evaluated for responses to the treatment given and overall patient outcomes.

Study Design

This retrospective study examined the medical records of 10 patients, 9 dogs and 1 cat, treated with ILE following severe intoxications between 2011 and 2014. Intoxications included baclofen alone, baclofen and tadalafil, methomyl, disulfoton, methamphetamine, dextroamphetamine sulfate (Adderall), amlodipine, ivermectin and spinosad plus milbemycin oxime, and bromethalin. Patient breeds and ages varied (3 months to 12 years).

RELATED:

• Code Green: The Risk From Toxic Household Plants
• 10 Most Common Household Pet Toxins

All cases were selected by the attending veterinarian to receive ILE based on severe clinical signs or a potentially lethal dose of toxin. Pertinent medical history, clinical signs, details of the intoxications, diagnostic values, and treatments given were collected from medical records, when available.

The ILE used in this study was a sterile 20% fat emulsion manufactured by Baxter Healthcare Corporation as a caloric and fatty acid source. The recommended dose of ILE by the ASPCA Animal Poison Control is a 1.5-mL/kg bolus followed by 0.25 to 0.5 mL/kg/minute constant-rate infusion; however, doses administered to patients in this study varied.

Results

All but 2 patients were alive at discharge. The two deaths were due to bromethalin rodenticide and an organophosphate pesticide toxicosis. Amlodipine, baclofen, carbamate, and ivermectin were most responsive to ILE therapy. Lipemia was reported in 60% (n = 6) of patients. No other adverse events were reported.

Conclusions

Multiple variables likely affected the patient outcomes in this study, including the 2 deaths recorded. The times between intoxication and administration of veterinary care, including ILE, varied from case to case. The optimal time of ILE administration is not known at this time, but it’s reasonable to assume that administration soon after ingestion of a toxin is likely to be more effective. Numerous additional variables were present in this study, such as patient metabolism, dose and half-life of toxins, drug-drug-interactions, and any comorbidities present prior to hospitalization.

The patient that died due to bromethalin toxicity was not seen by veterinary staff until the day after ingestion. Treatment following bromethalin ingestion is not generally effective once severe clinical signs are observed. It’s possible that a delay in treatment contributed to this patient’s death. The second death was due to a suspected ivermectin toxicity that was then compounded when a topical agent containing spinosad plus milbemycin was applied. Bromethalin is a fat-soluble compound, and organophosphates are lipophilic. Thus, ILE may be an effective treatment for these types of toxicities. In both cases, the investigators noted the patients may have benefited from more aggressive ILE therapy.

ILE was administered 5 days after ingestion of baclofen in another case. Baclofen has a wide range of half-life values in toxicity cases due to flooding metabolic pathways. The patient in this study responded well to ILE therapy; therefore, it may be pertinent to still consider ILE therapy in certain toxicity cases even several days following the initial ingestion if clinical signs are still present. Use of ILE to treat a variety of intoxications, such as lidocaine, permethrins, ibuprofen, moxidectin, and verapamil, have been reported. This is the first report of ILE being used to treat amlodipine, bromethalin carbamate, organophosphate, and amphetamine toxicities.

Severe adverse events are rare when using ILE. Some adverse events to consider and monitor when using ILE are lipemia, secondary pancreatitis, drug-drug interactions (especially for lipid-soluble drugs), allergies and hypersensitivity to soybean and egg proteins, and interference with laboratory values due to lipemia. Lipemia was the only adverse event reported in this study following ILE administration.

This was a retrospective study of medical records. Baseline characteristics and treatment protocols were not standardized, and thus definitive conclusions cannot be drawn from the data collected. Controlled, randomized studies are needed to establish optimal dosage and delivery schedule of ILE.

Dr. Bohn received her PhD and MS from Georgia State University and has been a practicing veterinary nurse for nearly 20 years. She provides freelance medical writing services through her business, Bohn Communications.