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Use of intravenous lipid emulsion treatment in veterinary toxicology
Dijkman M.A., Kan A.A., de Vries I.
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Introduction
The use of intravenous lipid emulsions (ILE) in human clinical toxicology has become a common practice as life-saving treatment for cardiotoxicity after local anaesthetics overdose. Because of the favourable safety profile of ILE much research is performed to determine the potential antidotal properties in intoxications caused by other lipophilic cardiotoxic substances. Human case reports indicate ILE may be useful in the resuscitation from toxicity induced by various tricyclic antidepressants (TCA), lipophilic β blockers and calcium channel blockers. In veterinary toxicology ILE has been primarily described as an antidote in the management of long-lasting neurotoxicity, like in permethrin intoxications in cats and ivermectin intoxications in dogs. In this lecture an overview of the current knowledge concerning the use of ILE in veterinary practice is provided(1), as well as practical treatment guidelines(2,3) .
ILE characteristics
Lipid emulsions have been used for years as a component of parenteral nutrition. They are oil-in-water solutions based on neutral triglycerides. The ready to use fluids can be administered via a peripheral catheter as they are isotonic. Concentrations of 10 to 30% are marketed but primarily the 20% is used as an antidote.
Mechanism of action
The mechanism of the antidotal effect of ILE is still not completely elucidated. Infusion of lipid emulsion provides a compartment for lipophilic drugs in the blood compartment, making them unavailable to act on their target organs. The lipophilic drug inside the lipid emulsion compartment is subsequently metabolized together with the liposomes in the liver and muscle tissue, and thus cleared from the body. This so-called lipid sink/shuttle is thought to be a major antidotal mechanism in neurotoxicity. Other mechanisms have been postulated to explain the antidotal effect on cardiac function, such as a direct effect on myocardial cells improving cardiac output.
Quality of data and cases
The veterinary literature on the efficacy of ILE therapy consists primarily of case reports and case series. This unfortunately limits interpretation as they represent low-quality evidence. Therefore these data should be evaluated with caution. Most case studies describe a clinical improvement after the initial standard therapies were unsuccessful, i.e. a marked reduction in the severity of neurological symptoms, tremors and convulsions became less or disappeared, animals awakened from their comatose state, shortly after ILE administration. In some studies measurements of blood drug concentrations before, during and after ILE treatment have been done during intoxication with ivermectin, naproxen, ibuprofen and lidocaine and provide a more objective assessment. Transient increase followed by a subsequent decrease in lipophilic drug blood concentration has been reported, suggestive of a successful utilisation of the lipophilic properties of the ILE. In general, the use of ILE may lead to a quicker recovery of the animal and a shorter, less intense admission period. However, often antidotes other than ILE are available with a more proven effect on the intoxication. Therefore, with current knowledge, ILE should not be considered first choice treatment. Currently its use in permethrin and avermectin poisoning may be considered in an early stage of treatment in case of severe poisoning.
Dosing protocols
Current dosing protocols are derived from protocols used for the treatment of local anaesthetic systemic toxicity in man; although these protocols seem safe, it remains obscure if these are the optimal dosing protocols in animals. For severe, protracted neurotoxicity, and potentially life-threatening cardiotoxicity, the following dosing protocols are proposed in Box 1 and Box 2 (3).
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