Podcasts

Join Now

Intravenous Lipid Emulsion Therapy for the Management of Toxicities in Dogs and Cats | VETgirl Veterinary Continuing Education Podcasts

Need Help?

March 2024

In today’s VETgirl online veterinary CE podcast, Dr. Justine Lee, DACVECC, DABT talks about the use of intravenous lipid emulsion (ILE) therapy for the management of toxicities in dogs and cats. Whether you’re a veterinarian in a general, specialty, or emergency practice, you’re bound to see poisoning cases. Thankfully, with aggressive supportive care and appropriate use of decontamination, the prognosis for most toxicants is fair to good.

A general approach to treatment of the poisoned patient may include:

  • Appropriate decontamination (e.g., inducing vomiting, administration of charcoal/cholestyramine)
  • Fluid therapy (e.g., to aid in perfusion, treatment of hypotension, aid in urinary elimination, vasodilate renal vessels, prevent hypernatremia, etc.)
  • Gastrointestinal support (e.g., to prevent vomiting, control nausea, treat diarrhea, etc.)
  • Cardiovascular support (e.g., to treat tachyarrhythmias or bradyarrhythmias, treat hypotension, etc.)
  • Neurologic support (e.g., to treat tremors or seizures, etc.)
  • Antidote therapy (e.g., if available)

The use of intravenous lipid emulsion therapy (ILE) had been used for parenteral nutrition (in the 1960s), for drug delivery (e.g., carrier for propofol), and more recently, as a promising treatment option for fat-soluble toxicants.[1-9] In the past 2 decades, it has been used extensively in both human and veterinary medicine.[1-16] It is now widely accepted for use in the treatment of life-threatening overdoses and toxicities, where it has been found to be particularly effective in treating lipophilic toxicants. The first successful report of ILE in human medicine was published in 2006 [5]. In the veterinary field, ILE was first used in the clinical management of a puppy with moxidectin toxicosis.[10] In this blog post, we are going to discuss the indications for ILE use, its mechanism of action, potential adverse effects, and the scientific data supporting its use for managing toxicities in dogs and cats.

What toxins warrant the use of ILE in veterinary medicine?
ILE is most effective in treating lipophilic compounds, which are compounds that are highly soluble in fats and oils. Veterinary literature describes the use of ILE for macrocyclic lactones (e.g., moxidectin, ivermectin),[10,12,14,17] local anesthetics (e.g., bupivacaine, lidocaine, mepivacaine, ropivacaine),[11] pyrethrins,[15] and calcium channel blocker toxicoses.[16] Recent publications have also advocated it for the use of ILE with beta-blockers (e.g., propranolol), cholecalciferol, marijuana, pentobarbital, non-steroidal anti-inflammatory drugs and several other human medications (e.g., clomipramine, bupropion, haloperidol, quetiapine, doxepin, carbamazepine, flecainide, hydroxychloroquine, etc.).[19] ASPCA Animal Poison Control Center has experienced anecdotal success with the use of ILE for certain additional medications with a narrow margin of safety (e.g., baclofen, cholecalciferol, β-blockers).[a] A state-of-the-art review by Fernandez et al provides a thorough discussion of the use of ILE in veterinary medicine.[13]=”472″ />

What is the mechanism of action of ILE?
The mechanism of action of ILE is not fully understood; however, there are several theories including:[7,13]

• Providing myocytes with energy substrates, thereby augmenting cardiac performance

• Restoring myocardial function by increasing intracellular calcium concentration

• Acting as a lipid sink by sequestration of lipophilic compounds into the newly created intravascular lipid compartment (a lipid or pharmacologic sink). With this lipid sink hypothesis, compartmentalization of the drug into the lipid phase results in a decreased free drug concentration available to tissues.

• Increasing the overall fatty acid pool, which overcomes inhibition of mitochondrial fatty acid metabolism (e.g., bupivacaine toxicosis).

Currently, the most supported hypotheses are that ILE improves cardiac performance and provides a lipid sink effect in the vascular compartment. This limits the toxicant’s distribution to organs and tissues and is thought to reduce its toxic effects.

What is the recommended dosing regimen for ILE?
The antidotal use of ILE is considered extra-label and there are various dosage recommendations that are extrapolated from human data. Several studies recommend a bolus of 20% ILE at 1.5 – 4 ml/kg over 1-2 minutes, followed by a CRI of 0.25 ml/kg/min IV, for 30 to 60 minutes.[7,13]
Some clinicians recommend using additional aliquots at 0.5 mL/kg/h until clinical signs improve if there is no initial response. Others recommend repeating the original bolus/CRI in 4-6 hours, or once the lipemia clears. If no improvement is seen within 12-24 hours, ILE should be discontinued and will unlikely be beneficial. (Please note errata in dosing in Fernandez et al State of the Art Review.)[13]

What are potential adverse effects that can occur with the use of ILE?
While ILE is generally considered safe and well-tolerated, there are some potential adverse effects to be aware of. Noted complications from the extra-label use of ILE in both human and veterinary medicine include fat overload syndrome, pyrogenic reactions, pancreatitis, hypersensitivity reactions,* acute kidney injury, acute lung injury, fat emboli, increased susceptibility to infection, persistent lipemia, hemolysis, coagulopathy, corneal clouding, cardiopulmonary arrest, and lack of efficacy.[7,13,20,21]

*ILE should not be used in patients with an allergy to egg or soy, as it is made from these products.

What’s the evidence for the use of ILE in the management of toxicosis in dogs and cats?
There is a growing body of scientific data supporting the use of ILE in the management of toxicities in dogs and cats. Many case reports and case series have reported successful outcomes when ILE is used as part of the treatment regimen. However, more research is needed to fully understand the mechanism of action and optimal dosing and administration protocols for ILE in veterinary medicine. As such, it is important to use ILE judiciously and in consultation with the ASPCA Animal Poison Control Center.

ASPCA Animal Poison Control Center logo

In the author’s opinion, the use of ILE should be reserved for life-threatening poisonings with severe clinical signs. If an effective therapy or antidote is already well established in the field of veterinary toxicology, its continued use is recommended over ILE due to the unknown effects of ILE administration. Keep in mind that certain therapeutics (e.g., anticonvulsants, CPR drugs, muscle relaxants, etc.) may be made ineffective with the administration of ILE; hence supportive therapy is always warranted prior to experimental use of ILE. However, if the patient has undergone cardiovascular collapse secondary to toxicosis or demonstrates significant clinical signs of toxicosis (e.g., from baclofen, ivermectin, or moxidectin), ILE should be considered.

Conclusion
ILE has emerged as a promising treatment option for managing toxicities in dogs and cats, particularly those caused by lipophilic compounds. While more research is needed to fully understand its mechanism of action, indications for use, and optimal administration protocols, the existing data supports its efficacy and safety in many cases. As a veterinarian, it is important to stay up to date on emerging treatment options like ILE and to use them judiciously and in consultation with experts in the field. By doing so, we can continue to improve the outcomes for our patients and advance the field of veterinary medicine as a whole.

References:
1. Krieglstein J, Meffert A, Niemeyer DH. Influence of emulsified fat on chlorpromazine availability in rabbit blood. Experientia 1974;30(8):924-926.
2. Weinberg GL, VadeBoncouer T, Ramaraju GA, et al. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology 1998;88:1071-1075.
3. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med 2003;28:198-202.
4. Weinberg G. Lipid infusion resuscitation for local anesthetic toxicity. Anesthesiology 2006;105:7-8.
5. Rosenblatt MA, Abel M, Fischer GW, et al. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 2006;105(1):217-218.
6. Turner-Lawrence DE, Kerns W II. Intravenous fat emulsion: a potential novel antidote. J Med Toxicol 2008;4(2):109-114.
7. Jamaty C, Bailey B, Laroque A, et al. Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies. Clin Toxicol 2010;48:1-27.
8. LipidRescue: Resuscitation for cardiac toxicity. Available at: http://lipidrescue.org. Accessed November 10, 2011.
9. Association of Anesthetists of Great Britain and Ireland. Available at: http://update.anaesthesiologists.org/wp-content/uploads/2009/12/Management-of-local-anaesthetic-toxicity.pdf Ac¬cessed November 25, 2012.
10. Crandell DE, Weinberg GL. Moxidectin toxicosis in a puppy successfully treated with intravenous lipids. J Vet Emerg Crit Care 2009; 19(2):181-186.
11. O’Brien TQ, Clark-Price SC, Evans EE, et al. Infusion of a lipid emulsion to treat lidocaine intoxication in a cat. J Am Vet Med Assoc 2010;237:1455-1458.
12. Clarke DL, Lee JA, Murphy LA, Reineke EL. Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border collie. J Am Vet Med Assoc 2011;239:(10):1328-1333.
13. Fernandez AL, Lee JA, Rahilly L, et al. The use of intravenous lipid emulsion as an antidote in veterinary toxicology. J Vet Emerg Crit Care 2011;21(4):309-320. NOTE: See updated errata also.
14. Wright HM, Chen AV, Talcott PA, et al. Intravenous fat emulsion for treatment for ivermectin toxicosis in three dogs homozygous for the ABCB1-1Δ gene mutation. J Vet Emerg Crit Care 2011; 21(6):666-672.
15. Brückner M, Schwedes CS. Successful treatment of permethrin toxicosis in two cats with an intravenous lipid administration. Tierärztl Prax 2012;40:129-134.
16. Maton BL, Simmonds EE, Lee JA, Alwood AJ. The use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem toxicosis in a dog. J Vet Emerg Crit Care 2013;23(3):321-327.
17. Epstein SE, Hollingsworth SR. Ivermectin-induced blindness treated with intravenous lipid therapy in a dog. J Vet Emerg Crit Care 2013;23(1):58-62.
18. Hayes BD, Gosselin S, Calello DP, et al. Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration. Clin Toxicol 2016;54:365-404.
19. Gwaltney-Brant SM, Lee JA, Fernandez AF. Drugs used to treat toxicosis. Kirk & Bonagura’s Current Veterinary Therapy XVI, 2019.
20. Kollef MH, McCormack MT, Caras WE, et al. The fat overload syndrome: successful treatment with plasma exchange. Ann Intern Med 1990;112(7):545-546.
21. Seitz MA, Burkitt-Creedon JM. Persistent gross lipemia and suspected corneal lipidosis following intravenous lipid therapy in a cat with permethrin toxicosis. J Vet Emerg Crit Care 2016;26(6):804-808.

Footnotes:
a. Personal communication, the ASPCA Animal Poison Control Center

NOTE: When in doubt, all drug dosages should be confirmed and cross-referenced with a veterinary pharmacology/drug reference guide.

Only VETgirl members can leave comments. Sign In or Join VETgirl now!