An Alternative Treatment Method for Poisoning in Veterinary Medicine: Intravenous Lipid Emulsion (ILE)

Year 2021, Volume: 10 Issue: 2, 66 - 73, 24.12.2021

Büşra Aslan Akyol , Cengiz Gökbulut

https://doi.org/10.53913/aduveterinary.992845

Abstract

Animal poison control centers receive numerous complaints about possible consumption of substances that can cause deadly toxicities in the home. In recent years, over-the-counter medications such as ibuprofen, acetaminophen, and herbal supplements are the most common toxic substances consumed by pets. Removal of the toxin and supportive treatment is recommended in case of exposure to a toxin that does not have a known antidote. There have been many studies in both human and veterinary medicine that supporting the use of intravenous lipid emulsions in the treatment of intoxications. Intravenous lipid emulsion (ILE) is an oil-in-water emulsion that consists of egg yolk phospholipids, water, glycerin and various oils such as soybean, fish, coconut and olive oil. It is defined as a microemulsion with a long history of use as a parenteral nutrition formulation in both adult and pediatric patients. Also used as a drug carrier in addition to parenteral nutrition. In recent years, it has been used as an effective antidote for the treatment of intoxications caused by compounds with high oil solubility in both human and veterinary medicine. The first efficacy of the use of intravenous lipid emulsions in treatments was demonstrated in the systemic toxicity of local anesthetics and nowadays it comes to the fore in the poisoning of various drugs and compounds. However, it can also be used as an antidote in various intoxication cases caused by different chemicals that do not have any known antidote. Although clinically positive responses are received, more research is needed to more clearly understand the effect of intravenous lipid emulsion.

Keywords

Antidote, Intravenous Lipid Emulsion, Poisoning, Toxicity

References

• Abdel-Hafez, A. A., & Abdel-Wahab, B. A. (2008). 5-(4-Chlorophenyl)-5,6-dihydro-1,3-oxazepin-7(4H)-one derivatives as lipophilic cyclic analogues of baclofen: Design, synthesis, and neuropharmacological evaluation. Bioorganic & Medicinal Chemistry, 16(17), 7983–7991. https://doi.org/10.1016/j.bmc.2008.07.064
• Aljadani, N. A., Elnaggar, M. H. R., & Assaggaff, A. I. (2020). The role of fish oil and evening primrose oil against the toxicity of fenitrothion pesticide in male rats. International Journal of Pharmaceutical Research & Allied Sciences, 9(2).
• ASPCA. (2021). Top 10 pet poisons of the year. American Society for the Prevention of Cruelty to Animals. https://www.aspca.org/news/announcing-top-10-pet-toxins (accessed 3 September 2021).
• Becker, M., & Young, B. (2017). Treatment of severe lipophilic intoxications with intravenous lipid emulsion: a case series (2011-2014). Veterinary Medicine: Research and Reports, 8, 77–85. https://doi.org/10.2147/VMRR.S129576
• Bellis, T. J., & Gibeon, L. (2018). The use of intralipid emulsion therapy to treat severe cardiotoxicity secondary to lamotrigine ingestion in a dog. Clinical Case Reports, 6(10), 1982–1988. https://doi.org/10.1002/ccr3.1733
• Bischoff, K., Smith, M. C., & Stump, S. (2014). Treatment of Pieris Ingestion in Goats with Intravenous Lipid Emulsion. Journal of Medical Toxicology, 10(4), 411–414. https://doi.org/10.1007/s13181-014-0426-z
• Bolfer, L., McMichael, M., Ngwenyama, T. R., & O’Brien, M. A. (2014). Treatment of Ibuprofen Toxicosis in a Dog with IV Lipid Emulsion. Journal of the American Animal Hospital Association, 50(2), 136–140. https://doi.org/10.5326/JAAHA-MS-5979
• Bruenisholz, H., Kupper, J., Muentener, C. R., Dally, A., Kraemer, T., Naegeli, H., & Schwarzwald, C. C. (2012). Treatment of Ivermectin Overdose in a Miniature Shetland Pony Using Intravenous Administration of a Lipid Emulsion. Journal of Veterinary Internal Medicine, 26(2), 407–411. https://doi.org/10.1111/j.1939-1676.2011.00865.x
• Cavana, P. (2020). Use of Intravenously Lipid Emulsion for Treatment of Baclofen Toxicosis in a Cat. Pakistan Veterinary Journal, 40(1), 133–135. https://doi.org/10.29261/pakvetj/2019.123
• Cave, G, Harrop Griffiths, W., Harvey, M., Meek, T., Picard, J., Short, T., & Weinberg, G. (2010). Safety Guideline, Management of Severe Local Anaesthetic Toxicity. https://anaesthetists.org/Portals/0/PDFs/Guidelines PDFs/Guideline_management_severe_local_anaesthetic_toxicity_v2_2010_final.pdf?ver=2018-07-11-163755-240&ver=2018-07-11-163755-240 (accessed 3 September 2021).
• Cave, G. & Harvey, M. (2009). Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. Academic Emergency Medicine, 16(9), 815–824. https://doi.org/10.1111/j.1553-2712.2009.00499.x
• Cave, G. & Harvey, M. G. (2014). Should we consider the infusion of lipid emulsion in the resuscitation of poisoned patients? Critical Care, 18(5), 457. https://doi.org/10.1186/s13054-014-0457-5
• Cave, G., Harvey, M. G., & Castle, C. D. (2005). Intralipid ameliorates thiopentone induced respiratory depression in rats: Investigative pilot study. Emergency Medicine Australasia, 17(2), 180–181. https://doi.org/10.1111/j.1742-6723.2005.00714.x
• Charbonneau, H., Marcou, T. A. P., Mazoit, J.-X., Zetlaoui, P. J., & Benhamou, D. (2009). Early Use of Lipid Emulsion To Treat Incipient Mepivacaine Intoxication. Regional Anesthesia and Pain Medicine, 34(3), 277–278. https://doi.org/10.1097/AAP.0b013e31819340be
• Chumbler, N. S., Schildt, J. C., Mawby, D. I., & Papich, M. G. (2020). Use of intravenous lipid therapy in a cat with carprofen overdose. Clinical Case Reports, 8(4), 653–657. https://doi.org/10.1002/ccr3.2772
• Collins-Nakai, R. L., Noseworthy, D., & Lopaschuk, G. D. (1994). Epinephrine increases ATP production in hearts by preferentially increasing glucose metabolism. American Journal of Physiology-Heart and Circulatory Physiology, 267(5), H1862–H1871. https://doi.org/10.1152/ajpheart.1994.267.5.H1862
• Crandell, D. E., & Weinberg, G. L. (2009). Moxidectin toxicosis in a puppy successfully treated with intravenous lipids. Journal of Veterinary Emergency and Critical Care, 19(2), 181–186. https://doi.org/10.1111/j.1476-4431.2009.00402.x
• Davy, R. B., Campos, S., & Lynch, A. M. (2019). Acute chlorfenapyr toxicity in 3 dogs from a single household. Journal of Veterinary Emergency and Critical Care, 29(6), 686–689. https://doi.org/10.1111/vec.12894
• DeGroot, W. D. (2014). Intravenous lipid emulsion for treating permethrin toxicosis in a cat. The Canadian Veterinary Journal, 55(1), 1253.
• Driscoll, D. F. (2006). Lipid Injectable Emulsions: Pharmacopeial and Safety Issues. Pharmaceutical Research, 23(9), 1959–1969. https://doi.org/10.1007/s11095-006-9092-4
• Edwards, P., Shihab, N., & Scott, H. W. (2014). Treatment of a case of feline baclofen toxicosis with intravenous lipid therapy. Veterinary Record Case Reports, 2(1). https://doi.org/10.1136/vetreccr-2014-000059
• Felice, K. L., & Schumann, H. M. (2008). Intravenous lipid emulsion for local anesthetic toxicity: A review of the literature. Journal of Medical Toxicology, 4(3), 184–191. https://doi.org/10.1007/BF03161199
• Fernandez, A. L., Lee, J. A., Rahilly, L., Hovda, L., Brutlag, A. G., & Engebretsen, K. (2011). The use of intravenous lipid emulsion as an antidote in veterinary toxicology. Journal of Veterinary Emergency and Critical Care, 21(4), 309–320. https://doi.org/10.1111/j.1476-4431.2011.00657.x
• Fettiplace, M. R., Akpa, B. S., Ripper, R., Zider, B., Lang, J., Rubinstein, I., & Weinberg, G. (2014). Resuscitation with lipid emulsion: dose-dependent recovery from cardiac pharmacotoxicity requires a cardiotonic effect. Anesthesiology, 120(4), 915–925. https://doi.org/10.1097/ALN.0000000000000142
• Fettiplace, M. R., & Weinberg, G. (2018). The Mechanisms Underlying Lipid Resuscitation Therapy. Regional Anesthesia and Pain Medicine, 43(2), 138–149. https://doi.org/10.1097/AAP.0000000000000719
• Gaens, D., Leithäuser, C., Hamann, M., & Geyer, J. (2019). Adverse Drug Reactions After Administration of Emodepside/Praziquantel (Profender®) in an MDR1-Mutant Australian Shepherd Dog: Case Report. Frontiers in Veterinary Science, 6, 296. https://doi.org/10.3389/fvets.2019.00296
• Harvey, M., & Cave, G. (2007). Intralipid Outperforms Sodium Bicarbonate in a Rabbit Model of Clomipramine Toxicity. Annals of Emergency Medicine, 49(2), 178-185.e4. https://doi.org/10.1016/j.annemergmed.2006.07.016
• Harvey, M. G., & Cave, G. R. (2008). Intralipid infusion ameliorates propranolol-induced hypotension in rabbits. Journal of Medical Toxicology, 4(2), 71–76. https://doi.org/10.1007/BF03160958
• Haworth, M. D., & Smart, L. (2012). Use of intravenous lipid therapy in three cases of feline permethrin toxicosis. Journal of Veterinary Emergency and Critical Care, 22(6), 697–702. https://doi.org/10.1111/j.1476-4431.2012.00804.x
• Heggem-Perry, B., McMichael, M., O’Brien, M., & Moran, C. (2016). Intravenous Lipid Emulsion Therapy for Bromethalin Toxicity in a Dog. J Am Anim Hosp Assoc, 52(4), 265–268. https://doi.org/10.5326/JAAHA-MS-6396
• Herring, J. M., McMichael, M. A., Corsi, R., & Wurlod, V. (2015). Intravenous lipid emulsion therapy in three cases of canine naproxen overdose. Journal of Veterinary Emergency and Critical Care, 25(5), 672–678. https://doi.org/10.1111/vec.12307
• Hiller, D. B., Di Gregorio, G., Kelly, K., Ripper, R., Edelman, L., Boumendjel, R., Drasner, K., & Weinberg, G. L. (2010). Safety of High Volume Lipid Emulsion Infusion. Regional Anesthesia and Pain Medicine, 35(2), 140–144. https://doi.org/10.1097/AAP.0b013e3181c6f5aa
• Hoegberg, L. C. G., Bania, T. C., Lavergne, V., Bailey, B., Turgeon, A. F., Thomas, S. H. L., Morris, M., Miller-Nesbitt, A., Mégarbane, B., Magder, S., & Gosselin, S. (2016). Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity. Clinical Toxicology, 54(3), 167–193. https://doi.org/10.3109/15563650.2015.1121270
• Hwang, T.-L., Huang, S.-L., & Chen, M.-F. (1990). Effects of Intravenous Fat Emulsion on Respiratory Failure. Chest, 97(4), 934–938. https://doi.org/10.1378/chest.97.4.934
• Johnson, T. (2011). Intravenous lipid emulsion (IVLE) therapy for selected toxicoses. Proeedings of the Interntional Veterinary Emergency and Critical Care Society, San Antonio, TX, USA.
• Kaplan, A., & Whelan, M. (2012). The Use of IV Lipid Emulsion for Lipophilic Drug Toxicities. Journal of the American Animal Hospital Association, 48(4), 221–227. https://doi.org/10.5326/JAAHA-MS-5761
• Kopke, M. A., & Yozova, I. D. (2020). Management of presumptive canine permethrin toxicosis using intravenous lipid emulsion as an adjunctive therapy. Veterinary Record Case Reports, 8(2), e001041. https://doi.org/10.1136/vetreccr-2019-001041
• Krieglstein, J., Meffert, A., & Niemeyer, D. H. (1974). Influence of emulsified fat on chlorpromazine availability in rabbit blood. Experientia, 30(8), 924–926. https://doi.org/10.1007/BF01938365
• Lelescu, C. A., Mureșan, C., Muste, A., Taulescu, M. A., Neagu, A. M., & Nagy, A. L. (2017). Successful treatment of metaldehyde toxicosis with intravenous lipid emulsion in a dog. Acta Veterinaria Brno, 86(4), 379–383. https://doi.org/10.2754/avb201786040379
• Levine, M., Hoffman, R. S., Lavergne, V., Stork, C. M., Graudins, A., Chuang, R., Stellpflug, S. J., Morris, M., Miller-Nesbitt, A., & Gosselin, S. (2016). Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity. Clinical Toxicology, 54(3), 194–221. https://doi.org/10.3109/15563650.2015.1126286
• Litz, R. J., Roessel, T., Heller, A. R., & Stehr, S. N. (2008). Reversal of Central Nervous System and Cardiac Toxicity After Local Anesthetic Intoxication by Lipid Emulsion Injection. Anesthesia & Analgesia, 106(5), 1575–1577. https://doi.org/10.1213/ane.0b013e3181683dd7
• Long, W. M., Sinnott, V. B., Bracker, K., & Thomas, D. (2017). Use of 20% intravenous lipid emulsion for the treatment of loperamide toxicosis in a Collie homozygous for the ABCB1-1∆ mutation. Journal of Veterinary Emergency and Critical Care, 27(3), 357–361. https://doi.org/10.1111/vec.12562
• Maton, B. L., Simmonds, E. E., Lee, J. A., & Alwood, A. J. (2013). The use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem toxicosis in a dog. Journal of Veterinary Emergency and Critical Care, 23(3), 321–327. https://doi.org/10.1111/vec.12053
• Mazoit, J.-X., Le Guen, R., Beloeil, H., & Benhamou, D. (2009). Binding of Long-lasting Local Anesthetics to Lipid Emulsions. Anesthesiology, 110(2), 380–386. https://doi.org/10.1097/ALN.0b013e318194b252
• Ng, D. (2001). Heparin in hypertriglyceridemia: Friend or foe? Journal of Laboratory and Clinical Medicine, 138(6), 356–358. https://doi.org/10.1067/mlc.2001.119433
• O’Brien, T. Q., Clark-Price, S. C., Evans, E. E., Di Fazio, R., & McMichael, M. A. (2010). Infusion of a lipid emulsion to treat lidocaine intoxication in a cat. Journal of the American Veterinary Medical Association, 237(12), 1455–1458. https://doi.org/10.2460/javma.237.12.1455
• Perry, B. H., McMichael, M., Rick, M., & Jewell, E. (2016). Reduction of serum 25-hydroxyvitamin D concentrations with intravenous lipid emulsion in a dog. The Canadian Veterinary Journal, 57(12), 1284.
• Picard, J., & Meek, T. (2006). Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia, 61(2), 107–109. https://doi.org/10.1111/j.1365-2044.2005.04494.x
• Pollio, D., Michau, T. M., Weaver, E., & Kuebelbeck, K. L. (2018). Electroretinographic changes after intravenous lipid emulsion therapy in a dog and a foal with ivermectin toxicosis. Veterinary Ophthalmology, 21(1), 82–87. https://doi.org/10.1111/vop.12410
• Robben, J. H., & Dijkman, M. A. (2017). Lipid Therapy for Intoxications. Veterinary Clinics of North America: Small Animal Practice, 47(2), 435–450. https://doi.org/10.1016/j.cvsm.2016.10.018
• Rosenblatt, M. A., Abel, M., Fischer, G. W., Itzkovich, C. J., & Eisenkraft, J. B. (2006). Successful Use of a 20% Lipid Emulsion to Resuscitate a Patient after a Presumed Bupivacaine-related Cardiac Arrest. Anesthesiology, 105(1), 217–218. https://doi.org/10.1097/00000542-200607000-00033
• Saqib, M., Abbas, G., & Mughal, M. N. (2015). Successful management of ivermectin-induced blindness in an African lion (Panthera leo) by intravenous administration of a lipid emulsion. BMC Veterinary Research, 11(1), 287. https://doi.org/10.1186/s12917-015-0603-6
• Schulz, P. E., Weiner, S. P., Haber, L. M., Armstrong, D. D., & Fishman, M. A. (1994). Neurological complications from fat emulsion therapy. Annals of Neurology, 35(5), 628–630. https://doi.org/10.1002/ana.410350521
• Shah, A. K., & Sawchuk, R. J. (1991). Effect of co-administration of intralipidTM on the pharmacokinetics of cyclosporine in the rabbit. Biopharmaceutics & Drug Disposition, 12(6), 457–466. https://doi.org/10.1002/bdd.2510120607
• Sines, D. (2016). Moxidectin intoxication in a dog — a patient care report. The Veterinary Nurse, 7(3), 182–186. https://doi.org/10.12968/vetn.2016.7.3.182
• Sirianni, A. J., Osterhoudt, K. C., Calello, D. P., Muller, A. A., Waterhouse, M. R., Goodkin, M. B., Weinberg, G. L., & Henretig, F. M. (2008). Use of Lipid Emulsion in the Resuscitation of a Patient With Prolonged Cardiovascular Collapse After Overdose of Bupropion and Lamotrigine. Annals of Emergency Medicine, 51(4), 412-415.e1. https://doi.org/10.1016/j.annemergmed.2007.06.004
• Straathof, D. J., Driessen, O., Meijer, J. W., Van Rees, H., Vermeij, P., & Vermeij, T. A. (1984). Influence of Intralipid infusion on the elimination of phenytoin. Archives Internationales de Pharmacodynamie et de Thérapie, 267(2), 180–186.
• Tampakis, K., Vogiatzakis, N., Kontogiannis, C., Spartalis, M., Ntalianis, A., Spartalis, E., Siafaka, I., Iacovidou, N., Chalkias, A., & Xanthos, T. (2020). Intravenous lipid emulsion as an antidote in clinical toxicology: a systematic review. European Review for Medical and Pharmacological Sciences, 24(12), 7138–7148. https://doi.org/10.26355/eurrev_202006_21708
• Tebbutt, S. (2006). Intralipid Prolongs Survival in a Rat Model of Verapamil Toxicity. Academic Emergency Medicine, 13(2), 134–139. https://doi.org/10.1197/j.aem.2005.08.016
• Turner-Lawrence, D. E., & Kerns, W. (2008). Intravenous fat emulsion: A potential novel antidote. Journal of Medical Toxicology, 4(2), 109–114. https://doi.org/10.1007/BF03160965
• Van de Velde, M., Wouters, P. F., Rolf, N., Van Aken, H., & Vandermeersch, E. (1998). Comparative hemodynamic effects of three different parenterally administered lipid emulsions in conscious dogs. Critical Care Medicine, 26(1), 132–137. https://doi.org/10.1097/00003246-199801000-00028
• Van de Velde, M., Wouters, P., Rolf, N., Van Aken, H., Flameng, W., & Vandermeersch, E. (1996). Long-chain triglycerides improve recovery from myocardial stunning in conscious dogs. Cardiovascular Research, 32(6), 1008–1015. https://doi.org/10.1016/S0008-6363(96)00165-4
• Venus, B., Smith, R. A., Patel, C., & Sandoval, E. (1989). Hemodynamic and Gas Exchange Alterations during Intralipid Infusion in Patients with Adult Respiratory Distress Syndrome. Chest, 95(6), 1278–1281. https://doi.org/10.1378/chest.95.6.1278
• Waitzberg, D. L., Torrinhas, R. S., & Jacintho, T. M. (2006). New Parenteral Lipid Emulsions for Clinical Use. Journal of Parenteral and Enteral Nutrition, 30(4), 351–367. https://doi.org/10.1177/0148607106030004351
• Weinberg, G. L., Di Gregorio, G., Ripper, R., Kelly, K., Massad, M., Edelman, L., Schwartz, D., Shah, N., Zheng, S., & Feinstein, D. L. (2008). Resuscitation with Lipid versus Epinephrine in a Rat Model of Bupivacaine Overdose. Anesthesiology, 108(5), 907–913. https://doi.org/10.1097/ALN.0b013e31816d91d2
• Weinberg, G. L., VadeBoncouer, T., Ramaraju, G. A., Garcia-Amaro, M. F., & Cwik, M. J. (1998). Pretreatment or Resuscitation with a Lipid Infusion Shifts the Dose-Response to Bupivacaine-induced Asystole in Rats. Anesthesiology, 88(4), 1071–1075. https://doi.org/10.1097/00000542-199804000-00028
• Weinberg, G, Ripper, R., Murphy, P., Edelman, L., Hoffman, W., Strichartz, G., & Feinstein, D. (2006). Lipid Infusion Accelerates Removal of Bupivacaine and Recovery From Bupivacaine Toxicity in the Isolated Rat Heart. Regional Anesthesia and Pain Medicine, 31(4), 296–303. https://doi.org/10.1016/j.rapm.2005.02.011
• Weinberg, Guy. (2003). Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Regional Anesthesia and Pain Medicine, 28(3), 198–202. https://doi.org/10.1053/rapm.2003.50041
• Weinberg, Guy. (2006). Lipid Infusion Resuscitation for Local Anesthetic Toxicity: Proof of clinical efficacy. Anesthesiology, 105(1), 7–8. https://doi.org/10.1097/00000542-200607000-00005
• West, N., & Rusbridge, C. (2021). Ethanol toxicity in a dog due to gin‐soaked sloe berry ( Prunus spinosa ) ingestion. Veterinary Record Case Reports, 9(1), e12. https://doi.org/10.1002/vrc2.12
• Westropp, J. L., Buffington, C. A. T., Chew, D., Ettinger, S. J., & Feldman, E. C. (2005). Textbook of Veterinary Internal Medicine. Elsevier Saunders Philadelphia.
• Williams, K., Wells, R. J., & McLean, M. K. (2015). Suspected synthetic cannabinoid toxicosis in a dog. Journal of Veterinary Emergency and Critical Care, 25(6), 739–744. https://doi.org/10.1111/vec.12378
• Wright, H. M., Chen, A. V, Talcott, P. A., Poppenga, R. H., & Mealey, K. L. (2011). Intravenous fat emulsion as treatment for ivermectin toxicosis in three dogs homozygous for the ABCB1-1Δ gene mutation. Journal of Veterinary Emergency and Critical Care, 21(6), 666–672. https://doi.org/10.1111/j.1476-4431.2011.00687.x
• Xenoulis, P. G., Suchodolski, J. S., Levinski, M. D., & Steiner, J. M. (2008). Serum liver enzyme activities in healthy Miniature Schnauzers with and without hypertriglyceridemia. Journal of the American Veterinary Medical Association, 232(1), 63–67. https://doi.org/10.2460/javma.232.1.63