Growing Use of Intralipid Therapy in Veterinary Medicine

The use of intralipid therapy has been gaining traction as a treatment option for an ever expanding range of toxicities. While it has not quite become the standard of care, it has been viable for patients in the veterinary field and has been reported as case studies in the human field.

Veterinary literature has reviewed intravenous lipid emulsion therapy (ILE) [1,2] and published case reports or studies are available noting efficacy in toxicities including macrocyclic lactones [3,4], baclofen [5], beta-blockers, calcium channel blockers [6], NSAID [7,8], bromethalin [9], lidocaine [10], permethrin toxicity [11,12], tricyclic antidepressants (13). Intravenous lipid emulsion (ILE) in human literature has been reported as a therapy for local anesthetic [14,15] calcium channel blocker [16,17], psychotropic medication [18] , glyphosatesurfactant herbicide toxicities[19] and even cocaine overdosage [20]. Original work performed by Weinberg noted a response in rats with bupivicaine induced systole with lipid emulsion [21]. How exactly ILE works is not certain but two theories are considered. The “lipid sink” theory is most commonly considered the primary mode of action. In this theory, the formation of a lipid compartment within the intravascular space can serve as a “sink” into which the lipophilic drug will be drawn into. The drug is then excreted/metabolized. Determination of a drug’s lipophilicity may be noted by its log P value. A value >1 indicates lipophilic compound which may move into the temporary lipid phase and be less distributed throughout the body. The formulation of ILE utilized may play a role and supports the “lipid-sink” theory based on one study [22]. This theory has been supported in two case reports that followed plasma ropivacaine [15] and serum verapamil concentrations [17]. An alternate theory is that the lipid provides an energy source for the cardiac myocytes by increasing the availability of FFA. The increase of FFA may also aid in increasing the activation of voltage-gated calcium channels in the myocardium, increasing cytosolic calcium channels This mechanism may be most important in cases of calcium-channel blockade [23,24].

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There has not been an absolute protocol established for administration of intralipid therapy. A commonly utilized protocol includes an IV bolus of 20% ILE (1.5 mL/kg) followed by a continuous rate infusion of 0.25 mL/kg/min for 30–60 minutes[1]. IntraLipid 20% (Baxter) is the most commonly referred to solution. It is composed 20% Soybean Oil, 1.2% Egg Yolk Phospholipids, 2.25% Glycerin, and Water for Injection. It may be infused through a peripheral intravenous catheter (350 mOsmol/kg water) without the use of a filter. The solution must be handled aseptically. Complications of ILE therapy may include fever, hyperlipemia, thrombocytopenia, hemolysis, prolonged coagulation times, seizures or anaphylactoid reactions to the soybean component. In one cat corneal lipidosis was suspected following treatment for ivermectin toxicity [12]. The ph of Intralipid may vary from 6-9 pending where it is is in its shelflife which should be taken into account in the individual patient. While the log P value predicts the lipophilicity of a drug, other factors such as distribution, patient pH, intravascular volume and oxygenation status affect response to ILE. Restoration of intravascular volume and oxygenation should be corrected prior to initiating ILE treatment.

Submitted by: William Pullin, DVM, DACVIM

1. Fernandez, AL, Lee JA, Rahilly L, et al. Use of intravenous lipid emulsion as an antidote in veterinary toxicology. J Vet Emerg Crit Care 2011 Aug;21(4):309-20. doi: 10.1111/j. 1476-4431.2011.00657.x

2. Gwaltney-Brant S, Meadows I. Use of intravenous lipid emulsions for treating certain poisoning cases in small animals. Vet Clie North Am Small Animal Pract. 2012 Mar;42(2): 251-62, vi. doi:10.1016/j.cvsm.2011.12.001

3. 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 Nov 15;239(10):1328-33. doi: 10.2460/javma.239.10.1328

4. Epstein SE, Hollingsworth SR. Ivermectin-induced blindness treated with intravenous lips therapy in a dog. J Vet Emerg Crit Care(San Antonio). 2013 Jan-Feb;23(1):58-62. don 10.1111/vec12016

5. Bates N, Chatterton J, Robbins C, et al. Lipid infusion in the management of poisoning: a report of 6 canine cases. Vet Rec. 2013 MAr 30;172(13):339. doi: 10.1136/vr.101036

6. Maton BL, Simonds EE, Lee JA, et al. Use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem overdose in a dog. J Vet Emerg Care. 2013 May/June ;23(3):321-7. don 10.1111/vec.12053

7. Herring JM, McMichael MA, Corsi R, Wurlod V. Intravenous lipid emulsion therapy in three cases of canine naproxen overdose. J Vet Emerg Crit Care (San Antonio). 2015 Sep-Oct; 25(5):672-8. doi: 10.1111/vec.12307

8. Bolfer L, McMichael M, Ngwenyama TR, O’Brien MA. Treatment of ibuprofen toxicosis in a dog with IV lipid emulsion. J AM Anim Host Assoc. 2014 MAr-Apr;50(2):136-40. doi: 10.5326/JAAHA-MS-5979

9. Heggem-Perry B, McMichael M, O’Brien M, Moran C. Intravenous lipid emulsion therapy for bromethalin toxicity in a dog. J Am Anim Hosp Assoc. 2016 Jul-Aug;52(4):265-8. doi: 10.5326/JAAHA-MS-6396

10. 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; 15;237(12):1455–1458. doi: 10.2460/javma. 237.12.1455.

11. Peacock R, Hosgood G, Swindells KL, Smart L. Randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats. J Vet Emerg Crit Care. 2015 Sep-Oct;25(5):597-605. doi: 10.1111/vec.12322

12. 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 Nov-Dec;26(6):804-8

13. Cave G, Harvey M, Shaw T, et al. Comparison of intravenous lipid emulsion, bicarbonate, and tailored liposomes in rabbit clomipramine toxicity. Acad Emerg Med. 2013 Oct;20(10): 1076-9. doi 10.111/acem.12224

14. Litz RJ, Roessel T, Heller AR, Stehr SN. Reversal of central nervous system and cardiac toxicity after local anesthetic intoxication by lipid emulsion injection. Anesth Analg. 2008;106:1575–1577. doi: 10.1213/ane.0b013e3181683dd7

15. Mizutani K, Oda Y, Sato H. Successful treatment of ropivacaine-induced central nervous system toxicity by use of lipid emulsion: effect on total and unbound plasma fractions. J Anesth. 2011 Jun;25(3):442-5

16. Young AC, Velez LI, Kleinschmidt KC. Intravenous fat emulsion therapy for intentional sustained-release verapamil overdose. Resuscitation. 2009;80:591–593. doi: 10.1016/ j.resuscitation.2009.01.023

17. French D Armenian P, Ryan W, et al. Serum verapamil concentrations before and after Intralipid therapy during treatment of overdose. Clin Toxicol (Phila). 2011 Apr;49(4):340-4. doi 10.3109/15563650.2011.572556

18. Nair F, Paul FK, Protopapas M. Management of near fatal mixed tricyclic antidepressant and selective serotonin reuptake inhibitor overdose with Intralipid 20% emulsion. Aneasth Intensive Care. 2013 Mar;41(2):264-5

19. Han SK, Jeong J, Yeom S, Ryu J, Park S. Use of a lipid emulsion in a patient with refractory hypotension caused by glyphosate-surfactant herbicide. Clin Toxicol (Phila) 2010;48(6):566– 568. doi: 10.3109/15563650.2010.496730

20. Jakkala-Saibaba R, Morgan PG, Morton GL. Treatment of cocaine overdose with lipid emulsion. Anaesthesia. 2011 Dec;66(12):1168-70. doi: 10.1111/j.1365-2044.2011.06895.x.)

21. (Weinberg GL, VadeBoncouer T, Ramaraju GA, et al. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivicaine-induced asystole in rats. Anesthesiology 1998; 88(4): 1071-1075.)

22. Mazoit JX, Le Guen R, Beloeil H, et al. Binding of long-lasting local anesthetics to lipid emulsions. Anesthesiology 2009;110(2):380-6

23. Turner-Lawrence DE, Kerns WI. Intravenous fat emulsion: a potential novel antidote. J Med Toxicol 2008; 4(2):109-114. doi: 10.1007/BF03160965

24. Rothschild L, Bern S, Oswald S, Weinberg G. Intravenous lipid emulsion in clinical toxicology. Scan J Trauma Resusc Emerg Med. 2010;18:51. doi: 10.1186/1757-7241-18-51

 

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