Download - Kelly Roehl, MS, RD, LDN, CNSC Rush University Medical Center June 2015 Updates in Parenteral Lipid Formulations – Science to Practice

Kelly Roehl, MS, RD, LDN, CNSC Rush University Medical Center June 2015 Updates in Parenteral Lipid Formulations Science to Practice

Disclosures 2 Kelly Roehl No Disclosures

Session Description This session addresses the role of parenteral lipids on the nutritional and health status of the adult nutrition support population. 3

Objectives 4 1.Briefly describe current intravenous lipid emulsion (IVLE) formulations available in the United States. 2.Describe availability and the current state of literature regarding IVLEs, including potential benefits or drawbacks of non-standard formulations. 3.Identify patient groups that may benefit from administration of alternative and specialized IVLE formulations, and describe strategies for judicious use of various formulations among patients requiring PN support.

What are lipids and why are they important? 5

What is a Lipid? Molecules soluble in organic solvents Functions: Source of energy (fatty acids thru B-oxidation) Provide vitamins Structural & metabolic functions within cell membranes, hormone production 6 Fatty Acid = Most Basic Form Hydrocarbon tail (hydrophobic)Carboxyl head (hydrophilic)

Fatty Acids Basis for all other lipids Classification: Chain length Degree of saturation Location of double bonds 7

Fatty Acid Classification Examples 8 Linoleic Acid (18:2, n-6) -Linolenic Acid (18:3, n-3) 18 Carbon chain length polyunsaturated Omega classification (location of first double bond from -end) end

Common Fatty Acids 9 Calder PC et al. Intensive Care Med. 2010;36:735-749. Common NameChemical NameStructureDietary Source Capric Decanoic 10:0Coconut Lauric Dedecanoic 12:0Coconut Myristic Tetradecanoic 14:0Milk Palmitic Hexadecanoic 16:0milk, eggs, meat, cocoa butter Palmitoleic 9-Hexadecenoic 16:1, n-7Fish Steric Octadecanoic 18:0Milk, eggs, meat, cocoa butter Oleic 9-Octadecenic 18:1, n-9Milk, eggs, meat, cocoa butter, olives Linoleic 9,12-Octadeadienoic 18:2, n-6Seed oil, egg, meat, animal fat Arachidonic 5,8,11,14-Eicosatetraenoic 20:4, n-6Meat, eggs, algal oils Alpha-Linolenic 59,12,15-Octadecatrienoic 18:3, n-3Seed oils, green leaves, nuts Eicosapentanoic 5,8,11,14,17- Eicosapentaenoic 20:5, n-3Fish Docosapentaenoic 7,10,13,16,19- Docosapentaenoic 22:5, n-3Fish Docosahexaenoic 4,7,10,13,16,19- Docosahexaenoic 22:6, n-3Fish, algal oils

Fatty Acids Chain Length Long-Chain Fatty Acids Triglycerides (LCTs) >14 carbons Medium Chain Fatty Acids Triglycerides (MCTs) 6-12 carbons Short-Chain Fatty Acids 2-4 carbons 10 American Diet >90% Palmitic acid (16:0), steric acid (18:0), oleic acid (18:1), and linoleic acid (18:2) Animal & plant fats/oils Butyric acid (4:0), lauric acid (12:0) and myristic acid (14:0) Milk fat & coconut oil Wanten GJ. Am J Clin Nutr. 2007;85:1171-84.

Triglycerides Intravenous Lipid Emulsions (IVLEs) contain fatty acids in the form of triglycerides 11 3 Fatty Acids + Glycerol = Triglyceride

Biochemical Pathways 12 Lipids

Why is Lipid Origin Important? 13. 1 Helfrick FW et al. J Pediatr. 1944;25:400-403. 2 Vanek VW et al. Nutr Clin Pract. 2012;27:150-192 3 Osborn HT et al. Compr Rev Food Sci Food Safety. 2002;3:110-120. *Slide adapted from Todd Canada, Mandy Corrigan Fatty acid composition of cell membranes determines structural properties, regulatory and immune functions Incorporated into cell membranes impacting: Membrane fluidity Membrane fluidity Production of bioactive mediators Cell signaling Regulation of gene expression

Fatty Acids, Inflammation, Immunoregulation 14 1 Vanek VW et al. Nutr Clin Pract. 2012;27:150-192.

Fatty Acids, Inflammation, Immunoregulation 15 1 Vanek VW et al. Nutr Clin Pract. 2012;27:150-192. 2 Calder PC. Am J Clin Nutr. 2006;83:S1505-S1519. 3 Calder PC. Eur J Clin Nutr. 2002;56:S14-S19. Release of lysosomal enzymes Release of chemotactic agents Vascular permeability Vasodilation IL-6 production Fever Pain Impact of Pro-Inflammatory Eicosanoids

Intravenous Lipid Emulsions (IVLEs) 16

Why are IVLEs used? Provide energy (2 kcal/mL) Cellular beta-oxidation Provide fat-soluble vitamins Prevent essential fatty acid deficiency (EFAD) 2-4% energy from linoleic acid 0.25-0.5% energy from -linolenic acid 17 1 Mirtallo J et al. JPEN 2004;28:S39-S70.

Essential Fatty Acid Deficiency (EFAD) Symptoms 1 Scaly skin, impaired wound healing and immune function, death 1 Triene-to-tetraene ratio >0.2 2 Prevention 3 2-4% energy from linoleic acid 0.25-0.5% energy from -linolenic acid 18 1 Hansen AE et al. J Nutr. 1958;66:565-576. 2 Holman R. Prog Chem Fats Other Lipids. 1971;9:275-348. 3 Mirtallo J et al. JPEN 2004;28:S39-S70.

Composition of IVLEs Fatty acids in form of triglycerides Designed to mimic chylomicrons (200-500 nm) Type of FAs depends on source of lipid Emulsifier to enhance stability Egg yolk or lecithin Fat-soluble vitamins A, E, D, K Phytosterols Structurally similar to cholesterol 19

IVLEs in Human Body 20 Mirtallo JM et al. Ann Pharmacother. 2010;44:668-700.

IVLEs in Human Body 21 Mirtallo JM et al. Ann Pharmacother. 2010;44:668-700.

IVLEs in Human Body Elevated TGs 22 X +++ X Mirtallo JM et al. Ann Pharmacother. 2010;44:668-700.

IVLEs in Human Body Elevated TGs 23 X +++ Mirtallo JM et al. Ann Pharmacother. 2010;44:668-700.

History of IVLEs 24 1944 1961 1984 1996 2000 2005 First use of ILVE (olive oil +lecithin) in a child 1 Pharmaceutical-grade SO-based IVLE introduced 2 MCT/LCT coconut/soy IVLE introduced 2 OO-based IVLE introduced 2 Structured lipids introduced (MCT/LCT) 3 FO-based IVFE introduced 2. 1 Helfrick FW et al. J Pediatr. 1944;25:400-403. 2 Vanek VW et al. Nutr Clin Pract. 2012;27:150-192 3 Osborn HT et al. Compr Rev Food Sci Food Safety. 2002;3:110-120. *Slide adapted from Todd Canada, Mandy Corrigan

25 Furhman T. Support Line. 2014;36(6):27-28.

IVLEs Available Internationally 26 Furhman T. Support Line. 2014;36(6):27-28. Calder PC et al. Intensive Care Med. 2010;36:735-749. ProductSourceFDA Approved Under FDA Approval Not Available in US Intralipid 20% (Fresenius Kabi/Baxter) 100% soy X Liposyn III 20% (Hospira) 100% soy X Nutrilipid 20% (B Braun) 100% soy X ClinOleic 20% (Baxter) 80% olive, 20% soy X SMOF 20% (Fresenius Kabi) 30% coconut, 30% soy, 25% olive, 15% fish X Omegaven 10% (Fresenius Kabi) 100% fish*compassionate use only Lipofundin 20% (B Braun) 50% coconut, 50% soy X Structolipid 20% (Fresenius Kabi) 36% coconut, 64% soy X Lipoplus 20% (B Braun) 50% coconut, 40% soy, 10% fish X

Characteristics of SO-based IVLE High omega 6 to omega 3 ratio 1 44-62% linoleic acid (n-6) 4-11% alpha-linolenic acid (n-3) Typical dosing strategies for SO-based IVLE: 15-30% total kcal, although only very low doses would be necessary to prevent EFAD 2 2-4% energy from linoleic acid 0.25-0.5% energy from -linolenic acid 27 1 Intralipid Package Insert. Deerfield, IL: Baxter Healthcare Corporation; 2006. 2 Mirtallo J et al. JPEN. 2004;28:S39-S70.

Why the Controversy with SO- ILVEs? SO-based IVLE associated with: Impaired immune function 1,2 Inflammation 2,3 Oxidative stress 4 Cholestasis 5,6 Until recently, only SO-based IVLEs have been available in the United States 28 1 Nordenstrom J et al. Am J Clin Nutr. 1979;32:2416-2422. 2 Sedman P et al. JPEN. 1990;14:12-17. 3 Jarstrand C et al. JPEN. 1978;2:663-670. 4 Roche LD. Oxid Antioxid Med Sci. 2013;1:11-14. 5 Clayton PT et al. Gastroenterology.1993;14:158-164. 6 Kurvinen A et al. J Pediatr Gastroenterol Nutr. 2012;54:803-811.

Soybean Oil (SO)-Based IVLE Increased TNF-, IL-6, neutrophils 1 Transient worsening of pulmonary function in ALI/ARDS patients 2-6 Increased pulmonary shunt Increased MPAP Increased A-a oxygen gradient Decreased PaO 2 /FiO 2 ratio IVLE doses >0.13 g/kg/hr = impaired RES function Phytosterol and high omega-6 fatty acid content associated with PNALD 7-8 29 1 Krogh-Madesn R et al. Am J Physiol Endocrinol Metab.2008;294:E371-E379. 2 Venus B et al. Chest. 1989;95:1278-12181. 3 Hwang T et al. Chest. 1990;97:934-948. 4 Mathru M et al. Chest. 1991;99:426-429. 5 Suchner U et al. Crit Care Medi 2001;29:1569-1574. 6 Seidner DL et al. JPEN. 1989;13:619-619. 7 Kurvinen A et al. J Pediatr Gastroenterol Nutr. 2012;54:803-811. 8 Kosters A et al. Semin Liver Dis. 2010;30:186-194.

Phytosterols & PNALD IVLE associated with cholestasis (PNALD) Pro-inflammatory omega-6 concentration Phytosterols IV phytosterols bypasses the initial hepatic elimination leading to high concentrations of serum phytosterols 1-3 Inhibition of FXR, resulting in reduced bile acid and bilirubin excretion, damage to the hepatocyte Improved liver enzymes with infusion of OO-and FO- based IVLEs 3-6 Lower phytosterol content 30 1 Iyer KR et al. J Pediatr Surg. 1998;33:1-6. 2 Carter BA et al. Pediatr Res. 2007;62:301-306. 3 El Kasmi KC et al. Sci Transl Medi 2013;5:1-10. 4 Kurvinen A et al. J Pediatr Gastroenterol Nutr. 2012;54:803-811. 5 Kosters A et al. Semin Liver Dis. 2010;30:186-194. 6 Vanek VW et al. Nutr Clin Pract. 2012;27:150-192.

Olive Oil (OO)-Based IVLEs Prospective, RCT comparing SO to OO-IVLE among critically ill patients 1 No differences in complications, glycemic control, inflammatory or oxidative stress markers, immune function, hospital or ICU LOS Systematic review of alternative IVLEs among critically ill patients 2 No differences in mortality or ICU LOS Significant reduction in duration of mechanical ventilation compared to SO-IVLE (P=0.01) Prospective, multicenter ICU study 3 Shorter ICU LOS (P

Download - Kelly Roehl, MS, RD, LDN, CNSC Rush University Medical Center June 2015 Updates in Parenteral Lipid Formulations – Science to Practice

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