Updates in Parenteral Lipid Formulations – Science to Practice

Slides:



Advertisements
Similar presentations
The Good, the Bad and the Truly Ugly!
Advertisements

FATS.
Parenteral Nutrition Graphic source:
Egg Nutrition Center Cardiovascular Disease Presentation.
Lipids: Not Just Fat BIOL 103, Chapter 6-1.
The Lipids Triglycerides Phospholipids Sterols Copyright 2005 Wadsworth Group, a division of Thomson Learning.
The Lipids: Triglycerides, Phospholipids, and Sterols
Chapter 5 The Lipids: Fats, Oils, Phospholipids, and Sterols
Triglycerides, Phospholipids, and Sterols
Lipids Composed of C, H and few O Basic unit is fatty acid (glyceride) Triglyceride is the major form of lipid = 3 fatty acids Fats and oils Monounsaturated.
Dietary Fats Jennifer Hillan, MSH, RD, LD/N Family, Youth, and Community Sciences University of Florida/IFAS.
FAT SUBSTITUTIONS IN FOODS ADRIENNE ORTEGA  APRIL 21, 2015.
Omega 3 Fatty Acids in Parenteral Nutrition Erin Buehler Lauryn Whitfield.
FATS.  Fats: an essential component of the diet needed for: energy vitamin absorption hormone production protection of vital organs  Each gram of fat.
Fatty Acids. Long-chain carboxylic acids that have an even number (usually 12-18) of carbon atoms. Long-chain carboxylic acids that have an even number.
1.Mouth – lingual lipase (enzyme) in the saliva digests some triglycerides Triglycerides Glyerol and fatty acids 2. Stomach – food is churned and the.
Midterm is 7 November in class Lectures 1-6 inclusive-50 multiple choice-50 points One short answer question-10 points Lecture October 2013 Most.
Lipids Triglycerides Fats and oils Phospholipids Sterols Lecithin
Diet & Cardiovascular System. Objectives Importance of fats Fats and CHD Different types of dietary Fats Mediterranean Diet Dietary factors affecting.
LIPIDS I.
The Macronutrients - Lipids Chapter 1. Lipids  Lipid is a general term for a heterogeneous group of compounds. Oils, fats, waxes, and related compounds.
FATS Chapter 6 Sports Nutrition FATS The Concentrated Energy Source.
LIPIDS. Objectives 2. Investigate the properties of carbohydrates, lipids, and proteins 2.3 Describe the relationship between fatty acids and fats by.
Nutritional Requirements: Types and Sources of Nutrients
The Lipids Triglycerides Phospholipids Sterols Copyright 2005 Wadsworth Group, a division of Thomson Learning.
CHEM 1152 Dr. Sheppard Spring 2015
Lipids Triglycerides –Fats and oils Phospholipids –Lecithin Sterols –Cholesterol.
The Lipids: Triglycerides, Phospholipids, and Sterols Unit #5.
Lipids B.4 3 Main Types of Lipids (B.4.1…) ‘lipid’ comes from lipos, the Greek word for fat all are hydrophobic (water-fearing/insoluble in water) greasy,
Diet &Cardiovascular System
Lipids Essential nutrients Provide energy Help transport fat- soluble nutrients Contribute to flavor and texture of food Photo © PhotoDisc.
Lipids Fats, Oils, and Waxes. Types of Lipids 1. Triglycerides 95% of all eaten/stored 2. Phospholipids Soluble in oil and water 3. Sterols 4 fused ring.
Mosby items and derived items © 2006 by Mosby, Inc. Slide 1 Chapter 3 Fats.
LIPIDS. Objectives 2. Investigate the properties of carbohydrates, lipids, and proteins 2.3 Describe the relationship between fatty acids and fats by.
Lipids.
The Lipids: Triglycerides, Phospholipids, and Sterols Chapter 5.
Agenda Function of Lipids Types of Lipids Structures of fatty acids
Agenda Function of Lipids Types of Lipids Structures of fatty acids
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Lipids.
Lipids Triglycerides Phospholipids Sterols Lipids Lipids are a class of nutrients that includes: –Triglycerides (fats and oils) –Phospholipids –Sterols.
LIPIDS AKA: FATS. LIPIDS- large nonpolar organic molecules 18%-25% of body weight fewer covalent bonds fat-marbled meats, egg yolks, milk, oils, waxes.
LIPIDS II. CLASSIFICATION OF FATTY ACIDS PRESENT AS GLYCERIDES IN FOOD FATS I. Saturated Fatty Acids Butyric ButanoicCH 3 (CH 2 ) 2 COOHbutterfat CaproicHexanoic.
© 2006 Thomson-Wadsworth The Lipids Triglycerides Phospholipids Sterols.
Lipids (fats) Concentrated energy molecules. I. LIPIDS: §Foods: butter, oil, Crisco, lard Commonly called fats & oils Contain more C-H bonds and less.
Lipids: What do you need to know? o Classification of major lipid groups o Structure of fatty acids o Physical properties of fatty acids o Structure &
Chp 5 -Nutrition: Concepts & Controversies, 12e Sizer/Whitney
CH 8: Lipids.
Mosby items and derived items © 2006 by Mosby, Inc. Slide 1 Chapter 3 Fats.
Lipids and Parenteral Nutrition. Disclosures Patent application submitted for Omegaven ® use.
Unit III: Biochemistry A. Biological Macromolecules B. Metabolism.
Summary  Diet is the collection of food consumed by an individual within a 24 hour period  Food nourishes the body, it contains nutrients that can be.
Lipids. Lipids Do not readily dissolve in water Do not readily dissolve in water Types of lipids: Types of lipids: –Triglycerides –Phospholipids –Sterols.
The Lipids: Triglycerides, Phospholipids and Sterols.
Lipids/Fats By Jennifer Turley and Joan Thompson © 2013 Cengage.
Nutrition for nursing Dr. Fahad Aldhafiri. lipids.
NOMENCLATURE OF FATTY ACIDS AND THEIR CLASSIFICATION.
Fats. What Are Fats/Lipids? Organic substances that are relatively insoluble in water and soluble in organic solvents.
Lipids.
Unit III: Biochemistry A. Biological Macromolecules B. Metabolism
The Lipids: Triglycerides, Phospholipids, and Sterols
LIPIDS Guiding Questions:
Chapter 5 Lipids: Triglycerides, Phospholipids, and Cholesterol
Fatty Acids: The Basics
Lipids A reserved fuel source that can be quickly stored and used depending on demand, 1gm of Fat is 9 KCALS Carbon, oxygen, hydrogen form a fatty acid.
Midterm -as per course syllabus
Lipids A reserved fuel source that can be quickly stored and used depending on demand, 1gm of Fat is 9 KCALS Carbon, oxygen, hydrogen form a fatty acid.
Lipids Part 4 Deng Zeyuan.
Bioorganic Lipids 12/5/2019 Dr Seemal Jelani Chem-160.
Presentation transcript:

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

Disclosures 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.

Objectives Briefly describe current intravenous lipid emulsion (IVLE) formulations available in the United States. Describe availability and the current state of literature regarding IVLEs, including potential benefits or drawbacks of non-standard formulations. 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?

Fatty Acid = Most Basic Form 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 Fatty Acid = Most Basic Form Hydrocarbon ‘tail’ (hydrophobic) Carboxyl ‘head’ (hydrophilic)

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

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

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

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 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.

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

Biochemical Pathways Lipids

Why is Lipid Origin Important? Fatty acid composition of cell membranes determines structural properties, regulatory and immune functions Incorporated into cell membranes – impacting: Membrane fluidity Production of bioactive mediators Regulation of gene expression Cell signaling *Slide adapted from Todd Canada, Mandy Corrigan . 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.

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

Fatty Acids, Inflammation, Immunoregulation Impact of Pro-Inflammatory Eicosanoids Release of lysosomal enzymes Release of chemotactic agents Vascular permeability Vasodilation IL-6 production Fever Pain 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.

Intravenous Lipid Emulsions (IVLEs)

Provide energy (2 kcal/mL) 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 α-linolenic acid 1 Mirtallo J et al. JPEN 2004;28:S39-S70.

Essential Fatty Acid Deficiency (EFAD) Symptoms1 Scaly skin, impaired wound healing and immune function, death1 Triene-to-tetraene ratio >0.22 Prevention3 2-4% energy from linoleic acid 0.25-0.5% energy from α-linolenic acid 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.

Fatty acids in form of triglycerides 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

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

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

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

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

History of IVLEs 1944 1961 1984 1996 2000 2005 Pharmaceutical-grade SO-based IVLE introduced2 OO-based IVLE introduced2 FO-based IVFE introduced2 MCT/LCT coconut/soy IVLE introduced2 Structured lipids introduced (MCT/LCT)3 First use of ILVE (olive oil +lecithin) in a child1 *Slide adapted from Todd Canada, Mandy Corrigan . 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.

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

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

Characteristics of SO-based IVLE High omega 6 to omega 3 ratio1 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 EFAD2 2-4% energy from linoleic acid 0.25-0.5% energy from α-linolenic acid 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 function1,2 Inflammation2,3 Oxidative stress4 Cholestasis5,6 Until recently, only SO-based IVLEs have been available in the United States 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-α, IL-6, neutrophils1 Transient worsening of pulmonary function in ALI/ARDS patients2-6 Increased pulmonary shunt Increased MPAP Increased A-a oxygen gradient Decreased PaO2/FiO2 ratio IVLE doses >0.13 g/kg/hr = impaired RES function Phytosterol and high omega-6 fatty acid content associated with PNALD7-8 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 phytosterols1-3 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 IVLEs3-6 Lower phytosterol content 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 patients1 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 patients2 No differences in mortality or ICU LOS Significant reduction in duration of mechanical ventilation compared to SO-IVLE (P=0.01) Prospective, multicenter ICU study3 Shorter ICU LOS (P<0.001), termination of mechanical ventilation while alive (P=0.02) among those receiving OO-IVLE compared to SO-IVLE Lower concentrates of phytosterols, omega-6 fatty acids  Less risk for PNALD4-5 1 Umpierrez GE et al. Crit Care Med. 2012;40:1792-1798. 2 Manzanares W et al. Intesive Care Med. 2013;39:1683-1694. 3 Edmunds CE et al. Crit Care Med. 2014;42:1168-1172. 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.

Fish Oil (FO)-Based IVLE Healthy volunteers, received FO-IVLE or placebo 24 and 48 hrs before injection of an endotoxin1 Decreased inflammatory response 2 hours after endotoxin injection Lower temperature, TNF-α, ACTH, cortisol, norepinephrine Minimal research available in the critically ill population Absence of phytosterols and potential anti-inflammatory omega-3 fatty acids associated with reversal of PNALD2-3 1 Pluess TT et al. Intensive Care Med. 2007;33:789-797. 2 El Kasmi KC et al. Sci Transl Medi 2013;5:1-10. 3 Vanek VW et al. Nutr Clin Pract. 2012;27:150-192.

Practice Guidelines SCCM/A.S.P.E.N.1,2 ESPEN3 Withhold SO-based IVLE during first 7 days in ICU Alternative IVLEs are safe and may be beneficial ESPEN3 IVLEs are safe and should be provided to the critically ill Alternative emulsions (OO and FO) may be beneficial Canadian Critical Care Nutrition4 When IVLEs are indicated, choose those that reduce n-6 load Insufficient data to provide recommendations on IVLE to replace n-6 rich emulsions 1 McClave SA et al. JPEN. 2009;33:277-316. 2 Vanek VW et al. Nutr Clin Pract. 2012;27:150-192. 3 Singer P et al. Clin Nutr. 2009;28:387-400. 4 Dhaliwal R et al. Nutr Clin Pract. 2014;29:29-43.

Soybean Oil-Sparing Strategies1-4 Withhold SO-based IVLE for first 7 days in critically ill patients Reduce dose of SO-based IVLE for those requiring short-term PN (<10 days) <1 g IVLE/kg/day <0.11 g/kg/hr (24 hour infusion), 0.15 g/kg/hr (cycled) Consider use of alternative IVLE among those with PNALD or requiring long-term PN Olive-oil based Fish-oil based (requiring FDA and IRB approval) 1 McClave SA et al. JPEN. 2009;33:277-316. 2 Hise M et al. The A.S.P.E.N. Adult Nutrition Support Cre Curriculum. 2nd ed. Silver Spring, MD: The American Society for Parenteral and Enteral Nutrition; 2012:63-82. 3 Manzanares W et al. JPEN 2014;38:653-654. Xu Z et al. Nutrients. 2012;4:904-921.

IVLE – Conclusion Infusion of IVLEs with high concentrations of omega- 6 fatty acids may result in a pro-inflammatory immunosuppressive state Plant-based IVLEs contain phytosterols, which may contributed to development of PNALD SO-based IVLEs contain the highest phytosterol concentrations Practice guidelines recommend to limit administration of omega-6 fatty acids by practicing ‘soybean oil sparing strategies’

Discussion