ESPEN Congress Madrid 2018
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1 ESPEN Congress Madrid 2018 Lipid Emulsions In Parenteral Nutrition The Abc Of Parenteral Lipid Emulsions P. Austin (UK)
2 ESPEN Congress, Madrid, September 2018 The ABC of parenteral lipid emulsions Dr Peter Austin, Pharmacist HEE/NIHR Clinical Lecturer Oxford Hospital and University College London, UK No conflict of interest related to this presentation
3 Learning objectives a) Understand the history of lipid emulsions in parenteral nutrition b) Know the biochemical nature and types of lipid emulsions, including phytosterols and peroxides c) Understand the main characteristics (compatibility, stability, clearance, ) and compounding issues
4 History Animals 1678: IV lipid (animals; C. Wren) 1869: SC fat (dogs) 1915: IV fat emulsion into animals Humans 1678: IV injection of lipid into animals 1869: SC fat (adult) 1920: IV fat emulsions (children in US) 1945: Commercial lipid preparations based on cotton seed oils 1961: Intralipid developed by Wretlind in Sweden 1964: FDA banned fat emulsions derived from cotton seed oils 1980-: New types of lipid emulsion
5 Typical lipid emulsion formulation Water for Injection q.s. Glycerol Egg phosphatides Sodium hydroxide q.s. Triglycerides = 20g/100mL in 20% w/v = lipid emulsion
6 Glycerol Triglycerides (TAG) Fatty acid Fatty acid Fatty acid
7 Fatty acids Saturated Unsaturated coconut oil caprylic capric n3 (PUFA) n6 (PUFA) n9 (MUFA) soybean oil fish oil linolenic* EPA DHA Linoleic* soybean oil oleic soybean & olive oils * = essential fatty acid
8 Fatty acid composition (% of total*) Examples of commercial lipid emulsions Fatty acid Soybean oil Intralipid 20% w/v Clinoleic 20% w/v Lipofundin 20% w/v SMOF 20% w/v Omegaven 10% w/v long chain Linolenic Linoleic Oleic medium chain Caprylic Capric very long chain EPA DHA % accounted for * = average (composition is subject to natural variability)
9 % w/w of lipid Phytosterols Natural product (soybean oil) Intralipid 20% w/v Clinoleic 20% w/v Lipofundin 20% w/v SMOF 20% w/v Omegaven 10% w/v Lipid emulsion (UK brand name) References: (1) Zaloga GP. JPEN 2015; 39(1 Suppl):39S-60S and (2) Xu Z, Harvey K, Pavlina T, et al. Nutrients 2012; 4:
10 Peroxidation Peroxidation is a chain reaction of lipid degradation: - affects PUFAs (e.g. from soybean and fish oils) - begins with an interaction between oxygen and hydrogen, and leads to the formation of free radicals - the extent is indicated by measuring lipid peroxides Relevant factors include: - availability of oxygen - presence of antioxidants (e.g. vitamins C and E) - presence of transition elements (e.g. copper or iron)
11 Vitamin K Vitamin K - a natural component of lipid emulsions - could block effect of warfarin or may need to supplement Vitamin K provision from examples of lipid emulsions Clinoleic SMOF Intralipid 500mL lipid emulsion μg Multivitamin* μg Total μg * One vial of Cernevit with Clinoleic, or 10mL Vitlipid N Adult with SMOF and Intralipid
12 General considerations Benefits include: - energy dense and low osmolarity compared to glucose - IV route bypasses the lymphatic system (chyle leak role) - prevents essential fatty acid deficiency Risks to manage include: - potential allergies to lipid emulsions - lipid particle size and filtration - lipid can accumulate inside IV catheter - other medicines e.g. propofol or heparin
13 Controversial considerations Selection of flush - compatibility of flush choice with lipid (and TPN formulation) Ratio of lipid to glucose Risk factor (adult patients) For a 30 to 60 year old male of 70kg Lipid 1g/kg 70g 700kcal Glucose 4g/kg 280g 1050kcal Parenteral energy 80% BEE 1270kcal Reference: (1) Cavicchi M, Beau P, Crenn P, et al. Ann Intern Med 2000; 132(7):
14 Compounding considerations Infection risk - lipid emulsion putatively supports strong microbial growth Formulation - assessment of stability (examples to follow)
15
16 Infection risk: microbial growth Reference: (1) Austin PD, Hand KS, Elia M. J Hosp Infect 2016; 94(4):
17 Stability: lipid emulsion dilution Likely stable Could be unstable If stable 1.5a Water Water 2.2a a b c Water Emulsifier Lipid emulsion Increase volume 1.5b 1.5c Emulsifier Lipid emulsion or Emulsifier Lipid emulsion b c Subject to other components or other differences
18 Stability: cation additions Water Lipid globule Coalescence Free oil Normal emulsion Aggregation Creaming Cracking
19 Recommended reading Stability assessment of lipid in parenteral nutrition Uploads/2017/06/NHS-PQAC-YCD -Std-Protocol-Chemical-Stability -Part-4-Parenteral-Nutrition -1 st -Edn-2016.pdf
20 In summary a) Available lipid emulsions vary in composition, which can result in different characteristics b) Prescription of lipid emulsions should account for each patient and also safety considerations c) Appropriate pharmaceutical assessment and compounding practices are required for lipid emulsions (and all parenteral nutrition)
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