INTRAVENOUS LIPIDS: CLINICAL & PRACTICAL UPDATES - NORA ALBANYAN, R.PH., SSC-PHP, SSCPN, BCNSP - IVPN
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Intravenous Lipids: Clinical & Practical Updates • Nora AlBanyan, R.Ph., SSC-PhP, SSCPN, BCNSP
Disclosure Information • I have no financial relationship to disclose. AND • I will not discuss off label use and/or investigational use in my presentation.
Learning Objectives At the completion of this activity, you will be able to: • Identify the importance of lipids in clinical nutrition • Explain the differences between lipid emulsions • Discuss clinical implication and guidelines
Attention!
IVFE
ILE
Do you think there is any difference between Fat and Lipids? Yes No
Lipids vs Fats
Lipids
Lipids are a broad
group of biomolecules
whereas fats are a
type of lipids
Fats
The History… William Courten 17th century • Intravenous olive oil 1g/kg given to a dog • Fatal outcome • Severe respiratory distress (Pulmonary embolism) Edward Hodder -1873 (Canada) • Milk infusion in 3 patients with cholera • 2/3 survived “effect magical” • Could not be reproduced by others • unmodified fats could not be given IV
The History…
1957 1960 1980 1990 Present
Cotton-seed Soybean Soybean + Olive Oil Fish Oil
oil MCT
Generations
1960 1980 1990 2006
Soybean Soybean + Olive Oil Fish Oil
MCT
1972 2013 2016 2018
FDA
Approval • Intralipid® • Clinolipid® • SMOFlipid® • Omegaven®
What Is Lipid • Source of energy • Provide structural and metabolically functional component of biological membranes • The lipid used in PN contain fatty acids in the form of triglycerides • A triglycerides consists of 3 fatty acid molecules bonded to a glycerol molecule
Lipid Function as…. A. Energy Production and Storage B. Essential Fatty Acids C. Cell Wall Structure D. Digestion and Absorption E. Inflammation Promotion (eicosanoids) and Resolution F. Hormone Production G. Antidote
Why Use Parenteral Lipids • Meet high caloric intake • Reduce risks from hyperglycemia • Reduce the osmolarity of the formulas • Enhances the bioavailability of fat soluble vitamins • Provide essential fatty acids Other Uses • Local anesthetic toxicity and drug overdoses • Treatment for recurrent miscarriage (off label indication)
Learning Objectives At the completion of this activity, you will be able to: • Identify the importance of lipids in clinical nutrition • Explain the differences between lipid emulsions • Discuss clinical implication and guidelines
Similar, but Different
What’s Common to ALL ILE Products
1 2 3 4
Water for 1.2% egg 2.25%-2.5% Sodium
injection yolk glycerin hydroxide
phospholipi
dsWhat’s Common to ALL ILE Products
1 2 3 4
Black Box
1.2% egg
Warning
Water for 2.25%-2.5% Sodium
Death in premature neonates
injection yolk
phospholipi
glycerin hydroxide
dsContraindications for ILE • Hypersensitivity to Lipid ingredients or excipients • Severe hyperlipidemia • Severe blood coagulation disorder • Acute shock and unstable conditions • Severe liver or renal insufficiency in patients with no access to hemofiltration or dialysis
What’s Different
1 2 3
Phytosterol Vitamin E Inflammator
content content y
characterist
ics
Typically not noted on the product label!Phytosterols • Plant sterols • Typically only small amounts absorbed by GI tract • Undergo hepatic metabolism • IV phytosterols reduce bile acid flow
Comparison of Lipid Emulsions
OIL Intralipid Lipofundin Omegaven Clinoleic SMOF lipid Lipidem/Lipo
plus
Soybean % 100 50 - 20 30 40
MCT % - 50 - - 20 50
Olive % - - - 80 25 -
Fish % - - 100 - 15 10
Glycerol g/100 mL 2.25 2.5 2.5 2.25 2.5 2.5
Egg Phospholipid 1.2 1.2 1.2 1.2 1.2 1.2
g/100ml
Phytosterols 439±5.7 278.1 ±5.1 3.66 274 ±2.6 207 NA
(mg/L)
Vitamin E mg/100 3.8 4 15-30 3.2 16 -23 24
mLVitamin E (alpha –tocopherol)
• Anti-oxidant
• Prevents hepatic injury (animal models)
• Prolonged use of soybean oil ILE may reduce α-tocopherol
concentrations in plasma lipoproteins
• Soybean oil contains γ-tocopherol
• Less bioactive than α-tocopherolComparison of Lipid Emulsions
OIL Intralipid Lipofundin Omegaven Clinoleic SMOF lipid Lipidem/Lipo
plus
Soybean % 100 50 - 20 30 40
MCT % - 50 - 20 50
Olive % - - - 80 25 -
Fish % - - 100 15 10
Glycerol g/100 mL 2.25 2.5 2.5 2.25 2.5 2.5
Egg Phospholipid 1.2 1.2 1.2 1.2 1.2 1.2
g/100ml
Phytosterols (mg/L) 439±5.7 278.1 ±5.1 3.66 274 ±2.6 207 NA
Vitamin E 3.8 4 15-30 3.2 16 -23 24
mg/100 mLInflammatory Profile & Immune Promotion Immune and Inflammatory Response Kelley DS. Nutrition. 2001;17(7-8):669-673. WolowczukI, et al. ClinDevImmunol. 2008;2008:639803. BattistellaFD, et al. J Trauma. 1997;43(1):52-58. Calder PC, et al. ClinNutr. 1994;13(2):69-74.
Optimal Outcome
RCT?
Evidence Statistical significance?
Clinical outcomes?
Guidelines? Biochemical
Clinical scenario? individuality &
Clinical
Availability?
Practice Patient monitoring response
Cost? and evolution
Physician or NST
expertise?IVLE Practical Aspects
EFA deficiency Premixed VS Compounded PN
Inflammatory profile + immune Central VS Peripheral PN
promotion
Comorbidities
Long term PN (home care)
Cost of lipid emulsion
Liver impact and cholestasis
Availability
Blood coagulation and platelet
aggregationIVLE
Soybeans Medium Chain Olive Oil Fish Oil
Triglycerides (MCT)
1st 2nd 3rd 4th
HIGH phytosterol LOW phytosterol LOWER phytosterol Trace phytosterol
content content content content
LOW α-tocopherol LOW α-tocopherol HIGH α-tocopherol Abundant α-tocopherol
content content content content
Inflammatory potential Immune “Neutral” Immune “Neutral” LESS pro-inflammatory
Easy Improved glucose
Metabolized tolerance
CONTAIN NO
ESSENTIAL FATTY
ACIDSLearning Objectives At the completion of this activity, you will be able to: • Identify the importance of lipids in clinical nutrition • Explain the differences between lipid emulsions • Discuss clinical implication and guidelines
Practical Considerations Adult
• Avoid EFA deficiency (3-4 % kcal from soy)
• Avoid IVLE instability
• Limit heparin quantity
• Respect calcium and phosphorus limits
• Caloric calculation
• 20 % IVLE = 10 kcal / gram
Individualize dose 0.5 –1.5 g/kg and choose wiselyPractical Considerations Pediatric • Presence of Phytosterols (plant sterols) • Lack of α-tocopherol (Vitamin E) • Fat overload syndrome • Parenteral nutrition associated liver disease (PNALD) Individualize dose 0.5 –3.5 g/kg and choose wisely
The Evidence Treatment of Intestinal failure-associated liver disease • Fish oil • SMOF lipid • 50/50 blend FO + SO • Reduced dose SO
Fish Oil: Hong Kong RCT
Fish Oil
D
billi D
Reversal billi
&
ALT IFALD at 4 &
Fish Oil 1.5 g/kg/day months SO 1.5 g/kg/day ALT
Rates of increase of D bili & ALT in SO group > FO group
13.5 vs.0.6 μmol/l/wk and 9.1 vs. 1.1 IU/l/wk (p = 0.03)
SO: Soybeans
Neonatology 2014;105:290-296SMOF Lipid • Birmingham Children’s • Case series infants/ children with PNALD while on SO & switched to SMOF lipid (n=8) • 1 patient died, 1 listed for transplant • Remaining 6: “sudden, often dramatic and sustained fall in bilirubin 1-3 months after switching to SMOF lipid”
50/50 FO + SO
Canada
• Retrospective cohort
• 12 patients with PNALD
1 g/kg/d SO + 1 g/kg/d FO
Complete resolution of PNALD occurred in 9 patients (75%)
J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):209-15Soy Lipid Restriction • Prospective • Control: 3 g/kg/d, • Intervention: 1 g/kg twice weekly, n = 31 each group Results: • 42% resolution (fat reduction) • 10% resolution control group J Pediatr. 2012 Mar;160(3):421-7.
Guidelines for Use • American Society for Parenteral and Enteral Nutrition • Canadian Critical Care Nutrition Guideline • European Society for Parenteral and Enteral Nutrition
Guidelines for Use
Which IVLE Is Optimum for My Patient?
100% LCT 50 % LCT 50 % 80 % Olive 20 % 30 % Soy, 30 %
MCT Soy MCT, 25 % Olive,
15 % Fish
Short term PN +++ +++ +++ +
Long term PN - + ++ +++
Peripheral PN +++ + +++ +
Surgical patient + + +++ +++
Critical patient - - ++ +++
Hyper - - + +++
inflammatory
Acidosis state - - ++ ++Conclusion • To select the best ILE take into account each patient characteristics and the specific clinical scenario • Same patient can use different ILE during their treatment or hospital stay • There is no good and bad ILE, better or worst, it depends on how and when you use it and alternative lipid emulsions are an excellent choice for many patients
Additional Literature/References • Waitzberg DL,Torrinhas RS. The complexity of prescribing intravenous lipid emulsions. World Rev Nutr Diet.2015;112:150-62 • Waitzberg DL, et al. New Parenteral Lipid Emulsions for Clinical Use. JPEN J Parenter Enteral Nutr. 2006;30(4):351-367. • Wanten GJA, Calder PC. Immune modulation by parenteral lipid emulsions. Am J ClinNutr. 2007;85(5):1171-1184. • Vanek VW,SeidnerDL,Allen P, et al. A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions. NutrClinPract.2012Apr;27(2):150-92 • PironiL, Guidett iM, Verrastro O, et al. Functional lipidomicsin patients on home parenteral nutrition: Effect of lipid emulsions. World J Gastroenterol.2017 Jul 7;23(25):4604-4614 • Abbasoglu O, Hardy G, Manzanares W, Pontes-ArrudaA. Fish Oil-Containing Lipid Emulsions in Adult Parenteral Nutrition: A Review of the Evidence. JPEN J Parenter Enteral Nutr. 2017 Aug 1:148607117721907 • Raman M, Almutairdi A, MulesaL, et al. Parenteral Nutrition and Lipids. Nutrients. 2017 Apr 14;9(4) • Mateude Antonio J, Florit-Sureda M. Effects unrelated to anti-inflammation of lipid emulsions containing fish oil in parenteral nutrition for adult patients. NutrHosp. 2017 Feb 1;34(1):193-203
Thank you
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