Intravenous Lipid Emulsions

  • Maximal daily provision = 2-2.5 g/kg/day
    • CAUTION: If providing >2 gram/kg/day (Weight risks/benefits with attending physician and family) 
  • Maximal infusion rate of 0.15-0.17 mg/kg/hour
  • Maximal lipid-to-energy ratio of 25%.
  • Types of intravenous lipid emulsions ilipids available in the US:
    • Intralipid (source of calories and essential fatty acids in patients who are parenteral nutrition dependent)
    • SMOFlipid (source of calories and essential fatty acids in adults who cannot receive them via oral or enteral route in July 2016)
    • Omegaven (Approved for children with PNALD in July 2018)

3-in-1 Fat Calculator

 
Goulet O, Lambe C. Intravenous lipid emulsions in pediatric patients with intestinal failure. Curr Opin Organ Transplant. 2017 Apr;22(2):142-148. doi: 10.1097/MOT.0000000000000396. Review. PubMed PMID: 28267037.
 
Nandivada P, Fell GL, Gura KM, Puder M. Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children. Am J Clin Nutr. 2016 Feb;103(2):629S-34S. doi: 10.3945/ajcn.114.103986. Epub 2016 Jan 20. Review. PubMed PMID: 26791189; PubMed Central PMCID: PMC4733251
 
Raman M, Almutairdi A, Mulesa L, Alberda C, Beattie C, Gramlich L. Parenteral Nutrition and Lipids. Nutrients. 2017 Apr 14;9(4). pii: E388. doi: 10.3390/nu9040388. Review. PubMed PMID: 28420095; PubMed Central PMCID: PMC5409727.
 

Intravenous lipid emulsion test dose intructions:

  • Infuse at 0.1 mL/minute for the first 10-15 minutes (i.e., 1.5ml dose over 15 minutes …..which would run at a rate of 6 ml/hr).  
  • If no reaction, then increase to the anticipated hourly rate of intravenous lipid emulsion. 
  • Observe patient receiving intravenous lipid emusion for 1 hour.
 
General intravenous lipid emulsion monitoring:
  • Check CBC with platelets every 1-3 months
  • Check triglycerides with lipid panel every 1-3 months
  • Check CRP every 1-3 months
  • Check liver tests with GGT every 1-3 months
  • Check PT/INR every 6 months.
  • Check essential fatty acid profile every 2-3 months in children
  • Check fibroscan yearly.
  • Check abdominal ultrasound with doppler yearly.
 
Intralipids (Soybean-based IV lipid emulsion)
Image result for intravenous lipids

https://www.fresenius-kabi.com/in/products/intralipid

Package insert

If using Intralipid in patients with long-term PN dependence, consider IV lipid minimization for reduced exposure to phytosterols: Average dose 1 gram/kg/day over 1 week for prevention of PN associated liver disease.

If cholestasis occurs on IV lipid minimization with soybean-based IV lipid emulsion, short-term lipid cessation may result in improvement in hyperbilirubinemia but can lead to complications like essential fatty acid deficiency and poor growth.

  • With short-term intravenous lipid emulsion cessation, consider checking fatty acid profile monthly and encourage enteral essential fat intake.
  • If patient is stable for 2-3 months, may space out lab monitoring. 

Typical dosing, soybean IV lipid dosing:

  • If 2-in-1, maximum daily 1 gram/kg/day
  • If 3-in-1, maximum daily 2 gram/kg/day
Image result for 1.2 micron in-line filter
Administration
  • Use 1.2 micron in-line filter.
  • Concentration: 0.2 grams/mL (2kcal/mL)
  • Dosage forms: 100 ml, 250 ml and 500 ml

Colomb V, Jobert-Giraud A, Lacaille F, Goulet O, Fournet JC, Ricour C. Role of lipid emulsions in cholestasis associated with long-term parenteral nutrition in children. JPEN J Parenter Enteral Nutr. 2000 Nov-Dec;24(6):345-50. PubMed PMID: 11071594.

Lam G, Strogach IG, Baron N, Thompson JF. Normal Growth and Essential Fatty Acid Status in Children With Intestinal Failure on Lipid Limitation. J Pediatr Gastroenterol Nutr. 2016 Feb;62(2):335-40. doi: 10.1097/MPG.0000000000000948. PubMed PMID: 26301616.

Rollins MD, Ward RM, Jackson WD, Mulroy CW, Spencer CP, Ying J, Greene T, Book LS. Effect of decreased parenteral soybean lipid emulsion on hepatic function in infants at risk for parenteral nutrition-associated liver disease: a pilot study. J Pediatr Surg. 2013 Jun;48(6):1348-56. doi: 10.1016/j.jpedsurg.2013.03.040. PubMed PMID: 23845629.

 
SMOFlipid
Image result for SMOFlipid
 
 
 
FDA approved in July 2016: Indicated in adults as a source of calories and essential fatty acids for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated
 
Image result for SMOFlipid
Administration
  • Use 1.2 micron in-line filter.
  • Concentration: 0.2 grams/mL (2kcal/mL)
  • Dosage forms: 100 ml, 250 ml and 500 ml

 

Goulet O, Antébi H, Wolf C, Talbotec C, Alcindor LG, Corriol O, Lamor M, Colomb-Jung V. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr. 2010 Sep-Oct;34(5):485-95. doi: 10.1177/0148607110363614. PubMed PMID: 20852176.
 
Klek S, Chambrier C, Singer P, Rubin M, Bowling T, Staun M, Joly F, Rasmussen H, Strauss BJ, Wanten G, Smith R, Abraham A, Szczepanek K, Shaffer J. Four-week parenteral nutrition using a third generation lipid emulsion (SMOFlipid)--a double-blind, randomised, multicentre study in adults. Clin Nutr. 2013 Apr;32(2):224-31. doi: 10.1016/j.clnu.2012.06.011. Epub 2012 Jul 12. PubMed PMID: 22796064.
Lam CKL, Church PC, Haliburton B, Chambers K, Martincevic I, Vresk L, Courtney-Martin G, Bandsma R, Avitzur Y, Wales PC, Mouzaki M. Long-term Exposure  of Children to a Mixed Lipid Emulsion Is Less Hepatotoxic Than Soybean-based Lipid Emulsion. J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):501-504. doi: 10.1097/MPG.0000000000001799. PubMed PMID: 29470321.

Omegaven (Intravenous Fish Oil Lipid Emulsion) 

FDA approved on June 27, 2018: Indicated as a source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis (PNAC)

No automatic alt text available.

https://www.fresenius-kabi.com/in/products/omegaven

Package insert

Indication:

  • Cholestasis due to parenteral nutrition (no other causes) with direct or conjugated bilirubin levels persistently ≧2 mg/dL (usually >1 week).
  • There is no evidence to suggest Omegaven prevents PN associated liver injury.  It should not be used prophylactically.  

 

Dosage: 1 gram/kg/day until direct bilirubin is

Monitoring

  • Check labs weekly if direct bilitubin > 2.0
  • Check labs monthly if direct bilirubin
Administration
  • Use 1.2 micron in-line filter.
  • Concentration: 0.1 grams/mL (2kcal/mL)
  • Dosage forms: 100 ml
  • Can be infused along with PN

Drug related concerns:

  • Prolonged bleeding has been reported in some patients taking high doses of enteral fish oil supplements.  
  • Hypertriglyceridemia -- hold lipids if triglycerids >1000
  • Known hypersensitivity to fish or egg -- consider test dose.
Belza C, Thompson R, Somers GR, de Silva N, Fitzgerald K, Steinberg K, Courtney-Martin G, Wales PW, Avitzur Y. Persistence of hepatic fibrosis in pediatric intestinal failure patients treated with intravenous fish oil lipid emulsion. J Pediatr Surg. 2017 May;52(5):795-801. doi: 10.1016/j.jpedsurg.2017.01.048. Epub 2017 Jan 30. PubMed PMID: 28189450.
 
 
 
Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion  in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar;121(3):e678-86. doi: 10.1542/peds.2007-2248. PubMed PMID: 18310188.
 
 
Nandivada P, Fell GL, Mitchell PD, Potemkin AK, O'Loughlin AA, Gura KM, Puder M. Long-Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure-Associated Liver Disease [Formula: see text]. JPEN J Parenter Enteral Nutr. 2017 Aug;41(6):930-937. doi: 10.1177/0148607116633796. Epub 2016 Mar 9. PubMed PMID: 26962059.

 

ClinoLeic (80% olive oil and 20% soybean oil)

Image result for ClinoLeic

  • Studied in pediatrics and adults.
  • Not FDA approved in US..

 

Goulet O, de Potter S, Antébi H, Driss F, Colomb V, Béréziat G, Alcindor LG, Corriol O, Le Brun A, Dutot G, Forget D, Perennec V, Ricour C. Long-term efficacy and safety of a new olive oil-based intravenous fat emulsion in pediatric patients: a double-blind randomized study. Am J Clin Nutr. 1999 Sep;70(3):338-45. PubMed PMID: 10479195.
 
Reimund JM, Rahmi G, Escalin G, Pinna G, Finck G, Muller CD, Duclos B, Baumann R. Efficacy and safety of an olive oil-based intravenous fat emulsion in adult patients on home parenteral nutrition. Aliment Pharmacol Ther. 2005 Feb 15;21(4):445-54. PubMed PMID: 15709996.

 

Hypertriglyceridemia
  • If triglycerides  > 200mg/dL, then hold lipids for 4 hours, and recheck.
  • If triglycerides remain elevated, consider decreasing intravenous lipid emulsion rate.
  • Neonates and malnourished patients may have difficulty clearing lipids due to decreased hepatic lipoprotein lipase activity
    • Consider supplementation with levocarnititine  8-16mg/kg/day
    • Consider supplementation of heparin to parentral nutrition (1 unit per mL) – induces lipoprotein lipase
 
Polyunsaturated fatty acid biosynthesis
nutrients-09-01165-g001.png
Chilton. Nutrients 2017, 9(11), 1165
 
Omega-3 and Omega-6 long-chain-polyunsaturated fatty acids are synthesized from dietary intake of essential fatty acids,  α-linolenic acid (ALA) and Linoleic acid (LA) through a series of enzamatic processes (elongase and desaturases).  However, it may be possible to shunt backwards and meet fatty acid needs as long as adequate docosahexaenoic acid (DHA) and arachadonic acid (ARA) are provided.
  • The Omega-3 pathway gives rise to eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA).
  • The Omega-6 pathway gives rise to γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), arachidonic acid (ARA), adrenic acid (ADA).  Ultimately, the inflammatory metabolites include: prostaglandin (PG), thromboxane (TX), leukotriene (LT).

 

Le HD, Fallon EM, Kalish BT, de Meijer VE, Meisel JA, Gura KM, Nose V, Pan AH, Bistrian BR, Puder M. The effect of varying ratios of docosahexaenoic acid and
arachidonic acid in the prevention and reversal of biochemical essential fatty acid deficiency in a murine model. Metabolism. 2013 Apr;62(4):499-508. doi:
10.1016/j.metabol.2012.10.003. Epub 2012 Nov 12. PubMed PMID: 23151438; PubMed Central PMCID: PMC3608741.

 

Chilton FH, Dutta R, Reynolds LM, Sergeant S, Mathias RA, Seeds MC. Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized
Supplementation Approaches for the Prevention and Management of Human Diseases. Nutrients. 2017 Oct 25;9(11). pii: E1165. doi: 10.3390/nu9111165. Review. PubMed PMID: 29068398; PubMed Central PMCID: PMC5707637

 

 

 
Essential fatty acid deficiency
 
Symptoms: 
  • Scaly skin
  • Growth failure
  • Alopecia 
Treat with Intralipid 1-1.2 gram/kg/day or Omegaven 1-1.5 gram/kg/day 
- Repeat essential fatty acid profile serum testing in 2-4 weeks to assess Triene/Tetraene ratio & Mead acid
- Reduce IV lipid emulsion dose as able
- Repeat essentialk fatty acid profile with standard monitoring once labs normalized.
 
 
Carey AN, Rudie C, Mitchell PD, Raphael BP, Gura KM, Puder M. Essential Fatty Acid Status in Surgical Infants Receiving Parenteral Nutrition With a Composite Lipid Emulsion: A Case Series. JPEN J Parenter Enteral Nutr. 2018 May 30. doi: 10.1002/jpen.1311. [Epub ahead of print] PubMed PMID: 29846008.
 
de Meijer VE, Le HD, Meisel JA, Gura KM, Puder M. Parenteral fish oil as monotherapy prevents essential fatty acid deficiency in parenteral nutrition-dependent patients. J Pediatr Gastroenterol Nutr. 2010 Feb;50(2):212-8. doi: 10.1097/MPG.0b013e3181bbf51e. PubMed PMID: 20038849; PubMed Central PMCID:PMC3365554.
HOLMAN RT. The ratio of trienoic: tetraenoic acids in tissue lipids as a measure of essential fatty acid requirement. J Nutr. 1960 Mar;70:405-10. PubMed PMID: 14402760.
 
Fat overload syndrome
 
Imbalance of substrate and lipoprotein lipase leading to lipid accumulation in platelets leading to dysfunction, changes in phospholipid composition in RBC membrane and hemolysis.
- Has been reported with Intralipid and SMOFlipid.
 
Acute symptoms of fat overload syndrome:
  • Fever
  • Headache
  • Jaundice
  • Hepatosplenomegaly
  • Respiratory distress w/ hypoxia
  • Spontaneous hemorrhage

 

  •  
  •  
Lab changes:
  • anemia, leukopenia,
  • thrombocytopenia
  • fibrinogen
  • coagulopathy
  • acidosis.

Lab monitoring:

  • Oxygen saturation
  • CBC with platelets
  • Liver panel
  • Chem-10
  • Coagulation profile, fibrinogen
  • Triglycerides
  • Amylase, lipase.
  • If triglycerides are elevated, repeat in 4 hours.
Treatment:
  • Supportive care
  • Withhold lipids
  • Supplemental oxygen
  • FFP
  • Vitamin K
  • Blood transfusions
 

Hojsak I, Kolaček S. Fat overload syndrome after the rapid infusion of SMOFlipid emulsion. JPEN J Parenter Enteral Nutr. 2014 Jan;38(1):119-21. doi: 10.1177/0148607113482001. Epub 2013 Mar 21. PubMed PMID: 23520135.

Gura KM, Puder M. Rapid infusion of fish oil-based emulsion in infants does not appear to be associated with fat overload syndrome. Nutr Clin Pract. 2010 Aug;25(4):399-402. doi: 10.1177/0884533610373770. PubMed PMID: 20702846.

Hayes BD, Gosselin S, Calello DP, Nacca N, Rollins CJ, Abourbih D, Morris M, Nesbitt-Miller A, Morais JA, Lavergne V; Lipid Emulsion Workgroup. Systematic review of clinical adverse events reported after acute intravenous lipid emulsion administration. Clin Toxicol (Phila). 2016 Jun;54(5):365-404. doi:10.3109/15563650.2016.1151528. Epub 2016 Apr 1. Review. PubMed PMID: 27035513.

 

 
 
Comparison and characteristics of 5 parenteral lipid emulsions (10 g fat/100 mL)
 
Product
Intralipid
Liposyn II
ClinOleic
SMOF lipid
Omegaven
Manufacturer
Baxter Healthcare/Fresenius Kabi
Hospira
Baxter Healthcare/Parenteral SA
Fresenius Kabi
Fresenius Kabi
Oil source (g)
 
 
 
 
Soy bean
10
5
2
3
0
Safflower
0
5
0
0
0
MCT
0
0
0
3
0
Olive oil
0
0
8
2.5
0
Fish oil
0
0
0
1.5
10
α -Tocopherol (mg/L)
38
NP
32
200
150-296
Phytosterols (mg/L)
348 ± 33
383
327± 8
47.6
0
Fat composition (g)a
 
 
 
 
Linoleic
5
6.5
0.9
2.9
0.1- 0.7
α-Linolenic
0.9
0.4
0.1
0.3
EPA
0
0
0
0.3
1.28 -2.82
DHA
0
0
0
0.05
1.44-3.09
Oleic
2.6
1.8
0.8
2.8
0.6 - 1.3
Palmitic
1
0.9
0.7
0.9
0.25 -1
Stearic
0.35
0.34
0.2
0.3
0.05-0.2
Arachidonic
0
0
0.03
0.05
0.1-0.4

 

 

Biesboer AN, Stoehr NA. A Product Review of Alternative Oil-Based Intravenous Fat Emulsions. Nutr Clin Pract. 2016 Oct;31(5):610-8. doi:10.1177/0884533616661174. Epub 2016 Aug 15. Review. PubMed PMID: 27528126.

 

ASPEN guidelines for PN associated liver disease