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662996

research-article2016
NCPXXX10.1177/0884533616662996Nutrition in Clinical PracticeAnez-Bustillos et al

Invited Review
Nutrition in Clinical Practice
Volume 31 Number 5
Intravenous Fat Emulsion Formulations for the Adult and October 2016 596­–609
© 2016 American Society
Pediatric Patient: Understanding the Differences for Parenteral and Enteral Nutrition
DOI: 10.1177/0884533616662996
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Lorenzo Anez-Bustillos, MD1; Duy T. Dao, MD1; Meredith A. Baker, MD1;
Gillian L. Fell, MD, PhD1; Mark Puder, MD, PhD1; and
Kathleen M. Gura, PharmD2

Abstract
Intravenous fat emulsions (IVFEs) provide essential fatty acids (EFAs) and are a dense source of energy in parenteral nutrition (PN).
Parenterally administered lipid was introduced in the 17th century but plagued with side effects. The formulation of IVFEs later on made
it a relatively safe component for administration to patients. Many ingredients are common to all IVFEs, yet the oil source(s) and its (their)
percentage(s) makes them different from each other. The oil used dictates how IVFEs are metabolized and cleared from the body. The
fatty acids (FAs) present in each type of oil provide unique beneficial and detrimental properties. This review provides an overview of
IVFEs and discusses factors that would help clinicians choose the optimal product for their patients. (Nutr Clin Pract. 2016;31:596-609)

Keywords
lipids; intravenous fat emulsions; parenteral nutrition; fatty acids

Elucidating the characteristics of each oil source over time has investigators attempted to compound such an emulsion by
resulted in an evolution of the different formulations currently using castor oil as the main ingredient. Numerous attempts
available. Emulsions have gone from being solely made with were made between 1920 and 1960 to create a safe emulsion
soybean oil (SO) to being combined with medium-chain tri- using a variety of oils and surfactants. A cottonseed oil–based
glycerides (MCT; ie, coconut oil), olive oil (OO), and, more emulsion (ie, Lipomul; 15% cottonseed oil, 4% soy phospho-
recently, fish oil (FO). Unfortunately, the lipid, among other lipids, 0.3% poloxamer 188) became the first IVFE approved
constituents in parenteral nutrition (PN) formulations, has been in the United States in 1957.2 This was later withdrawn from
associated with the development of liver disease. Lipid-sparing the market due to severe adverse reactions, including fat over-
or lipid reduction strategies have therefore been proposed to load syndrome.2–4 A soybean oil–based fat emulsion (SOFE)
avoid these complications. has been the predominant IVLE available to American practi-
The ideal intravenous fat emulsion (IVFE) would reverse or tioners since its introduction in Europe in 1961 and its
prevent essential fatty acid deficiency (EFAD) without leading subsequent approval in the United States in 1972. Other oil
to complications, while simultaneously providing energy to sources have been used outside the United States to create
facilitate normal growth and development. Modifications in
their ingredients, formulation, and dosing have made IVFEs a From the 1Vascular Biology Program and the Department of Surgery. Boston
relatively safe component alone or when added to PN formula- Children’s Hospital, Boston, Massachusetts, USA; and the 2Department of
tions. The ideal emulsion, however, has yet to be developed. Pharmacy, Boston Children’s Hospital, Boston, Massachusetts, USA.
Financial disclosure: Research funding is provided by the Boston
Children’s Hospital Surgical Foundation, Boston Children’s Hospital, the
Overview of Fat Emulsions Corkin and Maher Family Fund, National Institutes of Health (NIH) grant
5T32HL007734-22 (MAB), and NIH grant 1F32DK104525-01 (GLF).
IVFEs are a source of essential fatty acids (EFAs) and serve as
Conflicts of interest: A license agreement for the use of Omegaven has
a complement to carbohydrates by providing a dense source of been signed by Boston Children’s Hospital and Fresenius Kabi, and a
nonprotein energy in PN. Fatty acids (FAs) are important patent has been submitted by Boston Children’s Hospital on behalf of Mark
sources of energy and structural components of cell mem- Puder and Kathleen M. Gura, who also serve on the Scientific Advisory
branes. They are also precursors to key modulators involved in Boards for Pronova-BASF and Sancilio and Company. Kathleen M. Gura
also serves on the Pharmaceutical Advisory Board for B. Braun USA.
cellular pathways of the immune response.1 Parenterally
administered fat was first attempted in the 17th century when This article originally appeared online on August 16, 2016.
the English naturalist William Courten tried to infuse OO intra-
Corresponding Author:
venously in dogs, which resulted in pulmonary emboli.2 Over Kathleen M. Gura, PharmD, Department of Pharmacy, Boston Children’s
time, it was recognized that fat could be given intravenously Hospital, 300 Longwood Avenue, Boston, MA 02115 USA.
only in the form of an emulsion. In the 1920s, Japanese Email: Kathleen.Gura@childrens.harvard.edu

Downloaded from ncp.sagepub.com at American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) on October 31, 2016

plasma clearance. although the egg leci- DHA: docosahexaenoic acid thin currently used to manufacture IVFEs is highly purified EFA: essential fatty acid and unlikely to contain allergens thought to trigger hypersensi- EFAD: essential fatty acid deficiency tivity reactions.7. Examples include the very long- of approximately 200–500 nm in diameter that the human body chain FAs docosahexaenoic and eicosapentaenoic acids (DHA uses to transport hydrophobic fat in hydrophilic blood without and EPA. or polyunsatu- an overview of lipid emulsions and discuss factors that clini. The United States Pharmacopeia (USP) chapter <729> has LPL: lipoprotein lipase established value standards for globule size limits.07 mEq/g. Arvid Wretlind from the diet. causing embolic phenomena. IVFEs are suspensions of (PUFAs) are liquid at room temperature and include α-linolenic oil in an aqueous medium manufactured to possess properties acid (ALA) and linoleic acid (LA). One of the original indications for the use of IVFEs in patients ing agent to disperse the oil phase into the aqueous phase.10 In contrast.S. which makes the emulsion isotonic and HDL: high-density lipoprotein adds additional calories. highly unsaturated similar to natural chylomicrons.E. monounsaturated (1 double bond).Anez-Bustillos et al 597 developed the first safe IVFE for clinical use by using egg yolk Common abbreviations (in alphabetical order) phospholipid as an emulsifying agent. sodium hydroxide to maintain a pH range between 6 FOFE: fish oil–based fat emulsion and 9. Individuals with an egg ARA: arachidonic acid allergy may be unable to receive them. 2016 .7. O9FA: ω-9 fatty acid OO: olive oil PN: parenteral nutrition FAs: An Overview PUFA: polyunsaturated fatty acid RES: reticuloendothelial system IVFEs provide FAs. SOFE: soybean oil–based fat emulsion and muscle. and glycerol. They can be short (2–4 VLDL: very low-density lipoprotein carbons). IFALD: intestinal failure–associated liver disease Manufacturing IVFEs is difficult and requires very specific IVFE: intravenous fat emulsion pH and temperatures under a nitrogen rich-environment. Numerous agents had been tried not be synthesized in the body but rather need to be obtained to serve as emulsifiers without success.N. FAs from the ω-5.) on October 31. ω-7. and as triglycerides in adipose tissue.com at American Society for Parenteral and Enteral Nutrition (A. they can also be classified as saturated (no dou- IVFEs and may soon be available. long (14–21 carbons).P.5 Emulsions are unstable systems and undergo physical changes over time (eg. respectively). rated (>1 double bond). and ω-9 Downloaded from ncp. as phospholipids in cell SO: soybean oil membranes. Depending on the number of double bonds.2 All currently available ALA: α-linolenic acid IVFEs contain this emulsifying agent. These are FAs that can- resulting in a stable product. liver. blood. LA: linoleic acid Pharmacopeial specifications of IVFEs help determine embolic LCT: long-chain triglyceride risks. A classic example of this type of FA is butyric acid.05% MUFA: monounsaturated fatty acid (PFAT5).9.sagepub. O6FA: ω-6 fatty acid all commercially available IVFEs meet the USP standards. which are normally present as cholesterol SFA: saturated fatty acid esters in circulating lipoproteins. creaming. or very long (≥22 carbons) chains. bon chain. Polyunsaturated FAs All IVFEs share many components. Manufacturing an emulsion requires an emulsify. including a MA: Mead acid mean droplet diameter below 500 nm and a large globule con- MCT: medium-chain triglyceride tent (percentage of fat globules >5 µm) no greater than 0. Last. Monounsaturated FAs (MUFAs) are often liquid at room tem- perature and solid when cool. this potential risk EPA: eicosapentaenoic acid should be taken into consideration when prescribing IVFEs to FA: fatty acid patients with egg allergy.8 Currently. Given that such reactions have been described EN: enteral nutrition in the literature and noted in the package. and increased EFAs droplet size). FAs are the monomers of lipids and consist of TNA: total nutrient admixture hydrocarbon chains that vary in length. and beyond-use dating of the formula- LDL: low-density lipoprotein tion. Palmitoleic and oleic acids are What Is Common to All IVFEs? examples of MUFAs abundant in OO. This review aims to provide ble bonds). These are the spherical forms FAs have >3 double bonds. requiring PN was the provision of EFAs.6 IVFEs also contain sterile water for FO: fish oil injection. medium (6–12 carbons).8 Other specifications include a pH between 6 and 9 O3FA: ω-3 fatty acid and a free FA content no greater than 0. Saturated fatty acids (SFAs) are often cians should consider when choosing the optimal product for solid at room temperature and structurally have a straight car- their patients. aggregation.

E. They both compete for may influence immune functions. which is Downloaded from ncp. % 80 25   Fish oil.5 DHA. α-linolenic acid. sitosterol. eicosapentaenoic acid. or fish.7 3. and may even confer different pharmaceutical and therapeu.sagepub. ALA and LA have been considered the main mem.P.6 083 ALA. The ω-3 FAs (O3FAs) and ω-6 mal.15 Higher postoperative concentrations of interleukin-6 the third carbon in O3FAs and at the sixth carbon in O6FAs. olive.12–14 One study evaluated the effect of lipid active downstream products. FO-based fat emulsions (FOFEs) contain very little phytoster- tic benefits.16 Phytosterols. and clinical studies suggests that the type of IVFE used FAs (O6FAs) are the 2 families of EFAs. This difference may partially explain the potential benefit of FOFEs as a lipid source in PN-dependent patients with IFALD. immune function of patients subjected to gastric or colorectal nal methyl group is located. 2016 . families are nonessential.N. where they inhibit the enzyme 7α-hydroxylase.66 274 ± 2. 25% of the FAs in surprising given the short duration of the study. Typically. Provision free PN. has high levels of γ-tocopherol but low amounts of α-tocopherol vide structural support to cell membranes. safflower.16. FAs from these families differ struc. % 0 12. pro. Cholestasis did not develop in this group and is not (O3FA) of approximately 7:1. DHA.S.2 1. the intake of 40 kcal/kg/d) compared with those receiving lipid- true essentiality of ALA and LA has been questioned. SO contains high Phytosterol concentrations were higher in infants receiving concentrations of PUFAs with a ratio of LA (O6FA) to ALA 100% SOFE.4 24. docosahexaenoic acid. % 9 1.18.8 2 2. % 100 15 10 Glycerol. SO is naturally rich in phytosterols and antagonizing effect on the farsenoid X nuclear receptor. the nut. % 50 4. % 0 1–4 0 0. respectively. coco.25 2. the oil source(s) amounts in the gastrointestinal (GI) tract. elongases and desaturases) to generate their more pressive effects.10 The phytosterols present in SO are plant sterols thought to contribute to the development of intestinal failure–associated What Is Different Between IVFEs? liver disease (IFALD).25 2. The role of phy- SO come from the nonessential family of ω-9 FAs (O9FAs) in tosterols in hepatocyte damage has been demonstrated by their the form of oleic acid. This is the reason why many centers do not administer of their main downstream products (ie. respectively) is just as effective at preventing the greater detail below.5 EPA. mg/L 439 ± 5. absorption.5 2. IVFEs are manu.  Attributes of Widely Available Intravenous Fat Emulsions. phytosterols accumulate in the liver when given intra- factured with 1 of 5 types of oil: soybean.) on October 31. DHA and arachidonic 100% SOFE to critically ill patients. including campesterol.11 In addition.17 These plant sterols used and its (their) percentage(s) dictate the key differences decrease blood cholesterol levels by interfering with their GI between IVFEs. not available. ARA.2 Phytosterols.1 0 2 2.20. NA.2 0 3 3. emulsions with space within the cell membrane and are processed by the same a high content of O6FAs have been linked with immunosup- enzymes (ie. EPA.5 2.22 SOFEs have been widely used for decades.5 ALA. intake on the postoperative stress response and cell-mediated turally depending on where the first double bond from the termi. % 100 20 30 40 Medium-chain triglycerides. For instance.4 18. are typically absorbed only in small Despite sharing several common properties. g/100 mL 1. However. (20% of the energy intake in extremely high nonprotein calorie bers of the O3FA and O6FA families. linoleic acid.com at American Society for Parenteral and Enteral Nutrition (A. EFAs serve as an energy source. Each has unique inflammatory properties rate-limiting enzyme in bile acid synthesis.2 1.2 1.2 1. Component Intralipid Omegaven ClinoLipid/ClinOleic SMOFlipid Lipidem/Lipoplus Soybean oil. % 0 19.598 Nutrition in Clinical Practice 31(5) Table 1. mg/100 mL 3. % 30 50 Olive oil.15–0.5 ARA. g/100 mL 2.21 Unlike SOFEs.5 Egg phospholipid. development of biochemical EFAD. and are precursors to (bioactive form of vitamin E). Levels of plasma phytosterols were measured in preterm infants Soybean Oil receiving different IVFEs in a randomized controlled trial.11 Evidence from ex vivo. venously.8 15–30 3. which is discussed in acid [ARA].19 for prolonged periods (Table 1).6 207 NA125 Vitamin E. ols. Recently. LA. and stigmasterol. ani- important cellular metabolites. This makes them beneficial agents when taken orally tional benefits or detrimental effects. especially when used in patients with hypercholesterolemia and atherosclerosis. and C-reactive protein were seen in patients receiving a SOFE Historically.2 LA.5 21. arachidonic acid. These differences account for their addi.5 3. The first double bond thus occurs at surgery.2 16–23 24.

which is added to prevent the oxidation Healthcare Corporation. Clinolipid.com at American Society for Parenteral and Enteral Nutrition (A.26 In comparison to SOFEs. MCTs do not accumulate in the liver and conse.31 This product provides 30% of the PUFA branes accelerates the breakdown of these cells and increases content of standard SOFEs. B4. with none showing any significant difference in oxida- it was later reformulated as a 50/50 blend with SO.28 OO-containing IVFEs have been demonstrated to tolerate They are easily metabolized and lack proinflammatory proper.S. OO is considered immune neutral.E.38 The resistant to peroxidation and have protein-sparing effects not high content of O6FAs in SOFEs serves as a precursor to cyto- inferior to the ones seen with long-chain triglycerides (LCTs).11 These emulsions erance. risk of fat overload syndrome.28. Similar results were reported in several other ran- flower oil predisposed patients to develop O3FA deficiency domized controlled trials involving neonates receiving OO/SO when used as a sole source of fat in IVFEs. 2016 .23 In (range. when compounding admix- tures containing IVFE. DEHP exposure could allows the lipid phase to remain miscible with the aqueous potentially increase the risk of developing IFALD. PVC. tion of neutrophils as shown in animal models.21. In comparison to SO. The mean concentration of LA is 35.7 mg/mL (range. an OO-containing IVFE (4:1 OO/SO) was compared with Safflower Oil SOFE in preterm infants younger than 28 weeks’ gestational Safflower oil had been used in IVFEs alone or in combination age.0–8. OO has a lower content of phytosterols and abun. extraction compared with other IVFEs of the plasticizer di(2- dance of LCTs.27 For this reason. Baxter oxidant α-tocopherol.36 Another potential sion was introduced in Europe that contained a 50/50 mixture benefit of using OO-containing IVFE is improved glucose tol- of SO and MCTs derived from coconut oil.34. kines and proinflammatory prostaglandin E2 and leukotriene In addition.35 In another oil–based emulsions are not currently available due to raw investigation. Fish Oil OO-based emulsions were introduced in Europe in the 1990s. respectively) concen- trations and liver function tests were similar between the 2 groups. IL) is composed of 4 parts of its FAs.38 The eicosanoids produced from O3FAs explains why this oil source requires blending with an oil con.30 reasons. IVFE. Moreover. One OO-based IVFE (eg. FO-containing IVFEs are less proinflammatory than The relatively small amount of LA (approximately 5%) conventional SOFEs. Infants receiving 6–12 carbons long and include caprylic and capric acids. despite the significantly lower amount of PUFAs in the OO/SO safflower-based IVFE had higher concentrations of LA (77% IVFE. and high-density and material issues. Safflower tive stress in comparison to SOFE monotherapy. 1.38 A study comparing the inflammatory effects between quently do not impair hepatic function. both characteristics unique to this fat source. In comparison. low-density lipoprotein (HDL and LDL. It was developed as erated. MCTs are Unlike SO and FO. parison to those receiving the OO blend.sagepub. Very low-density lipoprotein (VLDL) concentrations Coconut Oil (MCTs) were statistically lower in neonates receiving SOFE in com- After the introduction of SOFEs.37 ties. MCTs are SFAs that are glycogenolysis and gluconeogenesis. a type of MUFA that is not considered essential.P.Anez-Bustillos et al 599 critical in regulating the level of intrahepatic bile acids. higher carbohydrate intake without developing hyperglycemia. α-Tocopherol is the form of vitamin E that is prefer- OO/1 part SO. FO is rich in the anti- dant α-tocopherol.29 However. and ALA is 4.0 mg/mL). observed.25 This type of mixed oil emulsion has replaced SOFE as the stan- dard IVFE in many countries. no difference in lipid peroxidation was vs 54%). regardless of oil source. Long-chain PUFA concentrations were similar in an alternative to SO and was hypothesized to decrease the infants receiving OO IVFE in comparison to the SOFE group. as it is not a precursor of eicosanoids. The use of saf. 27. more resistant to oxidative stress injuries from free radicals.40 For these phase of the emulsions for longer periods of time. Like OO.) on October 31. They may have a unique pharmaceutical benefit in that cantly higher in those receiving SOFE. The shorter chain length (6–12 carbons vs 18 ethylhexyl)phthalate (DEHP) if it is infused using a polyvinyl- carbons in SO) exerts less stress on the emulsifying agent and chloride (PVC) administration set. Deerfield.32 In 1 randomized controlled trial. Downloaded from ncp. MCT oils SOFE and OO-rich IVFE in preterm neonates demonstrated are devoid of EFAs and thus cannot be used as a sole source of that proinflammatory cytokine concentrations were signifi- fat. Olive Oil OO is rich in O9FAs (ie.24.39 One potential down- MCTs added to certain total nutrient admixtures (TNAs) results side for the use of an OO-containing IVFE is the greater risk of in a more stable lipid emulsion than those containing an abun.33 OO-containing IVFE was found to be safe and well tol- with SO in the United States since 1980. originating from O6FAs contained in SO. the incorporation of phytosterols in erythrocyte mem.5% vs 8%).N. oleic acid). cholesterol.or DEHP-coated containers should not be used.21 Phytosterols can also increase MUFAs that possess less proinflammatory properties and are the risk of sepsis by altering the migratory and phagocytic func. in FO are generally less inflammatory in comparison to those taining EFA. SO appears to enhance glucose production by means of reduce the O6FA content by 50%.6–44. a second-generation emul. triglyceride. although less ALA (0.8 mg/mL entially absorbed and accumulated in humans. addition.4 mg/mL). OO is rich in the bilirubin load to the liver.

respec- decrease the degradation of anti-inflammatory molecules.) on October 31. SO is rich in γ-tocopherol. 10% and 20%). 100% FOFE has been shown to from being solely made with SO in the 1960s to being com- effectively reverse preexisting EFAD and to prevent its devel. molecules with anti-inflammatory ance pathways of IVFEs. which end up using the released FAs. ARA.com at American Society for Parenteral and Enteral Nutrition (A. the fat source in IVFEs and their result- EPA. Depending epoxygenation pathways by decreasing the hepatic levels of on their concentration (ie.54. and.49 Thus.44–47 the circulation. O3FAs their phospholipid/triglyceride ratio (0. O3FAs also affect eicosanoid metabolism and the also seems to have an effect on clearance of IVFEs. bined with MCTs in the 1980s. (LPL).41. ARA and DHA.42 Subsequent work in ani. IVLEs differ in the enzyme-soluble epoxide hydrolase. respectively) and no Oil Sources: Impact on Clearance other EFA was shown to prevent EFAD and hepatic steatosis Triglycerides in IVFEs are hydrolyzed by lipoprotein lipase without negatively affecting growth or fertility. and bones. However. the hepatic lipase activity was more important in the elimina- Inflammatory Characteristics of IVFEs? tion of OO.E.53 G-protein-coupled receptor (GPR) family. FOFE has little LA by serving as the precursor to lipoxins and prostaglandin-medi- and ALA but contains their downstream metabolites.12 and 0.55 The oil source in some of the therapeutic benefits of O3FAs in tissues such as IVFEs strongly determines how the body clears them from the liver. The have been mentioned. which must be methylated to the 2-prostanoids and series 4-leukotrienes. different formulations over time. A study comparing the effects on plasma lipids and addition. molecules known to preferred bioactive α-tocopherol.  Evolution of fat sources in intravenous fat emulsions and their corresponding changes in the inflammatory profile. ARA present in SO leads to the formation of series trations of plasma triglycerides. the provision of only the downstream metabo- lites of LA and ALA (ie. medium-chain triglyceride. Recent evidence The remaining lipid particles are either hydrolyzed by hepatic demonstrates that the interaction with these receptors mediates lipases or cleared intact by other tissues. recently.11 Unlike SOFE. 2016 . more opment when dosed at 1 g/kg/d. In studies involving a murine model.48 By doing this. brain.N. MCT.sagepub. and DHA. Brouwer et al56 compared the elimination of intravenous (IV) OO and SO fat emulsions.50 ARA has also been developed to supplement conventional SOFE and not intended shown to have anti-inflammatory and pro-resolving properties for use as monotherapy. in humans. OO in the 1990s. In tively). ated lipoxins.600 Nutrition in Clinical Practice 31(5) Figure 1. accumulation of cholesterol Downloaded from ncp. O3FAs serve as precursors to pro-resolving mole.52. lipoproteins in 10% and 20% SOFE in low-birth-weight neo- cules that aid in the resolution of the inflammatory response.P. Emulsions have evolved therapy.06.S.48. The reticuloendothelial system (RES) EPA present in FO is a precursor to the series 5-leukotrienes and other tissues also play a role in the metabolism and clear- and series 3-prostanoids. FOFEs were originally be generally more proinflammatory. mal models has confirmed this concept. with FO51 (Figure 1). Although SOFE Do Oil Sources Determine the had a higher rate of elimination than OO-containing IVFE. The phospholipid concentration properties.11 The paucity of O6FAs has raised concerns ing inflammatory profile has dictated the evolution of the about the development of EFAD when FOFE is used as mono.49 nates demonstrated that 10% emulsions led to higher concen- In contrast.43 O3FAs pres. These findings suggested the presence of addi- Each emulsion has its own inflammatory characteristics based tional clearance pathways beyond the enzymatic ones that on the different oil source(s) and their predominant FA. This enzyme is located on the endothelial surface of ent in FO are also natural ligands to some receptors of the extrahepatic tissues.

and changes in stereotyped behavior. able to tolerate or adequately absorb nutrients administered tion of LCT emulsions. Several properties in can affect the stability of the admixture. postmarketing studies have described clinical low-birth-weight infants. IVFEs serve as a dense oxidation. phospholipids.81 O3FA defi- take advantage of the beneficial properties of each of the avail. and a reduced life span of IV catheters used for infusion. The use of these admixtures is controversial. including Prevention of EFAD the RES. mended to be used in neonates and children.82 Similarly. tioned dermatologic and hair changes in addition to dry eyes. the content of non- In vivo animal studies by Qi et al54 demonstrated that FOFEs essential FAs (ie. a nutrition indication). lower plasma levels of triglycerides. and alopecia. however. The isolated defi- ides and VLDL. release of LPL and hepatic lipases into the circulation. TNAs are not recom- the metabolism and clearance of MCTs make them poten. reason.66. It comprises the triene (ie. little as 7–10 days following EFA restriction. with much lower lipolytic when there is insufficient O6FAs and O3FAs. ARA. In vitro from oleic acid) increases.58 For this reason. MCT oils bind poorly to serum albumin and are Due to their high requirements for calcium and phosphorus that cleared more rapidly from the plasma.sagepub. and their entry into the mitochondria is mediated source of nonprotein energy and.78–80 Heparin stimulates intravascular lipolysis by promoting the Some of these findings have also been shown in humans. occlu- group also showed an increase in levels of lipoprotein X–like sion.70 are seen especially when O3FAs are not adequately supplied in The combination of oil sources in the newer IVFEs aims to critical periods of brain and retinal development. to be mediated by their tissue uptake rather than by the activity Values >0.2 are indicative of EFAD. ARA) ratio and can be easily calculated. First. microbial growth. occurs when less than 1%–2% of the total energy consumed the blood-brain barrier is permeable to highly soluble MCTs.N.60. EFAD is rare in the general This makes MCTs potentially toxic to the central nervous population and more commonly develops in patients with mal- system when present in high concentrations. The study comparing different concentrations of SOFE in criti. yet more vari- Addition of heparin is helpful when clearance of IVFEs is able results in those at term. a trienoic acid synthesized undergo faster clearance from the blood than SOFEs. MCT oils cannot be used as a sole Clinically. decreases in tissues. For example. addition of IVFEs to TNAs is also a common practice in certain cally ill adults. Bypassing oxidative pathways allows O3FAs to exert their dysrhythmias. these changes affect the hepatic ability to provide energy and EFAs (ie.77 MA is produced in states of EFAD studies have shown that ω-3 triglycerides are relatively resistant and is created from the elongation and desaturation of oleic acid to the hepatic and lipoprotein lipases. Downloaded from ncp. Animals fed actions but rather by clearance enhancement. The 10% ibility of medications with the IVFEs.81 Clinical manifestations in humans compromised.73 particles. The Holman activities than those seen with O6FA-rich emulsions. impaired growth. 2016 .9 Table 2 summarizes the beneficial effects on different targets.Anez-Bustillos et al 601 and phospholipids in LDL.71 differences between O3FA and O6FA deficiencies.P.69. ciency also leads to similar skin changes seen in patients with able fat options. These effects are not mediated by enzymatic ciency of O3FAs and/or O6FAs is even more rare. such as in premature neonates. Similar differences were seen in a differences in the various commercially available IVFEs.) on October 31. EFAD usually precede those seen clinically and appear in as ide clearance and inhibit the synthesis of endogenous triglycer. provide by a carnitine-independent FA transport (although carnitine the EFAs that avoid the development of EFAD. the combination of MCTs with EFAD.S. Mead acid [MA]. and depressive FO allows for MCTs to release their readily oxidizable FAs symptoms.57. plus hair loss.E. potentials. The main beneficiaries of IVFEs are those patients who are not tion in both human and animal models following administra. they undergo rapid through the oral and/or enteral route. Accumulation of lipids in macrophages from the RES has proven to negatively affect their immunologic func.59 Patients who received a 30% emulsion had settings. This condition may still be required for their oxidation). O6FA deficiency leads to the aforemen- while preventing O3FAs from entering oxidative pathways. FOFEs also accelerate triglycer.77 The biochemical signs of of the aforementioned lipases.28.54. comes from the EFAs ALA and LA. as absorption syndromes and in those who are PN dependent. polydipsia. incompat- cholesterol than those who received the 10% SOFE. a tetraenoic acid.63 Unfortunately.74 previously discussed. and the appearance of lipoprotein Clinical Considerations X–like particles. clearance of LDL and chylomicron remnants and delay the Studies used to support the approval process were statistically hydrolysis of circulating triglycerides.65 For this Index is used to diagnose EFAD. and free given concern for the potentially unstable emulsions. source of fat in IVFEs as they are devoid of EFAs. EFAD most typically leads to growth retardation. Altogether.74–76 As the content of be administered in combination with an LCT. underpowered to show meaningful differences in clinical out- 20% SOFE is preferred over 10% SOFE as an IVFE source in comes.com at American Society for Parenteral and Enteral Nutrition (A. they must eczematous dermatitis. and impaired growth.64 Moreover.72.68 including visual impairment in preterm infants.73 tially a more beneficial source of fat in septic or critically ill patients.61 Second. they do not accumulate in tissues.57 These particles decrease the rate of hydro- lysis by competing for LPL with other lipoproteins rich in Fat emulsions were initially brought to the market based on their triglycerides.62. the faster clearance of FOFEs relative to SOFEs seems MA) to tetraene (ie.67 O3FA-deficient diets showed impaired vision and visual evoked The presence of heparin affects the clearance of IVFEs. when dosed properly. As a result.

or days to regain birth hypocaloric nutrition and EFAD) if the patient is tolerating weight. The Cana. reached statistically significant differences. alternatives to SOFE alone being associated with important tion. duration of ventilation. and vomiting.”88 Although current Canadian guidelines Neither EFA status nor neurodevelopmental outcomes were recommend the use of SO-sparing strategies when the addition considered. sepsis.86 Similarly.91 summarized the findings from different In critically ill adults. and/or intestinal atresia. although SOFE-sparing alternatives are recommended. Manzanares et al90.) on October 31. trials in a recent systematic review and meta-analysis that com- viduals with prolonged suppression of GI activity following pared different alternatives to SOFE monotherapy in this set- severe trauma or surgery and in conditions associated with ting (Table 3). In children and preterm infants.85 In this population. A meta-analysis of 2 randomized studies evalu. In summary. mortality.602 Nutrition in Clinical Practice 31(5) Table 2. fatty acid provision. periventricular leukomalacia.sagepub. intraventricular hemor- different oils in addition to SOFE may explain why practice rhage [grades III and IV]. The guidelines for the management of pediatric of IVFE to PN is indicated. Dermatologic and hair changes Impaired growth.com at American Society for Parenteral and Enteral Nutrition (A. (<10 days). growth rate. option for its replacement. where such products patent ductus arteriosus. The availability of alternative IVFEs containing necrotizing enterocolitis [≥ stage 2].89 SOFEs.84 outcomes in 451 critically ill patients. expected. and receiving PN without prior/ critically ill adult should not be undertaken lightly. diarrhea.N. malrotation. Second- some enteral nutrition (EN) and requires a short course of PN ary outcomes (ie. many studies have attempted The use of lipid reduction strategies or finding alternatives to to determine which combination of oil sources translates into SOFEs is also recommended. Downloaded from ncp. duration of mechanical ventilation. pooled in a recent systematic review from the Cochrane Neo- ating the early addition of fat emulsions in PN found no natal Group and included the use of MCT/LCT. also suggesting the limited use of as they are not currently available in the United States. There is a trend toward significance of malabsorption such as prolonged ileus. MCT/FO. ASPEN and SCCM refrain from patients with intestinal failure from ASPEN are similar to the making recommendations about the use of alternatives to SOFE adult recommendations. SOFE mono- nutrients. mechanically Adult considerations.P. evi- mental inflammatory properties of emulsions rich in O6FAs dence is still lacking regarding which optimal blend of oil and in SO being an important component in most commercially sources is the most suitable in critically ill patients. individuals who FO-containing IVFEs were extubated and discharged sooner are able to tolerate (at least partially) enterally administered from the ICU alive than those receiving SOFE. mary outcomes. IFALD. hyperglycemia. Those who received either OO-containing or patients who are otherwise not malnourished. and hypertriglyceri- are considered “an integral part of PN for energy and to ensure demia) also failed to show any significant differences.92 None of the measured pri- are minimal concerns regarding withholding fat emulsions (ie.S.85 The basis of this recommendation lies in the detri. reviewed data from a prospective international multicenter tions resulting from major intestinal resections such as necro.83 This is different from circum. depression None described Other Polydipsia Dysrhythmias IVFE as Therapeutic Modalities better outcomes for critically ill. and borage/SO IVFEs (either in PN or complications when SOFE was held. Results from 15 studies were cern for EFAD. Inclusion criteria included adult patients in the ICU for >72 hours. OO/SO. there partial PN) in preterm neonates. gastric outlet obstruc. reductions in mortality. especially in infants at risk of developing IFALD. available IVFEs.  Clinical Differences Most Commonly Seen in ω-3 and ω-6 Fatty Acid Deficiency (Data From Animal and Human Studies). The initiation of IVFE therapy in the ventilated within 48 hours. recent recommendations from the American Society for Parenteral and Enteral Nutrition (ASPEN) and the Society of Critical Care Medicine (SCCM)87 suggest Pediatric considerations. withholding or limiting the use of SOFE during the first week the search for alternatives to SOFE has failed to find an ideal of PN administration to a maximum of 100 g/wk if there is con. MCT/OO/ difference in mortality rates but a large reduction in infectious FO.93 Given these recommendations. or those in whom a short-term course of PN is therapy was associated with a longer ICU stay.87. Patients who did not receive dian Clinical Practice Guidelines recommend withholding the any form of IVFE had the longest duration of mechanical ven- addition of pure SOFE for the first 10 days of PN therapy in tilation. Dermatologic and hair changes Visual symptoms Impaired vision and visual evoked potentials Dry eyes Neurologic symptoms Changes in stereotyped behavior. and stances that lead to PN dependency in premature infants and intensive care unit (ICU) length of stay. 2016 . guidelines are different in other countries. Edmunds et al86 children that include intestinal motility disorders and condi. PN-dependent patients.E. Manifestation ω-3 Fatty Acids ω-6 Fatty Acids Constitutional symptoms Impaired growth. study to determine the effects of different IVFEs on clinical tizing enterocolitis. fat-containing PN may be given to indi. concurrent EN for 5 or more days.

ClinOleic) vs Adverse events. TGs. The rise in RBP and recovery of nitrogen et al128 (2002) balance was greater in those receiving MCT/LCT Grecu et al129 Patients in ICU with abdominal FO (Omegaven. Lipofundin) Changes in IL-6 and HLA-DR expression. and mortality receiving parenteral FO. long-chain triglyceride. or in-hospital Montero least 10 days of PN (n = 72) (50/50. fish oil. cholesterol. and septic (n = 20) (50/50. energy intake/energy No difference in energy expenditure or energy intake/ et al130 (2005) trauma requiring mechanical SA. (1998) least 5 days of ventilator support. Baxter Energy expenditure. C-reactive protein. Fresenius Kabi. FO. Patients in ICU likely to require at LCT (Intralipid) vs LCT/MCT Metabolic and clinical effects No differences in ICU LOS. Changes in IL-10. hospital LOS. Surviving patients had a shorter hospital LOS Braun. LPS. Lipofundin. OO group ventilation (n = 33) MCT (50/50. parenteral nutrition. LFT. IL-6. and LCT/FO (50/40/10. Patients in ICU with severe burns LCT/OO (20/80. Fresenius Kabi. infection rate. Uppsala. lipid/glucose ratio in PN was different in experimental groups: 75/25 in LCT/OO vs 37/63 in LCT/MCT) Iovinelli et al131 Patients in ICU with COPD LCT (Intralipid) vs LCT/MCT Nutrition status. olive oil.S. HLA-DR. IL-10. Patients in LCT/MCT group showed a higher et al132 (2005) number of liver function abnormalities Friesecke Patients in ICU expected to require LCT/MCT (50/50. and need for surgery Barbosa et al135 Patients in medical ICU with SIRS LCT/MCT (50–50. duration of mechanical energy expenditure ratio between groups. Structolipid. and FFAs. ClinOleic) control. Lipofundin) mortality. Braun. duration of mechanical nutrition (n = 166) ventilation. Lipoplus. transferrin. Lipofundin) biochemical parameters groups. glycemic No differences noted in any of the measured outcomes 136 et al (2012) requiring PN for >5 days (n = 100) (20/80. ICU LOS. infection. NuTRIflex Plasma levels of eicosanoids and cytokines The FO group showed a greater decrease in levels of (2010) or sepsis (n = 25) Lipid special. PN. energy expenditure.) on October 31. B. SIRS. inflammatory and oxidative stress between groups markers. 603 interleukin-10. Daily serum lipids. Uppsala. and in LPS-stimulated whole-blood culture IL-6 and a smaller decrease in levels of IL-10. serum albumin. reoperation Decreased reoperation rate. glucose = 30) Kabi. Fresenius Kabi.E.  Summary of Findings From Randomized Trials Evaluating Strategies and Alternatives to Soybean Oil–Based Emulsions in Adult. ICU LOS. Germany) and mortality in the FO group Downloaded from ncp. OO. Trend toward higher total Melsungen. CRP. clinical outcomes. hospital LOS.com at American Society for Parenteral and Enteral Nutrition (A. ICU and hospital LOS. B. and 28-day mortality Wang et al134 Patients in ICU with severe acute LCT (Lipovenos. TG. CRP levels. Germany) bilirubin levels in the LCT group Lindgren Patients in ICU anticipated to LCT (Intralipid) vs LCT/MCT Nitrogen balance. ICU and hospital LOS in those (2003) sepsis (n = 54) Uppsala. metabolic rate. Metabolic and biochemical differences with No differences in energy expenditure. No differences in mortality Huschak Patients in ICU following major LCT/OO (20/80. lipopolysaccharide. length of stay. Secondary outcomes included nosocomial between groups calories provided by enteral Lipofundin) + FO (Omegaven) infections.sagepub. on PN. ClinOleic) vs The main objective of the study was No differences in secondary outcomes between groups et al137 (2012) (n = 406) LCT/MCT (not specified) to compare PN delivery systems (multichamber bag vs compounded) in incidence of BSI. ClinOleic. CD4+/CD8+ The group treated with FO showed a significant increase (2009) pancreatitis (n = 56) Uppsala. Authors (Year) Inclusion Criteria (n) Oil Sources Compared Measured Outcomes Conclusions 126 Nijveldt et al Patients in the surgical ICU with at LCT (Intralipid. ICU mortality. LCT. Lipofundin) ventilatory support and weaning weaning was shorter in those receiving LCT/MCT (n = 24) García-de. and Better 3-day cumulative nitrogen in the LCT/MCT group. time of No difference in duration of mechanical ventilation. Sweden) + LCT vs LCT rate. energy metabolism. Critically Ill Patients (Data From Manzanares et al91). Secondary measures included was no difference in days of ventilation.P. . Lipofundin) ventilation. and ICU LOS showed shorter duration of mechanical ventilation and ICU LOS (of note. LOS. Sweden) vs LCT/MCT special focus on liver enzymes LFTs. human leukocyte antigen–DR. Braun. B. interleukin-6. bloodstream infection. No difference seen in all of the measured outcomes et al133 (2008) PN for at least 6 days. Sweden) or TG levels during infusion Garnacho. No differences seen in CD4+/ (Lipoveno) + FO (Omegaven) CD8+ ratio. ICU LOS. et al127 (2001) require PN for at least 5 days (n (36/64. FFA. MCT. prealbumin. liver function test. Lessines. and granulocyte and monocyte functions Pontes-Arruda Patients in ICU requiring PN LCT/OO (20/80. and No difference in mortality and infection rates between Lorenzo requiring PN for 5–7 days (n = 22) LCT/MCT (50/50. COPD. systemic inflammatory response syndrome. mortality. Table 3. carnitine. ICU LOS. medium-chain triglyceride. chronic obstructive pulmonary disease. Sweden) alone vs LCT ratio. triglyceride. but (2007) requiring mechanical ventilation (50/50. and need for surgery in IL-10 and HLA-DR. Germany) vs MCT/ supernatants. retinol-binding protein. There Melsungen. intensive care unit. with <25% alone vs LCT/MCT (50/50. RBP.N. Melsungen. and 28-day mortality BSI. nitrogen balance. days of ventilation. Fresenius safety No differences in tolerance. Secondary outcomes included development of sepsis/shock. Belgium) vs LCT/ expenditure ratio. 2016 Umpierrez Patients in medical and surgical ICU LCT (Intralipid) vs LCT/OO Clinical outcomes. free fatty acid. ICU. HLA-DR.

103 In a study evaluating a safflower IVFE. and lar have significantly reduced chylomicron triglyceride half- depressed levels of coagulation factor V.94 Worsening of respiratory function may be due FOFE at an infusion rate that exceeded 0. efficiently.96 In 1 report.com at American Society for Parenteral and Enteral Nutrition (A. In 1 case report.99 clearance follows a biphasic pattern. DHA and EPA in particu- leukopenia. but promptly returned to acceptable levels. LPL. hepato. On the basis of these findings. Treatment included discontinuing both the PN and complications perhaps were due to the relatively low FOFE Downloaded from ncp.104 The dose was infused over 4 hours same complications seen with SOFE monotherapy.) on October 31.5 g/kg/d) and fresh-frozen plasma (10 mL/ those small for gestational age (606 mg/dL). LDL receptor.105 Infusion to increased pulmonary vascular constriction.E. Guidelines from one of the most common AEs and can predispose patients to the European Society of Parenteral and Enteral Nutrition elevations in hepatic enzymes.54 In 1 free FAs. those containing MCTs or FO. It is characterized by headaches. In exchange and may be due to diminished bioavailability of endo. The patient had many of the symp. apolipoprotein E. thrombocytopenia. she received extra platelets. and spontaneous hemor. leading to hypertension. IVFE was manifestations of respiratory distress. or hemorrhage. kg). Peak serum triglyceride levels averaged 592 mg/dL for fluid infusion. (ESPEN) recommend that IVFEs can be safely administered at tress. Rapid infusion rates (ie. FOFE appears to be with vasoconstriction. with an initial rapid clear- ance occurring within 10 minutes followed by a slower clear- ance phase of 10–25 minutes. jaundice. these findings suggest that FO does not discontinuing the IVFE. respiratory distress. 6 children received phage system. Most IVFE clearance from the Fat Overload Syndrome blood occurs within the first 2 minutes of an infusion in animal Fat overload syndrome is a well-known complication of IVFE models. These observed. Other potential consequences of prolonged administration a rate of 0. In 1 case report. transfusion of platelets. In contrast. be related to their clearance and also the small number of drome. Hypertriglyceridemia is than what is currently used in clinical practice. fever. In 1 case series. In addition. clearance of emulsion particles.17 g/kg/h child was successfully treated with supportive care combining limit. Interestingly. Oftentimes. and of fat overload syndrome. Unlike SOFE. FOFEs undergo less catabolism than SOFEs.7–1. these patients. FO was shown to accelerate triglyceride clearance by symptoms seen with fat overload syndrome include anemia. and increased the activity of preheparin simply reverse by stopping the IVFE infusion. erythrocyte trans- coagulopathies. and due to elevations in plasma triglyceride levels that occur when lactoferrin-sensitive pathways modulate the removal of chylo- the infusion rate exceeds the rate of hydrolysis.98 The rapid infusion of gested that the reason for the apparent absence of fat overload SOFE may negatively affect pulmonary gas diffusion and alter syndrome in patients receiving rapid infusions of FOFE may hemodynamic stability in adults with respiratory distress syn. The rhage. these will lives and particle sizes.25 g/kg/h).102 Most pub. low fibrinogen levels. jaundice.108 The (0. the authors recommended that The IVFE component in PN can cause several metabolic and IVFE doses should not exceed 4 g/kg/d. clearance of chy- rate of hydrolysis exceeds the rate of uptake and oxidation of lomicron-sized FOFE is independent of these pathways. plasma concentrations of FAs increase. 100 g over 10 hours).107 Taken together. Hyperbilirubinemia. when infused rapidly. This suggests that FOFEs do lished case reports of rapid infusions of IVFEs involve SOFEs not remain in the systemic circulation long enough and may or safflower IVFEs. AEs are are very different. very were given a 1 g/kg/d dose and were evaluated for triglyceride rapid infusion of a SO/MCT/OO/FO IVFE that showed the and free FA clearance. and substitution of appropriate gestational age newborns and slightly higher for serum albumin (0.S.17 g/kg/h. considerably higher physiological adverse effects (AEs).sagepub. facilitating LPL-mediated lipolysis. In one instance. reduce production of triglycerides but rather enhances the apy.5 g/kg over 12–24 hours. the presence of FOFEs dose of 5 g/kg/d for 5 weeks. in combination with SOFEs did not prevent the development toms of fat overload syndrome. and respiratory dis. which exceeded the recommended 0.96 In addition to LPL. plasma exchange was used.106 Lipid observed with slower infusion rates (ie. a 2-year-old girl bruising. 2016 .2–5 g/kg/h) without evidence of fat overload syndrome. IVFEs containing SO tend to clear more slowly than therapy. Whenever the micron-sized O6FA-rich IVFEs. supportive care is the mainstay of ther. and filgrastim due to a very low leukocyte count.95 Changes in the rates as high as 5 g/kg/h were accidentally administered (range. shown to worsen bronchopulmonary dysplasia in premature Transient elevations in serum triglyceride levels were observed infants.101 Other study. and elevations in transaminases were also fusion. 15 neonates developed fat overload syndrome as a result of accidental.604 Nutrition in Clinical Practice 31(5) Complications Associated With IVFEs IVFE for 72 hours and reintroducing the IVFE at a lower dose.88 of IVFEs include hematologic abnormalities with recurrent FOFE does not appear to exhibit similar complications thrombocytopenia and hyperactivation of the monocyte-macro. vital signs remained stable and none showed thelial-derived vascular relaxants. including fever.P.100 It has been described in several case reports in the mechanisms involved in the hydrolysis of FOFEs and SOFEs presence of rapid infusion and/or high doses of IVFE. a 10-month-old infant not predispose patients to the complications associated with developed fat overload syndrome while receiving a SOFE at a rapid infusion of SOFEs. alveolar-arteriolar oxygen gradient can lead to decreased gas 0. while significant vasodilation was cleared more rapidly from the intravascular space.97 The use of IVFE has also been known to cause vaso. The authors sug- constriction.106 Despite being cleared more splenomegaly.N. hemolysis. 100 g over 5 hours) were linked patients in this case series.

112 article. In a prospective study. trol cohort. No differences in the develop- from this study continue to suggest the role of FOFEs as a ment of cholestasis or growth were observed.E. use of FOFE in children with IFALD in the alone for the treatment of IFALD. ciency of amino acids.com at American Society for Parenteral and Enteral Nutrition (A. toward EFAD developed. triglyceride levels role. Nandivada et al116 reported the long- should be monitored for any IVFE being rapidly infused. risk surgical infants and compared them with a historical con- nated prematurely due to enrollment challenges. The use of FOFE to prevent and with a historical control cohort group.117 injury. but the combination of low its SOFE content (30%). Although readily available in Europe and Asia. Sanchez et al120 reported ized controlled trial by Lam et al115 assigned infants with the results of implementing a lipid reduction strategy in high- IFALD to receive either SOFE or FOFE. biochemical markers of liver Hepatic Complications disease returned to normal levels within the first year of FOFE The hepatic abnormalities induced by PN administration mani. children more commonly develop intrahepatic cholesta. In adults.) on October 31. Cober et al118 showed that in the pathogenesis of IFALD has been recognized. and toxicity/defi- infants and prolonged PN administration. torical cohort were almost twice as likely to develop IFALD in nemia and alanine aminotransferase (ALT) in comparison to comparison to those who were lipid restricted. Similarly. Diamond et al122 administered United States may only be done as part of a compassionate use both SOFE and FOFE (1 g/kg/d each) to 12 patients with short protocol.Anez-Bustillos et al 605 content of the SO/MCT/OO/FO IVFE (15%) in comparison to IFALD is yet to be fully elucidated. To date. or devel- opment of EFAD. In addition.110 In con. Regardless of the oil source.109. both of which can lead to potentially irreversible Other etiologic factors in PN that may contribute to the devel- changes such as fibrosis and cirrhosis if prolonged. Rollins et al119 tested the reverse the steatosis developed in a murine model of nonalco. This was associated in a more recent multicenter randomized controlled trial in pre- with a significant clinical improvement. A recent prospective double-blind random. but prelimi. Patients from the his- significantly slower increase in levels of direct hyperbilirubi. this alternative is not fications in the amount and combinations of oil sources have feasible in those patients who are unable to be weaned from PN been proposed for the treatment and prevention of IFALD in and achieve full enteral autonomy. provisions were made to increase SOFE intake if trends treated with SOFE. term effects of FOFE therapy and showed no increases in the risk of mortality.  In addition to FOFE monotherapy. recent findings from a retrospective reversible) transaminitis and hyperbilirubinemia. there have been no published levels of phytosterols. fat accumulation more often leads to the development of hepatic complications in PN-dependent benign. among others. although it may have term neonates.110 The details of how gical procedures. asymptomatic steatosis. Until then. The mechanism of action by which FOFE reverses bowel syndrome who developed IFALD. fest differently depending on whether they occur in adults or Many factors other than IVFE have also been implicated in children. 2016 . FOFE Other approaches. potentially safe and effective alternative for the treatment of IFALD. In this cohort. opment of IFALD include excessive administration of calories tors for the development of IFALD include prematurity in from overfeeding.  Combining other oil sources with FOFE has has yet to be approved by the U. The potential role of IVFEs children. and lack of enteral intake in both children these cause liver disease go beyond the scope of this review and adults.sagepub. Subsequently. aluminum contamination. complete Downloaded from ncp. high levels of α-tocopherol. modi- and/or treated IFALD. Risk fac. Findings showed a slower rate of rise of markers Based on findings from these experiments. For this reducing the dose of SOFE to neonates with IFALD from 3 g/ reason. frequent sur. sis was more common in those receiving higher daily doses of sis with resulting direct hyperbilirubinemia and hepatocellular dextrose after adjusting for daily lipid and protein intake. Close monitoring of EFA status is oped IFALD. Results SOFE at rates of 1 or 3 g/kg/d. SOFE-restricted patients. Food and Drug Administration been shown to be somewhat effective in comparison to SOFE (FDA). need for intestinal transplantation. The incidence of IFALD dropped significantly nary results showed that infants in the FOFE group had a following the adoption of this approach.N. The efficacy of those in the SOFE group. For example. review in preterm infants showed that PN-associated cholesta- trast. infants receiving FOFE lipid reduction strategies in preventing IFALD did not hold true were able to increase their intake of EN.121 Neonates younger than 2 days of life received also served as a confounder contributing to this effect. The study was termi. current strategies focus on changing the fat source and kg/d to 1 g/kg/d led to a decline in bilirubin levels compared reducing the IVFE dose. direct bilirubin and total bile acids) in the reported the reversal of cholestasis in 2 infants who had devel.P.S. the discontinuation of PN therapy and rein- stitution of EN were the only known measures that prevented Restriction of SOFE.112 More recently. sepsis. with mild to moderate (and patients.111. therapy.113 risk neonates. Unfortunately. Gura et al84 proved the safety and encouraged when adopting lipid reduction strategies given the efficacy of FOFE for the treatment of IFALD in a larger cohort marked reduction in FAs being administered. Until recently. Overall. same strategy in preventing the development of IFALD in high- holic fatty liver disease was first described by Alwayn et al. In the Cober of patients compared with a historical cohort that had been study.S. and a rela- reports of fat overload syndrome involving SO/OO or SO/ tive abundance of O3FA to O6FA in FO may play an important MCT IVFEs. Gura et al114 of cholestasis (ie.

The effect of 5 intravenous and K. Mayer K. and agree to be accountable for all aspects of work derived phytosterol. however. 2013. 1988. Atherosclerosis. Franke R. formulations. et al. New parenteral lipid emul- sions for clinical use.240(1-2):1-10. Plant sterols as cholesterol-lowering agents: clinical trials in patients with hypercholester- The ideal emulsion would be one that reversed or prevented olemia and studies of sterol balance.28(3):325-338. Yamazaki K. 1984. M. et al. Taylor OA. 26. physiology and pathology. Waitzberg DL. 10. J Pediatr Surg. Downloaded from ncp. All enteral nutrition: a randomized clinical trial.62(3):301-306. lipid emulsions on plasma phytosterols in preterm infants receiving par- and L.124 1998. comparing SMOFlipid with SOFE in preterm infants with 16. 2006. British Association of Paediatric Surgeons. 2013. Int J Pharm. Interestingly. 2006. 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G. of direct bilirubin levels. Lunn M. Holman RT. 7. Nutrition. 2006. Effect of total par- enteral nutrition with different lipid emulsions of human monocyte and died. 13. Katz DP. Zanatta L.11(12): 1. Parenteral use of medium- Nutrition. Br J Nutr.23(5):955-962. Seeger W. World J Surg. Driscoll DF. 1 listed for transplant). Jacintho TM. Muhammed et al123 reported results from a case series 11. 28. lymphocyte functions. Fatty acids and with those who remained on SOFE. BAPS prize lecture: new insight into mechanisms of parenteral nutrition–associated cholestasis: role of plant IFALD. 2016 . et al. trophils. Pastores SM. 2009. 25th Arvid Wretlind’s Lecture—silver cium uptake mediates anti-inflammatory effect in murine activated neu- anniversary. and sterols. After 6 months of treat. 4. Intralipid or Liposyn—comparable products? J Pediatr 3.62(1):1-10. Nutrition. Torrinhas RS. Gura KM. JPEN J Parenter Enteral Nutr. 1960. 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