Lipid Injectable Emulsions: Critical Care Recommendations and New Evidence
— By Meredith Hart, MBA, MS, RD, CNSC 
Medical Science Liaison, Fresenius Kabi USA
Meredith.Hart@fresenius-kabi.com 

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Lipid injectable emulsions (ILEs) are an important component of parenteral nutrition (PN) prescriptions, providing a source of fat to PN-dependent patients. Fat is a dense source of energy, though lipids can contribute additional functions beyond the provision of kcals. They provide essential fatty acids (α-linolenic acid [ALA] and linoleic acid [LA]), carry lipid-soluble vitamins (vitamins A, D, E, and K), protect organs, and provide structure to cell membranes. Furthermore, certain conditionally-essential fatty acids, namely arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), actively contribute to the production of inflammatory mediators (i.e. prostaglandins, leukotrienes, thromboxanes), specialized pro-resolving mediators (i.e. resolvins, maresins, lipoxins), gene regulators, hormones, and enzymes.1 
 

Because lipids contribute to a broad range of important structural, metabolic, and immunologic functions, daily provision is recommended. For the critically ill patient requiring PN, 2016 Nutrition Support Guidelines jointly published by ASPEN and the Society for Critical Care Medicine (SCCM) recommend providing <1 gram/kg/day of ILE.2 These guidelines further suggest withholding soybean oil (SO)-based ILEs for the first week following PN initiation unless there is concern for essential fatty acid deficiency, in which case a maximum of 100 grams/week (divided into two doses) can be provided. The quality of evidence for this recommendation is designated as “very low,” and it is the only recommendation in the guidelines to receive <70% consensus from the authors.2 The recommendation is based on two small clinical trials (<60 patients in each study) evaluating hypocaloric, lipid-free PN versus PN with SO ILE. While the 2000 McCowen et al. study did not find differences in infection rate between groups, the 1997 Battistella et al. study found decreased days of mechanical ventilation and ICU and hospital length of stay (LOS), and a lower number of infections, in the hypocaloric, lipid-free PN group.3,4 

The 2016 ASPEN/SCCM Guidelines go on to address alternative lipid emulsions, which are ILEs containing less than 100% SO plus one or more of the following oils: medium-chain triglycerides (MCT), olive oil (OO), and fish oil (FO). The ASPEN/SCCM recommendation for alternative ILEs states that, based on expert opinion and once available, alternative ILEs be considered for use in the critically ill patient who is an appropriate candidate for PN.2 Since 2016, the European Society for Parenteral and Enteral Nutrition (ESPEN) has published Expert Recommendations for Lipids in the ICU, Guidelines on Clinical Nutrition in the Intensive Care Unit, and Guidelines for Clinical Nutrition in Surgery.5-7 Collectively, these recommendations state that ILEs enriched with EPA and DHA (FO dose of 0.1-0.2 gram/kg/day) can be provided to patients requiring PN.7 Furthermore, FO-containing ILEs may provide clinical benefits to non-surgical ICU patients compared to SO or SO/MCT ILEs, and that MCT- or OO-containing ILEs can be used post-operatively in surgical ICU patients, though PN for these patients should probably include supplemental omega-3 fatty acids found in FO. FO-containing ILEs, also known as 4th generation ILEs, are recommended for patients with surgical complications.5,6 

Since the first commercially-available and Food and Drug Administration-approved alternative ILE was released in the U.S. in 2016, ASPEN has not provided additional guidance on their use in critical care populations.8 However, new data on their use continue to emerge in the published literature. The newest meta-analysis assessing alternative ILEs in critical care was e-published ahead of print in the Journal of Parenteral and Enteral Nutrition last month.9 Pradelli et al. evaluated omega-3 enriched PN in hospitalized (ICU and surgical) patients through analysis of 49 randomized controlled trials, including a total of 3641 patients. Results of this meta-analysis found FO-containing ILEs, compared to standard ILEs, significantly reduced infection rate by 40%, risk of sepsis by 56%, length of ICU stay by 1.95 days, and length of hospital stay by 2.14 days. Significant outcomes pertaining to non-clinical laboratory markers were also reported.9

With the release of new ILE-focused evidence, it is important to continuously re-evaluate approaches to PN management in critical care, including type, dose, initiation, and duration of ILE provision. ILEs provide energy, yet their contributions to functional, metabolic, and immunologic processes are worthy of consideration for the critically ill patient.