Intravenous lipid emulsions (IVLE) provide essential fatty acids (FA) 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 lipid emulsions later on made it a relatively safe component for administration to patients. Many ingredients are common to all IVLE, yet the oil source(s) and its (their) percentage(s) makes them different from each other. The oil used dictates how IVLE are metabolized and cleared from the body. The FA present in each type of oil provide unique beneficial and detrimental properties. This review provides an overview of IVLE and discuss factors that would help clinicians choose the optimal product for their patients. Elucidating the characteristics of each oil source over time has resulted in an evolution of the different formulations currently available. Emulsions have gone from being solely made with soybean oil, to being combined with medium-chain triglycerides (i.e., coconut oil), olive oil, and more recently, fish oil. Unfortunately, the lipid, among other constituents in PN formulations, has been associated with the development of liver disease. Lipid-sparing or lipid-reduction strategies have therefore been proposed to avoid these complications. The ideal IVLE would reverse or prevent essential FA deficiency without leading to complications, while simultaneously providing energy to facilitate normal growth and development. Modifications in their ingredients, formulation, and dosing have made IVLE a relatively safe component alone or when added to PN formulations. The ideal emulsion, however, has yet to be developed.

Micronutrients refer to a group of organic vitamins and inorganic trace elements that serve many functions in metabolism. Assessment of micronutrient status in critically ill children is challenging due to many complicating factors, such as evolving metabolic demands, immature organ function, and varying methods of feeding that affect nutritional dietary intake. Determination of micronutrient status, especially in children, usually relies on a combination of biomarkers, with only a few having been established as a gold standard. Almost all micronutrients display a decrease in their serum levels in critically ill children, resulting in an increased risk of deficiency in this setting. While vitamin D deficiency is a well-known phenomenon in critical illness and can predict a higher need for intensive care, serum concentrations of many trace elements such as iron, zinc, and selenium decrease as a result of tissue redistribution in response to systemic inflammation. Despite a decrease in their levels, supplementation of micronutrients during times of severe illness has not demonstrated clear benefits in either survival advantage or reduction of adverse outcomes. For many micronutrients, the lack of large and randomized studies remains a major hindrance to critically evaluating their status and clinical significance.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family. It contains an EGF-like domain as well as a heparin-binding domain that allows for interactions with heparin and cell-surface heparan sulfate. Soluble mature HB-EGF, a ligand of human epidermal growth factor receptors 1 and 4, is cleaved from the membrane-associated pro-HB-EGF by matrix metalloproteinase or a disintegrin and metalloproteinase in a process called ectodomain shedding. Signaling through human epidermal growth factor receptors 1 and 4 results in a variety of effects, including cellular proliferation, migration, adhesion, and differentiation. HB-EGF levels increase in response to different forms of injuries as well as stimuli, such as lysophosphatidic acid, retinoic acid, and 17β-estradiol. Because it is widely expressed in many organs, HB-EGF plays a critical role in tissue repair and regeneration throughout the body. It promotes cutaneous wound healing, hepatocyte proliferation after partial hepatectomy, intestinal anastomosis strength, alveolar regeneration after pneumonectomy, neurogenesis after ischemic injury, bladder wall thickening in response to urinary tract obstruction, and protection against ischemia/reperfusion injury to many cell types. Additionally, innovative strategies to deliver HB-EGF to sites of organ injury or to increase the endogenous levels of shed HB-EGF have been attempted with promising results. Harnessing the reparatory properties of HB-EGF in the clinical setting, therefore, may produce therapies that augment the treatment of various organ injuries.

The essentiality of fatty acids was determined by the Burrs in the 1920s. Subsequently, it is commonly accepted that provision of linoleic (LA) and alpha-linolenic acids (ALA) prevents and reverses essential fatty acid deficiency (EFAD). Development of alternative injectable lipid emulsions (ILE) low in LA and ALA has raised concern about their ability to prevent EFAD. This review provides biochemical evidence coupled with observations from animal and human studies that aim to characterize which fatty acids are truly essential to prevent EFAD. Retroconversion pathways and mobilization from body stores suggest that arachidonic and docosahexaenoic acids (ARA and DHA – the main derivatives of LA and ALA, respectively) also prevent EFAD. Our group first proposed the essentiality of ARA and DHA by feeding mice exclusively these fatty acids and proving that they prevent EFAD. Survival for 5 generations on this diet provides additional evidence that growth and reproductive capabilities are maintained. Moreover, the use of fish oil-based ILE, which contain minimal LA and ALA and abundant DHA and ARA, for treatment of intestinal failure-associated liver disease, does not result in EFAD. These findings challenge the essentiality of LA and ALA in the presence of ARA and DHA. Evidence discussed in this review supports the idea that ARA and DHA can independently fulfill dietary essential fatty acid requirements. The imminent introduction of new ILE rich in ARA and DHA in the United States highlights the importance of understanding their essentiality, especially when provision of ALA and LA is below the established daily minimum requirement.