Lipid Use in Hospitalized Adults Requiring Parenteral Nutrition

In hospitalized patients, lipid emulsions are an integral part of balanced parenteral nutrition. Traditionally, a single lipid source, soybean oil, has been given to patients and was usually regarded as just a source of energy and to prevent essential fatty-acid deficiency. However, mixtures of different lipid emulsions have now become widely available, including mixtures of soybean oil, medium-chain triglycerides, olive oil, and fish oil. Fish oil is high in the ω-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). There is a growing body of evidence that these ω-3 fatty acids can exert beneficial immunomodulatory, anti-inflammatory, and inflammation-resolution effects across a wide range of patient groups including surgical, cancer, and critically ill patients. At least in part, these effects are realized via potent specialized pro-resolution mediators (SPMs). Moreover, parenteral nutrition including ω-3 fatty acids can result in additional clinical benefits over the use of standard lipid emulsions, such as reductions in infection rates and length of hospital and intensive care unit stay. Clinical and experimental evidence is reviewed regarding lipid emulsion use in a variety of hospitalized patient groups, including surgical, critically ill, sepsis, trauma, and acute pancreatitis patients. Practical aspects of lipid emulsion use in critically ill patients are also considered, such as how to determine and fulfill energy expenditure, how and when to consider parenteral nutrition, duration of infusion, and safety monitoring.     

Lipids in Parenteral Nutrition: Biological Aspects

Lipid emulsions are an integral part of parenteral nutrition, and traditionally have been regarded as an energy-dense source of calories and essential fatty acids. For many years, lipids used in parenteral nutrition have been based on vegetable oils (eg, soybean-oil emulsions). However, soybean-oil emulsions may not have an optimal fatty-acid composition under some circumstances when used as the only lipid source, as soybean oil is particularly abundant in the ω-6 polyunsaturated fatty acid (PUFA), linoleic acid. Hence, a progressive series of more complex lipid emulsions have been introduced, typically combining soybean oil with 1 or more alternative oils, such as medium-chain triglycerides (MCTs) and/or olive oil and/or fish oil. The wide range of lipid emulsions now available for parenteral nutrition offers opportunities to alter the supply of different fatty acids, which potentially modifies functional properties, with effects on inflammatory processes, immune response, and hepatic metabolism. Fish oil has become an important component of modern, composite lipid emulsions, in part owing to a growing evidence base concerning its biological effects in a variety of preclinical models. These biological activities of fish oil are mainly attributed to its ω-3 PUFA content, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA and EPA have known mechanisms of action, anti-inflammatory, immunomodulatory, and antioxidative properties. Specialized proresolving mediators, such as resolvins, protectins, and maresins, are synthesized directly from DHA and EPA, are key for the resolution of inflammation, and improve outcomes in many cell- and animal-based models and, recently, in some clinical settings.     

Lipid Emulsion Use in Pediatric Patients Requiring Long-Term Parenteral Nutrition

The ability to deliver nutrients via parenteral nutrition (PN) has markedly improved the prognosis of infants and children with intestinal failure. Technical refinements and advances in knowledge have led to the development of highly sophisticated PN solutions that are tailored to meet the needs of pediatric patients. However, children who require long-term PN have an increased risk of complications such as catheter-related sepsis, liver disease, and bone disease. Although the pathogenesis of intestinal failure associated liver disease (IFALD) is multifactorial, studies have identified a possible link between the dose of lipid emulsions based on soybean oil and cholestasis, shown to occur with a significantly higher frequency in patients receiving >1 g lipids/kg/d. Potential contributing factors include oxidative stress, high ω-6 polyunsaturated fatty acid (PUFA) and phytosterol content, and relatively low α-tocopherol levels. Lipid emulsions containing fish oil offer potential advantages compared with traditional emulsions with a high soybean oil content, such as decreased ω-6 and increased ω-3 PUFA concentrations, high concentrations of α-tocopherol, and reduced phytosterol content. Studies in PN-dependent children at risk for IFALD have shown that lipid emulsions containing fish oil reduce the risk of cholestasis and improve biochemical measures of hepatobiliary function compared with pure soybean oil emulsions. This review summarizes evidence regarding the role of lipid emulsions in the management of pediatric patients with intestinal failure requiring long-term PN, with a particular focus on the prevention and treatment of IFALD.     

Bloodstream Infections in Patients Receiving Manufactured Parenteral Nutrition With vs Without Lipids

Background: This study compared overall bacterial and bloodstream infection rates in patients receiving premixed parenteral nutrition (PN) with vs without lipid emulsion. Methods: Data from hospitalized patients who were ≥18 years of age and receiving premixed PN between 2005 and 2007 were extracted from the Premier Perspective database. Data were categorized into 2 groups: patients who received premixed PN only and those receiving premixed PN with lipids. Multiple logistic regression was used to adjust for risk factors and potential confounders, reporting the probability of risk for an infection. Results: The group without lipids was observed to have lower rates of both overall bacterial infection (43.5% vs 53.5%) and bloodstream infection (14.5% vs 18.9%). However, after adjusting for baseline characteristics, there were no significant differences in overall risk of bacterial infections (51.4% vs 53.5%; odds ratio [OR] = 1.11; 95% confidence interval [CI], 0.96–1.27) or bloodstream infections (19.6% vs 19.2%; 0.97; 0.81–1.16). In a subset of patients in the intensive care unit for ≥3 days, lower overall bacterial infection rates (58.3% vs 67.3%) and bloodstream infection rates (31.0% vs 37.0%) were observed in the group without lipids. After adjustment, there were no significant differences in risk of overall bacterial infection (OR = 0.95; 95% CI, 0.75–1.22) or bloodstream infection (0.92; 0.71–1.19) between the 2 groups. Conclusions: When administered with premixed PN, lipid emulsion was not significantly associated with an increase in the risk of infectious morbidity when compared to omitting lipids from therapy.     

Ceramide in Lipid Emulsions Used in Parenteral Nutrition

Parenteral nutrition-associated liver disease is a prevalent and severe complication of long term parenteral nutrition. We present here for the first time data on the presence of ceramide, a bioactive compound involved in a variety of metabolic processes, in different lipid emulsions used in parenteral nutrition. Further research is needed to determine whether this potential harmful bioactive compound is involved in parenteral nutrition-associated liver disease.     

Parenteral Nutrition and Oxidant Load in Neonates

Neonates with preterm, gastrointestinal dysfunction and very low birth weights are often intolerant to oral feeding. In such infants, the provision of nutrients via parenteral nutrition (PN) becomes necessary for short-term survival, as well as long-term health. However, the elemental nutrients in PN can be a major source of oxidants due to interactions between nutrients, imbalances of anti- and pro-oxidants, and environmental conditions. Moreover, neonates fed PN are at greater risk of oxidative stress, not only from dietary sources, but also because of immature antioxidant defences. Various interventions can lower the oxidant load in PN, including the supplementation of PN with antioxidant vitamins, glutathione, additional arginine and additional cysteine; reduced levels of pro-oxidant nutrients such as iron; protection from light and oxygen; and proper storage temperature. This narrative review of published data provides insight to oxidant molecules generated in PN, nutrient sources of oxidants, and measures to minimize oxidant levels.     

Hypothyroidism and Iodine Deficiency in an Infant Requiring Total Parenteral Nutrition

While iodine deficiency remains a relatively rare cause of thyroid dysfunction in the United States, little is known about iodine status and deficiency in children requiring parenteral nutrition (PN). This population may be at an elevated risk of thyroid dysregulation and neurodevelopmental sequelae due to low concentrations in typical PN formulations. Furthermore, with the widespread practice of switching from iodine‐based antiseptics to chlorhexadine, previous inadvertent sources of iodine are being eliminated as well.     

Impact of Parenteral Lipid Emulsion Components on Cholestatic Liver Disease in Neonates

Total parenteral nutrition (TPN) is a life-saving intervention for infants that are unable to feed by mouth. Infants that remain on TPN for extended periods of time are at risk for the development of liver injury in the form of parenteral nutrition associated cholestasis (PNAC). Current research suggests the lipid component of TPN is a factor in the development of PNAC. Most notably, the fatty acid composition, vitamin E concentration, and presence of phytosterols are believed key mediators of lipid emulsion driven PNAC development. New emulsions comprised of fish oil and medium chain triglycerides show promise for reducing the incidence of PNAC in infants. In this review we will cover the current clinical studies on the benefit of fish oil and medium chain triglyceride containing lipid emulsions on the development of PNAC, the current constituents of lipid emulsions that may modulate the prevalence of PNAC, and potential new supplements to TPN to further reduce the incidence of PNAC.     

Changes in Antioxidant Defense System Using Different Lipid Emulsions in Parenteral Nutrition in Children after Hematopoietic Stem Cell Transplantation

Background: Traditionally, lipids used in parenteral nutrition (PN) are based on ω-6 fatty acid-rich vegetable oils, such as soybean oil, with potential adverse effects involving oxidative stress. Methods: We evaluated the antioxidant defense system in children, after hematopoietic stem cell transplantation (HSCT), who were randomized to use a lipid emulsion with fish oil or soybean oil. Blood samples at baseline, at 10 days, and at the end of the PN were taken to analyze plasma retinol, α-tocopherol, β-carotene, coenzyme Q9 and coenzyme Q10 levels, and catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPOX), and superoxide dismutase (SOD) levels in lysed erythrocytes. Results: An increase in plasma α-tocopherol levels in the group of patients receiving the fish oil-containing emulsion (FO) compared with the group receiving the soybean emulsion was observed at day 10 of PN. Concurrently, plasma α-tocopherol increased in the FO group and β-carotene decreased in both groups at day 10 compared with baseline levels, being more significant in the group receiving the FO emulsion. Conclusion: FO-containing emulsions in PN could improve the antioxidant profile by increasing levels of α-tocopherol in children after HSCT who are at higher risk of suffering oxidative stress and metabolic disorders.     

Low‐Dose Parenteral Soybean Oil for the Prevention of Parenteral Nutrition–Associated Liver Disease in Neonates With Gastrointestinal Disorders

Background: Neonates with gastrointestinal disorders (GDs) are at high risk for parenteral nutrition–associated liver disease (PNALD). Soybean‐based intravenous lipid emulsions (S‐ILE) have been associated with PNALD. This study's objective was to determine if a lower dose compared with a higher dose of S‐ILE prevents cholestasis without compromising growth. Materials and Methods: This multicenter randomized controlled pilot study enrolled patients with GDs who were ≤5 days of age to a low dose (~1 g/kg/d) (LOW) or control dose of S‐ILE (~3 g/kg/d) (CON). The primary outcome was cholestasis (direct bilirubin [DB] >2 mg/dL) after the first 7 days of age. Secondary outcomes included growth, PN duration, and late‐onset sepsis. Results: Baseline characteristics were similar between the LOW (n = 20) and CON groups (n = 16). When the LOW group was compared with the CON group, there was no difference in cholestasis (30% vs 38%, P = .7) or secondary outcomes. However, mean ± SE DB rate of change over the first 8 weeks (0.07 ± 0.04 vs 0.3 ± 0.09 mg/dL/wk, P = .01) and entire study (0.008 ± 0.03 vs 0.2 ± 0.07 mg/dL/wk, P = .02) was lower in the LOW group compared with the CON group. Conclusion: In neonates with GDs who received a lower dose of S‐ILE, DB increased at a slower rate in comparison to neonates who received a higher dose of S‐ILE. Growth was comparable between the groups. This study demonstrates a need for a larger, randomized controlled trial comparing 2 different S‐ILE doses for cholestasis prevention in neonates at risk for PNALD.     

Administration of an Intravenous Fat Emulsion Enriched with Medium-Chain Triglyceride/ω-3 Fatty Acids is Beneficial Towards Anti-Inflammatory Related Fatty Acid Profile in Preterm Neonates: A Randomized,Double-Blind Clinical Trial

Intravenous administration of pure soybean oil emulsions high in linoleic acid may lead to inflammation and lipid peroxidation in preterm neonates. We aimed to investigate the effects of a medium-chain triglyceride (MCT)/ω-3 polyunsaturated fatty acid (PUFA)-enriched intravenous fat emulsion (IVFE) on plasma fatty acid (FA) profile and serum interleukin-6 (IL-6) in preterm neonates. In this double-blind randomized study, 92 preterm neonates (gestational age < 32 weeks, birth weight < 1500 g) were assigned to receive either MCT/ω-3 PUFA-enriched IVFE (Intervention Group) or soybean oil-based IVFE (Control Group). Levels of FAs were measured at baseline (day 0) and day 15 of parenteral nutrition with gas-chromatography mass-spectrometry. Serum IL-6 was measured with sandwich ELISA in 59 neonates. Plasma FAs changed significantly over time; the MCT/ω-3 PUFA-IVFE group showed higher ω-3 PUFAs (p = 0.031), eicosapentaenoic acid (p = 0.000), and oleic acid (p = 0.003), and lower ω-6/ω-3 PUFAs ratio (p = 0.001) and ω-6 PUFAs (p = 0.023) compared to control group. Linoleic acid was higher in the soybean oil (SO)-based IVFE arm compared to the MCT/ω-3 PUFAs-IVFE arm (p = 0.006). Both fat emulsion types decreased IL-6 compared to baseline, but changes were insignificant between groups. Administration of MCT/ω-3 PUFA-enriched IVFE in preterm neonates is beneficial in changing the FA profile consistent with attenuated inflammatory response.     

Effects on Varying Intravenous Lipid Emulsions on the Small Bowel Epithelium in a Mouse Model of Parenteral Nutrition

Background: Injectable fat emulsions (FEs) are a clinically dependable source of essential fatty acids (FA). ω‐6 FA is associated with an inflammatory response. Medium‐chain triglycerides (MCT, ω‐3 FA), fish oil, and olive oil are reported to decrease the inflammatory response. However, the effect of these lipids on the gastrointestinal tract has not been well studied. To address this, we used a mouse model of parenteral nutrition (PN) and hypothesized that a decrease in intestinal inflammation would be seen when either fish oil and MCT or olive oil were added. Methods: Three FEs were studied in adult C57BL/6 mice via intravenous cannulation: standard soybean‐based FE (SBFE), 80% olive oil ‐supplemented FE (OOFE), or a combination of a soybean oil, MCT, olive oil, and fish oil emulsion (SMOF). PN was given for 7 days, small bowel mucosa‐derived cytokines, animal survival rate, epithelial cell (EC) proliferation and apoptosis rates, intestinal barrier function and mucosal FA composition were analyzed. Results: Compared to the SBFE and SMOF groups, the best survival, highest EC proliferation and lowest EC apoptosis rates were observed in the OOFE group; and associated with the lowest levels of tumor necrosis factor‐α, interleukin‐6, and interleukin‐1β expression. Jejunal FA content showed higher levels of eicosapentaenoic and docosapentaenoic acid in the SMOF group and the highest arachidonic acid in the OOFE group. Conclusion: The study showed that PN containing OOFE had beneficial effects to small bowel health and animal survival. Further investigation may help to enhance bowel integrity in patients restricted to PN.     

Impact of Providing a Combination Lipid Emulsion Compared With a Standard Soybean Oil Lipid Emulsion in Children Receiving Parenteral Nutrition

Background: Soybean oil lipid emulsion may compromise immune function and promote hepatic damage due to its composition of long‐chain fatty acids, phytosterols, high proportion of ω‐6 fatty acids, and low α‐tocopherol levels. Combination lipid emulsions have been developed using medium‐chain triglyceride oil, fish oil, and/or olive oil, which provide adequate essential fatty acids, a smaller concentration of ω‐6 fatty acids, and lower levels of phytosterols. The purpose of this systematic review is to determine if combination lipid emulsions have a more favorable impact on bilirubin levels, triglyceride levels, and incidence of infection compared with soybean oil lipid emulsions in children receiving parenteral nutrition. Methods: This study comprises a systematic review of published studies. Data were sufficient and homogeneous to conduct a meta‐analysis for total bilirubin and infection. Results: Nine studies met the inclusion criteria. Meta‐analysis showed that combination lipid emulsion decreased total bilirubin by a mean difference of 2.09 mg/dL (95% confidence interval, –4.42 to 0.24) compared with soybean oil lipid emulsion, although the result was not statistically significant (P = .08). Meta‐analysis revealed no statistically significant difference in incidence of infection between the combination lipid emulsion and the soybean oil lipid emulsion groups (P = .846). None of the 4 studies that included triglyceride as an outcome detected a significant difference in triglyceride levels between the combination lipid emulsion and soybean oil lipid emulsion groups. Conclusion: There is inadequate evidence that combination lipid emulsions offer any benefit regarding bilirubin levels, triglyceride levels, or incidence of infection compared with soybean oil lipid emulsions.     

Neonatal Parenteral Nutrition Hypersensitivity: A Case Report Implicating Bisulfite Sensitivity in a Newborn Infant

This report describes a case of parenteral nutrition hypersensitivity in a 37 weeks' gestation infant with congenital diaphragmatic hernia complicated by bowel necrosis and functional short bowel syndrome. The patient developed a rash with subsequent urticaria beginning on the 50th day of life. The reactions were confirmed with a positive rechallenge. After the amino acid solution was replaced with a non–bisulfite‐containing product, the infant was able to continue to receive nutrition support through parenteral nutrition without recurrence of symptoms. It is speculated that the bisulfite additive in the amino acid solution may have interacted with the lipid emulsion to sensitize the patient.     

谷胱甘肽防止幼兔全胃肠外营养所致肝损害

目的研究氧化损伤及凋亡在全胃肠外营养(TPN)相关肝损害机制中的作用,并探讨谷胱甘肽防止TPN相关肝损害的有效性。方法将35只出生后6～8天的新西兰兔分为3组:正常对照组(n=12,母乳喂养);PN组(n=12,全肠外营养组,持续静脉营养10天);PN+GSH组(n=11,全肠外营养+还原型谷胱甘肽20mg/kg·d)。10天后比较3组间肝功能、肝脏光镜和电镜病理变化、TUNEL法检测肝细胞凋亡以及肝组织丙二醛(MDA)含量。结果PN组血直接胆红素、胆汁酸均明显高于正常对照组和PN+GSH组(P<0.05)。PN+GSH组病理无胆管扩张和胆汁淤积表现,电镜超微结构变化与病理相符。PN组肝组织MDA含量及肝细胞凋亡阳性率明显高于对照组和PN+GSH组(P<0.05,P<0.01)。结论氧化损伤及凋亡在TPN相关肝损害机制中可能起着重要作用;谷胱甘肽可明显减轻TPN所致肝细胞损害,可能与其抗氧化、抗凋亡作用有关。