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Background and Aims: A limited number of randomized controlled trials (RCTs) have examined the use of lipid emulsions (LEs) of different compositions in home parenteral nutrition (HPN), and there are very few data on the long-term use of omega-3 (n-3) polyunsaturated fatty acids (PUFAs). The study's objective was to assess safety and tolerability of an n-3 PUFA-enriched LE in adult patients suffering from chronic intestinal failure (CIF) requiring long-term HPN., Methods: In this prospective, randomized, controlled, double-blind, multicentre, international clinical trial, which was conducted at eleven sites, adult patients in need of HPN including lipids received either the investigational product, an n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) LE, or the reference product, a standard MCT/LCT LE, for an average duration of eight weeks. The primary outcome was the sum of changes of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives included fatty acid pattern in plasma and red blood cells (RBCs) and triene:tetraene ratio in plasma., Results: 74 patients were enrolled up to premature study termination. Liver function parameters showed no clinically relevant differences between study groups and remained within normal ranges. The n-3 PUFAs EPA and DHA increased in plasma and RBCs in the Lipidem group and were higher in the Lipidem group than the reference group at the end of the study resulting in an increased n-3-index in RBCs with Lipidem. Average n-3-index was >8. The plasma triene:tetraene ratio decreased in both groups., Conclusion: This study is one of the largest comparing two LEs in the complex setting of HPN treatment of adult patients. Although it has been early terminated its results considerably contribute to the evidence on safety and efficacy of longer-term use of LEs in HPN treatment. The n-3 PUFA-enriched LE Lipidem was safe and well-tolerated, particularly in terms of liver function. Lipidem provided an additional supply of n-3 PUFAs and led to positive changes in fatty acid profiles of plasma and RBCs. The n-3-index was in the desirable range at the end of the study in patients receiving Lipidem. There was no evidence of essential fatty acid deficiency with Lipidem., Gov Identifier: NCT03282955., Trial Registration: EudraCT Number: 2015-000849-23., Competing Interests: Conflict of interest KSK has received speaker honoraria from B. Braun, Baxter, Fresenius, Nestle and Nutricia. KS received honoraria from B. Braun. MK received participation fees for scientific conferences, honoraria for lectures at scientific conferences, lectures and educational workshops from: Fresenius Kabi Polska, Baxter Polska, B. Braun. LP was engaged in advisory boards for Baxter, Napo therapeutics, Lionhealth, Nestlè, Takeda. SMS declares research support from B. Braun, Dr. Falk, Hanmi, Nestlé Health Science, Takeda, VectivBio and Zealand, consultancies for Axium mTech, Baxter, Nestlé Health Science, Pfizer, Takeda and VectivBio, speaker for Biocodex, Fresenius Kabi, Laboratoires Grand Fontaine, Nestlé Health Sciences, Nutricia and Takeda. SCC has worked with an NIHR grant supervising a PhD on vitamin D and IBD. PCC acts as an ad hoc advisor to B. Braun, Fresenius Kabi and Baxter Healthcare. SG declares consultancies for Alira Health, Protara Therapeutics, Zealand pharma, Takeda, Fresenius Kabi and Calea. AF has speaker engagements with B. Braun and Fresenius Kabi. The other authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In critical illness the regulation of inflammation and oxidative stress can improve patient outcomes, and thus omega-3 polyunsaturated fatty acids (PUFAs) have been used as part of parenteral nutrition (PN) owing to their potential anti-inflammatory effects. The international lipids in PN Summit, encompassed discussions and the production of consensus guidelines concerning PN intravenous lipid emulsion (ILE) use in critical care. The Lipid Summit participants agreed that the inclusion of fish oil in ILEs is associated with meaningful clinical benefits without signals of harm, based on a strong biological rationale and current clinical evidence. Decisions concerning ILE choice should be made based on current evidence, thus addressing clinical requirements for guidance, particularly as further definitive evidence seems unlikely to occur. In addition, a future of individualized ICU care is envisioned, yielding better clinical outcomes. This approach will require the greater use of intelligent study designs incorporating the use of biomarkers of omega-3 derivatives, inflammatory-resolving processes, and/or muscle protein breakdown., (© 2024. The Author(s).)

Background & Aims: Accumulating scientific evidence supports the benefits of parenteral nutrition (PN) with fish oil (FO) containing intravenous lipid emulsions (ILEs) on clinical outcomes. Yet, the question of the most effective ILE remains controversial. We conducted a network meta-analysis (NMA) to compare and rank different types of ILEs in terms of their effects on infections, sepsis, ICU and hospital length of stay, and in-hospital mortality in adult patients., Methods: MEDLINE, EMBASE, and Web of Science databases were searched for randomized controlled trials (RCTs) published up to May 2022, investigating ILEs as a part of part of PN covering at least 70% of total energy provision. Lipid emulsions were classified in four categories: FO-ILEs, olive oil (OO)-ILEs, medium-chain triglyceride (MCT)/soybean oil (SO)-ILEs, and pure SO-ILEs. Data were statistically combined through Bayesian NMA and the Surface Under the Cumulative RAnking (SUCRA) was calculated for all outcomes., Results: 1651 publications were retrieved in the original search, 47 RCTs were included in the NMA. For FO-ILEs, very highly credible reductions in infection risk versus SO-ILEs [odds ratio (OR) = 0.43 90% credibility interval (CrI) (0.29-0.63)], MCT/soybean oil-ILEs [0.59 (0.43-0.82)], and OO-ILEs [0.56 (0.33-0.91)], and in sepsis risk versus SO-ILEs [0.22 (0.08-0.59)], as well as substantial reductions in hospital length of stay versus SO-ILEs [mean difference (MD) = -2.31 (-3.14 to -1.59) days] and MCT/SO-ILEs (-2.01 (-2.82 to -1.22 days) were shown. According to SUCRA score, FO-ILEs were ranked first for all five outcomes., Conclusions: In hospitalized patients, FO-ILEs provide significant clinical benefits over all other types of ILEs, ranking first for all outcomes investigated., Registration No: PROSPERO 2022 CRD42022328660., Competing Interests: Conflict of interest L. Pradelli is a director and employee of AdRes, which has received project funding from Fresenius Kabi. K. Mayer has received fees from Abbott, AstraZeneca, Baxter, BBraun, Fresenius Kabi, MSD, Nestlé, Novartis, and Pfizer. S. Klek has received speaker’s honoraria from Baxter, Braun, Fresenius Kabi, Nestlé, Nutricia, Shire, and Vipharm and acted as an advisory board member for Fresenius Kabi, Shire, and Tracheron. M. Rosenthal has received fees from Fresenius, Nestle, and Abbott. M. Povero is an employee of AdRes, which has received project funding from Fresenius Kabi. A. R. Heller has received project funding from Fresenius Kabi. M. Muscaritoli has received speaker’s fees from Fresenius Kabi., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: ω-3 Fatty acid (FA)-containing parenteral nutrition (PN) is associated with improvements in patient outcomes and with reductions in hospital length of stay (HLOS) vs standard PN regimens (containing non-ω-3 FA lipid emulsions). We present a cost-effectiveness analysis of ω-3 FA-containing PN vs standard PN in 5 European countries (France, Germany, Italy, Spain, UK) and the US., Methods: This pharmacoeconomic model was based on estimates of ω-3 efficacy reported in a recent meta-analysis and data from country-specific sources. It utilized a probabilistic discrete event simulation model to compare ω-3 FA-containing PN with standard PN in a population of critically ill and general ward patients. The influence of model parameters was evaluated using probabilistic and deterministic sensitivity analyses., Results: Overall costs were reduced with ω-3 FA-containing PN in all 6 countries compared with standard PN, ranging from €1741 (±€1284) in Italy to €5576 (±€4193) in the US. Expenses for infections and HLOS were lower in all countries for ω-3 FA-containing PN vs standard PN, with the largest cost differences for both in the US (infection: €825 ± €4001; HLOS: €4879 ± €1208) and the smallest savings in the UK for infections and in Spain for HLOS (€63 ± €426 and €1636 ± €372, respectively)., Conclusion: This cost-effectiveness analysis in 6 countries demonstrates that the superior clinical efficacy of ω-3 FA-containing PN translates into significant decreases in mean treatment cost, rendering it an attractive cost-saving alternative to standard PN across different healthcare systems., (© 2020 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: Omega-3 (ω-3) fatty acid (FA)-containing parenteral nutrition (PN) is associated with significant improvements in patient outcomes compared with standard PN regimens without ω-3 FA lipid emulsions. Here, we evaluate the impact of ω-3 FA-containing PN versus standard PN on clinical outcomes and costs in adult intensive care unit (ICU) patients using a meta-analysis and subsequent cost-effectiveness analysis from the perspective of a hospital operating in five European countries (France, Germany, Italy, Spain, UK) and the US., Methods: We present a pharmacoeconomic simulation based on a systematic literature review with meta-analysis. Clinical outcomes and costs comparing ω-3 FA-containing PN with standard PN were evaluated in adult ICU patients eligible to receive PN covering at least 70% of their total energy requirements and in the subgroup of critically ill ICU patients (mean ICU stay > 48 h). The meta-analysis with the co-primary outcomes of infection rate and mortality rate was based on randomized controlled trial data retrieved via a systematic literature review; resulting efficacy data were subsequently employed in country-specific cost-effectiveness analyses., Results: In adult ICU patients, ω-3 FA-containing PN versus standard PN was associated with significant reductions in the relative risk (RR) of infection (RR 0.62; 95% CI 0.45, 0.86; p = 0.004), hospital length of stay (HLOS) (- 3.05 days; 95% CI - 5.03, - 1.07; p = 0.003) and ICU length of stay (LOS) (- 1.89 days; 95% CI - 3.33, - 0.45; p = 0.01). In critically ill ICU patients, ω-3 FA-containing PN was associated with similar reductions in infection rates (RR 0.65; 95% CI 0.46, 0.94; p = 0.02), HLOS (- 3.98 days; 95% CI - 6.90, - 1.06; p = 0.008) and ICU LOS (- 2.14 days; 95% CI - 3.89, - 0.40; p = 0.02). Overall hospital episode costs were reduced in all six countries using ω-3 FA-containing PN compared to standard PN, ranging from €-3156 ± 1404 in Spain to €-9586 ± 4157 in the US., Conclusion: These analyses demonstrate that ω-3 FA-containing PN is associated with statistically and clinically significant improvement in patient outcomes. Its use is also predicted to yield cost savings compared to standard PN, rendering ω-3 FA-containing PN an attractive cost-saving alternative across different health care systems., Study Registration: PROSPERO CRD42019129311.

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., (© 2020 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.)

The inclusion of ω-3 fatty acids as part of parenteral nutrition is associated with clinical benefits such as a reduced likelihood of infectious complications and shorter hospital and intensive care unit (ICU) stays. As healthcare resources are limited, pharmacoeconomic analyses have been performed, typically modeling studies, using cost and outcomes data to investigate the cost-effectiveness of parenteral nutrition regimens including ω-3 fatty acids from fish oil compared with standard parenteral nutrition without such ω-3 fatty acids. This review covers pharmacoeconomic studies encompassing Italian, French, German, and UK hospitals for ICU and non-ICU hospitalized patients, and for ICU patients in China. The results show that the use of parenteral nutrition including ω-3 fatty acids more than offsets any additional acquisition costs in all national scenarios investigated to date, indicating that parenteral nutrition including ω-3 fatty acids is a clinically and economically beneficial strategy compared with standard parenteral nutrition., (© 2019 American Society for Parenteral and Enteral Nutrition.)

This systematic review and meta-analysis investigated ω-3 fatty-acid enriched parenteral nutrition (PN) vs standard (non-ω-3 fatty-acid enriched) PN in adult hospitalized patients (PROSPERO 2018 CRD42018110179). We included 49 randomized controlled trials (RCTs) with intervention and control groups given ω-3 fatty acids and standard lipid emulsions, respectively, as part of PN covering ≥70% energy provision. The relative risk (RR) of infection (primary outcome; 24 RCTs) was 40% lower with ω-3 fatty-acid enriched PN than standard PN (RR 0.60, 95% confidence interval [CI] 0.49-0.72; P < 0.00001). Patients given ω-3 fatty-acid enriched PN had reduced mean length of intensive care unit (ICU) stay (10 RCTs; 1.95 days, 95% CI 0.42-3.49; P = 0.01) and reduced length of hospital stay (26 RCTs; 2.14 days, 95% CI 1.36-2.93; P < 0.00001). Risk of sepsis (9 RCTs) was reduced by 56% in those given ω-3 fatty-acid enriched PN (RR 0.44, 95% CI 0.28-0.70; P = 0.0004). Mortality rate (co-primary outcome; 20 RCTs) showed a nonsignificant 16% reduction (RR 0.84, 95% CI 0.65-1.07; P = 0.15) for the ω-3 fatty-acid enriched group. In summary, ω-3 fatty-acid enriched PN is beneficial, reducing risk of infection and sepsis by 40% and 56%, respectively, and length of both ICU and hospital stay by about 2 days. Provision of ω-3-enriched lipid emulsions should be preferred over standard lipid emulsions in patients with an indication for PN., (© 2019 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals, Inc. on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited., Methods/design: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs., Discussion: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN., Trial Registration: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017.