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Article

Parenteral Nutrition Containing Fish Oil for Hospitalized Non-Intensive Care Unit (ICU) Patients: A Systematic Review, Meta-Analysis, and Cost-Effectiveness Analysis

by
Lorenzo Pradelli
1,*,
Axel Rüdiger Heller
2,
Stanislaw Klek
3,
Konstantin Mayer
4,
Martin D. Rosenthal
5 and
Maurizio Muscaritoli
6
1
AdRes-Health Economics and Outcome Research, Via Vittorio Alfieri 17, 10121 Turin, Italy
2
Department of Anaesthesiology and Intensive Care Medicine, University of Augsburg, 86159 Augsburg, Germany
3
Surgical Oncology Clinic, The Maria Sklodowska-Curie National Cancer Institute, 31-115 Krakow, Poland
4
Department of Internal Medicine, University Hospital of Giessen and Marburg, Klinikstraße 33, 35392 Giessen, Germany
5
Department of Surgery, Division of Trauma and Acute Care Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA
6
Department of Clinical Medicine, Sapienza University of Rome, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2025, 17(7), 1284; https://doi.org/10.3390/nu17071284
Submission received: 14 March 2025 / Revised: 26 March 2025 / Accepted: 28 March 2025 / Published: 7 April 2025
(This article belongs to the Special Issue Functional Lipids and Human Health)
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Abstract

:
Background and aims: We investigated parenteral nutrition (PN) containing fish oil (FO-PN) vs. standard PN without fish oil (NF-PN) in adult patients hospitalized in the non-intensive care unit (general ward). Methods: Searches in Medline, Embase, and Web of Science (any date to 10 October 2024) were screened, data were extracted, and the quality of the studies was assessed by two independent researchers. Meta-analyses were performed, with outcomes included in random effects models, and heterogeneity for clinical outcomes was explored via subgroup analyses and meta-regression. Pharmacoeconomic analyses used data from the current meta-analysis. Results: In this study, 29 randomized controlled trials (RCTs) were included, with intervention and control groups given FO-PN and NF-PN, respectively, as part of PN covering ≥70% energy provision. Compared to NF-PN, FO-PN was associated with a 37% lower relative risk (RR) of infection (19 RCTs; RR 0.63, 95% confidence interval [CI] 0.50–0.78; p < 0.0001), 2.03 days shorter length of hospital stay (18 RCTs; 95% CI 1.23–2.84; p < 0.00001), and a 51% reduction in the risk of sepsis (10 RCTs; RR 0.49, 95% CI 0.32–0.74; p = 0.0009). There was a non-significant 54% reduction in the 30-day mortality rate (11 RCTs; RR 0.46, 95% CI 0.20–1.08; p = 0.07) for FO-PN. FO-PN was associated with better clinical outcomes and financial savings (i.e., dominance) compared to NF-PN in all five countries studied. Conclusions: FO-PN is a cost-effective option compared to NF-PN for adult patients hospitalized in a general ward across a range of healthcare systems.

1. Introduction

Malnutrition in hospitalized patients remains common and is both under-identified and under-treated [1]. Malnutrition can be associated with poorer outcomes, including an increased incidence of infectious and non-infectious complications and in-hospital mortality, and result in greater healthcare utilization (e.g., longer hospital or intensive care unit (ICU) stays, hospital (re)admissions, and increased medication use) [2]. Parenteral nutrition (PN) is useful for addressing malnutrition when oral or enteral nutrition is not possible, is insufficient, or is contraindicated, and it includes lipid emulsions as an essential component [3,4,5]. The lipid source in PN is also important. Early ‘first-generation’ lipid emulsions, used as part of PN, were based solely on soybean oil or soybean/safflower oil, providing high levels of omega-6 polyunsaturated fatty acids (PUFAs) [6,7]. Following concerns that the relatively high omega-6 PUFA concentration supplied by soybean oil lipid emulsions might be inflammatory and immunosuppressive, more complex composite blends were developed using mixed-oil sources, including medium-chain triglycerides (MCTs), olive oil, and fish oil [7,8,9,10].
Modern composite lipid PN emulsions frequently contain fish oil [10]. In part, this is because of accumulated evidence concerning the biological effects of fish oil, attributed principally to the omega-3 PUFAs, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) [10,11]. As well as having anti-inflammatory, immunomodulatory, and anti-oxidative effects, DHA and EPA are precursors of specialized pro-resolution mediators (i.e., resolvins, protectins, and maresins) that have been shown to exert potent beneficial effects in many animal disease models, including immune modulation and tissue repair [10,12]. Moreover, EPA and DHA may help preserve muscle mass and strength, which are important determinants of patient recovery following surgery, periods of immobility, or critical illness [13,14]. Thus, there is a firm biological rationale for the inclusion of fish oil in PN; so, numerous clinical trials have compared PN with and without fish oil in a variety of clinical conditions and patient groups.
The current analysis of adult hospitalized patients given PN focuses on hospitalized patients treated in a general ward, thus excluding ICU patients. Compared to those in the ICU, general ward patients requiring PN are a somewhat heterogeneous group, united by a need for PN in order to reach their energy requirements, although the majority are surgical patients with intestinal failure from a variety of causes [5,15]. PN for surgical patients may be most beneficial in undernourished patients when enteral nutrition is not feasible or not tolerated and in those with postoperative complications impairing gastrointestinal function who are unable to receive and/or absorb adequate oral/enteral nutrition for at least seven days [16]. In contrast with ICU patients requiring PN, general ward patients tend to be in a non-hypercatabolic state; thus, their protein and energy targets generally tend to be less than those of hypercatabolic patients.
We previously conducted a systematic review and meta-analyses that demonstrated notable clinical advantages of FO-PN in adult hospitalized patients, including a 40% and 56% reduction in the risks of infection and sepsis, respectively, as well as a decrease of approximately two days in both ICU and overall hospital stay [17]. As ICU and general ward patients formed distinct subgroups within this meta-analysis, a follow-up study further analyzed the ICU sub-population with regard to PN with and without fish oil [18]. The current study now seeks to investigate an updated general ward patient sub-population in greater detail as the initial analysis [17] did not allow clear conclusions to be drawn for the general ward patient population as they were grouped together with those in the ICU. Furthermore, general ward adult patients requiring PN represent a numerous and important group, comprising more than half of all patients in the initial meta-analysis that included both ICU and general ward patients [17]. Thus, the objective of this study was to perform a systematic review and meta-analysis, as well as a cost-effectiveness analysis, for adult patients hospitalized in a general ward, investigating the potential benefits of FO-PN vs. NF-PN.

2. Methods

2.1. Meta-Analysis

Registration and overview. This research followed current best practices, such as the prospective registration of methods with the international prospective register of systematic reviews (PROSPERO: PROSPERO 2021 CRD42021293972) [19] and adhering to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement for reporting systematic reviews and meta-analyses [20]. Prospectively identified outcomes from included studies were extracted, pooled, and meta-analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions [21]. This study concerns the assessment of clinical efficacy and safety in adult patients hospitalized in a general ward given FO-PN or NF-PN and also investigates how results vary by the type of comparator and patient characteristics. The methods included (a) setting the eligibility criteria, (b) identifying databases and formulating the search strategy, (c) conducting a structured literature search followed by the stepwise screening of titles, abstracts, and full texts, (d) extracting data and synthesizing results for the meta-analysis, and (e) performing a cost-effectiveness evaluation.

2.1.1. Eligibility Criteria

Study eligibility was defined using the PICOS framework (participants, interventions, comparisons, outcomes, and study designs) [21,22]. The included studies involved adult hospitalized patients outside the ICU (i.e., in medical or surgical wards) who received PN providing at least 70% of total energy requirements. Studies involving pediatric, neonatal, or ICU populations or those focused on enteral nutrition were excluded. (Note: for the purpose of subgroup analysis, ‘total PN’ studies were defined as those excluding any use of enteral and/or oral nutrition, whereas for ‘PN studies’, enteral and/or oral nutrition could contribute up to 30% of the total calories supplied.) FO-PN formed the intervention group, and NF-PN was the control group. Studies were excluded if they involved ‘off-label’ PN use (e.g., fish oil as the sole parenteral lipid source) or if enteral nutrition accounted for over 30% of daily energy intake. The co-primary clinical endpoints were infection rates and 30-day mortality. (In this analysis, 30-day mortality referred to deaths occurring within 30 days of receiving at least one dose of the intervention or before hospital discharge, depending on the data reported). The secondary main clinical outcomes were length of hospital stay, sepsis rate, and hospital readmissions. Additional outcomes included plasma phospholipid fatty acid composition and lipid parameters (α-tocopherol, EPA, DHA, and plasma triglyceride levels); inflammatory and antioxidant markers (changes in interleukin-6, leukotrienes B4 and B5, LTB5:LTB4 ratio, C-reactive protein, and TNF-α); and standard laboratory values such as urea, serum creatinine, platelet count, liver enzymes (ALT, AST, and GGT), and both total and direct bilirubin. The analysis was restricted to randomized controlled trials (RCTs) published in English in peer-reviewed journals that reported at least one pre-specified outcome.

2.1.2. Information Sources and Search Methods

A structured search strategy was formulated a priori using the PICOS criteria [19,21,22], and the search keywords were “parenteral nutrition”, “fish oil”, “lipids”, “emulsion”, and “randomised controlled trial”. No restrictions or filters were used, with an inclusion time interval prior to 30 September 2024. Medline (PubMed interface), Embase, and Web of Science were searched using search strings modified to fit each database’s requirements (Table S1). The results were combined to create a core database, eliminating duplicate records. Manual searches of included study reference lists were performed, along with reviews and meta-analyses on the subject, and any additional RCTs identified were added to the core database.

2.1.3. Study Selection, Data Collection, Summary Measures, and Individual Study Bias Assessment

Screening of core database publications by inclusion and exclusion criteria was performed independently by two authors, first looking at titles and abstracts and then at the full text of eligible papers. Conflicting opinions were resolved by consulting with a third review author. Data were extracted from included studies by two authors working independently using a predefined standardized collection grid, with disagreements addressed through consultation with the principal investigator. Outcomes shown only as figures were converted to numerical values using Engauge® software, version 12.1 [23]. Standard errors of the mean (SEMs) were converted to standard deviations (SDs) using established equations, while medians and interquartile ranges were transformed into estimated means and SDs following the method proposed by Wan et al. [24]. Continuous outcomes were summarized using the weighted mean difference with 95% confidence intervals (CIs) or the standardized mean difference when varying measurement scales were present. For dichotomous outcomes, risk ratios (RRs) with a 95% CI were calculated. Two authors independently evaluated the risk of bias in each study using the Cochrane Collaboration’s bias assessment tool [21]. Bias was judged as a graded set of response options (from ‘low’ to ‘some concerns’ to ‘high’). (Note: the prospectively defined methods [PROSPERO 2021 CRD42021293972] involved assessing the risk of bias according to the Risk of Bias [RoB] 1.0 tool, but in the current analysis, RoB 2.0 was used).

2.1.4. Synthesis of Results

Meta-analyses were conducted using Review Manager (RevMan 5.4), developed by the Nordic Cochrane Centre for the Cochrane Collaboration when studies were sufficiently homogeneous in terms of design and comparator. All outcomes were analyzed using random effects models. In cases of substantial heterogeneity (I2 > 50%), potential sources were investigated through subgroup analyses and meta-regression, with stratification based on patient profiles, intervention type, study features, and clinical context (i.e., age, sex, reason for PN, nutrition status, oncological setting, and PN/TPN), provided ≥5 studies reported on it.

2.2. Pharmacoeconomic Analysis

The pharmacoeconomic and associated sensitivity analyses were performed essentially as detailed previously for an ICU patient population [18]. In brief, this consisted of cost-effectiveness models using data from the current meta-analysis. Five cost-effectiveness models were based on a probabilistic discrete event simulation technique run over 10,000 iterations, developed and simulated for hospitals in France, Germany, Italy, Spain, and the UK, to compare FO-PN vs. NF-PN in adult patients hospitalized in a general ward. Studies included in the meta-analysis were used to value the weighted means for hospital length of stay and infection rate (weights based on patient number for the NF-PN arm of each study), and outcomes for the FO-PN group were simulated after applying relative efficacy estimates from the meta-analyses to the outcomes of the NF-PN group. Death rates were set as equal in both arms given the inconclusive results for this parameter in the meta-analysis. Economic parameters such as daily ward and infection costs are country-specific and have been reported previously [18]. Probabilistic sensitivity analyses were performed by drawing parameter values from their respective probability distributions, creating 1000 unique sets of parameter combinations. If data concerning uncertainty were missing, a 20% standard deviation of the mean value was used with an appropriate probability distribution. For deterministic sensitivity analyses, simulations were repeated while varying parameter values to their upper and lower CI limits and keeping other parameter values constant. Where CIs were unavailable, the lower and upper 95% CIs of the distribution used in probabilistic sensitivity analyses were assumed as parameter values.

3. Results

3.1. Study Selection and Characteristics

Data from 2587 patients enrolled in 29 randomized controlled trials were incorporated into the systematic review and meta-analytic synthesis (Figure 1 and Table 1) [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]. Risk-of-bias results are presented in Figure S1.

3.2. Clinical Outcomes

A total of 19 studies (1690 patients) reported nosocomial infections and were assessed for the co-primary outcome, infection rate. Compared to NF-PN, FO-PN resulted in a 37% reduction in infection rates (RR 0.63, 95% CI 0.50–0.78; p < 0.0001) (Figure 2). Subgroup analysis was not performed as heterogeneity was low (I2: 0%). Eleven studies (1246 patients) reported the co-primary outcome, namely, mortality rate. There was a non-significant 54% reduction trend in the 30-day mortality rate for FO-PN (RR 0.46, 95% CI 0.20–1.08; p = 0.07) (Figure 3). Again, subgroup analysis was not performed due to low heterogeneity (I2: 0%).
Length of hospital stay reports were found for 18 studies (1642 patients). The results showed a reduction in the length of hospital stay of 2.03 days (95% CI 1.23–2.84; p < 0.00001) with FO-PN (Figure 4). As the data for length of stay outcomes were classified as highly heterogeneous (I2 = 53%), subgroup analyses and meta-regression were performed. The subgroup analyses showed a significantly greater reduction in length of hospital stay for 8 total PN studies (680 patients) including fish oil (3.46 days; 95% CI 2.09–4.83) than for 10 PN studies (962 patients) including fish oil (1.29 days; 95% CI 0.46–2.13), with a significant (p = 0.008) test for differences between groups. (Note that ‘total PN’ studies were defined as those excluding any use of enteral and/or oral nutrition, whereas in ‘PN studies’, enteral and/or oral nutrition could contribute up to 30% of total calories supplied.) Thus, total PN may be associated with the observed reduction in the length of hospital stays for patients receiving omega-3 fatty acids. A similar subgroup analysis by oncological status did not reveal a significant difference (p = 0.4), meaning that the observed reduction in length of hospital stay might not be associated with the presence of an oncological diagnosis. Likewise, no association was observed when analyzing malnourished vs. non-malnourished subgroups (p = 0.75). Meta-regression for all predefined covariates showed that the best model describing heterogeneity includes both the proportion of males and total PN as these two covariates explain almost two-thirds of the between-study variance, with the I2 reducing from 53% to 30%. Residual unexplained heterogeneity may relate to the differences in patient characteristics and study procedures.
Out of the 29 included studies, 10 (1117 patients) distinguished between infection rate and the occurrence of sepsis, reporting both percentages independently. Compared to NF-PN, FO-PN significantly reduced the risk of sepsis by 51% (RR 0.49, 95% CI 0.32–0.74; p = 0.0009) (Figure 5). No subgroup analysis was performed as heterogeneity was low (I2: 0%). Meta-analyses were not performed on hospital readmissions as only one study reported this outcome.

3.3. Non-Clinical Outcomes

Of the 19 laboratory parameters assessed (Table S2), significant improvements were observed in 9 of them. These included reductions in liver enzyme markers (AST, ALT, and GGT), elevated antioxidant levels (α-tocopherol), and a decrease in inflammatory markers such as TNF-α. Fatty acid profiles improved, with increased concentrations of omega-3 fatty acids, DHA, and EPA. Additionally, a beneficial effect on leukotriene levels was noted, marked by a rise in LTB5 and an enhanced LTB5:LTB4 ratio.

3.4. Pharmacoeconomic Analyses

Model input data derived from clinical results were used for all five countries. These were a mean reduction of 1.99 days for length of hospital stay and a mean reduction of 841 infections per 10,000 patients, both in favor of FO-PN. Cost results and the cost-effectiveness analysis for the 10,000 patient-level simulations conducted for each country are shown in Table 2, and sensitivity analyses are also presented (Figures S2–S6). Taken together, these pharmacoeconomic results show that the use of FO-PN was associated with better expected clinical outcomes and concurrent savings (i.e., dominance) in the base case and all sensitivity tests conducted compared to standard PN.

4. Discussion

The current study indicates that FO-PN significantly reduces the risk of infections, sepsis, and length of hospital stays compared to standard PN in hospitalized general ward patients given PN to cover at least 70% of their nutritional needs. Furthermore, FO-PN has potential beneficial effects on marker liver enzyme levels, antioxidant status, and markers of inflammation and improves the fatty acid profile. The clinical outcomes can be compared to our previously published meta-analyses concerning FO-PN vs. NF-PN in the overall group of all hospitalized patients (ICU and general ward populations) [17], as well as the subgroup of ICU patients (Table S3) [18]. All three studies show similar (about 40%) significant reductions in infections and hospital length of stay (between 2 and 3 days). A significant (51%) reduction in sepsis is observed in the current study, as well as in the study including all hospitalized patients (RR 0.44, 95% CI 0.28–0.79; p < 0.0004) [17], but reductions in sepsis failed to reach a significant level within the ICU patient population (RR 0.56, 95% CI 0.26–1.19; p = 0.13) [18]. Reductions in 30-day mortality rates failed to reach significance in all three studies, but it is noticeable that a mortality reduction of 54% in the current study (RR 0.46, 95% CI 0.20–1.08; p = 0.07) is closer to a significant effect than within ICU populations (RR 0.90; 95% CI 0.69–1.16; p = 0.41) [18]. Improved clinical outcomes for PN with ILEs containing fish oil have also been found in many other meta-analyses conducted by a variety of research groups [54,55,56,57,58,59,60,61,62,63].
It should be noted, however, that the current study has several inherent weaknesses based on the moderate-to-low quality of most studies in this field. A major limitation is that all of the included clinical trials were conducted at a single center. Another limitation is a lack of reporting in certain studies, leading to ‘some concerns’ in risk-of-bias assessments in the majority of cases. In particular, for the outcome of sepsis, it would be prudent to interpret the study results with caution owing to a relatively low number of trials and variability in reporting (or lack of reporting) of sepsis definitions. Similarly, the interpretation of reductions in length of stay merits careful consideration; while the overall effect appears reassuringly significant, some degree of variation is to be expected across different patient populations requiring parenteral nutrition in hospital wards, as suggested by the observed heterogeneity in effect estimates.
The present study, encompassing 27 randomized controlled trials, has updated the search and meta-analysis for general ward patients that formed a subset of our previous publication on this topic [17]. This updated search and analysis was needed from a methodological perspective: according to guidance from the Cochrane Collaboration, updates to systematic reviews and meta-analyses are advised at intervals of no more than two years, where practicable [21]. Moreover, as there are potential differences in metabolic needs and nutritional requirements between ICU and general ward patients, it is necessary to conduct this analysis for general ward patients to determine if this subgroup benefitted in a similar fashion to previous analyses [17,18]. Furthermore, the current study extended the previous analysis by separately examining the cost-effectiveness within the population hospitalized in a general ward. Despite higher acquisition costs for FO-PN than standard PN, the use of FO-PN was, overall, a cost-saving strategy in the current study for patients hospitalized in a general ward, as has been found for the ICU population [18] and for the overall group of all hospitalized patients (ICU and general ward populations) [64]. It is noticeable that in countries where ward costs are highest, such as the UK, the greatest savings are likely with this strategy.

5. Conclusions

In summary, this meta-analysis and cost-effectiveness study confirms and extends previous results. It provides evidence that FO-PN provides significant clinical, non-clinical, and cost-effectiveness benefits over NF-PN within a patient population hospitalized in a general ward.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/nu17071284/s1, Figure S1. Risk of bias assessment results (A1. Individual study results, traffic light plot; A2. Infection rate: weighed summary, B2. Mortality rate: weighed summary, C2. Length of stay: weighed summary, D2. Sepsis: summary results); Figure S2a. Scatterplot of 1000 incremental cost-effectiveness ration (ICER) estimates in a probabilistic sensitivity analysis (PSA) for France, and associated tabulated data; Figure S2b. Deterministic sensitivity analyses (DSA) results (tornado plots) representing the sensitivity of cost savings with omega-3 fatty-acid enriched parenteral nutrition to variation in key parameters: patients in France; Figure S3a. Scatterplot of 1000 incremental cost-effectiveness ration (ICER) estimates in a probabilistic sensitivity analysis (PSA) for Germany, and associated tabulated data; Figure S3b. Deterministic sensitivity analyses (DSA) results (tornado plots) representing the sensitivity of cost savings with omega-3 fatty-acid enriched parenteral nutrition to variation in key parameters: patients in Germany; Figure S4a. Scatterplot of 1000 incremental cost-effectiveness ration (ICER) estimates in a probabilistic sensitivity analysis (PSA) for Italy, and associated tabulated data; Figure S4b. Deterministic sensitivity analyses (DSA) results (tornado plots) representing the sensitivity of cost savings with omega-3 fatty-acid enriched parenteral nutrition to variation in key parameters: patients in Italy; Figure S5a. Scatterplot of 1000 incremental cost-effectiveness ration (ICER) estimates in a probabilistic sensitivity analysis (PSA) for Spain, and associated tabulated data; Figure S5b. Deterministic sensitivity analyses (DSA) results (tornado plots) representing the sensitivity of cost savings with omega-3 fatty-acid enriched parenteral nutrition to variation in key parameters: patients in Spain; Figure S6a. Scatterplot of 1000 incremental cost-effectiveness ration (ICER) estimates in a probabilistic sensitivity analysis (PSA) for the UK, and associated tabulated data; Figure S6b. Deterministic sensitivity analyses (DSA) results (tornado plots) representing the sensitivity of cost savings with omega-3 fatty-acid enriched parenteral nutrition to variation in key parameters: patients in the UK; Table S1. Search strings used for MEDLINE (PubMed interface), EMBASE (Elsevier interface), and Web of Science Core Collection (WOS); Table S2. Summary of meta-analysis results for laboratory parameters; Table S3. Comparison of clinical outcomes and cost-effectiveness results from previous meta-analyses and the current study.

Author Contributions

L.P.: conceptualization, methodology, software, validation, formal analysis, data curation, investigation, writing–review and editing, supervision, and project administration. A.R.H.: conceptualization, investigation, and writing–review and editing. S.K.: conceptualization, investigation, and writing–review and editing. K.M.: conceptualization, investigation, and writing–review and editing. M.D.R.: conceptualization, investigation, and writing–review and editing. M.M.: conceptualization, investigation, and writing–review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

Fresenius Kabi GmbH provided financial support for this work. Medical writing (Dr. Richard Clark) and consultancy (Dr. Martina Sintzel) were funded by the sponsor in accordance with Good Publication Practice (GPP3) guidelines.

Institutional Review Board Statement

Not applicable, secondary data analysis.

Informed Consent Statement

Not applicable, secondary data analysis.

Data Availability Statement

All data generated or analyzed during this study are included in this published article (and its Supplementary Information Files).

Acknowledgments

The authors acknowledge Richard Clark (freelance medical writer, Dunchurch, UK) for preparing the initial manuscript draft and Martina Sintzel (medical communication services, Erlenbach, Switzerland) for her expert consultancy.

Conflicts of Interest

L.P. is a director and employee of AdRes, which received funding for this project from Fresenius Kabi. A.R. Heller has been a recipient of research funding from Fresenius Kabi. S.K. has received speaker honoraria from multiple companies (Baxter, Braun, Fresenius Kabi, Nestlé, Nutricia, Shire, and Vipharm) and has served on advisory boards for Fresenius Kabi, Shire, and Tracheron. K.M. has received compensation from Abbott, AstraZeneca, Baxter, BBraun, Fresenius Kabi, MSD, Nestlé, Novartis, and Pfizer. M.D.R. has been paid by Fresenius, Nestlé, and Abbott. M.M. has received speaker fees from Fresenius Kabi. Declaration of generative AI in scientific writing: Nothing to declare.

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Figure 1. Study selection and screening.
Figure 1. Study selection and screening.
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Figure 2. Infection rates: forest plot of a meta-analysis of random effects, showing individual study means and pooled estimates. [26,27,28,30,31,34,35,36,37,39,42,43,46,47,48,49,50,52,53].
Figure 2. Infection rates: forest plot of a meta-analysis of random effects, showing individual study means and pooled estimates. [26,27,28,30,31,34,35,36,37,39,42,43,46,47,48,49,50,52,53].
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Figure 3. Overview of 30-day mortality rates: forest plot from a meta-analysis of random effects, displaying individual study estimates and the overall pooled effect. [26,27,30,31,36,37,39,43,44,50,53].
Figure 3. Overview of 30-day mortality rates: forest plot from a meta-analysis of random effects, displaying individual study estimates and the overall pooled effect. [26,27,30,31,36,37,39,43,44,50,53].
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Figure 4. Length of hospital stay: forest plot of a meta-analysis of random effects, showing individual study means and pooled estimates. [25,26,27,28,30,31,32,34,35,36,39,41,43,44,49,50,52,53].
Figure 4. Length of hospital stay: forest plot of a meta-analysis of random effects, showing individual study means and pooled estimates. [25,26,27,28,30,31,32,34,35,36,39,41,43,44,49,50,52,53].
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Figure 5. Sepsis: forest plot of a meta-analysis of random effects, showing individual study means and pooled estimates. [25,26,27,30,31,34,36,37,47,50,52].
Figure 5. Sepsis: forest plot of a meta-analysis of random effects, showing individual study means and pooled estimates. [25,26,27,30,31,34,36,37,47,50,52].
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Table 1. Characteristics of the randomized controlled trials included (n = 29) [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53], showing extracted outcomes.
Table 1. Characteristics of the randomized controlled trials included (n = 29) [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53], showing extracted outcomes.
StudyCountryPatient Type (n a)PN TypeIntervention bComparatorClinical Outcomes cLaboratory Outcomes
Aliyazicioglu et al., 2013 [25]UKColorectal cancer surgery (n = 36)totalStandard TPN/FO (FO: 0.10–0.20 g/kg/day; % DLD not available)Standard TPNHLOS–
Al Leswas et al., 2020 [26]TurkeySevere acute pancreatitis(n = 45)totalSO/MCT/FO (FO: 0.20 g/kg/day; 10% DLD)SO/MCTMortality, infections, HLOS, and sepsisCRP, DHA, EPA, and TNF
Badia-Tahull et al., 2010 [27]SpainMajor intestinal surgery (n = 29)PNSO/OO/FO (FO: 0.12–0.17 g/kg/day; 16.6% DLD)SO/OOMortality, infections, HLOS, and sepsisALT, Cr, CRP, GGT, and PU
Chen et al., 2017 [28]ChinaGastric cancer surgery (n = 120)PNSO/MCT/OO/FO (FO: 0.15 g/kg/day; 15% DLD)SOInfections and HLOSALT, bilirubin, CRP, and IL-6
Demirer et al., 2016 [29]TurkeyMajor abdominal surgery (n = 52)PNSO/OO/FO (FO dose not available; 15% DLD)SO/OO or SO/MCT–CRP, IL-6, and TNF
Flores-López et al., 2023 [30]MexicoIntestinal failure (n = 20)totalSO/OO + FO (FO: 0.1–0.2 g/kg/day)SO/OOMortality, infections, HLOS, and sepsis–
Ge et al., 2024 [31]ChinaMajor abdominal surgery (n = 268)totalMCT/LCT + FO (FO: 0.2 g/kg/day)MCT/LCTMortality, infections, HLOS, and sepsisCRP, IL-6, and TNF
Grimm et al., 2006 [32]GermanyMajor abdominal surgery (n = 33)totalSO/MCT/OO/FO (FO: 0.23 g/kg/day; 15% DLD)SOHLOSalpha-T, DHA, EPA, LTB4, LTB5, and LTB ratio
Hallay et al., 2010 [33]HungaryGastrointestinal surgery (n = 41)totalSO/MCT/OO/FO(FO: 0.21 g/kg/day; 15% DLD)SO/MCT–ALT, AST, bilirubin, and GGT
Jiang et al., 2010 [34]ChinaGastrointestinal cancer surgery (n = 206)PNSO/FO (FO: 0.2 g/kg/day; 17% DLD)SOInfections, HLOS, and sepsisCr, IL-6, and TNF
Klek et al., 2005 [35]PolandGastric cancer surgery (n = 105, enrolled; n = 71, included in our analysis)PNSO/MCT/FO (FO: 0.10 g/kg/day; % DLD not available)SO/MCTInfections and HLOSALT, AST, Cr, and PU
Klek et al., 2008 [36]PolandGastrectomy or pancreaticoduodenectomy (n = 205)PNSO/MCT/FO (plus glutamine) (FO: 0.10 g/kg/day; % DLD not available)SO/MCTMortality, infections, HLOS, and sepsis–
Klek et al., 2011 [37]PolandGastrectomy or pancreaticoduodenectomy (n = 167)PNSO/MCT/FO (plus glutamine) (FO: 0.10 g/kg/day; % DLD not available)SO/MCTMortality, infections, and sepsis–
Koller et al., 2003 [38]GermanyMajor abdominal surgery (n = 30)totalSO/MCT/FO (FO: 0.07–0.14 g/kg/day; 10% DLD)SO–LTB4, LTB5, and LTB ratio
Liang et al., 2008 [39]ChinaRadical colorectal cancer resection (n = 41)totalSO/FO (FO: 0.20 g/kg/day; 17% DLD)SOMortality, infection, and HLOSGGT, IL-6, Plt, and TNF
Linseisen et al., 2000 [40]GermanyMajor abdominal surgery (n = 33)totalSO/MCT/FO(FO: 0.14 g/kg/day; 10% DLD)SO–alpha-T, DHA, and EPA
Ma et al., 2012 [41]TaiwanGastrointestinal tumor surgery (n = 40)PNSO/MCT/OO/FO (FO: 0.15–0.30 g/kg/day; 15% DLD)SO/MCTHLOSALT, AST, bilirubin, Cr, CRP, IL-6, PU, TG, and TNF
Ma et al., 2015 [42]TaiwanGastric and colorectal cancer surgery (n = 99)PNSO/MCT/FO (FO: 0.08–0.15 g/kg/day; 10% DLD)SO/MCTInfectionsALT, AST, bilirubin, CRP, GGT, IL-6, TG, and TNF
Makay et al., 2011 [43]TurkeyMajor gastric cancer surgery (n = 26)PNSO/FO (FO: 0.2 g/kg/day; 25% DLD)SOMortality, infections, and HLOSALT, AST, Cr, and PU
Mertes et al., 2006 [44]European—MulticenterAbdominal or thoracic surgery (n = 249)totalSO/MCT/OO/FO (FO: 0.23 g/kg/day; 15% DLD)SOMortality and HLOSALT, AST, bilirubin, GGT, and TG
Schauder et al., 2002 [45]GermanyLarge bowel surgery (n = 60)totalSO/FO (FO: 0.2 g/kg/day; 17% DLDSO–TNF
Senkal et al., 2007 [46]GermanyColorectal surgery (n = 40, received study treatments)totalSO/MCT/FO (FO: 0.14–0.28 g/kg/day; 10% DLD)SO/MCTInfectionsDHA, EPA
Wang et al., 2012 [47]ChinaGastrointestinal surgery (n = 64)totalSO/MCT/FO (FO: 0.04–0.08 g/kg/day; 10% DLD)SO/MCTInfections and sepsisALT, AST, bilirubin, CRP, GGT, IL-6, LTB ratio, Plt, TG, and TNF
Wei et al., 2014 [48]ChinaSurgical resection of gastric tumors (n = 52)totalSO/FO (FO dose not available; 20% DLD)SOInfectionsCRP, IL-6, and TNF
Wu et al., 2014 [49]TaiwanGastrointestinal surgery (n = 40)PNSO/MCT/OO/FO (FO 0.13 g/kg/day; 15% DLD)SO/MCTInfections and HLOSALT, AST, bilirubin, Cr, CRP, GGT, IL-6, PU, TG, and TNF
Zhang et al., 2017 [50]ChinaHepatectomy (n = 320)PNSO/MCT/FO (FO dose not available; % DLD not available)SO/MCTMortality, infections, HLOS, and sepsisALT, bilirubin, Cr, CRP, TG, Plt, and PU
Zhixue et al., 2018 [51]ChinaLiver cancer surgery (n = 75)PNSO/MCT/FO (FO dose not available; % DLD not available)SO/MCT–IL-6 and TNF
Zhu et al., 2012 [52]ChinaColorectal cancer surgery (n = 57, completed trial)totalSO/FO (FO: 0.2 g/kg/day; 17% DLD)SOInfection, HLOS, and sepsisIL-6 and TNF
Zhu et al., 2013 [53]ChinaPancreaticoduodenectomy (n = 76)totalSO/MCT/FO (FO: 0.2 g/kg/day; 18% DLD)SO/MCTMortality, infection, HLOS, and hospital readmissionALT, AST, and bilirubin
a The number of randomized patients is listed if available, but if was not available, an alternative descriptor was used for the patient population/number. b This column also shows, in parenthesis, the daily dose of fish oil and the approximate percentage of the daily lipid dose (DLD) supplied by fish oil if these data are available. c Sepsis outcomes encompassed events classified by the original study’s authors as either septic or consistent with systemic inflammatory response syndrome (SIRS). Alpha-T, alpha-tocopherol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Cr, serum creatinine; CRP, C-reactive protein; DHA, (%) docosahexaenoic acid content in serum/cellular membranes; EPA, (%) eicosapentaenoic acid content in serum/cellular membranes; FO, fish oil emulsion; GGT, γ-glutamyl transferase; HLOS, hospital length of stay; ICU, intensive care unit; LCT, long-chain triglycerides; LTB, leukotriene B; LTB ratio, LTB5:LTB4; MCT, medium-chain triglycerides; OO, olive oil emulsion; PU, plasma urea; Plt, platelet; SO, soybean oil emulsion; TGs, triglycerides; and TNF, tumor necrosis factor.
Table 2. Mean costs (Euro) based on model simulations for parenteral nutrition (PN) containing fish oil and NF-PN: results for France, Germany, Italy, Spain, and the UK.
Table 2. Mean costs (Euro) based on model simulations for parenteral nutrition (PN) containing fish oil and NF-PN: results for France, Germany, Italy, Spain, and the UK.
CountryCost TypePN Containing Fish Oil (€)Standard PN (€)Difference (€)ICER
FranceWard cost10,05411,617−1563
Infection cost166264−98
Treatment cost179181−2
Total10,39912,061−1662dominant
GermanyWard cost74448601−1157
Infection cost286455−169
Treatment cost580687−107
Total83109743−1433dominant
ItalyWard cost83699670−1301
Infection cost265421−156
Treatment cost409693−284
Total904310,784−1741dominant
SpainWard cost78079020−1213
Infection cost298473−175
Treatment cost88150−62
Total81929643−1451dominant
UKWard cost12,30914,223−1914
Infection cost125198−73
Treatment cost327386−59
Total12,76114,807−2046dominant
ICER, incremental cost-effectiveness ratio; FA, fatty acid; and PN, parenteral nutrition.
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MDPI and ACS Style

Pradelli, L.; Heller, A.R.; Klek, S.; Mayer, K.; Rosenthal, M.D.; Muscaritoli, M. Parenteral Nutrition Containing Fish Oil for Hospitalized Non-Intensive Care Unit (ICU) Patients: A Systematic Review, Meta-Analysis, and Cost-Effectiveness Analysis. Nutrients 2025, 17, 1284. https://doi.org/10.3390/nu17071284

AMA Style

Pradelli L, Heller AR, Klek S, Mayer K, Rosenthal MD, Muscaritoli M. Parenteral Nutrition Containing Fish Oil for Hospitalized Non-Intensive Care Unit (ICU) Patients: A Systematic Review, Meta-Analysis, and Cost-Effectiveness Analysis. Nutrients. 2025; 17(7):1284. https://doi.org/10.3390/nu17071284

Chicago/Turabian Style

Pradelli, Lorenzo, Axel Rüdiger Heller, Stanislaw Klek, Konstantin Mayer, Martin D. Rosenthal, and Maurizio Muscaritoli. 2025. "Parenteral Nutrition Containing Fish Oil for Hospitalized Non-Intensive Care Unit (ICU) Patients: A Systematic Review, Meta-Analysis, and Cost-Effectiveness Analysis" Nutrients 17, no. 7: 1284. https://doi.org/10.3390/nu17071284

APA Style

Pradelli, L., Heller, A. R., Klek, S., Mayer, K., Rosenthal, M. D., & Muscaritoli, M. (2025). Parenteral Nutrition Containing Fish Oil for Hospitalized Non-Intensive Care Unit (ICU) Patients: A Systematic Review, Meta-Analysis, and Cost-Effectiveness Analysis. Nutrients, 17(7), 1284. https://doi.org/10.3390/nu17071284

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