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Meta-Analysis
. 2019 Jan 24;1(1):CD012041.
doi: 10.1002/14651858.CD012041.pub2.

Immunonutrition for acute respiratory distress syndrome (ARDS) in adults

Ahilanandan Dushianthan  1 , Rebecca Cusack, Victoria A Burgess, Michael Pw Grocott, Philip C Calder
Affiliations
Meta-Analysis

Immunonutrition for acute respiratory distress syndrome (ARDS) in adults

Ahilanandan Dushianthan et al. Cochrane Database Syst Rev. .

Abstract

Background: Acute respiratory distress syndrome (ARDS) is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Pharmacotherapies that moderate inflammation in ARDS are lacking. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS.

Objectives: To systematically review and critically appraise available evidence on the effects of immunonutrition compared to standard non-immunonutrition formula feeding on mechanically ventilated adults (aged 18 years or older) with acute respiratory distress syndrome (ARDS).

Search methods: We searched MEDLINE, Embase, CENTRAL, conference proceedings, and trial registries for appropriate studies up to 25 April 2018. We checked the references from published studies and reviews on this topic for potentially eligible studies.

Selection criteria: We included all randomized controlled trials (RCTs) and quasi-randomized controlled trials comparing immunonutrition versus a control or placebo nutritional formula in adults (aged 18 years or older) with ARDS, as defined by the Berlin definition of ARDS or, for older studies, by the American-European Consensus Criteria for both ARDS and acute lung injury.

Data collection and analysis: Two review authors independently assessed the quality of studies and extracted data from the included trials. We sought additional information from study authors. We performed statistical analysis according to Cochrane methodological standards. Our primary outcome was all-cause mortality. Secondary outcomes included intensive care unit (ICU) length of stay, ventilator days, indices of oxygenation, cardiac adverse events, gastrointestinal adverse events, and total number of adverse events. We used GRADE to assess the quality of evidence for each outcome.

Main results: We identified 10 randomized controlled trials with 1015 participants. All studies compared an enteral formula or additional supplemental omega-3 fatty acids (i.e. eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)), gamma-linolenic acid (GLA), and antioxidants. We assessed some of the included studies as having high risk of bias due to methodological shortcomings. Studies were heterogenous in nature and varied in several ways, including type and duration of interventions given, calorific targets, and reported outcomes. All studies reported mortality. For the primary outcome, study authors reported no differences in all-cause mortality (longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids and antioxidants (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07; participants = 1015; studies = 10; low-quality evidence).For secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants reduces ICU length of stay (mean difference (MD) -3.09 days. 95% CI -5.19 to -0.99; participants = 639; studies = 8; very low-quality evidence) and ventilator days (MD -2.24 days, 95% CI -3.77 to -0.71; participants = 581; studies = 7; very low-quality evidence). We are also uncertain whether omega-3 fatty acids and antioxidants improve oxygenation, defined as ratio of partial pressure of arterial oxygen (PaO₂) to fraction of inspired oxygen (FiO₂), at day 4 (MD 39 mmHg, 95% CI 10.75 to 67.02; participants = 676; studies = 8), or whether they increase adverse events such as cardiac events (RR 0.87, 95% CI 0.09 to 8.46; participants = 339; studies = 3; very low-quality evidence), gastrointestinal events (RR 1.11, 95% CI 0.71 to 1.75; participants = 427; studies = 4; very low-quality evidence), or total adverse events (RR 0.91, 95% CI 0.67 to 1.23; participants = 517; studies = 5; very low-quality evidence).

Authors' conclusions: This meta-analysis of 10 studies of varying quality examined effects of omega-3 fatty acids and/or antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves the duration of ventilator days and ICU length of stay or oxygenation at day 4 due to the very low quality of evidence. Adverse events associated with immunonutrition are also uncertain, as confidence intervals include the potential for increased cardiac, gastrointestinal, and total adverse events.

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Conflict of interest statement

AD: none known.

RC: none known.

VB: none known.

MPWG: leads the Xtreme‐Everest Oxygen Research Consortium, which has received unrestricted grant funding from BOC Medical (Linde Group), Eli Lilly Critical Care, Smith Medical, Deltex Medical, London Clinic, and Rolex. None of this funding has been paid to Dr. Grocott; rather, all funds have been paid directly to the home institutions of researchers within the Consortium. Dr. Grocott has also received honoraria for speaking (not related to this review) and/or travel expenses from Baxter, Fresenius‐Kabi, BOC Medical (Linde Group), and Eli Lilly Critical Care (all before 2010). MG serves on the medical advisory board of Sphere Medical Ltd and receives funding paid via University of Southampton. MG has received unrestricted study funding from Sphere Medical Ltd and Pharmacosmos Ltd.

PCC: In the last three years, PCC has received advisory and/or speaking honoraria from Fresenius‐Kabi (2016 to 2018), Baxter Healthcare (2016), Abbott Nutrition (2017), and Danone/Nutricia (2016, 2017) ‐ sellers of parenteral and enteral feeds, some of which were used in the studies included in this review, and from Pronova BioPharma/BASF AS (2016, 2017, 2018) and Smartfish (2016, 2017, 2018) ‐ sellers of products containing omega‐3 fatty acids.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, outcome: 1.1 All‐cause mortality (longest period reported).
1.1
1.1. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 1 All‐cause mortality (longest period reported).
1.2
1.2. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 2 28‐day mortality.
1.3
1.3. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 3 ICU LOS.
1.4
1.4. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 4 ICU‐free days at day 28.
1.5
1.5. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 5 Ventilator days.
1.6
1.6. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 6 Ventilator‐free days at day 28.
1.7
1.7. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 7 Hospital LOS.
1.8
1.8. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 8 PaO₂/FiO₂ ratio at day 4.
1.9
1.9. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 9 PaO₂/FiO₂ ratio at day 7.
1.10
1.10. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 10 Patients with new organ failure.
1.11
1.11. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 11 Patients with nosocomial infection.
1.12
1.12. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 12 Adverse events ‐ cardiac.
1.13
1.13. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 13 Adverse events ‐ gastrointestinal.
1.14
1.14. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 14 Total adverse events.
1.15
1.15. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 15 Subgroup analysis for the primary outcome (all‐cause mortality) ‐ type of intervention.
1.16
1.16. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 16 Subgroup analysis for the primary outcome (all‐cause mortality) ‐ route of intervention.
1.17
1.17. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 17 Subgroup analysis for the primary outcome (all‐cause mortality) ‐ mode of intervention (bolus or continuous).
1.18
1.18. Analysis
Comparison 1 Omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 18 Subgroup analysis for the primary outcome (all‐cause mortality) ‐ duration of intervention.
2.1
2.1. Analysis
Comparison 2 Sensitivity analysis: omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 1 All‐cause mortality (longest period reported) excluding studies at high risk of bias.
2.2
2.2. Analysis
Comparison 2 Sensitivity analysis: omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 2 ICU LOS.
2.3
2.3. Analysis
Comparison 2 Sensitivity analysis: omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 3 ICU‐free days at day 28.
2.4
2.4. Analysis
Comparison 2 Sensitivity analysis: omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 4 Ventilator days.
2.5
2.5. Analysis
Comparison 2 Sensitivity analysis: omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 5 Ventilator‐free days at day 28.
2.6
2.6. Analysis
Comparison 2 Sensitivity analysis: omega‐3 fatty acids and antioxidants versus placebo or standard nutrition, Outcome 6 Hospital LOS.
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  • doi: 10.1002/14651858.CD012041

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References to other published versions of this review

Dushianthan 2016
    1. Dushianthan A, Cusack R, Grocott MPW. Immunonutrition for acute respiratory distress syndrome (ARDS) in adults. Cochrane Database of Systematic Reviews 2016, Issue 1. [DOI: 10.1002/14651858.CD012041] - DOI - PMC - PubMed

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