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Annals of Intensive Care

, 6:119

First Online: 12 December 2016Received: 16 June 2016Accepted: 27 November 2016DOI: 10.1186-s13613-016-0220-y

Cite this article as: Hofman, Z., Swinkels, S. & van Zanten, A.R.H. Ann. Intensive Care 2016 6: 119. doi:10.1186-s13613-016-0220-y


Background The role of plasma glutamine, fish oil and antioxidants concentrations in the treatment effect of immune-modulating high-protein versus high-protein enteral nutrition on 6-month mortality in critically ill patients is explored, as unexpected negative outcomes of recent large randomized controlled trials on immune-modulating nutrients have raised questions about safety of these interventions.

MethodsPost hoc analysis of the MetaPlus randomized controlled trial which was performed in a total of 301 medical, surgical and trauma critically ill patients in fourteen European intensive care units. Patients received either immune-modulating glutamine, fish oil and antioxidant enriched high-protein IMHP or isocaloric high-protein HP enteral nutrition. Six-month mortality and baseline, day 4 and day 8 plasma concentrations of glutamine, eicosapentaenoicacid + decosahexaenoicacid-long-chain fatty acid plasma level ratio epa + dha-lcf ratio, selenium, vitamin c, vitamin e and zinc were measured.

Results The harmful treatment effect of the IMHP versus HP enteral nutrition on 6-month mortality was only demonstrated in the medical subgroup HR 2.52, 95% CI 1.36–4.78, P = 0.004. Among medical patients, when corrected for age groups and APACHE-II scores, there were no statistically significant associations between baseline plasma levels and 6-month mortality, except for zinc HR 1.06, 95% CI 1.00–1.12, P = 0.026. IMHP feeding resulted in statistically significant increase in plasma levels of glutamine, vitamin e, vitamin c and epa + dha-lcf ratio from baseline to day 4, while only the change from baseline to day 4 of epa + dha-lcf ratio was statistically significant associated with 6-month mortality HR 1.18, 95% CI 1.02–1.35, P = 0.021 and identified as mediator for the harmful treatment effect of IMHP enteral nutrition among medical ICU patients.

ConclusionWe hypothesize that the harmful effect of IMHP compared to HP enteral nutrition in a heterogeneous group of critically ill patients is limited to the medical critically ill patients and mediated by an early increase in epa + dha-lcf ratio.

Trial Registration Dutch Trial Register 26 January 2010 NTR2181

KeywordsCritically ill Mortality Glutamine Fish oil Antioxidants Nutritional support Immune-modulating nutrients Enteral nutrition Clinical outcome Electronic supplementary materialThe online version of this article doi:10.1186-s13613-016-0220-y contains supplementary material, which is available to authorized users.

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Autor: Zandrie Hofman - Sophie Swinkels - Arthur R. H. van Zanten


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