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Cited by 378Clinical Nutrition and GastroenterologyHyperglycemia and glycemic control in critically ill and hospitalized patientsNosocomial Infections in ICU

Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials

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Elke, Gunnar, van Zanten, Arthur R. H., Lemieux, Margot, McCall, Michele, Jeejeebhoy, Khursheed N., Kott, Matthias, Jiang, Xuran, Day, Andrew G. +1 more·2016·Critical Care
DOI 10.1186/s13054-016-1298-1PMC PMC4851818
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Abstract

BACKGROUND: Enteral nutrition (EN) is recommended as the preferred route for early nutrition therapy in critically ill adults over parenteral nutrition (PN). A recent large randomized controlled trial (RCT) showed no outcome differences between the two routes. The objective of this systematic review was to evaluate the effect of the route of nutrition (EN versus PN) on clinical outcomes of critically ill patients. METHODS: An electronic search from 1980 to 2016 was performed identifying relevant RCTs. Individual trial data were abstracted and methodological quality of included trials scored independently by two reviewers. The primary outcome was overall mortality and secondary outcomes included infectious complications, length of stay (LOS) and mechanical ventilation. Subgroup analyses were performed to examine the treatment effect by dissimilar caloric intakes, year of publication and trial methodology. We performed a test of asymmetry to assess for the presence of publication bias. RESULTS: A total of 18 RCTs studying 3347 patients met inclusion criteria. Median methodological score was 7 (range, 2-12). No effect on overall mortality was found (1.04, 95 % CI 0.82, 1.33, P = 0.75, heterogeneity I(2) = 11 %). EN compared to PN was associated with a significant reduction in infectious complications (RR 0.64, 95 % CI 0.48, 0.87, P = 0.004, I(2) = 47 %). This was more pronounced in the subgroup of RCTs where the PN group received significantly more calories (RR 0.55, 95 % CI 0.37, 0.82, P = 0.003, I(2) = 0 %), while no effect was seen in trials where EN and PN groups had a similar caloric intake (RR 0.94, 95 % CI 0.80, 1.10, P = 0.44, I(2) = 0 %; test for subgroup differences, P = 0.003). Year of publication and methodological quality did not influence these findings; however, a publication bias may be present as the test of asymmetry was significant (P = 0.003). EN was associated with significant reduction in ICU LOS (weighted mean difference [WMD] -0.80, 95 % CI -1.23, -0.37, P = 0.0003, I(2) = 0 %) while no significant differences in hospital LOS and mechanical ventilation were observed. CONCLUSIONS: In critically ill patients, the use of EN as compared to PN has no effect on overall mortality but decreases infectious complications and ICU LOS. This may be explained by the benefit of reduced macronutrient intake rather than the enteral route itself.

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  • In polymorbid medical inpatients whose nutritional requirements cannot be met orally, EN may be superior to PN because of a lower risk of infectious and non-infectious complications and maintenance of gut integrity.

    “In polymorbid medical inpatients whose nutritional requirements cannot be met orally, the use of EN may be superior to PN because of a lower risk of infectious, non-infectious complications and maintenance of gut integrity.”

    From ESPEN guideline on nutritional support for polymorbid medical inpatients (2023) · cites this paper as [59]

    The Results report fewer infectious complications with EN, and the Background describes maintenance of gut integrity as a potential benefit. But the review concerns critically ill adults, not polymorbid medical inpatients generally. It does not establish fewer non-infectious complications with EN; the Discussion notes that PN had lower rates of vomiting and diarrhea in one trial. No page numbers are available in our copy. (LLM, conf=0.88)

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  • In a meta-analysis, EN compared to PN was associated with a reduction in ICU infections (RR 0.64, 95% CI 0.48-0.87, p=0.004, I2=47%).

    “In a meta-analysis of studies comparing enteral and parenteral routes independent of timing, Elke et al. [26] found a reduction in ICU infections with EN as compared to PN (RR 0.64, 95% CI 0.48e0.87,p ¼ 0.004, I 2 ¼ 47%).”

    From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [26]

  • The difference in ICU infections between EN and PN did not occur when the amount of energy administered by PN and EN was similar.

    “This difference did not occur when the amount of energy administered by PN and EN was similar (most recent studies), suggesting that caloric overfeeding may play a role in the infectious complications associated with PN and therefore in the decision process regarding the route, timing and the calorie target should also be taken into account.”

    From ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit (2023) · cites this paper as [26]

  • A meta-analysis of 18 RCTs (3347 patients) found no mortality benefit of EN compared to PN.

    “Specifically, a recent metaanalysis of 18 RCTs studying 3347 patients did not find benefits in terms of mortality.”

    From ESPEN guideline on nutritional support for polymorbid medical inpatients (2023) · cites this paper as [59]

  • In that meta-analysis, EN compared to PN was associated with a significant reduction in infectious complications (RR 0.64, 95% CI 0.48 to 0.87, p=0.004) and ICU LOS (WMD -0.80, 95% CI -1.23 to -0.37, p=0.0003, I2=0%), with no significant differences in hospital LOS and mechanical ventilation.

    “In that meta-analysis, EN compared to PN was associated with a significant reduction in infectious complications (RR 0.64, 95% CI 0.48 to 0.87, p ¼ 0.004) and with a significant reduction in ICU LOS (weighted mean difference [WMD] À0.80, 95% CI -1.23 to À0.37, p ¼ 0.0003, I 2 ¼ 0%), while no significant differences in hospital LOS and mechanical ventilation were observed.”

    From ESPEN guideline on nutritional support for polymorbid medical inpatients (2023) · cites this paper as [59]

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Research works printed but not linked: 45

  1. [1]Barrett M Demehri FR Teitelbaum DH Intestine, immunity, and parenteral nutrition in an era of preferred enteral feeding Curr Opin Clin Nutr Metab Care. 2015 18 496 500 10.1097/MCO.0000000000000208 26154279 PMC4589176 · DOI
  2. [2]McClave SA Heyland DK The physiologic response and associated clinical benefits from provision of early enteral nutrition Nutr Clin Pract. 2009 24 305 15 10.1177/0884533609335176 19483060 · DOI · Paper page
  3. [3]McClave SA Martindale RG Rice TW Heyland DK Feeding the critically ill patient Crit Care Med. 2014 42 2600 10 10.1097/CCM.0000000000000654 25251763 · DOI
  4. [4]Cahill NE Dhaliwal R Day AG Jiang X Heyland DK Nutrition therapy in the critical care setting: what is “best achievable” practice? An international multicenter observational study Crit Care Med. 2010 38 395 401 10.1097/CCM.0b013e3181c0263d 19851094 · DOI
  5. [5]Gungabissoon U Hacquoil K Bains C Prevalence, risk factors, clinical consequences, and treatment of enteral feed intolerance during critical illness J Parenter Enteral Nutr. 2015 39 441 8 10.1177/0148607114526450 24637246 · DOI
  6. [6]Braunschweig CL Levy P Sheean PM Wang X Enteral compared with parenteral nutrition: a meta-analysis Am J Clin Nutr. 2001 74 534 42 11566654
  7. [7]Gramlich L Kichian K Pinilla J Rodych NJ Dhaliwal R Heyland DK Does enteral nutrition compared to parenteral nutrition result in better outcomes in critically ill adult patients? A systematic review of the literature Nutrition. 2004 20 843 8 10.1016/j.nut.2004.06.003 15474870 · DOI
  8. [8]Heyland DK MacDonald S Keefe L Drover JW Total parenteral nutrition in the critically ill patient: a meta-analysis JAMA. 1998 280 2013 9 10.1001/jama.280.23.2013 9863853 · DOI
  9. [9]Peter JV Moran JL Phillips-Hughes J A metaanalysis of treatment outcomes of early enteral versus early parenteral nutrition in hospitalized patients Crit Care Med. 2005 33 213 20 10.1097/01.CCM.0000150960.36228.C0 15644672 · DOI
  10. [10]Dellinger RP Levy MM Rhodes A Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012 Crit Care Med. 2013 41 580 637 10.1097/CCM.0b013e31827e83af 23353941 · DOI · Paper page
  11. [11]Dhaliwal R Cahill N Lemieux M Heyland DK The Canadian critical care nutrition guidelines in 2013: an update on current recommendations and implementation strategies Nutr Clin Pract. 2014 29 29 43 10.1177/0884533613510948 24297678 · DOI · Paper page
  12. [12]McClave SA Taylor BE Martindale RG Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) J Parenter Enteral Nutr 2016 40 159 211 10.1177/0148607115621863 26773077 · DOI · Paper page
  13. [13]Singer P Berger MM Van den Berghe G Biolo G Calder P Forbes A ESPEN Guidelines on parenteral nutrition: intensive care Clin Nutr. 2009 28 387 400 10.1016/j.clnu.2009.04.024 19505748 · DOI · Paper page
  14. [14]Preiser JC van Zanten AR Berger MM Metabolic and nutritional support of critically ill patients: consensus and controversies Crit Care. 2015 19 35 10.1186/s13054-015-0737-8 25886997 PMC4310041 · DOI · Paper page
  15. [15]Singer P Hiesmayr M Biolo G Felbinger TW Berger MM Goeters C Pragmatic approach to nutrition in the ICU: expert opinion regarding which calorie protein target Clin Nutr. 2014 33 246 51 10.1016/j.clnu.2013.12.004 24434033 · DOI
  16. [16]Harvey SE Parrott F Harrison DA Bear DE Segaran E Beale R Trial of the route of aarly nutritional support in critically ill adults N Engl J Med. 2014 371 1673 84 10.1056/NEJMoa1409860 25271389 · DOI · Paper page
  17. [17]van Zanten AR Dhaliwal R Garrel D Heyland DK Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis Crit Care. 2015 19 294 10.1186/s13054-015-1002-x 26283217 PMC4539709 · DOI · Paper page
  18. [18]DerSimonian R Laird N Meta-analysis in clinical trials Control Clin Trials. 1986 7 177 88 10.1016/0197-2456(86)90046-2 3802833 · DOI · Paper page
  19. [19]Deeks J Higgins PT Statistical algorithms in Review Manager 5 2010
  20. [20]Rücker G Schwarzer G Carpenter J Arcsine test for publication bias in meta-analyses with binary outcomes Stat Med. 2008 27 746 63 10.1002/sim.2971 17592831 · DOI
  21. [21]Justo Meirelles CM de Aguilar-Nascimento JE Enteral or parenteral nutrition in traumatic brain injury: a prospective randomised trial Nutr Hosp. 2011 26 1120 4 22072362
  22. [22]Wang G Wen J Xu L Zhou S Gong M Wen P Effect of enteral nutrition and ecoimmunonutrition on bacterial translocation and cytokine production in patients with severe acute pancreatitis J Surg Res. 2013 183 592 7 10.1016/j.jss.2012.12.010 23726433 · DOI
  23. [23]Heyland DK Dhaliwal R Drover JW Gramlich L Dodek P Canadian CCCPGC Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients J Parenter Enteral Nutr. 2003 27 355 73 10.1177/0148607103027005355 12971736 · DOI
  24. [24]Moore FA Feliciano DV Andrassy RJ McArdle AH Booth FV Morgenstein-Wagner TB Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis Ann Surg 1992 216 172 83 10.1097/00000658-199208000-00008 1386982 PMC1242589 · DOI
  25. [25]Simpson F Doig GS Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle Intensive Care Med 2005 31 12 23 10.1007/s00134-004-2511-2 15592814 · DOI
  26. [26]Martindale RG Warren M Should enteral nutrition be started in the first week of critical illness Curr Opin Clin Nutr Metab Care. 2015 18 202 6 10.1097/MCO.0000000000000146 25635598 · DOI
  27. [27]Woodcock NP Zeigler D Palmer MD Buckley P Mitchell CJ MacFie J Enteral versus parenteral nutrition: a pragmatic study Nutrition. 2001 17 1 12 10.1016/S0899-9007(00)00576-1 11165880 · DOI
  28. [28]Dissanaike S Shelton M Warner K O’Keefe GE The risk for bloodstream infections is associated with increased parenteral caloric intake in patients receiving parenteral nutrition Crit Care. 2007 11 R114 10.1186/cc6167 17958913 PMC2556767 · DOI
  29. [29]Derde S Vanhorebeek I Güiza F Early parenteral nutrition evokes a phenotype of autophagy deficiency in liver and skeletal muscle of critically ill rabbits Endocrinology. 2012 153 2267 76 10.1210/en.2011-2068 22396453 · DOI
  30. [30]Hermans G Casaer MP Clerckx B Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial Lancet Respir Med. 2013 1 621 9 10.1016/S2213-2600(13)70183-8 24461665 · DOI
  31. [31]Arabi YM Aldawood AS Solaiman O Permissive underfeeding or standard enteral feeding in critical illness N Engl J Med. 2015 373 1175 6 26376142
  32. [32]National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network Rice TW Wheeler AP Thompson BT Steingrub J Hite RD Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial JAMA 2012 307 795 803 10.1001/jama.2012.137 22307571 PMC3743415 · DOI · Paper page
  33. [34]Doig GS Simpson F Sweetman EA Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial JAMA. 2013 309 2130 8 10.1001/jama.2013.5124 23689848 · DOI · Paper page
  34. [36]Sadique Z Grieve R Harrison D Rowan K Cost-effectiveness of early parenteral versus enteral nutrition in critically ill patients Value Health. 2015 18 A532 10.1016/j.jval.2015.09.1658 30224150 · DOI
  35. [37]Rapp RP Young B Twyman D The favorable effect of early parenteral feeding on survival in head-injured patients J Neurosurg. 1983 58 906 12 10.3171/jns.1983.58.6.0906 6406649 · DOI
  36. [38]Adams S Dellinger EP Wertz MJ Oreskovich MR Simonowitz D Johansen K Enteral versus parenteral nutritional support following laparotomy for trauma: a randomized prospective trial J Trauma. 1986 26 882 91 10.1097/00005373-198610000-00004 3095558 · DOI
  37. [39]Young B Ott L Twyman D Norton J Rapp R Tibbs P The effect of nutritional support on outcome from severe head injury J Neurosurg. 1987 67 668 76 10.3171/jns.1987.67.5.0668 3117982 · DOI
  38. [40]Peterson VM Moore EE Jones TN Rundus C Emmett M Moore FA Total enteral nutrition versus total parenteral nutrition after major torso injury: attenuation of hepatic protein reprioritization Surgery. 1988 104 199 207 2456626
  39. [41]Cerra FB McPherson JP Konstantinides FN Konstantinides NN Teasley KM Enteral nutrition does not prevent multiple organ failure syndrome (MOFS) after sepsis Surgery. 1988 104 727 33 3140403
  40. [42]Moore FA Moore EE Jones TN McCroskey BL Peterson VM TEN versus TPN following major abdominal trauma--reduced septic morbidity J Trauma. 1989 29 916 22 10.1097/00005373-198907000-00003 2501509 · DOI
  41. [43]Kudsk KA Croce MA Fabian TC Minard G Tolley EA Poret HA Enteral versus parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma Ann Surg 1992 215 503 11 10.1097/00000658-199205000-00013 1616387 PMC1242485 · DOI
  42. [44]Dunham CM Frankenfield D Belzberg H Wiles C Cushing B Grant Z Gut failure - predictor of or contributor to mortality in mechanically ventilated blunt trauma patients J Trauma. 1994 37 30 4 10.1097/00005373-199407000-00007 8028055 · DOI
  43. [45]Borzotta AP Pennings J Papasadero B Paxton J Mardesic S Borzotta R Enteral versus parenteral nutrition after severe closed head injury J Trauma. 1994 37 459 68 10.1097/00005373-199409000-00022 8083910 · DOI
  44. [47]Kalfarentzos F Kehagias J Mead N Kokkinis K Gogos CA Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial Br J Surg. 1997 84 1665 9 10.1002/bjs.1800841207 9448611 · DOI
  45. [48]Casas M Mora J Fort E Total enteral nutrition vs. total parenteral nutrition in patients with severe acute pancreatitis Rev Esp Enferm Dig 2007 99 264 9 10.4321/S1130-01082007000500004 17650935 · DOI

Cited by

Sorted by citations

Authors
Elke, G., van Zanten, A. R. H., Lemieux, M., McCall, M., Jeejeebhoy, K. N., Kott, M., Jiang, X., Day, A. G., & Heyland, D. K.
Affiliations
  • University Hospital Schleswig-Holstein (DE)
  • Queen's University (CA)
  • St. Michael's Hospital (CA)
Corresponding author
Heyland, Daren K.
ORCID
Venue
Critical Care
Publisher
Springer Science and Business Media LLC
Published
2016-04-29
Volume
20
Issue
1
Pages
117-117
ISSN
1364-8535 (ISSN-L)
DOI
10.1186/s13054-016-1298-1
PMC
PMC4851818
OpenAlex
W2344358128
Cited by
378
References
4
Citations by year
2026: 24 · 2025: 33 · 2024: 45 · 2023: 49 · 2022: 29 · 2021: 31 · 2020: 41 · 2019: 42 · 2018: 53 · 2017: 26 · 2016: 5
FWCI
5.62
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Critical Care (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Nosocomial Infections in ICU
Keywords
enteral nutrition, parenteral nutrition, critically ill patients, mortality, infectious complications, length of hospital stay, mechanical ventilation, energy intake, publication bias, intensive care unit outcomes
MeSH terms
Adult, Enteral Nutrition, Humans, Intensive Care Units, Nutritional Status, Parenteral Nutrition, Randomized Controlled Trials as Topic, Critical Illness

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