Early Enteral Versus Delayed Feeding in Critical Illness: A Narrative Review of Trials Since the Guideline Split
DOI:
https://doi.org/10.5281/zenodo.22278428Keywords:
Enteral nutrition, Critical illness, Timing, Meta-analysis, GuidelinesAbstract
Pooled analysis of 17 randomised trials in 1,725 critically ill adults found that enteral nutrition begun within 48 hours reduced
overall complications, with a risk ratio of 0.81 (95% CI 0.70 to 0.93), infectious complications at 0.68 (0.51 to 0.91) and
pneumonia at 0.76 (0.60 to 0.97), and shortened hospital stay by 1.61 days. No difference was found in mortality or multiple organ
failure. The benefit is therefore in morbidity rather than survival, and two qualifications follow it. Earlier meta-analyses using
different methods and different definitions of early reached contradictory conclusions, and what counts as early is variously 24 or
48 hours. In patients with high illness severity, early feeding has been associated with more gastrointestinal complications and
longer intensive care stay, so the direction of effect may not hold across severity. Guideline recommendations on supplemental
parenteral nutrition differ between the major societies.
References
Fuentes Padilla P, Martinez G, Vernooij RWM, Urrutia G, Roque i Figuls M, Bonfill Cosp X. "Early enteral nutrition (within 48 hours) versus delayed enteral nutrition (after 48 hours) with or without supplemental parenteral nutrition in critically ill adults". Cochrane Database Syst Rev (2019):CD012340.
Marik PE, Zaloga GP. "Early enteral nutrition in acutely ill patients: a systematic review". Crit Care Med 29(2001):2264-2270.
Doig GS, Heighes PT, Simpson F, Sweetman EA, Davies AR. "Early enteral nutrition, provided within 24 h of injury or intensive care unit admission, significantly reduces mortality in critically ill patients: a meta-analysis of randomised controlled trials". Intensive Care Med 35(2009):2018-2027.
McClave SA, Heyland DK. "The physiologic response and associated clinical benefits from provision of early enteral nutrition". Nutr Clin Pract 24(2009):305-315.
Kudsk KA. "Current aspects of mucosal immunology and its influence by nutrition". Am J Surg 183(2002):390-398.
Heyland DK, Dhaliwal R. "Early enteral nutrition vs. delayed enteral nutrition in critically ill patients". Crit Care 19(2015):P369.
Koretz RL, Avenell A, Lipman TO. "Nutritional support for liver disease". Cochrane Database Syst Rev (2012):CD008344.
Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. "Early versus late parenteral nutrition in critically ill adults". N Engl J Med 365(2011):506-517.
Bost RBC, Tjan DHT, van Zanten ARH. "Timing of (supplemental) parenteral nutrition in critically ill patients: a systematic review". Ann Intensive Care 4(2014):31.
Pooled analysis investigators. "Early versus delayed enteral nutrition in critically ill patients: a systematic review and meta-analysis of randomized controlled trials". Int J Clin Exp Med 12(2019):4576-4586.
Gastrointestinal bleeding meta-analysis authors. "Early enteral nutrition versus delayed enteral nutrition in patients with gastrointestinal bleeding: a PRISMA-compliant meta-analysis". Medicine 98(2019):e14864.
Paediatric review authors. "Early versus delayed enteral nutrition in critically ill children under 12 years of age: a systematic review and meta-analysis of randomised controlled trials". J Intensive Med (2025).
Tian F, Heighes PT, Allingstrup MJ, Doig GS. "Early enteral nutrition provided within 24 hours of ICU admission: a meta-analysis of randomized controlled trials". Crit Care Med 46(2018):1049-1056.
Huang HH, Chang SJ, Hsu CW, Chang TM, Kang SP, Liu MY. "Severity of illness influences the efficacy of enteral feeding route on clinical outcomes in patients with critical illness". J Acad Nutr Diet 112(2012):1138-1146.
Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, et al. "Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines". Intensive Care Med 43(2017):380-398.
Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, et al. "ESPEN guideline on clinical nutrition in the intensive care unit". Clin Nutr 38(2019):48-79.
Compher C, Bingham AL, McCall M, Patel J, Rice TW, Braunschweig C, et al. "Guidelines for the provision of nutrition support therapy in the adult critically ill patient: the American Society for Parenteral and Enteral Nutrition". JPEN J Parenter Enteral Nutr 46(2022):12-41.
Comparison review authors. "Comparison of early enteral nutrition versus early parenteral nutrition in critically ill patients: a systematic review and meta-analysis". Nutrients 17(2025):108.
Reignier J, Boisrame-Helms J, Brisard L, Lascarrou JB, Ait Hssain A, Anguel N, et al. "Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2)". Lancet 391(2018):133-143.
Harvey SE, Parrott F, Harrison DA, Bear DE, Segaran E, Beale R, et al. "Trial of the route of early nutritional support in critically ill adults". N Engl J Med 371(2014):1673-1684.
Arabi YM, Aldawood AS, Haddad SH, Al-Dorzi HM, Tamim HM, Jones G, et al. "Permissive underfeeding or standard enteral feeding in critically ill adults". N Engl J Med 372(2015):2398-2408.
Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, et al. "Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial". JAMA 307(2012):795-803.
Elke G, van Zanten ARH, Lemieux M, McCall M, Jeejeebhoy KN, Kott M, et al. "Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials". Crit Care 20(2016):117.
Reintam Blaser A, Preiser JC, Fruhwald S, Wilmer A, Wernerman J, Benstoem C, et al. "Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda". Crit Care 24(2020):224.
Deane AM, Chapman MJ, Reintam Blaser A, McClave SA, Emmanuel A. "Pathophysiology and treatment of gastrointestinal motility disorders in the acutely ill". Nutr Clin Pract 34(2019):23-36.
Heyland DK, Ortiz A, Stoppe C, Patel JJ, Yeh DD, Dukes G, et al. "Incidence, risk factors, and clinical consequence of enteral feeding intolerance in the mechanically ventilated critically ill: an analysis of a multicenter, multiyear database". Crit Care Med 49(2021):49-59.
Preiser JC, Arabi YM, Berger MM, Casaer M, McClave S, Montejo-Gonzalez JC, et al. "A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice". Crit Care 25(2021):424.
Wischmeyer PE. "Tailoring nutrition therapy to illness and recovery". Crit Care 21(2017):316.
Berger MM, Reintam-Blaser A, Calder PC, Casaer M, Hiesmayr MJ, Mayer K, et al. "Monitoring nutrition in the ICU". Clin Nutr 38(2019):584-593.
Patel JJ, Rice T, Heyland DK. "Safety and outcomes of early enteral nutrition in circulatory shock". JPEN J Parenter Enteral Nutr 44(2020):779-784.
Ohbe H, Jo T, Matsui H, Fushimi K, Yasunaga H. "Differences in effect of early enteral nutrition on mortality among ventilated adults with shock requiring low, medium, and high doses of noradrenaline: a propensity-matched analysis". Clin Nutr 39(2020):460-467.
Yeh DD, Fuentes E, Quraishi SA, Cropano C, Kaafarani H, Lee J, et al. "Adequate nutrition may get you home: effect of caloric and protein intake on outcomes in critically ill surgical patients". JPEN J Parenter Enteral Nutr 40(2016):37-44.
Ridley EJ, Davies AR, Parke R, Bailey M, McArthur C, Gillanders L, et al. "Supplemental parenteral nutrition versus usual care in critically ill adults: a pilot randomized controlled study". Crit Care 22(2018):12.
Allingstrup MJ, Kondrup J, Wiis J, Claudius C, Pedersen UG, Hein-Rasmussen R, et al. "Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre, randomised, outcome assessor-blinded EAT-ICU trial". Intensive Care Med 43(2017):1637-1647.
