Trial of the Route of Early Nutritional Support in Critically Ill Adults
Open accessAbstract
BACKGROUND: Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route. METHODS: We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days. RESULTS: We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients. CONCLUSIONS: We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. (Funded by the United Kingdom National Institute for Health Research; CALORIES Current Controlled Trials number, ISRCTN17386141.).
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In the second trial of nutritional support in shock, calorie and protein restriction was associated with lower complications, including less bowel ischemia and liver disease.
“In this study, calorie and protein restriction did not affect survival but was associated with lower complications, including less bowel ischemia and liver disease, and with shorter ICU stay.156”
From Malnutrition and Cachexia in Inpatients With Acute Cardiac Conditions: A Scientific Statement From the American Heart Association (2026) · cites this paper as [156]
The Methods (p. 1) describe a trial comparing parenteral with enteral delivery, not calorie and protein restriction in patients with shock. The Discussion (p. 8) reports no significant difference in ICU length of stay or infectious complications between groups, contrary to the cited sentence; it does not report reduced bowel ischemia or liver disease. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn the second trial of nutritional support in shock (including ≈18% with cardiogenic shock), calorie and protein restriction did not affect survival.
“In this study, calorie and protein restriction did not affect survival but was associated with lower complications, including less bowel ischemia and liver disease, and with shorter ICU stay.156”
From Malnutrition and Cachexia in Inpatients With Acute Cardiac Conditions: A Scientific Statement From the American Heart Association (2026) · cites this paper as [156]
The Study Interventions (p. 2) compare enteral with parenteral delivery, not calorie and protein restriction, and the Discussion (p. 11) says the study leaves nutritional dose unanswered. Although the Discussion (p. 8) reports no significant mortality difference by route, it also reports no significant difference in ICU length of stay, contrary to the cited sentence’s claim of a shorter stay. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn the second trial of nutritional support in shock, calorie and protein restriction was associated with shorter ICU stay.
“In this study, calorie and protein restriction did not affect survival but was associated with lower complications, including less bowel ischemia and liver disease, and with shorter ICU stay.156”
From Malnutrition and Cachexia in Inpatients With Acute Cardiac Conditions: A Scientific Statement From the American Heart Association (2026) · cites this paper as [156]
The Study Interventions (p. 2) describe a comparison of parenteral versus enteral feeding, not a trial of calorie and protein restriction in shock. The Discussion (p. 8) explicitly reports no significant difference in ICU length of stay between the groups, contrary to the claimed shorter stay. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredPrevious trials showed no outcome differences between the enteral and parenteral routes.
“More specifically, the feeding route during the acute phase was at the discretion of the bedside physicians, based on previous trials showing no outcome differences between the enteral and parenteral routes.21,22”
From Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3). (2023) · cites this paper as [22]
The Primary Outcome (p. 5) reports no significant difference in 30-day mortality between enteral and parenteral feeding. But the Secondary Outcomes (p. 5) report significantly less hypoglycemia and vomiting in the parenteral group, so the unqualified claim of no outcome differences overstates the trial's findings. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe 30-day mortality was not different between groups (33.1% vs. 34.2%: parenteral vs. enteral; p = 0.57).
“The 30-day mortality was not different between groups (33.1% vs. 34.2%: parenteral vs. enteral; p = 0.57).”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [40]
There was no difference in incidence of infections and a non-significant trend toward an increased risk of gastrointestinal complications with enteral feeding.
“There was no difference in incidence of infections and a non-significant trend toward an increased risk of gastrointestinal complications with enteral feeding [40].”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [40]
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- Authors
- Harvey, S. E., Parrott, F., Harrison, D. A., Bear, D. E., Segaran, E., Beale, R., Bellingan, G., Leonard, R., Mythen, M. G., & Rowan, K. M.
- Affiliations
- Imperial College Healthcare NHS Trust (GB)
- Intensive Care National Audit & Research Centre (GB)
- King's College London (GB)
- University College London Hospitals NHS Foundation Trust (GB)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2014-10-30
- Volume
- 371
- Issue
- 18
- Pages
- 1673-1684
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2109559031
- Cited by
- 618
- References
- 33
- Citations by year
- 2026: 34 · 2025: 34 · 2024: 39 · 2023: 50 · 2022: 38 · 2021: 50 · 2020: 70 · 2019: 50 · 2018: 69 · 2017: 59 · 2016: 58 · 2015: 63 · 2014: 3 · 2013: 1
- FWCI
- 56.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- UEA Digital Repository (University of East Anglia) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (07/52/03)
- 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 › Surgery › Enhanced Recovery After Surgery
- Keywords
- early nutritional support, parenteral nutrition, enteral nutrition, critically ill adults, intensive care unit, 30-day mortality, hypoglycemia, vomiting, infectious complications, energy intake, unplanned ICU admission, adverse events, 90-day mortality
- MeSH terms
- Adult, Aged, Energy Intake, Enteral Nutrition, Female, Humans, Hypoglycemia, Intensive Care Units, Male, Middle Aged, Parenteral Nutrition, Vomiting, Critical Illness
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