Energy-dense versus routine enteral nutrition in the critically ill
Open accessAbstract
BACKGROUND: The effect of delivering nutrition at different calorie levels during critical illness is uncertain, and patients typically receive less than the recommended amount. METHODS: We conducted a multicenter, double-blind, randomized trial, involving adults undergoing mechanical ventilation in 46 Australian and New Zealand intensive care units (ICUs), to evaluate energy-dense (1.5 kcal per milliliter) as compared with routine (1.0 kcal per milliliter) enteral nutrition at a dose of 1 ml per kilogram of ideal body weight per hour, commencing at or within 12 hours of the initiation of nutrition support and continuing for up to 28 days while the patient was in the ICU. The primary outcome was all-cause mortality within 90 days. RESULTS: There were 3957 patients included in the modified intention-to-treat analysis (1971 in the 1.5-kcal group and 1986 in the 1.0-kcal group). The volume of enteral nutrition delivered during the trial was similar in the two groups; however, patients in the 1.5-kcal group received a mean (±SD) of 1863±478 kcal per day as compared with 1262±313 kcal per day in the 1.0-kcal group (mean difference, 601 kcal per day; 95% confidence interval [CI], 576 to 626). By day 90, a total of 523 of 1948 patients (26.8%) in the 1.5-kcal group and 505 of 1966 patients (25.7%) in the 1.0-kcal group had died (relative risk, 1.05; 95% CI, 0.94 to 1.16; P=0.41). The results were similar in seven predefined subgroups. Higher calorie delivery did not affect survival time, receipt of organ support, number of days alive and out of the ICU and hospital or free of organ support, or the incidence of infective complications or adverse events. CONCLUSIONS: In patients undergoing mechanical ventilation, the rate of survival at 90 days associated with the use of an energy-dense formulation for enteral delivery of nutrition was not higher than that with routine enteral nutrition. (Funded by National Health and Medical Research Institute of Australia and the Health Research Council of New Zealand; TARGET ClinicalTrials.gov number, NCT02306746 .).
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The non-significantly lower all-cause mortality in the low group is in keeping with previous studies.
“All-cause mortality was non-significantly lower in the low versus the standard group, in keeping with previous studies.10,16-18”
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 [10]
The Outcomes section reports non-significantly lower 90-day mortality in the 1.0-kcal group than in the 1.5-kcal group (25.7% versus 26.8%; P = 0.41). But this paper compares routine (standard) nutrition with energy-dense nutrition, not a low-nutrition group with a standard group. It supports the direction and lack of statistical significance, but not the stated comparison. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn randomised trials, increasing the enteral calorie intake did not improve outcomes.
“In randomised trials, increasing the enteral calorie intake did not improve outcomes.10-12”
The TARGET trial found no benefits from increasing the enteral calorie supply.
“The TARGET trial found no benefits from increasing the enteral calorie supply.10”
The TARGET trial found that higher calorie delivery did not affect mortality, receipt of or liberation from organ support, or incidence of infective complications.
“Higher calorie delivery did not affect mortality, receipt of or liberation from organ support, or incidence of infective complications [22].”
From Nutrition in Sepsis: A Bench-to-Bedside Review. (2020) · cites this paper as [22]
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References 33 · Cited by 345
- Authors
- The TARGET Investigators
- Affiliations
- Wellington Hospital (NZ)
- Corresponding author
- The TARGET Investigators
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-11-08
- Volume
- 379
- Issue
- 19
- Pages
- 1823-1834
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2903692229
- Semantic Scholar
- 880e4c4a275c503287a4dfe2262b1f325ac501e7
- Cited by
- 345
- References
- 33
- Citations by year
- 2026: 31 · 2025: 55 · 2024: 34 · 2023: 35 · 2022: 35 · 2021: 41 · 2020: 65 · 2019: 48 · 2018: 1
- FWCI
- 32.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Health and Medical Research Council of Australia (107826)
- Health Research Council of New Zealand (15.141)
- 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, mechanical ventilation, critical illness, all-cause mortality, intensive care, nutritional support, organ support, infectious complications, intensive care unit
- MeSH terms
- Adult, Aged, Energy Intake, Double-Blind Method, Enteral Nutrition, Female, Gastrointestinal Diseases, Humans, Intensive Care Units, Male, Middle Aged, Respiration, Artificial, Survival Rate, Critical Illness, Intention to Treat Analysis
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