Early versus late parenteral nutrition in critically ill children
Open accessAbstract
BACKGROUND: Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear. METHODS: We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided. RESULTS: Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006). CONCLUSIONS: In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.).
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In the proinflammatory phase of acute trauma or infection, nutrition support may even delay healing due to potential interference with clearance of damage.
“In this circumstance, it is becoming likely that nutrition support may even delay healing due to potential interference with clearance of damage.150, 151, 152”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [151]
The Discussion (page not provided) reports fewer new infections and shorter ICU and hospital stays when parenteral nutrition was withheld for one week in critically ill children. A later discussion passage suggests that preservation of autophagy may help explain the benefit, but calls the mechanism speculative. The paper does not establish delayed healing through interference with damage clearance, and its finding concerns early parenteral nutrition in pediatric ICU patients rather than nutrition support generally during acute trauma or infection. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAdding parenteral nutrition to enteral nutrition to increase intakes was associated with longer ICU stays and higher infection rates.
“Adding parenteral nutrition to enteral nutrition to increase intakes was associated with longer ICU stays and higher infection rates.13,14”
In previous randomised trials, nutritional interventions affected time to readiness for ICU discharge but not mortality.
“In previous randomised trials, nutritional interventions affected time to readiness for ICU discharge but not mortality.13,14”
A similar strategy regarding the time to readiness for ICU discharge endpoint has been used previously in studies on nutrition in the ICU.
“A similar strategy regarding this endpoint has been used previously in studies on nutrition in the ICU.13,14”
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- Authors
- Fivez, T., Kerklaan, D., Mesotten, D., Verbruggen, S., Wouters, P. J., Vanhorebeek, I., Debaveye, Y., Vlasselaers, D., Desmet, L., Casaer, M. P., Garcia Guerra, G., Hanot, J., Joffe, A., Tibboel, D., Joosten, K., & Van den Berghe, G.
- Affiliations
- Erasmus MC - Sophia Children’s Hospital (NL)
- University of Alberta (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-03-24
- Volume
- 374
- Issue
- 12
- Pages
- 1111-1122
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2307805172
- Semantic Scholar
- 66acc13cbdfbe1051c3274e8302a09d4f4288c75
- Cited by
- 558
- References
- 36
- Citations by year
- 2026: 38 · 2025: 44 · 2024: 39 · 2023: 66 · 2022: 42 · 2021: 65 · 2020: 69 · 2019: 51 · 2018: 72 · 2017: 47 · 2016: 22 · 2015: 2 · 2014: 1
- FWCI
- 66.33
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- other-oa
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Lirias (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- European Commission
- Erasmus Universiteit Rotterdam
- Fonds NutsOhra
- KU Leuven
- Vereniging Trustfonds Erasmus Universiteit Rotterdam
- Vlaamse regering (METH/08/07, METH/14/06)
- Universitaire Ziekenhuizen Leuven, KU Leuven
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Keywords
- early parenteral nutrition, critically ill children, pediatric intensive care, infection acquisition, ICU length of stay, mechanical ventilation duration, renal replacement therapy, enteral nutrition, volume expansion, mortality, liver enzymes, bilirubin, prognostic factors
- MeSH terms
- Child, Child, Preschool, Enteral Nutrition, Female, Fluid Therapy, gamma-Glutamyltransferase, Humans, Infant, Infections, Length of Stay, Male, Parenteral Nutrition, Respiration, Artificial, Time Factors, Intensive Care Units, Pediatric, Critical Illness, Kaplan-Meier Estimate
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