Supplemental parenteral nutrition improves immunity with unchanged carbohydrate and protein metabolism in critically ill patients: The SPN2 randomized tracer study
Open accessAbstract
Background & aims Individualized supplemental parenteral nutrition (SPN) providing measured energy expenditure from day 4 reduced infectious complications in a previous study including 305 intensive care (ICU) patients. The study aimed at investigating the metabolic, and immune responses underlying the clinical response of the previous trial.Methods Randomized controlled trial enrolling 23 critically ill patients on day 3 (D3) of admission to the ICU who were fed less than 60% of their energy target by the enteral nutrition (EN) alone: allocation to either continued EN or to SPN to a target validated by indirect calorimetry. Protein and glucose metabolism (primary endpoint) were investigated with tracer isotopes on D4 and D9. Secondary endpoints: 1) immune response, investigated in serum and in stimulated peripheral blood mononuclear cells (PMBC), by dosing a panel of cytokines (infectious complications were recorded), and 2) Muscle mass was assessed by ultrasound of the thigh.Results Comparable at baseline, the SPN group (n = 11) received more energy (median 24.3 versus 17.8 kcal/kg/day: p < 0.001) and proteins (1.11 versus 0.69 g/kg/day: p < 0.001) than the control group during the five days' intervention, resulting in a less negative energy balance by D9 (p = 0.0027). Net protein breakdown and Glucose kinetics on D9 did not differ, within or between groups. In agreement with a decrease in infection rate, immune response in the SPN group showed decreased serum IL-6 (p = 0.024), IL-1β, IL-10 levels and TNF-α secretion by PBMC (p = 0.018) at D9. Muscle mass loss from D4 to D15 tended to be less in the SPN group (-16% versus -23%: p = 0.06). Clinical course by D28 did not differ.Conclusions Feeding patients to cover an individualised measured energy target with SPN from D4 to cover needs, was associated with improved immunity, less systemic inflammation and a trend to less muscle mass loss.Clinical trial registry NCT02022813 at https://clinicaltrials.gov/.
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The exclusion of some randomized studies guided by IC, including two trials showing reduction of infectious complications, was by design because they did not compare IC-guided strategy with equations.
“Fifth, another limitation is the non-conclusion of some randomized studies guided by IC, including two randomized trials showing a reduction of infectious complications in the patients receiving the energy determined by REE [5, 6]. This exclusion was by design as the two studies did not compare IC-guided strategy with equations.”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [5]
Further RCTs using IC as an energy target showed significant reduction in nosocomial infections and improved immunity or less systemic inflammation.
“Results from further RCTs using IC as a energy target showed significant reduction in nosocomial infections [9] and improved immunity or less systemic inflammation [5].”
From Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis (2021) · cites this paper as [5]
Cites
ESPEN guideline on clinical nutrition in the intensive care unit.
Singer, P., Blaser, A. R., Berger, M. M., Alhazzani, W., Calder, P. C., Casaer, M. P., Hiesmayr, M., Mayer, K., Montejo, J. C., Pichard, C., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.08.037 · Cited by 2,904 · see citing works
Self-citationDoig, G. S., Simpson, F., Heighes, P. T., Bellomo, R., Chesher, D., Caterson, I. D., Reade, M. C., & Harrigan, P. W. J. (2015) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00418-x · Cited by 308 · see citing works
Tappy, L., Schwarz, J.-M., Schneiter, P., Cayeux, C., Revelly, J.-P., Fagerquist, C. K., Jequier, E., & Chiolero, R. (1998) · Critical Care Medicine · doi:10.1097/00003246-199805000-00018 · Cited by 211 · see citing works
Self-citationIntensive Nutrition in Acute Lung Injury: A Clinical Trial (INTACT)
Braunschweig, C. A., Sheean, P. M., Peterson, S. J., Gomez Perez, S., Freels, S., Lateef, O., Gurka, D., & Fantuzzi, G. (2015) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607114528541 · Cited by 199 · see citing works
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Duan, J.-Y., Zheng, W.-H., Zhou, H., Xu, Y., & Huang, H.-B. (2021) · Critical Care · doi:10.1186/s13054-021-03508-6 · Cited by 122 · see citing works
Enteral nutrition in hospitalized adults
Gramlich, L., & Guenter, P. (2025) · New England Journal of Medicine · doi:10.1056/nejmra2406954 · Cited by 30 · see citing works
Comerlato, P. H., Stefani, J., & Viana, L. V. (2021) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab218 · Cited by 20 · see citing works
- Authors
- Berger, M. M., Pantet, O., Jacquelin-Ravel, N., Charrière, M., Schmidt, S., Becce, F., Audran, R., Spertini, F., Tappy, L., & Pichard, C.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- University of Lausanne (CH)
- University Hospital of Geneva (CH)
- Corresponding author
- Berger, Mette M.
- ORCID
- Venue
- Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 38
- Issue
- 5
- Pages
- 2408-2416
- ISSN
- 0261-5614 (ISSN-L)
- OpenAlex
- W2900303624
- Cited by
- 92
- References
- 4
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 20 · 2023: 10 · 2022: 11 · 2021: 20 · 2020: 11 · 2019: 7
- Type
- supplementary materials
- Language
- en
- Open access
- Locations
- Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Karolinska Institutet
- Université de Lausanne
- Novartis
- Pfizer
- 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 › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- supplemental parenteral nutrition, critically ill patients, intensive care unit, energy metabolism, protein metabolism, glucose kinetics, immune response, systemic inflammation, cytokines, interleukin-6, muscle mass loss, enteral nutrition, energy balance, infectious complications
- MeSH terms
- Aged, Blood Glucose, Cross Infection, Dietary Carbohydrates, Dietary Proteins, Female, Humans, Immunity, Male, Middle Aged, Parenteral Nutrition, Cytokines, Critical Illness
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