Effects of normocaloric vs. hypocaloric enteral nutrition on whole-body protein turnover in critically ill patients
https://doi.org/10.5878/b1e8-fg58
Enteral nutrition (EN) is a ubiquitous intervention in ICU patients but there is uncertainty regarding the optimal dose, timing and importance for patient-centered outcomes during critical illness. Our research group has previously found an improved protein balance during normocaloric versus hypocaloric parenteral nutrition in neurosurgical ICU patients. We now wanted to investigate if this could be demonstrated in a general ICU population with established enteral feeding, including patients on renal replacement therapy.
Patients with EN >80% of energy target as determined by indirect calorimetry were randomized to or 50% or 100% of current EN rate. After 24 hours, whole body protein kinetics were determined by enteral and parenteral stable isotope tracer infusions. Treatment allocation was then switched, and tracer investigations repeated 24 hours later in a crossover design with patients serving as their own controls.
The files give all data for calculating whole body protein kinetics and the amino acids and urea concentrations at the end of the two 24h intervention periods (day 1 and day 2).
The file "Tracer infusions" gives the details of the preparation of the tracers infused during the two days, including the volumes taken up in the syringes, the dilutions and the final weight of the syringes. All this information is used to calculate the exact rates of infusion in micromol per kg bodyweight per hour.
The file "Enrichments" includes the amount of the tracers (given as Molar Percent Excess) in the blood samples and in the dialysis samples as measured at the different time points during the 5 hours infusion of the tracers. The last 4 samples over the last 15 minutes of the two 24h periods are averaged and used for the calculations of the whole body protein turnover as specified in the publication.
The file "Amino acids and Urea" gives the concentrations of all amino acids in plasma and in the dialysate (if appropriate) and of urea in plasma at the end of the two 24h intervention periods (last sample only).
Citation and access
Citation and access
Data access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
No
Citation:
Language:
Method and outcome
Method and outcome
Population:
Adult ICU patients with invasive mechanical ventilation and an FiO2 of =/<0.6.
Study design:
- Experimental study
Time period(s) investigated:
Data format/data structure:
Data collection - Biological tests
Data collection - Biological tests
Mode of collection:
Biological tests
Time period(s) for data collection:
2017-02-15 - 2018-03-07
Source of the data:
- Biological samples
Geographic coverage
Geographic coverage
Geographic location:
Administrative information
Administrative information
Responsible department/unit:
Department of Clinical Science, Intervention and Technology [H9]
Contributor(s):
- Jan Wernerman – Karolinska Institutet
- Felix Liebau – Karolinska Institutet
Ethical Review
Ethical Review
Reviewer:
- Stockholm Ethical Review Board
Registration number:
2016/76-31/4
Funding
Funding
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2016-02375_VR
Award title:
Blockage of autophagy and critical illness related organ failure.
Funding information:
Organ failure is the main cause of mortality in critically ill patients treated in the ICU. The overall aim of this project is to elucidate the role of an impaired protein breakdown of damaged proteins by a block in the autophagy flux in the development of organ failure. We have developed a model for measuring autophagy flux that allows for screening of larger patients groups. The first results with this novel model suggest that there are factors in the blood of critically ill patient that can induce a block in autophagy. The specific aims of the project are to assess where in the autophagy pathway the block occurs, what in blood actually causes the block and what the cellular and physiological consequences of this block are. For this we will incubate primary human muscle cells and hepatocytes with serum from 100 critically ill patients and measure autophagy flux by in-cell western blotting and formation of the different stages in the autophagy pathway with confocal microscopy. We will use proteomics and metabolomics analyses to find the factors in serum that induce a block in the autophagy flux. To measure the cellular and physiological consequences of a block we will measure formation of damaged mitochondrial proteins and mitochondrial function. Within the project we will identify factors in the blood of critically ill patients with organ failure that can induce a block in autophagy. In addition we will find out if nutrition has a possible worsening effect on this.
Funding agency:
- Stockholm County Council
Award number:
563170
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2019-01629_VR
Award title:
Blockage of autophagy and critical illness related organ failure.
Funding information:
The main cause for mortality in acutely critically ill patients is multiple organ failure in which vital organs are failing and if not supported by intensive care, the patients will die. A few clinical studies have suggested that early nutrition in these patients prolongs their organ failure by inhibiting the clearance of intracellular damaged proteins by the autophagy system. We have been studying this process in more detail in an in vitro model and showed that only few patients probably have this problem and that nutrition is unlikely to be the key regulator of a block in autophagy.In the present project we will use the same model to verify that nutrition is not the primary factor in this, but that starvation might be a strategy to reverse the block in some patients. We will also try to identify signal that induces the autophagy block and the mechanism why this block in autophagy is happening in a subgroup of critically ill patients. In addition will we study the cellular consequences of a block in the autophagy to better understand the development of organ failure.With this project we like to elucidate the mechanisms behind the mortal organ failure in critically ill patients and the interaction with nutrition. This should in the future prevent undernutrition of patients that are already often malnourished. In addition, we should be able to detect find novel mechanism for the detrimental development of organ failure in critically ill patients.
Topic and keywords
Topic and keywords
Swedish Standard Classification of Research Subjects 2025:
Publications
Publications
Citation:
Rehal, M., Liebau, F., Wernerman, J., & Rooyackers, O. (2020). Whole-body protein kinetics in critically ill patients during 50 or 100% energy provision by enteral nutrition: A randomized cross-over study. In PLOS ONE (Vol. 15, Issue 10, pp. e0240045–e0240045). https://doi.org/10.1371/journal.pone.0240045
SwePub:
Citation:
Sundström, R. M., & Sundström, R. M. (2020). Energy expenditure and substrate utilization during critical illness. https://hdl.handle.net/10616/47295
ISBN:
SwePub:
Metadata
Metadata
Version 1
