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24-Hour protein, arginine and citrulline metabolism in fed critically ill children - A stable isotope tracer study
Carlijn T I de Betue1, Xiomara C Garcia Casal2, Dick A van Waardenburg3
1Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Insights
Stable isotope studies in critically ill children reveal high variability in amino acid appearance over 24 hours. This variability, not circadian rhythm, impacts protein and arginine metabolism assessments.
Area of Science:
- Metabolic research in pediatric intensive care.
- Nutritional science and amino acid metabolism.
Background:
- Current methods for studying protein and arginine metabolism in critically ill children rely on short-term (4-8h) stable isotope measurements extrapolated to 24 hours.
- This extrapolation may be inaccurate due to critical illness-related factors and potential circadian rhythms affecting 24-hour measurements.
Purpose of the Study:
- To investigate the 24-hour appearance of specific amino acids (phenylalanine, tyrosine, leucine, arginine, citrulline) using stable isotope techniques in continuously fed critically ill children.
- To assess the variability and potential circadian patterns in amino acid metabolism over a full 24-hour period.
Main Methods:
- A 24-hour stable isotope tracer protocol was conducted in eight critically ill children (0-10 years) receiving continuous parenteral nutrition.
- Intravenous and enteral stable isotopes of phenylalanine, tyrosine, leucine, arginine, and citrulline were infused, with hourly arterial blood sampling.
- Protein intake ranged from 1.0-3.7 g/kg/day.
Main Results:
- High coefficients of variation (14-26%) were observed for the 24-hour appearance of infused amino acids, indicating significant intra-individual variability.
- No evident circadian rhythm was detected in the amino acid appearances.
- The pattern and overall 24-hour level of whole-body protein balance varied considerably among individuals.
Conclusions:
- Amino acid appearances in continuously fed, stable critically ill children exhibit substantial variability over 24 hours.
- This high variability must be considered when designing and interpreting stable isotope studies in this patient population.
- No apparent circadian rhythm influences these amino acid measurements in this context.
Background & Aims:
The reference method to study protein and arginine metabolism in critically ill children is measuring plasma amino acid appearances with stable isotopes during a short (4-8 h) time period and extrapolate results to 24-h. However, 24-h measurements may be variable due to critical illness related factors and a circadian rhythm could be present. Since only short duration stable isotope studies in critically ill children have been conducted before, the aim of this study was to investigate 24-h appearance of specific amino acids representing protein and arginine metabolism, with stable isotope techniques in continuously fed critically ill children.
Methods:
In eight critically ill children, admitted to the pediatric (n = 4) or cardiovascular (n = 4) intensive care unit, aged 0-10 years, receiving continuous (par)enteral nutrition with protein intake 1.0-3.7 g/kg/day, a 24-h stable isotope tracer protocol was carried out. L-[ring-2H5]-phenylalanine, L-[3,3-2H2]-tyrosine, L-[5,5,5-2H3]-leucine, L-[guanido-15N2]-arginine and L-[5-13C-3,3,4,4-2H4]-citrulline were infused intravenously and L-[15N]-phenylalanine and L-[1-13C]leucine enterally. Arterial blood was sampled every hour.
Results:
Coefficients of variation, representing intra-individual variability, of the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline were high, on average 14-19% for intravenous tracers and 23-26% for enteral tracers. No evident circadian rhythm was present. The pattern and overall 24-h level of whole body protein balance differed per individual.
Conclusions:
In continuously fed stable critically ill children, the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline show high variability. This should be kept in mind when performing stable isotope studies in this population. There was no apparent circadian rhythm.
Clinical Trial Register:
NCT01511354 on clinicaltrials.gov.
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