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Intravenous citrulline generation test to assess intestinal function in intensive care unit patients

Authors Peters JH, Wierdsma NJ, Beishuizen A, Teerlink T, van Bodegraven AA

Received 30 August 2016

Accepted for publication 15 January 2017

Published 28 April 2017 Volume 2017:10 Pages 75—81

DOI https://doi.org/10.2147/CEG.S121100

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor Andreas M Kaiser


Job HC Peters,1 Nicolette J Wierdsma,2,3 Albertus Beishuizen,4,5 Tom Teerlink,6 Ad A van Bodegraven,3,7

1Department of Gastroenterology and Hepatology, Red Cross Hospital, Beverwijk, 2Department of Nutrition and Dietetics, VU University Medical Center, Amsterdam, 3Department of Gastroenterology, Small Bowel Disease Unit, VU University Medical Center, Amsterdam, 4Department of Intensive Care, VU University Medical Center, Amsterdam, 5Department of Intensive Care, Intensive Care Center, Medisch Spectrum Twente, Enschede, 6Department of Clinical Chemistry, Metabolic Laboratory, VU University Medical Center, Amsterdam, 7Department of Gastroenterology, Geriatrics, Intensive Care and Internal Medicin (Co-MIK), Zuyderland MC, Heerlen-Sittard-Geleen, the Netherlands


Background: Assessment of a quantifiable small intestinal function test is cumbersome. Fasting citrulline concentrations have been proposed as a measure of enterocyte function and elaborated into a citrulline generation test (CGT), which is applicable only when glutamine is administered orally. CGT is an oral test, limiting its use, for example, in critically ill patients.
Objective: Assessment of normative values and feasibility of an intravenously performed CGT in intensive care unit (ICU) patients with presumed gastrointestinal motility disturbances, especially when performed intravenously.
Design: CGT reference values were determined in 16 stable ICU patients using two different CGT methods, namely following either enteral or intravenous glutamine administration and both with simultaneous arterial and venous plasma citrulline sampling at six time-points. Plasma amino acid analysis was performed using reverse-phase high-performance liquid chromatography.
Results: The median total generation of citrulline in 90 min (CGT iAUCT90) was markedly higher with arterial citrulline sampling compared with venous citrulline sampling, being 724±585 and 556±418 µmol/L/min for enteral glutamine, respectively (p=0.02) and 977±283 and 769±231 µmol/L/min for intravenous glutamine, respectively (p=0.0004). The median slope (time-dependent increase) for plasma arterial and venous citrulline during the CGT was 0.20±0.16 and 0.18±0.12 µmol/L/min for enteral glutamine, respectively (p=0.004) and 0.22±0.16 and 0.19±0.05 µmol/L/min for intravenous glutamine, respectively (p=0.02).
Conclusion: Intravenous glutamine administration combined with arterial plasma citrulline sampling yielded the least variation in CGT characteristics in stable ICU patients. A 2-point measurement test had comparable test characteristics as a 6-point measurement CGT and seems promising.

Keywords: citrulline, citrulline generation test, critical illness, enterocyte, intestinal function, intensive care, ICU, glutamine, HPLC

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