• Jean-Marc Tadié, Clara Locher, Adel Maamar, Jean Reignier, Pierre Asfar, Morgane Commereuc, Mathieu Lesouhaitier, Murielle Gregoire, Estelle Le Pabic, Claude Bendavid, Caroline Moreau, Jean-Luc Diehl, Alain Gey, Eric Tartour, Le TulzoYvesYUMR 1236, Univ Rennes, INSERM, Établissement Français du Sang, LabexIGO, Rennes, France.SITI Laboratory, CHU Rennes, Rennes, France.Réanimation Médicale, CHU Rennes, Rennes, France., Ronan Thibault, Nicolas Terzi, Arnaud Gacouin, Mikael Roussel, Christophe Delclaux, Karin Tarte, and Luc Cynober.
• UMR 1236, Univ Rennes, INSERM, Établissement Français du Sang, LabexIGO, Rennes, France. jeanmarc.tadie@chu-rennes.fr.
• Crit Care. 2023 Oct 3; 27 (1): 381381.

BackgroundRestoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients.MethodsA randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6).ResultsOf 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected.ConclusionAmong mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo.Trial RegistrationClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).© 2023. BioMed Central Ltd., part of Springer Nature.

32 keywords...

hide…