Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial.
Adult
Humans
Female
Middle Aged
Aged
Male
Organ Dysfunction Scores
Shock, Septic
/ complications
Citrulline
/ pharmacology
Multiple Organ Failure
/ etiology
Critical Illness
/ therapy
Respiration, Artificial
/ adverse effects
Sepsis
/ drug therapy
Intensive Care Units
Dietary Supplements
Arginine
/ therapeutic use
Critical care
Immunonutrition
Plasma arginine
Plasma citrulline
SOFA score
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
03 10 2023
03 10 2023
Historique:
received:
24
05
2023
accepted:
18
09
2023
medline:
4
10
2023
pubmed:
3
10
2023
entrez:
2
10
2023
Statut:
epublish
Résumé
Restoring 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. A 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). Of 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. Among 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. ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).
Sections du résumé
BACKGROUND
Restoring 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.
METHODS
A 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).
RESULTS
Of 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.
CONCLUSION
Among 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 REGISTRATION
ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).
Identifiants
pubmed: 37784110
doi: 10.1186/s13054-023-04651-y
pii: 10.1186/s13054-023-04651-y
pmc: PMC10546668
doi:
Substances chimiques
Citrulline
29VT07BGDA
Arginine
94ZLA3W45F
Banques de données
ClinicalTrials.gov
['NCT02864017']
Types de publication
Randomized Controlled Trial
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
381Subventions
Organisme : Ministère des Affaires Sociales et de la Santé
ID : API14/R/001
Organisme : Ministère des Affaires Sociales et de la Santé
ID : API14/R/001
Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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