Immuno Nutrition by L-citrulline for Critically Ill Patients (Immunocitre)

The main objective of this study is to demonstrate that the only administration of L-citrulline, can improve immune functions in critically ill patients at high risk of nosocomial infection.

This is a multicentric therapeutic trial, randomized and double blind: standard enteral nutrition plus L-citrulline (5 grams/12 Hours for 5 days from the admission in Intensive Care Unit (ICU)) versus standard enteral nutrition plus placebo. Methods-Patients: Non-surgical patients admitted in medical intensive care unit, under mechanical ventilation for an expected duration > 2 days, without severe sepsis or septic shock, will be enrolled. Symptoms leading for ICU admission ongoing for five days maximum. On admission (before treatment), the severity will be evaluated with the Sepsis-related Organ Failure Assessment (SOFA) score together with an assessment of plasmatic arginine, cytokines (InterLeukin-6 (IL6) ), and expression of Human Leukocyte Antigen - antigen D Related (HLA-DR) by monocytes. The same evaluation will be repeated on day 3 (during treatment) and on day 7 (after treatment). The enrolment of 100 patients is statistically enough to demonstrate a decreased SOFA scores in the L-citrulline group as compared to the placebo group on day 7.

Binary criterion of success or failure : - Success is defined by: an improved SOFA score of at least 2 points from randomization to Day 7 or an improvement in the general condition yielding the release of the unit; - Failure is defined by an improved SOFA score but less than 2 points, no improvement or worsening of the SOFA score from randomization to Day 7 or the patient's death before J7;

Comparison of the plasmatic concentration of interleukin-6 between the L-citrulline group and the placebo group

Comparison of the percentage of expression of monocytic HLA-DR between the L-citrulline group and the placebo group

Comparison of the plasmatic concentration of L-arginine and its metabolites between the L-citrulline group and the placebo group

Mortality in intensive care and in hospital : Comparison between the L-citrulline group and the placebo group Duration of mechanical ventilation.

Inclusion Criteria: age > 18 years medical patient (absence of recent surgery or trauma) initial aggression < 5 days mechanically ventilated with expected duration of mechanical ventilation > 2 days exclusive enteral nutrition absence of previous immunosuppression Exclusion Criteria: severe sepsis septic shock obesity defined as BMI above 40 pregnancy