Introduction
Methods
Study design
Study population
Randomization and masking
Study interventions
Interventions
Outcomes
Protocole changes
Immune monitoring and amino acid plasma level measurements
Cytokine quantification
Amino acid quantification
Gating strategy for the identification of monocytic myeloid-derived suppressor cells (M-MDSCs) and monocyte subsets
Safety analysis
Statistical analysis
Role of the funding source
Results
Patients
L-citrulline (n = 60) | Control (n = 60) | |
---|---|---|
Demographic data, No. (%) | ||
Age (y), median (IQR) | 62 [48–74] | 63 [53–70] |
Male | 39 (65%) | 37 (62%) |
Female | 21 (35%) | 23 (38%) |
BMI (kg/m2), mean ± SD, | 26.3 ± 4.9 | 27.4 ± 5.4 |
Reason for ICU admission | ||
Cardiac arrest | 11 (18%) | 10 (17%) |
Cardiogenic shock | 2 (3%) | 5 (8%) |
Neurologic | 18 (30%) | 12 (20%) |
Respiratory | 18 (30%) | 20 (33%) |
Abdominal | 2 (3%) | 7 (11%) |
Metabolic or acute intoxication | 9 (15%) | 6 (10%) |
SOFA score, median [IQR] | 7 [5–9] | 8 [6–11] |
Delay between mechanical ventilation initiation and randomization (days), median [IQR] | 1 [0–2] | 1 [0–2] |
Plasma amino acid concentrations | ||
L-citrulline (μmol/l), (missing data) median [IQR] | (13) 14.3 [10.2–21.0] | (11) 17.1 [13.4–26.4] |
Arginine (μmol/l), (missing data) median [IQR] | (13) 35.3 [22.6–50.1] | (11) 36.7 [26.2–55.7] |
Glutamate (μmol/l), (missing data) median [IQR] | (13) 35.7 [20.9–50.9] | (11) 39.3 [23.0–52.4] |
Glutamine (μmol/l), (missing data) median [IQR] | (13) 458.7 [357.3–540.8] | (11) 428.0 [321.6–576.3] |
Ornithine (μmol/l), (missing data) median [IQR] | (13) 48.7 [30.3–61.9] | (11) 49.2 [32.9–63.3] |
Proline (μmol/l), (missing data) median [IQR] | (13) 107.8 [81.8–150.1] | (11) 116.8 [102.3–143.7] |
Tryptophan (μmol/l), (missing data) median [IQR] | (13) 32.5 [24.9–43.6] | (13) 28.9 [20.3–36.0] |
Kynurenine (μmol/l), (missing data) median [IQR] | (13) 2.4 [1.4–3.4] | (11) 2.3 [1.5–3.3] |
Primary and secondary outcomes
L-citrulline (n = 60) | Control (n = 60) | p value | |
---|---|---|---|
Primary outcome | |||
SOFA at day 7 | 4 [2–6] | 4 [2–7] | 0.77 |
Secondary outcomes | |||
SOFA at day 3 | 6 [4–7] | 5 [3–8] | 0.82 |
Rate of patients with a decrease of SOFA score ≥ 2 between day 1 and day 7 | 35 (58.3%) | 38 (63.3%) | 0.73 |
Nosocomial infections acquisition | 8 (13.3%) | 17 (28.3%) | 0.18 |
Pneumonia | 8 (13.3%) | 10 (16.7%) | 0.66 |
Positive urine culture | 0 (0%) | 5 (8.3%) | 0.06 |
Any bacteremia | 0 (0%) | 2 (3.3%) | 0.5 |
Hospital mortality | 13 (22%) | 11 (18%) | 0.46 |
ICU mortality | 12 (20%) | 11 (18%) | 0.81 |
Mechanical ventilation duration (days) | 7 [3–11] | 8 [5–14] | 0.08 |
ICU length of stay to discharge or death, median (IQR) | 9 [5–16] | 11 [7–18] | 0.10 |
Hospital length of stay to discharge or death, median (IQR) | 15 [9–25] | 19 [10–28] | 0.11 |