Electronic Supplementary Material (ESM) File

Electronic Supplementary Material (ESM) file

Title: Effects of a Recruitment Maneuver on Plasma Levels of Soluble RAGE in Patients with Diffuse Acute Respiratory Distress Syndrome: a prospective randomized crossover study.

Authors: Matthieu Jabaudon, Nacim Hamroun, Laurence Roszyk, Renaud Guérin, Jean-Etienne Bazin, Vincent Sapin, Bruno Pereira, Jean-Michel Constantin.

Initial ventilatory management of patients included in the study

Apart from experimental procedures described in the manuscript, our institutional standard initial ventilatory management of patients with early diffuse ARDS included:

- Patient positioning: proclive (30-45°)

- Volume-controlled ventilation

- Tidal volume: 6 ml/kg predicted body weight

- Inspiratory gas flow: 50-70 l/min

- End-inspiratory pause between 0 and 0.5 sec

- Inspiratory: expiratory time ratio ≤1/2

- Respiratory rate ≤ 35/min, with permissive hypercapnia (pH 7.20-7.45)

- Inspiratory fraction of oxygen: set in order to obtain SpO2 between 88 and 95% or PaO2 between 55 and 80 mmHg

- Positive end-expiratory pressure (PEEP) for inspiratory plateau pressure between 28 and 30 cmH2O

Table 2. Plasma levels of sRAGE (pg/mL), measured during sham (up) and RM (down) sequences. Time is expressed with regards to the application of the RM or the equivalent sham period (defined as T0).

SHAM SEQUENCE

Time / N / Mean / Standard deviation / Median
T0 - 5 min / 24 / 4483 / 4715 / 3203
T0 + 5 min / 24 / 5086 / 7400 / 3403
T0 + 30 min / 24 / 4712 / 5029 / 3468
T0 + 1 h / 24 / 4601 / 4886 / 3543
T0 + 4 h / 24 / 4279 / 3270 / 3444
T0 + 6 h / 24 / 4010 / 2592 / 3460

RM SEQUENCE

Time / N / Mean / Standard deviation / Median
T0 - 5 min / 24 / 4145 / 1899 / 3551
T0 + 5 min / 24 / 4219 / 2700 / 3521
T0 + 30 min / 24 / 3883 / 4084 / 2951
T0 + 1 h / 24 / 2680 / 2118 / 2038
T0 + 4 h / 24 / 2888 / 1761 / 2616
T0 + 6 h / 24 / 3211 / 1763 / 2960

Table 3. Evolution of main oxygenation and respiratory parameters in both RM and SHAM sequences. Data are expressed as means ± standard deviation, unless otherwise indicated, and are pooled from patients receiving each sequence, independently from randomization order. P values were calculated in order to detect differences between the 2 groups (RM-SHAM and SHAM-RM). Time is expressed with regards to the application of the RM or the equivalent sham period (defined as T0). Oxygenation index was calculated as: (FiO2 x Mean airway pressure) x PaO2.

RM sequence
(N=24) / SHAM sequence
(N=24) / p
Tidal volume
(ml/kg ideal body weight)
T0 - 5 min
T0 + 5 min
T0 + 30 min
T0 + 1 h
T0 + 4 h
T0 + 6 h / 6.5±0.6
6.6±0.7
6.5±0.8
6.5±0.8
6.9±1.7
7.0±1.9 / 6.8±0.9
6.7±1.1
6.6±0.7
6.6±0.7
6.6±0.7
6.6±0.7 / 0.2
0.7
0.6
0.4
0.4
0.2
Inspiratory plateau pressure (cmH2O)
T0 - 5 min
T0 + 5 min
T0 + 30 min
T0 + 1 h
T0 + 4 h
T0 + 6 h / 26.4±4.5
23.5±5.1
25.7±4.7
25.7±4.7
25.7±4.6
25.8±4.4 / 26.3±3.7
26.2 ± 3.7
24.8±6.1
25.5±3.7
26.2±4.1
25.1±4.9 / 0.7
0.004
0.5
0.8
0.5
0.4
PEEP (cmH2O)
T0 - 5 min
T0 + 5 min
T0 + 30 min
T0 + 1 h
T0 + 4 h
T0 + 6 h / 13.5±2.9
13.3±2.6
13.3±2.6
12.9±2.5
12.9±2.3
12.8±2.4 / 13.2±2.5
1321±2.5
13.2±2.5
13.0±2.4
13.3±2.2
13.1±2.5 / 0.5
0.8
0.9
0.8
0.2
0.3
PaO2 / FiO2 ratio (mmHg)
T0 - 5 min
T0 + 5 min
T0 + 30 min
T0 + 1 h
T0 + 4 h
T0 + 6 h / 133±49
151±62
144±57
141±55
156±65
156±64 / 136±50
140±52
134±39
135±38
145±40
142±41 / 1
0.2
0.2
0.5
0.2
0.2
Fraction of inspired oxygen (FiO2)
T0 - 5 min
T0 + 5 min
T0 + 30 min
T0 + 1 h
T0 + 4 h
T0 + 6 h / 0.6±0.2
0.5±0.2
0.5±0.2
0.5±0.2
0.5±0.2
0.5±0.2 / 0.6±0.2
0.6±0.2
0.6±0.2
0.6±0.2
0.6±0.1
0.6±0.2 / 0.5
0.2
0.1
0.4
0.4
0.3
Lung Injury Score
T0 - 5 min
T0 + 4 h / 3.2±0.3
2.6±0.6 / 3.1±0.3
2.7±0.6 / 0.4
0.6
Oxygenation index
T0 - 5 min
T0 + 5 min
T0 + 30 min
T0 + 1 h
T0 + 4 h
T0 + 6 h / 0.2±0.1
0.2±0.1
0.2±0.1
0.2±0.1
0.1±0.1
0.1±0.1 / 0.2±0.1
0.2±0.1
0.2±0.1
0.2±0.1
0.1±0.1
0.1±0.1 / 0.4
0.5
0.5
0.8
0.8
1
Static pulmonary compliance (ml/cmH2O)
T0 - 5 min
T0 + 5 min
T0 + 30 min
T0 + 1 h
T0 + 4 h
T0 + 6 h / 33±10
36±11
35±12
35±12
38±19
38±22 / 33±10
33±10
35±12
35±12
34±13
37±16 / 1
0.2
1
0.9
0.1
0.6

Table 4. Patient outcomes, and their correlation with plasma levels of sRAGE, as measured before and 1 hour after the RM. Correlations have been tested with the calculation of Spearman’s rank correlation coefficient r (rho). Comparisons of sRAGE levels between survivors and non-survivors on day 28, and between patients with or without ventilator-associated pneumonia up to day 28, have been tested with Kruskal-Wallis test.

Outcome / Correlation with plasma sRAGE (before RM) / Correlation with plasma sRAGE (1 hour after RM)
Length of stay in the ICU (days), mean±SD / 23±15 / r=0.03 (p=0.9) / r=0.2 (p=0.3)
Number of ventilator free-days at day 28, median [interquartile 25-75] / 1.5 [0-15] / r=0.4 (p=0.03) / r=0.2 (p=0.2)
Outcome / Baseline plasma sRAGE levels (pg/ml) / Plasma sRAGE levels 1 hour after RM (pg/ml)
Survival on day 28, n (%) / 16 (67) / 3412+/-1813 (alive) vs. 3811+/-2149 (dead), p=0.15 / 2601+/-1453 (alive) vs. 2839+/-3188 (dead), p=0.3
Ventilator-associated pneumonia, n (%) / 10 (42) / 3794+/-891 (VAP) vs. 4396+/-2381 (no VAP), p=0.9 / 2346+/-833 (VAP) vs. 2919 +/- 2703 (no VAP), p=0.6