Acute respiratory distress syndrome (ARDS) is associated with high mortality, some of which can be attributed to ventilator-induced lung injury (VILI) when artificial ventilation is not customized to the severity of lung injury. As ARDS is characterized by a decrease in aerated lung volume, reducing tidal volume (VT) from 12 to 6 mL/kg of predicted body weight (PBW) was shown to improve survival more than 20 years ago. Since then, the VT has been normalized to the PBW, meaning to the theoretical lung size (before the disease), rather than tailored to the severity of lung injury, i.e., to the size of aerated lung volume. During ARDS, the aerated lung volume is correlated to the respiratory system compliance (Crs). The driving pressure (ΔP), defined as the difference between the plateau pressure and the positive end expiratory pressure, represents the ratio between the VT and the Crs. Therefore, the ΔP normalizes the VT to a surrogate of the aerated lung available for ventilation of the diseased lung, rather than to the theoretical lung size of the healthy lung, and thus represents more accurately the actual strain applied to the lungs. In a post hoc analysis of 9 randomized controlled trials, Amato et al. found that higher ΔP was a better predictor of mortality than higher VT, with an increased risk of death when the ΔP \> 14 cm H2O. These findings have been confirmed in subsequent meta-analysis and large-scale observational data. In a prospective study including 50 patients, the investigators showed that a ΔPguided ventilation strategy targeting a ΔP between 12 and 14 cm H2O significantly reduced the mechanical power, a surrogate for the risk of VILI, compared to a conventional PBW-guided ventilation. In the present study, the investigators hypothesize that the physiological individualization of ventilation (ΔP-guided VT) may improve the outcome of patients with ARDS compared to traditional anthropometrical adjustment (PBW-guided VT)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
750
During volume assist control ventilation, the VT will be adjusted in supine position to target a 12 ≤ ΔP ≤ 14 cm H2O. The allowed minimal and maximal values of VT are consistent with usual practices reported in large observational studies 4 and 10 mL/kg of PBW, respectively, while keeping a plateau pressure below 30 cm H2O. The respiratory rate will then be adjusted to meet the pH target
Mortality
The primary endpoint is a ranked composite score that prioritizes 28-day mortality, followed by days free from mechanical ventilation through day 28 for the survivors. Thus, the score is calculated in such a manner that death constitutes a worse outcome than fewer days off the ventilator.
Time frame: 28 days
Number of days free from mechanical ventilation
The primary endpoint is a ranked composite score that prioritizes 28-day mortality, followed by days free from mechanical ventilation through day 28 for the survivors. Thus, the score is calculated in such a manner that death constitutes a worse outcome than fewer days off the ventilator.
Time frame: 28 days
Ventilator parameters
Time frame: up to Day 7
Arterial blood gases
Arterial blood gases (pH, PaO2, PaCO2, HCO3-), recorded in supine position between 6:00 and 12:00 a.m. once a day up to day 7
Time frame: up to Day 7
Mortality
ICU mortality and hospital mortality
Time frame: Day-28, Day 90
Number of days alive without ventilation
Number of days alive without ventilation between randomization and day 28;
Time frame: Up to Day 28
Sequential Organ Failure Assessment score (SOFA)
SOFA score
Time frame: Day 1, Day 3 and Day 7
Number of days alive without catecholamine
Number of days alive without catecholamine between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality;
Time frame: Up to Day 28
Number of days alive without continuous sedation
Number of days alive without continuous sedation between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality
Time frame: Up to Day 28
Number of days alive without neuromuscular blockers
Number of days alive without neuromuscular blockers between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality;
Time frame: UP to Day 28
Number of prone position sessions
Number of prone position sessions
Time frame: Up to Day 28
Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R
Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R
Time frame: Up to Day 28
Occurrence of ventilator-associated pneumothorax
Occurrence of ventilator-associated pneumothorax between randomization and day 28;
Time frame: Up to Day 28
Time to pressure support ventilation;
Time between randomization and transition to pressure support ventilation;
Time frame: Up to Day 28
Duration of weaning unreadiness
Duration of weaning unreadiness measured as the time between randomization and initiation of weaning from mechanical ventilation, defined as the day of the first spontaneous breathing trial;
Time frame: Up to Day 28
Duration of weaning
Duration of weaning, defined as the time between the first spontaneous breathing trial and successful extubation
Time frame: Up to day 28
The rate of tracheostomy
The rate of tracheostomy
Time frame: Up to Day 28
Total duration of mechanical ventilation
Total duration of mechanical ventilation, from intubation to successful extubation, defined as an extubation not followed by reintubation or death within the next 7 days;
Time frame: up to Day 7
Length of stay
Length of stay in the ICU and in hospital;
Time frame: up to Day 28
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