Acute Respiratory Distress Syndrome ARDS
Conditions
Keywords
Acute respiratory distress syndrome (ARDS), ventilator-induced lung injury (VILI), respiratory system compliance (Crs), tidal volume (VT), driving pressure (ΔP), predicted body weight (PBW)
Brief summary
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)
Interventions
OTHERTidal volume customization in the acute respiratory distress syndrome
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
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
comparing ΔP-guided VT to traditional PBW-guided VT during mechanical ventilation of patients with ARDS.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Invasive mechanical ventilation * Criteria for ARDS according to Berlin definition: * Bilateral infiltrates not fully explained by effusions, lobar/lung collapse, or nodules; * PaO2/FiO2 of 300 or less measured with a PEEP of at least 5 cm H2O * Respiratory failure not fully explained by cardiac failure or fluid overload These criteria must be observed for less than 72h * Affiliation to the social security system * Written consent obtained from the patients (from a support person, family member or a close relative if the patient is not able to expressing and sign consent) or inclusion without initial consent in case of emergency, if the patient is not able to express his/her consent and in the absence of support person, family member or a close relative
Exclusion criteria
* Known pregnancy * Lung transplantation * Evident significant decrease in chest wall compliance (e.g., abdominal compartment syndrome) * Moribund patient not expected to survive 24 hours * Presence of an advanced directive to withhold life-sustaining treatment or decision to withhold life-sustaining treatment * Chronic respiratory disease requiring home oxygen therapy or ventilation * ECMO before inclusion * Pneumothorax * Enrollment in an interventional ARDS trial with direct impact on VT * Subject deprived of freedom, subject under a legal protective measure (guardianship/curatorship)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 28 days | 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. |
| Number of days free from mechanical ventilation | 28 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Day-28, Day 90 | ICU mortality and hospital mortality |
| Number of days alive without ventilation | Up to Day 28 | Number of days alive without ventilation between randomization and day 28; |
| Sequential Organ Failure Assessment score (SOFA) | Day 1, Day 3 and Day 7 | SOFA score |
| Number of days alive without catecholamine | Up to Day 28 | Number of days alive without catecholamine between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality; |
| Number of days alive without continuous sedation | Up to Day 28 | Number of days alive without continuous sedation between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality |
| Number of days alive without neuromuscular blockers | UP to Day 28 | Number of days alive without neuromuscular blockers between randomization and day 28, assessed as a hierarchical endpoint prioritized on 28-day mortality; |
| Number of prone position sessions | Up to Day 28 | Number of prone position sessions |
| Ventilator parameters | up to Day 7 | — |
| Occurrence of ventilator-associated pneumothorax | Up to Day 28 | Occurrence of ventilator-associated pneumothorax between randomization and day 28; |
| Time to pressure support ventilation; | Up to Day 28 | Time between randomization and transition to pressure support ventilation; |
| Duration of weaning unreadiness | Up to Day 28 | 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; |
| Duration of weaning | Up to day 28 | Duration of weaning, defined as the time between the first spontaneous breathing trial and successful extubation |
| The rate of tracheostomy | Up to Day 28 | The rate of tracheostomy |
| Total duration of mechanical ventilation | up to Day 7 | 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; |
| Length of stay | up to Day 28 | Length of stay in the ICU and in hospital; |
| Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R | Up to Day 28 | Use of rescue procedures: inhaled nitric oxide, almitrine, ECMO, ECCO2R |
| Arterial blood gases | up to Day 7 | 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 |
Contacts
Primary ContactGuillaume CARTEAUX, Pr
Outcome results
None listed