Clinical trial NCT05578742: V/Q Matching Variations With PEEP in ARDS According to Compliance-based Phenotypes (France)
Official title: Effect of PEEP on Ventilartion/Perfusion Ratios According to Different Phenotypes in Patients With ARDS (France)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: ARDS
Keywords: pulmonary perfusion
ventilation-perfusion mismatch
compliance
recruitability
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2022-10-13
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Fifty patients will be enrolled, divided into 2 groups (n=26 each) according to a dynamic balanced sampling based on normalized respiratory system elastance (ERS) measured at PEEP 5 cmH2O with Vt 6-7 ml/kg PBW (\<2 cmH2O.mL-1.kg-1 vs. ≥2 cmH2O.mL-1.kg-1). Enrolment into each study group will be closed at 26 patients.

Then, patients will be randomized and allocated to one of the following strategies:

* Strategy A: PEEP 15 cmH2O → PEEP 5 cmH2O
* Strategy B: PEEP 5 cmH2O → PEEP 15 cmH2O

A parallel study will be conducted in Italy, to reach 50 more patients. Data will be shared between these two studies.
Primary purpose: TREATMENT

Brief summary: This study aim to compare the effect of Positive End Expiratory Pressure (PEEP) on ventilation/perfusion mismatch in two phenotypes of patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS), characterized by their respiratory system elastance (Ers). Ventilation/perfusion mismatch will be assessed by Electrical Impedance Tomography (EIT).

Detailed description: Acute Respiratory Distress Syndrome (ARDS) is characterized by hypoxemia caused by inflammatory lung injury. Recent studies showed an important variability in ARDS phenotypes . The recent COVID-19 crisis highlighted the presence of ARDS patients with severe hypoxemia and normal respiratory system compliance, and retrospective series confirmed the existence of this atypical ARDS pattern also in non-COVID etiologies.

The dissociation between mechanics and hypoxemia may be related to a specific diversity in the pattern of ventilation-perfusion matching (V/Q matching) among patients with normal compliance and ARDS. In patients with low compliance, V/Q mismatch may be characterized by right-to-left shunt, secondary to collapse of the gravity-dependent regions; while, in patients with normal compliance, V/Q mismatch may show a redistribution of blood flow to hypo-ventilated lung areas by larger dead space and impaired hypoxic vasoconstriction.

These differences may also influence the response to PEEP in terms of gas exchange and lung protection . It may also explain the failure for high PEEP levels to improve significantly mortality in the global ARDS population (i.e., with patients' selection only based on hypoxemia).

Electrical Impedance Tomography (EIT) is a device allowing to assess ventilation and perfusion distribution. Thus, EIT can be used to evaluate global and regional V/Q matching, and could be used to understand mechanisms of hypoxemia, especially in patients with normal mechanics and ARDS.

The aim of this study is to assess V/Q matching according to these different ARDS phenotypes, and to evaluate the effects of PEEP in each one.

Eligibility criteria: Inclusion criteria:

* intubated patients with moderate and severe ARDS (Berlin definition, PaO2/FiO2 ≤200 mmHg at PEEP 5 cmH2O)
* undergoing deep sedation
* on controlled mechanical ventilation
* between 24 hours and 5 days after intubation.

Exclusion criteria:

* age \<18 years old; pregnancy
* patient undergoing legal protection
* contra-indications to EIT (e. g. severe chest trauma or wounds)
* pneumothorax; patient undergoing ECMO
* patient with BMI ≥35 kg/m2
* hemodynamic instability with MAP \<60 mmHg despite vasopressors.

Primary outcomes:
measure: Difference in ventilation/perfusion mismatch between PEEP 5 and 15 cmH2O according to the two studied phenotypes
timeFrame: immediately after each intervention
Secondary outcomes:
measure: Difference in respiratory mechanics between PEEP 5 and 15 cmH2O according to the two studied phenotypes
timeFrame: immediately after each intervention
measure: Difference in oxygenation between PEEP 5 and 15 cmH2O according to the two studied phenotypes
timeFrame: immediately after each intervention
measure: Difference in carbon clearance between PEEP 5 and 15 cmH2O according to the two studied phenotypes
timeFrame: immediately after each intervention
measure: Difference in dead space measured by capnometric volumetry between PEEP 5 and 15 cmH2O according to the two studied phenotypes
timeFrame: immediately after each intervention
measure: Difference in dead space measured by calorimetry between PEEP 5 and 15 cmH2O according to the two studied phenotypes
timeFrame: immediately after each intervention
measure: Difference in venous oxygen saturation between PEEP 5 and 15 cmH2O according to the two studied phenotypes
timeFrame: immediately after each intervention
measure: Correlation between V/Q mismatch markers and recruitability
timeFrame: immediately after each intervention
measure: Correlations between V/Q mismatch assessed by EIT and dead space markers
timeFrame: immediately after each intervention
measure: Correlations between V.Q mismacth and overdisension and lung collapsus
timeFrame: immediately after each intervention
measure: Difference in stress index between PEEP 5 and 15 cmH2O according to the two studied phenotypes
timeFrame: immediately after each intervention
Other outcomes:
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