Open Lung Strategy, Gas Distribution and Right Heart Function in ARDS Patients

Study Overview
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Brief Summary
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The goal of this interventional crossover study, in intubated and mechanically ventilated Acute Respiratory Distress Syndrome (ARDS) patients, is to compare two positive end-expiratory pressure (PEEP) titration techniques regarding: respiratory mechanics, gas exchange, changes in aeration, ventilation/perfusion matching its impact on cardiac function, especially the right heart (RH). The PEEP titration techniques are: PEEP selection based on low PEEP/high FiO2 table (PEEPARDSnet) and lung recruitment maneuver (LRM) plus PEEPdec titration based on the best compliance of the respiratory system(PEEPLRM).

Detailed Description
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A recent large observational study published on JAMA showed that Acute Respiratory Distress Syndrome (ARDS) is associated with high mortality and developed in 10.4% of 29,144 patients admitted to the intensive care unit from 50 countries across 5 continents. Mechanical ventilation is the cornerstone for lung treatment during ARDS. Lung protective ventilation improved ARDS outcome significantly. However, it is still unclear what method should be used to select levels of positive end-expiratory pressure (PEEP). In the current study proposal, the investigators hypothesized that, when ARDS lungs are recruitable, a lung recruitment maneuver (LRM) and PEEP titration (PEEPLRM) improve ventilation/perfusion matching and decreased right heart workload when compared to the actual standard of care PEEP selection based on low PEEP/high FiO2 table (PEEPARDSnet). The investigators will test this hypothesis in an interventional crossover study. 50 patients with ARDS will be enrolled in a physiological and lung and heart imaging study. The protocol is divided in the following phases: A) PEEPARDSnet: setting PEEP according to the ARDSnet table (low PEEP/ high FiO2) B) Recruitability assessment sequence: P-V curve tool (Hamilton ventilator): evaluate patient recruitability, among three criteria, two must be positive to consider a subject recruitable: (1) Presence of a lower inflection point (2) Linear compliance measured more than 2 times higher than the dynamic compliance (3) Increase in volume of more than 300mL during the descendant limb of the PV curve at a same given pressure (20 cmH2O)(Hysteresis property). C)PEEPLRM: LRM plus PEEP decremental trial guided by best compliance. Lung and heart response to PEEPLRM: we will compare the driving pressure (DP) value (DP = Plateau pressure - PEEP) and transthoracic echocardiography (TTE) with the values at PEEPARDSnet. In the advent of an increased DP and/or new onset of abnormal values at the TTE, we will resume the PEEPARDSnet settings during the 48h follow-up phase. Before and after the lung recruitment maneuver and decremental PEEP trial, we will collect: Respiratory system mechanics Lung volumes Gas exchange Hemodynamic parameters Electrical Impedance Tomography (EIT) ventilation and perfusion data Transthoracic echocardiographic indices of RH function Follow-up phase: In 24 and 48 hours, if the subject did not present a negative response to PEEPLRM as described above , we will repeat the recruitment maneuver and the decremental PEEP trial and and we will collect: Respiratory system mechanics (i.e. driving pressure) Lung volumes Gas exchange Hemodynamic parameters EIT ventilation and perfusion data Transthoracic echocardiographic indices of RH function before and after the aforementioned intervention.

Official Title
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Open Lung Strategy, Gas Distribution and Right Heart Function in ARDS Patients: an Open Lung is a Better Heart

Conditions
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ARDS, Human, Lung Injury, Acute, Respiratory Distress Syndrome, Mechanical Ventilation Complication, Alveolar Edema, Right Heart Failure, Right Ventricular Dysfunction

Intervention / Treatment
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* Procedure: PEEP ARDSnet
* Procedure: PEEP LRM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ARDS diagnosis within 72h after intubation Severe to moderate ARDS (PaO2 / FiO2 < 200 mmHg) with PEEP>5 cmH2O Presence of an arterial line Between 18 and 85 years old Exclusion Criteria: Persistent systolic blood pressure < 90 mmHg and/or >180 mmHg despite the use of vasopressor or vasodilators Increment in vasopressors over the past two hour just before enrollment of: more than 15 mcg/min for norepinephrine and dopamine, more than 10 mcg/min in epinephrine; and more than 50 mcg/ min for phenylephrine. Advanced lung disease confirmed by computed tomography findings Presence or history of pneumothorax Severe coagulopathy (INR ≥ 4) Severe thrombocytopenia (Platelets count ≤ 5,000/mm3) Usage of any devices with electric current generation such as pacemaker or internal cardiac defibrillator Recent esophageal trauma or surgery Known presence of esophageal varices Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Physiologic crossover study. There is no randomization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEEP_titration<br>There is no randomization in this interventional, crossover, physiological study. All participants will receive the same procedures in the same order. The investigators will compare two PEEPs (PEEPARDSnet vs. PEEPLRM). Interventions: PEEP ARDSnet: we will select the PEEP based on low PEEP/high FiO2 table (ARDSnet). PEEP LRM: we will perform a lung recruitment maneuver (LRM) and select PEEP based on transpulmonary pressure. | Procedure: PEEP ARDSnet<br>* PEEP settings based on the low PEEP/high FiO2 table<br>Procedure: PEEP LRM<br>* A lung recruitment maneuver (LRM) followed by PEEP guided by transpulmonary pressure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Driving Pressure (cmH2O) | The primary endpoint of this study is to describe the airways driving pressures (defined as Plateau Pressure minus PEEP) during PEEP ARDSnet and PEEP LRM. | 1h (Phase A: PEEP ARDSnet) and 2h (Phase C: PEEP LRM) after the beginning of the study procedures | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, PEEP titration, Open Lung Strategy, Right heart function, Lung recruitment maneuver, Esophageal Pressure, Respiratory system compliance