Trans-pulmonary Pressure in ARDS

Study Overview
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Brief Summary
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Adequate PEEP selection in ARDS is still a matter of research. The main objectives of using PEEP in ARDS are improvement in oxygenation, lung recruitment at the end of expiration, prevention of opening and closing of terminal respiratory units at minimal hemodynamic compromise. The challenge is to carry out these objectives in a patient-centered approach based on individual characteristic of lung pathophysiology. Recently, it has been proposed to set PEEP from the trans-pulmonary end-expiratory pressure. Trans-pulmonary pressure (Ptp) is obtained from the difference between airway pressure and measured esophageal pressure (Pes). Measured Pes values have been found positive in the supine position in ARDS patients, leading to negative values of Ptp. The strategy proposed by Talmor and coworkers is to adjust PEEP up to get Ptp between 0 and 10 cm H2O. Whether this strategy improves survival is under investigation. Prone position ventilation significantly improves survival in severe ARDS as demonstrated by meta-analyses and a recent multicenter randomized controlled trial. The purpose of present project is to investigate Ptp at end-expiration in the prone position in severe ARDS. The project is centered on the question about what are the values of measured Pes in prone position. The hypothesis is that they are lower than in the supine position due to the relief of the weight of heart, mediastinum and lung and also to recruitment of dorsal lung regions. To investigate this hypothesis, measured Pes, Ptp, end-expiratory lung volume, overall lung recruitment (pressure-volume curve), and regional recruitment by using electrical impedance tomography. will be assessed in supine then in the prone position across two different strategies of PEEP selection, PEEP/FIO2 table and Talmor proposal.

Official Title
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Trans-Pulmonary Pressure and Prone Position in Ards Patients

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Device: level of positive end expiratory pressure (Prone Proseva)
* Device: level of positive end expiratory pressure (Prone Talmor)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ARDS intubated indication of proning no contra-indication of proning Exclusion Criteria: contra-indication to proning contra-indication to esophageal balloon proning before end of life decision legal protection pregnancy ECMO

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prone Proseva<br> | Device: level of positive end expiratory pressure (Prone Proseva)<br>* PEEP based on PEEP/FIO2 table vs PEEP based on the value of oesophageal pressure<br>|
| Active Comparator: Prone Talmor<br> | Device: level of positive end expiratory pressure (Prone Talmor)<br>* PEEP based on PEEP/FIO2 table vs PEEP based on the value of oesophageal pressure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Value of the esophageal pressure measured at the end of expiration | Oesophageal pressure is measured from a balloon inserted into the mid oesophagus at the end of expiration. Its value is subtracted to the airway pressure at the end of expiration leading to trans-pulmonary pressure at the end of expiration (Ptp,ee). The measurements are done first in the supine position. In the standardized condition PEEP is set from a PEEP/FIO2 table and Ptp,ee is measured. In the Talmor approach PEEP is set to obtain Ptp,ee between 0 and 10 cm H2O. The patient is then turned to the prone position. The measurements are repeated in the same way. Then for the rest of the proning session the patient receive either level of PEEP from each strategy. Measurements are repeated at the end of the session. | 6.5 hours after inclusion | 
| Value of the esophageal pressure measured at the end of expiration | Oesophageal pressure is measured from a balloon inserted into the mid oesophagus at the end of expiration. Its value is subtracted to the airway pressure at the end of expiration leading to trans-pulmonary pressure at the end of expiration (Ptp,ee). The measurements are done first in the supine position. In the standardized condition PEEP is set from a PEEP/FIO2 table and Ptp,ee is measured. In the Talmor approach PEEP is set to obtain Ptp,ee between 0 and 10 cm H2O. The patient is then turned to the prone position. The measurements are repeated in the same way. Then for the rest of the proning session the patient receive either level of PEEP from each strategy. Measurements are repeated at the end of the session. | 8.0 hours after inclusion | 
| Value of the esophageal pressure measured at the end of expiration | Oesophageal pressure is measured from a balloon inserted into the mid oesophagus at the end of expiration. Its value is subtracted to the airway pressure at the end of expiration leading to trans-pulmonary pressure at the end of expiration (Ptp,ee). The measurements are done first in the supine position. In the standardized condition PEEP is set from a PEEP/FIO2 table and Ptp,ee is measured. In the Talmor approach PEEP is set to obtain Ptp,ee between 0 and 10 cm H2O. The patient is then turned to the prone position. The measurements are repeated in the same way. Then for the rest of the proning session the patient receive either level of PEEP from each strategy. Measurements are repeated at the end of the session. | 10 hours after inclusion | 
| Value of the esophageal pressure measured at the end of expiration | Oesophageal pressure is measured from a balloon inserted into the mid oesophagus at the end of expiration. Its value is subtracted to the airway pressure at the end of expiration leading to trans-pulmonary pressure at the end of expiration (Ptp,ee). The measurements are done first in the supine position. In the standardized condition PEEP is set from a PEEP/FIO2 table and Ptp,ee is measured. In the Talmor approach PEEP is set to obtain Ptp,ee between 0 and 10 cm H2O. The patient is then turned to the prone position. The measurements are repeated in the same way. Then for the rest of the proning session the patient receive either level of PEEP from each strategy. Measurements are repeated at the end of the session. | 11.5 hours after inclusion | 
| Value of the esophageal pressure measured at the end of expiration | Oesophageal pressure is measured from a balloon inserted into the mid oesophagus at the end of expiration. Its value is subtracted to the airway pressure at the end of expiration leading to trans-pulmonary pressure at the end of expiration (Ptp,ee). The measurements are done first in the supine position. In the standardized condition PEEP is set from a PEEP/FIO2 table and Ptp,ee is measured. In the Talmor approach PEEP is set to obtain Ptp,ee between 0 and 10 cm H2O. The patient is then turned to the prone position. The measurements are repeated in the same way. Then for the rest of the proning session the patient receive either level of PEEP from each strategy. Measurements are repeated at the end of the session. | up to 26.5 hours after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elastance of the chest wall | The elastance of the chest wall is the change in esophageal pressure between expiration and inspiration in response to a change in lung volume. It is not substantially changed by PEEP but it is by the change in position. | 6.5 hours after inclusion | 
| Elastance of the chest wall | The elastance of the chest wall is the change in esophageal pressure between expiration and inspiration in response to a change in lung volume. It is not substantially changed by PEEP but it is by the change in position. | 8.0 hours after inclusion | 
| Elastance of the chest wall | The elastance of the chest wall is the change in esophageal pressure between expiration and inspiration in response to a change in lung volume. It is not substantially changed by PEEP but it is by the change in position. | 10 hours after inclusion | 
| Elastance of the chest wall | The elastance of the chest wall is the change in esophageal pressure between expiration and inspiration in response to a change in lung volume. It is not substantially changed by PEEP but it is by the change in position. | 11.5 hours after inclusion | 
| Elastance of the chest wall | The elastance of the chest wall is the change in esophageal pressure between expiration and inspiration in response to a change in lung volume. It is not substantially changed by PEEP but it is by the change in position. | up to 26.5 hours after inclusion | 
| Transpulmonary pressure at the end of expiration (Ptp,ee) | In the standardized condition, either in supine or prone, the transpulmonary pressure is the difference between airway pressure and esophageal pressure at the end of expiration. In the standardized approach, PEEP is set according to a PEEP/FIO2 table and Ptp,ee is dependent on the PEEP/FIO2 table. With the Talmor approach, Ptp,ee is directly set from measurement of esophageal pressure and PEEP set according to the PEEP/FIO2 table. | 6.5 hours after inclusion | 
| Transpulmonary pressure at the end of expiration (Ptp,ee) | In the standardized condition, either in supine or prone, the transpulmonary pressure is the difference between airway pressure and esophageal pressure at the end of expiration. In the standardized approach, PEEP is set according to a PEEP/FIO2 table and Ptp,ee is dependent on the PEEP/FIO2 table. With the Talmor approach, Ptp,ee is directly set from measurement of esophageal pressure and PEEP set according to the PEEP/FIO2 table. | 8.0 hours after inclusion | 
| Transpulmonary pressure at the end of expiration (Ptp,ee) | In the standardized condition, either in supine or prone, the transpulmonary pressure is the difference between airway pressure and esophageal pressure at the end of expiration. In the standardized approach, PEEP is set according to a PEEP/FIO2 table and Ptp,ee is dependent on the PEEP/FIO2 table. With the Talmor approach, Ptp,ee is directly set from measurement of esophageal pressure and PEEP set according to the PEEP/FIO2 table. | 10 hours after inclusion | 
| Transpulmonary pressure at the end of expiration (Ptp,ee) | In the standardized condition, either in supine or prone, the transpulmonary pressure is the difference between airway pressure and esophageal pressure at the end of expiration. In the standardized approach, PEEP is set according to a PEEP/FIO2 table and Ptp,ee is dependent on the PEEP/FIO2 table. With the Talmor approach, Ptp,ee is directly set from measurement of esophageal pressure and PEEP set according to the PEEP/FIO2 table. | 11.5 hours after inclusion | 
| Transpulmonary pressure at the end of expiration (Ptp,ee) | In the standardized condition, either in supine or prone, the transpulmonary pressure is the difference between airway pressure and esophageal pressure at the end of expiration. In the standardized approach, PEEP is set according to a PEEP/FIO2 table and Ptp,ee is dependent on the PEEP/FIO2 table. With the Talmor approach, Ptp,ee is directly set from measurement of esophageal pressure and PEEP set according to the PEEP/FIO2 table. | up to 26.5 hours after inclusion | 
| End expiratory lung volume (EELV) | EELV is the volume of gas at the end of expiration. It is measured from the ventilator by using the washout-washin technique after a small change in the FIO2. An increase in EELV can indicate recruitment (reopening of non aerated lung tissue) but some overinflation may also contribute to this increase. PEEP and prone position can increase EELV. | 6.5 hours after inclusion | 
| End expiratory lung volume (EELV) | EELV is the volume of gas at the end of expiration. It is measured from the ventilator by using the washout-washin technique after a small change in the FIO2. An increase in EELV can indicate recruitment (reopening of non aerated lung tissue) but some overinflation may also contribute to this increase. PEEP and prone position can increase EELV. | 8.0 hours after inclusion | 
| End expiratory lung volume (EELV) | EELV is the volume of gas at the end of expiration. It is measured from the ventilator by using the washout-washin technique after a small change in the FIO2. An increase in EELV can indicate recruitment (reopening of non aerated lung tissue) but some overinflation may also contribute to this increase. PEEP and prone position can increase EELV. | 10 hours after inclusion | 
| End expiratory lung volume (EELV) | EELV is the volume of gas at the end of expiration. It is measured from the ventilator by using the washout-washin technique after a small change in the FIO2. An increase in EELV can indicate recruitment (reopening of non aerated lung tissue) but some overinflation may also contribute to this increase. PEEP and prone position can increase EELV. | 11.5 hours after inclusion | 
| End expiratory lung volume (EELV) | EELV is the volume of gas at the end of expiration. It is measured from the ventilator by using the washout-washin technique after a small change in the FIO2. An increase in EELV can indicate recruitment (reopening of non aerated lung tissue) but some overinflation may also contribute to this increase. PEEP and prone position can increase EELV. | up to 26.5 hours after inclusion | 
| Regional lung ventilation | regional ventilation is measured by using electrical impedance tomography. The change in thoracic impedance in response to electric current of small amplitude (50 ms) is proportional to amount of air among other factors, which are less important in magnitude as compared to air. The lung is sampled into anterior and posterior regions. The location of better aeration with PEEP and position will be mapped. | 6.5 hours after inclusion | 
| Regional lung ventilation | regional ventilation is measured by using electrical impedance tomography. The change in thoracic impedance in response to electric current of small amplitude (50 ms) is proportional to amount of air among other factors, which are less important in magnitude as compared to air. The lung is sampled into anterior and posterior regions. The location of better aeration with PEEP and position will be mapped. | 8.0 hours after inclusion | 
| Regional lung ventilation | regional ventilation is measured by using electrical impedance tomography. The change in thoracic impedance in response to electric current of small amplitude (50 ms) is proportional to amount of air among other factors, which are less important in magnitude as compared to air. The lung is sampled into anterior and posterior regions. The location of better aeration with PEEP and position will be mapped. | 10 hours after inclusion | 
| Regional lung ventilation | regional ventilation is measured by using electrical impedance tomography. The change in thoracic impedance in response to electric current of small amplitude (50 ms) is proportional to amount of air among other factors, which are less important in magnitude as compared to air. The lung is sampled into anterior and posterior regions. The location of better aeration with PEEP and position will be mapped. | 11.5 hours after inclusion | 
| Regional lung ventilation | regional ventilation is measured by using electrical impedance tomography. The change in thoracic impedance in response to electric current of small amplitude (50 ms) is proportional to amount of air among other factors, which are less important in magnitude as compared to air. The lung is sampled into anterior and posterior regions. The location of better aeration with PEEP and position will be mapped. | up to 26.5 hours after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, prone position, PEEP, mechanical ventilation