Transpulmonary Pressure - Guided Mechanical Ventilation in Morbidly Obese ARDS Patients: a Feasibility Study.

Study Overview
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Brief Summary
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The goal of this clinical trial is to test a personalized intervention aiming to optimize the mechanical ventilator settings in morbidly obese patients suffering from moderate to severe Acute Respiratory Distress Syndrome (ARDS). The intervention consists of personalized measurements and calculations of the different pressures inside the thorax. The main question to answer is: • Will the evaluated esophageal pressure-guided strategy lead to different mechanical ventilator settings than suggested by a strategy largely used in ARDS patients in France? A specific nasogastric probe permitting to measure esophageal pressure will monitor participants. Esophageal pressure will act as an indicator of the pleural pressure. Other respiratory signals displayed by the mechanical ventilators will also be acquired. Further, ventilator settings will be adjusted to the evaluated esophageal pressure-guided strategy, with possible benefit of this personalized approach.

Detailed Description
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The goal of this clinical trial is to test a personalized intervention aiming to optimize the mechanical ventilator settings in morbidly obese patients suffering from moderate to severe Acute Respiratory Distress Syndrome (ARDS). Mechanical ventilation is the cornerstone of the ARDS symptomatic treatment. Individualization of mechanical ventilator settings could improve prognosis mainly by preventing or decreasing accumulation of fluid in the lung and hemodynamic impairment. It is likely that class III obesity ARDS patients (defined by body mass index (BMI) > 40 kg/m2), could benefit from a highly personalized approach, based on esophageal pressure monitoring. These patients have significantly higher esophageal pressures, acting as an indicator of pleural pressure, than the general ARDS population, while these patients have rather normal mechanical characteristics of the chest wall. Such features could suggest innovative mechanical ventilator settings, by integrating esophageal pressures values, aiming to obtain a slightly positive transpulmonary pressure at the end of expiration. The intervention consists of personalized measurements and calculations of the different pressures, including the esophageal one, inside the thorax. The main question to answer is: • Will the evaluated esophageal pressure-guided strategy lead to different mechanical ventilator settings, mainly the positive end-expiratory pressure (PEEP) setting, than suggested by a PEEP-strategy largely used in ARDS patients in France? A specific nasogastric probe permitting to measure esophageal pressure will monitor participants. The second generation esogastric multifunction Nutrivent catheter (SIDAM, Mirandola, Italy) will be used. It allows both enteral nutrition of the patients and monitoring of esophageal and gastric pressures during several days. Esophageal pressure will act as an indicator of the pleural pressure. Other respiratory signals displayed by the mechanical ventilators will also be acquired, permitting to calculate the trans-pulmonary pressures. Further, ventilator settings will be adjusted to the evaluated esophageal pressure-guided strategy, with possible benefits of this personalized approach. The main benefits for the research participants will be the application of highly personalized mechanical ventilator settings, aiming mainly to select the best PEEP setting with the goal of optimization of opening the lung while avoiding the respiratory and hemodynamic consequences of excessive lung inflation. Monitoring of the end-inspiratory transpulmonary pressures will help to prevent excessive lung inflation.

Official Title
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Transpulmonary Pressure - Guided Mechanical Ventilation in Morbidly Obese ARDS Patients: a Feasibility Study.

Conditions
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ARDS, Human, Obesity, Morbid

Intervention / Treatment
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* Other: Esophageal pressure-guided strategy,


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient (aged 18 years or older) Class III morbid obesity (BMI > 40 kg/m2) Moderate or severe ARDS criteria (according to the Berlin definition) Less than 72 hours between fulfilling moderate or severe ARDS criteria and inclusion Tracheal intubation and invasive mechanical ventilation Informed consent (patient, next of kin), with possibility of an emergency procedure with deferred consent Covid-19 and non-Covid-19 patients Exclusion Criteria: Contra-indication to nasogastric tube (uncontrolled coagulopathy, severe thrombocytopenia, nasal trauma, esophageal varices) Order to limit life-sustaining therapy ExtraCorporal Membrane Oxygenation (ECMO) in use Invasive mechanical ventilation > 96 hours Elevated intracranial pressure Active air-leak: pneumothorax, pneumomediastinum Pregnancy or breast feeding Patient on state medical aid

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esophageal pressure-guided strategy,<br>The second generation esogastric multifunction Nutrivent catheter (SIDAM, Mirandola, Italy) will be used to monitor esophageal and gastric pressures during several days. Ventilator settings will be adjusted to the evaluated esophageal pressure-guided strategy, aiming to obtain a slightly positive transpulmonary pressure at the end of expiration. | Other: Esophageal pressure-guided strategy,<br>* A catheter-balloon system will be positioned and calibrated in all included patients. The second generation esogastric multifunction Nutrivent catheter (SIDAM, Mirandola, Italy) will be used. It allows both enteral nutrition of the patients and monitoring of esophageal and gastric pressures during several days. A connection line will be inserted between the catheter (either esophageal or gastric balloon port) and the auxiliary pressure port of the mechanical ventilator (General Electric, R860, available in each center). Numeric recording of the respiratory signals will be achieved via the OhmedaCom Research Tool software, helping for centralization of the analyses, therefore ensuring reproducibility of the results.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The absolute value of the difference between the PEEP levels determined by esophageal pressure-guided strategy and by the PEEP level indicated by the maximal recruitment arm of the ExPress trial | To demonstrate that the evaluated esophageal pressure-guided strategy leads to significantly and clinically different mechanical ventilator settings (mainly PEEP setting) than the reference strategy. | during the first 24 hours after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ratio between the arterial partial pressure of oxygen (PaO2) on the inspired fraction of oxygenFiO2): PaO2/FiO2 ratio | To assess the efficacy of the esophageal pressure-guided strategy. | during the intervention | 
| The mortality rate of included patients. | To assess the efficacy and safety of the esophageal pressure-guided strategy. | Mortality rate will be determined at end of ICU stay, at Day 28 and at Day 90. | 
| Number of days alive and free for invasive mechanical ventilation | To assess the efficacy of the esophageal pressure-guided strategy. | The numbers of days alive and free for invasive mechanical ventilationwill be determined at Day-28 and Day-90 | 
| Occurrence of pneumothorax | To assess the safety of the esophageal pressure-guided strategy. | during the intervention | 
| Occurence of severe hemodynamic compromise defined by the need of vasoactive treatment | To assess the safety of the esophageal pressure-guided strategy. | during the intervention | 
| Percentage of included patients with inability to insert the Nutrivent catheter | To assess the feasibility of the esophageal pressure-guided strategy. | during the first 24 hours after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, Human, Obesity, morbid, Mechanical Ventilation, Transpulmonary pressure